Whole-Exome Sequencing (WES) Reveals Novel Sex-Specific Gene Variants in Non-Alcoholic Steatohepatitis (MASH).

Non-alcoholic steatohepatitis (NASH, also known as MASH) is a severe form of non-alcoholic fatty liver disease (NAFLD, also known as MASLD). Emerging data indicate that the progression of the disease to MASH is higher in postmenopausal women and that genetic susceptibility increases the risk of MASH-related cirrhosis. This study aimed to investigate the association between genetic polymorphisms in MASH and sexual dimorphism. We applied whole-exome sequencing (WES) to identify gene variants in 8 age-adjusted matched pairs of livers from both male and female patients. Sequencing alignment, variant calling, and annotation were performed using standard methods. Polymerase chain reaction (PCR) coupled with Sanger sequencing and immunoblot analysis were used to validate specific gene variants. cBioPortal and Gene Set Enrichment Analysis (GSEA) were used for actionable target analysis. We identified 148,881 gene variants, representing 57,121 and 50,150 variants in the female and male cohorts, respectively, of which 251 were highly significant and MASH sex-specific (p < 0.0286). Polymorphisms in CAPN14, SLC37A3, BAZ1A, SRP54, MYH11, ABCC1, and RNFT1 were highly expressed in male liver samples. In female samples, Polymorphisms in RGSL1, SLC17A2, HFE, NLRC5, ACTN4, SBF1, and ALPK2 were identified. A heterozygous variant 1151G>T located on 18q21.32 for ALPK2 (rs3809983) was validated by Sanger sequencing and expressed only in female samples. Immunoblot analysis confirmed that the protein level of ß-catenin in female samples was 2-fold higher than normal, whereas ALPK2 expression was 0.5-fold lower than normal. No changes in the protein levels of either ALPK2 or ß-catenin were observed in male samples. Our study suggests that the perturbation of canonical Wnt/ß-catenin signaling observed in postmenopausal women with MASH could be the result of polymorphisms in ALPK2.

Phytoconstituent analysis, anti-inflammatory, antimicrobial and anticancer effects of nano encapsulated Convolvulus arvensis L. extracts.

BACKGROUND: The Convolvulus genus is distributed all over the world and has a long history in traditional medicine. As nanotechnology expands its reach into areas like drug delivery and biomedicine, this study intends to assess the potential of Convolvulus arvensis L. extracts as anti-bacterial, anti-inflammatory and anti-cancer agents, along with chemical profiling of the methanolic (MeOH) extract active ingredients. METHODS: The chemical composition of an 85% MeOH extract was investigated by liquid chromatography with an electrospray source connected to mass spectrometry (LC-ESI-MS). Both the 85% MeOH extract and n-butanol fraction of C. arvensis were loaded for the first time on alginate/chitosan nanoparticles. The 85% MeOH extract, n-butanol fraction and their loaded nanoparticles were tested for their cytotoxicity, anticancer, anti-inflammatory and antibacterial activity (against pathogenic bacteria, E. coli and S. aureus). RESULTS: The chemical investigation of 85% MeOH extract of C. arvensis underwent LC-ESI-MS analysis, revealing twenty-six phenolic substances, of which 16 were phenolic acids, 6 were flavonoids, 1 glycolipid, 1 sesquiterpene and 2 unknown compounds. The FT-IR spectra confirmed the encapsulation of the 85% MeOH extract and n-butanol fraction onto alginate/chitosan nanoparticles and small size obtained by TEM maintained them nontoxic and enhanced their anti-inflammatory activity (the IC50 was decreased from 1050 to 175 µg/ml). The anti-cancer activity against HepG2 was increased and the cell viability was decreased from 28.59 ± 0.52 to 20.80 ± 0.27 at a maximum concentration of 1000 µg/ml. In addition, the MIC of encapsulated extracts was decreased from 31.25 to7.78 µg/ml in E. coli (Gm-ve) and from 15.56 to 7.78 µg/ml in S. aureus (Gm + ve) bacteria. CONCLUSION: Both alginate and chitosan are excellent natural polymers for the encapsulation process, which affects positively on the bioactive constituents of C. arvensis extracts and improves their biological properties.

Targeting C21orf58 is a Novel Treatment Strategy of Hepatocellular Carcinoma by Disrupting the Formation of JAK2/C21orf58/STAT3 Complex.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N-terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild-type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper-activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC.

Camptothecin bioprocessing from Aspergillus terreus, an endophyte of Catharanthus roseus: antiproliferative activity, topoisomerase inhibition and cell cycle analysis.

Attenuation of camptothecin (CPT) productivity by fungi with preservation and subculturing is the challenge that halts fungi to be an industrial platform of CPT production. Thus, screening for novel endophytic fungal isolates with metabolic stability for CPT production was the objective. Catharanthus roseus is one of the medicinal plants with diverse bioactive metabolites that could have a plethora of novel endophytes with unique metabolites. Among the endophytes of C. roseus, Aspergillus terreus EFBL-NV OR131583.1 had the most CPT producing potency (90.2 µg/l), the chemical identity of the putative CPT was verified by HPLC, FT-IR, NMR and LC-MS/MS. The putative A. terreus CPT had the same molecular mass (349 m/z), and molecular fragmentation patterns of the authentic one, as revealed from the MS/MS analyses. The purified CPT had a strong activity against MCF7 (5.27 µM) and UO-31 (2.2 µM), with a potential inhibition to Topo II (IC50 value 0.52 nM) than Topo 1 (IC50 value 6.9 nM). The CPT displayed a high wound healing activity to UO-31 cells, stopping their metastasis, matrix formation and cell immigration. The purified CPT had a potential inducing activity to the cellular apoptosis of UO-31 by ~ 17 folds, as well as, arresting their cellular division at the S-phase, compared to the control cells. Upon Plackett-Burman design, the yield of CPT by A. terreus was increased by ~ 2.6 folds, compared to control. The yield of CPT by A. terreus was sequentially suppressed with the fungal storage and subculturing, losing ~ 50% of their CPT productivity by 3rd month and 5th generation. However, the productivity of the attenuated A. terreus culture was completely restored by adding 1% surface sterilized leaves of C. roseus, and the CPT yield was increased over-the-first culture by ~ 3.2 folds (315.2 µg/l). The restoring of CPT productivity of A. terreus in response to indigenous microbiome of C. roseus, ensures the A. terreus-microbiome interactions, releasing a chemical signal that triggers the CPT productivity of A. terreus. This is the first reports exploring the potency of A. terreus, endophyte of C. roseus" to be a platform for industrial production of CPT, with an affordable sustainability with addition of C. roseus microbiome.

Retraction notice to "Dobera glabra (Forssk.) Poir. (Salvadoraceae); Phenolic constituents of the aqueous leaves extract and evaluation of its anti-inflammatory, analgesic activities" [Heliyon 7 (2021) e06205].

[This retracts the article DOI: 10.1016/j.heliyon.2021.e06205.].

Evaluation of graded recession of inferior oblique muscle for correction of different grades of V-pattern strabismus.

BACKGROUND: V pattern identification is essential for proper strabismus management. Graded recession is a tailored approach to treat inferior oblique overaction (IOOA). The aim is to evaluate the efficacy of graded recession of inferior oblique muscle for correction of different grades of V pattern. METHODS: Forty patients from 3 to 18 years old with V pattern strabismus and primary IOOA were evaluated by prism cover test to assess the grade of IOOA and amplitude of V-pattern. Graded recession of IO muscle depends on the amplitude of the V-pattern and degree of IOOA. Eight mm recession for amplitude 15 PD to 20 PD and mild IOOA (10 PD-15 PD or + 1) ,10 mm recession for amplitude 20-30 PD and moderate IOOA (15-25 PD or + 2) and maximum recession for amplitude more than 30 PD and marked IOOA (≥ 25 PD or + 3). Simultaneous correction of the horizontal deviation was performed. Follow up after I week,1 month ,3 month and 6-month. Trial Registration Number (TRN) (NCT05786053) on 23/3/2023. RESULTS: The mean age of the study patients was 9 ± 4.261. Twenty patients (50%) had V-pattern esotropia, 12 (30%) exotropia, 4 (10%) orthotropic and four (10%) had Dissociated vertical deviation (DVD). Four cases 10% were of grade 1, 20 cases (50%) grade 2 and 16 cases (40%) were of grade 3. Of eighty eyes, 66 eyes (82.5%) were fully corrected with no residual IOOA, and 14 eyes (17.5%) were under corrected. V-pattern was corrected in 28 cases 70% and only 12cases (30%) had residual V-pattern grade 1. CONCLUSIONS: Graded recession is an effective procedure for correction of V pattern strabismus with various grades of primary inferior oblique overaction. It can be tailored according to the the degree of IO overaction which is significantly related to the grade of V pattern. The 8 mm recession for IO was significantly related to recurrence or inadequate break of the V pattern in our studied cases. The grade of IOOA correlates with the amplitude of V-pattern. The amount of recession was planned according to preoperative IOOA and grade of V-pattern with frequent undercorrections obtained by the standard 8 mm recession. A + 2 overaction merits a 10-mm recession of the inferior oblique. A + 3 or + 4 overaction merits a 14-mm maximal recession.

Recombinant production, purification, and biochemical characterization of a novel L-lactate dehydrogenase from Bacillus cereus NRC1 and inhibition study of mangiferin.

Lactate dehydrogenase (LDH, EC 1.1.1.27) is one of the vital glycolytic conditions, especially during anaerobic conditions. It is a significant diagnostic, prognostic, and monitoring biomarker parameter. A 950-bp DNA fragment containing the gene (LDH) encoding LDH was amplified from Bacillus cereus NRC1. The deduced amino acid sequence reveals that B. cereus LDH (Bc-LDH) is highly homologous to the LDHs of Bacillus organisms. All LDH enzymes have a significant degree of conservation in their active site and several additional domains with unidentified functions. The gene for LDH, which catalyzes lactate synthesis, was cloned, sequenced (accession number: LC706200.1), and expressed in Escherichia coli BL21 (DE3). In this investigation, Bc-LDH was purified to homogeneity with a specific activity of 22.7 units/mg protein and a molecular weight of 35 kDa. It works optimally at pH 8.0. The purified enzyme was inhibited by FeCl2, CuCl2, ZnCl2, and NiCl, whereas CoCl2 was found to boost the activity of Bc-LDH. The molecular docking of the 3D model of the Bc-LDH structure with a natural inhibitor, mangiferin, demonstrated excellent LDH inhibition, with a free binding energy of -10.2 kcal/mol. Moreover, mangiferin is a potent Bc-LDH inhibitor that inhibits Bc-LDH competitively and has one binding site with a Ki value of 0.075 mM. The LDH-mangiferin interaction exhibits a low RMSF value (>1.5 Å), indicating a stable contact at the residues. This study will pave the way for more studies to improve the understanding of mangiferin, which could be considered an intriguing candidate for creating novel and improved LDH inhibitors.

Investigating a Library of Flavonoids as Potential Inhibitors of a Cancer Therapeutic Target MEK2 Using in Silico Methods.

The second leading cause of death in the world is cancer. Mitogen-activated protein kinase (MAPK) and extracellular signal-regulated protein kinase (ERK) 1 and 2 (MEK1/2) stand out among the different anticancer therapeutic targets. Many MEK1/2 inhibitors are approved and widely used as anticancer drugs. The class of natural compounds known as flavonoids is well-known for their therapeutic potential. In this study, we focus on discovering novel inhibitors of MEK2 from flavonoids using virtual screening, molecular docking analyses, pharmacokinetic prediction, and molecular dynamics (MD) simulations. A library of drug-like flavonoids containing 1289 chemical compounds prepared in-house was screened against the MEK2 allosteric site using molecular docking. The ten highest-scoring compounds based on docking binding affinity (highest score: -11.3 kcal/mol) were selected for further analysis. Lipinski's rule of five was used to test their drug-likeness, followed by ADMET predictions to study their pharmacokinetic properties. The stability of the best-docked flavonoid complex with MEK2 was examined for a 150 ns MD simulation. The proposed flavonoids are suggested as potential inhibitors of MEK2 and drug candidates for cancer therapy.

Role of four-dimensional computer tomography (4D-CT) in non-localising and discordant first-line imaging in primary hyperparathyroidism.

BACKGROUND: Accurate preoperative localisation of parathyroid adenoma is imperative for the success of minimally invasive parathyroidectomy (MIP). OBJECTIVE: Our study aimed to evaluate the role of four-dimensional computer tomography (4D-CT) scan as an imaging modality in patients with failed and discordant localisation reported in the first-line imaging modalities (ultrasonography and 99mTc-MIBI-SPECT/CT). METHODS: This is a prospective cohort study performed at a university teaching centre from March 2013 to July 2021. All patients with primary hyperparathyroidism who had failed localisation by ultrasonography and 99mTc-MIBI-SPECT/CT (SpCT), or discordance between them, had 4D-CT performed in this study. RESULTS: One hundred and two sporadic cases of pHPT with failed/discordant first-line imaging had 4D-CT imaging prior to parathyroidectomy. In 102 patients, 105 parathyroid adenomas were reported on histopathology. 4D-CT was able to localise 78% of them to the correct side and 64% to the correct quadrant in 102 patients, as compared with US (correct side 21%, correct quadrant 16%) and 99mTc-MIBI-SPECT/CT (correct side 36%, correct quadrant 31%). 4D-CT had a sensitivity, precision, accuracy and F1 score for correct quadrant localisation as 79%, 81%, 66% and 80%; and for correct side localisation as 82%, 98%, 80% and 89%, respectively. 4D-CT was able to identify three ectopic adenomas (two in superior mediastinum and one in the oesophageal wall) which were not detected on US or SpCT. CONCLUSION: 4D-CT was found to be sensitive and accurate in preoperative localising of the diseased parathyroid glands after failed/discordant US and SpCT. This led to more patients being offered MIP as the primary surgery and improved operative outcomes.

Computational Design and Experimental Evaluation of MERS-CoV siRNAs in Selected Cell Lines.

Middle East respiratory syndrome coronavirus (MERS-CoV) is caused by a well-known coronavirus first identified in a hospitalized patient in the Kingdom of Saudi Arabia. MERS-CoV is a serious pathogen affecting both human and camel health globally, with camels being known carriers of viruses that spread to humans. In this work, MERS-CoV genomic sequences were retrieved and analyzed by multiple sequence alignment to design and predict siRNAs with online software. The siRNAs were designed from the orf1ab region of the virus genome because of its high sequence conservation and vital role in virus replication. The designed siRNAs were used for experimental evaluation in selected cell lines: Vero cells, HEK-293-T, and Huh-7. Virus inhibition was assessed according to the cycle threshold value during a quantitative real-time polymerase chain reaction. Out of 462 potential siRNAs, we filtered out 21 based on specific selection criteria without off-target effect. The selected siRNAs did not show any cellular toxicity in the tested cell lines at various concentrations. Based on our results, it was obvious that the combined use of siRNAs exhibited a reduction in MERS-CoV replication in the Vero, HEK-293-T, and Huh-7 cell lines, with the highest efficacy displayed in the Vero cells.

In vitro and in vivo anthelmintic and chemical studies of Cyperus rotundus L. extracts.

BACKGROUND: Trichinellosis, a zoonosis caused by the genus Trichinella, is a widespread foodborne disease. Albendazole, one of the benzimidazole derivatives, is used for treating human trichinellosis, but with limited efficacy in killing the encysted larvae and numerous adverse effects. Cyperus rotundus L. is a herbal plant with a wide range of medicinal uses, including antiparasitic, and is frequently used in traditional medicine to treat various illnesses. METHODS: LC-ESI-MS was used to identify the active phytoconstituents in the methanol extract (MeOH ext.) of the aerial parts of C. rotundus and its derivate fractions ethyl acetate (EtOAc fr.), petroleum ether (pet-ether fr.), and normal butanol (n-BuOH fr.). The in vivo therapeutic effects of C. rotundus fractions of the extracts were evaluated using the fraction that showed the most promising effect after detecting their in vitro anti-Trichinella spiralis potential. RESULTS: C. rotundus extracts are rich in different phytochemicals, and the LC-ESI-MS of the 90% methanol extract identified 26 phenolic compounds classified as phenolic acids, flavonoids, and organic acids. The in vitro studies showed that C. rotundus extracts had a lethal effect on T. spiralis adults, and the LC50 were 156.12 µg/ml, 294.67 µg/ml, 82.09 µg/ml, and 73.16 µg/ml in 90% MeOH ext., EtOAc fr., pet-ether fr. and n-BuOH fr., respectively. The n-BuOH fr. was shown to have the most promising effects in the in vitro studies, which was confirmed by scanning electron microscopy. The in vivo effects of n-BuOH fr. alone and in combination with albendazole using a mouse model were evaluated by counting adults in the small intestine and larvae in the muscles, in addition to the histopathological changes in the small intestine and the muscles. In the treated groups, there was a significant decrease in the number of adults and larvae compared to the control group. Histopathologically, treated groups showed a remarkable improvement in the small intestine and muscle changes. Remarkably, maximal therapeutic effects were detected in the combination therapy compared to each monotherapy. CONCLUSION: Accordingly, C. rotundus extracts may have anti-T. spiralis potential, particularly when combined with albendazole, and they may be used as synergistic to anti-T. spiralis medication therapy.

Bacillus Species as Direct-Fed Microbial Antibiotic Alternatives for Monogastric Production.

Antibiotic growth promoters have been utilized for long time at subtherapeutic levels as feed supplements in monogastric animal rations. Because of their side-effects such as antibiotic resistance, reduction of beneficial bacteria in the gut, and dysbiosis, it is necessary to look for non-therapeutic alternatives. Probiotics play an important role as the key substitutes to antibacterial agents due to their many beneficial effects on the monogastric animal host. For instance, enhancement of the gut microbiota balance can contribute to improvement of feed utilization efficiency, nutrients absorption, growth rate, and economic profitability of livestock. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host." They are available in diverse forms for use as feed supplements. Their utilization as feed additives assists in good digestion of feed ingredients and hence, making the nutrients available for promoting growth. Immunity can also be enhanced by supplementing probiotics to monogastrics diets. Moreover, probiotics can help in improving major meat quality traits and countering a variety of monogastric animals infectious diseases. A proper selection of the probiotic strains is required in order to confer optimal beneficial effects. The present review focuses on the general functional, safety, and technological screening criteria for selection of ideal Bacillus probiotics as feed supplements as well as their mechanism of action and beneficial effects on monogastric animals for improving production performance and health status.

Post-irradiation physicochemical features of polymer composite for the removal of Co(II) and Nd(III) from aqueous solutions.

The scientific impact of this work is the protection of the environment from hazardous pollutants. Gamma irradiation was employed for the preparation of a new composite polymer by irradiating a mixture containing polyvinyl pyrrolidone (PVP), hydroxyethyl methacrylate (HEMA), and tannic acid (TA) to produce PVP-HEMA-TA. The sorption efficiency and capacity of PVP-HEMA-TA were evaluated by studying some factors affecting the sorption of Nd(III) and Co(II) from aqueous solutions. The results demonstrated that the maximum uptake was 92.4 and 75.3% for Nd(III) and Co(II), respectively. From the kinetic studies, the pseudo-second-order equation could better fit the data than the pseudo-first-order for the sorption of both ions. The sorption isotherm investigations illustrated that the Langmuir equation fits the gained data better than Freundlich equation. The Langmuir capacity was 64.5 and 60.8 mg/g for neodymium and cobalt ions, respectively. The applicability of Langmuir equation is strong evidence that the process is limited by a chemisorption mechanism. Findings of the work highlight the potential utilization of PVP-HEMA-TA as an effective and recyclable material for the elimination of Nd(III) and Co(II) from the aqueous phase.

Future Prospects, Approaches, and the Government's Role in the Development of a Hepatitis C Virus Vaccine.

Developing a safe and effective vaccine against the hepatitis C virus (HCV) remains a top priority for global health. Despite recent advances in antiviral therapies, the high cost and limited accessibility of these treatments impede their widespread application, particularly in resource-limited settings. Therefore, the development of the HCV vaccine remains a necessity. This review article analyzes the current technologies, future prospects, strategies, HCV genomic targets, and the governmental role in HCV vaccine development. We discuss the current epidemiological landscape of HCV infection and the potential of HCV structural and non-structural protein antigens as vaccine targets. In addition, the involvement of government agencies and policymakers in supporting and facilitating the development of HCV vaccines is emphasized. We explore how vaccine development regulatory channels and frameworks affect research goals, funding, and public health policy. The significance of international and public-private partnerships in accelerating the development of an HCV vaccine is examined. Finally, the future directions for developing an HCV vaccine are discussed. In conclusion, the review highlights the urgent need for a preventive vaccine to fight the global HCV disease and the significance of collaborative efforts between scientists, politicians, and public health organizations to reach this important public health goal.

Impact of the vertical division of the rectum on the decrease in reloading of the endostapler for a complete division in colorectal cancer

Background: Despite several improvements in surgical techniques, the intracorporeal division of the distal end of the rectum is still challenging, particularly when it is too deep in a narrow pelvis. Even though it helps avoid spillage, the double-stapling technique (DST) raises concerns regarding safety and anastomotic leakage if multiple stapler firings are essential to complete the rectal division. Objective: To assess the feasibility of vertically dividing the rectum and its impact in reducing the number of reloads essential for that division in non-low rectal cancer patients undergoing total mesorectal excision (TME). Materials and Methods A retroprospective study. Results: From January 2017 to November 2021, a total of 123 patients with sigmoid and rectal cancers were enrolled in the present study; their data were collected and analyzed, and 21 patients were excluded. The remaining sample of 102 subjects was composed of 47 male (46%) and 55 female (54%) patients with a median age of 54 years (range: 30 to 78 years). Only 1 reload was enough to complete the rectal division in 82 (80.39%) cases, and 2 reloads were used in the remaining 20 (19.61%) patients. Anastomotic leakage was clinically evident in 4 cases (3.9%). No statically significant difference was observed when firing one or two staplers. No 30-day mortality was recorded in this series. Conclusion: Our early experience indicates that this type of division has a real advantage in terms of decreasing the number of reloads needed and, in turn, lowering the incidence of anastomotic leakage after partial mesorectal excision (PME) or TME when applied with proper patient selection. (AU)

Anti-diabetic activities of phenolic compounds of Alternaria sp., an endophyte isolated from the leaves of desert plants growing in Egypt.

Six phenolic compounds (talaroflavone (1), alternarienoic acid (2), altenuene (3), altenusin (4), alternariol (5), and alternariol-5-O-methyl ether (6)) were isolated from the solid rice culture media of Alternaria sp., an endophyte isolated from the fresh leaves of three desert plants, Lycium schweinfurthii Dammer (Solanaceae), Pancratium maritimum L. (Amaryllidaceae) and Cynanchum acutum L. (Apocynaceae). Compounds 2, 3, and 4 exhibited potent α-glucosidase and lipase inhibitory activities suggesting that they might act as naturally occurring anti-diabetic candidates. The same compounds showed potent binding in the active site for both enzymes with desirable pharmacokinetic properties. The isolated bioactive compounds were not exclusive to a certain host plant which reveals the dominant ecological standpoints for consequent optimization. This could lead to a cost-effective and reproducible yield applicable to commercial scale-up.

In vivo evaluation of anticryptosporidial effects of wheat germ extracts in immunocompromised mice.

Cryptosporidium species is a prime cause of diarrheal disease in individuals with competent immunity. In patients with compromised immunity, infections are more severe particularly in developing countries. Wheat germ oil was described to have antiparasitic effect. This study was done to evaluate the possible role of wheat germ extracts in Cryptosporidium parvum (C. parvum) infected immunocompromised mice. Thirty white albino mice were classified into six groups as follow: four study groups, all immunosuppressed and infected with C. parvum oocysts. These four groups received treatments as follow: Group (I): treated with nitazoxanide. Group (II): treated with wheat germ oil. Group (III): treated with wheat germ extracted by hexane. Group (IV): treated with wheat germ extracted by ethanol. The remaining two groups were immunosuppressed control groups as follow: Group (V): only infected with C. parvum oocysts (Positive control). Group (VI): non-infected (Negative control). Stool samples were collected and examined to detect oocyst and the ileocecal region was subjected to histopathological and immunohistochemical examination. Wheat germ extracts showed a statistically significant effect against C. parvum specially wheat germ oil with P value: < 0.001, this effect was also confirmed by pathological and immunohistochemical examinations. C. parvum has an influence on human health by its effect in diarrheal disease. Wheat germ oil and its extracts has proved to be a reliable herb for C. parvum. treatment confirmed by different methodologies.

Ni-alginate hydrogel beads for establishing breakthrough curves of lead ions removal from aqueous solutions.

The scientific impact of this work is the protection of the environment from hazardous pollutants using a column technique. Besides its higher stability at working pH and its time persisting, Ni-alginate has a higher ability to remove lead ions compared to the other prepared beads (Sr-alginate, Co-alginate, and Ca-alginate). Also, Ni-alginate possessed a higher removal percent, 93.3%, toward Pb2+ than the other ions, taking the sorption order of Pb2+ > Sr2+ > Co2+ > Cd2+ > Zn2+. Therefore, this study focused on using Ni-alginate as a selective sorbent for lead ions. Fixed-bed column was employed for the sorption process. The results for that efficiency are presented as breakthrough curves in view of the impact of various parameters; influent flow rate (1.5, 3.0, and 5.0 mL/min), lead concentration (100, 150, and 200 mg/L), and bed depth of sorbent (3.0, 5.0, and 7.0 cm). Breakthrough modeling including Thomas and Yan models was employed. The outcomes indicated that Thomas theory is more applicable. The overall outcomes indicated that Ni-alginate is recommended for selective removal of Pb2+ from waste solutions.

Potential effect of methanol leaf extracts from three Podocarpus species on experimental cryptosporidiosis.

Cryptosporidiosis causes diarrhea in both immunocompetent and immunocompromised individuals, with acute manifestations occurring particularly in children and the elderly. Up till now, there is no curative therapy for cryptosporidiosis, so discovery of new classes of drugs are of great importance. This study aimed to examine the effect of methanol leaves extracts of the three Podocarpus species; P. macrophyllus (Thunb.), P. gracilior (Pilg.) and P. elongatus (Aiton) L' Hér. ex Pers and their combination on Cryptosporidium parvum (C. parvum) in experimentally infected mice in comparison with the commercially used drug, Nitazoxanide. As well as spectrophotometric estimation of the total phenolic and flavonoid content of these extracts was done. Results revealed that treatment with these three Podocarpus extracts and their combination showed a significant reduction of the number of C. parvum oocyst shed in the stool of infected mice compared to infected control group and Nitazoxanide- infected treated group at P < 0.001. The combination of the three Podocarpus extracts was the most effective treatment showing the lowest number of oocysts shedding in comparison with other used extracts and Nitazoxanide. Histopathological inspection of sections from ilium and colon displayed signs of improvement after treatment with P. macrophyllus and P. gracilior extracts and more remarkable improvement when the three extracts were combined. It was concluded that the three Podocarpus species extracts used in this study had a promising anti-Cryptosporidium activity especially when they were combined.

Perturbation of Wnt/ß-catenin signaling and sexual dimorphism in non-alcoholic fatty liver disease.

AIMS: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH) is higher in postmenopausal women than men. The aim of this study was to determine the molecular mechanisms underlying this sexual dimorphism in NAFLD. METHODS: A total of 24 frozen liver samples of both sexes (normal and NAFLD/NASH) were used in this study. Total RNAseq was first used to identify differentially expressed genes (DEGs) between samples. Enrichment analysis of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome were used to analyze biological pathways. RT2 profiler polymerase chain reaction (PCR) arrays were used to identify genes associated with the biological pathways. Immunoblotting was used to validate protein expression of certain genes. RESULTS: We identified 4362 genes that are differentially expressed between NAFLD/NASH and normal samples; of those 745 genes were characterized as sex specific in NAFLD/NASH. Multiple pathway analysis platforms showed that Wnt-signaling is a candidate shared for a common biological pathway-associated with NAFLD/NASH. Using Wnt pathway focused PCR array we identified many genes involved in canonical pathway (Wnt/ß-catenin activation) such as CTNNB1, c-Myc and CCND2 are overexpressed in female cases, whereas these genes are either not detected or downregulated in male cases. Immunoblot analysis validated the expression of CTNNB1 in female cases but not in male protein samples. CONCLUSIONS: Our study suggests, for the first time, that the activation of canonical Wnt signaling could be one of the main pathways associated with sexual dimorphism in NAFLD and NASH.