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There is need for advancing minimally invasive diagnostic techniques for sex differentiation at early life-stage classes in sea turtles. The objectives of this study were to determine whether there are sex-specific effects on the metabolome of the loggerhead sea turtle (Caretta caretta) and to identify potential biomarkers for sex classification at early life-stage classes (50 post-hatchling and 50 juvenile). Comprehensive analyses including plasma chemistry (n = 100) and untargeted (n = 48) metabolomic analyses were performed. Unlike with plasma chemistry analytes, there were significant differences in the metabolomic profiles between sexes. Nine metabolites differed significantly between sexes, with several metabolites deserving greater attention as potential biomarkers: C22H32O6 and pantothenic acid was higher in females than in males, and carboxylic acid ester (C10H16O5), 1-methylhistidine and C7H14N2O7 was higher in males than females. These differences remained constant both across and within the same life-stage class. This work identified a discernible effect on the metabolic profile based on sex of loggerhead sea turtles and it suggests that these metabolites and/or their ratios could serve as potential biomarker candidates for sex classification in this species. This study demonstrates a distinct metabolomic profile between male and female loggerhead turtles at different physiological stages (posthatchling and juvenile animals) and proposes biomarkers for sex classification. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the effects of pantothenic acid (PA) on the lipid metabolism, and antioxidant function of Apis mellifera workers. The results showed that ether extract (EE) content of bees' body was significantly decreased when workers were supplemented with 147 mg/kg PA (P < 0.05). Further, supplemental PA reduced triglycerides (TG) and total cholesterol (TCHO) content in the hemolymph (P < 0.05), while 39.2 mg/kg PA supplementation improved hemolymph high-density lipoprotein cholesterol (HDL-c) concentration, while 261.6 mg/kg PA reduced low-density lipoprotein cholesterol (LDL-c) concentration (P < 0.05). C12:0, C14:1, and C18:0 content values were notably increased in PA-supplemented groups, while those of C14:0, C18:2n-6, C20:4n-6, polyunsaturated fatty acids (PUFA), and PUFA/saturated fatty acids were decreased (P < 0.05), while levels correlated with those of dietary PA. Malondialdehyde (MDA) content showed a downward trend in response to PA supplementation; however, total superoxide dismutase (T-SOD) was increased (P < 0.05). Furthermore, fatty acid synthase (FAS) mRNA levels were significantly downregulated in bees supplemented 9.8, 19.6, and 39.2 mg/kg (P < 0.05) and lipase activity significantly improved following supplementation with 39.2, 78.4, and 147 mg/kg PA (P < 0.05). Thus, dietary PA significantly influenced worker bee lipid metabolism, and improved antioxidant function. [ABSTRACT FROM AUTHOR]

Simple Summary: Antimicrobial resistance is seen as a global threat to One Health, since it is associated with high rates of morbidity and mortality. To reduce the use of antimicrobials in farm animals, Bepanthene® was compared with an antibiotic-based spray in the healing of disbudding wounds in calves. Benpanthene® is based on dexpanthenol, a derivative of pantothenic acid, also known as provitamin B5, which protects and stimulates skin regeneration. The findings of the present study support the use of Bepanthene®, allowing for a reduction in the use of antimicrobials in production animals without impeding healing. The process of disbudding female calves is a common procedure in many dairy farms, avoiding injuries caused by horns and reducing feed bunk space requirements. The most common method for disbudding calves is by the use of a cautery iron, responsible for destroying the horn-generating tissue. After the procedure, wounds may be treated with an antibiotic-based spray. Nowadays, antimicrobial resistance is a worldwide concern in both human and veterinary medicine, highlighting the need to invest in the monitoring of antimicrobial use and in the development of alternative treatments in favour of One Health. The goal of this study is to promote a reduction in the use of antibiotics in farm animals by investigating an alternative treatment for disbudding wounds. Bepanthene® (dexpanthenol, a derivative of pantothenic acid, a component of the B vitamin complex) is a plausible option, since it is widely used in human medicine for the treatment of skin irritations and burns. The comparison of the healing process of disbudding wounds treated with Bepanthene® or a chlortetracycline-based spray was achieved through the presentation of a randomly-ordered sequence of images of the lesions to a panel of convenience-selected and blinded-to-treatment evaluators, composed of seven veterinarian practitioners, five veterinary medicine students, and five human medical field nurses. In order to classify the lesions, the panel applied an adapted format of a validated healing scale (Bates–Jensen Wound Assessment Tool), incorporating seven parameters of evaluation, culminating in the values used for statistical analyses. In the practitioners' evaluation, a statistically significant effect for the factors of time and treatment in favour of Bepanthene® was found for the parameters "Edges", "Necrotic Tissue Type", and "Skin Colour Surrounding Wound", indicating that Bepanthene® is superior to the spray when considering these parameters of healing. The assessment by the veterinary students showed a significant effect for the factors of time and treatment for the parameters "Necrotic Tissue Type", in favour of the Bepanthene®, and "Granulation Tissue", in favour of the antibiotic spray, demonstrating no clear benefit for either treatment. Lastly, the evaluation performed by nurses showed a significant effect for the factors of time and treatment, in favour of the Bepanthene®, for the parameters "Necrotic Tissue Type" and "Skin Colour Surrounding Wound", leading to the conclusion that Bepanthene® is associated with better and faster healing when compared to the spray. Overall, these findings lead us to suggest that Bepanthene® presents a better healing index compared to a chlortetracycline-based spray, allowing it to be safely used as a substitute to an antimicrobial agent. [ABSTRACT FROM AUTHOR]

Background: In recent years, minimally invasive treatment options for lumbar disc herniation, such as percutaneous laser disc decompression (PLDD), have been introduced to avoid more invasive surgical methods. Combining these minimally invasive approaches with nutraceuticals that are effective in neuroprotection and pain management may lead to better long-term outcomes. Methods: The present study evaluated the beneficial effects of a new oral food supplement composed of acetyl-L-carnitine, α-lipoic acid, quercetin, bromelain, pantothenic acid, and vitamins C, B1, B2, B6, and B12 in patients with neuropathic pain due to herniated lumbar discs treated with PLDD. Patients were divided into two groups of 26 patients each: group A underwent PLDD alone, while group B underwent PLDD followed by a dietary supplement for two months after surgery. Preoperative VAS scores for leg pain were recorded for both groups and no significant difference was observed (8.7 for Group A and 8.6 for Group B). Results: In Group A, the mean postoperative VAS score for leg pain at a 1-month follow-up was 2.5, which remained stable at 3 months. In Group B, the mean postoperative VAS score was 2.0 at 1-month and improved to 1.6 at the 3-month follow-up. According to self-reported leg pain assessments, 66.5% of the patients using the dietary supplement reported a significantly better pain condition, and 43.5% reported a somewhat better situation. In contrast, 7.7% of the patients who underwent PLDD alone reported no changes in leg pain at the final follow-up. Conclusions: The results of our study indicate that the oral food supplement could provide a safe and effective treatment in patients with painful radiculopathy, enhancing the recovery of sensory fiber function in lumbar nerve roots after surgical lumbar disc decompression. [ABSTRACT FROM AUTHOR]

The biosynthesis of antibiotics and other secondary metabolites (also named special metabolites) is regulated by multiple regulatory networks and cascades that act by binding transcriptional factors to the promoter regions of different biosynthetic gene clusters. The binding affinity of transcriptional factors is frequently modulated by their interaction with specific ligand molecules. In the last decades, it was found that the biosynthesis of penicillin is induced by two different molecules, 1,3-diaminopropane and spermidine, but not by putrescine (1,4-diaminobutane) or spermine. 1,3-diaminopropane and spermidine induce the expression of penicillin biosynthetic genes in Penicillium chrysogenum. Proteomic studies clearly identified two different proteins that respond to the addition to cultures of these inducers and are involved in β-alanine and pantothenic acid biosynthesis. These compounds are intermediates in the biosynthesis of phosphopantetheine that is required for the activation of non-ribosomal peptide synthetases, polyketide synthases, and fatty acid synthases. These large-size multidomain enzymes are inactive in the "apo" form and are activated by covalent addition of the phosphopantetheine prosthetic group by phosphopantetheinyl transferases. Both 1,3-diaminopropane and spermidine have a similar effect on the biosynthesis of cephalosporin by Acremonium chrysogenum and lovastatin by Aspergillus terreus, suggesting that this is a common regulatory mechanism in the biosynthesis of bioactive secondary metabolites/natural products. [ABSTRACT FROM AUTHOR]

Background: Data suggest that metabolites, other than blood phenylalanine (Phe), better and independently predict clinical outcomes in patients with phenylketonuria (PKU). Methods: To find new biomarkers, we compared the results of untargeted lipidomics and metabolomics in treated adult PKU patients to those of matched controls. Samples (lipidomics in EDTA-plasma (22 PKU and 22 controls) and metabolomics in serum (35 PKU and 20 controls)) were analyzed using ultra-high-performance liquid chromatography and high-resolution mass spectrometry. Data were subjected to multivariate (PCA, OPLS-DA) and univariate (Mann–Whitney U test, p < 0.05) analyses. Results: Levels of 33 (of 20,443) lipid features and 56 (of 5885) metabolite features differed statistically between PKU patients and controls. For lipidomics, findings include higher glycerolipids, glycerophospholipids, and sphingolipids species. Significantly lower values were found for sterols and glycerophospholipids species. Seven features had unknown identities. Total triglyceride content was higher. Higher Phe and Phe catabolites, tryptophan derivatives, pantothenic acid, and dipeptides were observed for metabolomics. Ornithine levels were lower. Twenty-six metabolite features were not annotated. Conclusions: This study provides insight into the metabolic phenotype of PKU patients. Additional studies are required to establish whether the observed changes result from PKU itself, diet, and/or an unknown reason. [ABSTRACT FROM AUTHOR]

Vitamins are essential components of enzyme systems involved in normal growth and function. The quantitative estimation of the proportion of dietary vitamins, that is in a form available for utilization by the human body, is limited and fragmentary. This review provides the current state of knowledge on the bioavailability of thirteen vitamins and choline, to evaluate whether there are differences in vitamin bioavailability when human foods are sourced from animals or plants. The bioavailability of naturally occurring choline, vitamin D, vitamin E, and vitamin K in food awaits further studies. Animal-sourced foods are the almost exclusive natural sources of dietary vitamin B-12 (65% bioavailable) and preformed vitamin A retinol (74% bioavailable), and contain highly bioavailable biotin (89%), folate (67%), niacin (67%), pantothenic acid (80%), riboflavin (61%), thiamin (82%), and vitamin B-6 (83%). Plant-based foods are the main natural sources of vitamin C (76% bioavailable), provitamin A carotenoid β-carotene (15.6% bioavailable), riboflavin (65% bioavailable), thiamin (81% bioavailable), and vitamin K (16.5% bioavailable). The overview of studies showed that in general, vitamins in foods originating from animals are more bioavailable than vitamins in foods sourced from plants. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether micronutrient intake from food as well as the regular uptake of specific vitamins and/or minerals are associated with leucocyte telomere length (LTL). Methods: This is a cross-sectional study using data from 422,693 UK Biobank participants aged from 40 to 69 years old, during 2006–2010. LTL was measured as the ratio of telomere repeat number to a single–copy gene and was loge-transformed and z-standardized (z-LTL). Information concerning supplement use was collected at baseline through the touchscreen assessment, while micronutrient intake from food were self-reported through multiple web-based 24 h recall diaries. The association between micronutrient intake or supplement use and z-LTL was assessed using multivariable linear regression models adjusting for demographic, lifestyle and clinical characteristics. Results: About 50% (n = 131,810) of the participants, with complete data on all covariates, self-reported regular supplement intake. Whilst overall supplement intake was not associated with z-LTL, trends toward shorter z-LTL with regular vitamin B (-0.019 (95% CI: -0.041; 0.002)) and vitamin B9 (-0.027 (-0.054; 0.000)) supplement intake were observed. z-LTL was associated with food intake of pantothenic acid (-0.020 (-0.033; -0.007)), vitamin B6 (-0.015 (-0.027; -0.003)), biotin (0.010 (0.002; 0.018)) and folate (0.016 (0.003; 0.030)). Associations of z-LTL with these micronutrients were differentiated according to supplement intake. Conclusion: Negative associations equivalent to a year or less of age-related change in LTL between micronutrient intake and LTL were observed. Due to this small effect, the clinical importance of the associations and any relevance to the effects of vitamin and micronutrient intake toward chronic disease prevention remains uncertain. [ABSTRACT FROM AUTHOR]

Objective: Gastrointestinal dysfunction are often associated with type 2 diabetes mellitus (T2DM), a complicated metabolic illness. Contributing factors have been proposed, including genetic predisposition, gene environmental, and lifestyle interactions, but the pathophysiology remains unknown. Methods: We aim to explore the possible causes behind gastrointestinal dysfunction caused by type 2 diabetes in this study. A comprehensive analysis of the gastric sinus metabolome, transcriptome, and proteome in db/db mice with gastrointestinal dysfunction was conducted. Results: The model group of mice had considerably lower small intestine propulsion and gastric emptying rates, higher blood glucose levels, and were significantly obese compared to the control group. We identified 297 genes, 350 proteins, and 1,001 metabolites exhibiting significant differences between db/db and control mice (p < 0.05). Moreover, multi-omics analysis revealed that the genes, proteins, and metabolites in the T2DM-induced gastroenteropathy mice group were involved in arachidonic acid metabolism, glycerophospholipid metabolism and vitamin digestion and absorption. Specifically, Cbr3, Etnppl, and Apob were the major mRNAs associated with T2DM-induced gastrointestinal dysfunction, while Cyp2b10, Cyp2b19, Pgs1, Gpat3, Apoa4, and Tcn2 were the major proteins associated with T2DM-induced gastrointestinal injury, and 16(R)-HET, 5-HETE, LysoPC (22:0), and Pantothenic acid were the major metabolites associated with T2DM-induced gastrointestinal disorders. Conclusion: The mechanism of action of diabetic gastroenteropathy may be related to vitamin digestion and absorption, glycerophospholipid metabolism, and arachidonic acid metabolism. [ABSTRACT FROM AUTHOR]

Simple Summary: Recent studies have shown a correlation between piglet diarrhea and the gut microbiota. However, the precise mechanism by which intestinal microorganisms and their metabolites influence diarrhea in weaned piglets remains unclear. This study explored differences in the gut microbiota and associated metabolites between healthy and diarrheic-weaned piglets using macrogenomic and metabolomic analyses. We identified microorganisms that differed markedly between the two groups. We noticed that the number and abundance of Bacteroidaceae bacterium were strongly negatively correlated with diarrhea in weaned piglets, whereas Caudoviricetes exhibited a strong positive correlation. Our screening for markedly different metabolites such as carnosine, pantothenic acid, pyridoxal, methylimidazoleacetic acid, indole-3-acetaldehyde and 5-hydroxyindoleacetic acid, along with the identification of metabolite-related metabolic pathways like tryptophan and vitamin B6 metabolism, identified important pathways associated with gut microbiota dysbiosis caused by post-weaning diarrhea in piglets. Conjoint analysis revealed that a substantial increase in the number and abundance of Caudoviricetes, coupled with a decrease in the number and abundance of Bacteroidaceae bacterium could potentially serve as microbial markers of post-weaning diarrhea. Recent studies have shown a correlation between piglet diarrhea and the gut microbiota. However, the precise mechanism by which intestinal microorganisms and their metabolites influence diarrhea in weaned piglets remains unclear. This study explored differences in the gut microbiota and associated metabolites between healthy and diarrheic-weaned piglets using macrogenomic and metabolomic analyses. The histomorphological results showed that diarrheic piglets had shorter jejunal and ileal villi, some of which were shed, compared to healthy piglets. Substantial differences in gut microbial diversity and metabolites were also observed, with Bacteroidaceae bacterium and Caudoviricetes being the main differential organisms that were strongly correlated with host status. Microbial functions, mainly the metabolism of carbohydrates, glycans, lipids, and amino acids, as well as related enzyme activities, were substantially different. The major differential metabolites were carnosine, pantothenic acid (vitamin B5), pyridoxal, methylimidazoleacetic acid, indole-3-acetaldehyde, and 5-hydroxyindoleacetic acid. These metabolites were enriched in beta-alanine, histidine, tryptophan, and vitamin B6 metabolism, and in the pantothenate and CoA biosynthesis pathways. Combined macrogenomic and metabolomic analyses revealed that carnosine, vitamin B5, and pyridoxal were negatively correlated with Caudoviricetes; methylimidazoleacetic acid, indole-3-acetaldehyde, and 5-hydroxyindoleacetic acid were positively correlated with Caudoviricetes. Whereas carnosine and vitamin B5 were positively correlated with Bacteroidaceae bacterium, 5-hydroxyindoleacetic acid was negatively correlated. The decreased abundance of Bacteroidaceae bacterium and the increased abundance of Caudoviricetes and related metabolites likely contribute to post-weaning diarrhea in piglets. Therefore, the abundance of Bacteroidaceae bacterium and Caudoviricetes can likely serve as potential markers for identifying and preventing diarrhea in post-weaning piglets. [ABSTRACT FROM AUTHOR]

Type-2 diabetes (T2D) is a rapidly growing multifactorial metabolic disorder that induces the onset of various diseases in the human body. The compositional and metabolic shift of the gut microbiota is a crucial factor behind T2D. Hence, gaining insight into the metabolic profile of the gut microbiota is essential for revealing their role in regulating the metabolism of T2D patients. Here, we have focused on the genome-scale community metabolic model reconstruction of crucial T2D-associated gut microbes. The model-based analysis of biochemical flux in T2D and healthy gut conditions showed distinct biochemical signatures and diverse metabolic interactions in the microbial community. The metabolic interactions encompass cross-feeding of short-chain fatty acids, amino acids, and vitamins among individual microbes within the community. In T2D conditions, a reduction in the metabolic flux of acetate, butyrate, vitamin B5, and bicarbonate was observed in the microbial community model, which can impact carbohydrate metabolism. The decline in butyrate levels is correlated with both insulin resistance and diminished glucose metabolism in T2D patients. Compared to the healthy gut, an overall reduction in glucose consumption and SCFA production flux was estimated in the T2D gut environment. Moreover, the decreased consumption profiles of branch chain amino acids (BCAAs) and aromatic amino acids (AAAs) in the T2D gut microbiota can be a distinct biomarker for T2D. Hence, the flux-level analysis of the microbial community model can provide insights into the metabolic reprogramming in diabetic gut microbiomes, which may be helpful in personalized therapeutics and diet design against T2D. [ABSTRACT FROM AUTHOR]

Summary: Fungal infections, a leading cause of mortality among eukaryotic pathogens, pose a growing global health threat due to the rise of drug-resistant strains. New therapeutic strategies are urgently needed to combat this challenge. The PCA pathway for biosynthesis of Co-enzyme A (CoA) and Acetyl-CoA (AcCoA) from vitamin B5 (pantothenic acid) has been validated as an excellent target for the development of new antimicrobials against fungi and protozoa. The pathway regulates key cellular processes including metabolism of fatty acids, amino acids, sterols, and heme. In this study, we provide genetic evidence that disruption of the PCA pathway in Saccharomyces cerevisiae results in a significant alteration in the susceptibility of fungi to a wide range of xenobiotics, including clinically approved antifungal drugs through alteration of vacuolar morphology and drug detoxification. The drug potentiation mediated by genetic regulation of genes in the PCA pathway could be recapitulated using the pantazine analog PZ-2891 as well as the celecoxib derivative, AR-12 through inhibition of fungal AcCoA synthase activity. Collectively, the data validate the PCA pathway as a suitable target for enhancing the efficacy and safety of current antifungal therapies. The PCA pathway, essential for synthesizing CoA and AcCoA from vitamin B5, plays a crucial role in fungal cellular processes. Targeting this pathway could enhance antifungal drug efficacy by affecting vacuolar morphology and drug detoxification. [ABSTRACT FROM AUTHOR]

Soil potassium deficiency is a common issue limiting agricultural productivity. Potassium-solubilizing bacteria (KSB) show significant potential in mitigating soil potassium deficiency, improving soil quality, and enhancing plant growth. However, different KSB strains exhibit diverse solubilization mechanisms, environmental adaptability, and growth-promoting abilities. In this study, we isolated a multifunctional KSB strain ZHS-1, which also has phosphate-solubilizing and IAA-producing capabilities. 16S rDNA sequencing identified it as Pantoea vagans. Scanning electron microscopy (SEM) showed that strain ZHS-1 severely corroded the smooth, compact surface of potassium feldspar into a rough and loose state. The potassium solubilization reached 20.3 mg/L under conditions where maltose was the carbon source, sodium nitrate was the nitrogen source, and the pH was 7. Organic acid metabolism profiling revealed that strain ZHS-1 primarily utilized the EMP-TCA cycle, supplemented by pathways involving pantothenic acid, glyoxylic acid, and dicarboxylic acids, to produce large amounts of organic acids and energy. This solubilization was achieved through direct solubilization mechanisms. The strain also secreted IAA through a tryptophan-dependent metabolic pathway. When strain ZHS-1 was inoculated into the rhizosphere of rice, it demonstrated significant growth-promoting effects. The rice plants exhibited improved growth and root development, with increased accumulation of potassium and phosphorus. The levels of available phosphorus and potassium in the rhizosphere soil also increased significantly. Additionally, we observed a decrease in the relative abundance of Actinobacteria and Proteobacteria in the rice rhizosphere soil, while the relative abundance of genera associated with acid production and potassium solubilization, such as Gemmatimonadota, Acidobacteria, and Chloroflexi, as well as Cyanobacteria, which are beneficial to plant growth, increased. These findings contribute to a deeper understanding of the potassium solubilization mechanisms of strain ZHS-1 and highlight its potential as a plant growth-promoting rhizobacteria. [ABSTRACT FROM AUTHOR]

Levulinic acid, a hydrolysis product of lignocellulose, can be metabolized into important compounds in the field of medicine and pesticides by engineered strains of Saccharomyces cerevisiae. Levulinic acid, as an intermediate product widely found in the conversion process of lignocellulosic biomass, has multiple applications. However, its toxicity to Saccharomyces cerevisiae reduces its conversion effciency, so screening Saccharomyces cerevisiae genes that can tolerate levulinic acid becomes the key. By creating a whole-genome knockout library and bioinformatics analysis, this study used the phenotypic characteristics of cells as the basis for screening and found the HMX1 gene that is highly sensitive to levulinic acid in the oxidative stress pathway. After knocking out HMX1 and treating with levulinic acid, the omics data of the strain revealed that multiple affected pathways, especially the expression of 14 genes related to the cell wall and membrane system, were significantly downregulated. The levels of acetyl-CoA and riboflavin decreased by 1.02-fold and 1.44-fold, respectively, while the content of pantothenic acid increased. These findings indicate that the cell wall-membrane system, as well as the metabolism of acetyl-CoA and riboflavin, are important in improving the resistance of Saccharomyces cerevisiae to levulinic acid. They provide theoretical support for enhancing the tolerance of microorganisms to levulinic acid, which is significant for optimizing the conversion process of lignocellulosic biomass to levulinic acid. [ABSTRACT FROM AUTHOR]

Background: Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease dementia (PDD), and Huntington's disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be. Objective: Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains. Methods: Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) across ten brain regions. Case–control differences were determined by nonparametric Mann–Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD. Results: Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum. Conclusions: Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions. Plain Language Summary: Decreases in a molecule called pantothenic acid (also known as vitamin B5) have been observed in several areas of the brain in multiple dementia disease, including Alzheimer's disease, Parkinson's disease dementia, and Huntington's disease. However, it is unknown whether such changes also occur in another dementia disease, dementia with Lewy bodies, which shows many of the same symptoms and molecular changes as these conditions. As such, this study was performed in order to determine if and where changes in pantothenic acid occur throughout the dementia with Lewy bodies brain. Using a methodology called liquid chromatography–mass spectrometry, which is able to measure pantothenic acid levels in a highly precise manner in brain tissues, we found that several regions of the dementia with Lewy bodies brain show decreases in pantothenic acid, including some involved in movement such as the substantia nigra and motor cortex, as well as regions associated with cognition and memory such as the hippocampus—looking most similar to the pattern of changes already seen in Alzheimer's disease. It is possible that these changes contribute to the progression of dementia with Lewy bodies; however, further studies need to be performed to determine at what point these changes happen during the disease and how they may contribute to the development of symptoms. [ABSTRACT FROM AUTHOR]

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of calcium D‐pantothenate for the renewal of its authorisation as a nutritional feed additive for all animal species. The additive calcium D‐pantothenate is already authorised for use in all animal species (3a841). The applicant provided evidence that the additive currently in the market complies with the existing conditions of the authorisation and that the production process has not been modified. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that the additive remains safe for all animal species, consumers and the environment. Calcium D‐pantothenate is not irritant to skin and eyes and is not a skin sensitiser. The present application for renewal of the authorisation does not include any modification proposal that would have an impact on the efficacy of the additive, and therefore, there is no need for re‐assessing the efficacy. [ABSTRACT FROM AUTHOR]

Nannochloropsis gaditana, a microalga known for its photosynthetic efficiency, serves as a cell factory, producing valuable biomolecules such as proteins, lipids, and pigments. These components make it an ideal candidate for biofuel production and pharmaceutical applications. In this study, we genetically engineered N. gaditana to overexpress the enzyme fructose-1,6-bisphosphatase (cyFBPase) using the Hsp promoter, aiming to enhance sugar metabolism and biomass accumulation. The modified algal strain, termed NgFBP, exhibited a 1.34-fold increase in cyFBPase activity under photoautotrophic conditions. This modification led to a doubling of biomass production and an increase in eicosapentaenoic acid (EPA) content in fatty acids to 20.78–23.08%. Additionally, the genetic alteration activated the pathways related to glycine, protoporphyrin, thioglucosides, pantothenic acid, CoA, and glycerophospholipids. This shift in carbon allocation towards chloroplast development significantly enhanced photosynthesis and growth. The outcomes of this study not only improve our understanding of photosynthesis and carbon allocation in N. gaditana but also suggest new biotechnological methods to optimize biomass yield and compound production in microalgae. [ABSTRACT FROM AUTHOR]

Food insecurity is a public health concern that affects children worldwide, yet it represents a particular burden for low- and middle-income countries. This study aims to utilize machine learning to identify the associations between food insecurity and nutrient intake among children aged 5 to 18 years. The study's sample encompassed 1040 participants selected from a 2022 food insecurity household conducted in the West Bank, Palestine. The results indicated that food insecurity was significantly associated with dietary nutrient intake and sociodemographic factors, such as age, gender, income, and location. Indeed, 18.2% of the children were found to be food-insecure. A significant correlation was evidenced between inadequate consumption of various nutrients below the recommended dietary allowance and food insecurity. Specifically, insufficient protein, vitamin C, fiber, vitamin B12, vitamin B5, vitamin A, vitamin B1, manganese, and copper intake were found to have the highest rates of food insecurity. In addition, children residing in refugee camps experienced significantly higher rates of food insecurity. The findings emphasize the multilayered nature of food insecurity and its impact on children, emphasizing the need for personalized interventions addressing nutrient deficiencies and socioeconomic factors to improve children's health and well-being. [ABSTRACT FROM AUTHOR]

Aspergillus cristatus is a crucial edible fungus used in tea fermentation. In the industrial fermentation process, the fungus experiences a low to high osmotic pressure environment. To explore the law of material metabolism changes during osmotic pressure changes, NaCl was used here to construct different osmotic pressure environments. Liquid chromatography–mass spectrometry (LC–MS) combined with multivariate analysis was performed to analyze the distribution and composition of A. cristatus under different salt concentrations. At the same time, the in vitro antioxidant activity was evaluated. The LC–MS metabolomics analysis revealed significant differences between three A. cristatus mycelium samples grown on media with and without NaCl concentrations of 8% and 18%. The contents of gibberellin A3, A124, and prostaglandin A2 related to mycelial growth and those of arabitol and fructose-1,6-diphosphate related to osmotic pressure regulation were significantly reduced at high NaCl concentrations. The biosynthesis of energy-related pantothenol and pantothenic acid and antagonism-related fluvastatin, aflatoxin, and alternariol significantly increased at high NaCl concentrations. Several antioxidant capacities of A. cristatus mycelia were directly related to osmotic pressure and exhibited a significant downward trend with an increase in environmental osmotic pressure. The aforementioned results indicate that A. cristatus adapts to changes in salt concentration by adjusting their metabolite synthesis. At the same time, a unique set of strategies was developed to cope with high salt stress, including growth restriction, osmotic pressure balance, oxidative stress response, antioxidant defense, and survival competition. [ABSTRACT FROM AUTHOR]

Background: Joint pain has been recognized as one of the major causes of limitations in mobility, functional decline, and consequently declined quality of life in older adults. Hence, this study aimed to identify the predictors, protective factors, and adverse outcomes of joint pain in community-dwelling older adults. Methods: In this Long-term Research Grant Scheme—Towards Useful Ageing (LRGS-TUA) longitudinal study, a total of 1005 older participants aged 60 years and above who were successfully followed up after five years were included in the analysis. The participants self-reported their joint pain status at baseline and during the fifth year. Subsequently, the baseline characteristics were used to predict changes in joint pain status. Adverse outcomes related to joint pain were evaluated based on the participants' joint pain statuses. Results: Results showed that being female, having diabetes mellitus, and higher body mass index were associated with the incidence of joint pain. Meanwhile, increased intake of pantothenic acid and higher levels of blood albumin levels were associated with recovery from joint pain. Participants with persistent joint pain at baseline and follow-up showed higher levels of depression and disability compared to individuals who never experience any joint pain. However, participants who had recovered from joint pain did not differ significantly from those without joint pain at baseline and follow-up in these measures. Conclusions: By identifying the modifiable risk factors, factors associated with recovery, and adverse outcomes related to joint pain, this study adds to current evidence that may contribute to further management strategies for joint pain in older adults. [ABSTRACT FROM AUTHOR]

This study investigates the effects of a 12-week brisk walking exercise regimen on motor function improvements in elderly women. Twenty-six elderly women, aged 84.2 ± 3.2 years, participated in a 12-week brisk walking exercise program. Fitness assessments and blood biomarker analyses (including CHO, HDLC, LDLC, TC) were conducted pre- and post-intervention. Additionally, targeted metabolomics was employed to measure short-chain fatty acids, amino acids, and vitamin metabolites. The intervention led to significant enhancements in participants' flexibility (p < 0.05), lower limb muscle strength (p < 0.01), and cardiorespiratory endurance (p < 0.01), while muscle mass showed no significant changes. Fifteen significant differential metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.8, and p < 0.05), with arginine, ornithine, aspartic acid, glutamine, phenylalanine, tyrosine, and pantothenic acid playing key roles across seven metabolic pathways. A 12-week brisk walking exercise program significantly enhanced flexibility, lower limb muscle strength, and cardiorespiratory endurance among elderly women. These improvements did not extend to muscle mass or upper limb muscle strength. The observed enhancement in exercise capacity may be attributed to improved regulation of neurotransmitters. [ABSTRACT FROM AUTHOR]

Introduction: Despite the ability of cancer cells to survive glucose deprivation, most studies on anti-cancer effect of metformin explored its impact on glucose metabolism. No study ever examined whether its anti-cancer effect is reversible. Existing evidences warrant understanding of glucose-independent non-cytotoxic anti-proliferative effect of metformin to rationalize its role in liver cancer. Objectives: Characterization of glucose-independent anti-proliferative metabolic effects of metformin as well as analysis of their reversibility in liver cancer cells. Methodology: The dose-dependent effects of metformin on HepG2 cells were examined in presence and absence of glucose. The longitudinal evolution of metabolome was analyzed along with gene and protein expression as well as their correlations with and reversibility of cellular phenotype and metabolic signatures. Results: Metformin concentrations up to 2.5 mM were found to be anti-proliferative irrespective of presence of glucose without significant increase in cytotoxicity. Apart from mitochondrial impairment, derangement of fatty acid desaturation, one-carbon, glutathione, and polyamine metabolism were associated with metformin treatment irrespective of glucose supplementation. Depletion of pantothenic acid, downregulation of essential amino acid uptake and metabolism alongside purine salvage were identified as novel glucose-independent effects of metformin. These were significantly correlated with cMyc expression and reduction in proliferation. Rescue experiments established reversibility upon metformin withdrawal and tight association between proliferation, metabotype, and cMyc expression. Conclusions: The derangement of multiple glucose-independent metabolic pathways, which are often upregulated in therapy-resistant cancer, and concomitant cMyc downregulation coordinately contribute to the anti-proliferative effect of metformin in liver cancer cells. These are reversible and may influence its therapeutic utility. [ABSTRACT FROM AUTHOR]

Objective To evaluate the potential causal relationship between blood metabolites and the risk of heart failure by two-sample Mendelian randomization. Methods Based on a genome-wide association study containing 486 blood metabolites, single nucleotide polymorphisms (SNPs) independently associated with blood metabolites was selected as instrumental variables. The heart failure data were derived from the Genome-Wide Association Study of the Molecular Epidemiology Research Consortium for Therapeutic Targets in Heart Failure. The potential causal relationship between them was analyzed by inverse variance weighting method, MR-Egger regression method, and weighted median method, and the sensitivity analysis was performed using MR-Egger regression intercept, Cochran Q test, MR-PRESSO, and leave-one-out method. Results In total 7 516 SNP associated with blood metabolites were selected as instrumental variables. The results of inverse variance weighting analysis showed that pantothenic acid was associated with heart failure (OR=1.29, 95% CI: 1.03-1.63). Sensitivity analysis results indicated that the results were robust. Conclusion This study suggests that there is a positive causal relationship between pantothenic acid and the risk of heart failure, which may provide new insights into the pathogenesis and drug targets of heart failure. [ABSTRACT FROM AUTHOR]

Dengue virus infection causes thrombocytopenia. Psidium guajava is widely used by people to increase platelet counts. This research aims to analyze in silico the molecular mechanisms of compounds in guava fruit in increasing platelets. The compounds in guava fruit were taken from Dr. Duke's Phytochemical and Ethnobotanical Databases, which include secondary metabolites such as flavonoids, terpenoids, tannins, alkaloids, and fatty acids. Target proteins were predicted using PharmMapper. Protein interaction networks were created using STRING, visualized, and analyzed using Cytoscape. Potential target proteins were identified by topology, modularity, functional, and KEGG pathway analysis. Degree and betweenness centrality are parameters in topological analysis and the cluster with the highest score is selected as the functional module. The results showed that MAPK1, MAPK14, and AKT1 are involved in many inflammatory pathways, and MMP9 is a target protein directly involved in increasing vascular permeability. The compounds arjunolic acid, farnesene, beta-carotene, and alphalinolenic acid inhibit MAPK1, citral, ellagic acid, palmitic acid, and oleanolic acid inhibit MAPK14, guaijaverin, pantothenic acid, and citric acid inhibit AKT1, guaijaverin and pantothenic acid inhibit MMP9. It was concluded that the bioactive compounds in guava fruit play a role in increasing platelets by inhibiting the MAPK, PI3K-Akt pathways, and leukocyte trans-endothelial migration, thereby inhibiting or reducing the production and expression of inflammatory mediators and vascular permeability. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application. [ABSTRACT FROM AUTHOR]

Citri Reticulatae Pericarpium, especially the pericarp of Citrus reticulata Blanco cv. Chachiensis (PCRC), is an important edible and medicinal ingredient for health and pharmacological properties. Citrus Huanglongbing, a devastating disease that currently threatens the citrus industry worldwide, is caused by a phloem-limited alpha-proteobacterium, "Candidatus Liberibacter asiaticus" (CLas). The industry of cultivar Chachiensis has been suffering from HLB. Although HLB affected the quality of citrus fruit, whether the quality of PCRC was affected by HLB remains unclear. In this study, we compared the metabolite profiles between HLB-affected and healthy PCRC from three sources: fresh, 6-month-old, and 9-year-old PCRC, through the untargeted LC–MS method. Compared to healthy controls, various types of bioactive compounds, mainly flavonoids, terpenoids, alkaloids, coumarins, polysaccharides, and phenolic acids, accumulated in HLB-affected PCRC, especially in the HLB-affected 9-year PCRC. In particular, isorhamnetin, isoliquiritigenin, luteolin 7-O-beta-D-glucoside, limonin, geniposide, pyrimidodiazepine, scoparone, chitobiose, m-coumaric acid, malonate, and pantothenic acid, which contributed to the pharmacological activity and health care effects of PCRC, were highly accumulated in HLB-affected 9-year-old PCRC compared to the healthy control. Multibioassay analyses revealed that HLB-affected 9-year-old PCRC had a higher content of total flavonoids and total polyphenols and exhibited similar antioxidant capacity as compared to healthy controls. The results of this study provided detailed information on the quality of HLB-affected PCRC. [ABSTRACT FROM AUTHOR]

Computational design advances enzyme evolution and their use in biocatalysis in a faster and more efficient manner. In this study, a synergistic approach integrating tunnel engineering, evolutionary analysis, and force‐field calculations has been employed to enhance the catalytic activity of D‐lactonohydrolase (D‐Lac), which is a pivotal enzyme involved in the resolution of racemic pantolactone during the production of vitamin B5. The best mutant, N96S/A271E/F274Y/F308G (M3), was obtained and its catalytic efficiency (kcat/KM) was nearly 23‐fold higher than that of the wild‐type. The M3 whole‐cell converted 20 % of DL‐pantolactone into D‐pantoic acid (D‐PA, >99 % e.e.) with a conversion rate of 47 % and space‐time yield of 107.1 g L−1 h−1, demonstrating its great potential for industrial‐scale D‐pantothenic acid production. Molecular dynamics (MD) simulations revealed that the reduction in the steric hindrance within the substrate tunnel and conformational reconstruction of the distal loop resulted in a more favourable"catalytic" conformation, making it easier for the substrate and enzyme to enter their pre‐reaction state. This study illustrates the potential of the distal residue on the pivotal loop at the entrance of the D‐Lac substrate tunnel as a novel modification hotspot capable of reshaping energy patterns and consequently influencing the enzymatic activity. [ABSTRACT FROM AUTHOR]

Summary: Salt stress negatively affects rice growth, development and yield. Metabolic adjustments contribute to the adaptation of rice under salt stress. Branched‐chain amino acids (BCAA) are three essential amino acids that cannot be synthesized by humans or animals. However, little is known about the role of BCAA in response to salt stress in plants.Here, we showed that BCAAs may function as scavengers of reactive oxygen species (ROS) to provide protection against damage caused by salinity. We determined that branched‐chain aminotransferase 2 (OsBCAT2), a protein responsible for the degradation of BCAA, positively regulates salt tolerance.Salt significantly induces the expression of OsBCAT2 rather than BCAA synthesis genes, which indicated that salt mainly promotes BCAA degradation and not de novo synthesis. Metabolomics analysis revealed that vitamin B5 (VB5) biosynthesis pathway intermediates were higher in the OsBCAT2‐overexpressing plants but lower in osbcat2 mutants under salt stress. The salt stress‐sensitive phenotypes of the osbcat2 mutants are rescued by exogenous VB5, indicating that OsBCAT2 affects rice salt tolerance by regulating VB5 synthesis.Our work provides new insights into the enzymes involved in BCAAs degradation and VB5 biosynthesis and sheds light on the molecular mechanism of BCAAs in response to salt stress. [ABSTRACT FROM AUTHOR]

Organic carbon in seawater plays a significant role in the global carbon cycle. The concentration and composition of dissolved organic carbon reflect the activity of the biological community and chemical reactions that occur in seawater. From 2016 to 2019, we repeatedly sampled the oligotrophic northwest Sargasso Sea in the vicinity of the Bermuda Atlantic Time‐series Study site (BATS) to quantitatively follow known compounds within the pool of dissolved organic matter in the upper 1000 m of the water column. Most metabolites showed surface enrichment, and 83% of the metabolites had significantly lower concentrations with increasing depth. Dissolved metabolite concentrations most notably revealed temporal variability. Fourteen metabolites displayed seasonality that was repeated in each of the 4 yr sampled. Concentrations of vitamins, including pantothenic acid (vitamin B5) and riboflavin (vitamin B2), increased annually during winter periods when mixed layer depths were deepest. During diel sampling, light‐sensitive riboflavin decreased significantly during daylight hours. The temporal variability in metabolites at BATS was less than the spatial variability in metabolites from a previous sample set collected over a broad latitudinal range in the western Atlantic Ocean. The metabolites examined in this study are all components of central carbon metabolism. By examining these metabolites at finer resolution and in a time‐series, we begin to provide insights into the chemical compounds that may be exchanged by microorganisms in marine systems, data which are fundamental to understanding the chemical response of marine systems to future changes in climate. [ABSTRACT FROM AUTHOR]

Bat feces have been reported in traditional Chinese medicine (TCM) books to have the effect of reducing fever and improving eyesight, but the mechanism of vision improvement still needs further research. To this end, we used 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and liquid chromatography/tandem mass spectrometry (LC/MS/MS) to analyze the antioxidant capacity of and the types of vitamins in bat feces. We hoped to screen the pharmacological components of bat feces and to explain the role that these components may play in treating visual deterioration. Our results found that bat feces had a good antioxidant capacity and mainly contained vitamins B1 (thiamine), B2 (riboflavin), B3 (nicotinamide), B3 (nicotinic acid), and B5 (pantothenic acid). Although these vitamins may help to maintain the health of the optic nerve and cornea, the vitamin content of bat feces is low, but the heavy metal content is high, as shown using inductively coupled plasma–mass spectrometry (ICP-MS) analysis. Therefore, we suggest that the use of bat feces as TCM to improve vision should be strictly restricted. [ABSTRACT FROM AUTHOR]

The article titled "Corrigendum to Conservation of beneficial microbes between the rhizosphere and the cyanosphere" in the journal New Phytologist acknowledges errors in several figures in a previously published article by Zheng et al. The errors were due to a discrepancy in the R-script used during the revision process, resulting in large error bars in the figures. The corrected figures and their associated legends are provided in the article. The authors apologize for the errors. [Extracted from the article]

Objective: This study explores vitamin drug conjugates, linking drugs to targeting moieties (Niacin and Pantothenic acid), aiming to enhance TB drug efficacy, reduce dosing frequency, and minimize toxicity. Methods: Isoniazid-Niacin (INH-NIA), Isoniazid-Pantothenic Acid (INH-PA), and Pyrazinamide-Niacin (PYZ-NIA) conjugates were synthesized. Their anti-mycobacterial activity against Mycobacterium smegmatis was evaluated. Molecular docking and molecular dynamics simulations assessed binding affinity and stability with MTb proteases. Drug-likeness and ADME properties were examined. Results: INH-NIA and PYZ-NIA demonstrated significant anti-mycobacterial activity, while INH-PA showed lower activity. Docking and simulations confirmed strong binding with MTb proteases. Drug-likeness and ADME properties supported their potential as antitubercular agents. Discussion: Combining antitubercular drugs with specific vitamins in vitamin drug conjugates offers a promising approach to enhance drug efficacy and reduce resistance. These conjugates provide targeted delivery and improved bioavailability, addressing critical challenges in TB treatment. Molecular dynamics simulations validate the stability of drug-target complexes, reinforcing their potential as antitubercular agents. Conclusions: Vitamin drug conjugates, especially INH-NIA and PYZ-NIA, hold significant promise in combating TB. Their innovative approach may revolutionize TB treatment by addressing drug resistance and improving patient outcomes. Further research is warranted to explore and develop these conjugates as effective tools in the fight against TB. This study underscores the importance of innovative strategies in addressing drug-resistant MTb strains and advancing TB treatment options. [ABSTRACT FROM AUTHOR]

Dexpanthenol (DEX), a subtype of vitamin B5, plays an important role in anabolic reactions, cellular energy and regeneration in the body. Nicotine has been shown to induce kidney damage through the mechanisms of oxidative stress and apoptosis. The purpose of this study was to investigate the potential protective effects of DEX against nicotine-induced kidney damage through modulation of the AKT/Nrf2/HO-1 signaling pathway. Male rats were intraperitoneally administered with 0.5 mg/kg/day nicotine and/or 500 mg/kg/day DEX for 8 weeks. Following administration, renal function tests were conducted on serum samples, and histopathological examinations and analysis of oxidative stress markers and antioxidant enzymes were performed on tissue samples. Protein levels of Akt, Nrf-2, HO-1, Bcl-xL, and Caspase-9 were also evaluated. Nicotine administration resulted in decreased protein levels of p-Akt, Nrf-2, HO-1, and Bcl-xL and increased Caspase-9 protein levels. In addition, nicotine administration caused an increase in MDA, TOS, and OSI levels and a decrease in GSH, GSH-Px, GST, CAT, SOD, and TAS levels. Additionally, BUN and Creatinine levels increased after nicotine administration. DEX administration positively regulated these parameters and brought them closer to control levels. Nicotine-induced kidney injury caused apoptosis and oxidative stress through Caspase-9 activation. DEX effectively prevented nicotine-induced kidney damage by increasing intracellular antioxidant levels and regulating apoptosis through Bcl-xL activation. These findings suggest that DEX has potential as a protective agent against nicotine-induced kidney damage. [ABSTRACT FROM AUTHOR]

Background: Biallelic pathogenic variants in SLC5A6 resulting in sodium‐dependent multivitamin transporter (SMVT) defect have recently been described as a vitamin‐responsive inborn error of metabolism mimicking biotinidase deficiency. To our knowledge, only 16 patients have been reported so far with various clinical phenotypes such as neuropathy and other neurologic impairments, gastro‐intestinal dysfunction and failure to thrive, osteopenia, immunodeficiency, metabolic acidosis, hypoglycemia, and recently severe cardiac symptoms. Methods: We describe a case report of a 5‐month‐old girl presenting two recurrent episodes of metabolic decompensation and massive cardiac failure in the course of an infectious disease. We compare clinical, biological, and genetic findings of this patient to previous literature collected from Pubmed database (keywords: Sodium‐dependent multivitamin transporter (SMVT), SMVT defect/disorder/deficiency, SLC5A6 gene/mutation). Results: We highlight the life‐threatening presentation of this disease, the stagnation of psychomotor development, the severe and persistent hypogammaglobulinemia, and additionally, the successful clinical response on early vitamin supplementation (biotin 15 mg a day and pantothenic acid 100 mg a day). Metabolic assessment showed a persistent increase of urinary 3‐hydroxyisovaleric acid (3‐HIA) as previously reported in this disease in literature. Conclusion: SMVT deficiency is a vitamin‐responsive inborn error of metabolism that can lead to a wide range of symptoms. Increased and isolated excretion of urinary 3‐hydroxyisovaleric acid may suggest, in the absence of markedly reduced biotinidase activity, a SMVT deficiency. Prompt supplementation with high doses of biotin and pantothenic acid should be initiated while awaiting results of SLC5A6 sequencing as this condition may be life‐threatening. [ABSTRACT FROM AUTHOR]

A 2-year-old boy with suspected lactose intolerance developed an extensive, itchy rash after using a nasal spray containing dexpanthenol. He was initially treated for a viral upper airway infection with ibuprofen, xylometazoline, and cetirizine. A switch to a drug containing dexpanthenol led to the appearance of the rash and subsequent sleep deprivation. No other possible cause of allergy was found. The withdrawal of all drugs but cetirizine led to full recovery. Dexpanthenol, an alcohol analog of vitamin B5, is present in many drugs for its positive impact on tissue repair. Although generally considered safe, it may rarely cause an allergic reaction, hence we underscore the importance of considering dexpanthenol oversensitivity in patients with unexplained widespread rashes, particularly in pediatric cases. [ABSTRACT FROM AUTHOR]

Vanin-1 is a pantetheinase that hydrolyzes pantetheine to pantothenic acid and cysteamine. Vanin-1 has become recognized to be associated with oxidative stress and inflammation. In animal models, vanin-1 was reported to accelerate atherosclerosis. However, no study has reported blood vanin-1 concentrations in patients with coronary artery disease (CAD). We investigated plasma vanin-1 concentrations in 388 patients undergoing elective coronary angiography for suspected CAD. Patients with acute coronary syndrome were excluded. Of the 388 study patients, CAD was found in 207 patients [1-vessel (1-VD), n = 88; 2-vessel (2-VD), n = 66; and 3-vessel disease (3-VD), n = 53]. Plasma vanin-1 concentrations were higher in patients with CAD than in those without CAD (median 0.59 vs. 0.46 ng/mL, P < 0.005). Vanin-1 concentrations in patients without CAD and those with 1-VD, 2-VD, and 3-VD were 0.46, 0.58, 0.57, and 0.61 ng/mL, respectively, and were highest in 3-VD (P < 0.05). A high vainin-1 concentration (> 0.48 ng/mL) was found in 46% of patients without CAD, 61% of 1-VD, 65% of 2-VD, and 66% of 3-VD (P < 0.01). Vanin-1 concentrations significantly correlated with the number of stenotic coronary segments (r = 0.14, P < 0.02). In the multivariate analysis, vanin-1 concentration was a significant factor associated with CAD independent of atherosclerotic risk factors. The odds ratio for CAD was 1.63 (95%CI = 1.04–2.55) for the high vanin-1 concentration of > 0.48 ng/mL. Thus, plasma vanin-1 concentrations in patients with CAD were found to be high and to be associated with the presence and severity of CAD. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is one of the mycotoxins that poses a serious threat to human and animal health. Curcumin (CUR) is a major bioactive component of turmeric that provides multiple health benefits. CUR can reduce the toxicities induced by mycotoxins, but the underlying molecular mechanisms remain largely unknown. To explore the effects of CUR on OTA toxicity and identify the key regulators and metabolites involved in the biological processes, we performed metabolomic and transcriptomic analyses of livers from OTA-exposed mice. We found that CUR can alleviate the toxic effects of OTA on body growth and liver functions. In addition, CUR supplementation significantly affects the expressions of 1584 genes and 97 metabolites. Integrated analyses of transcriptomic and metabolomic data showed that the pathways including Arachidonic acid metabolism, Purine metabolism, and Cholesterol metabolism were significantly enriched. Pantothenic acid (PA) was identified as a key metabolite, the exogenous supplementation of which was observed to significantly alleviate the OTA-induced accumulation of reactive oxygen species and cell apoptosis. Further mechanistical analyses revealed that PA can downregulate the expression level of proapoptotic protein BAX, enhance the expression level of apoptosis inhibitory protein BCL2, and decrease the level of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2). This study demonstrated that CUR can alleviate the adverse effects of OTA by influencing the transcriptomic and metabolomic profiles of livers, which may contribute to the application of CUR in food and feed products for the prevention of OTA toxicity. [ABSTRACT FROM AUTHOR]

Proteins are biomolecules with potential applications in agriculture, food sciences, pharmaceutics, biotechnology, and drug delivery. Interactions of hydrophilic and biocompatible polymers with proteins may impart proteolytic stability, improving the therapeutic effects of biomolecules and also acting as excipients for the prolonged storage of proteins under harsh conditions. The interactions of hydrophilic and stealth polymers such as poly(ethylene glycol), poly(trehalose), and zwitterionic polymers with various proteins are well studied. This study evaluates the molecular interactions of hydrophilic and optically active poly(vitamin B5 analogous methacrylamide) (poly(B5AMA)) with model proteins by fluorescence spectroscopy, nuclear magnetic resonance (NMR) spectroscopy, and circular dichroism (CD) spectroscopy analysis. The optically active hydrophilic polymers prepared using chiral monomers of R-(+)- and S-(−)-B5AMA by the photo-iniferter reversible addition fragmentation chain transfer (RAFT) polymerization showed concentration-dependent weak interactions of the polymers with bovine serum albumin and lysozyme proteins. Poly(B5AMA) also exhibited a concentration-dependent protein stabilizing effect at elevated temperatures, and no effect of the stereoisomers of polymers on protein thermal stability was observed. NMR analysis, however, showed poly(B5AMA) stereoisomer-dependent changes in the secondary structure of proteins. [ABSTRACT FROM AUTHOR]

Several gut microbial species within the Faecalibacterium genus have emerged as promising next‐generation probiotics (NGP) due to their multifunctional protective effects against gastrointestinal and systemic disorders. To enable clinical studies and further applications, improved methods for cultivating Faecalibacterium must be developed in compliance with current Good Manufacturing Practice regulations, which is complicated by its oxygen sensitivity and complex nutritional requirements. Different yeast‐based nutrients (YBNs), including yeast extracts (YEs) and yeast peptones (YPs), are ubiquitously used when cultivating microbes to supply a broad range of macro‐ and micronutrients. In this study, we evaluated six experimental YBNs, namely three YEs, two YPs and a yeast cell wall product (YCW), and eight B‐vitamins in the cultivation of Faecalibacterium duncaniae A2‐165, former Faecalibacterium prausnitzii, using growth assays in microtitre plates, dose‐effect studies in Hungate tube fermentations and fully controlled bioreactor experiments. We demonstrated that YEs promote F. duncaniae A2‐165 growth in a nutritionally limited medium, while YPs and YCW lacked essential growth factors for enabling cell propagation. High cell density was obtained in controlled bioreactors using a medium containing 2–4% of a selected YE and 1% casein peptone (3.4 ± 1.7 × 109–5.1 ± 1.3 × 109 cells mL−1). Among all tested B‐vitamins, we identified B5 as a strong growth promoter. Replacing casein peptone with YP and supplementing with vitamin B5 further increased biomass by approximately 50% (6.8 ± 1.7 × 109 cells mL−1). Hence, empirical selection of YE, YP and B5 allowed formulation of a high‐yielding animal allergen‐free nutritive medium to produce F. duncaniae A2‐165. Selecting nutritionally suitable YBNs and combining these with other key nutrients are important steps for optimizing production of NGP with high yields and lower cost. [ABSTRACT FROM AUTHOR]

[Objective] Based on non-targeted metabolomics approach, the metabolites in colostrum and mature milk of Holstein cows were identified and analyzed. [Method] Twelve healthy perinatal Holstein cows with similar age, body condition, expected delivery date and parity were selected and milk was collected at 1 h and 21 d after delivery. Then, milk was centrifuged and whey proteins were collected and marked s colostrum group (C_0) and mature milk group (C_21). Metabonomics technology was used to analyze whey of colostrum group and mature milk group. Combined with orthogonal partial least squares discriminant analysis (OPLS-DA) and student t test, differential metabolites were screened based on variable importance in projection (VIP)> 1 with significant differences (P<0.05), and then cluster analysis, significant difference metabolite screening and KEGG pathway analysis were performed. [Result] A total of 97 differential metabolites were screened from colostrum group (C_0) and mature milk group (C_21) of Holtein cows. The contents of most metabolites in colostrum group were higher than that in mature milk group. The differential metabolite random forest map showed that the top nine metabolites with significant difference were aconitic acid, limoconic acid, gentian acid, pantothenic acid, taurine, oxyglutaric acid, citric acid, 6'sialic lactose and spermine. The KEGG pathway enrichment analysis showed that the 8 major metabolic pathways were synthesis and degradation of ketones, taurine and hypoxanthine metabolism, pyruvate metabolism, purine metabolism, pyrimidine metabolism, amino sugar and nucleotide sugar metabolism, tricarboxylic acid cycle and butyric acid metabolism. [Conclusion] The contents of lipid, amino acid and nucleotide metabolites in colostrum of Holstein cows were higher than those in mature milk, while the contents of carbohydrate metabolites in mature milk were higher than those in colostrum. The differences in metabolite levels between colostrum and mature milk obtained in this study provided a basis for subsequent research on metabolite mechanisms. [ABSTRACT FROM AUTHOR]

The level of vitamin B group in human serum is an important index of human health. Among B vitamins, cyanocobalamin in serum is unstable and its content is extremely low. Rapid and simultaneous detection of multiple B vitamins including cyanocobalamin is a challenge. Herein, we have developed a rapid and stable method that can realize the determination of thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5‐methyltetrahydrofolate, and cyanocobalamin simultaneously in 6 min. The method was established based on protein precipitation with methanol and then chromatographic separation was achieved using Waters acquity ultra‐high‐performance liquid chromatography high strength silica T3 column, which was stable and sensitive especially for cyanocobalamin. Limit of quantification, precision, trueness, and matrix effect were validated according to the European Medicines Agency and United States Food and Drug guidelines and Clinical and Laboratory Standards Institute guidelines on bioanalytical method. The limit of quantification for thiamine, riboflavin, nicotinamide, pantothenic acid, pyridoxic acid, biotin, 5‐methyltetrahydrofolate, and cyanocobalamin was 0.4, 0.4, 0.8, 2.0, 0.4, 0.1, 0.4, and 0.04 ng/mL separately, respectively. Intra‐ and interday precisions were 1.1%–12.4% and 2.0%–13.5%, respectively. The relative errors were between 0.3% and 13.3%, and the matrix effects were between 2.6% and 10.4%. [ABSTRACT FROM AUTHOR]

Vitamin B5, also called D-pantothenic acid (D-PA), is a necessary micronutrient that plays an essential role in maintaining the physiological function of an organism. It is widely used in: food, medicine, feed, cosmetics, and other fields. Currently, the production of D-PA in industry heavily relies on chemical processes and enzymatic catalysis. With an increasing demand on the market, replacing chemical-based production of D-PA with microbial fermentation utilizing renewable resources is necessary. In this review, the physiological role and applications of D-PA were firstly introduced, after which the biosynthesis pathways and enzymes will be summarized. Subsequently, a series of cell factory development strategies for excessive D-PA production are analyzed and discussed. Finally, the prospect of microbial production of D-PA production has been prospected. [ABSTRACT FROM AUTHOR]

(R)‐Pantolactone, an intermediate in the syntheses of Vitamin B5 and coenzyme A, is an important chiral molecule often used as a food additive, chiral auxiliary, and chiral starting material for organic transformations. Enantioenriched pantolactones are predominantly produced by biological fermentation and chemical synthesis approaches. Herein, we present a review of recent developments in the asymmetric synthesis of pantolactone through different methods, and systematically summarize the characteristics and advantageous features of these strategies. Among the strategies discussed herein, the direct asymmetric catalysis of glyoxylate and isobutyraldehyde with small organocatalyst molecules has attracted growing attention owing to its good step‐economy, commercially available starting materials, absence of toxic reagents, mild reaction conditions, convenient operation, and low catalyst loading. These characteristics render the direct asymmetric route to pantolactone a particularly attractive procedure. This review provides valuable guidance for the design and synthesis of enantioenriched pantolactone and its analogs. [ABSTRACT FROM AUTHOR]