Sterculia lanceolata, an important tropical woody plant, has high ornamental and medicinal value. To our knowledge, only brown root disease in this plant has been reported. In Nanning, Guangxi, China, an outbreak of leaf blight disease was observed on S. lanceolata in June 2019, with the leaf infection rate ranging from 80% to 100%. The disease seriously affected the leaves of trees and caused economic loss. Eight isolates were recovered from the infected leaves of different trees, and the pathogenicity was then determined by the methods of mycelial disc and conidial suspension, fulfilling Koch's postulates. According to the morphological and molecular biological characteristics of isolates, the pathogen causing leaf blight on S. lanceolata was identified as Colletotrichum siamense. Accurate identification of the pathogen provides a reliable basis for the control of the disease.

Background: Osteoarthritis (OA) in articular cartilage is one of the most common degenerative joint disorders that causes deep pain. Articular cartilage is avascular and aneural in healthy condition, it emerges the ingrowth of nociceptive nerve fibres in OA condition, which may contribute to the pain. The pathogenetic mechanisms of the neural ingrowth in OA are not fully understood. Semaphorin 3A (Sema3A) is an axonal guidance molecule that repels nerves and Neuropilins (1 and 2) and plexins (A1-4) are the co-receptors for Sema3A.

Aims Although extracellular-regulated kinases (ERK) are a well-known central mediator in cardiac hypertrophy, no clinically available ERK antagonist has been tested for preventing cardiac hypertrophy. Selumetinib is a novel oral MEK inhibitor that is currently under Phase II and Phase III clinical investigation for advanced solid tumors. In this study, we investigated whether Selumetinib could inhibit the aberrant ERK activation of the heart in response to stress as well as prevent cardiac hypertrophy. Methods and Results In an in vitro model of PE-induced cardiac hypertrophy, Selumetinib significantly inhibited the ERK activation and prevented enlargement of cardiomyocytes or reactivation of certain fetal genes. In the pathologic cardiac hypertrophy model of ascending aortic constriction, Selumetinib provided significant ERK inhibition in the stressed heart but not in the other organs. This selective ERK inhibition prevented left ventricular (LV) wall thickening, LV mass increase, fetal gene reactivation and cardiac fibrosis. In another distinct physiologic cardiac hypertrophy model of a swimming rat, Selumetinib provided a similar anti-hypertrophy effect, except that no significant fetal gene reactivation or cardiac fibrosis was observed. Conclusions Selumetinib, a novel oral anti-cancer drug with good safety records in a number of Phase II clinical trials, can inhibit ERK activity in the heart and prevent cardiac hypertrophy. These promising results indicate that Selumetinib could potentially be used to treat cardiac hypertrophy. However, this hypothesis needs to be validated in human clinical trials.

Background: Golgi phosphoprotein 3 (GOLPH3) has been reported to be involved in the development of several human cancers. The present study was conducted to investigate the expression of GOLPH3 and its prognostic significance in renal cell carcinoma (RCC). Meanwhile, the function of GOLPH3 in human RCC was further investigated in cell culture models. Methods: Expression of GOLPH3 was examined in 43 fresh RCC tissues and paired adjacent normal renal tissues by real-time quantitative PCR and western blotting. Immunohistochemistry for GOLPH3 was performed on additional 218 RCC tissues. The clinical significance of GOLPH3 expression was analysed. Downregulation of GOLPH3 was performed using small-interfering RNA (siRNA) in Caki-1 and 786-O cells with high abundance of GOLPH3, and the effects of GOLPH3 silencing on cell proliferation, migration, invasion in vitro, and tumour growth in vivo were evaluated. Results: Expression of GOLPH3 was upregulated in the majority of the RCC clinical tissue specimens at both mRNA and protein levels. Clinicopathological analysis showed that GOLPH3 expression was significantly correlated with T stage (P < 0.001), lymphnode status (P=0.003), distant metastasis (P < 0.001), tumour-node-metastasis (TNM) stage (P < 0.001), and Fuhman grade (P=0.001). Expression of GOLPH3 was inversely correlated with both overall and recurrence-free survival of RCC patients. Multivariate analysis showed that GOLPH3 expression was an independent prognostic indicator for patient's survival. Knockdown of the GOLPH3 expression reduced cell proliferation, anchorage-independent growth, migration, invasion, and tumour growth in xenograft model mice. Conclusions: These results suggest that GOLPH3 expression is likely to have important roles in RCC development and progression, and that GOLPH3 is a prognostic biomarker and a promising therapeutic target for RCC.

Background: Hypoxia inducible factor-1 alpha (HIF-1 alpha) plays an important role in ischemia/reperfusion (I/R). It has been shown that miR- 494 could lead to cardioprotective effects against I/R-induced injury, but its functional relationship with HIF-1 alpha has not been fully clarified. This study was undertaken to determine if miR-494 is a regulator of HIF-1 alpha in hypoxia. Methods: We employed real-time PCR to investigate the expression pattern of miR-494 after 4, 8 and 16h of hypoxia in human liver cell line L02, and western blot to detect HIF-1 alpha expression after 8 and 16h of hypoxia. To investigate the role of miR-494 during hypoxia, L02 cells was transfected with mimic of miR-494. Transfected cells were harvested after 8h of hypoxia, and HIF-1 alpha expression detected by Western Blot. Apoptosis in miR-494-overexpressing L02 was also detected with AnnexinV by fluorescence microscope. Results: We found miR-494 was rapidly up-regulated after 4h of hypoxia in L02 by real-time PCR, decreased in following hypoxia. Western blot results showed the protein level of HIF-1 alpha was increased after 8h of hypoxia. Overexpression of miR-494 in hypoxia resulted in a significant increase of HIF-1α protein levels comparing with negative control. In miR-494 mimic group following 16h of hypoxia, we found over-expression of miR-494 could protect cells against hypoxia-mediated apoptosis. Conclusions: We found that miR-494 was up-regulated in cell hypoxia. During cell hypoxia, miR-494 participated in the regulation of HIF-1 alpha, and protected cells against hypoxia-mediated apoptosis. Thus, our results suggested that miR-494 might constitute a new therapeutic agent for the treatment of hepatic I/R injury.

Background: MicroRNAs (miRs) are non-coding RNAs that could regulate gene expression. Until now, very little is known about miRs' role during ischemia/reperfusion (I/R). It was reported that microRNA-21 (miR-21) was a strong anti-apoptotic factor in cancer cells. But its role in I/R in normal cell have not been fully clarified. So we investigated whether microRNA-21 can protect human umbilical vein endothelial cells (HUVECs) against apoptosis induced by hypoxia injury. Methods: We employed real-time RT-PCR to investigate the expression pattern of miR-21 after different durations of hypoxia in HUVECs. To investigate the anti-apoptotic role of miR-21 during hypoxia, HUVECs were transfected with miR-21 mimic. Cells were harvested after 16h of hypoxia, and apoptosis of HUVECs in each group was detected by Annexin V binding. As PTEN is a putative target of miR-21 and are involved in apoptosis regulation, PTEN expression in each group was detected by western blot after 4h and 16h of hypoxia. Results: Real-time RT-PCR analysis revealed that mature miR-21 levels was increased by approximately fivefold after 16h of hypoxia, and fifteen fold after 24h of hypoxia. Flow cytometry results showed Annexin V binding to HUVECs was reduced in miR-21 mimic group (25.2%) than in negative control group (34.6%), and western blot results demonstrated miR-21 over-expression reduced PTEN expression in both 4h and 16h duration times of hypoxia. Conclusion: Over-expression miR-21 protects HUVECs from apoptosis during hypoxia by targeting PTEN, which might have the therapeutic potential for the better management of I/R injury.

OBJECTIVES:This study was carried out to reveal functions and mechanisms of MEK/ERK and p38 pathways in chondrogenesis of rat bone marrow mesenchymal stem cells (BMSCs), and to investigate further any interactions between the mitogen-activated protein kinase (MAPK) and transforming growth factor-beta1 (TGF-beta1)/Smads pathway in the process.MATERIALS AND METHODS:Chondrogenic differentiation of rat BMSCs was initiated in micromass culture, in the presence of TGF-beta1, for 2 weeks. ERK1/2 and p38 kinase activities were investigated by Western Blot analysis. Specific MAPK inhibitors PD98059 and SB20350 were employed to investigate regulatory effects of MEK/ERK and p38 signals on gene expression of chondrocyte-specific markers, and TGF-beta1 downstream pathways of Smad2/3.RESULTS:ERK1/2 was phosphorylated in a rapid but transient manner, whereas p38 was activated in a slow and sustained way. The two MAPK subtypes played opposing roles in mediating transcription of cartilage-specific genes for Col2alpha and aggrecan. TGF-beta1-stimulated gene expression of chondrogenic regulators, Sox9, Runx2 and Ihh, was also affected by activity of PD98059 and SB203580, to different degrees. However, influences of MAPK inhibitors on gene expression were relatively minor when not treated with TGF-beta1. In addition, gene transcription of Smad2/3 was significantly upregulated by TGF-beta1, but was regulated more subtly by treatment with MAPK inhibitors.CONCLUSIONS:MAPK subtypes seemed to regulate chondrogenesis with a delicate balance, interacting with the TGF-beta1/Smads signalling pathway.

INTRODUCTION:Due to the organ supply shortage, the donor pool has been expanded to include non-heart-beating donors, where renal warm ischemia/reperfusion (I/R) injury is inevitable. This study was undertaken to determine whether Yisheng injection (YM) could attenuate renal warm I/R injury in mice.MATERIALS AND METHODS:Male C57BL/6 mice were divided into sham, ischemic, and YM-treated groups using 50 minutes of left kidney ischemia. Mice were humanely killed at 4 or 24 hours postreperfusion. We assayed the effects of YM on liver functional injury, neutrophil recruitment, and proinflammatory mediators after renal I/R injury.RESULTS:Renal I/R produced dramatic injuries in mouse kidneys. Administration of YM reduced liver function (urea nitrogen of untreated vs treated, 4.7 +/- 0.6 vs 26.6 +/- 1.5 mmol/L; P < .01) and histological injury (histological scores of untreated vs treated, 4.12 +/- 0.14 vs 0.98 +/- 0.07; P < .01). YM at doses of 5, 15, or 25 mg/kg reduced the serum levels of tumor necrosis factor-alpha (TNF-alpha) by about 32.9%, 55.1%, and 74.5%, respectively. Moreover, YM also suppressed the increase in messenger RNA (mRNA) and protein expressions of TNF-alpha and intercellular adhesion molecule-1 (ICAM-1), as well as abrogated neutrophil recruitment in a dose-dependent manner.CONCLUSION:YM protects murine kidneys from warm I/R injury, probably via decreasing functional injury, reducing neutrophil infiltration, and suppressing the overexpression of proinflammatory mediators and adhesion molecules.

Hypoxia/reoxygenation (H/R)-induced injury is the key factor associated with islet graft dysfunction. This study aims to examine the effect of mesenchymal stem cells (MSCs) on islet survival and insulin secretion under H/R conditions. Islets from rats were isolated, purified, cultured with or without MSCs, and exposed to hypoxia (O(2) ≤ 1%) for 8 h and reoxygenation for 24 and 48 h, respectively. Islet function was evaluated by measuring basal and glucose-stimulated insulin secretion (GSIS). Apoptotic islet cells were quantified using Annexin V-FITC. Anti-apoptotic effects were confirmed by mRNA expression analysis of hypoxia-resistant molecules, HIF-1α, HO-1, and COX-2, using semi-quantitative retrieval polymerase chain reaction (RT-PCR). Insulin expression in the implanted islets was detected by immunohistological analysis. The main results show that the stimulation index (SI) of GSIS was maintained at higher levels in islets co-cultured with MSCs. The MSCs protected the islets from H/R-induced injury by decreasing the apoptotic cell ratio and increasing HIF-1α, HO-1, and COX-2 mRNA expression. Seven days after islet transplantation, insulin expression in the MSC-islets group significantly differed from that of the islets-alone group. We proposed that MSCs could promote anti-apoptotic gene expression by enhancing their resistance to H/R-induced apoptosis and dysfunction. This study provides an experimental basis for therapeutic strategies based on enhancing islet function.

To analyze the risk factors affecting mini-percutaneous nephrolithotomy (MPCNL) in the population of patients over the age of 70, and explore the corresponding strategy.

Objectives. Ischemia-reperfusion injury (IRI) is a key factor that contributes to early and late dysfunction of liver graft. Although we have known that hepatocytes express death receptors for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), the effects of TRAIL on hypoxia/reoxygenation (H/R)-mediated apoptosis are unclear. This study sought to examine the effects of H/R on TRAIL cytotoxicity, as a cause of primary hepatic graft dysfunction, delayed graft refunction, and chronic graft dysfunction.Methods. Using an hepatocyte H/R model in vitro to mimic IRI in the grafted liver, normal human hepatocytes HL-7702 were exposed to hypoxia for 5 hours then reoxygenated for 0, 2, 4, 6, or 20 hours. In another experiment, hepatocytes were exposed to hypoxia for 0, 2, 4, 8, or 20 hours. Expressions of TRAIL-R2/Death receptor 5 (DR5) mRNA were measured by semiquantitative reverse-transcriptase polymerase chain reactions. After 16 hours of hypoxia, human hepatocytes were treated with TRAIL in different concentrations for 5 hours. The death of hepatocytes was confirmed by flow cytometer and methyl thiazolyl tetrazolium analysis.Result. After 5-hour hypoxia, the expressions of DR5 mRNA increased at all times of reoxygeriation. DR5 mRNA was up-regulated from 0 hour after reoxygenation, reaching a peak value at 2 hours after reoxygenation compared with the normoxia cultured cells. Moreover, DR5 mRNA was up-regulated gradually following prolonged hypoxia. TRAIL-mediated cell killing was concentration-dependent being greater in the hypoxia treatment group compared to the normoxia group.Conclusions. H/R up-regulated the expression of DR5 and enhanced TRAIL-mediated apoptosis in an human hepatocyte line. The TRAIL pathway might play a critical role hepatocyte apoptosis induced by IRI.