Article
Agriculture, Dairy & Animal Science
Mei Sun, Zinan Li, Yuanyuan Xing, Xiaojia Mu, Yue Cao, Yihong Hao, Jing Yang, Dabiao Li
Summary: This study showed that glucose availability within the range of 10.5 to 14 mM promoted alpha(S1)-casein synthesis, while higher concentrations of 17.5 to 21 mM inhibited it. The effects may be related to changes in glucose uptake, ATP content, and the phosphorylation of key proteins in the AMPK/mTOR signaling pathway.
JOURNAL OF ANIMAL SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Ling Lin, Yexin Zheng, Chao Wang, Pei Li, Duoling Xu, Wei Zhao
Summary: As zero-dimension nanoparticles, graphene oxide quantum dots (GOQDs) have the potential to regulate cell proliferation and differentiation. This study investigated the effect and molecular mechanism of GOQDs on the odontoblastic differentiation of dental pulp cells (DPSCs). The results showed that low concentrations of GOQDs promoted the proliferation and odontoblastic differentiation of DPSCs, possibly through the activation of the AMPK signaling pathway and inhibition of the mTOR signaling pathway.
Article
Pathology
Li Jia, Yan Chen, Fukun Chen, Juan Lv, Yanling Li, Fei Hou, Zhixian Yang, Zhiyong Deng
Summary: The study demonstrated that saRNA-mediated NIS expression plays a critical role in increasing iodide uptake through the AMPK/mTOR pathway in thyroid cancer. NIS-mediated autophagy regulates cell proliferation, apoptosis, and autophagy, ultimately affecting iodide uptake.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Biochemistry & Molecular Biology
Yingying Yue, Chang Zhang, Xiaoyun Zhao, Sasa Liu, Xiaoting Lv, Shitian Zhang, Jianming Yang, Liming Chen, Hongquan Duan, Youyi Zhang, Zhi Yao, Wenyan Niu
Summary: Research has shown that Tiam1 protein is part of an AMPK-Tiam1-Rac1 signaling pathway that mediates contraction-stimulated glucose uptake in skeletal muscle cells and tissue.
Article
Biochemistry & Molecular Biology
Camila Gherardelli, Pedro Cisternas, Joel Gutierrez, Milka Martinez, Nibaldo C. Inestrosa
Summary: Cerebral glucose hypometabolism is a common feature in many neurodegenerative diseases, and it has been shown that metabolic disturbances precede clinical symptoms. Andrographolide can enhance neuronal glucose uptake and metabolism, dependent on the activity of AMP-activated protein kinase.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Cell Biology
Tianhong Hu, Lin Wen, Liang Wang, Yang Qiao, Xie Cheng, Qigui Fan, Songqing Lai, Huan He, Ming He
Summary: Lut pretreatment can enhance autophagy to protect neonatal rat cardiomyocytes against anoxia-induced damage, possibly through upregulating 14-3-3 eta expression and affecting the AMPK alpha-mTOR/ULK1 pathway.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2023)
Article
Cell Biology
Dorota Gil, Marta Zarzycka, Joanna Pabijan, Ma lgorzata Lekka, Joanna Duli Dulinska-Litewka
Summary: Melanoma is resistant to chemotherapy and lacks fully effective targeted therapies. The mutations in melanoma lead to the hyperactivation of the MAPK and PI3K/AKT/mTOR pathways, which are responsible for abnormal protein synthesis. In this study, we investigated the effects of a specific PI3K/mTOR inhibitor, dactolisib, and Mnk inhibitor -CGP57380, alone and in combination on human melanoma cell lines. Both drugs showed inhibition of cell proliferation and migration when used individually, but their combination had additional antitumor effects. Simultaneous inhibition of both pathways may help overcome drug resistance.
CELLULAR SIGNALLING
(2023)
Article
Reproductive Biology
Chao Zhu, Qimin Liu, Yalong Deng, Lijuan Zheng, Yang Wang, Lijun Zhang, Xianpan Bu, Meng Qi, Fangxia Yang, Wuzi Dong
Summary: Appropriate additives can provide a suitable physiological environment for fish sperm storage and promote large-scale breeding. This study evaluated the effects of different concentrations of selenium nanoparticles on the quality of fish sperm during in vitro storage. Results showed that 0.5 mg/L selenium nanoparticles maintained the normal physiological state of fish sperm and enhanced glucose uptake capacity, thereby preserving sperm function.
Article
Nutrition & Dietetics
David C. Baron, Daniel M. Marko, Evangelia Tsiani, Rebecca E. K. MacPherson
Summary: Glucose is the primary metabolic substrate of neurons, and a decrease in glucose uptake is common in dementia. This study found that rosemary extract (RE) can increase neuronal glucose uptake, activate AMP-activated protein kinase (AMPK), and independently regulate glucose uptake in neurons.
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM
(2021)
Article
Pharmacology & Pharmacy
Eslam E. Abd El-Fattah, Sameh Saber, Mahmoud E. Youssef, Hanan Eissa, Eman El-Ahwany, Noha A. Amin, Mohammed Alqarni, Gaber El-Saber Batiha, Ahmad J. Obaidullah, Mohamed M. Y. Kaddah, Ahmed Gaafar Ahmed Gaafar, Ahmed A. E. Mourad, Gomaa Mostafa-Hedeab, Amir Mohamed Abdelhamid
Summary: This study demonstrates that sitagliptin inhibits the activation of HIF-1α by interfering with the AKT-AMPKα-mTOR axis and interrupting IKKβ, P38α, and ERK1/2 signals. Sitagliptin prolongs survival, improves liver function, inhibits angiogenesis and tissue invasion, promotes apoptosis, inhibits proliferation, reduces inflammation, and has antifibrotic potential.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Yuansheng Wu
Summary: Abnormal mitochondrial functions are a major pathophysiological basis of diabetic cardiomyopathy. This study found that activating AMPK can protect cardiomyocytes from high glucose-induced mitochondrial fragmentation and apoptosis, while inhibiting AMPK activity eliminates this protective effect.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Dorota Rogacka, Irena Audzeyenka, Patrycja Rachubik, Maria Szrejder, Marlena Typiak, Stefan Angielski, Agnieszka Piwkowska
Summary: In hyperglycemic conditions, the interaction between the protein deacetylase SIRT1 and adenosine monophosphate-dependent protein kinase (AMPK) in glomerular podocytes is altered. Modulating the NO synthase (NOS) / NO pathway can improve SIRT1 and AMPK activity, consequently enhancing glucose uptake.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Article
Food Science & Technology
Joo-Hui Han, Min-Tae Kim, Chang-Seon Myung
Summary: This study investigates the therapeutic effects and underlying mechanisms of Garcinia cambogia on glucose homeostasis in obesity-induced diabetes. The results show that Garcinia cambogia increases glucose uptake in muscle cells, activates signaling pathways, and regulates intracellular Ca2+ levels to facilitate glucose uptake. In a diabetes mouse model, Garcinia cambogia administration significantly lowers blood glucose levels.
MOLECULAR NUTRITION & FOOD RESEARCH
(2022)
Article
Agriculture, Dairy & Animal Science
Ziqi Liang, Chunjia Jin, Hanxun Bai, Gaofeng Liang, Xiaodong Su, Dangdang Wang, Junhu Yao
Summary: This study aimed to investigate the effects of reducing dietary rumen degradable starch (RDS) content by restricting corn processing on the growth performance and carcass traits of growing goats. The results showed that low RDS diet improved growth performance, increased glucose and amino acid utilization, and promoted protein synthesis in the skeletal muscle of goats. These findings suggest that reducing the content of dietary RDS enhances starch digestion and improves energy utilization in ruminants.
Article
Biochemistry & Molecular Biology
Ayumi Goto, Yuki Endo, Hitoshi Yamashita
Summary: The study investigates the role of CREG1 in skeletal muscle regeneration and glucose uptake. Results show that CREG1 stimulates glucose uptake in skeletal muscles partially through AMPK activation. This suggests that CREG1 plays an essential role in muscle regeneration by affecting glucose metabolism in skeletal muscles.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Education & Educational Research
Kimberly Vo, Mahbub Sarkar, Paul J. White, Elizabeth Yuriev
Summary: Problem solving is a fundamental skill that chemistry graduates should possess. This study explores the use of a metacognitive scaffold called Goldilocks Help to support structured problem solving and its impact on teaching and student learning. The findings reveal that teaching with the scaffold is beneficial, although initial student resistance was observed. The scaffold provides a common thinking structure between teaching associates and students, enabling easier identification of mistakes and addressing specific areas of concern.
CHEMISTRY EDUCATION RESEARCH AND PRACTICE
(2022)
Article
Chemistry, Medicinal
Navista Sri Octa Ujiantari, Seungmin Ham, Chisae Nagiri, Wataru Shihoya, Osamu Nureki, Dana Sabine Hutchinson, Daniela Schuster
Summary: This study utilized virtual screening and in vitro assays to confirm the biological activity of predicted β(3)-AR agonists. Several compounds showed activity against both human and mouse β(3)-AR.
MOLECULAR INFORMATICS
(2022)
Article
Pharmacology & Pharmacy
Jon Merlin, Julia Park, Teresa H. Vandekolk, Stewart A. Fabb, Jeanne Allinne, Roger J. Summers, Christopher J. Langmead, Darren M. Riddy
Summary: This study comprehensively shows how several natural mediators and synthetic ligands signal through three specialized proresolving mediator GPCRs using multiple ligands from different classes across four-six endpoint signaling assays. The potential of these receptors in treating specific autoimmune diseases, including rheumatoid arthritis, systemic scleroderma, and systemic lupus erythennatosus, is highlighted.
MOLECULAR PHARMACOLOGY
(2022)
Article
Chemistry, Organic
Jeroen P. J. Bruekers, Matthijs A. Hellinghuizen, Anne Swartjes, Paul Tinnemans, Paul B. White, Johannes A. A. W. Elemans, Roeland J. M. Nolte
Summary: The cadmium porphyrin cage compounds Cd1 and (113)Cd1 have been synthesized and form allosteric complexes with various positively charged guests. The X-ray structures of the coordination complexes were solved and Cd-113 NMR was employed to quantify the binding of guests and ligands to (113)Cd1.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Cheng Xue Qin, Lucy Norling, Elizabeth A. Vecchio, Eoin P. Brennan, Lauren T. May, Denise Wootten, Catherine Godson, Mauro Perretti, Rebecca H. Ritchie
Summary: This article discusses the pharmacology of formylpeptide receptor 2 (FPR2) and its complex biology. The authors propose that understanding FPR2 could lead to innovative treatments for chronic inflammatory conditions.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Jon Kyle Awalt, Anh T. N. Nguyen, Tim J. Fyfe, Bui San Thai, Paul J. White, Arthur Christopoulos, Manuela Joerg, Lauren T. May, Peter J. Scammells
Summary: The adenosine A(1) receptor is a therapeutic target for cardioprotection during myocardial ischemia and reperfusion injury. However, clinical translation of A(1)R agonists is hindered by dose-limiting adverse effects. The bitopic agonist VCP746, consisting of an adenosine pharmacophore linked to an allosteric moiety, has shown promising results in stimulating cardioprotective A(1)R signaling effects without unwanted bradycardia. This study investigates the structure-activity relationships of VCP746 and identifies the most potent A2BR agonist to date.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Anh T. N. Nguyen, Diep T. N. Nguyen, Huan Yee Koh, Jason Toskov, William MacLean, Andrew Xu, Daokun Zhang, Geoffrey I. Webb, Lauren T. May, Michelle L. Halls
Summary: The application of artificial intelligence in drug discovery for G protein-coupled receptors (GPCRs) is expanding rapidly. It can assist in understanding the actions of GPCRs, discovering new ligand-GPCR interactions, and predicting clinical responses. This article provides an overview of artificial intelligence concepts and its applications in different stages of GPCR drug discovery. The benefits and limitations of artificial intelligence are discussed, along with the potential for further development in assisting GPCR drug discovery.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Jo-Anne Baltos, Pablo M. Casillas-Espinosa, Ben Rollo, Karen J. Gregory, Paul J. White, Arthur Christopoulos, Patrick Kwan, Terence J. O'Brien, Lauren T. May
Summary: Epilepsy, a serious neurological condition, affects millions of people worldwide. Current pharmacotherapy only successfully controls seizures in about 70% of epilepsy patients, and many suffer from psychiatric and physical comorbidities. Adenosine, a natural substance, has shown potential as an anti-epileptic agent through its receptor activation. Recent advances have also shown that adenosine receptors can modulate epilepsy-associated comorbidities. This review provides an accessible resource on the use of the adenosine system as a therapeutic target for epilepsy and its associated comorbidities.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Bui San Thai, Ling Yeong Chia, Anh T. N. Nguyen, Chengxue Qin, Rebecca H. Ritchie, Dana S. Hutchinson, Andrew Kompa, Paul J. White, Lauren T. May
Summary: Heart failure remains a significant cause of morbidity and mortality worldwide. Current treatment options have limitations, leading to many patients progressing to advanced stages. Exploration of novel therapeutics targeting G protein-coupled receptors (GPCRs) has shown promise, but efficacy and unwanted effects remain as challenges.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Medicinal
Pierre Matricon, Anh T. N. Nguyen, Duc Duy Vo, Jo-Anne Baltos, Mariama Jaiteh, Andreas Luttens, Stefanie Kampen, Arthur Christopoulos, Jan Kihlberg, Lauren Therese May, Jens Carlsson
Summary: A structure-based virtual screening approach was used to design subtype-selective ligands for A1 and A2A adenosine receptors. The study identified a non-conserved subpocket in the binding sites that could be exploited to identify A1R selective ligands. Computational screening predicted 20 A1R selective ligands, with 7 of them exhibiting micromolar activities against A1R. Further optimization resulted in antagonists with nanomolar potency and up to 76-fold A1R-selectivity. This study demonstrates the potential of structure-based virtual screening in guiding the discovery and optimization of subtype-selective ligands, enabling the development of safer drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Endocrinology & Metabolism
Anh T. N. Nguyen, Quan L. Tran, Jo-Anne Baltos, Samantha M. McNeill, Diep T. N. Nguyen, Lauren T. May
Summary: G protein-coupled receptors (GPCRs) are targeted by approximately one-third of FDA-approved small molecule drugs. Among the four adenosine GPCR subtypes, the adenosine A(1) receptor (A(1)R) plays important physiological roles in humans. A(1)R has been identified as a potential therapeutic target for various conditions, but the development of small molecule drugs targeting A(1)R has been limited by unwanted effects. An alternative approach using A(1)R allosteric modulators that target a different binding site shows promise in overcoming these limitations. This review provides insights into the therapeutic potential of A(1)R and recent advances in understanding its allosteric modulation.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)