3-N-butylphthalide inhibits neuronal apoptosis in rats with cerebral infarction via targeting P38/MAPK.

OBJECTIVE: To study the effect of 3-n-butylphthalide (NBP) on neuronal apoptosis in rats with cerebral infarction (CI) through the p38/mitogen-activated protein kinase (MAPK) pathway. MATERIALS AND METHODS: A total of 30 rats were divided into control group (healthy rats, n=10), model group (CI rat model, n=10), and NBP group (CI rat model + intraperitoneal injection of NBP, n=10). Then, the neurological function, degree of cerebral ischemia, apoptosis of brain tissues, the protein and messenger ribonucleic acid (mRNA) expressions of p-p38 and MAPK in brain tissues were detected using the neurological score, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Reverse Transcription-Polymerase Chain Reaction (RT-PCR), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and Western blotting, respectively. RESULTS: In NBP group, the neurological score was significantly lower than in model group, and the difference was statistically significant (p<0.05). The results of TTC staining revealed that the area of the white region in brain slices was significantly larger in model group than in control group, indicating the successful establishment of middle cerebral artery occlusion (MCAO) model. Compared with model group, NBP group had a smaller area and lighter color of the white region in brain slices, suggesting that NBP markedly reduces the MCAO-induced CI. The apoptosis rate in NBP group was higher than in control group (p<0.05), but lower than in model group (p<0.05), while it was higher in model group than in control group (p<0.05). The protein expressions of p38 and MAPK in NBP group were higher than in control group (p<0.05), but lower than in model group (p<0.05), while they were higher in model group than in control group (p<0.05). Moreover, the mRNA expressions of p38 and MAPK were lower in control group than in model group (p<0.05), while they were higher in model group than in NBP group (p<0.05), but there was no significant difference in the mRNA expression of p38 between NBP group and control group (p>0.05). CONCLUSIONS: NBP alleviates neuronal apoptosis in CI by down-regulating the p38 signal and inhibiting the expression of MAPK, thereby treating CI.

[Risk factors related to HIV new infections among men who have sex with men in a cohort study].

Objectives: To analyze and understand the risk factors related to HIV new infections among men who have sex with men (MSM). Methods: A longitudinal observational study among MSM was conducted to collect information on HIV related behaviors and sero-conversion. Univariate and multivariate generalized estimating equations (GEE) were used to discuss the risk factors for HIV new infection. Results: A total number of 4 305 MSM were followed during 2013-2015. Among those self-reported MSM who are seeking partners on the Interner tended to have higher proportion on receptive anal intercourse and consistent condom use during anal intercourse than the subgroups seeking their partners in gay bars or bathrooms. HIV incidence among followed MSM during the study period appeared as 4.3/100 person years, with adjusted RR (aRR) of HIV infection for receptive anal intercourse as group 2.20 (95% CI: 1.49-3.24) times than that of insertion anal intercourse group. Those who used rush-poppers (aRR=1.55, 95% CI: 1.10-2.17), unprotected anal intercourse (aRR=2.24, 95%CI: 1.62-3.08), and those with syphilis infection (aRR=2.95, 95%CI: 2.00-4.35) were also risk factors for HIV new infections. After controlling other factors, the relationship between the ways of seeking partners and HIV new infection was not statistical significant. Conclusion: Risk factors for HIV new infection among MSM appeared complex and interactive, suggesting that further studies are needed to generate tailored strategies for the prevention of HIV epidemic among MSM population.

Feeding different dietary protein to energy ratios to Holstein heifers: effects on growth performance, blood metabolites and rumen fermentation parameters.

Eighteen Chinese Holstein heifers average age 230 ± 14 days were allocated to 1 of 3 dietary crude protein (CP) to metabolizable energy (ME) ratios to examine the effects on growth performance, blood metabolites and rumen fermentation parameters with 90-days experiment. Three different dietary CP:ME ratios were targeted based on the formulation of dietary CP contents of 10.85%, 12.78% and 14.63% on dry matter (DM) basis with similar ME contents (10.42 MJ/kg DM), which were categorized as low, medium and high dietary CP:ME ratios. The actual CP:ME ratios obtained in this study significantly increased from low to high CP:ME ratio groups with a value of 10.59, 11.83 and 13.38 g/MJ respectively. Elevated CP:ME ratios significantly increased CP intake (kg/day) and feed efficiency (FE) which was defined as dry matter intake as a proportion of average daily gain (ADG), whereas little difference was observed in body weight (kg), ADG (kg/day), DM intake (kg/day) and ME intake (MJ/day) among the three different CP:ME ratio groups. Increasing dietary CP to ME ratios significantly increased CP digestibility, whereas digestibility of DM and gross energy remained constant in the current experiment. Blood urea nitrogen and insulin-like growth factor-1 linearly increased with increasing dietary CP:ME ratios. There was significantly dietary treatment effect on rumen fermentation parameters including acetate, propionate, butyrate and total volatile fatty acids. Therefore, this study indicated that increasing dietary CP levels with similar energy content contributed to increased protein intake and its digestibility, as well as FE. Holstein heifers between 200 and 341 kg subjected to 13.38 dietary CP:ME ratio showed improved feed efficiency, nutrient digestibility, some blood metabolites and rumen fermentation characteristics for 0.90 kg/day rate of gain.

[HIV/STD prevalence and related behaviors among male STD clinic attendees in Xi'an and Xianyang cities, Shaanxi province].

Objective: To compare the prevalence of HIV/STD and related health care seeking behaviors among male STD clinic attendees between Xi'an and Xianyang cities. Methods: During June and July 2016, 206 male STD clinic attendees were studied in Xi'an city, with another 221 male STD clinic attendees in Xianyang city. Cross-sectional questionnaire survey was used to collect attendees'behavioral information. Blood samples were collected via HIV/HCV/Syphilis testing. Results: The prevalence rate of HIV infection was 2.4% (5/206) in Xi'an and 0.9% (2/221) in Xianyang, with no statistical significant difference between the two cities. The prevalence rate of syphilis was 4.9% (10/206) in Xi'an, which was significantly lower than 13.6% (30/221) in Xianyang. The proportion of respondents, diagnosed with other sexually transmitted diseases, in Xi'an was higher than that of Xianyang. The proportions of commercial heterosexual sex and sex with temporary sexual partners in the past 3 months were 18.0% (37/206) and 15.5% (32/206) in Xi'an, lower than 46.6% (103/221) and 15.8% (35/221) in Xianyang (χ(2)=39.70, Р<0.01; χ(2)=0.01, P=0.93) . The proportions of condom use with commercial sex workers or temporary sexual partners in the past 3 months among Xi'an were 37.8% (14/37) and 6.3% (2/32) , lower than 93.1% (95/102) and 57.1% (20/35) in Xianyang (χ(2)=49.06, Р<0.01; χ(2)=19.63, Р<0.01) . Conclusion: Differences were noticed between Xi'an and Xianyang city in terms of STD and HIV prevalences, behaviors related to commercial sex and use of condoms among the male STD clinic attendees that calling for targeted actions in control of high risk behavlors in both HIV/AIDS and STDs transmission.

Rotenone Susceptibility Phenotype in Olfactory Derived Patient Cells as a Model of Idiopathic Parkinson's Disease.

Parkinson's disease is a complex age-related neurodegenerative disorder. Approximately 90% of Parkinson's disease cases are idiopathic, of unknown origin. The aetiology of Parkinson's disease is not fully understood but increasing evidence implies a failure in fundamental cellular processes including mitochondrial dysfunction and increased oxidative stress. To dissect the cellular events underlying idiopathic Parkinson's disease, we use primary cell lines established from the olfactory mucosa of Parkinson's disease patients. Previous metabolic and transcriptomic analyses identified deficiencies in stress response pathways in patient-derived cell lines. The aim of this study was to investigate whether these deficiencies manifested as increased susceptibility, as measured by cell viability, to a range of extrinsic stressors. We identified that patient-derived cells are more sensitive to mitochondrial complex I inhibition and hydrogen peroxide induced oxidative stress, than controls. Exposure to low levels (50 nM) of rotenone led to increased apoptosis in patient-derived cells. We identified an endogenous deficit in mitochondrial complex I in patient-derived cells, but this did not directly correlate with rotenone-sensitivity. We further characterized the sensitivity to rotenone and identified that it was partly associated with heat shock protein 27 levels. Finally, transcriptomic analysis following rotenone exposure revealed that patient-derived cells express a diminished response to rotenone-induced stress compared with cells from healthy controls. Our cellular model of idiopathic Parkinson's disease displays a clear susceptibility phenotype to mitochondrial stress. The determination of molecular mechanisms underpinning this susceptibility may lead to the identification of biomarkers for either disease onset or progression.

Effects of diet forage proportion on maintenance energy requirement and the efficiency of metabolizable energy use for lactation by lactating dairy cows.

The objective of the present study was to examine the effect of dietary forage proportion (FP) on metabolizable energy (ME) requirement for maintenance (MEm) and the efficiency of ME use for lactation (kl) in lactating dairy cows. Data used were derived from 32 calorimetric chamber experiments undertaken at our institute between 1992 and 2010, including data from 818 Holstein-Friesian cows (HF), 50 Norwegian Red cows, and 62 crossbred cows (Jersey × HF or Norwegian Red × HF). Animals were offered forage-only rations (n=66) or forage and concentrate rations (n=864) with FP ranging from 18 to 100% (dry matter basis). The effect of FP was evaluated by dividing the whole data set into 4 groups according to the FP ranges, categorized as FP <30%, FP=30 to 59%, FP=60 to 99%, and FP=100%. The MEm for individual cows was calculated from heat production minus energy losses from inefficiencies of ME use for lactation, energy retention and pregnancy, and kl was obtained from milk energy output adjusted to zero energy balance (El(0)) divided by ME available for production. Increasing FP significantly reduced ME intake and milk energy output, although the differences between the 2 low FP groups were not significant. However, increasing FP significantly increased the ratio of heat production over ME intake and MEm (MJ/kg(0.75)), with the exception that the increases did not reach significance in heat production/ME intake between FP <30% and FP=30 to 59%, or in MEm between FP=60 to 99% and FP=100%. However, the FP had no significant effect on the kl values, which were similar among the 4 groups of cows. The effect of FP was also evaluated using the linear mixed regression technique relating El(0) to ME intake. The results demonstrated that with a common regression coefficient (slope), the regression constants (intercepts) taken as net energy requirement for maintenance significantly increased with increasing FP. However, the increase between the 2 high FP groups did not research significance. It is concluded that increasing diet FP had no effects on kl but significantly increased maintenance energy requirement (MJ/kg(0.75)). These results indicate that using the current energy feeding systems to ration dairy cows managed under low input systems may underestimate their nutrient requirements, because the majority of feeding systems adopted globally do not differentiate the maintenance energy requirements between low and high forage input systems.

Is there a relationship between genetic merit and enteric methane emission rate of lactating Holstein-Friesian dairy cows?

The present study was undertaken to examine the effect of cow genetic merit on enteric methane (CH4) emission rate. The study used a data set from 32 respiration calorimeter studies undertaken at this Institute between 1992 and 2010, with all studies involving lactating Holstein-Friesian dairy cows. Cow genetic merit was defined as either profit index (PIN) or profitable lifetime index (PLI), with these two United Kingdom genetic indexes expressing the expected improvement in profit associated with an individual cow, compared with the population average. While PIN is based solely on milk production, PLI includes milk production and a number of other functional traits including health, fertility and longevity. The data set had a large range in PIN (n=736 records, -£30 to +£63) and PLI (n=548 records, -£131 to +£184), days in milk (18 to 354), energy corrected milk yield (16.0 to 45.6 kg/day) and CH(4) emission (138 to 598 g/day). The effect of cow genetic merit (PIN or PLI) was evaluated using ANOVA and linear mixed modelling techniques after removing the effects of a number of animal and diet factors. The ANOVA was undertaken by dividing each data set of PIN and PLI into three sub-groups (PIN:£15, PLI:£67) with these being categorised as low, medium and high genetic merit. Within the PIN and PLI data sets there was no significant differences among the three sub-groups in terms of CH(4) emission per kg feed intake or per kg energy corrected milk yield, or CH(4) energy (CH(4)-E) output as a proportion of energy intake. Linear regression using the whole PIN and PLI data sets also demonstrated that there was no significant relationship between either PIN or PLI, and CH(4) emission per kg of feed intake or CH(4)-E output as a proportion of energy intake. These results indicate that cow genetic merit (PIN or PLI) has little effect on enteric CH(4) emissions as a proportion of feed intake. Instead enteric CH(4) production may mainly relate to total feed intake and dietary nutrient composition.

Comparison of maintenance energy requirement and energetic efficiency between lactating Holstein-Friesian and other groups of dairy cows.

The objectives of the present study were to investigate the effects of cow group on energy expenditure and utilization efficiency. Data used were collated from 32 calorimetric chamber experiments undertaken from 1992 to 2010, with 823 observations from lactating Holstein-Friesian (HF) cows and 112 observations from other groups of lactating cows including Norwegian (n=50), Jersey × HF (n=46), and Norwegian × HF (n=16) cows. The metabolizable energy (ME) requirement for maintenance (MEm) for individual cows was calculated from heat production (HP) minus energy losses from inefficiencies of ME use for lactation, energy retention, and pregnancy. The efficiency of ME use for lactation (kl) was obtained from milk energy output adjusted to zero energy balance (El(0)) divided by ME available for production. The effects of cow groups were first evaluated using Norwegian cows against HF crossbred cows (F1 hybrid, Jersey × HF and Norwegian × HF). The results indicated no significant difference between the 2 groups in terms of energy digestibility, ratio of ME intake over gross energy intake, MEm (MJ per kg of metabolic body weight, MJ/kg(0.75)), or kl. Consequently, their data were combined (categorized as non-HF cows) and used to compare with those of HF cows. Again, we detected no significant difference in energy digestibility, ratio of ME intake over gross energy intake, MEm (MJ/kg(0.75)), or kl between non-HF and HF cows. The effects were further evaluated using linear regression to examine whether any significant differences existed between HF and non-HF cows in terms of relationships between ME intake and energetic parameters. With a common constant, no significant difference was observed between the 2 groups of cows in coefficients in each set of relationships between ME intake (MJ/kg(0.75)) and MEm (MJ/kg(0.75)), El(0) (MJ/kg(0.75)), HP (MJ/kg(0.75)), MEm:ME intake, El(0):ME intake, or HP:ME intake. However, MEm values (MJ/kg(0.75)) were positively related to ME intake (MJ/kg(0.75)), irrespective of cow group. We concluded, therefore, that cow groups evaluated in the present study had no significant effects on energy expenditure or energetic efficiency. However, the maintenance energy requirement (MJ/kg(0.75)) was not constant (as adopted in the majority of energy rationing systems across the world) but increased with increasing feed intake.

Alpha-tocopheryl succinate induces apoptosis by targeting ubiquinone-binding sites in mitochondrial respiratory complex II.

Alpha-tocopheryl succinate (alpha-TOS) is a selective inducer of apoptosis in cancer cells, which involves the accumulation of reactive oxygen species (ROS). The molecular target of alpha-TOS has not been identified. Here, we show that alpha-TOS inhibits succinate dehydrogenase (SDH) activity of complex II (CII) by interacting with the proximal and distal ubiquinone (UbQ)-binding site (Q(P) and Q(D), respectively). This is based on biochemical analyses and molecular modelling, revealing similar or stronger interaction energy of alpha-TOS compared to that of UbQ for the Q(P) and Q(D) sites, respectively. CybL-mutant cells with dysfunctional CII failed to accumulate ROS and underwent apoptosis in the presence of alpha-TOS. Similar resistance was observed when CybL was knocked down with siRNA. Reconstitution of functional CII rendered CybL-mutant cells susceptible to alpha-TOS. We propose that alpha-TOS displaces UbQ in CII causing electrons generated by SDH to recombine with molecular oxygen to yield ROS. Our data highlight CII, a known tumour suppressor, as a novel target for cancer therapy.