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2021

Pharmacology

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Full-Text Articles in Life Sciences

Effects Of Fluoxetine/Simvastatin/Ascorbic Acid Combination Treatment On Neurogenesis And Functional Recovery In A Model Of Multiple Sclerosis, Olivia Cameron Webb Jan 2021

Effects Of Fluoxetine/Simvastatin/Ascorbic Acid Combination Treatment On Neurogenesis And Functional Recovery In A Model Of Multiple Sclerosis, Olivia Cameron Webb

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Whereas immune modulation has proven beneficial in multiple sclerosis (MS), we hypothesized that targeting down-stream modulators of neurogenesis and subsequent remyelination may offer an additional, if not superior, point of intervention in an attempt to repair damage and recover lost function. As such, the present study assessed the effectiveness of 30-day administration of the drug combination fluoxetine (5 mg/kg), simvastatin (1 mg/kg), and ascorbic acid (50 mg/kg) (FSA) on an early marker of neurogenesis, doublecortin (DCX), and functional recovery using the Montoya Staircase following lysolecithin-induced focal demyelination of the corpus callosum in middle-aged (10-11 month) male and female rats. Lysolecithin …


The Effect Of Circadian Clock Modulation On Cisplatin Cytotoxicity, Nadeen Nibal Ahmad Anabtawi Jan 2021

The Effect Of Circadian Clock Modulation On Cisplatin Cytotoxicity, Nadeen Nibal Ahmad Anabtawi

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Cisplatin is a DNA damage-based chemotherapeutic drug widely used to treat various types of cancers; however, the treatment's toxicity restricts its efficiency. Studies have shown that the circadian rhythm controls the DNA damage response and affects the repair pathways of cisplatin-induced DNA damage. Circadian clock modulation, therefore, has been proposed to be a potential mechanism for enhancing cisplatin tolerability. Here we used clock-enhancing molecules to evaluate the effect of pharmacological clock modulation on cisplatin cytotoxicity. Using cultured human cell lines, cisplatin cytotoxicity was found to be attenuated following treatment with circadian-enhancing molecules KS15 and SR8278. Moreover, the protein and mRNA …


Stress-Induced Senescence In Human Dermal Fibroblasts : Effects Of Creatine And Nicotinamide Post Stress Treatment, Venkata Sravya Arikatla Jan 2021

Stress-Induced Senescence In Human Dermal Fibroblasts : Effects Of Creatine And Nicotinamide Post Stress Treatment, Venkata Sravya Arikatla

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In skin connective tissue, dermal fibroblasts appear to be the most prevalent cell type. They are in charge of making the extracellular matrix that makes up the skin's connective tissue, and also involved in wound healing. Moreover, they produce Insulin-like growth factor-1 (IGF-1) which helps in activation of Insulin growth factor-1 receptor (IGF-1R). This receptor helps to control cell proliferation and responses to DNA-damaging substances such as UVB radiation, reactive oxygen species (ROS), and therapeutic drugs. According to our findings, lack of IGF-1 expression in the dermis of elderly patients due to fibroblast senescence (senescence is characterized by which cells …


Potential Involvement Of Micro Vesicle Particles In The Synergistic Effects Of Ultraviolet-B Radiation And Platelet -Activating Factor Receptor Agonists On Cytokine Production, Shweta Bhadri Jan 2021

Potential Involvement Of Micro Vesicle Particles In The Synergistic Effects Of Ultraviolet-B Radiation And Platelet -Activating Factor Receptor Agonists On Cytokine Production, Shweta Bhadri

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Cytokines play a pivotal role in regulating inflammation, which is a condition that makes the tissue vulnerable to different pathological and physiological conditions. Thus, how cytokines are regulated is an important area of study. Skin that receives ultraviolet B radiation (UVB), a major pro-oxidative stressor, results in the release of multiple cytokines and chemokines like tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. Previous studies from our group and others have demonstrated synergistic release of TNF-alpha when UVB is combined with IL-1 or the lipid mediator Platelet-activating factor (PAF). Of interest, subcellular microvesicle particles (MVP) have been proposed to play an …


The Protective Effects Of Mir-210 Modified Endothelial Progenitor Cells Released Exosomes In Hypoxia/Reoxygenation Injured Neurons, Sri Meghana Yerrapragada Jan 2021

The Protective Effects Of Mir-210 Modified Endothelial Progenitor Cells Released Exosomes In Hypoxia/Reoxygenation Injured Neurons, Sri Meghana Yerrapragada

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Endothelial progenitor cells (EPCs) have been shown to provide beneficial effects on oxidative stress. Exosomes (EXs) released from these stem cells could be one of the major contributors, as they are known to convey the benefit of one cell to another cell via microRNAs (miRNA). At first, we determined that EPCs release more EXs when they are serum-starved for 48 hours., and by determining the microRNA-210 (miR-210) levels in the EXs, we found that miRNA is being transferred from cells to EXs. Meanwhile, miR-210 is gaining popularity in reducing elevated oxidative stress levels. In this study, we investigated the role …


Functions Of Atr Kinase In Terminally Differentiated Human Epidermal Keratinocyles And In Human Ex-Vivo Skin After Exposure To Ultraviolet B Radiation, Vivek Shashank Nag Gogusetti Jan 2021

Functions Of Atr Kinase In Terminally Differentiated Human Epidermal Keratinocyles And In Human Ex-Vivo Skin After Exposure To Ultraviolet B Radiation, Vivek Shashank Nag Gogusetti

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The functions of Ataxia telangiectasia and Rad-3 related protein (ATR) is very much important in a cell, as it is a DNA damage response protein, which plays an important role in cell division, DNA repair and apoptosis. This protein helps in proliferation in the actively DNA dividing normal cells and in cancer cells. The functions of ATR in a proliferating cell are well studied and known to involve regulation of replication fork and cell cycle progression after DNA damage. Whereas, in a non-replicating cell, the functions of ATR are not so well known. In the human body, most of the …


Xeroderma Pigmentosum A Deficiency Results In Increased Generation Of Microvesicle Particles In Response To Ultraviolet B Radiation, Christian Lea Rajeshkumar Jan 2021

Xeroderma Pigmentosum A Deficiency Results In Increased Generation Of Microvesicle Particles In Response To Ultraviolet B Radiation, Christian Lea Rajeshkumar

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Xeroderma Pigmentosum is a genetic disorder in which ability to repair DNA damage such as from UV radiation is decreased. Nucleotide excision repair is known for repairing DNA damage caused by UV radiation and XPA plays a major role in recognizing and eliminating abnormal section of DNA. Therefore, XPA deficiency decreases repair efficiency of DNA. Of note, XPA deficiency is linked with photosensitivity. Microvesicle particles are membrane-bound particles which are released into the extracellular environment in response to multiple stimuli including the lipid Platelet activating factor (PAF). Previous studies have shown that XPA deficiency can induce increase production of reactive …


Extracellular Vesicles From Uvb Irradiated Keratinocytes Contain Cyclobutane Pyrimidine Dimers, Meghana Reddy Ginugu Jan 2021

Extracellular Vesicles From Uvb Irradiated Keratinocytes Contain Cyclobutane Pyrimidine Dimers, Meghana Reddy Ginugu

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Ultraviolet (UV) radiation induces the formation of cyclobutane pyrimidine dimers (CPDs) in genomic DNA, which are normally removed by nucleotide excision repair. However, the fate of these adducts remain largely unexplored. Detection of these photoproducts in body fluids could act as a predictor of UV exposure and enable a better understanding of the pathogenesis of photosensitive skin diseases, such as lupus. Using cultured human keratinocytes exposed to UVB radiation in vitro, ultracentrifugation of cell culture supernatants, and immunodot blot analysis of isolated DNA, we have found that a small fraction of CPDs is released from cells in a dose- and …