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Matrix Biology : Journal of the... Jun 2024Heparan sulfate (HS) is an important component of the kidney anionic filtration barrier, the glomerular basement membrane (GBM). HS chains attached to proteoglycan...
Heparan sulfate (HS) is an important component of the kidney anionic filtration barrier, the glomerular basement membrane (GBM). HS chains attached to proteoglycan protein cores are modified by sulfotransferases in a highly ordered series of biosynthetic steps resulting in immense structural diversity due to negatively charged sulfate modifications. 3-O-sulfation is the least abundant modification generated by a family of seven isoforms but creates the most highly sulfated HS domains. We analyzed the kidney phenotypes in the Hs3st3a1, Hs3st3b1 and Hs3st6 -knockout (KO) mice, the isoforms enriched in kidney podocytes. Individual KO mice show no overt kidney phenotype, although Hs3st3b1 kidneys were smaller than wildtype (WT). Furthermore, Hs3st3a1; Hs3st3b1 double knockout (DKO) kidneys were smaller but also had a reduction in glomerular size relative to wildtype (WT). Mass spectrometry analysis of kidney HS showed reduced 3-O-sulfation in Hs3st3a1 and Hs3st3b1, but not in Hs3st6 kidneys. Glomerular HS showed reduced HS staining and reduced ligand-and-carbohydrate engagement (LACE) assay, a tool that detects changes in binding of growth factor receptor-ligand complexes to HS. Interestingly, DKO mice have increased levels of blood urea nitrogen, although no differences were detected in urinary levels of albumin, creatinine and nephrin. Finally, transmission electron microscopy showed irregular and thickened GBM and podocyte foot process effacement in the DKO compared to WT. Together, our data suggest that loss of 3-O-HS domains disrupts the kidney glomerular architecture without affecting the glomerular filtration barrier and overall kidney function.
PubMed: 38944161
DOI: 10.1016/j.matbio.2024.06.006 -
Expert Review of Respiratory Medicine Jun 2024The Exacerbation of Chronic Obstructive Pulmonary Disease (ECOPD), especially if leading to hospitalization, increases the risk of death. Our scoping review aims to... (Review)
Review
INTRODUCTION
The Exacerbation of Chronic Obstructive Pulmonary Disease (ECOPD), especially if leading to hospitalization, increases the risk of death. Our scoping review aims to identify updated mortality risk factors in both short- and long-term periods.
AREAS COVERED
A comprehensive search, covering the period from January 2013 to February 2024, was performed to identify eligible studies that consider factors associated with death in hospitalized ECOPD. We considered short-term mortality, up to one year (including in-hospital mortality, IHM) and long-term mortality over one year, without time limits. We excluded studies concerning the intensive care area.
EXPERT OPINION
We considered 38 studies, 32 and 8 reporting data about short- and long-term mortality, respectively. Two studies consider both periods. Several factors, some already known, others newly identified, have been evaluated and discussed. Some of these were related to the characteristics and severity of COPD (age, body mass index, lung impairment), and some considered the response to ECOPD. In this last context, we focused on the increasing role of biomarkers in predicting the mortality of patients, particularly IHM. Our factors associated with a worse prognosis may be helpful in the clinical practice to identify patients at risk and, subsequently, determine a personalized approach.
PubMed: 38943613
DOI: 10.1080/17476348.2024.2375426 -
ESC Heart Failure Jun 2024New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET)...
AIMS
New tools are needed to identify heart failure (HF) risk earlier in its course. We evaluated the association of multidimensional cardiopulmonary exercise testing (CPET) phenotypes with subclinical risk markers and predicted long-term HF risk in a large community-based cohort.
METHODS AND RESULTS
We studied 2532 Framingham Heart Study participants [age 53 ± 9 years, 52% women, body mass index (BMI) 28.0 ± 5.3 kg/m, peak oxygen uptake (VO) 21.1 ± 5.9 kg/m in women, 26.4 ± 6.7 kg/m in men] who underwent maximum effort CPET and were not taking atrioventricular nodal blocking agents. Higher peak VO was associated with a lower estimated HF risk score (Spearman correlation r: -0.60 in men and -0.55 in women, P < 0.0001), with an observed overlap of estimated risk across peak VO categories. Hierarchical clustering of 26 separate CPET phenotypes (values residualized on age, sex, and BMI to provide uniformity across these variables) identified three clusters with distinct exercise physiologies: Cluster 1-impaired oxygen kinetics; Cluster 2-impaired vascular; and Cluster 3-favourable exercise response. These clusters were similar in age, sex distribution, and BMI but displayed distinct associations with relevant subclinical phenotypes [Cluster 1-higher subcutaneous and visceral fat and lower pulmonary function; Cluster 2-higher carotid-femoral pulse wave velocity (CFPWV); and Cluster 3-lower CFPWV, C-reactive protein, fat volumes, and higher lung function; all false discovery rate < 5%]. Cluster membership provided incremental variance explained (adjusted R increment of 0.10 in women and men, P < 0.0001 for both) when compared with peak VO alone in association with predicted HF risk.
CONCLUSIONS
Integrated CPET response patterns identify physiologically relevant profiles with distinct associations to subclinical phenotypes that are largely independent of standard risk factor-based assessment, which may suggest alternate pathways for prevention.
PubMed: 38943268
DOI: 10.1002/ehf2.14797 -
Particle and Fibre Toxicology Jun 2024Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have...
BACKGROUND
Today, nanomaterials are broadly used in a wide range of industrial applications. Such large utilization and the limited knowledge on to the possible health effects have raised concerns about potential consequences on human health and safety, beyond the environmental burden. Given that inhalation is the main exposure route, workers exposed to nanomaterials might be at risk of occurrence of respiratory morbidity and/or reduced pulmonary function. However, epidemiological evidence regarding the association between cumulative exposure to nanomaterials and respiratory health is still scarce. This study focused on the association between cumulative exposure to nanomaterials and pulmonary function among 136 workers enrolled in the framework of the European multicentric NanoExplore project.
RESULTS
Our findings suggest that, independently of lifelong tobacco smoking, ethnicity, age, sex, body mass index and physical activity habits, 10-year cumulative exposure to nanomaterials is associated to worse FEV and FEF, which might be consistent with the involvement of both large and small airway components and early signs of airflow obstruction. We further explored the hypothesis of a mediating effect via airway inflammation, assessed by interleukin (IL-)10, IL-1β and Tumor Necrosis Factor alpha (TNF-α), all quantified in the Exhaled Breath Condensate of workers. The mediation analysis results suggest that IL-10, TNF-α and their ratio (i.e., anti-pro inflammatory ratio) may fully mediate the negative association between cumulative exposure to nanomaterials and the FEV/FVC ratio. This pattern was not observed for other pulmonary function parameters.
CONCLUSIONS
Safeguarding the respiratory health of workers exposed to nanomaterials should be of primary importance. The observed association between cumulative exposure to nanomaterials and worse pulmonary function parameters underscores the importance of implementing adequate protective measures in the nanocomposite sector. The mitigation of harmful exposures may ensure that workers can continue to contribute productively to their workplaces while preserving their respiratory health over time.
Topics: Humans; Male; Nanostructures; Female; Occupational Exposure; Adult; Inhalation Exposure; Middle Aged; Lung; Pneumonia; Forced Expiratory Volume; Respiratory Function Tests; Cytokines; Air Pollutants, Occupational; Europe
PubMed: 38943182
DOI: 10.1186/s12989-024-00589-3 -
BMC Cancer Jun 2024Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating...
BACKGROUND
Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored.
METHODS
The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk.
RESULTS
MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers.
CONCLUSIONS
We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.
Topics: Humans; Lung Neoplasms; Male; Polymorphism, Single Nucleotide; Female; Genetic Predisposition to Disease; Middle Aged; Transcription Factors; Asian People; DNA-Binding Proteins; Transcription Factor MTF-1; Case-Control Studies; China; Aged; Genotype; Risk Factors; East Asian People
PubMed: 38943058
DOI: 10.1186/s12885-024-12516-y -
Journal of Cystic Fibrosis : Official... Jun 2024Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the...
BACKGROUND
Data on the impact of liver transplantation (LT) in cystic fibrosis (CF) on lung function and exacerbations are limited. The objective of this study was to summarize the literature on lung function, nutritional status, survival, and complications following LT in people with CF.
METHODS
Three databases were searched until September 2023, to identify the impact of LT in CF. Lung transplant prior to LT and simultaneous liver-lung transplant were excluded. Pooled hazard ratios were calculated using random-effects models.
RESULTS
Thirty studies were included in this review, with 3 and 9 studies included in meta-analyses for nutritional status and lung function, respectively. Eighty-three percent of the studies used data that was more than a decade old. There was a significant increase in percent-predicted forced expiratory volume with mean change of 7.16 % (2.13, 12.19; p = 0.005) one year post-LT. Pulmonary exacerbations decreased in the short-term, however there was no significant change in body mass index (BMI). One-year survival post-LT ranged between 75 and 100 %, while five-year survival was lower at 64-89 %.
CONCLUSION
Existing data suggest that LT improves lung function in the short term and does not increase the likelihood of pulmonary exacerbations, despite ongoing immunosuppression in the setting of chronic lung infection.
PubMed: 38942722
DOI: 10.1016/j.jcf.2024.06.012 -
Biochimica Et Biophysica Acta.... Jun 2024Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a...
Obesity is a risk factor for developing severe COVID-19. However, the mechanism underlying obesity-accelerated COVID-19 remains unclear. Here, we report results from a study in which 2-3-month-old K18-hACE2 (K18) mice were fed a western high-fat diet (WD) or normal chow (NC) over 3 months before intranasal infection with a sublethal dose of SARS-CoV2 WA1 (a strain ancestral to the Wuhan variant). After infection, the WD-fed K18 mice lost significantly more body weight and had more severe lung inflammation than normal chow (NC)-fed mice. Bulk RNA-seq analysis of lungs and adipose tissue revealed a diverse landscape of various immune cells, inflammatory markers, and pathways upregulated in the infected WD-fed K18 mice when compared with the infected NC-fed control mice. The transcript levels of IL-6, an important marker of COVID-19 disease severity, were upregulated in the lung at 6-9 days post-infection in the WD-fed mice when compared to NC-fed mice. Transcriptome analysis of the lung and adipose tissue obtained from deceased COVID-19 patients found that the obese patients had an increase in the expression of genes and the activation of pathways associated with inflammation as compared to normal-weight patients (n = 2). The K18 mouse model and human COVID-19 patient data support a link between inflammation and an obesity-accelerated COVID-19 disease phenotype. These results also indicate that obesity-accelerated severe COVID-19 caused by SARS-CoV-2 WA1 infection in the K18 mouse model would be a suitable model for dissecting the cellular and molecular mechanisms underlying pathogenesis.
PubMed: 38942338
DOI: 10.1016/j.bbadis.2024.167322 -
Ecotoxicology and Environmental Safety Jun 2024Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults....
Chromium (Cr) exposure is associated with various respiratory system diseases, but there are limited studies investigating its impact on lung function in young adults. The Cr exposure-related metabolomic changes are not well elucidated. This study recruited 608 students from a university in Shandong Province, China in 2019. We used cohort design fitted with linear mixed-effects models to assess the association between blood Cr concentration and lung function. In addition, we performed metabolomic and lipidomic analyses of baseline serum samples (N = 582) using liquid chromatography-mass spectrometry. Two-step statistical analysis (analysis of variance and mixed-linear effect model) was used to evaluate the effect of blood Cr exposure on metabolites. We found that blood Cr was associated with decreased lung function in young adults. Each 2-fold increase in blood Cr concentrations was significantly associated with decreased FEV and FVC by 35.26 mL (95 % CI: -60.75, -9.78) and 38.56 mL (95 % CI: -66.60, -10.51), respectively. In the metabolomics analysis, blood Cr exposure was significantly associated with 14 key metabolites. The changed metabolites were mainly enriched in six pathways including lipid metabolism, amino acid metabolism, and cofactor vitamin metabolism. Blood Cr may affect lung function through oxidative stress and inflammation related pathways.
PubMed: 38941662
DOI: 10.1016/j.ecoenv.2024.116594 -
Medicine Jun 2024The aim of this study is to delineate the distinctive high-resolution computed tomography features of pulmonary cryptococcosis in non-HIV-infected patients. This...
The aim of this study is to delineate the distinctive high-resolution computed tomography features of pulmonary cryptococcosis in non-HIV-infected patients. This retrospective analysis encompasses high-resolution computed tomography scans from 58 patients with histologically confirmed pulmonary cryptococcosis, focusing on the diagnostic challenges and the factors that lead to misdiagnosis. Analysis of computed tomography scans from these patients indicated that nodular or mass-like presentations were evident in 32 cases (55.2%), consolidation presentations in 7 cases (12.1%), and mixed presentations in 19 cases (32.8%). Lesions were predominantly located in the lower lobes of the lungs (40 cases, 69.0%) and in peripheral zones (55 cases, 94.8%). Notable radiographic signs included the presence of the burr sign in 55 cases (94.8%), lobulation sign in 53 cases (91.4%), halo sign in 53 cases (91.4%), and air bronchogram in 46 cases (79.0%). Moreover, 24 cases (41.4%) exhibited necrosis or cavitation, mediastinal lymphadenopathy was noted in 6 cases (10.3%), and pleural effusion was present in 5 cases (8.6%). Lesions were devoid of calcification. Pulmonary cryptococcosis ought to be contemplated in the differential diagnosis when computed tomography imaging exhibits patterns including, but not limited to, lower lobe and peripheral distribution, a broad base abutting the pleura, clustered growth with a propensity for fusion, air bronchogram within lesions, and peripheral halo sign.
Topics: Humans; Male; Female; Retrospective Studies; Middle Aged; Cryptococcosis; Tomography, X-Ray Computed; Lung Diseases, Fungal; Adult; Aged; Lung; Young Adult
PubMed: 38941424
DOI: 10.1097/MD.0000000000038671 -
Medicine Jun 2024Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic... (Observational Study)
Observational Study
Elevated neutrophil-to-lymphocyte ratio combined with decreased lymphocyte-to-monocyte ratio is associated with increased peripheral airway resistance in patients with hepatic steatosis.
Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS.
Topics: Humans; Male; Female; Middle Aged; Retrospective Studies; Neutrophils; Lymphocytes; Monocytes; Airway Resistance; Fatty Liver; Adult; Aged; Leukocyte Count; Lymphocyte Count
PubMed: 38941417
DOI: 10.1097/MD.0000000000038530