Trends in pharmacological sciences最新文献

Extracellular vesicle (EV)-based therapeutics have gained substantial interest in the areas of drug delivery, immunotherapy, and regenerative medicine. However, the clinical translation of EVs has been slowed due to limited yields and functional heterogeneity, as well as inadequate targeting. Engineering EVs to modify their inherent function and endow them with additional functions has the potential to advance the clinical translation of EV applications. Bio-orthogonal click chemistry is an engineering approach that modifies EVs in a controlled, specific, and targeted way without compromising their intrinsic structure. Here, we provide an overview of bio-orthogonal labeling approaches involved in EV engineering. We also present the isolation methods of bio-orthogonally labeled vesicles using magnetic beads, microfluidics, and microarray chip technologies. We highlight the in vivo applications of bio-orthogonal labeling EVs for diagnosis and therapy, especially the exciting potential of bio-orthogonal glycometabolic engineered EVs for targeted therapies.

Ulcerative colitis (UC) is one of the two forms of inflammatory bowel disease. It affects 5 million people globally, and is a chronic and recurring inflammation of the gastrointestinal tract with clinical presentation of abdominal pain, chronic diarrhea, rectal bleeding, and weight loss. The cause and the etiology of UC remain poorly understood. There is no cure and no ‘gold standard diagnostic’ for UC. The existing treatments are ineffective, and UC patients have a lower life expectancy with a risk of colorectal cancer. Recent studies in pathophysiology, clinical presentation, and biomarkers have significantly improved our understanding of UC. In this review we summarize recent advances in identifying novel clinical biomarkers, diagnostics, treatment targets, and emerging therapeutics. These insights are expected to assist in developing effective treatments for UC.

Human physiology is profoundly influenced by the gut microbiota, which generates a wide array of metabolites. These microbiota-derived compounds serve as signaling molecules, interacting with various cellular targets in the gastrointestinal tract and distant organs, thereby impacting our immune, metabolic, and neurobehavioral systems. Recent advancements have unveiled unique physiological functions of diverse metabolites derived from tryptophan (Trp) and bile acids (BAs). This review highlights the emerging chemophysiological diversity of these metabolites and discusses the role of chemical and biological tools in analyzing and therapeutically manipulating microbial metabolism and host targets, with the aim of bridging the chemical diversity with physiological complexity in host-microbe molecular interactions.

Sodium glucose cotransporters (SGLTs) transport glucose against its concentration gradient by harnessing the electrochemical potential gradient of sodium ions. SGLT inhibitors are widely prescribed to treat diabetes and other conditions. Recent structural studies have uncovered how chemically diverse SGLT inhibitors bind and inhibit the transporter at the atomic level.

Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has demonstrated significant success in treating cancers. The potential of CAR-T cells is now being explored in the context of autoimmune diseases. Recent clinical trials have shown sustained and profound elimination of autoreactive B cells by CAR-T cells, leading to promising autoimmune disease control with minimal safety concerns. These encouraging results have inspired further investigation into CAR-T cell applications for a broader range of autoimmune diseases and the development of advanced cell products with improved efficacy and safety. In this review, we discuss the mechanisms by which CAR-T cells target autoimmune conditions, summarize current preclinical models, and highlight ongoing clinical trials, including CAR-T therapy design, clinical outcomes, and challenges. Additionally, we discuss the limitations and future directions of CAR-T therapy in the treatment of autoimmune diseases.

Emerging preclinical autism research has shown the therapeutic promise of pharmacological inhibitors for epigenetic enzymes, such as histone deacetylases (HDAC), euchromatic histone methyltransferases (EHMT), and lysine-specific histone demethylase 1A (LSD1). These interventions restore gene expression, synaptic function, and behavioral performance in autism models, highlighting a new strategy for autism treatment.