Potential Surviving Effect of Cleome droserifolia Extract against Systemic Staphylococcus aureus Infection: Investigation of the Chemical Content of the Plant.

The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice's survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.

Chemotherapeutic potential of betanin/capecitabine combination targeting colon cancer: experimental and bioinformatic studies exploring NFκB and cyclin D1 interplay.

Introduction: Betanin (C24H26N2O13) is safe to use as food additives approved by the FDA with anti-inflammatory and anticancer effects in many types of cancer cell lines. The current experiment was designed to test the chemotherapeutic effect of the combination of betanin with the standard chemotherapeutic agent, capecitabine, against chemically induced colon cancer in mice. Methods: Bioinformatic approach was designed to get information about the possible mechanisms through which the drugs may control cancer development. Five groups of mice were assigned as, (i) saline, (ii) colon cancer, (iii) betanin, (iv) capecitabine and (v) betanin/capecitabine. Drugs were given orally for a period of six weeks. Colon tissues were separated and used for biological assays and histopathology. Results: In addition, the mRNA expression of TNF-α (4.58-fold), NFκB (5.33-fold), IL-1ß (4.99-fold), cyclin D1 (4.07-fold), and IL-6 (3.55-fold) and protein levels showed several folds increases versus the saline group. Tumor histopathology scores in the colon cancer group (including cryptic distortion and hyperplasia) and immunostaining for NFκB (2.94-fold) were high while periodic-acid Schiff staining demonstrated poor mucin content (33% of the saline group). These pathologic manifestations were reduced remarkably in betanin/capecitabine group. Conclusion: Collectively, our findings demonstrated the usefulness of betanin/capecitabine combination in targeting colon cancer and highlighted that betanin is a promising adjuvant therapy to capecitabine in treating colon cancer patients.

The impact of photoreceptor layer loss on different ocular tissues: Insights from FTIR spectroscopy.

Photoreceptor loss has significant consequences for visual function, and its management is a critical component for treating not only retinal diseases such as age-related macular degeneration and retinitis pigmentosa but also its ocular consequences. On the other hand, Fourier transform infrared spectroscopy is an excellent tool to investigate molecular structure and dynamics of biological samples, and as a non-destructive and label free measurement, it does not perturb the samples. In this study, detailed analyses of the recorded FTIR spectra from cornea, lens and sclera were performed to monitor the distribution of ocular abnormalities due to photoreceptor layer loss after 1, 3 and 6 days. FTIR data were statistically evaluated by multivariate analysis and Bonferroni means comparison. The obtained results revealed that ocular abnormalities associated with photoreceptor layer loss are varied among the investigated tissues, and comprise changes in both hydrogen bond network around proteins and lipid disorder. Structural modifications of protein secondary structure were reported in all investigated tissues. Clinically, the concluded information from FTIR data and its statistical evaluation can contribute to the development of therapeutic strategies for these heterogeneous changes.

Assessment of developmental toxicity and the potential mode of action underlying single and binary exposure to estrogenic endocrine disrupting chemicals in zebrafish (Danio rerio).

The current study investigated the effect of single and binary exposure to distinct xenoestrogens, including diethylstilbestrol (DES) and zearalenone (ZEN), on zebrafish embryos subjected to continuous exposure for 4 days starting from 4 h post fertilization. Noteworthy impact on cumulative mortality, hatchability, spinal and tail curvature, pericardial edema, and reduction in blood circulation were observed in DES-treated embryos, with lower incidence and intensity shown for ZEN at the same nominal concentration (3 µM). An interactive effect was seen for the combined exposure to DES and ZEN, in which deformities and circulatory failure mediated by DES were mitigated by co-treatment with low concentrations of ZEN. Similarly, ZEN-induced spinal and tail curvature, pericardial edema, and blood flow reduction declined dramatically following DES co-exposure at low concentrations. A significant counteracting effect has been observed against DES- and ZEN-induced developmental anomalies following co-treatment with an estrogen receptor (ER) antagonist, fulvestrant (FUL). The assessment of the aromatase gene (CYP19A1b) showed that DES strongly upregulated mRNA expression of CYP19A1b with a lower EC50 (1.1 × 10-3 nM) than a natural estrogen, 17ß-estradiol (2.5 nM). Similarly, ZEN induced CYP19A1b mRNA expression with an EC50 of 57 nM. Exposure to 10 or 20 µM FUL inhibited the expression of CYP19A1b induced by a single treatment of DES or ZEN. Overall, the competitive action against ER could be the main mechanism underlying the developmental toxicity induced by DES and ZEN.

Exploring novel anticancer pyrazole benzenesulfonamides featuring tail approach strategy as carbonic anhydrase inhibitors.

This study aimed to design potent carbonic anhydrase inhibitors (CAIs) based on pyrazole benzenesulfonamide core. Nine series of substituted pyrazole benzenesulfonamide compounds were synthesized with variable groups like sulphamoyl group as in compounds 4a-e, its bioisosteric carboxylic acid as in compounds 5a-e and 8e, ethyl carboxylate ester as in compounds 6a-e and 9a-e, which were designed as potential prodrugs, isothiazole ring as in compound 7, hydrazide derivative 10e, hydroxamic acid derivatives 11a-e and semicarbazide derivatives 12a-c,e. All the synthesized compounds were investigated for their carbonic anhydrase (CA) inhibitory activity against two human CA isoforms hCA IX and hCA XII and compared to acetazolamide (AAZ). Also, the compounds were assessed for their anticancer activity against 60 cancer cell lines according to the US NCI protocol. Compounds 4b, 5b, 5d, 5e, 6b, 9b, 9e and 11b revealed significant inhibitory activity against both isoforms hCA IX and hCA XII, while 6e, 9d, 11d and 11e showed significant inhibitory activity against hCA XII only compared to acetazolamide as a reference. This would highlight these compounds as promising anticancer drugs. Moreover, compound 6e revealed a remarkable cytostatic activity against CNS cancer cell line (SF-539; TGI = 5.58 µM), renal cancer cell line (786-0; TGI = 4.32 µM) and breast cancer cell line (HS 578 T; TGI = 5.43 µM). Accordingly, compound 6e was subjected to cell cycle analysis and apoptotic assay on the abovementioned cell lines at the specified GI50 (0.45, 0.89 and 1.18 µM, respectively). Also, it revealed the increment of total apoptotic cells percentage in 786-0 (53.19%), SF-539 (46.11%) and HS 578 T (43.55%) relative to the control cells (2.07, 2.64 and 2.52%, respectively). In silico prediction of BBB permeability showed that most of the calculations for compound 6e resulted as BBB (+), which is required for a compound targeting CNS. Further, the interaction of the most active compounds with the key amino acids in the active sites of hCA IX and hCA XII was highlighted by molecular docking analysis.

Preparation and Optimization of Itraconazole Transferosomes-Loaded HPMC Hydrogel for Enhancing Its Antifungal Activity: 23 Full Factorial Design.

Itraconazole (ITZ) is a triazole antifungal agent characterized by broad-spectrum activity against fungal infections. The main drawback of ITZ, when applied topically, is the low skin permeability due to the stratum corneum, the outermost layer of the skin, which represents the main barrier for drug penetration. Therefore, this study aimed to prepare itraconazole as transferosomes (ITZ-TFS) to overcome the barrier function of the skin. ITZ-TFSs were prepared by thin lipid film hydration technique using different surfactants, sodium lauryl sulfate (SLS) and sodium deoxycholate (SDC). The prepared ITZ-TFS were evaluated for entrapment efficiency (EE) %, particle size, polydispersity index (PDI), zeta potential, and in vitro drug release to obtain an optimized formula. The surface morphology of the optimized formula of ITZ-TFS was determined by transmission electron microscope (TEM). The optimized formulation was prepared in the form of gel using hydroxyl propyl methyl cellulose (HPMC) gel base. The prepared ITZ-TFS gel was evaluated for homogeneity, drug content, spreadability, pH, and in vitro antifungal activity in comparison with the free ITZ gel. The prepared ITZ-TFS formulations exhibited high EE% ranging from 89.02 ± 1.65% to 98.17 ± 1.28% with particle size ranging from 132.6 ± 2.15 nm to 384.1 ± 3.46. The PDI for all ITZ-TFSs was less than 0.5 and had a negative zeta potential. The TEM image for the optimized formulation (ITZ-TFS4) showed spherical vesicles with a smooth surface. The prepared gels had good spreadability, pH, and acceptable drug content. ITZ-TFS gel showed higher antifungal activity than free ITZ gel as determined by zone of inhibition. ITZ was successfully prepared in form of TFSs with higher antifungal activity than the free drug.

Decoding Diabetes Biomarkers and Related Molecular Mechanisms by Using Machine Learning, Text Mining, and Gene Expression Analysis.

The molecular basis of diabetes mellitus is yet to be fully elucidated. We aimed to identify the most frequently reported and differential expressed genes (DEGs) in diabetes by using bioinformatics approaches. Text mining was used to screen 40,225 article abstracts from diabetes literature. These studies highlighted 5939 diabetes-related genes spread across 22 human chromosomes, with 112 genes mentioned in more than 50 studies. Among these genes, HNF4A, PPARA, VEGFA, TCF7L2, HLA-DRB1, PPARG, NOS3, KCNJ11, PRKAA2, and HNF1A were mentioned in more than 200 articles. These genes are correlated with the regulation of glycogen and polysaccharide, adipogenesis, AGE/RAGE, and macrophage differentiation. Three datasets (44 patients and 57 controls) were subjected to gene expression analysis. The analysis revealed 135 significant DEGs, of which CEACAM6, ENPP4, HDAC5, HPCAL1, PARVG, STYXL1, VPS28, ZBTB33, ZFP37 and CCDC58 were the top 10 DEGs. These genes were enriched in aerobic respiration, T-cell antigen receptor pathway, tricarboxylic acid metabolic process, vitamin D receptor pathway, toll-like receptor signaling, and endoplasmic reticulum (ER) unfolded protein response. The results of text mining and gene expression analyses used as attribute values for machine learning (ML) analysis. The decision tree, extra-tree regressor and random forest algorithms were used in ML analysis to identify unique markers that could be used as diabetes diagnosis tools. These algorithms produced prediction models with accuracy ranges from 0.6364 to 0.88 and overall confidence interval (CI) of 95%. There were 39 biomarkers that could distinguish diabetic and non-diabetic patients, 12 of which were repeated multiple times. The majority of these genes are associated with stress response, signalling regulation, locomotion, cell motility, growth, and muscle adaptation. Machine learning algorithms highlighted the use of the HLA-DQB1 gene as a biomarker for diabetes early detection. Our data mining and gene expression analysis have provided useful information about potential biomarkers in diabetes.

Synthesis of new hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties as anti-inflammatory agents.

New hexahydropyrimido[1,2-a]azepine derivatives bearing functionalized aryl and heterocyclic moieties were synthesized as anti-inflammatory agents with better safety profiles. All synthesized compounds were assessed in vitro for their COX-1 and COX-2 inhibition activities. The most selective compounds, 2f, 5 and 6, were further evaluated for their in vivo anti-inflammatory activity and PGE2 inhibitory activity. To rationalize their selectivity, molecular docking within COX-1 and COX-2 binding sites was performed. Their physicochemical properties and drug-like nature profile were also calculated. The good activity and selectivity of compounds 2f, 5 and 6 were rationalized using a molecular docking study and supported by in vivo studies. These promising findings are encouraging for performing future investigations of these derivatives.

Diagnosis of Inflammatory Bowel Disease by Abdominal Ultrasound and Color Doppler Techniques.

BACKGROUND & AIMS: The utility of ultrasound and color Doppler in the diagnosis and evaluation of inflammatory bowel diseases (IBD) has not been studied enough. Therefore, the aim of the current study was to evaluate the importance of conventional abdominal ultrasound and color Doppler in diagnosing IBD and assessing disease activity. METHODS: The study was conducted at the National Hepatology and Tropical Medicine Research Institute (NHTMRI) between July 2018 and January 2019, in which 150 patients were suffering from diarrhea, dysentery, tenesmus, or rectal bleeding were evaluated by colonoscopy, high-resolution ultrasound, and color Doppler scans. RESULTS: The present study was conducted on 150 patients; 84 (56%) had ulcerative colitis (UC), 16 (10.7%) had Crohn's disease (CD), and 50 (33.3%) had normal colonoscopy results with a mean age 37.2 ± 9.059. The superior mesenteric Artery Peak Systolic Velocity (SMA-PSV) and End Diastolic Velocity (EDV) were significantly higher in both UC and CD than in the control group; however, pulsatility index (PI) was significantly higher in the control group than both UC and CD. However, there was no significant difference between UC and CD. The inferior mesenteric artery PSV and EDV were significantly higher in both UC and CD than in the control group. CONCLUSION: Doppler ultrasound findings of SMA and IMA correlate with the incidence of inflammatory bowel disease, the site of disease, and its activity.

Emerging therapeutic modality enhancing the efficiency of chemotherapeutic agents against head and neck squamous cell carcinoma cell lines.

The current work aimed to evaluate bee venom (BV) cytotoxic effect and its synergistic action when combined with cisplatin (CIS) against four types of head and neck squamous cell carcinoma (HNSCC) cell lines. 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cell viability, reverse transcription-polymerase chain reaction (RT-PCR) for expression of BCL2 associated X (BAX), B-cell lymphoma 2 (BCL2) and epidermal growth factor receptor (EGFR) genes and, flow cytometry for cell cycle analysis were performed. MTT assay revealed that BV caused an approximately 50% cell death for UMSCC12, UMSCC29, UMSCC38 and, UMSCC47 cell lines after 72 hr with 54.809 µg/ml, 61.287 µg/ml, 71.328 µg/ml and, 61.045 µg/ml, respectively. RT-PCR demonstrated a significant up-regulation of BAX gene and a significant down-regulation of BCL2 and EGFR genes among single or combined treatments with CIS and BV as compared to vehicle-treated. The cell lines treated with both BV and CIS showed marked elevation of BAX and a notable drop of BCL2 and EGFR expressions than single-treated groups. Cell cycle analysis via flow cytometry revealed significantly increased cells in the G2/M phase in single or combined-treated cell lines with CIS and BV when compared with vehicle-treated. Moreover, a significant decrease in cells in S phases among all single and combined treatments when matched with vehicle-treated. Briefly, the findings of the present study suggest that BV can exert an anti-cancer effect on HNSCC and may have the potentiality for potentiation of CIS cytotoxic effects and reduction of its adverse effects.

Efficacy and safety of ombitasvir/paritaprevir/ritonavir/ribavirin in management of Egyptian chronic hepatitis C virus patients with chronic kidney disease: A real-life experience.

Treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease was difficult in the past because of the use of interferon (IFN). It was associated with high risk IFN-related adverse reactions due to reduced renal clearance of IFN. This study aimed to evaluate the antiviral efficacy, safety, and tolerability of ombitasvir/paritaprevir/ritonavir/ribavirin in chronic kidney disease patients infected with chronic HCV.This observational, open-label prospective study was carried out on 103 patients infected chronic HCV with different grades of renal impairment. Paritaprevir/ritonavir and ombitasvir (75/50/12.5 mg) twice daily plus ribavirin were given to the patients for 12 weeks. Dose adjustment of ribavirin was done according to degree of renal impairment.Sustained virological response (12 weeks after the end of treatment) occurred in 101 patients (98.1%). Anemia occurred in 48 patients. No serious adverse events were observed in any patient.Paritaprevir/ritonavir and ombitasvir plus ribavirin for 12 weeks was considered to be safe and effective in the treatment of chronic HCV infected patients with varying degrees of renal impairment.

MiR-155 and MiR-665 Role as Potential Non-invasive Biomarkers for Hepatocellular Carcinoma in Egyptian Patients with Chronic Hepatitis C Virus Infection.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer associated death globally. Serum micro RNAs are full of potential as noninvasive biomarkers. Here, we aim to assess the performance of serum MicroRNA-155 and MicroRNA-665 as diagnostic biomarker for HCC comparing to AFP. METHODS: Serum samples were collected from 200 subjects (40 healthy control, 80 chronic hepatitis C patients with cirrhosis and without HCC (LC) and 80 HCC patients currently infected by hepatitis C infection and didn't start the treatment). The HCC patients didn't include alcoholic liver disease, nonalcoholic fatty liver disease nor autoimmune liver disease. MicroRNA-155 and MicroRNA-665 expression were measured by real-time quantitative PCR (RT-qPCR), while AFP level was assessed by ELISA method. RESULTS: Both miR-155 and miR-665 were significantly elevated in HCC group as compared to both control and LC groups. The comparison between LC and HCC patients revealed that the serum level of miR-155 was a significant increase in HCC patients compared to LC patients; however, the serum level of miR-665 didn't show any significant difference between the same two groups. MiR-665 expression level showed a direct correlation with tumor size in HCC patients. CONCLUSIONS: Using measurement against AFP level in serum, miR-665 is considered a promising serum biomarker for the diagnosis of HCC patients among the LC patients without HCC. MiR-155 didn't provide a better performance than serum AFP as a diagnostic biomarker among the same group. MiR-665 may serve as a good indicator for HCC prognosis.

Relationship Between Helicobacter pylori Infection and Nonalcoholic Fatty Liver Disease (NAFLD) in a Developing Country: A Cross-Sectional Study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a very common disease that affects 25-30% of the population in western countries. Many studies have observed the importance of H. pylori infection in the development of insulin resistance, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and liver fibrosis and cirrhosis. However, the evidence from different studies was controversial. The present study aimed to investigate the relationship between H. pylori infection and NAFLD in a developing country. PATIENTS AND METHODS: This cross-sectional study included all the attending outpatient clinics at four Major University hospitals and two research and clinical institutes in a developing country in the period between June and October 2019. Patients were assessed for the diagnosis of H. pylori infection as detected by H. pylori antigen in stool; they were also assessed for the diagnosis of NAFLD by ultrasound, fibroscan, and CAP. RESULTS: The study was conducted on 646 patients; H. pylori infection was found to be present in 538 patients (83.3%). NAFLD (diagnosed by both U/S and Fibroscan with CAP), ALT, AST, hepatomegaly, hypertension, fasting blood sugar were significantly higher in H. pylori +ve group than H. pylori -ve group. After performing Linear regression of independent risk factors of NAFLD to prove or to refute the role of Helicobacter; H. pylori positivity, total cholesterol, degree of fatty liver by ultrasound, fasting blood sugar and diastolic blood pressure were independent risk factors for NAFLD. CONCLUSION: Helicobacter pylori infection was independent risk factors for NAFLD and correlated with increased degree of steatosis.

Expression of pRb, Ki67 and HER 2/neu in gastric carcinomas: Relation to different histopathological grades and stages.

Gastric carcinoma is one of the aggressive malignancies with poor prognosis. The expression of pRb, Ki67, Her-2 in relation to tumor grade and stage in gastric carcinoma still needs more exploration. This study was performed aiming to study the immunohistochemical expression of altered retinoblastoma encoding protein (pRb), Ki67 and Her-2 in gastric carcinoma and to investigate their clinical and pathological significance. We studied tumor tissue specimens from 48 patients with gastric carcinoma. Paraffin sections were submitted for immunohistochemistry using pRb, Ki67 and Her-2. Statistical analysis was performed for clinical and pathological data of all studied cases. Altered pRb was expressed in 79% of the studied tumors, inversely correlated with tumor invasion and stage with no significant relation with tumor grade, age, and gender and tumor size. Ki67 LI was significantly associated with tumor grade and stage but not related to sex, age, tumor size, site, depth of invasion and lymph node metastasis. Her2 was expressed in 75% of studies tumors with significant association with tumor grade, the depth of invasion, lymph node metastasis and higher tumor stage. However, there was no significant association between Her-2 expression and gender, tumor site and size. In conclusion, altered pRb is frequently expressed in gastric carcinoma, inversely correlates with tumor invasion and tumor stage suggesting an early event in gastric carcinogenesis. Ki67 expression in gastric carcinoma is directly correlated with the tumor grade and depth of invasion. Her2 expression is significantly correlated with tumor grade, depth of invasion and stage.

Designing a course model for distance-based online bioinformatics training in Africa: The H3ABioNet experience.

Africa is not unique in its need for basic bioinformatics training for individuals from a diverse range of academic backgrounds. However, particular logistical challenges in Africa, most notably access to bioinformatics expertise and internet stability, must be addressed in order to meet this need on the continent. H3ABioNet (www.h3abionet.org), the Pan African Bioinformatics Network for H3Africa, has therefore developed an innovative, free-of-charge "Introduction to Bioinformatics" course, taking these challenges into account as part of its educational efforts to provide on-site training and develop local expertise inside its network. A multiple-delivery-mode learning model was selected for this 3-month course in order to increase access to (mostly) African, expert bioinformatics trainers. The content of the course was developed to include a range of fundamental bioinformatics topics at the introductory level. For the first iteration of the course (2016), classrooms with a total of 364 enrolled participants were hosted at 20 institutions across 10 African countries. To ensure that classroom success did not depend on stable internet, trainers pre-recorded their lectures, and classrooms downloaded and watched these locally during biweekly contact sessions. The trainers were available via video conferencing to take questions during contact sessions, as well as via online "question and discussion" forums outside of contact session time. This learning model, developed for a resource-limited setting, could easily be adapted to other settings.

Expression levels of ß-catenin and galectin-3 in meningioma and their effect on brain invasion and recurrence: a tissue microarray study.

OBJECTIVE: Meningiomas are neoplasms that arise from the meninges of the central nervous system (CNS). They constitute about 25.6% of CNS tumors diagnosed in Egypt. Some morphological variants of meningiomas display aggressive behavior, leading to brain-invasive growth pattern. Although meningiomas are usually treated by complete surgical excision, the risk of postoperative recurrence remains. Hence, additional biomarkers for predicting aggressive behavior must be discovered. This study aims to explore the clinical and biological relevance of the protein expression levels of ß-catenin and galectine-3 in meningioma and to understand the pathobiology of this neoplasm. METHODS: This retrospective study was carried out on 153 cases of meningioma by using tissue microarrays and immunohistochemistry for ß-catenin and galectine-3. RESULTS: High ß-catenin expression was significantly associated with transitional and meningiotheliomatous meningiomas, low tumor grade, low recurrence rate, and low incidence of brain invasion. Meanwhile, high galectin-3 expression was associated with brain invasion, recurrence, high tumor grade, and tumor type. Logistic regression analysis indicated that among all variables included in the model, ß-catenin and galactin-3 expression levels were significant predictors of tumor recurrence (P<0.001). CONCLUSIONS: Galectin-3 and ß-catenin are involved in meningioma recurrencebut not in brain invasion. These molecules could be important potential therapeutic targets and predictors for meningiomas.

Development of Bioinformatics Infrastructure for Genomics Research.

BACKGROUND: Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community. OBJECTIVES: H3ABioNet set out to develop core bioinformatics infrastructure and capacity for genomics research in various aspects of data collection, transfer, storage, and analysis. METHODS AND RESULTS: Various resources have been developed to address genomic data management and analysis needs of H3Africa researchers and other scientific communities on the continent. NetMap was developed and used to build an accurate picture of network performance within Africa and between Africa and the rest of the world, and Globus Online has been rolled out to facilitate data transfer. A participant recruitment database was developed to monitor participant enrollment, and data is being harmonized through the use of ontologies and controlled vocabularies. The standardized metadata will be integrated to provide a search facility for H3Africa data and biospecimens. Because H3Africa projects are generating large-scale genomic data, facilities for analysis and interpretation are critical. H3ABioNet is implementing several data analysis platforms that provide a large range of bioinformatics tools or workflows, such as Galaxy, the Job Management System, and eBiokits. A set of reproducible, portable, and cloud-scalable pipelines to support the multiple H3Africa data types are also being developed and dockerized to enable execution on multiple computing infrastructures. In addition, new tools have been developed for analysis of the uniquely divergent African data and for downstream interpretation of prioritized variants. To provide support for these and other bioinformatics queries, an online bioinformatics helpdesk backed by broad consortium expertise has been established. Further support is provided by means of various modes of bioinformatics training. CONCLUSIONS: For the past 4 years, the development of infrastructure support and human capacity through H3ABioNet, have significantly contributed to the establishment of African scientific networks, data analysis facilities, and training programs. Here, we describe the infrastructure and how it has affected genomics and bioinformatics research in Africa.

Serum Vitamin D Levels in Treatment-naïve Chronic Hepatitis B Patients.

BACKGROUND AND OBJECTIVES: According to the demographic health survey conducted in 2015, Egypt had 10% documented prevalence of anti-HBc positive patients aged 1-59 and 1% viremic patients amongst the population in the same age group, with a domination of genotype D. Several studies claimed the possible role of vitamin D deficiency in hepatitis B virus (HBV) replication and disease progression. PATIENTS AND METHODS: Serum vitamin D levels [25(OH D3] were assessed in 96 HBeAg negative non-cirrhotic chronic HBV patients and 25 healthy subjects classified as following: Group I: 48 chronic HBV patients with persistently normal ALT levels and HBV DNA level < 2000 IU/mL for ≥ 6 months; Group II: 48 chronic HBV patients with CHB with persistently elevated ALT and HBV DNA level ≥ 2000 IU/mL for ≥ 6 months; and Group III: 25 apparently healthy subjects with normal liver enzymes and negative hepatitis viral markers were taken as the control group. RESULTS: Vitamin D was much more deficient in group II than in group I and group III being 11.55 ± 3.97 ng/mL, 15.03 ± 3.45, 27.00 ± 6.76 ng/mL (P < 0.001), respectively, and a strong negative correlation was observed between vitamin D levels and HBV DNA levels (P = 0.043) in groups I and II. CONCLUSION: The current study showed high HBV DNA replication in patients with vitamin D deficiency suggesting the antimicrobial immunomodulatory role of vitamin D.

Aged garlic extract ameliorates immunotoxicity, hematotoxicity and impaired burn-healing in malathion- and carbaryl-treated male albino rats.

Malathion and carbaryl are the most widely used organophosphate and carbamate insecticides, respectively, especially in developing countries; they pose a potential health hazard for both humans and animals. Here, we evaluated the protective effects of an odorless (free from allicin) Kyolic aged garlic extract (AGE, containing 0.1% S-allylcysteine; 200 mg/kg body weight) on the toxicity induced by 0.1 LD50 of malathion (89.5 mg/kg body weight) and/or carbaryl (33.9 mg/kg body weight) in male Wistar rats. Doses were orally administered to animals for four consecutive weeks. The present study showed that AGE completely modulated most adverse effects induced by malathion and/or carbaryl in rats including the normocytic normochromic anemia, immunosuppression, and the delay in the skin-burning healing process through normalizing the count of blood cells (erythrocytes, leucocytes and platelets), hemoglobin content, hematocrit value, blood glucose-6-phosphodehydrogenase activity, weights and cellularity of lymphoid organs, serum γ-globulin concentration, and the delayed type of hypersensitivity response to the control values, and accelerating the inflammatory and proliferative phases of burn-healing. In addition, AGE completely modulated the decrease in serum reduced glutathione (GSH) concentration and the increase in clotting time in malathion alone and carbaryl alone treated rats. Moreover, AGE induced a significant increase (P < 0.001) in serum GSH concentration (above the normal value) and accelerating burn-healing process in healthy rats. In conclusion, AGE was effective in modulating most adverse effects induced in rats by malathion and carbaryl, and hence may be useful as a dietary adjunct for alleviating the toxicity in highly vulnerable people to insecticides intoxication. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 789-798, 2017.