Goal: With the improvement of living standards, people's diets tend to be more and more high-fat, and long-term high-fat diets may lead to obesity and other chronic health problems. Nearly 80% of obese patients are accompanied by varying degrees of hepatic steatosis, so there is an urgent need to seek a safe and effective treatment of obesity and lipid deposition. Methods: In this study, 3-week-old Sprague-Dawley rats were divided into normal control group (NC), high-fat group: control group (HC), light fasting group (HI), exercise group (HE), light fasting plus exercise group (HIE), and light fasting, and aerobic exercise were used as intervention methods for 10 weeks. Catabolic protein effects were investigated to explore the effects of both on hepatic lipid deposition, and the experimental data were statistically analyzed using SPSS 25.0, with one-way or two-way ANOVA tests to be used, and graphs were made using GraphPad Prism 8.0. Findings: (1) Weight was significantly higher in the HC group compared to the NC group (p < 0.01). Compared with the HC group, the intervention group had lower body weight (P < 0.05), with the HIE group having a greater reduction in body weight. (2) The results of HE and oil red staining after 10 weeks of intervention showed that the liver structure and histological morphology of high-fat rats underwent significant improvement (P < 0.05), and the effect was more significant in the HIE group. (3) Compared with the NC group, serum TG, TC, LDL, AST, ALT were elevated (P < 0.05) and HDL was reduced (P < 0.05) in the HC group; compared with the HC group, TG, TC, LDL, AST, ALT were reduced, and HDL was elevated (P < 0.05) in the intervention group. (4) Compared with the NC group, the expression of p-AMPK/AMPK, p-ACC/ACC, and CPT1 was significantly reduced in the liver tissues of mice in the HC group (P < 0.01). The expression of p-AMPK/AMPK, p-ACC/ACC, and CPT1 was elevated in the liver tissues of the intervention group compared with the HC group (P < 0.05). Discussion: The present study confirmed that the effect of light fasting plus exercise on the improvement of lipid deposition was better than that of one alone, which provided a new idea and direction for the improvement of obesity and lipid deposition; however, this study did not go into depth on the mechanism at the molecular level, which needs to be continued to be explored.
Essential hypertension is a notable threat for the older (age, ≥65 years) population. However, to the best of our knowledge, a real‑world study assessing olmesartan medoxomil‑amlodipine besylate (OM‑AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM‑AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM‑AML (20/5 mg) tablets (Sevikar®) were analyzed in a prospective, single‑arm, multi‑center, real‑world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM‑AML tablet administration were measured. The mean ± standard error change of SeSBP/SeDBP was ‑10.3±0.8/‑4.6±0.5 and ‑12.5±0.8/‑5.6±0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home‑measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug‑associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM‑AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline‑recommended BP targets in older Chinese patients with essential hypertension.
Abstract There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients’ and physicians’ satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug‐related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM‐AML tablet is one of the best antihypertensive agents in patients with essential hypertension.
Background Stress-induced cell premature senescence participates in a variety of tissue and organ remodeling by secreting such proteins as proinflammatory cytokines, chemokines, and growth factors. However, the role of cardiomyocyte senescence in heart remodeling after acute myocardial infarction has not been thoroughly elucidated to date. Therefore, we sought to clarify the impact of premature myocardial senescence on postinfarction heart function. Methods and Results Senescence markers, including p16 INK4a, p21 CIP1/WAF1, and SA -β-gal staining, were analyzed in several heart disease models by immunostaining. Both postinfarction mouse hearts and ischemic human myocardium demonstrated increased senescence markers. Additionally, senescence-related secretory phenotype was activated after acute myocardial infarction, which upregulated senescence-related secretory phenotype factors, including CCN family member 1 ( CCN 1), interleukin-1α, tumor necrosis factor α, and monocyte chemoattractant protein-1. In vivo, a tail vein injection of AAV 9- Gata4-sh RNA significantly attenuated senescence-related secretory phenotype secretion and aggravated postinfarction heart dysfunction. Furthermore, among activated senescence-related secretory phenotype factors, CCN 1 administration reduced myofibroblast viability in vitro and rescued the deleterious effect of AAV 9- Gata4-sh RNA in vivo. Conclusions Myocardial premature senescence was observed in the ischemic hearts and improved postinfarction heart function, partly through the GATA-binding factor 4- CCN 1 pathway.
Background: At present, Western medicine treatment methods for arrhythmia emerge in an endless stream, but the accompanying side effects are also exposed, which brings pressure on medical resources and social economy. In recent years, the advantages of acupuncture combined with traditional Chinese medicine (TCM) in the control of arrhythmia have become increasingly prominent. Neiguan (PC6) is the collateral point in pericardium meridian; acupuncture at Neiguan can nourish the heart and calm the mind, and also plays an important role in treating arrhythmias. There is currently a lack of evidence-based medical evidence for the combination of acupuncture and TCM in the treatment of arrhythmia. This study aimed to investigate the effect of acupuncture combined with oral TCM in the treatment of arrhythmia. Methods: Randomized controlled trials published from the inception of databases to June 2022 were reviewed by searching the PubMed, Cochrane Library, Embase, CNKI, VIP, and WanFang databases. Review Manager 5.4.1 was used for the meta-analysis after the reviewers scanned the literature, extracted information, and identified the risk of bias. Results: Eleven randomized controlled trials with 804 patients were reviewed, including 402 and 402 patients in the treatment and control groups, respectively. The results of the meta-analysis showed a significant benefit of acupuncture plus oral TCM in terms of clinical effectiveness compared with oral TCM alone (n = 696; relative risk (RR), 1.22; 95% confidence interval (CI) 1.14 to 1.30; P < .00001) and in lowering the number of premature beats in 24 hours (n = 374; standard mean difference, −10,55; 95% confidence interval (95% CI) −14.61 to −6.49; P < .00001). Acupuncture plus oral TCM was also found to improve the conversion rate (n = 168; RR, 1.32; 95% CI, 1.14–1.52; P = .0002) and increase the left ventricular ejection fraction (n = 250; mean difference, 6.57; 95% CI, 4.11–9.04; P < .00001), but it had no significant increase in adverse events (n = 262; RR, 0.57; 95% CI 0.30–1.09; P = .09). Conclusion: Compared with oral TCM alone, acupuncture combined with oral TCM showed a clear benefit in treating arrhythmias and had no increase in adverse events.
Epidemiological evidence from ambulatory blood pressure monitoring is needed to clarify the associations of particulate air pollution with blood pressure and potential lag patterns. We examined the associations of fine and coarse particulate matter (PM2.5, PM2.5-10) with ambulatory blood pressure among 7108 non-hypertensive participants from 7 Chinese cities between April 2016 and November 2020. Hourly concentrations of PM2.5 and PM2.5-10 were obtained from the nearest monitoring stations. We measured four blood pressure indicators, including systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP) and pulse pressure (PP). Linear mixed-effect models combined with distributed lag models were applied to analyze the data. Generally, very short-term exposure to PM2.5 was significantly associated with elevated blood pressure. These effects occurred on the same hour of blood pressure measurement, attenuated gradually, and became insignificant approximately at lag 12 h. An interquartile range (IQR, 33 μg/m3) increase of PM2.5 was significantly associated with cumulative increments of 0.58 mmHg for SBP, 0.31 mmHg for DBP, 0.38 mmHg for MAP, and 0.33 mmHg for PP over lag 0 to 12 h. The exposure-response relationship curves were almost linear without thresholds, but tended to be flat at very high concentrations. No significant associations were observed for PM2.5-10. Our study provides independent and robust associations between transient PM2.5 exposure and elevated blood pressure within the first 12 h, and reinforces the evidence for a linear and non-threshold exposure-response relationship, which may have implications for blood pressure management and hypertension prevention in susceptible population.
Rationale: Excessive myocardial fibrosis is the main pathological process in the development of cardiac remodeling and heart failure; therefore, it is important to prevent excessive myocardial fibrosis. We determined that microRNA-378 (miR-378) is cardiac-enriched and highly repressed during cardiac remodeling. We therefore proposed that miR-378 has a critical role in regulation of cardiac fibrosis, and examined the effects of miR-378 on cardiac fibrosis after mechanical stress. Methods: Mechanical stress was respectively imposed on mice through a transverse aortic constriction (TAC) procedure and on cardiac fibroblasts by stretching silicon dishes. A chemically modified miR-378 mimic (Agomir) or an inhibitor (Antagomir) was administrated to mice by intravenous injection and to cells by direct addition to the culture medium. MiR-378 knockout mouse was constructed. Cardiac fibroblasts were cultured in the conditioned media from the cardiomyocytes with either miR-378 depletion or treatment with sphingomyelinase inhibitor GW4869. Quantitative real-time polymerase chain reaction analysis of gene and miRNA expression, Western blot analysis, immunochemistry and electron microscopy were performed to elucidate the mechanisms. Results: Mechanical stress induced significant increases in fibrotic responses, including myocardial fibrosis, fibroblast hyperplasia, and protein and gene expression of collagen and matrix metalloproteinases (MMPs) both in vivo and in vitro. All these fibrotic responses were attenuated by treatment with a chemically modified miR-378 mimic (Agomir) but were exaggerated by treatment with an inhibitor (Antagomir). MiR-378 knockout mouse models exhibited aggravated cardiac fibrosis after TAC. Media from the cardiomyocytes with either miR-378 depletion or treatment with sphingomyelinase inhibitor GW4869 enhanced the fibrotic responses of stimulated cardiac fibroblasts, confirming that miR-378 inhibits fibrosis in an extracellular vesicles-dependent secretory manner. Mechanistically, the miR-378-induced anti-fibrotic effects manifested partially through the suppression of p38 MAP kinase phosphorylation by targeting MKK6 in cardiac fibroblasts. Conclusions: miR-378 is secreted from cardiomyocytes following mechanical stress and acts as an inhibitor of excessive cardiac fibrosis through a paracrine mechanism.
Objective Polyenylphosphatidylcholine (PPC), a significant therapeutic agent for liver repair, exhibits potent antioxidant and anti-inflammatory properties. Nonetheless, its impact on hypertension and hypertensive vascular diseases requires clarification. Our objective was to elucidate the protective role and mechanism of PPC in a spontaneously hypertensive rat model. Materials and methods Male WKY and SHRs were randomly assigned to four groups: WKY control, SHRs control, SHRs treated with Telmisartan (SHR-TS), and SHRs treated with PPC (SHR-PPC). Blood pressure was monitored biweekly during the treatment. Histological analyses assessed aortic vascular remodeling and cardiac and renal injuries. RNA-seq was performed on vascular smooth muscle cells (VSMCs) isolated from WKY or SHRs, and protein levels of target genes were quantified using Western blotting. Results In a dose-dependent screening test, we confirmed that PPC (200 mg/kg / day) effectively reduced blood pressure in SHRs. Treatment with PPC also mitigated cardiac and renal injury in SHRs by attenuating hypertrophy and fibrosis. Compared to WKY rats, SHRs exhibited increased intima thickness, reduced vascular tone, and heightened aortic fibrosis; however, PPC treatment significantly reversed vascular remodeling. Analysis of RNA-seq data revealed that downregulated genes were enriched in inflammation and oxidative stress pathways based on GO and KEGG enrichment analyses. PPC markedly inhibited genes such as Rela, Relb, Nfkb2, and others involved in the NF- κ B pathway. Given PPC's influence on glycerophospholipid synthesis and metabolism, and its role in NF- κ B-mediated transcription affecting oxidative stress and inflammation, changes in the PLAs, PLPs, and PLPPs families were analyzed in PPC-treated VSMCs. Among these, PPC notably inhibited Plpp3. Importantly, overexpression of Plpp3 significantly reversed the protective effects of PPC on hypertension-related cardiac and renal injuries, vascular fibrosis, remodeling, and tension. Conclusion We identified a new protective role for PPC in mitigating cardiac and renal injuries associated with hypertension, as well as in preventing aortic fibrosis and remodeling. Targeting the NF- κ B/Plpp3 pathway may offer a promising therapeutic strategy for treating vascular diseases related to hypertension.
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