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排序方式: 共有1073条查询结果,搜索用时 15 毫秒
1.
Yiliao Luo Mengxing Li Uday P. Pratap Suryavathi Viswanadhapalli Junhao Liu Prabhakar P. Venkata Kristin A. Altwegg Bridgitte E. Palacios Xiaonan Li Yihong Chen Manjeet K. Rao Andrew J. Brenner Gangadhara R. Sareddy Ratna K. Vadlamudi 《Molecular carcinogenesis》2020,59(3):281-292
Medulloblastoma (MB) is the most common and deadliest brain tumor in children. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein and its oncogenic signaling is implicated in the progression of several cancers. However, the role of PELP1 in the progression of MB remains unknown. The objective of this study is to examine the role of PELP1 in the progression of MB. Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in the MB specimens compared to normal brain. Knockdown of PELP1 reduced cell proliferation, cell survival, and cell invasion of MB cell lines. The RNA-sequencing analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation and extracellular matrix. Gene set enrichment analysis confirmed that the PELP1-regulated genes were negatively correlated with nuclear factor-κB (NF-κB), extracellular matrix, and angiogenesis gene sets. Interestingly, PELP1 knockdown reduced the expression of NF-κB target genes, NF-κB reporter activity, and inhibited the nuclear translocation of p65. Importantly, the knockdown of PELP1 significantly reduced in vivo MB progression in orthotopic models and improved the overall mice survival. Collectively, these results suggest that PELP1 could be a novel target for therapeutic intervention in MB. 相似文献
2.
Swapnil P. Borse Abu Sufiyan Chhipa Vipin Sharma Devendra Pratap Singh Manish Nivsarkar 《Medical principles and practice》2021,30(2):109
Type 2 diabetes mellitus (T2DM) accounts for >90% of the cases of diabetes in adults. Resistance to insulin action is the major cause that leads to chronic hyperglycemia in diabetic patients. T2DM is the consequence of activation of multiple pathways and factors involved in insulin resistance and β-cell dysfunction. Also, the etiology of T2DM involves the complex interplay between genetics and environmental factors. This interplay can be governed efficiently by lifestyle modifications to achieve better management of diabetes. The present review aims at discussing the major factors involved in the development of T2DM that remain unfocussed during the anti-diabetic therapy. The review also focuses on lifestyle modifications that are warranted for the successful management of T2DM. In addition, it attempts to explain flaws in current strategies to combat diabetes. The employability of phytoconstituents as multitargeting molecules and their potential use as effective therapeutic adjuvants to first line hypoglycemic agents to prevent side effects caused by the synthetic drugs are also discussed. 相似文献
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Andrew Murphy Jeffrey Cheng Jit Pratap Renae Redman John Coucher 《Journal of Medical Imaging and Radiation Sciences》2019,50(1):62-67
Introduction
Optimal opacification of the pulmonary vasculature is a fundamental factor of a diagnostic quality computed tomography pulmonary angiogram (CTPA). This retrospective study examined the feasibility of utilising a noise-optimised monoenergetic reconstruction of the dual-energy computed tomography pulmonary angiogram (DE-CTPA) as an additional protocol to increase vessel opacification.Method
The study involved a retrospective analysis of 129 patients, 69 males (average age 58 years), 60 females (average age 56 years) who underwent a DE-CTPA at a tertiary referral hospital. Linear blended 120 kilovoltage (kV) images (LB120) dual-energy (DE) data sets (50% 100 kV and 50% 140 kV) were compared to noise-optimised virtual monoenergetic image reconstruction (VMI+) at 40 kiloelectron volts (VMI+40). The attenuation of the pulmonary trunk measured in Hounsfield units (HU) between the equivalent axial slices of the LB120 data set and the VMI+40 data set underwent statistical analysis via a Wilcoxon paired-sample test.Results
VMI+40 (1161.500 HU) yielded a statistically significant increase in median attenuation within the pulmonary trunk compared to the LB120 (304.400 HU), with a median difference between monoenergetic reconstruction and standard dual energy of data sets of 827.5 HU (P < .001).Conclusions
VMI+40 of the DE-CTPA scan demonstrates a statistically significant increase in vessel attenuation in all cases and may have utility in reducing the rates of indeterminate or repeated studies. 相似文献6.
Bharat Bhusan Subudhi Pratap Kumar Sahu Vijay Kumar Singh Shaktiketan Prusty 《The AAPS journal》2018,20(6):110
Identification of renin-angiotensin system in the interplay of hypertension and neurodegeneration has paved the way for the repurposing of antihypertensive drugs against Parkinsonism. Losartan carboxylic acid (LCA), the potent AT1 blocker metabolite of losartan, suffers from poor bioavailability and brain access. Since ascorbate transporters have earlier shown enough flexibility as carriers, we have conjugated losartan carboxylic acid to ascorbic acid with the aim of achieving higher oral/brain availability. Ester of LCA and ascorbic acid (FED) was developed keeping in view the substrate specificity of ascorbate transporters. Oral/brain bioavailability was assessed using in vivo pharmacokinetic model. Effect on central nervous system (CNS) and protection against Parkinsonism was evaluated using in vivo models. FED enhanced bioavailability of LCA. The higher brain availability of LCA enabled CNS protection as evident from the increase in locomotor activity, improved motor coordination, and protection against drug-induced catatonia. In conclusion, FED offers an approach to repurpose LCA against Parkinsonism. This can encourage further investigation to simultaneously address hypertension and neurodegeneration. 相似文献
7.
According to the Hunter Serotonin Toxicity Criteria, the presence of either clonus or hyperreflexia is a must for making a diagnosis of serotonin syndrome (SS). We report five patients with SS who had areflexia because of associated polyneuropathy. None of the patients fulfilled the Hunter criteria for SS. However, all five patients had features suggestive of neuromuscular hyperactivity, autonomic hyperactivity and altered mental status and fulfilled the Sternbach criteria for SS. All patients responded to cyproheptadine within 5 days to 2 weeks duration. These cases highlight the limitations of the Hunter criteria for SS in patients with associated polyneuropathy. 相似文献
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Hong Chew Pratap Shetty Maqsood Elahi Zakir Akhunji 《General thoracic and cardiovascular surgery》2014,62(6):386-389
Chylous pericardial effusion is an uncommon entity that is most commonly associated with post-cardiac surgery, in particular aortic valve and minimally invasive cardiac surgery. Post-radiation therapy, infection, mediastinal neoplasm, lymphoma and a small group of idiopathic, spontaneous chylous pericardial effusion have also been reported as the causes. Here, we report a rare case of pericardial effusion secondary to chylous fistula in a 63-year-old man with Poland syndrome. The case highlights an unusual thoracic duct anomaly as a cause of our reported chylous pericardial effusion. 相似文献
10.
Vaishali L. Chudasama Anup Zutshi Pratap Singh Anson K. Abraham Donald E. Mager John M. Harrold 《Journal of pharmacokinetics and pharmacodynamics》2015,42(1):1-18
Bispecific antibodies (BAbs) are novel constructs that are under development and show promise as new therapeutic modalities for cancer and autoimmune disorders. The aim of this study is to develop a semi-mechanistic modeling approach to elucidate the disposition of BAbs in plasma and possible sites of action in humans. Here we present two case studies that showcase the use of modeling to guide BAb development. In case one, a BAb is directed against a soluble and a membrane-bound ligand for treating systemic lupus erythematosus, and in case two, a BAb targets two soluble ligands as a potential treatment for ulcerative colitis and asthma. Model simulations revealed important differences between plasma and tissues, when evaluated for drug disposition and target suppression. Target concentrations at tissue sites and type (soluble vs membrane-bound), tissue-site binding, and binding affinity are all major determinants of BAb disposition and subsequently target suppression. For the presented case studies, higher doses and/or frequent dosing regimens are required to achieve 80 % target suppression in site specific tissue (the more relevant matrix) as compared to plasma. Site-specific target-mediated models may serve to guide the selection of first-in-human doses for new BAbs. 相似文献