Maternal Betaine Supplementation Mitigates Maternal High Fat Diet-Induced NAFLD in Offspring Mice through Gut Microbiota.

Maternal betaine supplementation has been proven to alleviate non-alcoholic fatty liver disease (NAFLD) in offspring caused by maternal high-fat diet (MHFD). The gut-liver axis plays an important role in NAFLD pathogenesis. However, whether maternal betaine supplementation can alleviate NAFLD in offspring by the gut-liver axis is unknown. C57BL/6J mice were fed with high-fat diet for 4 weeks before mating, and supplemented with 1% betaine during pregnancy and lactation. After weaning, offspring mice were fed with standard diet to 10 weeks. Maternal betaine supplementation reduced hepatic triglyceride content and alleviated hepatic steatosis in offspring mice exposed to MHFD. Furthermore, the mRNA expression of PPARα, CPT1α and FATP2 was increased and TNFα was reduced by maternal betaine supplementation. Maternal betaine intake decreased the relative abundances of Proteobateria, Desulfovibrio and Ruminococcus, but increased the relative abundances of Bacteroides and Parabacteroides. Moreover, maternal betaine intake increased the concentrations of short-chain fatty acids (SCFAs), including acetic acid, butyric acid and valeric acid, in the feces. Gut microbiota and SCFAs were significantly correlated with hepatic triglyceride content and expression of the above genes. Maternal betaine intake had no effect on other gut microbiota-related metabolites (bile acid and trimethylamine-n-oxide). Altogether, maternal betaine supplementation ameliorated MHFD-induced NAFLD possibly through regulating gut microbiota and SCFAs in offspring mice.

A novel method for strict intranasal delivery of non-replicating RSV vaccines in cotton rats and non-human primates.

Respiratory syncytial virus (RSV) is the most common viral cause of bronchiolitis and pneumonia in children twelve months of age or younger and a significant cause of lower respiratory disease in older adults. As various clinical and preclinical candidates advance, cotton rats (Sigmodon hispidus) and non-human primates (NHP) continue to play a valuable role in RSV vaccine development, since both animals are semi-permissive to human RSV (HRSV). However, appropriate utilization of the models is critical to avoid mis-interpretation of the preclinical findings. Using a multimodality imaging approach; a fluorescence based optical imaging technique for the cotton rat and a nuclear medicine based positron emission tomography (PET) imaging technique for monkeys, we demonstrate that many common practices for intranasal immunization in both species result in inoculum delivery to the lower respiratory tract, which can result in poor translation of outcomes from the preclinical to the clinical setting. Using these technologies we define a method to limit the distribution of intranasally administered vaccines solely to the upper airway of each species, which includes volume restrictions in combination with injectable anesthesia. We show using our newly defined methods for strict intranasal immunization that these methods impact the immune responses and efficacy observed when compared to vaccination methods resulting in distribution to both the upper and lower respiratory tracts. These data emphasize the importance of well-characterized immunization methods in the preclinical assessment of intranasally delivered vaccine candidates.

Effective components screening and anti-myocardial infarction mechanism study of the Chinese medicine NSLF6 based on "system to system" mode.

BACKGROUND: Shuanglong formula (SLF), a Chinese medicine composed of panax ginseng and salvia miltiorrhiza exhibited significant effect in the treatment of myocardial infarction (MI) in clinical. Because of the complex nature and lack of stringent quality control, it's difficult to explain the action mechanism of SLF. METHOD: In this study, we present a "system to system" (S2S) mode. Based on this mode, SLF was simplified successively through bioactivity-guided screening to achieve an optimized minimal phytochemical composition (new formula NSLF6) while maintaining its curative effect for MI. RESULTS: Pharmacological test combining with the study of systems biology show that NSLF6 has activity for treatment MI through synergistic therapeutic efficacies between total ginsenosides and total salvianolic acids via promoting cardiac cell regeneration and myocardial angiogenesis, antagonistic myocardial cell oxidative damage. CONCLUSIONS: The present S2S mode may be an effective way for the discovery of new composite drugs from traditional medicines.

[Effect of compatibilities and proportions of shuanglong formula on acute myocardial infarction in rats].

OBJECTIVE: To verify the rational of Chinese medicine Shuanglong formula. METHOD: Rat models of acute myocardial ischemia were induced by hydrochloride isoproterenol. ECG J point change, myocardial infarction area and cellular enzyme (CK, LDH, SOD and MDA) levels were observed and detected to show protective effect of treatment groups. RESULT: The single drug prescriptions and compatibilities both could improve ECG performance, decrease levels of CK, LDH, SOD and MDA in serum, and reduce a certain myocardial infarct size. CONCLUSION: The Shuanglong formula at the high dose of 3:7 was proved to be more effective on myocardial ischemia.

Metabonomic study of Chinese medicine Shuanglong formula as an effective treatment for myocardial infarction in rats.

A UPLC/TOF-MS-based metabonomic study was conducted to assess the holistic efficacy of Traditional Chinese Medicine Shuanglong Formula (SLF) for myocardial infarction in rats. Thirty male Sprague-Dawley rats were randomly divided into five groups after surgery. The Panax ginseng group, Salvia miltiorrhiza group, and SLF group were treated with water extractions of Panax ginseng (PG), Salvia miltiorrhiza (SM), and SLF (the ratio of SM to PG was 3:7) at a dose of 5 g/kg·w·d for 21 consecutive days, respectively; the model group and sham surgery group were both treated with 0.9% saline solution. Urinary samples for metabonomic study, serum samples for biochemical measurement, and heart samples for histopathology were collected. As a result, metabonomics-based findings such as the PCA and PLS-DA plotting of metabolic state and analysis of potential biomarkers in urine correlated well to the assessment of serum biochemistry and histopathological assay, confirming that SLF exerted synergistic therapeutic efficacies to exhibit better effect on MI compared to PG or SM. The shifts in urinary TCA cycle as well as pentose phosphate pathway suggested that SLF may diminish cardiac injury of MI with its potential pharmacological effect in the regulation of myocardial energy metabolism.

Design and optimization of a multiplex anti-influenza peptide immunoassay.

Current flu vaccines are based on killed or attenuated virus vaccines that must be altered each year to include the hemagglutinin and neuraminidase genes from a strain of virus predicted to predominate in the coming year. A vaccine that could protect against multiple strains of influenza A and B would be a major asset in the fight against flu-related mortality and morbidity. To support development of such a vaccine, we have developed a Flu Multiplex Assay based on a Luminex platform to assess serum antibody levels to two conserved peptides derived from influenza A (M2 protein) and influenza B (hemagglutinin protein). The peptides were synthesized with a biotin label and subsequently coupled to two different LumAvidin microspheres. We then tested various sera against both types of peptide in the multiplex assay format. The data show that sera from Rhesus macaques immunized with a single peptide react only with the homologous peptide while Rhesus macaques immunized with both peptides respond well to both peptides. Additionally, we were able to specifically compete reactivity to both peptides. We have tested serial bleeds from 100 pediatric patients at ages ranging from 16 to 56 weeks as well as single bleeds from over 100 healthy adults. No overall trend in titer relative to pediatric age was detected. Both demographics exhibited a minimal response to either the A/M2 or B/HA0 peptides. However, the average titer for the pediatric serum samples was significantly lower than that found in the adult population. The adult population exhibited a higher prevalence of low reactive samples. Assay reagents and parameters have been optimized and the assay is shown to be repeatable and robust. The assay will be used to support clinical vaccine trials of a bivalent peptide vaccine.