Comparative evaluation of aflatoxin and mineral binding activity of molecular imprinted polymer designed for dummy template using in vitro and in vivo models

Toxicon ◽  
2019 ◽  
Vol 166 ◽  
pp. 66-75 ◽  
Author(s):  
Homa Arak ◽  
Mohammad Amir Karimi Torshizi ◽  
Mehdi Hedayati ◽  
Shaban Rahimi
Keyword(s):  
Comparative Evaluation ◽  
Binding Activity ◽  
Molecular Imprinted Polymer ◽  
Imprinted Polymer ◽  
In Vivo Models ◽  
Dummy Template ◽  
Mineral Binding

scholarly journals A base-resolution panorama of the in vivo impact of cytosine methylation on transcription factor binding

2021 ◽  
Author(s):  
Aldo Hernandez-Corchado ◽  
Hamed S Najafabadi
Keyword(s):  
Binding Site ◽  
Cytosine Methylation ◽  
Binding Activity ◽  
Cpg Methylation ◽  
In Vivo Models ◽  
Cpg Dinucleotides ◽  
Dna Accessibility ◽  
Dna Binding Activity

Methylation of the cytosine base at CpG dinucleotides is traditionally considered antagonistic to the DNA-binding activity of the majority of transcription factors (TFs). Recent in vitro studies of TF-DNA interactions have revealed a more complex picture, suggesting a heterogeneous cytosine methylation impact that varies across TFs, with over a third of TFs preferring methylated sequences. Expanding these in vitro observations to in vivo TF binding preferences, however, is challenging, as the effect of methylation of individual CpG sites cannot be easily isolated from the confounding effects of DNA accessibility and regional DNA methylation. As a result, the in vivo methylation preferences of most TFs remain uncharacterized. Here, we introduce Joint Accessibility-Methylation-Sequence (JAMS) models for inferring the effect of CpG methylation on TF binding in vivo. JAMS creates quantitative models that connect the strength of the binding signal observed in ChIP-seq to the DNA accessibility of the binding site, regional methylation level, DNA sequence, and base-resolution cytosine methylation. Furthermore, by jointly modeling both the control and pull-down signal in a ChIP-seq experiment, JAMS isolates the TF-specific effects from background effects, revealing how methylation of specific CpGs within the binding site alters the TF binding affinity in vivo. We show that JAMS can quantitatively model the TF binding strength and learn the accessibility-methylation-sequence determinants of TF binding. JAMS models are reproducible and generalizable across cell lines, and can faithfully recapitulate cell type-specific TF binding. Systematic application of JAMS to 2368 ChIP-seq experiments generated high-confidence models for 260 TFs, revealing that 45% of TFs are inhibited by methylation of their potential binding sites in vivo. In contrast, only 6% prefer to bind to methylated sites, including 11 novel methyl-binding TFs. Comparison of these in vivo models to in vitro data confirmed high precision of the methyl-preferences inferred by JAMS. Finally, among the CpG-binding proteins from the ZF-KRAB family of TFs, we observed a disproportionately high preference for methylated sequences (24%), highlighting the role of CpG methylation in determining the genome-wide binding profiles of the TFs from this family.

In vitro/in vivo study of novel anti-cancer, biodegradable cross-linked tannic acid for fabrication of 5-fluorouracil-targeting drug delivery nano-device based on a molecular imprinted polymer

RSC Advances ◽  
2016 ◽  
Vol 6 (43) ◽  
pp. 37308-37318 ◽  
Author(s):  
Ebadullah Asadi ◽  
Majid Abdouss ◽  
Roger M. Leblanc ◽  
Noushin Ezzati ◽  
James N. Wilson ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Drug Delivery ◽  
Tannic Acid ◽  
In Vivo Study ◽  
Molecular Imprinted Polymer ◽  
Imprinted Polymer ◽  
Fluorescent Image ◽  
Anti Cancer

The structure of a 5-fluorouracil carrier and fluorescent image of an animal after injection under a magnetic field.

scholarly journals Domain binding and isotype dictate the activity of anti-human OX40 antibodies

2020 ◽  
Vol 8 (2) ◽  
pp. e001557
Author(s):  
Jordana Griffiths ◽  
Khiyam Hussain ◽  
Hannah L Smith ◽  
Theodore Sanders ◽  
Kerry L Cox ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Expansion ◽  
Cd8 T Cell ◽  
Therapeutic Benefit ◽  
Binding Activity ◽  
In Vivo Models ◽  
Treg Depletion ◽  
T Cell Expansion

BackgroundPrevious data suggests that anti-OX40 mAb can elicit anti-tumor effects in mice through deletion of Tregs. However, OX40 also has powerful costimulatory effects on T cells which could evoke therapeutic responses. Human trials with anti-OX40 antibodies have shown that these entities are well tolerated but to date have delivered disappointing clinical responses, indicating that the rules for the optimal use of anti-human OX40 (hOX40) antibodies is not yet fully understood. Changes to timing and dosages may lead to improved outcomes; however, here we focus on addressing the role of agonism versus depleting activity in determining therapeutic outcomes. We investigated a novel panel of anti-hOX40 mAb to understand how these reagents and mechanisms may be optimized for therapeutic benefit.MethodsThis study examines the binding activity and in vitro activity of a panel of anti-hOX40 antibodies. They were further evaluated in several in vivo models to address how isotype and epitope determine mechanism of action and efficacy of anti-hOX40 mAb.ResultsBinding analysis revealed the antibodies to be high affinity, with epitopes spanning all four cysteine-rich domains of the OX40 extracellular domain. In vivo analysis showed that their activities relate directly to two key properties: (1) isotype—with mIgG1 mAb evoking receptor agonism and CD8+ T-cell expansion and mIgG2a mAb evoking deletion of Treg and (2) epitope—with membrane-proximal mAb delivering more powerful agonism. Intriguingly, both isotypes acted therapeutically in tumor models by engaging these different mechanisms.ConclusionThese findings highlight the significant impact of isotype and epitope on the modulation of anti-hOX40 mAb therapy, and indicate that CD8+ T-cell expansion or Treg depletion might be preferred according to the composition of different tumors. As many of the current clinical trials using OX40 antibodies are now using combination therapies, this understanding of how to manipulate therapeutic activity will be vital in directing new combinations that are more likely to improve efficacy and clinical outcomes.

Melatonin modifies tumor hypoxia and metabolism by inhibiting HIF-1α and energy metabolic pathway in the in vitro and in vivo models of breast cancer

2019 ◽  
Vol 2 (4) ◽  
pp. 83-98 ◽  
Author(s):  
André De Lima Mota ◽  
Bruna Vitorasso Jardim-Perassi ◽  
Tialfi Bergamin De Castro ◽  
Jucimara Colombo ◽  
Nathália Martins Sonehara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucose Metabolism ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Carbonic Anhydrases ◽  
In Vivo Models ◽  
Ca Ix ◽  
Gene And Protein Expression

Breast cancer is the most common cancer among women and has a high mortality rate. Adverse conditions in the tumor microenvironment, such as hypoxia and acidosis, may exert selective pressure on the tumor, selecting subpopulations of tumor cells with advantages for survival in this environment. In this context, therapeutic agents that can modify these conditions, and consequently the intratumoral heterogeneity need to be explored. Melatonin, in addition to its physiological effects, exhibits important anti-tumor actions which may associate with modification of hypoxia and Warburg effect. In this study, we have evaluated the action of melatonin on tumor growth and tumor metabolism by different markers of hypoxia and glucose metabolism (HIF-1α, glucose transporters GLUT1 and GLUT3 and carbonic anhydrases CA-IX and CA-XII) in triple negative breast cancer model. In an in vitro study, gene and protein expressions of these markers were evaluated by quantitative real-time PCR and immunocytochemistry, respectively. The effects of melatonin were also tested in a MDA-MB-231 xenograft animal model. Results showed that melatonin treatment reduced the viability of MDA-MB-231 cells and tumor growth in Balb/c nude mice (p <0.05). The treatment significantly decreased HIF-1α gene and protein expression concomitantly with the expression of GLUT1, GLUT3, CA-IX and CA-XII (p <0.05). These results strongly suggest that melatonin down-regulates HIF-1α expression and regulates glucose metabolism in breast tumor cells, therefore, controlling hypoxia and tumor progression. 

Current Challenges in the Development of Vaccines and Drugs Against Emerging Vector-borne Diseases

2019 ◽  
Vol 26 (16) ◽  
pp. 2974-2986 ◽  
Author(s):  
Kwang-sun Kim
Keyword(s):  
New Host ◽  
In Vivo Models ◽  
Vector Borne Diseases ◽  
Novel Drugs ◽  
Huge Impact ◽  
Tick Borne Disease ◽  
Vector Borne ◽  
Living Organisms

Vectors are living organisms that transmit infectious diseases from an infected animal to humans or another animal. Biological vectors such as mosquitoes, ticks, and sand flies carry pathogens that multiply within their bodies prior to delivery to a new host. The increased prevalence of Vector-Borne Diseases (VBDs) such as Aedes-borne dengue, Chikungunya (CHIKV), Zika (ZIKV), malaria, Tick-Borne Disease (TBD), and scrub typhus has a huge impact on the health of both humans and livestock worldwide. In particular, zoonotic diseases transmitted by mosquitoes and ticks place a considerable burden on public health. Vaccines, drugs, and vector control methods have been developed to prevent and treat VBDs and have prevented millions of deaths. However, development of such strategies is falling behind the rapid emergence of VBDs. Therefore, a comprehensive approach to fighting VBDs must be considered immediately. In this review, I focus on the challenges posed by emerging outbreaks of VBDs and discuss available drugs and vaccines designed to overcome this burden. Research into promising drugs needs to be upgraded and fast-tracked, and novel drugs or vaccines being tested in in vitro and in vivo models need to be moved into human clinical trials. Active preventive tactics, as well as new and upgraded diagnostics, surveillance, treatments, and vaccination strategies, need to be monitored constantly if we are to manage VBDs of medical importance.

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

2020 ◽  
Vol 26 (35) ◽  
pp. 4362-4372
Author(s):  
John H. Miller ◽  
Viswanath Das
Keyword(s):  
Natural Products ◽  
Neurodegenerative Diseases ◽  
In Vivo Models ◽  
Synthetic Compounds ◽  
Stabilizing Agents ◽  
Animal Models Of Disease ◽  
Model Studies ◽  
Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

A Review on Opuntia Species and its Chemistry, Pharmacognosy, Pharmacology and Bioapplications

2020 ◽  
Vol 16 (8) ◽  
pp. 1227-1244
Author(s):  
Dharmendra Kumar ◽  
Pramod K. Sharma
Keyword(s):  
Human Consumption ◽  
In Vivo Models ◽  
Sugar Amino Acids ◽  
Opuntia Species ◽  
Therapeutic Uses ◽  
Anti Inflammatory ◽  
Online Library ◽  
Different Parts

Background:: Opuntia species, locally known as prickly pear was used for various purposes as food, medicine, beverage, source of dye and animal food. Many studies have revealed its pharmacology activity from time to time. This review is a collection of chemistry, pharmacognosy, pharmacology and bioapplications of the cactus family. Methods: Many sources were used to collect information about Opuntia species such as Pub med, Google scholar, Agris, science direct, Embase, Merk index, Wiley online library, books and other reliable sources. This review contains studies from 1812 to 2019. Results: The plants from the cactus family offer various pharmacological active compounds including phenolic compounds, carotenoids, betalains, vitamins, steroids, sugar, amino acids, minerals and fibers. These bioactive compounds serve various pharmacological activities such as anticancer, antiviral, anti-diabetic, Neuroprotective, anti-inflammatory, antioxidant, Hepatoprotective, antibacterial, antiulcer and alcohol hangover. According to various studies, Opuntia species offer many bioapplications such as fodder for animal, soil erosion, prevention, human consumption and waste water decontamination. Finally, different parts of plants are used in various formulations that offer many biotechnology applications. Conclusion: Different parts of Opuntia plant (fruits, seeds, flowers and cladodes) are used in various health problems which include wound healing, anti-inflammatory and urinary tract infection from ancient times. Nowadays, researches have extended several pharmacological and therapeutic uses of Opuntia species as discussed in this review. Many in-vitro and in-vivo models are also discussed in this review as the proofs of research findings. Various research gaps have been observed in current studies that require attention in the future.

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