Isoleucine or valine deprivation stimulates fat loss via increasing energy expenditure and regulating lipid metabolism in WAT

There has been a growing interest in controlling body weight by increasing dietary levels of leucine recently. By contrast, we have focused on studying the effect of deficiency of branched-chain amino acids (BCAAs) leucine on lipid metabolism. We previously have shown that mice fed a leucine-deficient diet for 7 days exhibit significant changes in lipid metabolism as demonstrated by suppressed lipogenesis in the liver and increased fat mobilization in white adipose tissue, the latter of which was found to be caused by increased lipolysis in WAT and uncoupling protein 1 expression in brown adipose tissue. The goal of our current study is to investigate whether the above effects of leucine deficiency can be generalized to the deficiency of other BCAAs including valine and isoleucine. In our current study, we show that valine or isoleucine deficiency has similar effects on reducing fat mass to leucine deprivation, in a similar manner as those observed during leucine deprivation.     

Plasma total antioxidant capacity is associated with dietary intake and plasma level of antioxidants in postmenopausal women

Increased plasma total antioxidant capacity (TAC) has been associated with a high consumption of fruits and vegetables. However, limited information is available on whether plasma TAC reflects the dietary intake of antioxidants and the levels of individual antioxidants in plasma. By using three different assays, the study aimed to determine if plasma TAC can effectively predict dietary intake of antioxidants and plasma antioxidant status. Forty overweight and apparently healthy postmenopausal women were recruited. Seven-day food records and 12-h fasting blood samples were collected for dietary and plasma antioxidant assessments. Plasma TAC was determined by vitamin C equivalent antioxidant capacity (VCEAC), ferric-reducing ability of plasma (FRAP) and oxygen radical absorbance capacity (ORAC) assays. TAC values determined by VCEAC were highly correlated with FRAP (r=0.79, P<.01) and moderately correlated with ORAC (r=0.34, P<.05). Pearson correlation analyses showed that plasma TAC values by VCEAC and ORAC had positive correlation with plasma uric acid (r=0.56 for VCEAC; r=0.49 for ORAC) and total phenolics (r=0.63 for VCEAC; r=0.36 for ORAC). However, TAC measured by FRAP was correlated only with uric acid (r=0.69). After multivariate adjustment, plasma TAC determined by VCEAC was positively associated with dietary intakes of γ-tocopherol (P<.001), β-carotene (P<.05), anthocyanidins (P<.05), flavones (P<.05), proanthocyanidins (P<.01) and TAC (P<.05), as well as with plasma total phenolics (P<.05), α-tocopherol (P<.001), β-cryptoxanthin (P<.05) and uric acid (P<.05). The findings indicate that plasma TAC measured by VCEAC reflects both dietary and plasma antioxidants and represents more closely the plasma antioxidant levels than ORAC and FRAP.     

Determination of endotoxin through an aptamer-based impedance biosensor

Lipopolysaccharide (LPS) often referred to endotoxin is an undesirable impurity frequently entrained with various recombinant protein therapeutics and plasmid DNA (pDNA) vaccines of bacterial origin. The inherent toxicities (e.g. fever, hypotension, shock and death) of LPS render its early and sensitive detection essential for several biological assays and/or parenteral administrations of biotherapeutics. In this study, an electrochemical biosensor using an LPS specific single stranded DNA (ssDNA) aptamer as a probe was developed. Amine-terminated aptamer exhibiting high affinity (K(d)=11.9 nM) to LPS was immobilized on a gold electrode using 3-mercaptopropionic acid (MPA) as a linker. Each step of the modification process was characterized by cyclic voltammetry (CV) and electrochemical impendence spectroscopy (EIS). A good linear relationship of the changes in the charge-transfer resistance (ΔR(et)) and the logarithmic value of LPS concentration was demonstrated in a broad dynamic detection range of 0.001-1 ng/ml. Furthermore, the aptasensor showed a high selectivity to LPS despite the presence of pDNA, RNA and bovine serum albumin (BSA) and could be regenerated in low pH condition, offering a promising option for detecting LPS often present in a complex milieu.     

Do dietary betaine and the antibiotic florfenicol influence the intestinal autochthonous bacterial community in hybrid tilapia (<Emphasis Type="Italic">Oreochromis niloticus</Emphasis> ♀ × <Emphasis Type="Italic">O. aureus</Emphasis> ♂)?

The attractant betaine and the antibiotic growth promoter florfenicol are commonly used together in Chinese fresh water aquaculture, but there is no information about the effect of these two feed additive on the intestinal autochthonous bacterial community in hybrid tilapia (Oreochromis nilotica ♀ × O. aureas ♂). Hybrid tilapia (240 fish in total; 20 fish per net cage; three cages per group) were divided into four dietary groups: control group, no betaine or florfenical addition (CK); betaine group, 0.1% betaine added (B); florfenicol group, 0.002% florfenicol added (F); and combination group, 0.1% betaine and 0.002% florfenicol added together (BF). After 8 weeks of feeding, six fish from each cage were chosen randomly, the guts were sampled and pooled, and their intestinal autochthonous bacterial communities were analyzed by 16S rDNA-denaturing gradient gel electrophoresis. Enumeration of total gut autochthonous bacteria was analyzed by quantitative PCR with rpoB as the endogenous control. The results showed that the fish intestinal bacteria of group B were more diverse than that of CK, and that of F and BF groups was reduced in the total numbers and limited to certain bacterial species or genera (P < 0.05). This study revealed that betaine can promote some intestinal autochthonous bacteria, and florfenicol play a depressor role. When combined together, florfenicol may overshadow the effect of betaine on the predominant intestinal bacteria of tilapia.     

The DNA‐ and RNA‐binding protein FACTOR of DNA METHYLATION 1 requires XH domain‐mediated complex formation for its function in RNA‐directed DNA methylation

Studies have identified a sub‐group of SGS3‐LIKE proteins including FDM1–5 and IDN2 as key components of RNA‐directed DNA methylation pathway (RdDM). Although FDM1 and IDN2 bind RNAs with 5′ overhangs, their functions in the RdDM pathway remain to be examined. Here we show that FDM1 interacts with itself and with IDN2. Gel filtration suggests that FDM1 may exist as a homodimer in a heterotetramer complex in vivo. The XH domain of FDM1 mediates the FDM1–FDM1 and FDM1–IDN2 interactions. Deletion of the XH domain disrupts FDM1 complex formation and results in loss‐of‐function of FDM1. These results demonstrate that XH domain‐mediated complex formation of FDM1 is required for its function in RdDM. In addition, FDM1 binds unmethylated but not methylated DNAs through its coiled‐coil domain. RNAs with 5′ overhangs does not compete with DNA for binding by FDM1, indicating that FDM1 may bind DNA and RNA simultaneously. These results provide insight into how FDM1 functions in RdDM.     

Effects of nitrate on methane production, fermentation, and microbial populations in in vitro ruminal cultures

The objective of this study was to examine the effects of nitrate on methane production, important fermentation characteristics, Fibrobacter succinogenes, Ruminococcus albus, Ruminococcus flavefaciens, total bacteria, and methanogens using in vitro ruminal cultures. Potential adaptation of the above microbes and persistency of nitrate to mitigate CH₄ production were also evaluated. Methane production was reduced by 70% at 12 μmol ml⁻¹ and nearly completely at ?24 μmol ml⁻¹ nitrate. Production of volatile fatty acids (VFAs) was affected to different extents at different nitrate concentrations. Over a series of six consecutive cultures receiving 12 μmol ml⁻¹nitrate, production of CH₄ and VFA did not change significantly. R. albus and R. flavefaciens seemed to adapt to nitrate, while F. succinogenes and methanogens did not. Nitrate may be used in achieving persistent mitigation of CH4 production by ruminants.     

The effect of vindoline C-16 substituents on the biomimetic coupling reaction: synthesis and cytotoxicity evaluation of the corresponding vinorelbine analogues

A new series of vinorelbine analogues are designed and synthesized to explore the vindoline C-16 substituent effects on the biomimetic coupling with catharanthine, and the structure-activity relationships of these vinorelbine analogues as cytotoxic agents are also studied. The results show that introduction of severe steric hindrance and/or electron-withdrawing group at C-16 site are not propitious to improving the yields of the coupling reaction, and the SAR information collected so far suggests that small alkyl groups substituted at C-16 of vindoline are conductive to maintaining the cytotoxicity.     

Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase inhibitors and metal-chelating agents

A series of novel indanone derivatives was designed, synthesised and evaluated as potential agents for Alzheimer's disease. Among them, compound 6a, with a piperidine group linked to indone by a two-carbon spacer, exhibited the most potent inhibitor activity, with an IC(50) of 0.0018 μM for AChE; the inhibitory activity of this compound was 14-fold more potent than that of donepezil. Furthermore, these compounds also exhibited good metal-chelating ability.     

Indole-propionic acid derivatives as potent, S1P3-sparing and EAE efficacious sphingosine-1-phosphate 1 (S1P1) receptor agonists

Novel indole-propionic acid derivatives were developed as sphingosine-1-phosphate (S1P) receptor agonists through a systematic SAR study. The optimized and S1P(3) selective S1P(1) agonist 9f induced peripheral blood lymphocyte reduction in vivo and has an excellent efficacy in mouse experimental autoimmune encephalomyelitis (EAE).