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Chronic kidney disease (CKD) leads to deep changes in lipid metabolism and obvious dyslipidemia. The dysregulation of lipid metabolism in turn results in CKD progression and the complications of cardiovascular diseases. To obtain a profound insight into the associated dyslipidemia in CKD, we performed lipidomic analysis to measure lipid metabolites in the serum from a rat 5/6 nephrectomy (5/6 Nx) model of CKD as well as in the serum from CKD patients. HK-2 cells were also used to examine oxidative stress-induced sphingolipid changes. Totally 182 lipid species were identified in 5/6 Nx rats. We found glycerolipids, total free fatty acids, and sphingolipids levels were significantly upregulated in 5/6 Nx rats. The atypical sphingolipids, 1-deoxysphingolipids, were significantly altered in both CKD animals and human CKD patients. The levels of 1-deoxysphingolipids directly relevant to the level of oxidative stress in vivo and in vitro. These results demonstrate that 1-deoxysphingolipid levels are increased in CKD and this increase directly correlates with increased kidney oxidative stress. Image 1 • Sphingolipids were measured in blood in CKD patients and animal models • 1-deoxysphinganine and 1-deoxysphingosine increased in both CKD patients and animal models • The increase of 1-deoxysphingolipids is co-related with oxidative stress both in vivo and in vitro • 1-deoxysphingolipid levels are independent with sphingolipid de novo synthesis [ABSTRACT FROM AUTHOR]

Tengfu Jiangya Tablet (TJT) is a well accepted antihypertension drug in China and its major active components were Uncaria total alkaloids and Semen Raphani soluble alkaloid. To further explore treatment effects mechanism of TJT on essential hypertension, a serum proteomic study was performed. Potential biomarkers were quantified in serum of hypertension individuals before and after taking TJT with isobaric tags for relative and absolute quantitation (iTRAQ) coupled two-dimensional liquid chromatography followed electrospray ionization-tandem mass spectrometry (2D LC-MS/MS) proteomics technique. Among 391 identified proteins with high confidence, 70 proteins were differentially expressed (fold variation criteria, >1.2 or <0.83) between two groups (39 upregulated and 31 downregulated). Combining with Gene Ontology annotation, KEGG pathway analysis, and literature retrieval, 5 proteins were chosen as key target biomarkers during TJT therapeutic process. And the alteration profiles of these 5 proteins were verified by ELISA and Western Blot. Proteins Kininogen 1 and Keratin 1 are members of Kallikrein system, while Myeloperoxidase, Serum Amyloid protein A, and Retinol binding protein 4 had been reported closely related to vascular endothelial injury. Our study discovered 5 target biomarkers of the compound Chinese medicine TJT. Secondly, this research initially revealed the antihypertension therapeutic mechanism of this drug from a brand-new aspect. [ABSTRACT FROM AUTHOR]

• DHA alleviated PA-induced cytotoxicity in cardiomyoblast cells. • DHA ameliorated the progression of cardiomyopathy in a HFD-fed rat model of diabetes. • DHA improved palmitate-induced mitochondrial dysfunction both in vivo and in vitro. Regular consumption of n-3 polyunsaturated fatty acids is associated with decreased cardiovascular morbidity and mortality. This study assessed the therapeutic effect of docosahexaenoic acid (DHA) in palmitic acid (PA)-induced cytotoxicity in vitro and in rats fed a high-fat diet (HFD). H9C2 cells and rat primary cardiomyoblasts were exposed to PA or PA + DHA for 24 h. PA-induced lipotoxicity and mitochondrial dysfunction were evaluated by immunostaining, real-time PCR, cardiomyocyte contraction and transmission electron microscopy. The effects of dietary DHA on diabetic cardiomyopathy were evaluated in male Sprague-Dawley rats fed a reference diet rich in DHA, an HFD, or an HFD with added DHA for 16 weeks. Oxidative stress and lipotoxicity in rat heart tissue were assayed by Masson staining, immunohistochemistry, and TUNEL. In vitro studies showed that dietary DHA reduced the occurrence of cardiomyopathy and improved cardiac responses to PA. In the rat model, dietary DHA reduced mitochondrial oxidative stress in HFD-induced diabetic cardiomyopathy. Dietary DHA reduced mitochondrial oxidative stress and ameliorated PA-induced lipid toxicity. DHA consumption may have had direct effects on cardiovascular risk via myocardial protection. [ABSTRACT FROM AUTHOR]

Background: Recent insights suggest that remnant cholesterol (RC) plays a role in cellular senescence, yet its specific contribution to frailty remains indeterminate. Through the integration of observational and mendelian randomization (MR) studies, this research explores the impact of elevated serum RC levels on frailty susceptibility. Methods: A dual-method approach, combining an observational study with an MR study, was employed to investigate the connection between RC and frailty. The observational study included 11,838 participants from the National Health and Nutrition Examination Survey. Multivariable logistic regression and propensity score matching were employed to control for potential confounders. The non-linear relationship was assessed using restricted cubic splines. To circumvent observational study limitations, a two-sample MR analysis was conducted using the inverse-variance weighted method, leveraging genome-wide association studies (GWAS) data. Results: After adjusting for potential confounding variables, the observational study identified a significant association between high serum RC levels and frailty in middle-aged and older adults (odds ratio [OR] = 1.67, 95% confidence interval [CI] = 1.20 to 2.33, P = 0.003), exhibiting a non-linear dose–response correlation (non-linear P = 0.011). This association persisted after propensity score matching (OR = 1.53, 95% CI = 1.14 to 2.06, P = 0.005). The MR study echoed these results, demonstrating a causal association of RC with the frailty index (β = 0.059, 95% CI = 0.033 to 0.085, P = 1.05E-05), consistent with the observational findings (β = 0.017, 95% CI = 0.008 to 0.026, P = 4.51E-04). Conclusion: This study provides evidence that higher RC levels amplify frailty risk in middle-aged and older adults, implying that the reduction of RC levels may present a promising strategy for frailty prevention and management. [ABSTRACT FROM AUTHOR]

Objective Tengfu Jiangya tablet (TJT) is a traditional Chinese medicine formulation composed of Uncaria rhynchophylla and Semen raphani . It is a hospital preparation that is widely used in clinics for treating hypertension. A previous metabolomics study reported that TJT exerted a protective effect on hypertension by restoring impaired NO production, ameliorating the inflammatory state, and vascular remodeling. A clinical proteomics study also revealed five key target proteins during TJT intervention. This study aimed to integrate proteome and metabolome data sets for a holistic view of the molecular mechanisms of TJT in treating hypertension. Methods Serum samples from spontaneously hypertensive rats and Wistar Kyoto rats were analyzed using ultra-high performance liquid chromatography coupled to Q Exactive hybrid quadrupole-Orbitrap mass spectrometry (UPLC-Q-Exactive-MS)-based metabolomics technology and isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics technology. Moreover, we selected two candidate proteins and determined their expression levels in rat serum using an enzyme-linked immunosorbent assay (ELISA). Results A total of 20 potential biomarkers and 14 differential proteins in rat serum were identified. These substances were mainly involved in three biological pathways: the kallikrein–kinin pathway, the lipid metabolism pathway, and the PPARγ signaling pathway. Conclusions The results suggested that TJT could effectively treat hypertension, partially by regulating the above three metabolic pathways. The combination of proteomics and metabolomics provided a feasible method to uncover the underlying interventional effect and therapeutic mechanism of TJT on spontaneously hypertensive rats. [ABSTRACT FROM AUTHOR]

Radish seed (RS), the dried ripe seed of Raphanus sativus L., is widely used in traditional Chinese medicine (TCM) to reduce blood pressure. However, the molecular and pharmacological mechanisms underlying its therapeutic effects are still unclear. In this study, we analyzed the effects of RS in a rat model of prehypertension and assessed the mechanistic basis by integrating transcriptomics and metabolomics. RS administration significantly reduced blood pressure in prehypertensive male Wistar rats, negatively regulated endothelin-1, increased nitric oxide levels, and reduced the exfoliation of endothelium cells. In vitro vascular ring experiments further confirmed the effects of RS on vascular endothelial cells. Furthermore, we identified 65 differentially expressed genes (DEGs; P a d j < 0.05 and fold change (FC) > 2) and 52 metabolites (VIP > 1, P < 0.05 and FC ≥ 2 or ≤0.5) in the RS intervention group using RNA-seq and UPLC-MS/MS, respectively. A network of the DEGs and the metabolites was constructed,q which indicated that RS regulates purine metabolism, linoleic acid metabolism, arachidonic acid metabolism, circadian rhythm, and phosphatidylinositol signaling pathway, and its target genes are Pik3c2a, Hspa8, Dnaja1, Arntl, Ugt1a1, Dbp, Rasd1, and Aldh1a3. Thus, the antihypertensive effects of RS can be attributed to its ability to improve vascular endothelial dysfunction by targeting multiple genes and pathways. Our findings provide new insights into the pathological mechanisms underlying prehypertension, along with novel targets for the prevention and treatment of hypertension. [ABSTRACT FROM AUTHOR]

The mitochondrial unfolded protein response (UPRmt) is a cytoprotective response in response to cellular stress that is activated in response to mitochondrial stress to maintain intra-protein homeostasis, thereby protecting the cell from a variety of stimuli. The activation of this response has been linked to cardiovascular diseases. Here, we reviewed the current understanding of UPRmt and discussed its specific molecular mechanism, mainly in mammals, as well as addressing its protective role against cardiovascular diseases, so as to provide direction for further research on UPRmt and therapies targeting cardiovascular diseases in the future. ● UPRmt plays an important role in cardiac pathophysiology. ● Targeted UPRmt can delay the progress of cardiovascular diseases. ● Modern drugs and natural products can prevent and treat cardiovascular diseases by regulating UPRmt. [ABSTRACT FROM AUTHOR]

• Identification of ZXT and its components. • ZXT and its component mixtures showed in vivo hypotensive effects on SHR. • ZXT and its component mixture can improve RAAS indexes in SHR. • ZXT regulates metabolic pathways related to primary bile acid biosynthesis, arachidonic acid metabolism, and fatty acid degradation. High blood pressure is a serious human health problem and one of the leading risk factors for fatal complications in cardiovascular disease. The ZXT granules were prepared based on the Zhengan-Xifeng-Tang (ZXT) decoction. However, the therapeutic effects of ZXT granules on spontaneous hypertension and the metabolic pathways in which they may intervene are unclear. The aim of this study was to investigate the antihypertensive effect of ZXT granules on spontaneously hypertensive rats (SHR) and to analyze the metabolic pathway of intervention through chemical composition characterization, pharmacodynamics, and serum metabolomics analysis. After eight weeks of administration, serum and aortic arch samples were collected for biochemical, histopathology and serum metabolomics analysis to assess the effect of ZXT granules on SHR. The results showed that ZXT granules reduced aortic arch injury and blood pressure in SHR rats. Serum data from rats in each group was collected using LC-MS and 74 potential biomarkers were identified that showed significant differences between the model and control groups. Of these, 18 potential biomarkers were found to be deregulated after intervention with ZXT granules. These 18 potential differential metabolic markers are primarily involved in bile acid biosynthesis, arachidonic acid metabolism pathway, and fatty acid degradation. The results demonstrated that ZXT granules significantly affected blood lipids, aortic arch, and metabolic disorders in SHR rats. ZXT granules offer a new possibility for effective and convenient treatment of hypertensive patients. [ABSTRACT FROM AUTHOR]

Background: The prevalence rate of hypertension in the Chinese population is on the rise, and the control rate of hypertension is low. International guidelines, including the 2018 Chinese Guidelines for the Management of Hypertension, recommend optimized drug selection and combination therapy for patients with stage 2 hypertension and blood pressure ≥ 160/100 mmHg, including valsartan/amlodipine (Val/Aml). The traditional Chinese medicine (TCM) compound Tengfu Jiangya tablet (TJT; No. Z20110021, Shandong Provincial Food and Drug Administration) is prepared in the medical institution of Affiliated Hospital of Shandong University of Traditional Chinese Medicine. It is an effective compound preparation of TCM for the treatment of hypertension in the national clinical research base of TCM. The aim of this study was to evaluate the efficacy and safety of TJT combined with Val/Aml in the treatment of stage 2 hypertension with hyperactivity of liver yang.Methods: This randomized double-blind, placebo-controlled, multicenter trial will be conducted with a total of 288 participants with stage 2 hypertension at seven clinical trial centers. The stratified random method will be used, and the subcenter will be taken as the stratification factor. Eligible patients will be randomly assigned (1:1) into groups receiving either TJT or placebo three times daily for 28 days, both combined with Val/Aml 80/5 mg. The primary efficacy endpoint is the reduction in the mean sitting systolic blood pressure (msSBP) and the mean sitting diastolic blood pressure (msDBP) from baseline to week 4. Adverse events and laboratory test results will be monitored throughout the trial.Discussion: This is the first placebo-controlled randomized trial conducted to evaluate the efficacy and safety of a Chinese herbal extract combined with Val/Aml in patients with stage 2 hypertension. Our study may help to provide evidence-based recommendations of a complementary preventive measure for stage 2 hypertension.Trial Registration: Chinese Clinical Trial Registry ChiCTR2000030611 . Registered on 8 March 2020. [ABSTRACT FROM AUTHOR]

Vascular endothelial injury is the initial stage of atherosclerosis (AS). Stimulating and activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway can regulate the expression of vascular endothelial cytokines, thus affecting the occurrence and development of AS. In addition, the PI3K/Akt signaling pathway can regulate the polarization and survival of macrophages and the expression of inflammatory factors and platelet function, thus influencing the progression of AS. In recent years, traditional Chinese medicine (TCM) has been widely recognized for its advantages of fewer side effects, multiple pathways, and multiple targets. Also, the research of TCM regulation of AS via the PI3K/Akt signaling pathway has achieved certain results. This study aimed to analyze the characteristics of the PI3K/Akt signaling pathway and its role in the pathogenesis of AS, as well as the role of Chinese medicine in regulating the PI3K/Akt signaling pathway. The findings are expected to provide a theoretical basis for the clinical treatment and pathological mechanism research of AS. [ABSTRACT FROM AUTHOR]

Phenolic compounds are naturally present as secondary metabolites in plant-based sources such as fruits, vegetables, and spices. They have received considerable attention for their antioxidant, anti-inflammatory, and anti-carcinogenic properties for protection against many chronic disorders such as neurodegenerative diseases, diabetes, cardiovascular diseases, and cancer. They are categorized into various groups based on their chemical structure and include phenolic acids, flavonoids, curcumins, tannins, and quinolones. Their structural variations contribute to their specific beneficial effects on human health. The antioxidant property of phenolic compounds protects against oxidative stress by up-regulation of endogenous antioxidants, scavenging free radicals, and anti-apoptotic activity. Protocatechuic acid (PCA; 3,4-dihydroxy benzoic acid) and protocatechuic aldehyde (PAL; 3,4-dihydroxybenzaldehyde) are naturally occurring polyphenols found in vegetables, fruits, and herbs. PCA and PAL are the primary metabolites of anthocyanins and proanthocyanidins, which have been shown to possess pharmacological actions including antioxidant activity in vitro and in vivo. This review aims to explore the therapeutic potential of PCA and PAL by comprehensively summarizing their pharmacological properties reported to date, with an emphasis on their mechanisms of action and biological properties. [ABSTRACT FROM AUTHOR]

Two new three‐phase solvent systems combined with elution‐extrusion counter‐current chromatography mode were used to study the chemical constituents in Bidens pilosa Linn. var. radiata Sch. Bip. The first novel solvent system consisted of n‐hexane, acetonitrile, chloroform, and water in a ratio of 5:5:1:5, which was selected for elution‐extrusion counter‐current chromatography to separate the n‐hexane extraction part. A total of six constituents were obtained from this part in the up phase as the stationary phase and the middle phase as the mobile phase. The second novel solvent system, composed of n‐hexane‐butyl acetate‐acetonitrile‐water (3:1:4:3, v/v/v/v), was used for separating ethyl acetate extract of Bidens pilosa Linn. var. radiata Sch. Bip. Eight compounds were successfully isolated using elution‐extrusion counter‐current chromatography elution‐extrusion mode. Fourteen chemical constituents were identified as 2‐β‐D‐glucopyranosytoxy‐1‐hydroxy‐5(E)‐tridecene‐7,9,11‐triyne (Y1), 3‐β‐D‐glucopyranosyloxy ‐1‐hydroxy‐6(E)‐tetradecene‐8,10,12‐triyne (Y2), 1, 2‐dihydroxy‐5(E)‐tridecene‐7,9, 11‐triyne (Y3), isorhamnetin (Y4), kaempferol (Y5), icthyothereolacetate (Y6), quercetin‐3‐O‐β‐D‐ galactopyranosyl‐7‐O‐β‐D‐glucopyranoside (W1), quercetin 3‐O‐β‐L‐rhamnopyranoside (W2), neosperidin dihydrochalcone (W3), quercetin (W4), quercetagetin‐3,6,4' ‐trimethoxyl‐ 7‐O‐β‐D‐glucopyranoside (W5), taxifolin (W6), luteolin (W7), and apigenin (W8) by spectra of 1H‐NMR and 13C‐NMR data. Among them, compounds Y1, Y2, Y3, and Y6 belong to polyacetylene compounds, and the rest were flavonoids. In addition, counter‐current chromatography has been used to separate polyacetylene compounds for the first time. All compounds in this method were isolated from Bidens pilosa Linn. var. radiata Sch. Bip. for the first time. [ABSTRACT FROM AUTHOR]

Objectives. Yishenjiangyafang is a traditional Chinese medicine used to clinically treat hypertension. This study aimed to explore the effect of yishenjiangyafang on plasma metabolomics in senile spontaneously hypertensive rats (SHRs). Methods. Twelve 50-week-old SHR (6 males and 6 females) were randomly divided into two groups: a treatment group, in which rats were intragastrically administered with yishenjiangyafang (10.08 g kg−1·d−1), and a model group, in which all SHRs were administered the same volume of saline. Six age- and gender-matched Wistar–Kyoto (WKY) rats were used as the control group. Treatment was given for 6 days per week and lasted for 8 weeks. Systolic and diastolic blood pressures of the rats were measured with the noninvasive tail artery pressure measurement system. An ultraperformance liquid chromatography quadruple electrostatic field orbit (UPLC-Q-Exactive) was used to determine metabolite changes in the plasma of SHR rats before and after yishenjiangyafang treatment in the treatment group as well as in the model and control groups. Results. After yishenjiangyafang treatment, SHRs had significant lower blood pressure. Using UPLC-Q-Exactive, we identified 26 metabolic targets of yishenjiangyafang in aged SHRs and revealed that yishenjiangyafang targeted four major metabolic pathways, linoleic acid metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and steroid hormone biosynthesis. Conclusion. Yishenjiangyafang decreases the blood pressure of SHRs at least in part through targeting of four major metabolic pathways. Our study illustrates mechanisms underlying the clinical application of yishenjiangyafang in the treatment of hypertensive patients. [ABSTRACT FROM AUTHOR]

Jingfang Granules (JFG) originate from the traditional herbal formula Jingfang Baidu powder. It has the effects of inducing sweating and dispelling wind. It is a classic medication used for treating external pathogenic factors and viral diseases. However, the therapeutic mechanism of JFG for viral myocarditis needs further clarification. This study aimed to explore the therapeutic efficacy of JFG on coxsackievirus B3-induced viral myocarditis (VMC), along with the elucidation of its underlying mechanisms. C57 BL/6JNifdc mice were divided randomly into several groups: control, model, Jingfang Granule groups (0.23, 0.46, and 0.69 g/20g, respectively), and a positive group (oseltamivir, 19.33 mg/kg). Following the establishment of the VMC model, the mice underwent an 8 -week treatment regimen. Pathological alterations in cardiac tissues and inflammatory protein expression were monitored. Differential gene analysis was conducted utilizing transcriptomic techniques. The differential gene mucolipin 1 (Mcoln1) was knocked down by transfection with siRNA in H9C2 cell, and investigative techniques such as immunoblotting, qRT-PCR, immunofluorescence, JC-1 staining, reactive oxygen species (ROS) detection, and mitochondrial stress testing were employed to examine its mechanism of action. JFG significantly mitigates the pathological damage observed in the cardiac tissues of CVB3-induced VMC mice and attenuates the expression of inflammatory genes. Subsequently, differentially expressed genes are identified through transcriptomic analysis and validated via PCR. Among these, the upregulation of Mcoln1 promotes autophagy, facilitating the clearance of damaged mitochondria and excessive ROS. This has been substantiated through in vitro experiments. Excessive ROS precipitates a reduction in mitochondrial membrane potential, instigating cell apoptosis. In accordance with TUNEL staining results, JFG acts to inhibit cell apoptosis. To ascertain whether Mcoln1 is a crucial target for JFG in treating VMC, Mcoln1 was suppressed in H9C2 cells. The suppression of Mcoln1 hinders the elevation in autophagy levels post-JFG treatment, obstructs the enhancement of mitochondrial function, and impedes the clearance of ROS. Furthermore, the inhibitory effect of JFG on cell apoptosis is attenuated. The research findings indicate that JFG has a protective effect on CVB3-induced H9C2 cell injury. JFG may exert its effects in VMC treatment by enhancing autophagy to suppress cell apoptosis through the mitochondrial pathway, thereby counteracting cell damage. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel lysosome-targetable fluorescent probe Lys - HClO for HClO was fabricated. • The probe Lys - HClO displayed high selectivity and sensitivity toward HClO. • Lys - HClO was used for imaging of lysosome HClO in cells and zebrafish. • Lys - HClO was firstly utilized to image of lysosome HClO in atherosclerosis model. Atherosclerosis (AS) is a systemic vascular disease that typically takes decades before overt disease manifests itself. Due to this silent course, it is essential to create disease predictors before clinical lesions develop. In AS, dysfunction of lysosome induced by the accumulation of HClO changes cytokine secretion from macrophages. The formation of foam cells with an elevated HOCl level is regarded as an iconic feature of the early AS lesion. However, fluorescent probes targeting lysosome to monitor the variations of HClO level during the AS procedure have not reported. In this work, we firstly report a lysosome-targeted fluorescence probe, Lys - HClO , for evaluating AS by mapping the fluctuation of HClO with high selectivity and sensitivity. Meanwhile, probe Lys - HClO can be located in lysosome and successfully used to detected endogenous and exogenous HClO in cells. Furthermore, probe Lys - HClO was effectively applied to imaging endogenous HClO in zebrafish. Notably, with the assistance of probe Lys - HClO, we successfully monitored the significant up regulation of HClO in aorta of high-fat diet (HFD) -induced AS. These results indicate that Lys - HClO was a prospective image tool in studying early diagnosis of AS. [ABSTRACT FROM AUTHOR]

The occurrence of nonalcoholic fatty liver disease (NAFLD) is associated with major abnormalities of hepatic lipid metabolism. We propose that lipid abnormalities directly or indirectly contribute to NAFLD, especially fatty acid accumulation, arachidonic acid metabolic disturbance, and ceramide overload. The effects of lipid intake and accumulation on NAFLD and NAFLD treatment are explained with theoretical and experimental details. Overall, these findings provide further understanding of lipid metabolism in NAFLD and may lead to novel therapies. [ABSTRACT FROM AUTHOR]

Chronic inflammation plays a crucial role in vascular calcification. However, only a few studies have revealed the mechanisms underlying the development of inflammation under high-phosphate conditions in chronic kidney disease (CKD) patients. Here, we show that inflammation resulting from the activation of the TGFBR1/TAK1 pathway is involved in calcification in CKD rats or osteogenic medium-cultured human aortic smooth muscle cells (HASMCs). Moreover, miR-135a-5p is demonstrated to be a key regulator of the TGFBR1/TAK1 pathway, which has been reported to be decreased in CKD rats. We further reveal that farnesoid X receptor (FXR) activation increases miR-135a-5p expression, thereby inhibiting the activation of the TGFBR1/TAK1 pathway, ultimately resulting in the attenuation of vascular inflammation and calcification in CKD rats. Our findings provide advanced insights into the mechanisms underlying the development of inflammation in vascular calcification, and evidence that FXR activation could serve as a therapeutic strategy for retarding vascular calcification in CKD patients. Li et al. investigate the mechanism behind vascular inflammation and calcification in chronic kidney disease (CKD) and show that inflammation is due to activation of the confirmed TGFBR1/TAK1 pathway, with miR-135a-5p as a key regulator. They further show that farnesoid X receptor activation upregulates miR-135a-5p which attenuates vascular inflammation and calcification in CKD rats. [ABSTRACT FROM AUTHOR]

Background: Dysfunction of human respiratory and electro-cardiac activities could affect the ability of the heart to pump blood and the lungs to inhale oxygen. Thus, a device could simultaneously measure electro-cardiac signal and respiratory pressure could provide vital signs for predicting early warning of cardio-pulmonary function-related chronic diseases such as cardiovascular disease, and respiratory system disease. Results: In this study, a flexible device integrated with piezo-resistive sensing element and voltage-sensing element was developed to simultaneously measure human respiration and electro-cardiac signal (including respiratory pressure, respiration frequency, and respiration rhythm; electro-cardio frequency, electro-cardio amplitude, and electro-cardio rhythm). When applied to the measurement of respiratory pressure, the piezo-resistive performance of the device was enhanced by nano-copper modification, which detection limitation of pressure can reduce to 100 Pa and the sensitivity of pressure can achieve to 0.053 ± 0.00079 kPa−1. In addition, the signal-to-noise ratio during bio-electrical measurement was increased to 10.7 ± 1.4, five times better than that of the non-modified device. Conclusion: This paper presents a flexible device for the simultaneous detection of human respiration and cardiac electrical activity. To avoid interference between the two signals, the layout of the electrode and the strain sensor was optimized by FEA simulation analysis. To improve the piezo-resistive sensitivity and bio-electric capturing capability of the device, a feather-shaped nano-copper was modified onto the surface of carbon fiber. The operation simplicity, compact size, and portability of the device open up new possibilities for multi-parameter monitoring. [ABSTRACT FROM AUTHOR]

The incidence of chronic kidney disease (CKD) is associated with major abnormalities in circulating lipoproteins and renal lipid metabolism. This article elaborates on the mechanisms of CKD and lipid uptake abnormalities. The viewpoint we supported is that lipid abnormalities directly cause CKD, resulting in forming a vicious cycle. On the theoretical and experiment fronts, this inference has been verified by elaborately elucidating the role of lipid intake and accumulation as well as their influences on CKD. Taken together, these findings suggest that further understanding of lipid metabolism in CKD may lead to novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Circadian rhythms play a fundamental role in the progression of cardiovascular events. Almost all cardiovascular diseases have a circadian misalignment usually characterized by changes in metabolites. This study aimed to dynamically monitor rhythmic biomarkers, to elucidate the metabolic pathways that are potentially under circadian control in spontaneously hypertensive rats (SHRs), and to eventually establish a circadian metabolic phenotype strategy based on metabolomics.Methods: In this study, an untargeted metabolomics technology was used to dynamically monitor changes in serum metabolites between SHR model group and WKY control group. Liquid chromatography-mass spectrometry (LC-MS) combined with multivariate statistical analysis was applied to identify markers of hypertension rhythm imbalance. The concentrations of amino acids and their metabolites identified as markers were quantified by a subsequent targeted metabolomics analysis. Overall, these approaches comprehensively explored the rhythm mechanism and established a circadian metabolic phenotype strategy.Results: The metabolic profile revealed a disorder in the diurnal metabolism pattern in SHRs. Moreover, multivariate statistical analysis revealed metabolic markers of rhythm homeostasis, such as arginine, proline, phenylalanine, citric acid, L-malic acid, succinic acid, etc., accompanied by an imbalance in hypertension. The key metabolic pathways related to rhythm imbalance in hypertension were found by enrichment analysis, including amino acid metabolism, and the tricarboxylic acid cycle (TCA). In addition, the quantitative analysis of amino acids and their metabolites showed that the changes in leucine, isoleucine, valine, taurine, serine, and glycine were the most obvious.Conclusions: In summary, this study illustrated the relationship between metabolites and the pathways across time on hypertension. These results may provide a theoretical basis for personalized treatment programmes and timing for hypertension. [ABSTRACT FROM AUTHOR]

Pericyte dysfunction and loss contribute substantially to the destabilization and rupture of atherosclerotic plaques. Protocatechuic aldehyde (PCAD), a natural polyphenol, exerts anti-atherosclerotic effects. However, the effects and mechanisms of this polyphenol on pericyte recruitment, coverage, and pericyte function remain unknown. We here treated apolipoprotein E-deficient mice having high-fat diet-induced atherosclerosis with PCAD. PCAD achieved therapeutic effects similar to rosuvastatin in lowering lipid levels and thus preventing atherosclerosis progression. With PCAD administration, plaque phenotype exhibited higher stability with markedly reduced lesion vulnerability, which is characterized by reduced lipid content and macrophage accumulation, and a consequent increase in collagen deposition. PCAD therapy increased pericyte coverage in the plaques, reduced VEGF-A production, and inhibited intraplaque neovascularization. PCAD promoted pericyte proliferation, adhesion, and migration to mitigate ox-LDL-induced pericyte dysfunction, which thus maintained the capillary network structure and stability. Furthermore, TGFBR1 silencing partially reversed the protective effect exerted by PCAD on human microvascular pericytes. PCAD increased pericyte coverage and impeded ox-LDL-induced damages through TGF-β1/TGFBR1/Smad2/3 signaling. All these novel findings indicated that PCAD increases pericyte coverage and alleviates pericyte damage to improve the stability of atherosclerotic plaques, which is accomplished by regulating TGF-β1/TGFBR1/Smad2/3 signaling in pericytes. [Display omitted] • PCAD improves the stability of atherosclerotic plaques. • PCAD increases intraplaque pericyte coverage and restores pericyte function. • Targeting TGF-β signaling in pericytes is expected to enhance plaque stability. • PCAD increase plaque stability by TGF-β1/TGFBR1/Smad2/3 signaling in pericytes. [ABSTRACT FROM AUTHOR]

Ferroptosis is a form of programmed cell death mostly characterized by a serious misadjustment in the production and degradation of lipid reactive oxygen species (ROS). Meanwhile, numerous studies have indicated that ferroptosis is crucial to the progression and pathophysiology of acute kidney injury (AKI). ROS have been implicated as a pivotal causative factor in cell damage, peroxynitrite (ONOO−) is one of the most prominent ROS which is intimately correlated to ferroptosis-mediated AKI. Therefore, monitoring ONOO− levels in ferroptosis-mediated AKI is important for exploring its physiological and pathological roles. Nevertheless, no probes for detecting ONOO− in ferroptosis-mediated AKI have been reported. Meanwhile, resveratrol (Res) is a bioactive component and has been used to the treatment of AKI. However, the effect of Res on ferroptosis during AKI progression remains elusive. Herein, we evaluated the fluctuation of ONOO− during ferroptosis-mediated AKI using the near-infrared (NIR) fluorescence probe (NFP-ONOO) for the first time. The probe NFP-ONOO showed excellent specificity and sensitivity for the detection of ONOO−. Furthermore, utilizing this probe, we demonstrated Res effectively mitigates AKI induced by folic acid (FA) and cisplatin (CP) by inhibiting ferroptosis. Collectively, this work will provide a powerful guidance for the prophylaxis, diagnosis, and therapy of ferroptosis-mediated AKI. [Display omitted] • A novel near-infrared fluorescent probe NFP-ONOO for ONOO− was fabricated. • The probe NFP-ONOO displayed high selectivity and sensitivity toward ONOO−. • NFP-ONOO was used for imaging ONOO− in cells and zebrafish during ferroptosis. • NFP-ONOO was utilized to image ONOO− in ferroptosis-mediated AKI models. [ABSTRACT FROM AUTHOR]

The pathogenesis of coronary heart disease is a highly complex process, with lipid metabolism disorders being closely linked to its development. Therefore, this paper analyzes the various factors that influence lipid metabolism, including obesity, genes, intestinal microflora, and ferroptosis, through a comprehensive review of basic and clinical studies. Additionally, this paper delves deeply into the pathways and patterns of coronary heart disease. Based on these findings, it proposes various intervention pathways and therapeutic methods, such as the regulation of lipoprotein enzymes, lipid metabolites, and lipoprotein regulatory factors, as well as the modulation of intestinal microflora and the inhibition of ferroptosis. Ultimately, this paper aims to offer new ideas for the prevention and treatment of coronary heart disease. • This review focuses on the various factors that influence lipid metabolism, including obesity, genes, intestinal microflora, and ferroptosis. • A variety of intervention approaches and treatment methods were proposed, such as regulating lipoprotein enzyme, lipid metabolites, lipoprotein regulatory factors, intestinal flora, ferroptosis and so on. • The mechanisms of coronary heart disease and its associated treatments were illustrated. [ABSTRACT FROM AUTHOR]

Our previous studies have shown that Uncaria has an important role in lowering blood pressure, but its intervention mechanism has not been clarified completely in the metabolic level. Therefore, in this study, a combination method of HPLC-TOF/MS-based metabolomics and multivariate statistical analyses was employed to explore the mechanism and evaluate the antihypertensive effect of Uncaria. Serum samples were analyzed and identified by HPLC-TOF/MS, while the acquired data was further processed by partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to discover the perturbed metabolites. A clear cluster among the different groups was obtained, and 7 significantly changed potential biomarkers were screened out. These biomarkers were mainly associated with lipid metabolism (dihydroceramide, ceramide, PC, LysoPC, and TXA2) and vitamin and amino acids metabolism (nicotinamide riboside, 5-HTP). The result indicated that Uncaria could decrease the blood pressure effectively, partially by regulating the above biomarkers and metabolic pathways. Analyzing and verifying the specific biomarkers, further understanding of the therapeutic mechanism and antihypertensive effect of Uncaria was acquired. Metabolomics provided a new insight into estimate of the therapeutic effect and dissection of the potential mechanisms of traditional Chinese medicine (TCM) in treating hypertension. [ABSTRACT FROM AUTHOR]

The Golgi apparatus is a crucial component of the endomembrane system and is involved in various physiological and pathological processes. Recently, increasing evidence shows that Golgi participates in oxidative stress in sepsis-induced acute lung injury (ALI). As a kind of reactive oxygen species (ROS), peroxynitrite (ONOO−) plays a significant role in a range of oxidative stress-related diseases. Therefore, accurately monitoring the level of ONOO− in the Golgi apparatus is crucial for revealing the mechanism of Golgi ONOO− in the sepsis-induced ALI. Unfortunately, no such probe has been reported to detect Golgi ONOO− in sepsis-induced ALI model. In this work, a Golgi-targetable probe FC-ONOO was designed and synthesized for high sensitivity and selectivity monitoring ONOO− generation during the Golgi stress response in sepsis-induced ALI model. The probe displayed high sensitivity (about 57 nM of detection limit) and good selectivity towards ONOO−. Additionally, it was successfully applied in mapping the increase of ONOO− levels in the Golgi of live cells induced by different stimuli. More importantly, the substantial increases in ONOO− levels in the Golgi apparatus were observed in the sepsis-induced ALI of mice for the first time. Given all its outstanding advantages, it has great potential for application in other ONOO− related diseases. [Display omitted] • A novel Golgi-targetable fluorescent probe for ONOO− was developed. • The probe displayed high sensitivity and good selectivity towards ONOO−. • The probe was successfully used to track Golgi ONOO− produced in live cells induced by different stimuli. • The probe was successfully applied to bioimaging Golgi ONOO− fluxes during sepsis-induced ALI for the first time. [ABSTRACT FROM AUTHOR]

Rhizoma Alismatis , an important crude herb component in traditional Chinese medicine, has been commonly used for treating hypertension, but its mechanism has not been clarified in level of metabolic. Therefore, in the present work, metabolomics study coupled with ingenuity pathway analysis (IPA) have been performed to explore the potential mechanism in anti-hypertensive effect of Rhizoma Alismatis . Serum samples from SHRs and WKYs were analyzed with the use of high performance liquid chromatography coupled with time of flight mass spectrometry detection (HPLC–TOF/MS) in positive polarity. The obtained data sets were statistically analyzed using univariate and multivariate statistical analyses including the principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) for pattern recognition and selection of significant metabolites. 12 potential biomarkers in rat serum were screened out from HMDB, METLIN and KEGG databases. Furthermore, IPA was introduced and Glycerophospholipid metabolism and Purine metabolism were filtered out as potential target pathways. This metabolomic approach coupled with IPA provided a feasible way to understand the therapeutic mechanism of Rhizoma Alismatis on spontaneous hypertensive rats. [ABSTRACT FROM AUTHOR]

A HPLC/TOF-MS-based metabolomic study was conducted to investigate the holistic therapeutic effects of Tengfu Jiangya Tablet (TJT) on spontaneously hypertensive rats (SHRs). The SHRs were divided into valsartan (VST) group, TJT group and model group, in addition, the Wistar-Kyoto rats (WKY) were taken as normal control. Serum samples were separated and identified by HPLC/TOF-MS, while the obtained data was further processed by partial least-squares discriminant analysis (PLS-DA). A clear cluster among the four groups was observed, and we identified thirteen biomarkers involved involved in sphingolipid metabolism (sphinganine, lysosphingomyelin, ceramide), glycerophospholipid metabolism (phosphatidylcholines, phosphatidylethanolamine, lysophosphatidylcholines), arginine and proline metabolism ( l -proline, citrulline), tryptophan metabolism (xanthuiulrenic acid, l -kynurenine, l -tryptophan), arachidonic acid metabolism(leukotriene D4), and linoleic acid metabolism (gamma-linolenic acid). Altered metabolic pathways involved in impaired NO production, inflammation and vascular smooth muscle cells (VSMCs) apoptosis and proliferation, which suggesting the possible pathological state in SHRs. TJT as well as VST altered the metabolic state, suggesting a possible anti-hypertension role by improving NO production, and an extra cardiovascular protection role possibly by amelioration of inflammatory state and vascular remodeling. [ABSTRACT FROM AUTHOR]

• An integrated data filtering and identification strategy was developed. • Totally 47 GSLs containing 8 unknowns were identified in 25 Brassicaceae tissues. • Analysis of the MS/MS cleavage behavior and the characteristic diagnostic ions of GSLs. • The GSLs profiles of 25 Brassicaceae tissues were summarized and 11 markers of GSLs were found to distinguish the Brassica and Raphanus. Glucosinolates (GSLs) are secondary plant metabolites that occur mainly in the Brassicaceae plants, which are desirable compounds in human foods due to their diverse biological activities. In this study, we developed an integrated data filtering and identification strategy to characterize the GSLs. An in-depth GSLs profiling was performed on 25 commonly Brassicaceae tissues in Jinan, China. By comparison with the reference standards and previous researches, we tentatively identified 47 GSLs including 8 unknown ones. The GSLs profiles of 25 Brassicaceae tissues were established, and 11 markers of GSLs could be used to distinguish the Brassica and Raphanus. This approach enables accurately characterization the GSLs of Brassicaceae tissues, and demonstrates the potential of GSLs profiles for Brassicaceae species discrimination. [ABSTRACT FROM AUTHOR]

Vascular damage of hypertension has been the focus of hypertension treatment, and endothelial progenitor cells (EPCs) play an important role in the repair of vascular endothelial damage. Functional damage and decreased number of EPCs are observed in the peripheral circulation of hypertensive patients, but its mechanism is not yet elucidated. Here, we show that the number of EPCs in hypertensive patients is significantly lower than that of normal population, and the cell function decreases with a higher proportion of EPCs at later stages. A decrease in autophagy is responsible for the senescence and damage of EPCs induced by AngII. Moreover, lncRNA-p21 plays a critical regulator role in EPCs' senescence and dysfunction. Furthermore, lncRNA-p21 activates SESN2/AMPK/TSC2 pathway by promoting the transcriptional activity of p53 and enhances autophagy to protect against AngII-induced EPC damage. The data provide evidence that a reversal of decreased autophagy serves as the protective mechanism of EPC injury in hypertensive patients, and lncRNA-p21 is a new therapeutic target for vascular endothelial repair in hypertension. [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study is to provide new insights on the association of lipid metabolites, circadian genes and lipid metabolism associated genes in spontaneously hypertensive rats. An untargeted lipidomics using ultrahigh performance liquid chromatography-mass spectrometry metabolomics was used to identify the differentially expressed lipid metabolites over 24 h in Spontaneously hypertensive rats (SHR) with reference to Wistar-Kyoto rats (WKY). The expression of circadian clock genes (Bmal1 , Clock , Per1 , Per2 , Cry1 , Cry2) and lipid metabolism related genes (Rev-erbα , Pparα and Sirt1) was analysed RT-qPCR. Ten lipid metabolites with significant differences in their levels in SHR compared to WKY were identified. The levels of MG (25:0), PA (36:3) and PE (38:2) were lower and the levels of LysoPCs (20:0 and 20:3) and TGs (54:5, 59:12, 28:0, 60:10 and 60:13) were found to be higher in SHR. SHR showed obvious disorders in the expression of circadian genes and lipid metabolism associated genes. A strong association between the levels of lipid metabolites and circadian genes and lipid metabolism associated genes was found. Rhythm genes may further affect the 24-hour lipid metabolism level of spontaneously hypertensive rats by mediating lipid metabolism associated genes. This research provides new insights on the association of lipid metabolites, circadian genes and lipid metabolism associated genes in SHR. Unlabelled Image [ABSTRACT FROM AUTHOR]

The phytochemical investigations on the seeds of Raphanus sativus L. led to the isolation and identification of 15 compounds, including eleven sinapoyl derivatives (1 – 11), two terpenes (12–13), and two phenolic acids (14 – 15). All chemical structures were elucidated via 1H NMR and 13C NMR spectroscopic methods, and further supported by comparison with literature data. Compound 11 was isolated from the genus Raphanus for the first time. Notably, Compounds 7 , 9 , and 12–14 were reported in the Brassicaceae family for the first time. The chemotaxonomic significance of these compounds is discussed. • Compounds 7, 9, and 12-14were reported in the Brassicaceae family for the first time. • Compound 11 was isolated from R. sativus L. for the first time. • Sinapoyl derivatives could be considered as chemotaxonomic marker of vital importance for Raphani semen. • The chemotaxonomic significance of the compounds isolated from the Raphani semen was discussed. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

• A study of circadian misalignment in hypertension. • Uncaria can regulate neurotransmitter circadian metabolic homeostasis in SHRs. • A novel pharmacodynamic evaluation strategy was established from the perspective of time dimension. In the present study, we aimed to use metabolomics platforms to examine circadian-regulated neurotransmitters across a 24-h day and the effects of Uncaria administration on daily rhythmicity in order to establish a strategy for evaluating the spatiotemporal efficacy evaluation strategy of Uncaria. By using targeted ultrahigh performance liquid chromatography-mass spectrometry metabolomics, we quantified 32 neurotransmitter metabolites every 4 h over 24 h. To assess 24-h metabolite rhythmicity, we performed cosinor analysis. The expression of hypothalamic rhythm genes was detected by reverse transcription polymerase chain reaction (RT-PCR). Data revealed circadian loss of many neurotransmitters during the entire circadian cycle in the serum of group M, indicating that hypertension causes circadian rhythm disorders. Cosinor analysis of the rhythmic oscillations of the levels of 32 neurotransmitters in the three groups showed that the metabolite rhythms peaked at approximately the same time of day (ZT4 and ZT16). Moreover, the amplitudes of the metabolite rhythms were altered. After treatment with Uncaria , the amplitudes of 13 neurotransmitters reverted to normal. The change trends in the hypothalamic rhythm genes confirmed the rhythm changes in neurotransmitters. Collectively, a novel pharmacodynamic evaluation strategy was established to dynamically observe the holistic effects of Uncaria on 32 circulating neurotransmitters within 24 h from the perspective of time dimension. [ABSTRACT FROM AUTHOR]

Atherosclerosis (AS) is a chronic disease of the arterial wall where both innate and adaptive immunoinflammatory mechanisms are involved. Inflammation plays an important role in the pathological process of atherosclerosis at various stages. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also known as WWTR1) behave as a novel drug target against atherosclerosis. Therefore, the mechanism relationship of YAP/TAZ, inflammation and AS was explored in this study. Experiments demonstrated that serine dephosphorylation and nuclear translocation of YAP was increased in ECs and pericytes induced by oxidative low-density lipoprotein (ox-LDL), while the inhibition of YAP degraded the expression of downstream inflammatory factors. The expression of YAP/TAZ and inflammation proteins (JNK, NF-κB and TNF-α) in ECs and pericytes was suppressed through the application of Sal-B. Besides, Sal-B protects ECs and pericytes from oxidative stress and apoptosis. In vivo, Sal-B reduced en face and aortic root sinus lesions size, and decreased the expression of inflammation related factors (IL-6, IL-1β, TNF-α) and ox-LDL in serum sample of ApoE−/− mice fed a high fat diet. Therefore, our work provides a potential therapeutic strategy of using Sal-B to attenuate the development of atherosclerosis, the anti-atherosclerosis effects of Sal-B is related to regulate YAP/TAZ/JNK signaling pathway. • Inflammatory related markers were arised with the increase of YAP/TAZ. • Sal-B plays a therapeutic role in inflammation by inhibiting YAP/TAZ activation. • Sal-B therapy delays the development of atherosclerosis. • The pathway mechanism was elucidated using endothelial cells and pericytes. [ABSTRACT FROM AUTHOR]

From the Uncaria rhynchophlly (Miq.) Jacks, twelve monoterpene indole alkaloids, such as harman (1) , strictosamide (2) , vincosidelactam (3) , cadambine (4) , 3α-dihydrocadambine (5) , 7-epi-javaniside (6) , rhynchophylline (7) , isorhynchophylline (8) , hirsutine (9) , vincosamide-6′-O-β-D-glucopyranoside (10) , vincosamide-11-O-β-D-glucopyranoside (11) and 2′-O-[β-D-glucopyranosyl-(1 → 6)-β-D-glucopyranosyl]-11-hydroxyvincosamide (12) were isolated and identified. Structure elucidation of these compounds was performed on the basis of NMR spectroscopic data. Compounds 2, 5, 6, 10, 11 and 12 were obtained from this species for the first time. Chemotaxonomic significance of these compounds is described herein. • Compounds 2, 5, 6, 10, 11 and 12 were obtained from this species for the first time. • Expounded the significance of alkaloids in chemical chemotaxonomic, and the biomarkers were found. • A plausible biogenetic relationship of alkaloids in Uncaria. [ABSTRACT FROM AUTHOR]