Heart failure with preserved ejection fraction (HFpEF) is a complex cardiovascular disorder characterized by diastolic dysfunction, metabolic dysregulation and limited therapeutic options. Post-translational modifications (PTMs) are key regulators of cardiac metabolism, but the role of butyrylation in HFpEF pathogenesis remains unclear. This study explored the mechanistic role of butyrylation in myocardial energy metabolism of HFpEF and evaluate the therapeutic potential of ginsenoside Rb3 (G-Rb3). A "two-hit" (high-fat diet + L-NAME) mouse model and a phenylephrine (PE)-induced hypertrophic and metabolically stressed cellular model were established. Myocardial PTM screening identified butyrylation as the target for proteomic analysis. G-Rb3 efficacy was evaluated in vivo and in vitro, with mechanistic studies involving Sirtuin 4 (SIRT4) inhibitor and overexpression experiments to confirm its regulatory role. Male mice model displayed earlier and more severe HFpEF phenotypes than females, thus justifying their use in mechanistic studies. Butyrylome analysis revealed hyperbutyrylation of succinate-CoA ligase subunit alpha (SUCLG1) at K90, which impaired its enzymatic function in tricarboxylic acid (TCA) cycle, resulting in reduced succinate and ATP production. SIRT4 was identified as a key regulator of SUCLG1 debutylation, with downregulated SIRT4 expression leading to SUCLG1 hyperbutyrylation. G-Rb3 directly bound SIRT4, reversing SUCLG1 hyperbutyrylation, restoring TCA cycle flux and ATP levels, improving diastolic dysfunction and metabolic abnormalities. These effects were nullified by SIRT4 inhibition, confirming SIRT4 as G-Rb3’s critical target. Our study reveals SUCLG1 butyrylation as a novel metabolic regulator in the pathogenesis of HFpEF, orchestrated by SIRT4. G-Rb3, a SIRT4-interacting regulator, rescues this axis, offering a mechanism-based therapy for HFpEF.

Objective Macrophage ferroptosis plays a pivotal role in sepsis-induced acute lung injury (ALI). Tangeretin (TAN), derived from the traditional Chinese medicine Chen pi (Citrus reticulata), exhibits antiproliferative, anti-invasive, anti-metastatic, and antioxidant properties. This study investigated the protective effects of TAN against sepsis-induced macrophage ferroptosis in ALI and its underlying mechanism, while also exploring whether co-delivery via extracellular vesicle (EVs) could enhance its therapeutic efficacy. Materials and methods TAN's effects were evaluated in vivo using a cecal ligation and puncture (CLP)-induced sepsis mouse model and in vitro using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Mechanistic insights were obtained through HE staining, MASSON staining, TUNEL staining, immunofluorescence, network pharmacology, molecular docking, transmission electron microscopy, qRT-PCR, and Western blotting. Results TAN and T-EV significantly ameliorated lung histopathology in CLP-mice, suppressed inflammatory cytokines, and attenuated interstitial fibrosis. T-EV demonstrated superior efficacy compared to TAN alone. Furthermore, TAN inhibited ferroptosis in both models. Bioinformatics and molecular docking identified Lipoxygenase-5 (ALOX5) as a potential target; TAN significantly inhibited ALOX5 expression and downregulated acyl coenzyme A synthase long-chain family member 4 (ACSL4) protein levels in CLP-induced ferroptosis. Conclusions TAN mitigates sepsis-induced ALI by inhibiting macrophage ferroptosis through the ALOX5/ACSL4 signaling pathway, and notably, co-delivery via EVs significantly potentiates its therapeutic efficacy.

Background Valvular heart disease (VHD) is increasingly prevalent in aging populations, but the circulating proteomic features that precede incident disease remain incompletely characterized. We aimed to identify plasma proteins associated with incident VHD, prioritize genetically supported candidates, and assess the incremental value of proteomic information for risk discrimination. Methods After phenotype-proteome alignment, sample- and protein-level quality control, and removal of duplicate participant identifiers, we included 40,435 UK Biobank participants free of prevalent VHD at baseline. Associations of 2,745 Olink Explore proteins with incident broad VHD, mitral regurgitation, aortic stenosis, and aortic regurgitation were examined using multivariable Cox proportional hazards models adjusted for demographic and clinical covariates; in subtype-specific analyses, the remaining VHD subtypes were modeled as time-varying covariates. Genetic prioritization was performed using two-sample cis-Mendelian randomization (cis-MR) with deCODE cis-pQTL instruments and FinnGen R12 summary statistics for broad VHD and operated aortic stenosis. Secondary analyses included sex-stratified association testing and exploratory internally validated prediction modeling using logistic LASSO after an 80/20 train-test split. Results During a median follow-up of 11.0 years, 1,250 participants developed broad VHD, 391 developed mitral regurgitation, 303 developed aortic stenosis, and 105 developed aortic regurgitation. Across the four endpoints, 421 Bonferroni-significant protein-disease associations were identified, including 316 for broad VHD, 81 for mitral regurgitation, and 24 for aortic stenosis; none met the study-wide significance threshold for aortic regurgitation. The strongest broad-VHD signals included NPPB, ANGPT2, LTBP2, GDF15, and CRIM1. Cis-MR prioritized 20 proteins for broad VHD and 17 for aortic stenosis, with EPHB4, GHR, and SCARF2 supported by both prospective and genetic evidence. Broad-VHD effect estimates were highly concordant between women and men (Pearson r = 0.75), and no protein-by-sex interaction remained significant after false discovery rate correction. In exploratory prediction analyses, a 19-protein score improved internal discrimination for broad VHD beyond clinical variables alone (AUC, 0.772 vs 0.723; DeLong P = 5.1 × 10 − 5). Conclusions Large-scale plasma proteomics identified molecular features preceding incident VHD and prioritized a subset of genetically supported candidate proteins. Proteomic information may improve VHD risk discrimination, although predictive performance and clinical utility require validation in independent cohorts.

Background Water retention is one of the important factors in the development and exacerbation of chronic heart failure (CHF). Xinbao Pill (XBP) is widely used as an adjuvant therapy for CHF. However, the therapeutic effect of XBP on water retention in CHF remains unclear. Purpose Our research was aimed to investigate the effect and mechanism of XBP on water retention in CHF. Methods Male Sprague-Dawley (SD) rats underwent left anterior descending (LAD) artery ligation to establish the CHF model and were subsequently administrated with different doses of XBP or Qili Qiangxin (QLQX). Cardiac functions were assessed using M-mode echocardiography. Cardiac remodeling and myocardial fibrosis were observed using HE and Masson staining. Additionally, the expression of the CaSR/AQP2 signaling pathway in the renal was detected using western blotting analysis, quantitative PCR analysis, immunofluorescence staining, immunohistochemistry, and co-immunoprecipitation assays. Furthermore, CaSR inhibitor NPS2143 was used to confirm the role of CaSR on the effect of XBP for water retention. Results In the LAD-induced CHF rat model, XBP improved EF (ejection fraction) and LVFS (fractional shortening), and alleviated cardiac fibrosis. Importantly, XBP significantly increased the 24-h urine volume and decreased urinary protein level after CHF. Further mechanism studies showed that XBP treatment could decrease the expression of renal AQP2 at the protein and mRNA levels. Moreover, XBP promoted renal AQP2 ubiquitination by upregulating CaSR and p-p38-MAPK expression. Meanwhile, XBP suppressed the expression of p-CREB to inhibit the mRNA expression of AQP2 in the renal tissue. However, NPS2143 blocked the beneficial effects of XBP on cardiac function and water retention, even stopped the inhibitory effect on AQP2 expression by XBP. Conclusion Our study revealed that XBP improved water retention against CHF via promoting CaSR/p38-MAPK-mediated AQP2 ubiquitination and regulating CaSR/CREB-mediated AQP2 transcription.

OBJECTIVE:Xinyang Tablet (XYAT) and Xinyin Tablet (XYIT) have been used to treat chronic heart failure (CHF) for 20 years. This study investigated their pharmacodynamic material basis and underlying mechanisms of action. METHODS:Ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS) was used to identify the components of XYAT and XYIT, and to profile their metabolites in plasma and urine samples from both rats and human volunteers. Furthermore, the prototype compounds and their pharmacokinetics were evaluated using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Network pharmacology predicted potential targets and pathways, which were subsequently validated through flow cytometry and Western blot. The efficacy of XYAT, XYIT and their active components was evaluated in oxidative stress and cardiotoxicity models. RESULTS:A total of 162 and 130 compounds were detected in XYAT and XYIT, respectively; among these, 148 from XYAT and 119 from XYIT were structurally identified. A validated HPLC-MS/MS method quantified 20 key exposure components, five of which showed high systemic exposure and underwent pharmacokinetic analysis. Pharmacokinetic results indicated that the systemic exposure of most compounds was higher for XYAT than for XYIT. Using network pharmacology, seven candidate active compounds were identified, along with their predicted therapeutic targets and associated signaling pathways. Flow cytometry and Western blot confirmed that XYAT, XYIT, and their bioactive components alleviate CHF by modulating calcium signaling and phosphoinositide 3-kinase/protein kinase B signaling. Pharmacodynamic assays demonstrated that XYAT provides protection against hydrogen peroxide-induced injury, while XYIT mitigates doxorubicin-induced cytotoxicity. Further validation confirmed that 20(S)-ginsenoside Rg2 and 20(R)-ginsenoside Rh1 effectively reduced the H2O2-induced oxidative stress, while 20(S)-ginsenoside Rg2 and calycosin-7-O-β-d-glucoside significantly protected against doxorubicin-induced cytotoxicity. CONCLUSION:These findings provide mechanistic insights into the pharmacodynamic material basis and anti-CHF mechanisms of XYAT and XYIT. The integrated strategy established herein offers robust evidence that the superior systemic exposure of key components underpins the rationale for XYAT's formulation and warrants its continued development in modern cardiology. Please cite this article as: Lan YL, Chen SM, Dai BX, Wu CS, Wei Y, Yang L, Yan JL, Guo YQ, Wang DW, Li QG, Yang ZQ, Xian SX, Yuan TH. Bioactive components of Xinyang and Xinyin tablets for treating chronic heart failure: pharmacokinetics, network pharmacology and experimental validation. J Integr Med. 2026; 24(2):265-278.

Introduction: Prior research has suggested that herb-derived compounds from Radix Salviae decoction (RSD) may have anti-inflammatory, antioxidant, antithrombotic and cardiac function improvement properties in cardiovascular system diseases. However, the efficacy and mechanism of herb-derived compounds from RSD for modulating cell death of vascular smooth muscle cells (VSMC) have yet to be investigated. This study aimed to investigate the effects of RSD in modulating cell death of vascular smooth muscle cells and elucidate the underlying mechanisms. Methods: Chemical constituents were analyzed through literature and databases. Network pharmacological analysis identified targets for herb-derived compounds from RSD and cell death. A protein-protein interaction network was constructed using String, followed by GO and KEGG analyses to explore pathways affecting vascular smooth muscle cell death. Results: Network pharmacological analysis identified the targets for the three compounds from RSD (Tanshinone IIA (DST), Santalol (TXC), and Bornyl ester (LNZ)) and three kinds of cell death (pyroptosis, autophagy and apoptosis). Large nodes such as CASP8, CASP3, TP53, JUN and BAX were observed at the center of the targets network, suggesting that they play key roles in protein interaction networks. In serum-free medium (SFM) conditions of VSMC in vitro, treatment with the herb-derived compounds from RSD significantly promoted pyroptosis of VSMC indicated by increased mRNA levels of GSDMD and GSDME, and the increased mRNA levels of IL-1 beta. These compounds also inhibited autophagy, as they reduced the expression of ATG12, and decreased the LC3-II/I ratio in VSMC; and the compounds decreased the proportion of early apoptotic cells indicated by flow cytometry. Furthermore, cytokines of IL-6 and TNF-alpha were notably inhibited after treatment with these compounds. For the related cell signaling transduction, the herb-derived compounds from RSD suppressed PI3K-AKT while activating the NF-kappa B signaling pathway. Conclusion: This study reveals that treatment of nutrition-depleted VSMC with DST, TXC, and LNZ leads to the promotion of pyroptosis and downregulation of inflammatory factor expression, alongside reduction of autophagy and early apoptotic cells.

BACKGROUND:Sparstolonin B (SSNB) and Curcumin (Cur), from a pair of compatible herbs, were previously identified as anti-inflammation and T helper 17 (Th17) modulation reagents. However, their compatible roles in atherosclerosis (AS) and underlying mechanisms remain uninvestigated. METHODS:In vivo, the apoE-/- mice fed with high fat diet were used as mice model of AS. In vitro, macrophages, vascular smooth muscle cells (VSMC) were used in biological tests for vascular atherogenesis. For the Th17 differentiation, bone marrow-derived dendritic cells (DC) from wild-type mice were stimulated and co-cultured with sorted naïve CD4+T cells from mice spleen, and. Functional assessments included flow cytometry, Oil Red O staining, ELISA, Western blotting (WB), and label-free proteomics of mouse peripheral blood. Molecular docking and Surface plasmon resonance (SPR) was used for evaluating binding affinity of ligands to target proteins. RESULTS:The gene-disease interaction and hub gene network reveals Th17-associated genes in the pathogenesis of atherosclerosis. In vitro, SSNB and Cur reduced oxLDL-induced BMDC activation by downregulating CD36. SSNB showed stronger inhibition to inflammatory activation of DC, while Cur more intensively suppressed co-stimulatory molecules. For the Th17/Treg bias in co-culture of BMDC and CD4+T cells, SSNB exerted a more significant inhibitory effect on Th17 differentiation, whereas SSNB and Cur exerted stronger effect on promoting Treg expansion. Cur exerts a more significant inhibitory effect on macrophages inflammation, and SSNB showed better inhibition of oxLDL uptake in VSMC foam cell formation. In vivo, SSNB and Cur reduced aortic atherosclerotic lesions and IL-17A in aortic valve, inflammatory cells infiltration and related Th17 immune response in apoE-/- mice. Proteomics identified proteolysis, oxidation-reduction, protein phosphorylation and metabolic process as top biological processes in the effects of SSNB and Cur. WB indicated IL-17RA-TAK1-NF-κB interaction as the related underlying molecular pathways. SSNB mainly inhibited TAK1 phosphorylation, while Cur more directly inhibited NF-κB P65 phosphorylation. Molecular docking indicated SSNB was superior binding to TLR4 and CD36 than Cur, and the binding result was further confirmed by molecular dynamic simulations and SPR verification. CONCLUSION:Our findings reveal, for the first time, that SSNB and Cur alleviate AS by modulating Th17-stromal cell interactions, with the IL-17RA-TAK1-NF-κB pathway as a related mediator. Notably, SSNB and Cur exhibit distinct anti-atherogenic roles. SSNB primarily targets TLR4/CD36 to inhibit DC activation, Th17 differentiation, VSMC inflammation and mainly inhibited TAK1 phosphorylation, while Cur more significant inhibited macrophage inflammation, and more directly inhibited NF-κB P65 phosphorylation. This study will be valuable for developing novel and precise adjuvant therapies for AS.

Objectives This study aimed to investigate the knowledge, attitude and practice (KAP) towards worsening heart failure (WHF) among caregivers for older adults with chronic heart failure (CHF).Design A cross-sectional study was conducted between September and October 2023.Participants The study involved caregivers for older adults living with CHF in Guangzhou, China.Interventions None.Primary and secondary outcome measures The primary outcomes included KAP scores regarding WHF, while secondary outcomes involved the relationships among knowledge, caregiver strain, attitude and practice.Results A total of 538 valid questionnaires were included, with 326 (60.59%) caregivers being female. The median KAP scores were 30 (23–45) (possible range: 0–54), 42 (36–45) (possible range: 9–45) and 36 (29–41) (possible range: 9–45), respectively, indicating insufficient knowledge, positive attitude and moderate practice. Path analysis indicated that knowledge directly influenced attitude (β=0.213, p<0.001), caregiver strain (β=0.008, p<0.001) and practice (β=0.105, p<0.001). Furthermore, attitude (β=0.378, p<0.001) and caregiver strain (β=3.408, p<0.001) also had direct effects on practice. Mediation analysis revealed that the effect of knowledge on practice is mediated through attitude (r=0.081, p=0.005) and caregiver strain index (r=0.027, p=0.012).Conclusions Caregivers of older adults living with CHF exhibited insufficient knowledge, positive attitudes and moderate practices regarding WHF. This study underscores the necessity for tailored interventions to bridge knowledge gaps, promote positive attitudes and enhance practical skills among caregivers, ultimately improving WHF management in older adults.

Intravenous tissue plasminogen activator (tPA) is currently the only FDA-approved thrombolytic therapy for acute ischemic stroke (AIS), however, relative narrow therapeutic time window (within 4.5 h of AIS onset) and high risk of hemorrhagic transformation due to blood–brain barrier (BBB) disruption limit tPA therapeutic benefits for patients. In this study, we extended the time window of tPA administration (5 h after the occurrence of AIS) and investigated whether Chinese medicine classical formula Shengui Sansheng San (SSS) administration was able to alleviate BBB integrity worsening, and the mechanism was related to vasoactive intestinal peptide (VIP)/ VIP receptor 1 (VIPR1) pathway. SSS was extracted using aqueous heating method and SFE-CO2 technology, and quality control was performed using UHPLC/MS analysis. Male C57BL/6 mice were suffered from middle cerebral artery occlusion (MCAo), followed by the removal of a silicone filament after 5 h, then, t-PA was administered via tail vein injection at once, along with SSS administration by gavage. Hemoglobin levels and Evans blue leakage were measured to assess brain hemorrhagic transformation and BBB permeability, respectively. Transmission electron microscope (TEM) was utilized to present brain microvascular endothelial cells (BMECs) tight junction morphology. TTC staining and laser speckle contrast imaging were employed for infarct volume and cerebral blood flow measurements. The modified neurological severity score (mNSS) test was conducted to evaluate neurological function. The expressions of VIP, VIPR1, ZO-1, Occludin, Lectin, GFAP, NeuN were detected by immunofluorescence staining or western blotting. In vitro, bEnd.3 and N2a cells were insulted by oxygen–glucose deprivation (OGD), and VIPR1 siRNA, and VIP shRNA transfection were respectively performed, and the molecular docking was applied to verify the SSS in-serum active compounds interacted with VIPR1. The transwell system was utilized to detect OGD-insulted BMECs permeability. SSS treatment significantly reduced the infarct area, cerebral hemorrhage, and neurological deficits, and enhanced cerebral blood flow in AIS mice received intravenous tPA beyond 4.5 h time window. Simultaneously, the permeability of BBB declined, with increased expressions of tight junction proteins ZO-1, and Occludin and proper BMECs tight junction morphology, and it suggested that VIP was released by neurons rather than astrocytes or BMECs. It also showed high expressions of VIP and VIPR1 in the penumbra area. The inhibition of VIP in N2a cells or VIPR1 in bEnd.3 cells abolished the viability and integrity of OGD-insulted bEnd.3 cells treated by tPA after SSS-containing serum administration, and the SSS in-serum active compounds were proved have high affinity to VIPR1 by molecular docking. SSS alleviates the worsening of BBB integrity resulted from delayed tPA administration, reduces hemorrhagic transformation and infarction volume, and ameliorates brain blood flow and neurological function in AIS mice. The mechanisms are associated with the activation of VIP/VIPR1 pathway to enhance BMECs viability and maintain tight junction phenotype.

Coronary atherosclerotic heart disease (CHD) is one of the leading causes of death from cardiovascular disease worldwide and has significant inflammatory features. Macrophages play an important role in atherosclerotic plaque formation and inflammation. IL-17, as a pro-inflammatory cytokine, further exacerbates the development of CHD by interacting with macrophages. In recent years, there has been increasing evidence that traditional Chinese medicine (CM) has a wide range of applications in regulating the immune system and treating CHD. This article reviewed the role of CM in the regulation of IL-17-regulated macrophages, discussed the core components and targets of CM in the treatment of CHD, and laid a theoretical foundation for its clinical application. The results show that CM can effectively inhibit the formation of foam cells, stabilize vulnerable plaque and delay the progression of atherosclerosis by inhibiting inflammation, regulating the polarization of macrophages and promoting cholesterol outflow. In addition, CM can also regulate the expression and signaling pathway of IL-17, further inhibit inflammatory response and improve the symptoms of CHD, providing a new idea and method for the prevention and treatment of CHD.

The active ingredients of Citrus aurantium have been shown to possess a variety of biological activities, especially anti-inflammatory effects. However, its antiatherosclerotic effects need to be further investigated. The aim of this study is to identify compounds with antiatherosclerotic effects from C. aurantium and to further investigate their mechanisms. Three compounds were separated, and then their antiatherosclerotic effect on foam cells induced by oxidized low-density lipoprotein (ox-LDL) was screened by oil red O staining, BODIPY staining, and Dil-ox-LDL uptake measurement. Cholesterol uptake, cholesterol efflux, RT-PCR, and Western blot analysis were used to comprehensively and comparatively explore the potential mechanisms. Nobiletin (NOB), caffeine (CAF), and naringin (NARG), which were separated from C. aurantium, mainly inhibit the formation of foam cells in different ways. NOB reduced cholesterol uptake and enhanced cholesterol efflux and mainly regulated the expressions of ABCA1, ABCG1, and SRA1. CAF promoted cholesterol efflux, mainly by stimulating the expressions of ABCA1 and ABCG1. NARG was more effective in reducing the expression of SRA1 and CD36, which indicated that NARG mainly prevented atherosclerosis by blocking cholesterol uptake. The above results show in detail the antiatherosclerotic activity and mechanism of these compounds, making contributions to their potential applications.

Objective To systematically evaluate the causal effect of lipoproteins to the risk of coronary artery disease (CAD) by systematic review and meta-analysis of the associated Mendelian randomization (MR) studies. Methods This systematic review was registered in PROSPERO (ID CRD42023465430). Searches from the databases (e.g., PubMed, Embase, Cochrane, Web of Science) and non-database sources to collect MR studies. The search time frame was from the database inception to August 2023. After data extraction, quality evaluation was performed, and the meta-analysis with bias evaluation was carried out with RevMan software. Results A total of 5,828,409 participants from 21 records were included. Quality and bias assessment was performed by evaluating the internal three assumptions of MR studies. Meta-analysis for the causal association between non-HDL lipoproteins and CAD showed a significantly positive association between LDL and CAD (OR 1.37, 95% CI 1.26-1.49; P < 0.001, I-2 = 95%), apoB and CAD (OR 1.38, 95% CI 1.11-1.71; P = 0.003, I-2 = 98%), and Lp(a) and CAD (OR 1.21, 95% CI 1.12-1.31; P < 0.001, I-2 = 99%). Interestingly, although there was no statistical significance in the association between VLDL/apoA1 and CAD (both P > 0.05), the pooled non-HDL lipoproteins showed a significantly positive association with CAD (OR 1.28, 95% CI 1.22-1.34; P < 0.001, I-2 = 99%). For the HDL lipoproteins, the pooled OR showed a significantly negative association with CAD (OR 0.84, 95% CI 0.72-0.98; P = 0.002, I-2 = 72%). However, the protective effect of HDL on CAD diminished when analyzed together with apoA1 and/or apoB (both P > 0.05). The funnel plot did not show serious publication bias, and sensitivity analysis performed relatively well robustness of the causal association of LDL, apoB, Lp(a), and total cholesterol with CAD. Conclusion The present meta-analysis suggests an overall effect of causal association between lipoproteins and CAD. Most of the non-HDL lipoproteins (LDL, apoB, Lp(a)) promote CAD, while the protective effect of HDL in CAD still needs to be verified in the future.

OBJECTIVE:To synthesize the evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of Chinese patent medicine (CPM) on atherosclerosis (AS) or with a high risk of atherosclerosis. METHODS:All RCTs in three databases (PubMed, EMBASE, and Cochrane Library) were included from the inception of the database to September 20, 2019. The methodological evaluation of the included trials was carried out using the Cochrane Collaboration Risk of Bias Tool. Meta-analysis was conducted using RevMan 5.3 software. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the quality of evidence. RESULTS:Eighteen RCTs were included, involving a total of 3885 patients with AS or with a high risk of AS. Most trials had favorable methodology. Meta-analysis suggested significant differences in clinical endpoint (n = 1938, RR 0.53; 95% CI 0.40 to 0.69, P < 0.00001; I 2 = 0%); the change in carotid artery IMT (n = 1723, MD -0.09, 95% CI －0.14 to -0.04, P < 0.001; I 2 = 40%); change in FMD (n = 239, MD 0.87, 95% CI 0.52 to 1.21, P < 0.00001; I 2 = 0%); change in high sensitive C-reactive protein (hs-CRP) (n = 1527, MD －1.89, 95% CI －3.36 to －0.42, P = 0.01; I 2 = 94%) and incidence of total adverse events (RR 0.76, 95% CI 0.62 to 0.93, P = 0.009; I 2 = 40%) in favor of the experimental group. However, meta-analysis showed no significant differences in the change in low-density lipoprotein-C (LDL-C) (n = 2419, MD －0.19, 95% CI －0.50 to 0.12, P = 0.22, I 2 = 94%) between the experimental and control groups. CONCLUSION:CPM could have certain clinical efficacy in the treatment of AS. However, more double-blinded placebo-controlled RCTs are required in further evaluations to provide stronger evidence.

Partridge tea is a plant used as a speciality tea drink in Hainan Province, China. The aim of this study was to isolate polyphenols from partridge tea, investigate their main constituent compositions and ameliorative effects on insulin resistance in insulin resistant HepG2 (IR-HepG2) cells. PTP was obtained from partridge tea, then PTP1, PTP-2 and PTP-3 were obtained after further purification. The polyphenol contents of PTP, PTP-1, PTP-2, PTP3 were determined to be 15.9%, 51.4%, 42.51% and 22.74%, respectively. PTP and PTP-1 had similar compositions, and the contents of the main components of PTP-1 was higher than that of PTP. Structural compositions and contents of PTP-2 and PTP-3 differ significantly. Further analysis indicated that PTP failed to have significant hypoglycaemic activity, while other three polyphenols regulated the fat metabolism disorders caused by insulin resistance, thus improving the body's utilization of blood glucose. In addition, the three polyphenols reversed the damage caused by insulin resistance in IR-HepG2 cells by up-regulating the activities of HK (200 mu g/mL PTP-1: 2.8414 mol/min/mL) and PK (200 mu g/mL PTP-1: 10.7204 U/L), increasing the activity of SOD and CAT and decreasing the level of MDA. The mRNA results showed that PTP-1, PTP-2 and PTP-3 could achieve hypoglycaemic efficacy in the body by regulating the IRS-1/PI3K/AKT signal pathway. In summary, our results suggested that the polyphenols of partridge tea could be a promising natural source for preventing and treating hyperglycemia.

Breast cancer (BC) has become the most prevalent cancer worldwide, and further research is being conducted to deepen our understanding of its pathogenesis and treatment. Lipid metabolism disorder is a significant alteration in cancer cells, and the investigation into the role of Interleukin-17 (IL-17) in malignant tumors has emerged as a research focus in recent years. Thus, exploring changes in lipid metabolism and inflammatory factors in BC cells is crucial in identifying potential therapeutic targets. This article summarizes the progress made in the research on the main low-density cholesterol (LDL) transporter and IL-17 in lipid metabolism, and their potential involvement in the development of BC. The article aims to establish a theoretical foundation for the development of BC-related therapies.

Background and objectivesRestenosis is a serious complication for patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). In this prospective clinical study, we aimed to investigate the effects of Radix Salviae decoction (RSD) on coronary stenosis and restenosis in CHD patients.

Sparstolonin B (SsnB) is characterized as a new toll-like receptor (TLR)-2/4 antagonist. However, the effects of SsnB on different inflammatory diseases have not been systemically reviewed. We investigated the effects of SsnB on inflammatory diseases with data mining and network analysis of literature, including frequency description, cluster analysis, association rule mining, functional enrichment, and protein–protein interaction (PPI) mining. A total of 27 experimental reports were included. The ARRIVE 2.0 guidelines were used to evaluate the quality of animal studies. Frequency analysis revealed 13 different diseases (cardio-cerebrovascular system diseases account for 23.53

Background: Dysfunction in myocardial energy metabolism plays a vital role in the pathological process of Dilated Cardiomyopathy (DCM). However, the precise mechanisms remain unclear. This study aims to investigate the key molecular mechanisms of energy metabolism and potential therapeutic agents in the progression of dilated cardiomyopathy with heart failure.Methods: Gene expression profiles and clinical data for patients with dilated cardiomyopathy complicated by heart failure, as well as healthy controls, were sourced from the Gene Expression Omnibus (GEO) database. Gene sets associated with energy metabolism were downloaded from the Molecular Signatures Database (MSigDB) for subsequent analysis. Weighted Gene Co-expression Network Analysis (WGCNA) and differential expression analysis were employed to identify key modules and genes related to heart failure. Potential biological mechanisms were investigated through Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and the construction of a competing endogenous RNA (ceRNA) network. Molecular docking simulations were then conducted to explore the binding affinity and conformation of potential therapeutic drugs with hub genes.Results: Analysis of the left ventricular tissue expression profiles revealed that, compared to healthy controls, patients with dilated cardiomyopathy exhibited 234 differentially expressed genes and 2 genes related to myocardial energy metabolism. Additionally, Benzoylaconine may serve as a potential therapeutic agent for the treatment of dilated cardiomyopathy.Conclusion: The study findings highlight the crucial role of myocardial energy metabolism in the progression of Dilated Cardiomyopathy. Notably, Benzoylaconine emerges as a potential candidate for treating Dilated Cardiomyopathy, potentially exerting its therapeutic effects by targeted modulation of myocardial energy metabolism through NRK and NT5.