A comparison of interferential current efficacy in elderly intervertebral disc degeneration patients with or without sarcopenia: a retrospective study.

BACKGROUND: Intervertebral disc degeneration and sarcopenia are both age-related diseases without effective treatments. Their comorbidities may worsen the prognosis, and further studies on interaction and therapy are needed. The purpose of the study was to investigate the prevalence of sarcopenia in intervertebral disc degeneration, and to compare the characteristics of intervertebral disc degeneration with and without sarcopenia and effects of interferential current. METHODS: One hundred twenty disc degeneration patients were included from 2021 to 2022 in a single institute. Medical records, examination results and radiological reports were reviewed. Patients with sarcopenia were screened and grouped according to Asian Working Group for Sarcopenia 2019. VAS, ODI, SARC-F, SMI, gait speed (GS), grip strength, disc Pfirrmann grading, standard cross-sectional area (SCSA), degree of fatty infiltration (DFF), and nerve conduction velocity (NCV) were assessed before and after treatment. RESULTS: The prevalence of sarcopenia in intervertebral disc degeneration was 28.3%. The difference of VAS, ODI, disc Pfirrmann grading, SCSA, DFF and NCV between two groups were significant before intervention (P < 0.05), SCSA and DFF were related to the degree of disc degeneration. The improvement of SMI, GS, grip strength, VAS, SARC-F and ODI in intervertebral disc degeneration with sarcopenia group was significant after intervention, as well as SMI, GS, grip strength, VAS and ODI in those without sarcopenia (P < 0.05). The improvement of grip strength, GS, ODI and SARC-F in intervertebral disc degeneration with sarcopenia group were greater than the one without sarcopenia (P < 0.05), whereas there was no significance in improvement degree of other indicators between the two groups (P > 0.05). CONCLUSION: The prevalence of sarcopenia was high in intervertebral disc degeneration, and paravertebral muscles degeneration correlated with the degree of disc degeneration. Compared to those without sarcopenia, intervertebral disc degeneration patients with sarcopenia have more severe pain, poorer mobility and neurological function. Interferential current is effective in intervertebral disc degeneration patients and sarcopenia patients.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3.

Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3'-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

Activation of Keap1-Nrf2 signaling by 4-octyl itaconate protects human umbilical vein endothelial cells from high glucose.

High glucose (HG) induces oxidative injury to cultured human umbilical vein endothelial cells (HUVECs). Recent studies have discovered 4-octyl itaconate (OI) as a novel and cell permeable Nrf2 (nuclear-factor-E2-related factor 2) activator. Its potential activity in HG-treated HUVECs was tested here. In HUVECs OI disrupted Keap1-Nrf2 association, causing Nrf2 protein accumulation and nuclear translocation, as well as transcription and expression of Nrf2-ARE-dependent genes, including HO1, NQO1 and GCLM. Significantly, pretreatment with OI potently inhibited HG (40 mM glucose)-induced death and apoptosis of HUVECs. Moreover, OI potently inhibited HG-induced reactive oxygen species (ROS) production, lipid peroxidation, superoxide accumulation and mitochondrial depolarization in HUVECs. Activation of Nrf2 is required for OI-induced cytoprotection in HUVECs. Nrf2 shRNA or knockout (by CRISPR/Cas9 method) reversed OI-mediated HUVEC protection against HG. Further studies showed that Keap1 silencing or Cys151S mutation mimicked and nullified OI-induced activity in HUVECs. Taken together, we conclude that OI activates Keap1-Nrf2 signaling to protect HUVECs from HG.

Effectiveness of a PRECEDE-based education intervention on quality of life in elderly patients with chronic heart failure.

BACKGROUND: One of the most important challenges in public health is to improve the quality of life in patients with chronic heart failure (CHF). Depression, self-care capacity, and quality of life interact each other in these patients. It's difficult to treat with general education programs and conventional therapy. PRECEDE model is a comprehensive and exclusive theory-based education programs. Its effectiveness for reducing depression and increasing quality of life has been demonstrated in patients with coronary artery bypass grafting, type 2 diabetes, and the elderly. It has not been used in elderly patients with CHF. Thus, this study aims to investigate the effects of this model on self-care behaviors, depression, and quality of life in these patients. METHODS: Patients who met the inclusion criteria were randomly assigned to the intervention or control group. All the patients received conventional medical care. The patients in the intervention group also received 9 sessions of education intervention based on the PRECEDE model and then followed up for 3 months after the intervention. Data were collected before and 3 months after the intervention using 4 questionnaires, namely a PRECEDE-based questionnaire to evaluate predisposing, reinforcing, and enabling factors; the 9-item European Heart Failure Self-care Behavior Scale (EHFScBS-9); the 9-item Personal Health Questionnaire (PHQ-9); and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). RESULTS: No significant differences were found in the mean scores for the predisposing, enabling, and reinforcing factors, and the mean total scores in EHFScBS-9, PHQ-9, and MLHFQ before the intervention between the intervention and control groups. After the intervention, the scores for the predisposing, reinforcing, and enabling factors increased significantly, and the mean total scores in EHFScBS-9, PHQ-9, and MLHFQ decreased significantly in the intervention group. In addition, these scores significantly differed from those of the control group. Furthermore, the MLHFQ score significantly correlated with the EHFScBS-9 and PHQ-9 scores. CONCLUSION: This study demonstrates a trend that PRECEDE model of health education promotion is effective in relieving depression symptoms, enhancing self-monitoring, and improving the quality of life of elderly patients with CHF. TRIAL REGISTRATION: Trial registration number: ChiCTR-IOR-17012779 ; Trial registry: Chinese Clinical Trial Registry; Date registered: 22 Sep 2017; Retrospectively registered.

The influence of oxidation debris containing in graphene oxide on the adsorption and electrochemical properties of 1,10-phenanthroline-5,6-dione.

It is gradually accepted that graphene oxide, which is derived from the exfoliation of graphite oxide that is synthesized by the chemical oxidation of graphite, actually consists of partially oxidized graphene sheets and highly oxidized carbonaceous debris. The quantity of oxidation debris comprises around one third of the total mass of the graphene oxide. The presence of oxidation debris has a significant impact on the physical and chemical properties of graphene oxide. In this article, we address the influence of the oxidation debris on the surface properties of graphene oxide. We discovered that the surface adsorption of organic molecules on graphene oxide was improved greatly after the elimination of the oxidation debris. A typical redox mediator, 1,10-phenanthroline-5,6-dione, was studied as the model adsorbed molecule in terms of its adsorption quantity and electrochemical response. After removing the oxidation debris, a five-fold increase in adsorption capacity is achieved on the same amount of graphene oxide. Correspondingly, the electrochemical response for the oxidation of NADH mediated by the adsorbed 1,10-phenanthroline-5,6-dione was enhanced as well, which led to improved analytical performances in terms of the sensitivity, linear range and detection limit for the purified graphene oxide modified electrode.

The effects of statins on benign prostatic hyperplasia in elderly patients with metabolic syndrome.

PURPOSE: To evaluate the effects of simvastatin and atorvastatin in elderly male patients with benign prostatic hyperplasia (BPH) accompanied by metabolic syndrome (MetS). METHODS: Eligible patients aged >60 year with BPH accompanied by MetS were randomly assigned to receive 40 mg of simvastatin daily, 20 mg of atorvastatin daily or placebo (control group) treatment for 12 months. Serum lipids, interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), prostate-specific antigen, prostate volume (PV) and the International Prostate Symptom Score (IPSS) were tested before and after treatment. RESULTS: The levels of serum total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol, hs-CRP, IL-6 and IPSS was decreased, serum high-density lipoprotein cholesterol (HDL-C) was increased, and PV was reduced in the patients following treatments with statins. The PV of the patients who received simvastatin were reduced more than those of the patients who received atorvastatin. The decrease in PV was more significant in the obesity patients than in the normal weight patients and in the hyperlipidemia patients than in the normal-lipid patients following the statin interventions. The reduction in PV was positively related to the decreases in the levels of TC and IL-6 and to the increase in the level of HDL-C. CONCLUSIONS: Simvastatin and atorvastatin significantly reduced PV, improved lower urinary tract symptoms, and slowed the clinical progression of BPH possibly by lowering cholesterol and anti-inflammatory factors.

The relationship between fasting plasma glucose and MPO in patients with acute coronary syndrome.

BACKGROUND: Inflammation plays a critical role in the progression of atherosclerosis, and hyperglycemia is a common feature in patients with ACS. We investigated the relationship between fasting plasma glucose (FPG) levels and the levels of the inflammatory factor, myeloperoxidase (MPO), in patients with acute coronary syndrome (ACS). METHOD: A total of 85 patients with no prior history of diabetes mellitus were recruited. The patients were divided into three groups based on their FPG levels as follows: group A, FPG < 5.6 mmol/l; group B, 5.6 mmol/l ≤ FPG < 6.1 mmol/l; and group C, FPG ≥ 6.1 mmol/l. The FPG concentrations and plasma MPO levels were determined, coronary angioplasty was performed, and the Gensini scores were used to evaluate the severity of the coronary lesion. The MPO expression in peripheral blood mononuclear cells (PBMCs) in patients with ACS was determined using western blot analysis. RESULT: The results demonstrated that the levels of FPG were significantly and positively correlated with plasma MPO levels, Gensini scores, high sensitive C reaction protein(hs-CRP)levels, leukocyte and neutrophils count. In multivariate regression analyses the FPG levels were positively correlated with plasma MPO levels, Gensini score and hs-CRP. The plasma MPO levels in the group C [68.68(52.62-91.88) U/L] were significantly higher than in the group A [63.04(26.18-97.75) U/L] and group B [58.22(23.95-89.54) U/L]. The plasma hs-CRP concentrations are also higher in group C [42.28 (0.31-169.40) mg/L] than in the group A [12.51(0.28-176.25) mg/L] and group B [14.7 (0.14-89.68) mg/L]. CONCLUSION: This study demonstrates that FPG values are positively correlated with plasma MPO levels, suggesting MPO may play a role in the proatherogenesis of high FPG.

The expression of p66shc in peripheral blood monocytes is increased in patients with coronary heart disease and correlated with endothelium-dependent vasodilatation.

The objective of this study is to detect the p66shc mRNA and protein expression of the peripheral blood monocytes (PBMs) in coronary heart disease patients (CHD) and controls, to evaluate the correlation between the expression of p66shc mRNA in the PBMs and endothelium-dependent vasodilatation. This study included 78 coronary angiography-documented CHD patients (CHD group) and 38 non-CHD controls (control group). The p66shc mRNA and protein levels were determined by quantitative real-time PCR and western blotting. The flow-mediated dilatation (FMD, endothelium-dependent), nitroglycerine-induced dilatation (NID, endothelium-independent) and carotid intimal medial thickness (CIMT) were detected using high-resolution ultrasound. The p66shc mRNA and the protein expression levels in the PBMs were significantly higher in the CHD group compared with the control group (p = 0.007 and 0.001). The FMD (p < 0.001) and NID (p = 0.013) were significantly lower and the CIMT (p = 0.007) was significantly thicker in the CHD patients than in the controls. In the univariate analysis, the expression of the p66shc mRNA in the PBMs was significantly positively correlated with the serum LDL-C and homocysteine levels and the CIMT and was inversely correlated with the FMD and the NID (all p < 0.001). In the multiple linear regression analysis, the FMD (p < 0.001), LDL-C (p = 0.002) and homocysteine levels (p = 0.002) remained independently correlated with the p66shc mRNA expression. These findings highlight a pivotal role for the expression of p66shc in CHD and endothelial dysfunction, which might represent a molecular target to prevent endothelial dysfunction-related disease.

Impact of metabolic syndrome on benign prostatic hyperplasia in elderly Chinese men.

OBJECTIVE: The aim of the present study was to evaluate the impact of metabolic syndrome (MetS) on benign prostatic hyperplasia (BPH) in elderly Chinese men. METHODS: A total of 401 elderly BPH patients were divided into the without or with MetS group to assess the associations of MetS and components of MetS with BPH. Urologic evaluation included prostate volume, International Prostate Symptom Score, serum prostate-specific antigen, duration of concomitant lower urinary tract symptoms (LUTS) and maximum flow rate. RESULTS: Body mass index (BMI), waist circumference, fasting glucose, glycosylated hemoglobin, triglyceride, fasting insulin (FINS), insulin resistance assessed by homeostasis model assessment (HOMA-IR) were greater and high-density lipoprotein cholesterol (HDL-C) was lower in BPH patients with MetS than in those without MetS. The patients with MetS showed a significantly larger prostate volume (p = 0.000) and longer duration of LUTS (p = 0.006) than those without MetS. Prostate volume was positively correlated with BMI (p = 0.000), FINS (p = 0.001), HOMA-IR (p = 0.003) and inversely correlated with HDL-C (p = 0.000). Multiple linear regression analysis showed that prostate volume was significantly correlated with HOMA-IR (p = 0.015). CONCLUSIONS: Our results suggest that MetS, BMI, low HDL-C level, increased serum insulin and especially insulin resistance are considered risk factors for prostate enlargement in elderly Chinese men.

Decreased Left Ventricular Mass is Associated with Sarcopenia and its Severity in Elderly Inpatients.

Objective: Skeletal muscle mass and cardiac structure change with age. It is unclear whether the loss of skeletal muscle mass (SMM) is accompanied by a decrease in heart mass loss. The aim of this study is to investigate the relationship of left ventricular mass (LVM) with sarcopenia and its severity in elderly inpatients. Methods: Seventy-one sarcopenia subjects and 103 non-sarcopenia controls were enrolled in this study. Bioelectrical impedance analysis, handgrip strength, and 5-time chair stand test were used to evaluate SMM, muscle strength, and physical performance, respectively. Myocardial structure and function were assessed by echocardiography. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia criteria 2019. Results: Sarcopenic patients had smaller left ventricular sizes and LVM than non-sarcopenic controls. Severe sarcopenic patients had smaller left ventricular sizes and LVM than non-severe sarcopenic patients. In univariate regression analysis, body mass index (BMI), cardiac size, and LVM were positively correlated with SMM or SMI. In multivariate regression analysis, BMI and LVM were independently correlated with SMM and SMI. The combined measurement of LVM and BMI predicts sarcopenia with 66.0% sensitivity and 88.7% specificity (AUC: 0.825; 95% CI: (0.761, 0.889); p < 0.001). Conclusion: In hospitalized elderly patients, decreased left ventricular mass is associated with sarcopenia and its severity, and the combined measurement of LVM and BMI has a predictive value for sarcopenia.

Influence and pathophysiological mechanisms of simvastatin on prostatic hyperplasia in spontaneously hypertensive rats.

OBJECTIVE: To explore the effects and mechanisms of simvastatin on prostate hyperplasia in spontaneously hypertensive rats (SHRs). METHODS: Thirty-six male SHRs were randomly divided into three groups: the 10 and the 20 mg/kg/d simvastatin group and the control group. After 6 weeks the ultra-microscopic prostate structures were observed. The serum levels of interleukin-6 (IL-6), insulin-like growth factor (IGF-1) and angiotensin II (Ang-II) were measured by enzyme-linked immunosorbent assays. The endothelium-derived nitric oxide synthase (eNOS) expression was evaluated with immunohistochemistry. RESULTS: Compared to the control group, the 20 mg/kg/d simvastatin group presented with lower absolute (p = 0.005) and relative prostate weight (p = 0.009). The basal cells and columnar cells presented with edema, condensed heterochromatin in interstitial fibroblast nuclei, widened nucleus gaps, and decreased mitochondria and endoplasmic reticulum in the 10 mg/kg/d simvastatin group, these changes were more pronounced in the 20 mg/kg/d simvastatin group. The IL-6 levels in the 10 and 20 mg/kg/d simvastatin groups were lower than those of the controls (p = 0.005 and p = 0.008). The IGF-1 levels of the 20 mg/kg/d simvastatin group were reduced compared to the control group (p = 0.016). CONCLUSIONS: Simvastatin can delay and inhibit prostatic hyperplasia and progression in SHR. These actions may be mediated through the suppression of inflammatory and growth factors.

Characteristics of the fecal microbiome and metabolome in older patients with heart failure and sarcopenia.

Background: Increasing evidence supports that gut microbiota plays an important role in the development of cardiovascular diseases. The prevalence of sarcopenia is increasing in patients with heart failure. Muscle wasting is an independent predictor of death in heart failure patients. Aims: In this study, we aimed to explore the characteristics of gut microbiota and metabolites in heart failure patients with or without sarcopenia. Methods: Fecal samples of 33 heart failure patients without sarcopenia, 29 heart failure patients with sarcopenia, and 15 controls were collected. The intestinal microbiota was analyzed using 16S rRNA sequencing and the metabolites were detected using the gas chromatography-mass spectrometry method. Results: There were significant differences in the overall microbial community structure and diversity between control and heart failure patients with or without sarcopenia. However, no clear clustering of samples was observed in heart failure with and without sarcopenia patients. Several bacterial, particularly Nocardiaceae, Pseudonocardiaceae, Alphaproteobacteria, and Slackia were significantly enriched in the heart failure patients without sarcopenia, while Synergistetes was more abundant in the heart failure patients with sarcopenia. Isobutyric acid, isovaleric acid, and valeric acid were lower in heart failure patients with sarcopenia than that without sarcopenia but lacked significance. Conclusions: This study demonstrates that there are differences in the gut microbiota between control individuals and heart failure patients with or without sarcopenia. Modulating the gut microbiota may be a new target for the prevention and treatment of sarcopenia in heart failure patients.

Eupatilin inhibits pulmonary fibrosis by activating Sestrin2/PI3K/Akt/mTOR dependent autophagy pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive chronic inflammatory disease with poor clinical outcomes and ineffective drug treatment options. Eupatilin is a major component extracted from the traditional herbal medicine Artemisia asiatica Nakai. Notably, it was demonstrated to have an anti-fibrosis effect in endometrial fibrosis, vocal fold, and hepatic fibrosis. Its role and mechanism in IPF remain unclear. METHODS: This study used the TGF-ß1-induced human embryonic lung fibroblasts (MRC-5) activation, IPF lung fibroblasts, and bleomycin-induced lung fibrosis mice model. Western blot, immunofluorescence staining, quantitative real time-PCR, hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemistry were used to evaluate the effects of eupatilin on fibroblast activation, pulmonary fibrosis, and autophagy. The autophagosomes were observed with a transmission electron microscope (TEM). RNA sequencing was used to determine the signaling pathway and key regulator related to autophagy. RESULTS: Eupatilin significantly decreased the expression of Col1A1, fibronectin, α-SMA, and SQSTM1/p62. In contrast, it increased the expression of LC3B II/I and the number of autophagosomes in TGF-ß1 treated MRC-5, IPF lung fibroblasts, and bleomycin-induced lung fibrosis mice model; it also alleviated bleomycin-induced lung fibrosis. The KEGG pathway mapping displayed that PI3K/Akt and Sestrin2 were associated with the enhanced fibrogenic process. Eupatilin suppressed the phosphorylation of PI3K/Akt/mTOR. Autophagy inhibitor 3-methyladenine (3-MA) and Akt activator SC-79 abrogated the anti-fibrotic effect of eupatilin. Sestrin2 expression was also downregulated in TGF-ß1 treated lung fibroblasts and lung tissues of the bleomycin-induced pulmonary fibrosis mice model. Furthermore, eupatilin promoted Sestrin2 expression, and the knockdown of Sestrin2 significantly aggravated the degree of fibrosis, increased the phosphorylation of PI3K/Akt/mTOR, and decreased autophagy. CONCLUSION: These findings indicate that eupatilin ameliorates pulmonary fibrosis through Sestrin2/PI3K/Akt/mTOR-dependent autophagy pathway.

Aspirin alleviates pulmonary fibrosis through PI3K/AKT/mTOR-mediated autophagy pathway.

Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible lung disease with limited therapeutic options. Aspirin can alleviate liver, kidney, and cardiac fibrosis. However, its role in lung fibrosis is unclear. This study aims to investigate the effects of aspirin on lung fibroblast differentiation and pulmonary fibrosis. TGF-ß1-induced human embryonic lung fibroblasts, IPF lung fibroblasts, and bleomycin-induced lung fibrosis mouse model were used in this study. The results showed that aspirin significantly decreased the expression of Collagen 1A1, Fibronectin, Alpha-smooth muscle actin, and equestosome1, and increased the ratio of light chain 3 beta II/I and the number of autophagosome in vivo and in vitro; reduced bleomycin-induced lung fibrosis. Aspirin also decreased the ratios of phosphorylated phosphatidylinositol 3 kinase (p-PI3K)/PI3K, protein kinase B (p-AKT)/AKT, and mechanistic target of rapamycin (p-mTOR)/mTOR in vitro. Autophagy inhibitor 3-methyladenine, bafilomycin-A1, and AKT activator SC-79 abrogated the effects of aspirin. These findings indicate that aspirin ameliorates pulmonary fibrosis through a PI3K/AKT/mTOR-dependent autophagy pathway.

[Inhibitory effect of losartan on prostatic hyperplasia in spontaneous hypertension rats and its pathophysiological mechanism].

OBJECTIVE: To investigate the effect of losartan on prostatic hyperplasia in spontaneous hypertension rats (SHRs) and its pathophysiological mechanism. METHODS: We randomly divided 36 male SHRs into three groups of equal number to be treated intragastrically with high-dose losartan (30 mg per kg per d), low-dose losartan (15 mg per kg per d) and distilled water (control group). After 6 weeks of intervention, we measured the body weight and tail artery blood pressure of the rats and compared them with the baseline data. We collected blood from the heart for determination of the levels of serum angiotensin II (Ang II), insulin-like growth factor-1 (IGF-1) and interleukin-6 (IL-6) by enzyme-linked immunosorbent assay (ELISA), and harvested their prostates for measurement of their weight, observation of the tissue ultrastructures under the electron microscope and detection of the expression of endothelial nitric oxide synthase (eNOS) in the prostate tissue by immunohistochemistry. RESULTS: Compared with the control group, the low- and high-dose losartan groups showed significant decreases in systolic blood pressure ([203.75 +/- 10.28] vs [184.54 +/- 16.90] mmHg, P = 0.013; [203.75 +/- 10.28] vs [166.88 +/- 14.74] mmHg, P = 0.001) and diastolic blood pressure ([151.58 +/- 9.96] vs [136.71 +/- 14.28] mmHg, P = 0.022; [151.58 +/- 9.96] vs [122.71 +/- 11.56] mmHg, P < 0.001) of the lower tail artery after treatment, as well as in the prostate weight ([0.73 +/- 0.08] vs [0.64 +/- 0.10] mg, P = 0.011; [0.73 +/- 0.08 ] vs [0.50 +/- 0.17] mg, P < 0.001). Electron microscopy revealed edema of the basal and columnar epithelial cells, concentrated and marginated heterochromatin and widened nuclear gap of interstitial fibroblast nuclei, and reduced mitochondria and endoplasmic reticula in the low-dose losartan group, and even more obvious in the high-dose group. The level of serum Ang II was remarkably higher in the low- and high-dose losartan groups than in the control ([61.32 +/- 2.49] vs [54.85 +/- 7.20] pg/ml, P = 0.021; [65.49 +/- 6.78] vs [54.85 +/- 7.20] pg/ml, P < 0.001]) , that of serum IGF-1 was lower in high-dose losartan than in the control group ([1.50 +/- 0.11] vs [1.60 +/- 0.10] ng/ml, P = 0.03), but the serum IL-6 levels exhibited no significant differences among the three groups. The expression of eNOS in the prostate tissue was significantly higher in the losartan groups than in the controls (P = 0.022), even higher in the high-dose than in the low-dose group. CONCLUSION: Losartan can suppress the progression of prostate hyperplasia in spontaneous hypertension rats by inhibiting RAS, IGF-1 and angiogenesis.

[Reduced expression and secretion of apolipoprotein M in fat-fed, streptozotocin-diabetic rats is partially reversed by an artificial ligand of PPARγ].

OBJECTIVE: To investigate the effect of administration of rosiglitazone, an artificial ligand of PPARγ, on the expression and secretion of apolipoprotein (apoM) in fat-fed, streptozotocin-treated rats, an animal model for type 2-like diabetes. METHODS: Healthy male SD rats were divided into 4 groups: a control group (n=7), a high-fat chow group (HF group, n=8), a diabetes mellitus group (DM group, n=7), and a diabetes mellitus group with rosiglitazone intervention group (RSG group, n=7). Fasting blood glucose (FBG), fasting insulin (FINS), triglyceride (TG) and total cholesterol (TC) were measured at the beginning of the study. The diabetic rats model was established by feeding high fat chow and intraperitoneal injection of streprozotocin. Then the randomly selected treatment group was given rosiglitazone by daily gavage for 8 weeks. All the rats were killed at the fifteenth week, at which time blood and tissues (liver, kidney, adipose) were collected and prepared. The levels of FBG, FINS, TG and TC were assayed. The level of apoM in serum was measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) was used to determine apoM mRNA expression in liver, kidney, and adipose tissues. RESULTS: Compared with either control group or HF group, serum apoM concentration in the DM group was reduced significantly (P<0.05); compared with the DM group, however, serum apoM concentrations in RSG group were increased (P<0.05). The expression of apoM mRNA in liver was highest, in kidney medium, and in adipose tissue extremely low (P<0.05). ApoM mRNA expression in liver and kidney was decreased in both DM and HF groups compared to control group (P<0.05). But, as with serum apoM concentration, apoM mRNA in the liver, kidney and adipose tissues of the RSG group were all increased markedly (P<0.05). The level of serum apoM in SD rats correlated negatively with TG (r=-0.466, P=0.011), TC (r=-0.568, P= 0.001), FBS (r =-0.371, P<0.001), and FINS(r=-0.768, P= 0.048 ). CONCLUSION: These results suggest that apoM may participate in the glucose and lipid metabolism by the regulation of PPARγ.

Lipoprotein subfractions in patients with sarcopenia and their relevance to skeletal muscle mass and function.

OBJECTIVE: Loss of skeletal muscle mass is a characteristic of aging. Growing evidence suggests the role of fatty acids and their derived lipid intermediates in the regulation of skeletal muscle and function. However, the exact association between lipoprotein subfractions and sarcopenia in elderly individuals remains unclear. In this study, we aimed to investigate the levels of lipoprotein subfractions in sarcopenia patients and their relationship with skeletal muscle mass and function. METHODS: A total of 84 elderly Chinese subjects aged ≥65 years who did not have diseases that obviously affected lipid metabolism were included. Concentrations of lipoprotein subfractions, including total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), HDL2, HDL3, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), VLDL3, LDL-particle (LDL-P), lipoprotein(a) and remnant-like particle cholesterol (RLP-C), were determined by vertical auto profile. Triglyceride (TG) was measured by an enzymatic colorimetric assay. The skeletal muscle index (SMI) was assessed by bioelectrical impedance analysis. Handgrip strength was measured using a hand-held dynamometer. RESULTS: The levels of TC, TG, LDL-C, LDL-P, IDL, VLDL, VLDL3, RLP-C and C-reactive protein were significantly higher in sarcopenia patients than in controls (p < 0.05). Pearson Product-Moment Correlation Coefficient analysis showed that the TC, TG, LDL-C, IDL, VLDL, VLDL3, and RLP-C levels were negatively associated with the SMI; The TG, IDL, VLDL, VLDL3, and RLP-C were negatively correlated with handgrip strength. In multivariate stepwise regression analysis, the VLDL and RLP-C levels were significantly correlated with the SMI. The sensitivity and specificity of the combined measurement of VLDL and RLP-C in predicting sarcopenia were 69.8% and 92.5% (AUC: 0.831; 95% CI:(0.739, 0.924); p < 0.05). CONCLUSION: The occurrence of sarcopenia is associated with disorders of lipid metabolism, particularly VLDL and RLP-C.

Non-coding RNAs: Important participants in cardiac fibrosis.

Cardiac remodeling is a pathophysiological process activated by diverse cardiac stress, which impairs cardiac function and leads to adverse clinical outcome. This remodeling partly attributes to cardiac fibrosis, which is a result of differentiation of cardiac fibroblasts to myofibroblasts and the production of excessive extracellular matrix within the myocardium. Non-coding RNAs mainly include microRNAs and long non-coding RNAs. These non-coding RNAs have been proved to have a profound impact on biological behaviors of various cardiac cell types and play a pivotal role in the development of cardiac fibrosis. This review aims to summarize the role of microRNAs and long non-coding RNAs in cardiac fibrosis associated with pressure overload, ischemia, diabetes mellitus, aging, atrial fibrillation and heart transplantation, meanwhile shed light on the diagnostic and therapeutic potential of non-coding RNAs for cardiac fibrosis.

Obstructive Sleep Apnea Impacts Cardiac Function in Dilated Cardiomyopathy Patients Through Circulating Exosomes.

Background: Obstructive sleep apnea (OSA) is common and independently associated with heart failure. This study aimed to investigate the impact of OSA on heart function in patients with dilated cardiomyopathy (DCM) as well as the possible mechanism related to exosomes regulated autophagy. Methods and Results: A total of 126 patients with DCM who underwent sleep evaluations were analyzed retrospectively. Cardiomyocytes were treated with exosomes isolated from untreated OSA patients and healthy controls. Fibrotic and hypertrophic markers were evaluated, and Akt/mTOR pathway-mediated autophagy was investigated. DCM patients with severe OSA had larger right ventricular end-diastolic diameter (RVEDd) and right atrial diameter (RAD) and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than DCM patients without OSA. Moreover, NT-proBNP and diabetes mellitus were independently correlated with the apnea-hypopnea index in multiple linear regression analysis. Treatment with OSA-derived exosomes significantly increased Col1A1, ANP, and BNP protein expression and decreased the expression of the autophagy markers LC3B II/I and beclin1. Rapamycin treatment significantly increased the decreased autophagy markers and attenuated the increased expression of Col1A1, ANP and BNP induced by OSA-derived exosomes. Conclusion: The severity of OSA is significantly associated with cardiac injury and remodeling. The underlying mechanism may be related to changed autophagy levels, which are regulated by circulating exosomes via the Akt/mTOR signaling pathway. This study may provide a new clue for the treatment of heart failure with OSA.

Inhibition of Sirt2 Alleviates Fibroblasts Activation and Pulmonary Fibrosis via Smad2/3 Pathway.

Idiopathic pulmonary fibrosis (IPF) is a fatal disease with unknown cause and limited treatment options. Its mechanism needs to be further explored. Sirtuin2 (Sirt2), a nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, has been proved to be involved in the fibrosis and inflammation in the liver, kidney and heart. In this study, we aimed to evaluate the role of Sirt2 in pulmonary fibrosis. We found that Sirt2 expression was upregulated in transforming growth factor-ß1 (TGF-ß1) treated human embryonic lung fibroblasts. Sirt2 inhibitor AGK2 or the knockdown of Sirt2 expression by targeting small interfering RNA (siRNA) suppressed the fibrogenic gene α-SMA and Fibronectin expression in TGF-ß1 treated fibroblasts and primary lung fibroblasts derived from patients with IPF. In addition, Sirt2 inhibition suppresses the phosphorylation of Smad2/3. Co-immunoprecipitation (Co-IP) showed that there is interaction between Sirt2 and Smad3 in the TGF-ß1 treated lung fibroblasts. In bleomycin-induced pulmonary fibrosis in mice, AGK2 treatment significantly mitigated the degree of fibrosis and decreased the phosphorylation of Smad2/3. These data suggest that Sirt2 may participate in the development of IPF via regulating the Smad2/3 pathway. Inhibition of Sirt2 would provide a novel therapeutic strategy for this disease.