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Journal of Stroke and Cerebrovascular... May 2020Colchicine is a microtubule inhibitor with anti-inflammatory properties. As the body and quality of evidence regarding the efficacy of colchicine for cardiovascular... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colchicine is a microtubule inhibitor with anti-inflammatory properties. As the body and quality of evidence regarding the efficacy of colchicine for cardiovascular prevention is controversial, the aims of this study was to evaluate the effect of colchicine therapy on vascular events.
METHODS
A meta-analysis was performed of randomized controlled clinical trials of colchicine on high cardiovascular risk populations, reporting data from stroke, myocardial infarction, cardiovascular mortality and all-cause mortality, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A random-effects meta-analysis model was then applied.
RESULTS
Nine eligible trials of colchicine therapy, involving a total of 6630 patients, were considered eligible for analysis (3359 subjects were allocated to receive colchicine while 3271 subjects were allocated to the respective control arms). The stroke incidence was lower in the colchicine group compared with placebo arm (OR, .33; 95%CI, .15-.70; 6 studies evaluated). We did not find a significant reduction in the incidence of myocardial infarction, cardiovascular mortality or all-cause mortality.
CONCLUSIONS
Our data suggest that in a population with high cardiovascular risk, the use of colchicine results in significant reduction on stroke risk. Colchicine is an accessible drug that could be successfully utilized for the prevention of atherosclerotic cerebrovascular disease. The tolerability and benefits should be confirmed in ongoing clinical trials.
Topics: Anti-Inflammatory Agents; Colchicine; Humans; Incidence; Myocardial Infarction; Protective Factors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Stroke; Time Factors; Treatment Outcome
PubMed: 32160956
DOI: 10.1016/j.jstrokecerebrovasdis.2020.104756 -
Der Nervenarzt Oct 2018The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies.
BACKGROUND
The microtubule-associated tau protein is the defining denominator of a group of neurodegenerative diseases termed tauopathies.
OBJECTIVE
Provide a timely state of the art review on recent scientific advances in the field of tauopathies.
MATERIAL AND METHODS
Systematic review of the literature from the past 10 years.
RESULTS
Tau proteins are increasingly being recognized as a highly variable protein, underlying and defining a spectrum of molecularly defined diseases, with a clinical spectrum ranging from dementia to hypokinetic movement disorders. Genetic variation at the tau locus can trigger disease or modify disease risk. Tau protein alterations can damage nerve cells and propagate pathologies through the brain. Thus, tau proteins may serve both as a serological and imaging biomarker. Tau proteins also provide a broad spectrum of rational therapeutic interventions to prevent disease progression. This knowledge has led to modern clinical trials.
CONCLUSION
The field of tauopathies is in a state of dynamic and rapid progress, requiring close interdisciplinary collaboration.
Topics: Brain; Genetic Variation; Humans; Tauopathies; tau Proteins
PubMed: 30120488
DOI: 10.1007/s00115-018-0584-3 -
Frontiers in Pharmacology 2022The patent literature contains a large amount of information on the internal state of current industrial technologies that are not available in other literature...
The patent literature contains a large amount of information on the internal state of current industrial technologies that are not available in other literature studies. Scientific articles are the direct achievements of theoretical research in this field and can reveal how current theories in basic research have developed. In this study, the progress and status of natural anticancer products in this field were summarized, and the research hotspots were explored through the analysis of the relevant patent literature and scientific articles. Patent data were retrieved from the incoPat patent retrieval database, and paper data were retrieved from the Web of Science core set and PubMed. GraphPad Prism 8, Microsoft Excel 2010, and CiteSpace 5.8.R3 were used to perform visual processing. The analyzed patent literature includes the patent applicant type, country (or region), and technical subject. The analyzed scientific article includes academic groups, subject areas, keyword clustering, and burst detection. A total of 20,435 patent families and 38,746 articles were collected by 4 January 2022. At present, antitumor drugs derived from natural products mainly include 1) apoptosis inducers such as curcumin, gallic acid, resveratrol, Theranekron D6, and gaillardin; 2) topoisomerase inhibitors such as camptothecins, scaffold-hopped flavones, podophyllotoxin, oxocrebanine, and evodiamine derivatives; 3) telomerase inhibitors such as camptothecin and isoquinoline alkaloids of , amentoflavone, and emodin; 4) microtubule inhibitors such as kolaflavanone, tanshinone IIA analog, eugenol, and millepachine; 5) immunomodulators such as fucoidan, myricetin, bergapten, and atractylenolide I; 6) tumor microenvironment regulators such as beta-escin and icaritin; 7) multidrug resistance reversal agents such as berberine, quercetin, and dihydromyricetin; and 8) antiangiogenic and antimetastatic agents such as epigallocatechin-3-gallate, lupeol, ononin, and saikosaponin A. Anticancer natural product technology was introduced earlier, but the later development momentum was insufficient. In addition, scientific research activities are relatively closed, and technical exchanges need to be strengthened. Currently, the development of medicinal plants and the research on the anticancer mechanism of natural active products are still research hotspots, especially those related to immune checkpoints, essential oils, and metastatic cancer. Theories of traditional Chinese medicine (TCM), such as "restraining excessiveness to acquire harmony," "same treatment for different diseases," "Meridian induction theory," and "Fuzheng Quxie," have important guiding significance to the research of anticancer mechanisms and the development of new drugs and can provide new ideas for this process. : [https://sourceforge.net/projects/citespace/], identifier [000755430500001].
PubMed: 35784720
DOI: 10.3389/fphar.2022.903239 -
Andrology Sep 2019The primary cilium is a microtubule-based organelle that extends transiently from the apical cell surface to act as a sensory antenna. Initially viewed as a cellular...
BACKGROUND
The primary cilium is a microtubule-based organelle that extends transiently from the apical cell surface to act as a sensory antenna. Initially viewed as a cellular appendage of obscure significance, the primary cilium is now acknowledged as a key coordinator of signaling pathways during development and in tissue homeostasis.
OBJECTIVES
The aim of this review was to present the structure and function of this overlooked organelle,with an emphasis on its epididymal context and contribution to male infertility issues.
MATERIALS AND METHODS
A systematic review has been performed in order to include main references relevant to the aforementioned topic.
RESULTS
Increasing evidence demonstrates that primary cilia dysfunctions are associated with impaired male reproductive system development and male infertility issues.
DISCUSSION
While a large amount of data exists regarding the role of primary cilia in most organs and tissues, few studies investigated the contribution of these organelles to male reproductive tract development and homeostasis.
CONCLUSION
Functional studies of primary cilia constitute an emergent and exciting new area in reproductive biology research.
Topics: Animals; Cellular Microenvironment; Cilia; Ciliopathies; Epididymis; Humans; Infertility, Male; Male; Mechanotransduction, Cellular; Mice; Microtubules; Rete Testis; Signal Transduction; Sperm Tail
PubMed: 31131532
DOI: 10.1111/andr.12650 -
Brain Imaging and Behavior Dec 2022Computational imaging and quantitative biomarkers offer invaluable insights in the pre-symptomatic phase of neurodegenerative conditions several years before clinical... (Review)
Review
Computational imaging and quantitative biomarkers offer invaluable insights in the pre-symptomatic phase of neurodegenerative conditions several years before clinical manifestation. In recent years, there has been a focused effort to characterize pre-symptomatic cerebral changes in familial frontotemporal dementias using computational imaging. Accordingly, a systematic literature review was conducted of original articles investigating pre-symptomatic imaging changes in frontotemporal dementia focusing on study design, imaging modalities, data interpretation, control cohorts and key findings. The review is limited to the most common genotypes: chromosome 9 open reading frame 72 (C9orf72), progranulin (GRN), or microtubule-associated protein tau (MAPT) genotypes. Sixty-eight studies were identified with a median sample size of 15 (3-141) per genotype. Only a minority of studies were longitudinal (28%; 19/68) with a median follow-up of 2 (1-8) years. MRI (97%; 66/68) was the most common imaging modality, and primarily grey matter analyses were conducted (75%; 19/68). Some studies used multimodal analyses 44% (30/68). Genotype-associated imaging signatures are presented, innovative study designs are highlighted, common methodological shortcomings are discussed and lessons for future studies are outlined. Emerging academic observations have potential clinical implications for expediting the diagnosis, tracking disease progression and optimising the timing of pharmaceutical trials.
Topics: Humans; Frontotemporal Dementia; Magnetic Resonance Imaging; Mutation; tau Proteins; Progranulins; Gray Matter
PubMed: 35920960
DOI: 10.1007/s11682-022-00711-z -
Frontiers in Bioscience (Landmark... Jan 2024Microtubule-associated protein tau () mutations are one of the main causes of genetic Frontotemporal dementia (FTD) and are characterised by high clinical heterogeneity....
BACKGROUND
Microtubule-associated protein tau () mutations are one of the main causes of genetic Frontotemporal dementia (FTD) and are characterised by high clinical heterogeneity. A behavioural variant of FTD is the principal phenotype, but other rarer phenotypes are described, mostly reported as single cases. In this review, we provide an overview of the clinical phenotypes associated with mutations in order to define their characteristics and explore genotype-phenotype correlations.
METHODS
We performed systematic bibliographic research on the Pubmed database, focusing on articles published between 1998 and 2022. We analysed the clinical phenotype of 177 patients carrying mutations, focusing on the rarest ones. We performed a narrative synthesis of the results.
RESULTS
Regarding language phenotypes, the most frequent were the non-fluent variant and the semantic variant of Primary Progressive Aphasia (nfvPPA, svPPA), approximately in the same proportion. Almost 20% of the whole group of patients present a clinical phenotype belonging to the corticobasal syndrome-progressive supranuclear palsy (CBS-PSP) spectrum. While no clear genotype-phenotype correlation could be identified, some mutations were associated with a specific phenotype, while others gave origin to multiple clinical pictures and mixed phenotypes.
CONCLUSIONS
A high clinical heterogeneity exists in FTD associated with mutations without a clear phenotype-genotype correlation in most cases. However, some characteristics can be helpful to drive genetic testing. Deep phenotyping of patients, together with functional studies of single mutations, particularly those associated with atypical phenotypes, are necessary to better understand the biological mechanisms underlying this clinical variability.
Topics: Humans; Frontotemporal Dementia; tau Proteins; Mutation; Genetic Association Studies; Phenotype
PubMed: 38287807
DOI: 10.31083/j.fbl2901012 -
Journal of Neurotrauma Sep 2021Traumatic brain injury (TBI) is a major public health challenge that is also the third leading cause of death worldwide. It is also the leading cause of long-term...
Traumatic brain injury (TBI) is a major public health challenge that is also the third leading cause of death worldwide. It is also the leading cause of long-term disability in children and young adults worldwide. Despite a large body of research using predominantly and rodent models of brain injury, there is no medication that can reduce brain damage or promote brain repair mainly due to our lack of understanding in the mechanisms and pathophysiology of the TBI. The aim of this review is to examine TBI studies conducted from 2008-2018 to better understand the TBI model available in the literature. Specifically, our focus was to perform a detailed analysis of the experimental protocols used and their subsequent biological findings. Our review showed that the uniaxial stretch is the most frequently used way of load application, accounting for more than two-thirds of the studies reviewed. The rate and magnitude of the loading were varied significantly from study to study but can generally be categorized into mild, moderate, and severe injuries. The studies reviewed here examined key processes in TBI pathophysiology such as membrane disruptions leading to ionic dysregulation, inflammation, and the subsequent damages to the microtubules and axons, as well as cell death. Overall, the studies examined in this review contributed to the betterment of our understanding of TBI as a disease process. Yet, our review also revealed the areas where more work needs to be done such as: 1) diversification of load application methods that will include complex loading that mimics head impacts; 2) more widespread use of human brain cells, especially patient-matched human cells in the experimental set-up; and 3) need for building a more high-throughput system to be able to discover effective therapeutic targets for TBI.
Topics: Animals; Brain Injuries, Traumatic; Humans; In Vitro Techniques; Models, Biological
PubMed: 33563092
DOI: 10.1089/neu.2020.7402 -
European Journal of Dermatology : EJD Oct 2018In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with...
In this review, the current knowledge of cutaneous squamous cell carcinogenesis (cSCC) is outlined based on an appraisal of the different features of cSCC, with particular emphasis on genetic alterations underlying aetiopathogenesis. When appropriate, diagnostic and/or prognostic biomarkers for cSCC are also considered. This review is intended to aid future investigation into the molecular characterization of cSCC.
Topics: Carcinogenesis; Carcinoma, Squamous Cell; Cell Cycle Proteins; Cyclin D1; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Microtubule-Associated Proteins; Mutation; Prevalence; Retinoblastoma Binding Proteins; Risk Assessment; Skin Neoplasms; Tumor Suppressor Protein p53; Ubiquitin-Protein Ligases
PubMed: 30530431
DOI: 10.1684/ejd.2018.3403 -
Scientific Reports Dec 2020The increasing body of literature describing the role of host factors in COVID-19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and... (Meta-Analysis)
Meta-Analysis
The increasing body of literature describing the role of host factors in COVID-19 pathogenesis demonstrates the need to combine diverse, multi-omic data to evaluate and substantiate the most robust evidence and inform development of therapies. Here we present a dynamic ranking of host genes implicated in human betacoronavirus infection (SARS-CoV-2, SARS-CoV, MERS-CoV, seasonal coronaviruses). We conducted an extensive systematic review of experiments identifying potential host factors. Gene lists from diverse sources were integrated using Meta-Analysis by Information Content (MAIC). This previously described algorithm uses data-driven gene list weightings to produce a comprehensive ranked list of implicated host genes. From 32 datasets, the top ranked gene was PPIA, encoding cyclophilin A, a druggable target using cyclosporine. Other highly-ranked genes included proposed prognostic factors (CXCL10, CD4, CD3E) and investigational therapeutic targets (IL1A) for COVID-19. Gene rankings also inform the interpretation of COVID-19 GWAS results, implicating FYCO1 over other nearby genes in a disease-associated locus on chromosome 3. Researchers can search and review the gene rankings and the contribution of different experimental methods to gene rank at https://baillielab.net/maic/covid19 . As new data are published we will regularly update the list of genes as a resource to inform and prioritise future studies.
Topics: Algorithms; CD3 Complex; CD4 Antigens; COVID-19; Chemokine CXCL10; Computational Biology; Cyclophilin A; Cyclosporine; Databases, Genetic; Genome-Wide Association Study; Genomics; Humans; Immune System; Immunogenetics; Inflammation; Interleukin-1alpha; Microtubule-Associated Proteins; Proteomics
PubMed: 33339864
DOI: 10.1038/s41598-020-79033-3 -
The Lancet. Oncology Apr 2005Docetaxel is a semisynthetic taxane, a class of anticancer agents that bind to beta tubulin, thereby stabilising microtubules and inducing cell-cycle arrest and... (Review)
Review
Docetaxel is a semisynthetic taxane, a class of anticancer agents that bind to beta tubulin, thereby stabilising microtubules and inducing cell-cycle arrest and apoptosis. Docetaxel was first approved for the treatment of anthracycline-refractory metastatic breast cancer in the mid-1990s. Since then, several randomised trials have reported improved time-to-progression, overall survival, or both in metastatic breast cancer treated with single-agent docetaxel or docetaxel-based combination regimens. Data from two adjuvant trials have shown a survival benefit with the addition of docetaxel to standard anthracycline-based regimens in patients with high-risk early breast cancer. In four randomised studies, docetaxel improved survival in locally advanced or metastatic non-small-cell lung cancer. Moreover, two trials have shown that docetaxel combined with estramustine or corticosteroids improves survival in metastatic androgen-independent prostate cancer. Here, we review major randomised phase III trials with docetaxel in the treatment of solid malignant disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Docetaxel; Female; Humans; Lung Neoplasms; Male; Neoplasms; Ovarian Neoplasms; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis; Taxoids
PubMed: 15811618
DOI: 10.1016/S1470-2045(05)70094-2