Latest ArticlesIn the present work, we propose drug-target co-screening strategy, a novel technique for Chinese medicine development and evaluation, which leverages whole-genome pan-receptors and genetically encoded natural compound libraries from medicinal plants and animals. This paper outlines the core components of the strategy, focusing on the identification of novel disease and syndrome-related targets based on clinical efficacy of Chinese medicine, multi-component target screening technologies for herbal medicine, technologies for multi-component identification and target screening and artificial intelligence-powered approaches for discovering active ingredients and elucidating their mechanisms. The strategy demonstrates broad applicability in areas such as the discovery of disease (syndrome) targets, the development of new Chinese medicine drugs, the analysis of multi-target, multi-pathway mechanism of action of Chinese medicine, and the study of drug properties including the five flavors. Centered on whole-genome pan-receptors, drug-target co-screening strategy provides a powerful framework to address key challenges in Chinese medicine research—namely, the ambiguity of therapeutic targets and unclear mechanisms of action. This approach offers strong support for mechanistic studies and paves the way for a new paradigm in modernizing and innovating Chinese medicine drug development.
Gut microbiota, the largest microbial community in the body, plays an important role in maintaining the immune homeostasis of the intestinal system and even the extraintestinal organs. Recently, increasing evidence has highlighted the substantial impact of gut microbiota on the cancer progression and therapy. Intervention of gut microbiota is considered as a promising anti-tumor strategy. Though the molecular mechanisms remain mostly unknown, it is widely appreciated that microbiota-derived metabolites critically mediate the interplay between host and microbiota, triggering enthusiasm to understand the mechanism behind. This article summarizes the latest progress in understanding mechanisms of microbial metabolites in regulating host immune responses, in particular in antitumor immunity. With this, we hope to provide insights for new therapeutics from the perspective of microbiota intervention.
Steatotic liver disease (SLD) is a disease characterized by abnormal accumulation of lipids in hepatocytes, which includes metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, and metabolic dysfunction and alcohol-related liver disease. Most patients only have simple liver steatosis at an early stage, which will gradually develop into hepatitis, liver fibrosis, and cirrhosis as the progression of the disease. Mitochondria is a highly dynamic organelle, which changes its morphology, size, and location by continuous division and fusion. This process is known as mitochondrial dynamics. The imbalanced mitochondrial dynamics can cause the dysfunction of mitochondria, leading to increased lipid deposition in liver cells, as well as antioxidant capacity deficient associated reactive oxygen species accumulation and lipid peroxidation, resulting in increased lipotoxicity and liver injury. Therefore, mitochondrial dynamics play an important role in the development of steatotic liver disease. In this review, the relationship between mitochondrial dynamics and mitophagy, mitochondrial-associated endoplasmic reticulum membranes, and mitochondrial-dependent apoptosis in steatotic liver disease were discussed. In addition, the mechanism role of natural compounds in improving steatotic liver disease via regulating mitochondrial dynamics-related cell functions was also systematically reviewed, aiming to provide the basis and clues for the subsequent investigations and further clinical development and application of natural compounds in the treatment of steatotic liver disease.
Transmembrane protein 16A (TMEM16A) is a Ca2+-activated Cl- channel that is overexpressed in various malignant tumors. The gene is located in chromosome 11q13 region, and its amplification is one of the main reasons for the high expression of this protein. In addition, transcriptional regulation, epigenetic regulation and microRNAs (miRNAs) can promote TMEM16A expression in many cancer cells. TMEM16A not only activates a variety of signaling pathways that promote tumor cell proliferation, migration and invasion, but also plays an important role in inhibiting tumor cell apoptosis. Therefore, the development of anticancer drugs targeting TMEM16A is of great clinical significance. This article reviews the mechanism of TMEM16A in malignant tumors, summarizes the signaling pathways of TMEM16A in promoting tumor development, and analyzes the key role of TMEM16A as a potential biomarker in tumor development. TMEM16A inhibitors may become a new treatment for cancers with high expression of TMEM16A.
Cardiovascular diseases pose a serious threat to human life and health, with their incidence and mortality rates rapidly increasing in China in recent years. Inflammation resolution has become a key focus in cardiovascular research, and in-depth studies of this process have provided new insights into the potential mechanisms and treatments for cardiovascular diseases. Current research on inflammation resolution mechanisms primarily involves pro-resolution mediators, endogenous gases, and immune cells such as macrophages. Based on the important role of inflammation resolution in cardiovascular diseases and the potential therapeutic targets it may offer, this paper reviews the mechanisms of inflammation resolution, the research progress of inflammation resolution in cardiovascular diseases, and the current status of therapeutic strategies and drug research targeting inflammation resolution, with the aim of providing new treatment approaches for cardiovascular diseases.
Viruses infect humans and cause diseases through respiratory transmission, which is the most common pathogenic route for viruses. Viruses with respiratory transmission capabilities typically exhibit periodic and seasonal epidemic characteristics. Due to the wide variety of viruses and significant differences in their structures and life cycles, effective prevention and treatment drugs for various viruses are relatively scarce and have limited efficacy. In recent years, significant progress has been made in the repositioning of antiviral drugs, high-throughput screening and ligand-based drug design. This article systematically summarizes the approved drugs for several major viruses that primarily cause respiratory infections and reviews the latest research progress of antiviral drugs currently in clinical trials, aiming to provide a reference basis for the research and further development of antiviral drugs.
Ubiquitin-specific protease 7 (USP7) is one of the more widely studied members of the deubiquitinating enzyme family, which regulates the activity and function of a variety of proteins in cells. USP7 is closely associated with the tumor progression, which makes USP7 a highly promising target for drug therapy. However, no drug targeting USP7 has yet been approved for clinical trials, thus the development of drug targeting USP7 still requires in-depth research. This article reviews the structure and function of USP7 and the progress of drug research targeting USP7.
Seasonal influenza epidemics caused by influenza viruses continue to pose persistent threats to global public health. The core replication component RNA-dependent RNA polymerase (RdRp), distinguished by its highly conserved structure and functionally irreplaceable characteristics, has emerged as a critical target for antiviral drug development. This study systematically analyzes the structural and functional features of RdRp and the mechanisms of action of its inhibitors. It comprehensively reviews current screening technologies and emerging strategies for RdRp inhibitors across three levels: molecular, cellular, and animal model levels. By systematically evaluating the technical advantages and limitations of existing approaches, we propose future research directions to advance the development of novel high-efficiency RdRp inhibitors, thereby providing both theoretical foundations and technical frameworks for this crucial antiviral strategy.
4D printing technology represents a revolutionary breakthrough in the field of additive manufacturing. It not only inherits the spatial construction capabilities of 3D printing but also introduces the dimension of time, endowing printed objects with dynamic "life". This technology uses smart responsive materials that allow printed objects to change their shape, properties, or functions in response to specific environmental stimuli, such as temperature, magnetic fields, or light changes, as programmed in advance. This has shown great potential and application prospects in the fields of medical research and clinical applications. In this article, we first explore the smart responsive materials that enable 4D printing and introduce their unique physical and chemical properties and functions. Secondly, we review the innovative applications of these smart materials in the medical fields of tissue engineering, regenerative medicine, and drug delivery. Finally, we discuss the challenges faced by 4D printing technology in practical applications and look forward to the future development direction of the technology and its broader application potential in various fields.
Central nervous system (CNS) diseases are a global public health concern, exacerbated by the aging population. Nucleic acid drugs have shown great potential in this field. They target specific gene sequences through the principle of complementary base pairing, allowing intervention before protein expression. These drugs offer high specificity, good safety profiles, and relatively short development cycles. However, the presence of the blood-brain barrier (BBB) and the complexity of CNS pathologies restrict drug delivery, making effective delivery systems crucial for the therapeutic effect of nucleic acid drugs. This review introduces nucleic acid drugs developed for CNS disease treatment in recent years, along with their mechanisms of action. It analyzes the obstacles encountered in brain-targeted delivery of nucleic acid drugs, focusing on the physiological structure and function of the BBB, as well as potential pathways and associated mechanisms for achieving delivery. It details the mechanisms of utilizing viral vectors, nucleic acid drug modification techniques, lipid nanoparticles, polymeric nanoparticles, and exosomes to penetrate the blood-brain barrier, as well as their applications in the delivery of nucleic acid drugs. The aim of this review is to compile and analyze current strategies for enabling nucleic acid drugs to cross the BBB while improving targeting and stability. It explores methods to enhance delivery efficiency and provides guidance for future research and clinical application, ultimately promoting the development of nucleic acid therapeutics for CNS disease treatment.
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