Network-based drug repurposing identifies small molecule drugs as immune checkpoint inhibitors for endometrial cancer.

Endometrial cancer (EC) is the 6th most common cancer in women around the world. Alone in the United States (US), 66,200 new cases and 13,030 deaths are expected to occur in 2023 which needs the rapid development of potential therapies against EC. Here, a network-based drug-repurposing strategy is developed which led to the identification of 16 FDA-approved drugs potentially repurposable for EC as potential immune checkpoint inhibitors (ICIs). A network of EC-associated immune checkpoint proteins (ICPs)-induced protein interactions (P-ICP) was constructed. As a result of network analysis of P-ICP, top key target genes closely interacting with ICPs were shortlisted followed by network proximity analysis in drug-target interaction (DTI) network and pathway cross-examination which identified 115 distinct pathways of approved drugs as potential immune checkpoint inhibitors. The presented approach predicted 16 drugs to target EC-associated ICPs-induced pathways, three of which have already been used for EC and six of them possess immunomodulatory properties providing evidence of the validity of the strategy. Classification of the predicted pathways indicated that 15 drugs can be divided into two distinct pathway groups, containing 17 immune pathways and 98 metabolic pathways. In addition, drug-drug correlation analysis provided insight into finding useful drug combinations. This fair and verified analysis creates new opportunities for the quick repurposing of FDA-approved medications in clinical trials.

Drug repurposing for viral cancers: A paradigm of machine learning, deep learning, and virtual screening-based approaches.

Cancer management is major concern of health organizations and viral cancers account for approximately 15.4% of all known human cancers. Due to large number of patients, efficient treatments for viral cancers are needed. De novo drug discovery is time consuming and expensive process with high failure rate in clinical stages. To address this problem and provide treatments to patients suffering from viral cancers faster, drug repurposing emerges as an effective alternative which aims to find the other indications of the Food and Drug Administration approved drugs. Applied to viral cancers, drug repurposing studies following the niche have tried to find if already existing drugs could be used to treat viral cancers. Multiple drug repurposing approaches till date have been introduced with successful results in viral cancers and many drugs have been successfully repurposed various viral cancers. Here in this study, a critical review of viral cancer related databases, tools, and different machine learning, deep learning and virtual screening-based drug repurposing studies focusing on viral cancers is provided. Additionally, the mechanism of viral cancers is presented along with drug repurposing case study specific to each viral cancer. Finally, the limitations and challenges of various approaches along with possible solutions are provided.

A systematic review of computational approaches to understand cancer biology for informed drug repurposing.

Cancer is the second leading cause of death globally, trailing only heart disease. In the United States alone, 1.9 million new cancer cases and 609,360 deaths were recorded for 2022. Unfortunately, the success rate for new cancer drug development remains less than 10%, making the disease particularly challenging. This low success rate is largely attributed to the complex and poorly understood nature of cancer etiology. Therefore, it is critical to find alternative approaches to understanding cancer biology and developing effective treatments. One such approach is drug repurposing, which offers a shorter drug development timeline and lower costs while increasing the likelihood of success. In this review, we provide a comprehensive analysis of computational approaches for understanding cancer biology, including systems biology, multi-omics, and pathway analysis. Additionally, we examine the use of these methods for drug repurposing in cancer, including the databases and tools that are used for cancer research. Finally, we present case studies of drug repurposing, discussing their limitations and offering recommendations for future research in this area.

Wide-Range Humidity-Temperature Hybrid Flexible Sensor Based on Strontium Titanate and Poly 3,4 Ethylenedioxythiophene Polystyrene Sulfonate for Wearable 3D-Printed Mask Applications.

In this paper, we report a fast, linear wide-range hybrid flexible sensor based on a novel composite of strontium titanate (SrTiO3) and poly 3,4 ethylenedioxythiophene polystyrene sulfonate (PEDOT: PSS) as a sensing layer. Inter-digitate electrodes (IDEs) were printed for humidity monitoring (finger: 250 µm; spacing: 140 µm; length: 8 mm) whilst a meander-based pattern was printed for the temperature measurement (meander thickness: 180 µm; spacing: 400 µm) on each side of the PET substrate using silver ink. Moreover, active layers with different concentration ratios were coated on the electrodes using a spray coating technique. The as-developed sensor showed an excellent performance, with a humidity measurement range of (10-90% RH) and temperature measurement range of (25-90 °C) with a fast response (humidity: 5 s; temperature: 4.2 s) and recovery time (humidity: 8 s; temperature: 4.4 s). The reliability of the sensor during mechanical bending of up to 5.5 mm was validated with a reliable performance. The sensor was also used in real-world applications to measure human respiration. For this, a suggested sensor-based autonomous wireless node was included in a 3D-printed mask. The manufactured sensor was an excellent contender for wearable and environmental applications because of its exceptional performance, which allowed for the simultaneous measurement of both quantities by a single sensing device.

Effects of Substitution Position of Carbazole-Dibenzofuran Based High Triplet Energy Hosts to Device Stability of Blue Phosphorescent Organic Light-Emitting Diodes.

High triplet energy hosts were developed through the modification of the substitution position of carbazole units. Two carbazole-dibenzofuran-derived compounds, 9,9'-(dibenzo[b,d]furan-2,6-diyl)bis(9H-carbazole) (26CzDBF) and 4,6-di(9H-carbazol-9-yl)dibenzo[b,d]furan (46CzDBF), were synthesized for achieving high triplet energy hosts. In comparison with the reported hole transport type host, 2,8-di(9H-carbazol-9-yl)dibenzo[b,d]furan (28CzDBF), 26CzDBF and 46CzDBF maintained high triplet energy over 2.95 eV. The device performances of the hosts were evaluated with electron transport type host, 2-phenyl-4, 6-bis(3-(triphenylsilyl)phenyl)-1,3,5-triazine (mSiTrz), to comprise a mixed host system. The deep blue phosphorescent device of 26CzDBF:mSiTrz with [[5-(1,1-dimethylethyl)-3-phenyl-1H-imidazo[4,5-b]pyrazin-1-yl-2(3H)-ylidene]-1,2-phenylene]bis[[6-(1,1-dimethylethyl)-3-phenyl-1H-imidazo[4,5-b]pyrazin-1-yl-2(3H)-ylidene]-1,2-phenylene]iridium (Ir(cb)3) dopant exhibited high external quantum efficiency of 22.9% with a color coordinate of (0.14, 0.16) and device lifetime of 1400 h at 100 cd m-2. The device lifetime was extended by 75% compared to the device lifetime of 28CzDBF:mSiTrz (800 h). These results demonstrated that the asymmetric and symmetric substitution of carbazole can make differences in the device performance of the carbazole- and dibenzofuran- derived hosts.

3D printing for soft robotics - a review.

Soft robots have received an increasing attention due to their advantages of high flexibility and safety for human operators but the fabrication is a challenge. Recently, 3D printing has been used as a key technology to fabricate soft robots because of high quality and printing multiple materials at the same time. Functional soft materials are particularly well suited for soft robotics due to a wide range of stimulants and sensitive demonstration of large deformations, high motion complexities and varied multi-functionalities. This review comprises a detailed survey of 3D printing in soft robotics. The development of key 3D printing technologies and new materials along with composites for soft robotic applications is investigated. A brief summary of 3D-printed soft devices suitable for medical to industrial applications is also included. The growing research on both 3D printing and soft robotics needs a summary of the major reported studies and the authors believe that this review article serves the purpose.

Associations Between Fat Mass, Lean Mass, and Knee Osteoarthritis: The Fifth Korean National Health and Nutrition Examination Survey (KNHANES V).

As little is known about the associations between body composition (fat mass and lean mass) and knee OA, especially regarding body parts (upper body and lower limbs), the purpose of this study was to identify the association between the former and the prevalence of the latter according to body parts. This study was designed as a cross-sectional analysis, with 4194 people (1801 men and 2393 women) from the fifth Korean National Health and Nutrition Examination Survey (KNHANES V, 2010-2011) included. Body composition (fat mass and lean mass) was measured by using dual-energy X-ray absorptiometry, and knee OA was diagnosed based on the level of Kellgren-Lawrence grade. In multivariate logistic regression analysis, upper body composition was not significantly correlated with radiographic knee OA (P > 0.05), while participants with higher lean mass of lower limbs were less likely to have radiographic knee OA (aOR 0.57; 95 % CI 0.32-0.99). In stratified analysis, participants with higher lean mass of lower limbs were less likely to have a radiographic knee OA in 40-54 kg (P for trend = 0.05) and 55-70 kg stratum (P for trend = 0.03), while this trend slightly attenuated in 70-85 kg stratum (P for trend = 0.15). In conclusion, the increase in lean mass of lower limbs is inversely related to the prevalence of knee OA while upper body composition is not. This study suggests that the lean mass of lower limbs might be associated with reduction in the risk of knee OA.

Health inequalities in hypertension and diabetes management among the poor in urban areas: a population survey analysis in south Korea.

BACKGROUND: This study investigated whether the prevalence, awareness, treatment, and control of hypertension and diabetes differed by residential areas. In addition, the rate of good hypertension or diabetes control was examined separately in men and women, and in urban and rural areas. METHODS: This study used Korea National Health and Nutrition Examination V (2010-2012) data, a nationwide cross-sectional survey of general South Korean population. Residential areas were categorized into urban and rural areas. To examine differences between the residential areas in terms of prevalence, awareness, treatment, and control of hypertension and diabetes we performed a multivariate logistic regression adjusting for age, body mass index, physical activity, alcohol use, smoking, marital status, monthly income, and educational level. To investigate control of hypertension or diabetes within each residential area, we performed a subgroup analysis in both urban and rural areas. RESULTS: The prevalence of hypertension is higher among men in urban areas than among those in rural areas (OR = 0.80; 95 % CI = 0.67-0.96, reference group = urban areas). However, the subgroups did not differ in terms of diabetes prevalence, awareness, treatment, and control. Regardless of both sex and residential area, participants in good control of their hypertension and diabetes were younger. Inequality in good control of hypertension was observed in men who lived in urban (≤Elementary school, OR 0.74, 95 % CI 0.60-0.92) and rural areas (≤Elementary school, OR 0.67, 95 % CI 0.46-0.99). Inequality in health status was found in women who resided in urban areas (≤Elementary school, OR 0.53, 95 % CI 0.37-0.75). Good control of diabetes also showed inequalities in health status for both men (≤Elementary school, OR 0.61, 95 % CI 0.40-0.94; Middle/High school, OR 0.69, 95 % CI 0.49-0.96) and women in urban areas (≤1 million won, OR 0.56, 95 % CI 0.33-0.93) (Reference group = '≥College' for education and '>3 million' Korean won for income). CONCLUSIONS: After correction for individual socioeconomic status, differences by residential area were not observed. However, when the participants with good disease control were divided by region, inequality was confirmed in urban residents. Therefore, differentiated health policies to resolve individual and regional health inequalities are necessary.

Psychological Status and Associated Factors among Korean Cancer Survivors: a Cross-Sectional Analysis of the Fourth & Fifth Korea National Health and Nutrition Examination Surveys.

It is important to assess psychological distress after a diagnosis for cancer survivors, a population with a high risk for psychological distress. The aim of this study is to assess psychological distress among cancer survivors and to clarify the associated factors. In this cross-sectional analysis, data were obtained from standardized questionnaires administered to 1,163 cancer survivors and 49,243 non-cancer survivors who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Survey (2007-2012). We identified the adjusted rates for psychological distress and assessed factors associated with this kind of distress using multivariate logistic regression. Cancer survivors tended to have a higher adjusted rate of psychological distress than the general population. The current depressive symptom rate for cancer survivors was 16.69%, and the adjusted rate for history of depression in cancer survivors was 15.61%. The adjusted rate for higher level of stress was 25.51% in cancer survivors. Among the cancer survivors, younger subjects, female subjects, and those with limited social support were more prone to psychological distress. In addition, current smokers or risky drinkers, those with chronic diseases, and those with a poor self-perception of their health status were also identified as a high-risk group for psychological distress. As the number of cancer survivors has increased, the importance of assessing psychological distress after a cancer diagnosis should be emphasized among all cancer survivors. Further, psychological supportive care interventions for cancer survivors are needed to improve the survival rate and improve their quality of life.

Low-temperature roll-to-roll atmospheric atomic layer deposition of Al2O3 thin films.

The Al2O3 thin films deposition through conventional ALD systems is a well-established process. The process under low temperatures has been studied by few research groups. In this paper, we report on the detailed study of low-temperature Al2O3 thin films deposited via a unique in-house built system of roll-to-roll atmospheric atomic layer deposition (R2R-AALD) using a multiple-slit gas source head. Al2O3 thin films have been grown on polyethylene terephthalate substrates under a very low-temperature zone of room temperature to 50 °C and working pressure of 750 Torr, which is very near to atmospheric pressure (760 Torr). Al2O3 thin films with superior properties were achieved in the temperature range of the ALD window. An appreciable growth rate of 0.97 Å/cycle was observed for the films deposited at 40 °C. The films have good morphological features with a very low average arithmetic roughness (Ra) of 0.90 nm. The films also showed good chemical, electrical, and optical characteristics. It was observed that the film characteristics improve with the increase in deposition temperature to the range of the ALD window. The fabrication of Al2O3 films was confirmed by X-ray photoelectron spectroscopy (XPS) analysis with the appearance of Al 2p, Al 2s, and O 1s peaks at the binding energies of 74, 119, and 531 eV, respectively. The chemical composition was also supported by the Fourier transform infrared spectroscopy (FTIR). The fabricated Al2O3 films demonstrate good insulating properties and optical transmittance of more than 85% in the visible region. The results state that Al2O3 thin films can be effectively fabricated through the R2R-AALD system at temperatures as low as 40 °C.

Influenza vaccination and associated factors among Korean cancer survivors : a cross-sectional analysis of the Fourth & Fifth Korea National Health and Nutrition Examination Surveys.

Influenza vaccination is important for cancer survivors, a population with impaired immunity. This study was designed to assess influenza vaccination patterns among Korean cancer survivors. In this cross-sectional analysis, data were obtained from standardized questionnaires from 943 cancer survivors and 41,233 non-cancer survivors who participated in the Fourth and Fifth Korea National Health and Nutrition Examination Surveys (2007-2011). We identified the adjusted influenza vaccination rates and assessed factors associated with influenza vaccination using multivariate logistic regression. Cancer survivors tended to have a higher adjusted influenza vaccination rate than the general population. The rates for influenza vaccination in specific cancer types such as stomach, hepatic, colon, and lung cancers were significantly higher than non-cancer survivors. Among all cancer survivors, those with chronic diseases, elderly subjects, and rural dwellers were more likely to receive influenza vaccination; those with cervical cancer were less likely to receive influenza vaccination. Cancer survivors were more likely to receive influenza vaccinations than non-cancer survivors, but this was not true for particular groups, especially younger cancer survivors. Cancer survivors represent a sharply growing population; therefore, immunization against influenza among cancer survivors should be concerned as their significant preventative healthcare services.

Integrated ML-Based Strategy Identifies Drug Repurposing for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) affects an estimated global population of around 3 million individuals. IPF is a medical condition with an unknown cause characterized by the formation of scar tissue in the lungs, leading to progressive respiratory disease. Currently, there are only two FDA-approved small molecule drugs specifically for the treatment of IPF and this has created a demand for the rapid development of drugs for IPF treatment. Moreover, denovo drug development is time and cost-intensive with less than a 10% success rate. Drug repurposing currently is the most feasible option for rapidly making the drugs to market for a rare and sporadic disease. Normally, the repurposing of drugs begins with a screening of FDA-approved drugs using computational tools, which results in a low hit rate. Here, an integrated machine learning-based drug repurposing strategy is developed to significantly reduce the false positive outcomes by introducing the predock machine-learning-based predictions followed by literature and GSEA-assisted validation and drug pathway prediction. The developed strategy is deployed to 1480 FDA-approved drugs and to drugs currently in a clinical trial for IPF to screen them against "TGFB1", "TGFB2", "PDGFR-a", "SMAD-2/3", "FGF-2", and more proteins resulting in 247 total and 27 potentially repurposable drugs. The literature and GSEA validation suggested that 72 of 247 (29.14%) drugs have been tried for IPF, 13 of 247 (5.2%) drugs have already been used for lung fibrosis, and 20 of 247 (8%) drugs have been tested for other fibrotic conditions such as cystic fibrosis and renal fibrosis. Pathway prediction of the remaining 142 drugs was carried out resulting in 118 distinct pathways. Furthermore, the analysis revealed that 29 of 118 pathways were directly or indirectly involved in IPF and 11 of 29 pathways were directly involved. Moreover, 15 potential drug combinations are suggested for showing a strong synergistic effect in IPF. The drug repurposing strategy reported here will be useful for rapidly developing drugs for treating IPF and other related conditions.

Integrating Transcriptomic and Structural Insights: Revealing Drug Repurposing Opportunities for Sporadic ALS.

Amyotrophic lateral sclerosis (ALS) is a progressive and devastating neurodegenerative disorder characterized by the loss of upper and lower motor neurons, resulting in debilitating muscle weakness and atrophy. Currently, there are no effective treatments available for ALS, posing significant challenges in managing the disease that affects approximately two individuals per 100,000 people annually. To address the urgent need for effective ALS treatments, we conducted a drug repurposing study using a combination of bioinformatics tools and molecular docking techniques. We analyzed sporadic ALS-related genes from the GEO database and identified key signaling pathways involved in sporadic ALS pathogenesis through pathway analysis using DAVID. Subsequently, we utilized the Clue Connectivity Map to identify potential drug candidates and performed molecular docking using AutoDock Vina to evaluate the binding affinity of short-listed drugs to key sporadic ALS-related genes. Our study identified Cefaclor, Diphenidol, Flubendazole, Fluticasone, Lestaurtinib, Nadolol, Phenamil, Temozolomide, and Tolterodine as potential drug candidates for repurposing in sporadic ALS treatment. Notably, Lestaurtinib demonstrated high binding affinity toward multiple proteins, suggesting its potential as a broad-spectrum therapeutic agent for sporadic ALS. Additionally, docking analysis revealed NOS3 as the gene that interacts with all the short-listed drugs, suggesting its possible involvement in the mechanisms underlying the therapeutic potential of these drugs in sporadic ALS. Overall, our study provides a systematic framework for identifying potential drug candidates for sporadic ALS therapy and highlights the potential of drug repurposing as a promising strategy for discovering new therapies for neurodegenerative diseases.

Optimization of experimental parameters to determine the jetting regimes in electrohydrodynamic printing.

The harmony of ink and printing method is of importance in producing on-demand droplets and jets of ink. Many factors including the material properties, the processing conditions, and the nozzle geometry affect the printing quality. In electrohydrodynamic (EHD) printing where droplets or jets are generated by the electrostatic force, the physical as well as the electrical properties of the fluid should be taken into account to achieve the desired performance. In this study, a systematic approach was suggested for finding the processing windows of the EHD printing. Six dimensionless parameters were organized and applied to the printing system of ethanol/terpineol mixtures. On the basis of the correlation of the dimensionless voltage and the charge relaxation length, the jet diameter of cone-jet mode was characterized, and the semicone angle was compared with the theoretical Taylor angle. In addition, the ratio of electric normal force and electric tangential force on the charged surface of the Taylor cone was recommended as a parameter that determines the degree of cone-jet stability. The cone-jet became more stable as this ratio got smaller. This approach was a systematic and effective way of obtaining the Taylor cone of the cone-jet mode and evaluating the jetting stability. The control of the inks with optimized experimental parameters by this method will improve the jetting performance in EHD inkjet printing.

Psychosocial needs of cancer patients and related factors: a multi-center, cross-sectional study in Korea.

BACKGROUND: Identifying psychosocial needs and satisfying them are important issues to many cancer patients. The aim of this study was to investigate the psychosocial needs of cancer patients and its related factors, based on a nationwide sample of cancer patients in Korea. METHODS: A multi-center survey was administered to 2661 cancer patients from 10 cancer centers in Korea. The survey measured the needs for psychosocial support, using the Comprehensive Needs Assessment Tool in Cancer, and potential correlates, such as socio-demographic and clinical factors. Multivariate ordinal regression and binary logistic regression were conducted to identify factors that may predict psychosocial needs. RESULTS: On the measure for psychosocial needs, the median score of psychological problems was 2.73 points and that of social support was 1.92 points, as the standardized score on a scale of 10 points. Needs for psychological problems were positively correlated with intensive treatment, degree of stress, problems with EQ5-D, needs for information and education, needs for hospital facilities/services and needs for physical symptoms. The need for social support was positively correlated with problems with EQ5-D and other unmet needs of cancer patients. Income levels and the number of years since diagnosis were negatively correlated with the need for social support. CONCLUSION: Unmet psychosocial needs were common in cancer patients and have varied according to patients' socio-demographic and clinical factors. These results suggest that a psychosocial approach to treatment should be applied comprehensively and that such an approach should be matched to patients' socio-demographic and clinical circumstances.

Structural and electrical properties of Ag grid/poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) coatings for diode application through advanced printing technology.

This paper is focused on printed techniques for the fabrication of hybrid structure of silver (Ag) grid/poly(3,4-ethylenedioxythiophene): Poly(styrenesulfonate) (PEDOT:PSS) on polyethylene terepthalate (PET) as a flexible substrate. Ag grid has been printed on PET substrate by using gravure offset printing process, followed by PEDOT:PSS thin film deposition on Ag grid through electrohydrodynamic atomization (EHDA) technique. The important parameters for achieving uniform hybrid structure of Ag grid/PEDOT:PSS through printed techniques have been clearly discussed. Field emission scanning electron microscope studies revealed the uniformity of printed Ag grid with homogeneous deposition of PEDOT:PSS on Ag grid. The optical properties of Ag grid/PEDOT:PSS were measured by UV-visible spectroscopy, which showed nearly 80-82% of transparency in the visible region and it was nearly same as PEDOT:PSS thin film on PET substrate. Current-voltage (I-V) analysis of fabricated hybrid device by using printed Ag grid/PEDOT:PSS as a bottom electrode showed good rectifying behavior with possible interfacial mechanisms. Capacitance-voltage (C-V) analysis was carried over different frequencies. These results suggest that fabrication of hybrid structure through printed techniques will play a significant role in mass production of printed electronic devices for commercial application by using flexible substrate.

Fabrication of nanostructured copper indium diselenide (CIS) thin films by electrohydrodynamic atomization technique.

In this article, we report a non-vacuum electrohydrodynamic atomization (EHDA) technique for deposition of CulnSe2 (CIS) thin films. The CIS ink has been prepared with three different concentrations (7.5 wt.%, 12.5 wt.% and 15 wt.%) by using suitable solvent mixture (ethanol:terpineol as 1:1 molar ratio) with surfactant to achieve a stable dispersions. The important physical parameters for achieving homogeneous with non-agglomerated CIS layers through EHDA technique are investigated in detail. The X-ray diffraction pattern confirms the crystalline structure of CIS layers oriented in the chalcopyrite phase. The film uniformity has been investigated by field emission scanning electron microscopy. Different thickness of CIS layers has been achieved by varying the concentration of CIS particles in the precursor ink solution. The optical properties of CIS layers show the two optical band gaps in UV-visible and near infra-red (NIR) region with band gap of about 2.67-2.49 eV and 1.34-1.29 eV respectively. The energy band gap of CIS thin films have been decreased with the increase of film thickness. The X-ray photoelectron spectra confirmed presence of binding energy corresponding to CulnSe2. The electrical study observed the sheet resistivity 76-33 Omega cm with respect to film thickness.

Organ-on-Chip: Advancing Nutraceutical Testing for Improved Health Outcomes.

The recent global wave of organic food consumption and the vitality of nutraceuticals for human health benefits has driven the need for applying scientific methods for phytochemical testing. Advanced in vitro models with greater physiological relevance than conventional in vitro models are required to evaluate the potential benefits and toxicity of nutraceuticals. Organ-on-chip (OOC) models have emerged as a promising alternative to traditional in vitro models and animal testing due to their ability to mimic organ pathophysiology. Numerous studies have demonstrated the effectiveness of OOC models in identifying pharmaceutically relevant compounds and accurately assessing compound-induced toxicity. This review examines the utility of traditional in vitro nutraceutical testing models and discusses the potential of OOC technology as a preclinical testing tool to examine the biomedical potential of nutraceuticals by reducing the need for animal testing. Exploring the capabilities of OOC models in carrying out plant-based bioactive compounds can significantly contribute to the authentication of nutraceuticals and drug discovery and validate phytochemicals medicinal characteristics. Overall, OOC models can facilitate a more systematic and efficient assessment of nutraceutical compounds while overcoming the limitations of current traditional in vitro models.

Revolutionizing drug development: harnessing the potential of organ-on-chip technology for disease modeling and drug discovery.

The inefficiency of existing animal models to precisely predict human pharmacological effects is the root reason for drug development failure. Microphysiological system/organ-on-a-chip technology (organ-on-a-chip platform) is a microfluidic device cultured with human living cells under specific organ shear stress which can faithfully replicate human organ-body level pathophysiology. This emerging organ-on-chip platform can be a remarkable alternative for animal models with a broad range of purposes in drug testing and precision medicine. Here, we review the parameters employed in using organ on chip platform as a plot mimic diseases, genetic disorders, drug toxicity effects in different organs, biomarker identification, and drug discoveries. Additionally, we address the current challenges of the organ-on-chip platform that should be overcome to be accepted by drug regulatory agencies and pharmaceutical industries. Moreover, we highlight the future direction of the organ-on-chip platform parameters for enhancing and accelerating drug discoveries and personalized medicine.

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.