Article
Biochemistry & Molecular Biology
Ting Ling, Siyi Li, Huan Chen, Qiuping Wang, Jing Shi, Yirong Li, Wenjun Bao, Kunming Liang, Hai-long Piao
Summary: This study reveals the discovery of a GS SUMOylation deficient mutant that exhibits reduced response under glutamine starvation. The SUMOylation impairs the protein stability and enzymatic activity of GS. SAE1, Ubc9, and PIAS1 are identified as the assembly enzymes of GS SUMOylation, while Senp1/2 functions as a SUMO-specific protease to reverse the SUMOylation of GS.
Article
Cell Biology
Ying-chen Xia, Jian-hua Zha, Yong-Hua Sang, Hui Yin, Guo-qiu Xu, Jie Zhen, Yan Zhang, Ben-tong Yu
Summary: Activation of AMPK by ASP4132 effectively inhibits NSCLC cell growth in vitro and in vivo, inducing apoptosis, causing mitochondrial dysfunction and autophagy. AMPK activation also leads to downstream events including mTORC1 inhibition, receptor tyrosine kinase degradation, Akt inhibition, and programmed necrosis.
CELL DEATH & DISEASE
(2021)
Article
Cell & Tissue Engineering
Yu Liu, Xiangxian Zhang, Wei Wang, Ting Liu, Jun Ren, Siyuan Chen, Tianqi Lu, Yan Tie, Xia Yuan, Fei Mo, Jingyun Yang, Yuquan Wei, Xiawei Wei
Summary: Ammonia plays an important role in cellular metabolism but is considered toxic. Bone marrow-derived mesenchymal stem cells can convert ammonia and glutamate to glutamine via glutamine synthetase activity, supporting cell proliferation. Glutamine activates signaling pathways to stimulate cell proliferation.
Article
Veterinary Sciences
Caroline M. M. Loos, Kyle R. McLeod, Eric S. Vanzant, Sophie A. Stratton, Adam D. Bohannan, Robert J. Coleman, David A. van Doorn, Kristine L. Urschel
Summary: The objective of this study was to analyze the temporal changes of phosphorylation patterns of mTOR signaling proteins in horses with and without insulin dysregulation in response to two different dietary protein sources. The results showed that consuming higher quality protein sources resulted in greater postprandial activation of the mTOR pathway, and insulin dysregulation did not impair the postprandial activation of mTOR and rpS6 proteins.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Immunology
Chunhong Huang, Junwei Shao, Congcong Lou, Fengtian Wu, Tiantian Ge, Hainv Gao, Xiaoping Zheng, Xuejun Dong, Lichen Xu, Zhi Chen
Summary: Patients with decompensated HBV-related liver cirrhosis (HBV D-LC) exhibit compromised immune responses, leading to increased susceptibility to infections and reduced responsiveness to vaccines. This study found that B cells from HBV D-LC patients displayed impaired energy metabolism after T cell-dependent activation, characterized by decreased oxidative phosphorylation and glycolysis, potentially due to reduced glucose uptake, mitochondrial dysfunction, and attenuated activation of the AKT/mTOR pathway. Understanding the regulation of B cell metabolism and potential interventions may improve immune responses and vaccine sensitivity in these patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Geriatrics & Gerontology
Satoru Ato, Hiroshi Matsunami, Riki Ogasawara
Summary: The purpose of this study was to investigate if aging affects the influence of nutritional status on muscle protein metabolism during contraction. The study found that there were no differences in muscle protein synthesis between young and old mice in the fasted state. However, in the fed state, young mice had higher basal muscle protein synthesis and contraction only increased muscle protein synthesis in young mice. The results indicate that aging impairs the integration of signals from muscle contraction and nutrition, leading to anabolic resistance to muscle contraction in the postprandial state.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Medicine, Research & Experimental
Hui Gong, Xing Lyu, Yang Liu, Naling Peng, Shengyu Tan, Lini Dong, Xiangyu Zhang
Summary: Eupatilin alleviates pulmonary fibrosis through the Sestrin2/PI3K/Akt/mTOR-dependent autophagy pathway, reducing the expression of fibrotic markers. This study provides a new insight and potential drug target for the treatment of IPF.
Article
Physiology
Siriguleng, Teruhiko Koike, Yukie Natsume, Haiying Jiang, Lan Mu, Yoshiharu Oshida
Summary: This study found that EPA can enhance hypertrophy of the soleus muscle but not the plantaris muscle. In the soleus muscle, EPA administration did not enhance the expression or phosphorylation of the AKT-mTOR-S6K pathway.
PHYSIOLOGICAL RESEARCH
(2021)
Article
Chemistry, Medicinal
Lingli Li, Ping Liu, Yanbo Xie, Yunxiao Liu, Zhaolin Chen, Yadi Geng, Lei Zhang
Summary: The study evaluated the effect of xanthatin on the energy metabolism of human colon cancer cells, finding that xanthatin significantly inhibited cell migration and invasion by reducing ATP production and promoting lactate accumulation. Xanthatin also inhibited glycolysis and promoted oxidative phosphorylation, potentially through the inhibition of the mTOR signaling pathway. These results suggest that xanthatin may have potential as a botanical drug against abnormal tumor energy metabolism.
DRUG DEVELOPMENT RESEARCH
(2022)
Review
Immunology
Rajat Atre, Rahul Sharma, Gaponenko Vadim, Kundan Solanki, Khandu Wadhonkar, Neha Singh, Pramod Patidar, Rakhi Khabiya, Harshita Samaur, Sreeparna Banerjee, Mirza S. Baig
Summary: This review summarizes the importance of adaptor proteins in regulating immune responses and their roles in macrophage-mediated signaling in chronic diseases. Adaptor molecules serve as bridges between receptors and other molecules in different signaling pathways. Targeting these adaptors could be a promising therapeutic strategy against chronic inflammatory diseases.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Physiology
Satoru Ato, Takahiro Mori, Yuki Fujita, Taiga Mishima, Riki Ogasawara
Summary: The short-term high-fat diet induced lipid accumulation and insulin resistance, but did not affect the response of muscle protein synthesis to acute resistance exercise. The activation of mTORC1 and muscle protein synthesis in response to acute resistance exercise was not altered by the high-fat diet.
JOURNAL OF APPLIED PHYSIOLOGY
(2021)
Article
Orthopedics
Alexander R. Keeble, Camille R. Brightwell, Christine M. Latham, Nicholas T. Thomas, C. Brooks Mobley, Kevin A. Murach, Darren L. Johnson, Brian Noehren, Christopher S. Fry
Summary: ACL tear leads to muscle atrophy and deficits in protein synthesis and anabolic signaling. These deficits occur before significant muscle atrophy.
AMERICAN JOURNAL OF SPORTS MEDICINE
(2023)
Article
Oncology
Petra Hyrossova, Marc Arago, Juan Moreno-Felici, Xiarong Fu, Andres Mendez-Lucas, Pablo M. Garcia-Roves, Shawn Burgess, Agnes Figueras, Francesc Vinals, Jose C. Perales
Summary: PEPCK-M is implicated in the regulation of tumor growth phases and proteostasis mechanisms, with its activity affecting cell anabolism and survival. Inhibition or silencing of PEPCK-M under abundant glucose conditions leads to TCA cycle blockade and increased ROS, while downregulation of PKC-zeta tumor suppressor in glucose-limiting conditions enhances cell survival. The interplay between PEPCK-M and PKC-zeta highlights their co-regulation in glucose-deficient environments.
CANCER & METABOLISM
(2021)
Article
Biology
Mary Rose Branch, Cynthia L. Hsu, Kohta Ohnishi, Wen-Chuan Shen, Elian Lee, Jill Meisenhelder, Brett Winborn, Bryce L. Sopher, J. Paul Taylor, Tony Hunter, Albert R. La Spada
Summary: mTORC1 is a crucial regulator of cellular metabolism, particularly influenced by amino acid supply. The signaling pathway through which MAP4K3 controls mTORC1 activation has been unknown. This research demonstrates that MAP4K3 represses the LKB1-AMPK pathway by interacting with SIRT1 and phosphorylating it, thereby activating mTORC1 and dictating cellular metabolic disposition.
LIFE SCIENCE ALLIANCE
(2023)
Article
Multidisciplinary Sciences
Haiwen Li, Peipei Wang, Chen Zhang, Yuanbojiao Zuo, Yuan Zhou, Renzhi Han
Summary: In this study, Li et al. demonstrate that BVES acts as a negative feedback regulator of ADCY9-cAMP signaling in skeletal muscle, promoting muscle mass and function maintenance. BVES interacts with and negatively regulates ADCY9's activity, leading to the inhibition of the PKA signaling cascade and the prevention of ubiquitin proteasome degradation and autophagy initiation.
NATURE COMMUNICATIONS
(2023)
Article
Neurosciences
Victoria Flores, Alexandra B. Spicer, Michelle M. Sonsalla, Nicole E. Richardson, Deyang Yu, Grace E. Sheridan, Michaela E. Trautman, Reji Babygirija, Eunhae P. Cheng, Jennifer M. Rojas, Shany E. Yang, Matthew H. Wakai, Ryan Hubbell, Ildiko Kasza, Jay L. Tomasiewicz, Cara L. Green, Claudia Dantoin, Caroline M. Alexander, Joseph A. Baur, Kristen C. Malecki, Dudley W. Lamming
Summary: This study demonstrates that reducing dietary histidine levels can lead to weight loss, decreased fat and muscle mass, and improved metabolic health in male mice. The findings suggest that reducing dietary histidine may be a potential option for the treatment of obesity in humans.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Biochemistry & Molecular Biology
Minnie Jacob, Afshan Masood, Anas M. Abdel Rahman
Summary: Hyper-IgE Syndrome (HIES) is a group of primary immune-deficiency disorders characterized by high levels of IgE, eczema, and recurrent skin and lung infections. HIES can be caused by mutations in the STAT3 and PGM3 genes. Detecting HIES early is challenging but can be done through clinical suspicion and immunological assessments. Metabolomics, proteomics, and cytokine profiles of HIES patients were compared to patients with other immune-related conditions. Dysregulation of metabolites and proteins, as well as cytokine dysregulation, were observed in both STAT3 and PGM3 patients, indicating potential biomarkers for diagnosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rajaa Sebaa, Maha AlMogren, Wafaa Alseraty, Anas Abdel M. Rahman
Summary: Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is a common mitochondrial metabolic disease in newborns. Current diagnostic methods have limitations, so complementary approaches are needed. Untargeted metabolomics analysis of MCADD newborns and healthy controls identified potential metabolic biomarkers/pathways associated with MCADD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yuyang Liu, Kivanc Birsoy
Summary: Mitochondria are organelles with their own genomes and unique biochemical reaction networks. They must maintain a specific biochemical environment and coordinate with the host cell's metabolic networks. This coordination involves sensing and controlling metabolites and responding to metabolic stresses. Dysfunction in the regulatory circuits of mitochondrial metabolic sensing and control can lead to metabolic disorders with clinical manifestations. This review discusses the logic and molecular basis of metabolic sensing and control in mitochondria, highlighting gaps in current knowledge that can potentially be addressed with emerging technologies.
Review
Geriatrics & Gerontology
Michelle M. M. Sonsalla, Dudley W. W. Lamming
Summary: Alzheimer's disease (AD) is an age-associated neurodegenerative disease with increasing prevalence due to the aging population. Traditional drug development efforts for AD have been largely unsuccessful. However, targeting aging itself through geroprotective interventions shows potential for preventing or treating AD.
Article
Biochemistry & Molecular Biology
Rajaa Sebaa, Reem H. AlMalki, Wafaa Alseraty, Anas Abdel M. Rahman
Summary: Very long-chain acylcarnitine dehydrogenase deficiency (VLCADD) is a rare inherited metabolic disorder characterized by genetic mutations and accumulations of acylcarnitines. Current diagnostic methods have limitations, and additional tools are needed for improved performance. Metabolomics analysis identified distinct metabolic profiles and potential biomarkers for VLCADD diagnosis.
Article
Endocrinology & Metabolism
Hicham Benabdelkamel, Malak A. Jaber, Lina A. Dahabiyeh, Afshan Masood, Reem H. Almalki, Mohthash Musambil, Anas M. Abdel Rahman, Assim A. Alfadda
Summary: In this study, the metabolic changes in the plasma of patients with hypothyroidism after levothyroxine treatment were explored using metabolomics techniques. The findings revealed significant changes in multiple metabolites, lipids, and bile acids, providing valuable insights into the pathophysiology and therapeutic effects of levothyroxine on hypothyroidism at the molecular level.
EUROPEAN THYROID JOURNAL
(2023)
Article
Medical Laboratory Technology
Abeer K. Malkawi, Refat M. Nimer, Maha Almogren, Afshan Masood, Abdulrahman S. Alarfaj, Hicham Benabdelkamel, Anas M. Abdel Rahman, Mohamed Siaj
Summary: This study developed a novel liquid chromatography-tandem mass spectrometry method to accurately quantify soluble costimulatory molecules in human plasma as potential diagnostic biomarkers for rheumatoid arthritis (RA). The method showed a wide linear range and met international standards for reliability and accuracy. The plasma levels of sCTLA4, sCD80, and sCD86 were significantly elevated in RA patients, with sCTLA4 showing the highest diagnostic and clinical performance.
CLINICA CHIMICA ACTA
(2023)
Article
Biochemistry & Molecular Biology
Reem H. Almalki, Malak A. Jaber, Mysoon M. Al-Ansari, Khalid M. Sumaily, Monther Al-Alwan, Essa M. Sabi, Abeer K. Malkawi, Anas M. Abdel Rahman
Summary: According to studies, the microbiome, specifically E. coli, can alter the metabolism of breast cancer cells through its secretome by disrupting key metabolic pathways. Liquid chromatography-mass spectrometry (LC-MS) metabolomics was used to analyze the intracellular and extracellular metabolites of MCF-7 cells exposed to E. coli secretome. Significant alterations in 31 intracellular and 55 extracellular metabolites were observed, indicating the dysregulation of several metabolic pathways. These microbial metabolites from the secretome hold promise as biomarkers for drug resistance or innovative approaches for cancer treatment.
Article
Biochemistry & Molecular Biology
Mohamed Abu-Farha, Shibu Joseph, Anwar Mohammad, Arshad Channanath, Ibrahim Taher, Fahd Al-Mulla, Muhammad Mujammami, Thangavel Alphonse Thanaraj, Jehad Abubaker, Anas M. Abdel Rahman
Summary: This study used metabolomics to investigate the impact of the ANGPTL8 R59W variant on metabolites in Arab individuals. The results showed significant associations between the variant and concentrations of lipid- and inflammation-related metabolites, highlighting the importance of this gene in lipid metabolism.
Article
Chemistry, Medicinal
Awad Alshahrani, Ahmad Aljada, Afshan Masood, Muhammad Mujammami, Assim A. Alfadda, Mohthash Musambil, Ibrahim O. Alanazi, Mohammed Al Dubayee, Anas M. Abdel Rahman, Hicham Benabdelkamel
Summary: This study explores the proteomic changes associated with metformin treatment in obese patients (with or without T2DM) using a proteomic approach. The results suggest that metformin may alter the expression of potential biomarkers through pathways involving acute-phase response, inflammation, and oxidative response, which contributes to the understanding of metformin's mechanisms of action.
Article
Multidisciplinary Sciences
Hassan Ali, Hafiz Usman, Waseem Ashraf, Faleh Alqahtani, Sana Javaid, Farhan Siddique, Muhammad Fawad Rasool, Imran Imran, Tanveer Ahmad, Anas M. Abdel Rahman, Reem H. Almalki
Summary: This study scientifically validates the neuroprotective effects of the herbal product Demaghi, which is claimed to have memory-enhancing properties. The results show that Demaghi reduces anxiety and depression and improves memory in a mouse model of memory deficiency induced by AlCl3. Biochemical analysis also indicates a decrease in oxidative stress and histopathological changes in treated animals. These findings suggest that the phytoconstituents in Demaghi enhance cholinergic neurotransmission and protect against neurotoxin-induced oxidative stress.
Review
Cell Biology
Joan B. Mannick, Dudley W. Lamming
Summary: Lamming and Mannick discuss the research in the past decade showing the survival-promoting effects of rapamycin in multiple species and the recent clinical trials exploring the use of existing mTOR inhibitors in preventing, delaying or treating aging-related diseases in humans.
Article
Biophysics
Abeer K. Malkawi, Maziar Jafari, Leanne Ohlund, Lekha Sleno, Anas M. Abdel Rahman, Mohamed Siaj
Summary: In this study, a sensitive aptasensor was developed to detect sCD80 in human serum. A high-affinity aptamer was selected through conventional in-vitro selection process and immobilized on a screen-printed gold electrode. The aptasensor showed good assembly and distribution performance, with linear detection range and low detection limit. The sensor also demonstrated reliable performance in a biological matrix.
BIOSENSORS & BIOELECTRONICS
(2023)
Article
Biochemistry & Molecular Biology
Moudi A. Alwehaibi, Mysoon M. Al-Ansari, Assim A. Alfadda, Reem Al-Malki, Afshan Masood, Anas M. Abdel Rahman, Hicham Benabdelkamel
Summary: This study investigated the effects of Enterococcus faecalis on breast cancer cells and identified changes in the proteomic profiles of the cells after treatment. Several proteins were found to be potential markers for breast cancer treatment and diagnosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
