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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 -
Annals of Medicine Dec 2022Colchicine, because of its anti-inflammatory and possible anti-viral properties, has been proposed as potential therapeutic option for COVID-19. The role of colchicine...
INTRODUCTION
Colchicine, because of its anti-inflammatory and possible anti-viral properties, has been proposed as potential therapeutic option for COVID-19. The role of colchicine to mitigate "cytokine storm" and to decrease the severity and mortality associated with COVID-19 has been evaluated in many studies.
OBJECTIVE
To evaluate the role of colchicine on morbidity and mortality in COVID-19 patients.
METHODS
This systematic review was conducted in accordance with the PRISMA recommendations. The literature search was conducted in 6 medical databases from inception to February 17, 2021 to identify studies evaluating colchicine as a therapeutic agent in COVID-19. All included studies were evaluated for risk of bias (ROB) using the Revised Cochrane ROB tool for randomised controlled trials (RCTs) and Newcastle-Ottawa Scale (NOS) for case-control and cohort studies.
RESULTS
Four RCTs and four observational studies were included in the final analysis. One study evaluated colchicine in outpatients, while all others evaluated inpatient use of colchicine. There was significant variability in treatment protocols for colchicine and standard of care in all studies. A statistically significant decrease in all-cause mortality was observed in three observational studies. The risk of mechanical ventilation was significantly reduced only in one observational study. Length of hospitalisation was significantly reduced in two RCTs. Risk for hospitalisation was not significantly decreased in the study evaluating colchicine in outpatients. Very few studies had low risk of bias.
CONCLUSION
Based on the available data, colchicine shall not be recommended to treat COVID-19. Further high-quality and multi-center RCTs are required to assess the meaningful impact of this drug in COVID-19.KEY MESSAGESColchicine, an anti-inflammatory agent has demonstrated anti-viral properties in in-vitro studies by degrading the microtubules, as well as by inhibiting the production of pro-inflammatory cytokines.Colchicine has been studied as a potential therapeutic option for COVID-19, with variable results.Until further research can establish the efficacy of colchicine in COVID-19, the use of colchicine in COVID-19 shall be restricted to clinical trials.
Topics: Colchicine; Humans; Morbidity; Observational Studies as Topic; Respiration, Artificial; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35258357
DOI: 10.1080/07853890.2021.1993327 -
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 -
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 -
Cureus May 2021Background Peripheral neuropathy (PN), especially peripheral sensory neuropathy (PSN), is significant toxicity of taxanes, the most used class of microtubule inhibitors...
Relative Risk of Peripheral Neuropathy With Ado-Trastuzumab Emtansine (T-DM1) Compared to Taxane-Based Regimens in Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Cancers: A Systematic Review and Meta-Analysis.
Background Peripheral neuropathy (PN), especially peripheral sensory neuropathy (PSN), is significant toxicity of taxanes, the most used class of microtubule inhibitors for human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Ado-trastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate, consisting of trastuzumab and a microtubule inhibitor DM1, which has been approved for HER2-positive breast cancer. T-DM1 has also been found to cause significant PN, including PSN. Methods We conducted a systematic review and meta-analysis of phase 3 randomized controlled trials using T-DM1 in the experimental arm and a taxane-based regimen in the control arm to determine the relative risk of PN and PSN associated with T-DM1 as compared to taxanes. A total of 1,857 patients were included in the analysis. The Cochran-Mantel-Haenszel method and the random-effects model were used to calculate the pooled risk ratio (RR) with a 95% confidence interval (CI) for all-grade and grade ≥3 PN and PSN. Results The relative risks of all-grade PN and all-grade PSN were lower with T-DM1 compared to taxanes. The pooled RR of all-grade PN was 0.59, 95% CI: 0.39-0.89, P = 0.01, and the pooled RR of all-grade PSN was 0.58, 95% CI: 0.46-0.74, P < 0.0001. Conclusions Our meta-analysis demonstrated that T-DM1 is associated with a relatively lower risk of all-grade PN and PSN than the taxane-based regimens for HER2-positive cancers. It could be an area of consideration in selecting therapy for HER2-positive breast cancer patients at high risk of developing or having pre-existing PN and PSN.
PubMed: 34194883
DOI: 10.7759/cureus.15282 -
Medicine Jun 2021: Discovery of evidence of acute brain ischemia or hypoxia and its differentiation from agonal hypoxia represents a task of interest but extremely difficult in forensic...
BACKGROUND
: Discovery of evidence of acute brain ischemia or hypoxia and its differentiation from agonal hypoxia represents a task of interest but extremely difficult in forensic neuropathology. Generally, more than 50% of forensic autopsies indicate evidence of brain induced functional arrest of the organ system, which can be the result of a hypoxic/ischemic brain event. Even if the brain is the target organ of hypoxic/ischemic damage, at present, there are no specific neuropathological (macroscopic and histological) findings of hypoxic damage (such as in drowning, hanging, intoxication with carbon monoxide) or acute ischemia. In fact, the first histological signs appear after at least 4 to 6 hours. Numerous authors have pointed out how an immunohistochemical analysis could help diagnose acute cerebral hypoxia/ischemia.Data sources: This review was based on articles published in PubMed and Scopus databases in the past 25 years, with the following keywords "immunohistochemical markers," "acute cerebral ischemia," "ischemic or hypoxic brain damage," and "acute cerebral hypoxia".
OBJECTIVES
: Original articles and reviews on this topic were selected. The purpose of this review is to analyze and summarize the markers studied so far and to consider the limits of immunohistochemistry that exist to date in this specific field of forensic pathology.
RESULTS
: We identified 13 markers that had been examined (in previous studies) for this purpose. In our opinion, it is difficult to identify reliable and confirmed biomarkers from multiple studies in order to support a postmortem diagnosis of acute cerebral hypoxia/ischemia. Microtubule-associated protein 2 (MAP2) is the most researched marker in the literature and the results obtained have proven to be quite useful.
CONCLUSION
Immunohistochemistry has provided interesting and promising results, but further studies are needed in order to confirm and apply them in standard forensic practice.
Topics: Acute Disease; Animals; Autopsy; Biomarkers; Brain; Disease Models, Animal; Humans; Hypoxia-Ischemia, Brain; Immunohistochemistry; Microtubule-Associated Proteins; Reproducibility of Results; Time Factors
PubMed: 34160462
DOI: 10.1097/MD.0000000000026486 -
Critical Reviews in Oncology/hematology Apr 2021Glioblastoma, the most common primary brain malignancy, is an exceptionally fatal cancer. Lack of suitable biomarkers and efficient treatment largely contribute to the... (Review)
Review
Glioblastoma, the most common primary brain malignancy, is an exceptionally fatal cancer. Lack of suitable biomarkers and efficient treatment largely contribute to the therapy failure. Cytoskeletal proteins are crucial proteins in glioblastoma pathogenesis and can potentially serve as biomarkers and therapeutic targets. Among them, GFAP, has gained most attention as potential diagnostic biomarker, while vimentin and microtubules are considered as prospective therapeutic targets. Microtubules represent one of the best anti-cancer targets due to their critical role in cell proliferation. Despite testing in clinical trials, the efficiency of taxanes, epothilones, vinca-domain binding drugs, colchicine-domain binding drugs and γ-tubulin binding drugs remains to be confirmed. Moreover, tumor treating field that disrupts microtubules draw attention because of its high efficiency and is called "the fourth cancer treatment modality". Thereby, because of the involvement of cytoskeleton in key physiological and pathological processes, its therapeutic potential in glioblastoma is currently extensively investigated.
Topics: Biomarkers; Cytoskeletal Proteins; Glioblastoma; Humans; Prospective Studies; Tubulin
PubMed: 33667657
DOI: 10.1016/j.critrevonc.2021.103283 -
Frontiers in Neurology 2020Tau protein, a neuronal microtubule-associated protein, becomes hyperphosphorylated in several neurodegenerative diseases called tauopathies. Hyperphosphorylation of tau...
Similarities and Differences in the Pattern of Tau Hyperphosphorylation in Physiological and Pathological Conditions: Impacts on the Elaboration of Therapies to Prevent Tau Pathology.
Tau protein, a neuronal microtubule-associated protein, becomes hyperphosphorylated in several neurodegenerative diseases called tauopathies. Hyperphosphorylation of tau is correlated to its redistribution from the axon to the somato-dendritic compartment at early stages of tauopathies. Interestingly, tau hyperphosphorylation begins in different regions of the brain in each tauopathy. In some regions, both neurons and glial cells develop tau hyperphosphorylation. Tau hyperphosphorylation is also observed in physiological conditions such as hibernation and brain development. In the first section of present article, we will review the spatiotemporal and cellular distribution of hyperphosphorylated tau in the most frequent tauopathies. In the second section, we will compare the pattern of tau hyperphosphorylation in physiological and pathological conditions and discuss the sites that could play a pivotal role in the conversion of non-toxic to toxic forms of hyperphosphorylated tau. Furthermore, we will discuss the role of hyperphosphorylated tau in physiological and pathological conditions and the fact that tau hyperphosphorylation is reversible in physiological conditions but not in a pathological ones. In the third section, we will speculate how the differences and similarities between hyperphosphorylated tau in physiological and pathological conditions could impact the elaboration of therapies to prevent tau pathology. In the fourth section, the different therapeutic approaches using tau as a direct or indirect therapeutic target will be presented.
PubMed: 33488502
DOI: 10.3389/fneur.2020.607680 -
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 -
European Journal of Human Genetics :... Jun 2021Since a substantial difference in the prevalence of genetic causes of rod-cone dystrophy (RCD) was found among different populations, we conducted a systematic review of...
Since a substantial difference in the prevalence of genetic causes of rod-cone dystrophy (RCD) was found among different populations, we conducted a systematic review of the genetic findings associated with RCD in Arab countries. Of the 816 articles retrieved from PubMed, 31 studies conducted on 407 participants from 11 countries were reviewed. Next-generation sequencing (NGS) was the most commonly used technique (68%). Autosomal recessive pattern was the most common pattern of inheritance (97%) and half of the known genes associated with RCD (32/63) were identified. In the Kingdom of Saudi Arabia, in addition to RP1 (20%) and TULP1 (20%), gene defects in EYS (8%) and CRB1 (7%) were also prevalently mutated. In North Africa, the main gene defects were in MERTK (18%) and RLBP1 (18%). Considering all countries, RP1 and TULP1 remained the most prevalently mutated. Variants in TULP1, RP1, EYS, MERTK, and RLBP1 were the most prevalent, possibly because of founder effects. On the other hand, only ten Individuals were found to have dominant or X-linked RCD. This is the first time a catalog of RCD genetic variations has been established in subjects from the Arabi countries. Although the last decade has seen significant interest, expertise, and an increase in RCD scientific publication, much work needs to be conducted.
Topics: Carrier Proteins; Cone-Rod Dystrophies; Eye Proteins; Female; Gene Frequency; Genetic Heterogeneity; Genetic Testing; Humans; Male; Microtubule-Associated Proteins; Middle East; Mutation; c-Mer Tyrosine Kinase
PubMed: 33188265
DOI: 10.1038/s41431-020-00754-0