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.

PurposeThis study aims to investigate whether copper sulfide nanoparticles (CuS NPs) protect against fundus neovascularization diseases (FNDs) and to explore the underlying mechanism of the anti-angiogenesis.Materials and methodsThe characterization and biocompatibility of CuS NPs were assessed in human umbilical vein endothelial cells (HUVECs) and in retinas and major organs. Anti-angiogenic effects were evaluated in vitro using HUVECs through migration, sprouting, and proliferation assays. In vivo efficacy was tested in neonatal retinal vascular development, oxygen-induced retinopathy and laser-induced choroidal neovascularization mouse model. Transcriptomic analysis of CuS NPs-treated HUVECs was performed, followed by validation of key signaling pathways using real-time PCR and western blotting.ResultsSynthesized CuS NPs exhibited defined characteristics and demonstrated good biocompatibility at tested concentrations. They significantly inhibited HUVECs migration, sprouting, and proliferation. In vivo, CuS NPs attenuated retinal neovascularization and suppressed and choroidal neovascularization. Transcriptomic profiling and further validation revealed a significant downregulation of the nuclear factor-kappa B signaling pathway and its downstream cascades, coinciding with the observed anti-angiogenic outcomes upon CuS NPs treatment.ConclusionsCuS NPs may act as a promising therapeutic candidate for FNDs treatment.

ObjectivesThis study aimed to investigate the impact of low-intensity pulsed ultrasound (LIPUS) treatment on the miRNA and mRNA profiles of stem cell-derived extracellular vesicles (EVs). Specifically, it sought to identify key miRNAs and their target mRNAs associated with enhanced therapeutic efficacy in LIPUS-treated stem cell-derived EVs.MethodsUtilizing miRNA deep-sequencing data from the Gene Expression Omnibus database, differential gene analysis was performed. MiRNA-mRNA target analysis, functional and pathway enrichment analysis, protein-protein interaction network construction, and hub gene identification were conducted. Validation of differentially expressed miRNAs was performed via RT-qPCR in human umbilical cord mesenchymal stem cells (hUC-MSCs) treated with LIPUS.ResultsTen differentially expressed miRNAs were identified, with six upregulated and four downregulated miRNAs in LIPUS-treated stem cell-derived EVs. Functional enrichment analysis revealed involvement in biological processes such as regulation of metabolic processes, cellular component organization, and response to stress, as well as signaling pathways like cell cycle, MAPK signaling, and Hippo signaling. Protein-protein interaction network analysis identified key hub genes including MYC, GAPDH, HSP90AA1, EP300, JUN, PTEN, DAC1, STAT3, HSPA8, and HIF1A associated with LIPUS treatment. RT-qPCR validation confirmed differential expression of selected miRNAs (hsa-miR-933, hsa-miR-3943, hsa-miR-4633-5p, hsa-miR-592, hsa-miR-659-5p, hsa-miR-4766-3p) in LIPUS-treated hUC-MSCs.ConclusionThis study sheds light on the potential therapeutic mechanisms underlying LIPUS-treated stem cell-derived EVs. The identified differentially expressed miRNAs and their potential target mRNAs offer valuable insights into the biological processes influenced by LIPUS treatment. While further investigation is necessary to validate their roles as therapeutic targets, this study lays the groundwork for future research on optimizing SC-EV therapy with LIPUS preconditioning.

Background: Pancreatic carcinoma (PC), a severely malignant neoplasm of the digestive system, is characterized by an unfavorable prognosis. Neutrophil extracellular trap (NETosis) is a neutrophilic inflammatory form of cell death. However, it is still unknown how they relate to one another. This study aims to explore the part NETosis plays in the onset and progression of pancreatic cancer. Methods: Expression and clinical data for patients with pancreatic carcinoma were obtained from publicly accessible databases. Multigene features were constructed using the least absolute shrinkage and selection operator (LASSO). Bioinformatics analysis was combined with in vitro experiments to determine the relevant mechanism. Results: Seventeen NETosis-related genes were identified. LASSO analysis finally led to the generation of six gene characteristics, which were divided into two clusters according to the expression level. The survival outcomes of the high- and low-risk groups differ significantly, and their predictive performance is good (p < 0.05). Drug sensitivity analysis confirmed that the high-risk cohort could benefit more from 5-fluorouracil, gemcitabine, and epirubicin (p < 0.01). Using survival analysis and single-cell binding quantitative real-time polymerase chain reaction (RT-qPCR), the crucial gene LGALS3 was identified (p < 0.0001). In vitro experiments demonstrated that inhibiting LGALS3 expression may significantly decrease the proliferation and movement of PANC-1 and SW1990 cells (p < 0.05). Conclusion: We established a 6-gene risk scoring model and confirmed the effect of LGALS3 on the development of PC.

Atherosclerosis and vessel wall trauma induce vascular smooth muscle cell (VSMC) phenotypic modulation, leading to plaque cap growth and postintervention restenosis. Our systems biology approach identified RNA binding protein, mRNA processing factor (RBPMS) as a conserved, VSMC- specific gene associated with VSMC modulation in atherosclerosis. RBPMS gene expression positively correlates with VSMC contractile markers in human and murine atherosclerotic arteries as well as in two vascular injury models during the postinjury intimal hyperplasia phase. RBPMS promotes contractile VSMC differentiation, reduces plaque cap development in high- fat diet- fed apolipoprotein E- null (ApoE-/-) murine atherosclerotic arteries, and inhibits intimal hyperplasia. Mechanistically, the RBPMS protein interacts with the myocardin (MYOCD) pre-mRNA and enhances MYOCD_v3/MYOCD_v1 transcript balance through alternative exon 2a splicing. RBPMS promotes the VSMC contractile phenotype and reduces their fibroproliferative activity in a MYOCD_v3a- dependent manner. RBPMS enhances Myocd_ v3/Myocd_v1 transcript balance in both atherosclerotic and injured vessels. RBPMS may inhibit VSMC- driven plaque cap development and intervention- induced restenosis.

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.

Olfactory receptor 6A2 (OR6A2) signaling stimulates atherogenic NLRP3 inflammasome activation in vascular macrophages (Mϕs). Current evidence suggests that interleukin-1 receptor type 1 (IL-1R1)/Toll-like receptor (TLR) signaling may modulate this OR6A2-mediated inflammasome response. However, the role of and mechanism(s) by which IL-1R1/TLR signaling modulates the inflammasome response and resultant atherosclerosis remain unknown. We discovered that the interaction between β-arrestin-2 (βarr2) and OR6A2's intracellular loop 3 (OR6A2ICL3) mediates OR6A2 endocytosis, thereby inhibiting OR6A2-mediated Mϕ inflammasome activation. IL-1R1/TLR signaling promotes coupling of the coiled-coil domain of tumor necrosis factor receptor-associated factor 6 (TRAF6CCD) with βarr2, thereby blocking OR6A2ICL3-βarr2 binding, inhibiting βarr2/AP2-mediated OR6A2 internalization, and potentiating Mϕ inflammasome activation. Consistently, blocking TRAF6CCD-βarr2 coupling in vascular Mϕs inhibits octanal-induced atherosclerosis in high-cholesterol-diet-fed Ldlr-/- mice. Additionally, IL-1R1/TLR-activated βarr2K295 deSUMOylation drives TRAF6CCD-βarr2 coupling in Mϕs, and βarr2K295 deSUMOylation in vascular Mϕs promotes OR6A2-mediated atherosclerosis in high-cholesterol-diet-fed Ldlr-/- mice. In conclusion, IL-1R1/TLR-induced TRAF6CCD-βarr2 coupling, by inhibiting βarr2/AP2-mediated OR6A2 endocytosis, promotes atherogenic OR6A2-mediated NLRP3 inflammasome activation in vascular Mϕs.

Best's disease (BD), referred to as Best vitelliform macular dystrophy, is an autosomal dominant macular degeneration caused by mutations in the BESTROPHIN1 (BEST1) gene. Here, we generated an induced pluripotent stem cell (iPSC) line by the non-integrative Sendai-virus delivery system derived from peripheral blood mononuclear cells (PBMCs) of a patient with c.763C > T mutation in the BEST1 gene. The iPSC line was characterized and validated for the karyotype stability, pluripotency markers, and differentiation potential in vitro, which may serve as a powerful model for exploring the pathological mechanism and pharmaceutical development.

BackgroundMesenchymal stem cells (MSCs) are safe and effective in treating myocardial infarction (MI) and have broad application prospects. However, the heterogeneity of MSCs may affect their therapeutic effect on the disease. We recently found that MSCs derived from different segments of the same umbilical cord (UC) showed significant difference in the expression of genes that are related to heart development and injury repair. We therefore hypothesized that those MSCs with high expression of above genes are more effective to treat MI and tested it in this study.MethodsMSCs were isolated from 3 cm-long segments of the maternal, middle and fetal segments of the UC (maternal-MSCs, middle-MSCs and fetal-MSCs, respectively). RNA-seq was used to analyze and compare the transcriptomes. We verified the effects of MSCs on oxygen-glucose deprivation (OGD)-induced cardiomyocyte apoptosis in vitro. In vivo, a rat MI model was established by ligating the left anterior descending coronary artery, and MSCs were injected into the myocardium surrounding the MI site. The therapeutic effects of MSCs derived from different segments of the UC were evaluated by examining cardiac function, histopathology, cardiomyocyte apoptosis, and angiogenesis.ResultsCompared to fetal-MSCs and middle-MSCs, maternal-MSCs exhibited significantly higher expression of genes that are associated with heart development, such as GATA-binding protein 4 (GATA4), and myocardin (MYOCD). Coculture with maternal-MSCs reduced OGD-induced cardiomyocyte apoptosis. In rats with MI, maternal-MSCs significantly restored cardiac contractile function and reduced the infarct size. Mechanistic experiments revealed that maternal-MSCs exerted cardioprotective effects by decreasing cardiomyocyte apoptosis, and promoting angiogenesis.ConclusionOur data demonstrated that maternal segment-derived MSCs were a superior cell source for regenerative repair after MI. Segmental localization of the entire UC when isolating hUCMSCs was necessary to improve the effectiveness of clinical applications.

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.

Fluid-based triboelectric nanogenerators (F-TENGs) represent a cutting-edge technology that leverages fluids as a contact medium to harness renewable energy through contact electrification (CE) and electrostatic induction.

The differentiation imbalance in bone marrow mesenchymal stem cells(BMMSCs)is critical for the development of bone density diseases as the population ages.BMMSCs are precursor cells for osteoblasts and adipocytes;however,the chromatin organization landscapes during BMMSC differentiation remain elusive.In this study,we systematically delineate the four-dimensional genome and dynamic epigenetic atlas of BMMSCs by RNA sequencing,assay for transposase-accessible chromatin sequencing,and high-throughput chromosome conformation capture.The structure analyses reveal 17.5％common and 28.5％-30％specific loops among BMMSCs,osteoblasts,and adipocytes.The subsequent correlation of genome-wide association studies and expression quantitative trait locus(eQTL)data with multi-omics analysis reveal 274 genes and 3634 single nucleotide polymorphisms(SNPs)associated with bone degeneration and osteoporosis(OP).We hypothesize that SNP mutations affect transcription factor(TF)binding sites,thereby affecting changes in gene expression.Furthermore,26 motifs,260 TFs,and 291 SNPs are identified to affect the eQTL.Among these genes,DAAM2,TIMP2,and TMEM241 are found to be essential for diseases such as bone degeneration and OP and may serve as potential drug targets.

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.

The capacity of self-renewal and multipotent differentiation makes mesenchymal stem cells (MSC) one of the most widely investigated cell lines in preclinical studies as cell-based therapies. However, the low survival rate and poor homing efficiency of MSCs after transplantation hinder the therapeutic application. Exosomes derived from MSCs have shown promising therapeutic potential in many diseases. However, the heterogeneity of MSCs may lead to differences in the function of secreting exosomes. In this study, the therapeutic effects of hUC-Exos and hFP-Exos on the DSS-induced colitis mouse model were investigated. The colitis mouse models were randomly divided into four groups: (1) DSS administered for 7 days and euthanasia (DSS7D), (2) DSS administered for 7 days and kept for another 7 days without any treatment (DSS14D), (3) DSS administered for 7 days and followed with hUC-EVs infusion for 7 days (hUC-EVs) and (4) DSS administered for 7 days and followed with hFP-EVs infusion for 7 days (hFP-EVs). We analyzed colon length, histopathology, Treg cells, cytokines and gut microbiota composition in each group. A large amount of IL-6, IL-17 and IFN-γ were produced along with the decrease in the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells in DSS7D group, which indicated that Th17 cells were activated and Treg cells were suppressed. We found that the number of CD4 + Foxp3 + and CD8 + Foxp3 + cells increased in order to suppress inflammation, but the length of colon did not recover and the symotoms were worsened of the colonic tissue in DSS14D group. The subsequent infusion of either hUC-Exos or hFP-Exos mediated the transformation of Treg and Th17 cells in colitis mice to maintain immune balance. The infusion of hUC-Exos and hFP-Exos also both reduced the abundance of pro-inflammatory intestinal bacterial such as Verrucomicrobia and Akkermansia muciniphila to improve colitis. We found that Foxp3 + Treg cells can inhibit the inflammatory response, and the over-activated Treg cells can still further damage the intestinal mucosa. hUC-Exos and hFP-Exos can control inflammation by regulating the balance between Th17 cells and Treg cells. Decreased inflammatory response improved the structure of colon wall in mice and reduced the abundance of pro-inflammatory bacteria in the intestine. The improvement of intestinal wall structure provides conditions for the reproduction of beneficial bacteria, which further contributes to the reduction of colitis.

OBJECTIVES:To evaluate the association between maternal polymorphisms of NANOS3 rs2016163, HELQ rs4693089, PRIM1 rs2277339, TLK1 rs10183486, ERCC6 rs2228526, EXO1 rs1635501, DMC1 rs5757133, and MSH5 rs2075789 and fetal chromosomal abnormality. METHODS:This retrospective case-control study included 571 women with fetal chromosome abnormalities (330 pregnant women diagnosed with fetal aneuploidy, 241 with fetal de novo structural chromosome pregnancy) and 811 healthy pregnant women between January 2018 and April 2022. All the above polymorphisms were tested using SNaPshot. RESULTS:All the eight polymorphisms were analyzed for genotypes, alleles, under dominant and recessive genetic models. Significant distribution differences of TLK1 rs10183486 in fetal chromosome structural abnormality were found between the case group and control subjects who were <35 years of age [Genotype: p=0.029; Dominant: OR (95 %CI)=0.46 (0.25-0.82), p=0.01 and allele: OR (95 %CI)=0.47 (0.27-0.82), p=0.01 respectively], while no difference was found in the recessive model [OR (95 %CI)=2.49 (0.31-20.40), p=0.39]. In advanced age subgroups for fetal aneuploidy, significant differences were found in genotypes analysis of PRIM1 rs2277339 (p=0.008), allele analysis of TLK1 rs10183486 [OR (95 %CI)=0.62 (0.42-0.91), p=0.02]. For the fetal chromosome structural abnormality population, HELQ rs4693089 revealed a significant distribution difference (p=0.01) but not in the allele, dominant and recessive genetic models analysis (p>0.05 individually). CONCLUSIONS:For older women, maternal PRIM1 rs2277339 and TLK1 rs10183486 polymorphisms may be associated with fetal aneuploidy, while HELQ rs4693089 may be associated with fetal chromosome structural abnormality. Also, carriers of T allele of TLK1 rs10183486 have a lower risk of fetal chromosome structural abnormality in younger women.

Vitamin D deficiency is widespread in different populations and regions worldwide and has become a global health issue. The vitamin D status of the population in the Yunnan Province of Southwest China has not been evaluated to date. Therefore, in this study, we evaluated the vitamin D status according to the serum concentrations of 25-hydroxyvitamin D (25(OH)D) in individuals of Yunnan Province, a low-latitude, high-altitude and multiracial region in China. The data on 25(OH)D concentrations from October 2012 to December 2017 were retrospectively collected and assessed using the laboratory information system from 52 950 hospital-based participants (age, 1 day-96 years; females, 73.74%). The serum concentration of 25(OH)D was evaluated using a chemiluminescent immunoassay. The analysis was stratified by sex, age, sampling season, testing year, minority, residential district, latitude, altitude and meteorological factors. Vitamin D status was classified as follows: severe deficiency: <10 ng/mL; deficiency: <20 ng/mL; insufficiency: <30 ng/mL; and sufficiency: ≥30 ng/mL. The results showed that vitamin D deficiency is highly prevalent in Yunnan Province in a hospital-based cohort, with a deficiency and severe deficiency rate of 65.1% and a sufficiency rate of 5.30%. Significantly lower vitamin D levels and sufficiency rates were observed in females than in males (20.13 ± 7.22 ng/mL vs. 17.56 ± 6.66 ng/mL and 8.20% vs. 4.20%; p < 0.01, respectively); in spring and winter (16.93 ± 6.24 ng/mL; 2.97% and 16.38 ± 6.43 ng/mL; 3.06%, respectively) than in summer and autumn (20.23 ± 7.14 ng/mL; 8.02% and 19.10 ± 6.97 ng/mL; 6.61% [p < 0.01], respectively); and in older individuals (0-6 years: 28.29 ± 13.13 ng/mL vs. >60 years: 14.88 ± 8.39 ng/mL; p < 0.01). Relatively higher vitamin D levels were observed in individuals of Yi, Zhuang, Hani, Dai, Miao and Lisu minorities and lower levels in individuals of Hui and Zang minorities compared with those of the Han nationality (p < 0.01). The mean sunlight duration, mean air temperature, maximum ultraviolet value and latitude were significantly correlated with vitamin D levels (r = -0.53, 0.60, 0.31, -0.68, respectively; p < 0.05). These results suggest that vitamin D status is influenced by sex, age, minority, latitude and some meteorological factors in areas with high and low altitudes. Hence, new public health policies, such as advice on sunshine exposure, food fortification and nutrition education, as well as the implementation of vitamin D supplementation programmes must be considered to alleviate vitamin D deficiency in Yunnan province, Southwest China.

Background:To determine the congenital heart defect (CHD) prevalence and identify the associated risk factors in children within the multi-ethnic Yunnan Region of China.Methods:This is a prospective matched case-control screening study. Screening for CHD in children residing within 28 county districts of Yunnan Province during the period of January 2001 to December 2016 was conducted. A total of 2,421 and CHD cohort and 24,210 control cohort were derived from a total population of 400,855 children (under 18 years of age).Results:A total of 2,421 children were diagnosed with CHD, yielding a CHD prevalence of 6.04 cases per 1,000 children. The prevalence of CHD by sex was 6.54 per 1,000 females versus 5.59 per 1,000 males. The ethnic groups displaying the highest CHD prevalence were the Lisu (15.51 per 1,000), Achang (13.18 per 1,000), Jingpo (12.32 per 1,000), Naxi (9.68 per 1,000), and Tibetan (8.57 per 1,000), respectively. The most common CHD was atrial septal defect, amounting to 1.94 instances per 1,000 children. We identified a number of child-associated parameters that significantly correlated with greater CHD risk, such as lower mass at birth, shorter duration of gestation, and younger age at the time of screening. We also identified a number of maternal and familial risk factors.Conclusions:This ultrasonic color Doppler imaging study revealed a relatively commonplace prevalence of CHD. Moreover, the prevalence of CHD in Yunnan Region significantly varied with sex and ethnic status. Certain child-associated, maternal, and familial risk factors may contribute to CHD risk.

冠心病(CHD)是心血管疾病的重要分支,也是心血管疾病导致死亡的主要原因.随着基因检测技术的快速发展,依托各组学技术研究可以获取CHD遗传信息,从而进行CHD的预测、诊断、治疗.基于多组学的相互交融,可以深入研究CHD的遗传基础,进行风险预测及目标识别,进而降低CHD的患病率及死亡率.CHD转录组学研究已发现该疾病的早期诊断生物标志物并经临床研究验证,而CHD多组学研究也将对CHD疾病机制进行多维度解读.在总结前人的CHD相关成果基础上,构建并整合基因库、转录组学库、蛋白质组学库等融合分析可以为遗传研究提供借鉴,探索新方向,实现新突破.CHD多组学分析能够进一步明确CHD疾病遗传机制并提供风险评估.尽管CHD的不同组学已经有相关研究报道,然而多组学联合分析尚未进行深入研究探讨.本文将统筹多组学对CHD疾病进行深入探讨.

Myocardial infarction (MI) is a common cardiovascular disease that seriously endangers human health and complex pathophysiology (e.g., coronary artery obstruction, myocardial apoptosis, necrosis, inflammation, fibrosis, etc.) is involved. Therein, the loss of cardiomyocytes after MI in adults leads to gradual heart failure, which probably brings irreparable damage to the patient. Unfortunately, due to a cluster of limitations, currently used MI repair approaches always exhibit simple functions, low efficiency, and can hardly match the myocardial ischemia environment and clinical needs. In this study, we selected oncostatin M (OSM), a pleiotropic cytokine belonging to the interleukin-6 family that possesses an important role in cardiomyocyte dedifferentiation, cell proliferation, and regulation of inflammatory processes. Moreover, an injectable hydrogel with pH- and temperature-responsive behavior that can react with the acidic microenvironment of the ischemic myocardium was developed to deliver OSM locally. The functional hydrogel (poly (chitosan-co-citric acid-co-N-isopropyl acrylamide), P(CS-CA-NIPAM)) was fabricated by the facile reversible addition-fragmentation chain transfer polymerization and can be injected into the lesion site directly. After the gelation in situ, the OSM-loaded hydrogel exhibited continuous and localized release of OSM in response to specific pH and changes in MI rats, thereby accelerating angiogenesis and proliferation of cardiomyocytes, inhibiting myocardial fibrosis and improving cardiac function effectively. This study may provide a new perspective for the application of dual-sensitive hydrogels clinically, especially in tissue engineering for MI repair and drug delivery.