Dietary Fermented Soy Extract and Oligo-Lactic Acid Alleviate Chronic Kidney Disease in Mice via Inhibition of Inflammation and Modulation of Gut Microbiota.

Chronic kidney disease (CKD) is a global epidemic with an increasing prevalence worldwide. Effective preventive strategies are urgently needed. This study aimed to investigate the effect of nutraceutical components, a fermented soybean product (ImmuBalance, IMB) and an oligo-lactic acid product (LAP), on the prevention of adenine-induced CKD in mice. Female C57BL/6 mice were randomly assigned into following experimental groups: negative control; model control; and models treated with IMB at 250 or 1000 mg/kg body weight (BW), LAP at 1000 or 2000 mg/kg BW, and IMB/LAP combinations. The CKD model was established by intraperitoneal injection of adenine daily for 4 weeks, and treatments started 2 weeks before adenine injection and ended after 10 weeks. Compared with the model control, the treatments did not significantly alter the body weight or food intake. Both IMB and LAP, especially their combination, significantly inhibited tubular dilation, tubulointerstitial degeneration or atrophy, interstitial chronic inflammation and acute inflammation in the kidneys of CKD mice, and significantly decreased serum cystatin C levels. IMB or LAP significantly reversed CKD-associated increases of circulating and kidney levels of inflammatory cytokines, circulating levels of kidney injury biomarkers, and kidney levels of stem cell biomarkers, and significantly reversed CKD-associated reduction of cecum Clostridium leptum group. Our results suggest that dietary supplementation of IMB or LAP may significantly delay the development and/or progression of CKD.

Decreased Brain Levels of Vitamin B12 in Aging, Autism and Schizophrenia.

Many studies indicate a crucial role for the vitamin B12 and folate-dependent enzyme methionine synthase (MS) in brain development and function, but vitamin B12 status in the brain across the lifespan has not been previously investigated. Vitamin B12 (cobalamin, Cbl) exists in multiple forms, including methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl), serving as cofactors for MS and methylmalonylCoA mutase, respectively. We measured levels of five Cbl species in postmortem human frontal cortex of 43 control subjects, from 19 weeks of fetal development through 80 years of age, and 12 autistic and 9 schizophrenic subjects. Total Cbl was significantly lower in older control subjects (> 60 yrs of age), primarily reflecting a >10-fold age-dependent decline in the level of MeCbl. Levels of inactive cyanocobalamin (CNCbl) were remarkably higher in fetal brain samples. In both autistic and schizophrenic subjects MeCbl and AdoCbl levels were more than 3-fold lower than age-matched controls. In autistic subjects lower MeCbl was associated with decreased MS activity and elevated levels of its substrate homocysteine (HCY). Low levels of the antioxidant glutathione (GSH) have been linked to both autism and schizophrenia, and both total Cbl and MeCbl levels were decreased in glutamate-cysteine ligase modulatory subunit knockout (GCLM-KO) mice, which exhibit low GSH levels. Thus our findings reveal a previously unrecognized decrease in brain vitamin B12 status across the lifespan that may reflect an adaptation to increasing antioxidant demand, while accelerated deficits due to GSH deficiency may contribute to neurodevelopmental and neuropsychiatric disorders.

Bioactive tanshinone I inhibits the growth of lung cancer in part via downregulation of Aurora A function.

Lung cancer is the leading cause of cancer death in the world, and the searching for novel efficacious and safe agents for lung cancer prevention remains the top priority of lung cancer research. In the present study, we evaluated the effect of bioactive tanshinones from a Chinese herb Salvia miltiorrhiza, cryptotanshinone (CT), tanshinone I (T1) and tanshinone IIA (T2A), on the proliferation inhibition of lung cancer cell lines. Tanshinones inhibited the lung cancer cell proliferation in vitro, with T1 the most potent, via cell cycle arrest and apoptosis induction. Gene function assay showed that Aurora A knockdown by siRNA dramatically eliminated the T1 activity in vitro, suggesting that Aurora A is an important functional target for T1. We further evaluated the effectiveness of T1 on the growth of H1299 nonsmall lung cancer cell in a mouse model. Tanshinone I inhibited the growth of H1299 lung tumor in a dose-dependent manner. Tanshinone I at 200 mg/kg body weight significantly reduced final tumor weight by 34% (P < 0.05) associated with inhibiting proliferation and inducing apoptosis of lung cancer cells by 54% (P < 0.001) and 193% (P < 0.001), respectively, inhibiting lung tumor angiogenesis by 72% (P < 0.001), and reducing Aurora A expression by 67% (P < 0.001). On the other hand, T1 did not significantly alter food intake or body weight. Our results provided experimental evidence to suggest that T1 may be an efficacious and safe agent for the prevention of lung cancer progression and Aurora A may be an important molecular target for T1 action against lung cancer.