This study aimed to investigate the role of platelets in mediating lethal respiratory syncytial virus (RSV) infection and to explore the potential of antiplatelet therapy as a novel therapeutic approach for RSV infection. Ex vivo and in vivo experiments were used to study the effects of lethal RSV infection on platelet activation, aggregation, and thrombus formation. The emerging therapeutic effect of tirofiban, a GPIIb/IIIa inhibitor, in mitigating RSV-induced pneumonia was also evaluated. Mice infected with a highly virulent RSV strain (R96-5) developed severe RSV pneumonia and showed significantly increased mortality rates, along with extensive platelet infiltration and thrombus formation in the lungs. In situ hybridization revealed co-localization of RSV nucleocapsid RNA with the platelet GPIbα gene in lung tissue. RSV infection induced marked platelet aggregation through the GPIbα-vWF pathway. Notably, tirofiban significantly protected mice from severe pneumonia caused by R96-5. These findings highlight the critical involvement of platelet activation and aggregation in RSV infection and suggest that targeting platelet through the GPIbα-vWF signaling axis may represent a promising therapeutic strategy for severe RSV infection.

BACKGROUND:β-Sitosterol, a plant-derived sterol, has demonstrated potential therapeutic effects in cardiovascular diseases, particularly myocardial ischemia-reperfusion injury (MIRI). Our study investigates its underlying mechanism through regulation of pyroptosis. METHODS:To understand the role of β-sitosterol in protecting cardiomyocytes, MIRI rats were treated with β-sitosterol. Rats' cardiac functions were monitored, and hearts were harvested for histology and Western Blot analysis. Immunofluorescence, immunoblot, enzyme-linked immunosorbent assay, as well as overexpression and knockdown techniques were utilized in this study to investigate the molecular mechanisms underlying the cardioprotective effects of β-sitosterol. RESULTS:Our results showed that β-Sitosterol significantly reduced H/R-induced pyroptosis in cardiomyocytes by decreasing cleaved caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Immunofluorescence staining confirmed suppression of NLRP3 inflammasome activation. Notably, β-Sitosterol inhibited pyroptosis induced by ATP and ATP/LPS through the regulation of PPARγ2. Moreover, PPARγ2 upregulation promoted ATP and ATP/LPS-induced pyroptosis through the NLRP3/caspase-1/GSDMD pathway. In vivo, β-sitosterol alleviates myocardial ischemia-reperfusion injury-induced cardiac dysfunction and myocardial fibrosis in rats. CONCLUSIONS:These findings provide new evidence supporting β-sitosterol as a potential therapeutic agent for cardiovascular diseases involving ischemic injury. Its protective effects may be mediated through targeting PPARγ2 and modulating NLRP3-dependent pyroptosis.

AIMS:This study aimed to investigate the protective effects of 3'-Methoxypuerarin (3'-MOP) on myocardial ischemia-reperfusion injury (MIRI) and elucidate its underlying mechanisms. Specifically, we examined its role in modulating N6-methyladenosine (m6A) methylation and suppressing cardiomyocyte pyroptosis in both in vivo and in vitro models. RESULTS:In vivo, treatment with 3'-MOP markedly reduced myocardial infarct size, preserved cardiac function, and alleviated histopathological injury following ischemia/reperfusion. Consistently, 3'-MOP suppressed m6A methylation and significantly decreased the expression of pyroptosis-related proteins, including NLRP3, cleaved GSDMD, cleaved Caspase-1, IL-1β, and IL-18. In vitro, 3'-MOP decreased m6A methylation, destabilized NLRP3 mRNA, and inhibited pyroptosis in hypoxia/reoxygenation-induced cardiomyocytes. Mechanistically, 3'-MOP disrupted the interaction between insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1) and NLRP3 mRNA, regulated m6A modification at predicted NLRP3 sites, and promoted mRNA degradation, thereby mimicking the effects of si-IGF2BP1 and attenuating pyroptottenuating pyroptosis.Conclusion and Innovation:3'-MOP exerts cardioprotective effects against MIRI by modulating m6A methylation and inhibiting pyroptosis. This study is the first to demonstrate that 3'-MOP regulates cardiomyocyte pyroptosis via the m6A/IGF2BP1-NLRP3 axis, providing a novel epitranscriptomic mechanism for cardioprotection against MIRI. Antioxid. Redox Signal. 44, 103-117.

Background:Anemia is frequently observed in patients with acute myocardial infarction (AMI) and is associated with adverse clinical outcomes. However, the exact relationship between hemoglobin levels and long-term prognosis in patients with AMI undergoing percutaneous coronary intervention (PCI) remains unclear. We aimed to assess the correlation between hemoglobin levels and 6-month mortality in patients with AMI undergoing PCI. Elucidating the prognostic significance of hemoglobin levels could facilitate improved risk stratification and inform early clinical decision-making in patients with AMI. Methods:A secondary analysis based on the Korean patients with AMI who had successful PCI was conducted. A total of 13,104 patients with AMI treated from May 2010 to June 2015 at 15 centers funded by a grant from the Korea Centers for Disease Control and Prevention were recruited. Pre-PCI hemoglobin level was the primary exposure, and 6-month all-cause mortality was the primary outcome. Clinical covariates (e.g., demographic factors, cardiovascular risk factors, laboratory data. and in-hospital medications.) were assessed at baseline. Prognostic outcomes were evaluated through multivariate logistic regression and generalized additive models (GAMs), adjusting for key confounders. All patients were followed for six months post-discharge. Results:The study cohort had a mean age of 63.6±12.6 years, and 75.2% were male. The rates of 6-month all-cause death were significantly higher in the lower hemoglobin level group than in the higher hemoglobin level group. After adjustment for clinical covariates, a nonlinear correlation between hemoglobin levels and 6-month all-cause death was observed. With a hemoglobin ≥10.3 g/dL, an increase of 1 g/dL of hemoglobin was associated with a 30% reduction in the risk of death (odds ratio =0.7; 95% confidence interval: 0.6-0.8). However, with a hemoglobin level <10.3 g/dL, the relationship between pre-PCI hemoglobin and mortality at 6 months was not significant (P>0.05). Conclusions:In patients with AMI, a higher pre-PCI hemoglobin level was an independent protective factor against adverse events. A pre-PCI hemoglobin level ≥10.3 g/dL was negatively correlated with 6-month all-cause death. These findings suggest that routine assessment of hemoglobin prior to PCI may enhance early risk stratification and guide individualized management strategies.

Background:Programmed cell death (PCD) plays a pivotal role in the development and progression of cardiovascular disease (CVD), which remains the leading cause of mortality worldwide. Among the various types of PCD, autophagy, ferroptosis, necroptosis, and pyroptosis have garnered increasing attention due to their involvement in inflammation, oxidative stress, and cardiomyocyte survival. Although numerous studies have explored the underlying mechanisms of these pathways, their therapeutic potential in clinical practice remains limited. With the rapid growth of publications in this field, a comprehensive understanding of research trends and influential studies is essential to guide future investigations. This study aimed to characterize the progress and research hotspots of autophagy in CVD, ferroptosis in CVD, necroptosis in CVD, and pyroptosis in CVD through a bibliometric analysis to provide a comprehensive overview of PCD in CVD. Methods:Publications from January 1, 2009, to December 31, 2023, were analyzed using the "bibliometrix" R package to assess research output, key contributors, and influential journals in each field. Results:For the topic of autophagy in CVD, 6,426 articles published by 4,891 institutions from 90 countries/regions were retrieved. For the topic of necroptosis in CVD, 393 articles from 616 organizations in 53 countries/regions were retrieved. For the topic of pyroptosis in CVD, 640 publications from 754 institutions in 48 countries/regions were retrieved. Finally, for the topic of ferroptosis in CVD, 687 articles from 827 institutions in 49 countries/regions were retrieved. Key contributors included Adriana A (22 publications on necroptosis), Ge J, and Ye B (8 publications each on pyroptosis), and Ren J (lead contributor in autophagy and ferroptosis, with 120 and 10 publications, respectively). The most frequently co-cited journals were Cell, Nature, Free Radical Biology and Medicine, and the Journal of Biological Chemistry. Conclusions:This bibliometric analysis highlights the growing interest in PCD in CVD research, with autophagy and pyroptosis being the central themes. Future studies should examine therapeutic strategies targeting ferroptosis and necroptosis to improve CVD treatment. The findings provide a roadmap for researchers to navigate emerging research hotspots and foster interdisciplinary collaboration.

ObjectiveAging is the most significant contributor to the increasing prevalence of atrial fibrillation (AF). Dysbiosis of gut microbiota has been implicated in age-related diseases, but its role in AF development remains unclear. This study aimed to investigate the correlations between changes in the autonomic nervous system, short-chain fatty acids (SCFAs), and alterations in gut microbiota in aged rats with AF.MethodsElectrophysiological experiments were conducted to assess AF induction rates and heart rate variability in rats. 16S rRNA gene sequences extracted from fecal samples were used to assess the gut microbial composition. Gas and liquid chromatography–mass spectroscopy was used to identify SCFAs in fecal samples.ResultsThe study found that aged rats exhibited a higher incidence of AF and reduced heart rate variability compared to young rats. Omics research revealed disrupted gut microbiota in aged rats, specifically a decreased Firmicutes to Bacteroidetes ratio. Additionally, fecal SCFA levels were significantly lower in aged rats. Importantly, correlation analysis indicated a significant association between decreased SCFAs and declining heart rate variability in aged rats.ConclusionsThese findings suggest that SCFAs, as metabolites of gut microbiota, may play a regulatory role in autonomic nervous function and potentially influence the onset and progression of AF in aged rats. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF. These results provide novel insights into the involvement of SCFAs and autonomic nervous system function in the pathogenesis of AF.

This study aims to explore the relationship between STRN, TGF-β1, Caspase-3, PD-1 expression, and myocardial fibrosis in salt-sensitive hypertensive rats. It investigates the correlation between STRN expression and myocardial fibrosis, along with the protective effects of Sacubitril/Valsartan (ARNI). Fifteen 18-week-old rats were divided into three groups: Control, high salt (SSH), and ARNI+SSH. Blood pressure was monitored weekly for 8 weeks. Echocardiography evaluated cardiac parameters, while H&E and Masson staining visualized myocardial morphology and fibrosis. Immunohistochemistry measured protein expression of collagen-1, collagen-3, TGF-β1, PD-1, Caspase-3, and STRN. Western blot assessed STRN protein levels. High-salt diet increased fibrosis, collagen expression, TGF-β1, PD-1, Caspase-3, and reduced STRN expression compared to Control (P < 0.05). ARNI treatment decreased fibrosis, collagen expression, TGF-β1, PD-1, Caspase-3 (P <0.05), and increased STRN expression compared to SSH (P <0.05). STRN expression correlated positively with myocardial fibrosis. ARNI demonstrated potential in attenuating fibrosis by modulating STRN expression and suppressing apoptosis and inflammation in salt-sensitive hypertensive rats.

Cohort studies have increasingly shown associations between inflammatory markers and myocardial infarction (MI); however, the specific causal relationships between inflammatory markers and the development of MI remain unclear. By utilizing publicly accessible genome-wide association studies, we performed a two-sample Mendelian randomization (MR) analysis to explore the causal associations between inflammatory markers and myocardial infarction (MI). A random-effects inverse-variance weighted method was used to calculate effect estimates. The study included a total of 395,795 European participants for MI analysis and various sample sizes for inflammatory factors, ranging from 3,301 to 563,946 participants.Neutrophil count was found to increase the risk of MI (odds ratio [OR] = 1.08; 95

Aims/Background Coronary heart disease (CHD) and atrial fibrillation (AF) exhibit a close relationship, yet the existing body of research predominantly relies on observational study methodologies, posing challenges in establishing causal relationships. The objective of our study is to investigate the causal linkages between coronary atherosclerosis (CAAs), angina pectoris, myocardial infarction (MI), and AF. Methods This study utilizes a two-sample Mendelian randomization (TSMR) methodology, leveraging genetic variation as a means of evaluating causality. Mendelian randomization is grounded in three primary assumptions: (1) the genetic variant is linked to the exposure, (2) the genetic variant is independent of confounding factors, and (3) the genetic variant influences the outcome solely through the exposure. Results The results of our study suggest a genetic predisposition in which CAAs, angina, and MI may enhance susceptibility to AF, while AF may reciprocally elevate the risk of CAAs. Conclusion In light of these findings, it is recommended that patients with CHD undergo regular cardiac rhythm monitoring, and that patients with AF receive anticoagulant and antiplatelet therapy whenever feasible. This study posits a practical implication for clinical practice.

Gastric cancer is one of the common digestive system diseases in clinical practice, with a high mortality rate. Currently, the best method for treating gastric cancer is surgical treatment, which is inherently traumatic and destructive. In addition, the vast majority of patients also have certain stress reactions to surgery, leading to poor prognosis. The most common physiological stress reaction is malnutrition, Malnutrition can increase the incidence of postoperative complications, which can worsen the degree of malnutrition. This vicious cycle seriously affects the life safety of patients. This article reviews the perioperative nutritional management methods for gastric cancer patients, mainly discussing the screening and evaluation of nutritional risks, preoperative and postoperative nutritional management plans, in order to provide high-quality assurance for reducing the incidence of complications and physical rehabilitation of gastric cancer patients after surgery.

The association of Apolipoprotein A‐I (APOAI) with T cell subsets and interferon‐ү (IFN‐γ) in patients with coronary artery disease (CAD) has been not reported. Thus, this study aimed to investigate the association of APOAI with T cell subsets and IFN‐γ in CAD.

Acute coronary syndrome(ACS) is the leading cause of mortality and disability worldwide. Immune response has been confirmed to play a vital role in the occurrence and development of ACS. The objective of this prospective, multicenter, observational study is to define immune response and their relationship to the occurrence and progressive of ACS. This is a multicenter, prospective, observational longitudinal cohort study. The primary outcome is the incidence of major adverse cardiovascular events (MACE) including in-stent restenosis, severe ventricular arrhythmia, heart failure, recurrent angina pectoris, and sudden cardiac death, and stroke one year later after ACS. Demographic characteristics, clinical data, treatments, and outcomes are collected by local investigators. Furthermore, freshly processed samples will be stained and assessed by flow cytometry. The expression of S100A4, CD47, SIRPα and Tim-3 on monocytes, macrophages and T cells in ACS patients were collected. Follow-up: during hospitalization, 3, 6 and 12 months after discharge. It is expected that this study will reveal the possible targets to improve the prognosis or prevent from occurrence of MACE in ACS patients. Since it’s a multicenter study, the enrollment rate of participants will be accelerated and it can ensure that the collected data are more symbolic and improve the richness and credibility of the test basis. This study has been registered in Chinese Clinical Trial Registry Center. Ethical approval was obtained from the Affiliated Hospital of Guizhou Medical University. The dissemination will occur through the publication of articles in international peer-reviewed journals. Chinese Clinical Trial Registry: ChiCTR2200066382.

We aimed to examine the correlation of T-cell immunoglobulin and ITIM domain (TIGIT)-expressing CD3 + CD56 + cells (TNKS) with coronary artery disease (CAD), atherosclerotic lesion progression, and inflammatory environment. A total of 199 subjects, including 98 patients with acute coronary syndrome (ACS), 52 patients with chronic coronary syndrome (CCS), and 49 control subjects, were recruited in the study. The TIGIT-expressing TNKS were quantified by flow cytometric analysis; the severity of coronary artery lesions was evaluated by the Gensini score. Whole blood cells were stimulated with interleukin-2 (IL-2), interleukin-7 (IL-7), and interleukin-15 (IL-15) in presence or absence of STAT, PI3K, and P38 MAPK inhibitors, respectively. The TIGIT-expressing TNKS was significantly increased in patients with CAD, ACS, and CCS compared to the control group ( P < 0.05). The TIGIT-expressing TNKS were independent predictors of CAD, ACS and CCS ( P < 0.05). The TIGIT-expressing TNKS were positively associated with Gensini score ( P < 0.05). The TIGIT-expressing TNKS was positively correlated with age, and being male ( P < 0.05). The inflammatory microenviroment with increased IL-2, IL-7, and IL-15 contributed to upregulation of TIGIT expression in TNKS. PI3K and P38 MAPK inhibitors could inhibit the upregulation of TIGIT expression in TNKS induced by IL-2, IL-7, and IL-15. The TIGIT-expressing TNKS may be involved in common pathogenesis of ACS and CCS, and atherosclerotic lesion progression. Meanwhile, the increased TIGIT-expressing TNKS might be associated with a proatherogenic microenvironment or inflammatory microenvironment. PI3K and P38 MAPK signaling pathways were involved in the regulation of TIGIT expression.

BackgroundPrevious studies revealed the connection between left atrial appendage peak flow velocity (LAA-PEV) and postoperative persistent atrial fibrillation (AF) recurrence. Yet, this association is not necessarily generalizable to persistent AF patients undergoing initial cryoballoon ablation due to current gaps in the literature.MethodsWe prospectively studied 74 consecutive individuals with persistent atrial fibrillation undergoing a cryoballoon ablation for the first time between January 2018 and January 2020. Before ablation, LAA-PEV was documented by transesophageal echocardiography (TEE). Subsequently, demographic information and other clinical characteristics of these participants were collected. A 96-h continuous cardiac monitor was reviewed regularly for recurrence of atrial fibrillation. Cox proportional hazards regression was used to investigate LAA-PEV as well as other clinical characteristics as a predictor of AF recurrence.ResultsOur study found that AF recurrences had lower LAA-PEV than those without AF recurrence. A nonlinear relationship between the LAA-PEV and AF recurrence was observed in this study, which had an inflection point of 34.9. Subgroup analysis of female participants showed that LAA-PEV had a positive correlation with AF recurrence [β = 0.8, 95% CI (0.7, 0.9), p < 0.05].ConclusionA low LAA-PEV is related to recurrence of atrial fibrillation and may predict AF recurrence after initial cryoballoon ablation for persistent atrial fibrillation. This finding may help improve treatment and care strategies for patients with persistent atrial fibrillation.

Polymyositis (PM) and dermatomyositis (DM) are the two subtypes of idiopathic inflammatory myositis and are characterized as symmetrical progressive muscle weakness in the proximal extremities. PM/DM affect multiple organs and systems, including the cardiovascular, respiratory and digestive tract systems. An in-depth understanding of PM/DM biomarkers will facilitate development of simple and accurate strategies for diagnosis, treatment, and prognosis prediction. This review summarized the classic biomarkers of PM/DM, including antiaminoacyl tRNA synthetases (ARS) antibody, anti-Mi-2 antibody, anti-melanoma differentiation-associated gene 5 (MDA5) antibody, anti-transcription intermediary factor 1-& gamma; (TIF1-& gamma;) antibody, anti-nuclear matrix protein 2 (NXP2) antibody, among others. Among them, anti-aminoacyl tRNA synthetases antibody is the most classic. In addition, many potential novel biomarkers were also discussed in this review, including anti-HSC70 antibody, YKL-40, interferons, myxovirus resistance protein 2, regenerating islet-derived protein 3-& alpha;, interleukin (IL)-17, IL-35, microRNA (miR)-1 and so on. Among the biomarkers of PM/DM described in this review, classic biomarkers have become the mainstream biomarkers to assist clinicians in diagnosis due to their early discovery, indepth research, and widespread application. The novel biomarkers also have potential and broad research prospects, which will make immeasurable contributions to exploring biomarker-based classification standards and expanding their application value.

Objective: The authors investigated the predictive value of MALAT1 for persistent atrial fibrillation (PAF) recurrence after radiofrequency ablation. Methods: Serum MALAT1 level was determined. The correlation between MALAT1 and high-sensitivity C-reactive protein/left atrial diameter (LAD) was analyzed. The predictive value of MALAT1 was evaluated. The postoperative recurrence rate in patients with high/low MALAT1 was compared. Independent risk factors for postoperative recurrence were analyzed. Results: MALAT1 was elevated in PAF patients and positively correlated with high-sensitivity C-reactive protein/LAD. MALAT1/high-sensitivity C-reactive protein/LAD were enhanced in patients with recurrent PAF. Patients with high MALAT1 had a higher recurrence rate. Upregulated MALAT1 was an independent risk factor for postoperative PAF recurrence. Conclusion: Serum MALAT1 level >2.03 predicts postoperative recurrence of PAF, and PAF patients with high MALAT1 have a higher risk of postoperative recurrence.

Background The development of new-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is a clinical complication that requires a better understanding of the causative risk factors. This study aimed to explore the risk factors and the expression and function of miR-1 and miR-133a in new atrial fibrillation after AMI. Methods We collected clinical data from 172 patients with AMI treated with emergency percutaneous coronary intervention (PCI) between October 2021 and October 2022. Independent predictors of NOAF were determined using binary logistic univariate and multivariate regression analyses. The predictive value of NOAF was assessed using the area under the receiver operating characteristic (ROC) curve for related risk factors. In total, 172 venous blood samples were collected preoperatively and on the first day postoperatively; the expression levels of miR-1 and miR-133a were determined using the polymerase chain reaction. The clinical significance of miR-1 and miR-133a expression levels was determined by Spearman correlation analysis. Results The Glasgow prognostic score, left atrial diameter, and infarct area were significant independent risk factors for NOAF after AMI. We observed that the expression levels of miR-1 and miR-133a were significantly higher in the NOAF group than in the non-NOAF group. On postoperative day 1, strong associations were found between miR-133a expression levels and the neutrophil ratio and between miR-1 expression levels and an increased left atrial diameter. Conclusions Our findings indicate that the mechanism of NOAF after AMI may include an inflammatory response associated with an increased miR-1-related mechanism. Conversely, miR-133a could play a protective role in this clinical condition.

Objective:To study the drug activity and therapeutic targets of Niga-ichigoside F1 predicted based on network pharmacology and molecular docking.Methods:Download the 2D and 3D structures of Niga-ichigoside F1 from the PubChem database for target prediction and molecular docking,respectively.Target information was predicted by PharmMapper and swiss ADME databases,target gene names were extracted and rechecked by Uniprot database,and disease information corresponding to target was queried by TTD database.The enrichment analysis of GO and KEGG signal pathway was conducted by Metascape database.AutoDuck Vina was used for molecular docking of Niga-ichigoside F13D structure with key proteins of related diseases and common pathways.Finally,the conformation of molecular docking was visualized by PyMOL.Results:A total of 34 targets and 69 related disease information were obtained from the database screening.The targets with high degree of acquisition of the association network between target and disease were AR,F2,VDR,PDE10A,mTOR,and NR3C2,etc..Diseases with a high degree of relief were solid tumour,breast cancer,acute myeloid leukemia,hypertension,and thrombocytopenia,etc..The items with significance in GO analysis included positive regulation of transferase activity,protein autophosphorylation,negative regulation of cGMP-mediated signaling,intracellular receptor signaling pathway,regulation of cellular response to stress,blood vessel development,reactive oxygen species metabolic process,negative regulation of immune response,regulation of transcription from RNA polymerase Ⅱ promoter in response to stress,and nucleobase-containing small molecule metabolic process,etc..The items with significance in KEGG enrichment analysis(P<0.01)included Pathways in cancer,Purine metabolism,Focal adhesion,MAPK signaling pathway,GnRH signaling pathway,AGE-RAGE signaling pathway in diabetic complications,Ras signaling pathway,Leukocyte transendothelial migration and Platelet activation,etc..Molecular docking suggested that the target of Niga-ichigoside F1 had good binding ability with related diseases and key proteins of common pathways.Conclusion:According to the results of network pharmacology and molecular docking,Niga-ichigoside F1 has rich drug activity and may act on a variety of diseases.After comprehensive analysis,we proposed for the first time the high correlation between Niga-ichigoside F1 and cancer,as well as the possible association with acute myeloid leukemia and hypertension.It has the characteristics of multi-target and multi-pathway,which is worthy of further research,development and utilization.