S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

Effect of Morus alba extract sanggenon C on growth and proliferation of glioblastoma cells / 中国中药杂志

Glioblastoma is the most common primary cranial malignancy, and chemotherapy remains an important tool for its treatment. Sanggenon C(San C), a class of natural flavonoids extracted from Morus plants, is a potential antitumor herbal monomer. In this study, the effect of San C on the growth and proliferation of glioblastoma cells was examined by methyl thiazolyl tetrazolium(MTT) assay and 5-bromodeoxyuridinc(BrdU) labeling assay. The effect of San C on the tumor cell cycle was examined by flow cytometry, and the effect of San C on clone formation and self-renewal ability of tumor cells was examined by soft agar assay. Western blot and bioinformatics analysis were used to investigate the mechanism of the antitumor activity of San C. In the presence of San C, the MTT assay showed that San C significantly inhibited the growth and proliferation of tumor cells in a dose and time-dependent manner. BrdU labeling assay showed that San C significantly attenuated the DNA replication activity in the nucleus of tumor cells. Flow cytometry confirmed that San C blocked the cell cycle of tumor cells in G_0/G_1 phase. The soft agar clone formation assay revealed that San C significantly attenuated the clone formation and self-renewal ability of tumor cells. The gene set enrichment analysis(GSEA) implied that San C inhibited the tumor cell division cycle by affecting the myelocytomatosis viral oncogene(MYC) signaling pathway. Western blot assay revealed that San C inhibited the expression of cyclin through the regulation of the MYC signaling pathway by lysine demethylase 4B(KDM4B), which ultimately inhibited the growth and proliferation of glioblastoma cells and self-renewal. In conclusion, San C exhibits the potential antitumor activity by targeting the KDM4B-MYC axis to inhibit glioblastoma cell growth, proliferation, and self-renewal.

Rapid in vitro adventitious rooting and proliferation by leaf and nodal cultures of Momordica cymbalaria Fenzl.

An effective approach for rapid in vitro rooting and proliferation of leaf and nodal cultures of Momordicacymbalaria has been developed. To the ability of induction of rhizogenesis, both leaf and nodal explants wereused in culture on Murashige and Skoog (MS) medium. The effects of auxins such as α-naphthaleneaceticacid (NAA), indole-3-butyric acid (IBA), and indole-3-acetic acid (IAA) at different concentrations have beenstudied. The maximum number of roots was produced from nodal explants containing 1.5 mg/L of NAA (9.3 ±0.61), 1.0 mg/L of IBA (6.5 ± 0.41), and 1.0 mg/L of IAA (3.5 ± 0.66), and in leaf explants containing 1.0 mg/Lof NAA (5.7 ± 0.56), 1.0 mg/L of IBA (6.9 ± 0.61), and 1.5 mg/L of IAA (5.0 ± 0.73) on the half-strength MSmedium. For the root induction, NAA is the very effective auxin in node explants of M. cymbalaria. Moreover,a large amount of quercetin bioactive compound is presented in the roots, which is used in anticancer drugs, andwe have described an effective method for the in vitro rhizogenesis of the M. cymbalaria.

Effect of RNA interfering Kvl. 3 channel expression on regulatory T lymphocytes in rats / 中国药理学通报

To investigate the changes in activation and proliferation of Tregs after targeted RNA inter-ference of Kvl. 3 channel genes and in vitro administration of eplerenone (EPL). Methods After lenti-virus vector was transfected to regulatory T cells (Tregs) of rats, qPCR and whole-cell patch-clamp methods were used to detect gene knockout efficiency, and EOSA method was used to detect cytokine secretion IL-10 and TGF-p levels of Tregs group,Tregs + EPL group,RNAi-Tregs group,and RNAi-Tregs + EPL group. Results Lentivirus vector was successfully transfected into Tregs cells, and the mRNA level and current density of Kvl. 3 channel was 78% and 71.3% respectively; compared with Tregs group, extracellular and intracellular TGF-p levels in RNAi-Tregs group were significantly reduced (P < 0. 01), and extracellular and intracellular TGF-(3 levels in Tregs + EPL group were also reduced (P < 0. 05 ) ; compared with RNAi-Tregs group, extracellular and in-tracellular TGF-fJ levels in RNAi-Tregs + EPL group showed no change. However, IL-10 levels in Tregs group,Tregs + EPL group, RNAi-Tregs group, RNAi-Tregs + EPL group showed no significant change. Conclusions Kvl.3 channel mediates the activation and proliferation of Tregs cells, while EPL can reduce the activation and proliferation of Tregs cells by directly inhibiting Kvl.3 channel and reducing the secretion of TGF-fi levels, further indicating that EPL is a specific blocker of Kvl. 3 channel.

Synergistic Effect of Cold Plasma Treatment and RGD Peptide Coating on Cell Proliferation over Titanium Surfaces

The aim of this study was to investigate the synergistic effect of cold atmospheric plasma (CAP) treatment and RGD peptide coating for enhancing cellular attachment and proliferation over titanium (Ti) surfaces. The surface structure of CAP-treated and RGD peptide-coated Ti discs were characterized by contact angle goniometer and atomic force microscopy. The effect of such surface modification on human bone marrow derived mesenchymal stem cells (hMSCs) adhesion and proliferation was assessed by cell proliferation and DNA content assays. Besides, hMSCs' adhesion and morphology on surface modified Ti discs were observed via fluorescent and scanning electron microscopy. RGD peptide coating following CAP treatment significantly enhanced cellular adhesion and proliferation among untreated, CAP-treated and RGD peptide-coated Ti discs. The treatment of Ti surfaces with CAP may contribute to improved RGD peptide coating, which enables increased cellular integrations with the Ti surfaces.

Effect of ASIC1 a on hepatic fibrosis under high glucose / 中国药理学通报

Aim To investigate the effect of ASIC1 a ( acid-sensing ion channel 1 a ) on the pathological change of diabetes complication liver fibrosis and the proliferation and activation of hepatic stellate cell ( HSC-T6 ) stimulated by PDGF-BB under hyperglyce-mia. Methods Diabetes rats model was established by streptozotocin ( STZ) , and liver fibrosis rats model was induced by carbon tetrachloride ( CCl4 ) . Then, the liver extent of damage and the expression of ASIC1 a were observed in the diabetic rats, liver fibrosis rats and diabetes complication liver fibrosis rats. In vitro, after pretreated with amiloride, HSC-T6 was treated with high glucose for 24 h and then stimulated with PDGF-BB for another 24 h. The proliferation and acti-vation of HSC-T6 were observed, and the expression of ASIC1a, α-SMA and collagen Ⅰ were detected by Western blot. Results Compared with the control group, rats from diabetic group induced by STZ, liver fibrosis group induced by CCl4 , and the diabetes com-plication liver fibrosis rats co-induced by STZ and CCl4 were all observed with liver damage at different levels, and tissue injury of complication group was most seri-ous. However, the expression of ASIC1a in the three model groups was significantly increased compared to the control group. ASIC1a level was most obvious in the diabetes complication liver fibrosis rats. Amiloride pretreatment significantly decreased ASIC1 a expression and inhibited PDGF-BB mediated proliferation and the expression ofα-SMA and collagenⅠin HSC-T6 under high glucose environment. Conclusion High ambient glucose aggravates HSC activation and hepatic fibrosis, and this may be related with the increasing expression of ASIC1a.

Regulatory effects of TRPV4 on liver fibrosis of rats / 中国药理学通报

Aim To investigate the effect of TRPV4 on hepatic fibrosis of rats . Methods Liver fibrosis model of rats was induced by 50% CCl4 twice a week for 12 weeks. HE and Masson staining were used to evaluate the degree of hepatic fibrosis, and the levels of α-smooth muscle actin(α-SMA) and TRPV4 were detec-ted in fibrotic liver tissue by Western blot. HSC-T6 cells were activated by transforming growth factor β1 (TGF-β1),and the protein levels of α-SMA, TRPV4 were detected by Western blot. After using Ru and transfected with TRPV4-siRNA, HSC-T6 was stimula-ted with TGF-β1, the levels of α-SMA, TRPV4 and phosphorylation level of Akt were determined by West-ern blot. Results TRPV4 was highly expressed in model liver tissues and in activated HSC-T6 induced by TGF-β1 . The levels of α-SMA and phosphorylation of Akt decreased in TGF-β1-induced HSC, used with Ru or transfected with TRPV4-siRNA. Conclusions The expression of TRPV4 increases in fibrotic livers and ac-tivated hepatic stellate cells. Knockdown of TRPV4 can suppress the activation of hepatic stellate cells in-duced by TGF-β1 , and decrease the phosphorylation levels of Akt.

Common clinical types and management of secondary glaucoma after ocular trauma / 国际眼科杂志(Guoji Yanke Zazhi)

?Ocular trauma related glaucoma is one of secondary glaucoma, which can lead to serious visual loss. According to the complex clinical findings and pathogenesis of ocular trauma related glaucoma, we divide traumatic secondary glaucoma into hyphema related glaucoma, angle recession related, lens injury related, adhesion and proliferation related. The treatment of secondary traumatic glaucoma with ocular trauma were different, specific treatment measures should be given according to the specific case to protect visual function.

In vitro Enhancement of Pancreatic  Cells MIN6 Proliferation by Insulinotropic Gymnema sylvestre Aqueous Extracts: Evidence-based Regenerative Therapeutic Capacity of a Medicinal Herb.

Aim: To show that Gymnema sylvestre (Roxb.) Asclepiadaceae not only has antidiabetic propensities, but it most likely works by regeneration of pancreatic  cells which is imperative in anti-obesity-diabetes therapeutic applications of medicinal plants. Study Design: The present study design investigated the effects of G. sylvestre leaves crude aqueous extracts (AEs), traditionally utilized in diabetes treatment, on the pancreatic β-cell MIN6 proliferation and insulin secretion and extrapancreatic dietary carbohydrate and lipid digestion Place and Duration of Study: Faculty of Pharmacy, The University of Jordan, 2008-2012. Results: Comparable to GLP-1 (500 nM) pancreatic proliferative capacity; G. sylvestre AE concentrations (0.01 and 0.1 mg/mL) induced MIN6 monolayers expansion by respective 130.3% and 127.4% (P<0.001 vs. spontaneous control). Like L-alanine (10 mM) insulinotropic efficacy and without exerting cytotoxicity, glucose-stimulated insulin secretion was potentiated by G. sylvestre AEs (5, 10 and 25 mg/mL) (711.0%, 843.0% and 906.5%, respectively, P<0.001 vs. basal control). The potent plants’ insulin secretory bioactivities were abolished in the depleted Ca2+ conditions (P<0.001). Similar to orlistat antilipolytic efficacy, pancreatic lipase IC50 value for G. sylvestre AEs was 106.3±7.2 μg/mL. Unlike acarbose (100 μg/mL) dual inhibition of α-amylase/α-glucosidase, G. sylvestre AE was inactive at used doses. Dissimilar to guar gum (50 mg/mL) diffusional hindrance in a simple dialysis model, G. sylvestre AEs (10, 25 and 50 mg/mL) proved inactive. This in vitro ineffectiveness was mirrored in respective in vivo oral carbohydrate tolerance tests in overnight fasting normoglycemic rats. Conclusion: This evaluation has revealed that G. sylvestre leaves AEs augmented β-cell expansion and potentiated glucose-evoked Ca2+-regulated insulin secretion; combined with impressive antilipolytic activity. These actions depend on the bioactive water soluble phytoprinciples intact absorption in vivo. Future directives may assess the potential of G. sylvestre as a new alternative for anti-obesity-diabetes pharmacotherapy and prevention.

The mechanism of miR-26a inhibiting gastric cancer cells proliferation / 中国现代医生

Objective To explicit the expression and role of miR-26a in gastric cancer tissues, thus to reveal molecular mechanism that miR-26a functions in gastric cancer cells. Methods The qRT-PCR was conducted for detect the ex-pression of miR-26a in 71 cases of gastric cancers. AGS cells were transfected with miR-26a mimics, then Western blot was performed to detect the expressions of MTDH protein. The proliferation ability of AGS cells evaluated by MTT assy. Results qRF-PCR showed that miR-26a was down-regulated 0.44 times in 71 cases of gastric cancer tissues. Western blot showed that the expressions of MTDH protein was inhibited by restored miR-26a or MTDH siRNA in AGS cells. Overexpression of miR-26a or MTDH siRNA inhibited the proliferation of AGS cells. Their OD values of transfected miR-26a mimics and MTDH siRNA were (0.158±0.006),(0.201±0.006) respectively, and their OD values of transfected control were (0.515±0.032),(0.479±0.028) respectively,there were statistically significance(P<0.05). Con-clusion miR-26a suppresses cell proliferation by targeting MTDH in gastric cancer.

Effect of HI_(47) (CD_(20)) monoclonal antibody on human B Iymphocyte activation and proliferation / 中国免疫学杂志

We have previously reported that a CD_(20) monoclonal antibody (HI_(47)) had obvious inhibition to ~3H-TdR incorporation of tonsil B cells in SAC drived system. This paper describes that McAb HI_(47) also markedly inhibited ~3H-UdR uptake and enlargement of B lymphocytes induced by SAC. However, it had no effect on B cell activation in PMA and anti-immunoglobul in antibody drived systems and the proliferation of established T, B and myeloid cell lines. The non-specific inhibition of HI_(47) Fc fragment had been ruled out by the experiments with irrelative MoAbs, which Ig subclass was same as HI_(47) (IgG_3),and with HI_(47) F (ab')2 fragment. Exposure of tonsil B cell to either SAC or PMA resulted in an increase in expression of HI_(47) antigen. McAb HI_(47), neverthless, induced reduction of HI_(47) antigen expressed on B cells stimulated by SAC. but not by PMA. In conclusion, antigen HI_(47) (CD_(20)) only involved in the SAC-activation pathway. The modulation of HI47 antigen by McAb HI47 may be one of the mechanisms of the depressed SAC activation.