Local, bivariate relationships between coronavirus 2019 (COVID-19) infection rates and a set of demographic and socioeconomic variables were explored at the district level in Oman. To limit multicollinearity a principal component analysis was conducted, the results of which showed that three components together could explain 65% of the total variance that were therefore subjected to further study. Comparison of a generalized linear model (GLM) and geographically weighted regression (GWR) indicated an improvement in model performance using GWR (goodness of fit=93%) compared to GLM (goodness of fit=86%). The local coefficient of determination (R2) showed a significant influence of specific demographic and socioeconomic factors on COVID-19, including percentages of Omani and non-Omani population at various age levels; spatial interaction; population density; number of hospital beds; total number of households; purchasing power; and purchasing power per km2. No direct correlation between COVID- 19 rates and health facilities distribution or tobacco usage. This study suggests that Poisson regression using GWR and GLM can address unobserved spatial non-stationary relationships. Findings of this study can promote current understanding of the demographic and socioeconomic variables impacting the spatial patterns of COVID-19 in Oman, allowing local and national authorities to adopt more appropriate strategies to cope with this pandemic in the future and also to allocate more effective prevention resources.
Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays and relates PRLR expression to survival of ovarian cancer. A database, composed of transcript profiles from OC, was searched for PRLR expression and results were put in relation to survival. Expression of PRLR in OC tissue sections and OC cell lines SKOV3, OV2008 and OVSAHO was assessed using immunohistochemistry, western blots and quantitative real-time PCR. The biological function of PRLR was evaluated by proliferation, colony formation and wound healing assays. Levels of PRLR mRNA are related to survival; in epithelial OC a high PRLR mRNA expression is related to a shorter survival. Analysis of a tissue micro array consisting of 84 OC showed that 72% were positive for PRLR immuno-staining. PRLR staining tended to be higher in OC of high grade tumors compared to lower grades. PRLR mRNA and protein can further be detected in OC cell lines. Moreover, in vitro treatment with PRL significantly activated the JAK/STAT pathway. PRLR expression is associated with OC survivals. PRL and its receptor may play an onco-modulatory role and promote tumor aggressiveness in OC. Alternatively, increased PRLR levels may form a base for the development of PRLR antagonist or PRLR antagonist-drug conjugate to increase selective uptake of anti-cancer drugs.
One of the potential biomarkers for ovarian cancer patients is high serum level of prolactin (PRL), which is a growth factor that may promote tumor cell growth. The prolactin receptor (PRLR) and human cytomegalovirus (HCMV) proteins are frequently detected in ovarian tumor tissue specimens, but the potential impact of HCMV infection on the PRL system have so far not been investigated. In this study, HCMV’s effects on PRL and PRLR expression were assessed in infected ovarian cancer cells (SKOV3) by PCR and Western blot techniques. The levels of both PRL and PRLR transcripts as well as the corresponding proteins were highly increased in HCMV-infected SKOV3 cells. Tissue specimens obtained from 10 patients with ovarian cancer demonstrated high expression of PRLR, HCMV-IE, and pp65 proteins. Extensive expression of PRLR was detected in all examined ovarian tumor tissue specimens except for one from a patient who had focal expression of PRLR and this patient was HCMV-negative in her tumor. In conclusion, PRL and PRLR were induced to high levels in HCMV-infected ovarian cancer cells and PRLR expression was extensively detected in HCMV-infected ovarian tissue specimens. Highly induced PRL and PRLR by HCMV infection may be of relevance for the oncomodulatory role of this virus in ovarian cancer.
Inflammatory bowel disease (IBD) is an immunologically mediated chronic intestinal disorder. Growth hormone (GH) administration enhances mucosal repair and decreases intestinal fibrosis in patients with IBD. In the present study, we investigated the effect of cellular sensitivity to GH via suppressor of cytokine signaling 2 (SOCS2) deletion on colitis and recovery. To induce colitis, wild type and SOCS2 knockout (SOCS2−/−) mice were treated with 3% dextran sodium sulphate (DSS), followed by a recovery period. SOCS2−/− mice showed higher disease activity during colitis with increased mRNA expression of the pro-inflammatory cytokines nitric oxide synthase 2 (NOS2) and interleukin 1 β (IL1-β). At recovery time point, SOCS2−/− showed better recovery with less fibrosis measured by levels of α-SMA and collagen deposition. Protein and mRNA expressions of transforming growth factor beta β1 (TGF-β1) receptors were significantly lower in SOCS2−/− mice compared to wild-type littermates. Using an in vivo bromodeoxyuridine (BrdU) proliferation assay, SOCS2−/− mice showed higher intestinal epithelial proliferation compared to wild-type mice. Our results demonstrated that deletion of the SOCS2 protein results in higher growth hormone sensitivity associated with higher pro-inflammatory signaling; however, it resulted in less tissue damage with less fibrotic lesions and higher epithelial proliferation, which are markers of GH-protective effects in IBD. This suggests a pleiotropic effect of SOCS2 and multiple cellular targets. Further study is required to study role of SOCS2 in regulation of TGFβ-mothers against the decapentaplegic homolog (Smad) pathway.
Ulcerative colitis is a chronic inflammation of the colonic mucosa. Gum Arabic (GA) has been reported to exert anti-inflammatory and antifibrotic activity. This study aimed to evaluate the effect of GA on disease activity in an experimental model of colitis. Dextran sodium sulfate (DSS) was used to induce colitis in C57BL/6 mice and the animals were then switched to normal drinking water to monitor recovery. Mice received 140 g/L GA before (pre-GA group) or after (post-GA group) induction of colitis. Disease activity and recovery were assessed by changes in body weight, disease activity index (DAI), and histological assessment. Gene expression of proinflammatory, anti-inflammatory, and fibrotic markers was measured in colonic tissues. Mice in the pre-GA group showed an increase in body weight, with no differences in DAI scores, during the recovery phase and had lower histological colitis scores than mice in the post-GA group, which showed higher DAI and histological scores during the recovery phase. During the recovery phase, mice in the pre-GA group showed increased expression of proinflammatory markers, while gene expression of the fibrotic markers, transforming growth factor β1 (TGFβ1) and procollagen I, was reduced. The reduced fibrotic marker expression was associated with reduced collagen staining and increased epithelial cell proliferation. Administration of GA had protective and alleviative effects on the severity of DSS-induced colitis, with a reduction in colonic fibrosis and TGFβ1 expression. These data warrant further in vitro and in vivo investigations on the effect of GA on fibroblast activity.
Ovarian cancer (OC) is a gynecological cancer characterized by high morbidity and mortality associated with poor survival outcomes. Bisphenol F (BPF), a widely used analog of bisphenol A (BPA), has recently gained attention due to its potential endocrine-disrupting properties and ubiquitous environmental presence. However, the carcinogenic potential of BPF in OC has not been well explored. This study investigates the effects of BPF on ovarian carcinogenesis by assessing its pathological impact on cellular processes, including cell proliferation, wound healing, and cell invasion. OC cells, SKOV3 were treated with varying concentrations of BPF (0.01–250 µM). Cell viability was assessed using Alamar Blue assay, and migration ability was analyzed using wound-healing assay. Further, the total antioxidative capability (T-AOC) was measured. Statistical analysis was performed using student’s-t-test/ANOVA, with a significance set at p < 0.05. BPF exhibited a dual role in cell viability, enhancing cell proliferation at low concentrations (1 µM: p = 0.034; 10 µM: p = 0.012) while exerting cytotoxic effects at higher concentrations (250 µM: p = 0.021). Further, a wound-healing assay demonstrated that a lower concentration, 1 µM BPF promoted cell migration (p = 0.0345), indicating its involvement in OC. However, a non-significant difference was observed in the invasive potential and T-AOC of BPF-treated SKOV3 cells. Our findings provide key insights into the effects of BPF on cellular processes linked with ovarian carcinogenesis, emphasizing the need for future experiments to comprehend its mechanisms of action.