Network-based drug repurposing for HPV-associated cervical cancer

In women, cervical cancer (CC) is the fourth most common cancer around the world with average cases of 604,000 and 342,000 deaths per year. Approximately 50% of high-grade CC are attributed to human papillomavirus (HPV) types 16 and 18. Chances of CC in HPV-positive patients are 6 times more than HPV-negative patients which demands timely and effective treatment. Repurposing of drugs is considered a viable approach to drug discovery which makes use of existing drugs, thus potentially reducing the time and costs associated with de-novo drug discovery. In this study, we present an integrative drug repurposing framework based on a systems biology-enabled network medicine platform. First, we built an HPV-induced CC protein interaction network named HPV2C following the CC signatures defined by the omics dataset, obtained from GEO database. Second, the drug target interaction (DTI) data obtained from DrugBank, and related databases was used to model the DTI network followed by drug target network proximity analysis of HPV-host associated key targets and DTIs in the human protein interactome. This analysis identified 142 potential anti-HPV repurposable drugs to target HPV induced CC pathways. Third, as per the literature survey 51 of the predicted drugs are already used for CC and 33 of the remaining drugs have anti-viral activity. Gene set enrichment analysis of potential drugs in drug-gene signatures and in HPV-induced CC-specific transcriptomic data in human cell lines additionally validated the predictions. Finally, 13 drug combinations were found using a network based on overlapping exposure. To summarize, the study provides effective network-based technique to quickly identify suitable repurposable drugs and drug combinations that target HPV-associated CC

Silicone Elastomer Composites Fabricated with MgO and MgO-Multi-Wall Carbon Nanotubes with Improved Thermal Conductivity

The effect of multiwall carbon nanotubes (MWCNTs) and magnesium oxide (MgO) on the thermal conductivity of MWCNTs and MgO-reinforced silicone rubber was studied. The increment of thermal conductivity was found to be linear with respect to increased loading of MgO. In order to improve the thermal transportation of phonons 0.3 wt % and 0.5 wt % of MWCNTs were added as filler to MgO-reinforced silicone rubber. The MWCNTs were functionalized by hydrogen peroxide (H2O2) to activate organic groups onto the surface of MWCNTs. These functional groups improved the compatibility and adhesion and act as bridging agents between MWCNTs and silicone elastomer, resulting in the formation of active conductive pathways between MgO and MWCNTs in the silicone elastomer. The surface functionalization was confirmed with XRD and FTIR spectroscopy. Raman spectroscopy confirms the pristine structure of MWCNTs after oxidation with H2O2. The thermal conductivity is improved to 1 W/m·K with the addition of 20 vol% with 0.5 wt % of MWCNTs, which is an ~8-fold increment in comparison to neat elastomer. Improved thermal conductive properties of MgO-MWCNTs elastomer composite will be a potential replacement for conventional thermal interface materials

A comprehensive review of key factors affecting the efficacy of antibody drug conjugate

Antibody Drug Conjugate (ADC) is an emerging technology to overcome the limitations of chemotherapy by selectively targeting the cancer cells. ADC binds with an antigen, specifically over expressed on the surface of cancer cells, results decrease in bystander effect and increase in therapeutic index. The potency of an ideal ADC is entirely depending on several physicochemical factors such as site of conjugation, molecular weight, linker length, Steric hinderance, half-life, conjugation method, binding energy and so on. Inspite of the fact that there is more than 100 of ADCs are in clinical trial only 14 ADCs are approved by FDA for clinical use. However, to design an ideal ADC is still challenging and there is much more to be done. Here in this review, we have discussed the key components along with their significant role or contribution towards the efficacy of an ADC. Moreover, we also explained about the recent advancement in the conjugation method. Additionally, we spotlit the mode of action of an ADC, recent challenges, and future perspective regarding ADC. The profound knowledge regarding key components and their properties will help in the synthesis or production of different engineered ADCs. Therefore, contributes to develop an ADC with low safety concern and high therapeutic index. We hope this review will improve the understanding and encourage the practicing of research in anticancer ADCs development