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BioMed Research International 2022Arsenic is a known environmental carcinogenic agent. However, under certain circumstances, it may exert anticancer effects. In this systematic review, we aim to provide... (Review)
Review
Arsenic is a known environmental carcinogenic agent. However, under certain circumstances, it may exert anticancer effects. In this systematic review, we aim to provide information on recent developments in studies on arsenic antitumor effects in breast cancer. Research included in the review refers to experimental data from studies. The data was collected using search terms "breast cancer," "arsenic," and "anticancer" (25.05.2021). Only studies in English and published in the last 10 years were included. The search identified 123 studies from the EBSCOhost, PubMed, and Scopus databases. In the selection process, thirty full-texts were evaluated as eligible for the review. The literature of the last decade provides a lot of information on mechanisms behind anticancer effects of arsenic on breast cancer. Similar to arsenic-induced carcinogenesis, these mechanisms include the activation of the redox system and the increased production of free radicals. Targets of arsenic action are systems of cell membranes, mitochondria, pathways of intracellular transmission, and the genetic apparatus of the cell. Beneficial effects of arsenic use are possible due to significant metabolic differences between cancer and healthy cells. Further efforts are needed in order to establish modes and doses of treatment with arsenic that would provide anticancer activity with minimal toxicity.
Topics: Humans; Female; Arsenic; Breast Neoplasms; Carcinogenesis; Carcinogens; Free Radicals
PubMed: 36619302
DOI: 10.1155/2022/8030931 -
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 -
PloS One 2024Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually... (Meta-Analysis)
Meta-Analysis
Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that affects motor neurons, resulting in muscle weakness, paralysis, and eventually patient mortality. In recent years, neuromodulation techniques have emerged as promising potential therapeutic approaches to slow disease progression and improve the quality of life of ALS patients. A systematic review was conducted until August 8, 2023, to evaluate the neuromodulation methods used and their potential in the treatment of ALS. The search strategy was applied in the Cochrane Central database, incorporating results from other databases such as PubMed, Embase, CTgov, CINAHL, and ICTRP. Following the exclusion of papers that did not fulfil the inclusion criteria, a total of 2090 records were found, leaving a total of 10 studies. R software was used to conduct meta-analyses based on the effect sizes between the experimental and control groups. This revealed differences in muscle stretch measures with manual muscle testing (p = 0.012) and resting motor threshold (p = 0.0457), but not with voluntary isometric contraction (p = 0.1883). The functionality of ALS was also different (p = 0.007), but not the quality of life. Although intracortical facilitation was not seen in motor cortex 1 (M1) (p = 0.1338), short-interval intracortical inhibition of M1 was significant (p = 0.0001). BDNF showed no differences that were statistically significant (p = 0.2297). Neuromodulation-based treatments are proposed as a promising therapeutic approach for ALS that can produce effects on muscle function, spasticity, and intracortical connections through electrical, magnetic, and photonic stimulation. Photobiomodulation stands out as an innovative approach that uses specific wavelengths to influence mitochondria, with the aim of improving mitochondrial function and reducing excitotoxicity. The lack of reliable placebo controls and the variation in stimulation frequency are some of the drawbacks of neuromodulation.
Topics: Humans; Amyotrophic Lateral Sclerosis; Quality of Life; Neurodegenerative Diseases; Exercise Therapy; Muscle Spasticity
PubMed: 38551974
DOI: 10.1371/journal.pone.0300671 -
Molecular Psychiatry Mar 2012A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First,... (Meta-Analysis)
Meta-Analysis Review
A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (≈ 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.
Topics: Adenosine Triphosphate; Adolescent; Animals; Biomarkers; Brain; Child; Child Development Disorders, Pervasive; Comorbidity; Developmental Disabilities; Disease Models, Animal; Electron Transport; Energy Metabolism; Female; Gastrointestinal Diseases; Humans; Lactates; Male; Mitochondria; Mitochondrial Diseases; Neuroimaging; Prevalence; Pyruvic Acid; Seizures; Sex Distribution; Young Adult
PubMed: 21263444
DOI: 10.1038/mp.2010.136 -
Human & Experimental Toxicology Sep 2011Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as... (Review)
Review
Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.
Topics: Animals; Carbamates; Carbohydrate Metabolism; Databases, Bibliographic; Humans; Hydrocarbons, Chlorinated; Lipid Metabolism; Metabolic Diseases; Organophosphates; Oxidative Stress; Pesticides; Proteins
PubMed: 21071550
DOI: 10.1177/0960327110388959 -
International Journal of Molecular... Oct 2022Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy... (Meta-Analysis)
Meta-Analysis Review
Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included “mitochondria”, “exercise”, “aerobic capacity”, and “cardiovascular disease” in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I2 = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.
Topics: Humans; Antioxidants; Exercise; Cardiovascular Diseases; Mitochondria; Succinates
PubMed: 36293409
DOI: 10.3390/ijms232012559 -
Clinical and Translational Science Nov 2021Frailty is a condition of global impairment due to depletion of physiological reserves. However, the underlying biological mechanisms are poorly understood. The aims of... (Meta-Analysis)
Meta-Analysis
Frailty is a condition of global impairment due to depletion of physiological reserves. However, the underlying biological mechanisms are poorly understood. The aims of the current study were to identify the differences in mitochondrial function and iron metabolism between frail and nonfrail populations, and to investigate the contribution of different methodological approaches to the results. Searches were performed, using five online databases up to November 2019. Studies reporting measurements of mitochondrial function or iron metabolism in frail and nonfrail subjects or subjects with and without sarcopenia, were included. Pooled effect estimates were expressed as Standardized Mean Differences. Heterogeneity, expressed as I , was explored using regression analyses. In total, 107 studies, reporting 75 measures of mitochondrial function or iron metabolism, using six different experimental approaches, in three species were identified. Significant decreases in measures of oxygen consumption were observed for frail humans but not in animal models. Conversely, no differences between frail and nonfrail humans were observed for apoptosis and autophagy, in contrast to animal models. The most significant effect of the type of frailty assessment was observed for respiratory chain complexes where only subjects categorized as frail by the Fried Frailty Index showed a significant decrease in activity. We identified iron metabolism in frailty as an important knowledge gap, highlighted the need of consistent frailty diagnostic tools, and pointed out the limited translational potential of animal models. Inconsistency between studies evaluating the molecular mechanisms underlying frailty may present a barrier to the development of effective therapies.
Topics: Frailty; Humans; Iron; Mitochondria
PubMed: 34240568
DOI: 10.1111/cts.13101 -
Phytotherapy Research : PTR Jun 2017Cancers are usually treated by anticancer agents that are toxic for both normal and cancer cells, so these drugs have major side effects and they are not suitable and... (Review)
Review
Cancers are usually treated by anticancer agents that are toxic for both normal and cancer cells, so these drugs have major side effects and they are not suitable and enough effective for cancer prevention. Solamargine, a steroidal alkaloid glycoside found in Solanum species such as Solanum nigrum, displayed several therapeutic activities. We aim to review the use of solamargine in experimental cancer studies. Articles published in biology journals between 1975 and 2017 were retrieved from PubMed, Scopus, and Web of Science using relevant keywords. The scientific papers mainly focusing on solamargine with therapeutic efficacies against cancers were identified and tabulated. In addition, the reliability of experimental findings was determined under "Risk of Bias" criteria. The author manually reviewed 33 articles; 27 articles were found concerning the anti-cancer potential in cancer cells. Solamargine has been found to possess anticancer activities via its effect on a variety of biological pathways including cell survival pathways, tumor suppressor pathways, caspase activation pathway, mitochondrial pathways, death receptor pathways, protein kinase pathways, and signal pathways, which promote invasion/migration and multi drug resistance. Solamargine can be an anticancer agent candidate when complementary scientific evidences become available. Copyright © 2017 John Wiley & Sons, Ltd.
Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Humans; Mitochondria; Neoplasms; Reproducibility of Results; Signal Transduction; Solanaceous Alkaloids
PubMed: 28383149
DOI: 10.1002/ptr.5809 -
Life Sciences Oct 2023Flaviviruses infect arthropods and mammals and their pathologies are a considerable global health problem, affecting about 400 million people per year. The symptoms of... (Review)
Review
Flaviviruses infect arthropods and mammals and their pathologies are a considerable global health problem, affecting about 400 million people per year. The symptoms of these flaviviruses range from mild manifestations such as nausea, vomiting, and headache to more serious cases such as hemorrhage, meningitis, microcephaly, kidney, and liver failure. This review aims to compile the morphological changes that occur due to infections caused by dengue, yellow fever, and Zika viruses, as well as to describe possible mechanisms of action of such flaviviruses in the liver. PRISMA guidelines were used to search for studies associating flavivirus with liver disorders. Two independent reviewers selected the studies on PubMed/Medline, Web of Science, and Scopus search platforms. The SYRCLE software was used for the evaluation of the study's quality. Eighteen experimental articles were included. The experimental animals often used in experiments were monkeys (5 %), hamsters (10 %), chicken embryos (10 %), and mice (75 %). It is evident that there is a strong hepatic interaction with flaviviruses, and the main hepatic alterations found were steatosis, apoptosis, necrosis, hemorrhage, elevation of ALT and AST levels, and total bilirubin. Flavivirus infection, in general, trigger an upregulation of pro-inflammatory cytokines, leading to structural changes in mitochondria that activate cascades of cellular death and promote insulin resistance. The majority of the studies primarily focus on dengue and yellow fever viruses, while the findings related to Zika virus exposure are still relatively limited and require further investigation.
Topics: Chick Embryo; Humans; Cricetinae; Animals; Mice; Flavivirus; Yellow Fever; Liver Diseases; Zika Virus; Dengue; Zika Virus Infection; Mammals
PubMed: 37683724
DOI: 10.1016/j.lfs.2023.122074 -
Free Radical Biology & Medicine Dec 2009Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality in the intensive care unit. Recently mitochondrial dysfunction has been... (Review)
Review
Sepsis and multiple organ dysfunction syndrome (MODS) are major causes of morbidity and mortality in the intensive care unit. Recently mitochondrial dysfunction has been proposed as a key early cellular event in critical illness. A growing body of experimental evidence suggests that mitochondrial therapies are effective in sepsis and MODS. The aim of this article is to undertake a systematic review of the current experimental evidence for the use of therapies for mitochondrial dysfunction during sepsis and MODS and to classify these mitochondrial therapies. A search of the MEDLINE and PubMed databases (1950 to July 2009) and a manual review of reference lists were conducted to find experimental studies containing data on the efficacy of mitochondrial therapies in sepsis and sepsis-related MODS. Fifty-one studies were included in this review. Five categories of mitochondrial therapies were defined-substrate provision, cofactor provision, mitochondrial antioxidants, mitochondrial reactive oxygen species scavengers, and membrane stabilizers. Administration of mitochondrial therapies during sepsis was associated with improvements in mitochondrial electron transport system function, oxidative phosphorylation, and ATP production and a reduction in cellular markers of oxidative stress. Amelioration of proinflammatory cytokines, caspase activation, and prevention of the membrane permeability transition were reported. Restoration of mitochondrial bioenergetics was associated with improvements in hemodynamic parameters, organ function, and overall survival. A substantial body of evidence from experimental studies at both the cellular and the organ level suggests a beneficial role for the administration of mitochondrial therapies in sepsis and MODS. We expect that mitochondrial therapies will have an increasingly important role in the management of sepsis and MODS. Clinical trials are now required.
Topics: Animals; Antioxidants; Apoptosis; Cell Hypoxia; Coenzymes; Electron Transport; Free Radical Scavengers; Humans; Mitochondria; Mitochondrial Membranes; Multiple Organ Failure; Oxidative Stress; Recovery of Function; Sepsis
PubMed: 19715753
DOI: 10.1016/j.freeradbiomed.2009.08.019