Hierarchical semantic composition of biosimulation models using bond graphs

Simulating complex biological and physiological systems and predicting their behaviours under different conditions remains challenging. Breaking systems into smaller and more manageable modules can address this challenge, assisting both model development and simulation. Nevertheless, existing computational models in biology and physiology are often not modular and therefore difficult to assemble into larger models. Even when this is possible, the resulting model may not be useful due to inconsistencies either with the laws of physics or the physiological behaviour of the system. Here, we propose a general methodology for composing models, combining the energy-based bond graph approach with semantics-based annotations. This approach improves model composition and ensures that a composite model is physically plausible. As an example, we demonstrate this approach to automated model composition using a model of human arterial circulation. The major benefit is that modellers can spend more time on understanding the behaviour of complex biological and physiological systems and less time wrangling with model composition.     

COVID-19-related coagulopathy: A review of pathophysiology and pharmaceutical management

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of β-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.     

Cadmium and lead in rice grains and wheat breads in Isfahan (Iran) and human health risk assessment

This study was conducted to survey the levels of cadmium (Cd) and lead (Pb) in the main foods of Isfahan province (central Iran). The rice grains and wheat breads were collected from Isfahan city and villages around the Isfahan and Mobarakeh Steel companies. The food samples were wet-ashed by heating in the presence of concentrated nitric acid and hydrogen peroxide. The concentrations of Cd and Pb were determined by inductively coupled plasma-optical emission spectrometer (ICP-OES). The potential exposure risks were then estimated. Levels of Cd in the rice grains and Pb in the investigated foods (except Sangak beard) were above the maximum levels as set by the Codex Alimentarius and National standards of Iran. The wheat bread samples in Isfahan city and Mobarakeh Steel regions presented higher estimated weekly intake (EWI) of Pb (40.93 and 35.35 µg kg^–1 body weight, respectively) compared to other foods. The EWI for Cd and Pb in most samples was considerably above than the provisional tolerable weekly intake. In most cases, the target hazard quotients values were above one and consequently the consumption of foods in the investigated regions was a potentially serious health risk caused by exposure to the crops contaminated with Cd and Pb.     

Mitotic recombination and segregation of satellites in Bloom's syndrome

Mitotic recombination in satellite stalks — a phenomenon often difficult to distinguish from satellite association — was studied in a sister and a brother with Bloom's syndrome. Segregation after recombination was analyzed in the lymphocytes of the sister who had Q-bright satellites. Her cells varied greatly both in regard to the acrocentrics which displayed Q-bright satellites and the number of such satellites per cell. In 58 cells a total of 31 different patterns were seen. In 83 cells of 6 controls who also had Q-bright satellites on at least one acrocentric chromosome, not one cell was found in which the pattern differed from that characteristic of the person. Obviously exchanges between satellite stalks in patients with Bloom's syndrome are fairly frequent (estimated lower limit 6/1000) and very rare in persons who do not have this syndrome (estimated 0.1/1000).     

Polyethylenimine: A new differentiation factor to endothelial/cardiac tissue

Among different tissues, endothelial/cardiac types require specific factors to promote myocardial regeneration after occurred injuries. Herein, cardiac stem cells (CSCs) as the major cell population that involved in cardiovascular repair were selected to study the role of polyethyleneimine (PEI) agent on endothelial differentiation. After preparation of electrospun network of PEI with polyacrylonitrile, the related characterizations were carried out including scanning electron microscope (SEM), field-emission SEM, water contact angle, Fourier transform infrared spectroscopy and mechanical properties. Also, the release kinetic of the corresponding agent was studied up to 7 days. The cell differentiation studies were done in the following with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, Real-time polymerase chain reaction and immunostaining method. The whole obtained results approved the higher differentiation of CSCs into endothelial/cardiac cells. Finally, it is recommended that the PEI delivering increases the healing potency of CSCs and accordingly the regeneration speed of damaged cardiovascular tissue would be improved.     

Endothelins and their receptors in embryo implantation

As a critical stage of pregnancy, the implantation of blastocysts into the endometrium is a progressive, excessively regulated local tissue remodeling step involving a complex sequence of genetic and cellular interplay executed within an optimal time frame. For better understanding the causes of infertility and, more importantly, for developing powerful strategies for successful implantations and combating infertility, an increasing number of recent studies have been focused on the identification and study of newly described substances in the reproductive tree. The endothelins (ET), a 21-aminoacidic family of genes, have been reported to be responsible for the contraction of vascular and nonvascular smooth muscles, including the smooth muscles of the uterus. Therefore, this review aims to comprehensively discuss the physiological role of endothelins and signaling through their receptors, as well as their probable involvement in the implantation process.