Danqi Tablet () Regulates Energy Metabolism in Ischemic Heart Rat Model through AMPK/SIRT1-PGC-1α Pathway.

OBJECTIVE: To investigate the cardioprotective effect of Danqi Tablet (DQT, ) on ischemic heart model rats and the regulative effect on energy metabolism through peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). METHODS: Rat ischemic heart model was induced by ligation of left anterior descending coronary artery. Totally 40 Sprague-Dawley rats were randomly divided into sham group, model group, DQT group (1.5 mg/kg daily) and trimetazidine (TMZ) group (6.3 mg/kg daily) according to a random number table, 10 rats in each group. Twenty-eight days after continuous administration, cardiac function was assessed by echocardiography and the structures of myocardial cells were observed by hematoxylin-eosin staining. The level of adenosine triphosphate (ATP) in myocardial cells was measured by ATP assay kit. Expressions level of key transcriptional regulators, including PGC-1α, Sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK), and downstream targets of PGC-1α, such as mitofusin 1 (MFN1), mitofusin 2 (MFN2) and superoxide dismutase 2 (SOD2) were measured by Western blot. Expression level of PGC-1α was examined by immunohistochemical staining. RESULTS: The rat ischemic heart model was successfully induced and the heart function in model group was compromised. Compared with the model group, DQT exerted cardioprotective effects, up-regulated the ATP production in myocardial cells and inhibited the infiltration of inflammatory cells in the margin area of infarction of the myocardial tissues (P<0.01). The expressions of PGC-1α, SIRT1 and AMPK were increased in the DQT group (all P<0.05). Furthermore, the downstream targets, including MFN1, MFN2 and SOD2 were up-regulated (P<0.05 or P<0.01). Compared with the TMZ group, the expression levels of PGC-1α, MFN1 and SOD2 were increased by DQT treatment (P<0.05 or P<0.01). CONCLUSION: DQT regulated energy metabolism in rats with ischemic heart model through AMPK/SIRT1 -PGC-1α pathway. PGC-1α might serve as a promising target in the treatment of ischemic heart disease.

The effects of oral nutritional supplements in patients with maintenance dialysis therapy: A systematic review and meta-analysis of randomized clinical trials.

BACKGROUND/OBJECTIVE: This systematic review aims to determine the potential effects of oral nutritional supplements (ONS) in patients receiving maintenance dialysis therapy (MDT). METHODS: Electronic databases were searched without language limits through to July 2018. Randomized controlled trials (RCTs) that involved comparisons of ONS versus placebo or routine care are included in this meta-analysis. RevMan 5.3 statistical software was used for meta-analysis. RESULTS: 15 articles with 589 subjects were included in our study. There are insufficient comparable data of randomized trials to allow meta-analysis of mortality. Albumin levels may be improved by the macronutrient blends or protein/amino acid supplements in MDT patients. Compared with the control group, serum albumin levels and BMI in the ONS group were increased by 1.58 g/L (95% CI, 0.52-2.63, P = 0.003; I2 = 85%) and 0.40 kg/m2 (95% CI, 0.10-0.71, P = 0.01; I2 = 49%), respectively. In the subgroup analysis of patients receiving hemodialysis, albumin levels in ONS group were increased by 2.17 g/L (95% CI, 0.89-3.45, P<0.001; I2 = 90%). ONS may not influence serum phosphorus and potassium levels. CONCLUSIONS: Very low-quality evidence suggests that Short-term oral energy or protein/amino acid supplements may improve nutritional status by increasing serum albumin levels and BMI in MDT patients, without influence on serum potassium levels. High-quality and large RCTs, particularly regarding the effects of ONS on mortality and quality of life, are needed to further validate our findings.

Cardioprotective effects of Qishen Granule () on sarcoplasmic reticulum Ca2+ handling in heart failure rats.

OBJECTIVE: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Ca2+ handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms. METHODS: HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing. Intracellular Ca2+ concentration and sarco-endoplasmic reticulum ATPase 2a (SERCA2a) activity were detected by specifific assay kits. Expressions of the critical regulators in SR Ca2+ handling were evaluated by Western blot and real-time quantitative polymerase chain reaction. RESULTS: HF model of rats developed ventricular remodeling accompanied with calcium overload and defective Ca2+ release-uptake cycling in cardiomyocytes. Treatment with QSG improved contractive function, attenuated ventricular remodeling and reduced the basal intracellular Ca2+ level. QSG prevented defective Ca2+ leak by attenuating hyperphosphorylation of ryanodine receptor 2, inhibiting expression of protein kinase A and up-regulating transcriptional expression of protein phosphatase 1. QSG also restored Ca2+ uptake by up-regulating expression and activity of SERCA2a and promoting phosphorylation of phospholamban. CONCLUSION: QSG restored SR Ca2+ cycling in HF rats and served as an ideal alternative drug for treating HF.

[Morphological characteristics and gene expression of Chrysomya megacephala eggs in different developmental stages].

OBJECTIVE: To research the morphological characteristics and differential gene expression of Chrysomya megacephala eggs in different developmental stages. METHODS: After C. megacephala laid eggs (0 h), the eggs were collected every 2 h until eggs hatched into larvae. The morphological characteristics of C. megacephala eggs in different developmental stages were observed by stereo microscopy and scanning electron microscopy. The total RNA of the fly eggs was extracted. The expression levels of bicoid, slalom and chitin synthase genes was determined by real-time flourescence quantitative PCR. Statistic analyses were performed with SPSS 19.0. RESULTS: Under the stereomicroscope, at 0-4 h after egg laying, the morphological change of C. megacephala eggs was not obvious. At the 6th hour after egg laying, somites were formed. After 8 hours the eggs shriveled. At the 9th hour after egg laying, the eggs hatched into larvae. The scanning electron microscope images showed that the morphological change of eggs was not obvious in the first 4 hours, the end of micropyle slightly outward, the surface around the micropyle was smooth. At the 6th hour after egg laying, the end of micropyle began to sag and irregular protrusions formed around the micropyle. At the 8th hour the end of micropyle was obviously dented. After 9 hours larvae hatched from eggs. Real-time fluorescence quantitative PCR indicated that the expression levels of bicoid, slalom and chitin synthase genes from C. megacephala eggs regularly changed with the developmental stages. There was a significant difference in threshold cycle values among the three genes (P<0.05). CONCLUSION: The morphological characteristics of C. megacephala eggs change with the development stage. The levels of gene expression in different development period of C. megacephala eggs are different.

[Association between HPV DNA and disease specific survival in patients with penile cancer].

OBJECTIVE: To examine the prevalence of human papilloma virus (HPV) in penile squamous-cell carcinomas (SCCs), explore the relationship between HPV and clinicopathological variables and determine its value for predicting disease-specific survival. METHODS: We retrospectively collected clinicopathological data of 28 patients with penile squamous cell carcinomas from 2000 to 2009 at Beijing Cancer Hospital, Beijing Hospital and Peking University People's Hospital. Polymerase chain reaction (PCR) was used to detect the presence of HPV DNA in tumor specimens. Regular follow-ups were conducted. Disease-specific survival plots were drawn with the Kaplan-Meier method and compared with the Log-Rank test. Cox proportional hazard analysis was applied to assess the independent effects of several prognostic factors on survival. RESULTS: HPV DNA was detected in 7/28 samples. After sequencing, all 7 samples were confirmed to be HPV-16 type. The median follow-up period was 60 (6-150) months. By the time of analysis, 8/28 patients died. HPV DNA was not significantly associated with age, pathological grading, pathologic T stage or lymph node metastasis (P = 0.191, 0.165, 1.000, 0.639 respectively). Cox multivariate regression analysis indicated that lymph node status (HR = 5.5, P = 0.023) was an independent predictive factor of disease specific survival, followed by pathological T classification (HR = 11.0, P = 0.035) . The 5-year disease-specific survival in patients with HPV DNA positive was higher than that in those with HPV DNA negative (67% vs 58%) . But survival had no significant differences (P = 0.431). CONCLUSIONS: Higher pathologic T stage and lymph node metastasis are independent prognostic factors for worse survival. And mortality does not increase markedly in penile cancer patients with HPV DNA positive.

[Correlation of CD82 and hTERT expressions and HPV infection with penile cancer].

OBJECTIVE: To study the correlation of the expressions of CD82 and hTERT and HPV infection with the clinical pathological features of penile cancer and identify their prognostic significance in the lymphatic metastasis of the disease. METHODS: A total of 44 patients underwent partial or radical penectomy and lymph node dissection. The expressions of CD82 and hTERT were determined by immunohistochemistry, and HPV infection was detected by PCR. RESULTS: The positive rates of CD82, hTERT, and HPV DNA in penile carcinoma were 47.7%, 38.6% and 25.9%, respectively. The amplified HPV DNA was HPV-16. The pathological stage and hTERT expression were positively correlated with inguinal lymph node metastasis of penile cancer (P = 0.032, P = 0.041), and so was the pathological stage with the expression of CD82 (P = 0.045), but neither the pathological stage, nor the expression of CD82 or the positive rate of HPV DNA showed any correlation with lymph node metastasis (P = 0.627, P = 0.094, P = 0.633). CONCLUSION: The pathological grade and hTERT expression are independent prognostic factors for lymph node metastasis in penile carcinoma. These features help the prognosis and identification of the patient at the risk of nodal metastasis.

[Gene expression profiling study of HPV-16 positive and HPV-negative esophageal squamous cell carcinoma].

OBJECTIVE: To study the difference in gene expression between human papillomavirus (HPV)16-positive and HPV-negative esophageal squamous cell carcinoma(ESCC) . METHODS: Eight HPV 16-positive and seven HPV-negative ESCC specimens were evaluated by PCR. The samples were then determined for gene expression profiling using Solexa Sequencing Chip followed by bioinformatics analysis. RESULTS: A total of 796 differentially expressed genes between HPV 16-positive and HPV-negative ESCC were observed. Among them, 366 were up-regulated while 430 were down-regulated. Functional classification and pathway analysis showed that the functions of these genes were mostly related to tumor morphology, immune, and inflammatory response, cellular growth and proliferation and cellular movement. Of these, factors related to immune and inflammation were the most representative. CONCLUSION: Differences in immunologic factors may be associated with HPV infection in esophageal cancer.

Is microtubule disassembly a trigger for cold acclimation?

Cold acclimation was followed in three cultivars of winter wheat (Triticum aestivum L.) that differ in freezing tolerance, using root growth as the indicator. During acclimation (followed through 7 d at 4 degrees C), growth rate progressively recovered. The recovery was fast in the tolerant, slow in the sensitive cultivars. The development of freezing tolerance was followed by a challenging cold shock administered after various time intervals of acclimation. Acclimation proceeded faster in the tolerant cultivars. Microtubules were monitored during the acclimation period. A rapid, but transient partial disassembly in the tolerant cultivars preceded the formation of cold-stable microtubules and the recovery of growth rate. In contrast, this transient disassembly was absent in the sensitive cultivar. When a transient disassembly was artificially generated by a pulse-treatment with the antimicrotubular herbicide pronamide, this could induce freezing tolerance. The appearance of cold-stable microtubules was accompanied by a reduced abundance of type TUA1/2 alpha-tubulin isotypes. These findings are discussed with respect to a role of microtubule disassembly in the sensing of low-temperature stress.

The stability of cortical microtubules depends on their orientation.

Auxin controls the orientation of cortical microtubules in maize coleoptile segments. We used tyrosinylated alpha-tubulin as a marker to assess auxin-dependent changes in microtubule turnover. Auxin-induced tyrosinylated alpha-tubulin, correlated with an elevated sensitivity of growth to antimicrotubular compounds such as ethyl-N-phenylcarbamate (EPC). We determined the affinity of alpha-tubulin to EPC and found that it was dramatically increased when the tubulin was de-tyrosinylated. By proteolytic cleavage of the carboxy terminal tyrosine, such an increased affinity could be induced in vitro. Thus, the auxin-induced sensitivity of growth to EPC is not caused by an increased affinity for this inhibitor, but caused by a reduced microtubule turnover. Double visualization assays revealed that the transverse microtubules induced by auxin consist predominantly of tyrosinylated alpha-tubulin, whereas the longitudinal microtubules induced by auxin depletion contain de-tyrosinylated alpha-tubulin. The results are discussed in terms of direction-dependent differences in the lifetime of microtubules.