siRNA nanoparticle targeting Usp20 lowers lipid levels and ameliorates metabolic syndrome in mice.

Atherosclerotic cardiovascular disease is closely correlated with elevated low density lipoprotein-cholesterol. In feeding state, glucose and insulin activate mammalian target of rapamycin 1 that phosphorylates the deubiquitylase ubiquitin-specific peptidase 20 (USP20). USP20 then stabilizes HMG-CoA reductase, thereby increasing lipid biosynthesis. In this study, we applied clinically approved lipid nanoparticles to encapsulate the siRNA targeting Usp20. We demonstrated that silencing of hepatic Usp20 by siRNA decreased body weight, improved insulin sensitivity, and increased energy expenditure through elevating UCP1. In Ldlr-/- mice, silencing Usp20 by siRNA decreased lipid levels and prevented atherosclerosis. This study suggests that the RNAi-based therapy targeting hepatic Usp20 has a translational potential to treat metabolic disease.

Diversity and functional analysis of Chinese bumblebee gut microbiota reveal the metabolic niche and antibiotic resistance variation of Gilliamella.

Bumblebees play an important role in maintaining the balance of natural and agricultural ecosystems, and the characteristic gut microbiota of bumblebees exhibit significant mutualistic functions. China has the highest diversity of bumblebees; however, gut microbiota of Chinese bumblebees have mostly been investigated through culture-independent studies. Here, we analyzed the gut communities of bumblebees from Sichuan, Yunnan, and Shaanxi provinces in China through 16S ribosomal RNA amplicon sequencing and bacterial isolation. It revealed that the bumblebees examined in this study harbored two gut enterotypes as previously reported: one is dominated by Gilliamella and Snodgrassella, and the other is distinguished by prevalent environmental species. The gut compositions obviously varied among different individual bees. We then isolated 325 bacterial strains and the comparative genomic analysis of Gilliamella strains revealed that galactose and pectin digestion pathways were conserved in strains from bumblebees, while genes for the utilization of arabinose, mannose, xylose, and rhamnose were mostly lost. Only two strains from the Chinese bumblebees possess the multidrug-resistant gene emrB, which is phylogenetically closely related to that from the symbionts of soil entomopathogenic nematode. In contrast, tetracycline-resistant genes were uniquely present in three strains from the USA. Our results illustrate the prevalence of strain-level variations in the metabolic potentials and the distributions of antibiotic-resistant genes in Chinese bumblebee gut bacteria.

Correlation between Contrast-Enhanced Ultrasound and Microvessel Density via CD31 and CD34 in a rabbit VX2 lung peripheral tumor model.

AIM: To evaluate the tumor angiogenesis in lung peripheral VX2 tumor model by contrast-enhanced ultrasound (CEUS) and to determine the correlation between CEUS parameters and microvessel density (MVD) calculated via CD31 and CD34 expression. MATERIAL AND METHODS: VX2 pulmonary tumors were created in eight Japanese white rabbits by implanting a VX2 sarcoma into the lower portion of the right lung through ultrasound guidance. Tumors were allowed to grow for 14-21 days to achieve a diameter of 7-15 mm, and were examined by CEUS using a SonoVue contrast agent. The results were recorded as digital video images, and the time-intensity curves and hemodynamic parameters were analyzed. Pathological tumor specimens were immediately obtained after the ultrasound examinations. Tumor specimens were stained with hematoxylin and eosin (H&E) and expressed as CD31 and CD34. The different endothelial cell markers were determined by immunohistochemical staining. MVD was calculated via CD 31 and CD34, and the relationship between CEUS parameters and MVD was analyzed. RESULTS: Two distinct types of microvessels were identified in lung peripheral VX2 tumors: differentiated (CD34+) and undifferentiated (CD31+) vessels. A significant correlation was found between CEUS parameters and undifferentiated MVD (CD31+ vessels) in lung peripheral VX2 tumors (p<0.05). A reverse correlation was observed between different MVDs. CONCLUSIONS: Two different degrees of differentiation of vascular endothelial cells (CD31 and CD34) exist in the rabbit lung peripheral VX2 tumor model. CD31 MVD can more effectively evaluate tumor angiogenesis compared with CD34 MVD. CEUS, as a non-invasive imaging method, can effectively evaluate tumor angiogenesis in rabbit peripheral lung cancer.

Prolongation of satiety after low versus moderately high glycemic index meals in obese adolescents.

BACKGROUND: One in 5 American children is overweight, despite a decrease in total fat consumption. This has sparked an interest in the carbohydrate composition of diets, including the glycemic index (GI). OBJECTIVE: To investigate whether a low-GI meal replacement (LMR) produced similar metabolic, hormonal, and satiety responses in overweight adolescents as a low-GI whole-food meal (LWM) when compared with a moderately high-GI meal replacement (HMR). METHODS: Randomized, crossover study comparing LMR, HMR, and LWM in 16 (8 male/8 female) adolescents during 3 separate 24-hour admissions. The meal replacements consisted of a shake and a nutrition bar. Identical test meals were provided at breakfast and lunch. Metabolic and hormonal indices were assessed between meals. Measures of participants' perceived satiety included hunger scales and ad libitum food intake. RESULTS: The incremental areas under the curve for glucose were 46% and 43% lower after the LMR and LWM, respectively, compared with the HMR. Insulin's incremental area under the curve was also significantly lower after both low GI test meals (LMR = 36%; LWM = 51%) compared with the HMR. Additional food was requested earlier after the HMR than the LMR (3.1 vs 3.9 hours, respectively), although voluntary energy intake did not differ. CONCLUSIONS: Differences in insulin response between the meal replacements occurred, and prolongation of satiety after the LMR, based on time to request additional food, was observed. We speculate that the prolonged satiety associated with low GI foods may prove an effective method for reducing caloric intake and achieving long-term weight control.