GLP-1 receptor agonists for the treatment of obesity: Role as a promising approach.

Obesity is a complex disease characterized by excessive fat accumulation which is caused by genetic, environmental and other factors. In recent years, there has been an increase in the morbidity, disability rate,and mortality due to obesity, making it great threat to people's health and lives, and increasing public health care expenses. Evidence from previous studies show that weight loss can significantly reduce the risk of obesity-related complications and chronic diseases. Diet control, moderate exercise, behavior modification programs, bariatric surgery and prescription drug treatment are the major interventions used to help people lose weight. Among them, anti-obesity drugs have high compliance rates and cause noticeable short-term effects in reducing obese levels. However, given the safety or effectiveness concerns of anti-obesity drugs, many of the currently used drugs have limited clinical use. Glucagon-like peptide-1 receptor (GLP-1R) agonists are a group of drugs that targets incretin hormone action, and its receptors are widely distributed in nerves, islets, heart, lung, skin, and other organs. Several animal experiments and clinical trials have demonstrated that GLP-1R agonists are more effective in treating or preventing obesity. Therefore, GLP-1R agonists are promising agents for the treatment of obese individuals. This review describes evidence from previous research on the effects of GLP-1R agonists on obesity. We anticipate that this review will generate data that will help biomedical researchers or clinical workers develop obesity treatments based on GLP-1R agonists.

Hydroxyurea ameliorates atherosclerosis in ApoE-/- mice by potentially modulating Niemann-Pick C1-like 1 protein through the gut microbiota.

Rationale: The efficacy and mechanism of hydroxyurea in the treatment of atherosclerosis have rarely been reported. The goal of this study was to investigate the efficacy of hydroxyurea in high-fat diet-fed ApoE-/- mice against atherosclerosis and examine the possible mechanism underlying treatment outcomes. Methods: ApoE-/- mice were fed a high-fat diet for 1 month and then administered hydroxyurea by gavage continuously for 2 months. Aortic root hematoxylin-eosin (H&E) staining and oil red O staining were used to verify the efficacy of hydroxyurea; biochemical methods and ELISA were used to detect changes in relevant metabolites in serum. 16S rRNA was used to detect composition changes in the intestinal bacterial community of animals after treatment with hydroxyurea. Metabolomics methods were used to identify fecal metabolites and their changes. Immunohistochemical staining and ELISA were used for the localization and quantification of intestinal NPC1L1. Results: We showed that aortic root HE staining and oil red O staining determined the therapeutic efficacy of hydroxyurea in the treatment of atherosclerosis in high-fat diet-fed ApoE-/- mice. Serological tests verified the ability of hydroxyurea to lower total serum cholesterol and LDL cholesterol. The gut microbiota was significantly altered after HU treatment and was significantly different from that after antiplatelet and statin therapy. Meanwhile, a metabolomic study revealed that metabolites, including stearic acid, palmitic acid and cholesterol, were significantly enriched in mouse feces. Further histological and ELISAs verified that the protein responsible for intestinal absorption of cholesterol in mice, NPC1L1, was significantly reduced after hydroxyurea treatment. Conclusions: In high-fat diet-fed ApoE-/- mice, hydroxyurea effectively treated atherosclerosis, lowered serum cholesterol, modulated the gut microbiota at multiple levels and affected cholesterol absorption by reducing NPC1L1 in small intestinal epithelial cells.

Identification and characterization of a Masculinizer (Masc) gene involved in sex differentiation in Artemia.

The sex of relatively primitive animals such as invertebrates is mostly determined by environmental factors and chromosome ploidy. Heteromorphic chromosomes may also play an important role, as in the ZW system in lepidopterans. However, the mechanisms of these various sex determination systems are still largely undefined. In the present study, a Masculinizer gene (Ar-Masc) was identified in the crustacean Artemia franciscana Kellogg 1906. Sequence analysis revealed that the 1140-bp full-length open reading frame of Ar-Masc encodes a 380-aa protein containing two CCCH-type zinc finger domains having a high degree of shared identities with the MASC protein characterized in the silkworm Bombyx mori, which has been determined to participate in the production of male-specific splice variants. Furthermore, although Ar-Masc could be detected in almost all stages in both sexual and parthenogenetic Artemia, there were significant variations in expression between these two reproductive modes. Firstly, qRT-PCR and Western blot analysis showed that levels of both Ar-Masc mRNA and protein in sexual nauplii were much higher than in parthenogenetic nauplii throughout the hatching process. Secondly, both sexual and parthenogenetic Artemia had decreased levels of Ar-Masc along with the embryonic developmental stages, while the sexual ones had a relatively higher and more stable expression than those of parthenogenetic ones. Thirdly, immunofluorescence analysis determined that sexual individuals had higher levels of Ar-MASC protein than parthenogenetic individuals during embryonic development. Lastly, RNA interference with dsRNA showed that gene silencing of Ar-Masc in sexual A. franciscana caused the female-male ratio of progeny to be 2.19:1. These data suggest that Ar-Masc participates in the process of sex determination in A. franciscana, and provide insight into the evolution of sex determination in sexual organisms.

Molecular characterization and functional analyses of a diapause hormone receptor-like gene in parthenogenetic Artemia.

In arthropods, mature females under certain conditions produce and release encysted gastrula embryos that enter diapause, a state of obligate dormancy. The process is presumably regulated by diapause hormone (DH) and diapause hormone receptor (DHR) that were identified in the silkworm, Bombyx mori and other insects. However, the molecular structure and function of DHR in crustaceans remains unknown. Here, a DHR-like gene from parthenogenetic Artemia (Ar-DHR) was isolated and sequenced. The cDNA sequence consists of 1410bp with a 1260-bp open reading frame encoding a protein consisting of 420 amino acid residues. The results of real-time PCR (qRT-PCR) and Western blot analysis showed that the mRNA and protein of Ar-DHR were mainly expressed at the diapause stage. Furthermore, we found that Ar-DHR was located on the cell membrane of the pre-diapause cyst but in the cytoplasm of the diapause cyst by analysis of immunofluorescence. In vivo knockdown of Ar-DHR by RNA interference (RNAi) and antiserum neutralization consistently inhibited diapause cysts formation. The results indicated that Ar-DHR plays an important role in the induction and maintenance of embryonic diapause in Artemia. Thus, our findings provide an insight into the regulation of diapause formation in Artemia and the function of Ar-DHR.

Methods of isolation, expansion, differentiating induction and preservation of human umbilical cord mesenchymal stem cells.

OBJECTIVE: This literature review aims to summarize the methods of isolation, expansion, differentiation and preservation of human umbilical cord mesenchymal stem cells (hUCMSCs), for comprehensive understanding and practical use in preclinical research and clinical trials. DATA SOURCES: All the literature reviewed was published over the last 10 years and is listed in PubMed and Chinese National Knowledge Infrastructure (CNKI). Studies were retrieved using the key word "human umbilical cord mesenchymal stem cells". RESULTS: Explants culture and enzymatic digestion are two methods to isolate hUCMSCs from WJ and there are modifications to improve these methods. Culture conditions may affect the expansion and differentiating orientations of hUCMSCs. In addition, hUCMSCs can maintain their multi-potential effects after being properly frozen and thawed. CONCLUSION: Considering their multi-potential, convenient and non-invasive accessibility, low immunogenicity and the reported therapeutic effects in several different preclinical animal models, hUCMSCs have immense scope in regeneration medicine as a substitute for MSCs derived from bone marrow or umbilical cord blood.