[Feeding rhythm entrains circadian metabolism genes, but not the circadian clock, in brown adipose tissue].

The central circadian clock and feeding rhythm coordinately reset peripheral circadian clocks. Emerging evidence suggests that feeding rhythm resets peripheral circadian clocks in a tissue-specific manner. This study aimed to determine whether and how feeding rhythm regulates circadian rhythms of the circadian clock and metabolic genes in brown adipose tissue (BAT). We applied different regimens of time-restricted feeding (TRF) in wildtype and Per1/2 deficient C57BL/6 mice, and quantified the effects of sex, treatment duration, constant light, and circadian clock on circadian rhythms of the BAT circadian clock and metabolic genes by RT-qPCR; Representative circadian clock genes are Bmal1, Nr1d1, Dbp, and Per2, and representative metabolic genes are uncoupling protein 1 (Ucp1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (Pfkfb3) that controls the flux through glycolysis, pyruvate dehydrogenase kinase isozyme 4 (Pdk4) gating the tricarboxylic acid cycle, and carnitine palmitoyltransferase 1A (Cpt1a) that controls mitochondrial fatty acid oxidation. The results showed that, daytime-restricted feeding (DRF) moderately shifted the phase of the BAT circadian clock in female mice within 7 or 36 d, and resulted in the loss of circadian rhythm in Dbp and Per2 transcripts in males. DRF induced de novo oscillation of the Ucp1 transcript, and shifted the phase of representative metabolic genes, such as Pfkfb3, Pdk4, and Cpt1a, more than 7 h. Constant light is known to disrupt the synchrony of the central circadian clock. The results showed that constant light promoted phase entrainment of the circadian clock by DRF in BAT, but abolished the oscillation of the metabolic genes (except for Pdk4). Despite combined treatment with Per1/2 deficiency and constant darkness, DRF was sufficient to drive circadian rhythms of Bmal1 and Dbp, but not those of Nr1d1, Ucp1, Pfkfb3, and Cpt1a. Overall, the circadian clock of BAT has weak adaptation to altered feeding rhythms and sex differences. The central circadian clock antagonizes DRF in the entrainment of the BAT circadian clock, whereas DRF resets circadian rhythms of metabolic genes, such as Ucp1, Pfkfb3, and Cpt1a, in a circadian clock-dependent manner.

Design, synthesis and evaluation of dihydrotriazine derivatives-bearing 5-aryloxypyrazole moieties as antibacterial agents.

In the present investigation, a series of dihydrotriazine derivatives-bearing 5-aryloxypyrazole moieties were synthesized and their structures were confirmed by different spectral tools. The biological evaluation in vitro revealed that some of the target compounds exerted good antibacterial and antifungal activity in comparison with the reference drugs. Among these novel hybrids, compound 10d showed the most potent activity with minimum inhibitory concentration values (MIC) of 0.5 µg/mL against S. aureus 4220, MRSA 3506 and E. coli 1924 strain. The cytotoxic activity of the compounds 6d, 6m, 10d and 10g was assessed in MCF-7 and HeLa cells. Growth kinetics study showed significant inhibition of bacterial growth when treated with different conc. of 10d. In vitro enzyme study implied that compound 10d exerted its antibacterial activity through DHFR inhibition. Moreover, significant inhibition of biofilm formation was observed in bacterial cells treated with MIC conc. of 10d as visualized by SEM micrographs. Twenty-nine target compounds were designed, synthesized and evaluated in terms of their antibacterial and antifungal activities.

[Relationship Between LEP G2548A Polymorphism and Cholesterol Gallstone].

OBJECTIVES: To determine the associations of single nucleotide polymorphism (SNP) in leptin (LEP) genes and environmental factors with cholesterol gallstone in southeast Han populations. METHODS: A 1:2 matched case-control study was conducted involving 200 patients with cholesterol gallstone. Genotyping of the SNP was examined on the LightCycler480 PCR platform using in-house high resolution melting (HRM) approaches. Detection correctness was validated through direct sequencing. Multifactor dimensionality reduction (MDR) analysis was applied to examine the effects of potential gene-environment interactions. RESULTS: Three genotypes of LEP G2548A were obtained by HRM genotyping, including 52 cases of GG wild type, 192 cases of GA mutant heterozygosity and 356 cases of AA mutation homozygous type. The genotype distribution of the SNP locus in the control group was in line with the Hardy-Weinberg genetic balance (P>0.05). The AA genotype carriers of LEP G2548A had significantly higher serum leptin than the GA/GG genotype carriers (H=6.83, P<0.05). The conditional logistic regression revealed that high serum leptin [odds ratio (OR)=5.012, 95% confidence interval (CI): 3.248-7.734], AA genotype of LEP G2548A site (OR=2.292, 95%CI: 1.012-5.193), family history of gallstones (OR=2.984, 95%CI: 1.329-6.700), high SBP (OR=1.927, 95%CI: 1.140-3.255) and smoking (OR=1.717, 95%CI: 1.006-2.928) were predictors of cholesterol gallstone. However, regular drinking of strong tea (OR=0.552, 95%CI: 0.336-0.907) and exercise (OR=0.591, 95%CI: 0.395-0.882) were protecting factors for cholesterol gallstone. The results of MDR analysis indicated that tea drinking, genotype of LEP G2548A site and serum leptin formed the optimal gene-environment interaction model. CONCLUSIONS: Individuals who drink less tea, carry AA genotype and have high serum leptin are more susceptible to cholesterol gallstone.

[Epidural anesthesia with ropivacaine by computerized infusion pump].

OBJECTIVE: To explore the feasibility of epidural anesthesia with ropivacaine by computerized infusion pump. METHODS: Sixty patients scheduled for obstetric operation were divided into a continuous pump infusion group (Group A, n=30) and a conventional injection group (Group B, n=30). The initial doses of 0.75% ropivacaine 12 mL and 15 mL were respectively injected into the patient's epidural space in Group A and Group B. The dose of 6 mL of 0.75% ropivacaine per hour was continuously pumped to maintain the anesthesia till the end of the operation in Group A, and 6 mL of 0.75% ropivacaine was injected 80 min later in Group B. RESULTS: Blood pressure in some patients markedly decreased at 90 min after the first injection in Group B while it is relatively stable in Group A (P<0.05). The number of patients who had to inject ephedrine to raise the blood pressure in Group A was smaller than that in Group B during the operation (P<0.05). There was no significant difference in the anesthetic level between Group A and Group B (P>0.05). CONCLUSION: Epidural anesthesia with ropivacaine by computerized infusion pump is safe, which can not only provide an excellent anesthetic effect but also keep the hemodynamics stable.

[Clinical study of low molecular weight heparin therapy for sepsis].

OBJECTIVE: To investigate the therapeutic effect of low molecular weight heparin (LMWH) therapy on sepsis. METHODS: Forty sepsis patients were randomly divided into two groups: routine treatment group and LMWH treatment group. Score of acute physiology and chronic health evaluation II (APACHE II), the days in intensive care unit (ICU) and mortality rate in 28 days were observed, and the levels of interleukin-6 (IL-6), malondialdehyde (MDA), superoxide dismutase (SOD), coagulation function and platelet count (PLT) were determined before and after treatment in the two groups. RESULTS: Both APACHE II and IL-6 levels in LMWH group decreased with passage of time, the differences were significant between the results on day 7 and that of pretreatment (both P<0.05). In the routine treatment group, APACHE II and IL-6 levels decreased first and then increased, and they were higher than those in LMWH group 7 days after treatment (both P<0.05). In LMWH group, the time of stay in ICU was (9.92+/-6.81)days, the mortality rate in 28 days was 40.9%, and they all were lower than those in routine treatment group [(12.85+/-9.14)days and 50.0%], but the difference was not statistically significant (both P>0.05). After treatment SOD level elevated [(159.13+/-99.31) kU/L vs.(318.38+/-284.29) kU/L] and MDA level lowered [(17.72+/-14.89) micromol/L vs.(6.62+/-5.53) micromol/L] in LMWH group. The changes in MDA and SOD in routine treatment were reverse to those of the LMWH group [SOD: (180.99+/-169.40) kU/L vs. (135.16+/-107.73) kU/L; MDA: (17.25+/-15.74) micromol/L vs. (20.77+/-16.87) micromol/L]. The difference was significant between the two groups after treatment (both P<0.05). The difference in coagulation function and PLT was not significant between the two groups. CONCLUSION: LMWH can ameliorate sepsis by down-regulating the levels of pro-inflammatory cytokines, and suppressing the release of oxygen-derived free radicals. It is a promising treatment measure in sepsis patient with safety and no severe side effects.