Despite extensive studies on the multifaceted roles of morroniside, the main active constituent of iridoid glycoside from Corni Fructus, the effect of morroniside on osteoarthritis (OA) chondrocytes remains poorly understood. Here, we investigated the influence of morroniside on cultured human OA chondrocytes and a rat experimental model of OA. The results showed that morroniside enhanced the cell viability and the levels of proliferating cell nuclear antigen expression (PCNA), type II collagen and aggrecan in human OA chondrocytes, indicating that morroniside promoted chondrocyte survival and matrix synthesis. Furthermore, different doses of morroniside activated protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) in human OA chondrocytes, and in turn, triggered AKT/S6 and ERK/P70S6K/S6 pathway, respectively. The PI3K/AKT inhibitor LY294002 or the MEK/ERK inhibitor U0126 attenuated the effect of morroniside on human OA chondrocytes, indicating that the activation of AKT and ERK contributed to the regulation of morroniside in human OA chondrocytes. In addition, the intra-articular injection of morroniside elevated the level of proteoglycans in cartilage matrix and the thickness of articular cartilage in a rat experimental model of OA, with the increase of AKT and ERK activation. As a consequence, morroniside has chondroprotective effect on OA chondrocytes, and may have the therapeutic potential for OA treatment.
Abstract:It is known that phosphoinositide-specific phospholipases g1 (PLCg1) can trigger several signalling pathways to regulate cell proliferation, differentiation, and metastasis. However, whether this kinase is highly expressive and active in human gastric adenocarcinomas, and whether it can play an important role in the development of the cancer, have not yet been investigated. The aim of the study was to investigate the expression of PLCg1 in human gastric adenocarcinoma, while the question of whether PLCg1 can be activated through protein kinase B (Akt) signalling pathways to regulate cell migration was further explored using human gastric adenocarcinoma BGC-823 cell line. The expression of PLCg1 in human adenocarcinoma was detected using immunohistochemical staining. The BGC-823 cells were cultured and treated with inhibitors or transfected with plasmid construction. The cell migration of BGC-823 cells was measured with wound healing assay, cell migration assay, and the ruffling assay. The expression levels of PLCg1 and its related signal molecules in BGC-823 cells were assessed using Western blot analysis or gelatine zymography assay. PLCg1 was highly expressed in human gastric adenocarcinomas, especially in the region with lymph node metastasis. It was shown that migration of BGC-823 cells in vitro depends on PLCg1 activation. This activation is mediated through Akt, an upstream of PLCg1 that triggers the PLCg1/extracellular signal-regulated kinase (ERK)/matrix metalloproteinase (MMP) pathway in BGC-823 cells. PLCg1 activities play an important role in the metastasis of gastric adenocarcinoma, and may serve as a potential therapeutic target in this type of cancer.
Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation including extracellular matrix (ECM) degradation and cell loss. It is known that phosphoinositide-specific phospholipase γ1 (PLCγ1) can trigger several signaling pathways to regulate cell metabolism. However, whether this kinase is expressive and active in human OA chondrocytes and its role in the pathological progression of OA have not been investigated. The current study was designed to investigate the PLCγ1 expression in human OA cartilage, and whether PLCγ1 was involved in the ECM synthesis had been further explored using cultured human OA chondrocytes. Our results indicated that PLCγ1 was highly expressed in human OA chondrocytes. In our further study using the cultured human OA chondrocytes, the results demonstrated that the disruption of PLCγ1 by its inhibitor, U73122, and siRNA contributed to the ECM synthesis of human OA chondrocytes through regulating the expression of ECM-related signaling molecules, including MMP-13, Col II, TIMP1, Sox-9, and AGG. Furthermore, PLCγ1/IP3/Ca(2+)/CaMK II signaling axis regulated the ECM synthesis of human chondrocytes through triggering mTOR/P70S6K/S6 pathway. In summary, our results suggested that PLC-γ1 activities played an important role in the ECM synthesis of human OA chondrocytes, and may serve as a therapeutic target for treating OA.
Grass carp (Ctenopharyngodon idella) is a valuable aquacultural species in China, but it is highly vulnerable to infectious diseases, which consequently may cause tremendous economical loss. To reduce the risk of disease in the fish, antibiotics have been used in the fish diet, which in turn caused some negative effects on human health. In this study, we choose lactosucrose (LS) as antibiotic alternative added to the diet of the grass carp juveniles and then to evaluate the effects of 15 g Kg À1 LS in the diet on the gene transcript profiles. After the trial for 56 days, we observed that the weight gain rate, specific gain rate and feed conversion rate were increased by 14.2%, 9.2% and 10.1%, respectively, in the trial group compared with the control group. The gene expression levels in the liver tissues of grass carps were assayed using the zebrafish cDNA microarray technology and real-time RT-PCR. Comparing with the control group, 416 genes were identified, and among them, 266 genes were up-regulated and 150 were downregulated on the trial group. Among the up-regulated genes selected, most of them related to growth, immune reaction and sugar metabolism. Most of the down-regulated genes are RAS oncogene family members, V-myc viral oncogene homologue and programmed cell death-related factors. The apparent regulation of gene expression stimulated by LS suggests that the potential application of the LS in improving the growth performance and immunity on the grass carps. Together, this study provides convincing data in support of the use of LS as an alternative dietary antibiotic in fish.
The expression of the psbA, trnH-GUG and rps19' genes from spinach chloroplasts, coding respectively for the 32 kDa protein, the tRNA(His) (GUG), and the putative ribosomal protein CS19', has been studied by cloning, Northern hybridization and 3' and 5' S1 mapping experiments.It is demonstrated that the putative transcription termination signal of the psbA gene does not function as a rho-independent terminator of transcription in E. coli, whatever its orientation.Evidence is presented suggesting that, in spinach, the psbA and trnH-GUG genes are probably cotranscribed. The 3'-OH extremities of transcripts observed downstream from the putative psbA terminator are interpreted as resulting from processing of the psbA precursor.Using different approaches, it is shown that the rps19' gene, located on the other strand and overlapping the trnH-GUG gene, is not expressed.
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