IN VITRO EVALUATION OF IBUPROFEN HOT-MELT EXTRUDED PELLETS EMPLOYING DIFFERENT DESIGNS OF THE FLOW THROUGH CELL

Objective: Hot-melt extrusion technique (HME) was used to prepare a sustained release (SR) multiparticulate oral dosage form (pellets) containing Ibuprofen (IBU). Prepared IBU-HME pellets were in vitro evaluated by flow-through cell dissolution tester (FTC, USP Apparatus #4) using different flow conditions and FTC designs. Methods: In this study, Sucroester®WE15 was used as the polymeric carrier to prepare two different IBU loadings (60 % and 30 % w/w). In order to optimize the FTC conditions, different cell sizes, pellets loading and hydrodynamic conditions of FTC on IBU release rate from pellets were proposed. Results: The results showed that the IBU release rate was increased in the larger cell than the small cell. In addition, laminar flow showed more reproducible results than turbulent flow. It was found that the large cell with laminar flow rate and homogeneous mixing of the pellets with glass beads was the optimum conditions for in vitro evaluation of these preparations. Conclusion: Improper methods of sample loading as well as cell size may result in confusing or erroneous data if not analyzed carefully. Therefore, it might be critical to choose a specific cell design of the FTC for in vitro evaluation of pellets to obtain reliable and discriminative results reflecting the major as well as minor formulation variables

Phylogenetic characterization of two echinoid species of the southeastern Mediterranean, off Egypt

AbstractIn this study we investigated the phylogenetics of two sea urchin species, Arbacia lixula and Paracentrotus lividus from the Mediterranean Sea. Specimens were collected from the east coast of Alexandria City, Egypt. Pigmentation examination showed four sympatric color morphotypes (black, purple, reddish brown, and olive green). Mitochondrial DNA was extracted from specimens and mitochondrial cytochrome oxidase subunit I (COI) and 16S ribosomal RNA (16S) were sequenced. The results showed that all black specimens constituted the species A. lixula. All other colors belonged to P. lividus, with no apparent differentiation between color morphotypes. Moreover, P. lividus showed high haplotype diversity (COI; H=0.9500 and 16S; H=0.8580) and low values of nucleotide diversity (COI; π=0.0075 and 16S; π=0.0049), indicating a high degree of polymorphism within this species. This study represents the first attempt at DNA barcoding of echinoid species in the southeast Mediterranean off the Egyptian coast, and will provide a base for future phylogenetic analyses

A review on phytochemical, pharmacological and ethnopharmacological aspects of genus Trichodesma

The genus Trichodesma belongs to the family Boraginaceae. The plants of this genus are widely distributed in tropical and subtropical regions of Africa, Asia, and Australia. Phytochemically, scientific reports on Trichodesma species so far revealed more than one hundred compounds from this genus, including hydrocarbons, phenols, flavonoids, sterols, terpenes and alkaloids have been isolated or identified. Medicinally, various reported biological activities of Trichodesma such as antimicrobial, antiparasitic, cytotoxic, anti-infection, antioxidant, anti-inflammatory, anti-irritant, antidiarrheal, antispasmodic, antimalarial, analgesic, antipyretic, anti-diabetic, diuretic, and hepatoprotective effects were discussed in this review otherwise. Also, the ethnopharmacological effects of this genus were reviewed. Among all the Trichodesma species, T. indicum is regarded as the most important one regarding its pharmacological values. The volatile oil of T. africanum L. showed high antioxidant activity

Systems Biology Approaches Toward Understanding Primary Mitochondrial Diseases

Primary mitochondrial diseases form one of the most common and severe groups of genetic disease, with a birth prevalence of at least 1 in 5000. These disorders are multi-genic and multi-phenotypic (even within the same gene defect) and span the entire age range from prenatal to late adult onset. Mitochondrial disease typically affects one or multiple high-energy demanding organs, and is frequently fatal in early life. Unfortunately, to date there are no known curative therapies, mostly owing to the rarity and heterogeneity of individual mitochondrial diseases, leading to diagnostic odysseys and difficulties in clinical trial design. This review aims to discuss recent advances and challenges of systems approaches for the study of primary mitochondrial diseases. Although there has been an explosion in the generation of omics data, few studies have progressed toward the integration of multiple levels of omics. It is evident that the integration of different types of data to create a more complete representation of biology remains challenging, perhaps due to the scarcity of available integrative tools and the complexity inherent in their use. In addition, “bottom-up” systems approaches have been adopted for use in the iterative cycle of systems biology: from data generation to model prediction and validation. Primary mitochondrial diseases, owing to their complex nature, will most likely benefit from a multidisciplinary approach encompassing clinical, molecular and computational studies integrated together by systems biology to elucidate underlying pathomechanisms for better diagnostics and therapeutic discovery. Just as next generation sequencing has rapidly increased diagnostic rates from approximately 5% up to 60% over two decades, more recent advancing technologies are encouraging; the generation of multi-omics, the integration of multiple types of data, and the ability to predict perturbations will, ultimately, be translated into improved patient care

A review on phytochemical, pharmacological and ethnopharmacological aspects of genus Trichodesma

333-347The genus Trichodesma belongs to the family Boraginaceae. The plants of this genus are widely distributed in tropical and subtropical regions of Africa, Asia, and Australia. Phytochemically, scientific reports on Trichodesma species so far revealed more than one hundred compounds from this genus, including hydrocarbons, phenols, flavonoids, sterols, terpenes and alkaloids have been isolated or identified. Medicinally, various reported biological activities of Trichodesma such as antimicrobial, antiparasitic, cytotoxic, anti-infection, antioxidant, anti-inflammatory, anti-irritant, antidiarrheal, antispasmodic, antimalarial, analgesic, antipyretic, anti-diabetic, diuretic, and hepatoprotective effects were discussed in this review otherwise. Also, the ethnopharmacological effects of this genus were reviewed. Among all the Trichodesma species, T. indicum is regarded as the most important one regarding its pharmacological values. The volatile oil of T. africanum L. showed high antioxidant activity

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis.</p> <p>Methods</p> <p>Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl_<b>4</b>, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups.</p> <p>Results</p> <p>Histopathological examination of liver tissue from animals which received DENA-CCl₄only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated <it>β-catenin</it>, proliferating cell nuclear antigen (<it>PCNA</it>), <it>cyclin D </it>and <it>survivin </it>genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect.</p> <p>Conclusions</p> <p>Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.</p

AI-based investigation and mitigation of rain effect on channel performance with aid of a novel 3D slot array antenna design for high throughput satellite system

Rain attenuation poses a significant challenge for high-throughput communication systems. In response, this paper introduces an artificial intelligence (AI) model designed for predicting and mitigating rain-induced impairments in high-throughput satellite (HTS) to land channels. The model is based on three AI algorithms developed using 3D antenna design to characterize, analyze, and mitigate rain induced attenuation, optimizing channel quality specifically in the United Arab Emirates (UAE). The study evaluates various parameters, including rain-specific attenuation, effective slant path through rain, rain induced attenuation, signal carrier-to-noise ratio, and symbol error rate, for five conventional modulation schemes: Quadrature Phase-Shift Keying (QPSK), 8-Phase Shift Keying (8-PSK), 16-Quadrature Amplitude Modulation (16-QAM), 32-QAM, and 64-QAM. Additionally, the paper introduces a new database detailing rain-induced attenuation in HTS channels in the UAE at different frequencies using measured rainfall intensities. The paper concludes by proposing a smart antenna design with a frequency diversity technique for fade mitigation. Results indicate that rain-induced attenuation varies significantly based on rainfall rate and frequency. Specifically, at 25 GHz and a rainfall rate of 100 mm/h, the rain-induced attenuation can reach as high as 15 dB, resulting in a significant decline in signal quality and link performance. The proposed AI model demonstrates the ability to intelligently predict rain-induced attenuation and channel quality for various rainfall rates and frequencies. This information can be valuable for optimizing satellite link design and operation, ultimately enhancing the reliability and quality of satellite communications. The proposed two-slot smart antenna design utilizes frequency diversity to effectively mitigate rain attenuation, contributing to the overall improvement of link reliability and quality

Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV

A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV