IDENTIFICATION OF POTENTIAL INHIBITORS FOR LOWERING CHOLESTEROL LEVEL BY INHIBITING PCSK9

ABSTRACTObjective: PCSK9 has medical significance in lowering cholesterol levels. Inhibitors target and inactivate PCSK9 in the liver. Knocking out PCSK9 (proprotein convertase subtilisin kexin 9) reduces the amount of harmful LDL cholesterol circulating in the bloodstream. There are two known inhibitors for treating the cardiovascular disease Arilocumab†and Evalocumabâ€. However there are many side-effects. The current study is to identify natural and synthetic inhibitor using the pharmacophoric feature of the known inhibitor and validating the short listed candidates using Molecular dynamics and ADMET properties.Methods: Known inhibitors for the PCSK9 Protein were taken from the BINDING DATABASE. Molecular docking was performed for the known inhibitors with the PCSK9 protein. After docking the best inhibitor was selected and the docking result was then imported to find the pharmacophoric features.Results: The pharmacophore model was generated with 3 features containing  1 hydrogen bond acceptor(A),1 Hydrogen bond donor(B) and 1 Aromatic ring. The constructed e-pharmacophore model was screened with more than 20000 natural compounds. 5 compounds were short listed. Among them ZINC85625485 has  glide  score  of  -13.03  kcal/mol  with  glide  energy  was  -57.62 kcal/mol and ZINC85625406 has glide score of -8.1kcal/mol with glide energy was -39.33kcal/mol were taken as the best Hits.Conclusion: PCSK9 is known to be a therapeutic agent as it controls the plasma LDL cholesterol levels by posttranslational regulation of the LDL receptor. Therefore, up-regulation of PCSk9 can lead to elevated cholesterol level in such case inhibition of PCSK9 will be a effective remedy. In this study already known inhibitors were taken and pharmacophore feature was generated. Zinc database was screened to find out novel compounds with similar pharmacophore features that can act as potentially active compound against PCSK9. ZINC85625485 and ZINC85625406 were short listed as lead compounds with Molecular dynamics simulation and checking the ADMET properties. Keywords: PCSK9, Docking, ADMET, Molecular Dynamics.                                                            Â

ANN and RSM based Modeling of Moringa Stenopetala Seed Oil Extraction: Process Optimization and Oil Characterization

Moringa Stenopetala is a plant species that is endemic to the southern region of Ethiopia. It is primarily cultivated for its nutritional value and is considered an important food source. The present research aimed to analyse the physicochemical properties of Moringa Stenopetala seed oil (MSO) obtained through solvent extraction method utilising hexane as the solvent. The collection of seeds was conducted in Adama, which is situated in the East Shawa zone of Oromia, Ethiopia. Prior to the extraction procedure, the seeds' average moisture content, crude ash, fibre, protein, and oil content were analysed and found to be 6.27%, 7.8%, 2.7%, 26.5%, and 43.2%, respectively. Using the Response Surface Method (RSM) and Artificial Neural Network (ANN), the extraction process was modeled. The study utilised numerical solutions to determine the optimal process parameters for maximising oil yield during extraction. The results indicated that a particle size of 0.85mm, a temperature of 85°C, and an extraction time of 4.75 hours were the most effective parameters. Furthermore, an investigation was conducted on the physical and chemical properties of the oil obtained under optimised conditions

Efficient revocation and Data Retrieval in Cloud Storage using CP-ABE

As cloud computing ends up common, more encrypted data are being incorporated into the cloud. For the insurance of data protection, encrypted data more often than not need to be scrambled before redistributing, which makes powerful data usage an extremely difficult assignment. In this paper, we propose another technique to empower successful fuzzy keyword seek in a multi-client framework over encoded cloud data while keeping up catchphrase security. In this new framework, differential looking benefits are bolstered, which is accomplished with the strategy of characteristic based encryption. Data proprietors are inspired to store their profitable data in the cloud, now the issue emerges how to ensure significant data against assaults and dangers. In this paper we are presenting secure Attribute Based Encryption for ensuring profitable data and further quicker looking and getting to of encoded data dependent on programmed comment based seeking method

Community Seed system: Production and supply of sweet sorghum seeds

Under the NAIP project activities, it was aimed to develop a community seed system (community seed program) for multiplication of farmer selected sweet sorghum cultivars seeds to enhance their availability and benefit the project farmers. As there are not many seed companies producing seed of sweet sorghum, a community seed program was developed to address sustainability issue of regular seed supply to farmer selected varieties after completion of the project. Hence, a community-based seed system model was developed and implemented in the project area

Synthesis, Spectral Characterization and Antimicrobial Studies of Co(II) Complexes with Tetradentate Schiff bases Derived from Ortho-Phthalaldehyde

A series of cobalt (II) complexes have been synthesized with Schiff bases derived from ortho-phthalaldehyde and various amines in aqueous methanol solution. The newly synthesized Schiff bases and their Co (II) complexes have been characterized  by elemental analysis, magnetic susceptibility, thermal, conductance measurements, mass, IR, electronic, 1H,13C-NMR spectral techniques. These ligands act as tetradentate species and coordinate to the metal center through the different potential donor atoms such as N, O and S. The probable octahedral structures have been assigned to these complexes. All the synthesized Schiff base ligands and Co(II) metal complexes have also been screened for their antimicrobial activities and metal complexes found to be more active than respective Schiff-base ligands

Kloniranje, ekspresija i karakterizacija paraflagelarnog gena Rod 2 bičaša Trypanosoma evansi

Paraflagellar rod is the major structural component of the trypanosomatid flagellum and is identified as a complex lattice of filaments which runs parallel to the axoneme throughout most of the flagellar length. The present study was carried out to investigate the existence of the paraflagellar rod (PFR 2) gene in Trypanosoma evansi infecting Indian cattle. Local isolates of T. evansi collected from naturally infected cow were multiplied in Wistar rats. Complementary DNA (cDNA) was synthesized from the RNA of host cell free T. evansi parasites by reverse transcription. The gel purified PCR product (PFR 2 gene of T. evansi) was cloned into the pTZ57R/T vector system. The nucleotide sequence of the PFR 2 gene of the T. evansi S.V.V.U. isolate (Accession No. KT277497) obtained in the present study revealed 100% homology with T. evansi China isolate and 99% homology with T. evansi Izatnagar and Bikaner isolates. The recombinant protein was sub-cloned into pET 32a and expressed in the BL21 (DE3) pLysS expression system. The PFR 2 gene of T. evansi S.V.V.U. isolate was further characterized by determination of its protein profile with SDS-PAGE and western blotting. Indirect ELISA was optimized for detection of the specific antibody titre against the recombinant protein of the PFR 2 gene of T. evansi. In the kinetoplastid species the PFR 2 gene is highly conserved. Therefore the PFR 2 gene was suggested as a vaccine candidate, as well as a diagnostic antigen.Paraflagelarni štapić glavna je strukturna komponenta tripanosomskog biča i dio je kompleksa filamenaza koji teku paralelno s aksonemom duž biča. Istraživanje je provedeno kako bi se ispitalo postojanje paraflagelarnog gena Rod 2 (PFR2) u bičaša Trypanosoma evansi koji invadira goveda u Indiji. Lokalni izolat T. evansi prikupljen od prirodno invadiranih krava umnožen je u Wistar štakora. Komplementarna DNA (cDNA) sintetizirana je iz RNA obrnutom transkripcijom iz stanica neinvadiranih nositelja T. evansi parazita. Pročišćeni PCR produkt (gen PFR2 bičaša T. evansi) kloniran je u vektorski sustav pTZ57R/T. Nukleotidna sekvencija gena PFR2 bičaša T. evansi, izolat S.V.V.U. (pristupni broj KT277497) dobivena u ovom istraživanju pokazala je 100 %-tnu sličnost s izolatom T. evansi China i 99 %-tnu s izolatom T. evansi Izatnagar i Bikaner. Rekombinantni protein ponovno je kloniran u sustavu pET 32a i prikazan u sustavu BL21 (DE3) pLysS. Gen PFR2 bičaša T. evansi, izolat S.V.V.U. dalje je karakteriziran određivanjem proteinskog profila metodama SDS-PAGE i Western blotting. Indirektni test ELISA optimiziran je za dokaz titra specifičnih protutijela za rekombinantni protein gena PFR2 bičaša T. evansi. U kinetoplastida gen PFR2 izrazito je očuvan. Stoga bi se gen PFR2 mogao upotrijebiti za cjepivo te kao dijagnostički antigen