BMC Pulm Med BMC Pulm Med 64 bmcpm BMC Pulmonary Medicine 1471-2466 BMC PMC4657365 PMC4657365.1 4657365 4657365 26597174 10.1186/s12890-015-0140-x 140 1 Research Article Hypertonic saline (HS) for acute bronchiolitis: Systematic review and meta-analysis Maguire Chin c.maguire@sheffield.ac.uk Cantrill Hannah h.cantrill@sheffield.ac.uk Hind Daniel d.hind@sheffield.ac.uk Bradburn Mike m.bradburn@sheffield.ac.uk Everard Mark L. mark.everard@uwa.edu.au Clinical Trials Research Unit, University of Sheffield, Sheffield, UK School of Paediatrics and Child Health (SPACH), The University of Western Australia, Perth, Australia 23 11 2015 2015 15 249697 148 25 6 2015 10 11 2015 23 11 2015 25 11 2015 03 03 2025 © Maguire et al. 2015 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated. Background Acute bronchiolitis is the commonest cause of hospitalisation in infancy. Currently management consists of supportive care and oxygen. A Cochrane review concluded that, “nebulised 3 % saline may significantly reduce the length of hospital stay”. We conducted a systematic review of controlled trials of nebulised hypertonic saline (HS) for infants hospitalised with primary acute bronchiolitis. Methods Searches to January 2015 involved: Cochrane Central Register of Controlled Trials; Ovid MEDLINE; Embase; Google Scholar; Web of Science; and, a variety of trials registers. We hand searched Chest, Paediatrics and Journal of Paediatrics on 14 January 2015. Reference lists of eligible trial publications were checked. Randomised or quasi-randomised trials which compared HS versus either normal saline (+/− adjunct treatment) or no treatment were included. Eligible studies involved children less than 2 years old hospitalised due to the first episode of acute bronchiolitis. Two reviewers extracted data to calculate mean differences (MD) and 95 % Confidence Intervals (CIs) for length of hospital stay (LoS—primary outcome), Clinical Severity Score (CSS) and Serious Adverse Events (SAEs). Meta-analysis was undertaken using a fixed effect model, supplemented with additional sensitivity analyses. We investigated statistical heterogeneity using I 2 . Risk of bias, within and between studies, was assessed using the Cochrane tool, an outcome reporting bias checklist and a funnel plot. Results Fifteen trials were included in the systematic review ( n  = 1922), HS reduced mean LoS by 0.36, (95 % CI 0.50 to 0.22) days, but with considerable heterogeneity (I 2  = 78 %) and sensitivity to alternative analysis methods. A reduction in CSS was observed where assessed [ n  = 516; MD −1.36, CI −1.52, −1.20]. One trial reported one possible intervention related SAE, no other studies described intervention related SAEs. Conclusions There is disparity between the overall combined effect on LoS as compared with the negative results from the largest and most precise trials. Together with high levels of heterogeneity, this means that neither individual trials nor pooled estimates provide a firm evidence-base for routine use of HS in inpatient acute bronchiolitis. Electronic supplementary material The online version of this article (doi:10.1186/s12890-015-0140-x) contains supplementary material, which is available to authorized users. Keywords Bronchiolitis Bronchodilator agents Nebulizers and vaporizers Randomized controlled trials as topic Hypertonic saline Systematic review Meta-analysis pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY issue-copyright-statement © The Author(s) 2015 Background Acute bronchiolitis is the most common cause for hospitalisation in infancy and childhood, with 1–3 % of all infants admitted to hospital during their first winter [ 1 – 9 ]. Obstruction of the airways results in severe breathing difficulties caused by common respiratory viruses infecting the lungs [ 1 – 8 , 10 – 13 ]. The peak age of incidence is between 1 and 6 months for babies admitted with this conditi

J Glob Health J Glob Health 1902 jogh JGH Journal of Global Health 2047-2978 2047-2986 International Society for Global Health PMC7193539 PMC7193539.1 7193539 7193539 32395245 10.7189/jogh.10.010332 jogh-10-010332 1 Viewpoints Hypertonic saline nasal irrigation and gargling should be considered as a treatment option for COVID-19 Ramalingam Sandeep 1 Graham Catriona 2 Dove Jenny 1 Morrice Lynn 3 Sheikh Aziz 3 1 Department of Laboratory Medicine, Royal Infirmary of Edinburgh, Edinburgh, UK 2 Edinburgh Clinical Research Facility, University of Edinburgh, Western General Hospital, Edinburgh, UK 3 Centre of Medical Informatics, Usher Institute, The University of Edinburgh, Edinburgh, UK Correspondence to: 
Dr. Sandeep Ramalingam
Consultant Virologist
Royal Infirmary of Edinburgh
51 Little France Crescent
Edinburgh EH16 4SA
UK
 sandeep.ramalingam@nhslothian.scot.nhs.uk 6 2020 29 3 2020 10 1 352009 010332 29 03 2020 11 05 2020 14 05 2020 Copyright © 2020 by the Journal of Global Health. All rights reserved. 2020 https://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY Post-hoc secondary analysis of data from our recent Edinburgh and Lothians Viral Intervention Study (ELVIS) pilot randomised controlled trial (RCT) indicates that hypertonic saline nasal irrigation and gargling (HSNIG) reduced the duration of coronavirus upper respiratory tract infection (URTI) by an average of two-and-a-half days. As such, it may offer a potentially safe, effective and scalable intervention in those with Coronavirus Disease-19 (COVID-19) following infection with the betacoronavirus Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) [ 1 ]. ELVIS was undertaken in 66 adults with URTI. Results have been reported in detail elsewhere [ 2 ]. Briefly, volunteers with URTI were within 48 hours of symptom onset randomised to intervention (n = 32) or control (n = 34) arms. The intervention arm made hypertonic saline at home and performed HSNIG as many times as needed (maximum of 12 times/day). Control arm participants dealt with their URTI as they normally did. Nose swabs collected at recruitment and first thing in the morning on four consecutive days were sent to the laboratory for testing. Both arms kept a diary (which included the Wisconsin Upper Respiratory Symptom Survey-21 questionnaire) for a maximum of 14 days or until they were well for two consecutive days. Follow-up data were available for 92% of individuals (intervention arm: n = 30; control arm: n = 31). HSNIG reduced the duration of URTI by 1.9 days ( P  = 0.01), over-the-counter medication use by 36% ( P  = 0.004), transmission within household contacts by 35% ( P  = 0.006) and viral shedding by ≥0.5 log 10 /d ( P  = 0.04) in the intervention arm when compared to controls [ 2 ]. We also recently reported that epithelial cells mount an antiviral effect by producing hypochlorous acid (HOCl) from chloride ions [ 3 ]. HOCl is the active ingredient in bleach. Epithelial cells have this innate antiviral immune mechanism to clear viral infections. Since bleach is effective against all virus types [ 4 ], we tested to see if a range of DNA, RNA, enveloped and non-enveloped viruses were inhibited in the presence of chloride ions supplied via salt (NaCl). All the viruses we tested were inhibited in the presence of NaCl. The human viruses we tested were: DNA/enveloped: herpes simplex virus; RNA/enveloped: human coronavirus 229E (HCoV-229E), respiratory syncytial virus, influenza A virus; and RNA/non-enveloped: coxsackievirus B3 [ 3 ]. In COVID-19, high titres of SARS-CoV-2 are detectable in the upper respiratory tract of asymptomatic and symptomatic individuals [ 5 ]. The titres are higher in the nose than the throat suggesting measures that control the infection and viral shedding will help reduce transmission [ 5 ]. In the context of the COVID-19 pandemic, we have undertaken a post-hoc re-analysis of the ELVIS data with a focus on those infected with coronaviruses. Coronaviruses were the second most common cause of URTI (after rhinoviruses). Fifteen individuals were infected by a coronavirus: 7 in the intervention arm, 8 in the control arm. In the intervention arm, four participants were infected by an alphacoronavirus (HCoV 229E = 3, HCoV NL63 = 1) and three by a betacoronavirus (HCoV HKU1 = 3). In the control arm, two were

Sci Rep Sci Rep 1579 scirep Scientific Reports 2045-2322 Nature Publishing Group PMC6134045 PMC6134045.1 6134045 6134045 30206371 10.1038/s41598-018-31936-y 31936 1 Article Antiviral innate immune response in non-myeloid cells is augmented by chloride ions via an increase in intracellular hypochlorous acid levels http://orcid.org/0000-0001-7676-4267 Ramalingam Sandeep Sandeep.ramalingam@nhslothian.scot.nhs.uk 1 2 Cai Baiyi 2 Wong Junsheng 2 Twomey Matthew 2 Chen Rui 2 Fu Rebecca M. 2 Boote Toby 2 McCaughan Hugh 1 http://orcid.org/0000-0002-6782-4675 Griffiths Samantha J. 2 Haas Jürgen G. 1 2 1 0000 0001 0709 1919 grid.418716.d Department of Laboratory Medicine, NHS Lothian, Edinburgh Royal Infirmary, Edinburgh, UK 2 0000 0004 1936 7988 grid.4305.2 Division of Infection and Pathway Medicine, University of Edinburgh, Edinburgh, UK 11 9 2018 2018 8 304108 13630 23 10 2017 29 8 2018 11 09 2018 15 09 2018 06 04 2020 6134045 10.1038/s41598-018-31936-y 1 11 09 2018 7092270 10.1038/s41598-018-31936-y 2 11 09 2018 © The Author(s) 2018 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ . Phagocytes destroy ingested microbes by producing hypochlorous acid (HOCl) from chloride ions (Cl − ) and hydrogen peroxide within phagolysosomes, using the enzyme myeloperoxidase. HOCl, the active ingredient in bleach, has antibacterial/antiviral properties. As myeloperoxidase is needed for HOCl production, non-myeloid cells are considered incapable of producing HOCl. Here, we show that epithelial, fibroblast and hepatic cells have enhanced antiviral activity in the presence of increasing concentrations of sodium chloride (NaCl). Replication of enveloped/non-enveloped, DNA (herpes simplex virus-1, murine gammaherpesvirus 68) and RNA (respiratory syncytial virus, influenza A virus, human coronavirus 229E, coxsackievirus B3) viruses are inhibited in a dose-dependent manner. Whilst treatment with sodium channel inhibitors did not prevent NaCl-mediated virus inhibition, a chloride channel inhibitor reversed inhibition by NaCl, suggesting intracellular chloride is required for antiviral activity. Inhibition is also reversed in the presence of 4-aminobenzoic hydrazide, a myeloperoxidase inhibitor, suggesting epithelial cells have a peroxidase to convert Cl − to HOCl. A significant increase in intracellular HOCl production is seen early in infection. These data suggest that non-myeloid cells possess an innate antiviral mechanism dependent on the availability of Cl − to produce HOCl. Antiviral activity against a broad range of viral infections can be augmented by increasing availability of NaCl. SR is financially supported by NHS Research Scotland (NRS), through NHS Lothian. https://doi.org/10.13039/501100000265 Medical Research Council (MRC) MR/P011349/1 Haas Jürgen G. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY issue-copyright-statement © The Author(s) 2018 Introduction Chloride, the most abundant anion in humans, is an important prerequisite for the innate immune response mediated by phagocytes and neutrophils 1 . Resting neutrophils have a four- to five-fold higher intracellular Cl − concentration than expected for passive transfer 2 . Chloride transport across hydrophobic lipid membranes requires protein carriers such as chloride channels, anion-chloride exchangers or cation-chloride co-transporters 3 . Within phagosomes, myeloperoxidase (MPO) mediates the conversion of Cl − and hydrogen peroxide (H 2 O 2 ) to hypochlorous acid (HOCl) 1 . Both H 2 O 2 and HOCl have antimicrobicidal activity, however HOCl is much more potent 4 . An activated neutrophil is estimated to produce 1.6 × 10 6 molecules of HOCl per second 1 . Within phagosomes, an estimated 28–72% of the oxygen

Sci Rep Sci Rep 1579 scirep Scientific Reports 2045-2322 Nature Publishing Group PMC6355924 PMC6355924.1 6355924 6355924 30705369 10.1038/s41598-018-37703-3 37703 1 Article A pilot, open labelled, randomised controlled trial of hypertonic saline nasal irrigation and gargling for the common cold http://orcid.org/0000-0001-7676-4267 Ramalingam Sandeep sandeep.ramalingam@nhslothian.scot.nhs.uk 1 Graham Catriona 2 Dove Jenny 1 Morrice Lynn 3 Sheikh Aziz 3 1 0000 0001 0709 1919 grid.418716.d Department of Laboratory Medicine, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA UK 2 Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road South, Edinburgh, EH4 2XU UK 3 0000 0004 1936 7988 grid.4305.2 Centre of Medical Informatics, Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Medical School Doorway 3, Teviot Place, Edinburgh, EH8 9AG UK 31 1 2019 2019 9 327256 1015 4 5 2018 12 12 2018 31 01 2019 04 02 2019 08 04 2024 6355924 10.1038/s41598-018-37703-3 1 31 01 2019 7092285 10.1038/s41598-018-37703-3 2 31 01 2019 © The Author(s) 2019 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ . There are no antivirals to treat viral upper respiratory tract infection (URTI). Since numerous viruses cause URTI, antiviral therapy is impractical. As we have evidence of chloride-ion dependent innate antiviral response in epithelial cells, we conducted a pilot, non-blinded, randomised controlled trial of hypertonic saline nasal irrigation and gargling (HSNIG) vs standard care on healthy adults within 48 hours of URTI onset to assess recruitment (primary outcome). Acceptability, symptom duration and viral shedding were secondary outcomes. Participants maintained a symptom diary until well for two days or a maximum of 14 days and collected 5 sequential mid-turbinate swabs to measure viral shedding. The intervention arm prepared hypertonic saline and performed HSNIG. We recruited 68 participants (2.6 participants/week; November 2014-March 2015). A participant declined after randomisation. Another was on antibiotics and hence removed (Intervention:32, Control:34). Follow up data was available from 61 (Intervention:30, Control:31). 87% found HSNIG acceptable, 93% thought HSNIG made a difference to their symptoms. In the intervention arm, duration of illness was lower by 1.9 days (p = 0.01), over-the-counter medications (OTCM) use by 36% (p = 0.004), transmission within household contacts by 35% (p = 0.006) and viral shedding by ≥0.5 log 10 /day (p = 0.04). We hence need a larger trial to confirm our findings. Edinburgh and Lothians Health Foundation: Ref 10-303 pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement yes pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY issue-copyright-statement © The Author(s) 2019 Introduction The common cold is a viral upper respiratory tract infection (URTI). Adults and children get 2-3 and 6-7 attacks respectively of URTI annually 1 , 2 . In 2016 the UK lost 34.0 million work days (33.1% of total) due to minor illnesses such as URTI 3 . An episode of URTI cost €266.41, €273.36 in Cardiff and Southampton respectively 4 . In the US, 72% of respondents had URTI in the past year costing $40 billion annually 2 . Outbreaks of respiratory tract infections are common in hospitals and care homes with significant morbidity and mortality 5 . URTI can lead to lower respiratory tract infections (LRTI) such as pneumonia, or cause exacerbations in individuals with asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis 6 . Since URTI precedes LRTI, early intervention could prevent these complications. At present, there are no antiviral agents to treat the common cold.

Proc Natl Acad Sci U S A Proc. Natl. Acad. Sci. U.S.A 2 pnas PNAS Proceedings of the National Academy of Sciences of the United States of America 0027-8424 1091-6490 National Academy of Sciences PMC4311828 PMC4311828.1 4311828 4311828 25561542 10.1073/pnas.1411030112 201411030 1 Biological Sciences Immunology and Inflammation From the Cover Temperature-dependent innate defense against the common cold virus limits viral replication at warm temperature in mouse airway cells Temperature-dependent innate control of rhinovirus Foxman Ellen F. a b Storer James A. a 1 Fitzgerald Megan E. c d Wasik Bethany R. e 2 Hou Lin f Zhao Hongyu f Turner Paul E. e Pyle Anna Marie c d Iwasaki Akiko a c d 3 Departments of a Immunobiology and b Laboratory Medicine, Yale University School of Medicine , New Haven, CT 06520; c Department of Molecular, Cellular and Developmental Biology, e Department of Ecology and Evolutionary Biology, and d Howard Hughes Medical Institute, Yale University , New Haven, CT 06520; and f Department of Biostatistics, Yale University School of Public Health , New Haven, CT 06520 3 To whom correspondence should be addressed. Email: akiko.iwasaki@yale.edu . 1 Present address: Jounce Therapeutics, Cambridge, MA 02138. 2 Present address: Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, NY 14853. Edited by Tadatsugu Taniguchi, University of Tokyo, Meguro-ku, Japan, and approved December 5, 2014 (received for review June 12, 2014) Author contributions: E.F.F., M.E.F., A.M.P., and A.I. designed research; E.F.F., J.A.S., M.E.F., and B.R.W. performed research; J.A.S., L.H., H.Z., and P.E.T. contributed new reagents/analytic tools; E.F.F., J.A.S., M.E.F., B.R.W., L.H., H.Z., P.E.T., A.M.P., and A.I. analyzed data; and E.F.F., M.E.F., A.M.P., and A.I. wrote the paper. The authors declare no conflict of interest. 20 1 2015 5 1 2015 112 3 248641 827 832 20 07 2015 20 07 2015 20 02 2015 05 07 2023 In This Issue 112 3 20 1 2015 631 632 Proceedings of the National Academy of Sciences of the United States of America PMC4311816 Significance Rhinovirus is the most frequent cause of the common cold, as well as one of the most important causes of asthma exacerbations. Most rhinovirus strains replicate better at the cooler temperatures found in the nasal cavity than at lung temperature, but the underlying mechanisms are not known. Using a mouse-adapted virus, we found that airway epithelial cells supporting rhinovirus replication initiate a more robust antiviral defense response through RIG-I–like receptor (RLR)–dependent interferon secretion and enhanced interferon responsiveness at lung temperature vs. nasal cavity temperature. Airway cells with genetic deficiencies in RLR or type I interferon receptor signaling supported much higher levels of viral replication at 37 °C. Thus, cooler temperatures can enable replication of the common cold virus, at least in part, by diminishing antiviral immune responses. Most isolates of human rhinovirus, the common cold virus, replicate more robustly at the cool temperatures found in the nasal cavity (33–35 °C) than at core body temperature (37 °C). To gain insight into the mechanism of temperature-dependent growth, we compared the transcriptional response of primary mouse airway epithelial cells infected with rhinovirus at 33 °C vs. 37 °C. Mouse airway cells infected with mouse-adapted rhinovirus 1B exhibited a striking enrichment in expression of antiviral defense response genes at 37 °C relative to 33 °C, which correlated with significantly higher expression levels of type I and type III IFN genes and IFN-stimulated genes (ISGs) at 37 °C. Temperature-dependent IFN induction in response to rhinovirus was dependent on the MAVS protein, a key signaling adaptor of the RIG-I–like receptors (RLRs). Stimulation of primary airway cells with the synthetic RLR ligand poly I:C led to greater IFN induction at 37 °C relative to 33 °C at early time points poststimulation and to a sustained increase in the induction of ISGs at 37 °C relative to 33 °C. Recombinant type I IFN also stimulated more robust induction of ISGs at 37 °C than at 33 °C. Genetic deficiency of MAVS or the type I IFN receptor in infected airway cells permitted higher levels of viral replication, particularly at 37 °C, and partially rescued the temperature-dependent growth phenotype. These findings demonstrate that in mouse airway cells, rhinovirus replicates preferentially at nasal cavity temperature due, in part, to a less efficient antiviral defense response of infected cells at cool temperature. rhinovirus common cold airway RIG-I innate immunity HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 100000060 AI054359 HHS | NIH | National Institute of Allergy and Infectious Diseases (NIAID) 100000060 AI064705 Howard Hughes Medical Institute (HHMI) 100000011 Investigator award pmc-stat

pmc RSC Adv RSC Adv 4079 rscadv RA RSC Advances 2046-2069 Royal Society of Chemistry PMC12573239 PMC12573239.1 12573239 12573239 41181012 10.1039/d5ra06003f d5ra06003f 1 Chemistry Design, synthesis and applications of a coumarin based fluorescent probe for selective detection of hypochlorite ions and live cell imaging Zareen Wajeeha a https://orcid.org/0000-0001-6004-0037 Ahmed Nadeem a b Ismail Mostafa A. c Feroz Hafza a https://orcid.org/0009-0001-4439-3665 Khan Muhammad Ali a https://orcid.org/0000-0003-4088-8297 Shafiq Zahid a https://orcid.org/0000-0002-7739-2837 Gomha Sobhi M. d a Institute of Chemical Sciences, Bahauddin Zakariya University Multan 60800 Pakistan zahidshafiq@bzu.edu.pk b College of Chemistry & Chemical Engineering, Central South University Changsha Hunan 410083 China c Department of Chemistry, Faculty of Science, Research Center for Advanced Materials Science (RCAMS), King Khalid University P.O. Box 960 Abha 61421 Saudi Arabia d Department of Chemistry, Faculty of Science, Islamic University of Madinah Madinah 42351 Saudi Arabia smgomha@iu.edu.sa 30 10 2025 28 10 2025 15 49 499531 41691 41698 14 8 2025 21 10 2025 30 10 2025 31 10 2025 03 11 2025 This journal is © The Royal Society of Chemistry 2025 The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ This article is licensed under a Creative Commons Attribution 3.0 Unported Licence . You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given. The immune system's protection against invasive microorganisms and other biological functions in living things depend heavily on hypochlorous acid (HOCl). For the sensitive detection of HOCl, a turn-on fluorescent probe (W-HOCl) has been developed. The probe is well characterized by 1 HNMR, 13 CNMR, FTIR and HRMS. Through the oxidation of sulfide to sulfoxide caused by HOCl, the probe quickly identifies HOCl. The fluorescence was enhanced 42 times as a result of the reaction between W-HOCl and HOCl. The probe has excellent photophysical properties along with a detection limit as low as 6 nM. The imaging of HOCl in living cells showed the probe's potential as an HOCl biosensor. Therefore, the probe is predicted to be useful for the accurate detection of HOCl in complex biosystems. The immune system's protection against invasive microorganisms and other biological functions in living things depend heavily on hypochlorous acid (HOCl). Deanship of Scientific Research, King Khalid University 10.13039/501100023674 RGP-2/684/46 pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement yes pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pubstatus Paginated Article 1. Introduction In recent years, there has been growing interest in the function of anions in biology, industry, medicine, and the environment. Anion sensors with remarkable design and synthesis capabilities have attracted the attention of experts in inorganic catalysis, pharmaceutical synthesis, environmental analysis, and life sciences. Many fluorescent sensors have been reported for visualizing viscosity in dysfunction, inflammation, and Alzheimer's disease, and an allosteric hairpin switch-based isothermal amplification strategy for sensitive detection of bacterial detection. 1–3 Hypochlorous acid (HOCl)/hypochlorite (ClO − ) is a very active oxidation species that is essential for both environmental safety and biomedicine. 4,5 As is well known, we utilize HOCl to disinfect and purify water in our daily lives by getting rid of bacteria. Myeloperoxidase (MPO) catalyzes the reaction of hydrogen peroxide with chloride ions to form HOCl in biological systems. 6 It is essential for preserving the intracellular redox equilibrium, reducing inflammation, and fending off infections. 7,8 However, too much HOCl can result in the production of dangerous substances in water (such as trihalomethanes) and cause a number of oxidative stress-related illnesses in people, such as cancer, arthritis, cardiovascular disease, and neurodegeneration. In living things, highly active HOCl can aid in the chemical alteration and destruction of a variety of biomolecules, such as proteins, lipids, and nucleic acids. 9–14 Thus, it is necessary to develop an efficient technique for the real-time detection of HOCl/ClO in biological and environmental systems. Small-molecule fluorescent probes are highly sensitive, noninvasive, and detect in real time, they have attracted a lot of interest. 15–26 Using p -methoxyphenol as the recognition group, Yang's group discovered in 2008 that hypochlorous acid could be specifically detected in a variety of RO

Am J Physiol Lung Cell Mol Physiol Am J Physiol Lung Cell Mol Physiol 319 nihpa American journal of physiology. Lung cellular and molecular physiology 1040-0605 1522-1504 pmc-is-collection-domain yes pmc-collection-title NIHPA Author Manuscripts PMC12181047 PMC12181047.1 12181047 12181047 NIHMS2087864 40454714 10.1152/ajplung.00009.2025 NIHMS2087864 NIHPA2087864 1 Article ENaC contributes to macrophage dysfunction in cystic fibrosis Moran John 1 Pugh Courtney 2 Brown Nevian 2 Thomas Ashley 2 Zhang Shuzhong 2 McCauley Emily 2 Cephas Amelia 2 Shrestha Chandra L. 2 Partida-Sanchez Santiago 2 Bai Shasha 3 Bruscia Emanuela 4 Kopp Benjamin T. 1 * 1 Center for Cystic Fibrosis and Airways Disease Research (CF-AIR), Emory University, Atlanta, GA, USA 2 Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children’s Hospital, Columbus, OH, USA 3 Pediatric Biostatistics Core, Emory University School of Medicine, Atlanta, GA, USA 4 Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA Author contributions: Experimental performance: JM, CP, NB, AT, SZ, EM, AC, CLS. Study design and analysis: JM, CP, SZ, CS, BTK. Manuscript writing and editing: JM, CP, NB, SZ, EM, AC, CLS, SPS, SB, EB, BTK. Statistical analysis: SB, BTK. Grant support: BTK, SPS, EB. Recruitment: BTK. * To whom correspondence should be addressed: Benjamin Kopp, Emory Children’s Center, 2015 Uppergate Drive, Atlanta, GA 30322, btkopp@emory.edu Conflict of interest: The authors declare no relevant conflicts of interest. 01 7 2025 02 6 2025 329 1 491150 L61 L69 13 06 2025 01 07 2025 01 07 2025 22 06 2025 01 07 2025 ENaC contributes to macrophage dysfunction in cystic fibrosis 8 11 2024 2024.11.06.622340 bioRxiv 10.1101/2024.11.06.622340 PMC11580935 39574739 Cystic fibrosis (CF) is a chronic disease caused by dysfunctional or absent cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is expressed in immune cells and regulates innate immunity, both directly and indirectly. The epithelial sodium channel (ENaC) contributes to dysfunction in CF airway epithelial cells. However, the impact of non-CFTR ion channel dysfunction on CF immune responses is not understood. Improved understanding of how immune function is regulated by ion channels may allow antibiotic- and mutation-agnostic treatment approaches to chronic infection and inflammation. Therefore, we hypothesized that ENaC is aberrantly expressed in CF macrophages and directly contributes to impaired phagocytic and inflammatory functions. ENaC expression was characterized in immune cells isolated from CF and non-CF blood donors. Monocyte-derived macrophage (MDM) function and bacterial killing was tested with ENaC modulation. Baseline ENaC expression in human CF MDMs, lymphocytes, and granulocytes was increased at both the transcript and protein level relative to non-CF and persisted after infection. CFTR inhibition in non-CF MDMs resulted in ENaC overexpression. CFTR modulator treatment reduced but did not eliminate ENaC overexpression in CF MDMs. Interestingly, ENaC inhibition increased CFTR expression. Amiloride-treated CF MDMs also showed normalized ROS production, improved autophagy, and decreased pro-inflammatory cytokine production. Sodium channel expression in CF MDMs normalized after Amiloride treatment with minimal effect on other ion channels. In summary, ENaC modulation in immune cells is a novel potential therapeutic target for CF infection control, either in combination with CFTR modulators, or as a sole agent for people not eligible for CFTR modulators. Graphical Abstract cystic fibrosis macrophage immunity ion channels pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access no pmc-prop-olf no pmc-prop-manuscript yes pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes

J Biol Chem J. Biol. Chem 567 jbc JBC The Journal of Biological Chemistry 0021-9258 1083-351X American Society for Biochemistry and Molecular Biology PMC5777245 PMC5777245.1 5777245 5777245 29203528 10.1074/jbc.M117.805093 M117.805093 1 Immunology Elevated sodium chloride drives type I interferon signaling in macrophages and increases antiviral resistance High salt regulates type I interferon signaling http://orcid.org/0000-0002-8494-306X Zhang Wu-Chang ‡ § 1 Du Lin-Juan ‡ § ¶ 1 Zheng Xiao-Jun ‡ § ¶ 1 Chen Xiao-Qing ‖ Shi Chaoji ‡ § Chen Bo-Yan ‡ § Sun Xue-Nan ‡ § ¶ Li Chao ‡ § ¶ Zhang Yu-Yao ‡ § ¶ Liu Yan ‡ § Xiao Hui ** Leng Qibin ** Jiang Xinquan ‡ § Zhang Zhiyuan ‡ § Sun Shuyang ‡ § 2 Duan Sheng-Zhong ‡ § 3 From the ‡ Ninth People's Hospital, School of Stomatology and the § Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, the ¶ Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of the Chinese Academy of Sciences, Shanghai 200031, the ‖ Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, and the ** Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China 2 To whom correspondence may be addressed: Dept. of Oral and Maxillofacial-Head Neck Oncology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd., Shanghai 200011, China. Tel.: 86-13651629869 ; Fax: 8621-63136856 ; E-mail: shuyangs@shsmu.edu.cn . 3 To whom correspondence may be addressed: Laboratory of Oral Microbiota and Systemic Diseases, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 Zhizaoju Rd., Shanghai 200011, China. Tel.: 8621-23271699 (ext. 5962) ; Fax: 8621-63136856 ; E-mail: duansz@shsmu.edu.cn . 1 These authors contributed equally to this work. Edited by Charles E. Samuel 19 1 2018 4 12 2017 293 3 305212 1030 1039 2 7 2017 28 11 2017 04 12 2017 19 01 2019 27 03 2024 © 2018 by The American Society for Biochemistry and Molecular Biology, Inc. 2018 The American Society for Biochemistry and Molecular Biology, Inc. Type I IFN production and signaling in macrophages play critical roles in innate immune responses. High salt ( i.e. high concentrations of NaCl) has been proposed to be an important environmental factor that influences immune responses in multiple ways. However, it remains unknown whether high salt regulates type I IFN production and signaling in macrophages. Here, we demonstrated that high salt promoted IFNβ production and its signaling in both human and mouse macrophages, and consequentially primed macrophages for strengthened immune sensing and signaling when challenged with viruses or viral nucleic acid analogues. Using both pharmacological inhibitors and RNA interference we showed that these effects of high salt on IFNβ signaling were mediated by the p38 MAPK/ATF2/AP1 signaling pathway. Consistently, high salt increased resistance to vesicle stomatitis virus (VSV) infection in vitro. In vivo data indicated that a high-salt diet protected mice from lethal VSV infection. Taken together, these results identify high salt as a crucial regulator of type I IFN production and signaling, shedding important new light on the regulation of innate immune responses. interferon macrophage p38 MAPK viral immunology virus High salt High salt type I interferon macrophage virus p38 MAPK high salt type I interferon pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access no pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement yes pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes

pmc Molecules Molecules 3416 molecules molecules Molecules 1420-3049 Multidisciplinary Digital Publishing Institute (MDPI) PMC12736364 PMC12736364.1 12736364 12736364 41471700 10.3390/molecules30244669 molecules-30-04669 1 Article Tetraselmis chuii as Source of Bioactive Compounds Against Helicobacter pylori : An Integrated Proteomic and Bioactivity Approach Majchrzak Marta Methodology Software Formal analysis Investigation Data curation Writing – original draft 1 2 https://orcid.org/0000-0001-6845-7814 Paterson Samuel Methodology Formal analysis Investigation 1 3 https://orcid.org/0000-0002-2422-5744 Gómez-Cortés Pilar Conceptualization Resources Writing – review & editing Visualization Supervision Project administration Funding acquisition 1 https://orcid.org/0000-0001-8266-3761 Silvan Jose Manuel Writing – review & editing Supervision 1 https://orcid.org/0000-0002-6140-0732 Martinez-Rodriguez Adolfo J. Conceptualization Writing – review & editing Visualization Supervision Funding acquisition 1 * https://orcid.org/0000-0001-7192-6044 Hernández-Ledesma Blanca Conceptualization Resources Writing – review & editing Visualization Supervision Project administration Funding acquisition 1 * Leung George P.H. Academic Editor Li Jingjing Academic Editor Parang Keykavous Academic Editor 1 Institute of Food Science Research (CIAL, CSIC-UAM, CEI UAM + CSIC), Nicolás Cabrera 9, 28049 Madrid, Spain; marta.majchrzak@csic.es (M.M.); samuel.paterson@csic.es (S.P.); p.g.cortes@csic.es (P.G.-C.); jm.silvan@csic.es (J.M.S.) 2 Department of Applied Physical Chemistry, Autonoma University of Madrid, Francisco Tomás and Valiente, 7, 28049 Madrid, Spain 3 Department of Nutrition and Food Science, Complutense University of Madrid, Plaza de Ramón y Cajal, s/n, 28040 Madrid, Spain * Correspondence: adolfo.martinez@csic.es (A.J.M.-R.); b.hernandez@csic.es (B.H.-L.) 05 12 2025 12 2025 30 24 501963 4669 03 11 2025 26 11 2025 02 12 2025 05 12 2025 25 12 2025 31 12 2025 © 2025 by the authors. 2025 https://creativecommons.org/licenses/by/4.0/ Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). Microalgae represent sustainable sources of bioactive compounds with potential health benefits. This study conducted a comprehensive proteomic analysis of Tetraselmis chuii ( T. chuii ) biomass to identify proteins capable of generating bioactive peptides (BAPs) through simulated orogastric digestion. In silico digestion and bioinformatic predictions indicated the release of antioxidant, anti-inflammatory, and antibacterial peptides. Molecular docking demonstrated strong interactions with targets implicated in oxidative stress, inflammation, and Helicobacter pylori ( H. pylori ) virulence. Biochemical assays and cell-based models confirmed antioxidant and anti-inflammatory activities in both the biomass and its digest, although no significant antibacterial effect against H. pylori was observed under the tested conditions. Considering the role of chronic inflammation in H. pylori -associated pathologies, these findings suggest that T. chuii may serve as a candidate for mitigating tissue damage driven by oxidative and inflammatory stress. Further research is required to address compound stability and optimize delivery strategies. microalgae Tetraselmis chuii bioactive peptides in silico digestion Helicobacter pylori Project PID2021-122989OB-I00 MICIU/AEI/10.13039/501100011033 FEDER, EU, Project ILINK24023 Spanish National Research Council CYTED 124RT0164 CM PIPF-2022/BIO-24996 This work was supported through Project PID2021-122989OB-I00, financed by MICIU/AEI/10.13039/501100011033 and FEDER, EU, Project ILINK24023 financed by the Spanish National Research Council (CSIC. Authors (M.M., S.P., P.G.-C., J.M.S., A.J.M.-R. and B.H.-L.) are members of the INNOPROT network funded by CYTED (ref. 124RT0164). S.P. gratefully acknowledges the CM (PIPF-2022/BIO-24996) for his research contract. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement yes pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes 1. Introduction Microalgae are eukaryotic, photosynthetic, single-celled microorganisms that thrive in aquatic environments [ 1 ]. Beyond their role as a sustainable source of high-quality proteins, microalgae produce bioactive compounds such as omega-3 fatty acids (PUFAs), phytosterols, vitamins, carotenoids (e.g., lutein, astaxanthin, and β-carotene), and bioactive peptides (BAPs) [ 2 ]. These compounds exhibit health-promoting properties, inclu

Innate Immun Innate Immun 3730 innim INI Innate Immunity 1753-4259 1753-4267 SAGE Publications PMC7780350 PMC7780350.1 7780350 7780350 33287602 10.1177/1753425920966641 10.1177_1753425920966641 1 Original Articles Indoor-related microbe damage induces complement system activation in building users https://orcid.org/0000-0002-1100-4838 Atosuo Janne 1 2 Karhuvaara Outi 1 2 Suominen Eetu 1 2 https://orcid.org/0000-0001-5873-5921 Vilén Liisa 2 Nuutila Jari 1 https://orcid.org/0000-0001-7914-2017 Putus Tuula 2 1 The Laboratory of Immunochemistry, Department of Biochemistry, Faculty of Science and Engineering, University of Turku, Finland 2 Environmental Medicine and Occupational Health, Department of Clinical Medicine, Faculty of Medicine, University of Turku, Finland Janne Atosuo, Department of Biochemistry, Biocity, Tykistökatu 6, 6th floor, University of Turku, Finland, 20250 Turku, Finland. Email: janato@utu.fi 7 12 2020 1 2021 27 1 371902 15 22 3 8 2020 18 9 2020 25 9 2020 07 12 2020 13 01 2021 29 03 2024 © The Author(s) 2020 2020 SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses https://creativecommons.org/licenses/by/4.0/ Creative Commons CC BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( https://creativecommons.org/licenses/by/4.0/ ) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage ). In this comparative study, serum complement system antimicrobial activity was measured from 159 serum samples, taken from individuals from microbe-damaged (70 samples) and from reference buildings (89 samples). Antimicrobial activity was assessed using a probe-based bacterial Escherichia coli -lux bioluminescence system and comparison was made at a group level between the experimental and reference group. The complement activity was higher in users of microbe-damaged buildings compared with the reference group and the significant ( P  < 0.001) increase in activity was found in the classical reaction pathway. This study strengthens our notion that exposure to indoor-related microbe damage increases the risk for systemic subclinical inflammation and creates a health risk for building users. Complement system classical pathway exposure indoor mold and bacteria inflammation Työsuojelurahasto https://doi.org/10.13039/501100003128 180090 The Parliament of Finland pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY typesetter ts2 Introduction The human complement system is composed of about 50 soluble- and cell-bound plasma proteins and glycoproteins, which are essential components of human immune defense mechanisms. 1 – 3 The activation of complement by the classical, lectin, or alternative pathway eventually leads to the formation of inflammatory responses that mediate the normal host defenses and tissue homeostasis. 1 – 4 The complement system is a highly regulated, self-amplified proteolytic cascade producing various anaphylactic components that promote leucocyte activation and chemotaxis. 1 – 4 The formation of the lytic membrane attack complex directly kills and lyses the invading microorganisms, and the enhancement of opsonization and ingestion of the targets during phagocytosis are the direct antimicrobial processes of this system. Moreover, complement participates in Ab responses by augmenting their effects and this complementation is the basis for its name. 1 – 3 Finally, the complement system plays a critical role in immune system clearance and in immune complex formation. Complement functions are a fundamental part of the inflammatory process, and because these functions are able to occur in the absence of infection, the continuous, uncontrollable, and excessive activity constitutes a risk for the host in the form of autoimmune diseases and tissue destruction. The complement system includes three separate reaction pathways ( Figure 1 ). The classical activation pathway augments the effects of Abs and is a link connecting the adaptive and innate systems. The main activators are the IgG-class Abs, but also the less specific IgM-pentamer molecules can launch the cascade. 1 – 3 Acute phase effectors such as C-reactive protein and amylase are known to directly activate the classical pathway. 5 The lectin pathway is similar to the classical pathway, but the activation is less specific through the recognition of

Cochrane Database Syst Rev Cochrane Database Syst Rev 3102 cochrev 14651858 The Cochrane Database of Systematic Reviews 1469-493X 1361-6137 John Wiley and Sons, Inc. and the Cochrane Library PMC6513595 PMC6513595.1 6513595 6513595 30260472 10.1002/14651858.CD001506.pub4 CD001506.pub4 CD001506 1 CYSTIC FIBROSIS Child health Genetic disorders Lungs & airways Insurance medicine Nebulised hypertonic saline for cystic fibrosis Wark Peter peter.wark@hnehealth.nsw.gov.au McDonald Vanessa M Cochrane Cystic Fibrosis and Genetic Disorders Group Hunter Medical Research Institute, University of Newcastle Centre for Healthy Lungs 1 Kookaburra Close New Lambton New South Wales Australia 2305 The University of Newcastle School of Nursing and Midwifery, Priority Reseach Centre for Asthma and Respiratory Disease Locked Bag 1000 New Lambtion Newcastle NSW Australia 2305 27 9 2018 2018 19 9 2018 2018 9 334609 CD001506 27 09 2019 27 09 2019 20 08 2025 Copyright © 2018 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Nebulised hypertonic saline for cystic fibrosis 2023 6 14 6 2023 CD001506 The Cochrane Database of Systematic Reviews 10.1002/14651858.CD001506.pub5 PMC10265937 37319354 Nebulised hypertonic saline for cystic fibrosis. 2 15 4 2009 CD001506 CD001506 Cochrane Database Syst Rev 10.1002/14651858.CD001506.pub3 19370568 Abstract Background Impaired mucociliary clearance characterises lung disease in cystic fibrosis (CF). Hypertonic saline enhances mucociliary clearance and may lessen the destructive inflammatory process in the airways. This is an update of a previously published review. Objectives To investigate efficacy and tolerability of treatment with nebulised hypertonic saline on people with CF compared to placebo and or other treatments that enhance mucociliary clearance. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also searched ongoing trials databases. Date of most recent searches: 08 August 2018. Selection criteria Randomised and quasi‐randomised controlled trials assessing hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity). Data collection and analysis Two authors independently reviewed all identified trials and data, and assessed trial quality. The quality of the evidence was assessed using GRADE. Main results A total of 17 trials (966 participants, aged 4 months to 63 years) were included; 19 trials were excluded, three trials are ongoing and 16 are awaiting classification. We judged 14 of the 17 included trials to have a high risk of bias due to participants ability to discern the taste of the solutions. Hypertonic saline 3% to 7% versus placebo At four weeks, we found very low‐quality evidence from three placebo‐controlled trials (n = 225) that hypertonic saline (3% to 7%, 10 mL twice‐daily) increased the mean change from baseline of the forced expiratory volume at one second (FEV 1 ) (% predicted) by 3.44% (95% confidence interval (CI) 0.67 to 6.21), but there was no difference between groups in lung clearance index in one small trial (n = 10). By 48 weeks the effect was slightly smaller in one trial (n = 134), 2.31% (95% CI ‐2.72 to 7.34) (low‐quality evidence). No deaths occurred in the trials. Two trials reporting data on exacerbations were not combined as the age difference between the participants in the trials was too great . One trial (162 adults) found 0.5 fewer exacerbations requiring antibiotics per person in the hypertonic saline group; the second trial (243 children, average age of two years) found no difference between groups (low‐quality evidence). There was insufficient evidence reported across the trials to determine the rate of different adverse events such as cough, chest tightness, tonsillitis and vomiting (very low‐quality evidence). Four trials (n = 80) found very low‐quality evidence that sputum clearance was better with hypertonic saline. A further trial was performed in adults with an acute exacerbation of lung disease (n = 132). The effects of hypertonic saline on short‐term lung function, 5.10% higher (14.67% lower to 24.87% higher) and the time to the subsequent exacerbation post‐discharge, hazard ratio 0.86 (95% CI 0.57 to 1.30) are uncertain (low‐quality evidence). No deaths were reported. Cough and wheeze were reported but no serious adverse events (very low‐quality evidence). Hypertonic saline versus mucus mobilising treatments Three trials compared a similar dose of hypertonic saline to recombinant deoxyribonuclease (rhDNase); two (61 participants) provided data for inclusion in the review. There was insufficient evidence from one three

Hyperosmolarity of the airway surface liquid (ASL) has been proposed as the stimulus for hyperpnoea-induced asthma. We found previously that mucociliary clearance (MCC) was increased after isocapnic hyperventilation (ISH) with dry air, and we proposed that the increase related to transient hyperosmolarity of the ASL. We investigated the effect of increasing the osmolarity of the ASL on MCC, by administering an aerosol of concentrated salt solution. MCC was measured using 99mTc-sulphur colloid, g...

pmc Biomedicines Biomedicines 3168 biomedicines biomedicines Biomedicines 2227-9059 Multidisciplinary Digital Publishing Institute (MDPI) PMC8533244 PMC8533244.1 8533244 8533244 34680554 10.3390/biomedicines9101437 biomedicines-09-01437 1 Review Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine Carrasco-Hernández Laura 1 2 Quintana-Gallego Esther 1 2 Calero Carmen 1 2 Reinoso-Arija Rocío 1 Ruiz-Duque Borja 1 https://orcid.org/0000-0003-1703-1367 López-Campos José Luis 1 2 * Turner Alice M. Academic Editor 1 Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, 41013 Sevilla, Spain; lauracarrascohdez@gmail.com (L.C.-H.); esther.quintana@telefonica.net (E.Q.-G.); ccalero-ibis@us.es (C.C.); rocioreari@gmail.com (R.R.-A.); borja_994@hotmail.com (B.R.-D.) 2 Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28029 Madrid, Spain * Correspondence: lopezcampos@separ.es 10 10 2021 10 2021 9 10 392337 1437 31 7 2021 07 10 2021 10 10 2021 23 10 2021 26 04 2024 © 2021 by the authors. 2021 https://creativecommons.org/licenses/by/4.0/ Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein’s dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored. cystic fibrosis transmembrane conductance regulator COPD CFTR modulators ivacaftor icenticaftor pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY 1. Introduction Despite the considerable advances made in recent years, the mechanisms underlying the onset, pathogenesis and symptomatic development of chronic obstructive pulmonary disease (COPD) remain largely unknown. Although we know that prolonged exposure to tobacco smoke and other inhaled toxins (e.g., biomass [ 1 ], and occupational smokes [ 2 ]) is the main risk factor for the disease, not all patients exposed to tobacco smoke develop this clinical condition. Furthermore, even among those who do develop COPD, the clinical, functional and prognostic impact varies among patients and the conditioning factors of this different evolution are equally unknown [ 3 , 4 ]. In this context, the search for pathogenetic pathways that help us understand the biological pathways that cause COPD, and which determine its clinical impact, constitute the current challenges in the biomedical research of this disease [ 5 ]. In recent decades, numerous pathways were explored that we now know play an important role in the pathogenesis of COPD, including protease–antiprotease imbalance, oxidative and nitrosative stress, inflammatory mechanisms associated with alterations in innate and acquired immunity, and apoptosis or autoimmunity phenomena [ 6 ]. However, despite all these efforts, the factor which defines the patients who will develop COPD when exposed to tobacco still eludes us. For t

pmc Environ Microbiol Rep Environ Microbiol Rep 4425 emrep EMI4 Environmental Microbiology Reports 1758-2229 Wiley PMC12042213 PMC12042213.1 12042213 12042213 40304452 10.1111/1758-2229.70095 EMI470095 EMIR-2024-0279.R1 1 Research Article Research Article Halophilic and Non‐Halophilic Microbial Communities in Relation to Physico‐Chemical Characteristics of Salt Mine Air Puławska Aleksandra 1 Kalinowska Jolanta 2 Rachubik Michalina 2 Drzewiecka Dominika 3 Albuquerque Luciana 4 5 Egas Conceiçao 4 5 6 Krawczyk Krzysztof 2 Manecki Maciej 1 Locht Camille 2 7 Kowalewicz‐Kulbat Magdalena https://orcid.org/0000-0003-4447-0859 2 magdalena.kowalewicz@biol.uni.lodz.pl 1 Department of Mineralogy, Petrography and Geochemistry Faculty of Geology, Geophysics and Environmental Protection, AGH University of Kraków Kraków Poland 2 Department of Immunology and Infectious Biology Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz Lodz Poland 3 Department of Biology of Bacteria Institute of Microbiology, Biotechnology and Immunology, Faculty of Biology and Environmental Protection, University of Lodz Lodz Poland 4 CNC‐UC—Center for Neuroscience and Cell Biology University of Coimbra, UC‐Biotech Cantanhede Portugal 5 CIBB—Center for Innovative Biomedicine and Biotechnology University of Coimbra, UC‐Biotech Cantanhede Portugal 6 Genoinseq—Next Generation Sequencing Unit, Biocant Cantanhede Portugal 7 University of Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille U1019‐UMR9017‐CIIL‐Center for Infection and Immunity of Lille Lille France * Correspondence: Magdalena Kowalewicz‐Kulbat ( magdalena.kowalewicz@biol.uni.lodz.pl ) 30 4 2025 6 2025 17 3 487637 10.1111/emi4.v17.3 e70095 23 3 2025 21 11 2024 09 4 2025 30 04 2025 01 05 2025 01 05 2025 © 2025 The Author(s). Environmental Microbiology Reports published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. ABSTRACT Salt mines are often used for halotherapy against lung and skin diseases. In addition to salt, they also contain various types of microorganisms, which remain poorly characterised. Here, we examined culturable halophilic and non‐halophilic microbial populations in relation to the physico‐chemical characteristics in the air of four different sites of the Bochnia Salt Mine, a popular halotherapy resort in Southern Poland. At the mine entrance, the temperature was highest (20.8°C) and decreased with increasing distance from the entrance (15.5°C at 2671 m from entrance), while humidity increased from 55.9% to 77.0%, as did the NaCl concentration. At the entrance, non‐halophilic microorganisms prevailed, especially fungi that grew at 21°C. Halophiles gradually dominated with distance from the entrance, including halophilic archaea that grew at 28°C or 37°C on medium containing 15%, 20%, or 25% NaCl. Seven halophilic archaeal species were identified by 16S rRNA gene sequencing. The frequency of non‐halophiles was inversely related to distance from the entrance, humidity, and presence of ions, while the reverse was seen for halophiles. An exception was the site used for halotherapy, where non‐halophilic bacteria dominated. Thus, natural salt mines contain a wide variety of non‐halophilic and halophilic microorganisms, including archaea, which may contribute to the halotherapeutic effects. This study unveils the presence and densities of cultivable halophilic and non‐halophilic microorganisms present in the air sampled at four different sites of the Bochnia Salt Mine in Poland used for halotherapy. It highlights for the first time the presence of cultivable halophilic archaea in salt mine air in relation to the physico‐chemical characteristics of the aerosols and human activity during the summer season. National Science Centre, Poland 10.13039/501100004281 2021/41/N/ST10/02751 Narodowa Agencja Wymiany Akademickiej 10.13039/501100014434 BPN/ULM/2023/1/00090/U/00001 European Regional Development Fund 10.13039/501100008530 COMPETE 2020 FCT ‐ Foundation for Science and Technology LA/P/0058/2020 UIDB/04539/2020 UIDP/04539/2020 pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement yes pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes source-schema-version-number 2.0 cover-date June 2025 details-of-publishers-co

Cochrane Database Syst Rev Cochrane Database Syst Rev 3102 cochrev 14651858 The Cochrane Database of Systematic Reviews 1469-493X 1361-6137 John Wiley and Sons, Inc. and the Cochrane Library PMC10265937 PMC10265937.1 10265937 10265937 37319354 10.1002/14651858.CD001506.pub5 CD001506.pub5 CD001506 1 Child health Genetic disorders Lungs & airways Insurance medicine CYSTIC FIBROSIS Nebulised hypertonic saline for cystic fibrosis Cochrane Cystic Fibrosis and Genetic Disorders Group Wark Peter peter.wark@newcastle.edu.au McDonald Vanessa M Smith Sherie Centre for Healthy Lungs Hunter Medical Research Institute, University of Newcastle New Lambton Australia Centre of Excellence in Severe Asthma and Priority Research Centre for Healthy Lungs The University of Newcastle Newcastle Australia Division of Child Health, Obstetrics & Gynaecology (COG), School of Medicine University of Nottingham Nottingham UK Peter Wark, Centre for Healthy Lungs, Hunter Medical Research Institute, University of Newcastle, 1 Kookaburra Close, New Lambton, New South Wales, 2305, Australia. peter.wark@newcastle.edu.au . 14 6 2023 2023 2023 6 437104 CD001506 14 06 2024 14 06 2024 21 08 2025 Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Nebulised hypertonic saline for cystic fibrosis 2018 9 27 9 2018 CD001506 The Cochrane Database of Systematic Reviews 10.1002/14651858.CD001506.pub4 PMC6513595 30260472 Abstract Background Hypertonic saline enhances mucociliary clearance and may lessen the destructive inflammatory process in the airways. This is an update of a previously published review. Objectives To investigate efficacy and tolerability of nebulised hypertonic saline treatment in people with cystic fibrosis (CF) compared to placebo or other treatments that enhance mucociliary clearance. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Cystic Fibrosis Trials Register, comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also searched ongoing trials databases. Most recent search: 25 April 2022. Selection criteria We included randomised and quasi‐randomised controlled trials assessing hypertonic saline compared to placebo or other mucolytic therapy, for any duration or dose regimen in people with CF (any age or disease severity). Data collection and analysis Two authors independently reviewed all identified trials and data, and assessed trial quality. We assessed the certainty of the evidence using GRADE. For cross‐over trials we stipulated a one‐week washout period. We planned to use results from a paired analysis in the review, but this was only possible in one trial. For other cross‐over trials, we chose to treat the trials as if they were parallel. Main results We included 24 trials (1318 participants, aged one month to 56 years); we excluded 29 trials, two trials are ongoing and six are awaiting classification. We judged 15 of the 24 included trials to have a high risk of bias due to participants' ability to discern the taste of the solutions. Hypertonic saline 3% to 7% versus placebo (stable disease) We are uncertain whether the regular use of nebulised hypertonic saline in stable lung disease leads to an improvement in forced expiratory volume in one second (FEV 1 ) % predicted at four weeks, (mean difference (MD) 3.30%, 95% confidence interval (CI) 0.71 to 5.89; 4 trials, 246 participants; very low‐certainty evidence). In preschool children we found no difference in lung clearance index (LCI) at four weeks, but a small improvement after 48 weeks of treatment with hypertonic saline compared to isotonic saline (MD ‐0.60, 95% CI ‐1.00 to ‐0.19; 2 trials, 192 participants). We are also uncertain whether hypertonic saline made a difference to mucociliary clearance, pulmonary exacerbations or adverse events compared to placebo. Hypertonic saline versus control (acute exacerbation) Two trials compared hypertonic saline to control, but only one provided data. There may be little or no difference in lung function measured by FEV 1 % predicted after hypertonic saline compared to isotonic saline (MD 5.10%, 95% CI ‐14.67 to 24.87; 1 trial, 130 participants). Neither trial reported any deaths or measures of sputum clearance. There were no serious adverse events. Hypertonic saline versus rhDNase Three trials compared a similar dose of hypertonic saline to recombinant deoxyribonuclease (rhDNase); two trials (61 participants) provided data for inclusion in the review. We are uncertain whether there was an effect of hypertonic saline on FEV 1 % predicted after three weeks (MD 1.60%, 95% CI ‐7.96 to 11.16; 1 trial, 14 participants; very low‐certainty evidence). At three months, rhDNase may lead to a greater increase in FEV 1 % predicted than hypertonic saline (5 mL twice daily) at 12 weeks

pmc Healthcare (Basel) Healthcare (Basel) 2994 healthcare healthcare Healthcare 2227-9032 Multidisciplinary Digital Publishing Institute (MDPI) PMC10379990 PMC10379990.1 10379990 10379990 37510545 10.3390/healthcare11142104 healthcare-11-02104 1 Article Implications in Halotherapy of Aerosols from the Salt Mine Targu Ocna—Structural-Functional Characteristics Antonovici (Munteanu) Mihaela Orlanda Conceptualization Formal analysis Writing – original draft 1 Sandu Ioan Gabriel Data curation Writing – review & editing Visualization 2 3 * https://orcid.org/0000-0002-8866-3460 Vasilache Viorica Data curation Writing – review & editing Visualization 4 https://orcid.org/0000-0002-9292-749X Sandu Andrei Victor Data curation Writing – review & editing Visualization 2 3 5 Arcana Stefanita Validation Investigation 6 Arcana Raluca Ioana Validation Investigation 6 7 https://orcid.org/0000-0003-4088-8967 Sandu Ion Supervision Project administration 4 5 8 * Tittarelli Andrea Academic Editor 1 Doctoral School of Geosciences, Faculty of Geography and Geology, Alexandru Ioan Cuza University of Iași, 22 Carol I, Blvd., 700506 Iasi, Romania; mihaelamunteanu18@yahoo.com 2 Faculty of Material Science and Engineering, Gheorghe Asachi Technical University, 64 Dumitru Mangeron Blvd., 700050 Iasi, Romania; sav@tuiasi.ro 3 Romanian Inventors Forum, 3 Sf. Petru Movila St., L11, 3-3, 700089 Iasi, Romania 4 Arheoinvest Center, Department of Natural and Exact Sciences, Institute of Interdisciplinary Research, Alexandru Ioan Cuza University of Iasi, 22 Carol I Blvd., 700505 Iasi, Romania; viorica_18v@yahoo.com 5 Academy of Romanian Scientists, 54 Splaiul Independentei St., Sect. 5, 050094 Bucharest, Romania 6 Doctoral School of the Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania; arcana.stefan@gmail.com (S.A.); arcana.raluca@umfiasi.ro (R.I.A.) 7 Clinical Hospital of Pulmonary Diseases, Str. Dr. I Cihac, Nr. 30, 700115 Iasi, Romania 8 National Institute for Research and Development in Environmental Protection, 294 Splaiul Independentei, Sector 6, 060031 Bucharest, Romania * Correspondence: ioan-gabriel.sandu@academic.tuiasi.ro (I.G.S.); ion.sandu@uaic.ro (I.S.) 24 7 2023 7 2023 11 14 441796 2104 07 5 2023 13 7 2023 19 7 2023 24 07 2023 29 07 2023 31 07 2023 © 2023 by the authors. 2023 https://creativecommons.org/licenses/by/4.0/ Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). The paper presents the evolution of the concentration level for four particle size groups of microaerosols (1.0, 2.5, 4.0 and 10.0 µm) in correlation with the microclimatic characteristics (temperature, humidity, lighting, pressure and concentration in CO 2 and O 2 ) in three active areas of the Targu Ocna Saltworks, currently used in treatments with solions (hydrated aerosols): in the vicinity of the walls of the old mining salt room, where there is a semi-wet static regime (SSR); in the transition area between the old rooms of exploitation with the semi-wet dynamic regime (DSR); and in the area of the waterfall and the marshy lake with the dynamic wet regime (DWR). The first and last halochamber are the ones recommended for cardio–respiratory, immuno–thyroid and osteo–muscular conditions, as well as in psycho–motor disorders. Based on questionnaires carried out over the course of a year, between 1 September 2021–31 August 2022, in two periods of stationing/treatment: a cold one (15 September 2021–15 December 2021) and a warm one (1 May 2022–30 July 2022), correlated with the data from the Salina medical office, achieved the profile of the improvement rate of the patients’ ailments depending on the type of treatment (working regime in halochambers). These studies have allowed the optimization of the treatment conditions in the artificial surface halochambers in order to reduce the stationary period and optimize the treatment cycles. Aitken particle Solion salt micro-aeroanion glomerular cluster coordinated aquatemplation low packing salt micropolyhedra water pentahydrols halochambers prevention therapy This research received no external funding. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY 1. Introduction Currently, the effect of the environment in the salt mines is known, where along with the saline aerosols, the internal energy field of the rock salt block has a benefici

pmc Ann Transl Med Ann Transl Med 2592 anntransmed ATM Annals of Translational Medicine 2305-5839 2305-5847 AME Publications PMC9816841 PMC9816841.1 9816841 9816841 36618788 10.21037/atm-22-5632 atm-10-23-1279 1 Original Article Halotherapy relieves chronic obstructive pulmonary disease by alleviating NLRP3 inflammasome-mediated pyroptosis Zhang Chenyan 1 # Zhu Weijie 1 # Meng Qinghai 1 Lian Naqi 1 Wu Jingzhen 1 Liu Bowen 1 Wang Hao 1 Wang Xinyu 2 Gu Shujun 2 Wen Jingli 2 Shen Xiaoling 3 Li Yu 1 Qi Xu 2 4 1 School of Medicine & Holistic Integrative Medicine , Nanjing University of Chinese Medicine , Nanjing , China ; 2 Department of Respiratory Medicine , The First Affiliated Hospital of Nanjing Medical University , Nanjing , China ; 3 Nanjing Kuancheng Technology Co., Ltd. , Nanjing , China ; 4 The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University , Suzhou , China Contributions: (I) Conception and design: All authors; (II) Administrative support: Y Li, X Qi; (III) Provision of study materials or patients: Y Li, X Qi; (IV) Collection and assembly of data: C Zhang, W Zhu; (V) Data analysis and interpretation: C Zhang, W Zhu; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. # These authors contributed equally to this work. Correspondence to: Yu Li. School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Email: liyu@njucm.edu.cn ; Xu Qi. Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University, Suzhou 210046, China. Email: qixuly@163.com . 12 2022 12 2022 10 23 425534 1279 18 10 2022 29 11 2022 01 12 2022 07 01 2023 27 07 2023 2022 Annals of Translational Medicine. All rights reserved. 2022 Annals of Translational Medicine. https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 . Background Airway remodeling and inflammation are considered the main characteristics of chronic obstructive pulmonary disease (COPD). Cigarette smoke promotes the occurrence of inflammation, oxidative stress, and pyroptosis. Halotherapy has been shown to dilute secretions in the airways and promote drainage, but the mechanism remains unclear. In this study, we evaluated the anti-inflammatory and antioxidant effects of halotherapy in COPD rats and investigated the underlying mechanism. Methods A COPD rat model was constructed by cigarette smoke and lipopolysaccharide tracheal instillation. A total of 120 male Sprague-Dawley (SD) rats were randomly divided into control, model, halotherapy, terbutaline, halotherapy + terbutaline, and Ac-YVAD-CMK (Caspase-1 inhibitor) groups. After modeling and treatment, the pulmonary function of the rats was measured. Pathological changes in the lungs were measured by hematoxylin-eosin (H&E) staining. Serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and nitric oxide (NO) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in the lungs were determined by biochemical tests. The levels of cluster of differentiation 4 (CD4 + ) and CD8 + T cells in the blood were determined by flow cytometry. The expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), gasdermin-D (GSDMD), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), Caspase-1, and IL-1β in lung tissues were detected by immunohistochemistry, Western blotting, or quantitative polymerase chain reaction (qPCR). Results Halotherapy recovered the clinical symptoms of COPD rats, and reduced lung inflammatory cell infiltration and air wall attenuation. It also relieved oxidative stress in the lung tissue of COPD rats, reduced CD4 + and CD8 + T cell accumulation in lung tissue, and decreased inflammatory factor production in the serum of COPD rats. Furthermore, it inhibited the TLR4/NF-κB/GSDMD and NLRP3/ASC/Caspase-1 signaling pathways. Ac-YVAD-CMK could not completely inhibit the therapeutic effect of halotherapy on COPD rats. Conclusions Halotherapy improves lung function by inhibiting the NLRP3/ASC/Caspase-1 signaling pathway to reduce inflammation and pyroptosis in COPD rats, and may be a new option fo

J Med Life J Med Life 1155 jmedlife JMedLife Journal of Medicine and Life 1844-122X 1844-3117 SC Jurnalul pentru Medicina si Viata SRL PMC4391365 PMC4391365.1 4391365 4391365 25870681 JMedLife-07-83 1 Special Articles Surveys on therapeutic effects of “halotherapy chamber with artificial salt-mine environment” on patients with certain chronic allergenic respiratory pathologies and infectious-inflammatory pathologies Lazarescu H * Simionca I * Hoteteu M * Munteanu A * Rizea I * Iliuta A * Dumitrascu D * Dumitrescu E * * National Institute of Rehabilitation, Physical Medicine and Balneoclimatology, Bucharest, Romania Correspondence to: Horia Lăzărescu, MD National Institute of Rehabilitation, Physical Medicine and Balneoclimatology, 2 Sfântul Dumitru Street, Bucharest Phone/ Fax: 0213155050, E-mail: horialazarescu@yahoo.com 2014 7 Spec Iss 2 251630 83 87 01 03 2014 13 04 2015 27 04 2015 ©Carol Davila University Press 2014 https://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Halotherapy (HT), derived from speleotherapy in salt mines, is also a drug-free therapeutic method. HT effects vary depending on the therapeutic method and the structure of halotherapy environment. The purpose of this article is to show the HT effects of “halotherapy chamber with artificial salt-mine environment” of the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology (INRMFB), on patients with bronchial asthma and other chronic, infectious-inflammatory and allergic respiratory diseases, describing the clinical effects on certain nonspecific resistance factors, on markers of inflammatory processes and on certain immunological changes. Patients were clinically assessed, with the application of hematologic investigations, analysis of nonspecific resistance to infection and of inflammatory process markers, immunologic assessments, analysis of sodium and potassium concentrations, of mineralocorticoid function and other biochemical tests. For the experimental HT therapy performed in the “halotherapy chamber with artificial salt-mine environment” of INRMFB, 15 patients suffering from bronchial asthma, allergic rhinitis, chronic bronchitis, chronic obstructive bronchopneumopathy were selected, based on specific medical indications and contraindications and applying ethical principles, as well as 4 patients with similar pathologies for the control group, who underwent in-home drug treatment. After the specific halotherapy treatment on patients with bronchial asthma, chronic bronchitis and chronic obstructive bronchopneumopathy, which also showed other chronic, infectious-inflammatory and allergic respiratory pathologies, triggering of anti-inflammatory (and also anti allergic) mechanisms and healing effects on inflammatory process were noted. Data acquired also proved the halo therapeutic effect causing the reduction of sensitiveness of body in patients with bronchial asthma. Abbreviations: HT=Halotherapy, INRMFB=National Institute of Rehabilitation, Physical Medicine and Balneoclimatology Halotherapy bronchial asthma inflammatory process therapeutic effects pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY Introduction Halotherapy, derived from speleotherapy in salt mines, is also a drug-free therapeutic method, applied especially on patients with bronchial asthma and chronic bronchitis. Following the “survey for the innovative use of potentially therapeutic salt-mine environment factors, in health and balneoclimateric tourism; modeling solutions”, the conceptual model was elaborated, subsequently converted into an experimental functional model entitled “halotherapy chamber with artificial salt-mine environment”, destined for surface halotherapy and built within the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology. This model was followed by surveys in the underground salt-mine environment, destined to assess the presence and quality of factors with speleotherapeutic / halotherapeutic potential, medical-biological multi-discipline surveys, including organismic and cellular-level analysis, before and after the experimental halotherapy treatment, on lab animals – Wistar rats with pathology experimentally induced by sensitization with ovalbumin. Based on the experimental results acquired [ 1 , 2 ], the “Inception medical indications for

pmc Medicina (Kaunas) Medicina (Kaunas) 3494 medicina medicina Medicina 1010-660X 1648-9144 Multidisciplinary Digital Publishing Institute (MDPI) PMC12388252 PMC12388252.1 12388252 12388252 40870447 10.3390/medicina61081402 medicina-61-01402 1 Review Nasal Irrigations: A 360-Degree View in Clinical Practice https://orcid.org/0000-0002-9765-8006 Pecoraro Luca 1 * Di Muri Elisabetta 1 Lezzi Gianluca 1 Picciolo Silvia 2 De Musso Marta 2 https://orcid.org/0000-0001-7746-8267 Piazza Michele 3 Bosoni Mariangela 4 https://orcid.org/0000-0001-9789-7878 Indrio Flavia 5 Oliver Brian Academic Editor 1 Pediatric Unit, Ospedale Vito Fazzi, ASL Lecce, 73100 Lecce, Italy 2 Pediatric Department, University of Bari Aldo Moro, 70121 Bari, Italy 3 Pediatric Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, 37129 Verona, Italy 4 Private Practice Pediatric Allergist, 20100 Milan, Italy 5 Department of Experimental Medicine Pediatric Section, University of Salento Hospital “Vito Fazzi”, 73100 Lecce, Italy * Correspondence: luca.pecoraro@asl.lecce.it 01 8 2025 8 2025 61 8 495685 1402 25 6 2025 11 7 2025 22 7 2025 01 08 2025 28 08 2025 30 08 2025 © 2025 by the authors. 2025 https://creativecommons.org/licenses/by/4.0/ Published by MDPI on behalf of the Lithuanian University of Health Sciences. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). Nasal irrigation (NI) is an effective, safe, low-cost strategy for treating and preventing upper respiratory tract diseases. High-volume, low-pressure saline irrigations are the most efficient method for removing infectious agents, allergens, and inflammatory mediators. This article reviews clinical evidence supporting NI use in various conditions: nasal congestion in infants, recurrent respiratory infections, acute and chronic rhinosinusitis, allergic and gestational rhinitis, empty nose syndrome, and post-endoscopic sinus surgery care. NI improves symptoms, reduces recurrence, enhances the efficacy of topical drugs, and decreases the need for antibiotics and decongestants. During the COVID-19 pandemic, NI has also been explored as a complementary measure to reduce viral load. Due to the safe profile and mechanical cleansing action on inflammatory mucus, nasal irrigations represent a valuable adjunctive treatment across a wide range of sinonasal conditions. nasal irrigation upper respiratory tract infections mechanical cleansing viral load reduction sinonasal disorders This research received no external funding. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes 1. Introduction Nasal irrigation (NI) is an ancient healing practice of the upper respiratory tract that originated in the medical tradition from the ancient Hindu practice of Ayurveda, whose roots go back to the Vedas, a thousand years before Christ. Historically, “Neti” is an integral part of the yogic system of body cleansing techniques [ 1 ]. It is primarily intended to cleanse the first airways, the nose, throat, and pharynx, and has been used for thousands of years to relieve rhinosinusitis and allergy symptoms. The two main variants of Neti are those which use water poured into a nostril so that it comes out of the nostril against the side, and the more advanced sutra neti. “Sutra Neti” represents an alternative NI. It consists of a piece of wet string inserted through the nose into the mouth; holding both ends simultaneously, the string is alternately pulled in and out of the nose and pulled out of the mouth at the end of the procedure. Both techniques are used to rinse the nasal cavities, using gravity to make the water flow through the nose [ 2 ]. NI was introduced into Western medicine at the beginning of the 19th century [ 3 ] and has continued to gain popularity worldwide [ 4 ]. It is used alone or with other therapies in various conditions, including acute and chronic rhinosinusitis [ 5 , 6 , 7 , 8 ] and allergic rhinitis [ 9 , 10 ]. Furthermore, especially in children, it is prescribed to treat and prevent upper respiratory tract infections [ 11 ]. In general, otorhinolaryngologists and paediatricians play a crucial role in adopting NI as they consider it very effective. It is associated with significantly reducing the signs and symptoms of rhinosinus pathologies and prescribing drugs commonly used in these conditions [ 11 , 12 ]. Their endorsement and recommendation of NI can dramatically influence its acceptance and use in clinical prac

Int J Chron Obstruct Pulmon Dis Int J Chron Obstruct Pulmon Dis 692 copd International Journal of COPD International Journal of Chronic Obstructive Pulmonary Disease 1176-9106 1178-2005 Dove Press PMC3937102 PMC3937102.1 3937102 3937102 24591823 10.2147/COPD.S57511 copd-9-239 1 Review A review of halotherapy for chronic obstructive pulmonary disease Rashleigh Rachael 1 Smith Sheree MS 1 2 Roberts Nicola J 3 1 Family and Community Health University Research Group, School of Nursing and Midwifery, University of Western Sydney, Campbelltown Campus, Sydney, NSW, Australia 2 Centre for Pharmacology and Therapeutics, Division of Experimental Medicine, Imperial College, South Kensington, London, United Kingdom 3 Institute of Applied Health Research, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, Scotland Correspondence: Rachael Rashleigh, Family and Community Health University Research Group, School of Nursing and Midwifery, University of Western Sydney, Locked Bag 1797, Penrith, NSW 2751, Australia, Tel +61 2 4620 3532, Fax +61 2 4620 3199, Email rachael@rashleigh.com.au 2014 21 2 2014 9 231057 239 246 21 02 2014 03 03 2014 22 12 2015 © 2014 Rashleigh et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License 2014 https://creativecommons.org/licenses/by-nc/3.0/ The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/ . Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Background Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease and is treated with inhaled medication to optimize the patient’s lung health through decreasing their symptoms, especially breathlessness. Halotherapy is the inhalation of micronized dry salt within a chamber that mimics a salt cave environment. Recent media reports suggest that this therapy may help with the symptoms of COPD. Objective To critically evaluate and summarize the evidence for the use of halotherapy as a treatment for COPD. Design A review using systematic approach and narrative synthesis. Data sources Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, MEDLINE, EMBASE, CINAHL, and Google Scholar were searched. Two reviewers independently reviewed abstracts and selected eligible studies based on predetermined selection criteria. Results Of the 151 articles retrieved from databases and relevant reference lists, only one randomized controlled trial met the inclusion criteria. A meta-analysis was unable to be conducted due to the limited number of published studies. Inclusion criteria were subsequently expanded to allow three case-control studies to be included, ensuring that a narrative synthesis could be completed. From the pooled data of the four studies, there were 1,041 participants (661 in the intervention group and 380 in the control group). The assessment of methodological quality raised issues associated with randomization and patient selection. Three themes were identified from the narrative synthesis: respiratory function, quality of life, and medication use. Conclusion Themes generated from the narrative synthesis data reflect outcome measures regularly used for interventional research associated with COPD. From this review, recommendations for inclusion of halotherapy as a therapy for COPD cannot be made at this point and there is a need for high quality studies to determine the effectiveness of this therapy. Keywords salt therapy speleotherapy lung disease aerosol chronic disease salt cave pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY-NC Introduction Chronic obstructive pulmonary disease (COPD) is a chronic, progressive disease with symptoms of dyspnea, increased respiration rate, sputum production, and a reduced exercise intolerance. 1 In 2008, the World Health Organization estimated that COPD was the tenth most prevalent cause for moderate to severe disability, 2 and was the fourth leading cause of death, worldwide. 3 With this significant burden, the impact of this disease on individuals, families’ quality of life, and the associated health care expense, COPD is recognized as an international health priority. 1 , 3 , 4 COPD is managed with inhaled medication with the view to optimize the patient’s pulmonary function and reduce symptoms. Pulmonary rehabilitation is recommended for those patients with Medical Research Council dyspnea score of 3 or more 1 as there is substantial evidence

pmc Healthcare (Basel) Healthcare (Basel) 2994 healthcare healthcare Healthcare 2227-9032 Multidisciplinary Digital Publishing Institute (MDPI) PMC10379990 PMC10379990.1 10379990 10379990 37510545 10.3390/healthcare11142104 healthcare-11-02104 1 Article Implications in Halotherapy of Aerosols from the Salt Mine Targu Ocna—Structural-Functional Characteristics Antonovici (Munteanu) Mihaela Orlanda Conceptualization Formal analysis Writing – original draft 1 Sandu Ioan Gabriel Data curation Writing – review & editing Visualization 2 3 * https://orcid.org/0000-0002-8866-3460 Vasilache Viorica Data curation Writing – review & editing Visualization 4 https://orcid.org/0000-0002-9292-749X Sandu Andrei Victor Data curation Writing – review & editing Visualization 2 3 5 Arcana Stefanita Validation Investigation 6 Arcana Raluca Ioana Validation Investigation 6 7 https://orcid.org/0000-0003-4088-8967 Sandu Ion Supervision Project administration 4 5 8 * Tittarelli Andrea Academic Editor 1 Doctoral School of Geosciences, Faculty of Geography and Geology, Alexandru Ioan Cuza University of Iași, 22 Carol I, Blvd., 700506 Iasi, Romania; mihaelamunteanu18@yahoo.com 2 Faculty of Material Science and Engineering, Gheorghe Asachi Technical University, 64 Dumitru Mangeron Blvd., 700050 Iasi, Romania; sav@tuiasi.ro 3 Romanian Inventors Forum, 3 Sf. Petru Movila St., L11, 3-3, 700089 Iasi, Romania 4 Arheoinvest Center, Department of Natural and Exact Sciences, Institute of Interdisciplinary Research, Alexandru Ioan Cuza University of Iasi, 22 Carol I Blvd., 700505 Iasi, Romania; viorica_18v@yahoo.com 5 Academy of Romanian Scientists, 54 Splaiul Independentei St., Sect. 5, 050094 Bucharest, Romania 6 Doctoral School of the Faculty of Medicine, Grigore T. Popa University of Medicine and Pharmacy, 16 Universitatii Str., 700115 Iasi, Romania; arcana.stefan@gmail.com (S.A.); arcana.raluca@umfiasi.ro (R.I.A.) 7 Clinical Hospital of Pulmonary Diseases, Str. Dr. I Cihac, Nr. 30, 700115 Iasi, Romania 8 National Institute for Research and Development in Environmental Protection, 294 Splaiul Independentei, Sector 6, 060031 Bucharest, Romania * Correspondence: ioan-gabriel.sandu@academic.tuiasi.ro (I.G.S.); ion.sandu@uaic.ro (I.S.) 24 7 2023 7 2023 11 14 441796 2104 07 5 2023 13 7 2023 19 7 2023 24 07 2023 29 07 2023 31 07 2023 © 2023 by the authors. 2023 https://creativecommons.org/licenses/by/4.0/ Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). The paper presents the evolution of the concentration level for four particle size groups of microaerosols (1.0, 2.5, 4.0 and 10.0 µm) in correlation with the microclimatic characteristics (temperature, humidity, lighting, pressure and concentration in CO 2 and O 2 ) in three active areas of the Targu Ocna Saltworks, currently used in treatments with solions (hydrated aerosols): in the vicinity of the walls of the old mining salt room, where there is a semi-wet static regime (SSR); in the transition area between the old rooms of exploitation with the semi-wet dynamic regime (DSR); and in the area of the waterfall and the marshy lake with the dynamic wet regime (DWR). The first and last halochamber are the ones recommended for cardio–respiratory, immuno–thyroid and osteo–muscular conditions, as well as in psycho–motor disorders. Based on questionnaires carried out over the course of a year, between 1 September 2021–31 August 2022, in two periods of stationing/treatment: a cold one (15 September 2021–15 December 2021) and a warm one (1 May 2022–30 July 2022), correlated with the data from the Salina medical office, achieved the profile of the improvement rate of the patients’ ailments depending on the type of treatment (working regime in halochambers). These studies have allowed the optimization of the treatment conditions in the artificial surface halochambers in order to reduce the stationary period and optimize the treatment cycles. Aitken particle Solion salt micro-aeroanion glomerular cluster coordinated aquatemplation low packing salt micropolyhedra water pentahydrols halochambers prevention therapy This research received no external funding. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY 1. Introduction Currently, the effect of the environment in the salt mines is known, where along with the saline aerosols, the internal energy field of the rock salt block has a benefici

pmc Clin Cosmet Investig Dermatol Clin Cosmet Investig Dermatol 1442 ccid ccid Clinical, Cosmetic and Investigational Dermatology 1178-7015 Dove Press PMC12766120 PMC12766120.1 12766120 12766120 41498119 10.2147/CCID.S562171 562171 1 Original Research The Combination of Mineral Salts and Natural Antioxidants Agents Is Highly Effective in Atopic Dermatitis Yori et al Yori et al Yori Fiorella 1 Sarmiento Carlos 1 Gimeno Beltran Javier 2 http://orcid.org/0000-0001-5199-6811 Umbert Ignacio 1 1 Umbert Institute of Dermatology, Corachan Clinic , Barcelona , Spain 2 Unit of Pathology SLP, Corachan Clinic , Barcelona , Spain Correspondence: Ignacio Umbert, Umbert Institute of Dermatology, Corachan Clinic , Plaza Manuel Corachán 4 , Barcelona , 08017 , Spain , Tel +34-932804755 , Email info@idermumbert.com 31 12 2025 2025 18 478875 3695 3711 05 9 2025 18 12 2025 31 12 2025 06 01 2026 07 01 2026 © 2025 Yori et al. 2025 Yori et al. https://creativecommons.org/licenses/by-nc/4.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v4.0) License ( http://creativecommons.org/licenses/by-nc/4.0/ ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php ). Objective Intrinsic atopic dermatitis (AD) is a chronic inflammatory skin disease with pruritus and eczematous lesions of skin. A long-lasting cycle of itch-scratch roots results in substantial morbidities and discomfort. Treatment of patients with moderate to severe dermatitis is a challenge. To evaluate the efficacy of a treatment based on mineral salts and natural antioxidants agents in patients with AD. Patients and Methods In this prospective study, 34 patients with AD were treated for 14 days. Patients were evaluated before and after treatment. The effects were studied by the following clinical measurements: Eczema Area and Severity Index (EASI), Scoring Atopic Dermatitis (SCORAD), Body Surface Area (BSA), and Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD). Patient-reported measurements were also assessed: Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), and the pruritus Numeric Rating Scale (NRS). Biopsies were performed in 10 patients and immunohistochemistry tests in 7 patients. Results All clinical and patient-reported measurements showed a strong difference before and after treatment. The epidermis thickness was significantly reduced, as well as the lymphocyte infiltration and the reduction of CD3, CD4, CD8, CD20 and CD117 cells. No adverse events were observed. Conclusion This study shows that the severity of intrinsic dermatitis was drastically reduced with the treatment of mineral salts and natural antioxidants agents. This topic treatment was very well tolerated without adverse events. Plain Language Summary Atopic dermatitis is very frequent disease of the skin. The symptoms are itching and eczematous skin lesions. Patients suffering from atopic dermatitis can develop systemic infections, cardiovascular diseases and to some neuropsychiatric conditions, including depression, anxiety and hyperactivity disorders. The most widely used treatment so far are glucocorticoids, which have significant side effects. Based on the effects of Dead Sea Water and magnesium salts, we designed a formula with natural ingredients. We combined mineral salts and antioxidants agents. In our study, we included 34 patients with atopic dermatitis who used our compound for 14 days. All patients showed significant improvement in their skin, as can be seen in the photographs of the 33 patients shown. We have also performed biopsies before and after treatment, showing an important improvement in the skin. In short, we have developed a natural product that has no side effects that moisturizes the skin, cures itching, and has antioxidant activity. Graphical Abstract keywords dermatitis atopic mineral salts therapeutics pruritus scratching no funding to report There is no funding to report. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes Introduction Atopic dermatitis (AD) is a chronic inflammatory skin disease with exclusive clinical manifestations depending on age groups, race, or ethnicity. It is an important public health problem with a p

Front Physiol Front Physiol 1464 frontphysiol Front. Physiol. Frontiers in Physiology 1664-042X Frontiers Media SA PMC7645107 PMC7645107.1 7645107 7645107 33192558 10.3389/fphys.2020.561722 1 Physiology Original Research Cyclooxygenase-2 Modulates Glycosaminoglycan Production in the Skin During Salt Overload Agócs Róbert 1 † Pap Domonkos 2 † Sugár Dániel 1 Tóth Gábor 3 4 Turiák Lilla 3 Veréb Zoltán 5 6 7 Kemény Lajos 5 6 7 Tulassay Tivadar 1 2 Vannay Ádám 2 Szabó Attila J. 1 2 * 1 1st Department of Pediatrics, Semmelweis University , Budapest , Hungary 2 MTA-SE (Hungarian Academy of Sciences - Semmelweis University) Pediatrics and Nephrology Research Group, Hungarian Academy of Sciences and Semmelweis University , Budapest , Hungary 3 MS (Mass Spectrometry) Proteomics Research Group, Research Centre for Natural Sciences , Budapest , Hungary 4 Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics , Budapest , Hungary 5 Department of Dermatology and Allergology, University of Szeged , Szeged , Hungary 6 MTA-SZTE (Hungarian Academy of Sciences – University of Szeged) Dermatological Research Group, University of Szeged , Szeged , Hungary 7 HCEMM-USZ (Hungarian Centre of Excellence for Molecular Medicine - University of Szeged) Skin Research Group , Szeged , Hungary Edited by: Adriana Castello Costa Girardi, University of São Paulo, Brazil Reviewed by: Daria Ilatovskaya, Medical University of South Carolina, United States; Erika E. Nishi, Federal University of São Paulo, Brazil; Lajos Markó, Charité – Universitätsmedizin Berlin, Germany *Correspondence: Attila J. Szabó, szabo.attila@med.semmelweis-univ.hu , orcid.org/0000-0001-7321-9861 † These authors have contributed equally to this work This article was submitted to Renal and Epithelial Physiology, a section of the journal Frontiers in Physiology 23 10 2020 2020 11 351089 561722 13 5 2020 11 9 2020 23 10 2020 13 11 2020 30 04 2024 Copyright © 2020 Agócs, Pap, Sugár, Tóth, Turiák, Veréb, Kemény, Tulassay, Vannay and Szabó. 2020 Agócs, Pap, Sugár, Tóth, Turiák, Veréb, Kemény, Tulassay, Vannay and Szabó https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Sodium (Na + ) can accumulate in the skin tissue, sequestered by negatively charged glycosaminoglycans (GAGs). During dietary salt overload, the amount and charge density of dermal GAG molecules – e.g., hyaluronic acid (HA) and chondroitin sulfate (CS) – increases; however, the regulation of the process is unknown. Previously, it has been demonstrated that the level of cyclooxygenase-2 (COX-2) activity and the content of prostaglandin E2 (PGE2) are elevated in the skin due to high-salt consumption. A link between the COX-2/PGE2 system and GAG synthesis was also suggested. We hypothesized that in dermal fibroblasts (DFs) high-sodium concentration activates the COX-2/PGE2 pathway and also that PGE2 increases the production of HA. Our further aim was to demonstrate that the elevation of the GAG content is ceased by COX-2 inhibition in a salt overloaded animal model. For this, we investigated the messenger RNA (mRNA) expression of COX-2 and HA synthase 2 enzymes as well as the PGE2 and HA production of DFs by real-time reverse transcription PCR (qRT-PCR) and ELISA, respectively. The results showed that both high-sodium concentration and PGE2 treatment increases HA content of the media. Sodium excess activates the COX-2/PGE2 pathway in DFs, and COX-2 inhibition decreases the synthesis of HA. In the animal experiment, the HA- and CS disaccharide content in the skin of male Wistar rats was measured using high performance liquid chromatography-mass spectrometry (HPLC-MS). In the skin of rats receiving high-salt diet, the content of both HA‐ and monosulfated-CS disaccharides increased, whereas COX-2 inhibition blocked this overproduction. In conclusion, high-salt environment could induce GAG production of DFs in a COX-2/PGE2-dependent manner. Moreover, the COX-2 inhibition resulted in a decreased skin GAG content of the salt overloaded rats. These data revealed a new DF-mediated regulation of GAG synthesis in the skin during salt overload. sodium storage hypertonicity dermal fibroblast skin cyclooxygenase-2 prostaglandin E2 glycosaminoglycan hypertension János Bolyai Research Scholarship of the Hungarian Academy of Sciences &

pmc Eur Clin Respir J Eur Clin Respir J 2829 ecrj European Clinical Respiratory Journal 2001-8525 Taylor & Francis PMC12710255 PMC12710255.1 12710255 12710255 41416345 10.1080/20018525.2025.2604396 2604396 1 Version of Record Research Article Research Article Relation of changes in PEF and FEV 1 during bronchodilation in children L. L. CSONKA ET AL. EUROPEAN CLINICAL RESPIRATORY JOURNAL Csonka Leon L. a Tikkakoski Antti b Tikkakoski Anna P. a Karjalainen Jussi a c Lehtimäki Lauri a c a Faculty of Medicine and Health Technology, Tampere University , Tampere , Finland b Department of Clinical Physiology and Nuclear Medicine, Tampere University Hospital , Tampere , Finland c Allergy Centre, Tampere University Hospital , Tampere , Finland CONTACT Leon L. Csonka leon.csonka@tuni.fi Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, Tampere 33520, Finland 15 12 2025 2026 13 1 502564 2604396 15 12 2025 18 12 2025 19 12 2025 Integra 15 12 2025 Integra 15 12 2025 07 2 2025 10 12 2025 © 2025 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2025 The Author(s) https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. ABSTRACT INTRODUCTION Asthma diagnosis can be confirmed through the observation of significant bronchodilator response (BDR) measured by peak expiratory flow (PEF) during home monitoring or by forced expiratory volume in one second (FEV 1 ) with spirometry in a clinical setting. AIM To use salbutamol administration after an exercise challenge test in children as a model of bronchodilation to assess how well relative change in PEF reflects improvement in lung function, as defined by increase in FEV 1 . METHODS We retrospectively studied 326 free running exercise challenge tests with spirometry in children 6–16 years old. To assess congruency and differences between relative changes in PEF and FEV 1 during bronchodilation, a regression analysis was performed, and a Bland – Altman plot was constructed. ROC analysis, sensitivity, specificity, positive and negative predictive values and Cohen’s kappa coefficient were used to analyze how accurately increases in PEF predict an increase of 12% & 0.2 L in FEV 1 . RESULTS Relative change in PEF was, on average, greater than that in FEV 1 . In ROC analysis, the area under the curve for PEF change was 0.837, with an optimal operating point of 14.5% (95% CI, 7.5–21.0%). The currently recommended cut-off for handheld PEF meters during home monitoring (15% increase) yielded a sensitivity of 71% and a specificity of 78%. The highest kappa value was observed at a 20% PEF cut-off. CONCLUSION Increase in PEF is not an accurate measure of BDR compared with increase in FEV 1 . The patient populations identified using PEF and FEV 1 criteria differ markedly. KEYWORDS Asthma spirometry bronchodilation home monitoring diagnostics PEF Tampere Tuberculosis Foundation 10.13039/501100006706 Research Foundation of the Pulmonary Diseases 10.13039/501100008309 Foundation of the Finnish Anti-Tuberculosis Association Väinö and Laina Kivi foundation Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital Tampere University Hospital Support Foundation and the Finnish Medical Foundation This work was supported by funding from the Tampere Tuberculosis Foundation; the Research Foundation of the Pulmonary Diseases; the Foundation of the Finnish Anti-Tuberculosis Association; the Väinö and Laina Kivi foundation, the Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital; the Tampere University Hospital Support Foundation and the Finnish Medical Foundation. pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement yes pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes Introduction Asthma is one of the most important chronic illnesses affecting children globally [ 1 ]. It is characterized by bronchial hyperreactivity, which results in easily triggered airway constriction. This causes symptoms such as wheezing, chest tightness, breathlessness, and coughing, accompanied by fluctuating expiratory airflow limitation, which can be alleviated by bronchodilato

pmc Stem Cell Res Ther Stem Cell Res Ther 1238 stemcellres Stem Cell Research & Therapy 1757-6512 BMC PMC12538740 PMC12538740.1 12538740 12538740 41116195 10.1186/s13287-025-04737-0 4737 1 Research Human induced pluripotent stem cells for in vitro modeling of impaired mucociliary clearance in cystic fibrosis lung disease Klassen Mark-Christian 1 2 Balázs Anita 3 4 5 Zöllner Janina 1 2 Cleve Nicole 1 2 Czichon Laurien 1 2 von Schledorn Laura 1 2 Hegermann Jan 7 Nawroth Janna C. 8 9 10 Roth Doris 8 9 10 Mielenz Mia 11 Hedtfeld Silke 2 11 Stanke Frauke 2 11 Rubil Tihomir 3 4 5 Ius Fabio 2 12 Jonigk Danny 2 13 Hanrahan John W. 14 Ruhparwar Arjang 2 12 Olmer Ruth 1 2 Mall Marcus A. 3 4 5 6 Merkert Sylvia 1 2 Martin Ulrich Martin.Ulrich@mh-hannover.de 1 2 1 https://ror.org/00f2yqf98 grid.10423.34 0000 0001 2342 8921 Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Clinic for Cardiothoracic-, Transplantation and Vasuclar Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany 2 https://ror.org/00f2yqf98 grid.10423.34 0000 0000 9529 9877 Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover Medical School, 30625 Hannover, Germany 3 https://ror.org/001w7jn25 grid.6363.0 0000 0001 2218 4662 Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité-Universitätsmedizin, Berlin, Augustenburger Platz 1, 13353 Berlin, Germany 4 https://ror.org/03dx11k66 grid.452624.3 German Center for Lung Research (DZL), Associated Partner Site, Berlin, Germany 5 German Center for Child and Adolescent Heath (DZKJ), Partner Site Berlin, Berlin, Germany 6 https://ror.org/001w7jn25 grid.6363.0 0000 0001 2218 4662 Cluster of Excellence ImmunoPreCept, Charité - Universitätsmedizin Berlin, Berlin, Germany 7 https://ror.org/00f2yqf98 grid.10423.34 0000 0001 2342 8921 Institute of Functional and Applied Anatomy, Research Core Unit Electron Microscopy, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany 8 https://ror.org/00cfam450 grid.4567.0 0000 0004 0483 2525 Helmholtz Pioneer Campus and Institute of Biological and Medical Imaging, Bioengineering Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany 9 https://ror.org/02kkvpp62 grid.6936.a 0000000123222966 Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health, Technical University of Munich, 81675 Munich, Germany 10 https://ror.org/03dx11k66 grid.452624.3 Comprehensive Pneumology Center Munich, German Center for Lung Research (DZL), 81675 Munich, Germany 11 https://ror.org/00f2yqf98 grid.10423.34 0000 0001 2342 8921 Clinic for Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany 12 https://ror.org/00f2yqf98 grid.10423.34 0000 0001 2342 8921 Department of Cardiothoracic-, Transplantation and Vasuclar Surgery, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany 13 https://ror.org/02gm5zw39 grid.412301.5 0000 0000 8653 1507 Institute of Pathology, Universitätsklinikum Aachen, AöR, Pauwelsstraße 30, 52074 Aachen, Germany 14 https://ror.org/01pxwe438 grid.14709.3b 0000 0004 1936 8649 Department of Physiology, McGill University, 3655 Prom Sir-William-Osler, Montreal, QC H3G 1Y6 Canada 21 10 2025 2025 16 478640 573 22 7 2025 6 10 2025 21 10 2025 22 10 2025 22 10 2025 © The Author(s) 2025 2025 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . Severely impaired mucociliary airway function is the primary pathomechanism in Cystic Fibrosis (CF) lung disease. Despite significant advances in CF therapy, there is still a critical need for alternative, individualized treatment options, especially for patients with untreatable CFTR mutations. Although intestinal organoids and primary airway cells are widely used as preclinical models of CF, both systems exhibit limitations with regard to the proper modelling of mucociliary clearance or the availability of sufficient cell quant

Pediatr Rheumatol Online J Pediatr Rheumatol Online J 492 pedirheum Pediatric Rheumatology Online Journal 1546-0096 BMC PMC8130260 PMC8130260.1 8130260 8130260 34006290 10.1186/s12969-021-00529-x 529 1 Review Juvenile primary fibromyalgia syndrome: A Review- Treatment and Prognosis Coles Maya Levy 1 http://orcid.org/0000-0003-4655-1652 Uziel Yosef uziely@zahav.net.il 1 2 1 grid.415250.7 0000 0001 0325 0791 Department of Pediatrics, Meir Medical Center, Pediatric Rheumatology Unit, Kfar Saba, Israel 2 grid.12136.37 0000 0004 1937 0546 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 18 5 2021 2021 19 372345 74 18 2 2021 10 3 2021 18 05 2021 18 05 2021 21 05 2021 © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Juvenile primary fibromyalgia syndrome (JPFS) is a chronic musculoskeletal pain syndrome affecting children and adolescents. In part one of this review, we discussed the epidemiology, etiology, pathogenesis, clinical manifestations and diagnosis of JPFS. Part two focuses on the treatment and prognosis of JPFS. Early intervention is important. The standard of care is multidisciplinary, combining various modalities—most importantly, exercise and cognitive behavioral therapy. Prognosis varies and symptoms may persist into adulthood. Keywords Fibromyalgia Juvenile JPFS Chronic pain Musculoskeletal pain syndrome pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY issue-copyright-statement © The Author(s) 2021 Background Chronic musculoskeletal pain is a primary reason for referrals to pediatric rheumatologists [ 1 ]. It can be caused by a variety of inflammatory or non-inflammatory conditions, including arthritis, hypermobility, fibromyalgia (FM), growing pains and complex regional pain syndrome (CRPS) Amplified musculoskeletal pain syndrome is a generic, descriptive term used to describe chronic pain syndromes of unconfirmed etiology, such as FM, CRPS and idiopathic musculoskeletal pain. For individuals with this syndrome, pain signals are augmented; thus, mildly painful and nonpainful stimuli are registered by the body as very painful, which leads to attempts to avoid the induction of pain, leading to functional disability. Our previous review focused on CRPS [ 2 ]. Yunus and Masi were the first to describe and use the term juvenile primary fibromyalgia syndrome (JPFS), in a clinical study published in 1985, in which they suggested diagnostic criteria based on 33 juveniles ages 17 years or younger, who suffered from chronic pain. JPFS is defined by chronic diffuse musculoskeletal aching and pain, which is the hallmark of this condition, and multiple predictable tender points. Part one of this review summarized the current information regarding the epidemiology, etiology, clinical manifestations and diagnosis of JPFS [ 3 ]. This part of the review focuses on treatment and prognosis. Treatment The primary goal in the treatment of JPFS is to enhance quality of life through pain relief and improved function. A multidisciplinary approach, combining behavioral and exercise-based modalities is currently the standard of care for JPFS [ 4 , 5 ]. Treatment should begin with non-pharmacologic modalities, most importantly exercise. Other non-pharmacologic modalities include movement and meditative treatments, and Cognitive Behavioral Therapy (CBT) [ 6 ]. Reassurance is very important, including acknowledging that the patient’s pain is real, and emphasizing that it is not dangerous. Caregivers should communicate that although the pain may last for an unknown period

J Med Life J Med Life 1155 jmedlife JMedLife Journal of Medicine and Life 1844-122X 1844-3117 SC Jurnalul pentru Medicina si Viata SRL PMC4391365 PMC4391365.1 4391365 4391365 25870681 JMedLife-07-83 1 Special Articles Surveys on therapeutic effects of “halotherapy chamber with artificial salt-mine environment” on patients with certain chronic allergenic respiratory pathologies and infectious-inflammatory pathologies Lazarescu H * Simionca I * Hoteteu M * Munteanu A * Rizea I * Iliuta A * Dumitrascu D * Dumitrescu E * * National Institute of Rehabilitation, Physical Medicine and Balneoclimatology, Bucharest, Romania Correspondence to: Horia Lăzărescu, MD National Institute of Rehabilitation, Physical Medicine and Balneoclimatology, 2 Sfântul Dumitru Street, Bucharest Phone/ Fax: 0213155050, E-mail: horialazarescu@yahoo.com 2014 7 Spec Iss 2 251630 83 87 01 03 2014 13 04 2015 27 04 2015 ©Carol Davila University Press 2014 https://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Halotherapy (HT), derived from speleotherapy in salt mines, is also a drug-free therapeutic method. HT effects vary depending on the therapeutic method and the structure of halotherapy environment. The purpose of this article is to show the HT effects of “halotherapy chamber with artificial salt-mine environment” of the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology (INRMFB), on patients with bronchial asthma and other chronic, infectious-inflammatory and allergic respiratory diseases, describing the clinical effects on certain nonspecific resistance factors, on markers of inflammatory processes and on certain immunological changes. Patients were clinically assessed, with the application of hematologic investigations, analysis of nonspecific resistance to infection and of inflammatory process markers, immunologic assessments, analysis of sodium and potassium concentrations, of mineralocorticoid function and other biochemical tests. For the experimental HT therapy performed in the “halotherapy chamber with artificial salt-mine environment” of INRMFB, 15 patients suffering from bronchial asthma, allergic rhinitis, chronic bronchitis, chronic obstructive bronchopneumopathy were selected, based on specific medical indications and contraindications and applying ethical principles, as well as 4 patients with similar pathologies for the control group, who underwent in-home drug treatment. After the specific halotherapy treatment on patients with bronchial asthma, chronic bronchitis and chronic obstructive bronchopneumopathy, which also showed other chronic, infectious-inflammatory and allergic respiratory pathologies, triggering of anti-inflammatory (and also anti allergic) mechanisms and healing effects on inflammatory process were noted. Data acquired also proved the halo therapeutic effect causing the reduction of sensitiveness of body in patients with bronchial asthma. Abbreviations: HT=Halotherapy, INRMFB=National Institute of Rehabilitation, Physical Medicine and Balneoclimatology Halotherapy bronchial asthma inflammatory process therapeutic effects pmc-status-qastatus 0 pmc-status-live yes pmc-status-embargo no pmc-status-released yes pmc-prop-open-access yes pmc-prop-olf no pmc-prop-manuscript no pmc-prop-legally-suppressed no pmc-prop-has-pdf yes pmc-prop-has-supplement no pmc-prop-pdf-only no pmc-prop-suppress-copyright no pmc-prop-is-real-version no pmc-prop-is-scanned-article no pmc-prop-preprint no pmc-prop-in-epmc yes pmc-license-ref CC BY Introduction Halotherapy, derived from speleotherapy in salt mines, is also a drug-free therapeutic method, applied especially on patients with bronchial asthma and chronic bronchitis. Following the “survey for the innovative use of potentially therapeutic salt-mine environment factors, in health and balneoclimateric tourism; modeling solutions”, the conceptual model was elaborated, subsequently converted into an experimental functional model entitled “halotherapy chamber with artificial salt-mine environment”, destined for surface halotherapy and built within the National Institute of Rehabilitation, Physical Medicine and Balneoclimatology. This model was followed by surveys in the underground salt-mine environment, destined to assess the presence and quality of factors with speleotherapeutic / halotherapeutic potential, medical-biological multi-discipline surveys, including organismic and cellular-level analysis, before and after the experimental halotherapy treatment, on lab animals – Wistar rats with pathology experimentally induced by sensitization with ovalbumin. Based on the experimental results acquired [ 1 , 2 ], the “Inception medical indications for