Metabolically Dysfunctional-Associated Steatohepatitis (MASH), affecting approximately 5.27% of the global population, represents a critical unmet medical need with limited therapeutic options. The complex pathophysiology involving multiple interconnected pathways necessitates innovative therapeutic approaches beyond traditional targets. This review comprehensively examines emerging pharmacological targets for MASH treatment, focusing on novel mechanisms that address key pathogenic processes, including lipogenesis, inflammation, endoplasmic reticulum stress, and immune cell recruitment. We conducted a systematic analysis of preclinical and clinical evidence for six promising therapeutic targets: cyclophilins, ATP citrate lyase (ACLY), NLRP3 inflammasome, X-box binding protein 1 (XBP1), farnesoid X receptor (FXR), and chemokine receptors (CCR). Cyclophilin inhibitors (CRV431, NV556) demonstrate anti-fibrotic efficacy in Phase 2A trials by targeting mitochondrial dysfunction and collagen synthesis. ACLY inhibition offers advantages over acetyl-CoA carboxylase targeting by upstream modulation of de novo lipogenesis, with bempedoic acid showing clinical promise. NLRP3 inflammasome inhibitors (MCC950, JT001, GDC-2394) effectively reduce hepatic inflammation through caspase-1/IL-1β pathway modulation. XBP1 targeting addresses ER stress-mediated lipogenesis and inflammation crosstalk. FXR agonists (obeticholic acid, cilofexor, tropifexor) demonstrate robust clinical efficacy in improving steatosis, inflammation, and fibrosis. Chemokine receptor antagonists (cenicriviroc, AZD5069) show potential in reducing inflammatory cell recruitment, though mixed clinical results highlight the complexity of immune modulation. These novel targets represent a paradigm shift in MASH therapeutics, offering mechanistically distinct approaches that could enable personalized treatment strategies. The advanced clinical development of several candidates, particularly FXR agonists and cyclophilin inhibitors, suggests near-term therapeutic breakthroughs. Future combination therapies targeting multiple pathways simultaneously may optimize treatment efficacy for this multifaceted disease.

General anesthetics are indispensable for surgical procedures, procedural sedation, and intensive care, but their mechanisms of action in the human brain are not fully understood. Classical biochemical approaches have delineated key targets of general anesthetics, such as GABAA and NMDA receptors, ion channels, mitochondria, neurotransmission, and inflammatory pathways. However, animal models and two-dimensional cultures do not represent human-specific neurodevelopment, regional cellular diversity, or three-dimensional brain architecture. Human brain organoids offer a complementary system to investigate anesthetic effects during human development. Recent reports on cerebral, forebrain, and midbrain organoids indicate that propofol and sevoflurane may affect neural progenitor cell proliferation, neuronal differentiation, apoptosis, autophagy, mitochondrial metabolism, long non-coding RNA networks, synaptic gene programs, and regionspecific maturation. These results do not preclude clinically required anesthesia, particularly as large-scale human studies have failed to demonstrate deficits in general intelligence following single short-term exposures. Rather, organoid models help establish which types of neural cells, developmental stages, and molecular mechanisms might be vulnerable to anesthesia. This review highlights recent advances in organoid-based research on the mechanisms of general anesthesia, particularly for propofol and volatile anesthetics. It also explores how region-specific organoids, assembloids, vascularized systems, microglia-enriched models, and multi-omics techniques may help resolve developmental vulnerability and aid more targeted translational studies of anesthesia.

A notable mortality rate is related to cardiovascular disorders despite progress in therapy. Long non-coding RNAs (lncRNAs) play pivotal roles in diverse biological processes, and the abnormal regulation of their downstream signals is linked to a broad range of disorders. A lncRNA, Plasmacytoma Variant Translocation 1 (PVT1), has been found to be associated with the pathogenesis of human diseases. According to recent studies, lncRNA PVT1 participates in a variety of cellular processes, including proliferation, migration, and inflammation, via molecular axes with microRNAs and their downstream targets in neoplastic and non-neoplastic disorders. Given the involvement of these cellular processes in the pathogenesis of cardiovascular disease, we aim to clarify the function of the lncRNA PVT1 in this process. In addition, we aim to determine whether it is a prognostic factor or a potential therapeutic target in cardiovascular disorders.

Adipose tissue plays a central role in energy homeostasis, influencing metabolism, thermoregulation, and overall health. White adipose tissue (WAT) primarily stores energy, while brown adipose tissue (BAT) dissipates energy through heat production. This thermogenic capacity of BAT is mediated by uncoupling protein 1 (UCP1), an important therapeutic target for obesity and related metabolic disorders. The activity and function of BAT are strongly influenced by genetic factors, including genes involved in temperature regulation, mitochondrial function, and energy metabolism. Key regulators such as uncoupling protein 1 (UCP1), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha (PGC-1α), PR Domain Containing 16 (PRDM16), and Cell Death-Inducing DFFA-Like Effector A (CIDEA) modulate BAT activation and energy expenditure, providing potential avenues for therapeutic intervention in obesity. Moreover, genetic variants in the Fat Mass and Obesity-Associated gene (FTO), ADRB3, and LEP highlight the links between BAT activity, lipid metabolism, and obesity susceptibility. Ethnic differences in adiposity traits, including body mass index (BMI) and waist-to-hip ratio, further emphasize the need for population-specific approaches in genetic studies. This review synthesizes current knowledge on the genetic regulation of BAT and explores their practical implications for obesity management. Importantly, we highlight gaps in understanding, such as obstacles to implementing BAT-targeted therapies, and recommend future studies that integrate genetic diversity, functional analyses, and translational research to enhance strategies for improving energy balance and metabolic health.