PTHrP/PTHR1 and TGF-β Levels Are Inversely Associated in Liver Regeneration

Background. Transforming growth factor (TGF)-β provides growth control in liver regeneration. We have recently demonstrated that TGF-β induced parathyroid hormone-related protein (PTHrP) expression and secretion, and PTHrP mediated TGF-β-induced apoptosis in liver cells. However, whether PTHrP signaling pathway is altered during liver regeneration is unknown. Therefore we used a murine hepatectomy model in this study and tested the hypothesis that both PTHrP and TGF-β signaling pathways are upregulated during liver regeneration.    Methods. Swiss Webster mice received 70% hepatectomy or sham operation and euthanized at different time points post-surgery for analyses. Liver regeneration was determined by liver/body weight and proliferating cell nuclear antigen (PCNA) staining. mRNA levels of TGF-β1, TGF-β receptors, PTHrP, and PTHrP receptor 1 (PTHR1) were measured by real-time quantitative PCR. Protein levels of TGF-β1 were measured by ELISA and PTHrP and PTHR1 were measured by Western blotting.      Results. After 70% hepatectomy, the liver regeneration began at 24 hours and was restored to 82% of original liver mass at day 7. TGF-β1 and its receptor levels increased at 24 and 48 hours after hepatectomy, while PTHrP levels decreased at 12 hours and PTHR1 levels decreased at 12, 24 and 48 hours after hepatectomy. The levels of these molecules returned to similar levels as that in sham animals thereafter.    Conclusion. We demonstrated that an upregulation of the TGF-β and its receptors were associated with a down-regulation of PTHrP/PTHR1 expression during liver regeneration, which may contribute to hepatocyte proliferation and regeneration after hepatectomy

The association between new generation oral contraceptive pill and the development of inflammatory bowel diseases

Background/AimsTo examine the association between use of oral contraceptive pills (OCPs) and the risk of developing inflammatory bowel diseases (IBD), in a modern cohort.MethodsA prospective nested case-control study across sites in the Asia-Pacific region was conducted; involving female IBD cases and asymptomatic controls. Subjects completed a questionnaire addressing questions related to OCP use. Primary outcome was the risk of development of IBD of those exposed to OCP versus non-exposure. Secondary outcomes were development of Crohn's disease (CD) versus ulcerative colitis (UC), and whether age of first use of OCP use may be associated with risk of IBD.ResultsThree hundred and forty-eight female IBD cases (41% CD, median age: 43 years) and 590 female age-matched controls were recruited. No significant association was found between OCP use and the risk of IBD (odds ratio [OR], 1.65; 95% confidence interval, 0.77–3.13; P=0.22), CD (OR, 1.55) or UC (OR, 1.01). The lack of association persisted when results were adjusted for age and smoking. IBD cases commenced OCP use at a younger age than controls (18 years vs. 20 years, P=0.049).ConclusionsIn this large cohort of subjects from the Asia-Pacific region, we found a modest but not significantly increased risk of developing IBD amongst OCP users

Irritable bowel syndrome : an update on diagnosis and management

Irritable bowel syndrome (IBS) is a common chronic relapsing disorder. A positive diagnosis, in conjunction with a multimodal approach to management, which includes dietary and lifestyle modifications as first-line treatment, followed by pharmacological and psychological therapies, engages and supports patients with IBS

Comparing persistence of new biologics to conventional anti-TNF alphas in adult patients with inflammatory bowel disease: a systematic review and meta-analysis protocol

Background Biological therapy is a cornerstone of managing moderate-to-severe inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn’s disease (CD). New biologics have been evolving over the past 20 years and selection of an agent remains challenging.Drug persistence measures the duration of time from initiation to discontinuation of a therapy, which can be a surrogate marker of drug tolerance and efficacy.Objectives The study aimed to compare drug persistence of new generation biologics for the treatment of UC and CD (vedolizumab, ustekinumab, certolizumab, tofacitinib, natalizumab and golimumab) with conventional anti-tumor necroisis factor alphas (anti-TNF alphas) (adalimumab and infliximab) in adult patients with IBD. Results of the study may provide guidance on the preferred first and subsequent lines of biological treatments in patients with IBD.Methods and analysis Search via electronic databases including EMBASE, MEDLINE, PubMed and clinical trial databases will be conducted on 10 March 2023 with eligible studies included from inception of 2017 to 2023. The primary outcomes are 1-year persistence of individual biologics with comparison of new biologics versus conventional anti-TNF alphas. A meta-analysis will be conducted using Review Manager V.5 and outcome will be presented as relative risk. Heterogeneity will be assessed with forest plot, χ2 and I2, followed with sensitivity analysis and subgroup analysis. Finally, the Grading of Recommendations Assessment, Development and Evaluation system will be used to assess the quality of evidence.Ethics and dissemination Ethical approval is not required as no private information of participants will be used. Results of the present study will be disseminated in a peer-reviewed journal or conference presentation.PROSPERO registration number CRD42023392236

The TGF-β superfamily as potential therapeutic targets in pancreatic cancer

The transforming growth factor (TGF)-β superfamily has important physiologic roles and is dysregulated in many pathologic processes, including pancreatic cancer. Pancreatic cancer is one of the most lethal cancer diagnoses, and current therapies are largely ineffective due to tumor resistance and late-stage diagnosis with poor prognosis. Recent efforts are focused on the potential of immunotherapies in improving therapeutic results for patients with pancreatic cancer, among which TGF-β has been identified as a promising target. This review focuses on the role of TGF-β in the diseased pancreas and pancreatic cancer. It also aims to summarize the current status of therapies targeting the TGF-β superfamily and postulate potential future directions in targeting the TGF-β signaling pathways