Citations

ABSTRACT BACKGROUND War refugees are prone to psychiatric ailments due to multiple psychosocial stressors. Afghan refugees remain underrepresented in psychiatric studies. Therefore, a study exploring factors contributing to their mental health disorders is essential to guide rehabilitation efforts worldwide. METHODS This descriptive cross-sectional study evaluates the demographics, psychosocial stressors, psychiatric illnesses, and psychotropic drug use among Afghan refugees visiting the Psychiatry Outpatient Department (OPD) in Islamabad, Pakistan. Convenience sampling was employed on a sample population (n) of 75 participants. Data was collected via a structured questionnaire and analyzed using SPSS v21.0. Qualitative and quantitative variables were analyzed statistically. RESULTS Nearly 64%(n=48) of the participants were female. About 46.7%(n=35) of participants were uneducated, and 53.3%(n=40) were unemployed. 86.7%(n=65) of participants were married, while 2.7%(n=2) were divorced. 91%(n=61) of the married and divorced participants had an arranged marriage, 46.3%(n=31) had 5-8 children, and 67.2%(n=45) had experienced physical and/or emotional abuse. 74.7%(n=56) of the total participants reported a loss in the family, while 77.3%(n=58) had experienced trauma. 62.7%(n=47) had depression and associated psychotropic use, e.g., SSRIs (42.7%), TCAs (16%), and Benzodiazepines (13.3%). Alarmingly, 37.3%(n=28) reported a previous suicide attempt. CONCLUSION This study explores the psychosocial stressors faced by Afghan refugees in Pakistan, including displacement, abuse, trauma, and family/income loss. It emphasizes the importance of evidence-based psychiatric care, rehabilitative interventions, and culturally sensitive care to counter psychiatric morbidities and underscores the need for future research to improve the mental health of refugees globally.

Abstract Accurate, noninvasive biomarkers for diagnosis and longitudinal monitoring of metabolic dysfunction–associated steatohepatitis (MASH) remain an urgent unmet clinical need. Here, we describe an electrochemical immunoassay that involves capturing hepatic extracellular vesicles (EVs) on antibody-modified electrodes followed by detecting EV-borne biomarkers using redox active gold nanoparticles (AuNPs). The intensity of electrochemical redox signal represents a quantitative measure of biomarker abundance. Three MASH-associated biomarkers—S100A11, TNF-α, and TGF-β1—were analyzed on hepatic EVs to assess steatotic, inflammatory, and fibrotic states of the diseased liver. The electrochemical signals for individual biomarkers were added into a composite EV MASH score. Plasma samples from 28 patients with MASH, 22 healthy controls, and 27 patients with non-MASH liver disease were scored in this manner, revealing 100% accuracy in the training cohort and >90% accuracy in an independent validation cohort. Our electrochemical immunosensor represents a minimally invasive liquid liver biopsy, offering a promising alternative to solid liver biopsies for screening and monitoring of MASH. One Sentence Summary Circulating hepatic extracellular vesicles carry biomarkers of liver injury enabling accurate, minimally invasive MASH diagnosis in blood.

Age-related gastrointestinal dysfunction is common, but the mechanisms of aging-associated smooth muscle failure remain unclear. We show that aging in mice slows whole gut and colonic transit, increases regional stiffness, and reduces smooth muscle contractility. Inducible smooth muscle cell (SMC)– specific deletion of Piezo1 preserved youthful transit and force generation, whereas Piezo1 activation in young mice phenocopied aging-associated transit delay. Single-cell transcriptomics, RNA velocity, stiffness-controlled cell and tissue cultures, and pharmacologic studies revealed that Piezo1 couples increased stiffness to Ca 2+ –calcineurin–NFAT signaling, loss of contractile gene programs, leading to age- related contractile loss and contractile-to-synthetic SMC remodeling and gut wall stiffening. Human intestinal SMCs supported conservation of this pathway, and PIEZO1 gain-of-function carriers showed a trend toward delayed colonic transit. Thus, maladaptive SMC Piezo1 mechanotransduction is a targetable mechanism of aging-associated gut dysmotility. Aging alters organ structure, yet how these changes drive functional decline remains poorly defined. We show that progressive stiffening of the gut with age activates the mechanosensitive ion channel Piezo1 in smooth muscle cells, initiating a maladaptive response that impairs contractility and slows intestinal transit. On the other hand, deletion of smooth muscle Piezo1 prevents age-related gut dysmotility. These findings reveal that age-related physical shifts actively drive functional decline through mechanotransduction pathways. By identifying Piezo1 as a critical link between tissue mechanics and organ aging, this work provides a framework for understanding how mechanical cues contribute to age-related dysfunction in the gut and possibly other smooth muscle organs.

Matrix metalloproteinases (MMPs) have long been recognized as key mediators of tumor invasion and metastasis due to their capacity to degrade extracellular matrix components. However, clinical failure of broad-spectrum MMP inhibitors has revealed a more complex and context-dependent role for these proteases in cancer. Among them, macrophage metalloelastase, MMP-12, has emerged as a particularly intriguing enzyme with both tumor-promoting and tumor-suppressive functions. Predominantly expressed by tumor-associated macrophages, MMP-12 occupies a unique position at the interface of proteolysis, inflammation, and immune regulation within the tumor microenvironment. Accumulating evidence from experimental models and clinical studies demonstrates that MMP-12 can exert potent anti-tumorigenic effects, primarily through inhibition of angiogenesis. Mechanistically, MMP-12 generates angiostatin and other anti-angiogenic fragments, suppresses vascular endothelial growth factor signaling, and reduces tumor vascularization, thereby limiting tumor growth and metastatic expansion. In several cancer types, including lung, colorectal, and hepatocellular carcinoma, elevated MMP-12 expression has been associated with reduced tumor progression and improved patient outcomes. Conversely, MMP-12 can also promote tumor progression through extracellular matrix remodeling, facilitation of invasion, and modulation of inflammatory pathways, particularly in environments characterized by chronic inflammation or immunosuppressive macrophage phenotypes. These seemingly contradictory roles are governed by multiple context-dependent factors, including macrophage polarization, tumor type, disease stage, and microenvironmental cues such as hypoxia and cytokine signaling. In this review, we comprehensively examine the molecular regulation, functional mechanisms, and clinical relevance of MMP-12 in cancer. We highlight the dualistic nature of MMP-12 activity and discuss its implications for therapeutic strategies, emphasizing the need for selective and context-aware targeting approaches rather than broad inhibition of MMP activity.