Search

A series of digermylenes R(EGeL)

Objective. The accelerate loss of skeletal muscle mass, strength, and function, named sarcopenia, is a progressive and generalised skeletal muscle disorder, and it is always associated with increased outcomes including falls, frailty, and disability. Diabetes mellitus is associated with significant muscle and physical complications. We aimed at clarifying the changes and risk factors of skeletal muscle mass and strength in elderly with type 2 diabetes. Methods. The study consisted of patients with type 2 diabetes ( n = 120 ) and an older general population ( n = 126 ). The skeletal muscle mass and muscle strength, as well as the serum levels of chronic inflammation, oxidative stress, homocysteine, and insulin-like factor-1 were assessed, and the correlation and regression analysis were conducted to evaluate outcomes. Results. T2DM patients exhibited lower muscle strength compared with the non-T2DM subjects ( P < 0.01 ). Among T2DM patients, serum IGF-1 levels were positively correlated with muscle strength ( r = 0.255 , P < 0.01 ) and muscle mass ( r = 0.209 , P < 0.05 ), levels of 8-OHdG were inversely correlated with muscle strength ( r = − 0.252 , P < 0.01 ), and there was a negative association between HCY and muscle mass ( r = − 0.185 , P < 0.05 ). Muscle mass and strength of patients with higher education level were significantly higher than those with lower education level ( P < 0.05 ), in male patients, muscle mass and muscle strength were significantly lower in smokers ( P < 0.01 ), and muscle mass was lower in chronic drinkers ( P < 0.05 ). Conclusions. These findings suggest that diabetic patients may be more susceptible to sarcopenia at an older age. And it also provides evidences that among elderly with diabetes mellitus, oxidative damage and HCY as well as IGF-1 are important predictors of age-dependent sarcopenia.

Oxidative stress acts as an essential culprit factor in the development of stroke and Alzheimer’s disease. Norcepharadione B possesses various pharmacologic features as an extract obtained from Houttuynia cordata. Nevertheless, the anti-apoptotic and neuroprotective characteristics of norcepharadione B remain unclear. In this study, the neuronal protection effect provided by norcepharadione B against injury caused by hydrogen peroxide (H2O2) in HT22 cell as well as the fundamental mechanism was systematically explored. The neurotoxicity assays of hippocampal cells, which were co-cultured with H2O2, showed that norcepharadione B had the ability to insulate the toxicity induced by H2O2 with significant reduced cell apoptosis. Besides, norcepharadione B potentiated the activity of superoxide dismutase (SOD), increased the level of glutathione (GSH), and decreased malondialdehyde content. The H2O2-induced apoptotic protein Bax was suppressed, and the anti-apoptotic protein Bcl-2 was boosted by norcepharadione B. Norcepharadione B promoted Akt phosphorylation and further upregulated heme oxygenase (HO-1) in cells exposed to oxidative stress. However, the inductive effect of HO-1 by norcepharadione B was shut off via the PI3K/Akt inhibitor LY294002. Furthermore, 2-h incubation with H2O2 substantially increased cell volume in HT22 cells, while norcepharadione B effectively alleviated such effect by interrupting the activation of VSOR Cl− channel. Collectively, our data revealed protective properties of norcepharadione B in resisting oxidative stress induced by H2O2 through elevation of HO-1 in the dependence of PI3K/Akt and in inhibiting H2O2-induced cell swelling by VSOR Cl− channel obstruction in HT22 cells. Impact statement Norcepharadione B is an aporphine alkaloid compound extracted from Chinese herb Houttuynia cordata. It was well known for its anti-inflammatory, anti-cancer, and anti-platelet aggregation outcomes. Our study demonstrated that Norcepharadione B protected hippocampal neurons against oxidative stress and the resultant cell apoptosis upon H2O2 exposure. Meanwhile, Norcepharadione B also substantially reduced cell swelling induced by H2O2 via inhibiting VSOR Cl− channel in neurons. These findings uncovered the potential mechanisms of Norcepharadione B in protecting neuron apoptosis under oxidative stress and propose that Norcepharadione B may serve as a favorable herb medicine for restoring neuronal injury in the pathogenesis of stroke together with other neurodegenerative diseases.

The damage of vascular endothelial cells has become an indispensable factor in the occurrence and advancement of cardiovascular diseases. In the current study, we investigated the effect of Astragalus Polysacharin (APS) on H2O2-evoked oxidative injury in HUVECs. HUVECs cells were treated by H2O2 to induce oxidative damage. Cells viability, apoptosis and reactive oxygen species (ROS) level were detected through CCK8 assay and flow cytometry. The cell growth-related proteins and heme oxygenase-1(HO-1) and KLF2 expression were evaluated via Western blot assay. The functions of KLF2 in APS and H2O2 co-disposed HUVECs were explored after si-KLF2 transfection. MEK/ERK pathway was finally measured through Western blot. We found that H2O2 stimulation-evoked HUVECs oxidative damage meanwhile impeded HO-1 expression. APS treatment effectively suppressed H2O2-induced oxidative injury in HUVECs. KLF2 and Nrf2 expression were elevated by APS and KLF2 repression abolished the protective action of APS in H2O2-triggered cell injury. MEK/ERK pathway was activated by APS treatment. Furthermore, the MEK/ERK pathway inhibitor weakened the promoting effect of APS on the expression of KLF2. In conclusion, our study reveals that APS alleviates H2O2-triggered oxidative injury in HUVECs via elevating the expression of KLF2 via the MEK/ERK pathway.

Background: With the aggravation of social competition and work burden pressure, the health condition of the middle-aged and above population in China has declined significantly. Frailty can be used as a criterion for evaluating a person's unhealthy state. However, there is limited data on the prevalence and related factors of frail status in Chinese middle-aged and older people.The objective of this study was to explore the correlation between frail status, chronic diseases, abnormal physical examination indicators among middle-aged and older populations.Methods: Participants were 9,985 community-dwelling adults over the age of 40 years living in China. Data were from the 2015 China Health and Retirement Longitudinal Survey which was a nationally representative sample and frailty phenotype was based on Fried frailty criteria. We analyzed the demographics of participants and multivariate-adjusted related factors for frail and pre-frail population.Results: The overall prevalence of frailty and pre-frailty was 3.1% (95% CI: 2.8, 3.5) and 53.66% (95% CI: 52.7, 54.6) among the general Chinese population aged 40 years or older. Hypertension (OR: 1.8, 95% CI: 1.3, 2.593), pain (OR: 1.8, 95% CI: 1.3, 2.5), and hip fracture (OR: 2.2, 95% CI: 1.1, 4.4) were associated with prevalent frailty. Relative factors for frailty also included increased cystatin C (OR: 4.5, 95% CI: 3.0, 6.7) and glycated hemoglobin (OR: 1.2, 95% CI: 1.1, 1.4), as well as decreased peak expiratory flow (OR: 0.993, 95% CI: 0.991, 0.994).Conclusions: Fried-defined frailty and pre-frailty are highly prevalent in the Chinese population over 40 years older. Hypertension, pain, hip fracture, low education, and underweight are major related factors for frailty. The decrease in peak expiratory flow and the increase in cystatin C and glycated hemoglobin are good indicators for detecting frailty. Thus, frailty is an increasingly common condition and will become a major important health issue for people over middle age.

Oxidative stress acts as an essential culprit factor in the development of stroke and Alzheimer’s disease. Norcepharadione B possesses various pharmacologic features as an extract obtained from Houttuynia cordata. Nevertheless, the anti-apoptotic and neuroprotective characteristics of norcepharadione B remain unclear. In this study, the neuronal protection effect provided by norcepharadione B against injury caused by hydrogen peroxide (H(2)O(2)) in HT22 cell as well as the fundamental mechanism was systematically explored. The neurotoxicity assays of hippocampal cells, which were co-cultured with H(2)O(2), showed that norcepharadione B had the ability to insulate the toxicity induced by H(2)O(2) with significant reduced cell apoptosis. Besides, norcepharadione B potentiated the activity of superoxide dismutase (SOD), increased the level of glutathione (GSH), and decreased malondialdehyde content. The H(2)O(2)-induced apoptotic protein Bax was suppressed, and the anti-apoptotic protein Bcl-2 was boosted by norcepharadione B. Norcepharadione B promoted Akt phosphorylation and further upregulated heme oxygenase (HO-1) in cells exposed to oxidative stress. However, the inductive effect of HO-1 by norcepharadione B was shut off via the PI3K/Akt inhibitor LY294002. Furthermore, 2-h incubation with H(2)O(2) substantially increased cell volume in HT22 cells, while norcepharadione B effectively alleviated such effect by interrupting the activation of VSOR Cl(−) channel. Collectively, our data revealed protective properties of norcepharadione B in resisting oxidative stress induced by H(2)O(2) through elevation of HO-1 in the dependence of PI3K/Akt and in inhibiting H(2)O(2)-induced cell swelling by VSOR Cl(−) channel obstruction in HT22 cells. IMPACT STATEMENT: Norcepharadione B is an aporphine alkaloid compound extracted from Chinese herb Houttuynia cordata. It was well known for its anti-inflammatory, anti-cancer, and anti-platelet aggregation outcomes. Our study demonstrated that Norcepharadione B protected hippocampal neurons against oxidative stress and the resultant cell apoptosis upon H(2)O(2) exposure. Meanwhile, Norcepharadione B also substantially reduced cell swelling induced by H(2)O(2) via inhibiting VSOR Cl(−) channel in neurons. These findings uncovered the potential mechanisms of Norcepharadione B in protecting neuron apoptosis under oxidative stress and propose that Norcepharadione B may serve as a favorable herb medicine for restoring neuronal injury in the pathogenesis of stroke together with other neurodegenerative diseases.

The damage of vascular endothelial cells has become an indispensable factor in the occurrence and advancement of cardiovascular diseases. In the current study, we investigated the effect of Astragalus Polysacharin (APS) on H

In this report, protein of hairtail (Trichiurus japonicas) muscle was separately hydrolyzed using five kinds of proteases (alcalase, trypsin, neutrase, pepsin, and papain), and the papain- and alcalase-hydrolysates showed higher 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) and hydroxyl radical (HO•) scavenging activity than other three protease hydrolysates. Therefore, the protein hydrolysate of hairtail muscle (HTP) was prepared using binary-enzymes hydrolysis process (papain + alcalase). Subsequently, eight antioxidant peptides were purified from HTP using membrane ultrafiltration and chromatography technology, and their amino acid sequences were identified as Gln-Asn-Asp-Glu-Arg (TJP1), Lys-Ser (TJP2), Lys-Ala (TJP3), Ala-Lys-Gly (TJP4), Thr-Lys-Ala (TJP5), Val-Lys (TJP6), Met-Lys (TJP7), and Ile-Tyr-Gly (TJP8) with molecular weights of 660.3, 233.0, 217.1, 274.1, 318.0, 245.1, 277.0, and 351.0 Da, respectively. TJP3, TJP4, and TJP8 exhibited strong scavenging activities on DPPH• (EC50 0.902, 0.626, and 0.663 mg/mL, respectively), HO• (EC50 1.740, 2.378, and 2.498 mg/mL, respectively), superoxide anion radical (EC50 2.082, 2.538, and 1.355 mg/mL, respectively), and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical (EC50 1.652, 0.831, and 0.586 mg/mL, respectively). Moreover, TJP3, TJP4, and TJP8 showed higher reducing power and inhibiting ability on lipid peroxidation in a linoleic acid model system. These results suggested that eight isolated peptides (TJP1 to TJP8), especially TJP3, TJP4, and TJP8 might serve as potential antioxidants applied in the pharmaceutical and health food industries.

Dynamic modeling of surface ships is a prerequisite for intelligent navigation and ship motion control. It is easy to ignore the nonlinear and strong coupling of ship dynamics by using traditional mechanism modeling. Moreover, the obtained parameter errors will be large due to the influence of noise and multicollinearity, it is difficult to establish a high-precision ship dynamic model. This study use a data-driven nonparametric bayesian model based on gaussian process regression on dynamic modelling of ship, it can capture the strong nonlinearity and motion coupling in ship motion, and deal with the presence of uncertainty and noise. SG filter is used to smooth the data to reduce the influence of noise on modeling. The results indicate that the gaussian processes regression and the SG filter can reproduce the ship’s motion well, which is beneficial to the further development of ship control design.

Punicalagin (PUN), a major bioactive component in pomegranate juice, has been proven to exert neuroprotective effects against cerebral ischemia/reperfusion (I/R) insult via anti-oxidant properties. This study aims to investigate whether PUN provides cardioprotection against myocardial I/R (MI/R) injury and the underlying mechanisms. PUN (30[Formula: see text]mg/kg/d) or vehicle was intragastrically administered to Sprague-Dawley rats for one week before the operation. MI/R was induced by ligating the left anterior descending coronary artery for 30[Formula: see text]min and subsequent reperfusion for 3[Formula: see text]h. PUN pretreatment conferred cardioprotective effects against MI/R injury by improving cardiac function, limiting infarct size, reducing serum creatine kinase-MB and lactate dehydrogenase activities, and suppressing cardiomyocyte apoptosis. Moreover, PUN pretreatment inhibited I/R-induced myocardial oxidative stress as evidenced by decreased generation of superoxide content and malonaldialdehyde formation and increased antioxidant capability. Furthermore, PUN pretreatment increased adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation in I/R hearts. AMPK inhibitor compound c inhibited PUN-enhanced AMPK phosphorylation, and blunted PUN-mediated anti-oxidative effects and cardioprotection. These results indicate for the first time that PUN pretreatment protect against I/R-induced oxidative stress and myocardial injury via activation of AMPK.

In this report, protein of hairtail (Trichiurus japonicas) muscle was separately hydrolyzed using five kinds of proteases (alcalase, trypsin, neutrase, pepsin, and papain), and the papain- and alcalase-hydrolysates showed higher 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH&bull, ) and hydroxyl radical (HO&bull, ) scavenging activity than other three protease hydrolysates. Therefore, the protein hydrolysate of hairtail muscle (HTP) was prepared using binary-enzymes hydrolysis process (papain + alcalase). Subsequently, eight antioxidant peptides were purified from HTP using membrane ultrafiltration and chromatography technology, and their amino acid sequences were identified as Gln-Asn-Asp-Glu-Arg (TJP1), Lys-Ser (TJP2), Lys-Ala (TJP3), Ala-Lys-Gly (TJP4), Thr-Lys-Ala (TJP5), Val-Lys (TJP6), Met-Lys (TJP7), and Ile-Tyr-Gly (TJP8) with molecular weights of 660.3, 233.0, 217.1, 274.1, 318.0, 245.1, 277.0, and 351.0 Da, respectively. TJP3, TJP4, and TJP8 exhibited strong scavenging activities on DPPH&bull, (EC50 0.902, 0.626, and 0.663 mg/mL, respectively), HO&bull, (EC50 1.740, 2.378, and 2.498 mg/mL, respectively), superoxide anion radical (EC50 2.082, 2.538, and 1.355 mg/mL, respectively), and 2,2&prime, azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical (EC50 1.652, 0.831, and 0.586 mg/mL, respectively). Moreover, TJP3, TJP4, and TJP8 showed higher reducing power and inhibiting ability on lipid peroxidation in a linoleic acid model system. These results suggested that eight isolated peptides (TJP1 to TJP8), especially TJP3, TJP4, and TJP8 might serve as potential antioxidants applied in the pharmaceutical and health food industries.

// Yuesheng Xia 1,* , Yan Liu 1,* , Tong Xia 2,* , Xing Li 1 , Cong Huo 1 , Xin Jia 1 , Lin Wang 1 , Rong Xu 1 , Ning Wang 1 , Mingming Zhang 3 , Hong Li 1 and Xiaoming Wang 1 1 Department of Geriatrics, Xijing Hospital, Fourth Military Medical University, Xi’an, China 2 Department of Preventive Medicine, Sun Yat-sen University, Guangzhou, China 3 Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China * These authors have contributed equally to this work Correspondence to: Xiaoming Wang, email: // Keywords : ischemia/reperfusion injury, VSOR Cl - channel, reactive oxygen species, autophagy, cell death, Pathology Section Received : April 08, 2016 Accepted : June 03, 2016 Published : June 14, 2016 Abstract Excessive reactive oxygen species (ROS) plays an important role in myocardial ischemia/reperfusion (I/R) injury, which triggers not only myocardial cellular apoptosis but also autophagy-related cell death, in which volume-sensitive outwardly rectifying (VSOR) Cl - channel-activated by ROS contributes to cell apoptotic volume decrease, playing an incipient incident of cellular apoptosis. However, whether VSOR Cl - channel concurrently participates in autophagy-related cell death regulation remains unclear. To illuminate the issue, studies underwent in myocardial vitro and vivo I/R model. Rats were performed to ischemia 30 minutes and subsequent reperfusion 24-96 hours, ROS scavenger (NAC), VSOR Cl - channel blocker (DCPIB) and autophagy inhibitor (3MA) were administered respectively. Results showed that oxidative stress, LC3-II stain and inflammation in myocardial tissue were markedly increased, lysosome associated membrane protein-2 (LAMP2) were significantly reduced with I/R group as compared with sham group, reperfusion significantly led to damage in myocardial tissue and heart function, whereas the disorder could be rescued through these agents. Moreover, primary neonatal rat cardiomyocytes hypoxia/reoxygenation model were administered, results showed that VSOR Cl - channel-activated by reoxygenation could cause both cell volume decrease and intracellular acidification, which further increased LC3 and depleted of LAMP2, resulting in autophagy-related cell death. Interestingly, VSOR Cl - channel-blocked by DCPIB could stably maintain the cell volume, intracellular pH, abundant LAMP2 and autophagic intensity regardless of ROS intension derived from reoxygenation injury or adding H 2 O 2 . These results first demonstrate that VSOR Cl - channel-activated is a pivotal event to trigger autophagy-related death, which reveals a novel therapeutic target to decrease myocardial I/R injury.

Endoplasmic reticulum (ER) stress is key in the development of cardiovascular diseases. However, there is a lack of a systemic ER stress‑induced cardiomyocyte apoptosis model. In the present study, primary cultured neonatal rat cardiomyocytes were exposed to tunicamycin. Cell viability was determined by an MTT assay, and cell damage was detected by a lactose dehydrogenase assay. Flow cytometry was used and the activity of caspase‑3 was analyzed in order to measure apoptosis. Reverse transcription-quantitative polymerase chain reaction and western blotting were used to examine the expression of glucose‑regulated protein 78‑kDa (GRP78) and C/EBP homologous protein (CHOP). As a result, tunicamycin significantly increased cardiomyocyte injury, which occurred in a time- and concentration‑dependent manner. In addition, tunicamycin treatment resulted in apoptosis of cardiomyocytes. Molecularly, tunicamycin (100 ng/ml) increased the levels of GRP78 and CHOP 6 h after administration. In addition, GRP78 and CHOP reached maximum mRNA and protein levels 24 h after administration. In conclusion, the results implicate that the tunicamycin‑induced ER stress‑induced apoptotic model was successfully constructed in cultured neonatal rat cardiomyocytes. A 100 ng/ml concentration of tunicamycin was selected, and MTT, LDH release and flow cytometry assay was at 72 h. In addition, GRP78 and GRP94 were detected 24 h following administration. The results of the present study indicate a novel experimental basis for the investigation of ERS-induced cardiac apoptosis.

Many cardioprotective pharmacological agents failed to exert their protective effects in diabetic hearts subjected to myocardial ischemia/reperfusion (MI/R). Identify the molecular basis linking diabetes with MI/R injury is scientifically important and may provide effective therapeutic approaches. Dynamin-related protein 1 (Drp1)-mediated mitochondrial fission plays an important role in MI/R injury under non-diabetic conditions. Importantly, recent studies indicated that Drp1-mediated mitochondrial fission is enhanced in the myocardium of diabetic mice. The above evidences suggested that Drp1 may be one critical molecule linking diabetes with MI/R injury. We hypothesized that inhibition of Drp1 may be effective to reduce MI/R injury in diabetic hearts. High-fat diet and streptozotocin-induced diabetic mice were subjected to MI/R or sham operation. Mdivi-1 (1.2 mg/kg), a small molecule inhibitor of Drp1 or vehicle was administrated 15 min before the onset of reperfusion. Outcome measures included mitochondrial morphology, mitochondrial function, myocardial injury, cardiac function and oxidative stress. Mitochondrial fission was significantly increased following MI/R as evidenced by enhanced translocation of Drp1 to mitochondria and decreased mitochondrial size. Delivery of Mdivi-1 into diabetic mice markedly inhibited Drp1 translocation to the mitochondria and reduced mitochondrial fission following MI/R. Inhibition of Drp1 in diabetic hearts improved mitochondrial function and cardiac function following MI/R. Moreover, inhibition of Drp1 reduced myocardial infarct size and serum cardiac troponin I and lactate dehydrogenase activities. These cardioprotective effects were associated with decreased cardiomyocyte apoptosis and malondialdehyde production and increased activities of antioxidant enzyme manganese superoxide dismutase. Pharmacological inhibition of Drp1 prevents mitochondrial fission and reduces MI/R injury in diabetic mice. The findings suggest Drp1 may be a potential novel therapeutic target for diabetic cardiac complications.