Effect of simvastatin on bovine intramuscular and subcutaneous adipocytes proliferation and gene expression in vitro.

Simvastatin (SIM) is a widely used anticholesterolemic drug that blocks the biosynthesis of cholesterol. However, SIM also has pleiotropic effects on 3-hydroxy-3-methyglutary-CoA reductase (HMGR), cholesteryl ester transfer protein (CETP), and lipoprotein lipase (LPL), which are important genes in the cholesterol biosynthesis and transport processes. We investigated the effects of different concentrations of SIM on the mRNA expression of these genes in bovine intramuscular and subcutaneous adipocytes from the longissimus dorsi muscle and subcutaneous fat tissues of Luxi Yellow cattle. The results showed that SIM treatment showed dose-dependent toxicity on normal adipose cells, but no effect on cell proliferation. SIM decreased HMGR expression in a dose-dependent manner but showed no significant effect on CETP and LPL expression. Thus, SIM may lower the cholesterol content by decreasing the HMGR expression level, but CETP and LPL may be regulated through other mechanisms, which require further investigation.

Protective effects of astaxanthin on lipopolysaccharide-induced inflammation in bovine endometrial epithelial cells†.

Astaxanthin (AST), a natural antioxidant carotenoid, has been shown to exert anti-inflammatory effects. However, to our knowledge, no study has specifically addressed the potential protective effects of AST against bovine endometritis. The purpose of this study was to examine whether treatment with AST could protect endometrial epithelial cells against lipopolysaccharide (LPS)-induced inflammatory injury. Treatment of bovine endometrial (BEND) epithelial cell line with AST reduced LPS-induced production of interleukin-6 and tumor necrosis factor-alpha, increased the cellular activity of superoxide dismutase and catalase, decreased the proportion of apoptotic cells, and promoted the production of insulin-like growth factor and epithelial growth factor. The effects of AST were mediated through the downregulation of B-cell lymphoma 2 (Bcl-2) associated X, apoptosis regulator (Bax), and cleaved caspase-3 and through the upregulation of Bcl-2. Moreover, AST significantly increased the expression of the tight junction proteins (TJP) claudin, cadherin-1, and TJP1, which play an essential role in the maintenance of host endometrial defense barrier against pathogen infection. Collectively, these results demonstrated that treatment with AST protected against oxidative stress, prevented cell apoptosis, promoted BEND cells viability, and increased the production of growth factors, in addition to activating the endometrial defense barrier. Therefore, AST is a promising therapeutic agent for the prevention and treatment of endometritis. This finding is of utmost importance in the present times when the excessive use of antibiotics has resulted in the development of antibiotic-resistant bacteria.

Potential Clinical Risk of Inflammation and Toxicity from Rare-Earth Nanoparticles in Mice.

BACKGROUND: Nanotechnology is emerging as a promising tool to perform noninvasive therapy and optical imaging. However, nanomedicine may pose a potential risk of toxicity during in vivo applications. In this study, we aimed to investigate the potential toxicity of rare-earth nanoparticles (RENPs) using mice as models. METHODS: We synthesized RENPs through a typical co-precipitation method. Institute of Cancer Research (ICR) mice were randomly divided into seven groups including a control group and six experimental groups (10 mice per group). ICR mice were intravenously injected with bare RENPs at a daily dose of 0, 0.5, 1.0, and 1.5 mg/kg for 7 days. To evaluate the toxicity of these nanoparticles in mice, magnetic resonance imaging (MRI) was performed to assess their uptake in mice. In addition, hematological and biochemical analyses were conducted to evaluate any impairment in the organ functions of ICR mice. The analysis of variance (ANOVA) followed by a one-way ANOVA test was used in this study. A repeated measures' analysis was used to determine any significant differences in white blood cell (WBC), alanine aminotransferase (ALT), and creatinine (CREA) levels at different evaluation times in each group. RESULTS: We demonstrated the successful synthesis of two different sizes (10 nm and 100 nm) of RENPs. Their physical properties were characterized by transmission electron microscopy and a 980 nm laser diode. Results of MRI study revealed the distribution and circulation of the RENPs in the liver. In addition, the hematological analysis found an increase of WBCs to (8.69 ± 0.85) × 109/L at the 28th day, which is indicative of inflammation in the mouse treated with 1.5 mg/kg NaYbF4:Er nanoparticles. Furthermore, the biochemical analysis indicated increased levels of ALT ([64.20 ± 15.50] U/L) and CREA ([27.80 ± 3.56] µmol/L) at the 28th day, particularly those injected with 1.5 mg/kg NaYbF4:Er nanoparticles. These results suggested the physiological and pathological damage caused by these nanoparticles to the organs and tissues of mice, especially to liver and kidney. CONCLUSION: The use of bare RENPs may cause possible hepatotoxicity and nephritictoxicity in mice.

Rare-earth Nanoparticle-induced Cytotoxicity on Spatial Cognition Memory of Mouse Brain.

BACKGROUND: Luminescent rare-earth-based nanoparticles have been increasingly used in nanomedicine due to their excellent physicochemical properties, such as biomedical imaging agents, drug carriers, and biomarkers. However, biological safety of the rare-earth-based nanomedicine is of great significance for future development in practical applications. In particular, biological effects of rare-earth nanoparticles on human's central nervous system are still unclear. This study aimed to investigate the potential toxicity of rare-earth nanoparticles in nervous system function in the case of continuous exposure. METHODS: Adult ICR mice were randomly divided into seven groups, including control group (receiving 0.9% normal saline) and six experimental groups (10 mice in each group). Luminescent rare-earth-based nanoparticles were synthesized by a reported co-precipitation method. Two different sizes of the nanoparticles were obtained, and then exposed to ICR mice through caudal vein injection at 0.5, 1.0, and 1.5 mg/kg body weight in each day for 7 days. Next, a Morris water maze test was employed to evaluate impaired behaviors of their spatial recognition memory. Finally, histopathological examination was implemented to study how the nanoparticles can affect the brain tissue of the ICR mice. RESULTS: Two different sizes of rare-earth nanoparticles have been successfully obtained, and their physical properties including luminescence spectra and nanoparticle sizes have been characterized. In these experiments, the rare-earth nanoparticles were taken up in the mouse liver using the magnetic resonance imaging characterization. Most importantly, the experimental results of the Morris water maze tests and histopathological analysis clearly showed that rare-earth nanoparticles could induce toxicity on mouse brain and impair the behaviors of spatial recognition memory. Finally, the mechanism of adenosine triphosphate quenching by the rare-earth nanoparticles was provided to illustrate the toxicity on the mouse brain. CONCLUSIONS: This study suggested that long-term exposure of high-dose bare rare-earth nanoparticles caused an obvious damage on the spatial recognition memory in the mice.

Association between N-terminal proB-type Natriuretic Peptide and Depressive Symptoms in Patients with Acute Myocardial Infarction.

BACKGROUND: While depression and certain cardiac biomarkers are associated with acute myocardial infarction (AMI), the relationship between them remains largely unexplored. We examined the association between depressive symptoms and biomarkers in patients with AMI. METHODS: We performed a cross-sectional study using data from 103 patients with AMI between March 2013 and September 2014. The levels of depression, N-terminal proB-type natriuretic peptide (NT-proBNP), and troponin I (TnI) were measured at baseline. The patients were divided into two groups: those with depressive symptoms and those without depressive symptoms according to Zung Self-rating Depression Scale (SDS) score. Baseline comparisons between two groups were made using Student's t-test for continuous variables, Chi-square or Fisher's exact test for categorical variables, and Wilcoxon test for variables in skewed distribution. Binomial logistic regression and multivariate linear regression were performed to assess the association between depressive symptoms and biomarkers while adjusting for demographic and clinical variables. RESULTS: Patients with depressive symptoms had significantly higher NT-proBNP levels as compared to patients without depressive symptoms (1135.0 [131.5, 2474.0] vs. 384.0 [133.0, 990.0], Z = -2.470, P = 0.013). Depressive symptoms were associated with higher NT-proBNP levels (odds ratio [OR] = 2.348, 95% CI: 1.344 to 4.103, P = 0.003) and higher body mass index (OR = 1.169, 95% confidence interval [CI]: 1.016 to 1.345, P = 0.029). The total SDS score was associated with the NT-proBNP level (ß= 0.327, 95% CI: 1.674 to 6.119, P = 0.001) after multivariable adjustment. In particular, NT-proBNP was associated with three of the depressive dimensions, including core depression (ß = 0.299, 95% CI: 0.551 to 2.428, P = 0.002), cognitive depression (ß = 0.320, 95% CI: 0.476 to 1.811, P = 0.001), and somatic depression (ß = 0.333, 95% CI: 0.240 to 0.847, P = 0.001). Neither the overall depressive symptomatology nor the individual depressive dimensions were associated with TnI levels. CONCLUSIONS: Depressive symptoms, especially core depression, cognitive depression, and somatic depression, were related to high NT-proBNP levels in patients with AMI.

C/EBPα negatively regulates SIRT7 expression via recruiting HDAC3 to the upstream-promoter of hepatocellular carcinoma cells.

Mammalian Sirtuin proteins (SIRTs) are homologs of yeast Sir2, and characterized as class III histone deacetylases of NAD(+) dependence. Unlike their lower counterparts that are directly involved in the extending of lifespan, mammalian SIRTs mainly function in metabolism and cellular homeostasis, among them, SIRT7 is the least understood. SIRT7 is localized in the nucleus and rich in nucleoli associated with RNA polymerase I, and correlated with cell proliferation. In contrast, SIRT7 has recently been demonstrated to specifically deacetylate H3K18ac in the chromatin, and in most cases represses proliferation. Although MicroRNA as miR-125b has been reported to down-regulate SIRT7 by binding to its 3'UTR, however, how SIRT7 gene is regulated remains unclear. Here, we identified the transcription initiation site of human SIRT7 gene at the upstream 23rd A nucleotide respective to the translational codon, and the SIRT7 is a TATA-less and initiator-less gene. The sequences in the upstream region between -256 and -129 bp are identical with important functions in the three species detected. A C/EBPα responding element is found that binds both C/EBPα and C/EBPß in vitro. We showed TSA induced SIRT7 gene transcription and only the HDAC3, but not its catalytic domain depleted mutant, interacted with C/EBPα to occupy the C/EBPα element and repressed SIRT7 gene in the hepatocellular carcinoma cells. To our knowledge, this is the first report on the regulation mechanism of SIRT7 gene, in which, HDAC3 collaborated with C/EBPα to occupy its responding element in the upstream region of SIRT7 gene and repressed its expression in human cells.

[Analysis of relapse factors and risk assessment of adult acute lymphoblastic leukemia].

OBJECTIVE: To explore the risk factors of acute lymphoblastic leukemia (ALL) recurrence in adult patients and establish a prognosis index (PI) calculation model in order to improve the prevention strategy of ALL in adults. METHODS: 104 adult ALL patients from Blood Diseases Hospital & Chinese Academy of Medical Sciences between August 2008 and November 2011 were enrolled. COX proportional hazards regression stratified by Dummy variable was used to set up the prediction model; Kaplan-Meier method and Log-rank test were used to estimate and compare the survival. After calculated individual PI value, patients' expected survival should be estimated by groups. RESULTS: The overall median survival of adult ALL patients was 22.00 months (95% CI 17.00-27.00). COX regression analysis showed that chemotherapy group patients had a higher risk of recurrence than of ASCT group while setting treatment as the dummy variable (RR=2.052, 95%CI 0.877-4.799, P=0.007). Stratified Analysis showed that the risk factors of B-ALL recurrence in adult patients included HGB <100 g/L (RR=0.186, 95% CI 0.068-0.512, P=0.001), CNSL (RR=7.767,95% CI 2.951- 20.433, P=0.001), number of consolidation chemotherapy<3 (RR=0.445, 95% CI 0.211-0.940, P=0.034) and Ph chromosome positive (RR=2.771, 95% CI 1.353-5.674, P=0.005). Grouped by the PI value, the expected survival of each individual patient could be estimated as PI=0.58 base. CONCLUSION: HGB, CNSL, number of consolidation chemotherapy and Ph chromosome were independent risk factors of B-ALL recurrence in adult patients. PI value could predict the survival of adult ALL patients and provide reference for individual therapy and prognostic evaluation.

[Candidate gene analysis of high quality merino sheep].

Partial sequences of wool fiber constituent genes KAP1.1 and KAP1.3 and the exonic sequence of the KAP6.1 gene were chosen for polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis to assess their ability as candidate genes during indirect selection for fine wool traits. Results show that locus W08667 in the genes (KAP1.1, KAP1.3) which code the high sulfur protein associated-protein of keratin associated-protein family is significantly correlated with fine wool quality (P < 0.05). Among the high-glycine-tyrosine keratin associated- protein, the AA and BB genotypes of W06933 are also significantly correlated with fine wool quality (P < 0.05).