Prevalence of glucose-6-phosphate dehydrogenase deficiency (G6PDd), CareStart qualitative rapid diagnostic test performance,and genetic variants in two malaria-endemic areas in Sudan

Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common enzymopathy globally, and deficient individuals may experience severe hemolysis following treatment with 8-aminoquinolines. With increasing evidence of Plasmodium vivax infections throughout sub-Saharan Africa, there is a pressing need for population-level data at on the prevalence of G6PDd. Such evidence-based data will guide the expansion of primaquine and potentially tafenoquine for radical cure of P. vivax infections. This study aimed to quantify G6PDd prevalence in two geographically distinct areas in Sudan, and evaluating the performance of a qualitative CareStart rapid diagnostic test as a point-of-care test. Blood samples were analyzed from 491 unrelated healthy persons in two malaria-endemic sites in eastern and central Sudan. A pre-structured questionnaire was used which included demographic data, risk factors and treatment history. G6PD levels were measured using spectrophotometry (SPINREACT) and first-generation qualitative CareStart rapid tests. G6PD variants (202 G>A; 376 A>G) were determined by PCR/RFLP, with a subset confirmed by Sanger sequencing. The prevalence of G6PDd by spectrophotometry was 5.5% (27/491; at 30% of adjusted male median, AMM); 27.3% (134/491; at 70% of AMM); and 13.1% (64/490) by qualitative CareStart rapid diagnostic test. The first-generation CareStart rapid diagnostic test had an overall sensitivity of 81.5% (95%CI: 61.9 to 93.7) and negative predictive value of 98.8% (97.3 to 99.6). All persons genotyped across both study sites were wild type for the G6PD G202 variant. For G6PD A376G all participants in New Halfa had wild type AA (100%), while in Khartoum the AA polymorphism was found in 90.7%; AG in 2.5%; and GG in 6.8%. Phenotypic G6PD B was detected in 100% of tested participants in New Halfa while in Khartoum, the phenotypes observed were B (96.2%), A (2.8%), and AB (1%). The African A- phenotype was not detected in this study population. Overall, G6PDd prevalence in Sudan is low-to-moderate but highly heterogeneous. Point-of-care testing with the qualitative CareStart rapid diagnostic test demonstrated moderate performance with moderate sensitivity and specificity but high negative predicative value. The two sites harbored primarily the African B phenotype. A country-wide survey is recommended to understand GP6PD deficiencies more comprehensively in Sudan.     

Magnetic Fe3O4@graphene oxide improves the therapeutic effects of embryonic stem cells on acute liver damage

ObjectiveAcute liver failure is usually associated with inflammation and oxidation of hepatocytes and has high mortality and resource costs. Mesenchymal stem cell (MSCs) has occasionally been reported to have no beneficial effect due to poor transplantation and the survival of implanted cells. Recent studies showed that embryonic stem cell (ESC)‐derived MSCs are an alternative for regenerative medicine. On the other hand, graphene‐based nanostructures have proven useful in biomedicine. In this study, we investigated whether magnetic graphene oxide (MGO) improved the effects of ESC‐MSC conditioned medium (CM) on protecting hepatocytes and stimulating the regeneration of damaged liver cells.Materials and methodsTo provide a rat model of acute liver failure, male rats were injected intraperitoneally with carbon tetrachloride (CCl₄). The rats were randomly divided into six groups, namely control, sham, CCl₄, ESC‐MSC‐CM, MGO and ESC‐MSC‐CM + MGO. In the experimental groups, the rats received, depending on the group, 2 ml/kg body weight CCl₄ and either ESC‐MSC‐CM with 5 × 10⁶ MSCs or 300 μg/kg body weight MGO or both. Symptoms of acute liver failure appeared 4 days after the injection. All groups were compared and analysed both histologically and biochemically 4 days after the injection. Finally, the results of ESC‐MSC‐CM and MSC‐CM were compared.ResultsThe results indicated that the use of MGO enhanced the effect of ESC‐MSC‐CM on reducing necrosis, inflammation, aspartate transaminase, alanine aminotransferase and alkaline phosphatase in the CCl₄‐induced liver failure of the rat model. Also, the expression of vascular endothelial growth factor and matrix metalloproteinase‐9 (MMP‐9) was significantly upregulated after treatment with MGO. Also, the results showed that the ESC‐MSC‐CM has more efficient effective compared to MSC‐CM.ConclusionMagnetic graphene oxide improved the hepatoprotective effects of ESC‐MSC‐CM on acute liver damage, probably by suppressing necrosis, apoptosis and inflammation of hepatocytes.     

The Therapeutic Potential of Targeting Tumor Microenvironment in Breast Cancer: Rational Strategies and Recent Progress

The tumor microenvironment (TME) is cellular environment in addition to harboring carcinoma cells, consists of different components (e.g., blood vessels, immune cells, fibroblasts, bone marrow‐derived inflammatory cells, lymphocytes, signaling molecules, and the extracellular matrix) that have an essential role on drug activity and efficacy. There is growing body of evidence showing its involvement in the progression and metastasis of different cancers, including breast cancer (BC). These observations provide a proof of concept of targeting TME compartments as a novel potential therapeutic approach in treatment of this malignancy, which is the main interested for current review. J. Cell. Biochem. 119: 111–122, 2018. © 2017 Wiley Periodicals, Inc.     

An overview of toxicogenomics

Toxicogenomics is a rapidly developing discipline that promises to aid scientists in understanding the molecular and cellular effects of chemicals in biological systems. This field encompasses global assessment of biological effects using technologies such as DNA microarrays or high throughput NMR and protein expression analysis. This review provides an overview of advancing multiple approaches (genomic, proteomic, metabonomic) that may extend our understanding of toxicology and highlights the importance of coupling such approaches with classical toxicity studies.     

Polyurethane/Gelatin Nanofibrils Neural Guidance Conduit Containing Platelet-Rich Plasma and Melatonin for Transplantation of Schwann Cells

The current study aimed to enhance the efficacy of peripheral nerve regeneration using a biodegradable porous neural guidance conduit as a carrier to transplant allogeneic Schwann cells (SCs). The conduit was prepared from polyurethane (PU) and gelatin nanofibrils (GNFs) using thermally induced phase separation technique and filled with melatonin (MLT) and platelet-rich plasma (PRP). The prepared conduit had the porosity of 87.17 ± 1.89%, the contact angle of 78.17 ± 5.30° and the ultimate tensile strength and Young’s modulus of 5.40 ± 0.98 MPa and 3.13 ± 0.65 GPa, respectively. The conduit lost about 14% of its weight after 60 days in distilled water. The produced conduit enhanced the proliferation of SCs demonstrated by a tetrazolium salt-based assay. For functional analysis, the conduit was seeded with 1.50 × 10⁴ SCs (PU/GNFs/PRP/MLT/SCs) and implanted into a 10-mm sciatic nerve defect of Wistar rat. Three control groups were used: (1) PU/GNFs/SCs, (2) PU/GNFs/PRP/SCs, and (3) Autograft. The results of sciatic functional index, hot plate latency, compound muscle action potential amplitude and latency, weight-loss percentage of wet gastrocnemius muscle and histopathological examination using hematoxylin–eosin and Luxol fast blue staining, demonstrated that using the PU/GNFs/PRP/MLT conduit to transplant SCs to the sciatic nerve defect resulted in a higher regenerative outcome than the PU/GNFs and PU/GNFs/PRP conduits.     

Improved angiogenic activity of endothelial progenitor cell in diabetic patients treated with insulin plus metformin

Type 2 diabetes (T2DM) is associated with an increased vascular disease. Moreover, endothelial progenitor cell (EPC) function is impaired in diabetic patients. Decreased EPC number plays a critical role in reduced endothelial repair and development of the vascular disorder. To determine the effect of metformin and insulin plus metformin on functional activity of EPCs, 130 participants were divided into three groups (group 1: healthy control; group 2: metformin; group 3: insulin plus metformin). The concentration of EPCs in the circulation was first quantified. Thereafter, circulating EPCs (cEPCs) were harvested and the biological features of these cells including proliferative, clonogenicity, tubulogenic, and migratory properties were analyzed after expansion. The serum protein levels of some proangiogenic factors were also measured. Our results showed greater numbers of cEPCs in control and in diabetic patients treated with insulin plus metformin than in metformin-treated patients. Insulin plus metformin therapy was associated with augmented proliferative, clonogenicity, migratory, and tubulogenic activity of cEPCs in patients with T2DM. Increased serum concentrations of angiogenic factors were also observed in patients treated with insulin plus metformin. Western blot analysis showed increased protein levels of pTie-2/Tie2 and Pakt/AKT in cEPCs harvested from T2DM, treated with insulin metformin plus. This study showed that treatment with insulin plus metformin in diabetic patients is associated with increased mobilization of EPCs into the circulation, with potential beneficial effect in vascular protection in diabetic patients.     

Heat-shock-induced color-pattern changes of the blue pansy butterfly Junonia orithya: Physiological and evolutionary implications

Temperature shock to early pupae causes wing color-pattern changes in butterflies. These plastic changes are ascribed to the hemolymph level of the cold-shock hormone (CSH) in pupae as well as to other mechanisms. Here, we characterized heat-shock-induced color-pattern changes using the blue pansy butterfly Junonia orithya (Lepidoptera: Nymphalidae). In response to the 38-42 °C heat-shock treatments, parafocal elements (PFEs) were thinned and dislocated away from eyespots; this was the reverse of the direction of the cold-shock-induced changes. Somewhat surprisingly, in response to the lethal 44 °C heat shock, PFEs were modified as in the case of a cold-shock. These modifications were not affected by the removal of the head-prothorax portion of pupae. While the hemolymph-mediated transfer of the possible PFE-modification property induced by the 42 °C treatment was unsuccessful in the parabiosis experiment, the transfer of the factor induced by the 44 °C treatment was successful. In contrast, reduction of the blue background area was obtained not only by the 42 and 44 °C treatments but also by the injection of thapsigargin, a plant-derived stress inducer, in males. The result of this treatment was similar to the natural color patterns of other closely related Junonia species. We also observed an increase in orange coloration by the 42 °C treatment in females, and this change was similar to ecdysteroid-induced modifications. Taken together, the heat-shock-induced PFE modifications in J. orithya can be explained by the levels of CSH, and other modifications are likely to be caused by general stress responses and ecdysteroid effects. We conclude that phenotypic plasticity of the wing color patterns to heat shock results from a combined effect of at least a few different mechanisms. These mechanisms might have been exploited in the color-pattern evolution of some Junonia species.