A Review: Protein Interaction & Behavior Assessment in Host Cells after Novel Drug Compound Administration using Systems Biology Approach

To understand complex biological systems requires the integration of experimental and computational research; in other words systems biology approach. Computational biology, through via different software helps in exploration more than one gene expression at a time and also understanding the connectivity, Systems Biology provides a powerful foundation from which to address critical scientific questions head-on. The reviews in this Insight cover many different aspects of this energetic field, although all, in one way or another, illuminate the functioning of modular circuits, including their robustness, design and manipulation. Computational systems biology addresses questions fundamental to our understanding of life, yet progress here will lead to practical innovations in medicine, drug discovery and engineering, In this study we have evaluated th

Evaluation of efficacy of oral administration of pro-drug of triptolide against pancreatic cancer

296 Background: Pancreatic cancer is an aggressive disease. The current chemotherapy only marginally increases the survival of patients with PDAC. Hence there is an urgent need for novel therapies. We have shown that minnelide, a pro-drug of triptolide which is currently in phase I trials, when administered intra-peritoneally is very effective against pancreatic cancer in multiple animal models. In the current study we evaluated the efficacy of oral minnelide against pancreatic cancer, alone or in combination with standard therapy in PDAC. Methods: Xenograft, subcutaneous and orthotopic models were established using S2-VP10 and MIA PaCa-2 cell lines. Minnelide was used in doses ranging from 0.15-0.6 mg/kg/day either oral or i.p. and standard chemotherapy was gemcitabine 250 mg/kg/week + nab-paclitaxel 25 mg/kg/week. The tumor burden was compared between various treatment groups. Results: Minnelide i.p significantly decreased tumor mass in MIA PaCa-2 derived tumors and oral administration had equipotent effects. In the S2-VP10 model, combination of low doses of orally administered minnelide with gemcitabine + nab-paclitaxel was significantly more effective in decreasing the tumor burden leading to an increased survival of tumor bearing mice when compared with either therapy alone (p < 0.05). Combination therapy significantly reduced cancer-related morbidity by decreasing ascites and metastasis. Conclusions: Oral administration of minnelide is effective against pancreatic cancer at doses which have been shown to be safe in phase I clinical trial. Oral minnelide has great potential to emerge as novel therapy for pancreatic cancer

Minnelide synergizes with conventional chemotherapy by targeting both cancer and associated stroma components in pancreatic cancer

Addition of nab-paclitaxel to gemcitabine offers a survival benefit of only 6 weeks over gemcitabine alone at a cost of increased toxicity in PDAC. The goal of the present study is to evaluate the efficacy of Minnelide, a water-soluble prodrug of triptolide, in combination with the standard of care regimen for chemotherapy with the added advantage of reducing the doses of these drugs to minimize toxicity. Pancreatic cancer cell lines were implanted subcutaneously or orthotopically in athymic nude or C57BL/6J mice. Subsequently, animals were randomized and received saline or minnelide or full dose chemotherapy or low dose chemotherapy or minnelide in combination with low dose chemotherapy. Our results show that a combination of low doses of Minnelide with Gemcitabine + nab-paclitaxel significantly inhibited tumor progression and increased the survival of tumor-bearing mice in comparison with conventional chemotherapy alone. Moreover, combination therapy significantly reduced cancer-related morbidity by decreasing ascites and metastasis and effectively targeted both cancer and the associated stroma. In vitro studies with a combination of low doses of triptolide and paclitaxel significantly decreased the cell viability, increased apoptosis and led to significantly increased M-phase cell cycle arrest in various pancreatic cancer cell lines as compared to either drug alone. Our results show that Minnelide synergizes with conventional chemotherapy leading to a significant reduction in the doses of these toxic drugs, all the while achieving better efficacy in the treatment of PDAC. This combination effectively targeted both the cancer and the associated stromal components of pancreatic cancer

Child neurodevelopment after multidomain interventions from preconception through early childhood

ImportanceMultidomain interventions in pregnancy and early childhood have improved child neurodevelopment, but little is known about the effects of additional preconception interventions.ObjectiveTo evaluate the effect of a multifaceted approach including health; nutrition; water, sanitation, and hygiene (WASH); and psychosocial support interventions delivered during the preconception period and/or during pregnancy and early childhood on child neurodevelopment.Design, Setting, and ParticipantsIn this randomized trial involving low- and middle-income neighborhoods in Delhi, India, 13 500 participants were assigned to preconception interventions or routine care for the primary outcome of preterm births and childhood growth. Participants who became pregnant were randomized to pregnancy and early childhood interventions or routine care. Neurodevelopmental assessments, the trial’s secondary outcome reported herein, were conducted in a subsample of children at age 24 months, including 509 with preconception, pregnancy, and early childhood interventions; 473 with preconception interventions alone; 380 with pregnancy and early childhood interventions alone; and 350 with routine care. This study was conducted from November 1, 2020, through February 25, 2022.InterventionsHealth, nutrition, psychosocial care and support, and WASH interventions delivered during preconception, pregnancy, and early childhood periods.Main Outcomes and MeasuresCognitive, motor, language, and socioemotional performance at age 24 months, assessed using the Bayley Scales of Infant and Toddler Development 3 tool.ResultsThe mean age of participants at enrollment was 23.8 years (SD, 3.0 years). Compared with the controls at age 24 months, children in the preconception intervention groups had higher cognitive scores (mean difference [MD], 1.16; 98.3% CI, 0.18-2.13) but had similar language, motor, and socioemotional scores as controls. Those receiving pregnancy and early childhood interventions had higher cognitive (MD, 1.48; 98.3% CI, 0.49-2.46), language (MD, 2.29; 98.3% CI, 1.07-3.50), motor (MD, 1.53; 98.3% CI, 0.65-2.42), and socioemotional scores (MD, 4.15; 98.3% CI, 2.18-6.13) than did controls. The pregnancy and early childhood group also had lower incidence rate ratios (RRs) of moderate to severe delay in cognitive (incidence RR, 0.62; 98.3% CI, 0.40-0.96), language (incidence RR, 0.73; 98.3% CI, 0.57-0.93), and socioemotional (incidence RR, 0.49; 98.3% CI, 0.24-0.97) development than did those in the control group. Children in the preconception, pregnancy, and early childhood intervention group had higher cognitive (MD, 2.60; 98.3% CI, 1.08-4.12), language (MD, 3.46; 98.3% CI, 1.65-5.27), motor (MD, 2.31; 98.3% CI, 0.93-3.69), and socioemotional (MD, 5.55; 98.3% CI, 2.66-8.43) scores than did those in the control group.Conclusions and RelevanceMultidomain interventions during preconception, pregnancy and early childhood led to modest improvements in child neurodevelopment at 24 months. Such interventions for enhancing children’s development warrant further evaluation

Abstracts of Scientifica 2022

This book contains the abstracts of the papers presented at Scientifica 2022, Organized by the Sancheti Institute College of Physiotherapy, Pune, Maharashtra, India, held on 12–13 March 2022. This conference helps bring researchers together across the globe on one platform to help benefit the young researchers. There were six invited talks from different fields of Physiotherapy and seven panel discussions including over thirty speakers across the globe which made the conference interesting due to the diversity of topics covered during the conference. Conference Title:  Scientifica 2022Conference Date: 12–13 March 2022Conference Location: Sancheti Institute College of PhysiotherapyConference Organizer: Sancheti Institute College of Physiotherapy, Pune, Maharashtra, Indi