29 research outputs found

    Phytochemical fractions from Annona muricata seeds and fruit pulp inhibited the growth of breast cancer cells through cell cycle arrest at G(0)/G(1) phase

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    Introduction: Annona muricata (L.) (AM), commonly known as Soursop and Lakshmanaphala/Hanumaphala in India, has been extensively used in ethnomedicine for treating tuberculosis, urinary tract infections (UTIs) and cancers. The fruit is a rich source of antioxidants and antitumor agents. Methods: In this study, we have extracted phytochemicals that exhibited anti-cancer property from the (a) fruit pulp using methanol (AMPM) and water (AMPW); and (b) seeds using methanol (AMSM). Qualitative phytochemical analysis showed the presence of phenolics, tannins, alkaloids, flavonoids, sterols, terpenoids, carbohydrates and proteins in AMPM and AMPW. All three extracts were first checked for in vitro antioxidant and anti-inflammatory properties and then tested for efficacy against MCF-7 and MDA-MB-231. Results: Among these three extracts, AMSM showed the highest antioxidant power as well as similar to 80% inhibition at 320 mu g/ml concentration in both cell lines upon treatment for 24h. However, only about 40% inhibition was observed with 320 mu g/ml AMPM treatment, despite its highest anti-inflammatory potential. Water extract AMPW exhibited about 80% growth inhibition at 50% dilution. Since fruit pulp is the one consumed, the extracts AMPM and AMPW were further tested for apoptosis induction and cell cycle arrest. Analysis of the data showed increased apoptosis and G0/G1 cell cycle arrest upon exposure to AMPM and AMPW

    Presence of Salmonella pathogenicity island 2 genes in seafood-associated Salmonella serovars and the role of the sseC gene in survival of Salmonella enterica serovar Weltevreden in epithelial cells

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    The type III secretion system encoded by theSalmonellapathogenicity island 2 (SPI-2) has a central role in the pathogenesis of systemic infections bySalmonella. Sixteen genes (ssaU,ssaB,ssaR,ssaQ,ssaO,ssaS,ssaP,ssaT,sscB,sseF,sseG,sseE,sseD,sseC,ssaDandsscA) of SPI-2 were targeted for PCR amplification in 57 seafood-associated serovars ofSalmonella. ThesseCgene of SPI-2 was found to be absent in two isolates ofSalmonella entericaserovar Weltevreden, SW13 and SW39. Absence ofsseCwas confirmed by sequencing using flanking primers. SW13 had only 66 bp sequence of thesseCgene and SW39 had 58 bp sequence of this gene. A clinical isolate,S. Weltevreden – SW3, 10 : r : z6 – was used to construct a deletion mutant for thesseCgene. Significant reduction in the survival of SW3, 10 : r : z6 ΔsseCand natural mutants SW13 and SW39 in HeLa cells suggests thatsseChas a crucial role in the intracellular survival ofS. Weltevreden. Expression ofsseCwas upregulated during the intracellular phase of bothS. entericaserovar Typhimurium and clinical isolateS. Weltevreden SW3, 10 : r : z6, suggesting a crucial role for this gene in the survival ofS. Weltevreden inside host cells.</jats:p

    In silico examination of peptides containing selenium and ebselen Backbone To Assess Their Tumoricidal Potential

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    Introduction: Cancer has been one of the highest causes of morbidity and mortality in the world for decades. Owing to improved therapeutics along with detection, breast cancer mortality has been slowly reducing. The incidence of breast cancer, on the other hand, has increased gradually. More than 100 types of cancer have been identified with a wide range of treatment protocols comprising of chemotherapy, radiation therapy, hormone therapy, etc. In an attempt to curb the serious deleterious effects caused by the chemotherapeutic drugs, numerous peptide molecules are currently popular as alternatives to the standard chemotherapeutic drugs. Methods: In this study, we have carried out in silico investigations to ascertain the anti-proliferative potential of novel peptides based on selenium and ebselen, i.e. Eb-Trp-Asp, 13, Eb-Trp-Glu, 14, and Eb-Trp-Lys, 15. Analysis of protein-ligand interactions, resulting in protein-ligand complex formation, has been carried out using the AutoDockVina in PyRx aided molecular docking technique, which may be an essential indication of druggability of the test peptides. Results: The molecular docking results revealed that the screened ligands had extraordinarily strong binding interactions and affinity for the target. Conclusion: Findings suggested that novel peptide molecule Eb-Trp-Glu, 14 may be a potent anticancer agent

    3-Dimensional model making as an innovative tool for enhanced learning through student engagement among early professional medical graduates

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    Background: Various innovative teaching-learning methods have been introduced in the medical curriculum for a better understanding of the difficult topics. We introduced the 3-dimensional (3D) model-making as an innovative tool for enhanced learning through student engagement among early professional medical graduates. Methods: The study was conducted in the Department of Biochemistry of a Private Medical College. The phase I medical undergraduate students were divided into 20 groups with 10 students in each group. The topics taught by didactic lectures were allotted to each group by lottery method and were informed that the best model will be suitably rewarded after evaluation. Feedback was collected from the students on a five-point Likert scale after the submission and evaluation of the models. Results: About 92% of the students expressed that 3D model-making was an innovative method of learning in the medical profession, and 96.3% agreed that the topics allotted were relevant to the syllabus and helped in better understanding of the subject when compared to didactic lectures. The students also agreed that the 3D model-making activity enhanced their creativity and application of knowledge to learn biochemistry, developed a positive attitude, helped to coordinate with their peers, and improved communication skills. They suggested that this activity should be continued with the inclusion of more topics. Discussion: The 3D model-making activity helped the students to enjoy learning, think differently, understand better, expand their knowledge and recall information more comprehensively

    Epitope identification of rabies virus nucleoprotein using immunoinformatics approach

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    Abstract Background Rabies is a deadly and preventable disease. The nucleoprotein of rabies virus has been found to have group-specific antigenic determinants. The rabies virus nucleoprotein can shield dogs and mice from the lethal infection. Early diagnosis of rabies is crucial for the prevention of rabies. Methods In this study, B-cell epitopes of the nucleoprotein gene of the rabies virus were identified, and the characteristics of the epitopes were analyzed using various bioinformatics tools, such as the immune epitope database\u27s Bepipred Major Histocompatibility Complex II (IEDB MHC II) prediction tool, NetCTL 1.2, Vaxijen v20, AllerTOP v2.0 server. Results Fourteen epitopes were predicted in the nucleoprotein sequence of the rabies virus. We observed that B-cell epitopes have a high affinity for binding to major histocompatibility complex (MHC) II. Notably, the selected strain\u27s conserved region yielded a total of thirty weak binders and eight strong binders, all exhibiting a binding affinity with allele H-2-IAb. The study also ventured into antigenicity, allergenicity, and toxicity predictions. Three of the ten peptides were identified as potential allergens, while the remaining seven were classified as non-allergens. Interestingly, none of the peptides were found to be toxic. Conclusion B cells are a critical component of adaptive immunity, producing neutralizing antibodies, and are crucial in blocking viral entry and attachment. Henceforth, epitopes identified in this study can be utilized to produce monoclonal antibodies or vaccines for therapeutic purposes. The discovered epitope is a functional potential repertoire for developing serodiagnostic tests and epitope-based peptide vaccines

    Gaining molecular insights towards inhibition of foodborne fungi Aspergillus fumigatus by a food colourant violacein via computational approach

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    Abstract Filamentous Fungal Human Pathogens (FFHPs) such as Aspergillus fumigatus, are growing resistant to currently available antifungal drugs. One possible target, the Nucleoside diphosphate kinase (Ndk) is significant for nucleotide biosynthesis and crucial for fungal metabolism. Violacein, a natural food colorant, was examined for its antifungal effects against Aspergillus fumigatus via computational approach against the Ndk protein. Known and predicted interactions of Ndk with proteins was performed using the STRING application. Molecular docking was performed using Schrodinger Maestro software (V.14.1) under enhanced precision docking, with OPLS4 forcefield. MDS was performed for 500ns under OPLS4 forcefield and the TIP3P solvent system. The geometry optimization for DFT was performed using the Becke 3-parameter exchange functional (B3LYP) method. The Molecular Docking Studies revealed significant interactions with good binding energy between Violacein and Ndk. Subsequent MD Simulations confirmed the stability of Violacein-Ndk complex, compared to the reference ligand-complex, indicating a stable interaction between the protein and violacein. The energy band gap of violacein was found to be 0.072567 eV suggesting its softness with lower kinetic stability and higher chemical reactivity. The results suggest Violacein could potentially disrupt nucleotide metabolism by targeting Ndk, thus demonstrating antifungal activity. However, further experimental validation is required to confirm these computational findings and explore the practical use of Violacein in antifungal treatments

    Evaluation of a diagnostic model for aflatoxicosis in sheep: A prerequisite for future adoption of national surveillances

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    The aim of this research is to evaluate a diagnostic model for uncovering an aflatoxicosis outbreak in sheep. The diagnostic model is based on differentiation between an aflatoxicosis suspected herd (ASH) and a control herd (CH) including, clinical findings, feed analysis for aflatoxin and othernutrients, hemato-chemical and biochemical profiles, histopathologic changes, and residual aflatoxin levels in their organs. There was a significant difference between the sheep of the ASH and CH in relation to mortality percent, symptoms, aflatoxin B1 level in their feed and tissues, hematological and biochemical parameters, liver and kidney enzymes and metabolites, serum electrolytes, and vitamins A and E. The relationship of the histopathological lesions of affectedtissues to the aflatoxin B1 is discussed. This diagnostic model resulted in significant differences among many assigned parameters in ASH compared to the CH, allowing for its future adoption in national surveillances of aflatoxicosis in sheep.Alexander J., 2004, EFSA J, V34, P1; Alpsoy L, 2011, VITAM HORM, V86, P287, DOI 10.1016-B978-0-12-386960-9.00012-5; Alwakeel Suaad S, 2009, Pak J Biol Sci, V12, P637, DOI 10.3923-pjbs.2009.637.642; [Anonymous], 2007, 15550 DIN EN; [Anonymous], 2011, SPECULUM, V86, P1; AOAC, 1995, OFF METH AN; Bancroft JD, 1996, THEORIES PRACTICE HI; Cork SC, 2002, VETERINARY LAB FIELD; Dersjant-Li YM, 2003, NUTR RES REV, V16, P223, DOI 10.1079-NRR200368; Devegowda G., 2005, The mycotoxin blue book, P25; Drupt F, 1974, PHARM BIO, V9, P777; Feldman F, 2000, SCHALMS VETERINARY H; Gagini TB, 2010, BRAZ J MICROBIOL, V41, P345, DOI 10.1590-S1517-838220100002000013; HENDRICKSE R G, 1991, Annals Academy of Medicine Singapore, V20, P84; Iowa State University, 2009, AFL CORN; ITO Y, 1989, MUTAT RES, V222, P253, DOI 10.1016-0165-1218(89)90141-9; Kaaya AN, 2006, J APPL SCI, V52, P2401; KIND PRN, 1954, J CLIN PATHOL, V7, P322, DOI 10.1136-jcp.7.4.322; Mohamed A. M., 2009, Journal of Pharmacology and Toxicology, V4, P1, DOI 10.3923-jpt.2009.1.16; Orsi RB, 2007, CHEM-BIOL INTERACT, V170, P201, DOI 10.1016-j.cbi.2007.08.002; Ossati P., 1980, CLIN CHEM, V26, P227; Vinayak Patel, 2006, Pakistan Journal of Biological Sciences, V9, P1104; Peraica M, 1999, B WORLD HEALTH ORGAN, V77, P754; PETERS T, 1968, CLIN CHEM, V14, P1147; Probakaran JJ, 2009, ASIAN J BIOTECHNOL, V1, P104; RAISUDDIN S, 1993, MYCOPATHOLOGIA, V124, P189, DOI 10.1007-BF01103737; REITMAN S, 1957, AM J CLIN PATHOL, V28, P56; Riley RT, 1996, HUMAN ANIMAL RELATIO, P193; Saini SS, 2012, GLOBAL ADV RES J CHE, V1, P63; SEELIG H P, 1969, Aerztliche Laboratorium, V15, P34; Thoolen B, 2010, TOXICOL PATHOL, V38, p5S, DOI 10.1177-0192623310386499; TUNG HT, 1975, POULTRY SCI, V54, P1962; Yiannikouris A., 2002, INRA Productions Animales, V15, P3; Yousef MI, 2003, J ENVIRON SCI HEAL B, V38, P193, DOI 10.1081-PFC-1200184490

    Groundwater flow inverse modeling in non-MultiGaussian media: Performance assessment of the normal-score Ensemble Kalman Filter

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    [EN] The normal-score ensemble Kalman filter (NS-EnKF) is tested on a synthetic aquifer characterized by the presence of channels with a bimodal distribution of its hydraulic conductivities. This is a clear example of an aquifer that cannot be characterized by a multiGaussian distribution. Fourteen scenarios are analyzed which differ among them in one or various of the following aspects: the prior random function model, the boundary conditions of the flow problem, the number of piezometers used in the assimilation process, or the use of covariance localization in the implementation of the Kalman filter. The performance of the NS-EnKF is evaluated through the ensemble mean and variance maps, the connectivity patterns of the individual conductivity realizations and the degree of reproduction of the piezometric heads. The results show that (i) the localized NS-EnKF can characterize the non-multiGaussian underlying hydraulic distribution even when an erroneous prior random function model is used, (ii) localization plays an important role to prevent filter inbreeding and results in a better logconductivity characterization, and (iii) the NS-EnKF works equally well under very different flow configurations. © Author(s) 2012.The authors gratefully acknowledge the financial support by the Spanish Ministry of Science and Innovation through project CGL2011-23295. The two anonymous reviewers are gratefully acknowledged for their comments which helped improving the final version of the manuscript.Li, L.; Zhou, H.; Hendricks-Franssen, HJ.; Gómez-Hernández, JJ. (2012). Groundwater flow inverse modeling in non-MultiGaussian media: Performance assessment of the normal-score Ensemble Kalman Filter. 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