Article
Chemistry, Medicinal
Neng Jiang, Lin Jing, Qing Li, Sibiao Su, Qimeng Yang, Feng Zhou, Xinyu Chen, Jing Han, Chunli Tang, Weizhong Tang
Summary: Dual activation of the glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP-1R) can potentially lead to effective therapy for diabetes and obesity. Novel peptides with dual activity on GLP-1R and GCGR were discovered through rational design, with xGLP/GCG-15 showing promising anti-obesity and anti-diabetic effects in preclinical studies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Medicine, Research & Experimental
Chun Han, Yuqing Sun, Qimeng Yang, Feng Zhou, Xinyu Chen, Lintao Wu, Lidan Sun, Jing Han
Summary: The study identified a novel dual GLP-1R and GCGR agonist, which showed potential for treatment of diabetes and obesity by improving glucose control in vivo. The development of peptide 2c with balanced GLP-1R and GCGR activations and potent effects on glucose control suggests a promising new approach for antidiabetic and/or antiobesity drug development.
MOLECULAR PHARMACEUTICS
(2021)
Review
Endocrinology & Metabolism
Julian M. Yabut, Daniel J. Drucker
Summary: Glucagon-like peptide-1 (GLP-1) plays a significant role in improving liver health and is associated with the treatment of type 2 diabetes (T2D) and obesity using GLP-1 receptor agonists (GLP-1RA). GLP-1RA can reduce hepatic inflammation, steatosis, and fibrosis. They also decrease appetite and body weight, reduce lipoprotein secretion, and attenuate systemic and tissue inflammation, thus contributing to the improvement of metabolic-associated fatty liver disease (MAFLD).
Article
Integrative & Complementary Medicine
Li Qiang, Yang Qimeng, Han Jing, Liu Xiaohan, Fu Junjie, Yin Jian
Summary: Peptide dual agonists that target both GLP-1R and GCGR receptors have emerged as potential therapeutics for treating type 2 diabetes with obesity. O-GlcNAcylation was shown to improve the stability of a dual GLP-1R/GCGR agonist, leading to significant weight loss and hypoglycemic effects.
CHINESE JOURNAL OF NATURAL MEDICINES
(2022)
Review
Microbiology
Yuan Zeng, Yifan Wu, Qian Zhang, Xinhua Xiao
Summary: The gut microbiota and GLP-1 interact with each other, as gut microbiota metabolites stimulate GLP-1 secretion and affect its function and rhythm. The mechanism of action of GLP-1 on gut microbiota involves inflammatory response. Various interventions can affect the interaction between gut microbiota and GLP-1, which is of great significance for the treatment of metabolic diseases.
Review
Medicine, General & Internal
Stephanie A. Christenson, Benjamin M. Smith, Mona Bafadhel, Nirupama Putcha
Summary: Chronic obstructive pulmonary disease (COPD) is a global health problem that leads to high morbidity, mortality, and healthcare utilization. Its main causes are exposure to harmful particles, such as tobacco smoke and pollutants. Recent research has shown that various factors throughout the life course increase the risk of developing COPD. Innovations in omics and imaging techniques have provided greater understanding of the disease's pathophysiology, potentially leading to advancements in its prevention, diagnosis, and treatment. This review focuses on recent advances in the epidemiology, pathophysiology, imaging, diagnosis, and treatment of COPD.
Review
Respiratory System
Wenwen Wang, Aihua Mei, Hang Qian, Dongfeng Li, Hao Xu, Jishun Chen, Handong Yang, Xinwen Min, Chunlei Li, Li Cheng, Jun Chen
Summary: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease that causes progressive lung function decline and affects patients' quality of life. COPD patients are at increased risk of developing diabetes, and high blood glucose levels can worsen COPD progression. Glucagon-like peptide-1 receptor agonist (GLP-1RA), a new type of hypoglycemic agent, has potential benefits for COPD patients by reducing inflammation, oxidative stress, and airway remodeling. This study reviews the potential role of GLP-1RAs in COPD and proposes new ideas for COPD treatment.
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Chao-Shun Chan, Fong-Jhih Lin, Yao-Chang Chen, Yung-Kuo Lin, Satoshi Higa, Shih-Ann Chen, Yi-Jen Chen
Summary: GLP-1 receptor agonists reduce the risk of atrial fibrillation by regulating the activity of protein kinase A, calmodulin-dependent protein kinase II, and the Na+/Ca2+ exchanger, and by modulating intracellular calcium homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Xiaolong Zhang, Yuchen Cai, Zhihong Yao, Heng Chi, Yan Li, Jingjing Shi, Zhongbo Zhou, Lidan Sun
Summary: A novel GLP-1R/GCGR dual agonist, OXM-7, was discovered and shown to have potent and balanced efficacy on both receptors. In mice models, OXM-7 exhibited promising effects on glycemic control, weight loss, lipid metabolism, and hepatic steatosis reversal.
Article
Pharmacology & Pharmacy
Songfeng Zhao, Zhiming Yan, Yue Du, Zeyun Li, Chunli Tang, Lin Jing, Lidan Sun, Qimeng Yang, Xueling Tang, Yongliang Yuan, Jing Han, Neng Jiang
Summary: This study demonstrates the therapeutic potential of dual agonists targeting GLP-1/glucagon and GLP-1/CCK2 receptors in the treatment of obesity and diabetes. The newly developed peptide, xGLP-1/GCG/gastrin, showed significant anti-diabetes and anti-obesity effects in both in vitro and in vivo experiments.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Melek Tunc-Ata, Fatih Altintas, Hande Senol, Erol Nizamoglu, Vural Kucukatay
Summary: The study showed that ileal interposition surgery significantly improved hyperinsulinemia and lipid profile in a MetS rat model, normalized the Lee index and insulin resistance. The surgery did not affect GLP-1 secretion but increased pancreatic GLP-1R expression levels. These results suggest that ileal interposition may be beneficial in the treatment of MetS.
Article
Cell Biology
Yuanyuan Zhang, Xinyu Zhao, Xiaona Dong, Yuying Zhang, Haixia Zou, Yaoguang Jin, Wei Guo, Peng Zhai, Xu Chen, Alexei Kharitonenkov
Summary: Researchers have developed a GLP-1/GDF15 fusion protein and tested its potential for weight loss in animals. The molecule, QL1005, showed higher potency than the GLP-1 analog semaglutide in vitro. In obese mice, QL1005 led to reductions in body weight, food intake, insulin, fasting glucose, and triglycerides. In a cynomolgus monkey model of obesity, QL1005 dose-dependently reduced body weight, food intake, insulin, and glucose with limited side effects.
Article
Chemistry, Multidisciplinary
Siqi Wang, Yuqiong Wang, Long Lin, Zongjie Li, Fengyi Liu, Long Zhu, Jie Chen, Nianrong Zhang, Xinyu Cao, Sunman Ran, Genzheng Liu, Peng Gao, Weiliang Sun, Liang Peng, Jian Zhuang, Hua Meng
Summary: Intramuscular injection of BTX-A through dissolving microneedles in the gastric wall layers shows promising results in weight loss and metabolic improvement.
Review
Endocrinology & Metabolism
Junaid Iqbal, Hui-Xuan Wu, Nan Hu, Ying-Hui Zhou, Long Li, Fen Xiao, Ting Wang, Hong-Li Jiang, Shi-Na Xu, Bi-Ling Huang, Hou-De Zhou
Summary: This study provides an up-to-date systematic review and meta-analysis on the overall weight loss effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in adults with obesity and overweight without diabetes mellitus. The results show that GLP-1 RA leads to significant weight loss and improves glycemic control without increasing the risk of hypoglycemia. It also has positive effects on blood pressure and lipid levels.
Article
Cell Biology
Yan Liu, Zhenzhen Chen, Lei Liu, Haitao Tang, Huaqing Zhu, Songtao Tang
Summary: GLP-1 analogues exert a protective effect on endothelial barrier function in vascular diseases by inhibiting Moesin phosphorylation to maintain endothelial barrier integrity. Under diabetic conditions, the effects of GLP-1 on Moesin phosphorylation in endothelial cells are mediated through GLP-1R/cAMP/PKA activation and subsequent down-regulation of Rho/ROCK, p38, and PKC 13 signaling pathways.
CELLULAR SIGNALLING
(2022)
Article
Medicine, Research & Experimental
N. N. Ermakova, O. Pershina, M. A. Zhukova, A. Pakhomova, E. S. Pan, L. A. Sandrikina, V. A. Krupin, O. Yu Rybalkina, A. M. Dygai, E. G. Skurikhin
Summary: In female mice, damage to the mammary gland was observed at early stages, including epithelial and endothelial damage, inflammation, and fibrosis. However, no tumor was detected. Various stem cells, including cancer stem cells, hematopoietic stem cells, hematopoietic progenitor cells, and angiogenic precursors, were found in the blood and mammary gland. Cancer stem cells (CD44(+)CD24(-)) were proposed as early diagnostic markers for breast cancer, while short-living HSC, hematopoietic progenitor cells, and angiogenic precursors (CD45-CD117(+)FLK-1(+)) were predicted to be related to tumor microenvironment formation.
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Evgenii G. Skurikhin, Olga Pershina, Natalia Ermakova, Angelina Pakhomova, Darius Widera, Mariia Zhukova, Edgar Pan, Lubov Sandrikina, Lena Kogai, Nikolai Kushlinskii, Sergey G. Morozov, Aslan Kubatiev, Alexander Dygai
Summary: CD8(+) T-lymphocytes play a crucial role in the immune response against lung cancer. Reprogrammed T-lymphocytes, using MEK inhibitors and PD-1 blockers, show increased antitumor activity. This reprogramming approach demonstrates significant antitumor effects both in vitro and in vivo.
Article
Biochemistry & Molecular Biology
Evgenii G. Skurikhin, Natalia Ermakova, Mariia Zhukova, Olga Pershina, Edgar Pan, Angelina Pakhomova, Lena Kogai, Victor Goldberg, Elena Simolina, Victoria Skurikhina, Darius Widera, Aslan Kubatiev, Sergey G. Morozov, Nikolai Kushlinskii, Alexander Dygai
Summary: This study analyzed circulating tumor cells (CTCs) and cancer stem cells (CSCs) in patients with small cell lung cancer (SCLC) to search for new diagnostic and prognostic markers and novel approaches to improve the treatment of the disease. The results showed heterogeneity of CTCs and CSCs populations in blood, as well as resistance to chemotherapy. Additionally, a new approach using reprogrammed T-lymphocytes targeting CTCs and CSCs was demonstrated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
E. S. Pan, A. V. Pakhomova, N. N. Ermakova, S. A. Afanas'ev, T. Yu. Rebrova, M. A. Zhukova, L. A. Sandrikina, O. D. Putrova, L. V. Kogai, O. V. Pershina, A. M. Dygai, E. G. Skurikhin
Summary: The effect of ketanserin on inflammation, liver fibrosis, and microviscosity of the plasma and mitochondrial membranes of hepatocytes was studied on young and old male Wistar rats with experimental liver cirrhosis. Ketanserin reduced inflammation, area of connective tissue, and liver damage and improved serum biochemical parameters. In old rats, ketanserin had more pronounced effects, reducing the polarity of hepatocyte membranes and increasing effectiveness in treating liver cirrhosis.
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Evgenii G. G. Skurikhin, Olga Pershina, Natalia Ermakova, Angelina Pakhomova, Mariia Zhukova, Edgar Pan, Lubov Sandrikina, Darius Widera, Lena Kogai, Nikolai Kushlinskii, Aslan Kubatiev, Sergey G. G. Morozov, Alexander Dygai
Summary: This study demonstrates the potential of using a combination of MEK inhibitor and PD-1 blocker to reprogram human CD8(+) T-cells and target lung cancer cells, resulting in antimetastatic activity, decreased cancer cell and cancer stem cell numbers in the lungs, and increased T-cell numbers in the blood. These findings suggest a new approach to targeted lung cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Angelina Pakhomova, Olga Pershina, Pavel Bochkov, Natalia Ermakova, Edgar Pan, Lubov Sandrikina, Yulia Dagil, Lena Kogai, Wolf-Dieter Grimm, Mariia Zhukova, Sergey Avdeev
Summary: The study suggests that Longidaze is a new and promising drug for the treatment of idiopathic pulmonary fibrosis (IPF). It reduces pulmonary fibrosis and inhibits the inflammatory response, and has a greater therapeutic efficacy compared to the reference drug.