Sugar Alcohols Have a Key Role in Pathogenesis of Chronic Liver Disease and Hepatocellular Carcinoma in Whole Blood and Liver Tissues.

The major risk factors for hepatocellular carcinoma (HCC) are hepatitis C and B viral infections that proceed to Chronic Liver Disease (CLD). Yet, the early diagnosis and treatment of HCC are challenging because the pathogenesis of HCC is not fully defined. To better understand the onset and development of HCC, untargeted GC-TOF MS metabolomics data were acquired from resected human HCC tissues and their paired non-tumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to CLD (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The GC-TOF MS data yielded 194 structurally annotated compounds. The most strikingly significant alteration was found for the class of sugar alcohols that were up-regulated in blood of HCC patients compared to CLD subjects (p < 2.4 × 10-12) and CLD compared to healthy controls (p = 4.1 × 10-7). In HCC tissues, sugar alcohols were the most significant (p < 1 × 10-6) class differentiating resected HCC tissues from non-malignant hepatic tissues for all HCC patients. Alteration of sugar alcohol levels in liver tissues also defined early-stage HCC from their paired non-malignant hepatic tissues (p = 2.7 × 10-6). In blood, sugar alcohols differentiated HCC from CLD subjects with an ROC-curve of 0.875 compared to 0.685 for the classic HCC biomarker alpha-fetoprotein. Blood sugar alcohol levels steadily increased from healthy controls to CLD to early stages of HCC and finally, to late-stage HCC patients. The increase in sugar alcohol levels indicates a role of aldo-keto reductases in the pathogenesis of HCC, possibly opening novel diagnostic and therapeutic options after in-depth validation

Effect of ABCB1 (3435C>T) and CYP3A5 (6986A>G) genes polymorphism on tacrolimus concentrations and dosage requirements in liver transplant patients

AbstractBackgroundTacrolimus (TAC) is an immunosuppressant used in organtransplant recipients. It is a substrate of drug transporter ABCB1 as well as of cytochrome P4503A (CYP3A).AimTo assess the influence of ABCB1 (3435 C>T) and CYP3A5 (6986 A>G) genes polymorphism of liver transplant donors and recipients on blood level and dose requirements of oral tacrolimus, to help in designing an individualized tacrolimus regimen for liver transplant recipients.Subjects and methodsForty-eight adult liver transplant recipients and their matching living donors were prospectively enrolled in this study. TAC doses and blood concentration were recorded on 1st, 2nd and 3rd days, after 1 and 2weeks, and at 1, 3 and 6months postoperatively using ultra performance liquid chromatography Tandem mass spectrometry. Genotyping of ABCB1 (3435C>T) and CYP450 3A5 (6986A>G) genes were determined by Polymerase chain reaction followed by restriction fragment length polymorphism and by TaqMan allelic discrimination assay techniques, respectively.ResultsOf the enrolled 48 recipients, CYP3A5∗3/∗3 and CYP3A5∗1/∗3 genotypes were detected in 18 (37.5%) and in 20 (41.7%) recipients respectively, while ABCB1 CT and TT genotypes were detected in16 (33.3%) and 10 (20.8%) recipients respectively. TAC daily dose was significantly increased among recipients carrying ABCB1 CC genotype compared to recipients carrying CT and TT genotypes during and after the first month postoperatively. During 1st, 2nd days and 2weeks post-transplant, a significant increase of TAC concentration / dose ratio was observed among recipients carrying CYP3A5∗3∗3 genotype than recipients carrying 1∗1∗ and 1∗3∗ genotypes, and among recipients carrying ABCB1 CT and TT genotypes compared to those carrying CC genotype on 1st, 3rd days and at 3months postoperatively.ConclusionsABCB1 and CYP3A5 genetic polymorphism is one of the factors influencing TAC pharmacokinetics, screening for these SNPs prior to liver transplantation might be helpful for individualization of tacrolimus treatment

Microfluidic-Based Formulation of Essential Oils-Loaded Chitosan Coated PLGA Particles Enhances Their Bioavailability and Nematocidal Activity

In this study, poly (lactic-co-glycolic) acid (PLGA) particles were synthesized and coated with chitosan. Three essential oil (EO) components (eugenol, linalool, and geraniol) were entrapped inside these PLGA particles by using the continuous flow-focusing microfluidic method and a partially water-miscible solvent mixture (dichloromethane: acetone mixture (1:10)). Encapsulation of EO components in PLGA particles was confirmed by Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction, with encapsulation efficiencies 95.14%, 79.68%, and 71.34% and loading capacities 8.88%, 8.38%, and 5.65% in particles entrapped with eugenol, linalool, and geraniol, respectively. The EO components’ dissociation from the loaded particles exhibited an initial burst release in the first 8 h followed by a sustained release phase at significantly slower rates from the coated particles, extending beyond 5 days. The EO components encapsulated in chitosan coated particles up to 5 μg/mL were not cytotoxic to bovine gut cell line (FFKD-1-R) and had no adverse effect on cell growth and membrane integrity compared with free EO components or uncoated particles. Chitosan coated PLGA particles loaded with combined EO components (10 µg/mL) significantly inhibited the motility of the larval stage of Haemonchus contortus and Trichostrongylus axei by 76.9%, and completely inhibited the motility of adult worms (p < 0.05). This nematocidal effect was accompanied by considerable cuticular damage in the treated worms, reflecting a synergistic effect of the combined EO components and an additive effect of chitosan. These results show that encapsulation of EO components, with a potent anthelmintic activity, in chitosan coated PLGA particles improve the bioavailability and efficacy of EO components against ovine gastrointestinal nematodes

Investigation of the impact of Photovoltaic Sizing and Siting Modeling on Micro-grids Energy Management Optimization

The modeling of micro-grid’s PV units’ and loads’ size and distribution along its network could severely affect the accuracy of power losses calculation and; thus the amount of energy to be imported from the main-grid to balance the load. Also, it will affect the micro-grid’s optimal energy management results. Therefore, a comprehensive analysis is carried out to assess the impact of the PV’s and the load’s sizing and sitting (either lumped or distributed). Four case studies are carried out to illustrate the impact of the modeling on the micro-grid’s losses and the imported energy from the main-grid and their costs. The obtained results are used to implement the proposed energy management two-single objective optimization functions applying Genetic Algorithm. Then, a fifth case study is carried out to optimize the micro-grid energy management process through an optimal chagrining - discharging scheduling of a storage module. The obtained results, recommendations, and evaluations for choosing a proper sizing and siting modeling and the chagrining - discharging scheduling of a storage module under seasonal variations are reported and discussed

Recent Advances in Low-Dimensional Metal Oxides via Sol-Gel Method for Gas Detection

Low-dimensional metal oxides have drawn significant attention across various scientific domains due to their multifaceted applications, particularly in the field of environment monitoring. Their popularity is attributed to a constellation of unique properties, including their high surface area, robust chemical stability, and remarkable electrical conductivity, among others, which allow them to be a good candidate for detecting CO, CO2, H2, NH3, NO2, CH4, H2S, and volatile organic compound gases. In recent years, the Sol-Gel method has emerged as a powerful and versatile technique for the controlled synthesis of low-dimensional metal oxide materials with diverse morphologies tailored for gas sensing applications. This review delves into the manifold facets of the Sol-Gel processing of metal oxides and reports their derived morphologies and remarkable gas-sensing properties. We comprehensively examine the synthesis conditions and critical parameters governing the formation of distinct morphologies, including nanoparticles, nanowires, nanorods, and hierarchical nanostructures. Furthermore, we provide insights into the fundamental principles underpinning the gas-sensing mechanisms of these materials. Notably, we assess the influence of morphology on gas-sensing performance, highlighting the pivotal role it plays in achieving exceptional sensitivity, selectivity, and response kinetics. Additionally, we highlight the impact of doping and composite formation on improving the sensitivity of pure metal oxides and reducing their operation temperature. A discussion of recent advances and emerging trends in the field is also presented, shedding light on the potential of Sol-Gel-derived nanostructures to revolutionize the landscape of gas sensing technologies

Examining the influence of micro-grids topologies on optimal energy management systems decisions using genetic algorithm

Micro-grids’ Energy Management Systems (EMSs) are systems of tools used to monitor, control and optimize the generation, delivery, and/or consumption of energy within micro-grids and the imported energy from their main grids. Unfortunately, there is no single EMS that can be implemented to improve energy efficiency, reduce greenhouse gas emissions, decrease fuel usage, minimize the amount of imported energy from the main grid, and increase the use of renewable energy for all micro-grids at the same time. Therefore, the main concern of this paper is to investigate the impact of micro-grid’s topologies on developing an efficient micro-grid’s EMS and an optimization model using Genetic Algorithm (GA) that aim to optimally select the objective function that suits each individual micro-grid’s topology. Therefore, a comprehensive analysis is carried out taking into consideration three grid-connected micro-grids topologies; networks, loads profiles, embedded dispatchaple (biomass) and non-dispatchaple (PV) Distributed Generation (DG), storages elements, switching capacitors, and demand response. Three case studies (objective functions) are minimized; micro-grid’s energy loss, imported energy from the main grid, and CO2 emissions, to select the most optimal objective function that suits each individual micro-grid topology. The obtained results are reported, evaluated, and discussed. Keywords: Micro-grids, Genetic algorithm, Distributed generation, Energy management system

Biological Activity of Echinops spinosus on Inhibition of Paracetamol- Induced Renal Inflammation

This study was designed to evaluate the possible mechanisms through which Echinops Spinosus (ES) extract demonstrates nephroprotective effect on paracetamol (APAP)-induced nephrotoxicity in rat. Twenty-Four Swiss albino rats were divided into four groups (six rats each). Placebo group was orally administered sterile saline; APAP group received APAP (200 mg/kg/day i.p) daily; ES group was given orally ES extract (250 mg/kg); (APAP+ES) group: received APAP as for APAP group and administrated ES extract as for ES group. Pretreatment of methyl alcohol extract of ES reduced the protein expression of inflammatory parameters including cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) in kidney. It also reduced the mRNA gene expression of tumor necrosis factor-α (TNF-α) and Interleukin-1β (IL-1β). ES extract compensated deficits in the total antioxidant activity, suppressed lipid peroxidation and amended the APAP induced histopathological kidney alterations. Moreover, ES treatment restored the elevated levels of urea nitrogen in blood and creatinine in serum by acetaminophen. ES extract attenuated the acetaminophen-induced elevations in renal nitric oxide levels. We clarified that ES extract has the potential to defend kidney from APAP-induced inflammation, and protection mechanism might by through decreasing oxidative stress and regulating the inflammatory signaling pathway through modulating key signaling inflammatory biomarkers.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Influence of polymorphisms in candidate genes on carcass and meat quality traits in rabbits.

Candidate gene is a powerful approach to study gene-trait association and offers valuable information for genetic improvement using marker-assisted selection. The current work aimed to study the polymorphisms of four single nucleotide polymorphism (SNPs) at located growth hormone (GH), insulin-like growth factor-II (IGF-II), fat mass and obesity-associated (FTO), and insulin receptor substrate-1 (IRS-1) genes, and their association with the carcass, and meat quality traits in rabbits. The SNPs were genotyped using RFLP-PCR in New Zealand White and local Baladi rabbits. The results revealed that the heterozygous genotype was the most frequent in all cases, except for the FTO SNP in LB rabbits. There was a significant effect for GH genotypes on meat lightness after slaughter and hind-part weight. While, IGF-II mutation significantly affected slaughter, hot carcass, commercial carcass, and hind-part weights. The FTO SNP was associated with cooking loss and intramuscular fat weight, and the IRS-1 SNP was significantly associated with drip loss and intramuscular fat. Specific-breed effects were obtained for IGF-II SNP on cooking loss, and for the intramuscular fat. Although the results suggested that these mutations are useful candidate genes for selection, more research for detecting more variants associated with carcass and meat quality traits in rabbits are recommended

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a worldwide health problem. HCC patients show a 50% mortality within two years of diagnosis. To better understand the molecular pathogenesis at the level of lipid metabolism, untargeted UPLC MS&mdash;QTOF lipidomics data were acquired from resected human HCC tissues and their paired nontumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to chronic liver disease (CLD) (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The lipidomics data yielded 604 identified lipids that were divided into six super classes. Five-hundred and twenty-four blood lipids were found as significantly differentiated (p &lt; 0.05 and qFDR p &lt; 0.1) between the three study groups. In the blood of CLD patients compared to healthy control subjects, almost all lipid classes were significantly upregulated. In CLD patients, triacylglycerides were found as the most significantly upregulated lipid class at qFDR p = 1.3 &times; 10&minus;56, followed by phosphatidylcholines at qFDR p = 3.3 &times; 10&minus;51 and plasmalogens at qFDR p = 1.8 &times; 10-46. In contrast, almost all blood lipids were significantly downregulated in HCC patients compared to CLD patients, and in HCC tissues compared to nontumor hepatic tissues. Ceramides were found as the most significant lipid class (qFDR p = 1 &times; 10&minus;14) followed by phosphatidylglycerols (qFDR p = 3 &times; 10&minus;9), phosphatidylcholines and plasmalogens. Despite these major differences, there were also common trends in the transitions between healthy controls, CLD and HCC patients. In blood, several mostly saturated triacylglycerides showed a continued increase in the trajectory towards HCC, accompanied by reduced levels of saturated free fatty acids and saturated lysophospatidylcholines. In contrast, the largest overlaps of lipid alterations that were found in both HCC tissue and blood comparisons were decreased levels of phosphatidylglycerols and sphingolipids. This study highlights the specific impact of HCC tumors on the circulating lipids. Such data may be used to target lipid metabolism for prevention, early detection and treatment of HCC in the background of viral-related CLD etiology

Remodeling Lipids in the Transition from Chronic Liver Disease to Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a worldwide health problem. HCC patients show a 50% mortality within two years of diagnosis. To better understand the molecular pathogenesis at the level of lipid metabolism, untargeted UPLC MS-QTOF lipidomics data were acquired from resected human HCC tissues and their paired nontumor hepatic tissues (n = 46). Blood samples of the same HCC subjects (n = 23) were compared to chronic liver disease (CLD) (n = 15) and healthy control (n = 15) blood samples. The participants were recruited from the National Liver Institute in Egypt. The lipidomics data yielded 604 identified lipids that were divided into six super classes. Five-hundred and twenty-four blood lipids were found as significantly differentiated (p &lt; 0.05 and qFDR p &lt; 0.1) between the three study groups. In the blood of CLD patients compared to healthy control subjects, almost all lipid classes were significantly upregulated. In CLD patients, triacylglycerides were found as the most significantly upregulated lipid class at qFDR p = 1.3 × 10-56, followed by phosphatidylcholines at qFDR p = 3.3 × 10-51 and plasmalogens at qFDR p = 1.8 × 10-46. In contrast, almost all blood lipids were significantly downregulated in HCC patients compared to CLD patients, and in HCC tissues compared to nontumor hepatic tissues. Ceramides were found as the most significant lipid class (qFDR p = 1 × 10-14) followed by phosphatidylglycerols (qFDR p = 3 × 10-9), phosphatidylcholines and plasmalogens. Despite these major differences, there were also common trends in the transitions between healthy controls, CLD and HCC patients. In blood, several mostly saturated triacylglycerides showed a continued increase in the trajectory towards HCC, accompanied by reduced levels of saturated free fatty acids and saturated lysophospatidylcholines. In contrast, the largest overlaps of lipid alterations that were found in both HCC tissue and blood comparisons were decreased levels of phosphatidylglycerols and sphingolipids. This study highlights the specific impact of HCC tumors on the circulating lipids. Such data may be used to target lipid metabolism for prevention, early detection and treatment of HCC in the background of viral-related CLD etiology