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Background There is an increasing awareness that diet-related inflammation may have an impact on the stroke. Herein, our goal was to decipher the association of dietary inflammatory index (DII) with stroke in the US general population. Methods We collected the cross-sectional data of 44,019 participants of the National Health and Nutrition Examination Survey (NHANES) 1999–2018. The association of DII with stroke was estimated using weighted multivariate logistic regression, with its nonlinearity being examined by restricted cubic spline (RCS) regression. The least absolute shrinkage and selection operator (LASSO) regression was applied for identifying key stroke-related dietary factors, which was then included in the establishment of a risk prediction nomogram model, with the receiver operating characteristic (ROC) curve being built to evaluate its discriminatory power for stroke. Results After confounder adjustment, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for stroke across higher DII quartiles were 1.19 (0.94–1.54), 1.46 (1.16–1.84), and 1.87 (1.53–2.29) compared to the lowest quartile, respectively. The RCS curve showed a nonlinear and positive association between DII and stroke. The nomogram model based on key dietary factors identified by LASSO regression displayed a considerable predicative value for stroke, with an area under the curve (AUC) of 79.8% (78.2–80.1%). Conclusions Our study determined a nonlinear and positive association between DII and stroke in the US general population. Given the intrinsic limitations of cross-sectional study design, it is necessary to conduct more research to ensure the causality of such association.

Background Diet has long been recognized as an important modifiable risk factor for hypertension. Herein, our research goal was to decipher the association of healthy eating index-2015 (HEI-2015) with hypertension, and to explore potential gender differences. Methods We collected the cross-sectional data of 42,391 participants of the National Health and Nutrition Examination Survey (NHANES) 1999–2018. The association of HEI-2015 with hypertension was estimated using weighted multivariate logistic regression, with restricted cubic spline (RCS) regression being adopted to examine the nonlinearity of this association in both genders, and the stability of the results were examined by sensitivity analysis. We also performed subgroup analysis to detect potential difference in the link between HEI-2015 and hypertension stratified by several confounding factors. Results After eliminating potential confounding bias, the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for hypertension across higher HEI-2015 quartiles were 0.93 (0.85–1.03), 0.84 (0.77–0.93), and 0.78 (0.72–0.86) compared to the lowest quartile, respectively. HEI-2015 was nonlinearly and inversely associated with hypertension in all participants. The gender-specific RCS curves presented a U-shaped correlation in males, while showed a linear and inverse correlation in females. Besides, subgroup analyses showed a lower risk of hypertension in participants who were females, younger than 40 years, Whites, obese, and diabetic patients. Conclusions We determined a nonlinear and inverse association between HEI-2015 and hypertension in the US general population, and revealed a remarkable gender difference when adhering to a HEI-2015 diet for preventing hypertension.

Dietary intervention plays a vital role in improving the prognosis of people with diabetes mellitus (DM). Currently, there is a lack of systematic analysis of the relation between dietary nutrients and long-term mortality risk in people with DM. The study aims to establish models predicting long-term mortality and explore dietary nutrients associated with reduced long-term events to guide daily dietary decisions in people with DM. The retrospective cohort study collected 5060 participants with DM from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. The least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithm were applied to identify key mortality-related dietary factors, which were subsequently incorporated into risk prediction nomogram models. The receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA) were utilized to evaluate the performance of the models. The association of key dietary nutrients with all-cause and cardiovascular mortality were visualized by restricted cubic spline (RCS) models both in the whole and subgroups by sex, age, drinking and smoking status. The overall median age of the cohort was 62.0 years (interquartile range (IQR) 52.0–70.0), 2564 (50.67%) being male. During a median follow-up period of 56.0 months, 997 (19.70%) all-cause deaths were recorded, with 219 (21.97%) of which being ascribed to cardiovascular disease. The nomogram models based on key dietary nutrients identified by LASSO and RF demonstrated a significant predicative value for all-cause and cardiovascular mortality. Dietary fiber and magnesium were the common predictive nutrients in the two nomogram models. The RCS curve revealed that dietary fiber and magnesium were negatively associated with long-term mortality in the whole and subgroups of people with DM after adjustment of potential confounders. The diet of people with DM is closely associated with mortality. The nomogram models based on dietary nutrients can predict long-term mortality of people with DM, and the higher intake of dietary fiber and magnesium was associated with reduced risks of both long-term all-cause and cardiovascular mortality.

Alamandine (Ala) is the newest identified peptide of the renin-angiotensin system and has protective effect on myocyte hypertrophy. However, it is still unclear whether Ala can alleviate heart failure (HF). The aim of this study was to explore the effects of Ala on HF and the related cardiac fibrosis, and to probe the mechanism. HF model was induced by myocardial infarction (MI) in mice. Four weeks after MI, Ala was administrated by intraperitoneal injection for two weeks. Ala injection significantly improved cardiac dysfunction of MI mice in vivo. The cardiac fibrosis and the related biomarkers were attenuated after Ala administration in HF mice in vivo. The increases of collagen I, alpha-smooth muscle actin and transforming growth factor-beta induced by oxygen–glucose deprivation (OGD) in neonatal rat cardiac fibroblasts (NRCFs) were inhibited by Ala treatment in vitro. The biomarkers of apoptosis were elevated in NRCFs induced by OGD, which were attenuated after treating with Ala in vitro. The enhancement of oxidative stress in the heart of MI mice or in the NRCFs treated with OGD was suppressed by treating with Ala in vivo and in vitro. These effects of Ala were reversed by tBHP, an exogenous inducer of oxidative stress in vitro. These results demonstrated that Ala could alleviate cardiac dysfunction and attenuate cardiac fibrosis via inhibition of oxidative stress.

Epigenetics has significantly evolved and emerged as important players in the pathogenesis of neurodegenerative diseases. However, a scientometric synthesis of such changes over time is currently lacking. We conducted a comprehensive search of the Web of Science Core Collection from inception until November 5, 2022, using appropriate keywords. Our primary objective was to employ scientometric analysis to depict changes in keywords over time and to assess the structure and credibility of clusters. Additionally, we examined the network of research (countries, institutions, and authors) using CiteSpace and VOSviewer. We identified 25 clusters with well-structured networks ( = 0.82) and highly credible clustering ( = 0.91) from 16,181 articles published between 1999 and 2022. Our findings are as follows: (a) the literature and research interest concerning the epigenetics of neurodegenerative diseases are continuously growing; (b) the three most productive countries are the USA, China, and Germany; (c) international collaborative relationships exist, alongside small, isolated collaboration networks of individual institutions. The number and impact of global publications on the epigenetics of neurodegenerative diseases have expanded rapidly over the past 20 years. This review provides valuable guidelines for researchers interested in neurodegenerative diseases research.

Paclitaxel (PTX) is a famous anti-cancer drug with poor aqueous solubility. In clinical practices, Cremophor EL (polyethoxylated castor oil), a toxic surfactant, is used for dissolution of PTX, which accounts for serious side effects. In the present study, a single glucose-conjugated PTX prodrug (SG-PTX) and a double glucose-conjugated PTX prodrug (DG-PTX) were synthesized with a glycosylated strategy via succinate linkers. Both of the two prodrugs presented significant solubility improvement and drug-like lipophilicities. Compared to DG-PTX, SG-PTX manifested more promising release of the parent drug in serum. A high percentage of PTX released from SG-PTX could be detected after enzymatic hydrolysis of β-glucuronidase. Besides, both of the two prodrugs exhibited effective cytotoxicity against breast cancer cells and ovarian cancer cells, but presented reduced cytotoxicity against normal breast cells. Moreover, SG-PTX manifested impressive solubility in a low toxic formulation (without ethanol) with a different percentage of Cremophor EL. These results indicated that glycosylation is a promising strategy for PTX modification and SG-PTX may be a feasible and potential type of PTX prodrug. In addition, ethanol-free formulation with a low percentage of Cremophor EL might have the potential to develop a safer formulation for further studies of glycosylated PTX prodrugs.

Background Cardiovascular disease (CVD) remains a major health killer worldwide, and the role of epigenetic regulation in CVD has been widely studied in recent decades. Herein, we perform a bibliometric study to decipher how research topics in this field have evolved during the past 2 decades. Results Publications on epigenetics in CVD produced during the period 2000–2022 were retrieved from the Web of Science Core Collection (WoSCC). We utilized Bibliometrix to build a science map of the publications and applied VOSviewer and CiteSpace to assess co-authorship, co-citation, co-occurrence, and bibliographic coupling. In total, 27,762 publications were included for bibliometric analysis. The yearly amount of publications experienced exponential growth. The top 3 most influential countries were China, the United States, and Germany, while the most cited institutions were Nanjing Medical University, Harbin Medical University, and Shanghai Jiao Tong University. Four major research trends were identified: (a) epigenetic mechanisms of CVD; (b) epigenetics-based therapies for CVD; (c) epigenetic profiles of specific CVDs; and (d) epigenetic biomarkers for CVD diagnosis/prediction. The latest and most important research topics, including “nlrp3 inflammasome”, “myocardial injury”, and “reperfusion injury”, were determined by detecting citation bursts of co-occurring keywords. The most cited reference was a review of the current knowledge about how miRNAs recognize target genes and modulate their expression and function. Conclusions The number and impact of global publications on epigenetics in CVD have expanded rapidly over time. Our findings may provide insights into the epigenetic basis of CVD pathogenesis, diagnosis, and treatment.

Alamandine (Ala), a ligand of Mas-related G protein-coupled receptor, member D (MrgD), alleviates angiotensin II (AngII)-induced cardiac hypertrophy. However, the specific physiological and pathological role of MrgD is not yet elucidated. Here, we found that MrgD expression increased under various pathological conditions. Then, MrgD knockdown prevented AngII-induced cardiac hypertrophy and fibrosis via inactivating Gα i -mediacted downstream signaling pathways, including the phosphorylation of p38 (p-P38), while MrgD overexpression induced pathological cardiac remodeling. Next, Ala, like silencing MrgD, exerted its cardioprotective effects by inhibiting Ang II-induced nuclear import of MrgD. MrgD interacted with p-P38 and promoted its entry into the nucleus under Ang II stimulation. Our results indicated that Ala was a blocking ligand of MrgD that inhibited downstream signaling pathway, which unveiled the promising cardioprotective effect of silencing MrgD expression on alleviating cardiac remodeling. 1vKXCZb4BaEYhFYZUPiv-d Video Abstract

Hypertension and its associated complications, including vascular remodeling, pose a major burden on global public health. However, the role of Mas‐related G protein‐coupled receptor member D (MrgD) in hypertension remains incompletely understood. In this study, we observed upregulated MrgD expression in the arterial tissues of hypertensive patients and animal models. In Sprague‐Dawley rats, MrgD overexpression elevated blood pressure (BP) and promoted mesenteric vascular remodeling, whereas MrgD knockdown in spontaneously hypertensive rats normalized BP and ameliorated vascular remodeling. Consistently, MrgD knockout mice exhibited resistance to angiotensin II (Ang II)‐induced hypertension and vascular injury. Mechanistic investigations demonstrated that MrgD facilitated vascular remodeling in vascular smooth muscle cells (VSMCs) through the voltage‐gated L‐type Ca2+ channel (Cav1.2)‐Ca2+/calmodulin‐dependent protein kinase IIγ (CaMKIIγ) signaling axis. Co‐immunoprecipitation coupled with mass spectrometry and in vitro functional assays confirmed that Ang II enhanced the interaction among MrgD, CaMKIIγ, and Cav1.2, thereby promoting VSMC phenotypic switch. Through artificial intelligence‐driven screening combined with functional validation, we identified risperidone as a small‐molecule inhibitor of MrgD that effectively attenuated hypertension and vascular remodeling. These findings established MrgD as a key contributor to the pathogenesis of hypertension and underscore its potential as a promising therapeutic target for hypertension and its associated vascular complications. Targeting MrgD attenuated hypertension and alleviated hypertension‐associated vascular remodeling via repressing Cav1.2‐CaMKIIγ axis. Risperidone, a small‐molecule inhibitor of MrgD, could alleviate hypertension and artery remodeling induced by Ang II infusion.

Cardiac fibrosis is a hallmark of various end-stage cardiovascular diseases (CVDs) and a potent contributor to adverse cardiovascular events. During the past decades, extensive publications on this topic have emerged worldwide, while a bibliometric analysis of the current status and research trends is still lacking. We retrieved relevant 13,446 articles on cardiac fibrosis published between 1989 and 2022 from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks. We identified four major research trends: (1) pathophysiological mechanisms; (2) treatment strategies; (3) cardiac fibrosis and related CVDs; (4) early diagnostic methods. The most recent and important research themes such as left ventricular dysfunction, transgenic mice, and matrix metalloproteinase were generated by burst analysis of keywords. The reference with the most citations was a contemporary review summarizing the role of cardiac fibroblasts and fibrogenic molecules in promoting fibrogenesis following myocardial injury. The top 3 most influential countries were the United States, China, and Germany, while the most cited institution was Shanghai Jiao Tong University, followed by Nanjing Medical University and Capital Medical University. The number and impact of global publications on cardiac fibrosis has expanded rapidly over the past 30 years. These results are in favor of paving the way for future research on the pathogenesis, diagnosis, and treatment of cardiac fibrosis.