Mechanical environment for in vitro cartilage tissue engineering assisted by in silico models

Mechanobiological study of chondrogenic cells and multipotent stem cells for articular cartilage tissue engineering(CTE)has been widely explored.The mechanical stimulation in terms of wall shear stress,hydrostatic pressure and mechanical strain has been applied in CTE in vitro.It has been found that the mechanical stimulation at a certain range can accelerate the chondrogenesis and articular cartilage tissue regeneration.This review explicitly focuses on the study of the influence of the mechanical environment on proliferation and extracellular matrix production of chondrocytes in vitro for CTE.The multidisciplinary approaches used in previous studies and the need for in silico methods to be used in parallel with in vitro methods are also discussed.The information from this review is expected to direct facial CTE research,in which mechanobiology has not been widely explored yet.

Brain physiome:A concept bridging in vitro 3D brain models and in silico models for predicting drug toxicity in the brain

In the last few decades,adverse reactions to pharmaceuticals have been evaluated using 2D in vitro models and animal models.However,with increasing computational power,and as the key drivers of cellular behavior have been identified,in silico models have emerged.These models are time-efficient and cost-effective,but the prediction of adverse reactions to unknown drugs using these models requires relevant experimental input.Accordingly,the physiome concept has emerged to bridge experimental datasets with in silico models.The brain physiome describes the systemic interactions of its components,which are organized into a multilevel hierarchy.Because of the limitations in obtaining experimental data corresponding to each physiome component from 2D in vitro models and animal models,3D in vitro brain models,including brain organoids and brain-on-a-chip,have been developed.In this review,we present the concept of the brain physiome and its hierarchical organization,including cell-and tissue-level organizations.We also summarize recently developed 3D in vitro brain models and link them with the elements of the brain physiome as a guideline for dataset collection.The connection between in vitro 3D brain models and in silico modeling will lead to the establishment of cost-effective and time-efficient in silico models for the prediction of the safety of unknown drugs.

Effectiveness of intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine: An in silico pharmacological model

Objective:To explore the efficacy of intermittent preventive treatment in pregnancy(IPTp)with sulfadoxine and pyrimethamine(SP)against sensitive parasites.Methods:A pharmacological model was used to investigate the effectiveness of the previous recommended at least two-dose regimen,currently recommended three-dose regimen and 4,6,8-weekly regimens with specific focus on the impact of various nonadherence patterns in multiple transmission settings.Results:The effectiveness of the recommended three-dose regimen is high in all the transmission intensities,i.e.>99%,98%and 92%in low,moderate and high transmission intensities respectively.The simulated 4 and 6 weekly IPTp-SP regimens were able to prevent new infections with sensitive parasites in almost all women(>99%)regardless of transmission intensity.However,8 weekly interval dose schedules were found to have 71%and 86%protective efficacies in high and moderate transmission areas,respectively.It highlights that patients are particularly vulnerable to acquiring new infections if IPTp-SP doses are missed.Conclusions:The pharmacological model predicts that full adherence to the currently recommended three-dose regimen should provide almost complete protection from malaria infection in moderate and high transmission regions.However,it also highlights that patients are particularly vulnerable to acquiring new infections if IPTp doses are spaced too widely or if doses are missed.Adherence to the recommended IPTp-SP schedules is recommended.

Synthesis, in vitro antitumor activity and molecular modeling studies of a new series of benzothiazole Schiff bases

A new series of benzothiazole Schiff bases 3–29 was synthesized and screened for antitumor activity against cervical cancer（Hela） and kidney fibroblast cancer（COS-7） cell lines. Results indicated that compounds 3, 14, 19, 27 and 28 have promising activity against Hela cell line with IC50 values of 2.41,3.06, 6.46, 2.22 and 6.25 mmol/L, respectively, in comparison to doxorubicin as a reference antitumor agent（IC50 2.05 mmol/L）. In addition, compound 3 displayed excellent activity against COS-7 cell line with IC50 value of 4.31 mmol/L in comparison to doxorubicin（IC50 3.04 mmol/L）. In the present work,structure based pharmacophore mapping, molecular docking, protein-ligand interaction, fingerprints and binding energy calculations were employed in a virtual screening strategy to identify the interaction between the compounds and the active site of the putative target, EGFR tyrosine kinase. Molecular properties, toxicity, drug-likeness, and drug score profiles of compounds 3, 14, 19, 27, 28 and 29 were also assessed.

Investigation of transient and heterogeneous micro-climate around a human body in an enclosed personalized work environment

Heterogeneous distribution of indoor environmental quality is known to have a great impact on human health,comfort,and productivity.A personalized work environment,that creates a localized and independent environ-ment with capsules or partitions,is being developed worldwide to provide workers with a space that enables undisturbed concentration on studying and working.However,the minimized interior space of a personalized work environment can immediately cause adverse health impacts for occupant if the air quality and thermal en-vironment in the personalized work environment is not controlled appropriately.Particularly,constant breathing can sharply increase the CO 2 concentrations in an interior space with an insufficient ventilation rate.In order to design a healthy and comfortable indoor environment,especially in a personalized work environment,it is important to predict precisely and comprehensively the transient and heterogeneous structure of the indoor envi-ronment formed around a human body.With this background,we have developed an in silico human model that integrates a computational human model(virtual manikin combined with thermoregulation models)and respi-ratory model(virtual airway)for estimating indoor environmental quality,targeting the microclimate around a human body and breathing zone with high accuracy.In this study,we report the applicability of a comprehensive in silico human model to estimate the environ-mental quality in a personalized work environment.A coupled analysis of heat and contaminant transfer with computational fluid dynamics was conducted targeting the space around the in silico human model installed in a virtual personalized work environment.The informative data including human thermal comfort and breathing air quality were obtained,potentially forming the basis for the development of a digital twin of the personalized work environment and contributing to the design of a healthy,comfortable,and productive personalized work environment.