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International Journal of Environmental... Jan 2022Wolfram syndrome (WS) is a rare autosomal recessive disorder that is characterized by the presence of diabetes mellitus, optic atrophy and hearing loss, all of which are... (Review)
Review
BACKGROUND
Wolfram syndrome (WS) is a rare autosomal recessive disorder that is characterized by the presence of diabetes mellitus, optic atrophy and hearing loss, all of which are crucial elements for the diagnosis. WS is variably associated with diabetes insipidus, neurological disorders, urinary tract anomalies, endocrine dysfunctions and many other systemic manifestations. Since Wolfram and Wagener first described WS in 1938, new phenotypic/genotypic variants of the syndrome have been observed and the clinical picture has been significantly enriched. To date, two main subtypes of WS that associated with two different mutations are known: WS type 1 (WS1), caused by the mutation of the wolframine gene (WS1; 606201), and WS type 2 (WS2), caused by the mutation of the CISD2 gene (WS2; 604928).
METHODS
A systematic review of the literature was describe the phenotypic characteristics of WS2 in order to highlight the key elements that differentiate it from the classic form.
CONCLUSION
WS2 is the rarest and most recently identified subtype of WS; its clinical picture is partially overlapping with that of WS1, from which it traditionally differs by the absence of diabetes insipidus and the presence of greater bleeding tendency and peptic ulcers.
Topics: Diabetes Mellitus, Type 2; Humans; Membrane Proteins; Mitochondrial Diseases; Mutation; Optic Atrophy; Wolfram Syndrome
PubMed: 35055657
DOI: 10.3390/ijerph19020835 -
Advances in Therapy Dec 2019Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy...
Leber's hereditary optic neuropathy (LHON) is a relatively common, rapidly progressing inherited optic neuropathy wherein LHON-affected eyes undergo optic nerve atrophy due to retinal ganglion cell (RGC) loss. It is a maternally inherited (or sporadic) mitochondrial disorder caused primarily by mutations in genes that encode components of respiratory complex (RC)1 in mitochondria. Mitochondrial deficiency of RC1 compromises ATP production and oxidative stress management in RGCs. The most common LHON-causing mutations are 11778G>A, 3460G>A, and 14484T>C point mutations in MT-ND4, MT-ND1, and MT-ND6. The unusually high mitochondrial load of RGCs makes them particularly sensitive to these mutations. Patients with LHON may be prescribed ubiquinone (a component of RC3) or idebenone, a ubiquinone analogue with enhanced bioavailability to act downstream of RC1. The challenge of accessing the inner mitochondrial membrane with gene therapy for LHON, and other mitochondrial diseases, may be overcome by incorporation of a specific mitochondrion-targeting sequence (MTS) that enables allotropic expression of a nucleus-transcribed ND4 transgene. Because LHON penetrance is incomplete among carriers of the aforementioned mutations, identification of environmental factors, such as heavy smoking, that interact with genetics in the phenotypic expression of LHON may be helpful toward preventing or delaying disease development. LHON has become a model for mitochondrial and neurogenerative diseases owing to it having a clearly identified genetic cause and its early onset and rapid progression characteristics. Hence, LHON studies and genetic treatment advances may inform research of other diseases.
Topics: DNA, Mitochondrial; Electron Transport Complex I; Genetic Therapy; Humans; Mutation; Optic Atrophy, Hereditary, Leber; Phenotype; Point Mutation
PubMed: 31605306
DOI: 10.1007/s12325-019-01113-2 -
Journal of Clinical and Translational... Jan 2018Anthraquinones are a possible treatment option for oncological patients due to their anti-cancer properties. Cancer patients often exhaust a plethora of resources that...
BACKGROUND
Anthraquinones are a possible treatment option for oncological patients due to their anti-cancer properties. Cancer patients often exhaust a plethora of resources that ultimately fail to provide fully curative measures. Alternative treatments are subsequently sought in the hope of finding a therapeutic remedy. Po¬tential regimens include aloe-emodin and its related derivatives. This review therefore summarizes the effects of aloe-emodin and other aloe components in light of their anti-proliferative and anti-carcinogenic properties.
METHODS
A systematic search was performed in PubMed for aloe-emodin and cancer in humans. Sixty abstracts of studies were selected and reviewed with subsequent screening of the full text. Thirty-eight articles were summarized.
RESULTS
Aloe-emodin possesses multiple anti-proliferative and anti-carcinogenic properties in a host of human cancer cell lines, with often multiple vital pathways affected by the same molecule. The most notable effects include inhibition of cell proliferation, migration, and invasion; cycle arrest; induction of cell death; mitochondrial membrane and redox perturbations; and modulation of immune signaling. The effects of aloe-emodin are not ubiquitous across all cell lines but depend on cell type.
CONCLUSIONS
On the basis of this systematic review, the multiple consistent effects of aloe-emodin in hu¬man-derived cancer cell lines suggest that aloe-emodin is a potential anti-cancer agent that acts on cancer cells in a pleiotropic manner.
RELEVANCE FOR PATIENTS
Cancer patients often utilize alternative therapies as a result of suboptimal efficacy of conventional treatments. Aloe-emodin might become a therapeutic option for cancer patients if the basic research is confirmed in clinical trials.
PubMed: 30895270
DOI: No ID Found -
International Journal of Molecular... Sep 2023Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine... (Review)
Review
Cocaine abuse is a serious public health problem as this drug exerts a plethora of functional and histopathological changes that potentially lead to death. Cocaine causes complex multiorgan toxicity, including in the heart where the blockade of the sodium channels causes increased catecholamine levels and alteration in calcium homeostasis, thus inducing an increased oxygen demand. Moreover, there is evidence to suggest that mitochondria alterations play a crucial role in the development of cocaine cardiotoxicity. We performed a systematic review according to the Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) scheme to evaluate the mitochondrial mechanisms determining cocaine cardiotoxicity. Among the initial 106 articles from the Pubmed database and the 17 articles identified through citation searching, 14 final relevant studies were extensively reviewed. Thirteen articles included animal models and reported the alteration of specific mitochondria-dependent mechanisms such as reduced energy production, imbalance of membrane potential, increased oxidative stress, and promotion of apoptosis. However, only one study evaluated human cocaine overdose samples and observed the role of cocaine in oxidative stress and the induction of apoptosis though mitochondria. Understanding the complex processes mediated by mitochondria through forensic analysis and experimental models is crucial for identifying potential therapeutic targets to mitigate or reverse cocaine cardiotoxicity in humans.
Topics: Animals; Humans; Cardiotoxicity; Cocaine; Cocaine-Related Disorders; Heart; Mitochondria; Oxidative Stress
PubMed: 37833964
DOI: 10.3390/ijms241914517 -
Frontiers in Veterinary Science 2024Cryopreservation of sperm is an essential technique in assisted reproduction in cattle. The objective of the study was to systematically review and synthesize the...
Cryopreservation of sperm is an essential technique in assisted reproduction in cattle. The objective of the study was to systematically review and synthesize the literature on bull semen quality evaluation based on the comparison of morphological and metabolic parameters of cryopreserved bovine spermatozoa such as DNA integrity, mitochondrial status, plasma membrane alterations, total motility, and morphology (% of abnormal cells). The electronic databases PubMed, Web of Sciences, Scopus, and Google Scholar were searched up to December 2023. Studies and references were included if they reported the following parameters: DNA integrity, mitochondrial status, plasma membrane alterations, total motility, and morphological aberrations (% of abnormal cells) for conventional cryopreserved bovine spermatozoa. After an electronic search, out of 1,526 original studies, only 40 were included in the meta-analysis. Standardized mean differences (SMD) with 95% confidence intervals were estimated for the chosen studies, and a meta-analysis was performed using a random effects model. The tau-squared (tau) and inconsistency index () quantified heterogeneity among different studies. The regression analysis for the evaluated parameters showed a positive correlation between mitochondrial membrane potential (MMP), total motility, and abnormal morphology and a negative correlation between DNA fragmentation index (DFI) and total motility and MMP. Moreover, subgroup analysis demonstrated similar associations for dairy and non-dairy bull breeds, albeit with lower values. The presence of publication bias was confirmed by Egger's test, except for the MMP parameter. A multi-parametric analysis of morphological and metabolic parameters can address the existing limitations of cryopreserved bovine spermatozoa quality assessment. Combining imaging flow cytometry (IFC) with standardization of sperm pre-processing and optimization of the experimental protocols may help to differentiate sperm from cellular debris and cytoplasmic droplets of similar size and alleviate limitations demonstrated by conventional sperm analysis.
PubMed: 38721151
DOI: 10.3389/fvets.2024.1371586 -
Frontiers in Pharmacology 2023Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for...
Autophagy is a cellular process where damaged organelles or unwanted proteins are packaged into a double-membrane structure and transported to lysosomes for degradation. Autophagy plays a regulatory role in various hematologic malignancies, including acute myeloid leukemia (AML). However, there are few bibliometric studies on the role of autophagy in AML. The purpose of this study is to clarify the role of autophagy in acute myeloid leukemia through bibliometric analysis. The literature on autophagy and AML research from 2003 to 2023 was searched in Web of Science Core Collection, and bibliometric tools such as VOSviewer 1.6.18, Cite Space (6.1.R3), RStudio (R package bibliometrix), and Scimago Graphica were used to understand the current status and hotspots of autophagy and AML research. The study conducted an analysis of various dimensions including the quantity of publications, countries, institutions, journals, authors, co-references, keywords, and to predict future development trends in this field by drawing relevant visualization maps. A total of 343 articles were obtained, published in 169 journals, written by 2,323 authors from 295 institutions in 43 countries. The journals with the most publications were Blood and Oncotarget. China had the most publications, and Chongqing Medical University and Sun Yat-sen University had the most publications. The author with the highest number of publications was Tschan, Mario P. The main types of research included clinical research, experiments, experiments, public database information, and reviews, and the forms of therapeutic effects mainly focused on genetic regulation, traditional Chinese medicine combination, autophagy inhibitors, and drug targets. The research hotspots of autophagy and AML in the past 17 years have focused on genetic regulation, autophagy inhibition, and targeted drugs. Chemotherapy resistance and mitochondrial autophagy will be the forefront of research. The gradual increase in the literature on autophagy and AML research and the decline after 2022 could be a result of authors focusing more on the type of research and the quality of the literature. The current research hotspots are mainly genetic regulation, autophagy inhibition, and autophagy-related targeted drugs. In future, autophagy will remain the focus of the AML field, with research trends likely to focus more on AML chemotherapy resistance and mitochondrial autophagy.
PubMed: 38322702
DOI: 10.3389/fphar.2023.1291195 -
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