Biological age (BA) has been proposed as a complementary construct to chronological age (CA) for quantifying interindividual heterogeneity in aging trajectories. Biological aging clocks (BACs) integrate molecular, clinical and multi-omics biomarkers to estimate aging-related phenotypes beyond CA. This narrative review critically examines the biological foundations, statistical methodologies, interpretative challenges and translational applications of BACs. We discuss the mechanistic basis of BACs development within the frameworks of the hallmarks and domains of aging, emphasizing the roles of age-related methylome remodeling, immunosenescence, and chronic low-grade inflammation. BACs are classified into three major generations according to their training objectives: first-generation clocks optimized to predict CA, second-generation clocks designed to estimate morbidity and mortality risk, and third-generation clocks developed to quantify the pace of aging from longitudinal biomarker changes. We also review multi-omics and artificial intelligence-based approaches that aim to capture the multidimensional nature of aging. Important limitations remain regarding biological specificity, causal interpretation, reverse causation, confounding, generalizability and clinical applicability of BACs. Current evidence suggests that BACs represent distinct operationalizations of biological aging instead of interchangeable measures of a single construct. Future advances will require longitudinal, mechanistic and diverse population-based studies to improve interpretability, reproducibility, and translational utility.
Objective The aim of this study was to investigate the effects of SEPT9 on proliferation, migration, and apoptosis in endometriotic stromal cells and to explore the underlying mechanisms. Methods Immunohistochemistry and western blotting revealed that SEPT9 expression was significantly elevated in ectopic and eutopic endometrial tissues from patients with endometriosis compared with normal endometrial tissues (p<0.05). Using immortalized human eutopic and ectopic endometrial stromal cells, genetic recombination was applied to overexpress SEPT9 in eutopic cells and knock down SEPT9 in ectopic cells. Results Transwell migration, EdU proliferation, and flow cytometry assays showed that SEPT9 overexpression enhanced cell proliferation and migration, whereas SEPT9 silencing reduced these behaviors and increased apoptosis. Pathway analyses identified the PI3K/AKT signaling pathway as a downstream target of SEPT9. Consistently, western blotting and qRT-PCR following SEPT9 knockdown confirmed decreased expression of PI3K/AKT-related proteins and genes. Conclusion In conclusion, silencing SEPT9 inhibited proliferation and migration and promoted apoptosis in endometriotic stromal cells, potentially through suppression of the PI3K/AKT signaling pathway.
BACKGROUND:Maximal inspiratory (MIP) and expiratory (MEP) pressures indicate respiratory muscle strength. Published reference equations typically cover limited age ranges, causing artificial shifts in predicted values during age transitions. Our aim was to develop continuous MIP and MEP reference equations from childhood to advanced age. METHODS:We evaluated 892 healthy subjects aged 4.7-79 years (median: 14.3 years; 50.4% female) in Mexico City (2240m). MIP and MEP were measured following international guidelines. RESULTS:Reference equations and root mean square errors (RMSE) were: -MIP (cmH2O)=19.08654+(13.82336·sex)+(2.529469·age)-(0.0341694·age2)+(0.9130152·BMI); RMSE=20.595 MEP (cmH2O)=32.74452+(18.25912·sex)+(2.606639·age)-(0.0301438·age2)+(0.4891667 ·BMI); RMSE=25.157 where sex: male=1, female=0; age in years; BMI in kg/m2. Age exerted the greatest influence on respiratory pressures, followed by sex and BMI. CONCLUSION:These continuous reference equations span most of the lifespan, eliminating transitional gaps and improving the clinical assessment of maximal respiratory pressures.
Neurodegenerative diseases are biologically heterogeneous disorders characterized by progressive neuronal dysfunction, overlapping molecular pathologies, and limited disease-modifying therapies. Advances in biomarker development, molecular staging, and precision medicine are reshaping therapeutic strategies and clinical trial design across Parkinson's disease, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Huntington's disease, and related disorders. This review summarizes emerging therapeutic approaches, including monoclonal antibodies targeting protein aggregation, immune-modulating and metabolic interventions, antisense oligonucleotides, gene replacement and genome-editing strategies, stem cell-based therapies, and neurosurgical delivery platforms and neuromodulation technologies. It also examines evolving clinical trial methodologies such as biomarker-enriched recruitment, adaptive and delayed-start designs, platform trials, decentralized models, and master protocols. Additional emphasis is placed on diagnostic biomarkers, multimodal artificial-intelligence pipelines, systems-biology perspectives, network-based therapeutic strategies, and the reproducibility and interpretability requirements for computational tools. Despite recent progress, major challenges remain, including biological heterogeneity, limited translatability of preclinical models, delivery barriers, long-term safety concerns, and inequities in access to biomarker-based care and trial participation. Future directions will require combination therapies, integrated biomarker pipelines, preventive strategies, and pragmatic trial systems capable of translating biological advances into durable and equitable clinical benefit.
Objective Oral health and malnutrition are significant modifiable factors contributing to frailty in older adults. However, the intrinsic pathways through which they are associated with frailty, as well as the moderating mechanisms involving psychosocial factors, remain unclear. This study aims to explore the mediating role of nutritional status in the relationship between oral health and frailty among community-dwelling older adults from the Wenhui, Wenhe, and Shuangqiao Subdistricts and to examine the moderating effect of social isolation on the “nutrition-frailty” pathway. Methods Employing a cross-sectional design, 409 community-dwelling older adults were recruited through convenience sampling in Yangzhou, China, from October 2022 to March 2023. Data collection involved a structured questionnaire that included the general information questionnaire, Tilburg Frailty Indicator, Oral Health Assessment Tool, Mini Nutritional Assessment Short Form, and Lubben Social Network Scale-6. Mediation and moderation analyses were conducted using PROCESS 3.4.1. Results Nutritional status partially mediated the relationship between oral health status and frailty, with a mediation effect coefficient of 0.087 (95% CI: 0.051, 0.126) and a relative mediation effect of 16.54%. Social isolation significantly moderated the ‘nutrition → frailty’ pathway (interaction term β=0.20, P <0.01), with a moderation threshold of 4.875. Conclusion Oral health status is associated with frailty via nutritional status, while social isolation moderates the association between nutritional status and frailty.
Huntington's disease (HD) is a progressive, autosomal dominant neurodegenerative disorder caused by cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin gene (HTT), resulting in mutant huntingtin (mHTT) with toxic gain-of-function and partial loss of normal huntingtin function. This narrative review summarizes recent advances in genetics, pathophysiology, clinical features, diagnostic assessment, biomarkers, and therapeutic development. Genetic testing demonstrating an expanded HTT CAG repeat is the definitive diagnostic test and should be interpreted with genetic counseling and attention to allele categories. Pathophysiologically, HD involves CAG instability, age-dependent somatic expansion in vulnerable neurons, transcriptional dysregulation, proteostasis failure, mitochondrial dysfunction, excitotoxicity, and neuroinflammation, leading primarily to degeneration of striatal medium spiny neurons and later cortical involvement. Clinically, HD can begin from juvenile to late-adult life and manifests with motor, cognitive, psychiatric, and behavioral symptoms that evolve from premanifest biological change to functional decline. Current clinical care relies on symptom-directed treatment, whereas quantitative neuroimaging, cerebrospinal fluid biomarkers are mainly used for research and trial enrichment. Symptomatic management includes vesicular monoamine transporter type 2 inhibitors, antipsychotics, rehabilitation, nutritional support, and multidisciplinary care. Emerging disease-modifying approaches include HTT-lowering, somatic expansion inhibition, and gene-based therapies, but efficacy depends on target selectivity, timing, delivery route, dose, and patient selection.
BACKGROUND:Cannabis is the most used recreational drug, typically consumed by smoking. Its incomplete combustion produces pollutants similar to tobacco smoke, including carbon monoxide, particulate matter, and polycyclic aromatic hydrocarbons. However, the respiratory effects of cannabis smoke remain incompletely understood. This study aimed to explore and evaluate the impact of chronic cannabis smoking on respiratory health, particularly in individuals without tobacco used. METHODS:Individuals who had smoked cannabis for at least the past five years or on 100 or more occasions during the previous year were invited for an evaluation of respiratory health utilizing current standard methods: a questionnaire for symptoms (cough, phlegm, wheezing and dyspnea), pre and post-bronchodilator spirometry, IOS, DLCOsb, and a HRCT. RESULTS:Fifty-eight subjects were analyzed, including 20 exclusive cannabis smokers, 29 dual users, and 9 polysubstance users. Overall, 29% reported at least two chronic respiratory symptoms; 43% reported regular or poor general health; 66% had an abnormality in at least one lung-function test, with 57% showing an obstructive pattern; and 47% had at least one abnormality in the HRCT. No statistically significant differences were detected between groups; however, the study may have been underpowered to identify small between-group differences. CONCLUSION:In this exploratory study chronic cannabis users, either exclusive or in combination with other substances, a high frequency symptoms, functional abnormalities, and tomographic findings have been documented, despite their young age.
The evolution of statistical thinking within the scientific community has developed over nearly three centuries. The concept of "probability," commonly represented by the p-value, has been applied in medical research for more than a century. Its integration into hypothesis testing has played an important role in advancing medical science. Nevertheless, the p-value has also become one of the most misunderstood and misapplied statistical measures. The common practice of rigidly categorizing the probability value as being above or below the 0.05 threshold has often taken on a dogmatic quality, at times resembling a doctrine rather than a purely scientific criterion. In reporting experimental results and conducting hypothesis testing, references to "statistical significance" are frequently equated with "truth", while findings deemed "not statistically significant" are mistakenly interpreted as "false". This is a conflation and it is incorrect. The objective of this article is to provide a concise review of the history of statistics in medicine, clarify the development of the "probability value" concept, discuss its role in hypothesis testing, and consider its interpretation alongside clinical significance.
AIM:The aim of this study is to evaluate the correlation between psoriasis and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). This provides an important reference for formulating guidelines for the management of psoriasis comorbidities and improving the long-term prognosis of patients. METHODS:A systematic search was conducted across four databases: PubMed, Web of Science, Embase, and the Cochrane Library, covering the period from their inception to November 2025. A meta-analysis employing random-effects model (DerSimonian-Laird method) was conducted to assess the association between MASLD in psoriatic and non-psoriatic patients. Subgroup analyses were performed for psoriatic arthritis (PsA) and patients with moderate-to-severe psoriasis. RESULTS:This review included 13 studies comprising 6 case-control studies, 3 cohort studies, and 4 cross-sectional studies. Meta-analysis results indicated that individuals with psoriasis exhibited an increased risk of MASLD compared to those without psoriasis (OR=2.16, 95% CI: 1.65-2.83). Further subgroup analysis revealed that patients with moderate to severe psoriasis exhibited a heightened risk of MASLD compared to those with mild psoriasis (OR=2.81, 95% CI: 1.62-4.86). Additionally, the risk of MASLD among patients with PsA was not statistically significant (OR=1.48, 95% CI: 0.69-3.19). CONCLUSION:There is an association between psoriasis and MASLD, and patients with moderate to severe psoriasis have a higher risk of MASLD. Current evidence does not show a clear association between PsA and MASLD, but this conclusion is limited by the small number of included studies and requires further validation. This study provides a reference basis for formulating guidelines for the management of comorbidities in psoriasis, but it should be interpreted with caution due to the inherent limitations of observational studies.
Red blood cell transfusion in trauma surgery continues to be guided primarily by isolated hemoglobin (Hb) values despite the risks associated with over-transfusion. OBJECTIVE:This study aimed to evaluate whether the retrospective application of the peri-operative transfusion trigger score (POTTS) algorithm could reduce transfusion events in trauma patients. A one-year retrospective analysis was conducted comparing transfusions performed under standard clinical practice (liberal or restrictive management based on hemoglobin levels). The POTTS algorithm was applied, with suggestions to supplement it with the bleeding score and to further refine the algorithm for trauma patients (T-POTTS). RESULTS:The POTTS algorithm, which incorporates specific patient physiological parameters to determine a transfusion threshold, identified a significant number of potentially avoidable events and suggested that decisions based solely on Hb may not optimize the actual need for red blood cell transfusion in trauma patients. CONCLUSIONS:The use of POTTS in trauma patients could decrease unnecessary transfusion events, dismissing the importance of considering physiological parameters in transfusion decision-making.
BACKGROUND:Vitamin B12 deficiency is a reversible cause of hematologic and neurologic morbidity, but its etiologic spectrum in Latin American referral centers remains poorly defined. METHODS:We retrospectively studied consecutive adults with vitamin B12 deficiency evaluated in hematology and oncology clinics at a Mexican tertiary referral center from January 2013 to July 2023. Etiologies were classified as pernicious anemia, non-surgical malabsorption, post-surgical malabsorption, reduced intake, drug-related causes, or unknown, and pernicious anemia was compared with all other etiologies. RESULTS:Among 270 patients (median age 64 years; 52% female), pernicious anemia was the most frequent etiology (52.6%), followed by non-surgical malabsorption (28.1%) and post-surgical states (7.7%). Compared with other causes, pernicious anemia was associated with more comorbidities, lower hemoglobin, lower platelet counts, lower vitamin B12 levels, higher mean corpuscular volume, higher mean corpuscular hemoglobin, and higher indirect bilirubin. Weight loss, gastrointestinal symptoms, and neurologic alterations were common in both groups. CONCLUSIONS:In this tertiary Mexican cohort, pernicious anemia was the leading identified cause of vitamin B12 deficiency and showed greater hematologic and biochemical severity. Importantly, patients with non-pernicious etiologies had a median MCV within the normocytic range, supporting systematic etiologic evaluation and avoiding overreliance on macrocytosis alone.
Objective To investigate the association between early blood pressure variability (BPV) and 90-day prognosis in hypertensive patients with acute stroke who did not receive reperfusion therapy. Methods This prospective cohort study enrolled patients with a history of hypertension and acute stroke within 24h of onset. The main analysis cohort excluded those who received intravenous thrombolysis and/or endovascular treatment. Blood pressure was monitored within 24h after admission, and systolic blood pressure standard deviation (SBP-SD), coefficient of variation (SBP-CV), and average real variation (ARV) were calculated. According to the 90-day modified Rankin scale (mRS) score, outcomes were classified as good or poor. Subsequently, predictive variables were screened, and the impact of blood pressure variability on prognosis was assessed using a multivariate logistic regression model. Results Higher SBP-SD and SBP-CV were independent risk factors for poor prognosis at 90 days. The prediction model incorporating BPV indicators demonstrated good discriminant ability. Patients receiving reperfusion therapy (n=18) had higher BPV levels and a lower rate of good prognosis (22.2%). Conclusion For patients with hypertension complicated with acute stroke who did not undergo reperfusion therapy, higher systolic BPV within 24h after admission is an independent predictor of 90-day poor prognosis.
BACKGROUND:Cardiomyocyte apoptosis and inflammation are critical mediators in myocardial infarction (MI) progression. Sacubitril/valsartan (Sac/Val) is an angiotensin receptor-neprilysin inhibitor that has demonstrated therapeutic efficacy in MI treatment. Nonetheless, the exact mechanism by which Sac/Val exerts its cardioprotective effect in MI remains to be explored further. METHODS:Human cardiomyocytes (AC16) were pretreated with Sac/Val and exposed to hypoxia-oxygenation (H/R) to mimic MI in vitro. The conditioned medium (CM) of THP-1 macrophages was collected to co-culture with AC16 cells. CCK-8 assays were conducted to evaluate cell viability. A pharmacological inhibitor, TAK242, was utilized to block TLR4 signaling. Lactate dehydrogenase (LDH) release in the culture medium was estimated. Flow cytometry was performed for cell apoptosis analysis and macrophage marker detection. Western blotting was used to detect protein expression. RESULTS:Sac/Val pretreatment restored viability, alleviated apoptosis, and reduced proinflammatory cytokine production in H/R-exposed AC16 cells. Sac/Val hindered THP-1 cell polarization toward M1 phenotypes, while facilitating polarization toward M2 phenotypes, accompanied by TLR4/NF-κB signaling inhibition. Conditioned medium from Sac/Val- or TAK-242-treated THP-1 cells markedly reduced AC16 cell apoptosis and proinflammatory cytokine production under H/R exposure. CONCLUSION:Sac/Val attenuates H/R-triggered AC16 cell injury by promoting M2 macrophage polarization, associated with attenuated TLR4/NF-κB signaling.
BACKGROUND:Autosomal dominant polycystic kidney disease (ADPKD) is the leading monogenic cause of end-stage kidney disease (ESKD). Because disease-modifying therapy is costly and can cause adverse effects, identifying patients most likely to benefit is essential. We developed and internally validated a model to predict ESKD by age 80 in class 1 ADPKD, hypothesizing that combining baseline eGFR with an exponential estimate of kidney growth would improve forecasting. METHODS:We retrospectively analyzed 142 adults with class 1 ADPKD followed at a tertiary center in Mexico City (2012-2023). Total kidney volume (TKV) was measured by the ellipsoid method and eGFR by CKD-EPI 2021. Data were split 50/50 into derivation and validation sets. Future eGFR was modeled using baseline eGFR plus an exponential TKV growth surrogate; ESKD risk (eGFR <15ml/min/1.73m2) was derived from the standard normal cumulative distribution. Performance was compared with the Mayo Clinic Predictive Model (MCPM) and a Cox model. RESULTS:In validation, the model achieved adjusted R2=0.858 (vs. 0.830 for MCPM). ESKD prediction showed excellent discrimination (C-index=0.94) and calibration, comparable to Cox (C-index=0.95). CONCLUSIONS:This approach supports individualized lifetime ESKD risk prediction in class 1 ADPKD to guide targeted therapy and resource allocation.
BACKGROUND:In recent years, interest in the potential of liver enzymes has increased to serve as markers for cardiovascular disease (CVD) risk. This systematic review and meta-analysis aimed to examine the relationship between liver enzymes in blood tests and non-fatal cardiovascular disease events, focusing on retrospective and prospective cohort studies. METHODS:A methodical search was carried out across several academic databases, including Scopus, PubMed, and Web of Science. Relevant keywords were identified and categorized into two groups. Two reviewers independently reviewed the obtained papers to recognize related studies. Then, the authors independently gathered the necessary information. The quality of the papers was evaluated using the Newcastle-Ottawa Scale (NOS). Moreover, a meta-analysis was also performed on the values of the hazard ratio and odds ratio reported in some studies. RESULTS:36 articles were entered into the study. Most of the studies (89.3 percent) showed that there are positive significant relationships between gamma-glutamyl transferase (GGT) enzyme and non-fatal cardiovascular disease events. While only 50.0 percent of the studies on alanine aminotransferase (ALT) and 66.7 percent of the papers on aspartate aminotransferase (AST) revealed a positive significant association with non-fatal cardiovascular disease events. The pooled value of the hazard ratio related to the GGT, ALT, and AST levels for non-fatal cardiovascular disease events was computed by 1.28 (95% CI: 1.21-1.36), 1.23 (95%CI: 1.07-1.42), and 1.35 (95%CI: 1.17-1.55). CONCLUSIONS:There is a strong agreement on GGT for diagnosing cardiovascular diseases. These results can be applied as guidance for the diagnosis of cardiovascular diseases using liver enzymes as routine blood tests.
BACKGROUND:Interleukin-18 (IL-18) is a key inflammasome-related cytokine implicated in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. OBJECTIVE:This study investigated the diagnostic, prognostic, and immunogenetic relevance of IL-18 and its promoter polymorphism (-607C/A, rs1946518) in COVID-19 susceptibility, severity, and mortality among Kurdish coronavirus disease-2019 (COVID-19) patients. METHODS:A total of 100 unvaccinated COVID-19 patients and 80 healthy controls (HCs) were enrolled. COVID-19 patients were further classified into non-severe (n=60) and severe cases (n=40), and additionally into survived (n=75) and non-survived groups (n=25). Biochemical markers, CURB-65 scores, and clinical outcomes (severity and survival) were assessed. Genotyping of the IL-18 -607C/A polymorphism was performed using polymerase chain reaction - sequence-specific primer (PCR-SSP). RESULTS:COVID-19 patients exhibited markedly elevated IL-18 levels compared with HCs (509.1 vs. 228.8pg/mL, p<0.001). IL-18 showed a strong positive correlation with disease severity (r=0.77, p<0.001) and significantly distinguished non-severe from severe cases and survivors from non-survivors (both p<0.001). Severe and non-survived patients demonstrated higher D-dimer, ferritin, C-reactive protein (CRP), fibrinogen, neutrophils, and CURB-65 scores, alongside lower lymphocyte counts. Genotype analysis revealed that the CC genotype was significantly associated with higher IL-18 expression and more severe clinical phenotypes, including elevated CURB-65 scores and inflammatory biomarkers. In contrast, the A allele (CA and AA genotypes) conferred strong protection against severe disease (AA: OR=0.053; CA: OR=0.149) but showed no significant association with mortality. Statistical tests confirmed pronounced genotype-dependent differences in IL-18, D-dimer, ferritin, CRP, leukocyte profiles, and fibrinogen (p<0.05). Diagnostic evaluation showed that IL-18 accurately discriminated COVID-19 cases from HCs (area under curve (AUC)=0.991; sensitivity 95.0%; specificity 95.06%). As a prognostic marker for severe disease, IL-18 demonstrated moderate performance (AUC=0.671). CONCLUSION:The IL-18 -607C/A polymorphism influences COVID-19 susceptibility and severity, CC increases risk, while the A allele is protective, but it is not associated with mortality. IL-18 shows excellent diagnostic and moderate prognostic value and may enhance COVID-19 risk-stratification when combined with CURB-65 and genotypic data.
BACKGROUND:Accurate segmentation of blood vessels in glioma pathological images is crucial for understanding tumor vasculature and progression, yet remains challenging due to complex vessel morphology and image variations. OBJECTIVE:This study aimed to develop and evaluate a novel approach using a finetuned masked autoencoder self-attention mechanism (MedSAM) framework for interactive segmentation of glioma blood vessels in pathological images called GliomaVascularSAM. METHODS:We utilized a dataset of 2632 image patches derived from multiple glioma datasets. These patches were obtained from tissue samples of 879 patients from The Cancer Genome Atlas and 179 patients from three hospitals. The performance of GliomaVascularSAM was compared with convolutional neural network-based models (including nnU-Net, Pathology-nnU-Net, and nnSAM) and SAM-based segmentation methods. Model performance was evaluated using the dice similarity coefficient, sensitivity, and positive predictive value. RESULTS:The proposed GliomaVascularSAM outperformed traditional-based models, achieving a dice similarity coefficient of 0.784, sensitivity of 0.767, and positive predictive value of 0.820. Compared with the nnU-Net model (dice similarity coefficient: 0.652), our approach yielded a 13.2% improvement. CONCLUSION:GliomaVascularSAM significantly enhanced the accuracy and interactivity of glioma blood vessel segmentation in pathological images. This approach can assist clinicians in the precise analysis of glioma vasculature, thereby contributing to improved diagnosis and management of patients with glioma.
The protein tyrosine phosphatase 1B (PTP1B) participates in diseases such as cardiometabolic disorders and malignancies. We investigated in depth the expression and clinical significance of PTP1B in various solid tumors. The PTP1B clinical duality is evident. In HER2-positive breast cancer, gastric cancer, and non-small cell lung cancer, PTP1B often acts as an oncogene, which is linked to more advanced disease, more metastasis, and a worse prognosis. In breast cancer with ER+ and some kidney cancers, PTP1B works as a tumor suppressor, which is associated with better survival and a better response to treatment. This duality emphasizes that PTP1B's involvement in cancer is not specific and does determines specific clinical outcomes or therapeutic responses. We also analyzed how PTP1B can halt tumor growth by affecting pathways like PI3K/Akt and JAK/STAT, but it can also promote tumor growth by activating pathways like EGFR, RAS-MAPK, and Src signaling. We examined the existing landscape of PTP1B inhibitors, highlighting ongoing deficiencies in efficacy, selectivity, and bioavailability that have led to clinical failures. Ultimately, a better understanding of the mechanisms underlying PTP1B expression and its context-dependent influencing tumor behavior is crucial for advancing of cancer prevention and treatment, especially for patients with metabolic risk factors.
BACKGROUND:Asthma is a common chronic respiratory disease characterized by persistent airway inflammation. This study investigated the role of cinnamic acid (CA) in an in vitro model of asthma and its mechanisms. METHODS:Human small airway epithelial cells (HSAECs) were stimulated with platelet-activating factor (PAF), then exposed to CA (20, 50, or 100μM). Cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry. Inflammatory cytokine levels were measured by ELISA. Barrier function was evaluated via lucifer yellow permeability assay. Western blotting and RT-qPCR were used to measure levels of TGF-β1 pathway-related factors. To investigate whether CA acts through TGF-β1 inhibition, PAF-treated cells were co-incubated with CA and TGF-β1. RESULTS:CA treatment significantly reduced PAF-induced apoptosis in HSAECs. It also attenuated the PAF-induced upregulation of TNF-α, IL-1β, and IL-6 levels as well as the downregulation of PGE2 levels. CA improved epithelial barrier function by reducing permeability. CA downregulated TGF-β1 and Smad4 levels and inhibited Smad2 and Smad3 phosphorylation. Exogenous activation of TGF-β1 abolished the protective effects of CA against apoptosis, inflammation, and barrier integrity. CONCLUSION:Our findings demonstrate that CA inhibits apoptosis, inflammation, and barrier dysfunction in asthmatic airway cells by inhibiting the TGF-β1/Smad pathway.
