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Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
International Journal of Molecular... Dec 2023Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria... (Review)
Review
Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from HS and NH. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Intestinal Mucosa; Mitochondria
PubMed: 38069446
DOI: 10.3390/ijms242317124 -
Acta Paediatrica (Oslo, Norway : 1992) Aug 2021To systematically review human metabolomic studies investigating metabolic responses in septic neonates. (Review)
Review
AIM
To systematically review human metabolomic studies investigating metabolic responses in septic neonates.
METHODS
A systematic literature search was performed in the databases MEDLINE, EMBASE and Cochrane library up to the 1st of January 2021. We included studies that assessed neonatal sepsis and the following outcomes; (1) change in the metabolism compared to healthy neonates and/or (2) metabolomics compared to traditional diagnostic tools of neonatal sepsis. The screened abstracts were independently considered for eligibility by two researchers.
PROSPERO ID
CRD42020164454.
RESULTS
The search identified in total 762 articles. Fifteen articles were assessed for eligibility. Four studies were included, with totally 78 neonates. The studies used different diagnostic criteria and had between 1 and 16 sepsis cases. All studies with bacterial sepsis found alterations in the glucose and lactate metabolism, reflecting possible redistribution of glucose consumption from mitochondrial oxidative phosphorylation to the lactate and pentose phosphate pathway. We also found signs of increased oxidative stress and fatty acid oxidation in sepsis cases.
CONCLUSION
We found signs of metabolomic signatures in neonatal sepsis. This may lead to better understanding of sepsis pathophysiology and detection of new candidate biomarkers. Results should be validated in large-scale multicentre studies.
Topics: Anti-Bacterial Agents; Humans; Infant, Newborn; Metabolomics; Neonatal Sepsis; Research Design; Sepsis
PubMed: 33851423
DOI: 10.1111/apa.15874 -
Mitochondrion Jul 2021Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established... (Review)
Review
Metabolic reprogramming and mitochondrial dysfunction are central elements in a broad variety of physiological and pathological processes. While cell culture established itself as a versatile technique for the elaboration of physiology and disease, studying metabolism using standard cell culture protocols is profoundly interfered by the Crabtree effect. This phenomenon refers to the adaptation of cultured cells to a glycolytic phenotype, away from oxidative phosphorylation in glucose-containing medium, and questions the applicability of cell culture in certain fields of research. In this systematic review we aim to provide a comprehensive overview and critical appraisal of strategies reported to circumvent the Crabtree effect.
Topics: Cell Culture Techniques; Culture Media; Glucose; Glycolysis; Humans; Mitochondria; Mitochondrial Dynamics; Oxidative Phosphorylation
PubMed: 33812964
DOI: 10.1016/j.mito.2021.03.014 -
Frontiers in Aging Neuroscience 2023Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial...
Many lines of evidence suggest that mitochondria have a central role in aging-related neurodegenerative diseases, such as Alzheimer's disease (AD). Mitochondrial dysfunction, cerebral energy dysmetabolism and oxidative damage increase with age, and are early event in AD pathophysiology and may precede amyloid beta (Aβ) plaques. probes of mitochondrial function and energy metabolism are therefore crucial to characterize the bioenergetic abnormalities underlying AD risk, and their relationship to pathophysiology and cognition. A majority of the research conducted in humans have used F-fluoro-deoxygluose (FDG) PET to image cerebral glucose metabolism (CMRglc), but key information regarding oxidative phosphorylation (OXPHOS), the process which generates 90% of the energy for the brain, cannot be assessed with this method. Thus, there is a crucial need for imaging tools to measure mitochondrial processes and OXPHOS in the human brain. Phosphorus-magnetic resonance spectroscopy (P-MRS) is a non-invasive method which allows for the measurement of OXPHOS-related high-energy phosphates (HEP), including phosphocreatine (PCr), adenosine triphosphate (ATP), and inorganic phosphate (Pi), in addition to potential of hydrogen (pH), as well as components of phospholipid metabolism, such as phosphomonoesters (PMEs) and phosphodiesters (PDEs). Herein, we provide a systematic review of the existing literature utilizing the P-MRS methodology during the normal aging process and in patients with mild cognitive impairment (MCI) and AD, with an additional focus on individuals at risk for AD. We discuss the strengths and limitations of the technique, in addition to considering future directions toward validating the use of P-MRS measures as biomarkers for the early detection of AD.
PubMed: 37273652
DOI: 10.3389/fnagi.2023.1183228 -
Journal of the Neurological Sciences May 2020One of the most frequent cerebral lesions in mitochondrial disorders(MIDs) on imaging is the stroke-like lesion(SLL) clinically manifesting as stroke-like episode (SLE,... (Review)
Review
OBJECTIVES
One of the most frequent cerebral lesions in mitochondrial disorders(MIDs) on imaging is the stroke-like lesion(SLL) clinically manifesting as stroke-like episode (SLE, metabolic stroke). This review aims at discussing recent advances concerning the presentation, diagnosis, and treatment of SLLs.
METHODS
Systematic literature review using appropriate search terms.
RESULTS
SLLs are the hallmark of MELAS but occasionally occur in other MIDs. SLLs are best identified on multimodal, cerebral MRI. SLLs may present as uni-/multilocular, symmetric/asymmetric, cortical/subcortical, supra-/infratentorial condition, initially resembling a cytotoxic edema and later a vasogenic edema, or a variable mix between them. SLLs run through an acute and a chronic stage. The acute stage is characterised by a progressively expanding lesion over days, weeks, or months, showing up as increasing hyperintensity on T2/FLAIR, DWI, and PWI and by hyperperfusion, that does not conform to a vascular territory. ADC maps are initially hypointens to become hyperintens during the course. More rarely, a variable mixture of hyper- and hypointensities may be found. The chronic stage is characterised by hypoperfusion, gadolinium enhancement, and regression of hyperintensities to various endpoints. SLLs originate from an initial cortical lesion due to focal metabolic breakdown, which either remains stable or expands within the cortex or to subcortical areas. Some SLLs show spontaneous reversibility (fleeing cortical lesions) suggesting that neuronal/glial damage does not reach the threshold of irreversible cell death.
CONCLUSIONS
SLLs are a unique feature of various MIDs in particular MELAS. SLLs are dynamic and change their appearance over time. SLLs are accessible to treatment.
Topics: Contrast Media; Gadolinium; Humans; MELAS Syndrome; Magnetic Resonance Imaging; Stroke
PubMed: 32088469
DOI: 10.1016/j.jns.2020.116726 -
Frontiers in Oncology 2022Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by multiple cytogenetic and molecular abnormalities, with a very poor prognosis....
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by multiple cytogenetic and molecular abnormalities, with a very poor prognosis. Current treatments for AML often fail to eliminate leukemic stem cells (LSCs), which perpetuate the disease. LSCs exhibit a unique metabolic profile, especially dependent on oxidative phosphorylation (OXPHOS) for energy production. Whereas, normal hematopoietic stem cells (HSCs) and leukemic blasts rely on glycolysis for adenosine triphosphate (ATP) production. Thus, understanding the regulation of OXPHOS in LSCs may offer effective targets for developing clinical therapies in AML. This review summarizes these studies with a focus on the regulation of the electron transport chain (ETC) and tricarboxylic acid (TCA) cycle in OXPHOS and discusses potential therapies for eliminating LSCs.
PubMed: 35574326
DOI: 10.3389/fonc.2022.899502 -
Neurobiology of Disease Feb 2021Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD)... (Meta-Analysis)
Meta-Analysis
Neurodegenerative disorders such as Alzheimer's disease (AD), Lewy body diseases (LBD), and the amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum are defined by the accumulation of specific misfolded protein aggregates. However, the mechanisms by which each proteinopathy leads to neurodegeneration remain elusive. We hypothesized that there is a common "pan-neurodegenerative" gene expression signature driving pathophysiology across these clinically and pathologically diverse proteinopathies. To test this hypothesis, we performed a systematic review of human CNS transcriptomics datasets from AD, LBD, and ALS-FTD patients and age-matched controls in the Gene Expression Omnibus (GEO) and ArrayExpress databases, followed by consistent processing of each dataset, meta-analysis, pathway enrichment, and overlap analyses. After applying pre-specified eligibility criteria and stringent data pre-processing, a total of 2600 samples from 26 AD, 21 LBD, and 13 ALS-FTD datasets were included in the meta-analysis. The pan-neurodegenerative gene signature is characterized by an upregulation of innate immunity, cytoskeleton, and transcription and RNA processing genes, and a downregulation of the mitochondrial electron transport chain. Pathway enrichment analyses also revealed the upregulation of neuroinflammation (including Toll-like receptor, TNF, and NFκB signaling) and phagocytosis, and the downregulation of mitochondrial oxidative phosphorylation, lysosomal acidification, and ubiquitin-proteasome pathways. Our findings suggest that neuroinflammation and a failure in both neuronal energy metabolism and protein degradation systems are consistent features underlying neurodegenerative diseases, despite differences in the extent of neuronal loss and brain regions involved.
Topics: Alzheimer Disease; Amyotrophic Lateral Sclerosis; Brain; Energy Metabolism; Frontotemporal Dementia; Humans; Inflammation; Inflammation Mediators; Lewy Body Disease; Neurodegenerative Diseases; Proteostasis; Transcriptome
PubMed: 33347974
DOI: 10.1016/j.nbd.2020.105225 -
Mitochondrion Jan 2021Mitochondrial dysfunction is known to be associated with neurodegenerative diseases (NDDs), which is a major burden on the society. Therefore, understanding the...
Mitochondrial dysfunction is known to be associated with neurodegenerative diseases (NDDs), which is a major burden on the society. Therefore, understanding the regulation of mitochondrial dysfunctions and its implication in neurodegeneration has been major goal for exploiting these mechanisms to rescue neuronal death. The crosstalk between mitochondria and nucleus is important for different neuronal functions including axonal branching, energy homeostasis, neuroinflammation and neuronal survival. The decreased mitochondria capacity during progressive neurodegeneration leads to the altered OXPHOS activity and generation of ROS. The ROS levels in narrow physiological range can reprogram nuclear gene expression to enhance the cellular survival by phenomenon called mitohormesis. Here, we have systematically reviewed the existing reports of mitochondrial dysfunctions causing altered ROS levels in NDDs. We further discussed the role of ROS in regulating mitohormesis and emphasized the importance of mitohormesis in neuronal homeostasis. The emerging role of mitohormesis highlights its importance in future studies on intracellular ROS mediated rescue of mitochondrial dysfunction along with other prevailing mechanisms to alleviate neurodegeneration.
Topics: Cell Nucleus; Energy Metabolism; Gene Expression Regulation; Hormesis; Humans; Mitochondria; Neurodegenerative Diseases; Oxidative Phosphorylation; Reactive Oxygen Species
PubMed: 33220499
DOI: 10.1016/j.mito.2020.11.011 -
Cancers May 2020Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available... (Review)
Review
Several immunotherapy agents are the standard of care of many solid malignancies. Nevertheless, the majority of patients do not benefit from the currently available immunotherapies. It is therefore of paramount importance to identify the prognostic and predictive factors of tumor response/resistance and to design effective therapeutic strategies to overcome primary resistance and improve the efficacy of immunotherapy. The aim of this review is to underline the influence of the tumor and host metabolism on the antitumor immune response and to discuss possible strategies to improve the efficacy of available treatments by targeting the specific metabolic pathways in tumors or immune cells and by modifying patients' nutritional statuses. A systematic search of the Medline and EMBASE databases was carried out to identify scientific papers published until February 2020, which reported original research articles on the influence of tumor or host metabolism on antitumor immune response. The literature data showed the key role of glycolysis and mitochondrial oxidative phosphorylation, arginine, tryptophan, glutamine, lipid metabolism and microbiome on immune cell function. Moreover, specific nutritional behaviors, such as a low dietary intake of vitamin C, low glycemic index and alpha-linolenic acid, eicosapentenoic acid, docosahexaenoic acid, ornithine ketoglutarate, tryptophan and probiotic supplementation were associated with the potential clinical benefits from the currently available immunotherapies.
PubMed: 32375310
DOI: 10.3390/cancers12051153