Brenner tumor of ovary: an incidental finding: a case report

Brenner tumor of the ovary is very rare, mostly benign, small, and unilateral. Malignant brenner tumor is much rarer. Malignant brenner tumor of ovary closely resembles the transitional cell carcinoma of ovary. These tumors are believed to arise from urothelial metaplasia of ovarian surface epithelium. However the latter has a worse prognosis. Here we present a case of Brenner tumor of ovary in a postmenopausal woman treated surgically and its features are briefly discussed

Morbidly adherent placenta and it’s maternal and fetal outcome

Background: Morbidly adherent placenta, a grave complication of pregnancy is becoming an emerging cause of increased maternal morbidity and mortality. Objectives of present study are to evaluate the etiopathogenesis of MAP, its clinical mode of presentation and maternal and fetal outcome with the aim to reduce maternal morbidity and mortality.Methods: It was a retrospective and prospective study at Umaid Hospital, attached to Dr. S.N. Medical College, Jodhpur in which data of patients with clinical diagnosis of MAP were reviewed from October 2014 to January 2016.Results: In this study of 10 cases of morbidly adherent placenta of Umaid hospital from October-2014 to January 2016 were studied, it was found that the mean age of presentation was 30.2 year. 60% cases were unbooked and 40% cases were booked with regular ANC visit. 60% cases presented with bleeding per vagina as a chief complaint and 30% cases were admitted for elective LSCS. 60% cases were already diagnosed case of placenta praevia. 90% cases had a history of previous LSCS. 80% cases were given BT intraoperatively and postoperatively. 60% cases underwent caesarean hysterectomy, 80% cases were shifted to ICU, and there was one maternal death.Conclusions: The incidence of MAP is increasing due to higher cesarean section (C/S) rate. Antenatal diagnosis via USG and color-doppler imaging, preoperative counseling, planning and multidisciplinary approach is necessary to reduce morbidity and mortality associated with MAP

Comparative assessment of fetomaternal outcome in twin pregnancy with singleton pregnancy at tertiary care centre

Background: Multiple pregnancy remains one of the highest risk situations for the mother, foetus and neonate despite recent advances in obstetrics, perinatal and neonatal care. Twin pregnancies have increased rates of obstetric and perinatal complications compared to singletons Objective of present study was comparative assessment of fetomaternal outcome in twin pregnancy with singleton pregnancy in Obstetrics and Gynaecology Department of S.M.S. Medical College, Jaipur.Methods: This was a hospital based, prospective observational study done in the Department of Obstetrics and Gynaecology. S.M.S. Medical College, Jaipur from April 2015 to March 2016. 150 women with twin pregnancy and 150 women with singleton pregnancies at gestation age of 28 weeks and above coming for delivery and consented for the study were included in the study. Women with chronic medical disorder or chronic hypertension were excluded from the study. Maternal and neonatal outcome recorded and analysed.Results: Occurrence of twin in our study was 2.82%. Risk of preterm labour was about nine times higher in twin pregnancies than the singleton (OR: 2.74, 95% CI; 1.4494-5.1884, P value 0.001). The risk of premature rupture of membrane was increased by 2.74 times in twin pregnancies (OR:2.74; 95% CI: 1.4494-5.1884, p value .001). There was 3-time increased risk of malpresentation (OR 3.14; CI:1.7184-5.7480, p value .00002) and 2.28 times increase in hypertensive disorder (OR 2.28; 95% CI: 1.0727-4.8823, p value .03) in twin pregnancies. The risk of asphyxia and septicaemia was 2.5 times more in twins.Conclusions: Twin pregnancy is a high-risk pregnancy with more complications in mother and foetus and is a great challenge for obstetrician. So, it should be managed carefully at tertiary care centre to reduce the maternal and perinatal mortality and morbidity

Analogues designing for dephosphorylation of acetylcholinesterase enzyme

Organophosphate (OP) causes phosphorylation of acetylcholinesterase enzyme which leads to accumulation of acetylcholine. This phosphorylation generally occurs due to exposure of nerve agents and intake of pesticides, etc. Various standard drugs specifically oxime derivatives (HI-6, Obidoxime, 2-PAM, etc.) are used as AChE enzyme reactivation agents. These standard drugs show least penetration to CNS. Taking them into consideration with the help of structure and ligand based screened compounds, various small molecules analogues targeting CNS have been designed. These analogues pass all the pharmacokinetic parameters structurally and have also shown better results than that of standards. Among various charged and uncharged analogues, 4g, 4h and 4j have attained docking scores –13.11, –12.84 and –12.75Kcal/mol respectively which is better than that of the standard (HI-6) –12.13kcal/mol.

Analogues designing for dephosphorylation of acetylcholinesterase enzyme

856-865Organophosphate (OP) causes phosphorylation of acetylcholinesterase enzyme which leads to accumulation of acetylcholine. This phosphorylation generally occurs due to exposure of nerve agents and intake of pesticides, etc. Various standard drugs specifically oxime derivatives (HI-6, Obidoxime, 2-PAM, etc.) are used as AChE enzyme reactivation agents. These standard drugs show least penetration to CNS. Taking them into consideration with the help of structure and ligand based screened compounds, various small molecules analogues targeting CNS have been designed. These analogues pass all the pharmacokinetic parameters structurally and have also shown better results than that of standards. Among various charged and uncharged analogues, 4g, 4h and 4j have attained docking scores –13.11, –12.84 and –12.75Kcal/mol respectively which is better than that of the standard (HI-6) –12.13kcal/mol

Structure-Based Virtual Screening and in vitro and in vivo Analyses Revealed Potent Methyltransferase G9a Inhibitors as Prospective Anti-Alzheimer's Agents

G9a is a lysine methyltransferase able to di-methylate lysine 9 of histone H3, promoting the repression of genes involved in learning and memory. Novel strategies based on synthesizing epigenetic drugs could regulate gene expression through histone post-translational modifications and effectively treat neurodegenerative diseases, like Alzheimer's disease (AD). Here, potential G9a inhibitors were identified using a structure-based virtual screening against G9a, followed by in vitro and in vivo screenings. First, screening methods with the AD transgenic Caenorhabditis elegans strain CL2006, showed that the toxicity/function range was safe and recovered age-dependent paralysis. Likewise, we demonstrated that the best candidates direct target G9a by reducing H3 K9me2 in the CL2006 strain. Further characterization of these compounds involved the assessment of the blood-brain barrier-permeability and impact on amyloid-β aggregation, showing promising results. Thus, we present a G9a inhibitor candidate, F, with a novel and potent structure, providing both leads in G9a inhibitor design and demonstrating their participation in reducing AD pathology. Keywords: Alzheimer's disease; G9a methyltransferase; amyloid-β; epigenetics; structure based virtual screening

G9a Inhibition Promotes Neuroprotection through GMFB Regulation in Alzheimer’s Disease

Epigenetic alterations are a fundamental pathological hallmark of Alzheimer’s disease (AD). Herein, we show the upregulation of G9a and H3K9me2 in the brains of AD patients. Interestingly, treatment with a G9a inhibitor (G9ai) in SAMP8 mice reversed the high levels of H3K9me2 and rescued cognitive decline. A transcriptional profile analysis after G9ai treatment revealed increased gene expression of glia maturation factor β (GMFB) in SAMP8 mice. Besides, a H3K9me2 ChIP-seq analysis after G9a inhibition treatment showed the enrichment of gene promoters associated with neural functions. We observed the induction of neuronal plasticity and a reduction of neuroinflammation after G9ai treatment, and more strikingly, these neuroprotective effects were reverted by the pharmacological inhibition of GMFB in mice and cell cultures; this was also validated by the RNAi approach generating the knockdown of GMFB/Y507A.10 in Caenorhabditis elegans. Importantly, we present evidence that GMFB activity is controlled by G9a-mediated lysine methylation as well as we identified that G9a directly bound GMFB and catalyzed the methylation at lysine (K) 20 and K25 in vitro. Furthermore, we found that the neurodegenerative role of G9a as a GMFB suppressor would mainly rely on methylation of the K25 position of GMFB, and thus G9a pharmacological inhibition removes this methylation promoting neuroprotective effects. Then, our findings confirm an undescribed mechanism by which G9a inhibition acts at two levels, increasing GMFB and regulating its function to promote neuroprotective effects in age-related cognitive decline</p

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

Introduction: The COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. Methods: Extensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors. Results: Results revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. Discussion: The key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies.Peer Reviewe

COVID19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms.

Funder: Bundesministerium für Bildung und ForschungFunder: Bundesministerium für Bildung und Forschung (BMBF)We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective

Drug-target identification in COVID-19 disease mechanisms using computational systems biology approaches

IntroductionThe COVID-19 Disease Map project is a large-scale community effort uniting 277 scientists from 130 Institutions around the globe. We use high-quality, mechanistic content describing SARS-CoV-2-host interactions and develop interoperable bioinformatic pipelines for novel target identification and drug repurposing. MethodsExtensive community work allowed an impressive step forward in building interfaces between Systems Biology tools and platforms. Our framework can link biomolecules from omics data analysis and computational modelling to dysregulated pathways in a cell-, tissue- or patient-specific manner. Drug repurposing using text mining and AI-assisted analysis identified potential drugs, chemicals and microRNAs that could target the identified key factors.ResultsResults revealed drugs already tested for anti-COVID-19 efficacy, providing a mechanistic context for their mode of action, and drugs already in clinical trials for treating other diseases, never tested against COVID-19. DiscussionThe key advance is that the proposed framework is versatile and expandable, offering a significant upgrade in the arsenal for virus-host interactions and other complex pathologies