Mesenchymal Stem Cells Attenuates TGF-ß1-Induced EMT by Increasing HGF Expression in HK-2 Cells.

BACKGROUND: Mesenchymal stem cells (MSCs) have recently shown promise for the treatment of various types of chronic kidney disease models. However, the mechanism of this effect is still not well understood. Our study is aimed to investigate the effect of MSCs on transforming growth factor beta 1 (TGF-ß1)-induced epithelial mesenchymal transition (EMT) in renal tubular epithelial cells (HK-2 cells) and the underlying mechanism related to the reciprocal balance between hepatocyte growth factor (HGF) and TGF-ß1. METHODS: Our study was performed at Ningbo University, Ningbo, Zhejiang, China between Mar 2017 and Jun 2018. HK-2 cells were initially treated with TGF-ß1, then co-cultured with MSCs. The induced EMT was assessed by cellular morphology and the expressions of alpha-smooth muscle actin (α-SMA) and EMT-related proteins. MTS assay and flow cytometry were employed to detect the effect of TGF-ß1 and MSCs on HK-2 cell proliferation and apoptosis. SiRNA against hepatocyte growth factor (siHGF) was transfected to decrease the expression of HGF to identify the role of HGF in MSCs inhibiting HK-2 cells EMT. RESULTS: Overexpressing TGF-ß1 decreased HGF expression, induced EMT, suppressed proliferation and promoted apoptosis in HK-2 cells; but when co-cultured with MSCs all the outcomes were reversed. However, after treated with siHGF, all the benefits taken from MSCs vanished. CONCLUSION: TGF-ß1 was a motivating factor of kidney cell EMT and it suppressed the HGF expression. However, MSCs provided protection against EMT by increasing HGF level and decreasing TGF-ß1 level. Our results also demonstrated HGF is one of the critical factor in MSCs anti- fibrosis.

Dynamically Cross-Linked Polymeric Binder-Made Durable Silicon Anode of a Wide Operating Temperature Li-Ion Battery.

The colossal volumetric expansion (up to 300%) of the silicon (Si) anode during repeated charge-discharge cycles destabilizes the electrode structure and causes a drastic drop in capacity. Here in this work, commercial poly(acrylic acid) (PAA) is cross-linked by hydroxypropyl polyrotaxane (HPR) via reversible boronic ester bonds to achieve a water-soluble polymeric binder (PAA-B-HPR) for making the Si anode of the Li-ion battery. Slidable α-cyclodextrins of modified polyrotaxane are allowed to move around when the unwanted volume variation occurs in the course of lithiation and delithiation so that the accumulated internal stress can be equalized throughout the system, while the reversible boronic ester bonds are capable of healing the damages created during manufacturing and service to maintain the electrode integrity. As a result, the Li-ion battery assembled with the Si anode comprised of the PAA-B-HPR binder possesses outstanding specific capacity and cycle stability within a wide temperature range from 25 to 55 °C. Especially, the Si@PAA-B-HPR anode exhibits a discharge specific capacity of 1056 mA h/g at 1.4 A/g after 500 cycles under a higher temperature of 55 °C, and the corresponding capacity fading rate per cycle is only 0.10%. The present work opens an avenue toward the practical application of the Si anode for Li-ion batteries.

Implementation of the Pulley Effect of Polyrotaxane in Transparent Bulk Polymer for Simultaneous Strengthening and Toughening.

The fascinating pulley effect from moveable α-cyclodextrin (α-CD) based polyrotaxane favors toughening of hydrogels, but the strategy is rarely applied in bulk polymers because of the severe aggregation trend of α-CDs. Herein, the authors propose a simple approach to moderately modify the α-CDs of polyrotaxane by introducing large steric side groups and reactive CC so as to minimize the unwanted hydrogen bonds-induced aggregation of α-CDs and hydrophilicity of polyrotaxane. Accordingly, the proof-of-concept material, poly(methyl acrylate) crosslinked by the modified polyrotaxane, turns out to be rather homogeneous with optical transparency. The polyrotaxane crosslinks are movable under external force as disclosed by in situ small-angle X-ray scattering and other techniques, which is correlated to the relative amount of α-CDs. A few polyrotaxane crosslinkers prove to be sufficient to simultaneously improve strength and toughness of poly(methyl acrylate) owing to the stress equalization. The present work provides an expandable toolbox for enhancing polymers.

Correlation between SHBG gene polymorphism and male infertility in Han population of Henan province of China: A STROBE-compliant article.

Human sex hormone binding globulin (SHBG) level alteration and SHBG gene mutations, especially in rs6259 and rs727428 loci, are associated with male infertility. In this study, the rs6259 and rs727428 loci in SHBG gene were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to explore the direct relation between these 2 loci and male infertility in Han population of Henan province and to provide information for the pathogenesis, diagnosis, and treatment of male infertility.A total of 366 male Han individuals in Henan province were enrolled in this study. Of the 366 male individuals, 183 infertility patients were served as infertility group and other 183 normal individuals as a control group. SHBG gene rs6259 and rs727428 locus polymorphisms were detected by PCR-RFLP in all patients. Also, genotype frequencies, allele frequency, and haplotype were all analyzed in both groups.There were statistical differences in A allele frequency (P = .017) and GA genotype frequency (P = .016) of SHBG gene rs6259 locus and in CC genotype frequency of SHBG gene rs727428 locus (P = .034) between the 2 groups.Male infertility is associated with GA genotype and A allele of rs6259 locus, as well as CC genotype of rs727428 locus in SHBG gene.

Cantharidin induces G2/M arrest and triggers apoptosis in renal cell carcinoma.

The present study aimed to investigate the effects of cantharidin on cell cycle distribution, the induction of apoptosis, and Notch1 and Jagged1 expression in ACHN and Caki­1 renal cancer cells. Cell viability assay, flow cytometry, cell cycle and western blot analyses were performed for ACHN and Caki­1 cells. Immunohistochemistry was used to analyze the expression of Notch1 and Jagged1 in RCC tissues The results demonstrated that treatment with cantharidin exerted a dose­ and time­dependent effect on cell viability, apoptosis induction and G2/M phase cell cycle arrest. Exposure of ACHN and Caki­1 cells to 20 µM cantharidin reduced cell viability to 26 and 32% respectively, after 48 h. In addition, treatment with cantharidin enhanced the number of ACHN and Caki­1 cells in G2/M phase to 54.62 and 51.88% respectively, as compared with 17.16 and 16.53% in the control groups. In the ACHN and Caki­1 cells, treatment with cantharidin induced a marked increase in the proportion of apoptotic cells after 48 h. Furthermore, cantharidin enhanced the percentage ACHN and Caki­1 apoptotic cells to 57.23 and 62.34% respectively, as compared with 2.27 and 3.06% in the control groups. Detection of Notch1 and Jagged1 expression demonstrated that levels were significantly increased in carcinoma tissues. Conversely, cantharidin exhibited an inhibitory effect on Notch1 and Jagged1 expression after 48 h. Therefore, treatment with cantharidin may exert a promising effect on the inhibition of renal cancer, and may be of therapeutic importance for the treatment of renal cancer.

The effect of survivin on multidrug resistance mediated by P-glycoprotein in MCF-7 and its adriamycin resistant cells.

Although anticancer chemotherapeutic drugs have been designed to inhibit the growth of tumor cells, chemotherapy frequently fails due to the development of multidrug resistance (MDR). In this paper, the effect of survivin on multidrug resistance mediated by P-glycoprotein (Pgp) was investigated in breast cancer cells. Overexpression of survivin in MCF-7 cells transfected with survivin expression vector pEGFP/survivin results in decreasing sensitivity to anticancer drugs and activation of Pgp to export drug out of cells. Down regulation of survivin in MCF-7/adriamycin (ADR) transfected with RNAi directed against survivin vector psh1/survivin could increase the drug accumulation in cells by inhibiting Pgp. Downregulation of the expression of the Pgp with the specific inhibitor verapamil could markedly suppress the survivin mRNA expression, whereas the reverse impact was not observed. Survivin might modulate the turnover of Pgp or transport by Pgp in cells, which result in anti-apoptosis and drug resistance. Our results suggest that survivin might play a key role in MDR in the presence of Pgp, and this might represent a novel strategy for modulating MDR in cancer cells.

Cloning of a rat lung fibrogenic factor.

In a previous study a specific single polypeptide has been purified and characterized that it was capable of promoting human embryonic lung 2BS fibroblasts proliferation in vitro, whose N-terminal 15 amino acid have high sequence homology with members of the mammalian chitinase-like protein family. Here the cloning of the gene is reported. Its cDNA contains an open reading frame 1421 bp long and encodes a protein with a characteristic N-terminal 21 amino acid endoplasmic reticulum signal peptide and the putative protein is highly homologous to acidic mammalian chitinase (AMCase) precursor of mouse and human. Recombinant proteins demonstrate chitinolytic activity, therefore the gene is termed as rat AMCase. Sequence analysis indicates that the gene spanned a 46.2 kb region in rat chromosome 2. Its expression in several tissues other than alveolar macrophages suggests that it might play multiple biological roles in vivo. Our findings will facilitate studies on its roles in physiological and pathological processes.