Latest ArticlesHyperuricemia is a metabolic disease characterized by abnormally elevated level of serum uric acid, which is the key pathological basis of gout. Oral medications reduce blood uric acid level by inhibiting uric acid production and/or promoting uric acid excretion. Xanthine oxidoreductase is the rate-limiting enzyme for uric acid synthesis, by inhibiting its activity, the production of uric acid will be reduced. Urate transporter 1 (URAT1), one of the important proteins mediating uric acid reabsorption in kidney, is also a main target of anti-hyperuricemic drugs. By inhibiting URAT1 activity, the uric acid excretion will be promoted, thereby reducing the blood uric acid. At present, three xanthine oxidoreductase inhibitors and two urate transporter 1 inhibitors have been launched, and multiple compounds are currently in clinical trials. The physiological functions and metabolic pathways of uric acid, etiology of hyperuricemia and its therapeutic targets are introduced in this review. We analyze the efficacy and safety of oral therapeutic agents, to provide insights for the development of new drugs and the rational clinical use of medications in the treatment of hyperuricemia.
Ferroptosis, a novel programmed cell death mechanism characterized by the iron-dependent accumulation of lipid peroxides, is precisely regulated by multiple signaling pathways, including intracellular iron metabolism, lipid peroxidation, and antioxidant systems. Recent studies have highlighted the dual role of ferroptosis in the fate determination of hepatic stellate cells (HSCs) and hepatocytes, indicating its significant involvement in the progression of hepatic fibrosis. This is corroborated by ongoing research that explores the molecular mechanisms of ferroptosis and its potential as a therapeutic target in various liver diseases, including liver fibrosis. This article elucidates the key molecular mechanisms of ferroptosis and its dual role in liver fibrosis, while systematically reviewing the latest progress in anti-fibrotic research using natural products and synthetic compounds targeting key ferroptosis molecules. The study aims to offer a solid theoretical basis and strategic guidance for the development of innovative anti-fibrotic drugs by regulating ferroptosis pathways.
Atherosclerosis (AS) is a common pathological basis for cardiovascular and cerebrovascular diseases. Chinese ethnomedicine, with its distinct theoretical frameworks and abundant resources, shows unique potential in managing AS. This review systematically synthesizes the pathogenesis of AS and corresponding therapeutic strategies from various Chinese ethnomedical systems, revealing that "physiological imbalance" serves as a common underlying mechanism. We detail the mechanisms of these ethnomedicines, including improving the composition of gut microbiota, regulating lipid metabolism, mitigating oxidative stress, suppressing inflammation and modulating vascular homeostasis. Available clinical evidence is critically evaluated. Key challenges are discussed, such as the need for theoretical modernization, deeper mechanistic studies, and more rigorous clinical validation. Promising future research directions are also outlined.
Bile acids play a central role in maintaining cholesterol homeostasis and regulating lipid metabolism, exhibiting extensive medicinal value. However, conventional extraction, separation, and chemical synthesis methods are unable to meet the demands of current industrial production, rendering biocatalysis a highly promising alternative for bile acid manufacturing. Cytochrome P450 (CYP450) enzymes, which catalyze the hydroxylation of inert C(sp3)-H bonds, serve as the core enzymes in the bile acid biosynthetic pathway. Through strategies such as enzyme design, redox partner engineering, and optimization of catalytic systems, the catalytic efficiency of CYP450s has been significantly enhanced, enabling the efficient biosynthesis of various bile acids. This review summarizes the characteristics and synthetic strategies of bile acids, as well as the optimized application of CYP450 hydroxylases, providing a reference for the green production of bile acids and related drug research.
Papain-like protease (PLpro or PLP) is a key non-structural protein in the replication process of coronaviruses. It is responsible for the cleavage and processing of viral polyproteins, and has deubiquitination and deISGylation activities, which can inhibit the host's innate immune response. Due to the high conservation of PLpro among various coronaviruses such as SARS-CoV-2, SARS-CoV, and MERS-CoV, it has become an important target for the development of broad-spectrum coronavirus inhibitors. Since the outbreak of the COVID-19 pandemic, research on PLpro has advanced rapidly, and multiple classes of candidate molecules with clear structures and definite mechanisms have been identified, including non-covalent inhibitors (e.g., GRL0617 and its derivatives), covalent inhibitors (e.g., vinyl ester compounds), and inhibitors derived from natural products. This article reviews the research progress of PLpro-targeted inhibitors, covering their structural characteristics, activity data, mechanism of action, and discovery strategies, aiming to provide theoretical support and design ideas for the development of broad-spectrum anti-coronavirus drugs.
Toll-like receptors (TLR), as important pattern recognition receptors (PRR), are widely distributed on the endosomal membrane surface of immune cells such as macrophages and dendritic cells. Among them, TLR7 has attracted much attention due to its specific recognition of the molecular pattern of viral single-stranded RNA (ssRNA). After TLR7 recognizes single-stranded ribonucleic acid, it activates a series of signal cascade reactions, initiating a high level of systemic adaptive immune response to kill the virus. In recent years, artificially synthesized TLR7 agonists have been used in the clinical treatment of diseases such as HPV infection and basal cell carcinoma. They activate the immune microenvironment by mimicking the structure of viral RNA, significantly enhancing the function of antigen-presenting cells and promoting Th1-type immune response. This paper summarizes the research progress of TLR7 agonists in the past decade and their application in various diseases, aiming to provide references for relevant research and development.
Targeted anticancer agents have become a cornerstone of cancer therapy, specifically acting on targets such as enzymes, receptors, and proteins to inhibit the growth and proliferation of cancer cells. In addition to enhancing therapeutic efficacy, these agents significantly reduce adverse effects and improve patients' quality of life. Carboranes, a class of boron cluster compounds with unique structural features in medicinal chemistry, hold considerable potential for optimizing the performance of targeted anticancer drugs. Characterized by three-dimensional aromaticity, high hydrophobicity, and substantial steric bulk, carboranes have been incorporated into the molecular scaffolds of known targeted anticancer agents by numerous researchers. Their distinct physicochemical properties are exploited to modulate the biological behavior of parent molecules, thereby strengthening drug-target interactions, improving target selectivity, and enhancing metabolic stability. Furthermore, due to their exceptionally high boron content, carboranes serve as efficient boron carriers in boron neutron capture therapy. This review summarizes the latest research progress on the application of carboranes in the design of targeted anticancer drugs, aiming to provide valuable insights and references for the development of carborane-based targeted anticancer agents.
Triptolide, as a key active ingredient in the traditional Chinese medicine Tripterygium wilfordii, has shown significant potential in the treatment of kidney diseases. This article systematically reviews the research progress of its application in the treatment of kidney diseases, covering chemical properties, pharmacological and toxicological mechanisms, and targeted drug delivery strategies. In terms of pharmacological mechanisms, triptolide mainly exerts renal protection through multiple pathways such as protecting podocytes, inhibiting inflammation, and anti fibrosis. However, its significant toxicity is a key limiting factor for clinical applications, involving complex metabolic pathways, signaling pathways, and cellular processes. To enhance therapeutic efficacy and reduce toxicity, researchers have developed various targeted kidney delivery systems, such as delivery systems based on coupling technology, nanoparticles, polymer micelles, liposome modification, and derivative strategies. Although positive progress has been made in current research, in order to ensure safe clinical application, it is still necessary to further elucidate its pharmacological and toxicological mechanisms, and conduct long-term toxicological evaluations of existing strategies for enhancing efficacy and reducing toxicity. These works will contribute to the scientific evaluation of the clinical application prospects of triptolide and lay the foundation for its translational application in the treatment of kidney diseases.
Disruption of protein homeostasis is a central pathological mechanism in a variety of major diseases. However, traditional small-molecule inhibitors are often limited by issues such as undruggable targets and drug resistance, falling short of clinical needs. Targeted protein degradation (TPD) technologies offer a promising alternative by eliminating pathogenic proteins and thus overcoming key bottlenecks in conventional drug development. Among these, proteolysis-targeting chimera (PROTAC), which hijack the ubiquitin–proteasome system to degrade target proteins, have shown significant translational potential in the treatment of cancer and immune-related disorders. To further enhance the specificity and therapeutic index of PROTAC, bioorthogonal strategies have been increasingly explored in recent years for the development of next-generation degraders. These approaches not only reduce systemic toxicity but also enable spatiotemporal precision control, offering new avenues for the rational design of PROTAC.
This review focuses on recent advances in the component structure theory and associated research technologies for exploring the material basis of traditional Chinese medicine (TCM) preparations. The study first outlines the conceptual evolution of TCM "components" across three levels: individual compounds, synergistic groups, and integrated systems. It then introduces the development of the "component structure" theory from its initial three-tier structural framework (version 1.0), through quantitative proportionality modeling (version 2.0), to the current integration of in vivo phase states and biopharmaceutical disposition (version 3.0), which together form a unified theoretical system of element structure, quantity ratio structure, and phase structure. Furthermore, the technological progress of the fundamental research of Chinese medicine under the guidance of this theory is systematically summarized, covering the techniques of fine analysis of small molecules and macromolecules, the analysis and optimization of the component-volume ratio relationship and the analysis of the component-phase structure. Finally, it emphasizes the need for future research to build multidimensional analytical systems, integrate artificial intelligence and big data technologies, and promote standardization, in order to support the modernization and innovation of TCM.
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