Sarcopenia in older adults is associated with static postural control, fear of falling and fall risk: A study of Romberg test.

BACKGROUND: As a geriatric syndrome, sarcopenia may exacerbate static postural control and increase fall risk among older adults. The Romberg test, a simple method to assess static postural control, has the potential to predict fall, but has rarely been used to assess static postural control and fall risk in sarcopenic older adults. RESEARCH QUESTION: How does sarcopenia increase fall risk by affecting static postural control? METHODS: Forty-four older adults performed the Romberg test and were included for analyses. Romberg parameters, including Center of Pressure (CoP), Center of Mass (CoM) and Displacement Angle (DA), were collected under eyes-open/eyes-closed conditions. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Fall risk was assessed using the Morse Elderly Fall Risk Assessment Scale (MFS), and fear of falling was evaluated using the Falls Efficacy Scale-International (FES-I). Multivariate linear regression models were conducted to examine the associations of sarcopenia with Romberg test parameters, fear of falling, and fall risk. RESULTS: Sarcopenic older adults had higher scores of both fear of falling and fall risk (P<0.001 and =0.006, respectively), and worse static postural control parameters (P values ranging from <0.001-0.043) than healthy controls, demonstrated by the multivariate linear regression models. Most of the Romberg test parameters were significantly associated with fear of falling score, especially under eyes-closed condition, and fear of falling was further associated with higher fall risk score (ß=0.90, P=0.001). Meanwhile, the presence of sarcopenia also significantly increased fall risk score (ß=10.0, P<0.001). SIGNIFICANCE: Sarcopenia may increase fall risk in older adults via worsen static postural control ability and increase fear of falling. Paying attention and making efforts to prevent sarcopenia may help to alleviate postural control dysfunction, decrease fear of falling, so as to reduce fall risk and prevent severe injuries caused by fall accidents.

Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1.

This study aimed to explore the effects of tissue inhibitor of metalloproteinases-1 (TIMP-1) on levocarnitine (LC)-mediated regulation of angiotensin II (AngII)-induced myocardial fibrosis (MF) and its underlying mechanisms. H9C2 cells were treated with AngII for 24 h to induce fibrosis. The cells were then treated with LC or transfected with TIMP-1-OE plasmid/si­TIMP-1. Cell apoptosis, viability, migration, and related gene expression were analyzed. AngII treatment significantly upregulated Axl, α-SMA, and MMP3 expression (P < 0.05) and downregulated STAT4 and TIMP1 expression (P < 0.05) relative to the control levels. After transfection, cells with TIMP-1 overexpression/knockdown were successfully established. Compared with that of the control, AngII significantly inhibited cell viability and cell migration while promoting cell apoptosis (P < 0.05). LC and TIMP-1-OE transfection further suppressed cell viability and migration induced by Ang II and upregulated apoptosis, whereas si-TIMP-1 had the opposite effect. Furthermore, LC and TIMP-1-OE transfection downregulated Axl, AT1R, α-SMA, collagen III, Bcl-2, and MMP3 expression caused by AngII and upregulated caspase 3, p53, and STAT4 expression, whereas si-TIMP-1 had the opposite effect. TIMP-1 is therefore a potential therapeutic target for delaying MF progression.

Combination of Oxalobacter Formigenes and Veillonella Parvula in Gastrointestinal Microbiota Related to Bile-Acid Metabolism as a Biomarker for Hypertensive Nephropathy.

The human microbiome is a mixed group of microorganisms, which individually consists of 10-100 trillion symbiotic microbial cells. The relationship between gastrointestinal microbiota and blood pressure has been verified and the intestinal microbiota of chronic kidney disease (CKD) patients in the distribution of bacterial species is different from the flora of people with no CKD. The purpose of this research is to study the different intestinal microbiota of hypertensive patients with and without nephropathy and to find possible biomarkers of hypertensive nephropathy (H-CKD). The subjects of this research were divided into three groups, healthy control group, hypertension group, and hypertensive nephropathy group. Sequencing, bioinformatics, and statistical analysis were performed on the 16S rRNA gene of the subjects' stool samples. This research study showed the differences of intestinal flora as biomarkers in hypertension patients with and without nephropathy; it investigated the relationship of the differences in the intestinal microbiota with bile-acid metabolism; it also explored bile-acid metabolism mechanism of intestinal microbiota differences in hypertension with or without nephropathy. In summary, the difference in the combination of O. formigenes and V. parvula in the gastrointestinal microbiota is related to bile-acid metabolism in hypertensive patients and can be one of the factors causing CKD. It is the first time to report such a biomarker or pathogenic factor of H-CKD in the world.

Matrix metalloproteinase 3 regulates angiotensin II­induced myocardial fibrosis cell viability, migration and apoptosis.

Angiotensin II (AngII) is a central signaling molecule of the renin­angiotensin system that serves a vital role in myocardial fibrosis (MF). The present study aimed to investigate the effects of matrix metalloproteinase (MMP)3 on MF progression. To induce cellular fibrosis, H9C2 rat myocardial cells were treated with AngII for 24 h. Subsequently, cells were treated with levocarnitine, or transfected with small interfering (si)RNA­negative control or siRNA­MMP3 (1/2/3). Cell viability, apoptosis and migration were assessed by performing Cell Counting Kit­8, flow cytometry and Transwell assays, respectively. Reverse transcription­quantitative PCR (RT­qPCR) and western blotting were performed to determine the expression levels of MF biomarkers, including disease­, apoptosis­ and oxidative stress­related genes. Compared with the control group, AngII significantly inhibited H9C2 cell viability and migration, and significantly increased H9C2 cell apoptosis (P<0.05). However, compared with AngII­treated H9C2 cells, MMP3 knockdown significantly inhibited fibrotic H9C2 cell viability and migration, but increased fibrotic H9C2 cell apoptosis (P<0.05). The RT­qPCR results demonstrated that MMP3 knockdown significantly downregulated the expression levels of AXL receptor tyrosine kinase, AngII receptor type 1, α­smooth muscle actin and Collagen I in AngII­treated H9C2 cells (P<0.05). Moreover, compared with AngII­treated cells, MMP3 knockdown significantly decreased Bcl­2 expression levels , but significantly increased caspase­3 and p53 expression levels in AngII­treated cells (P<0.05). Additionally, compared with AngII­treated cells, MMP3 knockdown significantly decreased MMP3, MMP9, STAT3, p22Phox and p47Phox expression levels in AngII­treated cells (P<0.05). The present study indicated that MMP3 knockdown altered myocardial fibroblast cell viability, migration and apoptosis by regulating apoptosis­ and oxidative stress­related genes, thus delaying MF progression.

Efficacy and Safety of Policosanol Plus Fenofibrate Combination Therapy in Elderly Patients with Mixed Dyslipidemia: A Randomized, Controlled Clinical Study.

BACKGROUND: Policosanol is a mixture of long-chain alcohols isolated from sugar cane. This controlled, randomized clinical trial was designed to compare the efficacy and safety of fenofibrate, policosanol and a combination of these 2 in lowering low-density-lipoprotein cholesterol (LDL-C) in elderly patients with mixed dyslipidemia. METHODS: A total of 102 patients aged ≥60years were randomly assigned into 3 groups: patients receiving a 24-week therapy of fenofibrate (200 mg/day), policosanol (20 mg/day) or fenofibrate + policosanol combination. Lipids were evaluated at baseline, after 16 and after 24 weeks of therapy. Brachial-ankle pulse wave velocity (ba-PWV) was performed, and SF-36 questionnaires were used to evaluate the patients' quality of life. The primary endpoint was the percentage reduction in LDL-C. The secondary end points included percentage change in nonhigh density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC), triglyceride, high-density-lipoprotein cholesterol (HDL-C), ba-PWV and SF-36 scores. Safety was assessed by adverse events and laboratory parameters. RESULTS: LDL-C, non-HDL-C and TC were decreased, respectively after treatment with policosanol for 24 weeks (P < 0.01). Treatment with policosanol + fenofibrate resulted in significantly greater reductions in TC, non-HDL-C and LDL-C compared to fenofibrate alone (P < 0.01, respectively). There were significant increases in SF-36 scores in the policosanol and policosanol + fenofibrate groups (P < 0.05), and significant improvements of ba-PWV in the 2 groups (P < 0.01). There were no serious adverse events or significant changes in laboratory variables after any of the treatment regimens. CONCLUSIONS: Policosanol + fenofibrate combination therapy significantly improved lipid parameters, arterial stiffness, and quality of life, with good tolerability.

Effect of stem cell transplantation of premature ovarian failure in animal models and patients: A meta-analysis and case report.

Stem cell transplantation has been considered a promising therapeutic approach for premature ovarian failure (POF). However, to date, no quantitative data analysis of stem cell therapy for POF has been performed. Therefore, the present study performed a meta-analysis to assess the efficacy of stem cell transplantation in improving ovarian function in animal models of POF. In addition, a case report of a patient with POF subjected to stem cell treatment was included to demonstrate that stem cell therapy also contributes to the recovery of ovarian function in patients. Published studies were identified by a systematic review of the PubMed, Embase, and Cochrane's library databases, and references cited in associated reviews were also considered. Data regarding follicle-stimulating hormone (FSH), estradiol (E2), ovarian weight, follicle count, the number of pregnancies and other parameters, including delivery route and cell type, were extracted. Pooled analysis, sensitivity analyses, subgroup analyses and meta-regression were performed. In the case of POF, transvaginal ultrasound (TVS), abdominal ultrasound (TAS) and color Doppler flow imaging (CDFI) were performed to observe the endometrial morphology and blood flow signals in the patient. Overall, pooled results from 16 pre-clinical studies demonstrated that stem cell-based therapy significantly improved FSH levels [standardized mean difference (SMD)=-1.330; 95% confidence interval (CI), -(2.095-0.565); P=0.001], E2 levels (SMD=2.334; 95% CI, 1.350-3.319; P<0.001), ovarian weight (SMD=1.310; 95% CI, 0.157-2.463; P=0.026), follicle count (SMD=1.871; 95% CI, 1.226-2.516; P<0.001), and the number of pregnancies (risk ratio=1.715, 95% CI, 1.213-2.424; P=0.002). The results of TVS and TAS demonstrated improved ovarian size and endometrial thickness in the patient with POF after MSC treatment. Of note, a rich blood flow signal in the endometrium was observed on CDFI. It appeared that stem cell-based therapy may be an effective method for the resumption of ovarian function in a patient and in animal models of POF; however, large-scale and high-quality future studies are required to confirm the present findings due to heterogeneity.

Two NHX-type transporters from Helianthus tuberosus improve the tolerance of rice to salinity and nutrient deficiency stress.

The NHX-type cation/H+ transporters in plants have been shown to mediate Na+ (K+ )/H+ exchange for salinity tolerance and K+ homoeostasis. In this study, we identified and characterized two NHX homologues, HtNHX1 and HtNHX2 from an infertile and salinity tolerant species Helianthus tuberosus (cv. Nanyu No. 1). HtNHX1 and HtNHX2 share identical 5'- and 3'-UTR and coding regions, except for a 342-bp segment encoding 114 amino acids (L272 to Q385 ) which is absent in HtNHX2. Both hydroponics and soil culture experiments showed that the expression of HtNHX1 or HtNHX2 improved the rice tolerance to salinity. Expression of HtNHX2, but not HtNHX1, increased rice grain yield, harvest index, total nutrient uptake under K+ -limited salt-stress or general nutrient deficiency conditions. The results provide a novel insight into NHX function in plant mineral nutrition.

An RNA­sequencing study identifies candidate genes for angiotensin II­induced cardiac remodeling.

The present study aimed to reveal the underlying mechanism of angiotensin II (AngII)­induced cardiac remodeling and to identify potential therapeutic targets for prevention. Rat cardiac fibroblasts (CFs) were cultured with 10 nM AngII for 12 h, and CFs without AngII were used as the control. Following RNA isolation from AngII treated and control CFs, RNA­sequencing was performed to detect gene expression levels. Differentially­expressed genes (DEGs) were identified using the linear models for microarray analysis package in R software, and their functions and pathways were examined via enrichment analysis. In addition, potential associations at the protein level were revealed via the construction of a protein­protein interaction (PPI) network. The expression levels of genes of interest were validated via reverse transcription­quantitative polymerase chain reaction analysis. In total, 126 upregulated and 140 downregulated DEGs were identified. According to the enrichment analysis, acetyl coA carboxylase ß (ACACB), interleukin 1ß (IL1B), interleukin 1α (IL1A), nitric oxide synthase 2 (NOS2) and matrix metallopeptidase 3 (MMP3) were associated with the immune response, regulation of angiogenesis, superoxide metabolic process and carboxylic acid binding biological processes. Among them, ACACB and MPP3 were two predominant nodes in the PPI network. In addition, IL1B and MMP3 were demonstrated to be upregulated. These five genes, particularly IL1B and MMP3, may be used as candidate markers for the prevention of AngII­induced cardiac remodeling.

Prevalence and clinical characteristics of pseudohypertension in elderly patients prepared for coronary artery angiography.

BACKGROUND: Pseudohypertension (PHT) can cause adverse effects in the elderly owing to administration of antihypertension therapy. The present study aimed to determine the prevalence of PHT in the elderly and associated risk factors to investigate a noninvasive method of detection of PHT. METHODS: We recruited 151 patients (age ≥60 years) who underwent coronary angiography. Demographic and clinical data were collected from the patients. During coronary angiography, intrabrachial arterial pressure and indirect blood pressure were measured. Brachial-ankle pulse wave velocity (ba-PWV) was measured within 2 weeks after coronary angiography. RESULTS: Based on the differences between the direct and indirect pressure measurements, the patients were divided into a PHT group (n = 87) and a non-PHT group (n = 64). The prevalence of PHT was 57.6%, and the development of PHT was significantly associated with older age. Serum creatinine level and creatinine clearance rate were significantly higher in the non-PHT group than in the PHT group (P < .05). In addition, the PHT group had significantly higher ba-PWV and pulse pressure (PP) than the non-PHT group (P < .05). Receiver-operating characteristic curve analysis revealed that ba-PWV (AUC = 0.783) and PP (AUC = 0.791) showed a relatively good diagnostic performance for PHT. CONCLUSIONS: PHT was present in most of the elderly who had indications for coronary angiography and associated with age and renal function. The data from the present study also suggested that both PP and ba-PWV could be used to positively predict PHT.

[Algal oligosaccharides ameliorate osteoporosis via up-regulation of parathyroid hormone 1-84 and vascular endothelial growth factor].

OBJECTIVE: To determine whether algal oligosac- charide~ affects the levels of parathyroid hormone 1-84 (PTH1-84) and vascular endothelial growth fac- tor (VEGF). METHODS: An osteoporosis rat model was estab- lished via bilateral ovariectomy. The model rats were fed algal oligosaccharides (molecular weights: 600-1, 200 Da) for 4 months. Bone mineral density (BMD) was then measured. MG-63 human osteo- blastic cells were treated with algal oligosaccha- rides. The expression of PTH1-84 and VEGF was then examined. Oligosaccharide-treated cells were transfected with PTH1-84 short hairpin RNA (shR- NA), VEGF shRNA, and PTH1-84-VEGF small interfer- ing RNA (siRNA). The growth rates were then com- pared between transfected and non-transfected RESULTS: Algal oligosaccharides increased the BMD of the osteoporosis rat model compared with untreated controls (P < 0.05). When MG-63 cells were treated with algal oligosaccharides, the growth rate increased by 25% compared with the control group at day 3 (P < 0.05). In addition, the ex- pression of P.TH84 and VEGF was. enhanced. Con- versey w hen tecells were tranfected with PTH84 shRNA, VEGF shRNA, or PTH1-84-VEGF siR- NA, the growth rate was decreased by 17%, 35% and 70%, respectively, compared with controls at day 3 (P < 0.05). CONCLUSION: Algal oligosaccharides ameliorate osteoporosis via up-regulation of PTH1-84 and VEGF. Algal oligosaccharides should be developed as a potential drug for osteoporosis treatment.

Differential ERK1/2 Signaling and Hypertrophic Response to Endothelin-1 in Cardiomyocytes from SHR and Wistar-Kyoto Rats: A Potential Target for Combination Therapy of Hypertension.

Extracellular signal regulated kinase½ (ERK1/2) signaling is critical to endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy. This study was to investigate ERK1/2 signaling and hypertrophic response to ET-1 stimulation in cardiomyocytes (CMs) from spontaneous hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Primary neonatal SHR and WKY CMs were exposed to ET-1 for up to 24 hrs. Minimal basal ERK1/2 phosphorylation was present in WKY CMs, while a significant baseline ERK1/2 phosphorylation was observed in SHR CMs. ET-1 induced a time- and dose-dependent increase in ERK1/2 phosphorylation in both SHR and WKY CMs. However, ET-1-induced ERK1/2 activation occurred much earlier with significantly higher peak phosphorylation level, and stayed elevated for longer duration in SHR CMs than that in WKY CMs. ET-1-induced hypertrophic response was more prominent in SHR CMs than that in WKY CMs as reflected by increased cell surface area, intracellular actin density, and protein synthesis. Pre-treatment with ERK1/2 phosphorylation inhibitor PD98059 completely prevented ET-1-induced ERK1/2 phosphorylation and increases in cell surface area and protein synthesis in SHR and WKY CMs. The specific PI3 kinase inhibitor LY294002 blocked ET-1-induced Akt and ERK1/2 phosphorylation, and protein synthesis in CMs. These data indicated that ERK1/2 signaling was differentially enhanced in CMs, and was associated with increased cardiac hypertrophic response to ET-1 in SHR. ET-1-induced ERK1/2 activation and cardiac hypertrophy appeared to be mediated via PI3 kinase/Akt signaling in SHR and WKY. The differential ERK1/2 activation in SHR CMs by ET-1 might represent a potential target for combination therapy of hypertension.

Adventitial gene transfer of catalase attenuates angiotensin II-induced vascular remodeling.

Vascular adventitia and adventitia­derived reactive oxygen species (ROS) contribute to vascular remodeling following vascular injury. A previous ex vivo study in adventitial fibroblasts showed that catalase, one of most important anti­oxide enzymes, was downregulated by angiotensin II (AngII). The aim of the present study was to investigate whether adventitial gene transfer of catalase affects AngII­induced vascular remodeling in vivo. Adenoviruses co­expressing catalase and enhanced green fluorescent protein (eGFP) or expressing eGFP only were applied to the adventitial surface of common carotid arteries of Sprague­Dawley rats. Alzet minipumps administering AngII (0.75 mg/kg/day) were then implanted subcutaneously for 14 days. Systolic blood pressure and biological parameters of vascular remodeling were measured in each group. Adventitial fibroblasts were cultured and p38 mitogen­activated protein kinase (MAPK) phosphorylation was measured using western blot analysis. The results showed that adventitial gene transfer of catalase had no effect on AngII­induced systolic blood pressure elevation. However, catalase adenovirus transfection significantly inhibited AngII­induced media hypertrophy compared with that of the control virus (P<0.05). In addition, catalase transfection significantly attenuated AngII­induced ROS generation, macrophage infiltration, collagen deposition and adventitial α­smooth muscle actin expression. Furthermore, catalase transfection significantly inhibited the AngII­induced increase in p38MAPK phosphorylation. In conclusion, the results of the present study demonstrated that adventitial gene transfer of catalase significantly attenuated AngII­induced vascular remodeling in rats via inhibition of adventitial p38MAPK phosphorylation.

[Association between total antioxidant status and atherosclerosis in elderly patients with essential hypertension].

OBJECTIVE: To investigate the association between plasma total antioxidant status (TAS) and association with brachial-ankle pulsewave velocity (baPWV) in the elderly patients with essential hypertension(EH). METHODS: A total of 133 consecutive EH patients older than 60 years were enrolled and another 92 elderly non-EH healthy subjects served as control. According to blood pressure level, EH patients were further classified into three subgroups. The concentration of plasma total antioxidant status was measured by using chemical luminescence method. High-sensitive CRP, urine microalbumin, uric acid, blood lipids and blood glucose levels were also measured. Carotid intima-media thickness was determined by color Doppler ultrasonography and the degree of arteriosclerosis was investigated with baPWV and ankle-brachial index (ABI). RESULTS: (1) Plasma levels of TAS in EH patients were significant lower than in control group [(1.123 ± 0.126)mmol/L vs. (1.258 ± 0.125) mmol/L, P < 0.05], and were similar among hypertension subgroups (P > 0.05).(2) Stepwise multiple regression analysis showed that age, gender, body mass index, systolic blood pressure, diastolic blood pressure, high-sensitive CRP, UA were dependent variables of TAS. Multivariate regression analysis showed that high-sensitivity CRP, UA were independent factors affecting TAS (ß = -0.03, standardized ß = -0.01, P < 0.05). (3) Compared with the control group, baPWV was significantly higher in elderly EH patients left baPWV (1914 ± 341) cm/s vs. (1817 ± 322) cm/s, right baPWV (1899 ± 330) cm/s vs. (1772 ± 345) cm/s(P < 0.05)and baPWV tended to increase with the level of blood pressure of EH group (P < 0.05) . (4) After adjusting for age, CRP, UA, partial correlation analysis showed that plasma TAS was negatively correlated with baPWV (r = -0.459, P < 0.05). CONCLUSIONS: Our results indicate that TAS and arterial elasticity are decreased while arterial stiffness is increased in elderly hypertensive patients. The decline in antioxidant capacity may be responsible for vascular damage and arterial elasticity decrease in elderly EH patients.

Gamma-glutamyltransferase level and risk of hypertension: a systematic review and meta-analysis.

BACKGROUND: Several prospective observational studies suggest that gamma-glutamyltransferase(GGT) level is positively associated with risk of hypertension. However, these studies draw inconsistent conclusions. Therefore, we conducted a systematic review and meta-analysis to evaluate the exact association between GGT level and subsequent development of hypertension. METHODS: We searched Pubmed, Embase, and Science Citation Index (ISI Web of Science) for prospective cohort studies examining the association between GGT level and hypertension. Then, pooled effect estimates (RRs) for the association between GGT level and hypertension were calculated. RESULTS: A total of 13 prospective cohort studies including 43314 participants and 5280 cases of hypertension were included. The pooled RR of hypertension was 1.94(95%CI: 1.55-2.43; P<0.001) when comparing the risk of hypertension between the highest versus lowest category of GGT levels. Moreover, the risk of hypertension increased by 23% (summary RR: 1.23; 95%CI: 1.13-1.32; P<0.001) per 1 SD logGGT increment. Subgroup analyses showed significant positive associations in each subgroup except in ≧160/95 subgroup (RR: 2.56, 95%CI: 0.87-7.54; P = 0.088) and nondrinkers subgroup (RR: 1.76, 95%CI: 0.88-3.53; P = 0.113). Sensitivity analyses showed no single study significantly affects the pooled RRs. No publication bias was found in our meta-analysis. CONCLUSIONS: GGT level is positively associated with the development of hypertension. Further studies are needed to confirm our findings and elucidate the exact mechanisms between GGT level and the incidence of hypertension.

Angiotensin II downregulates catalase expression and activity in vascular adventitial fibroblasts through an AT1R/ERK1/2-dependent pathway.

Angiotensin II (Ang II) plays a profound regulatory effect on NADPH oxidase and the functional features of vascular adventitial fibroblasts, but its role in antioxidant enzyme defense remains unclear. This study investigated the effect of Ang II on expressions and activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in adventitial fibroblasts and the possible mechanism involved. Ang II decreased the expression and activity of CAT in a dose- and time-dependent manner, but not that of SOD and GPx. The effects were abolished by the angiotensin II type 1 receptor (AT1R) blocker losartan and AT1R small-interfering RNA (siRNA). Incubation with polyethylene glycol-CAT prevented the Ang II-induced effects on reactive oxygen species (ROS) generation and myofibroblast differentiation. Moreover, Ang II rapidly induced phosphorylation of ERK1/2, which was reversed by losartan and AT1R siRNA. Pharmacological blockade of ERK1/2 improved Ang II-induced decrease in CAT protein expression. These in vitro results indicate that Ang II induces ERK1/2 activation, contributing to the downregulation of CAT as well as promoting oxidative stress and adventitial fibroblast phenotypic differentiation in an AT1R-mediated manner.

Peroxisome proliferator-activated receptor γ regulates angiotensin II-induced catalase downregulation in adventitial fibroblasts of rats.

Peroxisome proliferator-activated receptor (PPAR) γ ligands oppose the effect induced by angiotensin II (Ang II) to reduce oxidative stress and improve antioxidant status. In this study, Ang II inhibited catalase (CAT) and peroxisome proliferator-activated receptor γ (PPAR γ) protein and mRNA expressions. Transfection with PPAR γ small-interfering RNA (siRNA) led to a reduction in CAT expression. PPAR γ ligands enhanced CAT expression and inhibited extracellular signal-regulated kinase 1/2 activation. We further reveal that Ang II type 1 receptor is not involved in the inhibitory effects of PPAR γ ligands on Ang II stimulatory events.

Differential expression of alpha-enolase in the normal and pathological cardiac growth.

OBJECTIVES: It was found that alpha-enolase was dramatically up-regulated in the hypertrophic hearts of SHR in our previous study. The purposes of this study were to examine the expression pattern of alpha-enolase in pre- and postnatal myocardium of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats, and to explore the relationship between the overexpression of alpha-enolase and left ventricular hypertrophy. METHODS: HE staining was used for the measurement of cardiac hypertrophy. Immunohistochemical technique was used to evaluate the location of alpha-enolase. The expressions of alpha-enolase in the left cardiac ventricles at different development times were examined by Real-time RT-PCR and Western blot. RESULTS: Cardiac hypertrophy was found in SHR rats at 4 weeks of age and remained up to 24 weeks of age. The signals of alpha-enolase protein were strong and existed extensively in hypertrophic myocardium in SHR, while in the normal myocardium of WKY, the signals were scarcely found and weak. The levels of alpha-enolase mRNA and protein in SHR and WKY hearts during fetal stage and newborn stage were similar, while from 4 weeks of age to 24 weeks of age, accompanied by the cardiac hypertrophy, the levels of alpha-enolase mRNA and protein in left ventricle of SHR were significantly higher than that in WKY. CONCLUSIONS: The expressions of alpha-enolase in the left ventricle of the rats during normal and pathological cardiac development were different. This phenomenon provides the potential clues to understanding pathophysiological mechanisms in cardiac hypertrophy of SHR.

Circulating endothelial progenitor cells in Chinese patients with acute stroke.

To test the hypothesis that a mobilization of endothelial progenitor cells (EPCs) occurs after acute cerebrovascular diseases, we evaluated the number of EPCs in the process of acute stroke. A total of 203 individuals were examined, including 100 patients with ischemic strokes, 36 patients with hemorrhagic strokes and 67 healthy controls. Ninety-eight patients were observed at days 1, 7, 14 and 28 after acute stroke. Circulating EPCs were defined by the surface markers CD133/KDR and analyzed by flow cytometry. Serum high sensitivity C-reactive protein (hs-CRP) concentrations were determined by particle-enhanced immunonephelometry using the N high sensitivity CRP Reagent. Patients with acute stroke had lower numbers of EPCs (0.037+/-0.001/100 peripheral blood mononuclear cells (PMNCs) vs. 0.06+/-0.002/100 PMNCs, P<0.05) and higher levels of serum hs-CRP (1.99 vs. 0.03 mg per 100 ml, P<0.05) than control subjects after adjusting for age, sex, body mass index (BMI) and blood pressure. There were no differences in EPCs counts or serum hs-CRP levels between patients with ischemic and hemorrhagic stroke. In univariate analyses, BMI, age, systolic blood pressure (SBP), diastolic blood pressure, low-density lipoprotein (LDL), total cholesterol (T-cho), blood glucose and hs-CRP (P<0.001) were inversely correlated with EPCs counts. Multivariate analyses showed SBP and total cholesterol as independent predictors of EPCs levels. The number of EPCs gradually increased at day 7 after acute onset, remained elevated at day 14; and returned to baseline by day 28. Our results suggest a possible contribution of circulating EPCs in acute stroke. SBP and total cholesterol are independent factors of reduced EPCs numbers. A transient early increment of EPCs may result from the mobilization of EPCs in response to stroke stress.

Efficacy and safety of benidipine therapy of essential hypertension in elderly Chinese patients.

BACKGROUND: Benidipine (CAS 105979-17-7) is a dihydropyridine calcium channel blocker used in the treatment of hypertension and angina pectoris. OBJECTIVE: To examine the efficacy and safety of therapy with benidipine in elderly hypertensive patients. METHODS: Chinese patients >60 years of age with mild to moderate essential hypertension were enrolled. The patients were prescribed benidipine at the dose of 8 mg once daily for 12 weeks. Detailed laboratory examinations and 24-h ambulatory blood pressure monitoring were performed before and after the treatment. RESULTS: One hundred and sixty-four of the 180 patients enrolled completed the 12-week active treatment phase. Sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) reductions at the end of treatment were 21.50 +/- 12.83 and 10.60 +/- 8.04 mmHg, respectively; the proportion of patients showing a good treatment response was 95.1% for SBP and 96.9% for DBP. Benidipine significantly reduced the mean 24-h ambulatory blood pressure (p < 0.001 vs. baseline) exhibiting smooth, sustained effects and high trough-to-peak ratios (T/P ratio) (0.87 for SBP and 0.72 for DBP). Moreover, benidIpine significantly reduced the systolic morning blood pressure surge and urinary albumin, and it was well tolerated. No serious adverse events were noted. CONCLUSION: Benidipine was welltolerated and effective in elderly Chinese patients with essential hypertension.