Liver regeneration is impaired in patients suffering from alcohol-associated liver (ALD) diseases. Wnt ligands and their FZD receptors are dysregulated in diseased livers. R-spondin and their receptors are known to regulate Wnt activity via the stabilization of FZD receptors. Here, we investigated the components of the Wnt and R-Spondin-signaling pathways and their activity in patients with ALD. We found that while hepatocytes retained high levels of differentiation markers such as ASGR1 and ASGR2 , the expression of two R-spondin co-receptors, LGR4 and LGR5 , and of CYP1A2 and Wnt target genes were strongly reduced.SZN-043, a hepatocyte-targeted R-Spondin mimetic, is a new investigational drug that stimulates the physiological Wnt repair pathway and proliferation of hepatocytes. Here, we show that SZN-043 induced hepatocyte proliferation in all models tested, including humanized mouse livers, a chronic-binge alcohol-induced liver injury, and a CCl 4 -induced fibrosis mouse model. Altogether, SZN-043 could be beneficial for the treatment of ALD.
Abstract Background Disruption of the colon epithelial barrier is a characteristic of ulcerative colitis (UC), allowing luminal microbes to come into contact with intestinal immune cells resulting in inflammation. All approved UC treatments are anti-inflammatory drugs and because they do not directly heal the epithelial barrier, the intestinal immune system continues to be exposed to gut microbes, resulting in low remission rates. Physiological Wnt signaling is fundamental to intestine epithelial homeostasis and renewal. Modulation of Wnt signaling might present an opportunity to achieve histological remission, which is associated with an improved clinical course, in UC. Previously, in vivo overexpression or administration of exogenous R-Spondin (RSPO), which amplifies Wnt signaling by increasing the amount of Wnt receptors on the cell surface, was reported to show effects on the intestine epithelium and helped regenerate intestine epithelium in various injury models. However, RSPO was also reported, to induce hyperplasia in normal intestine epithelium. Wnt signaling may also be modulated with recently developed Wnt mimetics which mimic endogenous Wnt proteins and activate downstream β-catenin signaling upon engaging with receptors of Wnts. The objective of the current study was to compare the effect of these two approaches in an acute DSS model. Methods Utilizing a mouse acute DSS colitis model, we compared the epithelial healing effects of a Surrozen proprietary Wnt mimetic, R2M3-26, RSPO2, and combination treatments of R2M3-26 and RSPO2. Animals received 4% (wt/vol) dextran sulfate sodium (DSS) in drinking water for 7 days followed by 1% DSS in drinking water from day 8. Protein treatments began on day 4. Disease activity, body weight (BW), fecal score, and occult blood were measured daily. Animals were terminated on day 10 for colon and small intestine histology as well as a serum cytokine panel. Results DSS damage to the colon epithelium was visible by H&E stain at day 4 and day 7 and continued to progress. We observed reduced mRNA expression of Wnt target genes and Wnt ligands in the colon, suggesting compromised Wnt signaling in the tissue. R2M3-26, RSPO2, and the combination treatments were efficacious in improving Disease Activity Index (DAI) and reducing serum cytokine levels. However, both RSPO treatments and combination treatments caused hyperproliferation of epithelium in the small intestine and the colon, consistent with what was reported in normal mice. Conclusion The Surrozen Wnt mimetic, R2M3-26, repaired the DSS damaged colon epithelium without causing hyperproliferation of epithelial cells in the intestine, making it a potential therapeutic platform for IBD.
Background During the COVID-19 pandemic, telemedicine is a quickest expanding service solution to provide improved access to sophisticated healthcare that is efficient, cost-effective, and time-consuming. Methods This analysis is evaluated on the basis of several studies that look at the history, benefits, various techniques, challenges, uses, and impact of telemedicine in the treatment of heart failure and cardiac rehabilitation as during COVID-19 outbreak. Results Patients avoided or refused medical treatment during COVID-19 pandemic despite the risk of illness and the threat of infections spreading. Telemedicine has become a non-traditional form of care delivery due to better access and high-end technologies such as virtual consultations, face-to-face video, smartphone visits, two-way text communication, distant patient history, and distal characteristic assessment. Remote monitoring can help manage cardiovascular disease risk factors and increase patient participation in blood pressure, heart failure data, and workout or other activity progress. Conclusion Based on the findings of past studies, we can infer that telemedicine is still an emerging subject in the treatment and management of cardiovascular disease. Telemedicine and similar technologies will also revolutionize healthcare services by expanding their reach and providing a big pool of database for better research and analysis.
BACKGROUND: Chronic migraine (CM) is a common neurologic disorder that imposes substantial burden on payers, patients, and society. Low rates of persistence to oral migraine preventive medications have been previously documented; however, less is known about persistence and costs associated with innovative nonoral migraine preventive medications.
Background Engineered nanoparticles (ENPs) such as TiO2 are widely used in products such as cosmetics, clothing, food packaging, drug delivery systems, etc. due to their unique physicochemical properties. This has increased the liklihood of ENP exposure in humans. As the ENPs are having small size and high diffusion coefficient, they can migrate rapidly in the air. Therefore, inhalation is considered to be the primary route of exposure to such ENPs. Hence, in the present study an attempt was made to assess the potential toxicological effects of TiO2 NPs in human alveolar cell line (A549).
Background Postoperative atrial fibrillation (POAF) is one of the most common complications following cardiac surgery. POAF is associated with increased hospitalization costs, but its long-term economic burden is not well defined.
Evaluate real-world persistence rates and costs among patients with chronic migraine (CM) treated with onabotulinumtoxinA (onabotA [BOTOX®]) or calcitonin gene–related peptide monoclonal antibody (CGRP mAb).
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