Glucagon-like peptide-1 (GLP-1) receptor agonists as an effective approach for type 2 diabetes mellitus (T2DM) has been explored extensively, multi agonists based on GLP-1 may have better clinical benefits on obesity, Nonalcoholic steatohepatitis (NASH) and other metabolic diseases. To get multi agonists based on GLP-1, 15 conjugates were designed, synthesized, and tested for biological activity. GLP-1/glucagon dual receptor agonist E1 showed moderate long-acting hypoglycemic effect, CY-5 and CY-16 with GLP-1/GIP dual receptor agonistic activity exhibited longer duration of continuous blood glucose stabilization. The long-acting hypoglycemic effect was equal to that of semaglutide. Although they have lost the agonistic activity on glucagon receptor, chronic in vivo studies on T2DM mice and diet-induced obesity (DIO) mice showed that CY-5 can effectively reduce food intake, inhibit body weight gain, repair islets damage and improve the glucose tolerance. One month treatment on NASH mice showed that CY-5 can significantly lower the TG, TC, AST, ALT and LDL-C and increase the HDL-C. CY-5 can also improve the liver vacuolation, reduce fat accumulation and delay the process of the fibrosis. The liver protection effect is better than that of semaglutide. In summary, CY-5 is a promising candidate for the treatment of metabolic diseases and worthy for further development.
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http://dx.doi.org/10.1016/j.bioorg.2020.104492 | DOI Listing |
Nutrients
January 2025
Department of Anesthesiology, Cathay General Hospital, Taipei 280, Taiwan.
Knee osteoarthritis (OA) is a common and debilitating disorder marked by joint degradation, inflammation, and persistent pain. This study examined the possible therapeutic effects of curcumin and vitamin D on OA progression and pain in a rat knee OA model by anterior cruciate ligament transection and meniscectomy (ACLT + MMx). Male Wistar rats were categorized into five groups: control, curcumin-treated (100 mg/kg/day), vitamin D-treated (25 µg/kg/day), a combination of vitamin D and curcumin, and sham-operated.
View Article and Find Full Text PDFPharmaceuticals (Basel)
January 2025
School of Pharmacy and Pharmaceutical Sciences, Panoz Institute, Trinity College Dublin, D02 PN40 Dublin, Ireland.
The synthesis of ()-1-(1,3-diphenylallyl)-1-1,2,4-triazoles and related compounds as anti-mitotic agents with activity in breast cancer was investigated. These compounds were designed as hybrids of the microtubule-targeting chalcones, indanones, and the aromatase inhibitor letrozole. : A panel of 29 compounds was synthesized and examined by a preliminary screening in estrogen receptor (ER) and progesterone receptor (PR)-positive MCF-7 breast cancer cells together with cell cycle analysis and tubulin polymerization inhibition.
View Article and Find Full Text PDFMolecules
January 2025
College of Life Science, Liaoning Normal University, Dalian 116081, China.
Liver-expressed antimicrobial peptide 2 (LEAP-2) was originally discovered as an antimicrobial peptide that plays a vital role in the host innate immune system of various vertebrates. Recent research discovered LEAP-2 as an endogenous antagonist and inverse agonist of the GHSR1a receptor. By acting as a competitive antagonist to ghrelin, LEAP-2 influences energy balance and metabolic processes via the ghrelin-GHSR1a signaling pathway.
View Article and Find Full Text PDFGenes (Basel)
December 2024
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Background: Acute promyelocytic leukemia (APL) is characterized by abnormal promyelocytes and t(15;17)(q24;q21) . Rarely, patients may have cryptic or variant rearrangements. All-trans retinoic acid (ATRA)/arsenic trioxide (ATO) is largely curative provided that the diagnosis is established early.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Medigene Immunotherapies GmbH, 82152 Planegg-Martinsried, Germany.
Background/objectives: MDG1011 is an autologous TCR-T therapy developed as a treatment option for patients with myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). It is specific for the target antigen PReferentially expressed Antigen in MElanoma (PRAME). The recombinant TCR used in MDG1011 recognizes PRAME VLD-peptide presented by HLA-A*02:01-encoded surface molecules.
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