Influence of 1-[(E)-2-(2-Methyl-4-Nitrophenyl)Diaz-1-enyl]Pyrrolidine-2-Carboxylic Acid and Diphenyliodonium Chloride on Ruminal Protein Metabolism and Ruminal Microorganisms

The effects of 1-[(E)-2-(2-methyl-4-nitrophenyl)diaz-1-enyl]pyrrolidine-2-carboxylic acid (LY29) and diphenyliodonium chloride (DIC) on the degradation of protein to ammonia were determined in a mixed rumen microbial population taken from sheep on a grass hay-concentrate diet. Both compounds decreased NH₃ production by inhibiting deamination of amino acids. LY29, but not DIC, inhibited growth of the high-activity ammonia-producing species, Clostridium aminophilum and Clostridium sticklandii.     

Rational design of a hydrolysis-resistant mycobacterial phosphoglycolipid antigen presented by CD1c to T cells

Whereas proteolytic cleavage is crucial for peptide presentation by classical major histocompatibility complex (MHC) proteins to T cells, glycolipids presented by CD1 molecules are typically presented in an unmodified form. However, the mycobacterial lipid antigen mannosyl-β1-phosphomycoketide (MPM) may be processed through hydrolysis in antigen presenting cells, forming mannose and phosphomycoketide (PM). To further test the hypothesis that some lipid antigens are processed, and to generate antigens that lead to defined epitopes for future tuberculosis vaccines or diagnostic tests, we aimed to create hydrolysis-resistant MPM variants that retain their antigenicity. Here, we designed and tested three different, versatile synthetic strategies to chemically stabilize MPM analogs. Crystallographic studies of CD1c complexes with these three new MPM analogs showed anchoring of the lipid tail and phosphate group that is highly comparable to nature-identical MPM, with considerable conformational flexibility for the mannose head group. MPM-3, a difluoromethylene-modified version of MPM that is resistant to hydrolysis, showed altered recognition by cells, but not by CD1c proteins, supporting the cellular antigen processing hypothesis. Furthermore, the synthetic analogs elicited T cell responses that were cross-reactive with nature-identical MPM, fulfilling important requirements for future clinical use.     

The COVID-19 infection in children and its association with the immune system,prenatal stress,and neurological complications

The Coronavirus disease 2019 (COVID-19)” caused by the “severe acute respiratory syndrome corona virus 2 (SARS-CoV-2)” has caused huge losses to the world due to the unavailability of effective treatment options. It is now a serious threat to humans as it causes severe respiratory disease, neurological complications, and other associated problems. Although COVID-19 generally causes mild and recoverable symptoms in children, it can cause serious severe symptoms and death causing complications. Most importantly, SARS-CoV-2 can cause neurological complications in children, such as shortness of breath, myalgia, stroke, and encephalopathy. These problems are highly linked with cytokine storm and proinflammatory responses, which can alter the physiology of the blood-brain barrier and allow the virus to enter the brain. Despite the direct infection caused by the virus entry into the brain, these neurological complications can result from indirect means such as severe immune responses. This review discusses viral transmission, transport to the brain, the associated prenatal stress, and neurological and/or immunological complications in children.     

Aflatoxins and kwashiorkor: a study in Sudanese children.

Blood and urine samples from 252 Sudanese children were investigated for their aflatoxin content by high-performance liquid chromatography. The children comprised 44 with kwashiorkor, 32 with marasmic kwashiorkor, 70 with marasmus, and 106 age-matched, normally nourished controls. Aflatoxins were detected more often and at higher concentrations in sera from children with kwashiorkor than in the other malnourished and control groups. Aflatoxicol, a metabolite of aflatoxins B1 and B2, was detected in the sera of children with kwashiorkor and marasmic kwashiorkor but not in the controls and only once in a marasmic child. The difference between children with kwashiorkor or marasmic kwashiorkor and those in the control or marasmus groups was significant. Urinary aflatoxin was most often detected in children with kwashiorkor but their mean concentration was lower than in the other groups. Aflatoxicol was not detected in urine in any group. These findings suggest either that the children with kwashiorkor have a greater exposure to aflatoxins or that their ability to transport and excrete aflatoxins is impaired by the metabolic derangements associated with kwashiorkor. The presence of aflatoxicol in the sera of children with kwashiorkor but not in the others suggests a difference in metabolism between the two groups. Further studies are needed, and measurement of aflatoxins in the food eaten by these children is already underway.     

Molecular docking of phenolic compounds and screening of antioxidant and antidiabetic potential of Moringa oleifera ethanolic leaves extract from Qassim region,Saudi Arabia

IntroductionOxidative stress is crucial in diabetic pathophysiology, hence the prerequisite of ingesting naturally derived antioxidants as a remedial target. This study investigates the naturally occurring antioxidant and antidiabetic potential of Moringa oleifera ethanolic leaves extract.MethodsMoringa oleifera leaves were macerated (MOLE) by using 70% ethanol. Physiochemical and phytochemical examinations of MOLE was assayed using standard methods. The antioxidant activity was analyzed by DPPH (1, 1-diphenyl-2-picrylhydrazil) radical scavenging assay. In vitro antidiabetic was analyzed by pancreatic α-amylase enzyme inhibitory assay. The molecular docking was performed using AutoDock Vina v1.1.2 in PyRx 30.8.ResultsEthanolic extraction of MOLE by maceration technique, 14 % yield. Loss on drying, foreign organic matters and total ash value of OLE showed 0.27 w/w, 0.8 % and 19 %, respectively. Phytochemical test on MOLE confirmed starch, carbohydrate, flavonoid, gum, glycoside, saponin, tannin, and phenol presences. The total phenolic and flavonoid contents of MOLE are 260 mg GAE/g and 755 mg RUE/g of extract. MOLE (IC 50 55.6 ± 0.18 µg/mL) showed functional DPPH scavenging assay comparable to ascorbic acid (IC 50 46.71 ± 0.24 µg/mL). In the alpha-amylase inhibitory activity, Acarbose showed an IC 50 value of 19.45 ± 0.26 µg/mL, while MOLE portrayed an IC 50 value of 27.54 ± 0.07 µg/mL. Docking studies revealed that most phenolic compounds found within MOLE have minimum docking scores and high binding affinity against Human pancreatic alpha-amylase.ConclusionsThe invitro and docking results suggest that MOLE has been a viable natural bioactive source and might be a great potential source for future antidiabetic medicine.     

Aflatoxins levels in vegetable oils in Khartoum State,Sudan

Vegetable oil (n = 81) for human consumption from Khartoum State in Sudan were analyzed for aflatoxins (AFs), using high-performance liquid chromatography (HPLC) with fluorescence detection following extraction with methanol:water (80:20) and clean-up using petroleum ether. Sampling included sesame oil (n = 14), peanut oil (n = 21), and sunflower oil (n = 19) purchased from retail shops, and mixed oil produced by two local manufacturers (factory A, n = 15; factory B, n = 12). AF contamination was found in 80/81 (98.8%) samples, with total AF levels ( AFB₁ + AFB₂ + AFG₁ + AFG₂ ) \left( {{\hbox{AF}}{{\hbox{B}}_{\rm{1}}} + {\hbox{AF}}{{\hbox{B}}_{\rm{2}}} + {\hbox{AF}}{{\hbox{G}}_{\rm{1}}} + {\hbox{AF}}{{\hbox{G}}_{\rm{2}}}} \right) of 0.43–339.9 μg/kg and mean level of 57.5 μg/kg. All sesame oils had total AF levels that were much higher than the United States Food and Drug Administration acceptable limit of 20 μg/kg. The percentage of samples with total AF values <20 μg/kg in other oils varied and was 57.14% in peanut oil, 36.8% in sunflower oil, 66.7% (mixed oil from factory A), and 91.7% (mixed oil from factory B). In conclusion, the levels of total AFs in edible oil as available in Khartoum State are quite alarming. To reduce the health hazards for the consumers, an intervention strategy to manage AFs in food commodities from Sudan is urgently required.     

Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization

Fanconi anemia (FA) is an autosomal recessive disease characterized by genomic instability, cancer susceptibility, and cellular hypersensitivity to DNA-cross-linking agents. Eight complementation groups of FA (FA-A through FA-H) have been identified. Two FA genes, corresponding to complementation groups FA-A and FA-C, have been cloned, but the functions of the encoded FAA and FAC proteins remain unknown. We have recently demonstrated that FAA and FAC interact to form a nuclear complex. In this study, we have analyzed a series of mutant forms of the FAA protein with respect to functional activity, FAC binding, and nuclear localization. Mutation or deletion of the amino-terminal nuclear localization signal (NLS) of FAA results in loss of functional activity, loss of FAC binding, and cytoplasmic retention of FAA. Replacement of the NLS sequence with a heterologous NLS sequence, derived from the simian virus 40 T antigen, results in nuclear localization but does not rescue functional activity or FAC binding. Nuclear localization of the FAA protein is therefore necessary but not sufficient for FAA function. Mutant forms of FAA which fail to bind to FAC also fail to promote the nuclear accumulation of FAC. In addition, wild-type FAC promotes the accumulation of wild-type FAA in the nucleus. Our results suggest that FAA and FAC perform a concerted function in the cell nucleus, required for the maintenance of chromosomal stability.