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The function of vascular non-inflammatory molecule 1 (Vanin-1), an enzyme essential for vitamin B5 synthesis, has not been studied yet in chronic obstructive pulmonary disease (COPD).In this study, we aimed to evaluate the expression of Vanin-1 in sera and lung tissues of COPD, and infer its possible roles in COPD.We collected blood and lung tissue specimens from 99 COPD patients and 62 non-COPD subjects. Enzyme-linked immunosorbent assay was used to determine levels of Vanin-1, pantothenic acid, interleukin-6 (IL-6), tumor necrotic factor α (TNFα), and reactive oxygen species (ROS). The receiver operating characteristics (ROC) curve was used for analysis of the diagnostic value of Vanin-1 in COPD patients. Pearson's correlation assay was used to determine the correlation between Vanin-1 and levels of inflammatory cytokines and ROS.Vanin-1 expression was significantly higher in the sera and lung tissues of COPD patients compared to non-COPD subjects. ROC analysis showed that the area under the curve (AUC) was greater than 0.5 for both sera (AUC = 0.7342) and lung tissues (AUC = 0.9061). Pantothenic acid was also upregulated in COPD patients. IL-6, TNFα and ROS showed strong positive correlations to Vanin-1 levels in sera.Vanin-1 upregulation in sera and lung tissue is a potentially valuable biomarker for COPD. Vanin-1 showed positive correlations to levels of pro-inflammatory cytokines and ROS. Together, our results support the further development of Vanin-1 as a new target for the diagnosis or treatment of COPD.

Vitamin deficiencies are known to cause disorders in human beings. Siddique et al. discovered that vitamin B5 biosynthesis in cyst nematodes requires steps in their host plants. Disruption of an Arabidopsis thaliana 'susceptibility gene', which is involved in the production of vitamin B5 precursors, results in reduced parasitism.

The vanins are ectoenzymes with pantetheinase activity and are involved in recycling pantothenic acid (vitamin B5) from pantetheine. Elevated levels of vanin have been linked with the development and severity of several diseases, including steatosis, diabetes, skin diseases, cancer, inflammatory diseases etc. Therefore, vanins have previously been used as a potential drug target to combat related diseases. In this study, we used a molecular docking and molecular dynamic simulation-based approach to screen dual inhibitors of hVnn1, and hVnn2 from a library of 120 chemical candidates. Molecular docking of drug candidates with hVnn1, and hVnn2 using GOLD and MOE revealed that the chemical compound "methotrexate (CID: 126941)" has the highest binding affinity against both the target enzymes which was further validated through molecular dynamic simulation. Toxicity profiling of drug candidates evaluated using Lipinski's rule of five and Molsoft tool, and AdmetSar 2.0 confirms the drug suitability of methotrexate, therefore, suggesting its use as a potential therapeutic agent to inhibit the activity of vainin enzyme in related disease conditions.

We aimed to evaluate the prospective association of vitamin B5 with all-cause mortality and explore its potential modifiers in Chinese adults with hypertension. A nested, case-control study was conducted in the China Stroke Primary Prevention Trial, including 505 deaths of all causes and 505 matched controls. The median follow-up duration was 4.5 years. The primary outcome measure in this investigation was all-cause mortality, which encompassed deaths for any reason. The mean plasma vitamin B5 concentration for cases (43.7 ng/mL) was higher than that in controls (40.9 ng/mL) (p = .001). When vitamin B5 was further assessed as quintiles, compared with the reference group (Q1: 33.0 ng/mL), the risk of all-cause mortality increased by 29% (OR = 1.29, 95% CI: 0.83-2.01) in Q2, 22% (OR = 1.22, 95% CI: 0.77-1.94) in Q3, 62% (OR = 1.62, 95% CI: 1.00-2.62) in Q4, and 77% (OR = 1.77, 95% CI: 1.06-2.95) in Q5. The trend test was significant (p = .022). When Q4-Q5 were combined, a significant 41% increment (OR = 1.41, 95% CI: 1.03-1.95) in all-cause death risk was found compared with Q1-Q3. The adverse effects were more pronounced in those with normal folate levels (p-interaction = .019) and older people (p-interaction = .037). This study suggests that higher baseline levels of plasma vitamin B5 are a risk factor for all-cause mortality among Chinese patients with hypertension, especially among older adults and those with adequate folate levels. The findings, if confirmed, may inform novel clinical and nutritional guidelines and interventions to optimize vitamin B5 levels.

Background Nearly a third of young US children take multivitamin/mineral (MVM) dietary supplements, yet it is unclear how formulations compare with requirements. Objective Describe the number and amounts of micronutrients contained in MVMs for young children and compare suggested amounts on product labels to micronutrient requirements. Design Cross-sectional. Setting All 288 MVMs on the market in the United States in the National Institutes of Health’s Dietary Supplement Label Database in 2018 labeled for children 1 to Main outcome measures Number of MVM products and amounts per day of micronutrients in each product suggested on labels compared with requirements represented by age-appropriate Daily Values (DV). Micronutrients of public health concern identified by the Dietary Guidelines for Americans (DGA) 2015-2020 (DGA 2015) and DGA 2020-2025 (DGA 2020) or those of concern for exceeding the upper tolerable intake levels. Statistical analyses Number of products and percent DV per day provided by each micronutrient in each product. Results The 288 MVMs contained a mean of 10.1 ± 2.27 vitamins and 4.59 ± 2.27 minerals. The most common were, in rank order, vitamins C, A, D, E, B6, B12; zinc, biotin, pantothenic acid, iodine, and folic acid. For micronutrients denoted by the DGA 2015 and DGA 2020 of public health concern, 56% of the 281 products containing vitamin D, 4% of the 144 with calcium, and none of the 60 containing potassium provided at least half of the DV. The upper tolerable intake level was exceeded by 49% of 197 products with folic acid, 17% of 283 with vitamin A, and 14% of 264 with zinc. Most MVMs contained many of 16 other vitamins and minerals identified in national surveys as already abundant in children’s diets. Conclusions A reexamination of the amounts and types of micronutrients in MVMs might consider formulations that better fill critical gaps in intakes and avoid excess.

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.

As an expansion investigation of drug-drug interaction (DDI) from previous clinical trials, additional plasma endogenous metabolites were quantitated in the same subjects to further identify the potential biomarkers of organic anion transporter (OAT) 1/3 inhibition. In the single dose, open label, three-phase with fixed order of treatments study, 14 healthy human volunteers orally received 1000 mg probenecid alone, or 40 mg furosemide alone, or 40 mg furosemide at 1 hour after receiving 1000 mg probenecid on days 1, 8, and 15, respectively. Endogenous metabolites including kynurenic acid, xanthurenic acid, indo-3-acetic acid, pantothenic acid, p-cresol sulfate, and bile acids in the plasma were measured by liquid chromatography–tandem mass spectrometry. The Cmax of kynurenic acids was significantly increased about 3.3- and 3.7-fold over the baseline values at predose followed by the treatment of probenecid alone or in combination with furosemide respectively. In comparison with the furosemide-alone group, the Cmax and area under the plasma concentration–time curve (AUC) up to 12 hours of kynurenic acid were significantly increased about 2.4- and 2.5-fold by probenecid alone, and 2.7- and 2.9-fold by probenecid plus furosemide, respectively. The increases in Cmax and AUC of plasma kynurenic acid by probenecid are comparable to the increases of furosemide Cmax and AUC reported previously. Additionally, the plasma concentrations of xanthurenic acid, indo-3-acetic acid, pantothenic acid, and p-cresol sulfate, but not bile acids, were also significantly elevated by probenecid treatments. The magnitude of effect size analysis for known potential endogenous biomarkers demonstrated that kynurenic acid in the plasma offers promise as a superior addition for early DDI assessment involving OAT1/3 inhibition. SIGNIFICANCE STATEMENT This article reports that probenecid, an organic anion transporter (OAT) 1 and OAT3 inhibitor, significantly increased the plasma concentrations of kynurenic acid and several uremic acids in human subjects. Of those, the increases of plasma kynurenic acid exposure are comparable to the increases of furosemide by OAT1/3 inhibition. Effect size analysis for known potential endogenous biomarkers revealed that plasma kynurenic acid is a superior addition for early drug-drug interaction assessment involving OAT1/3 inhibition.

To investigate the relationship between peripheral blood micronutrient levels and 4 kinds of oral mucosal diseases (minor recurrent aphthous ulcer, angular cheilitis, cheilitis and geographic tongue) in children aged 0~14 years.One hundred and fifty-two children with oral mucosal lesions (COML) and 65 healthy children (health control group, HC) were included. The clinical data of each group were recorded separately to compare whether there existed differences in the levels of serum water-soluble vitamins (vitamins B1, B2, B3, B5, B6, B7, B9, B12, C), serum fat-soluble vitamins [vitamins A, E, K, 25(OH)D2, 25(OH)D3], zinc and serum calcium. Whether peripheral blood micronutrients were risk factors associated with the onset of COML was analyzed through disorder multiclass logistic regression with SPSS 23.0 software package.Peripheral blood micronutrients differed in children with minor recurrent aphthous ulcers, cheilitis, and geographic tongue (P＜0.05). Compared with HC group, children in minor recurrent aphthous ulcer group had significantly lower levels of vitamin B1, B6, B7, C, A, and 25(OH)D3 (P＜0.05), and relatively higher rates of vitamin B6 (50.00% vs 13.85%), vitamin B7 (36.76% vs 9.23%), 25(OH)D3 (64.71% vs 36.92%) deficiency and vitamin K excess (8.82% vs 0.00%)(P＜0.005). Multiclass logistic regression analysis showed that vitamin B1, vitamin C, vitamin A deficiency, vitamin B5, and vitamin K excess were risk factors for incidence in children with minor recurrent aphthous ulcer, and each element was independent for each other. Compared with HC group, the levels of vitamin B7 and 25(OH)D3 in children with cheilitis were significantly lower(P＜0.05), and the rate of vitamin B7 deficiency was significantly higher (P＜0.005). Multiclass logistic regression analysis showed that vitamin B7 and vitamin A deficiency were risk factors for cheilitis in children, and the two were independent for each other. Compared with the HC group, vitamin K excess rate was significantly higher in children with geographic tongue (7.14% vs 0.00%) (P＜0.005). Multiclass logistic regression analysis showed that vitamin C deficiency and vitamin K excess were risk factors for the incidence of geographic tongue, and the two were independent for each other. Compared with other groups, peripheral blood micronutrients had no correlation with the pathogenesis of angular cheilitis (P＞0.05).The occurrence of COML is closely related to peripheral blood micronutrient levels, which suggests that children with COML need to monitor vitamin and mineral levels and supplement treatment when necessary.

Linalool showed a broad-spectrum antibacterial effect, but few studies have elucidated the antibacterial mechanism of linalool on

The importance of B complex vitamins starts early in the human life cycle and continues across its different stages. At the same time, numerous reports have emphasized the critical role of adequate B complex intake. Most studies examined such issues concerning a specific vitamin B or life stage, with the majority reporting the effect of either excess or deficiency. Deep insight into the orchestration of the eight different B vitamins requirements is reviewed across the human life cycle, beginning from fertility and pregnancy and reaching adulthood and senility, emphasizing interactions among them and underlying action mechanisms. The effect of sex is also reviewed for each vitamin at each life stage to highlight the different daily requirements and/or outcomes. Thiamine, riboflavin, niacin, pyridoxine, and folic acid are crucial for maternal and fetal health. During infancy and childhood, B vitamins are integrated with physical and psychological development that have a pivotal impact on one’s overall health in adolescence and adulthood. A higher intake of B vitamins in the elderly is also associated with preventing some aging problems, especially those related to inflammation. All supplementation should be carefully monitored to avoid toxicity and hypervitaminosis. More research should be invested in studying each vitamin individually concerning nutritional disparities in each life stage, with extensive attention paid to cultural differences and lifestyles.

Coenzyme A (CoA) is an essential co-factor at the intersection of diverse metabolic pathways. Cellular CoA biosynthesis is regulated at the first committed step— phosphorylation of pantothenic acid—catalyzed by pantothenate kinases (PANK1,2,3 in humans, PANK3 being the most highly expressed). Despite the critical importance of CoA in metabolism, the differential roles of PANK isoforms remain poorly understood. Our investigations of PANK proteins as precision oncology collateral lethality targets (PANK1 is co-deleted as part of the PTEN locus in some highly aggressive cancers) were severely hindered by a dearth of commercial antibodies that can reliably detect endogenous PANK3. While we successfully validated commercial antibodies for PANK1 and PANK2 using CRISPR knockout cell lines, we found no commercial antibody that could detect endogenous PANK3. We therefore set out to generate a mouse monoclonal antibody against human PANK3 protein. We demonstrate that clone (Clone MDA-299-62A) can reliably detect endogenous PANK3 protein in cancer cell lines, with band-specificity confirmed by CRISPR PANK3 knockout cell lines. Sub-cellular fractionation indicates that PANK3 is overwhelmingly cytosolic and expressed broadly across cancer cell lines. PANK3 monoclonal antibody MDA-299-62A should prove a valuable tool for researchers investigating this understudied family of metabolic enzymes in health and disease.

Co-targeting of O-GlcNAc transferase (OGT) and the transcriptional kinase cyclin-dependent kinase 9 (CDK9) is toxic to prostate cancer cells. As OGT is an essential glycosyltransferase, identifying an alternative target showing similar effects is of great interest. Here, we used a multiomics approach (transcriptomics, metabolomics, and proteomics) to better understand the mechanistic basis of the combinatorial lethality between OGT and CDK9 inhibition. CDK9 inhibition preferentially affected transcription. In contrast, depletion of OGT activity predominantly remodeled the metabolome. Using an unbiased systems biology approach (weighted gene correlation network analysis), we discovered that CDK9 inhibition alters mitochondrial activity/flux, and high OGT activity is essential to maintain mitochondrial respiration when CDK9 activity is depleted. Our metabolite profiling data revealed that pantothenic acid (vitamin B5) is the metabolite that is most robustly induced by both OGT and OGT+CDK9 inhibitor treatments but not by CDK9 inhibition alone. Finally, supplementing prostate cancer cell lines with vitamin B5 in the presence of CDK9 inhibitor mimics the effects of co-targeting OGT and CDK9.

Gentle cleansing of the skin without further compromising its barrier function and moisture content and being simultaneously devoid of adverse effects on the skin microbiome are important features of body cleansers for atopic-prone skin sufferers. For this population, a new dexpanthenol-containing liquid cleanser (DCLC) was developed.Two prospective 4-week studies have been conducted. Study 1 investigated the effect of once-daily DCLC on stratum corneum (SC) hydration, transepidermal water loss (TEWL), skin pH, and skin microbiome (all on the volar forearm) in adult subjects with dry skin (N = 44). Study 2 explored the cutaneous tolerability of DCLC and its effect on the microbiome biodiversity of the volar forearm skin in infants/children with atopic-prone skin (N = 33, aged 6 months to 6 years). In the latter study, DCLC was applied 2-3 days/week in combination with an emollient applied at least twice daily.In Study 1, on Day 29, the mean change in skin surface capacitance from baseline was significantly greater in the forearm test area treated with DCLC than in the contralateral test area (control) treated with water only (5.16 vs. 3.65 a.u.; p = 0.011), suggesting long-term SC hydration. DCLC use was not associated with changes in TEWL, skin pH, or microbiome biodiversity if compared to control. In Study 2, the 4-week use of DCLC in combination with an emollient was well tolerated according to pediatrician skin assessment, and no flare-ups were recorded. The microbiome biodiversity did not shift during the study.These findings support the use of DCLC in subjects with atopic-prone skin.

Combination therapy with biotin and dexpanthenol is a well-known practice in preventing and treating hair loss, however, it is not well studied. In this study, we compared the efficacy of the 6-week treatment with two brands of biotin and dexpanthenol for the treatment of diffuse hair loss. Fifty eligible patients with diffused pattern hair loss, (41 women and 9 men) were randomized in a 1:1 ratio to receive either 6 weekly injections of dexpanthenol ampoule 250 mg/2 ml and biotin ampoule 5 mg/1 ml, manufactured by Pars Behvarzan or Bayer Company. Combing test, Standard scalp photography and trichoscan assessment were performed before the first treatment session and one and 8 weeks after the last one. Patients' satisfaction and drug adverse reactions were also recorded. One and eight weeks after the last treatment session, hair fall count and total hair density significantly improved in both groups (p-value0.01 for hair fall count and 0.04 and 0.02, for hair density in Pars and Bayer groups, respectively). There was no significant difference between the two groups in any other trichoscan parameter, except for improvement in terminal/vellus hair ratio in the Bayer group in both follow up visits, compared to the Pars group (p-value = 0.02 and 0.033 for weeks one and eight). Six-week treatment with both brands of biotin and dexpanthenol was effective and safe in people with diffused pattern hair loss.

Aim Although the most common age-related neurodegenerative disease defined by memory loss is Alzheimer's disease (AD), only symptomatic therapies are present. A complex pathway for the AD pathogenesis that includes an increase in inflammation has recently been suggested. Since in previous animal experiments dexpanthenol has anti-inflammatory and neuroprotective activities, effects and role of dexpanthenol in an intracerebroventricular (ICV)-streptozotocin (STZ) induced sporadic-AD(memory impairment) animal model have been examined. Design and methods In total, 18 adult sprague-dawley rats were classified into 3 groups; control (n = 6), STZ + Saline (n = 6) and STZ + Dexpanthenol (n = 6). Twelve AD-induced rats through STZ-injection (3 mg/kg) into both lateral ventricles via stereotaxy were separated into two groups five days after STZ administration: one of these groups was treated with dexpanthenol (1000 mg/kg/day, i.p.) for 3 weeks and the other with saline. A passive avoidance learning (PAL) test was used after treatment, followed by brain tissue extraction in all subjects. Brain levels of tumor necrosis factor-alpha (TNF-alpha) and choline acetyl transferase (ChAT) were measured and Cresyl violet staining was used to count neurons in cornu ammonis-1 (CA1) and cornu ammonis-3 (CA3). Results It was observed that ICV-STZ significantly shortened PAL latency, increased levels of TNF-alpha in brain, decreased activity of ChAT in brain, and number of hippocampal neurons. However, dexpanthenol significantly reduced all of those STZ-induced harmful effects. Conclusion Dexpanthenol significantly prevented the memory deficit induced by ICV-STZ through mitigating neuronal loss in hippocampus, cholinergic deficiency and neuroinflammation in rats. These findings suggest that dexpanthenol may be beneficial for treating memory impairment.

The Plasmodium parasites that cause malaria are adept at developing resistance to antimalarial drugs, necessitating the search for new antiplasmodials. Although several amide analogs of pantothenate (pantothenamides) show potent antiplasmodial activity, hydrolysis by pantetheinases (or vanins) present in blood rapidly inactivates them. We report herein the facile synthesis and biological activity of a small library of pantothenamide analogs in which the labile amide group is replaced with a variety of heteroaromatic rings. Several of the new analogs display antiplasmodial activity in the nanomolar range against P. falciparum and/or P. knowlesi in the presence of pantetheinase. A previously reported triazole and an isoxazole derivative presented here were further characterized and found to possess high selectivity indices, medium or high Caco-2 permeability, and medium or low microsomal clearance in vitro. Although we show here that the two compounds fail to suppress proliferation of P. berghei in vivo, pharmacokinetic and contact time data presented provide a benchmark for the compound profile required to achieve antiplasmodial activity in mice and should facilitate lead optimization.

[English] This study determined if supplementation with pantothenic acid (PA) for 16 weeks could increase skeletal muscle coenzyme A (CoASH) content and exercise performance. Trained male cyclists (n = 14) were matched into control or PA (6 g·day1) groups. At 0, 4, 8, and 16 weeks, subjects performed an incremental time to exhaustion cycle with muscle biopsies taken prior to and following exercise. Prolonged PA supplementation did not change skeletal muscle CoASH and acetyl- CoA contents or exercise performance. Novelty: Supplementation with pantothenic acid for 16 weeks had no effect on skeletal muscle CoASH and acetyl-CoA content or exercise performance in trained male cyclists. [French] Cette étude détermine si une supplémentation en acide pantothénique (« PA ») pendant 16 semaines peut augmenter la teneur en coenzyme A (« CoASH ») du muscle squelettique et la performance à l’exercice. Les cyclistes masculins entraînés (n = 14) sont appariés dans des groupes témoins ou PA (6 g·jour−1). Aux semaines 0, 4, 8 et 16, les sujets effectuent un exercice incrémental de pédalage au cours duquel on mesure la durée jusqu’à épuisement ; des biopsies musculaires sont prélevées avant et après l’exercice. Une supplémentation prolongée en PA ne modifie pas les teneurs en CoASH et en acétyl-CoA du muscle squelettique ni la performance à l’exercice. [Traduit par la Rédaction]

Aim To determine the rate of a decreased oral function using questions from the Kihon checklist corresponding to the Questionnaire for Latter-stage Elderly People and to clarify nutrient intake in older persons. Methods This study targeted 511 older people (217 men, 294 women, average age 73.1±5.6 years old). Their oral function was evaluated using questions on the masticatory function and swallowing function from the Kihon checklist, corresponding to questions on the oral function in the Questionnaire for Latter-stage Elderly People. Participants who had at least one symptom measured were defined as the applicable group (AG). In addition, to evaluate the nutrient intake of the participants, interviews were conducted using the Food Frequency Questionnaire Based on Food Groups. Results The rate of inclusion in the AG was 32.9% for the total sample, 28.2% for early-stage elderly people, and 40.1% for latter-stage elderly people. The AG rates did not differ significantly between men and women. For latter-stage elderly people, the protein-energy ratio and intakes of total energy, protein, pantothenic acid, folic acid, vitamin B6, niacin, vitamin K, copper, zinc, phosphorus, magnesium, potassium, and total dietary fiber were significantly lower in the AG than in the non-AG. Conclusion The evaluation of placement in the AG through questions on the oral function from the Kihon checklist corresponding to the Questionnaire for Latter-stage Elderly People demonstrated that the rate of a decreased oral function was higher in latter-stage elderly people than in early-stage elderly people. In addition, the latter-stage elderly people in the AG had a lower nutrient intake.

Experimental dermatology 30(5), 745-750 (2021). doi:10.1111/exd.14266, Published by Blackwell, Oxford

We examined the association between nutrient intake and prefrailty. Data from 815 older people (63% women) who participated in a community-based health check survey (Tarumizu Study) were analyzed. Prefrailty were defined using five parameters (exhaustion, slowness, weakness, low physical activity, and weight loss). Participants with one or more components were considered to belong to the prefrailty group. Nutrition intake was estimated from a validated brief-type self-administered diet history questionnaire. Among the participants, 154 men (52%) and 278 women (54%) were found to be in a status of prefrailty. In men, there were no significant associations between nutrient intake and prefrailty. In women, carbohydrate intake was slightly higher in prefrailty group. Vitamins K, B1, B2, folic acid, pantothenic acid, phosphorus, potassium, calcium, magnesium, iron, zinc, and copper intake was significantly lower in the prefrailty group. Among the nutrients, magnesium was identified as a significant covariate of prefrailty using a stepwise regression method. In women adjusted ORs (95%CI, p value) for prefrailty in the first, second, third, and fourth quartiles of magnesium intake were 1.00 (reference), 0.52 (0.29-0.92, 0.024), 0.51 (0.28-0.95, 0.033), and 0.38 (0.19-0.74, 0.005), respectively, by multivariate logistic regression analysis (variates: age, body mass index, energy intake, supplement use, osteoporosis, magnesium, and protein intake). Protein intake did not related to prefrailty. Protein intake might be sufficient to prevent prefrailty in the present study. We propose magnesium to be an important micronutrient that prevents prefrailty in community-dwelling older Japanese women.

Mutations in the human PANK2 gene are implicated in neurodegenerative diseases such as pantothenate kinase-associated neurodegeneration (PKAN) and result in low levels of coenzyme-A (CoA) in the CNS due to impaired production of phosphopantothenic acid (PPA) from vitamin B5. Restoration of central PPA levels by delivery of exogenous PPA is a recent strategy to reactivate CoA biosynthesis in PKAN patients. Fosmetpantotenate is an oral PPA prodrug. We report here the development of a new PANk2-/- knockout model that allows CoA regeneration in brain cells to be evaluated and describe two new series of cyclic phosphate prodrugs of PPA capable of regenerating excellent levels of CoA in this system. A proof-of-concept study in mouse demonstrates the potential of this new class of prodrugs to deliver PPA to the brain following oral administration and confirms incorporation of the prodrug-derived PPA into CoA.

Vanin-1 (VNN1) is a glycosylphosphatidylinositol (GPI)-anchored ectoenzyme which hydrolyzes pantetheine to pantothenic acid and cysteamine. It has emerged as a promising drug target for many human diseases associated with oxidative stress and inflammatory pathways. In the present study we used structure-based virtual screening approach for the identification of small molecule inhibitors of vanin-1. A chemical library consisting of natural compounds, synthetic compounds and RRV analogs were screened for drug-like molecules. The filtered molecules were subjected to molecular docking studies. Three potential hits-ZINC04073864 (Natural compound), CID227017 (synthetic compound) and CID129558381 (RRV analog)-were identified for the target enzyme. The molecules form good number of hydrogen bonds with the catalytic residues such as Glu79, Lys178 and Cys211. The apo-VNN1 and VNN1-ligand complexes were subjected to molecular dynamics (MD) simulation for 30 ns. The geometric properties such as root mean square deviation, radius of gyration, solvent accessible surface area, number of hydrogen bonds and the distance between the catalytic triad residues-Glu79, Lys178 and Cys211 were altered upon binding of the compounds. Essential dynamics and entropic studies further confirmed that the fluctuations in VNN1 decrease upon binding of the compounds. The lead molecules were stable throughout the simulation time period. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) studies showed that Van der Waals interaction energy contributes significantly to the total binding free energy. Thus, our study reveals three lead molecules-ZINC04073864, CID227017 and CID129558381 as potential inhibitors of Vanin-1 which can be validated through further studies. Communicated by Ramaswamy H. Sarma.

Metabolic rewiring is essential for Th17 cells' functional identity to sense and interpret environmental cues. However, the environmental metabolic checkpoints with specific regulation of Th17 cells, manifesting potential therapeutic opportunities to autoimmune diseases, remain largely unknown. Here, by screening more than one hundred compounds derived from intestinal microbes or diet, we found that vitamin B5 (VB5) restrains Th17 cell differentiation as well as related autoimmune diseases such as experimental autoimmune encephalomyelitis and colitis. Mechanistically, VB5 is catabolized into coenzyme A (CoA) in a pantothenate kinase (PANK)-dependent manner, and in turn, CoA binds to pyruvate kinase isoform 2 (PKM2) to impede its phosphorylation and nuclear translocation, thus inhibiting glycolysis and STAT3 phosphorylation. In humans, reduced serum VB5 levels are found in both IBD and MS patients. Collectively, our study demonstrates a role of VB5 in Th17 cell metabolic reprograming, thus providing a potential therapeutic intervention for Th17 cell-associated autoimmune diseases.

There are only a few drugs that have been used for the treatment of female pattern hair loss (FPHL).Through use of the Dermatologic Life Quality Index (DLQI) and a modified hair growth questionnaire, we aimed to evaluate the effect of dexpanthenol (DXP) as a new option for FPHL.Women who received 500 mg intramuscular DXP weekly for FPHL were included in this study. They were evaluated in terms of DLQI and laboratory characteristics, before and after DXP treatment, and were examined with a modified hair growth questionnaire.Overall satisfaction with the appearance of the hair was described by the patients as 57.1% " I am satisfied," 28.6% "I am very satisfied," and 14.3% "I am neutral (neither satisfied nor dissatisfied)." There was a statistical difference between the mean DLQI scores before and after DXP treatment (P .001). No statistical difference was found in the laboratory characteristics of the patients before and after DXP treatment (P 0.05). No side effect was reported during DXP treatment.Dexpanthenol is a safe and novel drug that may increase the quality of life in patients with FPHL.

Fibromyalgia (FM) is a chronic noncommunicable disorder characterized by a constellation of symptoms that include fatigue, depression and chronic pain. FM affects 2%–8% of the U.S. population, 2% of the global population, with 61%–90% of FM diagnoses attributed to women. Key causal factors leading to the development and severity of FM-related symptoms have not yet been identified. The purpose of this article is to report relationships among identified metabolites and levels of fatigue, depression, pain severity, and pain interference in a sample of 20 women with FM. In this secondary analysis, we conducted global metabolomic analysis and examined the data for relationships of metabolite levels with self-reported symptoms of fatigue, depression, pain severity, and pain interference. Results revealed six metabolites (6-deoxy-hexose; pantothenic acid; ergothioneine; l-carnitine; n-acetylserotonin; butyrobetaine) and their associated metabolic pathways such as carnitine synthesis, lipid oxidation, tryptophan metabolism, beta-alanine metabolism and pantothenic and Coenzyme-A biosynthesis that were either positively or inversely related to pain severity, pain interference, or both. The preliminary data presented suggest that metabolites representing energy, amino acid, or lipid classification may be associated with pain symptom severity and interference in women with FM. Future work will confirm these findings in a large, comparative cohort, targeting metabolites and metabolite pathways to better understand the relationships of metabolites and symptomology.

Background Parkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson’s Study (n = 147 typical PD cases, n = 162 controls). Results All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. Conclusion Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.

Background Metabolomics has proven useful for detecting objective biomarkers of diet that may help to improve dietary measurement. Studies to date, however, have focused on a relatively narrow set of lipid classes. Objective The aim of this study was to uncover candidate dietary biomarkers by identifying serum metabolites correlated with self-reported diet, particularly metabolites in underinvestigated lipid classes, e.g. triglycerides and plasmalogens. Methods We assessed dietary questionnaire data and serum metabolite correlations from 491 male and female participants aged 55-75 y in an exploratory cross-sectional study within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Self-reported intake was categorized into 50 foods, food groups, beverages, and supplements. We examined 522 identified metabolites using 2 metabolomics platforms (Broad Institute and Massachusetts General Hospital). Correlations were identified using partial Pearson's correlations adjusted for age, sex, BMI, smoking status, study site, and total energy intake [Bonferroni-corrected level of 0.05/(50 × 522) = 1.9 × 10-6]. We assessed prediction of dietary intake by multiple-metabolite linear models with the use of 10-fold crossvalidation least absolute shrinkage and selection operator (LASSO) regression. Results Eighteen foods, beverages, and supplements were correlated with ≥1 serum metabolite at the Bonferroni-corrected significance threshold, for a total of 102 correlations. Of these, only 5 have been reported previously, to our knowledge. Our strongest correlations were between citrus and proline betaine (r = 0.55), supplements and pantothenic acid (r = 0.46), and fish and C40:9 phosphatidylcholine (PC) (r = 0.35). The multivariate analysis similarly found reasonably large correlations between metabolite profiles and citrus (r = 0.59), supplements (r = 0.57), and fish (r = 0.44). Conclusions Our study of PLCO participants identified many novel food-metabolite associations and replicated 5 previous associations. These candidate biomarkers of diet may help to complement measures of self-reported diet in nutritional epidemiology studies, though further validation work is still needed.

Background Thiamine and pantothenic acid play a critical role in numerous metabolic reactions and are typically supplemented in infant and adult nutritional formulas as thiamine chloride hydrochloride and calcium pantothenate salts. Objective A rapid compliance method for the analysis of thiamine and pantothenic acid applicable to infant formula and milk-based nutritional products is described. Method Proteins are removed by centrifugal ultrafiltration, followed by analysis by reversed-phase liquid chromatography‒tandem mass spectrometry (LC-MS/MS), with quantitation accomplished by internal standard technique. Results The method was shown to be accurate, with acceptable recovery (thiamine, 99.3–101.1%; pantothenic acid, 99.2–108.6%). A certified reference material (NIST 1849a), showed no statistical bias (α = 0.05) for thiamine (P = 0.64); although a statistically significant bias (P Conclusions This rapid method is intended for use in high-throughput laboratories as part of routine product compliance release testing of thiamine and pantothenic acid in manufactured infant and milk-based nutritional products.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. Recent research has shown the importance of MNs in common pathologies, with significant deficiencies impacting the outcome. OBJECTIVE: This guideline aims to provide information for daily clinical nutrition practice regarding assessment of MN status, monitoring, and prescription. It proposes a consensus terminology, since many words are used imprecisely, resulting in confusion. This is particularly true for the words "deficiency", "repletion", "complement", and "supplement". METHODS: The expert group attempted to apply the 2015 standard operating procedures (SOP) for ESPEN which focuses on disease. However, this approach could not be applied due to the multiple diseases requiring clinical nutrition resulting in one text for each MN, rather than for diseases. An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL. The search focused on physiological data, historical evidence (published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: There was a limited number of interventional trials, preventing meta-analysis and leading to a low level of evidence. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90% of votes. Altogether the guideline proposes sets of recommendations for 26 MNs, resulting in 170 single recommendations. Critical MNs were identified with deficiencies being present in numerous acute and chronic diseases. Monitoring and management strategies are proposed. CONCLUSION: This guideline should enable addressing suboptimal and deficient status of a bundle of MNs in at-risk diseases. In particular, it offers practical advice on MN provision and monitoring during nutritional support. ispartof: Clinical Nutrition vol:41 issue:6 ispartof: location:England status: Published online

International audience; Vitamin B5 (panthotenic acid), the precursor of coenzyme A (CoA), is contained in most food items and is produced by the intestinal microbiota. A recent study published in Cell Metabolism reports that vitamin B5 and CoA favor the differentiation of CD8 + cytotoxic T cells into interleukin-22 (IL-22)-producing Tc22 cells, likely through fueling mitochondrial metabolism. Importantly, in a small cohort of melanoma patients, the plasma levels of vitamin B5 positively correlate with responses to PD-1-targeted immunotherapy. Moreover, in mice, supplementation with vitamin B5 increases the efficacy of PD-L1-targeted cancer immunotherapy, and in vitro culture of T cells with CoA enhances their antitumor activity upon adoptive transfer into mice. These finding suggest that vitamin B5 is yet another B vitamin that stimulates anticancer immunosurveillance.

Sodium-dependent multivitamin transporter (SMVT) deficiency is a recently described multivitamin-responsive inherited metabolic disorder (IMD) of which the phenotypic spectrum and response to treatment remains to be elucidated. So far, four pediatric patients have been described in three case reports with symptoms ranging from severe neurodevelopmental delay to feeding problems and failure to thrive, who demonstrated significant improvement after initiation of enhancement of targeted multivitamin treatment (biotin, pantothenic acid, and lipoic acid). We describe a fifth case of a patient presenting at the relatively mild end of the phenotypic spectrum with failure to thrive, frequent vomiting and metabolic acidosis with hypoglycemia, and mild osteopenia, who was diagnosed with SMVT deficiency due to compound heterozygous variants in

Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP, β-catenin, versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-β1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation, was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles.

Pantetheinase (also known as Vanin-1) is highly expressed in the liver, kidneys, and intestine and is closely associated with a number of diseases. Vanin-1 can hydrolyze pantetheine to pantothenic acid (vitamin B5) and cysteamine and participate in the synthesis of glutathione (GSH). GSH is highly expressed in tumor cells and plays a major role in the resistance of tumor cells to cisplatin. Therefore, we urgently need a method to monitor the activity level of Vanin-1 in tumor cells and tissues and elucidate the relationship between the role of Vanin-1 in GSH synthesis and tumor resistance. Herein, we report a Cy-Pa fluorescent probe for imaging Vanin-1 in cells and in vivo that can qualitatively and quantitatively detect the fluctuation of Vanin-1 concentrations in HepG2 and HepG2/DDP cells or tumor tissues of tumor-bearing mice. This probe shows excellent potential in in situ real-time monitoring of endogenous Vanin-1. Moreover, we proved that Vanin-1 can inhibit GSH synthesis using the probe. When the Vanin-1 inhibitor RR6 was used in combination with cisplatin, HepG2 and HepG2/DDP cells showed increased resistance to cisplatin, while the therapeutic efficiency of cisplatin was reduced in HepG2 and HepG2/DDP xenografts. In this study, Vanin-1 was shown to play an important role in the treatment of cancer, and the study of Vanin-1 may provide an idea for the treatment of cancer in the future.

Gastric Cancer (GC) is the most common cancer among Iranian men. We conducted a case-control study to investigate the association between patterns of nutrient intake and the risk of GC in Iran. We enrolled 178 GC patients and 271 controls matched for age and sex. We collected dietary intakes using a validated diet history questionnaire. We performed factor analysis on 28 nutrients using multivariate logistic regression models on tertiles of factor scores and estimated odds ratios (OR) and 95% confidence intervals (95% CI). We identified three nutrient patterns. The first pattern included pantothenic acid, riboflavin, zinc, animal protein, and calcium. Selenium, thiamin, carbohydrate, vegetable protein, niacin and low intake of vitamin E loaded the second pattern, and the third pattern was abundant in fiber, carotene, vitamin C and A. We found no significant association between GC and any of the dietary patterns. However, in the first patterns, men in the highest tertile had significantly higher odds of GC than the lowest (OR = 2.15, 95% CI: 1.13–4.09, p trend = 0.02). A dietary pattern loaded by animal products may increase the risk of GC among Iranian men. Larger studies are required to approve these findings in overall and in different subgroups. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1931697. acceptedVersion

Fosmetpantotenate; Randomized controlled trial Fosmetpantotenato; Ensayo controlado aleatorizado Fosmetpantotenat; Assaig controlat aleatoritzat Background Pantothenate kinase–associated neurodegeneration (PKAN) currently has no approved treatments. Objectives The Fosmetpantotenate Replacement Therapy pivotal trial examined whether treatment with fosmetpantotenate improves PKAN symptoms and stabilizes disease progression. Methods This randomized, double-blind, placebo-controlled, multicenter study evaluated fosmetpantotenate, 300 mg oral dose three times daily, versus placebo over a 24-week double-blind period. Patients with pathogenic variants of PANK2, aged 6 to 65 years, with a score ≥6 on the PKAN-Activities of Daily Living (PKAN-ADL) scale were enrolled. Patients were randomized to active (fosmetpantotenate) or placebo treatment, stratified by weight and age. The primary efficacy endpoint was change from baseline at week 24 in PKAN-ADL. Results Between July 23, 2017, and December 18, 2018, 84 patients were randomized (fosmetpantotenate: n = 41; placebo: n = 43); all 84 patients were included in the analyses. Six patients in the placebo group discontinued treatment; two had worsening dystonia, two had poor compliance, and two died of PKAN-related complications (aspiration during feeding and disease progression with respiratory failure, respectively). Fosmetpantotenate and placebo group PKAN-ADL mean (standard deviation) scores were 28.2 (11.4) and 27.4 (11.5) at baseline, respectively, and were 26.9 (12.5) and 24.5 (11.8) at week 24, respectively. The difference in least square mean (95% confidence interval) at week 24 between fosmetpantotenate and placebo was −0.09 (−1.69 to 1.51; P = 0.9115). The overall incidence of treatment-emergent serious adverse events was similar in the fosmetpantotenate (8/41; 19.5%) and placebo (6/43; 14.0%) groups. Conclusions Treatment with fosmetpantotenate was safe but did not improve function assessed by the PKAN-ADL in patients with PKAN. The FORT trial was supported by Retrophin, Inc.

Objective To demonstrate the in vitro activities of panthenol, palmitoylethanolamide (PEA), and niacinamide (NAM) and determine the biophysical properties, clinical safety, tolerability together with efficacy of two developmental anti‐redness (AR) formulations containing these ingredients, in alleviating facial redness associated with winter xerosis in healthy volunteers with sensitive skin. Methods The anti‐inflammatory and skin protective properties of panthenol, PEA and NAM were evaluated in vitro. The physical properties of the AR formulations were analysed using measurement of water vapour transport rate (WVTR) and infrared spectroscopy. Clinical studies were performed between the months of December and April (2014–2015) with efficacy assessed during the winter. Facial redness, irritation, sensitization potential, photo‐irritation, and photo‐sensitization were evaluated. Self‐assessed adverse reactions were reported in diaries of use. Results Panthenol and PEA reduced prostaglandin E2, interleukin‐6, and thymic stromal lymphopoietin levels in vitro, while NAM induced nicotinamide adenine dinucleotide (NAD) levels and the keratinocyte differentiation markers: filaggrin (2‐fold increase, P, This article demonstrates the in vitro activities of panthenol, palmitoylethanolamide (PEA), and niacinamide (NAM) and determines the biophysical properties, clinical safety, tolerability together with efficacy of two developmental anti‐redness formulations containing these ingredients, in alleviating facial redness associated with winter xerosis in healthy volunteers with sensitive skin.

The wound healing process is a multifaceted sequence of activities associated with tissue restoration. Novel approaches for the perfection of wound healing have been determined as a stitch in time saves nine. Dysregulation of the immune response is a key element in the pathogenesis of rheumatic diseases and serves as a potential target for novel therapeutic strategies. Vitamin B5 (VB5), also known as pantothenate or "anti-stress vitamin," is the precursor of coenzyme A, which is essential in every micro-organism. Many pantothenic acid amides acquire persuasive antimicrobial activity. Pantothenic acid improves surgical wounds healing with moisturizing and skin barrier enhancing potential. Its deficiency leads to reduced cortisol production, increased arthritic pain, myalgia, fatigue, headache, depression, insomnia, and widespread "proinflammatory" effects on the immune-system. VB5 triggers immune cells to produce cytokines and is multifunctional. The paradoxical effect of VB5 on the switch of anti-inflammatory and proinflammatory cytokines has been revealed. This review aims to present the long research journey of B5 as it is becoming a forerunner in the healing of wounds and in enhancing the immune function, thus providing potentially important therapeutic implications. As its role in healing a wound stitch is promising, amending the immune system damage too is a hopeful target.

Background Numerous studies have revealed that diet has been considered as an important pathogenic factor for nonalcoholic fatty liver disease (NAFLD). The Index of Nutritional Quality (INQ) is a method of quantitative and qualitative evaluation of single foods and diets, which has special significance in recognizing clinical nutritional problems. Materials and Methods This study included 295 patients with NAFLD and 704 controls. The dietary intake was assessed through a valid and reliable food frequency questionnaire. INQ was calculated from the questionnaire data and was compared between the 2 groups. Results The controls had higher INQ of vitamin D, vitamin E, thiamin, riboflavin, niacin, vitamin B12; biotin, pantothenic acid, magnesium and zinc compared to the patients with NAFLD. After controlling for several covariates, positive associations were observed between NAFLD risk and INQs of riboflavin (ORriboflavin = 0.49, 95% confidence interval [CI]: 0.28-0.78; ORbiotin = 0.35, 95% CI: 0.18-0.76; ORpantothenic = 0.28, 95% CI: 0.12-0.64; ORmagnesium = 0.28, 95% CI: 0.11-0.75; ORzinc = 0.15 95% CI: 0.05-0.42). Conclusions Findings of the present study suggest that subjects who follow a more healthy and nutrient-rich diet, especially in terms of vitamins D, B1, B2, B12, B3 and zinc, are at a lower risk of NAFLD compared to those who consume unhealthy and nutrient-poor diet.

Abstract. Adequate dietary intake is vital for infants’ growth and development. The aim was to analyse food consumption and energy and nutrient intakes in a group of healthy Spanish infants and toddlers. Cross-sectional study. 154 infants were assessed at 6 months, and followed at 12 and 30 months. Clinical history, anthropometry, type of feeding, food consumption and energy and nutrient intakes (24-hours recall) were estimated. Advice about food consumed, estimated average requirements, the prevalence of inadequate intakes and percentage of adequacy of the recommended dietary allowance were applied. Toddlers had an excessive daily consumption of meat (>51.3g/day), milk (>545g/day), fish (>20.8g/day) and free-sugar foods (>30.5g/day). This consumption was related to a very high intake of proteins (>18%) and free sugars (>10%), at 12 and 30 months, as a percentage of daily energy intake. The mean prevalence of inadequacy intakes was above 48% for iron at 6 months, and 68% and 87% for vitamin D at 12 and 30 months, respectively. At 6 months, infants who were breastfed had greater adequacy in energy and nutrients to recommended dietary, while infants fed infant formula had a higher intake (>120% compared with RDA) in vitamins E, C, B1, B2, pantothenic acid, B6, B12 and folic acid. The contribution of micronutrients in infant formula should be reviewed, appropriate protein and free sugars should be provided during complementary feeding, as well as strategies to avoid vitamin D deficiency since childhood; and continue with the promotion of breastfeeding.

BackgroundBreast milk is the sole source of nutrition for exclusively breastfed infants in the first 6 mo of life, yet few studies have measured micronutrient concentrations in breast milk in light of maternal diet and subsequent infant micronutrient intakes.ObjectivesWe evaluated the adequacy of micronutrient intakes of exclusively breastfed Indonesian infants by measuring milk volume and micronutrient concentrations and assessed maternal micronutrient intakes and their relationship with milk concentrations.MethodsMother-infant (2-5.3 mo) dyads (n=113) were recruited for this cross-sectional study. Volume of breast-milk intake via the deuterium dose-to-mother technique over 14 d and analyzed micronutrient concentrations were used to calculate micronutrient intakes of exclusively breastfed infants. Maternal 3-d weighed food records were collected to assess median (IQR) micronutrient intakes. Multivariate regression analyses examined the association of usual maternal micronutrient intakes with milk micronutrient concentrations after adjustment for confounding variables.ResultsMean±SD intake of breast-milk volume was 787±148 mL/d. Median daily infant intakes of iron, zinc, selenium, magnesium, sodium, and B-vitamins (thiamin, riboflavin, niacin, pantothenic acid, B-6, and B-12) were below their respective Adequate Intakes. Inadequacies in maternal intakes (as %40% for calcium, niacin, and vitamins A, B-6, and B-12. Significant positive associations existed between maternal usual intakes of vitamin A, niacin and riboflavin and milk retinol, nicotinamide, and free riboflavin concentrations in both unadjusted and adjusted (for infant age, milk volume, and parity) analyses (all P&nbsp

Background The present study aimed to examine how different meal and snack patterns are associated with micronutrient intakes and diet quality among a nationally representative sample of Greek children and adolescents aged 1-19 years from the cross-sectional Hellenic National Nutrition and Health Survey (n = 598). Methods Meal and snack patterns were derived using 24-h dietary recalls. Mean adequacy ratio (MAR) was used as an overall measure of diet quality. Multiple linear regression adjusted for covariates was conducted to examine associations between eating patterns, nutrient intakes and MAR. Results Four most frequently reported eating schemes were identified including breakfast (B), lunch (L), dinner (D) and two snacks (S) (20.9%); B, L, D and 1S (16.2%); B, L, D and 3S (10.8%); and B, L and D (7.9%). Based on these schemes, the daily consumption of all main meals from the majority of the sample was highlighted. In children and adolescents aged 4-19 years, increasing snack frequency was positively associated with intakes of vitamin D, vitamin K, riboflavin, niacin, pantothenic acid, folate, magnesium, copper and selenium. An inverse association was recorded for vitamin E, vitamin B6 , calcium and iron. Among children aged 1-3 years, only niacin and copper were significantly associated with number of snacks, with the group of 'B-L-D-2S' presenting the highest intake. As for the overall diet quality, among all participants, there was no significant association of MAR with the type of meal and snack pattern, and thus the snack frequency. Conclusions Snacking behaviour is a common practice among children and adolescents. Modifying current snack foods with nutrient-rich choices could lead to an improvement of their diet's nutritional quality.

Summary Background & aims Despite the growing evidence about dietary patterns, this study aimed at the association between patterns of nutrients intake and psychological disorders. Methods In this cross-sectional study, diet and psychological factors including anxiety, depression, and general health (GHQ) were assessed through self-administered questionnaires in 3846 Iranian adults. Daily intakes of 57 nutrients and bioactive compounds were calculated. Nutrient patterns (NPs) were derived using factor analysis. Results Three NPs were identified: 1) high in individual amino acids, cobalamin, zinc, phosphorus, saturated fatty acids, cholesterol and pantothenic acid named as “omnivore”; 2) high in thiamin, folate, selenium, iron, starch, maltose, betaine, calcium, riboflavin, and niacin; named as “grains and dairy”. Mono-unsaturated fats, vitamin E and polyunsaturated fats were inversely associated with this pattern; 3) “fruits and vegetables” NP high in copper, vitamin C, glucose, fructose, potassium, dietary fiber, sucrose, vitamin A, magnesium and vitamin K. After adjustment for confounders, men in the top tertile of the omnivore NP had lower anxiety score than those in the bottom tertile (P = 0.04). Men in the highest tertile of the first NP were less likely to be depressed (OR = 0.50, 95%CI: 0.26–0.96; P-trend = 0.04). Women in the highest tertile of this pattern had lower GHQ scores than those in the bottom tertile (P = 0.01) and had lower odds of psychological distress (OR = 0.75, 95%CI: 0.57–0.99, P-trend = 0.0.04). Conclusions An “omnivore” like diet high in amino acids, cobalamin, zinc, phosphorus, saturated fat, cholesterol and pantothenic acid is associated with reduced psychological disorders. Prospective studies are recommended to confirm our results.

Background: Dexpanthenol is a widely used humectant in hair care products, especially anti-hairfall products. The hair care industry is highly regulated in East Asia and treats products containing the combination of dexpanthenol, zinc pyrithione, and nicotinamide (vitamin B3) as quasi-drugs. Objective: Because dexpanthenol lacks a UV chromophore, existing methodologies for analysis in finished products include pretreatments and/or HPLC-UV analysis at low wavelengths at which poor signal-to-noise is observed.These time-consuming methods lack the robustness needed for routine use in quality laboratories. This has resulted in the need for a simple, fast, accurate, and robust UHPLC-MS method to quantify dexpanthenol in hair care products that could be easily adapted in quality laboratories. Methods: The MS detection was performed in positive ionmode with data acquired in single-ion recordingfor dexpanthenol (206.14 m/z), dexpanthenol-d6 (212.29 m/z), and Leucine Enkephalin acetate salt (556.28 m/z). Quantitation was performed using peak area ratio of dexpanthenol to the internal standard. Results: The resulting linearcurve R2 was 0.9998 with sample precision RSDs

Post-acne hyperpigmentation (PAH) occurs secondary to acne vulgaris and may cause significant adverse effects. Although may occur in any skin types, PAH has been found to be more common and severe in people with colored skin. This study aimed to assess the effectiveness of combination serum containing galactomyces ferment filtrate (GFF), dexpanthenol, and

Scope: B vitamers are co-enzymes involved in key physiological processes including energy production, one-carbon, and macronutrient metabolism. Studies profiling B vitamers simultaneously in parent–child dyads are scarce. Profiling B vitamers in parent–child dyads enables an insightful determination of gene–environment contributions to their circulating concentrations. We aimed to characterise: (a) parent–child dyad concordance, (b) generation (children versus adults), (c) age (within the adult subgroup (age range 28–71 years)) and (d) sex differences in plasma B vitamer concentrations in the CheckPoint study of Australian children. Methods and Results: 1166 children (11 ± 0.5 years, 51% female) and 1324 parents (44 ± 5.1 years, 87% female) took part in a biomedical assessment of a population-derived longitudinal cohort study: The Growing Up in Australia’s Child Health CheckPoint. B vitamer levels were quantified by UHPLC/MS-MS. B vitamer levels were weakly concordant between parent–child pairs (10–31% of variability explained). All B vitamer concentrations exhibited generation-specificity, except for flavin mononucleotide (FMN). The levels of thiamine, pantothenic acid, and 4-pyridoxic acid were higher in male children, and those of pantothenic acid were higher in male adults compared to their female counterparts. Conclusion: Family, age, and sex contribute to variations in the concentrations of plasma B vitamers in Australian children and adults.

Whereas the prevalence of several cancer types is decreasing, skin malignancies are growing more common every year. Malignant melanoma is the most aggressive form of skin cancer with high metastatic capacity. In most cases, malignant melanoma shows acquired therapy resistance. We evaluated the ability of Ocoxin, a natural compound-based antioxidant and anti-inflammatory nutritional complement, to exert an antitumor effect in melanoma. To do so, the cytotoxicity of Ocoxin in a panel of BRAF-mutated murine and human melanoma cell lines was tested alone and in combination with BRAF inhibitor Vemurafenib. Our results revealed a potent cytotoxic effect of Ocoxin against melanoma cells and a synergic effect when combined with Vemurafenib, reducing viability and increasing apoptosis. Besides, Ocoxin interferes with the cell cycle, impairs the inherent and fibroblast-mediated melanoma cell migration, and reduces resistance to BRAF inhibition. Proteomic analysis revealed reduced tumor secretion of inflammatory factors Galectin-1, Osteopontin, CCL5, and CCL9 upon treatment with Ocoxin. Moreover, RNASeq showed that Ocoxin downregulated the cell cycle and proliferation-related genes. In vivo, Ocoxin reduced the number of lung metastasis of YUMM-1.7 melanoma cells. Therefore, Ocoxin arises as a good candidate for clinical trials analyzing the beneficial effects in patients suffering from this cutaneous malignancy. This research was partly funded by Catalysis S.L.

Objective Our study aimed to find potential biomarkers for drug resistance in liver cancer cells using metabolomics and further to evaluate the potential of psoralen-loaded polymer lipid nanoparticles (PSO-PLNs) to reverse the resistance of cells to doxorubicin. Methods We used LC-MS-based non-targeted metabolomics, also known as global metabolite profiling, to screen in serum and urine of mice engrafted with a liver cancer cell line sensitive (HepG2/S) or resistant to doxorubicin (HepG2/ADR) for differentially regulated metabolites. We subsequently quantified the abundance of these metabolites in serum and the urine of mice. The mice were engrafted with HepG2 cells resistant against doxorubicin and were treated with I) doxorubicin, II) a combination of doxorubicin and psoralen and III) a combination of doxorubicin and psoralen packed in polymer lipid nanoparticles. Results Metabolites found to be differentially present in urine of mice engrafted with resistant HepG2 cells were: hippuric acid, hyaluronic acid, pantothenic acid, and betaine; retinoic acid and α-linolenic acid were found to be reduced in serum samples of mice with HepG2 cells resistant to doxorubicin. The targeted analysis showed that the degree of regression of metabolic markers in groups differed: treatment group 2 had stronger degree of regression than treatment group 1 and the negative control group had the smallest, which indicates that the PSO-PLNs have superior properties compared with other treatments. Conclusion Psoralen reverses drug resistance of liver cancer cells and its efficacy can be increased by encapsulation in polymer lipid nanoparticles.

The bacterial pathogen Mycobacterium tuberculosis can enter into a persistent state in which M. tuberculosis can evade host immunity, thereby reducing the effectiveness of current tuberculosis vaccines. Understanding the factors that contribute to persistence would enable the rational design of vaccines effective against persisters., Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, can enter into a persistent state that confers resistance to antibacterial agents. Many observations suggest that persistent M. tuberculosis cells also evade the antimycobacterial immune mechanisms, thereby reducing the effectiveness of the current tuberculosis vaccine. Understanding the factors that contribute to persistence may enable the rational design of vaccines that stimulate effective immune killing mechanisms against persister cells. Independent mutations targeting the methionine and arginine biosynthetic pathways are bactericidal for M. tuberculosis in mice. However, in this study, we discovered that the addition of leucine and pantothenate auxotrophy altered the bactericidality of methionine auxotrophy. Whereas the leucine/pantothenate/methionine auxotrophic M. tuberculosis strain H37Rv ΔleuCD ΔpanCD ΔmetA was eliminated in immunocompetent mice, this strain persisted in multiple organs of immunodeficient Rag1−/− mice for at least a year. In contrast, the leucine/pantothenate/arginine auxotroph H37Rv ΔleuCD ΔpanCD ΔargB was eliminated in both immunocompetent and immunodeficient Rag1−/− mice. Our results showed that leucine and pantothenate starvation metabolically blocked the sterilization mechanisms of methionine starvation but not those of arginine starvation. These triple-auxotrophic strains should be invaluable tools for unravelling the bacterial and host factors that enable persistence and for vaccine development studies to assess the efficacy of vaccines that boost immune recognition of M. tuberculosis in the persistent state. The sterilization of the ΔleuCD ΔpanCD ΔmetA auxotroph in immunocompetent mice, but not in mice lacking an adaptive immune response, could provide a new system for studying the antimycobacterial killing mechanisms of adaptive immunity.