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Journal of Cancer 2022Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the... (Review)
Review
Rho-GTPases control a variety of cellular functions mainly by regulating microtubule and actin dynamics, affecting the cytoskeleton, and are important regulators of the structural plasticity of dendrites and spines. Members of the Rho-GTPase family include Ras-related C3 botulinum toxin substrate 1 (Rac1), RhoA (Ras homologous), and cell division control protein 42 (Cdc42). Cdc42 is involved in the regulation of a variety of tumor and non-tumor diseases through a cascade of multiple signaling pathways. Active Cdc42 can regulate intercellular adhesion, cytoskeleton formation, and cell cycle, thus affecting cell proliferation, transformation, and dynamic balance as well as migration and invasion of tumor cells by regulating the expression of effector proteins. Here we discuss the role of Cdc42 in promoting metastasis, invasion, epithelial-mesenchymal transformation and angiogenesis in malignant tumors. The significant role of Cdc42 in non-tumor diseases is also discussed. Since Cdc42 plays a central role in the development of various diseases, small molecule inhibitors targeting Cdc42 have important clinical significance in the prevention and treatment of these diseases.
PubMed: 35154449
DOI: 10.7150/jca.65415 -
Cancer Cell International Sep 2023Paclitaxel is a natural anticancer compound with minimal toxicity, the capacity to stabilize microtubules, and high efficiency that has remained the standard of... (Review)
Review
Paclitaxel is a natural anticancer compound with minimal toxicity, the capacity to stabilize microtubules, and high efficiency that has remained the standard of treatment alongside platinum-based therapy as a remedy for a variety of different malignancies. In contrast, polyphenols such as flavonoids are also efficient antioxidant and anti-inflammatory and have now been shown to possess potent anticancer properties. Therefore, the synergistic effects of paclitaxel and flavonoids against cancer will be of interest. In this review, we use a Boolean query to comprehensively search the well-known Scopus database for literature research taking the advantage of paclitaxel and flavonoids simultaneously while treating various types of cancer. After retrieving and reviewing the intended investigations based on the input keywords, the anticancer mechanisms of flavonoids and paclitaxel and their synergistic effects on different targets raging from cell lines to animal models are discussed in terms of the corresponding involved signaling transduction. Most studies demonstrated that these signaling pathways will induce apoptotic / pro-apoptotic proteins, which in turn may activate several caspases leading to apoptosis. Finally, it can be concluded that the results of this review may be beneficial in serving as a theoretical foundation and reference for future studies of paclitaxel synthesis, anticancer processes, and clinical applications involving different clinical trials.
PubMed: 37743502
DOI: 10.1186/s12935-023-03052-z -
The Science of the Total Environment Feb 2023Cardiovascular disease (CVD) and cancer are collectively responsible for tens of millions of global deaths each year. These rates are projected to intensify as the... (Review)
Review
Cardiovascular disease (CVD) and cancer are collectively responsible for tens of millions of global deaths each year. These rates are projected to intensify as the COVID-19 pandemic has caused delays in individualized diagnostics, or exacerbated prevalence due to Post Acute Coronavirus (COVID-19) Syndrome. Wastewater-based epidemiology (WBE) has successfully been employed as a useful tool for generating population-level health assessments, and was examined here in this systematic scoping literature review to (i) identify endogenous human biomarkers reported to indicate CVD or cancer in clinical practice, (ii) assess specificity to the indicated diseases, (iii) evaluate the utility for estimating population-level disease prevalence in community wastewater, and (iv) contextualize the obtained information for monitoring CVD and cancer presence via WBE. A total of 48 peer-reviewed papers were critically examined identifying five urinary protein biomarkers: cardiac troponin I (cTnI) (heart attack/heart failure), cystatin C (atherosclerosis), normetanephrine (tumor presence), α-fetoprotein (prostate and liver cancer), and microtubule assisted serine/threonine kinase 4 (MAST4) (breast cancer). Next, urinary excretion information was utilized to predict biomarker concentrations extant in community wastewater, resulting in average healthy concentrations ranging from 0.02 to 1159 ng/L, and disease-indicating thresholds from 0.16 to 3041 ng/L. Finally, estimating prevalence-adjusted wastewater measurements was explored in order to assess community-level CVD and cancer presence utilizing U.S. reported prevalence rates. Results obtained suggest that WBE can serve as a viable tool in support of current methods for CVD and cancer assessment to reduce morbidities and mortalities worldwide.
Topics: Humans; Wastewater-Based Epidemiological Monitoring; Cardiovascular Diseases; Pandemics; COVID-19; Neoplasms; Microtubule-Associated Proteins; Protein Serine-Threonine Kinases
PubMed: 36370774
DOI: 10.1016/j.scitotenv.2022.160103 -
Journal of Cellular Physiology Sep 2019Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays a pivotal part in the formation of spindles. There is... (Review)
Review
Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a microtubule-associated protein that plays a pivotal part in the formation of spindles. There is accumulating evidence that the expression of TPX2 is upregulated in many kinds of human cancers and that this protein is involved in the occurrence and progression of tumors. The purpose of this meta-analysis was to investigate the relationship between the overexpression of TPX2 and poor prognosis in cancer patients. A total of 18 eligible studies encompassing 3115 patients were included by searching relevant databases. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled under random-/fixed-effect models. After calculation, the results showed that patients with increased TPX2 expression had a significantly shorter overall survival (HR = 2.21; 95% CI: 1.70-2.86), and disease-free survival (HR = 2.10; 95% CI: 1.67-2.64). In addition, it was found that increased TPX2 expression was significantly associated with TNM stage (OR = 2.17; 95% CI:1.42-3.32), lymph node metastasis (OR = 2.98; 95% CI: 2.28-3.89), distant metastasis (OR = 2.25; 95% CI:1.03-4.92), and vascular invasion (OR = 2.22; 95% CI:1.26-3.91). Nevertheless, there was no significant correlation between increased expression of TPX2 and either gender, tumor differentiation, or tumor size. Thus, we can come to the conclusion that the overexpression of TPX2 is related to poor clinical outcomes and can be used as a biomarker for the prognosis of patients with cancer.
PubMed: 30779127
DOI: 10.1002/jcp.28343 -
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 -
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 -
Cells Dec 2022Mutations in genes encoding proteins associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex within the nuclear envelope cause different diseases... (Review)
Review
Mutations in genes encoding proteins associated with the linker of nucleoskeleton and cytoskeleton (LINC) complex within the nuclear envelope cause different diseases with varying phenotypes including skeletal muscle, cardiac, metabolic, or nervous system pathologies. There is some understanding of the structure of LINC complex-associated proteins and how they interact, but it is unclear how mutations in genes encoding them can cause the same disease, and different diseases with different phenotypes. Here, published mutations in LINC complex-associated proteins were systematically reviewed and analyzed to ascertain whether patterns exist between the genetic sequence variants and clinical phenotypes. This revealed is the only LINC complex-associated gene in which mutations commonly cause distinct conditions, and there are no clear genotype-phenotype correlations. Clusters of variants causing striated muscle disease are located in exons 1 and 6, and metabolic disease-associated variants are frequently found in the tail of lamin A/C. Additionally, exon 6 of the emerin gene, , may be a mutation "hot-spot", and diseases related to , encoding nesprin-1, are most often caused by nonsense type mutations. These results provide insight into the diverse roles of LINC-complex proteins in human disease and provide direction for future gene-targeted therapy development.
Topics: Humans; Cytoskeleton; Microtubules; Nuclear Envelope; Nuclear Matrix; Mutation
PubMed: 36552829
DOI: 10.3390/cells11244065 -
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