Research of inflammatory factors and signaling pathways in knee osteoarthritis / 中国骨伤

Knee osteoarthritis is the most common type of arthritis, which is manifested by the deformation and degeneration of articular cartilage and the discomfort of patients with joint pain, which affects the quality of life of patients and aggravates the medical burden of society. The pathogenesis of knee osteoarthritis is very complex. This paper reviews the inflammatory factors and signal pathways involved in knee osteoarthritis. It is found that most of the inflammatory factors involved are interleukin, such as IL-1 β, IL-6, IL-15, IL-17, IL-18, and tumor necrosis factors, such as TNF-α. These inflammatory factors aggravate knee osteoarthritisby activating corresponding pathways and promoting the release of inflammatory mediators. The inflammatory signaling pathways involved in knee osteoarthritis are complex. Notch pathway, Wnt pathway, SDF-1 / CXCR4 pathway, TLRs pathway, MAPKs pathway, hippo Yap pathway, OPG-RANK-RANKL pathway and TGF-β pathway are all involved in the regulation of knee osteoarthritis, and the pathways related to inflammatory mechanism are mainly MAPKs pathway and TLRs pathway. Different signaling pathways can cause the destruction of articular cartilage, promote the apoptosis of chondrocytes, and finally lead to the further imbalance of homeostasis in the knee joint. At the same time, the activation of signal pathway can promote the release of inflammatory factors, so under the cascade reaction of inflammatory factors and signal pathway, knee osteoarthritis is aggravating.

Expression of Apollon and Caspase 9 in gastric carcinoma and their relationship / 临床与实验病理学杂志

Purpose To explore the expression,significance and relationship of apoptosis related gene Apollon and Caspase 9 in gastric carcinoma. Methods The SP immunohistochemical method was used to detect the expression of Apollon and Caspase 9 in 105 cases of gastric carcinoma,38 adjacent tissues and 29 normal tissues,and the expression of Apollon and Caspase 9 was analyzed with relation to clinicopathologic factors. Results The numbers of positive expression of Apollon gene in gastric carcinoma tissues,adjacent tissues and normal tissues were 82(78. 10％) ,8(21. 05％) and 2(6. 90％) respectively, there was significant difference between gastric carcinoma tissues, adjacent tissues and normal tissues (P < 0. 01) . The expression of Apollon in gastric carcinoma was positively correlated with degree of tumor differentiation,TNM staging and lymph node metastasis (P < 0. 05) ,but not with other clinicopathologic factors (P > 0. 05) . The numbers of positive expression of Caspase 9 gene in gastric carcinoma tissues,adjacent tissues and normal tissues were 21 (20. 00％) ,23 (60. 53％) and 21 (72. 41％) ,respectively,and there was significant difference between gastric carcinoma tissues,adjacent tissues and normal tissues (P < 0. 01) . The expression of Caspase 9 in gastric carcinoma was positively correlated with degree of tumor differentiation, TNM staging and lymph node metastasis (P < 0. 01) ,but not with other clinicopathologic factors (P > 0. 05) . The expression of Apollon was negatively correlated to Caspase 9 in gastric carcinoma with statistical significance (r = - 0. 541 1,P < 0. 01) . Conclusions The interaction of Apollon and Caspase 9 may be involved in the gastric carcinogenesis and progression. Apollon is closely related with invasion and metastasis of gastric carcinoma,and it may be a potential treatment target.

Synthesis and protective effect of ligustrazine intermediates against CoCl2-induced neurotoxicity in differentiated PC12 cell / 中国中药杂志

Ligustrazine, one of the major effective components of the Chinese traditional medicinal herb Ligusticum Chuanxiong Hort, has been reported plenty of biological activities, such as protect cardiovascular and cerebrovascular, neuroprotection and anti-tumor, et al. Because of its remarkable effects, studies on structural modification of ligustrazine have attracted much attention. Ligustrazine synthetic derivatives reported in recent decades are mainly derived from four primary intermediates (TMP-COOH, TMP-OH, TMP-NH2, HO-TMP-OH). To explore the neuroprotection activitiy of ligustrazine intermediates, six ligustrazine intermediates (2, 5, 8, 11, 12, 13) were synthesized and their protective effects against CoCl2-induced neurotoxicity in differentiated PC12 cells were studied. The target compounds were prepared via different chemical methods, including oxidation, substitution, esterification and amidation without changing the structure nucleus of ligustrazine. Compared with TMP (EC50 = 56.03 micromol x L(-1)), four compounds (2, 5, 12 and 13) exhibited higher activity (EC50 < 50 micromol x L(-1)) respectively, of which, compound 2 displayed the highest protective effect against the damaged PC12 cells (EC50 = 32.86 micromol x L(-1)), but target compounds 8 and 11 appeared lower activity (EC50 > 70 micromol x L(-1)). By structure-activity relationships analysis, the introduction of carboxyl, amino to the side chain of ligustrazine and appropriately increase the proportion of ligustrazine may contribute to enhance its neuroprotective activity, which provides a reference for the design, synthesis and activity screening of relevant series of ligustrazine derivatives in the future.