Article
Biochemistry & Molecular Biology
Nives Skorja Milic, Klemen Dolinar, Katarina Mis, Urska Matkovic, Marusa Bizjak, Mojca Pavlin, Matej Podbregar, Sergej Pirkmajer
Summary: Inhibition of pyruvate dehydrogenase kinase (PDK) by Dichloroacetate (DCA) can reduce the abundance of PDK isoenzymes in a cell-type-specific manner via both transcriptional and post-transcriptional mechanisms. The differential response of PDK isoenzymes to DCA in cancer cells and muscle cells highlights the importance of understanding the pharmacological effects of DCA in different cell types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tianyang Lan, Kang Zhang, Feifei Lin, Qifu He, Shenghui Wu, Zhiming Xu, Yong Zhang, Fusheng Quan
Summary: MICU1 modulators enhance mitochondrial activity, pyruvate metabolism, and developmental competence of thawed oocytes after vitrification. Vitrification leads to adverse effects on mitochondrial function, but these effects can be mitigated by MICU1 activation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Mohamad Hafizi Abu Bakar, Nor Shafiqah Nor Shahril, Mohamad Shamil Faris Mohamad Khalid, Sharifah Mohammad, Khairul Anuar Shariff, Thiruventhan Karunakaran, Rabeta Mohd Salleh, Mohamad Norisham Mohamad Rosdi
Summary: The present study reveals the therapeutic potential of celastrol in attenuating obesity and insulin resistance by improving glucose utilization and mitochondrial oxidative metabolism. Celastrol administration increased the activity of key enzymes and altered the levels of metabolites involved in glycolysis and TCA cycle. It also enhanced the activity of mitochondrial oxidative functions and promoted ATP production and mitochondrial biogenesis.
TOXICOLOGY AND APPLIED PHARMACOLOGY
(2022)
Review
Medicine, Research & Experimental
Russel J. Reiter, Ramaswamy Sharma, Carmen Rodriguez, Vanesa Martin, Sergio Rosales-Corral, Debora Aparecida Pires de Campos Zuccari, Luiz Gustavo de Almeida Chuffa
Summary: This paper explores the relationship between endogenous melatonin and solid tumors, highlighting the potential of using melatonin to influence cancer cell metabolism. It suggests that solid tumors exhibit a healthier metabolic state at night, potentially reducing proliferation and invasiveness. The paper also proposes using melatonin in a time-sensitive treatment paradigm and combining it with traditional chemotherapy for improved outcomes in cancer treatment.
Article
Biology
Rabina Mainali, Manal Zabalawi, David Long, Nancy Buechler, Ellen Quillen, Chia-Chi Key, Xuewei Zhu, John S. Parks, Cristina Furdui, Peter W. Stacpoole, Jennifer Martinez, Charles E. McCall, Matthew A. Quinn
Summary: Metabolic reprogramming occurs in the immune system during sepsis, particularly in the liver, with changes in lipid metabolism, mitochondrial energy, and redox balance. Targeting mitochondrial energy metabolism can rebalance the transcriptional and metabolic manifestations of sepsis in the liver.
Review
Biochemistry & Molecular Biology
Min-Ji Kim, Hoyul Lee, Dipanjan Chanda, Themis Thoudam, Hyeon-Ji Kang, Robert A. Harris, In-Kyu Lee
Summary: Pyruvate metabolism is crucial for energy homeostasis and mitochondrial quality control. Dysregulation in pyruvate flux and mitochondrial quality control is associated with metabolic diseases and inflammation. This article reviews the emerging role of pyruvate metabolism in mitochondrial quality control and its impact on metabolic and inflammatory diseases.
MOLECULES AND CELLS
(2023)
Article
Biochemistry & Molecular Biology
Aikaterini G. Karra, Ioannis Tsialtas, Foteini D. Kalousi, Achilleas Georgantopoulos, Evangelia Sereti, Konstantinos Dimas, Anna-Maria G. Psarra
Summary: Mitochondria are crucial for cellular physiology as they generate energy and regulate biological functions. Dysregulation of mitochondrial function is associated with various pathologies, including cancer. The mitochondrial glucocorticoid receptor (mtGR) plays a role in regulating mitochondrial transcription, metabolism, energy production, apoptosis, and oxidative stress. The interaction between mtGR and pyruvate dehydrogenase (PDH), a key player in cancer metabolism, suggests the involvement of mtGR in cancer development. In this study, using a xenograft mouse model, overexpression of mtGR in hepatocarcinoma cells was found to promote tumor growth, reduce OXPHOS biosynthesis and PDH activity, and alter glucose metabolism, similar to the Warburg effect. Autophagy activation in mtGR-associated tumors further supports tumor progression. Increased mitochondrial localization of mtGR is suggested to contribute to tumor progression via mtGR/PDH interaction, suppressing PDH activity and modulating mtGR-induced mitochondrial transcription, favoring glycolytic energy production in cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Xiangyun Chen, Bingjie Hao, Dan Li, Russel J. Reiter, Yidong Bai, Baigenzhin Abay, Guojie Chen, Shumeng Lin, Tiansheng Zheng, Yanbei Ren, Xiao Xu, Ming Li, Lihong Fan
Summary: The study found that melatonin can inhibit lung cancer growth by activating Sirt3 and PDH, leading to a reversal of the Warburg effect and an enhancement of mitochondrial energy metabolism.
JOURNAL OF PINEAL RESEARCH
(2021)
Article
Cell Biology
Jennifer Maurer, Xinjie Zhao, Martin Irmler, Anders Gudiksen, Nanna S. Pilmark, Qi Li, Thomas Goj, Johannes Beckers, Martin Hrabe de Angelis, Andreas L. Birkenfeld, Andreas Peter, Rainer Lehmann, Henriette Pilegaard, Kristian Karstoft, Guowang Xu, Cora Weigert
Summary: Metformin treatment leads to lactate production and secretion, as well as reduced glucose consumption. It inhibits respiratory chain complex I and alters cellular redox state, decreasing pyruvate oxidation. These findings suggest that metformin induces dose-dependent lactate production in skeletal muscle by shifting the equilibrium of lactate dehydrogenase reaction.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Hoyul Lee, Jae Han, Yu-Jeong Lee, Mi-Jin Kim, Woong Hee Kwon, Dipanjan Chanda, Themis Thoudam, Haushabhau S. Pagire, Suvarna H. Pagire, Jin Hee Ahn, Robert A. Harris, Eun Soo Kim, In-Kyu Lee
Summary: This study found that PDK4 expression increased during the development of colitis. Deletion of PDK4 from CD4(+) T cells can mitigate the development of colitis by modulating metabolism and calcium signaling. These findings suggest that PDK4 may be a potential therapeutic target for inflammatory bowel disease.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Article
Endocrinology & Metabolism
Chris E. Shannon, Mukundan Ragavan, Juan Pablo Palavicini, Marcel Fourcaudot, Terry M. Bakewell, Ivan A. Valdez, Iriscilla Ayala, Eunsook S. Jin, Muniswamy Madesh, Xianlin Han, Matthew E. Merritt, Luke Norton
Summary: Insulin resistance and altered hepatic mitochondrial function are key features of type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). This study found that insulin sensitization with pioglitazone can mitigate mitochondrial dysfunction in the liver, which is independent of changes in hepatic lipid accumulation. The research highlights potential therapeutic targets for T2D and NAFLD, emphasizing the benefits of insulin sensitization in managing obesity-related diseases.
MOLECULAR METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Kyle S. McCommis, Brian N. Finck
Summary: Pyruvate is a crucial metabolic product that needs to be transported to the mitochondrial matrix for energy utilization or to become the building block of new biomolecules. The mitochondrial pyruvate carrier (MPC) has emerged as a target for therapeutic intervention in diseases related to altered mitochondrial and intermediary metabolism. In this review, the role of MPC and related metabolic pathways in the liver in regulating energy metabolism and the current state of targeting this pathway to treat liver diseases are discussed. Inhibiting MPC in hepatocytes and other liver cells has shown beneficial effects in treating type 2 diabetes and nonalcoholic steatohepatitis, although there are still gaps in our understanding of the pleiotropic effects of MPC inhibition.
Article
Chemistry, Multidisciplinary
Ning Sheng, Zhihui Zhang, Hao Zheng, Congyu Ma, Menglin Li, Zhe Wang, Lulu Wang, Jiandong Jiang, Jinlan Zhang
Summary: This study discovered a molecule called scutellarin (SG) that can treat neurodegenerative diseases by regulating energy metabolism and repairing mitochondrial damage. The molecule was found to protect mitochondria through the PDK-PDC axis and mitochondrial glucose oxidation.
Article
Biochemistry & Molecular Biology
Konstantin S. Plokhikh, Semen V. Nesterov, Yuriy M. Chesnokov, Anton G. Rogov, Roman A. Kamyshinsky, Aleksandr L. Vasiliev, Lev S. Yaguzhinsky, Raif G. Vasilov
Summary: In this study, cryo-electron tomography was used to investigate the localization of 2-oxoacid dehydrogenase complexes (OADCs) in cardiac mitochondria and their interaction with respirasomes. The results showed that OADCs were localized in densely packed lamellar cristae of cardiac mitochondria and in ruptured mitochondrial samples. This study highlights the importance of understanding mitochondrial complex coupling.
Article
Oncology
Caroline E. Nunes-Xavier, Janire Mingo, Maite Emaldi, Karine Flem-Karlsen, Gunhild M. Maelandsmo, Oystein Fodstad, Roberto Llarena, Jose I. Lopez, Rafael Pulido
Summary: This study revealed heterogeneous expression of PDH complex components in PCa tumors, with PDH complex components being related to AR signaling and PDK2 expression associated with poor PCa prognosis. These findings highlight the potential of targeting PDH complex components for intervention in PCa.
FRONTIERS IN ONCOLOGY
(2022)
Article
Geriatrics & Gerontology
Hannah Crossland, Matthew S. Brook, Jonathan Quinlan, Martino Franchi, Bethan E. Phillips, Daniel J. Wilkinson, Constantinos N. Maganaris, Paul L. Greenhaff, Nathaniel J. Szewczyk, Kenneth Smith, Marco Narici, Philip J. Atherton
Summary: This study investigates the molecular changes in patellar tendons with ageing and the responses to different exercise types in young and old individuals. The findings suggest that exercise training can increase tendon protein synthesis, but the transcriptional responses differ between age groups and exercise types.
Article
Geriatrics & Gerontology
Colleen S. Deane, Bethan E. Phillips, Craig R. G. Willis, Daniel J. Wilkinson, Ken Smith, Nahoko Higashitani, John P. Williams, Nathaniel J. Szewczyk, Philip J. Atherton, Atsushi Higashitani, Timothy Etheridge
Summary: Resistance exercise training (RET) can improve negative features of muscle ageing, but older individuals have reduced adaptive capacity to RET. Proteomic analysis reveals that older muscles have impaired RET-induced adaptations in body composition and show altered expression of cytoskeletal proteins. RET improves mitochondrial function and glucose metabolism in older muscles, but does not correct the altered expression of cytoskeletal proteins.
Article
Geriatrics & Gerontology
Matthew S. Brook, Daniel J. Wilkinson, Janelle Tarum, Kyle W. Mitchell, Jonathan L. Lund, Bethan E. Phillips, Nathaniel J. Szewczyk, Fawzi Kadi, Paul L. Greenhaff, Ken Smith, Philip J. Atherton
Summary: Ageing limits the growth capacity of skeletal muscle in response to resistance exercise, but the role of satellite cell function in driving this phenomenon is poorly understood.
Article
Nutrition & Dietetics
E. J. Hardy, C. S. Deane, J. N. Lund, B. E. Phillips
Summary: Despite the implementation of ERAS protocols, major abdominal surgery still leads to significant muscle mass and function loss in the post-operative period. Dietary intake in this period is poorly characterised, with energy and protein intake falling far below the recommended guidelines. Innovative dietary interventions, taking patient dietary preference into account, are needed to address this issue.
EUROPEAN JOURNAL OF CLINICAL NUTRITION
(2023)
Article
Gastroenterology & Hepatology
H. Javanmard-Emamghissi, B. Doleman, J. N. Lund, J. Frisby, S. Lockwood, S. Hare, S. Moug, G. Tierney
Summary: This study aimed to define a timeframe for quantitative futility in emergency laparotomy and investigate predictors of futility. The results showed that quantitative futility occurred in 4% of patients, and there were quantifiable risk factors associated with this, which should be qualitatively incorporated into shared decision-making discussions with extremely high-risk patients by the multidisciplinary team.
TECHNIQUES IN COLOPROCTOLOGY
(2023)
Review
Anesthesiology
Brett Doleman, Ole Mathiesen, Alex J. Sutton, Nicola J. Cooper, Jon N. Lund, John P. Williams
Summary: This study used network meta-analysis to identify non-opioid analgesics that may reduce chronic postsurgical pain. Lidocaine, ketamine, and gabapentinoids were found to be potentially effective. However, the low confidence in these findings is due to bias risk and imprecision.
BRITISH JOURNAL OF ANAESTHESIA
(2023)
Article
Gastroenterology & Hepatology
Laurie Smith, Alexandra Coxon-Meggy, Michael Shinkwin, Julie Cornish, Alan Watkins, Greg Fegan, Jared Torkington, HART Trial Collaborators
Summary: This study aimed to assess the rates of incisional hernia (IH) at 1 year following abdominal wall closure between junior and senior surgeons in patients undergoing elective colorectal surgery. The results showed that patients closed by trainees had a higher rate of IH (20%) compared to those closed by consultants (12%). Additionally, age, sex, and closure method were identified as risk factors for IH.
COLORECTAL DISEASE
(2023)
Article
Gastroenterology & Hepatology
J. E. M. Blackwell, P. J. J. Herrod, B. Doleman, H. R. Boyd-Carson, D. Dolan, L. Wheldon, S. R. Brown, A. Banerjea, S. Moug, J. N. Lund, Michael Wong, POMPOMM Collaborative
Summary: This study investigated the relationship between preoperative radiologically defined lean muscle measures and adverse clinical outcomes in patients undergoing surgery for colorectal cancer. The results showed that measures of lean muscle quality and quantity can be quickly and easily taken from routine preoperative imaging, and they can predict important clinical outcomes.
TECHNIQUES IN COLOPROCTOLOGY
(2023)
Review
Nutrition & Dietetics
Isabel A. Ely, Bethan E. Phillips, Kenneth Smith, Daniel J. Wilkinson, Mathew Piasecki, Leigh Breen, Mads S. Larsen, Philip J. Atherton
Summary: This review highlights the anabolic effects of leucine (LEU) supplementation in the context of aging, exercise, and unloading states. LEU has been shown to increase muscle protein synthesis (MPS) and maximize muscle anabolism, especially when combined with resistance exercise. Low doses of LEU-enriched protein/essential amino acids (EAA) can achieve maximal MPS stimulation without the need for larger protein doses, making LEU supplementation a promising strategy for promoting muscle growth and net protein accretion.
CLINICAL NUTRITION
(2023)
Article
Gastroenterology & Hepatology
Katie L. R. Cross, Steven R. Brown, Jos Kleijnen, James Bunce, Melanie Paul, Sophie Pilkington, Oliver Warren, Oliver Jones, Jon Lund, Henry J. Goss, Michael Stanton, Tatenda Marunda, Artaza Gilani, L. Wee Sing Ngu, Philip Tozer
Summary: This article aims to update the old guidelines on the management of anal fissures and provide recommendations on the most effective treatment for patients with anal fissures using a multidisciplinary, rigorous guideline methodology.
COLORECTAL DISEASE
(2023)
Review
Gastroenterology & Hepatology
J. A. Bunce, J. J. S. Wall, J. N. Lund, G. M. Tierney
Summary: The aim of this scoping review is to describe the current evidence base on risk stratification in emergency abdominal surgery for inflammatory bowel disease (IBD). It is likely that age, the American Society of Anesthesiologists grade, comorbidity, and organ dysfunction play a similar role in risk stratification in IBD patients as in other emergency abdominal surgery cohorts. However, there is variability in the reporting of what is considered an IBD emergency.
COLORECTAL DISEASE
(2023)
Review
Gastroenterology & Hepatology
M. Paul, T. F. Smart, B. Doleman, S. Toft, J. P. Williams, J. N. Lund, B. E. Phillips
Summary: Postoperative aerobic exercise training has beneficial effects on improving aerobic function for patients who have had surgery for intra-abdominal cancer. The exercise can be safely delivered in various formats, including home-based or group/supervised.
TECHNIQUES IN COLOPROCTOLOGY
(2023)
Article
Geriatrics & Gerontology
Jessica Cegielski, Joseph J. Bass, Ruth Willott, Adam L. Gordon, Daniel J. Wilkinson, Ken Smith, Philip J. Atherton, Bethan E. Phillips
Summary: This study investigates how different definitions influence the prevalence of sarcopenia in older adults. The results show that the prevalence varies greatly depending on the criteria used, such as muscle mass, gait speed, and handgrip strength.
AGING CLINICAL AND EXPERIMENTAL RESEARCH
(2023)
Letter
Surgery
Hannah Javanmard-Emamghissi, Jonathan N. Lund, Gillian M. Tierney
BRITISH JOURNAL OF SURGERY
(2023)