Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis.

Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis.

Developing Clinical Phenotype Data Collection Standards for Research in Africa.

Modern biomedical research is characterised by its high-throughput and interdisciplinary nature. Multiproject and consortium-based collaborations requiring meaningful analysis of multiple heterogeneous phenotypic datasets have become the norm; however, such analysis remains a challenge in many regions across the world. An increasing number of data harmonisation efforts are being undertaken by multistudy collaborations through either prospective standardised phenotype data collection or retrospective phenotype harmonisation. In this regard, the Phenotype Harmonisation Working Group (PHWG) of the Human Heredity and Health in Africa (H3Africa) consortium aimed to facilitate phenotype standardisation by both promoting the use of existing data collection standards (hosted by PhenX), adapting existing data collection standards for appropriate use in low- and middle-income regions such as Africa, and developing novel data collection standards where relevant gaps were identified. Ultimately, the PHWG produced 11 data collection kits, consisting of 82 protocols, 38 of which were existing protocols, 17 were adapted, and 27 were novel protocols. The data collection kits will facilitate phenotype standardisation and harmonisation not only in Africa but also across the larger research community. In addition, the PHWG aims to feed back adapted and novel protocols to existing reference platforms such as PhenX.

Ultrastructural changes and IgA modulatory effect of commercial prebiotic and probiotic in murine giardiasis.

Giardiasis, a parasitic infection of the gastrointestinal tract, is prevalent worldwide. The integrity of the intestinal epithelial barrier plays an important defensive role in giardiasis, and as Oral supplementation with prebiotics and probiotics is known to reinforce the intestinal barrier in many gastrointestinal diseases, this study assessed the effects of prebiotic and probiotic supplementation in giardiasis and compared the results with those obtained after nitazoxanide therapy. Swiss albino male lab-bred mice (n = 50) were divided into three major groups; Group I (control group), i.e., negative (noninfected nontreated) and positive controls (infected nontreated); Group II (preventive group), in which mice were provided prebiotic, probiotic, or a combination for 7 days before of infection, and Group III (therapy group), in which mice were administered prebiotic, probiotic, combined supplements and nitazoxanide from day 12 post-infection. The assessment was achieved through Giardia cyst count, histopathological examination and ultrastructure study. Also, Serological and immunohistochemical parameters were done to evaluate the modulation of IgA levels. Oral supplementation with prebiotic and probiotic, either before or after infection (in preventive or therapy groups respectively) resulted in a significant reduction in Giardia cyst shedding. Remarkable histological and ultrastructure improvement in the intestinal changes, along with a significant increase in the serological and immunohistochemical IgA levels, were seen in mice provided combined supplements and nitazoxanide (in therapy group). Thus, our results indicate that combined prebiotic and probiotic supplementation has promising anti-Giardia activity and that it can restore intestinal structures and modulate IgA response, apart from providing synergistic effects when added to nitazoxanide.

The effect of Alnus incana (L.) Moench extracts in ameliorating iron overload-induced hepatotoxicity in male albino rats.

Iron overload causes multiorgan dysfunction and serious damage. Alnus incana from the family Betulaceae, widely distributed in North America, is used for treating diseases. In this study, we investigated the iron chelating, antioxidant, anti-inflammatory, and antiapoptotic activities of the total and butanol extract from Alnus incana in iron-overloaded rats and identified the bioactive components in both extracts using liquid chromatography-mass spectrometry. We induced iron overload in the rats via six intramuscular injections of 12.5 mg iron dextran/100 g body weight for 30 days. The rats were then administered 60 mg ferrous sulfate /kg body weight once daily using a gastric tube. The total and butanol extracts were given orally, and the reference drug (deferoxamine) was administered subcutaneously for another month. After two months, we evaluated the biochemical, histopathological, histochemical, and immunohistochemical parameters. Iron overload significantly increased the serum iron level, liver biomarker activities, hepatic iron content, malondialdehyde, tumor necrosis factor-alpha, and caspase-3 levels. It also substantially (P < 0.05) reduced serum albumin, total protein, and total bilirubin content, and hepatic reduced glutathione levels. It caused severe histopathological alterations compared to the control rats, which were markedly (P < 0.05) ameliorated after treatment. The total extract exhibited significantly higher anti-inflammatory and antiapoptotic activities but lower antioxidant and iron-chelating activities than the butanol extract. Several polyphenolic compounds, including flavonoids and phenolic acids, were detected by ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) analysis. Our findings suggest that both extracts might alleviate iron overload-induced hepatoxicity and other pathological conditions characterized by hepatic iron overload, including thalassemia and sickle-cell anemia.

Transcriptome-wide association analyses identify an association between ARL14EP and polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder, which is accompanied by a variety of comorbidities including metabolic, reproductive, and psychiatric disorders. Genome-wide association studies have identified several genetic variants that are associated with PCOS. However, these variants often occur outside of coding regions and require further investigation to understand their contribution to PCOS. A transcriptome-wide association study (TWAS) was performed to uncover heritable gene expression profiles that are associated with PCOS in two independent cohorts. Causal gene prioritization was subsequently performed and expression of genes prioritized through these analyses was examined in 49 PCOS patients and 30 controls. TWAS analyses revealed that increased expression of ARL14EP was significantly associated with PCOS risk in the discovery (P = 1.6 × 10-6) and replication cohorts (P = 2.0 × 10-13). Gene prioritization pipelines provided further evidence that ARL14EP is the most likely causal gene at this locus. ARL14EP gene expression was shown to be significantly different between PCOS cases and controls, after adjusting for body mass index, age and testosterone levels (P = 1.2 × 10-13). This study has provided evidence for the role of ARL14EP in PCOS. Given that ARL14EP has been reported to play an important role in chromatin remodeling, variants affecting the expression of ARL14EP may also affect the expression of other genes that contribute to PCOS pathogenesis.

Do Probiotics Prevent Clostridium difficile-Associated Diarrhea?

Clostridium difficile is a bacterium that affects the gastrointestinal tract and is the leading cause of antibiotic-associated diarrhea. A wide range of probiotics has been studied and used to prevent or treat Clostridium difficile-associated diarrhea (CDAD). Probiotics are microorganisms with unique characteristics that suppress dangerous gut bacteria through several mechanisms. The main objective of this study is to evaluate the efficacy and safety of probiotics in the prevention of CDAD. In this literature review, we searched PubMed and Google Scholar databases to gather related articles depending on predetermined eligibility criteria and found 13 papers of different study designs. We found that probiotics have promising effects in preventing CDAD. Additionally, they were safe and well-tolerated. Further randomized clinical trials with larger sample sizes and various patient groups are needed to better understand the advantages of probiotics and recommend the best dose and duration of probiotic treatment.

Hypoxia pretreatment enhances the therapeutic potential of mesenchymal stem cells (BMSCs) on ozone-induced lung injury in rats.

Ozone (O3) gas is a double-sided weapon. It provides a shield that protects life on earth from the harmful ultraviolet (UV) rays, but ground-level O3 is considered an urban air pollutant. So, a rat model of chronic O3 inhalation was established to assess the biochemical and morphological alterations in the lung tissue and to investigate the ameliorative effects of bone marrow-derived mesenchymal stem cells (BMSCs) with or without hypoxia pre-treatment. Forty-two adult male albino rats were divided into four groups: control, ozone-exposed, normoxic BMSC-treated, and hypoxic BMSC-treated groups. Lung tissue sections were processed for light and electron microscope examination, immunohistochemical staining for caspase 3, and iNOS. Quantitative real-time PCR for IL-1α, IL-17, TNF-α, and Nrf2 mRNA gene expression were also performed. Chronic O3 exposure caused elevated inflammatory cytokines and decreased antioxidant Nrf2 mRNA expression. Marked morphological alterations with increased collagen deposition and elevated apoptotic markers and iNOS were evident. BMSC treatment showed immunomodulatory (decreased inflammatory cytokine gene expression), antioxidant (increased Nrf2 expression and decreased iNOS), and anti-apoptotic (decreased caspase3 expression) effects. Consequently, ameliorated lung morphology with diminished collagen deposition was observed. Hypoxia pretreatment enhanced BMSC survival by MTT assay. It also augmented the previously mentioned effects of BMSCs on the lung tissue as proved by statistical analysis. Lung morphology was similar to that of control group. In conclusion, hypoxia pretreatment represents a valuable intervention to enhance the effects of MSCs on chronic lung injury.

African Genomic Medicine Portal: A Web Portal for Biomedical Applications.

Genomics data are currently being produced at unprecedented rates, resulting in increased knowledge discovery and submission to public data repositories. Despite these advances, genomic information on African-ancestry populations remains significantly low compared with European- and Asian-ancestry populations. This information is typically segmented across several different biomedical data repositories, which often lack sufficient fine-grained structure and annotation to account for the diversity of African populations, leading to many challenges related to the retrieval, representation and findability of such information. To overcome these challenges, we developed the African Genomic Medicine Portal (AGMP), a database that contains metadata on genomic medicine studies conducted on African-ancestry populations. The metadata is curated from two public databases related to genomic medicine, PharmGKB and DisGeNET. The metadata retrieved from these source databases were limited to genomic variants that were associated with disease aetiology or treatment in the context of African-ancestry populations. Over 2000 variants relevant to populations of African ancestry were retrieved. Subsequently, domain experts curated and annotated additional information associated with the studies that reported the variants, including geographical origin, ethnolinguistic group, level of association significance and other relevant study information, such as study design and sample size, where available. The AGMP functions as a dedicated resource through which to access African-specific information on genomics as applied to health research, through querying variants, genes, diseases and drugs. The portal and its corresponding technical documentation, implementation code and content are publicly available.

Histological and immunohistochemical study of the effect of ozone versus erythropoietin on induced skeletal muscle ischemia-reperfusion injury in adult male rats.

Ischemia reperfusion (IR) injury of skeletal muscles is a serious problem because of its local and systemic complications. Previous studies reported that ozone and erythropoietin could alleviate IR effect on several organs. The current research is established to evaluate the possible protective role of ozone versus erythropoietin following IR injury of the gastrocnemius muscle. Fifty rats were equally divided into five groups: I control, II ischemia reperfusion (IR), III post-reperfusion ozone treated, IV post-reperfusion erythropoietin-treated, and V recovering post-reperfusion without treatment groups. The right femoral arteries of all rats were clamped for three hours to induce ischemia then clamps were released to allow reperfusion for two hours. Rats of group II were scarified immediately after reperfusion period. Rats of group III were injected with ozone just after reperfusion for 14 days. Animals of group IV were injected with erythropoietin just after reperfusion for 14 days. Rats of group V rats were kept for 2 weeks following reperfusion without treatment. Blood samples were obtained to estimate lactate dehydrogenase (LDH) and creatine kinase (CK) enzymes. Gastrocnemius muscle was processed for measurement of tissue malondialdehyde (MDA), as well as examination by light and electron microscopes. iNOS and PCNA immunohistochemistry and statistical analysis were applied. The current results indicated that both ozone and erythropoietin could be used as protective agents reducing the muscular damage induced by IR injury.

Evaluation of the anti-atherogenic potential of Egyptian artichoke leaf extract in hypercholesterolemic rats.

OBJECTIVES: The current research seeks to assess the anti-atherogenic activity of Egyptian artichoke leaf extract in hypercholesterolemic rats. MATERIALS AND METHODS: Male albino rats were categorized into five groups; control group, high cholesterol diet treated group (HCD), HCD + low dose of artichoke, HCD + high dose of artichoke and HCD + Atorvastatin. RESULTS: Both doses of artichoke extract significantly decreased the concentration of serum cholesterol, triglycerides, and LDL-C in HCD rats as compared to that of their matching controls, p < .05. The treatment with artichoke led to the inhibition of the liver hydroxymethylglutaryl-CoA (HMG-CoA) reductase. Besides, the extract was proven to be cardioprotective effective by increasing antioxidant activity. The effect of the highest dose of artichoke was more apparent than the effect of the lowest one. The biochemical data was reinforced by the histopathological studies. DISCUSSION AND CONCLUSION: Artichoke may act as a natural source for the elimination of cardiovascular ailments.

Evaluation of the cardioprotective effect of Casuarina suberosa extract in rats.

The aim of the current study was to examine and compare the cardioprotective activities of the chloroform and petroleum extracts the leaves of Casuarina suberosa in isoproterenol (ISO)-induced cardiac tissue oxidative stress. Rats were categorized into 6 groups as follows: control group, vehicle or Tween 80-treated group, ISO-treated group, chloroform extract + ISO treated group, petroleum ether extract + ISO treated group and Reference drug (Captopril) + ISO treated group. ISO injection significantly (p < 0.05) increased the activities of cardiac marker enzymes (CK-MB, LDH, ALT, and AST), cardiac troponin-I, levels of lipid peroxides (MDA), nitric oxide (NO), and vascular endothelial growth factor (VEGF), serum angiotensin-converting enzyme (ACE) activity and neutrophil infiltration marker; myeloperoxidase (MPO) in the cardiac tissues. Pretreatment with chloroform or petroleum ether extracts significantly (p < 0.05) prevented the ISO-induced alteration; they upregulated VEGF expression. Histopathological findings corroborated biochemical results. These extracts exerted a cardioprotective effect by alleviating oxidative stress.

Antidiabetic and hypolipidemic potentials of Solidago virgaurea extract in alloxan-induced diabetes type 1.

OBJECTIVES: The aim of the current study is to investigate the antidiabetic and hypolipidemic potentials of Solidago virgaurea extract in alloxan-induced diabetic rats. MATERIALS AND METHODS: Alloxan-induced diabetic rats were orally administered a dose of Solidago virgaurea extract (250 mg/kg body weight) daily for 15 days. Then blood glucose, insulin, serum lipid profile, amylase, tumour necrosis factor-α (TNF- α), and liver glycogen were determined. Besides, superoxide dismutase (SOD), catalase activities, and malondialdehyde (MDA) levels in pancreatic tissue were assessed. RESULTS: Solidago virgaurea extract significantly reduced blood glucose level, serum amylase activity, TNF-α level, and pancreatic MDA level as well as increasing the serum insulin, liver glycogen level, pancreatic SOD, and catalase activities in comparison with their corresponding diabetic rats, p < .05. CONCLUSION: The findings of this study support the ethnomedicinal use of Solidago virgaurea extract as an antidiabetic and antihyperlipidemic in the management of diabetes mellitus.

The Extent and Impact of Variation in ADME Genes in Sub-Saharan African Populations.

Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied-which has implications for drug safety and effective use in Africa. Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations. Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.

Implication of High-mobility group box-1 and skin post mortem changes in estimation of time passed since death: Animal and human study.

Determination of postmortem interval (PMI) is one of the goals of the forensic autopsy. The study aimed to correlate the postmortem skin changes and High-mobility group box-1 (HMGB1) alterations in serum and skin immunohistochemical staining with time since death. We used animal and human specimens; forty adult male albino rats were dissected to obtain samples at PMI (0, 3, 6, 12, 24 h); forty human medicolegal autopsy cases with a known time of death (within the first 24 h PMI). Cases were classified into 5 groups according to the PMI: I (0 h); II (≤3h); III (4 to 6); IV (7 to 12); V (13 to 24) hour intervals after death; blood and full-thickness skin samples were collected from both models. Results showed a significant time-dependent elevation in serum HMGB1 levels along with its overexpression in immunohistochemically stained skin tissue. Also, the degree of histopathological changes in epidermis, dermis, and hypodermis progressively increased with PMI in both models. The timetable of postmortem skin histological changes, serum HMGB1 concentration, and immunoexpression for HMGB1 proteins in skin tissues has a profile that could serve as actual and simply convenient parameters for accurate determination of postmortem intervals in both models. HMGB1 displayed a pivotal role in the estimation of PMI at the examined periods.

Yellow phosphorus and Potash for SOX and NOX removal.

Flue gases emitted from the industries and other emission sources are considered the main atmospheric issues. The main Flue gases emitted are sulfur oxides SOX and Nitrogen oxides NOX. The study was about methods of removing SOX and NOX from emitted gases and the possibility of deriving useful byproducts. The process for removing was investigated using different absorbers, process conditions, and phosphorus allotropes. The yellow phosphorus (P4) was applied for removal accompanied by Potash. The simultaneous removal achieved higher removing efficiency for SOX than NOX. Yellow phosphorus emulsion proved to be one of the effective SOX and NOX removal techniques. Byproducts produced from SOX and NOX proved to contain the complete fertiliser Nitrogen Phosphorus Potassium NPK. The obtained results showed that several useful byproducts can be derived from SOX and NOX removal process.

H3ABioNet genomic medicine and microbiome data portals hackathon proceedings.

African genomic medicine and microbiome datasets are usually not well characterized in terms of their origin, making it difficult to find and extract data for specific African ethnic groups or even countries. The Pan-African H3Africa Bioinformatics Network (H3ABioNet) recognized the need for developing data portals for African genomic medicine and African microbiomes to address this and ran a hackathon to initiate their development. The two portals were designed and significant progress was made in their development during the hackathon. All the participants worked in a very synergistic and collaborative atmosphere in order to achieve the hackathon's goals. The participants were divided into content and technical teams and worked over a period of 6 days. In response to one of the survey questions of what the participants liked the most during the hackathon, 55% of the hackathon participants highlighted the familial and friendly atmosphere, the team work and the diversity of team members and their expertise. This paper describes the preparations for the portals hackathon and the interaction between the participants and reflects upon the lessons learned about its impact on successfully developing the two data portals as well as building scientific expertise of younger African researchers. Database URL: The code for developing the two portals was made publicly available in GitHub repositories: [https://github.com/codemeleon/Database; https://github.com/codemeleon/AfricanMicrobiomePortal].

Human OMICs and Computational Biology Research in Africa: Current Challenges and Prospects.

Following the publication of the first human genome, OMICs research, including genomics, transcriptomics, proteomics, and metagenomics, has been on the rise. OMICs studies revealed the complex genetic diversity among human populations and challenged our understandings of genotype-phenotype correlations. Africa, being the cradle of the first modern humans, is distinguished by a large genetic diversity within its populations and rich ethnolinguistic history. However, the available human OMICs tools and databases are not representative of this diversity, therefore creating significant gaps in biomedical research. African scientists, students, and publics are among the key contributors to OMICs systems science. This expert review examines the pressing issues in human OMICs research, education, and development in Africa, as seen through a lens of computational biology, public health relevant technology innovation, critically-informed science governance, and how best to harness OMICs data to benefit health and societies in Africa and beyond. We underscore the disparities between North and Sub-Saharan Africa at different levels. A harmonized African ethnolinguistic classification would help address annotation challenges associated with population diversity. Finally, building on the existing strategic research initiatives, such as the H3Africa and H3ABioNet Consortia, we highly recommend addressing large-scale multidisciplinary research challenges, strengthening research collaborations and knowledge transfer, and enhancing the ability of African researchers to influence and shape national and international research, policy, and funding agendas. This article and analysis contribute to a deeper understanding of past and current challenges in the African OMICs innovation ecosystem, while also offering foresight on future innovation trajectories.

Short term chronic toxicity of tributyltin on the testes of adult albino rats and the possible protective role of omega-3.

The declining rate of male fertility is a growing concern. Tributyltin (TBT) is a well-known endocrine disruptor (ED), that induces imposex in female gastropods and is widely used in various industrial applications. The aim of this study was to evaluate the toxic effects of TBT on the testes of adult albino rats and the possible role of omega-3. Forty two adult male albino rats were divided into five groups; control group (Group I) and four experimental groups: omega-3 treated group, TBT treated group, TBT & omega-3 treated group and follow up group. At the end of the study, the rats were subjected to biochemical, histological, immunohistochemical staining for Ki-67 and seminal examinations. Our results clarfied that TBT induced a significant decrease in testosterone, FSH, LH and serum glutathione peroxidase levels and a significant increase in the serum Malondialdehyde as compared to the control group. Tributyltin induced disorganization and shrinkage of seminiferous tubules, apoptosis, cellular damage and marked reduction in the germinal epithelium. A significant decrease in the cell proliferation and arrested spermatogenesis were also detected. Seminal analysis of TBT group showed a significant affection of all parameters as compared to other groups. Omega-3 ameliorated all of these hazardous effects. Follow up group still showed toxic effects. In conclusion, TBT has a toxic effect on the testis. Increased testicular oxidative stress, cellular damage and arrest of spermatogenesis with attenuation in antioxidant defenses are all contributing factors. Omega-3 can protect against TBT induced reproductive toxicity.