Fecal bacteria were studied in healthy elderly volunteers (age, 63 to 90 years; n ‫؍‬ 35) living in the local community, elderly hospitalized patients (age, 66 to 103; n ‫؍‬ 38), and elderly hospitalized patients receiving antibiotic treatment (age, 65 to 100; n ‫؍‬ 21). Group-and species-specific primer sets targeting 16S rRNA genes were used to quantitate intestinal bacteria by using DNA extracted from feces and real-time PCR. The principal difference between healthy elderly volunteers and both patient cohorts was a marked reduction in the Bacteroides-Prevotella group following hospitalization. Reductions in bifidobacteria, Desulfovibrio spp., Clostridium clostridiiforme, and Faecalibacterium prausnitzii were also found in the hospitalized patients. However, total 16S rRNA gene copy numbers (per gram of wet weight of feces) were generally lower in the stool samples of the two groups of hospitalized patients compared to the number in the stool samples of elderly volunteers living in the community, so the relative abundance (percentage of the group-and species-specific rRNA gene copies in relation to total bacterial rRNA gene copies) of bifidobacteria, Desulfovibrio spp., C. clostridiiforme, and F. prausnitzii did not change. Antibiotic treatment resulted in further reductions in the numbers of bacteria and their prevalence and, in some patients, complete elimination of certain bacterial communities. Conversely, the numbers of enterobacteria increased in the hospitalized patients who did not receive antibiotics, and due to profound changes in fecal microbiotas during antibiotic treatment, the opportunistic species Enterococcus faecalis proliferated.

Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic β-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N = 15) or diabetic (BMI- and age-matched; N = 14); b) lean or obese (N = 53 totally) and c) fasting and 2 hours following a defined meal (N = 12). Serum lipasin levels were determined by the enzyme-linked immunosorbent assay. Lipasin levels [mean ± SEM] were increased by more than two fold (P < 0.001) in the diabetic patients (5.56 ± 0.73 ng/mL) as compared to the control subjects (2.19 ± 0.24 ng/mL). Serum lipasin levels were positively correlated with BMI (rho = 0.49, P < 0.001), and showed a 35% increase 2 hours following a defined meal (P = 0.009). Therefore, lipasin/betatrophin is nutritionally-regulated hepatokine that is increased in human type 2 diabetes and obesity.

No abstract

We previously showed that genistein, the major bioactive component of soy isoflavones, acts as a radiosensitizer and potentiates prostate tumor cell killing by radiation in vitro and in animal tumor models in vivo. However, when given alone in vivo, pure genistein promoted increased lymph node metastasis, which was not observed with a soy isoflavone mixture consisting of genistein, daidzein, and glycitein. In this study, we show that soy inhibits tumor cell growth and potentiates radiation-induced cell killing in vitro like pure genistein. In an orthotopic model, combining soy isoflavones with tumor irradiation inhibited prostate tumor growth. To determine the molecular mechanisms by which soy isoflavones potentiate radiotherapy, we investigated apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) and nuclear factor KB (NF-KB), two signaling molecules involved in survival pathways. Soy isoflavones decreased APE1/Ref-1 expression in vitro, whereas radiation up-regulated it. Pretreatment with soy isoflavones followed by radiation inhibited APE1/Ref-1 expression. APE1/Ref-1 decrease correlated with decreased DNA-binding activity of NF-KB mediated by soy isoflavones and radiation, thus promoting cell killing. In vivo treatment of prostate tumors with soy isoflavones and radiation downregulated APE1/Ref-1 protein expression and NF-KB activity, confirming the molecular alterations observed in vitro. The down-regulation of APE1/Ref-1 and NF-KB by isoflavones, in vitro and in vivo, supports our hypothesis that these markers represent biological targets of isoflavones. Indeed, a 2-fold increase in APE1/Ref-1 expression, obtained by cDNA transfection, resulted in a 2-fold increase in NF-KB DNA-binding activity, and both of which were downregulated by soy isoflavones, confirming the cross-talk between these molecules and, in turn, causing radiosensitization. [Cancer Res 2007;67(5):2141-9]