A GLP-1/GLP-2 receptor dual agonist to treat NASH: Targeting the gut-liver axis and microbiome.

BACKGROUND AND AIMS: Currently there is no Food and Drug Administration-approved drug to treat NAFLD and NASH, the rates of which are increasing worldwide. Although NAFLD/NASH are highly complex and heterogeneous conditions, most pharmacotherapy pipelines focus on a single mechanistic target. Considering the importance of the gut-liver axis in their pathogenesis, we investigated the therapeutic effect of a long-acting dual agonist of glucagon-like peptide (GLP)-1 and GLP-2 receptors in mice with NAFLD/NASH. APPROACH AND RESULTS: C57BL/6J mice were fed a choline-deficient high-fat diet/high fructose and sucrose solution. After 16 weeks, mice were randomly allocated to receive vehicle, GLP1-Fc, GLP2-Fc, or GLP1/2-Fc fusion (GLP1/2-Fc) subcutaneously every 2 days for 4 weeks. Body weight was monitored, insulin/glucose tolerance tests were performed, feces were collected, and microbiome profiles were analyzed. Immobilized cell systems were used to evaluate direct peptide effect. Immunohistochemistry, quantitative PCR, immunoblot analysis, tunnel assay, and biochemical assays were performed to assess drug effects on inflammation, hepatic fibrosis, cell death, and intestinal structures. The mice had well-developed NASH phenotypes. GLP1/2-Fc reduced body weight, glucose levels, hepatic triglyceride levels, and cellular apoptosis. It improved liver fibrosis, insulin sensitivity, and intestinal tight junctions, and increased microvillus height, crypt depth, and goblet cells of intestine compared with a vehicle group. Similar effects of GLP1/2-Fc were found in in vitro cell systems. GLP1/2-Fc also changed microbiome profiles. We applied fecal microbiota transplantation (FMT) gain further insight into the mechanism of GLP1/2-Fc-mediated protection. We confirmed that FMT exerted an additive effect on GLP1-Fc group, including the body weight change, liver weight, hepatic fat accumulation, inflammation, and hepatic fibrosis. CONCLUSIONS: A long-acting dual agonist of GLP-1 and GLP-2 receptors is a promising therapeutic strategy to treat NAFLD/NASH.

Clinical Efficacy of 1% CHX Gluconate Gel and 0.12% CHX Solution: A Randomized Controlled Trial.

Chlorhexidine (CHX) is an effective antibacterial agent and is used in dental treatment in several formulations. The aim of this study was to compare the effectiveness of CHX solution and CHX gel on dental plaque inhibition and gingivitis relief by a randomized clinical trial. Thirty-eight participants were randomly divided into two groups: control group (0.12% CHX solution) and test group (1% CHX gel). Participants were provided with CHX products and were instructed to use each product in the morning and evening for 1 week. Clinical results were evaluated by analyzing the collected data of Turesky et al. the modified Quigley-Hein Plaque Index (TQHPI), gingival index (GI) and the BANA test. Measurements were conducted 4 weeks and 8 weeks after using chlorhexidine products. The results were analyzed using repeated measured ANOVA and paired t-test. TQHPI and GI were significantly different after treatments in both groups (p < 0.001). The GI decreased more in the test group compared to the control group 4 weeks and 8 weeks later. In both groups, the BANA score also significantly decreased (p < 0.001) after 8 weeks, though the BANA score decreased relatively more in the CHX gel group than the CHX solution group. These results suggest that 1% CHX gel is more effective in reducing gingivitis and bacteria of periodontal disease than the 0.12% CHX solution. Therefore, the 1% CHX gel is expected to be actively used for non-surgical treatment of periodontal disease patients.

Physicians' attitudes towards the media and peer-review selection of the 'best cancer doctor': comparison of two different selection methods.

OBJECTIVES: The choice of doctor is an important issue for patients with cancer, and the reputation of the doctor is the single most important factor for patients to choose a doctor. Media are providing information about the 'best cancer doctor', but they vary widely in their selection methodology. We investigated cancer physicians' attitudes towards the selection of the 'best cancer doctor' by the media, by comparing two different selection methodologies: selection by media personnel or selection through peer-review system. DESIGN: Nationwide, cross-sectional survey. SETTING: National Cancer Center and 12 Regional Cancer Centers across Korea. PARTICIPANTS: A total of 680 cancer care physicians participated in the survey (75.5% participation rate), and two were excluded due to incomplete response. MAIN OUTCOME MEASURES: Physicians' opinions on the credibility, fairness, validity, helpfulness to patients, their intention to use the information and helpfulness to improve the quality of cancer care of the two different methods. RESULTS: Only a few physicians believed that the selection method of the 'best cancer doctor' by the media personnel was credible (9.1%), fair (6.1%) or valid (10.0%). In contrast, the majority agreed that the peer-selection method of the 'best doctor' is credible (74.7%), fair (64.7%) and valid (67.4%). More physicians believed the latter methods would be useful for patients when selecting their doctor (38.5% vs 82.2%) and may lead to improvement of the quality of cancer care from the perspective of the healthcare system (12.6% vs 59.8%). The need for ensuring objectiveness and transparency was also raised. CONCLUSION: Physicians showed different attitudes towards two different selection methods. Regulations or guidelines for selecting the 'best cancer doctor' and for disclosing the information should be considered in order to control the quality of the information and to protect the customers.

Reduced serum level of antibodies against amyloid beta peptide is associated with aging in Tg2576 mice.

Both active and passive immunization to eliminate amyloid plaques from the brain of patients with Alzheimer's disease (AD) have confirmed that amyloid beta (Abeta) vaccination does not only result in clearance of Abeta plaques but improves behavioral-cognitive deficits in animal models of AD. In the present study, the levels of naturally occurring serum antibodies against Abeta were measured in Tg2576 mice at various ages using ELISA to determine the relationship between aging and the level of anti-Abeta autoantibody. The level of anti-Abeta antibody fell significantly at the age of 9 months, at the age when amyloid plaques started to appear in the brain of Tg2576 mice, and was persistently low thereafter. However, serum immunoglobulin (Ig) level was elevated in older transgenic mice compared with younger transgenic mice suggesting that the reduced level of anti-Abeta autoantibody was not merely due to deterioration of the immune response in aged Tg2576 mice.