Urine Metabolomics Reveals Overlapping Metabolic Associations Between Preeclampsia and Gestational Diabetes.

Pregnancy is associated with numerous metabolic adaptations to meet the demands of the growing foetus. These adaptations could be perturbed during pregnancy due to preeclampsia (PE) and gestational diabetes (GDM). As these two obstetric aliments show some overlapping pathophysiology and similar biochemical dysregulation, the present study was undertaken to compare urine metabolome of PE and GDM with normal pregnancy (NT) in all trimesters of gestation using nuclear magnetic resonance spectroscopy-based metabolomics analysis to ascertain and compare metabolome in the study groups. We observed overlapping metabolic perturbations in PE and GDM. Though a study with a small sample size, this is the first report which confirms significantly differential metabolites in urine of both PE and GDM. Dimethylglycine and oxoglutaric acid were decreased while benzoic acid was increased in both the cases in all trimesters. Alanine, aspartate and glutamate metabolism, aminoacyl-tRNA biosynthesis, citrate and butanoate metabolism were the most perturbed pathways in both PE and GDM across pregnancy. These pathways have an association with energy metabolism, glucose homeostasis, insulin sensitivity and oxidative stress which play an important role in the development and progression of PE and GDM. In conclusion, our study showed that urine metabolome could reflect metabolic associations between PE and GDM and also in the identification of biomolecules that could be used as potential biomarker(s) for early detection of the metabolic diseases in pregnancy. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01103-2.

Physiochemical analyses and molecular characterization of heavy metal-resistant bacteria from Ilesha gold mining sites in Nigeria.

BACKGROUND: The contribution of the processes involved and waste generated during gold mining to the increment of heavy metals concentration in the environment has been well established. While certain heavy metals are required for the normal functioning of an organism, certain heavy metals have been identified for their deleterious effects on the ecosystem and non-physiological roles in organisms. Hence, efforts aimed at reducing their concentration level are crucial. To this end, soil and water samples were collected from Ilesha gold mining, Osun State, Nigeria, and they were subjected to various analyses aimed at evaluating their various physicochemical parameters, heavy metal concentration, heavy metal-resistant bacteria isolation, and other analyses which culminated in the molecular characterization of heavy metal-resistant bacteria. RESULTS: Notably, the results obtained from this study revealed that the concentration of heavy metal in the water samples around the mining site was in the order Co > Zn > Cd > Pb > Hg while that of the soil samples was in the order Co > Cd > Pb > Hg > Zn. A minimum inhibitory concentration test performed on the bacteria isolates from the samples revealed some of the isolates could resist as high as 800 ppm of Co, Cd, and Zn, 400 ppm, and 100 ppm of Pb and Hg respectively. Molecular characterization of the isolates revealed them as Priestia aryabhattai and Enterobacter cloacae. CONCLUSION: Further analysis revealed the presence of heavy metal-resistant genes (HMRGs) including merA, cnrA, and pocC in the isolated Enterobacter cloacae. Ultimately, the bacteria identified in this study are good candidates for bioremediation and merit further investigation in efforts to bioremediate heavy metals in gold mining sites.

Microbiome analysis of saliva from oral squamous cell carcinoma (OSCC) patients and tobacco abusers with potential biomarkers for oral cancer screening.

Oral squamous cell carcinoma (OSCC) is the most common type of oral cancer and accounts for about 95% of all head and neck cancers with high mortality, usually at a late stage. Dysbiosis in the oral microbiome can lead to chronic inflammatory responses and may predispose to the development and progression of OSCC. Tobacco abuse plays an essential role in oral microbiome dysregulation and OSCC pathogenesis. We used 16S rRNA gene amplicon next-generation sequencing to examine microbial signatures unique to saliva from OSCC patients, tobacco abusers (TA) and controls (n = 10 for each group) to elucidate oral microbiome changes associated with tobacco abuse and OSCC. Overall, the oral microbiome compositions of class Betaproteobacteria and Epsilonproteobacteria, order Neisseriales, Burkholderiales and Campylobacterales, family Burkholderiaceae and Campylobacteraceae and genera Campylobacter and Leptotrichia revealed significant differences among OSCC patients, TA and control. Our preliminary pilot study not only serves as a basis for future studies with large sample size but also gives an indication of microbiome-based potential non-invasive biomarkers for early screening and monitoring of oral carcinogenesis transition due to tobacco abuse.

Unravelling the anti-inflammatory mechanism of Allium cepa: an integration of network pharmacology and molecular docking approaches.

Allium cepa, commonly known as onion, is a widely consumed spice that possesses numerous pharmacological properties. A. cepa bioactive components are often explored in the treatment of inflammation-related complications. However, the molecular mechanism via which they exert their anti-inflammatory effects remains unknown. Therefore, this study aimed to elucidate the anti-inflammatory mechanism of A. cepa bioactive components. Consequently, the bioactive compounds of A. cepa were obtained from a database, while the potential targets of the sixty-nine compounds with desirable pharmacokinetic properties were predicted. Subsequently, the targets of inflammation were acquired from the GeneCards database. The protein-protein interaction (PPI) between the sixty-six shared targets of the bioactive compounds and inflammation was retrieved from the String database and visualized using Cytoscape v3.9.1 software. Gene Ontology (GO) analysis of the ten core targets from the PPI network revealed that A. cepa bioactive compounds could be involved in regulating biological processes such as response to oxygen-containing compounds and response to inflammation while Kyoto Encyclopaedia of Genes and Genomes (KEGG) analysis revealed that A. cepa compounds might modulate pathways including AGE-RAGE signaling pathway, interleukin (IL)-17 signalling pathway, and tumor necrosis factor signaling pathway. Molecular docking analysis showed that 1-O-(4-Coumaroyl)-beta-D-glucose, stigmasterol, campesterol, and diosgenin have high binding affinities for core targets including EGFR, ALB, MMP9, CASP3, and CCL5. This study successfully elucidated the potential anti-inflammatory mechanism of A. cepa bioactive compounds, hence, providing new insights into the development of alternative anti-inflammatory drugs.

Soursop juice enhanced seminal antioxidant defence and semen quality of rabbit bucks in extremely dry climatic condition of Southwestern Nigeria.

Heat induced stress associated with dry climatic conditions in the tropics does have adverse effects reproduction in rabbits, and this in-turn impacts negatively on the income of rabbit farmers. However, natural products might prove to be a reliable, safe and cheap remedy for ameliorating reproductive such anomalies in rabbits. The potential of soursop for mitigating heat induced reproductive deficiency in rabbit bucks was investigated during the peak of dry climatic conditions in southwestern Nigeria. Sixty mixed breed (New Zealand white x Chinchilla) adult rabbit bucks were allotted to five treatments of four replicates (3 bucks per replicate) each in a completely randomized design. Soursop (Annona muricata) fruit was processed into juice using standard procedures and was designated as soursop juice. The juice was administered orally daily per kg body weight (BW), 0.55ml/kgBW distilled water (control), 0.55 ml/kgBW soursop juice, 1.11 ml/kgBW soursop juice, 1.67 ml/kgBW soursop juice and 2.22 ml/kgBW soursop juice to designated treatments 1 to 5, respectively for 56 days. Semen samples were collected with an improvised artificial vagina on the 28th and 56th day of the study, semen quality and seminal oxidative status were evaluated using standard procedures. Results showed that rabbit buck exposed to heat stress had lower semen quality, seminal antioxidants and increased seminal lipid peroxidation. However, the consumption of soursop juice lowered lipid peroxidation and enhanced (p < 0.05) antioxidant production in the seminal fluid of heat-stressed bucks than bucks on control group. Bucks' semen quality and antioxidant status peaks in heat-stressed bucks gavaged 2.22 ml/kgBW soursop juice and gives 100% recovery from the effects of heat induced stress. It can be concluded that 2.22 ml/kgBW soursop juice administered for 56 days did enhance spermatozoa quality and mitigated lipid peroxidation by improving antioxidant capacity of male rabbits in a dose dependent manner on extremely dry climatic conditions.

Potential of watermelon (Citrullus lanatus) to maintain oxidative stability of rooster semen for artificial insemination.

Fruits with antioxidant enrichment can be an economically affordable supplement for mitigating oxidative damage prone spermatozoa membrane pathologies. Computer-assisted sperm analyzer and oxidative status were utilized to evaluate the impact of watermelon (Citrullus lanatus) fortification of dextrose saline as diluent for rooster semen and fertility response of hens inseminated. Watermelon juice and dextrose saline were used to formulate diluent of 7 treatments consisting of unextended semen (positive control), 10%, 20%, 30%, 40%, 50% and only dextrose saline (negative control) designated as Treatments 1-7. Pooled semen was obtained from fertile roosters and equilibrated with diluents at ratio 1:2 in the various treatments and were evaluated using computer software coupled microscope and seminal oxidative status assay. 168 laying hens randomly divided into 7 treatment of 8 replicates and 3 hen per replicate. Hen were everted, and semen (2 × 108 Spermatozoa) deposited intra-vagina and eggs collected over 8 weeks to assess fertility and hatchability of eggs laid. The result obtained revealed that watermelon-dextrose saline rooster semen diluent enhanced progressive motility, sperm kinetics and lowered non-progressive motility in T2-T6 compared to T7 over the 3 hours of evaluation. Watermelon addition to rooster semen diluent enhance the antioxidant capacity of rooster semen and lowered lipid peroxide generation. The percentage fertility was highest in T3 (81.01%) and T4 (81.24%) with lowest value obtained in T7 (73.46%). The hatchability of eggs set of hens inseminated with undiluted semen (71.46%) was lower than values for hens inseminated with watermelon inclusive extended semen (75.71%-80.39%). The optimal inclusion of 30%-40% watermelon in dextrose saline diluent enhance rooster semen kinetics, seminal oxidative stability and egg fertility.

Reproductive characteristics, semen quality, seminal oxidative status, steroid hormones, sperm production efficiency of rabbits fed herbal supplements.

Today, orthodox medicine has almost exceeded its limits in resolving subfertility problems in animals, thus making phytomedicine a primary tool in the treatment of infertility. In this work, three herbal supplements obtained from freshly air-dried Moringa oleifera, Phyllanthus amarus and Viscum album leaves were evaluated to ascertain their comparative effect on the reproductive potentials of bucks. Sixty bucks were allotted four diets made up of standard grower rabbit ration without supplement and with 5% Moringa, Mistletoe and Phyllanthus supplementation for 84 days. Semen samples were collected from all bucks using artificial vagina, for semen quality and seminal oxidative stress markers. The organ weights, testicular and epididymal spermatozoa reserves were assessed to determine sperm production potentials using standard procedures. The result obtained revealed that spermatozoa concentration, progressive motility, curvilinear velocity, average path velocity and the amplitude of lateral head was significantly (p < 0.05) higher in the group fed with mistletoe supplemented diet compared to that recorded in the control groups. The inclusion of herbal supplements linearly (p < 0.05) increased the seminal total antioxidant activity with a corresponding decrease in the seminal lipid peroxidation across the herbal supplemented treatments compared to the control. The gonadal and extra-gonadal sperm reserves of bucks fed on the herbal supplements were depleted compared to bucks on control. Bucks on mistletoe supplementation rivalled the superior daily sperm production and testicular sperm reserve in bucks without herbal supplements. In conclusion, Viscum album supplements in bucks' diets encouraged daily sperm production, testicular sperm reserves, testosterone, as well as spermatozoa kinetics. The three herbal supplements did enhance semen oxidative stability.

Plasma metabolomic study in perinatally HIV-infected children using 1H NMR spectroscopy reveals perturbed metabolites that sustain during therapy.

BACKGROUND: Perinatally HIV-infected children on anti-retroviral treatment (ART) are reported to have metabolic abnormalities such as dyslipidemia, lipodystrophy, and insulin resistance which potentially increase the risk of diabetes, kidney, liver and cardiovascular disease. OBJECTIVE: To elucidate HIV-mediated metabolic complications that sustain even during ART in perinatally HIV-infected children. METHOD: We have carried out metabolic profiling of the plasma of treatment-naïve and ART-suppressed perinatally HIV-infected children and uninfected controls using 1H nuclear magnetic resonance (NMR) spectroscopy followed by statistical analysis and annotation. RESULT: Validated multivariate analysis showed clear distinction among our study groups. Our results showed elevated levels of lactate, glucose, phosphoenolpyruvic acid, propionic acid, 2-ketobutyric acid and tricarboxylic acid (TCA) cycle metabolites in untreated HIV-infected children compared to uninfected controls. ART normalized the levels of several metabolites, however the level of lactate, phosphoenolpyruvic acid, oxoglutaric acid, oxaloacetic acid, myoinositol and glutamine remained upregulated despite ART in HIV-infected children. Pathway analysis revealed perturbed propanoate metabolism, amino acid metabolism, glycolysis and TCA cycle in untreated and ART-suppressed HIV-infected children. CONCLUSION: Developing therapeutic strategies targeting metabolic abnormalities may be beneficial for preventing diabetes, cardiovascular disease or other associated complications in perinatally HIV-infected children.

Development of multiepitope subunit protein vaccines against Toxoplasma gondii using an immunoinformatics approach.

Approximately one-third of the world's human population is estimated to have been exposed to the parasite Toxoplasma gondii. Its prevalence is reportedly high in Ethiopia (74.80%) and Zimbabwe (68.58%), and is 40.40% in Nigeria. The adverse effect of this parasite includes a serious congenital disease in the developing fetus of pregnant women. After several efforts to eliminate the disease, only one licensed vaccine 'Toxovax' has been used to avoid congenital infections in sheep. The vaccine has been adjudged expensive coupled with adverse effects and short shelf life. The potential of vaccine to likely revert to virulent strain is a major reason why it has not been found suitable for human use, hence the need for a vaccine that will induce T and B memory cells capable of eliciting longtime immunity against the infection. This study presents immunoinformatics approaches to design a T. gondii-oriented multiepitope subunit vaccine with focus on micronemal proteins for the vaccine construct. The designed vaccine was subjected to antigenicity, immunogenicity, allergenicity and physicochemical parameter analyses. A 657-amino acid multiepitope vaccine was designed with the antigenicity probability of 0.803. The vaccine construct was classified as stable, non-allergenic, and highly immunogenic, thereby indicating the safety of the vaccine construct for human use.

Stringent response protein as a potential target to intervene persistent bacterial infection.

More than half of the world's population is infected with persistent bacterial infections, consequently, persisters are gradually becoming a major public health concern. During the persistent phase, bacterial pathogens deploy many regulatory strategies to compensate unfavorable host environmental conditions. The stringent response is one of such gene regulatory mechanisms which is stimulated by nutrient starvation. It is regulated by the synthesis of highly phosphorylated signaling nucleotides, (p)ppGpp or alarmone. (p)ppGpp is synthesized by ppGpp synthetases, and these proteins are classified as RelA/SpoT homolog (RSH) proteins. Subsequently, (p)ppGpp modulate several molecular and biochemical processes ranging from transcription to metabolism. Imperativeness of (p)ppGpp synthetases has been investigated by numerous approaches including microbiology and animal studies, thereby establishing that Rel enzyme deleted strains of pathogenic bacteria were unable to transform in persister form. In this review, we summarize recent findings to corroborate the rationality to consider (p)ppGpp synthetase as a potential target in discovering a novel class of antimicrobial agents to combat persistent infections. Moreover, inhibition studies on Mycobacterium tuberculosis (p)ppGpp synthetase shows that these inhibitors prevent dormant state transition and biofilm formation. Also, we have highlighted the structural biology of (p)ppGpp synthetases, which may provide significant information that could be used in structure-based inhibitor design.

FTO Gene Associates and Interacts with Obesity Risk, Physical Activity, Energy Intake, and Time Spent Sitting: Pilot Study in a Nigerian Population.

Fat mass and obesity-associated (FTO) gene influences obesity but studies have shown that environmental/lifestyle variables like physical activity (PA), time spent sitting (TSS), and energy intake might mediate the effect. However, this is poorly understood in Nigeria due to scarce studies. We demystified association and interaction between FTO rs9939609, obesity, PA, TSS, and energy intake in Nigeria. FTO gene variant was genotyped by restriction fragment length polymorphism and gene sequencing analysis in 103 people with obesity and 98 controls. Anthropometrics and environmental variables were measured using standard procedures. Significant associations were found between FTO rs9939609 with obesity and environmental/lifestyle variables before and after adjusting for age. Carriers of allele A have significantly higher odds of being overweight/obese using BMI [0.191 (0.102-0.361), p < 0.001] but this was attenuated by PA (p[interaction] = 0.029); odds of being overweight reduced from 0.625 (0.181-2.159) to 0.082 (0.009-0.736) for low and high PA, respectively. Mediation analysis of total indirect effect also confirmed this by showing a simultaneous mediating role of total PA, energy intake, and TSS in the relationship between FTO and BMI (unstandardized-coefficient = 1.68; 95% CI: 1.26-2.22). This study shows a relationship between FTO and obesity phenotype and environmental/lifestyle factors might be an important modulator/mediator in the association.

Sexual dimorphism in ratio of second and fourth digits and its relationship with metabolic syndrome indices and cardiovascular risk factors.

BACKGROUND: Ratio of second and fourth digit (2D:4D) is known to be germane in analyzing utero concentrations of testosterone and estrogen in human and other vertebrates. 2D:4D had been linked to several traits like athletes' abilities, reproductive success, risk of cancer and cardiovascular disease (CVD). Metabolic syndrome (MetS) is a clustering of several cardiovascular risk factors. Waist circumference (WC), neck circumference (NC), body mass index (BMI) and waist-to-height ratio (WHtR) are important in measuring MetS. This study investigated sexual dimorphism in 2D:4D and its relationship with MetS indices and CVD factors among adult residing in Ilorin, North central Nigeria. MATERIALS AND METHODS: This is a cross-sectional, stratified multi-staged sampling study. Participants residing in different neighborhoods were visited at home where finger lengths and anthropometric traits were measured. Participants include 801 healthy adults aged 18-44 years (56% male) who had been living in the area for more than 3 years. RESULTS: Males showed significantly lower 2D:4D than females (unpaired t-test; t [699] = 11.49, P = 0.001). A significant positive correlation was observed in MetS markers and 2D:4D. WHtR showed the highest correlation with 2D:4D in male (r = 0.461, P ≤ 0.001) and female (r = 0.408, P ≤ 0.001) when compared with BMI, NC and WC. All positive correlations recorded in this study were high in male and right hand. CONCLUSION: Our results showed that 2D:4D is sexual dimorphic and right hand 2D:4D as a predictor of MetS is better. We concluded that 2D:4D is a proxy for MetS and CVD risk factors in Ilorin.