QSAR studies on Withanolide analogs for anticancer activity

Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian systems of medicine. Withanolides are basically steroidal lactones (highly oxygenated C-28 phytochemicals) and similar to ginsenosides activity. Some of the withanolides that have been reported possess immunomodulatory, and anticancer activities. In the present investigation, a quantitative structure activity relationship (QSAR) model based on forward stepwise multiple linear regression (MLR) has been developed against the MCF7, MCF7/BUS, and SK-Br-3 human solid tumor breast cancer cell lines. Relationship correlation coefficient (r2) and cross validation correlation coefficient (r2CV) of QSAR model were 0.77 and 0.73 for MCF7, 0.91 and 0.85 for MCF7/BUS, 0.93 and 0.90 for SK-Br-3 respectively. Developed QSAR model was also evaluated for prediction accuracy through internal, external and randomization validation methods. The QSAR study indicates that chemical descriptors viz., atom count (all atoms), connectivity index (order 2, standard), for MCF7, Connectivity Index (order 0, standard), Dipole Vector X (debye), Molar Refractivity, Shape Index (basic kappa, order 2) for SK-Br-3 and Atom Count (all atoms), Dielectric Energy (kcal/mole), Total Energy (Hartree), Heat of Formation (kcal/mole) for MCF7/BUS are correlate well with the breast cancer activity, Moreover, on the basis of screening for oral bioavailability, in silico ADME and toxicity risk assessment, we concluded that compounds W3, W4, W8 have markedly higher anticancer activity compared to control. These results can offer useful references for directing the molecular design of lead compound(s) based on withanolide or analogous template with improved activity

Detection of substrate binding motifs for morphine biosynthetic pathway intermediates in novel wound inducible (R,S)-reticuline 7-O-methyltransferase of Papaver somniferum

The benzylisoquinoline alkaloids (BIA) comprise a large and diverse group of nitrogen-containing secondary metabolites with about 2500 compounds identified in plants. BIA biosynthesis begins with the condensation of the tyrosine derived precursors dopamine and p-hydroxyphenylacetaldehyde to (S)-norcoclaurine. Subsequent regiospecific O- and N-methylations and aromatic ring hydroxylation lead to (S)-reticuline, which is the central intermediate for almost all BIAs. For morphinan alkaloid biosynthesis, (S)-reticuline undergoes an inversion of stereochemistry to (R)-reticuline, followed by C-C phenol coupling catalyzed by a unique cytochrome P450-dependent monooxygenase to yield salutaridine. The cDNA sequence of enzymes leading to (S)-reticuline, as well as those involved in the conversion of (R)-reticuline to salutaridine-7-O-acetate are already characterized. The inversion of (S)-reticuline to (R)-reticuline represent the important steps in morphine biosynthesis. Wound induced transcript accumulation in Papaver reveals a novel wound inducible EST (NCBI DbEST: GO238757) showing homology with (R,S)-reticuline 7-O-methyltransferase (ID: Q6WUC2) isolated from Papaver somniferum. We compare the substrate binding homology of this novel wound inducible (R,S)-reticuline 7-O-methyltransferase (7-OMT) using template of P. somniferum (Q6WUC2; gb|AAQ01668) as experimental control. Homology modeling with 70% identity & 85% similarity with catalytic site of template protein i.e., (Q6WUC2) short chain dehydrogenase/reductase (SDR), showed docking energy -69.9 and -75.8 kcal/mol with (S)-Reticuline (CID:439653) and (R)-Reticuline (CID:440586) respectively, which are comparable with experimental control binding site interaction energies. Docking of S- & R-reticuline into the active site revealed eight (F(5), E(18), W(24), C(47), F(44), P(45), C(46) and I(47) amino acids presumably responsible for the high substrate specificity of (R,S)-reticuline 7-O-methyltransferase

A STUDY ON CORPORATE SOCIAL RESPONSIBILITY (CSR) IN INDIA - ISSUES AND CHALLENGES

CSR as an important topic of public policy has taken a crucial position in the Indian corporate landscape, as it has established a sustainable connection with society at large alongside the rising socio-regulatory pressures. The concept of social responsibility posits that an organization or individual has a duty to act in ways that benefit society as a whole. Social responsibility encompasses the obligation of every individual or organization to carry out actions that ensure a balance between economic growth and ecological sustainability. The initial mention of the term corporate social responsibility appeared in the document ‘Social Responsibilities of Business’ penned by William Bowen in 1953. In India, there has been a continual close business engagement with social issues for the purpose of national development, referred to as social duty or charitable contributions, philanthropy, and community service, now specifically labeled as CSR. foundation. The primary aim of this research is to examine the attitudes towards Corporate Social Responsibility (CSR) among the upcoming business leaders of India. In India, companies such as Tata and Nestle have been engaging in Corporate Social Responsibility (CSR) for decades, well before CSR became a well-known concept. Despite having such prominent examples, Corporate Social Responsibility (CSR) in India is currently in a very nascent stage. Numerous large corporations are conducting these Corporate Social Responsibility (CSR) initiatives superficially and showcasing these efforts in the media. This research paper revolves around finding and reviewing the issues and challenges faced by Corporate Social Responsibility (CSR) practices in India

QSAR and Docking Studies of Gallic Acid Derivatives for Anticancer and Immunomodulatory Activity

Immuno-modulation is the process of alteration in immune response due to foreign intrusion of molecules inside the body. In the present communication QSAR and molecular docking studies for immuno-modulatory activity of derivatives of gallic acid were performed. Molecular docking studies showed higher binding affinity with INFα-2, IL-6, and IL-4 receptors. Binding site residues indicate hydrogen bonds formation with gallic acid derivative compounds G-3, G-4, G-5, G-6, G-7 and G-10. Further screening through quantitative structure activity relationship model establishes the immuno-modulatory activity of the compounds G-4, G-7, G-9, G-10, G-12 and G-13. Activity was predicted through a robust statistical model, developed by forward feed multiple linear regression method with leave-one-out approach. Relationship correlating measure (r2) and prediction accuracy (rCV2) of QSAR model were 0.99 and 0.96, respectively. QSAR studies indicate that dipole moment, steric energy, amide group count, λ max (UV-visible) and molar refractivity correlate well with their activities, while decrease in dipole moment, steric energy and molar refractivity have negative correlation. Moreover, on the basis of bioavailability, in-silico ADME and toxicity risk assessment screening, we concluded that compounds G-4, G-7, G-9, G-10, G-12 and G-13 have marked immuno-modulatory activity comparable to standard drugs

A Comprehensive Review of Anatomical Variations and their Clinical Significance in Surgical Procedures

Anatomical variations represent deviations from the standard anatomical structures of the human body, encompassing differences in organs, tissues, and neurovascular pathways. Although often asymptomatic, these variations can significantly impact surgical procedures by increasing the risk of complications if unrecognized. A thorough understanding of these anatomical differences is critical for healthcare professionals, particularly surgeons and radiologists, to enhance procedural accuracy, reduce intraoperative errors, and improve patient outcomes. This study provides a comprehensive review of the clinical significance of anatomical variations and their implications across various surgical disciplines. This study aims to analyze the clinical relevance of anatomical variations, assess common surgical challenges they pose, and emphasize the importance of incorporating anatomical variation education into surgical training. A retrospective literature review methodology will be employed, utilizing peer-reviewed articles, case reports, and imaging studies. Ultimately, this research underscores the need for increased vigilance and education regarding anatomical diversity to ensure safer and more effective surgical practices

Navigating family planning: unveiling rural-urban disparities among women in India: insights from Indian demographic health survey-5

Background: Over the past few years, there has been an increase in the usage of family planning methods. Female sterilization remains the most commonly used method of contraception. However, there are still disparities in the use of family planning methods between urban and rural areas in India, which can be attributed to differences in education levels, cultural factors, and socio-economic factors. The study aimed to evaluate contraceptive prevalence and urban-rural disparities among married women in India. Methods: The study was based on the data collected under the National family health survey 2019-21. The NFHS-5 covered 5,12,408 currently married women (women in the age group 15-49). Descriptive and analytical analyses were used. The chi-square test and Bivariate logistic regression model were used to find the association between background characteristics and contraception use. Results: The study showed that 65.7% of the participants were using contraception, with female contraception being the most common method of contraception. The use of contraception in urban and rural settings was 67.9% and 65% respectively. Conclusions: The use of contraception has increased, with woman’s age, religion, caste, educational level, wealth index, place of residence and other factors such as total children living, total children ever born, exposure to mass media, son preference and ideal number of children being significant determinants

Comparative evaluation of antigen detection ELISA and reverse transcriptase PCR in acute stage of Japanese encephalitis prevalent in endemic areas of North-Eastern part of Uttar Pradesh, India

Background: Objective of current study was to compare and evaluate different diagnostic tests to establish a reliable and less time consuming diagnostic test for prompt diagnosis of acute Japanese encephalitis cases mainly amongst children and young adults from North-Eastern part of Uttar Pradesh.  Methods: A total of 100 subjects, including 50 suspected cases and 50 diseased controls were investigated to establish the diagnosis of JE in acute encephalitis patients. All CSF samples were subjected to MAC-ELISA, virus cultivation and RT-PCR.Results: Out of 50 cases, 6 showed negative results by all the three tests. 50% (22 out of 44), 47.5% (21 out of 44), and 66% (23 out of 44) were found positive by MAC-ELISA, Virus cultivation and RT-PCR respectively. The rate of detection by Virus cultivation and RT-PCR was higher in case of MAC-ELISA negative cases (57.1% and 78.5%) than that of MAC-ELISA positive cases (22.7% and 27.2%) respectively. Mean age of the patients was 12.5 years, which ranged from 1-24 years with male to female ratio of 3:1.Conclusions: The RT-PCR was found most reliable, sensitive and specific method amongst the three chosen methods for detection of JEV in suspected encephalitis patients

Three magical words of mathematics

In teaching the preparation of a lecture plan is very important in the sense that in which order the chapter (or subject) must be planned and taught, so that the students can easily grasp the subject matter as well as the curriculum can be completed within fixed time period to get the optimum outcome. Generally a mathematics teacher follows three magical words in teaching from primary school to colleges and universities for primary to graduate and postgraduate level students as well as for research scholars for doctoral and post doctoral works. These three magical words are: assumptions, properties and applications. Assumptions give the base for the development of the chapter (subject), the properties provide the base for their applications and the applications show the importance of the chapter (subject). These three words are the foundations of all subjects of arts, commerce, science, management, engineering, etc. and rule the complete education, the human civilizations, and the universe

Research on Various Display Properties of a Room-Temperature Twisted Nematic Display Material 6CHBT by Doping Single-Walled Carbon Nanotubes

Present studies concentrate on the optical, dielectric, and electro-optical properties of single-walled carbon nanotubes (SWCNTs) doped in the nematic matrix of the liquid crystalline material 4-(trans-4¢-n-hexylcyclohexyl)isothiocyanatobenzene (6CHBT). 6CHBT is the nematic liquid crystalline substance that was employed in the investigation. SWCNTs having a diameter of around 0.8-1.4 nm and a length of about 100-300 nm have been inserted into it. For displays, the nematic liquid crystalline material 6CHBT is a perfect basis material due to its nematic phase temperature range of 12.5 - 43.0 °C. SWCNTs have been doped in 6CHBT in two different concentrations i.e., 0.01 and 0.02% (weight ratio). For higher concentrations, CNTs were observed to be bundled at different locations. For this reason, higher concentrations were not studied.  Using electro-optical and dielectric spectroscopy, the effects of SWCNTs doping on a number of display characteristics, including threshold voltage, dielectric anisotropy, and splay elastic constant, have been investigated. SWCNTs alignment parallel to the nematic direction is supported by the nematic phase. Nevertheless, in the nematic phase, the SWCNTs improve the molecules\u27 local orientational arrangement. Consequently, the use of SWCNTs considerably reduces the threshold voltage required to change the geometry of the molecules from planar (bright state) to homeotropic (dark state)

10 years after the birth of India’s first cloned farm animal, where is buffalo cloning heading

191-192India owns the best buffalo breeds, particularly Murrah which is famous all over the world for high milk production. India’s white and pink revolution cannot be imagined without the contribution of buffalo and to achieve these, the best productive animals need to be produced through scientific interventions. Animal cloning is a technique used to produce multiple copies of the best animals without normal reproduction. In India, buffalo cloning has already happened and India’s first cloned buffalo was produced in 2009. Later, several buffalo clones were produced and attempts are ongoing to produce stock of more elite animals. Buffalo cloning has made its way from scientific curiosity to farmer’s farm. In this viewpoint article, we provide an overview of the progress of buffalo cloning and we discuss some of the public perceptions of animal cloning such as aging and food safety of cloned animal products