An integrated computational study for screening medicinal plant phytochemicals for possible inhibitors of the human bile salt exporter pump

Background: The primary carrier of bile acids in humans is the bile salt export pump (BSEP). which are crucial for the digestion and absorption of fat. Type 2 progressive familial intrahepatic cholestasis (PFIC-2), which is brought on when BSEP is suppressed and causes a decrease in bile flow and a buildup of cytotoxic bile salts in the liver, is one of the main causes of cholestasis in Saudi Arabia. Elucidate the inhibitory potential with minimal or no adverse effects.Methods: The structure (6LR0) was downloaded from the PDB. Protein active sites were anticipated because these are pockets where ligands can bind and perform reactions to treat an infection. The PubChem zinc and mpd3 databases were used to get the ligands' structures. Molecular operating environment (MOE) was utilized to perform molecular docking of 1600 phytochemicals against BSEP. LigX was used to observe the docking hits for interaction analysis. Results: identification of 4 potential candidates for binding to the BSEP active site. then, Protox II-was used to forecast toxicity for the selected hits. Molecular dynamics simulations were also used to assess the binding complex's stability in water for 100 nanoseconds. The strong binding affinity of high-ranked drugs was predicted by our molecular docking and simulation.Conclusions: This approach could be useful in determining the efficiency of a therapeutic molecule in the therapy of the BSEP. The aim of this research is to identify novel -BSEP drug targets, and in future in vitro and in vivo research could prove its clinical efficiency

The role of transthyretin in oligodendrocyte maturation

Transthyretin (TTR) is a protein that binds and distributes thyroid hormones (THs). While TTR has long been known to be synthesised in the liver and in the choroid plexus of the brain, recent investigation have revealed that it is also synthesised by different neuronal cells, such as neurons, astrocytes, transit amplifying cells and Schwann cells. To the best of our knowledge, the roles of TTR synthesised by these neuronal cells have not yet been clearly elucidated. The TTR synthesised by the choroid plexus has a role in moving THs from the blood to the brain and in distributing THs in the cerebrospinal fluid. Previously two reports suggested that TTR null mice were hypothyroid in the central nervous system compared with wild-type mice. Therefore, we decided to investigate a well-characterised TH-dependent process in the brains of wild type and TTR null mice: the maturation of oligodendrocyte precursor cells into oligodendrocytes that myelinate axons of neurons in the corpus callosum and anterior commissure of the brain. Accordingly, four different age groups were chosen (P7, P14, P21 and weeks) to investigate key time points for oligodendrocyte maturation in the brains of wild type and TTR null mice. Interestingly, in complete contrast to what we expected, we observed hypermyelination in the brains of the TTR null mice during development. This hypermyelination phenotype was synchronous with a substantial increase in the density of oligodendrocytes in the medial area of the corpus callosum and in the anterior commissure during development from P7 until 12 weeks of age. Thus, we studied the maturation of oligodendrocyte precursor cells (OPCs) isolated from the cortices of P7 and E18 mouse brains. Interestingly, we found that the absence of TTR enhanced the proliferation and migration of the OPCs, as well as decreased the rate of apoptosis and affected the progression of the OPC cycle. Furthermore, the NSCs isolated from the subventricular zone of P21 TTR null mice showed that the absence of TTR promoted NSC differentiation into glial lineages. We have also shown, for the first time, that oligodendrocytes synthesise TTR, and the TTR synthesised by OPCs is not secreted. This is in contrast to TTR synthesised by the liver and choroid plexus (which is secreted). Taken together, these data indicate that TTR has a role in the regulation of myelination; where the absence of TTR accelerates NSC and OPC maturation and enhances myelination. Therefore, We hypothesised that endogenous TTR, which has been shown to be synthesised by OPCs, holds T4 in the cytosol of the cells; this controls the level of T4 available for deiodinated to T3, the functional form of THs. Elucidation the mechanism of the regulatory role of TTR in NSC and OPC biology could lead to potential therapeutic strategies for treatment of demyelination disease such as Multiple Sclerosis

Determination of VCSEL laser structures based InGaAsN / GaAs for fiber optic communication

The objective of this work is to study the electronic properties of GaInNAs semiconductor alloy in order to obtain quantum well GaInNAs/GaAs structures emitting at wavelengths around 1.3 μm to 1.55 μm, to use as active layers in laser diodes for fiber-optic communication. The incorporation of nitride in the GaInAs alloy gave very particular and attractive properties, the most important being the reduction of the energy of band gap. The anticrossing band model describes these properties; using this model, we determined the effect of nitrogen on the conduction band and the energy gap. We observed that the incorporation of nitrogen decreases the energy of the band gap and increases the emission wavelength. We found a compromise between the concentrations of In and N in order to determine the optimal structures for use in fiber-optic communication

Myeloid-Derived Suppressor Cells and Pancreatic Cancer: Implications in Novel Therapeutic Approaches

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating human malignancy with poor prognosis and low survival rates. Several cellular mechanisms have been linked with pancreatic carcinogenesis and also implicated in inducing tumor resistance to known therapeutic regimens. Of various factors, immune evasion mechanisms play critical roles in tumor progression and impeding the efficacy of cancer therapies including PDAC. Among immunosuppressive cell types, myeloid-derived suppressor cells (MDSCs) have been extensively studied and demonstrated to not only support PDAC development but also hamper the anti-tumor immune responses elicited by therapeutic agents. Notably, recent efforts have been directed in devising novel approaches to target MDSCs to limit their effects. Multiple strategies including immune-based approaches have been explored either alone or in combination with therapeutic agents to target MDSCs in preclinical and clinical settings of PDAC. The current review highlights the roles and mechanisms of MDSCs as well as the implications of this immunomodulatory cell type as a potential target to improve the efficacy of therapeutic regimens for PDAC

Characteristics and anticancer properties of Sunitinib malate-loaded poly-lactic-co-glycolic acid nanoparticles against human colon cancer HT-29 cells lines

Purpose: To develop poly-lactic-co-glycolic acid (PLGA) -based nanoparticles (NPs) for the delivery of sunitinib malate (STM) to colon cancer cells.Methods: Three different formulations (F1 – F3) were developed by nano-precipitation technique using various concentrations of PLGA. The NPs were evaluated for particle size, polydispersity index, zeta potential, drug entrapment, and drug loading, using differential scanning calorimetry (DSC), Fouriertransform infrared spectroscopy (FTIR), x-ray diffraction (XRD), and scanning electron microscopy (SEM). Furthermore, in vitro drug release and anticancer studies were carried out on the formulations.Results: Among the three NPs, optimized NP (F3) of STM was chosen for in vitro anti-cancer study against H-29 human colon cancer cells lines based on its particle size (132.9 nm), PDI (0.115), zeta potential (-38.12 mV), entrapment efficiency (52.42 %), drug loading (5.24 %), and drug release (91.26 % in 48 h). A significant anti-cancer activity of the optimized NPs was observed, relative to free STM.Conclusion: These findings suggest that STM-loaded NPs possess significant anti-cancer activity against human colon cancer HT-29 cells lines.Keywords: Sunitinib malate, Poly-lactic-co-glycolic acid, Nanoparticles, Colon cance

How is Learning Fluctuating? FutureLearn MOOCs Fine-Grained Temporal Analysis and Feedback to Teachers

Data-intensive analysis of massive open online courses (MOOCs) is popular. Researchers have been proposing various parameters conducive to analysis and prediction of student behaviour and outcomes in MOOCs, as well as different methods to analyse and use these parameters, ranging from statistics, to NLP, to ML, and even graph analysis. In this paper, we focus on patterns to be extracted, and apply systematic data analysis methods in one of the few genuinely large-scale data collection of 5 MOOCs, spread over 21 runs, on FutureLearn, a UK-based MOOCs provider, that, whilst offering a broad range of courses from many universities, NGOs and other institutions, has been less evaluated, in comparison to, e.g., its American counterparts. We analyse temporal quiz solving patterns; specifically, the less explored issue on how the first number of weeks of data predicts activities in the last weeks; we also address the classical MOOC question on the completion chance. Finally, we discuss the type of feedback a teacher or designer could receive on their MOOCs, in terms of fine-grained analysis of their material, and what personalisation could be provided to a student

Assessment of knowledge, attitude and practice of diabetic people in Najran, Kingdom of Saudi Arabia

Background: This cross-sectional hospital based study aimed at determining the level of knowledge, attitude and practice of diabetes among local people of Najran, Saudi Arabia.Methods: We aimed to investigate the levels of knowledge, attitude and practice among diabetic people in Najran area.Results: 10% of the participants scored >7, 28% scored >5 and 62% scored 5 and less in Knowledge questionnaire. None [0.00%] of the participants scored 7 or more out of the attitude questionnaire. 100% of the participants scored 5 and less out of 12. 100% of the participants scored >6 and 0% scored 12 or more in the practice questionnaire.Conclusions: Our study revealed that the level of knowledge, attitude and practice of diabetes in the area of Najran is very poor. We suggest that a structured educational program to be adopted by the health authorities in Saudi Arabia