XB130 inhibits healing of diabetic skin ulcers through the PI3K/Akt signalling pathway.

BACKGROUND: Diabetic skin ulcers, a significant global healthcare burden, are mainly caused by the inhibition of cell proliferation and impaired angiogenesis. XB130 is an adaptor protein that regulates cell proliferation and migration. However, the role of XB130 in the development of diabetic skin ulcers remains unclear. AIM: To investigate whether XB130 can regulate the inhibition of proliferation and vascular damage induced by high glucose. Additionally, we aim to determine whether XB130 is involved in the healing process of diabetic skin ulcers, along with its molecular mechanisms. METHODS: We conducted RNA-sequencing analysis to identify the key genes involved in diabetic skin ulcers. We investigated the effects of XB130 on wound healing using histological analyses. In addition, we used reverse transcription-quantitative polymerase chain reaction, Western blot, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining, immunofluorescence, wound healing, and tubule formation experiments to investigate their effects on cellular processes in human umbilical vein endothelial cells (HUVECs) stimulated with high glucose. Finally, we performed functional analysis to elucidate the molecular mechanisms underlying diabetic skin ulcers. RESULTS: RNA-sequencing analysis showed that the expression of XB130 was up-regulated in the tissues of diabetic skin ulcers. Knockdown of XB130 promoted the healing of skin wounds in mice, leading to an accelerated wound healing process and shortened wound healing time. At the cellular level, knockdown of XB130 alleviated high glucose-induced inhibition of cell proliferation and angiogenic impairment in HUVECs. Inhibition of the PI3K/Akt pathway removed the proliferative effects and endothelial protection mediated by XB130. CONCLUSION: The findings of this study indicated that the expression of XB130 is up-regulated in high glucose-stimulated diabetic skin ulcers and HUVECs. Knockdown of XB130 promotes cell proliferation and angiogenesis via the PI3K/Akt signalling pathway, which accelerates the healing of diabetic skin ulcers.

Association of conventional risk factors for cardiovascular disease with IMT in middle-aged and elderly Chinese.

To study the association between known risk factors for cardiovascular disease and intima-media thickness (IMT) in the carotid and popliteal arteries in middle-aged and elderly Chinese adults. 686 middle aged and elderly Chinese adults from the China Da Qing Diabetes Prevention Study who had full clinical, laboratory, ultrasound examination results were enrolled in the study. Common carotid artery (CCA) and popliteal artery (PA) IMT were obtained using high resolution ultrasound machine. Pearson's or Spearman's correlation analysis and logistic regression analysis were used to determine association between risk factors [age, gender, tobacco smoking, body mass index (BMI), diabetes mellitus (DM), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, total triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, glycosylated hemoglobin (HbA1c)] and CCA- or PA-IMT. The age range of the study population was 45-87 years, 384 of them (56 %) were women. The prevalence of high blood pressure and DM was 60.6 and 68.8 %, respectively. Participants in DM group tended to be older, had greater value for SBP, HbA1c and PA-IMT, but smaller value for DBP than those in control group. Smoke status, BMI, blood lipids and CCA-IMT were not statistically different between groups. Pearson's or Spearman's rank correlation analysis showed that CCA-IMT had a positive correlation with age, gender, DM, SBP, BMI and HbA1c, negative correlation with HDL-C. PA-IMT showed a positive correlation with age, gender and SBP. Univariate logistic regression analysis showed that elevation of age, SBP, BMI, HbA1c and having DM were significant predictors of CCA-IMT thickening, so was reduction of HDL-C. Risk factors that predicted significant thickening of PA-IMT were age, gender, tobacco smoking. After adjusted for age and gender, except HDL-C, the other four risk factors (SBP, BMI, HbA1c and having DM) that predicted CCA-IMT thickening remained significant; however none of the risk factors predicted PA-IMT thickening after adjusted for age and gender. The current results provide evidence that CCA-IMT is a superior marker for atherosclerosis compared with PA-IMT. Aggressive control of SBP, HbA1c and proper control of weight may postpone thickening of CCA-IMT.