Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease (ILD). Pulmonary fibroblasts play an important role in the development of IPF. Emerging evidence indicates that pulmonary endothelial cells could be the source of pulmonary fibroblasts through endothelial mesenchymal transition (EndoMT), which contributes to pulmonary fibrosis. EndoMT is a complex process in which endothelial cells lose their expression of endothelial markers and give rise to the characteristics of mesenchymal cells, including morphological fibroblast-like change and the expression of mesenchymal markers, which result in cardiac, renal, and dermal fibroses. Furthermore, EndoMT inhibition attenuates pulmonary fibrosis. Herein, we demonstrate that nintedanib, a tyrosine kinase receptor inhibitor, ameliorated murine bleomycin (BLM)-induced pulmonary fibrosis and suppressed the in vivo and in vitro models of EndoMT. We demonstrated that the activity of focal adhesion kinase (FAK), a key EndoMT regulator, increased in murine lung tissues and human pulmonary microvascular endothelial cells after BLM stimulation. Nintedanib treatment inhibited BLM-induced FAK activation and thus suppressed both in vivo and in vitro BLM-induced EndoMT. Importantly, we found that the VEGF/FAK signaling pathway was involved in nintedanib regulating EndoMT. These novel findings help us understand the mechanism and signaling pathway of EndoMT to further develop more efficacious drugs for IPF treatment.

Background: Coronavirus disease 2019 (COVID-19) is a global outbreak disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cytomegalovirus (CMV) infection can occur in critical COVID-19 patients and is associated with adverse clinical outcomes. Objective: The aim of this study was to explore the clinical characteristics and outcome of CMV infection in critical COVID-19 patients. Design: This was a retrospective cohort study. Methods: From May to September 2021, SARS-CoV-2 reverse transcription polymerase chain reaction (RT–PCR)-confirmed COVID-19 patients with intensive care unit (ICU) admission were enrolled. CMV infection was confirmed by PCR. Baseline characteristics, critical illness data and clinical outcomes were recorded and analyzed. Results: Seventy-two RT–PCR-confirmed COVID-19 patients with ICU admission were included during the study period and 48 (66.7%) patients required mechanical ventilation (MV). Overall, in-hospital mortality was 19.4%. Twenty-one (29.2%) patients developed CMV infection. Patients with CMV infection had a higher likelihood of diabetes, higher lactate dehydrogenase and lactate levels, and higher proportions of MV, anticoagulant, and steroid use. Patients with CMV infection were associated with longer duration of SARS-CoV-2 shedding, longer ICU and hospital stay, and fewer ventilator-free days. The independent risk factor for development of CMV infection was a higher accumulative steroid dose. Conclusion: CMV infection adversely impacted the outcomes of critical COVID-19 patients, resulting in longer ICU stays, longer mechanical ventilation uses and prolonged shedding of SARS-CoV-2.

Objectives: This study explored the clinical outcomes and association of prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding in patients with severe coronavirus disease 2019 (COVID-19) infection who developed nosocomial pneumonia. Methods: This was a retrospective study conducted in a medical center in Taiwan. From May to September 2021, patients from four intensive care units were enrolled after SARS-CoV-2 was confirmed through quantitative polymerase chain reaction and all cases were compatible with the definitions of severe COVID-19 infection. Baseline characteristics, disease severity, clinical outcomes, and times of viral shedding were recorded. Results: A total of 72 patients were diagnosed as having severe COVID-19 infection and 30 developed nosocomial pneumonia, comprising hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). The patients with severe COVID-19 infection and concomitant HAP/VAP had longer intensive care unit (ICU) stays and fewer ventilator-free days at Day 28. An independent risk factor for nosocomial pneumonia was a greater SOFA score at admission. Furthermore, the patients with severe COVID-19 infection who developed HAP/VAP had a significantly longer duration of SARS-CoV-2 shedding (19.50 days vs. 15.00 days, p = 0.006). Conclusions: Patients with severe COVID-19 infection who developed nosocomial pneumonia had longer SARS-CoV-2 shedding days, more complications, and worse outcomes.

This article reviews the advancements made in the diagnosis and treatment of metabolic dysfunction–associated steatotic liver disease (MASLD) and its progression to metabolic dysfunction–associated steatohepatitis (MASH). For inhibition of the MASLD progression, newly approved thyroid hormone receptor β agonists and potential agents, including farnesoid X receptor (FXR) agonists, peroxisome proliferator-activated receptor (PPAR) agonists, glucagon-like peptide-1 (GLP-1) receptor agonists, GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists, and or GIP/GLP-1/glucagon receptor co-agonists, offering new prospects for the pharmacological management of MASLD. Lifestyle interventions, particularly personalized dietary and exercise regimens, as well as multidisciplinary collaboration, are recognized as vital components of treatment strategies. Although surgical options can yield significant benefits in certain cases, their risks and the criteria for patient selection necessitate more stringent research and guidance. Given the complexity of MASLD-related hepatocellular carcinoma (HCC), various insulin resistance, oxidative stress, gut-liver axis dysregulation, genetics, and epigenetics-based anti-tumor treatments have been ongoing explored to improve outcomes. Considering the global prevalence of MASLD and the relatively young age of disease onset, healthcare providers should be more vigilant in the timely diagnosing of MASLD progression to MASH, cirrhosis, and HCC. Likewise, regular medical check-ups are essential for early disease diagnosis and prevention before the development of complications, thereby improving their overall quality of life. Significant progress has been made in the research surrounding MASLD, MASH, and HCC, instilling new hope for future clinical practices.

The link between aging and pulmonary function decline is well-established, but the underlying mechanisms have yet to be fully revealed. Serum follistatin, a myokine implicated in muscle degeneration, may play a role in age-related pulmonary changes. This study aims to investigate the relationship between serum follistatin levels and pulmonary function decline in community-dwelling older adults, and evaluate their combined association with all-cause mortality. This longitudinal cohort study utilized data from 751 participants aged ≥50 years in the I-Lan Longitudinal Aging Study between 2018-2019. Serum follistatin levels, spirometry results, demographic and clinical data were retrieved. Participants were stratified based on their follistatin levels. Survival curves and group comparisons based on follistatin levels and decline in peak expiratory flow (PEF) using Kaplan-Meier analysis and log-rank tests. Multivariate Cox proportional hazards models were further used to identify independent predictors of all-cause mortality during the 52-month follow-up. Elevated follistatin levels significantly correlated with worse pulmonary function, particularly decreased PEF (p = 0.030). Kaplan-Meier analysis revealed the combination of elevated follistatin levels and decreased PEF was associated with increased risk of all-cause mortality (Log-rank p = 0.023). Cox proportional hazards models further identified that concurrent presence of higher follistatin levels and decreased PEF predicted higher risk of all-cause mortality (adjusted HR 3.58, 95% CI: 1.22-10.53, p = 0.020). Higher serum follistatin levels correlate with decreased pulmonary function, specifically PEF decline, in community-dwelling older adults. Furthermore, the coexistence of elevated follistatin levels and decreased PEF was associated with risk of all-cause mortality. Follistatin may serve as a biomarker for pulmonary aging and related adverse outcomes.

Protective role of adenosine A_2AR receptor (A_2AR) and AC-cAMP-PKA signaling against nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) possibly via its actions on adipocytes is well known in the past decade. Thus, this study evaluates pharmacological activities of A_2AR agonist PSB0777, which has already demonstrated to treat NASH. In this study, the inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A_2AR with A_2AR agonist PSB0777 improves the hepatic and cardiac dysfunction of high-fat diet (HFD)-induced NASH mice.