Suchergebnisse

PURPOSE: Cordycepin, a natural product isolated from the fungus Cordyceps militaris, is a potential candidate for breast cancer therapy. However, due to its structural similarity with adenosine, cordycepin is rapidly metabolized into an inactive form in the body, hindering its development as a therapeutic agent. In the present study, we have prepared cordycepin as nanoparticles in poly(lactic-co-glycolic acid) (PLGA) and compared their cellular uptake, cytotoxicity and hemolytic potential with free cordycepin. MATERIALS AND METHODS: Cordycepin-loaded PLGA nanoparticles (CPNPs) were prepared by the double-emulsion solvent evaporation method. Physico-chemical characterization of the nanoparticles was done by zetasizer, transmission electron microscopy (TEM) and reverse-phase high-pressure liquid chromatography (RP-HPLC) analyses. Cellular uptake and cytotoxicity of CPNPs and free drug were tested in human breast cancer cells (MCF7). Hemolytic potential of both of these forms was evaluated in rat red blood cells (RBCs). RESULTS: Physico-chemical characterization revealed that CPNPs were spherical in shape, possessed a size range of 179–246 nm, and released the encapsulated drug sustainably over a period of 10 days. CPNPs exhibited a high level of cellular uptake and cytotoxicity than the free drug in MCF-7 cells. While CPNPs were not toxic to rat RBCs even at high concentrations, free cordycepin induced hemolysis of these cells at relatively low concentration. CONCLUSION: Our results reveal that delivery as CPNPs could enhance the clinical efficacy of cordycepin substantially.

Gregory Marslin,1– 3 Vinoth Khandelwal,4 Gregory Franklin5 1School of Pharmacy, Sathyabama Institute of Science and Technology, Jeppiaar Nagar, Rajiv Gandhi Salai, Chennai 600119, India; 2Ratnam Institute of Pharmacy and Research, Nellore, 524346, India; 3College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong, Shaanxi, People's Republic of China; 4Department of Translational Pharmacology, Santa Maria Imbaro, Italy; 5Institute of Plant Genetics of the Polish Academy of Sciencs, StrzeszyÅ"ska 34, PoznaÅ" 60-479, Wielkopolska, PolandCorrespondence: Gregory Marslin; Gregory Franklin Tel +91 4424502344Email marslingregory@gmail.com; fgre@igr.poznan.plPurpose: Cordycepin, a natural product isolated from the fungus Cordyceps militaris, is a potential candidate for breast cancer therapy. However, due to its structural similarity with adenosine, cordycepin is rapidly metabolized into an inactive form in the body, hindering its development as a therapeutic agent. In the present study, we have prepared cordycepin as nanoparticles in poly(lactic-co-glycolic acid) (PLGA) and compared their cellular uptake, cytotoxicity and hemolytic potential with free cordycepin.Materials and Methods: Cordycepin-loaded PLGA nanoparticles (CPNPs) were prepared by the double-emulsion solvent evaporation method. Physico-chemical characterization of the nanoparticles was done by zetasizer, transmission electron microscopy (TEM) and reverse-phase high-pressure liquid chromatography (RP-HPLC) analyses. Cellular uptake and cytotoxicity of CPNPs and free drug were tested in human breast cancer cells (MCF7). Hemolytic potential of both of these forms was evaluated in rat red blood cells (RBCs).Results: Physico-chemical characterization revealed that CPNPs were spherical in shape, possessed a size range of 179– 246 nm, and released the encapsulated drug sustainably over a period of 10 days. CPNPs exhibited a high level of cellular uptake and cytotoxicity than the free drug in MCF-7 cells. While CPNPs were not toxic to rat RBCs even at high concentrations, free cordycepin induced hemolysis of these cells at relatively low concentration.Conclusion: Our results reveal that delivery as CPNPs could enhance the clinical efficacy of cordycepin substantially.Keywords: cordycepin, nanoparticles, PLGA, cellular uptake, cytotoxicity, breast cancer cells, hemolysis

Hypericum perforatum (St John's wort) is a reservoir of diverse classes of biologically active and high value secondary metabolites, which captured the interest of both researchers and the pharmaceutical industry alike. Several studies and clinical trials have shown that H. perforatum extracts possess an astounding array of pharmacological properties. These properties include antidepressant, anti-inflammatory, antiviral, anti-cancer, and antibacterial activities; and are largely attributed to the naphtodianthrones and xanthones found in the genus. Hence, improving their production via genetic manipulation is an important strategy. In spite of the presence of contemporary genome editing tools, genetic improvement of this genus remains challenging without robust transformation methods in place. In the recent past, we found that H. perforatum remains recalcitrant to Agrobacterium tumefaciens mediated transformation partly due to the induction of plant defense responses coming into play. However, H. perforatum transformation is possible via a non-biological method, biolistic bombardment. Some research groups have observed the induction of hairy roots in H. perforatum after Agrobacterium rhizogenes co-cultivation. In this review, we aim at updating the available methods for regeneration and transformation of H. perforatum. In addition, we also propose a brief perspective on certain novel strategies to improve transformation efficiency in order to meet the demands of the pharmaceutical industry via metabolic engineering. ; GF and PS are financed from the BIOTALENT project (GA621321) funded by the European Union Seventh Framework Programme (FP7) ERA Chairs Pilot Call and co-financed by funds allocated for education through project no W26/7.PR/2015 [GA 3413/7.PR/2015/2] for the years 2015-2019. This work was partially supported by Fundacao para a Ciencia e a Tecnologia (FCT) project (PTDC/AGR-GPL/119211/2010). WEE acknowledges the financial support provided by the FCT (SFRH/BD/52561/2014), under the Doctoral Programme ...

Article ID 578323 ; The latest report by the National Crime Records Bureau has positioned Tamil Nadu as the Indian state with highest suicide rate. At least in part, this is happening due to exam pressure among adolescents, emphasizing the imperative need to understand the pattern of anxiety and various factors contributing to it among students. The present study was conducted to analyze the level of state anxiety among board exam attending school students in Tamil Nadu, India. A group of 100 students containing 50 boys and 50 girls from 10th and 12th grades participated in the study and their state anxiety before board exams was measured by Westside Test Anxiety Scale. We found that all board exam going students had increased level of anxiety, which was particularly higher among boys and 12th standard board exam going students. Analysis of various demographic variables showed that students from nuclear families presented higher anxiety levels compared to their desired competitive group. Overall, our results showing the prevalence of state anxiety among board exam going students in Tamil Nadu, India, support the recent attempt taken by Tamil Nadu government to improve student's academic performance in a healthier manner by appointing psychologists in all government schools. ; Gregory Marslin and Caroline J. Sheeba were supported by Fundacao para a Ciencia e a Tecnologia (FCT), Portugal, Grants nos. SFRH/BD/72809/2010 and SFRH/BPD/89493/2012, ...

In the recent years, the "tumor microenvironment" has been receiving growing attention due to its involvement in neoplastic transformation, tumor growth, invasion, and protection of tumor cells from host immune response. All these events are facilitated by chemical signals produced by the tumor as well as the surrounding stromal cells. This review is divided into two main parts in which the first part discusses the receptor tyrosine kinase (RTK)-mediated growth factor signaling, steroid hormone (SH) signaling, ancient signaling pathways, and other molecules that are involved in tumorigenesis and how they interact with each other to create a complex tumor microenvironment. In the second part, we bring together the recent nanocarrier-mediated drug delivery approaches to target the signaling pathways/molecules present in the tumor microenvironment. ; Foundation for Science and Technology (FCT) [(SFRH/BPD/89493/2012]; FCT [SFRH/BD/72809/2010]; Portuguese Government; FCT national funds (PIDDAC) [PTDC/AGR-GPL/119211/2010, PEst-C/AGR/UI4033/2011]; European Fund for Regional Development (FEDER) through COMPETE Operational Programme Competitive Factors (POFC) ; info:eu-repo/semantics/publishedVersion

The latest report by the National Crime Records Bureau has positioned Tamil Nadu as the Indian state with highest suicide rate. At least in part, this is happening due to exam pressure among adolescents, emphasizing the imperative need to understand the pattern of anxiety and various factors contributing to it among students. The present study was conducted to analyze the level of state anxiety among board exam attending school students in Tamil Nadu, India. A group of 100 students containing 50 boys and 50 girls from 10th and 12th grades participated in the study and their state anxiety before board exams was measured by Westside Test Anxiety Scale. We found that all board exam going students had increased level of anxiety, which was particularly higher among boys and 12th standard board exam going students. Analysis of various demographic variables showed that students from nuclear families presented higher anxiety levels compared to their desired competitive group. Overall, our results showing the prevalence of state anxiety among board exam going students in Tamil Nadu, India, support the recent attempt taken by Tamil Nadu government to improve student's academic performance in a healthier manner by appointing psychologists in all government schools.

Gregory Marslin,1 Ann Mary Revina,2,3 Vinoth Kumar Megraj Khandelwal,4 Krishnamoorthy Balakumar,5 Jose Prakash,6 Gregory Franklin,1,* Caroline J Sheeba2,3,7,*1AgroBioPlant Group, Centre for the Research and Technology of Agro-Environment and Biological Sciences (CITAB), University of Minho, Braga, Portugal; 2Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal; 3ICVS/3B's – PT Government Associate Laboratory, Braga/Guimarães, Portugal; 4Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy; 5Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore, Tamil Nadu, India; 6Department of Pharmaceutics, Vels University, Chennai, Tamil Nadu, India; 7Regenerative Medicine Program, Department of Biomedical Sciences and Medicine, University of Algarve, Faro, Portugal*These authors contributed equally to this workAbstract: Clinical effectiveness of imatinib mesylate in cancer treatment is compromised by its off-target cardiotoxicity. In the present study, we have developed physically stable imatinib mesylate-loaded poly(lactide-co-glycolide) nanoparticles (INPs) that could sustainably release the drug, and studied its efficacy by in vitro anticancer and in vivo cardiotoxicity assays. MTT (methylthiazolyldiphenyl-tetrazolium bromide) assay revealed that INPs are more cytotoxic to MCF-7 breast cancer cells compared to the equivalent concentration of free imatinib mesylate. Wistar rats orally administered with 50 mg/kg INPs for 28 days showed no significant cardiotoxicity or associated changes. Whereas, increased alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels, and reduced white blood cell, red blood cell, and hemoglobin content were observed in the animals administered with free drug. While the histological sections from hearts of animals that received INPs did not show any significant cardiotoxic symptoms, loss of normal architecture and increased cytoplasmic vacuolization were observed in the heart sections of animals administered with free imatinib mesylate. Based on these results, we conclude that nano-encapsulation of imatinib mesylate increases its efficacy against cancer cells, with almost no cardiotoxicity.Keywords: imatinib nanoparticles, cytostoxicity, cardiotoxicity, hematology

The client for this capstone is the North American Strategy for Competitiveness (NASCO), a nonprofit voluntary coalition of North American governments, businesses, and educational institutions. One of NASCO's core missions is improving the competitiveness of the North American supply chain. NASCO is concerned that regulatory efforts at the state and local level are creating barriers to trade along the North American Free Trade Agreement (NAFTA) corridor. This capstone will provide NASCO with a careful description of the trade frictions that occur as a product moves across national and state boundaries and a framework for dealing with regulations that impose undue burdens on the free flow of goods and services in North America.