Showing papers by "Fifth Affiliated Hospital of Xinjiang Medical University published in 2018"

The paxillin-plectin-EPLIN complex promotes apical elimination of RasV12-transformed cells by modulating HDAC6-regulated tubulin acetylation.

Abstract: Recent studies have revealed that newly emerging RasV12-transformed cells are often apically extruded from the epithelial layer. During this cancer preventive process, cytoskeletal proteins plectin and Epithelial Protein Lost In Neoplasm (EPLIN) are accumulated in RasV12 cells that are surrounded by normal cells, which positively regulate the apical elimination of transformed cells. However, the downstream regulators of the plectin-EPLIN complex remain to be identified. In this study, we have found that paxillin binds to EPLIN specifically in the mix culture of normal and RasV12-transformed cells. In addition, paxillin is accumulated in RasV12 cells surrounded by normal cells. Paxillin, plectin and EPLIN mutually influence their non-cell-autonomous accumulation, and paxillin plays a crucial role in apical extrusion of RasV12 cells. We also demonstrate that in RasV12 cells surrounded by normal cells, acetylated tubulin is accumulated. Furthermore, acetylation of tubulin is promoted by paxillin that suppresses the activity of histone deacetylase (HDAC) 6. Collectively, these results indicate that in concert with plectin and EPLIN, paxillin positively regulates apical extrusion of RasV12-transformed cells by promoting microtubule acetylation. This study shed light on the unexplored events occurring at the initial stage of carcinogenesis and would potentially lead to a novel type of cancer preventive medicine.

A novel PTCH1 mutation underlies nonsyndromic cleft lip and/or palate in a Han Chinese family.

Abstract: OBJECTIVES Cleft lip and/or palate (CL/P) is the most common craniofacial congenital disease, and it has a complex aetiology. This study aimed to identify the causative gene mutation of a Han Chinese family with CL/P. SUBJECTS AND METHODS Whole exome sequencing was conducted on the proband and her mother, who exhibited the same phenotype. A Mendelian dominant inheritance model, allele frequency, mutation regions, functional prediction and literature review were used to screen and filter the variants. The candidate was validated by Sanger sequencing. Conservation analysis and homology modelling were conducted. RESULTS A heterozygous missense mutation c.1175C>T in the PTCH1 gene predicting p.Ala392Val was identified. This variant has not been reported and was predicted to be deleterious. Sanger sequencing verified the variant and the dominant inheritance model in the family. The missense alteration affects an amino acid that is evolutionarily conserved in the first extracellular loop of the PTCH1 protein. The local structure of the mutant protein was significantly altered according to homology modelling. CONCLUSIONS Our findings suggest that c.1175C>T in PTCH1 (NM_000264) may be the causative mutation of this pedigree. Our results add to the evidence that PTCH1 variants play a role in the pathogenesis of orofacial clefts.

Protective effects ROS up-regulation on premature ovarian failure by suppressing ROS-TERT signal pathway.

Abstract: OBJECTIVE Premature ovarian failure (POF) refers to the condition of pre-onset ovarian function failure, and is one commonly occurred disease in gynecology. Its pathogenic mechanism, however, is still unclear. Early study found decreased activity of telomerase reverse transcriptase (TERT). As an important factor to suppress TERT, oxidative stress has not been studied in POF. We, thus, investigated the role of reactive oxygen species (ROS)-TERT in POF. MATERIALS AND METHODS Rat POF model was induced by a single intraperitoneal injection of cyclophosphamide plus 12 mg/kg busulfan. Level of follicle stimulating hormone (FSH) and inhibin B was measured by enzyme-linked immunosorbent assay (ELISA), along with hematoxylin and eosin (HE) staining to confirm successful generation of models. Western blot was applied to measure TERT expression, and N-acetyl-cysteine (NAC) or TERT small interfere RNA (siRNA) was injected to suppress ROS or TERT level, followed by HE staining to observe POF condition. RESULTS In POF model, ovary tissues showed atrophy, less follicles, and more follicular atresia, plus mesenchymal hyperplasia. FSH and inhibin B level were significantly up-regulated and down-regulated, respectively (p<0.05). In POF rat, ROS level was elevated (p<0.05) whilst TERT level was decreased. NAC inhibited ROS level and enhanced TERT expression. In contrast, TERT siRNA further aggravated POF condition. CONCLUSIONS ROS up-regulation inhibits TERT expression, suppresses TERT activity and facilitates POF. The ROS-TERT pathway may work as the target for treating POF.

Correction: Epidemiological investigation into the prevalence of abnormal inter-arm blood pressure differences among different ethnicities in Xinjiang, China.

Abstract: Objectives The prevalence of and risk factors for IAD among different ethnicity groups was unknown. Our aim was to investigate the prevalence of and risk factors for IAD among Han, Uygur and Kazakh ethnicities in Xinjiang. China. Methods In total, 14,618 adult participants (7,799 males and 6,819 females) were recruited from the Cardiovascular Risk Survey. A 4-stage stratified cluster random sampling method was used. The participants’ personal information and medical history were assessed by questionnaire. IAD was diagnosed by a noninvasive arteriosclerosis analyzer. Results The prevalence of abnormal IAD among the general population was 14.3%, with 12.5% in the Han, 14.9% in the Uygur, and 16.4% in the Kazakh populations. The prevalence of abnormal IAD among the hypertensive population was 19.4%, with 17.0% in the Han, 18.1% in the Uygur, and 22.7% in the Kazakh populations. The prevalence of abnormal IAD increased with age (all P 0.05). Multivariate logistic regression analysis showed that age more than 45 years, obesity and hypertriglyceridemia were significantly associated with a higher prevalence of IAD. There were different risk factors for abnormal IAD in different ethnicities. Middle or old age, obesity, ABI and diabetes mellitus were risk factors for the Han population, smoking was a risk factor in the Uygur population, and obesity and PAD were risk factors in the Kazakh population. Conclusion The prevalence of abnormal IAD in the Kazakh participants was higher than that in the Han and Uygur populations among both the general population and the hypertensive population in Xinjiang, China. The main risk factors of IAD were age, obesity, and triglyceride levels. Different ethnicities had different kinds of risk factors for IAD.

[Comparative study of proximal femoral nail anti-rotation and dynamic hip screw in the unstable intertrochanteric fractures in the elderly].

Abstract: Objective: To compare the effect of proximal femoral nail anti-rotation and dynamic hip screw in treating the femoral intertrochanteric fractures in elderly patients. Methods: From June 2011 to June 2014, totally 158 elderly patients of femoral intertrochanteric fracture were treated by surgery, among whom 68 cases were treated with dynamic hip screws (DHS), and 90 patients were treated with proximal femoral nail anti-rotation (PFNA). The operative time, hospitalization time, weight-bearing time, fracture-healing time, blood loss and the hip function score after the operation were compared between the two groups by using the t test; and the incidence of the postoperative complication was compared between the two groups by using the Chi square test. Results: All the patients were followed-up for 6 to 18 months (12. 6 months on average). There was no statistic differences in the gender, age, the surgical time after injury and the fracture type between the two groups (χ(2)=0.025, t=1.461, 1.329, χ(2)=2.070, all P>0.05). While, the operative time, blood loss, hospitalization time and the weight-bearing time in the PFNA group were all significantly lower than those in the DHS group[(47±14) vs (114±20) min, (121±26) vs (281±44) ml, (10.2±3.3) vs (13.5±2.8) d, (29±8) vs (53±10) d, t=8.376, 6.669, 2.176, 2.664, all P 0.05]. Moreover, the incidence of complications in the DHS group was 16.2% while it was 7.8% in the PFNA group, the latter was obviously lower (χ(2)=4.801, P<0.05). Conclusions: DHS is suitable for the patients with good physical condition or for the patients with stable fracture types. While, PFNA has the advantages of firmly fixation, less tissue damage, lower complications and wide indications. So, it is superior in the femoral intertrochanteric fractures.

[Effects of bone marrow mesenchymal stem cell transplantation on the expression of stromal cell-derived factor-1α and vascular endothelial growth factor in rats with acute hepatic failure].

Abstract: Objective: To investigate the curative effect of bone marrow mesenchymal stem cells (BMSCs) transplantation on the expression of stromal cell-derived growth factor (SDF-1 α) and vascular endothelial growth factor (VEGF) in rats with acute hepatic failure, and to compare the effects of two transplantation pathways. Methods: Eighty-four rats with acute liver failure (ALF) induced by D-galactosamine combined with lipopolysaccharide were randomly divided into control group, tail vein and portal vein transplantation group. The latter two groups were injected allogenic BMSCs into the tail vein and portal vein. Blood samples and liver tissue samples were collected at 24, 72, 120, and 168h after transplantation to detect serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The improvement of liver function before and after BMSCs transplantation was compared. The expression of VEGF and SDF-1a in liver tissue was detected by immunofluorescence and Western blot. Data measurement between two groups was performed by analysis of variance and the correlation analysis was performed by Spearman's rank correlation coefficient. Results: Serum ALT and AST levels in the tail vein and portal vein transplantation group peaked at 24 h after transplantation, which were (134.60 ± 58.08 IU/L), (179.20 ± 86.68 IU/L), and (131.00 ± 54.47 IU/L), (173.50 ± 93.10 IU/L). In addition, 168h after transplantation it decreased to (46.10 ± 8.40 IU/L), (95.67 ± 13.80 IU/L) and (19.30 ± 1.30 IU/L), (54.30 ± 6.00 IU/L). After 120 and 168 hours of BMSCs transplantation, the levels of serum ALT and AST in tail vein and portal vein transplantation group were significantly higher than control group (F ≥ 12.51, P 0.05). Correlation analysis showed that the expression levels of SDF-1α and VEGF in liver tissues were positively correlated (r = 0.923, P < 0.05). Conclusion: BMSCs transplantation can promote the secretion of VEGF for recovery of liver function to reduce the degree of inflammation and necrosis in rats with ALF.

Inhibitory effects of candesartan on KCa3.1 potassium channel expression and cell culture and proliferation in peripheral blood CD4+T lymphocytes in Kazakh patients with hypertension from the Xinjiang region.

Abstract: BACKGROUND AND AIM Increasing evidence confirms that potassium channels are essential for lymphocyte activation, suggesting an involvement in the development of hypertension. Moreover, chronic inflammation is regarded as a direct or indirect manifestation of hypertension, highlighting the theoretical mechanisms. In this study, we investigated changes in KCa3.1 potassium channel expression in the blood of hypertensive and healthy Kazakh people in north-west China. METHODS Flow cytometry technology was used for T-lymphocyte subtype analysis. Changes in the messenger RNA and protein expression of the KCa3.1 potassium channel in CD4+ T lymphocytes were detected using real-time quantitative polymerase chain reaction and western blots, using CD4+ T-cell samples from hypertensive Kazakh patients divided into candesartan and TRAM-34 treatment groups, and healthy case controls. Peripheral blood CD4+ T lymphocytes were activated and proliferated in vitro and then incubated for 0, 24, and 48 h under various treatment conditions. Changes in CD4+ T-lymphocytic proliferation were determined using Cell Counting Kit-8 and electron microscope photography. RESULTS Expression of KCa3.1 was significantly higher in the hypertensive patients than in the controls (p < 0.05). Compared with the healthy group, Kazakh hypertensive patients had a reduced proportion of CD4+ T lymphocytes (p < 0.05).Candesartan and TRAM-34 intervention for 24 h and 48 h inhibited the expression of Kv1.3 and KCa3.1 at mRNA and protein level (p < 0.05). CONCLUSIONS Increase in functional KCa3.1 channels expressed in CD4+ T lymphocytes of Kazakh patients with hypertension was blocked by candesartan, providing theoretical support for hypertension treatment at the cellular ion channel level. Candesartan may potentially regulate hypertensive inflammatory responses by inhibiting T-lymphocytic proliferation and KCa3.1 potassium channel expression in CD4 + T lymphocytes.