Sphingobacterium tenebrionis sp. nov., isolated from intestine of mealworm.

A bacterial strain designated PU5-4T was isolated from the mealworm (the larvae of Tenebrio molitor) intestines. It was identified to be Gram-stain-negative, strictly aerobic, rod-shaped, non-motile, and non-spore-forming. Strain PU5-4T was observed to grow at 10-40 °C, at pH 7.0-10.0, and in the presence of 0-3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain PU5-4T should be assigned to the genus Sphingobacterium. The 16S rRNA gene sequence similarity analysis showed that strain PU5-4T was closely related to the type strains of Sphingobacterium lactis DSM 22361T (98.49 %), Sphingobacterium endophyticum NYYP31T (98.11 %), Sphingobacterium soli NCCP 698T (97.69 %) and Sphingobacterium olei HAL-9T (95.73 %). The predominant isoprenoid quinone is MK-7. The major fatty acids were identified as iso-C15 : 0, iso-C17 : 03-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 9 (iso-C17 : 0 ω9c). The polar lipids are phosphatidylethanolamine, one unidentified phospholipid, and six unidentified lipids. The genomic DNA G+C content of strain PU5-4T is 40.24 mol%. The average nucleotide identity of strain PU5-4T exhibited respective values of 73.88, 73.37, 73.36 and 70.84 % comparing to the type strains of S. lactis DSM 22361T, S. soli NCCP 698T, S. endophyticum NYYP31T and S. olei HAL-9T, which are below the cut-off level (95-96 %) for species delineation. Based on the above results, strain PU5-4T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium temoinsis sp. nov. is proposed. The type strain is PU5-4T (=CGMCC 1.61908T=JCM 36663T).

Efficient conversion of aromatic and phenylpropanoid alcohols to acids by the cascade biocatalysis of alcohol and aldehyde dehydrogenases.

Benzyl and phenylpropanoid acids are widely used in organic synthesis of fine chemicals, such as pharmaceuticals and condiments. However, biocatalysis of these acids has received less attention than chemical synthesis. One of the main challenges for biological production is the limited availability of alcohol dehydrogenases and aldehyde dehydrogenases. Environmental microorganisms are potential sources of these enzymes. In this study, 129 alcohol dehydrogenases and 42 aldehyde dehydrogenases from Corynebacterium glutamicum, Pseudomonas aeruginosa, and Bacillus subtilis were identified and explored with various benzyl and phenylpropanoid alcohol and aldehyde substrates, among which four alcohol dehydrogenases and four aldehyde dehydrogenases with broad substrate specificity and high catalytic activity were obtained. Moreover, a cascade whole-cell catalytic system including ADH-90, ALDH-40, and the NAD(P)H oxidase LreNox was established, which showed high efficiency in converting cinnamyl alcohol and p-methylbenzyl alcohol into the respective carboxylic acids. Remarkably, this biocatalytic system can be easily scaled up to gram-level production, facilitating preparation purposes.

PPARγ Mediates the Anti-Epithelial-Mesenchymal Transition Effects of FGF1ΔHBS in Chronic Kidney Diseases via Inhibition of TGF-ß1/SMAD3 Signaling.

Podocytes are essential components of the glomerular basement membrane. Epithelial-mesenchymal-transition (EMT) in podocytes results in proteinuria. Fibroblast growth factor 1 (FGF1) protects renal function against diabetic nephropathy (DN). In the present study, we showed that treatment with an FGF1 variant with decreased mitogenic potency (FGF1ΔHBS) inhibited podocyte EMT, depletion, renal fibrosis, and preserved renal function in two nephropathy models. Mechanistic studies revealed that the inhibitory effects of FGF1ΔHBS podocyte EMT were mediated by decreased expression of transforming growth factor ß1 via upregulation of PPARγ. FGF1ΔHBS enhanced the interaction between PPARγ and SMAD3 and suppressed SMAD3 nuclei translocation. We found that the anti-EMT activities of FGF1ΔHBS were independent of glucose-lowering effects. These findings expand the potential uses of FGF1ΔHBS in the treatment of diseases associated with EMT.

FGF1ΔHBS prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression.

As a classically known mitogen, fibroblast growth factor 1 (FGF1) has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection. Here, we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy (DCM) patients, indicating that FGF1 is a potential therapeutic target for DCM. We found that treatment with a FGF1 variant (FGF1∆HBS) with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function. RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1∆HBS treatment. Both in vivo and in vitro studies indicate that FGF1∆HBS exerted these beneficial effects by markedly reducing mitochondrial fragmentation, reactive oxygen species (ROS) generation and cytochrome c leakage and enhancing mitochondrial respiration rate and ß-oxidation in a 5' AMP-activated protein kinase (AMPK)/Nur77-dependent manner, all of which were not observed in the AMPK null mice. The favorable metabolic activity and reduced proliferative properties of FGF1∆HBS testify to its promising potential for use in the treatment of DCM and other metabolic disorders.

Piperine Inhibits Cell Proliferation and Induces Apoptosis of Human Gastric Cancer Cells by Downregulating Phosphatidylinositol 3-Kinase (PI3K)/Akt Pathway.

BACKGROUND Piperine has been reported to inhibit proliferation and induce apoptosis in various cancer cells. This study aimed to explore the efficacy and underlying mechanism of piperine in human gastric cancer. MATERIAL AND METHODS MTT assay was performed to examine the effect of piperine (concentrations of 0-300 µM) on the proliferation of human gastric cancer SNU-16 cells and normal human gastric epithelial GES-1 cells. Flow cytometry and Western blot were used to determine cell apoptosis and the expression level of protein (Cyto C, cleaved PARP, cleaved caspase-3, Bax, Bcl-2, Bad, Bcl-xl, PI3K, pPI3K, Akt, and pAkt), respectively. To further investigate the anti-tumor mechanism of piperine in SNU-16 cells, we used a small-molecule Akt activator SC79 in this study. The in vivo mechanism of piperine against gastric cancer was evaluated using a xenograft tumor model. RESULTS The results showed that piperine inhibited proliferation and induced apoptosis of SNU-16 cells. Piperine upregulated the protein expression of Bax, Bad, Cyto C, cleaved PARP, and cleaved caspase-3, but downregulated the protein expression of Bcl-2, Bcl-xl, pPI3k, and pAkt. However, SC79 reversed the function of piperine on the apoptosis-related proteins. An in vivo study revealed that, compared with the control group, the tumor volume of mice treated with piperine was significantly reduced. Piperine enhanced cleaved caspase-3 expression but decreased Ki-67 expression in a dose-dependent manner. Moreover, the nontoxicity effect of piperine was confirmed by H&E staining analysis in kidney and heart tissues of mice. CONCLUSIONS Our findings suggest that piperine inhibits proliferation and induces apoptosis of human gastric cancer cells through inhibition of the PI3K/Akt signaling pathway.

FGF1ΔHBS ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation.

Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1ΔHBS, which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1ΔHBS exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1WT) in renal tissues. RNA-seq analysis revealed that FGF1ΔHBS inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1ΔHBS prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1ΔHBS on oxidative stress and inflammation were mediated by activation of the GSK-3ß/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1ΔHBS. This finding expands the potential uses of FGF1ΔHBS for the treatment of various kinds of CKD associated with oxidative stress and inflammation.