AIM:To compare the effects of atorvastatin at different doses on the function of endothelial proge-nitor cells (EPCs) in the patients with ST-segment elevation myocardial infarction (STEMI).METHODS:The patients of STEMI (n=40) were chosen.According to treatment with different doses of atorvastatin calcium tablet, they were randomly divided into a group of 20 mg and a group of 40 mg (20 cases in each group).The EPCs isolated from the patients were identified and quantitatively analyzed at different time points (before the treatment and on days 5, 10, 15, 20, 30, 60, 90 and 120 after the treatment) by flow cytometry.The surface markers of the EPCs, CXC chemokine receptor 4 (CXCR4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and silent information regulator 1 (SIRT1), were also detected.RESULTS:On the 5th day, the group of 40 mg demonstrated stronger cell proliferation capability and higher expression levels of CXCR4, VEGF and bFGF than the group of 20 mg (P<0.05).From the 10th day to 120th day, the group of 20 mg revealed stronger cell proliferation capability and higher expression levels of CXCR4, VEGF and bFGF than the group of 40 mg (P<0.05).Within 30 d, the expression of SIRT1 showed no significant diffe-rence between the 2 groups, yet it witnessed a marked change after that and peaked on the 60th day with a drop afterwards.At each time point, the SIRT1 expression level in the group 20 mg was observed higher than that in the group of 40 mg (P<0.05).CONCLUSION:In the acute phase, the repair function of the body treated with atorvastatin at dose of 40 mg is better than that with 20 mg.However, in a long term the low concentration of statin therapy works better in improving the vascular intima and promoting the angiogenesis than high concentration.

Polyamide is a synthetic small molecule that recognizes predetermined sequences in the minor groove of DNA with affinities and specificities compared to those of DNA-binding proteins. Polyamide can suppress gene transcription by interfering with the attachment of natural transcription factors and DNA. The alkylating polyamides represent a novel approach for sequence-specific gene silencing, which might be applied to gene therapy. The research on suppression of gene transcription by polyamide was reviewed in this paper.
Animals ; Gene Silencing ; drug effects ; HIV ; genetics ; Humans ; Neoplasms ; genetics ; Nylons ; pharmacology ; Transcription, Genetic ; drug effects

Objective To investigate the role of KAT7 in cartilage cell and tissue ageing by establishing an over-replicating-induced primary mouse cartilage cell ageing model and a mouse natural ageing model.Methods Chon-drocytes of the mouse knee joint were obtained by type Ⅱ collagenase digestion and identified by toluidine blue stai-ning and Col Ⅱ staining.The age-related proteins and KAT7 expression levels in cartilage cells from different gener-ations of mice were discovered using Western blot and cellular immunofluorescence techniques,and the aging of the cells was assessed by SA-β-Gal coloring.The pathological alterations were examined in the joints of 22-month-old mice compared to 2-month-old mice using HE staining and safranin O-solid green staining.Additionally,immuno-histochemical analysis was done to observe the expression of KAT7 and p53 in mouse joint tissue.Results Com-pared with the control group,the expression levels of KAT7 protein and p21 and p53 in aged mouse chondrocytes significantly increased.WM-3835,a commonly inhibitor of KAT7 that possess the capacity on halting the protein expression procedure of gene KAT7 as well as p21 in ageing chondrocytes.SA-β-Gal staining showed a significant increase in positive staining of chondrocytes in the eighth generation(P8)compared to the first generation(P1).Compared with the cartilage tissue of young mice,the cartilage tissue of elderly mice presents a near-bone distribu-tion,with a decrease in cartilage surface integrity,a significant increase in the number of hypertrophic chondro-cytes,and more KAT7 and p53 cells that were positive.Conclusion The expression of KAT7 increases in the ageing chondrocytes and the cartilage tissue of ageing mice,reveales the potential significance of KAT7 correlated to cellular aging process in cartilage.

Objective : To examine the impact and partial mechanism of bupivacaine sustained-release drug ( code PB21) in combination with low-dose dexamethasone ( Dex) on the analgesic time of rats with knee osteoarthritis (KOA) ． Methods : Using the techniques of anterior cruciate ligament transection and meniscus instability，a rat KOA model was created．After eight weeks，SD mice were split into three groups at random : a group for the model， one for Dex (50 μg) ，one for PB21 ( 1. 5 mg) ，and one for combined administration ( 1. 5 mg PB21 /50 μg Dex) ， with a control group that received a sham operation．The pain thresholds of KOA rats were measured using a Pres- sure Application Measurement (PAM) at different intervals before to delivery and 4，24，36，and 48 hours following administration ; to gauge changes in discomfort，a CatWalk was used to assess the rats' average foot strength and maximum contact area before，four，twenty-four，and forty-eight hours after treatment．A portion of the rats were put to sleep at four，twenty-four，and forty-eight hours following the injection，and the joint synovium was removed for paraffin sectioning．Immunohistochemistry was used to identify the expression of GAP43 in the synovium，whereas immunofluorescence was used to identify the expression of CGRP in the same tissue. Results : The average strength and maximum contact area of the foot and claw decreased (P ＜0. 01 ) ，and the pain threshold decreased (P < 0. 01) in the model group compared to the sham operation group．The PB21 + Dex group experienced a delayed pain threshold lowering time delay when compared to the PB21 and Dex treatment groups alone．Up to 48 hours lat- er，the combination administration group's average strength and maximum contact area of the foot paw remained ele- vated，and there was a statistically significant difference (P ＜0. 05 ) between the combined administration group and PB21 and Dex alone．GAP43 and CGRP expression levels in synovial tissue were detected．The results indica- ted that PB21 and Dex alone could lower protein expression levels at 4 and 24 h at the two time points，and that the PB21 + Dex group could still significantly lower GAP43 and CGRP expression levels at 48 h．At the 48 h time point，the PB21 + Dex group was statistically significant when compared to the PB21 and Dex alone administration group(P＜0. 05) ． Conclusion In summary low dose dexamethasone can prolong the analgesic effect of PB21 on KOA rats，which is connected to reducing the expression of pain related proteins CGRP and GAP43 .

Objective : To study the protective effect and mechanism of iPSC⁃MSCs on cartilage matrix in knee oste⁃ oarthritis (KOA) patients in vitro. Methods : Cartilage tissues removed from KOA patients with joint replacement surgery were collected and subjected to tissue and cellular experiments , respectively. Cartilage tissue was cut into small pieces and randomly divided into a control group , an IL⁃1β ( 10 ng/ml) induction group , and iPSC⁃MSCs 96 h and then co⁃cultured with different amounts of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. For in tissues , the pathological changes of isolated cartilage tissues were examined by HE staining. The levels of ADAMTS⁃4 , ADAMTS⁃5 , and type II collagen expression were analyzed by immunohistochemistry , while the levels of MMP13 , IL⁃6 , and IL⁃10 in culture supernatants were detected by ELISA kits. The 2 to 5 generations of chondrocytes , which were extracted from cartilage tissue of KOA patients , were stimulated with IL⁃1β ( 10 ng/ml) for 48 h and then co⁃cultured with different concentrations of iPSC⁃MSCs ( 1 × 104 , 1 × 105 , 1 × 106 ) cells for 72 h. Immunofluorescence and Western blot detected the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 in chondrocytes. Results : Comparison with the control group , in the IL⁃1β⁃induced group , the levels of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 increased , the level of type II collagen decreased , the levels of MMP⁃13 and IL⁃6 in the culture supernatant increased ( P < 0. 05) , and the level of IL⁃10 decreased ( P < 0. 05) ; Compared with the IL⁃1β⁃induced decreased the expression of RUNX2 , ADAMTS⁃4 , and ADAMTS⁃5 , promoted type II collagen expression and elevated IL⁃10 levels. Conclusion iPSC⁃MSCs inhibited ADAMTS⁃4 and ADAMTS⁃5 expression in vitro , reduced cartilage extracellular matrix degradation , and played a role in articular cartilage protection.