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International Journal of Oncology Aug 2020Over the past two decades, quantitative proteomics has emerged as an important tool for deciphering the complex molecular events involved in cancers. The number of...
Over the past two decades, quantitative proteomics has emerged as an important tool for deciphering the complex molecular events involved in cancers. The number of references involving studies on the cancer metastatic process has doubled since 2010, while the last 5 years have seen the development of novel technologies combining deep proteome coverage capabilities with quantitative consistency and accuracy. To highlight key findings within this huge amount of information, the present review identified a list of tumor invasive biomarkers based on both the literature and data collected on a biocollection of experimental cell lines, tumor models of increasing invasiveness and tumor samples from patients with colorectal or breast cancer. Crossing these different data sources led to 76 proteins of interest out of 1,245 mentioned in the literature. Information on these proteins can potentially be translated into clinical prospects, since they represent potential targets for the development and evaluation of innovative therapies, alone or in combination. Herein, a systematical review of the biology of each of these proteins, including their specific subcellular/extracellular or multiple localizations is presented. Finally, as an important advantage of quantitative proteomics is the ability to provide data on all these molecules simultaneously in cell pellets, body fluids or paraffin‑embedded sections of tumors/invaded tissues, the significance of some of their interconnections is discussed.
Topics: Animals; Biomarkers, Tumor; Cell Line, Tumor; Disease Models, Animal; Humans; Neoplasm Invasiveness; Neoplasms; Proteomics
PubMed: 32468071
DOI: 10.3892/ijo.2020.5075 -
Frontiers in Neuroscience 2022There is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and...
Tooth Loss-Associated Mechanisms That Negatively Affect Cognitive Function: A Systematic Review of Animal Experiments Based on Occlusal Support Loss and Cognitive Impairment.
BACKGROUND
There is a dose-response relationship between tooth loss and cognitive impairment, while tooth loss can be an independent risk factor for Alzheimer's disease (AD) and vascular dementia (VaD). Tooth loss can also accelerate nerve damage and neurodegeneration. However, the associated mechanisms remain poorly understood.
OBJECTIVE
To conduct a systematic review of animal experiments on cognitive decline caused by the loss of occlusal support performed over the past 10 years and summarize the possible underlying mechanisms.
METHODS
"Tooth Loss," "Edentulous," "Tooth Extraction and Memory Loss," "Cognition Impairment," and "Dementia" were used as keywords to search PubMed, Embase, SCI, ScienceDirect, and OpenGrey. A total of 1,317 related articles from 2010 to 2021 were retrieved, 26 of which were included in the review after screening according to predetermined inclusion and exclusion criteria. Comprehensiveness was evaluated using ARRIVE guidelines and the risk of bias was assessed using SYCLE'S risk of bias tool.
RESULTS
The putative mechanisms underlying the cognitive impairment resulting from the loss of occlusal support are as follows: (1) The mechanical pathway, whereby tooth loss leads to masticatory motor system functional disorders. Masticatory organ activity and cerebral blood flow decrease. With reduced afferent stimulation of peripheral receptors (such as in the periodontal membrane) the strength of the connections between neural pathways is decreased, and the corresponding brain regions degenerate; (2) the aggravation pathway, in which tooth loss aggravates existing neurodegenerative changes. Tooth loss can accelerates nerve damage through apoptosis and mitochondrial autophagy, increases amyloid deposition in the brain; and (3) the long-term inflammatory stress pathway, which involves metabolic disorders, microbial-gut-brain axis, the activation of microglia and astrocytes, and inflammatory cascade effect in central nervous system.
CONCLUSION
The loss of occlusal support may lead to cognitive dysfunction through the reduction of chewing-related stimuli, aggravation of nerve damage, and long-term inflammatory stress.
PubMed: 35221901
DOI: 10.3389/fnins.2022.811335 -
Frontiers in Neuroscience 2021Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique,...
Iron has been increasingly implicated in the pathology of neurodegenerative diseases. In the past decade, development of the new magnetic resonance imaging technique, quantitative susceptibility mapping (QSM), has enabled for the more comprehensive investigation of iron distribution in the brain. The aim of this systematic review was to provide a synthesis of the findings from existing QSM studies in neurodegenerative diseases. We identified 80 records by searching MEDLINE, Embase, Scopus, and PsycInfo databases. The disorders investigated in these studies included Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Wilson's disease, Huntington's disease, Friedreich's ataxia, spinocerebellar ataxia, Fabry disease, myotonic dystrophy, pantothenate-kinase-associated neurodegeneration, and mitochondrial membrane protein-associated neurodegeneration. As a general pattern, QSM revealed increased magnetic susceptibility (suggestive of increased iron content) in the brain regions associated with the pathology of each disorder, such as the amygdala and caudate nucleus in Alzheimer's disease, the substantia nigra in Parkinson's disease, motor cortex in amyotrophic lateral sclerosis, basal ganglia in Huntington's disease, and cerebellar dentate nucleus in Friedreich's ataxia. Furthermore, the increased magnetic susceptibility correlated with disease duration and severity of clinical features in some disorders. Although the number of studies is still limited in most of the neurodegenerative diseases, the existing evidence suggests that QSM can be a promising tool in the investigation of neurodegeneration.
PubMed: 33679303
DOI: 10.3389/fnins.2021.618435 -
Frontiers in Neuroscience 2022Neurodegenerative diseases (NDs) are generally considered proteinopathies but whereas this may initiate disease in familial cases, onset in sporadic diseases may...
Neurodegenerative diseases (NDs) are generally considered proteinopathies but whereas this may initiate disease in familial cases, onset in sporadic diseases may originate from a gradually disrupted organellar homeostasis. Herein, endolysosomal abnormalities, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and altered lipid metabolism are commonly observed in early preclinical stages of major NDs, including Parkinson's disease (PD) and Alzheimer's disease (AD). Among the multitude of underlying defective molecular mechanisms that have been suggested in the past decades, dysregulation of inter-organellar communication through the so-called membrane contact sites (MCSs) is becoming increasingly apparent. Although MCSs exist between almost every other type of subcellular organelle, to date, most focus has been put on defective communication between the ER and mitochondria in NDs, given these compartments are critical in neuronal survival. Contributions of other MCSs, notably those with endolysosomes and lipid droplets are emerging, supported as well by genetic studies, identifying genes functionally involved in lysosomal homeostasis. In this review, we summarize the molecular identity of the organelle interactome in yeast and mammalian cells, and critically evaluate the evidence supporting the contribution of disturbed MCSs to the general disrupted inter-organellar homeostasis in NDs, taking PD and AD as major examples.
PubMed: 35801175
DOI: 10.3389/fnins.2022.900338 -
Pharmacological Research Nov 2018Myocardial remodeling and dysfunction caused by accelerated oxidative damage is a widely reported phenomenon within a diabetic state. Altered myocardial substrate...
Myocardial remodeling and dysfunction caused by accelerated oxidative damage is a widely reported phenomenon within a diabetic state. Altered myocardial substrate preference appears to be the major cause of enhanced oxidative stress-mediated cell injury within a diabetic heart. During this process, exacerbated free fatty acid flux causes an abnormal increase in mitochondrial membrane potential leading to the overproduction of free radical species and subsequent cell damage. Uncoupling proteins (UCPs) are expressed within the myocardium and can protect against free radical damage by modulating mitochondrial respiration, leading to reduced production of reactive oxygen species. Moreover, transgenic animals lacking UCPs have been shown to be more susceptible to oxidative damage and display reduced cardiac function when compared to wild type animals. This suggests that tight regulation of UCPs is necessary for normal cardiac function and in the prevention of diabetes-induced oxidative damage. This review aims to enhance our understanding of the pathophysiological mechanisms relating to the role of UCPs in a diabetic heart, and further discuss known pharmacological compounds and hormones that can protect a diabetic heart through the modulation of UCPs.
Topics: Animals; Cardiotonic Agents; Diabetes Mellitus; Heart; Humans; Mitochondria, Heart; Mitochondrial Uncoupling Proteins
PubMed: 30223086
DOI: 10.1016/j.phrs.2018.09.013 -
Nutrients Jun 2020Exercise overproduces oxygen reactive species (ROS) and eventually exceeds the body's antioxidant capacity to neutralize them. The ROS produce damaging effects on the...
Exercise overproduces oxygen reactive species (ROS) and eventually exceeds the body's antioxidant capacity to neutralize them. The ROS produce damaging effects on the cell membrane and contribute to skeletal muscle damage. Selenium (Se), a natural mineral trace element, is an essential component of selenoproteins that plays an important role in antioxidant defense. The activity of the enzyme glutathione peroxidase (GPx), a highly-efficient antioxidant enzyme, is closely dependent on the presence of Se. These properties of Se may be potentially applicable to improve athletic performance and training recovery. We systematically searched for published studies to evaluate the effectiveness of Se supplementation on antioxidant defense system, muscle performance, hormone response, and athletic performance among physically active individuals. We used the Preferred Reporting Elements for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and searched in SCOPUS, Web of Science (WOS), and PubMed databases to identify published studies until March 2020. The systematic review incorporated original studies with randomized controlled crossover or parallel design in which intake of Se administered once a day was compared with the same placebo conditions. No exclusions were applied for the type of physical exercise performed, the sex, nor the age of the participants. Among 150 articles identified in the search, 6 met the criteria and were included in the systematic review. The methodological quality of the studies was evaluated using the McMaster Critical Review Form. Oral Se supplementation with 180 µg/day or 240 µg/day (selenomethionine) and 200 µg/day (Sodium Selenite), significantly decreased lipid hydroperoxide levels and increased GPx in plasma, erythrocyte, and muscle. No significant effects were observed on athletic performance, testosterone hormone levels, creatine kinase activity, and exercise training-induced adaptations on oxidative enzyme activities or on muscle fiber type myosin heavy chain expression. In addition, Se supplementation showed to have a dampening effect on the mitochondria changes in chronic and acute exercise. In summary, the use of Se supplementation has no benefits on aerobic or anaerobic athletic performance but it may prevent Se deficiencies among athletes with high-intensity and high-volume training. Optimal Se plasma levels may be important to minimize chronic exercise-induced oxidative effects and modulate the exercise effect on mitochondrial changes.
Topics: Adult; Antioxidants; Athletic Performance; Dietary Supplements; Exercise; Humans; Muscle, Skeletal; Selenium; Selenomethionine; Sodium Selenite; Testosterone
PubMed: 32560188
DOI: 10.3390/nu12061790 -
Current Reviews in Clinical and... 2022PI3K/AKT/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin) signaling pathway is an important signal transduction pathway mediated by...
Targeting Abnormal PI3K/AKT/mTOR Signaling in Intracerebral Hemorrhage: A Systematic Review on Potential Drug Targets and Influences of Signaling Modulators on Other Neurological Disorders.
PI3K/AKT/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin) signaling pathway is an important signal transduction pathway mediated by enzyme-linked receptors with many biological functions in mammals. This pathway modulates the epigenetic modification of DNA and target gene histones and plays a significant role in regulating biological activity, disease progression, oncogenesis, and cancer progression. PI3K/AKT/mTOR signaling pathway involves and mediates many cellular processes such as nutrient uptake, proliferation, anabolic reactions, and cell survival. Several studies have shown that PI3K/AKT/mTOR has been a promising therapeutic approach to intracerebral hemorrhage (ICH). ICH is characterized by the progressive development of hematoma, which leads to the structural destabilization of the neurons and glial cells, leading to neuronal deformation, further contributing to mitochondrial dysfunction, membrane depolarization, oligaemia, and neurotransmitter imbalance. Partial suppression of cell metabolism and necrosis can occur, depending on the degree of mitochondrial dysfunction. Therefore in the following review, we discuss whether or not the activation of the PI3K/AKT/mTOR signaling pathway could minimize neuronal dysfunction following ICH. We further elaborate the review by discussing the updated pathophysiology of brain hemorrhage and the role of molecular targets in other neurodegenerative diseases. This review provides current approachable disease treatment in various disease states, single and dual PI3K/AKT/mTOR signaling pathway modulators.
Topics: Animals; Cerebral Hemorrhage; Mammals; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases
PubMed: 34455956
DOI: 10.2174/1574884716666210726110021 -
Acta Oto-laryngologica Jul 2017Most of the cases with gene mutations of intra-cochlear etiology showed relatively good CI outcomes. To progress toward more solid evidence-based CI intervention, a... (Review)
Review
CONCLUSION
Most of the cases with gene mutations of intra-cochlear etiology showed relatively good CI outcomes. To progress toward more solid evidence-based CI intervention, a greater number of reports including CI outcomes for specific gene mutations are desired.
BACKGROUND
Cochlear implantation (CI) is the most important and effective treatment for patients with profound sensorineural hearing loss. However, the outcomes of CI vary among patients. One of the reasons of this heterogeneous outcome for cochlear implantation is thought to be the heterogeneous nature of hearing loss. Indeed, genetic factors, the most common etiology in severe-to-profound hearing loss, might be one of the key determinants of outcomes for CI and electric acoustic stimulation (EAS). Patients with genetic causes involving an 'intra-cochlear' etiology show good CI/EAS outcomes.
REVIEW
This review article aimed to summarize the reports on CI/EAS outcomes in patients with special genetic causes as well as to assist in future clinical decision-making. Most of the cases were suspected of an intra-cochlear etiology, such as those with GJB2, SLC26A4, and OTOF mutations, which showed relatively good CI outcomes. However, there have only been a limited number of reports on patients with other gene mutations.
Topics: Actins; Cadherin Related Proteins; Cadherins; Cochlear Implantation; Connexin 26; Connexins; Genes, Mitochondrial; Hearing Loss; Humans; Membrane Proteins; Membrane Transport Proteins; Neoplasm Proteins; Serine Endopeptidases; Sulfate Transporters; Usher Syndromes; Waardenburg Syndrome
PubMed: 28498079
DOI: 10.1080/00016489.2016.1276303 -
Journal of Photochemistry and... Jan 2021Photobiomodulation (PBM) is reported to impart a range of clinical benefits, from the healing of chronic wounds to athletic performance enhancement. The increasing...
Photobiomodulation (PBM) is reported to impart a range of clinical benefits, from the healing of chronic wounds to athletic performance enhancement. The increasing prevalence of this therapy conflicts with the lack of understanding concerning specific cellular mechanisms induced by PBM. Herein, we systematically explore the literature base, specifically related to PBM (within the range 600-1070 nm) and its influence on dermal fibroblasts. The existing research in this field is appraised through five areas: cellular proliferation and viability; cellular migration; ATP production and mitochondrial membrane potential; cellular protein expression and synthesis; and gene expression. This review demonstrates that when fibroblasts are irradiated in vitro within a set range of intensities, they exhibit a multitude of positive effects related to the wound healing process. However, the development of an optimal in vitro framework is paramount to improve the reliability and validity of research in this field.
Topics: Cell Line; Cell Movement; Cell Proliferation; Cell Survival; Fibroblasts; Gene Expression Regulation; Humans; In Vitro Techniques; Low-Level Light Therapy; Proteins; Skin; Wound Healing
PubMed: 33316625
DOI: 10.1016/j.jphotobiol.2020.112100 -
American Journal of Cancer Research 2024Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this... (Review)
Review
Cancer is one of the leading causes of death worldwide. In recent years, African countries have been faced with a rapid increase in morbidity and mortality due to this pathology. Management is often complicated by the high treatment costs, side effects and the increasing occurrence of resistance to treatments. The identification of new active ingredients extracted from endemic medicinal plants is definitively an interesting approach for the implementation of new therapeutic strategies: their extraction is often lower cost; their identification is based on an ethnobotanical history and a tradipratic approach; their use by low-income populations is simpler; this can help in the development of new synthetic molecules that are more active, more effective and with fewer side effects. The objective of this review is to document the molecules derived from African medicinal plants whose anti-cancer activities and the mechanisms of molecular actions have been identified. From the scientific databases , PubMed and Google Scholar, we searched for publications on compounds isolated from African medicinal plants and having activity on cancer cells in culture. The data were analyzed in particular with regard to the cytotoxicity of the compounds and their mode of action. A total of 90 compounds of these African medicinal plants were selected. They come from nine chemical groups: alkaloids, flavonoids, polyphenols, quinones, saponins, steroids, terpenoids, xanthones and organic sulfides. These compounds have been associated with several cellular effects: i) Cytotoxicity, including caspase activation, alteration of mitochondrial membrane potential, and/or induction of reactive oxygen species (ROS); ii) Anti-angiogenesis; iii) Anti-metastatic properties. This review points out that the cited African plants are rich in active ingredients with anticancer properties. It also stresses that screening of these anti-tumor active ingredients should be continued at the continental scale. Altogether, this work provides a rational basis for the selection of phytochemical compounds for use in clinical trials.
PubMed: 38590420
DOI: 10.62347/AUHB5811