Calcitriol attenuates liver fibrosis through hepatitis C virus nonstructural protein 3-transactivated protein 1-mediated TGF ß1/Smad3 and NF-κB signaling pathways.

BACKGROUND: Hepatic fibrosis is a serious condition, and the development of hepatic fibrosis can lead to a series of complications. However, the pathogenesis of hepatic fibrosis remains unclear, and effective therapy options are still lacking. Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1 (NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis, but its role in diseases including hepatic fibrosis remains undefined. Therefore, additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment. AIM: To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1. METHODS: Twenty-four male C57BL/6 mice were randomized and separated into three groups, comprising the normal, fibrosis, and calcitriol treatment groups, and liver fibrosis was modeled by carbon tetrachloride (CCl4). To evaluate the level of hepatic fibrosis in every group, serological and pathological examinations of the liver were conducted. TGF-ß1 was administered to boost the in vitro cultivation of LX-2 cells. NS3TP1, α-smooth muscle actin (α-SMA), collagen I, and collagen III in every group were examined using a Western blot and real-time quantitative polymerase chain reaction. The activity of the transforming growth factor beta 1 (TGFß1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected. The statistical analysis of the data was performed using the Student's t test. RESULTS: NS3TP1 promoted the activation, proliferation, and differentiation of hepatic stellate cells (HSCs) and enhanced hepatic fibrosis via the TGFß1/Smad3 and NF-κB signaling pathways, as evidenced by the presence of α-SMA, collagen I, collagen III, p-smad3, and p-p65 in LX-2 cells, which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference. The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression, as shown by the luciferase assay. NS3TP1 inhibited the apoptosis of HSCs. Moreover, both Smad3 and p65 could bind to NS3TP1, and p65 increased the promoter activity of NS3TP1, while NS3TP1 increased the promoter activity of TGFß1 receptor I, as indicated by coimmunoprecipitation and luciferase assay results. Both in vivo and in vitro, treatment with calcitriol dramatically reduced the expression of NS3TP1. Calcitriol therapy-controlled HSCs activation, proliferation, and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice. Furthermore, calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1. CONCLUSION: Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique, prospective therapeutic target in hepatic fibrosis.

Difference and clinical value of metabolites in plasma and feces of patients with alcohol-related liver cirrhosis.

BACKGROUND: Alterations in plasma and intestinal metabolites contribute to the pathogenesis and progression of alcohol-related liver cirrhosis (ALC). AIM: To explore the common and different metabolites in the plasma and feces of patients with ALC and evaluate their clinical implications. METHODS: According to the inclusion and exclusion criteria, 27 patients with ALC and 24 healthy controls (HCs) were selected, and plasma and feces samples were collected. Liver function, blood routine, and other indicators were detected with automatic biochemical and blood routine analyzers. Liquid chromatography-mass spectrometry was used to detect the plasma and feces metabolites of the two groups and the metabolomics of plasma and feces. Also, the correlation between metabolites and clinical features was analyzed. RESULTS: More than 300 common metabolites were identified in the plasma and feces of patients with ALC. Pathway analysis showed that these metabolites are enriched in bile acid and amino acid metabolic pathways. Compared to HCs, patients with ALC had a higher level of glycocholic acid (GCA) and taurocholic acid (TCA) in plasma and a lower level of deoxycholic acid (DCA) in the feces, while L-threonine, L-phenylalanine, and L-tyrosine increased simultaneously in plasma and feces. GCA, TCA, L-methionine, L-phenylalanine, and L-tyrosine in plasma were positively correlated with total bilirubin (TBil), prothrombin time (PT), and maddrey discriminant function score (MDF) and negatively correlated with cholinesterase (CHE) and albumin (ALB). The DCA in feces was negatively correlated with TBil, MDF, and PT and positively correlated with CHE and ALB. Moreover, we established a P/S BA ratio of plasma primary bile acid (GCA and TCA) to fecal secondary bile acid (DCA), which was relevant to TBil, PT, and MDF score. CONCLUSION: The enrichment of GCA, TCA, L-phenylalanine, L-tyrosine, and L-methionine in the plasma of patients with ALC and the reduction of DCA in feces were related to the severity of ALC. These metabolites may be used as indicators to evaluate the progression of alcohol-related liver cirrhosis.

Structural Visualization of Septum Formation in Staphylococcus warneri Using Atomic Force Microscopy.

Cell division of Staphylococcus adopts a "popping" mechanism that mediates extremely rapid separation of the septum. Elucidating the structure of the septum is crucial for understanding this exceptional bacterial cell division mechanism. Here, the septum structure of Staphylococcus warneri was extensively characterized using high-speed time-lapse confocal microscopy, atomic force microscopy, and electron microscopy. The cells of S. warneri divide in a fast popping manner on a millisecond timescale. Our results show that the septum is composed of two separable layers, providing a structural basis for the ultrafast daughter cell separation. The septum is formed progressively toward the center with nonuniform thickness of the septal disk in radial directions. The peptidoglycan on the inner surface of double-layered septa is organized into concentric rings, which are generated along with septum formation. Moreover, this study signifies the importance of new septum formation in initiating new cell cycles. This work unravels the structural basis underlying the popping mechanism that drives S. warneri cell division and reveals a generic structure of the bacterial cell.IMPORTANCE This work shows that the septum of Staphylococcus warneri is composed of two layers and that the peptidoglycan on the inner surface of the double-layered septum is organized into concentric rings. Moreover, new cell cycles of S. warneri can be initiated before the previous cell cycle is complete. This work advances our knowledge about a basic structure of bacterial cell and provides information on the double-layered structure of the septum for bacteria that divide with the "popping" mechanism.

Is CuO Suitable for Improving the Electrochemical Properties of g-C3N4?

G-C3N4 has a bright application prospect as an electrode material of supercapacitors, which makes it a concern. In order to increase the specific capacitance of g-C3N4, we consider to combine it with a metal oxide with high theoretical specific capacitance and utilize the synergistic effect. As a common metal oxide, CuO has the characteristics of high theoretical capacitance, high chemical stability, simple preparation and environmental friendliness. A composite containing CuO nanobelts and graphitic C3N4 (g-C3N4) was successfully synthesized by a chemical precipitation method. Various testing methods were used to explore its composition, microstructure and electrochemical properties to discuss whether CuO is suitable for improving the electrochemical properties of g-C3N4.

Chachezhania antarctica gen. nov., sp. nov., a novel member of the family 'Rhodobacteraceae' isolated from Antarctic seawater.

A Gram-stain-negative, aerobic, non-flagellated, rod-shaped bacterium, designated strain SM1703T, was isolated from Antarctic seawater collected near the Chinese Antarctic Great Wall Station, King George Island, West Antarctica. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain SM1703T formed a distinct phylogenetic lineage within the family 'Rhodobacteraceae', sharing high 16S rRNA gene sequence similarity with Marivita litorea (95.5%). The strain grew at 10-37 °C (optimum, 25 °C) and with 0.5-13% (w/v) NaCl (optimum, 3-5%). The major cellular fatty acids were C19:0 cyclo ω8c, C18:1ω7c, C18:1 2-OH and C16:0 2-OH. The major polar lipids were phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid and an unidentified lipid. The genomic DNA G+C content of strain SM1703T was 64.6 mol%. Based on the results of the polyphasic characterization for strain SM1703T, it is classified as the representative of a novel species in a new genus of the family 'Rhodobacteraceae', for which the name Chachezhania antarctica gen. nov., sp. nov. is proposed. The type strain of Chachezhania antarctica is SM1703T (= MCCC 1K03470T = KCTC 62794T = CCTCC AB 2018351T).

Poseidonibacter antarcticus sp. nov., isolated from Antarctic intertidal sediment.

A Gram-reaction-negative, aerobic, flagellated and coccoid-shaped bacterial strain, designated SM1702T, was isolated from Antarctic intertidal sediment collected off Ardely Island, West Antarctica. The strain grew at 0-30 °C and with 0.5-5.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences and single-copy orthologous clusters both showed that strain SM1702T, together with Poseidonibacter lekithochrous, occupied an independent phylogenetic branch, sharing the highest 16S rRNA gene sequence similarity with type strain of the latter (95.6 %). The major fatty acids were summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c), C16 : 0, and summed feature 2 (C14 : 0 3-OH and/or iso-C16 : 1 I). Polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The genomic DNA G+C content of strain SM1702T was 27.1 mol%. Based on the results of the polyphasic characterisation for strain SM1702T, it is identified as the representative of a novel species of Poseidonibacter, for which the name Poseidonibacter antarcticus sp. nov. is proposed. The type strain of Poseidonibacter antarcticus is SM1702T (=MCCC 1K03471T=KCTC 62796T).

Muricauda nanhaiensis sp. nov., isolated from seawater of the South China Sea.

A Gram-stain-negative, aerobic, oxidase- and catalase-positive, non-flagellated, non-gliding, yellow-pigmented, and rod-shaped bacterium with appendages, designated strain SM1704T, was isolated from surface seawater collected from the South China Sea. The strain grew at 15-42 °C and with 1-10 % NaCl. It hydrolysed aesculin, but did not hydrolyse gelatin and Tween 80 nor reduce nitrate to nitrite. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SM1704T was affiliated with the genus Muricauda, sharing 94.1-95.9 % sequence similarities with type strains of recognized Muricauda species. The major fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH and the main polar lipids were phosphatidylethanolamine, three unidentified lipids and three unidentified aminolipids. The major respiratory quinone was menaquinone-6. The genomic DNA G+C content of strain SM1704T was 40.7 mol%. On the basis of results from polyphasic analysis of strain SM1704T, it is considered to represent a novel species within the genus Muricauda, for which the name Muricaudananhaiensis sp. nov. is proposed. The type strain is SM1704T (=KCTC 62797T=MCCC 1K03557T).

Atomic Force Microscopy of Side Wall and Septa Peptidoglycan From Bacillus subtilis Reveals an Architectural Remodeling During Growth.

Peptidoglycan is the fundamental structural constituent of the bacterial cell wall. Despite many years of research, the architecture of peptidoglycan is still largely elusive. Here, we report the high-resolution architecture of peptidoglycan from the model Gram-positive bacterium Bacillus subtilis. We provide high-resolution evidence of peptidoglycan architecture remodeling at different growth stages. Side wall peptidoglycan from B. subtilis strain AS1.398 changed from an irregular architecture in exponential growth phase to an ordered cable-like architecture in stationary phase. Thickness of side wall peptidoglycan was found to be related with growth stages, with a slight increase after transition to stationary phase. Septal disks were synthesized progressively toward the center, while the surface features were less clear than those imaged with side walls. Compared with previous studies, our results revealed slight differences in architecture of peptidoglycan from different B. subtilis strains, expanding our knowledge about the architectural features of B. subtilis peptidoglycan.

Effects of soybean isoflavones on reproductive parameters in Chinese mini-pig boars.

BACKGROUND: Soybean isoflavones are structurally similar to mammalian estrogens and therefore may act as estrogen agonists or antagonists. However, it has not been determined if they have any negative effects on reproductive parameters in male livestock. Therefore, the objective of this study was to evaluate the effects of soybean isoflavones on male reproduction using Chinese mini-pig boars as a model. Fifty Xiang boars were randomly divided into five groups and fed diets containing 0, 125, 250, or 500 ppm soybean isoflavones or 0.5 ppm diethylstilbestrol for 60 days. RESULTS: Dietary supplementation with 250 ppm of soy isoflavones markedly increased the testis index (P < 0.05), fructose content (P < 0.05), and α-glycosidase content in testicular tissue (P < 0.01), as well as increased the number of viable germ cells (P < 0.01) and the level of Bcl-2 protein (P < 0.01). However, 500 ppm of soybean isoflavones significantly reduced both testis and epididymis indexes (P < 0.05) and lactate dehydrogenase levels (P < 0.01), as well as reduced serum LH and testosterone levels (P < 0.05). High levels of soybean isoflavones also increased malondialdehyde levels (P < 0.05), as well as increased the numbers of early and late apoptotic germ cells (P < 0.01) and the level of Bax proteins (P < 0.05) in the testis. CONCLUSIONS: The results of this study indicate that consumption of soy isoflavones at dietary levels up to 250 ppm did not adversely affect reproductive parameters in Chinese mini-pig boars whereas higher levels of soy isoflavones may adversely affect male reproduction.