Inhibition of glycolysis by targeting lactate dehydrogenase A facilitates hyaluronan synthase 2 synthesis in synovial fibroblasts of temporomandibular joint osteoarthritis.

OBJECTIVE: Although associations between dysregulated glucose metabolism and human rheumatoid arthritis have been reported, the disturbance and influence of glycolytic metabolism on temporomandibular joint osteoarthritis remains unclear. This study aimed to investigate the expression level and metabolite profile of the critical glycolytic enzyme, lactate dehydrogenase A (LDHA) in synovial fibroblasts (SFs) of TMJOA, assess the effect of glycolytic inhibition on synthesis of hyaluronan synthase 2 (HAS2) and inflammation progression in these cells. METHODS: Immunohistochemistry and western blotting were performed to detect the expression of LDHA in the lining and sub-lining layers of synovial tissue and SFs. MTT and EdU assays were used to measure the cell proliferation. The cell apoptosis were demonstrated by TUNEL staining and Annexin V/PI double staining. A potent and specific inhibitor of LDHA, GSK2837808A, was administrated to suppress the activity of LDHA and detect the potential efficacy on HAS2. RESULTS: LDHA expression was dramatically higher in the synovial tissue and SFs from TMJOA patients compared to control groups. LDHA inhibition impaired active LDHA performance, suppressed the glucose uptake and decreased lactate concentration. Furthermore, GSK2837808A reversed the occurrence of low ratio of ATP/AMP, high level of Adenosine Monophosphate-activated Protein Kinase (AMPK) activation, disturbed HAS2 synthesis and hyaluronic acid (HA) production by inhibiting LDHA. The cellular viability and cell cycle were not affected by GSK2837808A at the working concentration. CONCLUSIONS: Targeting LDHA using its specific suppressant GSK2837808A impeded lactate secretion and contributed to HAS2 and HA synthesis in TMJOA SFs, providing the vital role of LDHA associated with TMJOA pathogenesis and a novel therapeutic approach for TMJOA.

Angiotensin II Type 2 Receptor Decreases Transforming Growth Factor-ß Type II Receptor Expression and Function in Human Renal Proximal Tubule Cells.

Transforming growth factor-ß (TGF-ß), via its receptors, induces epithelial-mesenchymal transition (EMT) and plays an important role in the development of renal tubulointersitial fibrosis. Angiotensin II type 2 receptor (AT2R), which mediates beneficial renal physiological functions, has received attention as a prospective therapeutic target for renoprotection. In this study, we investigated the effect and underlying mechanism of AT2R on the TGF-ß receptor II (TGF-ßRII) expression and function in human proximal tubular cells (HK-2). Here, we show that the AT2R agonist CGP42112A decreased TGF-ßRII protein expression in a concentration- and time-dependent manner in HK-2 cells. The inhibitory effect of the AT2R on TGF-ßRII expression was blocked by the AT2R antagonists PD123319 or PD123177. Stimulation with TGF-ß1 enhanced EMT in HK-2 cells, which was prevented by pre-treatment with CGP42112A. One of mechanisms in this regulation is associated with the increased TGF-ßRII degradation after activation of AT2R. Furthermore, laser confocal immunofluorescence microscopy showed that AT2R and TGF-ßRII colocalized in HK-2 cells. AT2R and TGF-ßRII coimmunoprecipitated and this interaction was increased after AT2R agonist stimulation for 30 min. The inhibitory effect of the AT2R on TGF-ßRII expression was also blocked by the nitric oxide synthase inhibitor L-NAME, indicating that nitric oxide is involved in the signaling pathway. Taken together, our study indicates that the renal AT2R regulates TGF-ßRII expression and function via the nitric oxide pathway, which may be important in the control of renal tubulointerstitial fibrosis.

Comparative study of biological characters and paeoniflorin content of wild and asexual cultivated Paeonia lactiflora growing at Duolun county, Inner Mongolia / 中国中药杂志

This study aims to investigate whether the cultivation peony, can take the place of wild herbaceous peony by comparing the biological traits and paeoniflorin content between them. The result showed that the biomass of the stem, leaf, crown, fleshy root and fine root of wild plants were all smaller than that of bud asexual cultivated plants, while there was no significant differences in below-ground and aboveground biomass ratio between these two plants. The stele diameter, the proportion of stele, and the ratio of stele diameter to cortex thickness of wild plants were significantly higher than that of bud asexual cultivated plants, while the cortex thickness and the proportion of cortex were significantly smaller than bud asexual cultivated plants. Although the biological traits of bud asexual cultivated plants have changed significantly, the paeoniflorin content in fleshy roots has no significant difference between wild and bud asexual cultivated plants. Therefore, it is feasible to use the bud asexual cultivation to the conservation and large-scale cultivation of Paeonia laciflora, which is an endangered species.

Bioinformatics analysis reveals connection of squamous cell carcinoma and adenocarcinoma of the lung.

Squamous cell carcinoma and adenocarcinoma are the major histological types of non-small cell lung cancer. Because they differ on the basis of histopathological and clinical characteristics and their relationship with smoking, their etiologies may be different; for example, different tumor suppressor genes may be related to the genesis of each type. We used microarray data to construct three regulatory networks to identify potential genes related to lung adenocarcinoma and squamous cell carcinoma and investigated the similarity and specificity of them. In the network, some of the observed transcription factors and target genes had been previously proven to be related to lung adenocarcinoma and squamous cell carcinoma. We also found some new transcription factors and target genes related to SCC. The results demonstrated that regulatory network analysis is useful in connection analysis between lung adenocarcinoma and squamous cell carcinoma.

A green approach to the synthesis of graphene nanosheets.

Graphene can be viewed as an individual atomic plane extracted from graphite, as unrolled single-walled carbon nanotube or as an extended flat fullerene molecule. In this paper, a facile approach to the synthesis of high quality graphene nanosheets in large scale through electrochemical reduction of exfoliated graphite oxide precursor at cathodic potentials (completely reduced potential: -1.5 V) is reported. This method is green and fast, and will not result in contamination of the reduced material. The electrochemically reduced graphene nanosheets have been carefully characterized by spectroscopic and electrochemical techniques in comparison to the chemically reduced graphene-based product. Particularly, FTIR spectra indicate that a variety of the oxygen-containing functional groups have been thoroughly removed from the graphite oxide plane via electrochemical reduction. The chemically converted materials are not expected to exhibit graphene's electronic properties because of residual defects. Indeed, the high quality graphene accelerates the electron transfer rate in dopamine electrochemistry (DeltaE(p) is as small as 44 mV which is much smaller than that on a glassy carbon electrode). This approach opens up the possibility for assembling graphene biocomposites for electrocatalysis and the construction of biosensors.

Preparation of microcapsules containing two-phase core materials.

Urea-formaldehyde (UF) microcapsules containing two-phase core materials in which phthalocyanine blue BGS (beta-CuPc) particles were homodispersed in tetrachloroethylene (TCE) were prepared by in situ polymerization. The effects of the various process parameters, including the type of surface modifier, the viscosity of UF prepolymer, the type of water-soluble surfactant, and the concentration of oil-soluble surfactant in the capsule core on the dispersity of beta-CuPc particles in TCE and the properties of the capsule wall and the adsorption of beta-CuPc particles on the internal surface of capsule wall were experimentally investigated. It was shown that using octadecylamine (ODA) to modify beta-CuPc particles resulted in a significant increase of the dispersing extent (DE) and the electrophoresis velocity of the particles in TCE (about 4 and 20 times more than that of unmodified). In addition, the optimal reaction conditions of the synthesis UF prepolymer were obtained by the orthogonal test. On the other hand, as the oil/water interfacial tension of emulsion was big enough, the microcapsule formed. The concentration of Span-80 in TCE was no less than 0.062 mM; the adsorption of beta-CuPc particles on internal surface of wall were restrained. Finally, the microcapsules in which beta-CuPc particles possess reversible response to dc electric field were obtained.