Effects of Synbiotic Supplementation on Metabolic Syndrome Traits and Gut Microbial Profile among Overweight and Obese Hong Kong Chinese Individuals: A Randomized Trial.

In view of the limited evidence showing anti-obesity effects of synbiotics via modulation of the gut microbiota in humans, a randomized clinical trial was performed. Assessment of the metabolic syndrome traits and profiling of the fecal gut microbiota using 16S rRNA gene sequencing in overweight and obese Hong Kong Chinese individuals before and after dietary intervention with an 8-week increased consumption of fruits and vegetables and/or synbiotic supplementation was conducted. The selected synbiotic contained two probiotics (Lactobacillus acidophilus NCFM and Bifidobacterium lactis HN019) and a prebiotic (polydextrose). Fifty-five overweight or obese individuals were randomized and divided into a synbiotic group (SG; n = 19), a dietary intervention group (DG; n = 18), and a group receiving combined interventions (DSG; n = 18). DSG showed the greatest weight loss effects and number of significant differences in clinical parameters compared to its baseline values-notably, decreases in fasting glucose, insulin, HOMA-IR, and triglycerides and an increase in HDL-cholesterol. DSG lowered Megamonas abundance, which was positively associated with BMI, body fat mass, and trunk fat mass. The results suggested that increasing dietary fiber consumption from fruits and vegetables combined with synbiotic supplementation is more effective than either approach alone in tackling obesity.

Integrated mRNA and microRNA transcriptome sequencing characterizes sequence variants and mRNA-microRNA regulatory network in nasopharyngeal carcinoma model systems.

Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in Southeast Asia among the Chinese population. Aberrant regulation of transcripts has been implicated in many types of cancers including NPC. Herein, we characterized mRNA and miRNA transcriptomes by RNA sequencing (RNASeq) of NPC model systems. Matched total mRNA and small RNA of undifferentiated Epstein-Barr virus (EBV)-positive NPC xenograft X666 and its derived cell line C666, well-differentiated NPC cell line HK1, and the immortalized nasopharyngeal epithelial cell line NP460 were sequenced by Solexa technology. We found 2812 genes and 149 miRNAs (human and EBV) to be differentially expressed in NP460, HK1, C666 and X666 with RNASeq; 533 miRNA-mRNA target pairs were inversely regulated in the three NPC cell lines compared to NP460. Integrated mRNA/miRNA expression profiling and pathway analysis show extracellular matrix organization, Beta-1 integrin cell surface interactions, and the PI3K/AKT, EGFR, ErbB, and Wnt pathways were potentially deregulated in NPC. Real-time quantitative PCR was performed on selected mRNA/miRNAs in order to validate their expression. Transcript sequence variants such as short insertions and deletions (INDEL), single nucleotide variant (SNV), and isomiRs were characterized in the NPC model systems. A novel TP53 transcript variant was identified in NP460, HK1, and C666. Detection of three previously reported novel EBV-encoded BART miRNAs and their isomiRs were also observed. Meta-analysis of a model system to a clinical system aids the choice of different cell lines in NPC studies. This comprehensive characterization of mRNA and miRNA transcriptomes in NPC cell lines and the xenograft provides insights on miRNA regulation of mRNA and valuable resources on transcript variation and regulation in NPC, which are potentially useful for mechanistic and preclinical studies.

Gene expression profiling identifies lobe-specific and common disruptions of multiple gene networks in testosterone-supported, 17beta-estradiol- or diethylstilbestrol-induced prostate dysplasia in Noble rats.

The xenoestrogen diethylstilbestrol (DES) is commonly believed to mimic the action of the natural estrogen 17beta-estradiol (E2). To determine if these two estrogens exert similar actions in prostate carcinogenesis, we elevated circulating levels of estrogen in Noble (NBL) rats with E(2/DES-filled implants, while maintaining physiological levels of testosterone (T) in the animals with T-filled implants. The two estrogens induced dysplasia in a lobe-specific manner, with E2 targeting only the lateral prostate (LP) and DES impacting only the ventral prostate (VP). Gene expression profiling identified distinct and common E2-disrupted versus DES-disrupted gene networks in each lobe. More importantly, hierarchical clustering analyses revealed that T + E2 treatment primarily affected the gene expression pattern in the LP, whereas T + DES treatment primarily affected the gene expression profile in the VP. Gene ontology analyses and pathway mapping suggest that the two hormone treatments disrupt unique and/or common cellular processes, including cell development, proliferation, motility, apoptosis, and estrogen signaling, which may be linked to dysplasia development in the rat prostate. These findings suggest that the effects of xenoestrogens and natural estrogens on the rat prostate are more divergent than previously suspected and that these differences may explain the lobe-specific carcinogenic actions of the hormones.

Endocytosis in the shiitake mushroom Lentinula edodes and involvement of GTPase LeRAB7.

Endocytosis is the process by which substrates enter a cell without passing through the plasma membrane but rather invaginate the cell membrane and form intracellular vesicles. Rab7 regulates endocytic trafficking between early and late endosomes and between late endosomes and lysosomes. LeRab7 in Lentinula edodes is strongly homologous to Rab7 in Homo sapiens. Receptors for activated C kinase-1 (LeRACK1) and Rab5 GTPase (LeRAB5) were isolated as interacting partners of LeRab7, and the interactions were confirmed by in vivo and in vitro protein interaction assays. The three genes showed differential expression in the various developmental stages of the mushroom. In situ hybridization showed that the three transcripts were localized in regions of active growth, such as the outer region of trama cells, and the subhymenium of the hymenophore of mature fruiting bodies and the prehymenophore of young fruiting bodies. The existence of endocytosis in the mycelium and hymenophores was confirmed by the internalization of FM4-64. LeRAB7 was partially colocalized with the AM4-64 and was located in the late endocytic pathway. This is the first report of the presence of endocytosis in homobasidiomycetes. LeRAB7, LeRAB5, and LeRACK1 may contribute to the growth of L. edodes and cell differentiation in hymenophores.