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251.
Chandrateja Uppuluri Ashraf Sultana Shaik Tao Han Atul Nayak Karthik J. Nair Benjamin R. Whiteside Buchi N. Nalluri Diganta B. Das 《AAPS PharmSciTech》2017,18(5):1495-1506
The present study was aimed to investigate the effect of salient microneedle (MN) geometry parameters like length, density, shape and type on transdermal permeation of rizatriptan (RIZ). Studies were carried out using two types of MN devices viz. AdminPatch® arrays (ADM) (0.6, 0.9, 1.2 and 1.5 mm lengths) and laboratory-fabricated polymeric MNs (PMs) of 0.6 mm length. In the case of the PMs, arrays were applied three times at different places within a 1.77-cm2 skin area (PM-3) to maintain the MN density closer to 0.6 mm ADM. Histological studies revealed that PM, owing to their geometry/design, formed wider and deeper microconduits when compared to ADM of similar length. Approximately 4.9- and 4.2-fold increases in the RIZ steady-state flux values were observed with 1.5 mm ADM and PM-3 applications when compared to the passive studies. A good correlation between different dimensionless parameters like the amount of RIZ permeated (C t /C s), thickness (h/L) and surface area (S a/L 2) of the skin was observed with scaling analyses. Numerical simulations provided further information regarding the distribution of RIZ in MN-treated skin after application of different MNs. Overall, the study suggests that MN application enhances the RIZ transdermal permeation and the geometrical parameters of MNs play an important role in the degree enhancement. 相似文献
252.
Sterile α motif and HD domain-containing protein 1 (SAMHD1) is a mammalian dNTP hydrolase (dNTPase) that regulates intracellular dNTP balance. We have previously reported that SAMHD1 mRNA and protein levels are significantly downregulated in CD4+ T-cells of patients with cutaneous T-cell lymphoma (CTCL), a disease characterized by infiltration of neoplastic CD4+ T-lymphocytes into the skin. However, functional significance of SAMHD1 in CTCL development and progression remains unknown. Here we investigate the mechanism by which SAMHD1 induces apoptosis in CTCL-derived CD4+ T-cells. We stably expressed exogenous SAMHD1 in the CTCL-derived HuT78 T-cell line containing a very low level of endogenous SAMHD1 protein. We found that low-level exogenous expression of SAMHD1 led to a significant reduction in HuT78 cell growth, proliferation, and colony formation. Exogenous SAMHD1 expression in HuT78 cells also resulted in increased spontaneous and Fas ligand (Fas-L)-induced apoptosis levels via activation of the extrinsic pathway, including caspase-8, ?3 and ?7. Additionally, increased SAMHD1 significantly reduced the protein and mRNA expression of the short isoform of cFLIP (cFLIPS), an important negative regulator of Fas-L-mediated apoptotic signaling. Our results indicate that exogenous SAMHD1 expression inhibits HuT78 cell growth and proliferation in part by increasing apoptosis. These findings implicate that SAMHD1 acts as an inhibitor in CTCL cell growth, suggesting that downregulation of SAMHD1 expression in neoplastic T-cells can facilitate uncontrolled cell proliferation. 相似文献
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Background
Emergence of drug resistant varieties of tuberculosis is posing a major threat to global tuberculosis eradication programmes. Although several approaches have been explored to counter resistance, there has been limited success due to a lack of understanding of how resistance emerges in bacteria upon drug treatment. A systems level analysis of the proteins involved is essential to gain insights into the routes required for emergence of drug resistance. 相似文献254.
Devarajan K 《PLoS computational biology》2008,4(7):e1000029
In the last decade, advances in high-throughput technologies such as DNA microarrays have made it possible to simultaneously measure the expression levels of tens of thousands of genes and proteins. This has resulted in large amounts of biological data requiring analysis and interpretation. Nonnegative matrix factorization (NMF) was introduced as an unsupervised, parts-based learning paradigm involving the decomposition of a nonnegative matrix V into two nonnegative matrices, W and H, via a multiplicative updates algorithm. In the context of a pxn gene expression matrix V consisting of observations on p genes from n samples, each column of W defines a metagene, and each column of H represents the metagene expression pattern of the corresponding sample. NMF has been primarily applied in an unsupervised setting in image and natural language processing. More recently, it has been successfully utilized in a variety of applications in computational biology. Examples include molecular pattern discovery, class comparison and prediction, cross-platform and cross-species analysis, functional characterization of genes and biomedical informatics. In this paper, we review this method as a data analytical and interpretive tool in computational biology with an emphasis on these applications. 相似文献
255.
Katarzyna Justyna Chojnacka Praveenraj Elancheliyan Ben Hur Marins Mussulini Karthik Mohanraj Sylvie Callegari Aleksandra Gosk Tomasz Banach Tomasz Gral Karolina Szczepanowska Peter Rehling Remigiusz Adam Serwa Agnieszka Chacinska 《Molecular biology of the cell》2022,33(4)
Assembly of the dimeric complex III (CIII2) in the mitochondrial inner membrane is an intricate process in which several accessory proteins are involved as assembly factors. Despite numerous studies, this process has yet to be fully understood. Here we report the identification of human OCIAD2 (ovarian carcinoma immunoreactive antigen–like protein 2) as an assembly factor for CIII2. OCIAD2 was found to be deregulated in several carcinomas and also in some neurogenerative disorders; however, its nonpathological role had not been elucidated. We have shown that OCIAD2 localizes to mitochondria and interacts with electron transport chain (ETC) proteins. Complete loss of OCIAD2 using gene editing in HEK293 cells resulted in abnormal mitochondrial morphology, a substantial decrease of both CIII2 and supercomplex III2+IV, and a reduction in CIII enzymatic activity. Identification of OCIAD2 as a protein required for assembly of functional CIII2 provides a new insight into the biogenesis and architecture of the ETC. Elucidating the mechanism of OCIAD2 action is important both for the understanding of cellular metabolism and for an understanding of its role in malignant transformation. 相似文献
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257.
Mancarella S Wang Y Deng X Landesberg G Scalia R Panettieri RA Mallilankaraman K Tang XD Madesh M Gill DL 《The Journal of biological chemistry》2011,286(52):44788-44798
The endoplasmic reticulum Ca2+-sensing STIM proteins mediate Ca2+ entry signals by coupling to activate plasma membrane Orai channels. We reveal that STIM-Orai coupling is rapidly blocked by hypoxia and the ensuing decrease in cytosolic pH. In smooth muscle cells or HEK293 cells coexpressing STIM1 and Orai1, acute hypoxic conditions rapidly blocked store-operated Ca2+ entry and the Orai1-mediated Ca2+ release-activated Ca2+ current (ICRAC). Hypoxia-induced blockade of Ca2+ entry and ICRAC was reversed by NH4+-induced cytosolic alkalinization. Hypoxia and acidification both blocked ICRAC induced by the short STIM1 Orai-activating region. Although hypoxia induced STIM1 translocation into junctions, it did not dissociate the STIM1-Orai1 complex. However, both hypoxia and cytosolic acidosis rapidly decreased Förster resonance energy transfer (FRET) between STIM1-YFP and Orai1-CFP. Thus, although hypoxia promotes STIM1 junctional accumulation, the ensuing acidification functionally uncouples the STIM1-Orai1 complex providing an important mechanism protecting cells from Ca2+ overload under hypoxic stress conditions. 相似文献
258.
Sribala Viswanathan Karthik Kanagaraj Venkateswarlu Raavi Shanmugapriya Dhanasekaran Vinod Kumar Panicker Krishnamoorthy R Adayabalam S. Balajee Venkatachalam Perumal 《Journal of cellular biochemistry》2019,120(4):5722-5728
In vitro human lymphocyte culture methodology is well established yet certain confounding factors such as age, medical history as well as individual’s blood type may potentially modulate in vitro proliferation response. These factors have to be carefully evaluated to release reliable test report in routine cytogenetic evaluation for various genetic conditions, radiation biodosimetry, etc. With this objective, the current study was focused on analyzing the proliferation response of lymphocytes drawn from 90 individuals (21-29 years) with different blood types. The proliferation response was assessed in the cultured lymphocytes by cell cycle, mitotic index (MI), and nuclear division index (NDI) after stimulation with phytohaemagglutinin (PHA). To investigate the toxic effect on proliferation, MI was calculated in representative samples of each blood type were X-irradiated. The results showed that there was no significant difference among the cell cycle phases of lymphocytes in different blood types (P > 0.05). Similarly, both MI and NDI of lymphocytes derived from different blood types also did not show significant difference ( P > 0.05). The extensive interindividual variation within and among the blood types is likely responsible for the lack of significant difference in lymphocyte proliferation. Although spontaneous proliferation efficiency of lymphocytes of different blood types after PHA stimulation was grossly similar, the MI observed after radiation exposure showed a significant difference ( P < 0.05) indicating a differential proliferation response among the blood types. Our results suggest that the blood types did not have any impact on PHA-induced proliferation; however, a specific differential lymphocyte proliferation observed after radiation exposure needs to be considered. 相似文献
259.
Alison M. Kurimchak Vikas Kumar Carlos Herrera-Montvez Katherine J. Johnson Nishi Srivastava Karthik Davarajan Suraj Peri Kathy Q. Cai Gina M. Mantia-Smaldone James S. Duncan 《Molecular & cellular proteomics : MCP》2020,19(12):2068-2090
Highlights
- •SRPK1 is overexpressed in endometrial cancer and associated with poor survival.
- •SRPK1 promotes endometrial cancer cell growth under nutrient-deprived conditions.
- •Activation of EGFR-IGF1R-AKT signaling promotes resistance to SRPK1 inhibitors.
- •Co-targeting SRPK1 and EGFR-IGF1R synergize blocking endometrial cancer cell growth.
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