Novel biallelic variants expand the SLC5A6-related phenotypic spectrum

The sodium (Na+):multivitamin transporter (SMVT), encoded by SLC5A6, belongs to the sodium:solute symporter family and is required for the Na+-dependent uptake of biotin (vitamin B7), pantothenic acid (vitamin B5), the vitamin-like substance α-lipoic acid, and iodide. Compound heterozygous SLC5A6 variants have been reported in individuals with variable multisystemic disorder, including failure to thrive, developmental delay, seizures, cerebral palsy, brain atrophy, gastrointestinal problems, immunodeficiency, and/or osteopenia. We expand the phenotypic spectrum associated with biallelic SLC5A6 variants affecting function by reporting five individuals from three families with motor neuropathies. We identified the homozygous variant c.1285 A > G [p.(Ser429Gly)] in three affected siblings and a simplex patient and the maternally inherited c.280 C > T [p.(Arg94*)] variant and the paternally inherited c.485 A > G [p.(Tyr162Cys)] variant in the simplex patient of the third family. Both missense variants were predicted to affect function by in silico tools. 3D homology modeling of the human SMVT revealed 13 transmembrane helices (TMs) and Tyr162 and Ser429 to be located at the cytoplasmic facing region of TM4 and within TM11, respectively. The SLC5A6 missense variants p.(Tyr162Cys) and p.(Ser429Gly) did not affect plasma membrane localization of the ectopically expressed multivitamin transporter suggesting reduced but not abolished function, such as lower catalytic activity. Targeted therapeutic intervention yielded clinical improvement in four of the five patients. Early molecular diagnosis by exome sequencing is essential for timely replacement therapy in affected individuals.

Apolipoprotein E and sex modulate fatty acid metabolism in a prospective observational study of cognitive decline

Background Fatty acids play prominent roles in brain function as they participate in structural, metabolic and signaling processes. The homeostasis of fatty acids and related pathways is known to be impaired in cognitive decline and dementia, but the relationship between these metabolic disturbances and common risk factors, namely the ɛ4 allele of the apolipoprotein E (ApoE-ɛ4) gene and sex, remains elusive. Methods In order to investigate early alterations associated with cognitive decline in the fatty acid-related serum metabolome, we here applied targeted metabolomics analysis on a nested case-control study (N=368), part of a prospective population cohort on dementia. Results When considering the entire study population, circulating levels of free fatty acids, acyl-carnitines and pantothenic acid were found to be increased among those participants who had greater odds of cognitive decline over a 12-year follow-up. Interestingly, stratified analyses indicated that these metabolomic alterations were specific for ApoE-ɛ4 non-carriers and women. Conclusions Altogether, our results highlight that the regulation of fatty acids and related metabolic pathways during ageing and cognitive decline depends on complex inter-relationships between the ApoE-ε4 genotype and sex. A better understanding of the ApoE-ɛ4 and sex dependent modulation of metabolism is essential to elucidate the individual variability in the onset of cognitive decline, which would help develop personalized therapeutic approaches.

In vitro propagation of select tomatillo (Physalis ixocarpa Brot. ex Horm.) plant families

The objective was to propagate select Physalis ixocarpa plants in vitro, acclimatize them and describe their phenological cycle. The in vitro response of stem apices was evaluated in families from the Tecozautla 04, Manzano Tepetlixpa and Morado San Miguel varieties. The apices were cultured in a medium containing Murashige and Skoog inorganic salts (100 %), supplemented with 0.4 mg·L-1 thiamine, 60 mg·L-1 L-cysteine, 100 mg·L-1 myo-inositol, 0.5 mg·L-1 nicotinic acid, 0.5 mg·L-1 pantothenic acid, 3 % sucrose and 7 g·L-1 agar, without growth regulators and the pH adjusted to 5.7 ± 0.1. in vitro rooting was done for 30 days, with 16 h of light at 3,000 μmol∙m-2∙s-1. The variables evaluated in vitro were seedling height, vigor, callus presence, root length, and number of leaves, roots, stems and buds. Plants produced in vitro were acclimatized and transplanted in greenhouses to follow their phenological cycle. The variables evaluated in acclimatization and phenological cycle were plant height and number of leaves, buds, flowers and set fruits. A completely randomized design was used for the in vitro evaluation, and randomized complete blocks for the greenhouse. The families with the best morphogenic responses in vitro were Tecozautla 04 and Manzano, and in phenological development they presented greater plant height. In acclimatization, survival was 100 % in all clones. in vitro responses, acclimatization and phenology depended on the variety and families.

Effect of Selected Cations and B Vitamins on the Biosynthesis of Carotenoids by Rhodotorula mucilaginosa Yeast in the Media with Agro-Industrial Wastes

In recent years, there has been an increase in the search for novel raw materials for the production of natural carotenoids. Among yeasts, Rhodotorula species have the ability to synthesize carotenoids, mainly β-carotene, torulene, and torularhodin, depending on the culture conditions. This study aimed to determine the effect of selected cations (barium, zinc, aluminum, manganese) and B vitamins (biotin, riboflavin, niacin, pantothenic acid) on the biosynthesis of carotenoids by Rhodotorula mucilaginosa MK1 and estimate the percentages of β-carotene, torulene, and torularhodin synthesized by the yeast. The cultivation was carried out in a medium containing glycerol (waste resulting from biodiesel production) as a carbon source and potato wastewater (waste resulting from potato starch production) as a nitrogen source. Carotenoid biosynthesis was stimulated by the addition of aluminum (300 mg/L) or aluminum (300 mg/L) and niacin (100 µg/L) to the medium. The number of carotenoids produced by R. mucilaginosa MK1 in the medium containing only aluminum and in the medium with aluminum and niacin was 146.7 and 180.5 µg/gd.m., respectively. This content was 101% and 147% higher compared to the content of carotenoids produced by yeast grown in the control medium (73.0 µg/gd.m.). The addition of aluminum and barium seemed to have a positive effect on the biosynthesis of torulene, and the percentage of this compound increased from 31.86% to 75.20% and 68.24%, respectively. Niacin supplementation to the medium increased the percentage of torularhodin produced by the yeast from 23.31% to 31.59–33.79%. The conducted study showed that there is a possibility of intensifying carotenoid biosynthesis by red yeast and changing the percentages of individual carotenoids fractions by adding cations or B vitamins to the medium. Further research is needed to explain the mechanism of action of niacin on the stimulation of torularhodin biosynthesis.

Cholesterol modified DP7 and pantothenic acid induce dendritic cell homing to enhance the efficacy of dendritic cell vaccines

Dendritic cell (DC)-based cancer vaccines have so far achieved good therapeutic effects in animal experiments and early clinical trials for certain malignant tumors. However, the overall objective response rate in clinical trials rarely exceeds 15%. The poor efficiency of DC migration to lymph nodes (LNs) (< 5%) is one of the main factors limiting the effectiveness of DC vaccines. Therefore, increasing the efficiency of DC migration is expected to further enhance the efficacy of DC vaccines. Here, we used DP7-C (cholesterol modified VQWRIRVAVIRK), which can promote DC migration, as a medium. Through multiomics sequencing and biological experiments, we found that it is the metabolite pantothenic acid (PA) that improves the migration and effectiveness of DC vaccines. We clarified that both DP7-C and PA regulate DC migration by regulating the chemokine receptor CXCR2 and inhibiting miR-142a-3p to affect the NF-κB signaling pathway. This study will lay the foundation for the subsequent use of DP7-C as a universal substance to promote DC migration, further enhance the antitumor effect of DC vaccines, and solve the bottleneck problem of the low migration efficiency and unsatisfactory clinical response rate of DC vaccines.

Regulatory Effect of Resveratrol on Inflammation Induced by Lipopolysaccharides via Reprograming Intestinal Microbes and Ameliorating Serum Metabolism Profiles

The purpose of this study was to explore the regulatory effect of resveratrol (RES) on lipopolysaccharide (LPS)-induced inflammation and its influence on intestinal microorganisms and serum atlas in murine models during the development of inflammation to explore a novel method for the regulation of inflammation. Mice were randomly assigned to three groups: control (CON), LPS, and RES–LPS. The results showed that RES mitigated the inflammatory damage to the intes-tines and liver induced by LPS. Compared with the LPS group, RES treatment decreased the levels of TNF-α, IL-6, IFN-γ, myeloperoxidase, and alanine aminotransferase in the liver. Serum metabolic profile monitoring showed that, compared with the CON group, LPS decreased the levels of five metabolites, including cycloartomunin and glycerol triundecanoate, and increased the levels of eight metabolites, including N-linoleoyl taurine and PE(O-16:0/20:5(5Z), 8Z, 11Z, 14Z, 17Z). Conversely, RES treatment increased the levels of eight metabolites, including pantothenic acid, homovanillic acid, and S-(formylmethyl)glutathione, and reduced seven metabolites, including lysoPE(20:4(8Z,11Z,14Z,17Z)/0:0) and 13-cis-retinoic acid, etc., in comparison with the LPS group. Moreover, RES treatment alleviated the negative effects of LPS on intestinal microbes by reducing, for instance, the relative abundance of Bacteroidetes and Alistipes, and increasing the relative abundance of Lactobacillus. These results suggest that RES has great potential for preventing in-flammation.

Myo-Inositol Levels in the Dorsal Hippocampus Serve as Glial Prognostic Marker of Mild Cognitive Impairment in Mice

Dementia is a devastating age-related disorder. Its therapy would largely benefit from the identification of susceptible subjects at early, prodromal stages of the disease. To search for such prognostic markers of cognitive impairment, we studied spatial navigation in male BALBc vs. B6N mice in combination with in vivo magnetic resonance spectroscopy (1H-MRS). BALBc mice consistently showed higher escape latencies than B6N mice, both in the Water Cross Maze (WCM) and the Morris water maze (MWM). These performance deficits coincided with higher levels of myo-inositol (mIns) in the dorsal hippocampus before and after training. Subsequent biochemical analyses of hippocampal specimens by capillary immunodetection and liquid chromatography mass spectrometry-based (LC/MS) metabolomics revealed a higher abundance of glial markers (IBA-1, S100B, and GFAP) as well as distinct alterations in metabolites including a decrease in vitamins (pantothenic acid and nicotinamide), neurotransmitters (acetylcholine), their metabolites (glutamine), and acetyl-L-carnitine. Supplementation of low abundant acetyl-L-carnitine via the drinking water, however, failed to revert the behavioral deficits shown by BALBc mice. Based on our data we suggest (i) BALBc mice as an animal model and (ii) hippocampal mIns levels as a prognostic marker of mild cognitive impairment (MCI), due to (iii) local changes in microglia and astrocyte activity, which may (iv) result in decreased concentrations of promnesic molecules.

The Use of ‘Omics for Diagnosing and Predicting Progression of Chronic Kidney Disease: A Scoping Review

Globally, chronic kidney disease (CKD) contributes substantial morbidity and mortality. Recently, various ‘omics platforms have provided insight into the molecular basis of kidney dysfunction. This scoping review is a synthesis of the current literature on the use of different ‘omics platforms to identify biomarkers that could be used to detect early-stage CKD, predict disease progression, and identify pathways leading to CKD. This review includes 123 articles published from January 2007 to May 2021, following a structured selection process. The most common type of ‘omic platform was proteomics, appearing in 55 of the studies and two of these included a metabolomics component. Most studies (n = 91) reported on CKD associated with diabetes mellitus. Thirteen studies that provided information on the biomarkers associated with CKD and explored potential pathways involved in CKD are discussed. The biomarkers that are associated with risk or early detection of CKD are SNPs in the MYH9/APOL1 and UMOD genes, the proteomic CKD273 biomarker panel and metabolite pantothenic acid. Pantothenic acid and the CKD273 biomarker panel were also involved in predicting CKD progression. Retinoic acid pathway genes, UMOD, and pantothenic acid provided insight into potential pathways leading to CKD. The biomarkers were mainly used to detect CKD and predict progression in high-income, European ancestry populations, highlighting the need for representative ‘omics research in other populations with disparate socio-economic strata, including Africans, since disease etiologies may differ across ethnic groups. To assess the transferability of findings, it is essential to do research in diverse populations.

Water-soluble vitamins in honeys of various botanical origin and their change during storage of honey

The richest chemical composition of honey determines its extremely high biological activity. The composition and concentration of bioactive compounds of honey largely depend on its botanical origin, i.e. they are determined by nectar and the pollen chemical composition of the nectariferous plant, on the soil on which they grow, as well as on climate and weather conditions. Along with enzymes and minerals, vitamins are found in honey in small but measurable amounts. Vitamins of honey are mainly represented by B-group vitamins. The content of vitamins in honey varies according to its botanical origin. The following types of honey were used for the study: acacia, sunflower, chestnut, linden, buckwheat. The quantitative determination of water-soluble B-group vitamins (thiamine, riboflavin, pyridoxine, pantothenic acid, nicotinic acid) in honey of various botanical origin was carried out in the accredited laboratory of the direction of chemical and biological research of beekeeping products of the Federal Research Center of Beekeeping by the method of capillary electrophoresis. It was revealed that chestnut and buckwheat honey present the highest levels of water-soluble vitamins content; that confirms the prospects of their use as a source of vitamins. Vitamins are unstable compounds that can be easily destroyed by various factors. Under the impact of daylight, the studied water-soluble vitamins contained in honey are destroyed during storage. The dynamics of changes in the vitamins content was traced during the storage of honey for 12 months in a dark place and in the light. Riboflavin andnicotinic acid, which is significantly reduced, is caracterized by a higher sensitivity to the action of daylight during storage of honey.

Growth responses of C3 and C4 crops to soil physico-chemical properties in Rivers State, Nigeria

This study evaluated the growth responses of C3 and C4 crops to soil physico-chemical properties in Rivers State. The C3 crop refers to Pumpkin and Cucumber while C4 crop refers to Amaranthus in this study. The research work made use of three crops (Pumpkin, Cucumber and Amaranthus in some selected sites in Rivers State and the study was carried out both in the dry and wet seasons. Soil samples were collected from both topsoil (0-15cm) and subsoil (15-30cm). The crops and soil samples were taken to the laboratory for further analysis. Mean values and standard deviations were used to describe the analysis while analysis of variance (ANOVA), Duncan, and Kruskal Wallis were used to test the hypotheses. All analyses were carried out using Statistical Package for Social Sciences (SPSS) 21.1 Version. Findings showed that sand content in Oyigbo had the highest in the topsoil at 95.37% while Etche had highest in silt content at 1.87%. For the subsoil, Oyigbo also had the highest sand content at 93.30% while Ikwerre had the highest clay content at 6.63% in subsoil. For chemical properties of soil, total organic carbon and magnesium were highest in Oyigbo at 1.91% and 24.00% respectively for topsoil while for subsoil potassium was highest in Ikwerre at 8.30%. It was also discovered C3 and C4 crops planted in Oyigbo, Etche and Ikwerre varied from the nutrients standards recommended by USDA (2014). The following nutrients and minerals were considered: energy, carbohydrates, protein, total fat, cholesterol, dietary fiber, vitamins, folates, niacin, pantogenic acid, pyridoxine, riboflavin, thiamin, Electrolytes, sodium, potassium, calcium, iron, magnesium, manganese phosphorus, and zinc. For standards recommended by (USDA 2014), only energy, iron, zinc, manganese, vitamin E, riboflavin, pyridoxine, niacin and pantothenic acid at Oyigbo met the standards, also Riboflavin and iron at Ikwerre met the (USDA 2014) standards while only folates at Etche met the (USDA 2014) standards. The study recommended that the soil nutrients and pH should be improved across the three locations and the acidic nature of both topsoil and subsoil should be improved by neutralizing the soil with lime.