Search

Purpose: Mitophagy reduces mitochondrial dysfunction and accumulation of reactive oxygen species (ROS) to prevent myocardial injury in diabetic cardiomyopathy (DCM). Accumulated studies have confirmed that metformin enhances autophagy to maintain mitochondrial homeostasis and scavenge ROS. However, whether and how metformin regulates mitophagy in cardiomyocytes remain unclear. Methods: Diabetic cardiomyopathy was modeled in H9c2 Cardiomyocytes treated with high glucose (30 mM) . Then high Glucose-stimulated H9C2 cells were exposed to metformin, AMPKα inhibitor and Sirt1 inhibitor for 24 h. Mitochondrial dysfunction and mitophagy were detected by fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), mitochondrial membrane potential(MMP), flow cytometry and western blot. Resluts: We found that the protein expression of Parkin, ROS level, and mitochondrial membrane potential showed dynamic changes in H9C2 cells under the stimulation of high glucose. Importantly, metformin enhanced mitophagy, scavenged ROS, improved mitochondrial function and inhibited apoptosis in H9C2 cells treated with high glucose. Mechanistically, metformin increased the protein expression of p-AMPKα, Sirt1, Parkin, and LC3-II in H9C2 cells after a high glucose challenge. Depletion of AMPKα and Sirt1 abolished the increase of protein levels of Parkin and LC3-II and mitophagy levels induced by metformin. Conclusion: Our data indicated that metformin improves mitochondrial dysfunction of H9C2 cells under hyperglycemia by activating AMPKα/Sirt1/Parkin-mediated mitophagy, which provides novel evidence for the treatment of DCM.

The impact of beta2-agonists (B2As) on heart failure (HF) remains controversial. This study aimed to investigate whether inhaled B2As increased in-hospital mortality in ICU patients with HF.The Multiparameter Intelligent Monitoring in Intensive Care III database was initially searched to identify adult patients (≥ 18 years old) with HF in ICU. Then, patients using or not using inhaled B2As were matched using propensity score matching on a 1:1 basis to control for baseline confounders. In-hospital mortality was compared between the two groups, and logistic regression analysis was performed to assess the association between B2As and in-hospital mortality.The initial search retrieved 2345 eligible patients with HF from the database. After propensity score matching, 705 pairs of patients were included in the final analysis. Patients using B2As had markedly higher in-hospital mortality than those not using B2As (4.68% versus 2.27%; P = 0.013). In the multivariate logistic regression analysis, B2A use (odd ratios (OR), 2.471; 95% confidence interval (CI), 1.289-4.734; P = 0.006), stroke (OR, 4.581; 95% CI, 1.621-12.948; P = 0.004), and simplified acute physiology score II (SAPS-II) scores (OR, 1.090; 95% CI, 1.064-1.116; P < 0.001) were significantly associated with increased risk of in-hospital mortality, whereas renin angiotensin system inhibitor use (OR, 0.396; 95% CI, 0.202-0.778; P = 0.007) was significantly associated with decreased risk of in-hospital mortality. Subgroup analysis further indicated that the association between B2A use and mortality was significant only in patients with HF without chronic pulmonary disease (OR, 2.427; 95% CI, 1.351-4.362; P = 0.003), but not in those with chronic pulmonary disease (OR, 2.094; 95% CI, 0.582-7.537; P = 0.258).In ICU patients with HF but without chronic pulmonary disease, the use of inhaled B2As is associated with increased in-hospital mortality.

Recent studies and guidelines have indicated that lipoprotein(a) [Lp(a)]was an independent risk factor of arteriosclerotic cardiovascular disease (ASCVD). This study aimed to determine the relationship between serum Lp(a) levels and the risk of periprocedural myocardial injury following percutaneous coronary intervention (PCI) in coronary heartdisease (CHD) patients. This study enrolled 528 nonacute myocardial infarction (AMI) coronary heart disease (CHD) patients who successfully underwent PCI. Fasting serum lipids including Lp(a) were tested before PCI. High‐sensitivity cardiac troponin I (hs‐cTnI) was tested before PCI and 24 h after PCI. Univariate and multivariate logistic regression analyses were used to determine the relationship between preprocedural Lp(a) levels and postprocedural cTnI elevation from 1 × upper limit of normal (ULN) to 70 × ULN. As a continuous variable, multivariate analyses adjusting for conventional covariates and other serum lipids revealed that increased Lp(a) levels were independently associated with the risk of elevated postprocedural cTnI values above 1 × ULN (odds ratio [OR] per log‐unit higher: 1.31, 95% confidence interval [CI]: 1.02–1.68, P = 0.033], 5 × ULN (OR: 1.25, 95%CI: 1.02–1.53, P = 0.032), 10 × ULN (OR: 1.48, 95%CI: 1.18–1.86, P = 0.001) and 15 × ULN (OR: 1.28, 95%CI: 1.01–1.61, P = 0.038). As a categorical variable, Lp(a) > 300 mg/L was an independent risk factor of postproceduralc TnI≥1 × ULN (OR 2.17, 95%CI 1.12–4.21, P = 0.022), ≥5 × ULN (OR 1.82, 95%CI 1.12–2.97, P = 0.017) and ≥10 × ULN (OR 2.17, 95%CI 1.33–3.54, P = 0.002). Therefore, it could be concluded that elevated preprocedural Lp(a) levels were associated with the risk of PCI‐related myocardial injury in non‐AMI CHD patients.

Objective: Observe the clinical characteristics of children with SLE, namely, to observe the symptoms and laboratory examinations, such as blood routine, blood lipid, immunoglobulin, complement, autoantibodies, serum 25 (OH) D and other indicators, and to explore the clinical characteristics, the difference and the significance of vitamin D supplements between male and female SLE patients in children respectively. Methods: We enrolled 64 cases of SLE patients in children who were admitted into the department of pediatrics and rheumatology of the third affiliated hospital of sun yat-sen university in guangzhou from May 1, 2011 to February 1, 2019, They were analyzed retrospectively, adopting ?² test for statistical analysis. Results: 64 cases of SLE in children, which included 10 cases of male and 54 cases of female. Clinical manifestations: facial skin rash in 48 patients (75%), fever in 38 cases (59.4%), arthritis in 28 cases (43.8%), oral ulcer in 18 cases (28.1%), serositis in13 cases (20.3%), and the sun allergy in 9 cases (14.1%), the damage of central nervous system in 7 cases (10.9%) . Laboratory examination: 30 cases of leukopenia (46.9%), anemia in 30 cases (46.9%), thrombocytopenia in 12 cases (18.8%), hematuria in 18 cases (28.1%), proteinuria in 33 cases (51.2%), 6 patients with renal impairment (9.4%), antinuclear antibody positive in 63 cases (98.4%), anti-double-stranded DNA (dsDNA) antibody positive in 48 cases (75%), anti SSA antibody positive in 44 cases (68.7%), SSB antibody positive in 33 cases (51.6%), Sm antibody positive in 40 cases (62.5%), nucleosome antibody positive in 28 cases (43.8%) .Among these children, male SLE patients were higher than female children with SLE in the damage of kidney, Sm antibodies and resisting nucleosome antibody positive rates (?²= 4.451, 8.336, 6.803, P

Free fatty acids (FFAs) increase in visceral fat and are inferred to be one of the underlying inducers of adipose tissue inflammation. In our previous study, it was demonstrated that ginsenoside Rb1 stimulates endothelial nitric oxide synthase (eNOS) and Sirtuin 1 to protect against endothelial cell senescence. In the present study, 3T3‑L1 adipocytes were exposed to 0.5 mM FFAs with or without Rb1 (10‑40 µM). Monocyte chemotactic protein‑1 (MCP‑1) and interleukin‑6 (IL‑6) secretion was measured using ELISA. Tumor necrosis factor‑α (TNF‑α) expression and nuclear factor‑κB (NF‑κB) p65 phosphorylation were detected using western blot analysis. Oxidative stress was determined via measuring intracellular reactive oxygen species (ROS) and nitric oxide (NO) production. The results demonstrated that MCP‑1 and IL‑6 secretion, as well as TNF‑α expression, were significantly increased following FFA treatment, which was attenuated by Rb1 in a dose‑dependent manner. Furthermore, Rb1 attenuated FFA‑induced NF‑κB phosphorylation, suggesting that the inhibitory effect of Rb1 on inflammatory cytokines was partially mediated through blockade of NF‑κB phosphorylation. Further experiments demonstrated that Rb1 ameliorated FFA‑induced ROS generation and NO reduction through upregulation of superoxide dismutase 2 and eNOS expression. Taken together, these results demonstrate proinflammatory and pro‑oxidant effects of FFA on 3T3‑L1 adipocytes, which are effectively ameliorated by Rb1. Suppression of inflammatory responses and oxidative stress may be a novel mechanism for attenuating the effect of Rb1 on adipocyte dysfunction.

The present study aimed to investigate the protective effects of salidroside on chronic heart failure (CHF) in rats and to explore the underlying mechanisms. One hundred SD rats were randomly divided into sham-operated, model, and low-, medium- and high-dose salidroside groups. The CHF model was established in later 4 groups. The later 3 groups were intragastrically administrated with 6, 12 and 24 mg/kg salidroside, respectively, once a day, for continuous 4 weeks. Finally, the serum levels of brain natriuretic peptide (BNP) and interleukin 6 (IL-6), cardiac function indexes, and expression levels of myocardial cysteinyl aspartate-specific proteinase (Caspase)-3, Caspase-9, matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein were determined. Results showed that, after treatment, compared with model group, in high-dose salidroside group the heart function indexes were significantly improved (P < 0.05), the serum levels of BNP and IL-6 were significantly decreased (P < 0.05), the expression levels of myocardial Caspase-3, Caspase-9 and MMP-1 protein were significantly decreased (P < 0.05), and the expression level of TIMP-1 protein was significantly increased (P < 0.05). In conclusion, salidroside has obvious protective effects on CHF in rats. The mechanisms may be related to its regulation of cardiomyocyte apoptosis and ventricular remodelingregulation related protein expressions.

This study aimed to investigate whether recombinant human brain natriuretic peptide (rhBNP) regulated hypoxia-induced injury in H9c2 cardiomyocytes through lncRNA EGOT. H9c2 cardiomyocytes were cultured under normoxia and hypoxia (21% and 3% O2) conditions, and whether hypoxia induced injury by assessing cell viability, apoptosis and autophagy. H9c2 cells were then treated with different doses of exogenous rhBNP (200, 600 and 900 nmol/L, respectively) and the effects of rhBNP on hypoxia-induced injury in H9c2 cells as well as the expression of EGOT were studied. In addition, the regulatory relationships between rhBNP and EGOT as well as between rhBNP and PI3K/AKT/mTOR pathway in hypoxia-treated H9c2 cells were investigated. Hypoxia significantly induced injury in H9c2 cells (inhibited cell viability and promoted cell apoptosis and autophagy) and decreased the expression of EGOT. However, administration of rhBNP alleviated hypoxia-induced injury in H9c2 cells and elevated expression of EGOT. Suppression of EGOT significantly reversed the effects of rhBNP on hypoxia-induced injury in H9c2 cells. Further studies showed that the effects of EGOT on cell viability and apoptosis were by positively regulating the expression of Cyclin D1. Moreover, rhBNP alleviated hypoxia-induced cell injury by activating PI3K/AKT/mTOR pathway in H9c2 cells. Our results reveal that rhBNP may play a protective role in attenuating hypoxia-induced injury in H9c2 cardiomyocytes via regulating lncRNA EGOT/Cyclin D1/PI3K/AKT/mTOR pathway axis. The findings will provide a new strategy for the treatment of heart failure induced by hypoxia.

This study aimed to investigate the effects and mechanisms of long noncoding RNA SRA1 on regulating hypoxia-induced injury in H9c2 cardiomyocytes. The H9c2 cardiomyocytes were cultured under hypoxic (3% O(2)) conditions and whether hypoxia induced injury was assessed by detecting cell viability, apoptosis and autophagy. Then, SRA1 was overexpressed and suppressed in H9c2 cardiomyocytes by transfection with pc-SRA1 and sh-SRA1, and the effects of SRA1 dysregulation on cell viability, apoptosis, and autophagy of H9c2 cardiomyocytes under hypoxia condition were detected. Furthermore, the regulatory relationship between SRA1 and PPARγ was explored, as well as the association between SRA1 and NF-κB signaling. Hypoxia induced injury to H9c2 cardiomyocytes, such as inhibiting cell viability, and promoting cell apoptosis and autophagy. Moreover, hypoxia resulted in a decreased expression of SRA1 in H9c2 cardiomyocytes, and overexpression of SRA1 alleviated hypoxia-induced injury, while suppression of SRA1 indicated the contrary results. Further studies showed that SRA1 positively regulated PPARγ. Overexpression of SRA1 alleviated hypoxia injury by activating PPARγ. Besides, suppression of SRA1 activated NF-κB pathway in hypoxia-treated H9c2 cardiomyocytes, which were significantly reversed after suppression of SRA1 and overexpression of PPARγ at the same time. Our findings indicated that suppression of SRA1 may aggravate hypoxia-induced injury to H9c2 cardiomyocytes by positive regulation of PPARγ and activation of NF-κB pathway. SRA1 may serve as a promising perspective for the therapy of heart failure induced by hypoxia.

The present meta-analysis examined the diagnostic value of novel biomarkers for heart failure (HF), including copeptin, galectin-3, hs-cTnT, MR-proANP, MR-proADM, and ST2. English (EMBASE, Cochrane, and PubMed) and Chinese (Wanfang data, CNKI, SinoMed) databases were searched to identify suitable studies that were published before 1 December 2016. Data were extracted using standard forms. Pooled diagnostic statistics were calculated using DerSimonian–Laird random-effects models. The analysis comprised 45 studies. The pooled sensitivities of all biomarkers were 0.80–0.86, along with pooled specificities of 0.60–0.82, positive predictive values (PPVs) of 0.52–0.80, and negative predictive values (NPVs) of 0.70–0.87. Among them, hs-cTnT had the highest sensitivity (0.86 [95% CI: 0.84–0.88]), specificity (0.82 [95% CI: 0.79–0.84]), PPV (0.80 [95% CI: 0.77–0.83]), and NPV (0.87 [95% CI: 0.85–0.89]), while MR-proADM had the lowest sensitivity (0.80 [95% CI: 0.75–0.84]), specificity (0.60 [95% CI: 0.56–0.64]), and PPV (0.52 [95% CI: 0.47–0.56]). Copeptin had the lowest NPV (0.70 [95% CI: 0.66–0.74]). The positive likelihood ratio (LR+) of all biomarkers ranged from 1.97 to 3.21, and the negative likelihood ratio (LR−) from 0.20 to 0.36. MR-proADM had the lowest LR+ and highest LR−; galectin-3 had the highest LR+ and MR-proANP had the lowest LR−. The area under the curve (AUC) was as low as 0.68 for MR-proADM, while AUCs for the other biomarkers ranged from 0.83 to 0.89. The overall diagnostic accuracy of copeptin, galectin-3, hs-cTnT, MR-proANP, and ST2 was relatively good. MR-proADM had a poor capacity to confirm or exclude HF. Improving the diagnostic accuracy of HF by a combination of biomarkers could be considered in the future.

Vascular disease is one of the most significant threats to the lives of patients suffering from diabetes, and chronic exposure of vascular endothelial cells to high glucose has been shown to significantly contribute to the process of endothelial cell dysfunction, one of the earliest events in diabetes-associated vascular disease. Nucleotide oligomerization domain (NOD)-like receptor pyrin domain-containing 3 (NLRP3) inflammasome plays a key role in initiating the inflammatory process by facilitating the production of interleukin-1β (IL-1β) and IL-18. ASC and caspase 1 are also implicated in NLRP3 inflammasome-mediated chronic inflammation. While under normal conditions, a balance exists between oxidants and antioxidants, exposure to high glucose significantly increases the production of ROS, which is enhanced by NOX4 expression. In the present study, we explored the role of orexin A, an endogenous peptide produced in the hypothalamus, in high glucose-induced activation of the NLRP3 inflammasome, oxidative stress, and expression of several key cytokines. Our findings demonstrate that orexin A exerts potent antioxidant effects in human aortic endothelial cells exposed to high glucose by inhibiting mitochondrial ROS and expression of NOX4 at both the mRNA and protein levels as revealed by MitoSOX staining, real-time PCR, and Western blot analysis. We also show that orexin A inhibits high glucose-induced expression of TxNIP, which is crucial to the activation of the NLRP3 inflammasome, as well as that of HMGB1. We confirmed via real-time PCR and Western blot analysis that orexin A suppressed the production of the inflammatory cytokines IL-1β and IL-18. Additionally, through SIRT1 knockdown siRNA experimentation, we confirmed that SIRT1 knockdown abolishes the effects of orexin A described above, thereby indicating a critical role of SIRT in the capacity of orexin A to ameliorate high glucose-induced oxidative stress and activation of NLRP3 inflammasome.

To study the mechanism of the oxidative damage in Ginsenoside Rb1 against the intrinsic aging of mouse brain. Female C57BL/6 mice were divided into three groups randomly: control group(4 months, n=12); model group(24 months, n=12) and drug group(24 months, n=12). In drug group, ginsenoside Rb1(20mg

Overweight and obesity have become a public health problem. In obese state, abundant fatty free acids (FFA) were released from hyperplastic adipose tissue and were release to adipocytes, skeletal muscle, liver, then leading to adipocytes inflammation and insulin resistance. Ginsenoside Rb1 was

To study the mechanism of the mTOR in Ginsenoside Rb1 against the intrinsic aging of mouse brain. Female C57BL/6 mice were divided into three groups randomly: control group(4 months, n=12); model group(24 months, n=12) and drug group(24 months, n=12). In drug group, ginsenoside Rb1(20mg.kg-1.d-1)