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941.
Ajeet K. Srivastav Divya Dubey Deepti Chopra Jyoti Singh Sandeep Negi Syed Faiz Mujtaba Ashish Dwivedi Ratan Singh Ray 《Journal of cellular biochemistry》2020,121(2):1273-1282
Prolonged exposure of the earth's surface to the sun's ultraviolet radiation may result in various skin diseases and cataract. Carbazole (CBZ), as a polycyclic-aromatic hydrocarbon (PAH), is blended with a five-member nitrogen-containing ring. It is found in cigarette smoke, coal, eye kohl, tattoo ink, and wood combustion and affects various types of flora and fauna. Our findings suggest that CBZ generates reactive oxygen species (ROS) like through type-I photodynamic reaction and causes phototoxicity in the human keratinocyte cell line (HaCaT), which has been proved by mitochondrial dehydrogenase and neutral red uptake assays. CBZ induces single strand DNA damage. We have investigated the involvement of the apoptotic pattern of cell death and confirmed it by cytochrome C release from mitochondria and caspase-9 activation. Similarly, photo-micronuclei formation was associated to CBZ-induced phototoxicity. The results of this study strongly support that the upregulation of bax, cyto-C, apaf-1, casp-9 and down regulation of bcl2, keap-1, nrf-2, and hmox-1 genes cause apoptopic cell death. Downregulation of antioxidant genes showed a significant amount of ROS generation by photosensitized CBZ. Therefore, the current study will be a step forward to safeguard human beings from sunlight-induced photosensitive CBZ prolonged exposure. 相似文献
942.
Avinash K. Kudva Naveen Kaushal Sonia Mohinta Mary J. Kennett Avery August Robert F. Paulson K. Sandeep Prabhu 《PloS one》2013,8(12)
Previous studies have demonstrated the ability of an eicosapentaenoic acid (EPA)-derived endogenous cyclopentenone prostaglandin (CyPG) metabolite, Δ12-PGJ3, to selectively target leukemic stem cells, but not the normal hematopoietic stems cells, in in vitro and in vivo models of chronic myelogenous leukemia (CML). Here we evaluated the stability, bioavailability, and hypersensitivity of Δ12-PGJ3. The stability of Δ12-PGJ3 was evaluated under simulated conditions using artificial gastric and intestinal juice. The bioavailability of Δ12-PGJ3 in systemic circulation was demonstrated upon intraperitoneal injection into mice by LC-MS/MS. Δ12-PGJ3 being a downstream metabolite of PGD3 was tested in vitro using primary mouse bone marrow-derived mast cells (BMMCs) and in vivo mouse models for airway hypersensitivity. ZK118182, a synthetic PG analog with potent PGD2 receptor (DP)-agonist activity and a drug candidate in current clinical trials, was used for toxicological comparison. Δ12-PGJ3 was relatively more stable in simulated gastric juice than in simulated intestinal juice that followed first-order kinetics of degradation. Intraperitoneal injection into mice revealed that Δ12-PGJ3 was bioavailable and well absorbed into systemic circulation with a Cmax of 263 µg/L at 12 h. Treatment of BMMCs with ZK118182 for 12 h resulted in increased production of histamine, while Δ12-PGJ3 did not induce degranulation in BMMCs nor increase histamine. In addition, in vivo testing for hypersensitivity in mice showed that ZK118182 induces higher airways hyperresponsiveness when compared Δ12-PGJ3 and/or PBS control. Based on the stability studies, our data indicates that intraperitoneal route of administration of Δ12-PGJ3 was favorable than oral administration to achieve effective pharmacological levels in the plasma against leukemia. Δ12-PGJ3 failed to increase histamine and IL-4 in BMMCs, which is in agreement with reduced airway hyperresponsiveness in mice. In summary, our studies suggest Δ12-PGJ3 to be a promising bioactive metabolite for further evaluation as a potential drug candidate for treating CML. 相似文献
943.
Sandeep Kumar Deepak Sharma Rajesh Kumar 《Biochimica et Biophysica Acta - Proteins and Proteomics》2014,1844(3):641-655
The effect of denaturants on the structural fluctuation of M80-containing Ω-loop of ferrocytochrome c was determined by measuring the rate coefficient of CO-association with ferrocytochrome c under varying concentrations of urea and alkylureas (methylurea (MU), N,N'-dimethylurea (DMU), ethylurea (EU), tetramethylurea (TMU)) at pH 7.0, 25 °C. As denaturant concentration is increased within the subdenaturing limit, the CO-association reaction is decelerated indicating that subdenaturing concentrations of denaturant reduce the structural fluctuation of the Ω-loop. Structural fluctuation of the Ω-loop is reduced more for urea and least for TMU. Intermolecular docking between horse cytochrome c and denaturant molecule (urea, MU, DMU, EU and TMU) reveals that polyfunctional interactions between the denaturant and different groups of Ω-loop and other part of protein decrease with an increase of alkyl group on urea molecule, which suggests that the decrease in the extent of restricted dynamics of Ω-loop with a corresponding increase of alkyl groups on urea molecule is due to the decrease of denaturant-mediated cross-linking interactions. These denaturant-mediated interactions are expected to reduce the conformational entropy of protein. Analysis of rate-temperature data shows a progressive decrease in conformational entropy of protein in the native to subdenaturing region. Thermodynamic analysis of denaturant (urea, MU, DMU, EU, TMU) effects on the thermal unfolding of ferrocytochrome c reveals that (i) thermodynamic stability of protein decreases with increasing concentration of denaturant or hydrophobicity of urea derivatives, (ii) water activity plays an important role in stabilization of ferrocytochrome c, and (iii) destabilization of ferrocytochrome c by denaturant occurs through the disturbance of hydrophobic interactions and hydrogen-bonding. 相似文献
944.
Siva Rama Krishna Vanjari I. Deepthi K. Sandeep Bharadwaj Amrutur Navakanta Bhat Sampath Srinivasan 《Biotechnology and Bioprocess Engineering》2012,17(2):309-315
This paper presents a modified cellulose acetate membrane prepared using a dry casting technique that can be used to perform
lysis of erythrocytes and isolation of hemoglobin. Isolation of hemoglobin is thus achieved without the use of lysis buffers.
Cellulose acetate (CA) membranes are embedded with ammonium chloride (NH4Cl) and potassium bicarbonate (KHCO3), which act as lysing agents. The presence of embedded salts is confirmed using EDS analysis. The pores in the CA membrane
act as filters. The average pore size in these membranes is designed to be 1.5 μM, as characterized by SEM analysis, so that
they allow hemoglobin to pass through and block all other cells and unlysed erythrocytes present in blood. When a drop of
blood is added to the membrane, the NH4Cl and KHCO3 embedded in the membrane dissolve in plasma and lyse the erythrocytes. The filtered hemoglobin is characterized using UV-Vis
Spectroscopy. The results indicate extraction of higher concentration of hemoglobin compared with conventional methods. 相似文献
945.
Trishna Dutta Sandeep Sharma Jesús E. Maldonado Hemendra Singh Panwar John Seidensticker 《PloS one》2015,10(5)
Sloth bears (Melursus ursinus) are endemic to the Indian subcontinent. As a result of continued habitat loss and degradation over the past century, sloth bear populations have been in steady decline and now exist only in isolated or fragmented habitat across the entire range. We investigated the genetic connectivity of the sloth bear meta-population in five tiger reserves in the Satpura-Maikal landscape of central India. We used noninvasively collected fecal and hair samples to obtain genotypic information using a panel of seven polymorphic loci. Out of 194 field collected samples, we identified 55 individuals in this meta-population. We found that this meta-population has moderate genetic variation, and is subdivided into two genetic clusters. Further, we identified five first-generation migrants and signatures of contemporary gene flow. We found evidence of sloth bears in the corridor between the Kanha and Pench Tiger Reserves, and our results suggest that habitat connectivity and corridors play an important role in maintaining gene flow in this meta-population. These corridors face several anthropogenic and infrastructure development threats that have the potential to sever ongoing gene flow, if policies to protect them are not put into action immediately. 相似文献
946.
947.
948.
Goverdhan Surineni Sandeep Kumar Marvadi Perumal Yogeeswari Dharmarajan Sriram Srinivas Kantevari 《Bioorganic & medicinal chemistry letters》2018,28(9):1610-1614
Herein described the design, synthesis and antitubercular evaluation of novel series of dibenzofuran, dibenzothiophene and N-methyl carbazole tethered 2-aminothiazoles and their cinnamamide analogs. One pot condensation of N-methyl carbazole, dibenzofuran and dibenzothiophene methyl ketones with thiourea in the presence of Iodine and CuO gave respective 2-aminothiazoles 4–6 in very good yields. Aminothiazoles were further coupled with substituted cinnamic acids using acid-amine coupling conditions to give desired cinnamamide analogs 8a–e, 9a–e and 10a–e. All the newly synthesized compounds were fully characterized by their NMR and mass spectral analysis. In vitro screening of new derivatives against Mycobacterium tuberculosis H37Rv (Mtb) resulted 8c, 10d and 10e (MIC: 0.78?µg/mL) and 2-aminothiazoles 5 and 6 (MIC: 1.56?µg/mL) as potent compounds with lower cytotoxicity profile. 相似文献
949.
950.
Sandeep Kumar Shaily Shah Hai Michael Tang Matthew Smith Teresa Borrás John Danias 《PloS one》2013,8(8)
Tissue plasminogen activator, a serine protease encoded by the PLAT gene is present in the trabecular meshwork (TM) and other ocular tissues and has been reported to be downregulated by treatment with steroids in vitro. Steroids are known to cause changes in outflow facility of aqueous humor in many species. In the present study, we tested whether overexpression of PLAT can prevent and/or reverse the outflow facility of mouse eyes treated with steroids. Animals received bilateral injection with 20 µl of triamcinolone acetonide (TA) (40mg/ml) suspension subconjunctivally to induce outflow facility changes. Some animals received unilateral intracameral injection with 2 µl of adenoviral suspension [3-4x1012 virus genomes per milliliter (vg/ml)] carrying sheep PLAT cDNA (AdPLAT) either concurrently with TA injection or one week after TA injection, whereas others received bilateral intracameral injection with 2µl of adenoviral suspension (9x1012 vg/ml) carrying no transgene (AdNull) concurrently with TA injection. Animals were sacrificed one week after AdPLAT or AdNull treatment. Endogenous mRNA expression levels of mouse PAI-1 and MMP-2, -9 and -13 were also measured using qRT-PCR. Outflow facility one week after AdPLAT administration was increased by 60% and 63% respectively for animals that had not or had been pretreated with steroids. Overexpression of PLAT significantly upregulated expression of PAI-1, MMP-2, -9 and -13 compared to the levels found in TA only treated eyes. These findings suggest that overexpression of PLAT in TM of mouse eyes can both prevent and reverse the decrease in outflow facility caused by steroid treatment and is associated with upregulation of MMPs. 相似文献