53 research outputs found

    Comparative efficacy of epigallocatechin gallate and its nano-formulation in prostate cancer 3D spheroids model

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    Background: Prostate cancer (PCa) remains one of the clinically relevant pathologies that needs pragmatic and effective treatment approaches. The current study aimed to evaluate the anticancer potential of epigallocatechin gallate (EGCG) and EGCG-loaded nanoparticles (EGCG NP) for the treatment of prostate cancer in in-vitro 3D spheroid model.Methods: The EGCG NPs was synthesized by using polymeric method as reported in our previous study. A 3D spheroid assay was conducted using human prostate specific cell lines (PC3 and 22Rv1) cultured on poly-HEMA-covered plates at different time points. Once formed, the spheroids were treated with either EGCG alone or with EGCG NPs continuously for 6 days. Simultaneously, specific controls were also taken for comparison purpose. CellROX dye was used to quantitate the formation of reactive oxygen species (ROS) in response to EGCG and EGCG NPs to 22Rv1 and PC3, 3D spheroids. The treated spheroids were also evaluated to measure modulation in mitochondrial membrane potential and the quantification of apoptotic and live cells using a flow cytometer.Results: The spheroid sizes of both studied cell lines were found to be significantly (p < 0.05) reduced after the treatment with EGCG and its nanoformulation. The significant increase in ROS formation was observed in PC3 cells in response to EGCG and EGCG-NPs treatment. However, no significant change in ROS formation was observed in 22Rv1 cells. Similarly, both compounds (EGCG and EGCG NPs) did not show any significant changes in mitochondrial membrane potential in 22Rv1 and PC3 spheroids. Interestingly, EGCG treatment showed a significant change between live and apoptotic cells in both 22Rv1 and PC3 spheroids but its nanoformulation didn't show any significant change in the number of apoptotic and live cells. Our study observed a significant anticancer potential of EGCG and EGCG NPs at clinically relevant doses highlighting the possible advantage of 3D spheroid model specifically in our studied cancer cells. However, further preclinical in vivo studies are recommended in a suitable model to decipher our in vitro data and exploit EGCG and EGCG NPs against prostate cancer.Conclusion: Our results indicate the anticancer efficacy of EGCG and EGCG NPs in 3D spheroids of PCa cell lines

    Development of (−)-epigallocatechin-3-gallate-loaded folate receptor-targeted nanoparticles for prostate cancer treatment

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    In continuation of our previous studies, we developed polymeric epigallocatechin 3-gallate (EGCG)-loaded nanoparticles (NPs) coupled with folic acid (FA), able to dually bind the human folate receptor alpha (FOLR1), and prostate-specific membrane antigen (PSMA+) in prostate cancer (PCa) model. After a preliminary computational molecular recognition of NP′ ligand binding on the FOLR1 active site, we synthesized the biocompatible block-copolymer PLGA-PEG-FA to prepare EGCG-targeted NPs (EGCG-T-NPs). The obtained NPs were characterized by various analytical techniques, and anticancer efficacy was determined by different sets of experiments in a 3D culture of PCa using PC3 and 22Rv1 cell lines. Results showed a significant reduction in spheroid size by EGCG-T-NPs, especially in PSMA+ (22Rv1) cells. The targeted NPs significantly enhanced the antiproliferative activity of EGCG against PCa cell lines, especially toward the PSMA+ cells, known to have higher FOLR1 expression. We did not observe any changes in the reactive oxygen species formation in both studied cell lines. However, significant changes in mitochondrial depolarization (15%) and polarization (18%) were recorded in response to EGCG-T-NP compared to control in 22Rv1. Similarly, EGCG-T-NP treatment also showed an increase in the number of dead apoptotic cells in 22Rv1 spheroids. Collectively, the obtained results support our hypothesis about the role of these targeted nanoprototypes in the increasing cellular uptake of EGCG payload into PCa cells, thus enhancing its antitumor efficacy

    Endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage after failed endoscopic retrograde cholangiopancreatography: a meta-analysis

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    Ramkaji Baniya, Sunil Upadhaya, Seetharamprasad Madala, Subash Chandra Subedi, Tabrez Shaik Mohammed, Ghassan Bachuwa Hurley Medical Center, Michigan State University, Flint, MI, USA Abstract: The failure rate of endoscopic retrograde cholangiopancreatography for biliary cannulation is approximately 6%–7% in cases of obstructive jaundice. Percutaneous transhepatic biliary drainage (PTBD) is the procedure of choice in such cases. Endoscopic ultrasound-guided biliary drainage (EGBD) is a novel technique that allows biliary drainage by echoendoscopy and fluoroscopy using a stent from the biliary tree to the gastrointestinal tract. Information in PubMed, Scopus, clinicaltrials.gov and Cochrane review were analyzed to obtain studies comparing EGBD and PTBD. Six studies fulfilled the inclusion criteria. Technical (odds ratio (OR): 0.34; confidence interval (CI) 0.10–1.14; p=0.05) and clinical (OR: 1.48; CI 0.46–4.79; p=0.51) success rates were not statistically significant between the EGBD and PTBD groups. Mild adverse events were nonsignificantly different (OR: 0.36; CI 0.10–1.24; p=0.11) but not the moderate-to-severe adverse events (OR: 0.16; CI 0.08–0.32; p≤0.00001) and total adverse events (OR: 0.34; CI 0.20–0.59; p≤0.0001). EGBD is equally effective but safer than PTBD. Keywords: failed endoscopic retrograde cholangiopancreatography, percutaneous transhepatic biliary drainage, endoscopic ultrasound-guided biliary drainage, technical success, clinical succes

    Mechanisms of laminar organization of hippocampal excitatory synapses

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    The hippocampus has well-defined laminae with specified neuronal pathways. In the hippocampus, I investigated the developmental expression and functional roles of prominent synapse organizers, leucine-rich-repeat transmembrane neuronal proteins (LRRTMs). LRRTM1 and LRRTM2 are compartmentalised to the stratum radiatum (SR) and stratum lacunosum moleculare (SLM), respectively, with specific expression impacting synaptic architecture and cognitive behaviours. Using immunohistochemistry, I demonstrated that LRRTM1 and LRRTM2 exhibit distinct temporal and spatial expression patterns in the hippocampal laminae: LRRTM1 is predominantly localized in the SR, and LRRTM2 in the SLM. My findings indicate that LRRTM2 expression in the SLM corresponds with excitatory synapse formation and maturation in the cortical temporoammonic cortical inputs to the CA1. However, the functional significance of LRRTM2 compartmentalization in the SLM was not known. To this end, I conducted a suite of behavioural assays in mice lacking LRRTM2 in the dorsal CA1 (Lrrtm2-CA1-cKO). My studies revealed that Lrrtm2-CA1-cKO mice display anxiety-associated phenotype, but only in female mice.May 202

    Laparoscopic esophageal myotomy versus pneumatic dilation in the treatment of idiopathic achalasia: a meta-analysis of randomized controlled trials

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    Ramkaji Baniya, Sunil Upadhaya, Jahangir Khan, Suresh Kumar Subedi, Tabrez Shaik Mohammed, Balvant K Ganatra, Ghassan Bachuwa Department of Internal Medicine, Hurley Medical Center, Michigan State University, Flint, MI, USA Background: Achalasia is a primary esophageal motility disorder of unknown etiology associated with abnormalities in peristalsis and lower esophageal sphincter relaxation. The disease is incurable; however, definitive treatment procedures like pneumatic dilation (PD)/balloon dilation and laparoscopic esophageal myotomy (LEM) are performed to relieve dysphagia and related symptoms. Currently, there is paucity of data comparing the outcomes of these procedures. The aim of this meta-analysis is to compare the short- and long-term success rates of PD and LEM. Methods: A thorough systematic search of PubMed, Scopus, clinicaltrials.gov, and Cochrane library was conducted for randomized controlled trials (RCTs) comparing the outcomes of PD versus LEM in the treatment of achalasia. The Mantel-Haenszel method and random effect model were used to analyze the data. RCTs with outcome data at 3-month, 1-year, and 5-year intervals were analyzed. Results: A total of 437,378 and 254 patients at 3-month, 1-year, and 5-year intervals were analyzed for outcome data. At 3 months and 1 year, PD was not as effective as LEM (odds ratio [OR]: 0.50; confidence interval [CI] 0.31–0.82; P = 0.009 and OR: 0.47; CI 0.22–0.99; P = 0.21) but at 5 years, one procedure was non-inferior to the other (OR: 0.62; 0.33–1.19; P = 0.34). Conclusion: PD was as effective as LEM in relieving symptoms of achalasia in the long-term. Keywords: achalasia, balloon dilation, pneumatic dilation, laparoscopic myotomy, Heller’s myotom

    Rebirth of Opt-in System in Copyright: Analysis in the Light of ‘Google Books’ Controversy

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    500-508The recent copyright controversy, the Google Books litigation, has revived interest in the role that opt-in requirements can play in copyright law. Google Books sought to make every book in the English language text-searchable. To realize this goal, however, Google intended to scan the text of each such book – thereby making a copy – the right to which was vested in different persons around the world. This number of persons amounted to millions and gaining access to all was an onerous task. So, when the company failed to get permission from all the copyright owners, it gave two options to the authors either to opt-out of the copyright or agree to it by as per the result of a class action litigation. In both these circumstances, the user of the copyright had the right to exploit, without authorization, unless the copyright holder took affirmative action. It is the essence of opt-in system in copyright which reared its head once more along with this controversy. This paper critically examines the protection regime in copyright law and the philosophy of protection given to any author over his/her original creation in the light of the above mentioned controversy bearing a potential impact over the fair use doctrine in copyright law. In the present context of highly digitalized society, the dilemma is whether an opt-out system is the need of the hour or the opt-in system should regain its place
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