Latest ArticlesThe serum bactericidal assay (SBA), a gold standard recommended by the World Health Organization for detecting antibody levels against Neisseria meningitidis (Nm), was utilized in this study. Based on the classic Nm bactericidal antibody detection methodology, we optimized experimental parameters including sample volume, complement selection, Nm target bacterial concentration, bactericidal reaction time, and positive reference serum concentration to establish a serogroup X Nm bactericidal antibody detection protocol. The specificity, repeatability, and stability of the positive reference serum were systematically validated. The established method was applied to analyze bactericidal antibody levels in 508 serum samples of healthy individuals under 5 years old from Hennan, Jiangsu, Anhui and Shanxi provinces. Geometric mean titers (GMT) were calculated and statistically analyzed by region and age group. Results demonstrated that 95.7% serum samples exhibited serogroup X Nm bactericidal antibody titers below 8, with an overall GMT of 2.20. No statistically significant regional differences in GMT were observed (H = 6.688, P = 0.083). Age-stratified analysis revealed that 6.37% of infants aged 0-11 months displayed antibody titers greater than or equal to 8. This proportion progressively declined with age, reaching 0.49% in the 2-5 years group. However, no significant inter-group differences in GMT were detected among age cohorts (H = 4.756, P = 0.093). The findings indicate that the serum bactericidal antibody titers against Neisseria meningitidis serogroup X (Nm X) are relatively low among healthy children under 5 years of age in China. This study has developed a reliable detection method for Nm X SBA with good specificity, stability, and reproducibility. Furthermore, it has provided the data on Nm X SBA levels among children under 5 years old from various regions, offering scientific guidance for the future prevention and control of serogroup X meningococcal disease in China. All the serum used in this experiment were approved by Henan Provincial Center for Disease Control and Prevention Ethics Review Committee (approval number: 2019YM-005-02), Jiangsu Provincial Center for Disease Control and Prevention Ethics Review Committee (approval number: JSJK202-A054-02), and Shanxi Provincial Center for Disease Control and Prevention Ethics Review Committee (approval number: SXCDCIRBP2020050001).
Cardiovascular complications triggered by stroke are known as stroke-heart syndrome (SHS). Emerging evidence indicates that stroke triggers dysfunction of the suprachiasmatic nucleus (SCN) through direct neural injury or indirect regulatory pathways, leading to disruption of the endogenous circadian rhythm system. This circadian disruption manifests as sleep-wake cycle dysregulation. It serves as a critical pathological driver of secondary cardio-cerebrovascular events via three interconnected mechanisms: rhythmic dysregulation of immune-inflammatory responses, destabilization of gut microbial homeostasis, and neuroendocrine hormonal imbalance. This paper innovatively proposed a cascade response of "stroke-circadian disturbance-heart syndrome", systematically elaborating on the circadian rhythm-targeted therapy strategy for SHS, including rhythm regulation of immune inflammatory pathways, synergistic regulation of gut microbiota circadian clock, and melatonin rhythm remodeling, as well as the potential of traditional Chinese medicine intervention, providing new perspectives and ideas for clinical prevention and treatment of SHS.
Ferroptosis, a form of non-apoptotic cell death, mainly depends on iron and reactive oxygen species (ROS) to trigger oxidative-reduction imbalance, causing membrane lipid peroxidation, cell membrane damage, and subsequent cell death. Recently, its crucial roles in embryonic development, metabolic regulation, neurodegenerative diseases, and cancer therapy have been unveiled. This article delves into the dynamic balance of cell membrane lipid peroxidation injury and repair mechanisms during ferroptosis, and dissects the multifaceted functions of mitochondria, lysosomes, etc., in regulating ferroptosis. The imbalance between membrane damage and repair is a hallmark of ferroptosis. The antioxidant system maintains membrane integrity by regulating lipid metabolism and redox homeostasis, while membrane repair mechanisms prevent cell death by removing lipid peroxides. Moreover, organelles interact dynamically through iron metabolism, ROS signaling, and lipid peroxide diffusion, modulating ferroptosis sensitivity. This article encapsulates the latest progress in ferroptosis mechanisms and highlights the potential of targeting membrane repair and organelle interactions for disease therapy, offering novel insights for precise disease intervention.
Silicosis is a progressive disease of the lungs triggered by inhalation of crystalline silica dust, characterized mainly by chronic lung inflammation and fibrosis with silicosis nodules. Epidemiological data show that the disease is highly prevalent in occupationally exposed populations, such as mining and building construction, and has become a major occupational health problem worldwide. The pathological process involves complex interactions between multiple cell types, including alveolar macrophages, epithelial cells and fibroblasts, with imbalances in the regulation of the adaptive immune system, particularly T lymphocytes, receiving much attention in recent years, and the mechanisms are not well understood. In this paper, we summarize the roles of CD4+ helper T cells and CD8+ cytotoxic T cells in silicosis, including the imbalance between different types of T cells (Th1/Th2/Th17/Treg subpopulations), the imbalance of cytokines secreted by the same type of T cells and the balance between their different cellular functions, which accelerate the development of silicosis, and the different specificity of this dynamic imbalance in different pathological stages. This dynamic imbalance presents different specificities at different pathological stages, and excessive immune disorders can lead to a variety of complications such as dyspnoea and autoimmune diseases. Therefore, maintaining the immune balance of pulmonary T-cells is essential for the prevention and treatment of silicosis. At the same time, clinical interventions are still limited to dust exposure control, glucocorticoid symptomatic treatment and end-stage lung transplantation, and there is a lack of specific therapies to address the pathogenic mechanisms. Novel therapeutic strategies based on T-cell subpopulation rebalancing have also shown potential value and may provide new therapeutic ideas for silicosis. Overall, this paper provides a systematic review of the dual regulatory mechanisms of T cells in silicosis and explores therapeutic perspectives for disease control through immune homeostasis reestablishment.
Cancer therapeutic drugs include traditional chemotherapy drugs, targeted therapy drugs, monoclonal antibodies, as well as novel antibody-drug conjugates (ADCs) and peptide-drug conjugates (PDCs). PDCs have demonstrated significant clinical advantages in cancer treatment, but they still face limitations such as poor stability and insufficient targeting specificity. In recent years, the application of multivalent targeting peptide strategies and dual targeting peptide strategies has significantly improved the targeting precision of PDCs. Meanwhile, molecular engineering approaches such as peptide cyclization, unnatural amino acid substitution, and fatty acid chain modification have effectively enhanced the in vivo stability of PDCs. These innovative strategies have markedly strengthened the pharmacological activity of PDCs and their therapeutic efficacy in tumors. Based on the structural characteristics and research progress of PDCs, this article systematically reviews the latest strategies for improving the targeting ability, stability, and cell membrane penetration efficiency of PDCs, aiming to provide a theoretical foundation and research insights for the development of PDC-based anticancer drugs with superior pharmacodynamic properties.
Polypyridine derivatives represent a significant class of ligands in coordination chemistry, renowned for their stable coordination capabilities and low toxicity to biological systems, making them ideal candidates for constructing anticancer complexes. Their metal complexes exhibit potential anticancer activity against various malignancies, including breast cancer, prostate cancer, myeloid leukemia, and pancreatic cancer. The iron group elements (iron, cobalt, nickel) have garnered extensive attention from researchers due to their unique redox activities and biochemical properties. To address the issue of drug resistance in existing anticancer therapies, researchers have begun exploring the application of iron group elements in the field of anticancer research. Through extensive structural modifications of polypyridine ligands, a series of metal complexes with novel structures and excellent biological activities have been successfully synthesized. This article reviews the synthesis, cytotoxicity, mechanisms of action, and application potential of polypyridine-based iron group metal complexes over the past decade, providing a theoretical foundation and innovative insights for the development of new anticancer drugs.
At present, all known marine-derived 1,6-naphthyridine natural products have been isolated from sponge organisms. Research indicates that these compounds exhibit significant biological activities in various fields, including antitumor, antioxidant, and antibacterial properties, demonstrating broad potential for drug development. This article systematically reviews the sources, chemical structures, biological activities, and mechanisms of action of 42 marine-derived 1,6-naphthyridine natural products. This study aims to systematically summarize the biological activities of these natural products, thereby identifying novel structures and prominent active compounds as potential leads for new drug development. At the same time, these studies lay the foundation for the development of highly effective and low-toxicity new drugs, thereby making an important contribution to human health.
Polysaccharides from marine organisms are an important source for researching and developing innovative carbohydrate-based drugs. Echinoderms, such as sea cucumber, starfish, sea urchin, and brittle star, are rich in resources. The polysaccharides from these species exhibit unique structural features and possess extensive, potent pharmacological activities, making them promising lead compounds for carbohydrate drug development. In recent years, significant progress has been made in the isolation and purification, structural analysis, and activity evaluation of marine echinoderm polysaccharides. Notably, the fine structures of several polysaccharides have been elucidated, and several novel polysaccharides with nanomolar-level activity have been identified. However, numerous challenges and deficiencies remain in the research areas related to structural elucidation, structure-activity relationships, and mechanisms of action. This review systematically summarizes the progress and breakthroughs in the study of marine echinoderm polysaccharides and provides new insights and suggestions, which may offer important reference information for the research and development of low-toxicity, high-efficiency marine carbohydrate drugs, thereby advancing the field of marine-derived pharmaceuticals.
With the rapid development of artificial intelligence technology, the application of large language model (LLM) in the field of biomedical and clinical applications has gradually deepened. Drug-drug interaction (DDI) prediction is a kind of safety study with complex characteristics in drug development and use, and traditional methods rely on experimental validation or rule-based computational models, which are time-consuming and lagging in updating. Big language models provide a new paradigm for drug interaction prediction through semantic modeling and integrating knowledge-based reasoning on polymorphic data. In this paper, we systematically review the technical progress, application cases and technical difficulties of deep learning and big language modeling in DDI prediction. Based on the performance of five mainstream big language models, namely ChatGPT-4, DouBao, ERNIE Bot, Kimi Chat, and DeepSeek-R1, in the verifiable drug combination DDI analysis task, we explore the value of the application of big language models in drug interaction prediction and provide an outlook on the future development trend, and system development, individualized prediction optimization, and standardized system development, individualized prediction optimization, and the construction of a standardized DDI prediction framework, with a view to promoting the translation process of LLM from the laboratory to the clinic.
Traditional chemotherapy methods lack tumor targeting and cause obvious systemic adverse reactions. The development of nano-drug particles delivery systems has ushered in a new chapter in precision tumor treatment. Due to the enhanced permeability and retention (EPR) effect caused by anomalous tumor blood vessels, nanoparticles can passively target tumor tissues. However, most nanoparticles are rapidly cleared by the mononuclear phagocytic system, limiting their anti-tumor efficacy. In recent years, cell membrane-coated nanoparticles (CNPs) have shown great potential for application in tumor therapy. CNPs are nano-drug particles wrapped by cell membranes, which can not only exhibit excellent biocompatibility, but also retain some of the biological characteristics of the original cell membrane. CNPs from erythrocyte can extend the blood circulation duration of drugs. CNPs from platelet, CNPs from immunocyte, and CNPs from stem cell all demonstrate a tumor-targeting capability, CNPs from immunocyte can also regulate anti-tumor immunity. CNPs from tumor cell have been extensively researched for their excellent homogenous targeting properties. In this review, we outline the construction process of CNPs, and introduce the roles of CNPs based on various cell membranes in tumor therapy, and discuss their future application prospects and challenges.