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Cancer Management and Research 2019Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools... (Review)
Review
INTRODUCTION
Thyroid cancer (TC) is an important common endocrine malignancy, and its incidence has increased in the past decades. The current TC diagnosis and classification tools are fine-needle aspiration (FNA) and histological examination following thyroidectomy. The metabolite profile alterations of thyroid cells (oncometabolites) can be considered for current TC diagnosis and management protocols.
METHODS
This systematic review focuses on metabolite alterations within the plasma, FNA specimens, and tissue of malignant TC contrary to benign, goiter, or healthy TC samples. A systematic search of MEDLINE (PubMed), Scopus, Embase, and Web of Science databases was conducted, and the final 31 studies investigating metabolite biomarkers of TC were included.
RESULTS
A total of 15 targeted studies and 16 untargeted studies revealed several potential metabolite signatures of TC such as glucose, fructose, galactose, mannose, 2-keto-d-gluconic acid and rhamnose, malonic acid and inosine, cholesterol and arachidonic acid, glycosylation (immunoglobulin G [IgG] Fc-glycosylation), outer mitochondrial membrane 20 (TOMM20), monocarboxylate transporter 4 (MCT4), choline, choline derivatives, myo-/scyllo-inositol, lactate, fatty acids, several amino acids, cell membrane phospholipids, estrogen metabolites such as 16 alpha-OH E1/2-OH E1 and catechol estrogens (2-OH E1), and purine and pyrimidine metabolites, which were suggested as the TC oncometabolite.
CONCLUSION
Citrate was suggested as the first most significant biomarker and lactate as the second one. Further research is needed to confirm these biomarkers as the TC diagnostic oncometabolite.
PubMed: 30881111
DOI: 10.2147/CMAR.S188661 -
Biochimica Et Biophysica Acta.... Nov 2023This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
Integration of systematic review, lipidomics with experiment verification reveals abnormal sphingolipids facilitate diabetic retinopathy by inducing oxidative stress on RMECs.
OBJECTIVE
This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR).
METHODS
Systematic review of diabetic metabolomics was used to screen the differential metabolites and related pathways during the development of DM. Non-targeted lipidomics of rat plasma was performed to explore the differential metabolites in the development of DM into DR in vivo. To verify the effects of differential metabolites in inducing retinal microvascular endothelial cells (RMECs) injury by increasing oxidative stress, high glucose medium containing differential metabolites was used to induce rat RMECs injury and cell viability, malondialdehyde (MDA) contents, superoxide dismutase (SOD) activities, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in vitro. Network pharmacology was performed to explore the potential mechanism of differential metabolites in inducing DR.
RESULTS
Through the systematic review, 148 differential metabolites were obtained and the sphingolipid metabolic pathway attracted our attention. Plasma non-targeted lipidomics found that sphingolipids were accompanied by the development of DM into DR. In vitro experiments showed sphinganine and sphingosine-1-phosphate aggravated rat RMECs injury induced by high glucose, further increased MDA and ROS levels, and further decreased SOD activities and MMP. Network pharmacology revealed sphinganine and sphingosine-1-phosphate may induce DR by regulating the AGE-RAGE and HIF-1 signaling pathways.
CONCLUSIONS
Integrated systematic review, lipidomics and experiment verification reveal that abnormal sphingolipid metabolism facilitates DR by inducing oxidative stress on RMECs. Our study could provide the experimental basis for finding potential biomarkers for the diagnosis and treatment of DR.
Topics: Rats; Animals; Diabetic Retinopathy; Reactive Oxygen Species; Sphingolipids; Lipidomics; Endothelial Cells; Oxidative Stress; Glucose; Superoxide Dismutase; Biomarkers; Diabetes Mellitus
PubMed: 37659619
DOI: 10.1016/j.bbalip.2023.159382 -
International Journal of Molecular... Nov 2022Thymoquinone (TQ), a plant-based bioactive constituent derived from the volatile oil of , has been shown to possess some anti-neoplastic activities. The present study...
Thymoquinone (TQ), a plant-based bioactive constituent derived from the volatile oil of , has been shown to possess some anti-neoplastic activities. The present study aimed to investigate the mitochondria and apoptosis observed when TQ is applied against hepatocellular carcinoma (HepG2) and cholangiocarcinoma (HuCCT1) cells, two of the most common primary tumors of the liver. All cell lines were treated with increasing concentrations of TQ for varying durations. The anti-proliferative effect of TQ was measured using the methoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and resulted in dose- and time-dependent growth inhibition in both cell lines. Cell cycle, apoptosis, and assessment of mitochondria viability by morphology assessment and evaluation of the mitochondrial membrane potential were investigated. The present study confirms that TQ caused cell cycle arrest at different phases and induced apoptosis in both cell lines. A systematic review of rodent animal models was also carried out. Overall, our data seem to represent the most robust results, suggesting that TQ possesses promising therapeutic potential as an anti-tumor agent for the treatment of hepatocellular carcinoma and cholangiocarcinoma.
Topics: Animals; Carcinoma, Hepatocellular; Cell Line, Tumor; Liver Neoplasms; Benzoquinones; Apoptosis; Cholangiocarcinoma; Mitochondria; Bile Ducts, Intrahepatic; Bile Duct Neoplasms
PubMed: 36498999
DOI: 10.3390/ijms232314669 -
International Journal of Molecular... Dec 2023Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and... (Review)
Review
Atrial fibrillation (AF) is a cardiac arrhythmia caused by electrophysiological anomalies in the atrial tissue, tissue degradation, structural abnormalities, and comorbidities. A direct relationship exists between AF and altered mitochondrial activity resulting from membrane potential loss, contractile dysfunction, or decreased ATP levels. This review aimed to elucidate the role of mitochondrial oxidative mechanisms in AF pathophysiology, the impact of mitochondrial oxidative stress on AF initiation and perpetuation, and current therapies. This review followed the Preferred Reporting Items for Systematic Reviews and the Meta-Analysis Extension for Scoping Reviews. PubMed, Excerpta Medica Database, and Scopus were explored until June 2023 using "MESH terms". Bibliographic references to relevant papers were also included. Oxidative stress is an imbalance that causes cellular damage from excessive oxidation, resulting in conditions such as AF. An imbalance in reactive oxygen species production and elimination can cause mitochondrial damage, cellular apoptosis, and cardiovascular diseases. Oxidative stress and inflammation are intrinsically linked, and inflammatory pathways are highly correlated with the occurrence of AF. AF is an intricate cardiac condition that requires innovative therapeutic approaches. The involvement of mitochondrial oxidative stress in the pathophysiology of AF introduces novel strategies for clinical treatment.
Topics: Humans; Atrial Fibrillation; Cardiac Conduction System Disease; Heart Diseases; Mitochondrial Diseases; Oxidative Stress
PubMed: 38203704
DOI: 10.3390/ijms25010535 -
BMC Musculoskeletal Disorders Jan 2016The physiological background of exercise-induced muscle fatigue(EIMUF) is only poorly understood. Thus, monitoring of EIMUF by a single or multiple biomarkers(BMs) is... (Review)
Review
BACKGROUND
The physiological background of exercise-induced muscle fatigue(EIMUF) is only poorly understood. Thus, monitoring of EIMUF by a single or multiple biomarkers(BMs) is under debate. After a systematic literature review 91 papers were included.
RESULTS
EIMUF is mainly due to depletion of substrates, increased oxidative stress, muscle membrane depolarisation following potassium depletion, muscle hyperthermia, muscle damage, impaired oxygen supply to the muscle, activation of an inflammatory response, or impaired calcium-handling. Dehydration, hyperammonemia, mitochondrial biogenesis, and genetic responses are also discussed. Since EIMUF is dependent on age, sex, degree of fatigue, type, intensity, and duration of exercise, energy supply during exercise, climate, training status (physical fitness), and health status, BMs currently available for monitoring EIMUF have limited reliability. Generally, wet, volatile, and dry BMs are differentiated. Among dry BMs of EIMUF the most promising include power output measures, electrophysiological measures, cardiologic measures, and questionnaires. Among wet BMs of EIMUF those most applicable include markers of ATP-metabolism, of oxidative stress, muscle damage, and inflammation. VO2-kinetics are used as a volatile BM.
CONCLUSIONS
Though the physiology of EIMUF remains to be fully elucidated, some promising BMs have been recently introduced, which together with other BMs, could be useful in monitoring EIMUF. The combination of biomarkers seems to be more efficient than a single biomarker to monitor EIMUF. However, it is essential that efficacy, reliability, and applicability of each BM candidate is validated in appropriate studies.
Topics: Biomarkers; Clinical Trials as Topic; Exercise; Humans; Motor Activity; Muscle Fatigue; Muscle, Skeletal; Volatilization; Wettability
PubMed: 26790722
DOI: 10.1186/s12891-016-0869-2 -
Journal of Advanced Research Jan 2018With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in... (Review)
Review
With the development of nanotechnology, silver nanoparticles (Ag-NPs) have become one of the most in-demand nanoparticles owing to their exponential number of uses in various sectors. The increased use of Ag-NPs-enhanced products may result in an increased level of toxicity affecting both the environment and living organisms. Several studies have used different model cell lines to exhibit the cytotoxicity of Ag-NPs, and their underlying molecular mechanisms. This review aimed to elucidate different properties of Ag-NPs that are responsible for the induction of cellular toxicity along with the critical mechanism of action and subsequent defense mechanisms observed . Our results show that the properties of Ag-NPs largely vary based on the diversified synthesis processes. The physiochemical properties of Ag-NPs (e.g., size, shape, concentration, agglomeration, or aggregation interaction with a biological system) can cause impairment of mitochondrial function prior to their penetration and accumulation in the mitochondrial membrane. Thus, Ag-NPs exhibit properties that play a central role in their use as biocides along with their applicability in environmental cleaning. We herein report a current review of the synthesis, applicability, and toxicity of Ag-NPs in relation to their detailed characteristics.
PubMed: 30046482
DOI: 10.1016/j.jare.2017.10.008 -
Frontiers in Molecular Neuroscience 2021This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural... (Review)
Review
Effects of Mdivi-1 on Neural Mitochondrial Dysfunction and Mitochondria-Mediated Apoptosis in Ischemia-Reperfusion Injury After Stroke: A Systematic Review of Preclinical Studies.
This systematic review sought to determine the effects of Mitochondrial division inhibitor-1 (Mdivi-1) on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in ischemia/reperfusion (I/R) injury after ischemic stroke. Pubmed, Web of Science, and EMBASE databases were searched through July 2021. The studies published in English language that mentioned the effects of Mdivi-1 on neural mitochondrial dysfunction and neural mitochondria-mediated apoptosis in I/R-induced brain injury were included. The CAMARADES checklist (for studies) and the TOXRTOOL checklist (for studies) were used for study quality evaluation. Twelve studies were included (median CAMARADES score = 6; TOXRTOOL scores ranging from 16 to 18). All studies investigated neural mitochondrial functions, providing that Mdivi-1 attenuated the mitochondrial membrane potential dissipation, ATP depletion, and complexes I-V abnormalities; enhanced mitochondrial biogenesis, as well as inactivated mitochondrial fission and mitophagy in I/R-induced brain injury. Ten studies analyzed neural mitochondria-mediated apoptosis, showing that Mdivi-1 decreased the levels of mitochondria-mediated proapoptotic factors (AIF, Bax, cytochrome , caspase-9, and caspase-3) and enhanced the level of antiapoptotic factor (Bcl-2) against I/R-induced brain injury. The findings suggest that Mdivi-1 can protect neural mitochondrial functions, thereby attenuating neural mitochondria-mediated apoptosis in I/R-induced brain injury. Our review supports Mdivi-1 as a potential therapeutic compound to reduce brain damage in ischemic stroke (PROSPERO protocol registration ID: CRD42020205808). [https://www.crd.york.ac.uk/prospero/], identifier [CRD42020205808].
PubMed: 35002619
DOI: 10.3389/fnmol.2021.778569 -
Mitochondrion Jul 2021Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology.... (Review)
Review
Cell-free mitochondrial DNA (cf-mtDNA) is a marker of inflammatory disease and a predictor of mortality, but little is known about cf-mtDNA in relation to psychobiology. A systematic review of the literature reveals that blood cf-mtDNA varies in response to common real-world stressors including psychopathology, acute psychological stress, and exercise. Moreover, cf-mtDNA is inducible within minutes and exhibits high intra-individual day-to-day variation, highlighting the dynamic regulation of cf-mtDNA levels. We discuss current knowledge on the mechanisms of cf-mtDNA release, its forms of transport ("cell-free" does not mean "membrane-free"), potential physiological functions, putative cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. A review of in vitro, pre-clinical, and clinical studies shows conflicting results around the dogma that physiological forms of cf-mtDNA are pro-inflammatory, opening the possibility of other physiological functions, including the cell-to-cell transfer of whole mitochondria. Finally, to enhance the reproducibility and biological interpretation of human cf-mtDNA research, we propose guidelines for blood collection, cf-mtDNA isolation, quantification, and reporting standards, which can promote concerted advances by the community. Defining the mechanistic basis for cf-mtDNA signaling is an opportunity to elucidate the role of mitochondria in brain-body interactions and psychopathology.
Topics: Brain; Cell-Free Nucleic Acids; DNA, Mitochondrial; Humans; Mitochondria; Signal Transduction
PubMed: 33839318
DOI: 10.1016/j.mito.2021.04.002 -
Frontiers in Genetics 2022Heparan sulfate modified proteins or proteoglycans (HSPGs) are an abundant class of cell surface and extracellular matrix molecules. They serve important co-receptor...
Heparan sulfate modified proteins or proteoglycans (HSPGs) are an abundant class of cell surface and extracellular matrix molecules. They serve important co-receptor functions in the regulation of signaling as well as membrane trafficking. Many of these activities directly affect processes associated with neurodegeneration including uptake and export of Tau protein, disposition of Amyloid Precursor Protein-derived peptides, and regulation of autophagy. In this review we focus on the impact of HSPGs on autophagy, membrane trafficking, mitochondrial quality control and biogenesis, and lipid metabolism. Disruption of these processes are a hallmark of Alzheimer's disease (AD) and there is evidence that altering heparan sulfate structure and function could counter AD-associated pathological processes. Compromising presenilin function in several systems has provided instructive models for understanding the molecular and cellular underpinnings of AD. Disrupting presenilin function produces a constellation of cellular deficits including accumulation of lipid, disruption of autophagosome to lysosome traffic and reduction in mitochondrial size and number. Inhibition of heparan sulfate biosynthesis has opposing effects on all these cellular phenotypes, increasing mitochondrial size, stimulating autophagy flux to lysosomes, and reducing the level of intracellular lipid. These findings suggest a potential mechanism for countering pathology found in AD and related disorders by altering heparan sulfate structure and influencing cellular processes disrupted broadly in neurodegenerative disease. Vertebrate and invertebrate model systems, where the cellular machinery of autophagy and lipid metabolism are conserved, continue to provide important translational guideposts for designing interventions that address the root cause of neurodegenerative pathology.
PubMed: 36699460
DOI: 10.3389/fgene.2022.1012706 -
BMC Geriatrics Aug 2022Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in...
INTRODUCTION
Healthy aging relies on mitochondrial functioning because this organelle provides energy and diminishes oxidative stress. Single nucleotide polymorphisms (SNPs) in TOMM40, a critical gene that produces the outer membrane protein TOM40 of mitochondria, have been associated with mitochondrial dysfunction and neurodegenerative processes. Yet it is not clear whether or how the mitochondria may impact human longevity. We conducted this review to ascertain which SNPs have been associated with markers of healthy aging.
METHODS
Using the PRISMA methodology, we conducted a systematic review on PubMed and Embase databases to identify associations between TOMM40 SNPs and measures of longevity and healthy aging.
RESULTS
Twenty-four articles were selected. The TOMM40 SNPs rs2075650 and rs10524523 were the two most commonly identified and studied SNPs associated with longevity. The outcomes associated with the TOMM40 SNPs were changes in BMI, brain integrity, cognitive functions, altered inflammatory network, vulnerability to vascular risk factors, and longevity.
DISCUSSIONS
Our systematic review identified multiple TOMM40 SNPs potentially associated with healthy aging. Additional research can help to understand mechanisms in aging, including resilience, prevention of disease, and adaptation to the environment.
Topics: Aging; Healthy Aging; Humans; Longevity; Membrane Transport Proteins; Mitochondrial Precursor Protein Import Complex Proteins; Polymorphism, Single Nucleotide
PubMed: 35964003
DOI: 10.1186/s12877-022-03337-4