Miniaturized culture systems of hepatic cells are emerging as a strong tool facilitating studies related to liver diseases and drug discovery. However, the experimental optimization of various parameters involved in the operation of these systems is time-consuming and expensive. Hence, developing numerical tools predicting the function of such systems can significantly reduce the associated cost. In this paper, a perfusion-based three dimensional (3D) bioreactor comprising encapsulated human liver hepatocellular carcinoma (HepG2) spheroids are analyzed. The flow and mass transfer equations for oxygen as well as different metabolites such as albumin, glucose, glutamine, ammonia, and urea were solved in three different domains, i.e., free flow, hydrogel, and spheroid porous media sections. Since the spheroids were encapsulated inside the hydrogel, shear stress imposed on them were found to be less than tolerable thresholds. The predicted cumulative albumin concentration over the 7 days of culture period showed a good agreement with the experimental data. Based on the critical role of oxygen supply to the hepatocytes, a parametric study was performed and the effect of various parameters was investigated. Results illustrated that convection mechanism was the dominant transport mechanism in the main-stream section contrary to the intra spheroids parts where the diffusion was the prevailing transport mechanism. In the hydrogel parts, the rate of diffusion and convection mechanisms were almost identical. As expected, higher perfusion rate would provide high oxygen level for the cells and, smaller spheroids with a diameter of 100 μm were at the low risk of hypoxic conditions due to short diffusive oxygen penetration depth. Numerical results evidenced that spheroids with diameter size >200 μm at low porosities (ε = 0.2–0.3) were at risk of oxygen depletion, especially at locations near the core center. Therefore, these results could be beneficial in preventing hypoxic conditions during in vitro experiments. The presented numerical model provides a numerical platform which can help researchers to design and optimize complex bioreactors and obtain numerical indexes of the main metabolites in a very short time prior to any fabrications. Such numerical indexes can be helpful in certifying the outcomes of forensic investigations.

Introduction. Leishmaniasis is a neglected tropical and subtropical disease caused by over 20 protozoan species. Hypothesis. Treatment of this complex disease with traditional synthetic drugs is a major challenge worldwide. Natural constituents are unique candidates for future therapeutic development. Aim. This study aimed to assess the in vivo anti-leishmanial effect of the Gossypium hirsutum extract, and its fractions compared to the standard drug (Glucantime, MA) in a murine model and explore the mechanism of action. Methodology. Footpads of BALB/c mice were infected with stationary phase promastigotes and treated topically and intraperitoneally with G. hirsutum extract, its fractions, or Glucantime, 4 weeks post-infection. The extract and fractions were prepared using the Soxhlet apparatus with chloroform followed by the column procedure. Results. The crude extract significantly decreased the footpad parasite load and lesion size compared to the untreated control group (P<0.05), as revealed by dilution assay, quantitative real-time PCR, and histopathological analyses. The primary mode of action involved an immunomodulatory role towards the Th1 response in the up-regulation of IFN-γ and IL-12 and the suppression of IL-10 gene expression profiling against cutaneous leishmaniasis caused by Leishmania major. Conclusion. This finding suggests that the extract possesses multiple combinatory effects of diverse bioactive phytochemical compositions that exert its mechanisms of action through agonistic-synergistic interactions. The topical extract formulation could be a suitable and unique candidate for future investigation and pharmacological development. Further studies are crucial to evaluate the therapeutic potentials of the extract alone and in combination with conventional drugs using clinical settings.

Hematology tests, considered as an initial step in the patient diagnostic process, require laboratory equipment and technicians which is a time- and labor-consuming procedure. Such facilities may be available in a few central laboratories in under-resourced countries. The growing need for low cost and rapid diagnostic tests contributes to point-of-care (POC) medical diagnostic devices providing convenient and rapid test tools particularly in areas with limited medical resources. In the present study, a comprehensive numerical simulation of a POC blood cell separation device (POC-BCS) has been modeled using a finite element method. Tag-less separation of blood cells, i.e., platelets, red blood cells, and white blood cells, was carried out using standing surface acoustic waves (SSAWs) generated by interdigital transducers (IDTs) located at lateral sides of the microfluidic channel. Blood sample intake along with sheath flow was introduced via two symmetrical tilted angle inlets and a middle inlet, respectively. Superposition of acoustic radiation force applied by SSAWs accompanied by drag force caused by medium flow drove the blood cells toward different path lines correlated to their size. White blood cells were sorted out in the middle outlet and red blood cells and platelets were sorted out through the separate locations of the side outlets. Each cell was then guided to their respected visualization chamber for further image processing analysis. The results of the presented numerical study would be very promising in designing and optimizing the POC blood testing device.

Background and Aim: Neonates of diabetic mothers are more prone to congenital heart diseases than others. These abnormalities are the leading cause of fetal death in diabetic neonates. Therefore, the determination of a screening method and evaluation of its value seems necessary in such neonates. The present study investigated the various ...

Ammonia detoxification is one of the main functions of the liver results in production of urea. In this study ammonia elimination and urea production was simulated in a microchannel mimicking the hepatic porto central axis. Navier- Stockes equations along with convection equations were solved for the related species in the entire domain. Since the Reynolds number was small (~1) the fluid flow regime was laminar. Urea cycle was modeled regarding its four main enzymes. Twelve rate equations were also solved in order to obtain the concentration of each metabolites participating in urea cycle. Concentration of the urea reached its maximum ca. 1.2e-5 M at the end of the channel which is in good agreement with experimental results.

One of the important functionality of liver cells is ammonia detoxification and urea production. In this study, a numerical model of urea cycle in hepatocytes have been developed. Navier Stokes along with convection equations have been employed to study the process of ammonia elimination and urea production using a microfluidic channel.The concentration of urea and ammonia throughout the channel were obtained. Furthermore, the urea cycle was modeled regarding its four main enzymes. This resulted in twelve rate equations which were solved to determine the concentration of each metabolites participating in the urea cycle. Application of results were implied to common disorders such as Hyperammonemia type I and II and argininosuccinicaciduria type I and II. Result of this study indicated that there is 80% of reduction in concentration of Citrulline, Argininosuccinate, Arginin, Carbamoyl phosphate, Phosphate and Fumarate in hyperammonemia type II. A 10 fold increase of Argininosuccinate concentration was observed in both argininosuccinicaciduria I and II. The predicted result may be useful in better understanding and control of metabolite deficiencies in patient abnormalities.