Hepatocyte growth factor (HGF) gene transfer inhibits liver fibrosis by regulating aberrant cellular functions, while mutant matrix metalloproteinase-9 (mMMP-9) enhances matrix degradation by neutralizing the elevated tissue inhibitor of metalloproteinase-1 (TIMP-1). It was shown that ASH1 and EZH2 methyltransferases are involved in development of liver fibrosis; however, their role in the resolution phase of liver fibrosis has not been investigated. This study evaluated the role of ASH1 and EZH2 in two mechanistically different therapeutic modalities, HGF and mMMP-9 gene transfer in CCl4 induced rat liver fibrosis. Liver fibrosis was induced in rats with twice a week intraperitoneal injection of CCl4 for 8 weeks. Adenovirus vectors encoding mMMP-9 or HGF genes were injected through tail vein at weeks six and seven and were sacrificed one week after the second injection. A healthy animal group was likewise injected with saline to serve as a negative control. Rats treated with mMMP-9 showed significantly lower fibrosis score, less Sirius red stained collagen area, reduced hydroxyproline and ALT concentration, decreased transforming growth factor beta 1 (TGF-β1) mRNA and lower labeling indices of α smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) stained cells compared with HGF- or saline-treated rats. Furthermore, TIMP-1 protein expression in mMMP-9 group was markedly reduced compared with all fibrotic groups. ASH1 and EZH2 protein expression was significantly elevated in fibrotic liver and significantly decreased in mMMP-9- and HGF-treated compared to saline-treated fibrotic livers with further reduction in the mMMP-9 group. Conclusion: Gene transfer of mMMP-9 and HGF reduced liver fibrosis in rats. ASH1 and EZH2 methyltransferases are significantly reduced in mMMP-9 and HGF treated rats which underlines the central role of these enzymes during fibrogenesis. Future studies should evaluate the role of selective pharmacologic inhibitors of ASH1 and EZH2 in resolution of liver fibrosis.
Background/aims Extracorporeal shockwave therapy might be a considerable substitute to present treatment alternatives to reduce spasticity and improve range of motion in patients with cerebral palsy, which could improve their quality of life and gait pattern. The aim of this study was to investigate the effect of extracorporeal shockwave therapy on gait parameters in children with spastic diplegic cerebral palsy. Methods A total of 34 children with spastic diplegia (19 boys and 15 girls) participated in the study. Their ages ranged from 5–7 years (mean 5.8 ± standard deviation 1.2 years). They were randomly assigned into two equal groups, the study and the control group. Both groups received the traditional physiotherapy programme, three sessions a week consecutively for 3 months. Children in the study group also received extracorporeal shockwave therapy one session a week for 3 months. Results There was a significant improvement of spasticity, step length and stride width in the control group (P=0.017, 0.015, 0.033 respectively). Walking speed did not show a significant change in the control group (P=0.1). In the study group, there was a significant improvement in spasticity, stride length, stride width, and walking speed (P=0.0001, 0.005, 0.029, 0.014 respectively). Comparing the gained improvement in the study and the control group, the results showed that the improvement in the study group significantly exceeded that of the control group in spasticity, stride length, stride width and walking speed (P=0.0003, 0.011, 0.043, 0.002 respectively). Conclusions Extracorporeal shockwave therapy is effective in reducing spasticity and improving gait patterns in children with spastic diplegia cerebral palsy.
This study investigated the impact of the 2019 coronavirus disease (COVID-19) pandemic on health-related quality of life (HRQoL) and psychological status among Saudi adults, and whether physical activity modifies this association. The participants were 518 adults aged ≥18 years (67.4% men). Using an online survey, data regarding demographic information, the impact of COVID-19 (assessed by the Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders-5), HRQoL (Short Form-8), psychological distress (Depression, Anxiety and Stress Scale), and physical activity behavior (International Physical Activity Questionnaire-Short Form) were collected. The results demonstrate that adults reporting moderate or high levels of impact of COVID-19 had a lower HRQoL and higher psychological distress than adults reporting a low impact. HRQoL was higher for adults reporting any level impact (low, moderate, or high) of COVID-19 when they participated in recommended levels of physical activity (≥600 metabolic equivalent (MET)-min/week of total physical activity). Psychological distress was lower for adults reporting a high level of impact when they participated in recommended physical activity. Moderate or high levels of impact of COVID-19 were associated with a significantly lower HRQoL and higher psychological distress than the low impact of COVID-19. However, these associations were moderated by the recommended levels of physical activity.
Breast cancer is the leading cause of cancer-related death among women in Saudi Arabia. Many studies have suggested a strong correlation between vitamin D and multiple types of cancer. This study included 100 female Saudi patients with early or locally advanced breast cancer. Patients were recruited from King Faisal Hospital in Taif City, Saudi Arabia, from January 2020 to September 2020. We aimed to study the association between serum vitamin D, calcium, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and chemerin and breast cancer progression. The control group consisted of 100 healthy individuals. Serum levels of vitamin D, calcium, IL-6, TNF-α and chemerin were measured in all participants. Vitamin D was significantly decreased in patients with high-grade tumours ( p < 0.0001), obesity ( p = 0.013), negative oestrogen receptors ( p < 0.0001), negative progesterone receptors ( p < 0.0001) and positive HER2 receptors ( p < 0.0001). Vitamin D was also decreased in patients with large tumours ( p < 0.0001), axillary lymph node involvement ( p < 0.0001) and advanced-stage cancers ( p < 0.0001). Moreover, higher levels of IL-6, TNF-α and chemerin were significantly associated with the presence of breast cancer, particularly in its advanced stages. Vitamin D deficiency and elevated levels of IL-6, TNF- α and chemerin were associated with adverse clinicopathological features of breast cancer. Vitamin D deficiency and elevated inflammatory cytokines (IL-6, TNF-α and chemerin) were associated with the clinicopathological features of breast cancer in female Saudi patients.
Background/Aim: Vitamin D deficiency accelerates the onset of type 2 diabetes mellitus (T2DM). Polymorphisms in the vitamin D receptor (VDR) have been linked to coronary artery disease (CAD). This study aimed to evaluate the association of vitamin D deficiency and VDR polymorphism with CAD in T2DM. Patients and Methods: A total of 150 adult male and female subjects, aged from 40 to 60 years, were divided into three groups, each with 50 subjects; control group, T2DM, and T2DM with CAD. Fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), HDL-C, LDL-C, glycosylated hemoglobin (HbA1c), and 25-hydroxyvitamin D (25-OH D) were assessed. VDR genotypes (BsmI, Taq1 and FOK1) were investigated by polymerase chain reaction fragment length polymorphism. Results: There was a significant negative correlation between serum 25-OH D and FBG, TC, TG, and LDL-C levels, and a positive correlation with HDL-C levels in all diabetic patient groups. The risk of CAD was markedly higher in the group of T2DM with CAD in comparison to the control (p<0.0001) and the T2DM group. Regarding Taq1, there was also a significantly higher risk of CAD in Tt+tt genotypes and t allele in the T2DM with CAD group compared to control (p<0.001, 0.031 respectively). In addition, 25-OH D concentrations and the prevalence of VDR polymorphisms (BsmI, Taq1) were correlated with the risk of CAD. Conclusion: Deficiency of vitamin D and the prevalence of VDR polymorphisms (BsmI, Taq1) can serve as important markers for CAD.
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