J Nephrol. 2022 Jul 15. doi: 10.1007/s40620-022-01392-z. Online ahead of print.

ABSTRACT

INTRODUCTION: The clinical trajectory of post-operative acute kidney injury (AKI) following lung transplantation for cystic fibrosis is unknown.

METHODS: Incidence and risk factors for post-operative AKI, acute kidney disease (AKD) and chronic kidney disease (CKD) were retrospectively analyzed in cystic fibrosis patients undergoing lung transplantation. Logistic regressions, Chi-square, Cuzick rank tests, and Cox-proportional hazard models were used.

RESULTS: Eighty-three patients were included. Creatinine peaked 3[2-4] days after transplantation, with 15(18%), 15(18%), and 20(24%) patients having post-operative AKI stages 1, 2, and 3, while 15(18%), 19(23%) and 10(12%) developed AKD stage 1, stage 2 and 3, respectively. Higher AKI stage was associated with worsening AKD (p = 0.009) and CKD (p = 0.015) stages. Of the 50 patients with AKI, 32(66%) transitioned to AKD stage > 0, and then 27 (56%) to CKD stage > 1. Female sex, extracorporeal membrane oxygenation support as a bridge to lung transplant and at the end of the surgery, the use of intraoperative blood components, and cold-ischemia time were associated with increased risk of post-operative AKI and AKD. Higher AKI stage prolonged invasive mechanical ventilation (p = 0.0001), ICU stay (p = 0.0001), and hospital stay (p = 0.0001), and increased the incidence of primary graft dysfunction (p = 0.035). Both AKI and AKD stages > 2 worsened long-term survival with risk ratios of 3.71 (1.34-10.2), p = 0.0131 and 2.65(1.02-6.87), p = 0.0443, respectively.

DISCUSSION: AKI is frequent in cystic fibrosis patients undergoing lung transplantation, it often evolves to AKD and to chronic kidney disease, thereby worsening short- and long-term outcomes.

PMID:35838909 | DOI:10.1007/s40620-022-01392-z

Environ Microbiol. 2022 Jul 15. doi: 10.1111/1462-2920.16136. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa is an important Gram-negative pathogen with intrinsic resistance to many clinically used antibiotics. It is particularly troublesome in nosocomial infections, immunocompromised patients, and individuals with cystic fibrosis. Antimicrobial resistance (AMR) is a huge threat to global health, with a predicted 10 million people dying from resistant infections by 2050. A promising therapy for combatting AMR infections is phage therapy. However, more research is required to investigate mechanisms that may influence the efficacy of phage therapy. An important overlooked aspect is the impact of membrane lipid remodelling on phage binding ability. P. aeruginosa undergoes changes in membrane lipids when it encounters phosphorus stress, an environmental perturbation that is likely to occur during infection. Lipid changes include the substitution of glycerophospholipids with surrogate glycolipids and the over-production of ornithine-containing aminolipids. Given that membrane lipids are known to influence the structure and function of membrane proteins, we propose that changes in the composition of membrane lipids during infection may alter phage binding and subsequent phage infection dynamics. Consideration of such effects needs to be urgently prioritised in order to develop the most effective phage therapy strategies for P. aeruginosa infections. This article is protected by copyright. All rights reserved.

PMID:35837865 | DOI:10.1111/1462-2920.16136

Front Artif Intell. 2022 Jun 28;5:918888. doi: 10.3389/frai.2022.918888. eCollection 2022.

ABSTRACT

Research on rare diseases has received increasing attention, in part due to the realized profitability of orphan drugs. Biomedical informatics holds promise in accelerating translational research on rare disease, yet challenges remain, including the lack of diagnostic codes for rare diseases and privacy concerns that prevent research access to electronic health records when few patients exist. The Integrated Clinical and Environmental Exposures Service (ICEES) provides regulatory-compliant open access to electronic health record data that have been integrated with environmental exposures data, as well as analytic tools to explore the integrated data. We describe a proof-of-concept application of ICEES to examine demographics, clinical characteristics, environmental exposures, and health outcomes among a cohort of patients enriched for phenotypes associated with cystic fibrosis (CF), idiopathic bronchiectasis (IB), and primary ciliary dyskinesia (PCD). We then focus on a subset of patients with CF, leveraging the availability of a diagnostic code for CF and serving as a benchmark for our development work. We use ICEES to examine select demographics, co-diagnoses, and environmental exposures that may contribute to poor health outcomes among patients with CF, defined as emergency department or inpatient visits for respiratory issues. We replicate current understanding of the pathogenesis and clinical manifestations of CF by identifying co-diagnoses of asthma, chronic nasal congestion, cough, middle ear disease, and pneumonia as factors that differentiate patients with poor health outcomes from those with better health outcomes. We conclude by discussing our preliminary findings in relation to other published work, the strengths and limitations of our approach, and our future directions.

PMID:35837616 | PMC:PMC9274244 | DOI:10.3389/frai.2022.918888

Front Immunol. 2022 Jun 28;13:927049. doi: 10.3389/fimmu.2022.927049. eCollection 2022.

ABSTRACT

Non-tuberculous mycobacteria (NTM) are ubiquitous environmental microorganisms capable of a wide range of infections that primarily involve the lymphatic system and the lower respiratory tract. In recent years, cases of lung infection sustained by NTM have been steadily increasing, due mainly to the ageing of the population with underlying lung disease, the enlargement of the cohort of patients undergoing immunosuppressive medications and the improvement in microbiologic diagnostic techniques. However, only a small proportion of individuals at risk ultimately develop the disease due to reasons that are not fully understood. A better understanding of the pathophysiology of NTM pulmonary disease is the key to the development of better diagnostic tools and therapeutic targets for anti-mycobacterial therapy. In this review, we cover the various types of interactions between NTM and lymphoid effectors of innate and adaptive immunity. We also give a brief look into the mechanism of immune exhaustion, a phenomenon of immune dysfunction originally reported for chronic viral infections and cancer, but recently also observed in the setting of mycobacterial diseases. We try to set the scene to postulate that a better knowledge of immune exhaustion can play a crucial role in establishing prognostic/predictive factors and enabling a broader investigation of immune-modulatory drugs in the experimental treatment of NTM pulmonary disease.

PMID:35837393 | PMC:PMC9273994 | DOI:10.3389/fimmu.2022.927049

Front Pharmacol. 2022 Jun 28;13:935995. doi: 10.3389/fphar.2022.935995. eCollection 2022.

ABSTRACT

BRCA1 is a major tumor suppressor that functions in the accurate repair of DNA double-strand breaks via homologous recombination (HR). Nonsense mutations in BRCA1 lead to inactive truncated protein products and are associated with high risk of breast and ovarian cancer. These mutations generate premature termination codons (PTCs). Different studies have shown that aminoglycosides can induce PTC suppression by promoting stop codon readthrough and restoring full-length (FL) protein expression. The use of these compounds has been studied in clinical trials for genetic diseases such as cystic fibrosis and Duchenne muscular dystrophy, with encouraging results. Here we show proof-of-concept data demonstrating that the aminoglycoside G418 can induce BRCA1 PTC readthrough and restore FL protein synthesis and function. We first demonstrate that G418 treatment restores BRCA1 FL protein synthesis in HCC1395, a human breast tumor cell line carrying the R1751X mutation. HCC1395 cells treated with G418 also recover HR DNA repair and restore cell cycle checkpoint activation. A set of naturally occurring BRCA1 nonsense variants encoding different PTCs was evaluated in a GFP C-terminal BRCA1 construct model and BRCA1 PTC readthrough levels vary depending on the stop codon context. Because PTC readthrough could generate FL protein carrying pathogenic missense mutations, variants representing the most probable acquired amino acid substitutions in consequence of readthrough were functionally assessed by a validated transcription activation assay. Overall, this is the first study that evaluates the readthrough of PTC variants with clinical relevance in the breast and ovarian cancer-predisposing gene BRCA1.

PMID:35837282 | PMC:PMC9273842 | DOI:10.3389/fphar.2022.935995

Pediatr Pulmonol. 2022 Jul 14. doi: 10.1002/ppul.26077. Online ahead of print.

ABSTRACT

BACKGROUND: Antibiotics have altered pharmacokinetics (PK) in persons with cystic fibrosis (PwCF) during treatment for an acute pulmonary exacerbation (APE). The Cystic Fibrosis Foundation (CFF) Pulmonary Guidelines-Treatment of Pulmonary Exacerbations-do not provide specific recommendations for treatment of methicillin-resistant Staphylococcus aureus (MRSA) lung infections. However, the American Thoracic Society Guidelines recommend vancomycin as first line therapy. Only one study has previously described a single dose of intravenous (IV) vancomycin PK in adult PwCF. Our study aimed to describe intermittent IV vancomycin PK at steady-state in adult PwCF.

METHODS: Adult PwCF who were admitted to University of Utah Hospital between May 11, 2014 and August 31, 2020 and received intermittent IV vancomycin for the treatment of an APE were included in this study. The primary outcome was to describe the drug volume of distribution (Vd), drug clearance, elimination half-life, and total daily dose of vancomycin. Secondary outcomes were rates of acute kidney injury (AKI), liver injury, and infusion related reactions.

RESULTS: Thirteen patients were included. The mean Vd was 0.54 L/kg on day 3 and 0.53 L/kg on day 7. Vancomycin clearance was 5.11 L/hr on day 3 and 4.69 L/hr on day 7. Zero patients experienced an AKI,2 patients experienced liver injury, and no patients experienced infusion related reactions.

CONCLUSIONS: Our results demonstrate that in PwCF intermittent IV vancomycin steady-state PK are similar to previously reported single dose IV vancomycin.. Additionally, vancomycin clearance minimally changes from day 3 to day 7, although this study was not powered to detect a difference. This article is protected by copyright. All rights reserved.

PMID:35836330 | DOI:10.1002/ppul.26077

Pediatr Pulmonol. 2022 Jul 14. doi: 10.1002/ppul.26073. Online ahead of print.

ABSTRACT

Antibiotic allergy is a big problem that may affect the treatment and life quality of the patients with cystic fibrosis (CF).

AIM: To evaluate predictive factors for confirmed antibiotic hypersensitivity in children with CF.

METHODS: In this case-controlled study, we examined 15 patients with CF who had been confirmed with antibiotic allergy. Additionally, we included a control group of age- and gender-matched 45 CF patients with no antibiotic allergy. The diagnosis of antibiotic allergy was confirmed in the presence of a compatible history and a positive response in the drug skin test or provocation test. Multiple drug hypersensitivity was classified according to the temporal relationship of antibiotics: (i) distant, (ii) simultaneous, and (iii) sequential. The data were analyzed by conditional logistic regression.

RESULTS: β-lactam allergy was confirmed in 8 patients (ceftazidime n=5, piperacillin-tazobactam n=3) and non-β-lactam allergy was confirmed in 2 patients (ciprofloxacin n=1, azithromycin n=1). Additionally, multiple drug hypersensitivity in 5 patients (distant n=4, sequential n=1), among whom two patients showed hypersensitivity against ceftazidime/piperacillin-tazobactam+ ciprofloxacin/levofloxacin, two patients showed hypersensitivity against ceftazidime+ ciprofloxacin n=2, and one patient showed hypersensitivity against piperacillin-tazobactam+ amikacin+ trimethoprim-sulfamethoxazole. All patients (n=13) with confirmed β-lactam allergy were meropenem tolerant. Multivariate analysis indicated that immediate reactions (, P<0.001) and allergic evaluation in the first six months after the reaction (P=0.036) were significant risk factors for the prediction of antibiotic hypersensitivity.

CONCLUSION: Beta-lactam antibiotic allergy is the most commonly confirmed drug allergy in children with CF. However, unlike normal children, ceftazidime and piperacillin-tazobactam account for the majority. This article is protected by copyright. All rights reserved.

PMID:35833362 | DOI:10.1002/ppul.26073

Expert Rev Respir Med. 2022 Jul 14. doi: 10.1080/17476348.2022.2100350. Online ahead of print.

ABSTRACT

INTRODUCTION: The airway epithelium is a key system within the lung. It acts as a physical barrier to inhaled factors, and can actively remove unwanted microbes and particles from the lung via the mucociliary escalator. On a physiological level, it senses the presence of pathogens and initiates innate immune responses to combat their effects. Hydration of the airways is also controlled by the epithelium. Within the cystic fibrosis (CF) lung these properties are suboptimal and contribute to the pulmonary manifestations of CF.

AREAS COVERED: In this review, we discuss how various host and microbial factors can contribute to airway epithelium dysfunction in the CF lung focusing on mechanisms relating to the mucociliary escalator and protease expression and function. We also explore how alterations in microRNA expression can impact the behaviour of the airway epithelium.

EXPERT OPINION: Notwithstanding the unprecedented benefits that CFTR modulator drugs now provide to the health of CF sufferers, it will be important to delve more deeply into additional mechanisms underpinning CF lung disease such as those illustrated here in an attempt to counteract these aberrant processes and further enhance quality of life for people with CF.

PMID:35833354 | DOI:10.1080/17476348.2022.2100350

Pediatr Pulmonol. 2022 Jul 13. doi: 10.1002/ppul.26080. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to investigate depression, burnout, attitude, and burden of caregivers of children with cystic fibrosis (CF), and especially caregivers of children with primary ciliary dyskinesia (PCD) due to limited number of studies on this topic, and to compare them according to their children's clinical status.

METHODS: Clinical features and demographic data of children and their families were asked to caregivers in four pediatric pulmonology centers. Beck Depression Inventory, Maslach Burnout Inventory, Zarit Caregiver Burden Scale, and Parental Attitude Research Instrument were administered to caregivers in both groups. Results were compared between the two groups.

RESULTS: In total, 131 children with CF and 39 with PCD and their caregivers were involved in study. All primary caregivers were mothers in both groups. Depression, burnout, and burden scores of mothers of children with CF were significantly higher than mothers of children with PCD (p=0.017, p=0.024, p=0.038, respectively). Burnout was higher in both CF and PCD groups with low family income (p=0.022, p=0.034). Number of hospital visits in the previous six months was correlated with burnout in both CF and PCD groups (r=0.207, p=0.034; r=0.352, p=0.044).

CONCLUSIONS: Although mothers with children with CF have higher levels of depression, burnout, burden and negative attitudes towards children than mothers with children with PCD, these are also significantly high in mothers with children with PCD. Psychological problems of mothers of children with CF and PCD may increase with frequent hospital visits, hospitalizations, low family income, number of children, and chronic disease in another child. This article is protected by copyright. All rights reserved.

PMID:35833227 | DOI:10.1002/ppul.26080

Front Pediatr. 2022 Jun 27;10:914790. doi: 10.3389/fped.2022.914790. eCollection 2022.

ABSTRACT

Cystic fibrosis (CF) is a common disorder of autosomal recessive inheritance, that once conferred a life expectancy of only a few months. Over recent years, significant advances have been made to CF therapeutic approaches, changing the face of the disease, and facilitating the partial restoration of pancreatic function. This mini review summarizes the current landscape of exocrine pancreatic management in CF and explores areas for future direction and development.

PMID:35832587 | PMC:PMC9271761 | DOI:10.3389/fped.2022.914790

Respirology. 2022 Jul 13. doi: 10.1111/resp.14327. Online ahead of print.

NO ABSTRACT

PMID:35831227 | DOI:10.1111/resp.14327

J Epidemiol Community Health. 2022 Jul 13:jech-2022-219074. doi: 10.1136/jech-2022-219074. Online ahead of print.

ABSTRACT

BACKGROUND: Peptic ulcer disease (PUD) and gastric cancer (GC) are more prevalent in individuals with low socioeconomic status (SES) and share several risk factors. The aim of this study was to investigate the mediating role of PUD in the association between established risk factors and GC.

METHODS: We conducted a pooled analysis of 12 studies from the Stomach Cancer Pooling Project Consortium, including a total of 4877 GC cases and 11 808 controls. We explored the mediating role of PUD in the association between SES, tobacco smoking, heavy alcohol drinking and salt intake, and GC. Also, we assessed the ORs and 95% CIs of the risk factors and both PUD and GC.

RESULTS: PUD mediated 36% of the smoking effect mainly among men. Other risk factors were only slightly mediated by PUD (SES, 5.3%; heavy alcohol drinking, 3.3%; and salt intake, 2.5%). No significant difference was found when excluding PUD diagnosed within 2 years from GC.

CONCLUSIONS: Our study provides innovative information on the mechanism of stomach mucosal damage leading to PUD and GC, with respect to the effect of tobacco smoking in particular.

PMID:35831132 | DOI:10.1136/jech-2022-219074

Disabil Rehabil. 2022 Jul 13:1-7. doi: 10.1080/09638288.2022.2099588. Online ahead of print.

ABSTRACT

PURPOSE: The 2010 Lung Allocation Score (LAS) version considers the estimated survival benefit offered by lung transplantation (LTx) and uses 6-minute Walk Test (6MWT) distance as a dichotomous covariate of whether an individual can walk more than 150 ft or 45.7 m in 6 min. This study aimed to provide evidence that 6MWT gives no clinically meaningful information to be used in the current LAS for candidates to LTx with cystic fibrosis (CF).

MATERIALS AND METHODS: We collected data from 6MWTs performed since 2003 at our CF centre. A joint model was fitted to describe the effect of changes in walked distance on the hazard of LTx or death.

RESULTS: Up to 2019, 552 6MWTs were performed on 163 individuals with CF. None of the individuals included walked for less than 45.7 m during the 6MWT. Based on the joint modelling, the association of walked distance with the hazard ratio (HR) of LTx or death was significant (HR 0.99, 95% Credible Interval [CI]: 0.99 to 1.00).

CONCLUSIONS: When adopted dichotomously for LAS calculation, walked distance does not add any useful information about exercise capacity. Longitudinal trajectories of walked distance may provide complementary information about prognosis in individuals with CF.Implications for rehabilitationDichotomized walked distance does not contribute to lung allocation score in candidates to lung transplantation with cystic fibrosisChanges in the longitudinal trajectory of walked distance can be clinically meaningful for prognostication.Sensitive outcomes to be incorporated in the lung allocation scoring system for individuals with CF are yet needed to catch rapid falls in functional capacity.

PMID:35830371 | DOI:10.1080/09638288.2022.2099588

Eur J Gastroenterol Hepatol. 2022 Jul 14. doi: 10.1097/MEG.0000000000002408. Online ahead of print.

ABSTRACT

OBJECTIVE: To provide data on the use of infliximab biosimilars (IFX-BioS) in children with inflammatory bowel disease (IBD).

METHODS: A multicenter, observational, retrospective study was performed among the cohort of the Sicilian Network for IBD. All consecutive IBD children who had at least completed the induction with IFX-BioS from its introduction in Sicily to January 2021 were enrolled. Clinical remission at weeks 14 and 52, treatment persistence, and adverse events were the study outcomes.

RESULTS: Eighty-seven patients [Crohn's disease (CD): 57.5% and ulcerative colitis (UC): 42.5%] were included: 75 (86.2%) were antitumor necrosis factor-α (anti-TNF-α) agent naïve, while three (3.45%) were switched from the originator to IFX-BioS. Twenty (23%) patients were multiply switched from the biosimilar CT-P13 to SB2 or GP1111 or vice versa. The median follow-up time was 15 months. Clinical remission was achieved by 55.2 and 65.5% of patients at weeks 14 and 52, respectively, with no differences between CD and UC. Dose escalation was needed in 8.0 and 35.7% of patients during induction and maintenance, respectively. Nine adverse events occurred (incidence rate: 6.13/100 person-year). Treatment persistence was 90.8% at 1 year and 75.7% at 2 years (patients on IFX-BioS at 2 years, n = 28). The risk of treatment discontinuation was higher in patients with extraintestinal manifestations (P = 0.018) and in those who were nonnaïve to anti-TNF-α (P = 0.027).

CONCLUSION: This is the largest cohort of pediatric IBD patients treated with IFX-BioS. Real-life data show that IFX-BioS is efficacious in IBD children, with high percentages of treatment persistence and a low incidence of nonserious adverse events.

PMID:35830365 | DOI:10.1097/MEG.0000000000002408

Front Aging. 2022 Apr 29;3:736835. doi: 10.3389/fragi.2022.736835. eCollection 2022.

ABSTRACT

Metformin may potentially reverse various age-related conditions; however, it is unclear whether metformin can also mitigate or delay the deterioration of immunological resilience that occurs in the context of infections that are commonly observed in older persons. We examined whether metformin promotes the preservation of immunological resilience in an acute S. pneumoniae (SPN) infection challenge in young adult mice. Mice were fed metformin (MET-alone) or standard chow (controls-alone) for 10 weeks prior to receiving intratracheal inoculation of SPN. A subset of each diet group received pneumococcal conjugate vaccine at week 6 (MET + PCV and control + PCV). Compared to controls-alone, MET-alone had significantly less infection-associated morbidity and attenuated inflammatory responses during acute SPN infection. Metformin lowered the expression of genes in the lungs related to inflammation as well as shorter lifespan in humans. This was accompanied by significantly lower levels of pro-inflammatory cytokines (e.g., IL6). MET + PCV vs. control + PCV manifested enhanced SPN anticapsular IgM and IgG levels. The levels of SPN IgM production negatively correlated with expression levels of genes linked to intestinal epithelial structure among MET + PCV vs. control + PCV groups. Correspondingly, the gut microbial composition of metformin-fed mice had a significantly higher abundance in the Verrucomicrobia, Akkermansia muciniphila, a species previously associated with beneficial effects on intestinal integrity and longevity. Together, these findings indicate metformin's immunoprotective potential to protect against infection-associated declines in immunologic resilience.

PMID:35821804 | PMC:PMC9261336 | DOI:10.3389/fragi.2022.736835

ERJ Open Res. 2022 Jul 11;8(3):50171-2019. doi: 10.1183/23120541.50171-2019. eCollection 2022 Jul.

ABSTRACT

[This corrects the article DOI: 10.1183/23120541.00171-2019.].

PMID:35821756 | PMC:PMC9271753 | DOI:10.1183/23120541.50171-2019

Life Sci Alliance. 2022 Jul 12;5(11):e202201458. doi: 10.26508/lsa.202201458. Print 2022 Nov.

ABSTRACT

Alveolar macrophages (AMs) reside on the luminal surface of the airways and alveoli, ensuring proper gas exchange by ingesting cellular debris and pathogens, and regulating inflammatory responses. Therefore, understanding the heterogeneity and diverse roles played by AMs, interstitial macrophages, and recruited monocytes is critical for treating airway diseases. We performed single-cell RNA sequencing on 113,213 bronchoalveolar lavage cells from four healthy and three uninflamed cystic fibrosis subjects and identified two MARCKS+LGMN+IMs, FOLR2+SELENOP+ and SPP1+PLA2G7+ IMs, monocyte subtypes, DC1, DC2, migDCs, plasmacytoid DCs, lymphocytes, epithelial cells, and four AM superclusters (families) based on the gene expression of IFI27 and APOC2 These four AM families have at least eight distinct functional members (subclusters) named after their differentially expressed gene(s): IGF1, CCL18, CXCL5, cholesterol, chemokine, metallothionein, interferon, and small-cluster AMs. Interestingly, the chemokine cluster further divides with each subcluster selectively expressing a unique combination of chemokines. One of the most striking observations, besides the heterogeneity, is the conservation of AM family members in relatively equal ratio across all AM superclusters and individuals. Transcriptional data and TotalSeq technology were used to investigate cell surface markers that distinguish resident AMs from recruited monocytes. Last, other AM datasets were projected onto our dataset. Similar AM superclusters and functional subclusters were observed, along with a significant increase in chemokine and IFN AM subclusters in individuals infected with COVID-19. Overall, functional specializations of the AM subclusters suggest that there are highly regulated AM niches with defined programming states, highlighting a clear division of labor.

PMID:35820705 | DOI:10.26508/lsa.202201458

Am J Physiol Lung Cell Mol Physiol. 2022 Jul 12. doi: 10.1152/ajplung.00065.2022. Online ahead of print.

ABSTRACT

The balance of gas exchange and lung ventilation is essential for the maintenance of body homeostasis. There are many ion channels and transporters in respiratory epithelial cells, including epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator, and some transporters. These ion channels/transporters maintain the capacity of liquid layer on the surface of respiratory epithelial cells, and provide an immune barrier for the respiratory system to clear off foreign pathogens. However, in some harmful external environment and/or pathological conditions, the respiratory epithelium is prone to hypoxia, which would destroy the ion transport function of the epithelium and unbalance the homeostasis of internal environment, triggering a series of pathological reactions. Many respiratory diseases associated with hypoxia manifest an increased expression of hypoxia-inducible factor-1, which mediates the integrity of the epithelial barrier and affects epithelial ion transport function. It is important to study the relationship between hypoxia and ion transport function, whereas the mechanism of hypoxia-induced ion transport dysfunction in respiratory diseases is not clear. This review focuses on the relationship of hypoxia and respiratory diseases, as well as dysfunction of ion transport and tight junctions in respiratory epithelial cells under hypoxia.

PMID:35819839 | DOI:10.1152/ajplung.00065.2022

J Physiol Biochem. 2022 Jul 11. doi: 10.1007/s13105-022-00909-1. Online ahead of print.

ABSTRACT

Pyroptosis is commonly induced by the gasdermin (GSDM) family and is accompanied by the release of inflammatory cytokines such as IL-1β and IL-18. Recently, increasing evidence suggests that pyroptosis plays a role in respiratory diseases. This review aimed to summarize the roles and mechanisms of pyroptosis in inflammation-related respiratory diseases. There are several pathways involved in pyroptosis, such as the canonical inflammasome-induced pathway, non-canonical inflammasome-induced pathway, caspase-1/3/6/7/GSDMB pathway, caspase-8/GSDMC pathway, caspase-8/GSDMD pathway, and caspase-3/GSEME pathway. Pyroptosis may be involved in asthma, chronic obstructive pulmonary disease (COPD), lung cancer, acute lung injury (ALI), silicosis, pulmonary hypertension (PH), and tuberculosis (TB), in which the NLRP3 inflammasome-induced pathway is mostly highlighted. Pyroptosis contributes to the deterioration of asthma, COPD, ALI, silicosis, and PH. In addition, pyroptosis has dual effects on lung cancer and TB. Additionally, whether pyroptosis participates in cystic fibrosis (CF) and sarcoidosis or not is largely unknown, though the activation of NLRP3 inflammasome is found in CF and sarcoidosis. In conclusion, pyroptosis may play a role in inflammation-related respiratory diseases, providing new therapeutic targets.

PMID:35819638 | DOI:10.1007/s13105-022-00909-1

ACS Appl Mater Interfaces. 2022 Jul 12. doi: 10.1021/acsami.2c05979. Online ahead of print.

ABSTRACT

Activity tests for synthetic antimicrobial compounds are often limited to the minimal inhibitory concentration assay using standard media and bacterial strains. In this study, a family of acrylamide copolymers that act as synthetic mimics of antimicrobial peptides were synthesized and shown to have a disruptive effect on bacterial membranes and structural integrity through microscopy techniques and membrane polarization experiments. The polymers were tested for their antimicrobial properties using media that mimic clinically relevant conditions. Additionally, their activity was compared in two different strains of the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Pseudomonas aeruginosa. We showed that the medium composition can have an important influence on the polymer activity as there was a considerable reduction in minimal inhibitory concentrations against S. aureus grown in synthetic wound fluid (SWF), and against P. aeruginosa grown in synthetic cystic fibrosis sputum media (SCFM), compared to the concentrations in standard testing media. In contrast, we observed a complete loss of activity against P. aeruginosa in the serum-containing SWF. Finally, we made use of an emerging invertebrate in vivo model, using Galleria mellonella larvae, to assess toxicity of the polymeric antimicrobials, showing a good correlation with cell line toxicity measurements and demonstrating its potential in the evaluation of novel antimicrobial materials.

PMID:35819416 | DOI:10.1021/acsami.2c05979