Narges Fereydouni

Cardiac involvement in systemic sclerosis (SSc) is mechanistically heterogeneous, driven by concurrently operative processes spanning right ventricular dysfunction, pulmonary microvascular remodeling, and mitochondrial damage. The existing literature rarely synthesizes these domains simultaneously, leaving substantive gaps in mechanistic understanding and the clinical management of SSc cardiac disease. An integrative review of original primary research was conducted using PubMed, Scopus, and Web of Science. Search terms combined “systemic sclerosis,” “right ventricular dysfunction,” “echocardiographic strain,” “pulmonary microvascular disease,” “nailfold capillaroscopy,” “mitochondrial dysfunction,” “oxidative stress,” and “cardiac biomarkers.” Eligible articles were required to report original empirical findings in SSc or SSc-related pulmonary arterial hypertension populations, encompassing echocardiographic, microvascular, molecular, or biomarker outcomes. Right ventricular function is compromised across multiple echocardiographic dimensions—from an elevated myocardial performance index and impaired ventriculoarterial coupling to prognostically significant speckle-tracking strain abnormalities—independent of overt pulmonary hypertension. Pulmonary microvascular disease, quantified by nailfold capillaroscopy and flow-mediated dilation, correlates directly with cardiac magnetic resonance tissue characterization in SSc-related pulmonary arterial hypertension. Mitochondrial dysfunction involving respiratory chain impairment, abnormal fusion dynamics, and altered mitochondrial DNA (mtDNA)copy number is demonstrable across dermal fibroblasts, monocytes, and immune cell populations. Circulating cardiac biomarkers complement echocardiographic findings and predict cardiopulmonary mortality. The integrative framework linking right ventricular remodeling, peripheral vasculopathy, and mitochondrial injury offers substantially richer insight into SSc cardiac pathophysiology than any single-domain perspective can provide, with direct implications for early detection and therapeutic targeting.

This review evaluates injectable bioactive hydrogels as localized pharmacological platforms for post-myocardial infarction (MI) cardiac repair, focusing on therapeutic cargo engineering, stimuli-responsive release systems, mechanistic signaling pathways, and translational potential. A critical narrative synthesis was conducted drawing upon the most recent original research published in leading journals in the field, emphasizing hydrogel composition, pharmacological cargo classes, release mechanisms, molecular targets, animal models, and clinical evidence. The review integrates studies involving small molecules, exosomes, conductive nanomaterials, nanobodies, extracellular matrix-derived systems, and gene delivery vectors. Injectable hydrogels demonstrated the capacity to provide spatially localized and temporally controlled therapy within the infarcted myocardium. Stimuli-responsive systems exploiting pH, reactive oxygen species, and enzymatic microenvironments enabled phase-matched therapeutic release. Major pharmacological effects included macrophage immunomodulation, angiogenesis promotion, oxidative stress reduction, fibrosis attenuation, and restoration of electrical conductivity. Convergent signaling pathways across studies included PI3K/AKT, AMPK-mTOR, VEGF, and TGF-β-related networks. Preclinical studies consistently reported improvements in ventricular remodeling and cardiac function, while early clinical translation with VentriGel established feasibility and procedural safety in human patients. Injectable bioactive hydrogels represent a promising pharmacological strategy for post-MI cardiac repair by integrating biomaterial engineering with localized multi-dimensional drug delivery. Despite substantial preclinical progress, challenges including long-term safety, mechanistic standardization, large-animal validation, and regulatory complexity remain critical barriers to clinical translation.

QT prolongation causes torsades de pointes sudden death from heritable, pharmacologic, metabolic, nutritional triggers. Its dimensions have been studied separately. This integrative review synthesizes research on molecular pathogenesis, acquired/metabolic/nutritional risks, clinical stratification, therapy, and AI prediction. Dual‐function channel mutations and post‐translational defects underlie congenital LQTS beyond classic three genes. Drug–gene–metabolic interactions amplify acquired risk; insulin resistance, NAFLD, and adiposity are independent risk factors. Nutritional exposures (grapefruit juice, licorice, energy drinks) compound arrhythmic risk. QTc threshold alone is insufficient; T‐wave morphology, genotype, electromechanical window dynamics, and M‐FACT score add prognostic value. Nonpenetrant LQTS carries near‐population‐level event risk. Genotype‐targeted mexiletine and left cardiac sympathetic denervation are validated alternatives. Machine learning outperforms clinical scores; deep learning distinguishes congenital from acquired QT prolongation on ECG. Precision QT management requires integrated strategies including nutritional and metabolic determinants, QTc measurement, and AI‐enhanced prediction. Prospective data remain essential before algorithmic tools guide decisions.

Introduction: Major depressive disorder (MDD) is strongly associated with suicidal ideation and significant help-seeking barriers, particularly in rural populations. This study examined MDD prevalence, help-seeking attitudes, and suicidal ideation among rural Iranian youth aged 15-34 years. Methods: This cross-sectional study included 2,923 participants from the Fasa Youth Cohort in rural Iran. MDD was assessed using the Composite International Diagnostic Interview (CIDI) 2.1. Help-seeking attitudes and suicidal ideation were evaluated using validated questionnaires. Logistic regression analyses examined associations between MDD, help-seeking attitudes, and suicidality, stratified by gender. Results: MDD prevalence was 26.2%, with significantly higher rates in males (30.4%) than females (20.5%, P < 0.001). Men with MDD showed increased willingness to seek help (adjusted OR = 1.64, 95% CI: 1.15-2.24, P = 0.005), while women with MDD experienced greater embarrassment about using services. MDD was strongly associated with suicidal outcomes, with adjusted odds ratios ranging from 4.40 for thoughts about death to 7.28 for suicide attempts. Associations were consistently stronger in females. Paradoxically, individuals with suicidal ideation demonstrated reduced help-seeking intentions and increased stigma concerns. Conclusion: Rural Iranian youth exhibit high MDD prevalence with gender-specific patterns. The help-negation paradox among individuals with suicidal ideation represents a critical treatment gap requiring targeted, culturally adapted interventions addressing stigma and improving access to mental health services.

Bone tissue engineering (BTE) requires biomaterials that can replicate the extracellular matrix while supporting osteogenesis and angiogenesis. Collagen, especially type I, is central to BTE. Fish-derived collagen (FC) and hydroxyapatite (HAp) provide sustainable and biocompatible alternatives to mammalian sources, offering comparable structural and biological properties with reduced immunogenic risk. This review highlights recent progress, emphasizing quantitative benchmarks and mechanistic insights that distinguish fish-derived biomaterials from conventional counterparts. A systematic analysis of studies on fish collagen-based scaffolds, fish-derived bioceramics, coatings, and decellularized fish scales was conducted. Data on mechanical properties (compressive strength, elastic modulus), porosity, degradation profiles, and biological outcomes (osteogenesis, angiogenesis, immunomodulation) were compared with existing mammalian-derived scaffolds. FC-based scaffolds demonstrated compressive strength of 2–5 MPa, elastic modulus of 50–150 MPa, and porosity of 60–90%, values within cancellous bone ranges. Degradation rates of 4–12 weeks aligned with bone remodeling. Decellularized fish scales exhibited superior stiffness (50–120 MPa) and hierarchical collagen–apatite architecture, supporting cell adhesion and VEGF-mediated angiogenesis. Fish bone–derived bioceramics showed controlled ion release, enhancing RUNX2 and BMP-2 expression. Compared to mammalian collagen, FC scaffolds exhibited improved osteoconductivity, tunable degradation, and lower immunogenicity. Fish-derived biomaterials provide quantifiable structural and biological advantages over conventional scaffolds, combining biomimetic architecture, osteoinductive signaling, and immunomodulatory effects. While challenges remain in mechanical reinforcement and clinical validation, evidence supports their translational potential, especially in composite and 3D-printed platforms for bone regeneration.

Background and Aims: The escalation of chronic wounds necessitates advanced therapeutic strategies beyond current interventions. Hydrogel dressings, particularly injectable hydrogels, offer promising solutions due to their water absorption capacity, structural resilience, and ease of application. Combining exosomes with injectable hydrogels enhances wound healing through mechanisms such as re‐epithelization and tissue regeneration. This review aims to explore the synergistic effects of exosome‐loaded injectable hydrogels in creating a conducive microenvironment for wound healing, emphasizing their potential as a cell‐free therapeutic approach for skin regeneration. Methods: This narrative review employed electronic databases and keyword search strategies to identify pertinent sources. Databases including Google Scholar, Scopus, Web of Science, and PubMed were utilized to retrieve relevant information. Selection criteria for sources were based on their alignment with the review's purpose, ensuring relevance and appropriateness for inclusion. Results: This investigation delineates various avenues for sourcing exosomes to be incorporated into injectable hydrogels, with particular emphasis on adipose‐derived mesenchymal stem cells, macrophages, and polymorphonuclear neutrophils as primary sources. Moreover, it underscores that while existing research underscores the considerable potential of combining exosomes with injectable hydrogels in advancing skin regeneration, numerous hurdles persist in effectively characterizing, isolating, facilitating large‐scale production for therapeutic applications, and ensuring the optimal storage conditions for exosomes. Simultaneously, challenges abound in augmenting the mechanical robustness of injectable hydrogels, accurately assessing cytotoxicity, establishing biocompatibility, enhancing adhesion properties, and ensuring controlled release mechanisms. Conclusion: Although exosome‐loaded injectable hydrogels have shown significant effectiveness in treating various types of wounds, their synthesis and application pose significant challenges and limitations. Overcoming these hurdles comprehensively is crucial for researchers to improve the feasibility and efficacy of these advanced therapeutics. Doing so will maximize their potential in wound management practices.

Diabetic foot ulcers (DFUs) are chronic, hard-to-heal wounds requiring dressings that can address infection, oxidative stress, and impaired tissue regeneration simultaneously. This study aimed to develop chitosan-based thermoresponsive hydrogels co-loaded with repaglinide (Ripa) and difluorinated curcumin (dfCur) and evaluate their physicochemical properties, antibacterial activity, and cytocompatibility. Hydrogels were synthesized using chitosan and β-glycerophosphate, loaded with Ripa (3% w/v), dfCur (1% w/v), or both. Morphology, chemistry, swelling, porosity, degradation, and drug release were characterized using FESEM, ATR-FTIR, gravimetric methods, and UV–Vis spectrophotometry. Cytocompatibility was assessed via MTT assay with NIH3T3 fibroblasts, and antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. Data were analyzed using one-way ANOVA with p < 0.05 considered significant. Dual-drug hydrogels exhibited the highest swelling capacity (~ 115%) and fastest degradation (46–48% mass retained at day 28), with sustained release of both drugs over 7 days. Fibroblast viability was significantly enhanced for dual-drug hydrogels (128.4 ± 3.2%, p < 0.001 vs. control), and antibacterial activity was strongest in dfCur-containing formulations, showing inhibition zones of 21.6 ± 1.4 mm for S. aureus and 19.3 ± 1.2 mm for E. coli. The co-loading of Ripa and dfCur into a thermoresponsive chitosan hydrogel produced a synergistic platform with enhanced biocompatibility, potent antibacterial effects, and controlled drug release. This multifunctional dressing shows promise for advanced DFU management and warrants further in vivo evaluation.

ZIF-8 nanocrystals modulate diabetic wound healing through antibacterial action, oxidative stress reduction, and immune regulation. They promote angiogenesis by enhancing endothelial cell migration and vascular remodeling in damaged tissue.