Development of cucurbocitrin based nutraceutical formulation: A potential adjuvant herbal therapy in the management of hypertension

Nearly half of the hypertensive patients fail to manage their blood pressure despite pharmacological interventions, which reflects the dire need for adjuvant anti-hypertensive therapies. Nutraceutical formulations are attractive in this regard owing to their efficacy, ease of availability, and moderate pricing. The current investigation involves the formulation of cucurbocitrin nutraceutical tablets by direct compression method and evaluated for its anti-hypertensive effect in the management of hypertension. Cucurbocitrin is a natural compound prepared from Citrullus lanatus seeds belonging to the family Cucurbitaceae. The powder blend was examined for pre-compression studies such as angle of repose, bulk density, tapped density, Carr’s index, Hausner's ratio, etc. Based on acute-oral toxicity results, two tablet formulations were prepared using a different dose of cucurbocitrin and evaluated for post-compression parameters such as friability, hardness, weight variation, disintegration time, and in vitro drug release studies. In vivo studies were also performed for both formulations using a 10% Glucose solution-induced hypertension model in albino rats to observe its anti-hypertensive activity. The study indicated that nutraceutical formulation was found to be effective in reducing hypertension in an animal model

PHAROH lncRNA regulates Myc translation in hepatocellular carcinoma via sequestering TIAR.

Hepatocellular carcinoma, the most common type of liver malignancy, is one of the most lethal forms of cancer. We identified a long non-coding RNA, Gm19705, that is over-expressed in hepatocellular carcinoma and mouse embryonic stem cells. We named this RNA Pluripotency and Hepatocyte Associated RNA Overexpressed in HCC, or PHAROH. Depletion of PHAROH impacts cell proliferation and migration, which can be rescued by ectopic expression of PHAROH. RNA-seq analysis of PHAROH knockouts revealed that a large number of genes with decreased expression contain a Myc motif in their promoter. MYC is decreased at the protein level, but not the mRNA level. RNA-antisense pulldown identified nucleolysin TIAR, a translational repressor, to bind to a 71-nt hairpin within PHAROH, sequestration of which increases MYC translation. In summary, our data suggest that PHAROH regulates MYC translation by sequestering TIAR and as such represents a potentially exciting diagnostic or therapeutic target in hepatocellular carcinoma

Implementing Decision Tree for Software Development Effort Estimation of Software Project

ABSTRACT: Effort estimation is one of the biggest problems faced by software industry. In software planning estimation of the effort is one of the most critical responsibilities. It is necessary to have good effort estimation in order to conduct well budget. The accuracy of the effort estimation of software projects is vital for the competitiveness of software companies. For the forecasting of software effort, it is important to select the correct software effort estimation techniques. Inaccurate effort estimation can be risky to an IT industry's economics and certainty due to poor quality or trait and stakeholder's disapproval with the software product. This paper presents M5P decision tree Technique, for effort evaluation in the field of software development

Possibility of the Existence of Donor–Acceptor Interactions in Bis(azole)amines: An Electronic Structure Analysis

Donor-stabilized divalent N­(I) systems have recently gained attention in the field of organic chemistry. Existence of low-valent nitrogen­(I) species with moderate nucleophilicities in several pharmacophoric functionalities is prompting extensive exploration in this field. Quantum chemical analysis on the imidazole, oxazole, and thiazole derivatives of thiazole-2-amine indicated that these species preferably exist in the iminic state. Electronic structure analysis of these systems suggested the existence of hidden divalent N­(I) character in a neutral state (L → N–R) and the explicit divalent N­(I) character (L → N ← L)⁺ in the protonated state. The strength of L → N interaction in these systems was analyzed, and the variations in the nucleophilicity trend at the coordinating nitrogen center were rationalized by estimating the electronic (TEP (Tolman electronic parameter) and MESP minimum (<i>V</i>_min)) as well as steric parameters (<i>r</i>-repulsiveness and Δ<i>H</i> elimination of CO group, in L → Ni­(CO)₃) of the coordinating ligands L. The importance of energetically preferred ionic and tautomeric representations of thiazol-2-amine derivatives in iminic and aminic forms was also demonstrated by carrying out comparative docking analysis with the enzyme lymphocyte-specific kinase (Lck)

Battle Against Coronavirus: Repurposing Old Friends (Food Borne Polyphenols) for New Enemy (COVID-19)

In the era of extreme scientific development where the scientific community have reached beyond moon, the entire world today is facing an immense problem due to deadly effect of COVID-19 (coronavirus disease), originated in Wuhan. Coronavirus is having dexterity to target immune compromised people very easily and swiftly get transmitted to healthy individuals from infected ones. Coronavirus infections are spreading very rapidly, and almost all the countries around the world are having corona positive people and asymptomatic carriers. This pandemic has created havoc both to human health and economy in lack of an effective treatment against this disease. Due to time limitations and urgency to find cure for COVID 19 we have undertaken the help of structure assisted drug design approach which mainly involves virtual screening program which identifies the structural leads which can target COVID-19 main protease (Mpro). This protease is the key enzyme of coronavirus which plays crucial role in virus replication and transcription, which can be targeted to retard the growth of virus inside the host. In the present work, the Phenol explorer database (version 3.6) containing 751 different food borne polyphenols were screened against the (Mpro) to identify suitable structural leads with potential to inhibit this protease though High throughput modelling and molecular docking approach. We identified six potential polyphenols belonging to Sanguiin, Theaflavin gallate, Theaflavin digallate, Kaempferol, Punicalagin and Protocatechuic acid chemical classes. All the six polyphenols have much higher docking scores ≥ -9.8 kcal/mol as compared to peptidomimetic inhibitor (N3) of COVID 19 virus Mpro. Pharmacokinetic and Drug likeness predictions of these polyphenols were done using SwissADME web tool where Protocatechuic acid shown fairly good results (1 Lipinski violation). The studies suggest the dietary intake of “black tea” can improve the resistance to fight against COVID 19 virus in early stages of human infection. Importantly though, the enriched subset of six compounds identified from the larger library has to be validated experimentally. </p