713,867 results match your criteria Metabolic Disease & Stroke - MELAS


Drug Metab Dispos 2022 Jun 29. Epub 2022 Jun 29.

Lab. Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Japan

Arylamine -acetyltransferases (NATs) are drug-metabolizing enzymes essential for the metabolism of endogenous substrates and xenobiotics. The molecular characteristics of NATs have been extensively investigated in humans but remain to be investigated in common marmosets and pigs, animal species that are often used in drug metabolism studies. In this study, marmoset NAT1 and pig NAT1 cDNAs were isolated from liver samples and were characterized by molecular analyses and drug-metabolism assays. Read More

View Article and Full-Text PDF

Safety and efficacy of exercise training in children and adolescents with congenital heart disease: a systematic review and descriptive analysis.

Am Heart J 2022 Jun 26. Epub 2022 Jun 26.

Centre for Research on Exercise, Physical Activity and Health, School of Human Movement and Nutrition Sciences, The University of Queensland, Brisbane, St Lucia, 4072, Queensland, Australia.

Background: While exercise training is beneficial in the prevention and management of many chronic diseases, the role of exercise training in children and adolescents with congenital heart disease is less understood. We sought to determine the safety and efficacy of exercise training in children and adolescents with congenital heart disease.

Methods: We conducted a systematic search of the following databases: PubMed, CINAHL, EMBASE, Web of Science and SportDiscus. Read More

View Article and Full-Text PDF

Replication stress triggered by nucleotide pool imbalance drives DNA damage and cGAS-STING pathway activation in NAFLD.

Dev Cell 2022 Jun 23. Epub 2022 Jun 23.

Team Proliferation, Stress and Liver Physiopathology, Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université Paris-Cité, 75006 Paris, France. Electronic address:

Non-alcoholic steatotic liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD has a major effect on the intrinsic proliferative properties of hepatocytes. Here, we investigated the mechanisms underlying the activation of DNA damage response during NAFLD. Read More

View Article and Full-Text PDF

G6PD inhibition sensitizes ovarian cancer cells to oxidative stress in the metastatic omental microenvironment.

Cell Rep 2022 Jun;39(13):111012

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USA; Terasaki Institute for Biomedical Innovation, Los Angeles, CA 90024, USA. Electronic address:

Ovarian cancer (OC) is the most lethal gynecological malignancy, with aggressive metastatic disease responsible for the majority of OC-related deaths. In particular, OC tumors preferentially metastasize to and proliferate rapidly in the omentum. Here, we show that metastatic OC cells experience increased oxidative stress in the omental microenvironment. Read More

View Article and Full-Text PDF

BAFFR activates PI3K/AKT signaling in human naive but not in switched memory B cells through direct interactions with B cell antigen receptors.

Cell Rep 2022 Jun;39(13):111019

Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Hugstetterstr. 55, 79106 Freiburg, Germany; Faculty of Medicine, University of Freiburg, Breisacherstr. 153, 79110 Freiburg, Germany; Center for Chronic Immunodeficiency, Medical Center - University of Freiburg, Breisacherstr. 115, 79106 Freiburg, Germany. Electronic address:

Binding of BAFF to BAFFR activates in mature B cells PI3K/AKT signaling regulating protein synthesis, metabolic fitness, and survival. In humans, naive and memory B cells express the same levels of BAFFR, but only memory B cells seem to survive without BAFF. Here, we show that BAFF activates PI3K/AKT only in naive B cells and changes the expression of genes regulating migration, proliferation, growth, and survival. Read More

View Article and Full-Text PDF

Full humanization of the glycolytic pathway in Saccharomyces cerevisiae.

Cell Rep 2022 Jun;39(13):111010

Department of Biotechnology, Delft University of Technology, Van Der Maasweg 9, 2629 Delft, the Netherlands. Electronic address:

Although transplantation of single genes in yeast plays a key role in elucidating gene functionality in metazoans, technical challenges hamper humanization of full pathways and processes. Empowered by advances in synthetic biology, this study demonstrates the feasibility and implementation of full humanization of glycolysis in yeast. Single gene and full pathway transplantation revealed the remarkable conservation of glycolytic and moonlighting functions and, combined with evolutionary strategies, brought to light context-dependent responses. Read More

View Article and Full-Text PDF

Flattening of circadian glucocorticoid oscillations drives acute hyperinsulinemia and adipocyte hypertrophy.

Cell Rep 2022 Jun;39(13):111018

Department of Chemical and Systems Biology, Stanford University, Stanford, CA 94305, USA; Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Biochemistry and the Gale and Ira Drukier Institute of Children's Health, Weill Cornell Medical College of Cornell University, New York, NY, USA; Weill Center for Metabolic Health, Division of Endocrinology, Diabetes and Metabolism, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medical College of Cornell University, New York, NY, USA. Electronic address:

Disruption of circadian glucocorticoid oscillations in Cushing's disease and chronic stress results in obesity and adipocyte hypertrophy, which is believed to be a main source of the harmful effects of obesity. Here, we recapitulate stress due to jet lag or work-life imbalances by flattening glucocorticoid oscillations in mice. Within 3 days, mice achieve a metabolic state with persistently high insulin, but surprisingly low glucose and fatty acids in the bloodstream, that precedes a more than 2-fold increase in brown and white adipose tissue mass within 3 weeks. Read More

View Article and Full-Text PDF

Proinflammatory signaling in islet β cells propagates invasion of pathogenic immune cells in autoimmune diabetes.

Cell Rep 2022 Jun;39(13):111011

Department of Medicine and the Kovler Diabetes Center, The University of Chicago, Chicago, IL 60637, USA. Electronic address:

Type 1 diabetes is a disorder of immune tolerance that leads to death of insulin-producing islet β cells. We hypothesize that inflammatory signaling within β cells promotes progression of autoimmunity within the islet microenvironment. To test this hypothesis, we deleted the proinflammatory gene encoding 12/15-lipoxygenase (Alox15) in β cells of non-obese diabetic mice at a pre-diabetic time point when islet inflammation is a feature. Read More

View Article and Full-Text PDF

IL-18 Serum Levels in Patients with Obesity, Prediabetes and Newly Diagnosed Type 2 Diabetes.

Iran J Immunol 2022 Jun;19(2)

Clinic of Endocrinology, University Hospital "Alexandrovska", Department of internal medicine, Medical University-Sofia, Bulgaria.

Background: Obesity and diabetes are related to chronic low-grade inflammation. As a pro-inflammatory cytokine, IL-18 stimulates various cell types and has pleiotropic functions.

Objective: To assess the levels of IL-18 in subjects from the entire spectrum of glycemic disorders. Read More

View Article and Full-Text PDF

The effect of pregnancy on metabolic scaling and population energy demand in the viviparous fish Gambusia affinis.

Integr Comp Biol 2022 Jun 29. Epub 2022 Jun 29.

School of Environment, The University of Auckland, New Zealand.

Metabolism is a fundamental attribute of all organisms that influences how species affect and are affected by their natural environment. Differences between sexes in ectothermic species may substantially alter metabolic scaling patterns, particularly in viviparous or live-bearing species where females must support their basal metabolic costs and that of their embryos. Indeed, if pregnancy is associated with marked increases in metabolic demand and alters scaling patterns between sexes, this could in turn interact with natural sex ratio variation in nature to affect population-level energy demand. Read More

View Article and Full-Text PDF

The development of cigarette smoke induced chronic pancreatitis in mice is associated with increased expression of K-Ras and NF-κB.

Ann Agric Environ Med 2022 Jun 21;29(2):246-251. Epub 2021 Dec 21.

Department of Gastroenterology and Internal Medicine, Medical University, Bialystok, Poland.

Introduction And Objective: Epidemiological studies have demonstrated a strong association between cigarette smoking (CS) and chronic pancreatitis (CP); however, the exact mechanisms of this phenomenon remains unknown. The authors have previously shown that increased Ras expression activates the NF-κB mediated pathway and promotes development of CP. However, it is unclear whether a similar phenomenon occurs in CS-induced CP. Read More

View Article and Full-Text PDF

Magnetic resonance spectroscopy as a promising modality for assessing ketogenic diet impact on the level of cerebral metabolites in the treatment of certain neurological disorders.

Ann Agric Environ Med 2022 Jun 28;29(2):201-206. Epub 2021 Dec 28.

Chair and Department of Epidemiology and Clinical Research Methodology, Medical University, Lublin, Poland.

Introduction And Objective: The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet that is getting more and more widespread in medicine. This dietary intervention causes changes in cerebral metabolism, which are considered potentially beneficial in patients with neurological disorders, but its impact should be controlled and assessed individually. The aim of this review is to provide an update of existing evidence concerning the utility of magnetic resonance spectroscopy (MRS) in monitoring shifts in the cerebral metabolism during ketogenic diet in patients with neurological disorders. Read More

View Article and Full-Text PDF

R-spondin 3 inhibits high glucose-induced endothelial activation through LGR4/Wnt/β-catenin pathway.

J Cardiovasc Pharmacol 2022 May 10. Epub 2022 May 10.

Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua, Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

Abstract: High glucose-induced endothelial activation plays critical roles in the development of diabetic vascular complications. R-spondin 3 could inhibit inflammatory damage, and diabetic vascular inflammation is secondary to endothelial activation. Here we identify R-spondin 3 as a novel regulator of high glucose-induced endothelial activation. Read More

View Article and Full-Text PDF

Squalene epoxidase metabolic dependency is a targetable vulnerability in castration-resistant prostate cancer.

Cancer Res 2022 Jun 29. Epub 2022 Jun 29.

Xinhua hospital, school of medicine, shanghai Jiao Tong university, China.

Considering the dismal prognosis of castration-resistant prostate cancer (CRPC), it is critical to identify novel therapeutic targets in this disease. Malignant cells have metabolic dependencies distinct from their healthy counterparts, resulting in therapeutic vulnerabilities. While PTEN and TP53 are the most frequently co-mutated or co-deleted driver genes in lethal CRPC, the metabolic dependencies underlying PTEN/p53 deficiency-driven CRPC for therapeutic intervention remain largely elusive. Read More

View Article and Full-Text PDF

PTX3 Inhibits Complement-Driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Am J Respir Crit Care Med 2022 Jun 29. Epub 2022 Jun 29.

University of Minho, Braga, Portugal;

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown.

Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Read More

View Article and Full-Text PDF

Metabolic reprogramming of skeletal muscle by resident macrophages points to CSF1R inhibitors as muscular dystrophy therapeutics.

Sci Transl Med 2022 Jun 29;14(651):eabg7504. Epub 2022 Jun 29.

Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.

The role of tissue-resident macrophages during tissue regeneration or fibrosis is not well understood, mainly due to the lack of a specific marker for their identification. Here, we identified three populations of skeletal muscle-resident myelomonocytic cells: a population of macrophages positive for lymphatic vessel endothelial receptor 1 (LYVE1) and T cell membrane protein 4 (TIM4 or TIMD4), a population of LYVE1TIM4 macrophages, and a population of cells likely representing dendritic cells that were positive for CD11C and major histocompatibility complex class II (MHCII). Using a combination of parabiosis and lineage-tracing experiments, we found that, at steady state, TIM4 macrophages were replenished from the blood, whereas TIM4 macrophages locally self-renewed [self-renewing resident macrophages (SRRMs)]. Read More

View Article and Full-Text PDF

Global variation in diversification rate and species richness are unlinked in plants.

Proc Natl Acad Sci U S A 2022 Jul 29;119(27):e2120662119. Epub 2022 Jun 29.

Department of Biology, Aarhus University, 8000 Aarhus C, Denmark.

Species richness varies immensely around the world. Variation in the rate of diversification (speciation minus extinction) is often hypothesized to explain this pattern, while alternative explanations invoke time or ecological carrying capacities as drivers. Focusing on seed plants, the world's most important engineers of terrestrial ecosystems, we investigated the role of diversification rate as a link between the environment and global species richness patterns. Read More

View Article and Full-Text PDF

NAC1 modulates autoimmunity by suppressing regulatory T cell-mediated tolerance.

Sci Adv 2022 Jul 29;8(26):eabo0183. Epub 2022 Jun 29.

Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, Bryan, TX 77807, USA.

We report here that nucleus accumbens-associated protein-1 (NAC1), a nuclear factor of the Broad-complex, Tramtrack, Bric-a-brac/poxvirus and zinc finger (BTB/POZ) gene family, is a negative regulator of FoxP3 in regulatory T cells (T) and a critical determinant of immune tolerance. Phenotypically, NAC1 mice showed substantial tolerance to the induction of autoimmunity and generated a larger amount of CD4 T that exhibit a higher metabolic profile and immune-suppressive activity, increased acetylation and expression of FoxP3, and slower turnover of this transcription factor. Treatment of T with the proinflammatory cytokines interleukin-1β or tumor necrosis factor-α induced a robust up-regulation of NAC1 but evident down-regulation of FoxP3 as well as the acetylated FoxP3. Read More

View Article and Full-Text PDF

The central clock suffices to drive the majority of circulatory metabolic rhythms.

Sci Adv 2022 Jul 29;8(26):eabo2896. Epub 2022 Jun 29.

Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), 08028 Barcelona, Spain.

Life on Earth anticipates recurring 24-hour environmental cycles via genetically encoded molecular clocks active in all mammalian organs. Communication between these clocks controls circadian homeostasis. Intertissue communication is mediated, in part, by temporal coordination of metabolism. Read More

View Article and Full-Text PDF

Follow-up PET/CT of alveolar echinococcosis: Comparison of metabolic activity and immunodiagnostic testing.

PLoS One 2022 29;17(6):e0270695. Epub 2022 Jun 29.

Division of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Purpose: To investigate the potential role of follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in therapy control of inoperable patients with alveolar echinococcosis.

Materials And Methods: In this single-center retrospective cohort study, 48 PET/CT of 16 patients with confirmed alveolar echinococcosis were analysed. FDG-uptake of the most active echinococcosis manifestation was measured (i. Read More

View Article and Full-Text PDF

What effect have NHS commissioners' policies for body mass index had on access to knee replacement surgery in England?: An interrupted time series analysis from the National Joint Registry.

PLoS One 2022 29;17(6):e0270274. Epub 2022 Jun 29.

Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Learning and Research Building, Level 1, Southmead Hospital, Bristol, United Kingdom.

Objective: To assess the impact of local commissioners' policies for body mass index on access to knee replacement surgery in England.

Methods: A Natural Experimental Study using interrupted time series and difference-in-differences analysis. We used National Joint Registry for England data linked to the 2015 Index of Multiple Deprivation for 481,555 patients who had primary knee replacement surgery in England between January 2009 and December 2019. Read More

View Article and Full-Text PDF

Mitochondrial dysfunction is associated with lipid metabolism disorder and upregulation of angiotensin-converting enzyme 2.

PLoS One 2022 29;17(6):e0270418. Epub 2022 Jun 29.

Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden.

Thymidine kinase 2 (TK2) deficiency in humans leads to a myopathic form of mitochondrial DNA (mtDNA) deficiency. Here we present a skeletal and cardiac muscle specific TK2 knockout mouse (mTk2 KO). The mice showed dilated hearts and markedly reduced adipose tissue during week 12 to 16. Read More

View Article and Full-Text PDF

Primary Aldosteronism: State-of-the-Art Review.

Am J Hypertens 2022 Jun 29. Epub 2022 Jun 29.

Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School.

We are witnessing a revolution in our understanding of primary aldosteronism. In the past two decades, we have learned that primary aldosteronism is a highly prevalent syndrome that is largely attributable to pathogenic somatic mutations, that contributes to cardiovascular, metabolic, and kidney disease, and that when recognized, can be adequately treated with widely available mineralocorticoid receptor antagonists and/or surgical adrenalectomy. Unfortunately, primary aldosteronism is rarely diagnosed, or adequately treated, mainly because of a lack of awareness and education. Read More

View Article and Full-Text PDF

Efficient assembly of long DNA fragments and multiple genes with improved nickase-based cloning and Cre/loxP recombination.

Plant Biotechnol J 2022 Jun 29. Epub 2022 Jun 29.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, South China Agricultural University, Guangzhou, China.

Functional genomics, synthetic biology and metabolic engineering require efficient tools to deliver long DNA fragments or multiple gene constructs. Although numerous DNA assembly methods exist, most are complicated, time-consuming and expensive. Here, we developed a simple and flexible strategy, unique nucleotide sequence-guided nicking endonuclease (UNiE)-mediated DNA assembly (UNiEDA), for efficient cloning of long DNAs and multigene stacking. Read More

View Article and Full-Text PDF

Glucagon Receptor-mediated Regulation of Gluconeogenic Gene Transcription is Endocytosis-dependent in Primary Hepatocytes.

Mol Biol Cell 2022 Jun 29:mbcE21090430. Epub 2022 Jun 29.

San Francisco State University, Department of Biology.

A number of G protein-coupled receptors (GPCRs) are now thought to use endocytosis to promote cellular cAMP signaling that drives downstream transcription of cAMP-dependent genes. We tested if this is true for the Glucagon Receptor (GCGR), which mediates physiological regulation of hepatic glucose metabolism via cAMP signaling. We show that epitope-tagged GCGRs undergo clathrin and dynamin-dependent endocytosis in HEK293 and Huh-7-Lunet cells after activation by glucagon within 5 minutes, and transit via EEA1-marked endosomes shown previously to be sites of GPCR/Gs-stimulated production of cAMP. Read More

View Article and Full-Text PDF

A Survey of the Metabolic Landscape of the Developing Cerebellum at Single-Cell Resolution.

Cerebellum 2022 Jun 29. Epub 2022 Jun 29.

Queensland Institute of Medical Research Berghofer Research Institute, Herston, QLD, Australia.

The use of cell-culture models to investigate development and disease of the cerebellum is a recent advance, facilitated by the discovery that patterning of precursors is capable of giving rise to cells with specific neuronal identity. Pluripotent stem cell-derived organoids, which exhibit self-organisational characteristics reminiscent of early cerebellar tissue, present a number of challenges including recapitulation of conditions resembling the mature brain. An understanding of the processes driving fetal and postnatal maturation is required to reproduce these conditions in vitro and advance the capability of the system to model adult-onset disease. Read More

View Article and Full-Text PDF

Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC).

Endocrine 2022 Jun 29. Epub 2022 Jun 29.

Division of Nuclear Medicine, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria.

Purpose: Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC. Read More

View Article and Full-Text PDF

Increased eHSP70-to-iHSP70 ratio in prediabetic and diabetic postmenopausal women: a biomarker of cardiometabolic risk.

Cell Stress Chaperones 2022 Jun 29. Epub 2022 Jun 29.

Research Group in Physiology, Regional University of Northwestern Rio Grande Do Sul State (UNIJUI), Ijuí, RS, Brazil.

Decreased estrogen levels in menopause are associated with anthropometric, metabolic, and inflammatory impairments, predisposing women to cardiometabolic risk factors such as diabetes. Menopause and type two diabetes (DM2) are marked by altered heat shock response (HSR), shown by decreased expression of the 70-kDa heat shock protein in the intracellular milieu (iHSP70). While iHSP70 plays an anti-inflammatory role, extracellular HSP70 (eHSP70) may mediate pro-inflammatory pathways and has been associated with insulin resistance in DM2. Read More

View Article and Full-Text PDF

Genomic insight into iron acquisition by sulfate-reducing bacteria in microaerophilic environments.

Biometals 2022 Jun 29. Epub 2022 Jun 29.

Faculty of Biology, University of Warsaw, Miecznikowa 1, 02-096, Warsaw, Poland.

Historically, sulfate-reducing bacteria (SRB) have been considered to be strict anaerobes, but reports in the past couple of decades indicate that SRB tolerate exposure to O and can even grow in aerophilic environments. With the transition from anaerobic to microaerophilic conditions, the uptake of Fe(III) from the environment by SRB would become important. In evaluating the metabolic capability for the uptake of iron, the genomes of 26 SRB, representing eight families, were examined. Read More

View Article and Full-Text PDF