AIM:The study aimed to investigate the relationship between neutrophil-percentage-to-albumin ratio (NPAR) and diabetic kidney disease (DKD), and to evaluate its potential for predicting DKD progression. METHODS:This cross-sectional study utilised data from the National Health and Nutrition Examination Survey (NHANES). We employed weighted multivariable logistic regression and restricted cubic splines (RCS) to examine nonlinear relationships between NPAR levels and DKD. Additionally, subgroup analyses were performed to assess heterogeneity across demographic strata. Machine learning (ML) algorithms were employed to develop DKD prediction models and receiver operating characteristic (ROC) curves for each model were plotted on the test set to evaluate predictive performance. Finally, the study applied Shapley Additive Explanations (SHAP) to interpret feature contributions to predictions. RESULTS:A total of 10,526 participants were included. After full covariate adjustment, the continuous variable NPAR was positively associated with the prevalence of DKD (OR = 1.16, 95% CI: 1.11-1.22, p < 0.001). The results of the RCS showed a significant nonlinear trend in the correlation between NPAR and DKD (P-non-linear < 0.0001). Subgroup analysis discovered that NPAR was generally associated with an increased possibility of developing DKD, but the subgroup differences were not statistically significant. Predictive modelling revealed NPAR had a good performance in assessing the risk of DKD incidence. CONCLUSION:In the general population, high NPAR is positively associated with the development of DKD, and predictive modelling of DKD that includes NPAR has shown excellent performance. These findings provide a rationale for NPAR as a potential non-invasive biomarker for early detection of DKD.

AIMS:Protein glycosylation regulated by glycosyltransferases is an important type of post-translational modification. The role of the glycosyltransferase genes (GTGs) in heart failure (HF) remains unclear and requires further investigation. METHODS:Differential expression analysis was performed on the transverse aortic constriction (TAC)-related dataset GSE36074 to screen out the differentially expressed GTGs. Enrichment and protein-protein interaction analyses explored their functional mechanisms and interconnections. Pearson correlation analysis revealed the relationship between GTGs and pathological cardiac remodelling. The upstream miRNAs of GTGs were predicted using corresponding online databases, and the downstream target genes were identified by weighted correlation network analysis (WGCNA). Computer virtual screening and molecular docking predicted potential therapeutic drugs. The identified GTGs were validated in vivo, in vitro and in the human HF-related dataset GSE57338. RESULTS:Twenty-one differentially expressed GTGs were identified, and these genes were significantly up-regulated in the TAC model except for C1galt1, Extl2 and Pigh. Pearson correlation analysis revealed that 11 GTGs were significantly associated with pathological cardiac remodelling. Fifty-six miRNAs and 31 drugs were predicted to target these GTGs. WGCNA indicated that these GTGs were associated with lipid metabolism-related genes and pathways. Up-regulation of B3gnt9, C1galt1, Gcnt1, Gxylt2 and Mgat5b was observed in the TAC model. GXYLT2 is up-regulated and has high disease-predictive value in patients with dilated cardiomyopathy and ischaemic cardiomyopathy. Knockdown of GXYLT2 in human AC16 cardiomyocytes significantly attenuated angiotensin II (AngII)-induced hypertrophy. CONCLUSIONS:Dysregulation of GTG expression may affect TAC-induced HF through metabolic pathways, and GXYLT2 may be a new potential therapeutic target for HF.

Background:Chronic total occlusion (CTO) of coronary arteries is a significant challenge in percutaneous coronary intervention (PCI). Despite successful revascularization, patients often develop diffuse coronary lesions, increasing the risk of restenosis and necessitating complex stent strategies. Objective:This study aimed to compare the clinical outcomes of drug-eluting stents (DES) combined with drug-coated balloon (DCB) angioplasty versus DES-only treatment in patients with revascularized CTO and diffuse coronary artery disease. Methods:Patients with successfully revascularized CTO and diffuse lesions were divided into DES-only (n = 191) and DES plus DCB (n = 100) groups. The primary endpoint was major adverse cardiovascular events (MACE), including all-cause death, cardiac death, stroke, and revascularization. The secondary endpoint was the rate of cardiovascular-related hospitalization. Symptom improvement was evaluated using the Canadian Cardiovascular Society (CCS) classification. Results:At 24-month follow-up, the DES plus DCB group had significantly lower MACE incidence (26.00 % vs. 41.36 %, P = 0.008) and cardiovascular-related hospitalization (20.00 % vs. 36.65 %, P = 0.005) compared to the DES-only group. CCS classification improved more significantly in the DES plus DCB group (P < 0.001). Multivariate Cox regression identified DES plus DCB as an independent protective factor against MACE (HR, 0.57; 95 % CI, 0.33-0.99; P = 0.046). Conclusion:In patients with revascularized CTO and diffuse coronary artery disease, the combined DES plus DCB strategy was associated with a lower incidence of MACE and reduced cardiovascular-related hospitalization compared to DES-only treatment. This approach may represent a superior therapeutic option for managing complex coronary lesions.

BACKGROUND:Dysregulated cell death machinery and an excessive inflammatory response in Coxsackievirus B3(CVB3)-infected myocarditis are hallmarks of an abnormal host response. Complement C4 and C3 are considered the central components of the classical activation pathway and often participate in the response process in the early stages of virus infection.METHODS:In our study, we constructed a mouse model of CVB3-related viral myocarditis via intraperitoneal injection of Fer-1 and detected myocarditis and ferroptosis markers in the mouse myocardium. Then, we performed co-IP and protein mass spectrometry analyses to explore which components interact with the ferroptosis gene transferrin receptor (TFRC). Finally, functional experiments were conducted to verify the role of complement components in regulating ferroptosis in CVB3 infection.RESULTS:It showed that the ferroptosis inhibitor Fer-1 could alleviate the inflammation in viral myocarditis as well as ferroptosis. Mechanistically, during CVB3 infection, the key factor TFRC was activated and inhibited by Fer-1. Fer-1 effectively prevented the consumption of complement C3 and overload of the complement product C4b. Interestingly, we found that TFRC directly interacts with complement C4, leading to an increase in the product of C4b and a decrease in the downstream complement C3. Functional experiments have also confirmed that regulating the complement C4/C3 pathway can effectively rescue cell ferroptosis caused by CVB3 infection.CONCLUSIONS:In this study, we found that ferroptosis occurs through crosstalk with complement C4 in viral myocarditis through interaction with TFRC and that regulating the complement C4/C3 pathway may rescue ferroptosis in CVB3-infected cardiomyocytes.

Lipid metabolism is an important part of the heart's energy supply. The expression pattern and molecular mechanism of lipid metabolism-related genes (LMRGs) in acute myocardial infarction (AMI) are still unclear, and the link between lipid metabolism and immunity is far from being elucidated. In this study, 23 Common differentially expressed LMRGs were discovered in the AMI-related mRNA microarray datasets GSE61144 and GSE60993. These genes were mainly related to "leukotriene production involved in inflammatory response", "lipoxygenase pathway", "metabolic pathways", and "regulation of lipolysis in adipocytes" pathways. 12 LMRGs (ACSL1, ADCY4, ALOX5, ALOX5AP, CCL5, CEBPB, CEBPD, CREB5, GAB2, PISD, RARRES3, and ZNF467) were significantly differentially expressed in the validation dataset GSE62646 with their AUC>0.7 except for ALOX5AP (AUC=0.699). Immune infiltration analysis and Pearson correlation analysis explored the immune characteristics of AMI, as well as the relationship between these identified LMRGs and immune response. Lastly, the up-regulation of ACSL1, ALOX5AP, CEBPB, and GAB2 was confirmed in the mouse AMI model. Taken together, LMRGs ACSL1, ALOX5AP, CEBPB, and GAB2 are significantly upregulated in AMI patients' blood, peripheral blood of AMI mice, myocardial tissue of AMI mice, and therefore might be new potential biomarkers for AMI.

Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide, particularly among complex high-risk and indicated patients (CHIP). Revascularization is often beneficial for these patients; however, it requires thorough risk stratification and close multidisciplinary collaboration between cardiologists and cardiac surgeons to optimize outcomes. Personalized treatment plans, including percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), are crucial in this context. In this report, we present a case of a 70-year-old man with left main trunk bifurcation lesions, referred to as a "Four Forks Lesion," who was successfully revascularized using a PCI strategy, resulting in a favorable prognosis.

(1) Background: The molecular mechanism of oxidative stress-related genes (OSRGs) in myocardial ischemia-reperfusion injury (MIRI) has not been fully elucidated. (2) Methods: Differential expression analysis, enrichment analysis, and PPI analysis were performed on the MIRI-related datasets GSE160516 and GSE61592 to find key pathways and hub genes. OSRGs were obtained from the Molecular Signatures Database (MSigDB). The expression pattern and time changes of them were studied on the basis of their raw expression data. Corresponding online databases were used to predict miRNAs, transcription factors (TFs), and therapeutic drugs targeting common differentially expressed OSRGs. These identified OSRGs were further verified in the external dataset GSE4105 and H9C2 cell hypoxia-reoxygenation (HR) model. (3) Results: A total of 134 DEGs of MIRI were identified which were enriched in the pathways of "immune response", "inflammatory response", "neutrophil chemotaxis", "phagosome", and "platelet activation". Six hub genes and 12 common differentially expressed OSRGs were identified. A total of 168 miRNAs, 41 TFs, and 21 therapeutic drugs were predicted targeting these OSRGs. Lastly, the expression trends of Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 were confirmed in the external dataset and HR model. (4) Conclusions: Aif1, Apoe, Arg1, Col1a1, Gpx7, and Hmox1 may be involved in the oxidative stress mechanism of MIRI, and the intervention of these genes may be a potential therapeutic strategy.

Cardiac maturation is crucial for postnatal cardiac development and is increasingly known to be regulated by a series of transcription factors. However, post-translational mechanisms regulating this process remain unclear. Here we report the indispensable role of neddylation in cardiac maturation. Mosaic deletion of NAE1, an essential enzyme for neddylation, in neonatal hearts results in the rapid development of cardiomyopathy and heart failure. NAE1 deficiency disrupts transverse tubule formation, inhibits physiological hypertrophy, and represses fetal-to-adult isoform switching, thus culminating in cardiomyocyte immaturation. Mechanistically, we find that neddylation is needed for the perinatal metabolic transition from glycolytic to oxidative metabolism in cardiomyocytes. Further, we show that HIF1α is a putative neddylation target and that inhibition of neddylation accumulates HIF1α and impairs fatty acid utilization and bioenergetics in cardiomyocytes. Together, our data show neddylation is required for cardiomyocyte maturation through promoting oxidative metabolism in the developing heart.

AIMS:Studies have confirmed that viral myocarditis (VMC) is one of the risk factors for dilated cardiomyopathy (DCM). The molecular mechanisms underlying the progression from VMC to DCM remain unclear and require further investigation. METHODS AND RESULTS:The mRNA microarray datasets GSE57338 (DCM) and GSE1145 (VMC) were obtained from the Gene Expression Omnibus database. The candidate key genes were further screened using weighted correlation network analysis (WGCNA), protein-protein interaction and external dataset validation, and the correlation between the candidate key genes and immune cells and the signalling pathways of the candidate key genes were observed by enrichment analysis and immune infiltration analysis. The expression of key genes was validated in the external dataset GSE35182. The crosstalk genes between DCM and VMC were mainly enriched in 'transcriptional misregulation in cancer', 'FoxO signalling pathway', 'AGE-RAGE signalling pathway in diabetic complications', 'thyroid hormone signalling pathway', 'AMPK signalling pathway', and other signalling pathways. The immune infiltration analysis indicated that VMC was mainly associated with resting dendritic cells and M0 macrophages, while DCM was mainly associated with monocytes, M0 macrophages, CD8+ T cells, resting CD4 memory T cells, naive CD4+ T cells, and resting mast cells. In DCM-related dataset GSE57338 and VMC-related dataset GSE1145, a total of 18 candidate key genes were differentially expressed. BLC6, FOXO1, and UBE2M were identified as the key genes that lead to the progression from VMC to DCM by GSE35182. CONCLUSIONS:Three key genes (BLC6, FOXO1, and UBE2M) were identified and provided new insights into the diagnosis and treatment of VMC with DCM.

Background:Ferroptosis is a form of regulatory cell death (RCD) caused by iron-dependent lipid peroxidation. The role of ferroptosis in the process of acute myocardial infarction (AMI) is still unclear and requires further study. Therefore, it is helpful to identify ferroptosis related genes (FRGs) involved in AMI and explore their expression patterns and molecular mechanisms.Methods:The AMI-related microarray datasets GSE66360 and GSE61144 were obtained using the Gene Expression Omnibus (GEO) online database. GO annotation, KEGG pathway enrichment analysis and Protein-protein interaction (PPI) analysis were performed for the common significant differential expression genes (CoDEGs) in these two datasets. The FRGs were obtained from the FerrDb V2 and the differentially expressed FRGs were used to identify potential biomarkers by receiver operating characteristic (ROC) analysis. The expression of these FRGs was verified using external dataset GSE60993 and GSE775. Finally, the expression of these FRGs was further verified in myocardial hypoxia model.Results:A total of 131 CoDEGs were identified and these genes were mainly enriched in the pathways of "inflammatory response," "immune response," "plasma membrane," "receptor activity," "protein homodimerization activity," "calcium ion binding," "Phagosome," "Cytokine-cytokine receptor interaction," and "Toll-like receptor signaling pathway." The top 7 hub genes ITGAM, S100A12, S100A9, TLR2, TLR4, TLR8, and TREM1 were identified from the PPI network. 45 and 14 FRGs were identified in GSE66360 and GSE61144, respectively. FRGs ACSL1, ATG7, CAMKK2, GABARAPL1, KDM6B, LAMP2, PANX2, PGD, PTEN, SAT1, STAT3, TLR4, and ZFP36 were significantly differentially expressed in external dataset GSE60993 with AUC ≥ 0.7. Finally, ALOX5, CAMKK2, KDM6B, LAMP2, PTEN, PTGS2, and ULK1 were identified as biomarkers of AMI based on the time-gradient transcriptome dataset of AMI mice and the cellular hypoxia model.Conclusion:In this study, based on the existing datasets, we identified differentially expressed FRGs in blood samples from patients with AMI and further validated these FRGs in the mouse time-gradient transcriptome dataset of AMI and the cellular hypoxia model. This study explored the expression pattern and molecular mechanism of FRGs in AMI, providing a basis for the accurate diagnosis of AMI and the selection of new therapeutic targets.

Objective: To investigate whether auricular acupuncture (AA) attenuates bodyweight and obese inflammation through the release of irisin from muscle tissue in mice. Methods: Sixty 4-week-old mice were fed a high fat diet (HFD) for 4 weeks. These animals were divided into six groups that remained untreated (HFD) or underwent electrical AA (HFD+EAA), sham EAA (HFD+SEAA), adrenalectomy (HFD+AD), adrenalectomy and EAA (HFD+AD+EAA), or adrenalectomy and injection of recombinant lentivirus expressing fibronectin type III domain-containing protein 5 (rFNDC) (HFD+AD+rFNDC) in the ninth week. The EAA and SEAA were performed at two traditional auricular acupuncture points daily for 4 weeks. An additional 10 mice fed a control diet were included as a normal control (NC) group. At the end of the study, norepinephrine (NE) in the serum, tumour necrosis factor α (TNFα) and interleukin 1β (IL-1β) in the serum and white adipose tissue, irisin in the serum and muscle, uncoupling protein-1 (UCP-1) in the brown adipose tissue (BAT), and FNDC5 in the muscle, were analysed. Results: The AD+EAA group exhibited better control of bodyweight and inflammation compared with the AD+SEAA and untreated HFD model groups (P<0.05), especially regarding the increased expression of NE, FNDC5, irisin and UCP-1 (P<0.05). After adrenalectomy, mice receiving EAA had less NE, FNDC5, irisin and UCP-1 as well as greater expression of inflammatory cytokines and bodyweight. However, lentiviral overexpression of rFNDC successfully reversed this situation in the AD mice and mimicked the effects of EAA on bodyweight, inflammation and expression of FNDC5, irisin and UCP-1, although it did not impact NE. Conclusions: EAA promoted NE release from the adrenal gland leading to further expression of FNDC5, irisin and UCP-1, which contributed to weight management and inflammatory inhibition.

Forkhead box-O1 (FOXO1) is a downstream target of AKT and plays crucial roles in cell cycle control, apoptosis, metabolism and adipocyte differentiation. It is thought that FOXO1 affects adipocyte differentiation by regulating lipogenesis and cell cycle. With the deepening in the understanding of this field, it is currently believed that FOXO1 translocation between nuclei and cytoplasm is involved in the regulation of FOXO1 activity, thus affecting adipocyte differentiation. Translocation of FOXO1 depends on its post-translational modifications and interactions with 14-3-3. Based on these modifications and interactions, FOXO1 could regulate lipogenesis through PPARγ and the adipocyte cell cycle through p21 and p27. In this review, we aim to provide a comprehensive FOXO1 regulation network in adipocyte differentiation by linking together distinct functions mentioned above to explain their effects on adipocyte differentiation and to emphasize the regulatory role of FOXO1. In addition, we also focus on the novel findings such as the use of miRNAs in FOXO1 regulation and highlight the improvable issues, such as RNA modifications, for future research in the field.

Brown adipose tissue (BAT) plays important roles in regulating energy homeostasis and combating obesity. Accordingly, increasing the abundance and/or activating BAT would be effective and promising approaches to combat obesity and obesity-relative diseases. Our previous data in vitro have shown that osteopontin (OPN) induces the brown adipogenesis in 3T3-L1 cells via a phosphatidylinositol 3 kinase (PI3K)-AKT pathway. However, it is currently unknown whether OPN exerts such an effect on animals in vivo. Therefore, in the study we sought to investigate the pro-browning effects of OPN and to explore its underlying mechanisms by transfecting with Ad-GFP-aP2-OPN-shRNA to specifically down-regulate the OPN of white adipose tissue (WAT) in mice. Our present results show that downregulation of OPN in WAT exacerbates obesity and inhibits WAT-browning. Moreover, immunohistochemical results also exhibit that the downregulation of OPN significantly diminishes the expression and sub-cellular localization of UCP-1, PRDM16 and PGC-1α. Besides, the western blotting results reveal that the expression levels of PI3K, AKT-pS473 and PPARγ markedly reduce. Consequently, we conclude that the downregulation of OPN inhibits the browning of WAT through inhibiting the expression of PPARγ mediated by the PI3K-AKT pathway. The findings suggest that OPN is involved in regulation of WAT-browning and regulating its expression would become a potential strategy to combat obesity and obesity-relative metabolic diseases.

Indomethacin (IDMT), a non-selective inhibitor of cycloxygenase-2 (COX-2), plays important roles in anti-inflammation and analgesia and it is commonly used to treat the patients with rheumatic and rheumatoid arthritis. Besides, various literatures reported that IDMT is a synthetic ligand of peroxisome proliferator activated receptor gamma (PPAR gamma). Rosiglitazone (RSG), an insulin-sensitizer, is also a synthetic ligand and applied clinically to cure the patients with type 2 diabetes mellitus. However, up to date little is known about whether IDMT ameliorates endothelial insulin resistance (IR). Accordingly, the purpose of this study is to investigate the effects of IDMT on endothelial IR and its underlying mechanism. Our present results showed that IDMT improved the endothelial IR induced by high glucose and fat concentration (HG/HF) in a concentration and time-dependent manner. Intriguingly, we further identified that 0.25 mM of IDMT noticeably induced the expression levels of PPAR gamma, AKT and endothelial nitric oxide synthase (eNOS) but failed to notably reverse the increases in expression levels of COX-2, inhibitory kappa B kinase (IKK) and tumor necrosis factor alpha (TNF alpha) induced by HG/HF; whereas 1.0 mM of IDMT exerted opposite effects compared with 0.25 mM of IDMT. Therefore, we conclude that IDMT ameliorates the endothelial IR induced by HG/HF through two distinct pathways, i.e., a lower concentration of IDMT through a PPAR gamma-AKT-eNOS pathway while a higher concentration mainly via an IKK-COX-2/TNF alpha pathway. The findings might provide a novel clinical use for IDMT to cure IR-related disorders.

Epigallocatechin-3-gallate (EGCG) is a pivotal effective component of green tea. It is known that EGCG has antioxidant activity, anti-angiogenesis, anti-tumor, cardiovascular protection and blood lipid regulation functions. Forkhead box-O1 (FOXO1) is one of the downstream signals of protein kinase B (AKT) and takes part in adipogenesis. The purpose of this study is to investigate the effects of EGCG on adipose differentiation and the likely mechanisms. 3T3-L1 cells were induced by DMI for 2, 4, 6 and 8 days, respectively. During induction, the cells were treated with EGCG (5 μM, 10 μM, 50 μM and 100 μM) or DMSO for the first 2 days. In addition, another batch of 3T3-L1cells were treated with SC-3036 (PI3K activator, 10 µM), or LY294002 (PI3K inhibitor, 10 µM) alone or combined with EGCG (100 μM) for the indicated times. Medium glucose concentration, lipid accumulation, the levels of TNF-α, resistin, adiponectin and leptin and the expression of FOXO1, phosphorylated-FOXO1 (P-FOXO1), PPARγ, fatty acid synthase (FAS) were detected, respectively. The present study demonstrated that EGCG inhibited glucose uptake, lipid accumulation and adipokine secretion in a concentration-dependent manner during adipogenesis, which suggests that EGCG inhibits adipocyte's differentiation, maturation and functions. Moreover, EGCG also down-regulated the expression levels of PPARγ and P-FOXO1. Conversely, the PI3K activator reversed these changes caused by EGCG, suggesting that the inhibitory effects of EGCG may be mediated by PI3K-AKT-FOXO1 pathway to negatively regulate the expression of PPARγ. The findings will provide a solid foundation for EGCG to prevent and cure the obesity-associated diseases.

Epigallocatechin-3-gallate (EGCG), a major component in green tea, functions as extensive bioactivities including anti-inflammation, anti-oxidation, and anti-cancer. However, little is known about its anti-adipogenesis and underlying mechanisms. The purport of this study sought to investigate effects of EGCG on 3T3-L1 preadipocyte differentiation and to explore its possible mechanisms. The 3T3-L1 cells were induced to differentiate under the condition of pro-adipogenic cocktail with or without indicated EGCG concentrations (10, 50, 100, 200µM) for 2, 4, 6 and 8 days, respectively. Also, another batch of 3T3-L1 cells was induced under the optimal EGCG concentration (100µM) with or without SC3036 (PI3K activator, 10µM) or SC79 (AKT activator, 0.5µM) for 8 days. Subsequently, the cell viability was examined by MTT assay and the cell morphology was visualized by Oil red O staining. Finally, the mRNA levels including peroxisome proliferator activated receptor γ (PPARγ) and fatty acid synthase (FAS) were detected by quantitative real time PCR, while the protein levels of PPARγ, FAS, phosphatidylinositol 3 kinase (PI3K), insulin receptor substrate1(IRS1), AKT, and p-AKT were measured by immunoblotting analysis. Our results showed that EGCG inhibited adipogenesis of 3T3-L1 preadipocyte in a concentration-dependent manner. Moreover, the inhibitory effects were reversed by SC3036 or SC79, suggesting that the inhibitory effects of EGCG are mediated by PI3K-AKT signaling to down-regulate PPARγ and FAS expression levels. The findings shed light on EGCG anti-adipogenic effects and its underlying mechanism and provide a novel preventive-therapeutic potential for obesity subjects as a compound from Chinese green tea.

6-Gingerol (6-Gin), an active constituent of Zingiber officinale, has been reported to have anti-inflammatory, anti-oxidative, anti-cancerous etc. bioactivities. However, little is known about its endothelial protective effects and the underlying mechanisms. In this study, our purpose was to investigate the protective effects of 6-Gin and its underlying mechanisms. HUVECs were exposed to high glucose (HG, 33mM glucose) for 48h, followed by 50μM 6-Gin with or without LY294002 (10μM), AKT inhibitor IV (0.5μM) or L-NAME (5mM) for another 24h. Cell viability, levels of NO, LDH and ROS were detected. In addition, the expression levels of IKK, IRS-1, PI3K, AKT, eNOS and their phosphorylated proteins were measured by western blots. Compared with the control, HUVECs were significantly impaired by HG, characterized by decreased levels of the cell viability, NO, pY458-PI3K, pS473-AKT and pS1177-eNOS while increased levels of LDH, pS176-IKK, and p-S312-IRS-1. Conversely, 6-Gin remarkably protected HUVECs against HG-induced injury in a concentration- and time-dependent manner. However, the protective effects of 6-Gin were abolished by co-treatment with LY294002, AKT inhibitor IV or L-NAME at the HG state. Collectively, 6-Gin attenuated the injury of HUVECs induced by HG through the activation of PI3K-AKT-eNOS signal pathway. The findings provide a novel potential for 6-Gin to prevent and treat the angiopathy resulting from diabetes mellitus.

This study was designed to examine whether resveratrol exerts the protective effects on LPS and cigarette smoke (LC)-induced COPD in a murine model. In lung histopathological studies, H&E, Masson's trichrome, and AB-PAS staining were performed. The cytokines (IL-6, IL-17, TGF-β, and TNF-α) and inflammatory cells in BALF were determined. The Beclin1 level in the lungs of mouse was analyzed. Compared with the LC-induced mouse, the level of inflammatory cytokines (IL-17, IL-6, TNF-α, and TGF-β) of the BALF in the resveratrol + cigarette smoke-treated mouse had obviously decreased. Histological examination of the lung tissue revealed that the resveratrol treatment attenuated the fibrotic response and mucus hypersecretion. In addition, resveratrol inhibited the expression of the Beclin1 protein in mouse lungs. The presented findings collectively suggest that resveratrol has a therapeutic effect on mouse LC-induced COPD, and its mechanism of action might be related to reducing the production of the Beclin1 protein.