Xiexin Tang (XXT) is a classic Chinese medicine formula that can be used to treat Atherosclerosis (AS). This study aimed to investigate the mechanism by which XXT regulated AS lipid levels. Firstly, the mixture components of XXT were analyzed by High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Then, the AS model based on Apolipoprotein E knockout (ApoE-/-) mice was established. Cytokines related to lipid metabolism and bile acid metabolism were detected by Quantitative Real-time PCR (qRT-PCR). 16S rDNA gene sequencing was performed to analyze differential bacterial populations, and the mechanism of XXT regulation of bile acids affecting lipid metabolism was further explored by targeted metabolomics. Further, antibiotic-treated mice were used to investigate the role of gut microbiota in the anti-AS effect of XXT. The results showed that XXT attenuated the lipid levels and reversed the abnormal elevation of cytokines, such as hepatic lipid metabolism and inflammatory reaction in AS mice. XXT also repaired the gut barrier damage and reversed gut microbiota disorders in AS mice. Furthermore, the metabolic levels of bile acids were reshaped by XXT. Whereas, in the absence of gut microbiota, XXT failed to attenuate lipid levels and inhibit the expression of cytokines related to inflammation and bile acid metabolism in AS mice and failed to play a role in ultimately treating AS. In conclusion, XXT could effectively inhibit the inflammatory reaction and lipid accumulation in AS mice, and this effect was closely related to its remodeling of gut microbiota to regulate bile acid metabolism.

Midkine (MK) is a member of a small protein family that includes pleiotrophin. MK levels are elevated in obese patients and have a pro-arthrogenic effect through various pathophysiological processes including vascular inflammation and atherogenesis. This study aimed to investigate the association between serum MK levels and several atherosclerotic risk factors in patients with type 2 diabetes mellitus (T2DM).

Ninety subjects were enrolled in this study, comprising 60 T2DM patients and 30 age-matched healthy subjects (HS). The patients were categorized into two groups based on dyslipidemia: group 1 consisted of 30 patients with dyslipidemia, while group 2 included 30 patients without dyslipidemia. Laboratory tests were conducted using routine assays at the National Diabetes Center. MK levels were analyzed using enzyme-linked immunosorbent assay (ELISA).

MK levels were significantly higher in patients with dyslipidemia compared to those without dyslipidemia and HS (P ≤ 0.0001). A significant negative correlation was observed between MK levels and the atherogenic index of plasma (AIP), Castelli's risk index-1 (CRI-I), and Castelli's risk index-2 (CRI-II) (r = - 0.489, p = 0.005; r = - 0.465, p = 0.008; r = - 0.421, p = 0.018, respectively) in patients with dyslipidemia. Furthermore, a significant positive correlation was found between MK levels and HDL-C (r = 0.524, p = 0.002) in patients without dyslipidemia. MK, AIP, and CRI-I were identified as predictors of atherosclerosis in DM patients, with MK indicating very good discriminate power (AUC = 0.805) in identifying T2DM patients with dyslipidemia at a cut-off value of ≤ 4.457 ng/ml.

These findings suggest that MK could be considered a predictive biomarker for dyslipidemia associated with DM. MK levels correlate significantly with atherogenic risk factors, indicating its potential as a sensitive risk predictor for atherosclerosis in patients with T2DM.

Malignant melanoma, a highly malignant tumor predominantly found on the skin surface, has exhibited an alarming rise in both incidence and mortality rates annually since 2012. Despite its relatively low occurrence among skin malignancies, the mortality rate of malignant melanoma remains disproportionately high. The prognosis relies heavily on early stage detection, with a significant disparity in survival rates between stage I and stage IV patients. Studies exploring insulin resistance (IR) as a potential risk factor for malignant melanoma are scarce. The present study therefore investigated the association between the triglyceride glucose (TyG) index, an indicator of IR, and malignant melanoma incidence. Retrospective data from patients diagnosed with malignant melanoma at the First Affiliated Hospital of Nanjing Medical University (Nanjing, China) between January 2019 and January 2024 were collected. Basic information, including age, sex and body mass index, and hematological test results, such as those for fasting triglycerides and fasting blood glucose, were analyzed. Logistic regression analysis and receiver operating characteristic (ROC) curve analysis were employed to explore the association between melanoma risk and the TyG index. A total of 403 participants, including 272 patients with malignant melanomas and 131 patients with nevi, were included in the study. The melanoma group exhibited significantly higher levels of the TyG index compared with the control group (P<0.001). Univariate and multivariable logistic regression analyses revealed the TyG index as an independent risk factor for melanoma incidence (OR, 6.33; 95% CI, 3.56-11.27; P<0.001). Incidence rates of melanoma significantly increased across tertiles of the TyG index (P<0.001). The ROC curve analysis identified a clinically acceptable predictive cutoff point for the TyG index. The present study therefore provides evidence that the TyG index is a significant risk factor for the incidence of malignant melanoma. The findings underscore the potential utility of the TyG index as a biomarker for diagnosing melanoma and suggest new avenues for melanoma treatment strategies.

Atherosclerosis (AS) is the pathological basis of many cardiovascular and cerebrovascular diseases. To further the investigation of treatments for AS, this research analyzed the role of lncRNA MBNL1-AS1.

MBNL1-AS1 expression in the serum of AS patients and healthy controls were detected by qPCR. Its diagnostic value in AS was assessed by receiver operating characteristic curve (ROC). Additionally, the link between MBNL1-AS1, carotid intima-media thickness (CIMT) and C-reactive protein (CRP) was examined using the Spearman correlation coefficient. The prognostic value of MBNL1-AS1 in AS was assessed using the Kaplan-Meier survival curve and univariate and multivariate Cox regression analysis.

The present study consisted of 103 patients with AS and 92 healthy patients (HC) and comparison of baseline data between the two groups revealed no remarkable difference (P>0.05) except for CRP (P<0.0001). The serum of AS patients exhibited a considerably higher expression of MBNL1-AS1 in comparison to the HC group. Furthermore, MBNL1-AS1 was highly expressed in patients following higher CIMT and CRP values, which was positively linked with both, respectively (r>0.5, P<0.001). Meanwhile. MBNL1-AS1 has enhanced diagnostic accuracy in AS patients (AUC=0.893) and can be utilized as an independent prognostic factor for AS. Patients with high MBNL1-AS1 expression have a higher likelihood of cardiovascular events. (log rang P=0.0025).

Elevated MBNL1-AS1p can be used as a potential marker for the clinical diagnosis of AS and is linked to a poor prognosis of AS.

5-Methoxytryptophan (5-MTP), a new endothelial factor with vasoprotective and anti-inflammatory effects, reduces aortic chondrogenesis and calcification during atherosclerosis. The aim of this study was to investigate the effects of aerobic exercise on aortic chondrogenesis and calcification during atherosclerosis in rats. To investigate the effect of aerobic exercise on the expression of 5-MTP/P38 MAPK signaling pathway. To lay a theoretical foundation for the therapeutic effect of exercise in rat atherosclerosis model.

Establishment of a rat model of atherosclerosis using a high-fat diet combined with intraperitoneal injection of vitamin D3 (VD3). The aerobic exercise group underwent moderate-intensity aerobic exercise on an exercise treadmill for 8 weeks, while the atherosclerosis model group and the control group did not exercise. After exercise, blood and aortic samples were collected from all rats to evaluate the levels of serum triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDLC), aortic chondrogenesis, calcification, 5-MTP level, collagen II, P38MAPK, pp38 MAPK, and IL-6 protein content.

(1)8 weeks of aerobic exercise significantly reduced aortic chondrogenesis, area of calcification, serum LDL-C, TC levels, atherosclerotic index and serum IL-6 levels in rats (p < 0.01), and lowered TG levels (p < 0.05);(2)8 weeks of aerobic exercise significantly increased aortic 5-MTP levels (p < 0.01) and decreased the content of aortic pp38MAPK, collagen II and IL-6 proteins significantly (p < 0.01). The pp38MAPK/P38MAPK ratio was also decreased (p < 0.01).

8 weeks of aerobic exercise training improved dyslipidemia and reduced aortic chondrogenesis and calcification formation in AS rats. The mechanism may be related to increasing aortic 5-MTP levels and inhibiting the P38MAPK/ IL-6 signaling pathway.

Dynamic high-pressure microfluidization (DHPM) is an emerging treatment technology and has been widely used for the recovery of natural polysaccharides. The aim of the present contribution is to discuss the DHPM-assisted extraction and processing of polysaccharides from some foods and by-products by reviewing the instrument and working principle, procedures, key parameters, and effects of DHPM on the structures, food properties, and bioactivities of resulting polysaccharides. It was found that a DHPM instrument with Z-type chamber is preferable for extracting polysaccharides, and a DHPM with Y-type chamber is applicable for processing polysaccharides. The solid-to-liquid ratio (or concentration), pressure, and number of passes are the key parameters influencing the outcome of DHPM extraction and processing. The DHPM under suitable conditions is conducive to boosting the extraction yields of polysaccharides, enriching the carbohydrates and uronic acids in polysaccharides, lowering the protein impurities, and transforming insoluble dietary fibers into soluble ones. In most cases, DHPM treatment improved the food properties of polysaccharides via decreasing viscosity, molecular weight, and particle size, as well as losing the surface morphology. More importantly, DHPM is a mild treatment technique that barely affects the chain backbones of polysaccharides. DHPM-assisted extraction and processing endowed polysaccharides with enhanced antioxidant, hypolipidemic, and hypoglycemic activities, exhibiting potential for the treatment of cardiovascular disease. In addition, DHPM-treated polysaccharides exerted certain potential in whitening cosmetics via inhibiting tyrosinase. In conclusion, DHPM is a mild, efficient, and green technology to recover and modify polysaccharides from natural resources, especially foods and by-products. © 2025 Society of Chemical Industry.

People with diabetes mellitus (DM) are at a higher risk (2-4 times) for cardiovascular (CV) death and atherosclerotic CV disease (ASCVD) than the general population. A multifactorial approach is recommended to reduce CV risk. Since low-density lipoprotein cholesterol (LDL-C) is a major causal and cumulative risk factor for ASCVD, the management of lipids is a fundamental element in global risk reduction. Intensive lipid lowering therapy (LLT), such as the addition of a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), to achieve LDL-C goals and reduce the risk of first or recurrent CV events in people with DM at very high CV risk (VHCVR) of ASCVD (i.e. acute coronary syndrome, coronary artery disease, peripheral artery disease) is often required. Alirocumab, a monoclonal antibody against PCSK9, as lipid-lowering therapy offers significant CV benefits and a favourable safety profile in people with DM and a VHCVR, with or without previous CV events. This review highlights the role of LDL-C in the complex pathogenesis of atherosclerosis, summarises the guidelines for CV risk reduction related to LDL-C in patients with DM and a VHCVR, and focuses on the role of alirocumab in managing LDL-C and consequent CV risk reduction in these patients.

This study aims to evaluate the correlation between the uric acid (UA) to albumin (ALB) ratio (UAR) and carotid atherosclerosis (CAS) in patients with type 2 diabetes mellitus (T2DM), as well as to assess the predictive value of UAR for CAS.

A cross-sectional, single-center study was conducted, retrospectively analyzing hematological parameters from 259 T2DM patients with CAS (T2DM-CAS) and 131 T2DM patients without CAS (T2DM-WCAS). Carotid intima-media thickness (IMT) and carotid plaques (CAP) were measured using Doppler ultrasound.

The UAR level in the T2DM-CAS group was significantly higher than that in the T2DM-WCAS group (P <  0.001). Multivariate logistic regression analysis revealed that UAR is an independent risk factor for T2DM-CAS (P <  0.001). The area under the ROC curve (AUC) for UAR in predicting T2DM-CAS was 0.712, with a Youden index of 0.278.

High levels of UAR are closely associated with the occurrence of T2DM-CAS and may serve as a useful biomarker for predicting T2DM-CAS.

Stromal interaction molecule 1 (STIM1), a key regulator of calcium signaling located in the endoplasmic reticulum, is crucial for platelet function. While elevated STIM1 expression is observed in platelets from diabetic patients, its role in diabetes-induced platelet hyperreactivity remains unclear. In this study, we found a positive correlation between STIM1 expression and agonist-induced platelet aggregation in platelets from patients with type 2 diabetes mellitus (T2DM). Platelets with high STIM1 expression exhibited enhanced aggregation, P-selectin release, integrin αIIbβ3 activation, spreading, and clot retraction compared to those with low STIM1 expression. Similar findings were observed in db/db mice. Furthermore, the store-operated calcium entry channel inhibitor CM4620 demonstrated superior antiplatelet and antithrombotic efficacy compared to aspirin in both db/db mice and patients with T2DM. Our results suggest that elevated STIM1 expression contributes to enhanced platelet reactivity in diabetes, and targeting STIM1 may offer a promising novel therapeutic approach for thrombosis prevention in this patient population.

Atherosclerosis is a closely related complication of diabetes mellitus (DM), driven by endothelial dysfunction, inflammation, and oxidative stress. The progression of atherosclerosis is accelerated by hyperglycemia, insulin resistance, and hyperlipidemia. Novel antidiabetic agents, SGLT2 inhibitors, and GLP-1 agonists improve glycemic control and offer cardiovascular protection, reducing the risk of major adverse cardiovascular events (MACEs) and heart failure hospitalization. These agents, along with nonsteroidal mineralocorticoid receptor antagonists (nsMRAs), promise to mitigate metabolic disorders and their impact on endothelial function, oxidative stress, and inflammation. This review explores the potential molecular mechanisms through which these drugs may prevent the development of atherosclerosis and cardiovascular disease (CVD), supported by a summary of preclinical and clinical evidence.

Epimedium polysaccharide (EPS) is a bioactive compound derived from the traditional Chinese herb Epimedium brevicornum. The objective of this study was to investigate the protective effects of EPS on ulcerative colitis (UC) and to elucidate the underlying mechanisms involved.

The findings showed that EPS treatment mitigated UC symptoms, including weight loss, anal bleeding, elevated disease activity index (DAI), and colon shortening. Hematoxylin and eosin (H&E) and Alcian blue-periodic acid-Schiff (AB-PAS) staining demonstrated that EPS alleviated histopathological damage and improved the integrity of the colonic mucosa. Mechanistically, EPS was found to substantially decrease inflammation by inhibiting the Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway and to alleviate oxidative stress through modulation of the Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (Keap1/Nrf2) pathway. Notably, EPS failed to exert protective effects against dextran sulfate sodium (DSS)-induced UC in Nrf2-knockout (Nrf2-/-) mice. Additionally, Western blotting and immunohistochemical analysis demonstrated that EPS facilitated autophagy via the adenosine monophosphate-dependent protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway. In vitro experiments revealed that EPS effectively suppressed lipopolysaccharide (LPS)-mediated cellular damage and oxidative stress by regulating Keap1/Nrf2 pathway. Transcriptomic analysis of LPS-treated Caco-2 cells following EPS treatment revealed a significant up-regulation of Nrf2 expression.

In conclusion, the findings of this study suggest that EPS exerts protective effects against DSS-induced UC through the inhibition of the TLR4/NF-κB signaling pathway, regulation of the Keap1/Nrf2 pathway, and promotion of autophagy via the AMPK/mTOR pathway. Consequently, EPS may represent a potential therapeutic target for the treatment of UC. © 2024 Society of Chemical Industry.

Stroke poses a substantial threat to global public health. The triglyceride glucose-waist height ratio (TyG-WHtR), which incorporates the TyG metric with obesity-related WHtR, has demonstrated superior diagnostic and predictive value compared to the TyG index alone. Nevertheless, there is still a lack of in-depth exploration into the relationship between TyG-WHtR and stroke. This study seeks to address this gap by extracting information from the National Health and Nutrition Examination Survey (NHANES) to elucidate the potential association between TyG-WHtR levels and stroke.

This study included 8,757 individuals from four research cycles conducted between 2011 and 2018. To examine the potential relationship between TyG-WHtR and stroke, we conducted multivariable logistic regression analysis. In addition, smooth curve fitting was applied to display the nonlinear association. Subgroup analyses and sensitivity analyses contributed to examining the robustness and consistency of the relationship between TyG-WHtR and stroke. The receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic capability of TyG-WHtR and TyG.

After adjusting for relevant covariates, a positive association between TyG-WHtR levels and stroke occurrence was observed (OR: 1.26, 95% CI: 1.02-1.55). Specifically, each unit increase in TyG-WHtR was associated with a 26% higher likelihood of stroke. The findings of sensitivity analysis further demonstrated the stability of this positive relationship. Subgroup analysis revealed that this association was significant among participants who did not engage in moderate exercise and those without coronary heart disease or angina pectoris. ROC analysis demonstrated that TyG-WHtR exhibited superior predictive value compared to TyG.

This study identified an association between elevated TyG-WHtR levels and an increased prevalence of stroke, suggesting that TyG-WHtR may serve as a valuable predictive tool for stroke risk, with potential implications for clinical prevention and early intervention.

Cardiovascular disease (CVD) represents a significant global health challenge, characterized by high incidence rates and substantial morbidity and mortality. A newer index, the Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index, has been proposed as a potential diagnostic tool for metabolic disorders but has not been investigated for its ability to predict CVD risk. This study aims to evaluate the predictive efficacy of the CHG index in comparison to the well-established Triglyceride-Glucose (TyG) index.

In this cohort study, 6249 adults aged 45 and older were recruited from the CHARLS database, with data collected from 2011 to 2020. CVD events were tracked over a nine-year follow-up. The TyG and CHG indices were calculated, and their relationships with CVD risk were assessed using univariate and multivariate Cox regression models. Additionally, restricted cubic spline (RCS) analysis was performed to further explore these associations. Receiver operating characteristic (ROC) analysis was conducted to compare the predictive performance of both indices, and subgroup analysis evaluated their applicability in different populations.

Among the 6249 participants, 1667 (26.68%) developed CVD during the nine-year follow-up. In unadjusted Cox regression models, the TyG index had a hazard ratio (HR) of 1.18 (95% confidence interval CI 1.10-1.27, p < 0.001), while the CHG index showed a higher HR of 1.35 (95% CI 1.21-1.51, p < 0.001). In the adjusted models, the relationship still persisted. The RCS models showed that the TyG index exhibited a non-linear relationship with the risk of CVD, while the CHG index demonstrated a positive linear correlation. ROC curve analysis revealed comparable predictive performance for both indices. The subgroup analysis indicated that there was no interaction between the subgroups and the both indices (p for interaction > 0.05).

An elevated CHG index is significantly correlated with an increased risk of CVD, demonstrating a linear relationship. Furthermore, it exhibits predictive capabilities comparable to those of the TyG index in assessing CVD risk.

Not applicable.

Endothelin-1 (ET-1) levels are altered in atherosclerosis, while the roles of the endothelin receptors ETAR and ETBR during the pathogenesis of atherosclerosis remain unclear. Therefore, the focus of this study was to clarify how endothelin receptors are expressed in advanced human atherosclerotic plaques and how this is related to atherosclerotic risk factors. Ex vivo expression analysis was performed by quantitative real-time PCR (qRT-PCR) of 98 atherosclerotic plaques and controls that were obtained from adult patients undergoing vascular surgery. Correlation analyses of atherosclerosis-promoting factors were accomplished using a linear regression model. We found an overall reduced expression of ET receptors and smooth muscle actin (SMA), a marker of healthy vascular smooth muscle cells, in atherosclerotic plaques, whereas the levels of ET-1 and matrix metalloproteinase 2 (MMP-2), a marker of atherosclerosis progression, remained unchanged. Reduced expression was predominantly correlated with hypertension, which affects both receptors as well as SMA. Age, body mass index (BMI) and gender also correlated with either ETAR, ETBR or SMA expression in advanced plaques. In contrast, no effect of diabetes mellitus or smoking was found, indicating an ancillary effect of those risk factors. The results of our study indicate that endothelin receptor expression during the pathogenesis of atherosclerosis is predominantly correlated with hypertension.

Atherosclerosis risk is elevated in diabetic patients, but the underlying mechanism such as the involvement of macrophages remains unclear. Here, we investigated the underlying mechanism related to the pro-inflammatory activation of macrophages in the development of diabetic atherosclerosis. Bioinformatics tools were used to analyze the macrophage-related transcriptome differences in patients with atherosclerosis and diabetic mice. LDLR-/- mice with DDIT4 depletion were generated and fed a Western diet to induce atherosclerosis. DDIT4 expression was elevated in diabetic mice and patients with atherosclerosis. Macrophage proinflammatory factors F4/80, Il-6, and TNFα were reduced in DDIT4-/-LDLR-/- mice and necrotic areas were decreased in the aortic root. Atherosclerotic plaque stability was increased in DDIT4-/-LDLR-/- mice, as evidenced by increased collagen and smooth muscle cell content. DDIT4, regulated by ETV5, acted on macrophages, affecting lipid accumulation, migration capacity, and pro-inflammatory responses. Knockdown of ETV5 increased expression of DDIT4 and pro-inflammatory factors in macrophages, increased necrotic core area in the aortic root, and decreased stability of atherosclerotic plaques in mice, which was abated by DDIT4 knockdown. The findings provide new insight into how diabetes promotes atherosclerosis and support a model wherein loss of ETV5 sustains transcription of DDIT4 and the pro-inflammatory activation of macrophages.

Ischemic stroke is a prevalent clinical condition that poses a significant global challenge. Developing innovative strategies to address this issue is crucial. Annexin A1 (ANXA1), a key member of the annexin superfamily, performs various functions, such as inhibiting inflammatory factor release, promoting phagocytosis, and blocking leukocyte migration. Evidence indicates that ANXA1 plays a pivotal role in the pathogenesis of ischemic stroke. The present article reviews involvement of ANXA1 in anti‑atherosclerosis, inflammatory processes, blood‑brain barrier protection, platelet aggregation and anti‑apoptotic mechanisms. The potential applications of ANXA1 in treating ischemic stroke are also explored.

The endoplasmic reticulum (ER) is a crucial cellular organelle involved in protein synthesis, folding, modification, and transport. Exposure to internal and external stressors can induce endoplasmic reticulum stress (ERS), leading to abnormal protein folding and ER malfunction. This stress can disrupt lipid synthesis, metabolism, and transport processes. Fatty acid oxidation is the primary energy source for the renal system. When energy intake exceeds the storage capacity of adipose tissue, lipids accumulate abnormally in non-adipose tissues, including kidneys, liver, and pancreas. Lipids accumulate in the kidneys of nearly all cell types, including thylakoid membranous, pedunculated, and proximal renal tubular epithelial cells. Intracellular free fatty acids can significantly disrupt renal lipid metabolism, contributing to ischemia-reperfusion acute kidney injury, diabetic nephropathy, renal fibrosis, and lupus nephritis. Consequently, this study delineated the primary signaling pathways and mechanisms of the ERS-induced unfolded protein response, explored the mechanistic link between ERS and lipid metabolism, and elucidated its role in renal lipid metabolism. This study aimed to offer new perspectives on managing and treating renal disorders.

Disorders of glycolipid metabolism are important pathogenic factors leading to coronary artery disease, and there is no safe and effective comprehensive treatment, while acupuncture has a certain efficacy in heart disease and disorders of glycolipid metabolism. To assess the effects of acupuncture on glycolipid metabolism in patients with coronary heart disease, we conducted a systematic review and meta-analysis.

From the time of library construction to August 18, 2023, Searches were conducted in eight databases, with no language restriction. Only RCTs that included acupuncture as a sole or secondary effect on glucose-lipid metabolism in coronary heart disease were included.Our primary outcome indicators were Low-density lipoprotein cholesterol(LDL-C), Hemoglobin A1c(HbA1c). Our analyses were conducted in strict accordance with the PRISMA statement, and the researchers used the Cochrane Handbook for literature screening and data extraction, the "Risk of Bias" tool (ROB.2) for assessing risk of bias, and RevMan (version 5.3) for meta-analysis of outcome metrics, and the GRADE criteria for assessing quality of evidence. Assessing the quality of acupuncture literature using the Standards for reporting interventions in clinical trials of acupuncture.

Our analysis included 18 eligible RCTs (N = 1346 participants). For the primary outcome metrics, acupuncture combined with standard treatment was effective in reducing LDL-C (SMD =-0.56; 95 % CI, -0.75 to -0.38; P < 0.00001), and HbA1c (MD = -1.15; 95 % CI, -1.73 to -0.58; P < 0.0001). For secondary outcome measures, combination therapy improved TC (SMD = -0.97; 95 % CI, -1.44 to -0.51; P < 0.0001), TG (MD = -0.39; 95 % CI, -0.58 to -0.20; P < 0.0001), hs-CRP (MD = -0.98; 95 % CI, -1.43 to -0.52; P <0.0001), 2hPG (MD = -1.45; 95 % CI, -1.74 to -1.16; P < 0.00001), and ORR (RR, 1.27; 95 % CI, 1.19-1.36; P < 0.00001) levels more than standard therapy alone.However, the combination therapy did not prevail in lowering HDL-C (MD = 0.11; 95 % CI, 0.07-0.14; P < 0.00001) compared with standard therapy alone. Meanwhile heterogeneity analysis showed that After coronary heart disease intervention, acupuncture was able to reduce TC (SMD = -0.85; 95 % CI, -1.37 to -0.33; P = 0.001), TG (MD = -0.14; 95 % CI, -0.24 to -0.04; P = 0.004) levels, but did not dominate in lowering LDL-C.

Acupuncture effectively regulates glycolipid metabolism in coronary artery disease, serving as an adjuvant treatment. It may aid post-PCI healing via lipid metabolism regulation, but rigorous, large-scale, long-term RCTs are needed for validation.

The global rise in diabetes prevalence has significantly contributed to the increasing burden of atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality in this population. Diabetes accelerates atherosclerosis through mechanisms such as hyperglycemia, oxidative stress, chronic inflammation, and epigenetic dysregulation, leading to unstable plaques and an elevated risk of cardiovascular events. Despite advancements in controlling traditional risk factors like dyslipidemia and hypertension, a considerable residual cardiovascular risk persists, highlighting the need for innovative therapeutic approaches. Emerging treatments, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, epigenetic modulators, and RNA-based therapies, are showing promise in addressing the unique challenges of diabetes-associated ASCVD. Precision medicine strategies, such as nanoparticle-based drug delivery and cell-specific therapies, offer further potential for mitigating cardiovascular complications. Advances in multiomics and systems biology continue to deepen our understanding of the molecular mechanisms driving diabetes-associated atherosclerosis. This review synthesizes recent advances in understanding the pathophysiology and treatment of diabetes-related atherosclerosis, offering a roadmap for future research and precision medicine approaches to mitigate cardiovascular risk in this growing population.

Ischemic heart disease (IHD) is the leading cause of mortality in the world with an increasing incidence. One of the interventions to treat IHD is coronary artery bypass grafting (CABG) and people with diabetes mellitus (DM) account for approximately one quarter of all patients who undergo coronary revascularization. Furthermore, people with DM have a higher risk of mortality due to heart failure (HF).

We aim to describe the risk of developing HF after CABG in patients with versus without DM.

Through a large nationwide register-based cohort study, patients who underwent CABG from January 1, 2000 to December 31, 2020 were included. In addition to Cox regression, g-formula methods based on multivariable Cox regression were performed to estimate the absolute risk (AR) and risk difference (RD) of the association between DM status and HF outcome, and between DM status and mortality.

A total of 34,855 patients were included in this study, consisting of 6909 (19.8%) DM patients. The AR of HF after CABG in the 10th year was 35.1% versus 26.4% for patients with versus without DM (p < 0.001), respectively. The RD of HF for each exceeding year (3.7 percentage point (pp.) in the 1st year versus 8.6 pp. in the 10th year) was higher for patients with DM compared to those without DM.

The risk of HF was significantly higher up to ten years after CABG in patients with DM compared to those without DM.

Insulin resistance (IR) has emerged as a risk factor for coronary artery disease (CAD), but there are currently insufficient data on the association of non-insulin-based IR indexes [triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, triglyceride and glucose (TyG) index, and metabolic score for IR (METS-IR)] with the postoperative prognosis in patients undergoing coronary artery bypass grafting (CABG). Therefore, the present study aimed to examine the predictive power of the above non-insulin-based IR indexes for postoperative prognosis of CABG patients, and to further compare the predictive power of the three indexes. This study included 1472 consecutive CABG patients from June 2014 to January 2019. These patients were divided into two groups based on major adverse cardiovascular events (MACE): without MACE (n = 1136) and with MACE (n = 336). Formulas were used to calculate TyG index, TG/HDL-C, and METS-IR. The Cox regression was done. The study examined how TyG index, TG/HDL-C, and METS-IR improved model performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were used to evaluate this. The evaluation of model goodness-of-fit was conducted by employing the Akaike information criterion (AIC), Bayesian information criterion (BIC), and χ2 likelihood ratio test. During follow-up, 336 patients experienced the MACE. The associations of TyG index, TG/HDL-C, and METS-IR with MACE were significant. Patients with higher TyG index were at higher risk of MACE (Kaplan-Meier analysis: log-rank P < 0.001; Cox regression: HR = 2.077; 95% CI 1.549-2.784, P < 0.001). The TyG index had the highest area under the curve (AUC) value of 0.593 (95% confidence interval [CI]: 0.557-0.629). The addition of the TyG index yielded a significant improvement in prognostic prediction and model fit [continuous NRI (95% CI): 0.274 (0.1533-0.395), P < 0.001; IDI (95% CI): 0.01(0.0042-0.0159), P < 0.001; AIC: 4662.01; BIC: 4738.35; likelihood ratio test: P < 0.001). The study highlights the prognostic significance of the TyG index, TG/HDL-C, and METS-IR in individuals with CABG. Among these markers, the TyG index had the most robust capacity for predicting MACE. It resulted to be a valuable marker for risk classification and long-term outcome prediction.

Traditional risk factors cannot accurately predict cardiovascular events (CVE) in type 2 diabetes (T2D). The LIPOCAT study aimed to prospectively evaluate the clinical utility of advanced lipoprotein characteristics and glycoproteins to predict future cardiovascular events (CVE) in a large cohort of subjects with type 2 diabetes mellitus (T2D).

From four different Spanish prospective cohorts, a total of 933 T2D subjects were selected to form the LIPOCAT study. Advanced 1H-Nuclear Magnetic Resonance (1H-NMR) analysis included lipoprotein (Liposcale®) and glycoprotein (Glycoscale) profiling. Random forest classification models and Area Under the Receiver Operating Characteristics (AUROC) analysis were used to assess the differential contribution of advanced variables in predicting CVE. Validation was performed using an external cohort.

Out of 933 T2D subjects, 104 reported a CVE during follow-up. Analysis of Liposcale®/Glycoscale uncovered elevations in the circulating VLDL-cholesterol(C), remnant IDL-triglycerides (TG) and LDL-TG in subjects with CVE, along with glycoproteins (Glyc) A and B. Moreover, the incorporation of advanced Liposcale® variables to a base model constructed with traditional risk factors significantly improved the prediction of CVE, as evidenced by 1.5-fold increase in the C statistic (AUROC), reaching AUROC values of 0.756. In the independent validation cohort, similar improvements in AUROC values were observed by adding the advanced variables to the traditional models.

Advanced 1H-NMR analysis revealed previously hidden lipoprotein and glycoprotein characteristics associated with CVE in T2D subjects.

Sphingosine 1-phosphate (S1P) is a key mediator of lipid signaling with strong immunomodulatory and anti-inflammatory effects. Circulating S1P levels including S1P in high-density lipoproteins (HDL) were demonstrated to be inversely associated with cardiovascular diseases (CVD). However, no studies are available regarding a potential implication of S1P on the risk of CVD in type 2 diabetes (T2D). The objective of this study is to determine if the increased CVD risk in T2D may involve an alteration of circulating S1P species as well as their precursors.

A total of 168 and 31 patients with T2D (154 men and 45 women) with available Coronary artery calcification (CAC) score from the DIACART and CERABIAB cohorts, respectively, were included in the study. Quantification of S1P species and their precursors was carried out by LC-MS/MS in plasma and isolated HDL. CAC score was modeled as a binary variable (0/1 below or equal/above 100) using CAC < 100 for reference. S1P species or precursors were modeled as binary variables dichotomized at the median (0/1: below or equal/above the median). The relationships between S1P species and CAC score modeled as a binary variable (below or equal/above 100) was evaluated by linear regression analyses. In vitro experiments were conducted to evaluate the contribution of HDL-S1P content on anti-inflammatory properties of HDL particles.

Multivariate analysis revealed that plasma S1P levels, especially d18:1-S1P, and sphingosine in HDL were inversely associated with the high risk of CVD (CAC > 100) in patients with T2D. Clustering of HDL according to their concentration in S1P species and their precursors revealed that S1P-impoverished HDL is a major feature of patients with a CAC > 100. In vitro analysis of monocyte adhesion and inflammation in human umbilical vein endothelial cells as well as inflammatory phenotype of human macrophages demonstrated that low HDL-S1P exhibited impaired anti-inflammatory properties in comparison to high HDL-S1P.

This study unraveled that circulating S1P and their precursors are biomarkers of coronary atherosclerosis in T2D, which may underlie the lower abundance of S1P and anti-inflammatory activities of HDL. Trial registration ClinicalTrials.gov number, NCT02431234.

Oral insulin administration has gained attention as a promising alternative to injections. However, its effectiveness is hindered by the major challenge of degradation by gastric acid. Biopolymer-based nanocarriers have been explored as a solution to address this challenge. This study examines levan, a biopolymer derived fromBacillus licheniformisBK1, for its viability as a nanocarrier for insulin. Levan was modified through acetylation, and both levan (I-Lv) and its acetylated (I-ALv) form were utilized as carriers for insulin in a nanoparticles (NPs) delivery system. The resulting NPs were spherical, with diameters ranging from 250 to 500 nm and encapsulation efficiencies of 78.64% and 88.30%, respectively. The insulin release from I-Lv NPs in simulated gastric fluid exhibited a burst release pattern that was more rapid than that of I-ALv. To further evaluate, the conformational stability of insulin in NPs was analyzed by measuring the transition enthalpy of secondary and tertiary structures. The stability of the secondary structure was determined through alpha-helix content using circular dichroism, while the tertiary structure stability was evaluated via the fluorescence intensity of tryptophan residues. The result revealed that insulin in I-ALv NPs exhibited enhanced conformational stability compared to free-state (FS) insulin and I-Lv NP, with transition enthalpies of 0.91 ± 0.62 and 4.42 ± 0.46 kcal mol-1for secondary and tertiary structures, respectively. Moreover, preliminaryin vivostudies revealed that I-ALv had a significant impact compared to FS insulin and I-Lv, demonstrating reduction in blood glucose levels. These findings highlight the potential of I-ALv as a promising candidate for antidiabetic therapy and an efficient oral delivery system.

Continuous glucose monitoring (CGM) and flash glucose monitoring (FGM) are widely used in diabetes management and increasingly being considered for type 2 diabetes mellitus (T2DM) prevention. This scoping review aims to summarize the literature published to date on CGM and FGM use in adults at risk of T2DM.

A systematic search of four databases (CINAHL, PsycINFO, MEDLINE, Cochrane Library) was conducted, covering studies from 1985 to 2024. Eligible studies used CGM or FGM in interventional settings targeting adults at risk of T2DM. Rayyan software facilitated article screening, and the Johns Hopkins Evidence-Based Practice tool assessed study quality.

From 13 644 articles, 12 studies were included, reporting on 1144 participants (353 at-risk, mean age 47 ± 12.8 years) across eight countries. Ten studies employed FGM, focusing on health-related behaviors (diet, physical activity, or both). Significant improvements in glucose control and anthropometrics were reported in 75% and 50% of the studies, respectively, along with reductions in glycated hemoglobin, fasting glucose, and insulin resistance. Seven studies used qualitative methods, with recurrent themes including perceived benefits and motivators for behavior change and acceptability and feasibility of device use. Three studies were rated as "high" level and scored a "B" for evidence quality, while the remaining studies were lower for both level and evidence quality.

Existing published studies deploying glucose monitoring technologies show promise in supporting interventions aimed at preventing T2DM in at-risk adults. Further robust studies are required to confirm the long-term acceptability and efficacy of these technologies.

Diabetes mellitus is a chronic metabolic disorder that affects multiple organs, including the stomach. This research examines the effects of naringin and/or zinc on stomach and pancreatic tissues of streptozotocin-induced diabetic rats. Type 2 diabetes is induced by intraperitoneal injection of nicotinamide and streptozotocin. Three weeks after diabetes induction, rats receive eight weeks of treatment. Malondialdehyde and total antioxidant capacity are estimated colorimetrically. Asprosin and P-selectin levels are assessed via ELISA. Quantitative RT-PCR analysis of nuclear factor kappa B (NF-кB), peroxisome proliferator-activated receptor gamma (PPAR γ), and nuclear factor erythroid 2-related factor 2 (Nrf-2) genes is carried out. Tumor necrosis factor-alpha (TNF-α) is assessed immunohistochemically, and stomach and pancreatic tissues are examined histologically. Combined naringin and zinc treatment significantly reduces gastric Malondialdehyde, serum asprosin, and P-selectin levels in serum, stomach, and pancreas compared to diabetic rats. Additionally, gastric NF-кB expression is significantly lower, while PPAR γ and Nrf-2 expressions are significantly higher compared to diabetic rats. Immunohistochemical analysis and histopathological examination confirm these findings. In conclusion, combined naringin and zinc treatment significantly improves gastric alterations in diabetic rats by reducing oxidative stress and inflammation. Nonetheless, it shows no additional impacts on pancreatic tissue compared to naringin or zinc alone.

Type 2 diabetes (T2D) is increasingly recognized as a significant global health challenge, with a rising prevalence of hyperlipidemia among diabetic patients. Effectively predicting and reducing the risk of hyperlipidemia in T2D patients to mitigate their cardiovascular risk remains an urgent issue.

The research sought to determine early clinical indicators that could predict the onset of hyperlipidemia in patients with T2D and to establish a predictive model that integrates clinical and laboratory indicators.

A cohort of T2D patients, excluding those with pre-existing hyperlipidemia or confounding factors, was analyzed. Clinical and laboratory data were used in a LASSO regression model to select key predictive variables. A nomogram was then constructed and evaluated using receiver operating characteristic (ROC) analysis and calibration.

Among 269 participants, PCSK9 levels were significantly elevated in T2D patients with hyperlipidemia and exhibited a positive correlation with several lipid markers. LASSO regression identified six predictors: BMI, TG, TC, LDL-C, HbA1c, and PCSK9. The nomogram model exhibited robust predictive performance (AUC, 0.89 (95% CI: 0.802-0.977)) and showed good calibration.

This method effectively predicts the risk of hyperlipidemia in patients with T2D and provides a valuable tool for early intervention. PCSK9, as a key predictor, highlights its potential role in the pathogenesis of diabetes with hyperlipidemia and offers new avenues for targeted therapy.

Atherosclerosis, a condition characterized by the accumulation of lipids and a culprit behind cardiovascular events, has long been studied. However, in recent years, there has been an increase in interest in its initiation, with researchers shifting focus from traditional pathways involving the vascular infiltration of oxidized lipids and towards the novel presence of chronic inflammatory pathways. The accumulation of pro-inflammatory cytokines, in combination with the activation of transcription factors, creates a positive feedback loop that drives the creation and progression of atherosclerosis. From the upregulation of the nod-like receptor protein 3 (NLRP3) inflammasome and the Notch and Wnt pathways to the increased expression of VEGF-A and the downregulation of connexins Cx32, Cx37, and Cx40, these processes contribute further to endothelial dysfunction and plaque formation. Herein, we aim to provide insight into the molecular pathways and mechanisms implicated in the initiation and progression of atherosclerotic plaques, and to review the risk factors associated with their development.

The effects of wheat and oat dietary fiber (DF) alone or combined on T2DM remain unclear. In this research, db/db diabetic mice were fed with diets containing 10% insoluble wheat dietary fiber (WDF), 10% insoluble oat dietary fiber (ODF), and 10% WODF (mixture of WDF and ODF, WDF : ODF = 1 : 1) for 8 weeks. The results showed that WDF, ODF, and WODF all reduced the body weight and fasting blood glucose (FBG) and improved oral glucose tolerance in db/db mice. WDF and ODF alone further relieved insulin resistance and decreased the levels of glycated hemoglobin A1c (GHbA1c), and glycosylated serum protein (GSP). In addition, WDF and ODF alone decreased the levels of TNF-α, IL-6, and IL-1β in serum. The colon function was improved and similar changes were observed in the gut microbiota structure and abundance in all the DF groups. The change of gut microbiota mainly manifested as reducing F/B ratio at the phylum level, while at the genus level as decreasing Enterococcus, Escherichia-Shigella, Erysipelatoclostridium, and unclassified_f_Lachnospiraceae and increase of norank_f_Muribaculaceae, Bacteroides, and Alistipes. Further testing of colonic bile acids (BAs) revealed that WDF, ODF, and WODF all significantly changed the composition of BAs, mainly reducing the levels of UDCA, HDCA, and 3β-UDCA. WODF further decreased DCA and increased β-MCA, LCA-3S, and 12-KCDCA. Importantly, WODF reduced the values of 12-OH-BAs/non-12-OH-BAs. Moreover, the TGR5 level was up-regulated in both the liver and colon, and the FXR level was up-regulated in the liver while down-regulated in the colon in all the DF groups. Furthermore, for the protein level, IRS-1, p-PI3K/PI3K, and AKT were up-regulated in the liver in all the DF groups, while for the mRNA expression level, GLUT4 was up-regulated, and FOXO1, GSK3β, PEPCK, and PGC-1α were down-regulated. WDF and WODF further up-regulated the mRNA expression levels of GYS and down-regulated that of G6Pase. These results suggested that WDF, ODF, and WODF all can alleviate T2DM through the gutmicrobiota-BAs-TGR5/FXR axis and liver IRS-1/PI3K/AKT pathway in db/db mice. WDF and ODF alone are beneficial for improving glucose metabolism and inflammation indicators, while WODF helps improve BAs' profile more in the colon.

Diabetic wound healing presents significant challenges due to impaired angiogenesis, chronic inflammation, and cellular dysfunction. Building on previous research, this study further explores the potential of a plant-derived glucosyloxybenzyl 2-isobutylmalates (B-CGT) hydrogel in promoting diabetic wound healing. Network pharmacology and molecular docking analyses suggest that B-CGT may regulate key mechanisms, such as apoptosis, inflammation, and matrix remodeling, through core targets including SIRT1, CASP8, and MMP8. In vivo studies further demonstrated that B-CGT hydrogel significantly accelerated wound closure in diabetic mice, enhanced angiogenesis, promoted collagen deposition, and achieved immune balance by modulating macrophage polarization, thereby shifting the inflammatory environment toward a repair state. Moreover, B-CGT hydrogel significantly improved the wound microenvironment by upregulating VEGF expression and exerting antioxidant effects. By combining theoretical predictions with experimental validation, this study elucidates the multi-target synergistic regulatory mechanisms of B-CGT hydrogel. These findings provide new research directions for addressing immune imbalance and angiogenesis defects in diabetic wound healing and lay a scientific foundation for the optimization and application of chronic wound treatment strategies.

This research endeavor seeks to delve into the potential mechanisms by which pharmaceutical and personal care products (PPCPs), recognized as emerging pollutants, could contribute to the human metabolic disorders and then trigger metabolic diseases. Therefore, we have selected lipid and atherosclerosis, Alzheimer's disease, and type Ⅱ diabetes mellitus as representative metabolic diseases, aiming to systematically explore the critical molecular pathways that may be disrupted by PPCPs for the metabolic disease development. By employing advanced network toxicology and molecular docking techniques, we have successfully elucidated the molecular mechanisms that trigger the three diseases. We pinpointed the potential targets associated with the disease by leveraging databases including PubChem, ADEMTlab2.0, SwissADME, and GeneCards. We further employed STRING analysis and Cytoscape software to pinpoint the core targets that were most significantly associated with these metabolic diseases. In addition, enrichment analysis of these core targets was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways within the David database. To obtain the structural aspects of the target proteins, we also employed AlphaFold 3 for protein structure prediction. Finally, we validated the binding affinity of PPCPs to these target proteins using molecular docking with AutoDock Vina. Our findings suggested that PPCPs could potentially trigger metabolic diseases by modulating the expression of microRNAs, influencing cellular apoptosis and proliferation, and affecting signal transduction pathways. Interestingly, we also found the correlations among lipid and atherosclerosis, Alzheimer's disease, and type Ⅱ diabetes mellitus. Taken together, our study provides innovative insights into both the mechanisms of how environmental pollutants trigger human diseases and revealing the correlations among different diseases, thereby laying a theoretical foundation for disease prevention and treatment.

Familial hypercholesterolemia (FH) is a genetic condition characterized by high low-density lipoprotein cholesterol (LDL-C). The presence of risk modifiers could promote the atherosclerotic injury beyond LDL-C. Our aim was to evaluate metabolic and innate immunity profiles in FH subjects with or without subclinical atherosclerosis.

In this cross-sectional observational study, we evaluated 211 genetically confirmed FH subjects on LDL-C target and without cardiovascular diseases. Biochemical analyses, LDL-C burden (LCB) calculation and vascular profile evaluation were obtained from all subjects. Study population was divided into two groups according to subclinical atherosclerosis: the subclinical atherosclerosis (SA) group and non-subclinical atherosclerosis (NSA) group.

SA group had higher LDL-C at diagnosis (288.35 ± 24.52 vs 267.92 ± 23.86, p < 0.05) and LCB (13,465.84 ± 3617.46 vs 10,872.63 ± 3594.7, p < 0.001) than NSA group. SA group had higher white blood cell count (WBCC, 6.9 ± 1.66 vs 6.1 ± 1.16), neutrophil count (NC, 4.2 ± 1.3 vs 3.6 ± 1.11), monocyte count (MC, 0.8 ± 0.2 vs 0.4 ± 0.1), triglyceride to high-density lipoprotein ratio (TG/HDL, 1.73 ± 0.72 vs 1.45 ± 0.69), triglyceride-glucose index (TyG, 8.29 ± 0.35 vs 8.01 ± 0.33) than NSA group (p value for all < 0.01). Multivariate logistic regression analysis showed that LCB (p < 0.01), WBCC (p < 0.01), NC (p < 0.05), MC (p < 0.05) were associated with subclinical atherosclerosis. Simple linear regression analyses showed that LCB was associated with WBCC, NC, MC (p value for all < 0.01).

An increased LCB and an impaired innate immunity profile were found in FH subjects with subclinical atherosclerosis and they were independently associated with atherosclerotic injury. LCB could modulate the innate immunity profile.

Metabolic dysfunction-associated fatty liver disease (MAFLD) and air pollution are both significant health concerns. However, their combined effects on multi-system morbidity and all-cause mortality remain poorly understood.

We analyzed data from 434,417 UK Biobank participants, categorizing them into four groups: non-MAFLD, MAFLD-diabetes, MAFLD-lean, and MAFLD-overweight/obesity. To evaluate the long-term effects of air pollution exposure, we used time-varying Cox proportional hazard models to assess four air pollutants: particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5), PM10, nitrogen dioxide (NO2), and nitrogen oxides (NOx). We examined the associations between these air pollutants, MAFLD subtypes, and their joint impact on multi-system morbidity and all-cause mortality. Furthermore, we explored the additive and multiplicative interactions between air pollutants and MAFLD subtypes.

At baseline, 15,325 participants were classified as MAFLD-diabetes, 3341 as MAFLD-lean, and 140,934 as MAFLD-overweight/obesity. Among these groups, MAFLD-diabetes was most strongly associated with adverse outcomes compared to other subtypes. Air pollution exposure had a synergistic effect on cirrhosis risk across all MAFLD subtypes, with the most pronounced effects observed for PM2.5 [relative excess risk due to interaction (RERI): 2.10 (0.94, 3.26)] and NO2 [RERI:1.85 (0.67, 3.04)] in MAFLD-lean group. Positive additive and multiplicative interactions between air pollutants and MAFLD subtypes were also observed for coronary artery disease (CAD), with the exception of nitrogen oxide in the MAFLD-lean group. Additionally, only the MAFLD-diabetes demonstrated significant positive additive interactions with all four air pollutants in relation to chronic kidney disease (CKD).

This study highlights the distinct impacts of MAFLD subtypes on multi-system morbidity and all-cause mortality, underscoring the critical need for targeted prevention and treatment strategies, particularly for individuals with MAFLD-diabetes. Our findings reveal significant additive and synergistic effects of air pollution exposure on the risks of cirrhosis, CAD, and CKD among MAFLD patients.

Hyperglycemia, one of the major risk factors for atherosclerosis, leads to the accumulation of advanced glycation end products (AGEs), contributing to cardiovascular complications. Such accumulation may accelerate the progression of vascular disease in patients with diabetes. Reverse cholesterol transport (RCT) protein, ATP-binding membrane cassette transporters A1 and G1 (ABCA1 and ABCG1) and cholesterol 27-hydroxylase facilitate cholesterol removal from macrophages. AGE inhibits RCT by reducing the expression of ABCA1 and ABCG1. This study aimed to evaluate whether plasma from poorly controlled adolescents with type 1 diabetes (T1D) disrupts cholesterol homeostasis in human monocytes/macrophages. Twenty healthy controls (HCs) and 20 patients with type 1 diabetes mellitus (T1DM), 10-19 years old, were enrolled. Naïve THP-1 macrophages were exposed to plasma from each HC and patient with T1D. Following incubation, mRNA for cholesterol efflux (ABCA1, ABCG1, and 27-hydroxylase) and cholesterol uptake (CD36, ScR-A1, lectin oxidized low-density lipoprotein (LOX)-1, and CXCL16) were isolated. Foam cell formation was quantified to confirm the pro-atherogenic effects of T1D plasma on macrophages. Results showed that T1D plasma had an elevated level of N-(carboxymethyl)-lysine-modified proteins and upregulated CXCL16 and, to a lesser degree, ScR-A1. This change in gene expression in the presence of T1D plasma is associated with increased lipid accumulation and foam cell formation by THP-1 macrophages. In our study, these cells' uptake of an AGE product occurred mainly through the SR-A1 and CXCL16 receptors, leading to increased intracellular oxidized low-density lipoprotein. We conclude that AGEs may contribute to accelerated atherosclerosis in diabetes through effects on both forward and reverse cholesterol movement.

Globally, diabetes mellitus (DM) and its complications are considered among the most significant public health problems. According to numerous scientific studies, Plants and their bioactive compounds may reduce inflammation and oxidative stress (OS), leading to a reduction in the progression of DM. Moringa oleifera (MO), widely used in Ayurvedic and Unani medicine for centuries because of its health-promoting characteristics, particularly its ability to control DM and its related complications. MO is a multi-purpose plant that has an impressive range of nutritional components including proteins, amino acids (Essential and non-essential amino acids), carbs, fats, fiber, vitamins, and phenolic compounds. In the modern era, scientists have paid close attention to the anti-diabetic, anti-oxidative and anti-inflammatory attributes and other medicinal properties, of MO leaves and seeds. MO leaves and seeds have modulatory effects on DM that are likely influenced by multiple mechanisms. Some of these mechanisms include direct effects, but other mechanisms involve inhibition the production of inflammatory markers, modulation of the gut microbiome, reduction of OS, enhancement of glucose metabolism through hexokinase and glucose 6-phosphate dehydrogenase, improve insulin sensitivity and glucose uptake in the liver and muscles. Overall, these findings suggest that MO may play a role in lowering the risk of DM and its related outcomes. The purpose of this review is to provide a comprehensive overview of the nutritional and bioactive profiles of MO leaves and seeds, as well as to investigate their possible anti-diabetic effects by modulating oxidative stress and inflammation. Our results indicate that MO may be a beneficial natural resource for management of DM and related issues by lowering oxidative stress and inflammation. Furthermore, studies on MO has yielded promising findings in diabetic animal models, indicating antioxidant and anti-inflammatory properties. However, human trials have shown less solid results, most likely due to a lack of studies, different techniques, and dosages. More clinical research is needed to fully understand MO's anti-diabetic potential, notably in lowering oxidative stress and inflammation, both of which are critical in controlling diabetes complications.

Despite enormous advances in the treatment of cardiovascular diseases, including I/R injury and heart failure, heart diseases remain a leading cause of mortality worldwide. Inositol-requiring enzyme 1 (IRE1) is an evolutionarily conserved sensor endoplasmic reticulum (ER) transmembrane protein that senses ER stress. It manages ER stress induced by the accumulation of unfolded/misfolded proteins via the unfolded protein response (UPR). However, if the stress still persists, the UPR pathways are activated and induce cell death. Emerging evidence shows that, beyond the UPR, IRE1 participates in the progression of cardiovascular diseases by regulating inflammation levels, immunity, and lipid metabolism. Here, we summarize the recent findings and discuss the potential therapeutic effects of IRE1 in the treatment of cardiovascular diseases.

This study aims to explore the association between the triglyceride-glucose (TyG) index and the risk of carotid atherosclerosis (CAS) among Chinese steelworkers. This is a cross-sectional study involving a total of 4,203 Chinese steelworkers. The TyG index was calculated using the formula: TyG = Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL) / 2]. The association between the TyG index and CAS was analyzed using multivariable logistic regression and restricted cubic spline (RCS) models. The association between TyG and CAS was evaluated across different subgroups, including sex, age, lifestyle, medical history, and the state of occupational exposure. In addition, the TyG index was used to perform calibration and risk reclassification analyses on the fully adjusted model. Feature importance and predictive models were generated using LASSO regression and machine learning methods. In the fully adjusted model, compared to the lowest quartile group, the odds ratios (OR, 95% CI) for CAS, increased CIMT, and plaque in the highest quartile group of the TyG index were 3.199 (2.423 ~ 4.223), 2.877 (2.149 ~ 3.851), and 3.738 (2.700 ~ 5.177), respectively. Steelworkers exposed to occupational hazards had a higher risk of CAS compared to those not exposed. There was a nonlinear positive correlation between the TyG index and CAS (P < 0.05), and the risk of CAS increased when TyG > 8.72. Additionally, the TyG index demonstrated additional predictive capability beyond existing risk factors, significantly improving discriminatory performance (P < 0.05). In LASSO regression, TyG index and other covariables are screened as important feature variables to be incorporated into the development of machine learning models. The TyG index is associated with an increased risk of CAS among steelworkers, underscoring its potential as a reliable and practical predictive tool for assessing CAS risk in this population. Steelworkers with a TyG index>8.72 should receive additional CAS screening and health interventions. In addition, attention should be paid to those exposed to occupational hazards. The TyG index may serve as a simple, rapid, and reliable assessment tool for identifying high-risk individuals with CAS among steelworkers.

Many natural angiotensin-converting enzyme inhibitory (ACEI) peptides have been widely studied. However, their stability in vivo is poor in most cases. In this study, peptides were initially digested from broccoli in vitro, and absorption was simulated by Caco2 cells transport and then analyzed by Peptideomics and molecular docking. Subsequently, the mechanisms were verified using a high glucose-induced vascular smooth muscle cells (VSMCs) dysfunction model. Results showed that ACEI activity of broccoli crude peptide increased by 70.73 ± 1.42% after digestion. The enzymatic hydrolysates of crude broccoli peptides before and after digestion were detected by HPLC. The digested crude peptides were highly stable (with a stability level > 90%) in the intestine and possessed a strong absorptive potential. Five peptides with high stability and strong permeability were first identified, including HLEVR, LTEVR, LEHGF, HLVNK, and LLDGR, which exhibited high activity with IC50 values of 3.19 ± 0.23 mM, 17.07 ± 1.37 mM, 0.64 ± 0.02 mM, 0.06 ± 0.01 mM, and 2.81 ± 0.12 mM, respectively. When the VSMCs model was exposed to Ang II, the expressions of PCNA, MMP2, and Bcl2 were increased, while the expression of BAX was inhibited. When the VSMCs was exposed to high glucose (HG), the Ang II concentration significantly increased. This indicates that HG elevated Ang II levels. Finally, five peptides significantly attenuated Ang II-induced VSMCs proliferation and migration by down-regulating AT1R expression and inhibiting ERK and p38 MAPK phosphorylation. Notably, in exploring VSMCs dysfunction on a high glucose-induced model, ACEI peptides resulted in down-regulation of ACE and up-regulation of ACE2 expression. Therefore, it can be further referenced for the functional food against hypertension and cardiovascular diseases.

Aims: This cross-sectional study is aimed at determining whether systemic inflammation, diabetic autoantibodies, and islet β cell dysfunction play a role in the progression of macrovascular complications in patients with autoimmune diabetes. Methods: 202 patients with autoimmune diabetes aged ≥ 35 years and hospitalized in Peking Union Medical College Hospital were enrolled in this study. The patients were divided into three groups based on the severity of peripheral atherosclerosis. Biomarkers of systemic inflammation, diabetes autoantibodies, islet β cell function, and other covariates validated to be associated with macrovascular complications were collected. Correlations between the severity of peripheral atherosclerosis and systemic inflammation, diabetic autoantibodies, and islet β cell function were examined using an ordinal logistic regression model. Results: Of the enrolled patients, 39.1% were male, with a median age of 53 (43, 60) years and a diabetes duration of 96 (36, 216) months. 58 patients had no lesions in the peripheral arteries, 72 had atherosclerosis in the carotid or lower extremity arteries, and the rest had lesions in both arteries. In the multifactor ordinal logistic regression test, positive islet cell cytoplasmic antibody (ICA) and long-term use of lipid-lowering agents were independently associated with peripheral atherosclerosis after adjusting for age and diabetes duration. Conclusions: The correlation between positive ICA and atherosclerosis suggests inflammation at an early stage plays a role in macrovascular complications in autoimmune diabetes. The association between long-term use of lipid-lowering agents and atherosclerosis suggests the need for early screening and intervention for dyslipidemia in patients with autoimmune diabetes.