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Future Cardiology Aug 2022Colchicine, a microtubule-disassembling (antitubulin) agent used for centuries for the treatment of gout and autoimmune diseases, is a drug of growing interest in the... (Meta-Analysis)
Meta-Analysis Review
Colchicine, a microtubule-disassembling (antitubulin) agent used for centuries for the treatment of gout and autoimmune diseases, is a drug of growing interest in the cardiovascular field. While in the last decades it has become cornerstone of pericarditis treatment, it has also emerged in the last few years as a promising drug in the management of coronary artery disease, atrial fibrillation and heart failure. This systematic review and meta-analysis aimed to assess the efficacy of colchicine in patients with cardiovascular diseases. Systematic search in electronic databases (MEDLINE/PubMed, Scopus, BioMed Central, the Cochrane Collaboration Database of Randomized Trials, ClinicalTrials.gov, EMBASE, Google Scholar) was performed to identify randomized controlled trials (RCTs) up to February 2021. Random-effects meta-analysis was performed to assess the risk of cardiovascular events, defined according to clinical setting. Among 15,569 pooled patients from 21 RCTs, colchicine was superior to placebo in the reduction of cardiovascular events. In the setting of pericardial diseases, it was associated with a lower risk of recurrent pericarditis (17 vs 34%, RR = 0.50, 95% CI: 0.42-0.60, I = 10%). In other studies assessing coronary artery disease patients, colchicine was associated with a reduced risk of major adverse cardiovascular events (MACE) such as myocardial infarction, stroke, cardiovascular death, coronary revascularisation and hospitalization (6.3 vs 9%, RR = 0.67, 95% CI: 0.54-0.84, I = 55). Among patients with atrial fibrillation, it was associated with lower rates of recurrence (20 vs 30%, RR = 0.68, 95% CI: 0.58-0.81, I = 0). In the single RCT on heart failure, colchicine was not associated with improved NYHA class. Colchicine is a valuable anti-inflammatory agent for the prevention of cardiovascular events in patients with inflammatory cardiac conditions such as pericardial diseases, coronary artery disease and atrial fibrillation.
Topics: Atrial Fibrillation; Colchicine; Coronary Artery Disease; Heart Failure; Humans; Pericarditis
PubMed: 35787150
DOI: 10.2217/fca-2020-0206 -
Medicine Apr 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Dementia severity was assessed mainly through cognitive function, psychobehavioral symptoms, and daily living ability. Currently, there are not many drugs that can be selected to treat mild to moderate AD, and the value of drugs remains controversial.
OBJECTIVE
The aim of this study is to quantitatively evaluate the efficacy and safety of cholinesterase inhibitors (ChEIs), memantine, and sodium oligomannate (GV-971) in the treatment of patients with AD. Additionally, molecular docking analysis will be used to investigate the binding affinities of donepezil, galantamine, rivastigmine, and memantine with key receptor proteins associated with AD, including beta-amyloid (Abeta), microtubule-associated protein (MAP), apolipoprotein E4 (APOE4), and Mitofusin-2 (MFN2), to further validate the results of the meta-analysis.
METHODS
We obtained clinical trials characterized by randomization, placebo control, and double-blinded methodologies concerning ChEIs, memantine, and GV-971. Statistical analysis was performed using Review Manager Version 5.4 software. Molecular docking was also conducted to evaluate the results.
RESULTS
All drugs improved the cognitive function, with the effect value ranging from -1.23 (95% CI -2.17 to -0.30) for 20 mg memantine to -3.29 (95% CI -4.14 to -2.45) for 32 mg galantamine. Although 32 mg galanthamine and GV-971 did not improve the clinicians' Global Impression of Change scale, other drugs showed significant results compared with placebo. On NPI, only 10 mg of donepezil and 24 mg of galantamine had improvement effects. On ADCS/ADL, only 20 mg memantine and 900 mg GV-971 had no significant difference from the placebo. Donepezil 5 mg and GV-971 900 mg did not increase the drug withdrawal rates due to various reasons or adverse reactions when compared to the placebo. Donepezil demonstrated superior binding to the protein and exhibited greater efficacy compared to other drugs.
CONCLUSION
ChEIs, memantine, and GV-971 all can slow the progression of AD but have different effects on respective assessments. Donepezil and GV-971 were relatively well tolerated.
Topics: Humans; Alzheimer Disease; Donepezil; Galantamine; Memantine; Molecular Docking Simulation; Cholinesterase Inhibitors; Rivastigmine
PubMed: 38640313
DOI: 10.1097/MD.0000000000037799 -
Computational and Structural... 2023Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological... (Review)
Review
Filamentous structures are ubiquitous in nature, are studied in diverse scientific fields, and span vastly different spatial scales. Filamentous structures in biological systems fulfill different functions and often form dynamic networks that respond to perturbations. Therefore, characterizing the properties of filamentous structures and the networks they form is important to gain better understanding of systems level functions and dynamics. Filamentous structures are captured by various imaging technologies, and analysis of the resulting imaging data addresses two problems: (i) identification (tracing) of filamentous structures in a single snapshot and (ii) characterizing the dynamics (., tracking) of filamentous structures over time. Therefore, considerable research efforts have been made in developing automated methods for tracing and tracking of filamentous structures. Here, we provide a systematic review in which we present, categorize, and discuss the state-of-the-art methods for tracing and tracking of filamentous structures in sparse and dense networks. We highlight the mathematical approaches, assumptions, and constraints particular for each method, allowing us to pinpoint outstanding challenges and offer perspectives for future research aimed at gaining better understanding of filamentous structures in biological systems.
PubMed: 36618983
DOI: 10.1016/j.csbj.2022.12.023 -
Cancer Treatment Reviews Dec 2015Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation... (Review)
Review
BACKGROUND
Taxanes, including paclitaxel and docetaxel, are indispensable for treatment of cancer. Development of toxicity frequently necessitates dose reduction or discontinuation of therapy, despite clinical response.
OBJECTIVE
Pharmacogenetic studies were reviewed for identification of genetic variants possibly underlying individual susceptibility to adverse events.
METHOD
We conducted a systematic search in Pubmed and Embase for pharmacogenetic reports with focus on commonly reported taxane-related gastrointestinal, hematological and neurological toxicities in adult patients with solid tumors. The findings from a total of 51 eligible studies are presented in a comprehensive way.
RESULTS
Most frequently investigated single nucleotide polymorphisms (SNPs) were located in genes encoding proteins affecting pharmacokinetics, such as drug transporters and genes of the cytochrome P450 family. Inconclusive data for risk of toxicity as well as for effects on drug exposure were reported on variants in ABCB1, CYP3A4, CYP3A5 and, for paclitaxel, CYP2C8. Interest is also dedicated towards genes involved in pharmacodynamics, such as detoxification of reactive oxygen species, DNA repair, neuronal processes and microtubule function. Recent studies include variants in TUBB2A, EPHA5 and EPHA6 for a possible association with neurotoxicity. Variations in methodological approach, sample size, study design, treatment schedule and end-point of toxicity affect consistency of results.
CONCLUSION
This review illustrates the complexity to well design pharmacogenetic studies for validation of SNPs that may clarify differences in taxane-induced toxicities among individuals. Novel genes encoding cellular targets of taxanes deserve further analysis by means of robust patient cohorts and definition of objective end-points.
Topics: ATP Binding Cassette Transporter, Subfamily B; Antineoplastic Agents; Cytochrome P-450 CYP2C8; Cytochrome P-450 CYP3A; Docetaxel; Gastrointestinal Diseases; Hematologic Diseases; Humans; Neurotoxicity Syndromes; Paclitaxel; Pharmacogenetics; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Receptor, EphA5; Receptor, EphA6; Taxoids; Tubulin
PubMed: 26585358
DOI: 10.1016/j.ctrv.2015.10.010 -
Frontiers in Psychiatry 2022Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and...
Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate βamyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.
PubMed: 36387000
DOI: 10.3389/fpsyt.2022.1038122 -
Seminars in Cell & Developmental Biology May 2023Normal axon development depends on the action of mechanical forces both generated within the cytoskeleton and outside the cell, but forces of large magnitude or rate... (Review)
Review
Normal axon development depends on the action of mechanical forces both generated within the cytoskeleton and outside the cell, but forces of large magnitude or rate cause damage instead. Computational models aid scientists in studying the role of mechanical forces in axon growth and damage. These studies use simulations to evaluate how different sources of force generation within the cytoskeleton interact with each other to regulate axon elongation and retraction. Furthermore, mathematical models can help optimize externally applied tension to promote axon growth without causing damage. Finally, scientists also use simulations of axon damage to investigate how forces are distributed among different components of the axon and how the tissue surrounding an axon influences its susceptibility to injury. In this review, we discuss how computational studies complement experimental studies in the areas of axon growth, regeneration, and damage.
Topics: Axons; Cytoskeleton; Microtubules; Neurogenesis; Computer Simulation
PubMed: 35474150
DOI: 10.1016/j.semcdb.2022.04.019 -
Tumour Biology : the Journal of the... Aug 2014Use of the autophagy-related markers beclin-1 (BECN1) and microtubule-associated protein light chain 3B (LC3B) as prognostic markers has been extensively investigated in... (Meta-Analysis)
Meta-Analysis Review
Use of the autophagy-related markers beclin-1 (BECN1) and microtubule-associated protein light chain 3B (LC3B) as prognostic markers has been extensively investigated in various kinds of cancers. However, their prognostic roles are still controversial and not firmly validated. We systematically reviewed the evidence from various studies concerning the relationship between BECN1 and LC3B expression in cancers and overall survival (OS)/disease-free survival (DFS) to elucidate this issue. PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched in July 2013 (then updated in April 2014) to identify eligible cohort studies that reported associations between BECN1 or LC3B expression and OS/DFS in cancer patients. Combined hazard ratios (HRs) with 95 % confidence intervals (95 % CIs) were pooled using fixed-effects or random-effects models according to heterogeneity in different groups. A total of 23 studies in distinct cancers were eligible for systematic review and meta-analysis. Our pooled results identified that a high expression of BECN1 is associated with favorable OS in gastric cancer (HR = 0.49, 95 % CI = 0.34-0.72) and lymphoma (HR = 0.25, 95 % CI = 0.11-0.57), whereas a high expression of LC3B predicts adverse OS in breast cancer (HR = 1.98, 95 % CI = 1.25-3.13). This systematic review and meta-analysis indicated that the autophagy-related marker BECN1 might be a predictive factor of favorable prognosis in gastric cancer, breast cancer, and lymphoma and LC3B might predict unfavorable prognosis of breast cancer. Nevertheless, due to the limited number and retrospective design of the original studies, more powerful prospective cohorts are required to verify these conclusions.
Topics: Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Disease-Free Survival; Humans; Membrane Proteins; Microtubule-Associated Proteins; Neoplasms; Prognosis
PubMed: 24838948
DOI: 10.1007/s13277-014-2060-4 -
Critical Reviews in Clinical Laboratory... Feb 2024KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as... (Review)
Review
KIF2C/MCAK a prognostic biomarker and its oncogenic potential in malignant progression, and prognosis of cancer patients: a systematic review and meta-analysis as biomarker.
KIF2C/MCAK (KIF2C) is the most well-characterized member of the kinesin-13 family, which is critical in the regulation of microtubule (MT) dynamics during mitosis, as well as interphase. This systematic review briefly describes the important structural elements of KIF2C, its regulation by multiple molecular mechanisms, and its broad cellular functions. Furthermore, it systematically summarizes its oncogenic potential in malignant progression and performs a meta-analysis of its prognostic value in cancer patients. KIF2C was shown to be involved in multiple crucial cellular processes including cell migration and invasion, DNA repair, senescence induction and immune modulation, which are all known to be critical during the development of malignant tumors. Indeed, an increasing number of publications indicate that KIF2C is aberrantly expressed in multiple cancer entities. Consequently, we have highlighted its involvement in at least five hallmarks of cancer, namely: genome instability, resisting cell death, activating invasion and metastasis, avoiding immune destruction and cellular senescence. This was followed by a systematic search of KIF2C/MCAK's expression in various malignant tumor entities and its correlation with clinicopathologic features. Available data were pooled into multiple weighted meta-analyses for the correlation between KIF2C protein or gene expression and the overall survival in breast cancer, non-small cell lung cancer and hepatocellular carcinoma patients. Furthermore, high expression of KIF2C was correlated to disease-free survival of hepatocellular carcinoma. All meta-analyses showed poor prognosis for cancer patients with KIF2C expression, associated with a decreased overall survival and reduced disease-free survival, indicating KIF2C's oncogenic potential in malignant progression and as a prognostic marker. This work delineated the promising research perspective of KIF2C with modern and technologies to further decipher the function of KIF2C in malignant tumor development and progression. This might help to establish KIF2C as a biomarker for the diagnosis or evaluation of at least three cancer entities.
PubMed: 38344808
DOI: 10.1080/10408363.2024.2309933 -
Cognitive Neuropsychology May 2021The imaging genetics of specific reading disabilities (SRD) is an emerging field that aims to characterize the disabilities' neurobiological causes, including atypical... (Meta-Analysis)
Meta-Analysis
The imaging genetics of specific reading disabilities (SRD) is an emerging field that aims to characterize the disabilities' neurobiological causes, including atypical brain structure and function and distinct genetic architecture. The present review aimed to summarize current imaging genetics studies of SRD, characterize the effect sizes of reported results by calculating Cohen's complete a Fisher's Combined Probability Test for genes featured in multiple studies, and determine areas for future research. Results demonstrate associations between SRD risk genes and reading network brain phenotypes. The Fisher's test revealed promising results for the genes and Future research should focus on exploratory approaches to identify previously undiscovered genes. Using comprehensive neuroimaging (e.g., functional and effective connectivity) and genetic (e.g., sequencing and epigenetic) techniques, and using larger samples, diverse stages of development, and longitudinal investigations, would help researchers understand the neurobiological correlates of SRD to improve early identification.
Topics: Brain; Dyslexia; Humans; Microtubule-Associated Proteins; Nerve Tissue Proteins; Neuroimaging; Receptors, Immunologic
PubMed: 34529546
DOI: 10.1080/02643294.2021.1969900 -
Phytomedicine : International Journal... Nov 2023Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative... (Review)
Review
BACKGROUND
Verbascoside is a natural and water-soluble phenylethanoid glycoside found in several medicinal plants. It has extensive pharmacological effects, including antioxidative and antineoplastic actions, and a wide range of therapeutic effects against depression.
PURPOSE
In this review, we appraised preclinical and limited clinical evidence to fully discuss the anti-depression capacity of verbascoside and its holistic characteristics that can contribute to better management of depression in vivo and in vitro models, as well as, its toxicities and medicinal value.
METHODS
This review was prepared according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A systematic review of 32 preclinical trials published up to April 2023, combined with a comprehensive bioinformatics analysis of network pharmacology and molecular docking, was conducted to elucidate the antidepressant mechanism of action of verbascoside. Studies included in the systematic review were obtained from 7 electronic databases: PubMed, Scopus, Web of Science, Cochrane, ResearchGate, ScienceDirect, and Google Scholar.
RESULTS
Studies on the antidepressant effects of verbascoside showed that various pharmacological mechanisms and pathways, such as modulating the levels of monoamine neurotransmitters, inhibiting hypothalamic-pituitary-adrenal (HPA) axis hyperfunction and promoting neuroprotection may be involved in the process of its action against depression. Verbascoside promotes dopamine (DA) biosynthesis by promoting the expression of tyrosine hydroxylase mRNA and protein, upregulates the expression of 5-hydroxytryptamine receptor 1B (5-HT1B), prominence protein, microtubule-associated protein 2 (MAP2), hemeoxygenase-1 (HO-1), SQSTM1, Recombinant Autophagy Related Protein 5 (ATG5) and Beclin-1, and decreases the expression of caspase-3 and a-synuclein, thus exerting antidepressant effects. We identified seven targets (CCL2, FOS, GABARAPL1, CA9, TYR, CA12, and SQSTM1) and three signaling pathways (glutathione metabolism, metabolism of xenobiotics by cytochrome P450, fluid shear stress and atherosclerosis) as potential molecular biological sites for verbascoside.
CONCLUSIONS
These findings provide strong evidence that verbascoside exerts its antidepressant effects through various pharmacological mechanisms. However, further multicentre clinical case-control and molecularly targeted fishing studies are required to confirm the clinical efficacy of verbascoside and its underlying direct targets.
Topics: Glycosides; Molecular Docking Simulation; Neuroprotection; Sequestosome-1 Protein
PubMed: 37657207
DOI: 10.1016/j.phymed.2023.155027