Aims This study aims to explore the relationship between aortic aneurysm and dissection (AAD) and cognitive impairment, with an emphasis on uncovering the potential biological mechanisms. Methods Utilizing the UK Biobank database, a matched cohort study was performed to assess the association between AAD and the risk of Alzheimer's disease. Cognitive function was evaluated in a β-aminopropionitrile (BAPN)-induced AAD mouse model through a series of behavioral assays. Drug-target Mendelian randomization analysis was conducted to identify candidate genes implicated in this association. Expression levels of PRDX6 were examined in brain tissues from Alzheimer's disease patients using datasets from the Gene Expression Omnibus (GEO), as well as in aortic tissues and blood samples obtained from both AAD patients and AAD model mice. Correlative analyses between PRDX6 and pro-inflammatory cytokines (IL-1β and TNF-α) were performed in mouse hippocampal tissues of the mouse model. Additionally, in vitro experiments employing SH-SY5Y cells were carried out to investigate the functional role of PRDX6 in modulating synaptic protein expression and inflammatory responses. Results Competing risk regression analysis indicated that AAD is significantly associated with an increased incidence of cognitive impairment. Behavioral testing revealed that AAD model mice exhibited deficits in cognitive performance. Mendelian randomization prioritized PRDX6 was prioritized as a candidate gene of interest. Elevated PRDX6 expression was observed in brain tissues from Alzheimer's disease patients. Both AAD patients and AAD model mice demonstrated markedly increased PRDX6 levels in aortic tissues and circulating blood; notably, PRDX6 expression was also upregulated in the hippocampus of AAD mice. In the hippocampus, PRDX6 expression positively correlated with levels of IL-1β and TNF-α expression in AAD mice. In SH-SY5Y cells, silencing of PRDX6 resulted in increased expression of synaptic proteins, reduced pro-inflammatory cytokine production, and decreased apoptosis, whereas overexpression of PRDX6 elicited inverse effects. Conclusions The present findings establish a significant association between AAD and heightened risk of cognitive impairment. PRDX6 has been identified as a potential mediator in this relationship, and PRDX6-related neuroinflammation is proposed as a plausible mechanistic pathway linking AAD to cognitive dysfunction.

BackgroundVascular injury is a major contributor to the development of cardiovascular diseases. Following vascular damage, macrophages migrate to the injury site and, during the later stages of vascular repair, secrete cytokines such as interleukin-10 (IL-10) and transforming growth factor-β1a (TGFB1A), thereby promoting vascular regeneration. Previous studies have demonstrated that macrophage recruitment to sites of tissue injury is mediated by the CXCR4A-CXCL12B signaling axis. In a screening of traditional Chinese medicinal herbs for cardiovascular therapeutic potential, Salvia miltiorrhiza root was identified as a promising source of bioactive compounds capable of enhancing vascular repair through modulation of the CXCR4A-CXCL12B axis.MethodsEstablishing a vascular injury model in transgenic zebrafish lines Tg (flk1:eGFP; gata1:dsRed) using a two-photon microscopy laser system. Dynamic monitoring of vascular repair via two-photon microscopy. Evaluate macrophage migration capacity in a Tg (mpeg1:eGFP) zebrafish vascular injury model using confocal microscopy. Detection of il-10 and tgfb1a expression released by macrophages via qPCR experiments. Detect CXCR4A-CXCL12B expression at the site of zebrafish vascular injury via fluorescence in situ hybridization coupled with antibody staining.ResultsWe confirm that compounds from the selected extract promote macrophage migration to vascular injury sites by upregulating the CXCR4A-CXCR12B signaling axis. This process accelerates repair of damaged blood vessels in zebrafish by inducing the release of cytokines such as il-10 and tgfb1a.ConclusionsThis study confirms that Salvia miltiorrhiza, a traditional Chinese medicinal plant, is a valuable source of bioactive compounds with pro-angiogenic properties. Our findings provide scientific support for the traditional use of Salvia miltiorrhiza active components in treating vascular injuries.

ABSTRACT Background Aortic aneurysm and aortic dissection (AAD) are lethal cardiovascular emergencies characterized by sudden onset and extremely high early mortality. The pro-inflammatory polarization of macrophages is one of the core factors driving the pathogenesis of AAD, but its underlying mechanism remains unclear. This study focuses on the aberrant expression of glycogen synthase 2 (GYS2) in the AAD microenvironment and its role in driving macrophage polarization toward the pro-inflammatory M1 phenotype. Methods Proteomic analysis was conducted to identify protein heterogeneity associated with AAD. Clinical and animal samples were used to evaluate the correlation between GYS2 expression and AAD progression. Whole-body GYS2 knockout mice and adeno-associated virus (AAV)-mediated macrophage-specific gain- and loss-of-function models were utilized to investigate the regulatory role of GYS2 in macrophage polarization and complement activation. Downstream molecular pathways were identified and validated through in vitro stimulation and in vivo exogenous C5a rescue experiments. Results GYS2 expression was significantly upregulated in AAD tissues and primarily localized in macrophages. Activation of GYS2 by LiCl or macrophage-specific overexpression of GYS2 exacerbated aortic dilation and extracellular matrix degradation, and increased mortality in AAD mice. Conversely, whole-body GYS2 knockout or macrophage-specific GYS2 knockdown suppressed inflammatory factors, significantly reduced the incidence of AAD, and attenuated vascular injury. Mechanistically, excessive GYS2 in macrophages specifically triggered the complement-coagulation cascade, promoting the generation of the potent anaphylatoxin C5a. C5a further bound to its receptor C5AR1, activating the downstream PLCβ3/NF-κB signaling pathway, thereby inducing M1 macrophage polarization and matrix metalloproteinase-mediated extracellular matrix degradation. In vivo exogenous C5a rescue completely reversed the vascular protective effects conferred by GYS2 deficiency. Conclusions This study demonstrates that highly expressed GYS2 regulates the pro-inflammatory polarization of macrophages and extracellular matrix degradation via the complement C5a/PLCβ3/NF-κB signaling axis, which is a key mechanism driving AAD progression. Specific inhibition of macrophage GYS2 can effectively alleviate aortic vascular inflammation and prevent AAD progression, providing a promising novel strategy for the clinical conservative treatment of AAD.

Walnut dreg is a high-quality protein resource rich in a variety of bioactive peptides. However, the research on pancreatic lipase inhibitory peptides from walnuts is limited. In this study, different molecular-weight fractions of alkaline protein hydrolysate from walnut dreg were found to exhibit inhibitory activities against pancreatic lipase, with the u0026lt; 1 kDa fraction exhibiting the most prominent activity, followed by the 1u20133, 5u201310, and 3u20135 kDa fractions, showing IC50 values of 12.22, 13.60, 17.23, and 37.65 mg/mL, respectively. Within the u0026lt; 1 kDa fraction, 5 peptides (VIAFP, LVAFP, IAFP, LTYP, and LFDP) with the strongest binding ability (u221210.03 to u221211 kcal/mol) to pancreatic lipase were screened by molecular docking technique. Among them, LFDP (IC50 = 6.931 mmol/L) exhibited the strongest pancreatic lipase inhibitory activity and reversible competitive pancreatic lipase inhibition. LFDP induced fluorescence bursts and structural changes in pancreatic lipase and exhibited strong biological activity even under high temperatures, strong acidic and alkaline conditions, exposure to metal ions, and gastrointestinal digestion conditions. In addition, LFDP significantly inhibited lipid accumulation in 3T3-L1 adipocytes. In conclusion, these results suggest that the peptide LFDP from walnut dregs is a potential pancreatic lipase inhibitor.

Due to the lack of effective drug therapies, aortic dissection is associated with extremely high mortality rates. Previous studies have demonstrated that FOS-like antigen 1 (FOSL1) plays a role in atherosclerosis and tumor progression. However, the mechanism of FOSL1 in AD remains largely unknown. Therefore, in this study, we aimed to clarify the potential mechanism of FOSL1 in AD and provide a theoretical basis for clinical applications. AD is a life-threatening cardiovascular emergency characterized by a tear in the inner layer of the aorta, resulting in separation of the wall layers and associated with high morbidity and mortality. Understanding the molecular mechanisms driving AD is essential for developing targeted therapies. This study explores the role of the transcription factor FOSL1, known for its involvement in stress response, fibrosis, and cellular differentiation, in AD pathogenesis, with specific focus on collagen deposition and fibroblast-to-myofibroblast transition. Understanding the molecular mechanisms underlying AD is critical for developing novel therapeutic strategies. This study aimed to investigate the role of FOSL1, a transcription factor implicated in cellular differentiation, stress response, and fibrosis, in the pathogenesis of AD and its relationship with collagen deposition and fibroblast phenotype transformation. The role of FOSL1 was investigated by analyzing the Gene Expression Omnibus dataset and evaluating in vitro and in vivo models. Immunohistochemistry and Immunofluorescence assays were used to determine the functional localization of FOSL1 in cells. The effect of FOSL1 expression levels on the efficacy of Naringenin in treating AD was analyzed through combined in vivo and in vitro Naringenin experiments. FOSL1 expression was upregulated in AD, and FOSL1 promoted the proliferation of aortic adventitial fibroblasts in vitro and in vivo. FOSL1 overexpression significantly increased collagen-related protein expression and induced fibroblast phenotype transformation. However, Naringenin reduced AD incidence and severity in vitro and in vivo. Notably, a decrease in FOSL1 expression enhanced the therapeutic effect of Naringenin in AD. FOSL1 is a key regulator in adventitial remodeling during AD, contributing to the proliferation and fibroblast phenotype transformation of adventitial fibroblasts. FOSL1 could serve as a potential target to improve the sensitivity of Naringenin-based therapy.

Transplant rejection remains a significant barrier to the long-term success of organ transplantation. Biopsy, although considered the gold standard, is invasive, costly, and unsuitable for routine monitoring. Traditional biomarkers, such as creatinine and troponin, offer limited predictive value owing to their low specificity, and conventional imaging techniques often fail to detect early organ damage, increasing the risk of undiagnosed rejection episodes. Considering these limitations, emerging noninvasive biomarkers and molecular imaging techniques hold promise for the early and accurate detection of transplant rejection, enabling personalized management strategies. This review highlights noninvasive biomarkers that predict, diagnose, and assess transplant prognosis by reflecting graft injury, inflammation, and immune responses. For example, donor-derived cell-free DNA (dd-cfDNA) is highly sensitive in detecting early graft injury, whereas gene expression profiling effectively excludes moderate-to-severe acute rejection (AR). Additionally, microRNA (miRNA) profiling enhances the diagnostic specificity for precise AR detection. Advanced molecular imaging techniques further augment the monitoring of rejection. Fluorescence imaging provides a high spatiotemporal resolution for AR grading, ultrasound offers real-time and portable monitoring, and magnetic resonance delivers high tissue contrast for anatomical assessments. Nuclear imaging modalities such as single photon emission computed tomography and positron emission tomography, enable dynamic visualization of immune responses within transplanted organs. Notably, dd-cfDNA and nuclear medicine imaging have already been integrated into clinical practice, thereby demonstrating the translational potential of these techniques. Unlike previous reviews, this work uniquely synthesizes advancements in both noninvasive biomarkers and molecular imaging, emphasizing their complementary strengths. Biomarkers deliver molecular-level insights, whereas imaging provides spatial and temporal resolution. Together, they create a synergistic framework for comprehensive and precise transplant monitoring. By bridging these domains, this review underscores their individual contributions and collective potential to enhance diagnostic accuracy, improve patient outcomes, and guide future research and clinical applications in transplant medicine.

Significant efforts have been made to deliver immunosuppressants-loaded nanoparticles (NPs) to lymph nodes (LNs) to mitigate transplant rejection. However, conventional administration techniques encounter challenges in enhancing the retention of NPs in the LNs. Attributing the strong affinity of tannic acid (TA) molecules to the elastin of LN conduits, we developed a novel formulation of NPs encapsulating Tacrolimus (FK506), and subsequently modified with TA to produce TA-FNP with a final diameter of approximately 86.07 ± 2.78 nm. These particles could traverse the the intercellular gaps in the lymphatic endothelial cells layers, enter the paracortex through LN capsule-associated conduits, and releases FK506 to inhibit the activation and proliferation of allogeneic T cells. Our finding demonstrated that TA-FNP could accumulate in LNs, significantly increasing the local concentration of FK506 from 69.06 ± 21.96 ng/g to 1041.28 ± 343.59 ng/g compared to the free FK506 treatment group. Subsequently, the therapeutic efficacy of TA-FNP was assessed in heart transplantation model, where treatment with TA-FNP resulted in decreased T cells infiltration within the grafts, reduced rejection grades, and a significant extension of graft survival time. In contrast, FNP without TA showed relatively poor therapeutic outcomes. Consequently, this study reveals a promising strategy utilizing TA to enhance the prolonged retention of FK506 within LNs, underscoring its potential therapeutic application in preventing heart transplant rejection.

Diabetes mellitus (DM) is a metabolic disease influenced by both genetic and environmental factors. The global incidence of DM is rising, and its multiple complications seriously affect patients’ quality of life and create a huge economic burden. At present, the prevention and treatment of DM mainly rely on oral or subcutaneous drugs, although oral drugs are more acceptable, they may produce more side effects and have limited effect on the treatment of diabetic complications. Artesunate (ART) is a first-line antimalarial drug widely used worldwide. Whether orally or intravenously, ART has high bioavailability and excellent pharmacokinetic properties in humans, and has shown good tolerance and safety in patients of multiple ages. Recent pharmacological studies have shown that, except for its antimalarial properties, ART also has a wide range of therapeutic potential for DM and its complications. This review aims to synthesize the latest research results, summarize and discuss the current role and mechanism of ART in improving diabetes and its complications, and provide a theoretical basis for the subsequent exploration of the anti-diabetes mechanism and the development of new antidiabetic agents based on ART, which has great clinical significance for strengthening the prevention and treatment effects of DM and its complications.

Background and Objectives: Multiple System Atrophy (MSA) is a progressive neurodegenerative disorder with no effective treatment. This research aims to identify novel potential therapeutic targets for MSA using systematic druggable genome-wide Mendelian Randomization (MR). Methods: The cis-expression quantitative trait locus information for drug-accessible genes was utilized as an instrumental variable in MR analysis. The primary outcomes were classified into Dfinite MSA and Clinically Probable MSA. MR analysis was complemented by Steiger filter analysis and Bayesian colocalization analysis. Furthermore, phenome-wide association studies (PheWAS) were conducted to evaluate the genetic safety of the drug target genes. Results : After correcting for the False Discovery Rate (FDR), genetically predicted expression of eight specific genes (PIP4K2B, MAST3, TRPC3, GLB1, HLA-DPA1, CDC42, NOTCH1, WFIKKN1) showed significant causal associations with Dfinite MSA, while only the TNF gene was be associated with Clinically Probable MSA. Additionally, Bayesian colocalization analysis provided further evidence supporting the causal relationship between the TRPC3 gene and Dfinite MSA. MR analysis revealed that increased TRPC3 expression was associated with a reduced risk of Dfinite MSA (Inverse Variance Weighting OR: 0.502, 95% CI: 0.364-0.693, p = 2.78e-05). Furthermore, there was no significant evidence to support the presence of heterogeneity and pleiotropy. PheWAS results suggested a potential a harmful impact of TRPC3 on cardiovascular disease. Conclusions: These findings suggest TRPC3 as a promising therapeutic target for Dfinite MSA, highlighting further exploration in clinical research.

OBJECTIVE:Pulmonary hypertension (PH) is characterized by excessive vascular cell proliferation, leading to vascular remodeling. In this study, we aimed to investigate the molecular mechanisms underlying the regulation of vascular cell proliferation in the context of HMGB2 and its potential involvement in the pathogenesis of PH. METHODS:Animals and pulmonary vascular smooth muscle cells (PASMCs) were exposed to hypoxia. Pathological changes in pulmonary vessels were detected by HE and Masson staining. The effect of HMGB2 on cell proliferation was detected by siRNA transfections and recombinant protein treatment. miR-21 inhibitor and mimics were applied, and TPM1 expression was detected. HMGB2-/- mice were applied to observe the possible preventive effect of HMGB2 in PH development. RESULTS:HMGB2 expression was increased in hypoxic rats and PASMCs. Silencing ZDHHC5 reduced HMGB2 expression and cell proliferation. Cell proliferation was inhibited by knocking down HMGB2 and promoted by its over-expression. Hypoxia-induced miR-21 upregulation and TPM1 downregulation were mediated by HMGB2. 8-Br-cGMP suppressed HMGB2-induced PASMC proliferation and increased SOX2 expression by activating the cGMP/PKG signaling pathway. HMGB2-/- attenuated pulmonary vascular remodeling and fibrosis in hypoxia induced PH mice. CONCLUSIONS:HMGB2 promotes PASMC proliferation through the cGMP/PKG-SOX2-miR-21-TPM1 pathway, which provides a new theoretical basis and possible targets for the pathogenesis and clinical prevention of PH.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical manifestations. Understanding the molecular mechanisms of SLE is crucial for developing effective therapeutic strategies. This study downloaded microarray datasets from the Gene Expression Omnibus (GEO) database. Single-cell RNA sequencing (scRNA-seq) data was processed to identify 19 clusters and annotated five major cell types. Then we calculated mitochondrial-related genes (MRGs) and ferroptosis-related genes (FRGs) scores. FRGs scored the highest in Megakaryocytes, while MRGs scored the highest in B cells. By employing pseudotime analysis, cell-cell communication analysis, and Single-Cell Regulatory Network Inference and Clustering (SCENIC) analysis, we explored the heterogeneity of cells in SLE. Hub genes were identified using high-dimensional weighted correlation network analysis (hdWGNCA) and machine learning algorithms, leading to the development of a predictive diagnostic model with high predictive accuracy. Immune infiltration analysis revealed significant correlations between diagnostic biomarkers and various immune cells. Lastly, molecular docking studies suggested Doxorubicin may exert therapeutic effects by affecting these diagnostic biomarkers. This study offers new insights into the pathogenesis of SLE and provide valuable directions for future therapeutic research.

Aortic dissection (AD) is a critical cardiovascular condition with high mortality risk, and elevated lactate levels are linked to increased postoperative mortality in AD patients. CXCL2 is recognized for its significant involvement in cardiovascular pathologies. Nevertheless, the mechanisms by which CXCL2 regulates lactate levels in AD remain to be fully elucidated. We assessed CXCL2, CXCR2, p38/JNK, C-myc, MCT1, and MCT4 expression using Western blotting, real-time PCR, and immunostaining on AD patient samples, mouse models, and human aortic vascular smooth muscle cells (HAVSMCs). Lactate levels were measured with a lactate assay kit, and we investigated CXCL2's role in AD through vessel incubation. CXCL2 and CXCR2 expression was significantly upregulated in AD, accompanied by increased lactate secretion. Overexpression of CXCL2 not only stimulated lactate secretion but also expedited AD progression. In contrast, CXCR2 inhibition effectively countered the effects of CXCL2. Furthermore, CXCL2 elevated the expression of MCT1 and MCT4; inhibition of them alleviated CXCL2-induced AD and lactate accumulation. CXCL2 also activated the p38 and JNK signaling pathways and upregulated C-myc expression, leading to enhanced lactate secretion in HAVSMCs. Blocking these pathways reversed the effects induced by CXCL2. The CXCL2–CXCR2 axis regulated lactate secretion and drove the progression of AD through the activation of the p38/JNK/C-myc signaling pathways. These findings provide new insights into the molecular mechanisms underlying AD and identify potential therapeutic targets for clinical intervention.

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality, need the exploration of novel biomarkers and therapeutic targets. The c-Met receptor tyrosine kinase（RTK）, activated by hepatocyte growth factor (HGF), plays multifaceted roles in cellular proliferation, survival, angiogenesis, and tissue repair. While extensively studied in oncology, emerging evidence highlights its dual regulatory functions in CVDs pathogenesis. This review synthesizes current knowledge on c-Met signaling in cardiovascular health and disease, emphasizing its context-dependent roles. In atherosclerosis, c-Met exhibits paradoxical effects-promoting vascular smooth muscle cell proliferation and inflammation while exerting anti-apoptotic and anti-fibrotic actions. Preclinical studies reveal its cardioprotective potential in myocardial infarction by enhancing cardiomyocyte survival, angiogenesis, and cardiac repair, yet aberrant c-Met activation may exacerbate pulmonary arterial hypertension via smooth muscle hyperplasia. Furthermore, c-Met influences inflammatory cell dynamics in myocarditis and modulates heart failure progression through interactions with neurohormonal pathways. Therapeutic strategies targeting c-Met, including CAR-M cell therapy, small-molecule inhibitors, and monoclonal antibodies, show promise in preclinical models but require rigorous clinical validation. Key challenges include reconciling its dual roles across disease stages and optimizing therapeutic specificity. Future research must elucidate spatiotemporal c-Met signaling mechanisms to harness its reparative potential while mitigating pathological effects, ultimately advancing precision therapies for CVDs.

BACKGROUND AND AIMS:Inflammatory processes are closely associated with the pathogenesis of aortic dissection (AD). Pyroptosis, a caspase-dependent programmed cell death mechanism, plays a pivotal role in amplifying inflammatory cascades. High-mobility group box 2 (HMGB2), a pro-inflammatory mediator released by immune cells, has emerged as a critical regulator in cardiovascular pathologies. However, its specific involvement in AD development remains poorly characterized. METHODS:Ascending aortic specimens from AD patients were analyzed to evaluate HMGB2 expression and pyroptosis-related markers. An AD mouse model with aortic HMGB2 overexpression was established to assess histopathological progression. In vitro, human aortic vascular smooth muscle cells (HAVSMCs) were stimulated with angiotensin II (Ang II) to investigate pyroptosis dynamics following HMGB2 knockdown or overexpression. Mitochondrial parameters, including morphology, activity, membrane potential, and reactive oxygen species (ROS) generation, were systematically analyzed. RESULTS:HMGB2 expression was significantly elevated in AD patient aortas, correlating with enhanced pyroptotic activity. HMGB2 overexpression exacerbated pyroptosis and accelerated AD progression in murine models. Mechanistically, HMGB2 silencing attenuated Ang II-induced pyroptosis in HAVSMCs by suppressing the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling axis. Pharmacological inhibition of TLR4 effectively abrogated HMGB2-mediated pyroptotic activation. Furthermore, HMGB2 knockdown mitigated Ang II-triggered mitochondrial dysfunction, evidenced by restored membrane potential, reduced ROS overproduction, and preserved NADPH levels. CONCLUSIONS:Our findings demonstrate that HMGB2 orchestrates pyroptosis in HAVSMCs through dual regulation of ROS generation and TLR4/NF-κB pathway activation. This study unveils HMGB2 as a novel molecular nexus linking oxidative stress, inflammation, and vascular cell death in AD pathogenesis, providing a conceptual framework for developing targeted diagnostic and therapeutic strategies.

Introduction: Aortic dissection (AD) is caused by inflammatory responses and extracellular matrix (ECM) degradation processes, in which S100A9, a proinflammatory protein, may play a role. This study explored the role S100A9/P38 MAPK/HSPB1 signaling axis in AD pathogenesis and the therapeutic potential of targeting this pathway. Methods: S100A9 expression in the aortic tissues of patients with AD/healthy controls were analyzed using bioinformatics, ELISA, qPCR, western blotting, and immunohistochemistry. In an AD mouse model induced by beta-aminopropionitrile and angiotensin II (Ang-II), S100A9 expression was inhibited using specific inhibitors to assess its relationship with AD, and proteomics were performed to explore the pathways related to S100A9 expression. Human aortic vascular smooth muscle cells (HVSMC) were treated with Ang-II, S100A9 knockdown, P38 MAPK inhibitors, and HSPB1 knockdown, and experimental methods were used to assess changes in inflammatory cytokines, ECM remodeling, cell proliferation, and apoptosis. Rescue experiments validated the role of the S100A9/P38 MAPK/HSPB1 axis. Results: S100A9 was significantly upregulated in patients with AD, while levels of inflammatory cytokines and matrix metalloproteinases (MMPs) were elevated. S100a9 inhibition reduced the incidence of AD, improved survival, and stabilized the aortic structure in mice, with reduced collagen deposition and SMC apoptosis in vitro. S100A9 knockdown reduces Ang-II-induced HVSMC proliferation, apoptosis resistance, and ECM degradation. Mechanistic studies revealed that the S100A9/P38 MAPK/HSPB1 axis regulates inflammatory cytokine and MMPs release. Conclusion: S100A9 regulates inflammation and ECM degradation through the P38 MAPK/HSPB1 axis, influencing HVSMC proliferation and apoptosis and promoting AD development. This pathway may be a promising therapeutic target for AD treatment.

Aims Non-invasive myocardial work offers a promising echocardiographic method to evaluate left ventricular (LV) function as it integrates myocardial deformation and afterload. The study sought to investigate the association of myocardial work indices with post-operative LV dysfunction in patients with chronic severe aortic regurgitation (AR). Methods and results Pre-operative LV ejection fraction (LVEF), LV global work index (LV GWI), LV global constructive work (LV GCW), LV global wasted work (LV GWW), and LV global work efficiency (LV GWE) were measured. Post-operative LV dysfunction was defined as LVEF < 50% at 12 months after surgery. One hundred and forty-one patients with chronic severe AR and preserved LVEF (52 (42-58) years; 74.5% men) who underwent aortic valve surgery were studied. Twenty-six patients (18%) developed post-operative LV dysfunction. Patients with post-operative LV dysfunction had lower LV GWI, LV GCW, and LV GWE compared with those without (all P < 0.05). In multivariate analysis, LV GWI (adjusted odds ratio (OR): 0.99; 95% CI: 0.98-1.00; P < 0.001), and LV GCW (adjusted OR: 0.99; 95% CI: 0.99-1.00; P < 0.001) were associated with post-operative LV dysfunction. Moreover, a multivariate logistic regression model with LV GWI (Akaike information criterion = 108.023, Bayesian information criterion = 119.818, C-statistics = 0.836) showed the best capability in predicting post-operative LV dysfunction. The comparative analysis of C-statistics across the three models-LV GWI, LV GCW, and LV GLS-did not reveal statistically significant differences (all P > 0.05). Conclusion In patients with chronic severe AR and preserved LVEF, impaired myocardial work indices are associated with post-operative LV dysfunction. Myocardial work has potential value for risk stratification and surgical decision-making in such a population.

PurposeThe impact of aortic stenosis (AS) severity on multidirectional myocardial function in patients with bicuspid aortic valve (BAV) remains unclear, despite the recognized presence of early left ventricular longitudinal myocardial dysfunction in BAV patients with normal valve function. The aim of the study was to evaluate the multidirectional myocardial functions of BAV patients.MethodsA total of 86 BAV patients (age 46.71 ± 13.62 years, 69.4% men) with normally functioning (BAV-nf), mild AS, moderate AS, and severe AS with preserved left ventricular ejection fraction (LVEF ≥ 52%) were included. 30 healthy volunteers were recruited as the control group. Multidirectional strain and volume analysis were performed by three-dimensional speckle tracking echocardiography(3D-STE).ResultsGlobal longitudinal strain (GLS), and global radial strain (GRS) were reduced in BAV-nf patients compared with the controls. With each categorical of AS severity from BAV-nf to severe AS, there was an associated progressive impairment of GLS and GRS (all P < 0.001). Global circumferential strain (GCS) did not show a significant decrease from BAV-nf to mild AS but began to decrease from moderate AS. Multiple linear regressions indicated that indexed aortic valve area (AVA/BSA), as a measure of AS severity, was an independent determinant of GLS, GCS and GRS.ConclusionsLeft ventricular longitudinal myocardial reduction is observed even in patients with well-functioning bicuspid aortic valves. With each categorical increase in the grade of AS severity from normally functioning to severe aortic stenosis, there was an associated progressive impairment of longitudinal myocardial function. Furthermore, circumferential myocardial function was starting damaged from moderate AS. AVA/BSA was independently associated with multidirectional myocardial function injuries.

Numerous contemporary diseases are linked to food contamination. Pathogenic agents might stem from certain food ingredients or result from pollution stemming from food processing or packaging. One such contaminant is 3-Chloro-1,2-propanediol (3-MCPD), it has been previously reported to be produced during the preparation of chemical sauces, as well as during the heating of baked goods. Yet, uncertainty surrounds its potential to induce embryonic developmental toxicity. In this study, zebrafish were employed as the focal point to assess the impact of 3-MCPD on initial embryonic development, heart functionality, and behavior. The research unveiled that exposure of zebrafish embryos to 18, 36, and 54 mM 3-MCPD led to cardiac anomalies, including pericardial edema, reduced heart rate, and elongated SV-BA distance. Additionally, 3-MCPD exposure triggered aberrations in cardiac-related gene expression and an elevation in oxidative stress. Notably, behavioral changes were observed in 3-MCPD-exposed zebrafish embryos, while vascular development appeared unaffected. This study introduces a novel basis for comprehensive exploration of 3-MCPD toxicity.

Cardiac myxoma is the most common primary cardiac tumor in adults. The histogenesis and cellular composition of myxoma are still unclear. This study aims to reveal the role of myxoma cell components and their gene expression in tumor development. We obtained single living cells by enzymatic digestion of tissues from 4 cases of surgically resected cardiac myxoma. Of course, there was 1 case of glandular myxoma and 3 cases of nonglandular myxoma. Then, 10× single-cell sequencing was performed. We identified 12 types and 11 types of cell populations in glandular myxoma and nonglandular myxoma, respectively. Heterogeneous epithelial cells are the main components of glandular myxoma. The similarities and differences in T cells in both glandular and nonglandular myxoma were analyzed by KEGG and GO. The most important finding was that there was active communication between T cells and epithelial cells. These results clarify the possible tissue occurrence and heterogeneity of cardiac myxoma and provide a theoretical basis and guidance for clinical diagnosis and treatment.

People with type 1 diabetes (T1D) have a significantly elevated risk of stroke, but the mechanism through which T1D worsens ischemic stroke remains unclear. This study was aimed at investigating the roles of T1D-associated changes in the gut microbiota in aggravating ischemic stroke and the underlying mechanism. Fecal 16SrRNA sequencing indicated that T1D mice and mice with transplantation of T1D mouse gut microbiota had lower relative abundance of butyric acid producers, f_Erysipelotrichaceae and g_Allobaculum, and lower content of butyric acid in feces. After middle cerebral artery occlusion (MCAO), these mice had poorer neurological outcomes and more severe inflammation, but higher expression of myeloid differentiation factor 88 (MyD88) in the ischemic penumbra; moreover, the microglia were inclined to polarize toward the pro-inflammatory type. Administration of butyrate to T1D mice in the drinking water alleviated the neurological damage after MCAO. Butyrate influenced the response and polarization of BV2 and decreased the production of inflammatory cytokines via MyD88 after oxygen-glucose deprivation/reoxygenation. Knocking down MyD88 in the brain alleviated neurological outcomes and decreased the concentrations of inflammatory cytokines in the brain after stroke in mice with transplantation of T1D mouse gut microbiota. Poor neurological outcomes and aggravated inflammatory responses of T1D mice after ischemic stroke may be partly due to differences in microglial polarization mediated by the gut microbiota-butyrate-MyD88 pathway. These findings provide new ideas and potential intervention targets for alleviating neurological damage after ischemic stroke in T1D.