Inhibition of gap junctional Intercellular communication in WB-F344 rat liver epithelial cells by triphenyltin chloride through MAPK and PI3-kinase pathways

<p>Abstract</p> <p>Background</p> <p>Organotin compounds (OTCs) have been widely used as stabilizers in the production of plastic, agricultural pesticides, antifoulant plaints and wood preservation. The toxicity of triphenyltin (TPT) compounds was known for their embryotoxic, neurotoxic, genotoxic and immunotoxic effects in mammals. The carcinogenicity of TPT was not well understood and few studies had discussed the effects of OTCs on gap junctional intercellular communication (GJIC) of cells.</p> <p>Method</p> <p>In the present study, the effects of triphenyltin chloride (TPTC) on GJIC in WB-F344 rat liver epithelial cells were evaluated, using the scrape-loading dye transfer technique.</p> <p>Results</p> <p>TPTC inhibited GJIC after a 30-min exposure in a concentration- and time-dependent manner. Pre-incubation of cells with the protein kinase C (PKC) inhibitor did not modify the response, but the specific MEK 1 inhibitor PD98059 and PI3K inhibitor LY294002 decreased substantially the inhibition of GJIC by TPTC. After WB-F344 cells were exposed to TPTC, phosphorylation of Cx43 increased as seen in Western blot analysis.</p> <p>Conclusions</p> <p>These results show that TPTC inhibits GJIC in WB-F344 rat liver epithelial cells by altering the Cx43 protein expression through both MAPK and PI3-kinase pathways.</p

Indigenous Case of Disseminated Histoplasmosis, Taiwan

We report the first indigenous case of disseminated histoplasmosis in Taiwan diagnosed by histopathology of bone marrow, microbiologic morphology, and PCR assay of the isolated fungus. This case suggests that histoplasmosis should be 1 of the differential diagnoses of opportunistic infections in immunocompromised patients in Taiwan

Evaluation of the In Vivo

Background. Radix Paeoniae Rubra (Chi Shao) contains several phytochemicals with hypoglycemic actions. Current research aims to explore potential insulinotropic effects and long-term therapeutic efficacy of such herb against type 2 diabetes. Methods. Composition analysis for the ethanol extract (PRExt) was executed by high performance liquid chromatography. Polyphenol-enriched fraction was characterized by high pressure size exclusion chromatography. Multiple cell platforms were employed to evaluate hypoglycemic bioactivities. In animal experiments, blood glucose, the homeostasis model assessment (HOMA)-index assessment, glucose tolerance test, and in vivo glucose uptake were all measured. Additional effects of PRExt on obesity and hepatic steatosis were evaluated by serum and histological analysis. Results. PRExt provides multiple hypoglycemic effects including the enhancement of glucose-mediated insulin secretion. Pentagalloylglucose and polyphenol-enriched fraction are two insulinotropic constituents. Moreover, PRExt intraperitoneal injection causes acute hypoglycemic effects on fasted db/db mice. Oral administration of PRExt (200 mg/kg b.w.) gradually reduces blood glucose in db/db mice to the level similar to that in C57J/B6 mice after 30 days. The improvement of glucose intolerance, HOMA-index, and in vivo glucose uptake is evident in addition to the weight loss effect and attenuation of hepatic steatosis. Conclusion. PRExt is an effective antidiabetic herbal extract with multiple hypoglycemic bioactivities

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

A prospective randomized study comparing transnasal and peroral 5-mm ultrathin endoscopy

Differences in patient tolerance, acceptance, and satisfaction of esophagogastroduodenoscopy (EGD) between transnasal (TN) and peroral (PO) routes using a 5-mm video endoscope. Methods: A total of 220 enrolled patients were assigned randomly to two groups undergoing EGD—110 patients each for TN and PO. The successful rate, procedure time, and adverse events were recorded. After the procedure, patients answered a validated questionnaire of tolerance, acceptance, and satisfaction. Results: There were 6 failures (5.7%) of nasal intubation and two nasal bleeding (2%) among 105 TN-EGD procedures. All PO patients (n=102) completed EGD successfully without adverse event. Compared to PO, the procedure of TN achieved lower successful rate (94% vs. 100%, p=0.01), was complicated with epistaxis (2% vs. 0%) and took longer (mean±SD 19.9±6.1 min vs. 16.8±6.4 min, p=0.0001). The patients undergoing TN-EGD indicated less discomfort during passing pharynx (scores of 2.1±2.0 vs. 3.1±2.6, p=0.011) but more pain during inserting scope (scores of 2.2±1.6 vs. 1.5±1.8, p=0.0001). Eventually, there were no significant differences between TN and PO regarding the overall procedure discomfort (scores of 10.7±6.6 vs. 11.1±7.8 scores, p=0.9), satisfaction (scores of 41.2±4.2 vs. 41.3±4.6, p=0.91), and acceptability (87.8% vs. 94.2%, p=0.91). Conclusion: PO intubation seems an excellent alternative method when using a 5-mm ultrathin endoscopy because it achieves comparable patient tolerance, acceptance, and satisfaction as TN intubation, takes less time and causes lower intubation failure and epistaxis

Bioactive phytochemicals from the tubers of <i>Bletilla striata</i> Rchb.f

Thirty-four phytochemicals were isolated from dry tubers of Bletilla striata Rchb.f. The compounds were classified as bibenzyls 1–14, dihydrophenanthrenes 15, 17, 20, 21, phenanthrenes 16, 18, 19, simple benzoids 22–24, a fatty acid 25, glucosyloxybenzyl 2-isobutylmalates 26–32, and glucosyloxybenzyl cinnamates 33, 34. Compounds 1–4, 7, 8, 11, 12, and 16 inhibited melanogenesis (17.96–55.27%) induced by α-MSH in B16F10 cells at 10–40 μM. However, compounds 9, 10, 17, 18, and 21 exhibited significant cytotoxicity against melanomas, with IC50 values of 12–34 μM. Additionally, compounds 15, 17, 19, 20, 23, 31, and 33 reduced the ROS generation induced by H2O2 in HaCaT cells at 6.25–100 μM. In particular, compounds 15, 19, and 20 strongly inhibited ROS generation, with IC50 values of 2.15–9.48 μM. Consequently, compounds 1–4, 7–12, and 15–21 may be the strongest leads to follow in B. striata extract for further research on the skin disorders, hyperpigmentation, melanoma, and ageing.</p

Recurrent HBV Integration Targets as Potential Drivers in Hepatocellular Carcinoma

Chronic hepatitis B virus (HBV) infection is the major etiology of hepatocellular carcinoma (HCC), frequently with HBV integrating into the host genome. HBV integration, found in 85% of HBV-associated HCC (HBV–HCC) tissue samples, has been suggested to be oncogenic. Here, we investigated the potential of HBV–HCC driver identification via the characterization of recurrently targeted genes (RTGs). A total of 18,596 HBV integration sites from our in-house study and others were analyzed. RTGs were identified by applying three criteria: at least two HCC subjects, reported by at least two studies, and the number of reporting studies. A total of 396 RTGs were identified. Among the 28 most frequent RTGs, defined as affected in at least 10 HCC patients, 23 (82%) were associated with carcinogenesis and 5 (18%) had no known function. Available breakpoint positions from the three most frequent RTGs, TERT, MLL4/KMT2B, and PLEKHG4B, were analyzed. Mutual exclusivity of TERT promoter mutation and HBV integration into TERT was observed. We present an RTG consensus through comprehensive analysis to enable the potential identification and discovery of HCC drivers for drug development and disease management

Effect of two maximal isometric contractions on eccentric exercise-induced muscle damage of the elbow flexors

This study investigated the time wise protective effect conferred by two maximal voluntary isometric contractions (2MVCs) at 20 elbow flexion on muscle damage induced by 30 maximal isokinetic (60 s-1) eccentric contractions of the elbow flexors (MaxECC). Sixty-five young untrained men were randomly assigned to a control group that did not perform 2MVCs, or one of four experimental groups (n = 13 per group) who performed 2MVCs either immediately (0d), 2 (2d), 4 (4d) or 7 days (7d) before MaxECC. Changes in maximal isokinetic (60 s-1) concentric torque (MVC-CON), optimum angle (OA), range of motion, upper arm circumference, muscle soreness, plasma creatine kinase activity and myoglobin concentration, and ultrasound echo-intensity following MaxECC were compared among the groups by a two-way repeated measures ANOVA. No significant changes in any variables were evident following 2MVCs. The 2d and 4d groups showed 16-62 % smaller (P \u3c 0.05) changes in all variables following MaxECC than the control, 0d and 7d groups. The 2d group showed 14-34 % smaller (P \u3c 0.05) changes in all variables except for OA compared with the 4d group. The changes in the variables were similar among the control, 0d and 7d groups. These results show that 2MVCs that were performed between 2 and 4 days before MaxECC attenuated the magnitude of muscle damage, but no such effect was evident if the 2MVCs were performed immediately or 7 days before MaxECC. It is concluded that the protective effect conferred by 2MVCs is relatively short-lived, and there is a window for the effect to be conferred

α-Viniferin and ε-Viniferin Inhibited TGF-β1-Induced Epithelial-Mesenchymal Transition, Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression

Resveratrol has well-known anticancer properties; however, its oligomers, including α-viniferin, ε-viniferin, and kobophenol A, have not yet been well investigated. This is the first study examining the anti-epithelial-mesenchymal transition (EMT) effects of α-viniferin and ε-viniferin on A549, NCI-H460, NCI-H520, MCF-7, HOS, and U2OS cells. The results showed that α-viniferin and ε-viniferin significantly inhibited EMT, invasion and migration in TGF-β1- or IL-1β-induced non-small cell lung cancer. α-Viniferin and ε-viniferin also reversed TGF-β1-induced reactive oxygen species (ROS), MMP2, vimentin, Zeb1, Snail, p-SMAD2, p-SMAD3, and ABCG2 expression in A549 cells. Furthermore, ε-viniferin was found to significantly inhibit lung metastasis in A549 cell xenograft metastatic mouse models. In view of these findings, α-viniferin and ε-viniferin may play an important role in the prevention of EMT and cancer metastasis in lung cancer