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

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

A study of feto-maternal outcome in case of premature rupture of membrane at a tertiary care center

Background: Premature rupture of membranes is the rupture of the fetal membranes in the absence of uterine contraction or before the onset of labor. When this occurs before 37 weeks of gestation, it is termed as preterm premature rupture of membranes. Management depends upon gestational age and the presence of complicating factors. An accurate assessment of gestational age and knowledge of the maternal, fetal and neonatal risks are essential to appropriate evaluation, counselling, and care of patients with PROM. The purpose of the study is timely diagnosis and appropriate management of the cases of PROM and PPROM to improve maternal and neonatal outcomes. Methods: A Prospective study was performed at the department of obstetrics and gynecology, at a tertiary care center from August 2020 to December 2021. A clinical data sheet was made for recording all information about the pregnant women after taking their consent. And their maternal and neonatal outcomes were recorded. Results: a total of 150 cases of PROM and PPROM were taken during our study out of which 53.33% belong to the younger age group, 43.33% were primi gravida, 66.66% belonged to the lower socioeconomic class, 25.33% had a previous history of abortion followed by dilatation and evacuation, rate of cesarean delivery was 34.66% and rate of NICU admission of neonates was 15.78% and 57.87% babies had low birth weight and rate of stillbirth was 1.97%. whereas 34.66% of cases had various complications related to PROM. Conclusions: Individualized management of PROM cases depending on the gestational age and risk of complications and antibiotic coverage is the best way to achieve a good fetomaternal outcome

Modulation of Cytochrome P450 Metabolism and Transport across Intestinal Epithelial Barrier by Ginger Biophenolics

Natural and complementary therapies in conjunction with mainstream cancer care are steadily gaining popularity. Ginger extract (GE) confers significant health-promoting benefits owing to complex additive and/or synergistic interactions between its bioactive constituents. Recently, we showed that preservation of natural ‘‘milieu’’ confers superior anticancer activity on GE over its constituent phytochemicals, 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S), through enterohepatic recirculation. Here we further evaluate and compare the effects of GE and its major bioactive constituents on cytochrome P450 (CYP) enzyme activity in human liver microsomes by monitoring metabolites of CYPspecific substrates using LC/MS/MS detection methods. Our data demonstrate that individual gingerols are potent inhibitors of CYP isozymes, whereas GE exhibits a much higher half-maximal inhibition value, indicating no possible herb-drug interactions. However, GE’s inhibition of CYP1A2 and CYP2C8 reflects additive interactions among the constituents. In addition, studies performed to evaluate transporter-mediated intestinal efflux using Caco-2 cells revealed that GE and its phenolics are not substrates of P-glycoprotein (Pgp). Intriguingly, however, 10G and 6S were not detected in the receiver compartment, indicating possible biotransformation across the Caco-2 monolayer. These data strengthen the notion that an interplay of complex interactions among ginger phytochemicals when fed as whole extract dictates its bioactivity highlighting the importance of consuming whole foods over single agents. Our study substantiates the need for an indepth analysis of hepatic biotransformation events and distribution profiles of GE and its active phenolics for the design of safe regimens

Study of impact of increased number of devotees on indoor environmental quality of heritage temples of goddess Mahalaxmi at Kolhapur, Maharashtra, India.

India has a great cultural heritage of temples across the country. There is a wide variety of temples of variety of deities constructed from East to West and North to South of India. Most of the temples are built centuries ago and still are in good condition and the centre of cultural activities. Mahalaxmi temple precinct is a very old precinct in Kolhapur, built in 8th century by Chalukyan rulers. Every year lacs of devotees are visiting this temple of goddess Mahalaxmi from most of the part of India. The temple is constructed of basalt stone with beautiful intricate carving on it. This paper focus on indoor environmental quality of the temple which is deteriorated due to the impact of increased number of devotees. Some of the devotees face the problem of suffocation, fatigue, fainting, irritation, nasal congestion; as provision of vents are absent and natural ventilation is not available inside the shrine of goddess Mahalaxmi. Due to lack of air exchange and natural ventilation the indoor environmental quality is deteriorated. It is observed that the CO2 level is increased, decreased in O2 level, rise in temperature and humidity above the standard level causing discomfort

Mayer–Rokitansky–Kuster–Hauser syndrome: Syndrome of Mullerian agenesis – A report of two cases

The Mayer–Rokitansky–Kuster–Hauser syndrome (MRKH syndrome), simply called Rokitansky syndrome or vaginal aplasia of the uterus, is a congenital condition that is characterized by the absence of the uterus and vagina, but ovaries are present and the external genitalia are normal. It affects at least 1 out of 4500 women. MRKH may be isolated (Type I), but it is more frequently associated with renal, vertebral, and to a lesser extent, auditory and cardiac defects (MRKH Type II or Mullerian duct aplasia, Renal dysplasia, and Cervical Somite anomalies association - mullerian duct aplasia, renal dysplasia, and cervical somite anomalies). There were very few cases of MRKH syndrome reported in the literature. Here, we report two cases of MRKH syndrome, one in a 20-year-old woman who presented with primary amenorrhea (MRKH Type I) and the other in a 65-year-old woman with primary amenorrhea and associated renal malformations and a rare ovarian sertoliform variant of endometrioid tumor (MRKH Type II)

Nano-ZnO Catalyzed Green and Efficient One-Pot Four-Component Synthesis of Pyranopyrazoles

An efficient zinc oxide nanoparticle catalyzed one-pot, four-component synthesis of 6-amino-3-methyl-5-cyano-4-aryl-1,4-dihydropyrano[2,3-c]pyrazoles from aromatic aldehyde, malononitrile, ethyl acetoacetate, and hydrazine hydrate in aqueous medium is described. Since water was employed as the reaction medium, it serves as a green route for the synthesis of pyrano[2,3-c]pyrazoles. The advantages associated with the present protocol include nonchromatographic purification technique, use of recyclable heterogeneous nano-ZnO catalyst in aqueous medium, and short reaction time. It combines successfully the synergistic effect of green chemistry with nanocatalysis

Cell-free chromatin particles released from dying host cells are global instigators of endotoxin sepsis in mice.

We have earlier reported that cell-free chromatin (cfCh) particles that are released from dying cells, or those that circulate blood, can readily enter into healthy cells, illegitimately integrate into their genomes and induce dsDNA breaks, apoptosis and intense activation of inflammatory cytokines. We hypothesized that sepsis is caused by cfCh released from dying host cells following microbial infection leading to bystander host cell apoptosis and inflammation which are perpetuated in a vicious cycle with release of more cfCh from dying host cells. To test this hypothesis we used three cfCh inactivating agents namely 1) anti-histone antibody complexed nanoparticles which inactivate cfCh by binding to histones; 2) DNase I which inactivates cfCh by degrading its DNA component, and 3) a novel pro-oxidant combination of Resveratrol and Copper which, like DNase I, inactivates cfCh by degrading its DNA component. Female C57 BL/6 mice, 6-8 weeks old, were administered a single i.p. injection of LPS at a dose of 10 mg/Kg or 20 mg/Kg with or without concurrent treatment with the above cfCh inactivating agents. Administration of cfCh inactivating agents concurrently with LPS resulted in prevention of following pathological parameters: 1) release of cfCh in extra-cellular spaces of brain, lung and heart and in circulation; 2) release of inflammatory cytokines in circulation; 3) activation of DNA damage, apoptosis and inflammation in cells of thymus, spleen and in PBMCs; 4) DNA damage, apoptosis and inflammation in cells of lung, liver, heart, brain, kidney and small intestine; 5) liver and kidney dysfunction and elevation of serum lactate; 6) coagulopathy, fibrinolysis and thrombocytopenia; 7) lethality. We conclude that cfCh that are released from dying host cells in response to bacterial endotoxin represents a global instigator of sepsis. cfCh inactivation may provide a novel approach to management of sepsis in humans

Effects of GE and its active constituents on the activity of CYP3A4 with substrates, (A) midazolam and (B) testosterone upon incubation with human liver microsomes.

<p>The corresponding positive control, (Ai and Bi) ketoconazole's inhibitory activity was tested followed by (Aii, Bii) 6G, 8G, 10G, 6S and (Aiii, Biii) GE. Data shown are averages of duplicate experiments for GE and positive controls.</p

PLOS ONE Humane Endpoints Checklist.

Metastatic dissemination following successful treatment of the primary tumour remains a common cause of death. There is mounting evidence that therapeutic interventions themselves may promote development of metastatic disease. We earlier reported that cell-free chromatin particles (cfChPs) released from dying cancer cells are potentially oncogenic. Based on this observation we hypothesized that therapeutic interventions may lead to the release of cfChPs from therapy induced dying cancer cells which could be carried via the blood stream to distant organs to transform healthy cells into new cancers that would masquerade as metastasis. To test this hypothesis, we generated xenografts of MDA-MB-231 human breast cancer cells in severe combined immune-deficient mice, and using immuno-fluorescence and FISH analysis looked for cfChPs in their brain cells. We detected multiple human DNA signals representing cfChPs in nuclei of brain cells of mice which co-localized with eight human onco-proteins. No intact MDA-MB-231 cells were detected. The number of co-localizing human DNA and human c-Myc signals increased dramatically following treatment with chemotherapy, localized radiotherapy or surgery, which could be prevented by concurrent treatment with three different cfChPs deactivating agents. These results suggest that therapeutic interventions lead to the release cfChPs from therapy induced dying cancer cells carrying oncogenes and are transported via the blood stream to brain cells to potentially transform them to generate new cancers that would appear as metastases. cfChPs induced metastatic spread of cancer is preventable by concurrent treatment with agents that deactivate cfChPs.</div