Lihong Jiang

Protein corona on coronary stents largely drives stent-related thrombosis and inflammation, while effective strategies to modify this corona remain limited. This study adopted a patient whole-blood incubation model and label-free quantitative proteomics to compare plasma protein adsorption on two commercial drug-eluting stents, and evaluate the regulatory effects of surface pre-treatment with human serum albumin (HSA), hyaluronic acid (HA) and high-density lipoprotein (HDL). Both stents quickly adsorbed abundant complement and coagulation-related proteins after blood exposure. HSA caused no obvious changes, and HA only induced mild non-specific protein variations. Notably, HDL profoundly remodeled the protein corona. It elevated the adsorption of anticoagulant and complement-inhibitory proteins, yet reduced procoagulant factors. Further assays confirmed that HDL pretreatment lowered neutrophil recruitment, leukocyte activation and platelet degranulation, and decreased surface prothrombin fragments. In conclusion, HDL functionalization converts stent surfaces from prothrombotic and proinflammatory into anticoagulant and anti-inflammatory phenotypes, offering a promising strategy to improve the long-term biocompatibility of coronary stents.

Organoids are three-dimensional in vitro models that mimic the anatomical and functional complexity of biological tissues, evolving into a powerful platform for studying human development and disease. Organoid-derived extracellular vesicles have been revealed as important intercellular messengers within organoid systems. Participating in the transport of functional substances such as proteins, lipids, and nucleic acids, these lipid-coated nanometer-scale carriers play a role in regulating biological responses. Unlike extracellular vesicles derived from 2D culture, organoid-derived extracellular vesicles carry tissue-specific molecular information and offer unique advantages in terms of targeting precision and biocompatibility. Strategies for engineering organoid-derived extracellular vesicles-such as loading them with specific drugs, surface-modifying them with targeting ligands, or modulating the microenvironment governing vesicle secretion-are currently being extensively explored to enhance their therapeutic potential and targeting capabilities. At the same time, the specific genetic instructions carried by organoid-derived extracellular vesicles hold great promise for early disease diagnosis and prognosis assessment. However, urgent challenges remain, including the heterogeneity of organoids and their in vivo microenvironments, low efficiency in vesicle isolation and purification, and the lack of established standardized production and quality control systems. This paper focuses on two potential applications of organoid-derived extracellular vesicles: as novel therapeutic agents and as tools for improving disease models. It also explores their application prospects in targeted drug delivery, regenerative medicine, and biomarker identification, with the aim of providing insights and guidance for research on the use of organoid-derived extracellular vesicles as multifunctional platforms and carriers in precision medicine.

Background: Coronary heart disease (CHD) and type 2 diabetes (T2D) represent a significant global comorbidity burden, with shared yet incompletely understood molecular mechanisms. This study aimed to identify shared diagnostic biomarkers and elucidate core pathways linking CHD and T2D pathogenesis. Methods: Integrated bioinformatics of CHD/T2D transcriptomes identified shared differentially expressed genes (DEGs) and co-expression modules via Weighted Gene Co-expression Network Analysis (WGCNA). Receiver operating characteristic (ROC) analysis selected CPD, GGCT, SUZ12, and ZMYM2 as top diagnostic biomarkers. These predictions were validated using C57BL/6 and ApoE ^−/− mouse models of T2D/CHD. Aortic tissues underwent histopathology (Hematoxylin and Eosin (H&E), Oil Red O, Sirius Red) and multi-level molecular assays (immunofluorescence, Western blot, reverse transcription quantitative polymerase chain reaction (RT-qPCR). Results: Bioinformatics revealed 328 shared DEGs, with CPD, GGCT, SUZ12, and ZMYM2 showing high diagnostic efficacy. T2D mice exhibited persistent hyperglycemia. Aortic histopathology confirmed disease-specific changes: atherosclerotic plaques in CHD and vascular basement membrane thickening in T2D. Critically, all four biomarkers showed concurrent upregulation in diseased vessels at both protein (immunofluorescence, Western blot) and mRNA (RT-qPCR) levels. Conclusion: This study establishes CPD, GGCT, SUZ12, and ZMYM2 as shared CHD/T2D diagnostic biomarkers. Their validated co-upregulation highlights their dual-disease diagnostic and therapeutic potential.

Atherosclerosis is primarily an inflammatory reaction of the cardiovascular system caused by endothelial damage, leading to progressive thickening and hardening of the vessel walls, as well as extensive necrosis and fibrosis of the surrounding tissues, the most necessary pathological process causing cardiovascular disease. When the body responds to harmful internal and external stimuli, excess oxygen free radicals are produced causing oxidative stress to occur in cells and tissues. Simultaneously, the activation of inflammatory immunological processes is followed by an elevation in oxygen free radicals, which directly initiates the release of cytokines and chemokines, resulting in a detrimental cycle of vascular homeostasis abnormalities. Oxidative stress contributes to the harm inflicted upon vascular endothelial cells and the decrease in nitric oxide levels. Nitric oxide is crucial for maintaining vascular homeostasis and is implicated in the development of atherosclerosis. This study examines the influence of oxidative stress on the formation of atherosclerosis, which is facilitated by the vascular milieu. It also provides an overview of the pertinent targets and pharmaceutical approaches for treating this condition.

Sepsis-induced cardiomyopathy (SIC) is an important manifestation of sepsis, and abnormal cardiac function affects the development of sepsis. Notoginsenoside R1 (NG-R1) is a unique bioactive component of Panax notoginseng with anti-inflammatory and antioxidant effects. However, the effects and possible mechanisms of NG-R1 on SIC are not clear. The purpose of this study was to identify the potential targets and regulatory mechanisms of the action of NG-R1 on SIC. To investigate the potential mechanism, we used network pharmacology, molecular docking, qRT-PCR, and immunofluorescence. The results showed that NG-R1 ameliorated myocardial fibrosis in septic mice. Validation of network pharmacology and molecular docking results revealed that NG-R1 reduced tumor necrosis factor-Alpha (TNF-α) expression in myocardial tissues and AC16 cardiomyocytes in mice, as well as inflammatory factor release in AC16 cells, so TNF-α may be a potential target of NG-R1 against SIC. The present study demonstrated that NG-R1 could protect against SIC and by regulating the expression of TNF-α inflammatory factors, providing a new idea for sepsis drug development.

Cardiovascular diseases rank the highest incidence and mortality worldwide. As the most common type of cardiovascular disease, myocardial infarction causes high morbidity and mortality. Recent studies have revealed that extracellular vesicles, including exosomes, show great potential as a promising cell-free therapy for the treatment of myocardial infarction. However, low heart-targeting efficiency and short plasma half-life have hampered the clinical translation of extracellular vesicle therapy. Currently, four major types of strategies aiming at enhancing target efficiency have been developed, including modifying EV surface, suppressing non-target absorption, increasing the uptake efficiency of target cells, and utilizing a hydrogel patch. This presented review summarizes the current research aimed at EV heart targeting and discusses the challenges and opportunities in EV therapy, which will be beneficial for the development of effective heart-targeting strategies.

Objective: Sepsis is life-threatening organ dysfunction caused by the dysregulated host response to infection. Endoplasmic reticulum stress (ERS)-mediated inositol-requiring enzyme 1 α (IRE1α) inflammatory signaling pathway is involved in sepsis. NLRP3 inflammasome plays a key role in the activation of caspase-1 and the maturation of IL-1β and IL-18, and finally enhances the inflammatory response. More and more evidences show that ERS is an endogenous trigger of NLRP3 inflammasome. Thioredoxin-1 (Trx-1) is a small ubiquitous thiol-1 protein with redox/inflammation modulatory properties relevant to sepsis pathogenesis. In this study, we investigated the role of Trx-1 in ERS mediated IRE1α/NLRP3 signaling pathway in Raw 264.7 cells. Methods: Raw 264.7 cells stimulated by LPS were used to construct an inflammation model of sepsis in vitro, and the expression of proteins related to the IRE1α/NLRP3 pathway was detected through using western blot and qRT-PCR. The expression of IL-18 and IL-1β in cell supernatant was also measured by ELISA, and caspase 1 activity and ROS expression in cells were detected by kits. Results: Our study shows that IRE1α signaling pathway related to endoplasmic reticulum stress in sepsis can activate inflammation related genes, and stimulate to produce a large number of pro-IL-1β. At the same time, IRE1α can activate NLRP3 inflammasome and promote activation and maturation of pro-IL-1β. Finally leads to excessive inflammatory response and ROS release, and promotes the progress of sepsis. Conclusions: Trx-1 may inhibit NLRP3 activity and pro-IL-Iβ production by inhibit IRE1α pathway of ER stress. So as to inhibit inflammatory response and ROS of cells, and play a protective role in sepsis.

Purpose Gasdermin D (GSDMD) is a cytoplasmic protein that is encoded by the gasdermin family GSDMD gene and is the ultimate executor of pyroptosis. Pyroptosis is a mode of lysis and inflammation that regulates cell death, ultimately leading to cell swelling and rupture. In sepsis, a dysregulated host response to infection frequently results in hyperinflammatory responses and immunosuppression, eventually leading to multiple organ dysfunction. Pyroptosis regulates innate immune defenses and plays an important role in the process of inflammatory cell death, and the absence of any link in the entire pathway from GSDMD to pyroptosis causes bacterial clearance to be hampered. Under normal conditions, the process of pyroptosis occurs much faster than apoptosis, and the threat to the body is also much greater. Materials and methods We conducted a systematic review of relevant reviews and experimental articles using the keywords sepsis, Gasdermin D, and Pyroptosis in the PubMed, Scopus, Google Scholar, and Web of Science databases. Conclusion Combined with the pathogenesis of sepsis, it is not difficult to find that pyroptosis plays a key role in bacterial inflammation and sepsis. Therefore, GSDMD inhibitors may be used as targeted drugs to treat sepsis by reducing the occurrence of pyroptosis. This review mainly discusses the key role of GSDMD in sepsis.

Original Article Prevalence and risk factors for congenital heart defects among children in the Multi-Ethnic Yunnan Region of China Yu Cao, Rongzhong Huang, Ruize Kong, Hongrong Li, Hong Zhang, Yaxiong Li, Liwen Liang, Da Xiong, Shen Han, Liang Zhou, Junyin Guo, Guolin Dai, Mingyao Meng, Hongbo Lou, Zongliu Hou, Lihong Jiang