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

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

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

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

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

Single walled carbon nanotubes decorated vanadyl phthalocyanine composite for electrochemical oxygen reduction in fuel cells

Vanadyl phthalocyanine (VOPc) has been immobilized on single walled carbon nanotubes by the adsorption process and characterized using UV-vis spectroscopy, infrared spectroscopy and X-ray diffraction techniques. Electrochemical characterization of VOPc immobilized SWCNTs (SWCNTs-VOPc) has been done by coating an aqueous colloid of SWCNTs-VOPc on glassy carbon electrode (represented as GC/SWCNTs-VOPc). GC/SWCNTs-VOPc exhibits a pair of peaks at –265 and –97 mV (at 20 mV s-1 in 0.1 M H2SO4) due to the characteristic redox process, VIV/III of VOPc. Further, electrocatalytic reduction of oxygen is analysed using GC/SWCNTs-VOPc electrode by cyclic voltammetry. GC/SWCNTs-VOPc electrode efficiently reduces oxygen in 0.1 M H2SO4 with a low onset potential of 0.16 V. Also, GC/SWCNTs-VOPc exhibits significant storage stability, retaining 91% of its original catalytic reduction current after 10 days storage at room temperature in air and dry conditions.

Assessment of quality of life of type-2 diabetes mellitus patients in tertiary care teaching hospital in North India

Background: Quality of life (QoL) is a standard indicating a person’s life in better condition as compared to a diseased person or patient. Diabetes itself is not a dangerous disease if managed properly, but it becomes life-threatening after a certain time period because of the patient’s poor interest in disease management and treatment adherence. Diabetes mellitus is an endocrine system disorder that invokes lack of insulin secretion in the bloodstream. The study was conducted to assess the QoL of type-2 diabetes mellitus patients with QoL instrument.Methods: Questionnaire based cross-sectional, prospective study was conducted at Teerthanker Mahaveer Hospital, Moradabad, for a duration of 6 months from January - June 2019, on 196 patients of type-2 diabetes mellitus.Results: On an average 56.5% people have accepted that due to the diabetic condition their working proficiency is decreased. 80.3% of patients have accepted that they were facing problems due to diabetic symptoms. Similarly, 84% of patients have accepted that the ongoing treatment was quite expensive than their expectations. Finally, the last section of the patient’s emotional/mental satisfaction showed that 49.7% of patients were very satisfied with their family support while 13.7% of patients were not satisfied.Conclusions: QOL instrument for Indian diabetes patient’s instrument helped to evaluate the patient’s physical strength, psychological strength of the patient during disease condition, the response provided from the family members and relatives, the economical status of the patient and its effects on their living

Pregnancy outcome in isolated oligohydramnios diagnosed in third trimester

Background: The aim of this study was to compare the outcomes of pregnancies complicated by isolated oligohydramnios with the low risk pregnancies with normal amniotic fluid volume.Methods: The present study is a retrospective cohort study of singleton pregnancies diagnosed with Isolated oligohydramnios (AFI≤5) in their third trimester (N=35). Pregnancy outcome was compared with a matched control group of low risk pregnancies with amniotic fluid volume >5 (N=30).Results: The overall incidence of Isolated oligohydramnios was 0.7-0.8%. In oligohydramnios group, significant association were found in null-parity (60% vs 23.33%, p-value<0.005), Fetal growth retardation (25.71% vs 0% p-value<0.02), preterm delivery (22.85% vs 3.33%, p-value 0.025), rate of Induction of labor (40% vs 10%) and cesarean rate for non-reassuring fetal heart rate (20% vs 3.33%, p-value<0.001). Likewise, the incidence of low birth weight was (54.28% vs 13.33%, p-value<0.001) and NICU admissions was (20% vs 0%, p-value<0.01), but there was no difference in Apgar score finding. NICU stay was of short duration and all babies discharged in stable condition, there were no stillbirth or early neonatal death in both groups.Conclusions: Isolated oligohydramnios has an adverse influence on pregnancy and neonatal outcome in the form of FGR, preterm delivery, increased rate of Induction and cesarean section. Despite the high incidence of low birth weight and NICU admissions, the overall early neonatal outcome was similar to the other low risk pregnancies