scholarly journals Oral Carcinoma and Therapeutic Approaches of Nanotechnology: From Fundamental Concepts, Incidence, Molecular Mechanism to Emerging Treatment Techniques

2021 ◽  
Vol 12 (3) ◽  
pp. 3900-3937
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Polymeric Nanoparticles ◽  
Systems Design ◽  
Multistep Method ◽  
Oral Carcinoma ◽  
Alcoholic Beverages ◽  
Methylation Of Dna ◽  
Treatment Techniques ◽  
Pubmed Database

Oral carcinoma is the most general, with a large fatality rate and aggressive cancer that can cause metastasis as it attacks other tissues. The prevalence of carcinoma is a multistep method, requiring the collection of many hereditary changes influenced by a patient's hereditary predisposition and environmental effects, including nicotine, alcoholic beverages, chronic infection, and viral contamination. The data were searched using focal keywords, including oral cancer, molecular mechanisms, treatments, and nanotechnology, through various search engines and the Pubmed database. There are two major types of carcinogenesis genetic manipulation, i.e., tumor suppressor genes and oncogenes. Tumor suppression genes can be inactivated throughout genetic phenomena, such as mutations, loss of heterozygosity, deletion, or epigenetic alterations such as methylation of DNA or dynamic modification of chromatin. Oncogenes can be activated through overexpression due to gene amplification, enhanced transcription, or a variation in structure due to mutation, leading to enhanced transforming activity. The current review focused on enhancing cancer therapy techniques using nanomedicines, including nanoscale medicine transfer systems' design, characterization, production, and utilization. Instruments for diagnostic investigations and medical devices are for nanotechnologies-based therapies are polymeric nanoparticles, nanostructured lipid carriers, gold nanoparticles, and cyclodextrin complexes, which are promising apparatuses for symptomatic tests and helpful treatment gadgets. The present investigation's keen interest was the molecular mechanisms of oral carcinogenesis and the application of biologic therapies to target altered molecules in oral carcinoma and nano-based drug delivery system.

scholarly journals Modernized Tools for Streamlined Genetic Manipulation and Comparative Study of Wild and Diverse Proteobacterial Lineages

mBio ◽  
2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Travis J. Wiles ◽  
Elena S. Wall ◽  
Brandon H. Schlomann ◽  
Edouard A. Hay ◽  
Raghuveer Parthasarathy ◽  
...  
Keyword(s):  
Comparative Study ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Functional Characterization ◽  
Symbiotic Bacteria ◽  
Bacterial Isolates ◽  
Major Barrier ◽  
Allelic Exchange ◽  
Genetic Techniques

ABSTRACTCorrelating the presence of bacteria and the genes they carry with aspects of plant and animal biology is rapidly outpacing the functional characterization of naturally occurring symbioses. A major barrier to mechanistic studies is the lack of tools for the efficient genetic manipulation of wild and diverse bacterial isolates. To address the need for improved molecular tools, we used a collection of proteobacterial isolates native to the zebrafish intestinal microbiota as a testbed to construct a series of modernized vectors that expedite genetic knock-in and knockout procedures across lineages. The innovations that we introduce enhance the flexibility of conventional genetic techniques, making it easier to manipulate many different bacterial isolates with a single set of tools. We developed alternative strategies for domestication-free conjugation, designed plasmids with customizable features, and streamlined allelic exchange using visual markers of homologous recombination. We demonstrate the potential of these tools through a comparative study of bacterial behavior within the zebrafish intestine. Live imaging of fluorescently tagged isolates revealed a spectrum of distinct population structures that differ in their biogeography and dominant growth mode (i.e., planktonic versus aggregated). Most striking, we observed divergent genotype-phenotype relationships: several isolates that are predicted by genomic analysis andin vitroassays to be capable of flagellar motility do not display this trait within living hosts. Together, the tools generated in this work provide a new resource for the functional characterization of wild and diverse bacterial lineages that will help speed the research pipeline from sequencing-based correlations to mechanistic underpinnings.IMPORTANCEA great challenge in microbiota research is the immense diversity of symbiotic bacteria with the capacity to impact the lives of plants and animals. Moving beyond correlative DNA sequencing-based studies to define the cellular and molecular mechanisms by which symbiotic bacteria influence the biology of their hosts is stalling because genetic manipulation of new and uncharacterized bacterial isolates remains slow and difficult with current genetic tools. Moreover, developing tools de novo is an arduous and time-consuming task and thus represents a significant barrier to progress. To address this problem, we developed a suite of engineering vectors that streamline conventional genetic techniques by improving postconjugation counterselection, modularity, and allelic exchange. Our modernized tools and step-by-step protocols will empower researchers to investigate the inner workings of both established and newly emerging models of bacterial symbiosis.

Mutagenicity, Metabolism, and DNA Interactions of Urethane

1990 ◽  
Vol 6 (1) ◽  
pp. 71-108 ◽  
Author(s):  
Rene E. Sotomayor ◽  
Thomas F.X. Collins
Keyword(s):  
Molecular Mechanisms ◽  
Case Reports ◽  
The Body ◽  
Alcoholic Beverages ◽  
Fermented Foods ◽  
X Rays ◽  
Spermatogenic Cells ◽  
Dna Interactions ◽  
Specific Locus ◽  
Vinyl Carbamate

Urethane, a known animal carcinogen, has been the subject of intensive research efforts spanning 40 years. Recent concerns have focused on the presence of urethane in a variety of fermented foods and alcoholic beverages, although no epidemiological studies or human case reports have been published. Much information is available about the mutagenesis, metabolism, and DNA interactions of urethane in experimental systems. Urethane is generally not mutagenic in bacteria although in some instances it acts as a weak mutagen. Urethane is not mutagenic in Neurospora but is weakly mutagenic in Saccharomyces. Drosophila appear to be the only organisms that consistently give positive mutagenic results with urethane, but its mutagenicity is weak and in many cases shows no clear dose dependence. Urethane is a good clastogen in mammalian somatic cells in vivo, but it shows variable results with cells in vitro. It efficiently induces sister chromatid exchanges in a variety of cells. Mammalian spermatogenic cells are insensitive to the induction of specific locus and dominant lethal mutations by urethane. Mutational synergism has been reported to occur between ethyl methanesulfonate and urethane when administered two generations apart, and some investigators have suggested possible synergism for cancer-causing mutations in mice exposed to X-rays and urethane one generation apart. These studies are controversial and have not been confirmed. Studies on the induction of cancer-causing dominant mutations by urethane are at variance with results from extensive studies with the specific locus test in mice. Urethane studies with the unscheduled DNA synthesis assay in mouse spermatogenic cells and with the sperm abnormality test have given negative results. Urethane is rapidly and evenly distributed in the body. The rate of elimination of urethane from plasma is a saturable process and varies according to the strain and age of the animal. Recent studies have concentrated on the effect of ethanol on urethane metabolism. At concentrations similar to those in wine, ethanol inhibits the tissue distribution of urethane in mice. These results are important because they suggest a lower carcinogenic/mutagenic risk than expected from exposure to urethane in alcoholic beverages. Although research on the metabolic activation of urethane has been extensive, no conclusive results have been obtained about its active metabolite, at one time thought to be N-hydroxyurethane. More recently, it has been postulated that urethane is actived to vinyl carbamate and that this metabolite is capable of reacting with DNA. Vinyl carbamate is more carcinogenic and more mutagenic than the parental compound, but despite intensive efforts it has not been identified as a metabolite in animals treated with urethane. Urethane binding to DNA appears to correlate well with tissue susceptibility to cancer. Various studies have attempted to elucidate the molecular nature of the bound molecule and the binding site. Some results have indicated the formation of a single DNA adduct, 7-(2-oxoethyl)guanine. This adduct may isomerize to O6,7-(1'-hydroxyethano)guanine, which might be more mutagenic than the 2-oxoethyl adduct; however, this possibility seems unlikely. Despite extensive research, urethane's metabolism and molecular mechanisms of mutation are still not clearly understood.

scholarly journals Blister like aneurysm: a review about its surgical management / Aneurismas blister-like: uma revisão sobre seu manejo cirúrgico

2019 ◽  
Vol 64 (2) ◽  
pp. 131
Author(s):  
Rodrigo Salmeron de Toledo Aguiar ◽  
Guilherme Brasileiro de Aguiar ◽  
Rafael Gomes dos Santos ◽  
André Freitas Nunes ◽  
Renan Maximilian Lovato ◽  
...  
Keyword(s):  
Surgical Management ◽  
Intracranial Aneurysms ◽  
Surgical Techniques ◽  
Vascular Lesion ◽  
High Morbidity ◽  
Good Efficiency ◽  
Treatment Techniques ◽  
Pubmed Database ◽  
Surgical Methods ◽  
Ruptured Intracranial Aneurysms

ABSTRACT Introduction: Blister aneurysms are of uncertain pathogenesis and are a vascular lesion located in the brain. Overall, they represent 0.3% - 1.0% of all intracranial aneurysms and 0.9% - 6.5% of ruptured intracranial aneurysms. They are associated with high morbidity and mortality. Even with the first description being from 1969, there is still debate in the literature about which type of treatment is the best: surgical or endovascular. In this review, we focus on the surgical management. Method: The authors performed a review of available surgical techniques used for blood blister-like aneurysms treatment. Pubmed database was used as search source introducing blister-like aneurysm and blister aneurysms as keywords. The most relevant articles and those that focused on surgical treatment techniques were selected. Discussion: The most used surgical methods are clipping, trapping, wrapping and bypass. As main features of each technique, we can highlight clipping with good efficiency, when there is good neck exposure; trapping being employed in ruptured aneurysm; wrapping for avulsion and bypass that promotes vascularization to the distal territory of the aneurysm. Conclusion: The endovascular method has shown to be promising and efficient. However, different surgical techniques are still being employed based on their efficiency when facing certain surgical scenarios.Keywords: Neurosurgery, Subarachnoid hemorrhage, Intracranial aneurysm, Endovascular proceduresRESUMOIntrodução: Aneurismas cerebrais blister-like são lesões vasculares de patogenia incerta. De modo geral, representam 0.3%-1.0% de todos aneurismas intracranianos e 0.9% - 6.5% dos aneurismas intracranianos que rompem. Estão associados a alta morbimortalidade. Mesmo com a primeira descrição sendo de 1969, ainda há debate na literatura sobre qual tipo de tratamento é o melhor: cirúrgico ou endovascular. Nessa revisão, focamos no tratamento cirúrgico. Métodos: Os autores realizaram uma revisão das técnicas cirúrgicas utilizadas para tratamento de aneurismas blister-like. A plataforma Pubmed foi utilizada para a pesquisa das palavras chaves “blister-like aneurysm” e “blister aneurysm”. Os artigos de maior relevância e aqueles que enfatizam as técnicas cirúrgicas foram selecionados. Discussão: Os métodos cirúrgicos empregados são clipagem, trapping, wrapping e bypass. Quanto às características de cada método, podemos salientar a eficácia da clipagem, quanto melhor for a exposição do aneurisma; o uso do trapping em situações de rompimento do aneurisma; wrapping para casos em que houve avulsão do aneurisma e by-pass que promove a vascularização distal ao aneurisma. Conclusão: O método endovascular tem se mostrado promissor e efetivo. No entanto, as diferentes técnicas cirúrgicas ainda são empregadas e defendidas devido a sua eficiência frente certos cenários cirúrgicos.Descritores: Neurocirurgia, Hemorragia subaracnóidea, Aneurisma intracraniano, Procedimentos endovasculares

scholarly journals A simple Agrobacterium-mediated stable transformation technique for the hornwort model Anthoceros agrestis

2021 ◽  
Author(s):  
Eftychios Frangedakis ◽  
Manuel Waller ◽  
Tomoaki Nishiyama ◽  
Hirokazu Tsukaya ◽  
Xia Xu ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Fluorescent Proteins ◽  
Land Plant ◽  
Plant Evolution ◽  
Stable Transformation ◽  
35S Promoter ◽  
Low Light ◽  
Transformation Technique ◽  
High Transformation

We have developed a simple Agrobacterium-mediated method for the stable transformation of the hornwort Anthoceros agrestis, the fifth bryophyte species for which a genetic manipulation technique becomes available. High transformation efficiency was achieved by using thallus tissue grown under low-light conditions. We generated a total of 216 transgenic A. agrestis lines expressing the β-Glucuronidase (GUS), cyan, green, and yellow fluorescent proteins under the control of the CaMV 35S promoter and several endogenous promoters. Nuclear and plasma membrane localization with multiple color fluorescent proteins was also confirmed. The transformation technique described here should pave the way for detailed molecular and genetic studies of hornwort biology, providing much needed insight into the molecular mechanisms underlying symbiosis, carbon-concentrating mechanism, RNA editing, and land plant evolution in general.

scholarly journals Intracellular survival ofBurkholderia cepaciacomplex in phagocytic cells

2015 ◽  
Vol 61 (9) ◽  
pp. 607-615 ◽  
Author(s):  
Miguel A. Valvano
Keyword(s):  
Burkholderia Cepacia ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Genetic Manipulation ◽  
Intracellular Survival ◽  
Burkholderia Cenocepacia ◽  
Burkholderia Cepacia Complex ◽  
Host Responses ◽  
Current View ◽  
Phagocytic Cells

Burkholderia cepacia complex (Bcc) species are a group of Gram-negative opportunistic pathogens that infect the airways of cystic fibrosis patients, and occasionally they infect other immunocompromised patients. Bcc bacteria display high-level multidrug resistance and chronically persist in the infected host while eliciting robust inflammatory responses. Studies using macrophages, neutrophils, and dendritic cells, combined with advances in the genetic manipulation of these bacteria, have increased our understanding of the molecular mechanisms of virulence in these pathogens and the molecular details of cell-host responses triggering inflammation. This article discusses our current view of the intracellular survival of Burkholderia cenocepacia within macrophages.

Analysis of the molecular mechanisms by flavonoids with potential use for osteoporosis prevention or therapy

2021 ◽  
Vol 28 ◽  
Author(s):  
Valeria Rodríguez ◽  
María Rivoira ◽  
Gabriela Picotto ◽  
Gabriela Díaz de Barboza ◽  
Alejandro Collin ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Osteoporosis Treatment ◽  
Epidemiological Studies ◽  
Common Mechanism ◽  
Osteoporotic Bone ◽  
Osteoporosis Prevention ◽  
Mineral Density ◽  
Pubmed Database ◽  
Molecular Aspects ◽  
Potential Use

Background: Osteoporosis is the most common skeletal disorder worldwide. Flavonoids have the potential to alleviate bone alterations in osteoporotic patients with the advantage of being safer and less expensive than the conventional therapies. Objective: The main objective is to analyze the molecular mechanisms triggered in bone by different subclasses of flavonoids. In addition, this review provides an up-to-date overview on the cellular and molecular aspects of osteoporotic bones versus healthy bones, and a brief description of some epidemiological studies indicating that flavonoids could be useful for osteoporosis treatment. Methods: The PubMed database was searched in the range of years 2001- 2021 using the keywords osteoporosis, flavonoids, and their subclasses such as flavones, flavonols, flavanols, isoflavones, flavanones and anthocyanins, focusing the data on the molecular mechanisms triggered in bone. Results: Although flavonoids comprise many compounds that differ in structure, their effects on bone loss in postmenopausal women or in ovariectomized-induced osteoporotic animals are quite similar. Most of them increase bone mineral density and bone strength, which occur through enhancement of osteoblastogenesis and osteoclast apoptosis, decrease in osteoclastogenesis as well as increase in neovascularization on the site of the osteoporotic fracture. Conclusion: Several molecules of signaling pathways are involved in the effect of flavonoids on osteoporotic bone. Whether all flavonoids have a common mechanism or they act as ligands of estrogen receptors remain to be established. More clinical trials are necessary to know better their safety, efficacy, delivery and bioavailability in humans, as well as comparative studies with conventional therapies.

scholarly journals Single-cell RNA-seq analysis revealed long-lasting adverse effects of tamoxifen on neurogenesis in prenatal and adult brains

2020 ◽  
Vol 117 (32) ◽  
pp. 19578-19589 ◽  
Author(s):  
Chia-Ming Lee ◽  
Liqiang Zhou ◽  
Jiping Liu ◽  
Jiayu Shi ◽  
Yanan Geng ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Single Cell ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Lineage Tracing ◽  
In Vitro Assays ◽  
Fetal Mortality ◽  
Neural Lineage ◽  
Cortical Neurogenesis

The CreER/LoxP system is widely accepted to track neural lineages and study gene functions upon tamoxifen (TAM) administration. We have observed that prenatal TAM treatment caused high rates of delayed delivery and fetal mortality. This substance could produce undesired results, leading to data misinterpretation. Here, we report that administration of TAM during early stages of cortical neurogenesis promoted precocious neural differentiation, while it inhibited neural progenitor cell (NPC) proliferation. The TAM-induced inhibition of NPC proliferation led to deficits in cortical neurogenesis, dendritic morphogenesis, synaptic formation, and cortical patterning in neonatal and postnatal offspring. Mechanistically, by employing single-cell RNA-sequencing (scRNA-seq) analysis combined with in vivo and in vitro assays, we show TAM could exert these drastic effects mainly through dysregulating the Wnt-Dmrta2 signaling pathway. In adult mice, administration of TAM significantly attenuated NPC proliferation in both the subventricular zone and the dentate gyrus. This study revealed the cellular and molecular mechanisms for the adverse effects of TAM on corticogenesis, suggesting that care must be taken when using the TAM-induced CreER/LoxP system for neural lineage tracing and genetic manipulation studies in both embryonic and adult brains.

Risk factors for pregnancy-associated venous thromboembolism: a review

2014 ◽  
Vol 42 (4) ◽  
Author(s):  
Barry Kevane ◽  
Jennifer Donnelly ◽  
Mary D’Alton ◽  
Sharon Cooley ◽  
Roger J.S. Preston ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Molecular Mechanisms ◽  
Case Control Studies ◽  
Search Terms ◽  
Specific Risk ◽  
Pubmed Database ◽  
Multiplicative Effect ◽  
Incident Rate ◽  
Rate Ratios

AbstractTo critically evaluate current understanding of risk factors for pregnancy-associated venous thromboembolism (VTE) and to describe underlying molecular mechanisms.A literature search was undertaken using the national library of medicine PubMed database. The search terms used were “pregnancy” and “venous thromboembolism”. Following exclusion of unsuitable data sources, studies were identified that described specific risk factors for pregnancy-associated VTE and suggested possible underlying molecular mechanisms. Adjusted odds ratios and incident rate ratios for these specific risk factors were identified in each study and tabulated.A series of mainly retrospective cohort and case control studies over the past two decades have reported specific risk factors for pregnancy-associated VTE. Recent published literature has highlighted the interaction between commonly occurring risk factors, particularly the potential for a multiplicative effect on overall VTE risk, and have led to improvements in our understanding of the molecular mechanisms underlying these risk factors.Mortality from pregnancy associated VTE continues despite prevention strategies. A detailed understanding of specific risk factors, their interactions and underlying molecular mechanisms is required to identify women at highest risk and to guide development of thromboprophylaxis strategies.

Cellular and molecular mechanisms of hypoxia-inducible factor driven vascular remodeling

2007 ◽  
Vol 97 (05) ◽  
pp. 774-787 ◽  
Author(s):  
Norbert Weissmann ◽  
Friedrich Grimminger ◽  
Werner Seeger ◽  
Frank Rose ◽  
Jörg Hänze
Keyword(s):  
Vascular Remodeling ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
Genetic Manipulation ◽  
Hypoxia Inducible Factor ◽  
Ischemic Disease ◽  
Hypoxic Conditions ◽  
Concomitant Reduction ◽  
Adaptive Processes

SummaryHypoxia-inducible factor (HIF) is an oxygen-dependent transcription factor that activates a diverse set of target genes, the products of which are involved in adaptive processes to hypoxia. Employing genetic manipulation of HIF expression, in-vivo and cellular studies have focused on HIF as a crucial factor affecting hypoxia-induced vascular remodeling.Vascular remodeling comprises processes which establish and improve blood vessel supply such as vasculogenesis, angiogenesis and arteriogenesis. These processes are observed during ontogenesis, tumor progression, ischemic disease or physical training. Furthermore, under hypoxic conditions, a pulmonary-specific type of vascular remodeling called pulmonary arterial remodeling occurs that is characterized by thickening of the vessel wall with a concomitant reduction in the vessel lumen area, thereby limiting blood flow.This response results in pulmonary hypertension with right ventricular hypertrophy, a lethal disease. In this review, we summarize and discuss mechanisms by which HIF interferes with the different vascular remodeling processes.

scholarly journals New insights into the functions of Cox-2 in skin and esophageal malignancies

2020 ◽  
Vol 52 (4) ◽  
pp. 538-547 ◽  
Author(s):  
Hyeongsun Moon ◽  
Andrew C. White ◽  
Alexander D. Borowsky
Keyword(s):  
Experimental Evidence ◽  
Molecular Mechanisms ◽  
Genetic Manipulation ◽  
Tumor Development ◽  
Cancer Type ◽  
Tumor Initiation ◽  
Cells Of Origin ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Necessary And Sufficient

Abstract Understanding the cellular and molecular mechanisms of tumor initiation and progression for each cancer type is central to making improvements in both prevention and therapy. Identifying the cancer cells of origin and the necessary and sufficient mechanisms of transformation and progression provide opportunities for improved specific clinical interventions. In the last few decades, advanced genetic manipulation techniques have facilitated rapid progress in defining the etiologies of cancers and their cells of origin. Recent studies driven by various groups have provided experimental evidence indicating the cellular origins for each type of skin and esophageal cancer and have identified underlying mechanisms that stem/progenitor cells use to initiate tumor development. Specifically, cyclooxygenase-2 (Cox-2) is associated with tumor initiation and progression in many cancer types. Recent studies provide data demonstrating the roles of Cox-2 in skin and esophageal malignancies, especially in squamous cell carcinomas (SCCs) occurring in both sites. Here, we review experimental evidence aiming to define the origins of skin and esophageal cancers and discuss how Cox-2 contributes to tumorigenesis and differentiation.

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