1,738,391 research outputs found
Douglas College Physics 1207
No full textDouglas College for Physics 1207, based on Open Stax Physics. This textbook focuses on electricity, magnetism, optics and modern physics.open accessPublished. This PDF is a representation of the book as at October 3, 2021. The online version may have been updated. For the most recent version, please visit the online book linked in this record.physic
Controlled release of MT-1207 using a novel gastroretentive bilayer system comprised of hydrophilic and hydrophobic polymers
No full textIn the present study, novel gastroretentive bilayer tablets were developed that are promising for the once-a-day oral delivery of the drug candidate MT-1207. The gastroretentive layer consisted of a combination of hydrophilic and hydrophobic polymers, namely polyethylene oxide and Kollidon® SR. A factorial experiment was conducted, and the results revealed a non-effervescent gastroretentive layer that, unlike most gastroretentive layers reported in the literature, was easy to prepare, and provided immediate tablet buoyancy (mean floating lag time of 1.5 s) that lasted over 24 h in fasted state simulated gastric fluid (FaSSGF) pH 1.6, irrespective of the drug layer, thereby allowing a 24-hour sustained release of MT-1207 from the drug layer of the tablets. Furthermore, during in vitro buoyancy testing of the optimised bilayer tablets in media of different pH values (1.0, 3.0, 6.0), the significant difference (one-way ANOVA, p < 0.001) between the respective total floating times indicated that stomach pH effects on tablet buoyancy are important to be considered during the development of non-effervescent gastroretentive formulations and the choice of dosing regimen. To the best of our knowledge, this has not been reported before, and it should probably be factored in when designing dosing regimens. Finally, a pharmacokinetic study in Beagle dogs indicated a successful in vivo 24-hour sustained release of MT-1207 from the optimised gastroretentive bilayer tablet formulations with the drug plasma concentration remaining above the estimated minimum effective concentration of 1 ng/mL at the 24-hour timepoint and also demonstrated the gastroretentive capabilities of the hydrophilic and hydrophobic polymer combination. The optimised formulations will be forwarded to clinical development
Caṅgadeva’s inscription of 1207
No full textK. Ramasubramanian, Takao Hayashi, Clemency Montelle, "Caṅgadeva’s inscription of 1207," Bhāskara-prabhā (2019): 3-22Bhāskarācārya's grandson Caṅgadeva established a college (maṭha) for the propagation of his grandfather's works (śrī-bhāskarācārya-nibaddha-śāstravistāra- hetoḥ) and announced this fact in an inscription in 1207
MicroRNA 1207-3P in Prostate Cancer
No full textProstate cancer (PCa) is the most commonly diagnosed male cancer and the second leading cause of cancer-related death for men in the United States. Understanding the molecular mechanisms involved in progression from the asymptomatic androgen-dependent PCa to the lethal castration resistant prostate cancer (CRPC) is a major challenge. MicroRNAs (miRNAs), are known to be dysregulated in PCa. MicroRNA-1207-3p (miR-1207-3p) is encoded by the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of miR-1207-3p in PCa is unclear. We have discovered that miR-1207-3p is significantly underexpressed in PCa cell lines compared to normal prostate epithelial cells. Moreover, the increased expression of miR-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of Fibronectin type III domain containing 1 (FNDC1) and consequent loss of expression of fibronectin (FN1), and consequent loss of expression of the androgen receptor (AR). PCa cell lines and patient-derived tissues revealed significant overexpression of FNDC1, FN1 and AR which are factors that positively correlate with aggressive PCa. Also, metastatic PCa displayed concurrent overexpression of FNDC1, FN1 and AR. Taken together, this is the first description of a novel miR-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa. For the unbiased discovery of the molecular targets of miR-1207-3p, we designed and synthesized a novel synthetic biotinylated miR-1207-3p duplex (NB1207), and a novel synthetic biotinylated scramble duplex (NB1). We observed that NB1207, but not the scrambled duplex NB1, directly targets the 3’UTR of FNDC1 and more effectively inhibits proliferation, inhibits migration and increases apoptosis of PCa cells including those aggressively tumorigenic. Interestingly, the location of miR-1207-3p on the 8q24 human chromosomal region is downstream of the proto-oncogene, c-MYC. c-MYC has been linked to castration resistant prostate cancer (CRPC). However, the mechanisms regulating c-MYC remain unclear in CRPC. In this study, we discovered that c-MYC is regulated and therapeutically targetable via the miR-1207-3p/FNDC1/FN1/AR pathway in CRPC. miR-1207-3p negatively correlates with c-MYC in prostate tumors with Gleason score ≥8. Additionally, we discovered that overexpression of miR-1207-3p significantly inhibited proliferation and increased apoptosis in CRPC cells. We also compared the efficacy of NB1207 and NB5, two novel synthetic analogs of miR-1207-3p, with the currently used therapies against CPRC: abiraterone, enzalutamide, and apalutamide (phase 3 clinical trial). Treatment with NB1207 and NB5 resulted in increased inhibition of AR-V7 protein expression, and more significant inhibition of proliferation and increases in apoptosis of CRPC cells compared to abiraterone, enzalutamide and apalutamide. These results demonstrate that synthetic analogs of miR-1207-3p, such as NB5 and NB1207, may be a novel strategy for successful therapeutic targeting of c-MYC via the miR-1207-3p/FNDC1/FN1/AR pathway in CRPC. In summary, the present study indicates that miR-1207-3p may have potential diagnostic, prognostic, and therapeutic applications in PCa
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