Thiamine Research Articles

Thiamine hydrochloride as a recyclable organocatalyst for the efficient and chemoselective N-tert-butyloxycarbonylation of amines

Thiamin hydrochloride promoted highly efficient and ecofriendly approach has been described for the chemoselective N-tert-butyloxycarbonylation of amines under solvent-free conditions at ambient temperature. The demonstrated approach has been applicable for the N-Boc protection of variety of aliphatic, aryl, heteroaryl amines. The chemoselective protection of amino group occurs in chiral amines and amino alcohol without racemization in high yield. Thiamin hydrochloride is stable, economical, easy to handle and environmentally friendly.

Widely Targeted Metabolomics Analysis to Reveal Transformation Mechanism of Cistanche Deserticola Active Compounds During Steaming and Drying Processes.

Cistanche deserticola is one of the most precious plants, traditionally as Chinese medicine, and has recently been used in pharmaceutical and healthy food industries. Steaming and drying are two important steps in the processing of Cistanche deserticola. Unfortunately, a comprehensive understanding of the chemical composition changes of Cistanche deserticola during thermal processing is limited. In this study, ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based widely targeted metabolomics analysis was used to investigate the transformation mechanism of Cistanche deserticola active compounds during steaming and drying processes. A total of 776 metabolites were identified in Cistanche deserticola during thermal processing, among which, 77 metabolites were differentially regulated (p < 0.05) wherein 39 were upregulated (UR) and 38 were downregulated (DR). Forty-seven (17 UR, 30 DR) and 30 (22 UR, 8 DR) differential metabolites were identified during steaming and drying, respectively. The most variation of the chemicals was observed during the process of steaming. Metabolic pathway analysis indicated that phenylpropanoid, flavonoid biosynthesis, and alanine metabolism were observed during steaming, while glycine, serine, and threonine metabolism, thiamine metabolism, and unsaturated fatty acid biosynthesis were observed during drying. The possible mechanisms of the chemical alterations during thermal processing were also provided by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Furthermore, the blackening of the appearance of Cistanche deserticola mainly occurred in the steaming stage rather than the drying stage, which is associated with the metabolism of the amino acids. All results indicated that the formation of active compounds during the processing of Cistanche deserticola mainly occurred in the steaming stage.

310 Growth Performance and Carcass Characteristics of Beef Steers Consuming Finishing Diets with an Added Nutritional Packet

Abstract The effects of a nutritional packet fed to beef steers during the final 64 d of the feedlot finishing phase on growth performance and carcass characteristics were evaluated. Crossbred-Angus steers (n = 120; initial BW = 544 ± 52 kg) were assigned to 30 pens (4 steers/pen; 15 pens/treatment) in a randomized complete block design where pen represented the experimental unit. A steam-flaked corn-based finishing diet was fed ad libitum, and treatments were applied as follows: 1) control and 2) 30 g/steer-daily (DM-basis) of the nutritional packet (containing live yeast [8.7 Log CFU of Saccharomyces cerevisiae], vitamin C [5.4 g/kg of Ascorbic acid], vitamin B1 [13.33 g/kg of Thiamine hydrochloride], sodium chloride [80 g/kg] and potassium chloride [80 g/kg]). The nutritional packet used ground corn as a carrier and was included at 1 % of diet DM. Orts were quantified daily (if any) and subtracted from the total dietary DM offered to calculate DM intake. Unshrunk BW were collected on d 0, 21, 42 and 64 before daily feeding at 0630 h. Data were analyzed using the GLIMMIX procedure of SAS. Average daily gain (P = 0.89), dry matter intake (P = 0.57) and, gain:feed (P = 0.66) were not affected by the inclusion of the nutritional packet. The 12th rib fat deposition was increased (P ≤ 0.02) for cattle fed the nutritional packet compared with control (15.70 vs. 13.36 mm, respectively). Consequently, calculated yield grade was also increased (P ≤ 0.03) for cattle consuming the nutritional packet (3.32 vs. 3.02). An improved carcass fat-deposition without any deleterious effects on growth performance potentially warrant less days on feed when cattle receive such nutritional packet.

P58.01 Dysbiosis of Fecal Microbiome in Advanced Non-Small-Cell Lung Cancer

Emerging evidence has demonstrated that fecal microbiome is significantly associated with non-small-cell lung cancer (NSCLC) tumorigenesis and immunotherapy efficacy. In addition, fecal microbiota transplant has shown its potential augmenting the efficacy of PD1/PD-L1 blockers in preclinical and early phase clinical studies. However, few studies have focused on fecal microbiome in patients with advanced NSCLC. In this study, we aimed to characterize the fecal microbiome in advanced NSCLC patients and healthy population, and to investigate the differences of fecal microbiome before and after anti-tumor therapy. Fecal samples from a total of 91 NSCLC patients and 39 healthy volunteers were collected from August 2018 to January 2020, including 10 patients with paired samples collected before and after chemotherapy or immunotherapy, respectively. The hypervariable V3-V4 regions of the 16S rRNA in fecal samples were sequenced. All patients were diagnosed with advanced NSCLC, including stage III (n=11) and stage IV (n=80). Of the 91 patients, 57 were diagnosed with adenocarcinoma, 30 were squamous cell carcinoma and 4 were others. 11 patients didn’t receive any therapy before samples collection. Alpha diversity of the fecal microbiome in lung cancer patients was significantly lower than that of healthy population (Chao1 P=0.038, faith_pd P=0.027). Beta diversity, described by unweighted principal coordinate analysis (PCoA), revealed that the composition significantly differed between patients and healthy controls at species and genus levels. Advanced NSCLC patients had higher levels of Parabacteroides, Lactobacillus, Veillonella but lower abundance of Prevotella, Faecalibacterium, Lachnospira, Phascolarctobacterium, Roseburia, and Subdoligranulum (P<0.05). Higher levels of Butyricicoccus (P=0.0625) and Dialister (P=0.0625), along with a lower abundance of Hungatella (P=0.125),were found after chemotherapy compared to baseline. After immunotherapy, the levels of Anaerostipes, Blautia, Butyricicoccus, and Hungatella tended to increase(P=0.125), while the level of Lactobacillus tended to decrease(P=0.125). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that altered microbiota observed between lung cancer group and healthy control group was enriched in pathways including valine, leucine and isoleucine biosynthesis, peptidoglycan biosynthesis, thiamine metabolism and etc. Advanced NSCLC patients have lower diversity and characteristic bacterial community in comparison with healthy volunteers. Identified microbiota might serve as new biomarkers for advanced NSCLC patients and predict the efficacy of chemotherapy or immunotherapy. However, further studies are warranted to confirm. Targeting on the enriched microbiome-related pathways might be a potential research direction to improve patients' survival.

The Damage Caused by Decline Disease in Bayberry Plants through Changes in Soil Properties, Rhizosphere Microbial Community Structure and Metabolites.

Decline disease causes serious damage and rapid death in bayberry, an important fruit tree in south China, but the cause of this disease remains unclear. The aim of this study was to investigate soil quality, microbial community structure and metabolites of rhizosphere soil samples from healthy and diseased trees. The results revealed a significant difference between healthy and diseased bayberry in soil properties, microbial community structure and metabolites. Indeed, the decline disease caused a 78.24% and 78.98% increase in Rhizomicrobium and Cladophialophora, but a 28.60%, 57.18%, 38.84% and 68.25% reduction in Acidothermus, Mortierella, Trichoderma and Geminibasidium, respectively, compared with healthy trees, based on 16S and ITS amplicon sequencing of soil microflora. Furthermore, redundancy discriminant analysis of microbial communities and soil properties indicated that the main variables of bacterial and fungal communities included pH, organic matter, magnesium, available phosphorus, nitrogen and calcium, which exhibited a greater influence in bacterial communities than in fungal communities. In addition, there was a high correlation between the changes in microbial community structure and secondary metabolites. Indeed, GC–MS metabolomics analysis showed that the healthy and diseased samples differed over six metabolic pathways, including thiamine metabolism, phenylalanine–tyrosine–tryptophan biosynthesis, valine–leucine–isoleucine biosynthesis, phenylalanine metabolism, fatty acid biosynthesis and fatty acid metabolism, where the diseased samples showed a 234.67% and 1007.80% increase in palatinitol and cytidine, respectively, and a 17.37–8.74% reduction in the other 40 metabolites compared to the healthy samples. Overall, these results revealed significant changes caused by decline disease in the chemical properties, microbiota and secondary metabolites of the rhizosphere soils, which provide new insights for understanding the cause of this bayberry disease.

Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4

BackgroundThiamine metabolism dysfunction syndrome 4 (THMD4, OMIM #613710) is an autosomal recessive inherited disease caused by the deficiency of SLC25A19 that encodes the mitochondrial thiamine pyrophosphate (TPP) transporter. This disorder is characterized by bilateral striatal degradation and progressive polyneuropathy with the onset of fever of unknown origin. The limited number of reported cases and lack of functional annotation of related gene variants continue to limit diagnosis.ResultsWe report three cases of encephalopathy from two unrelated pedigrees with basal ganglia signal changes after fever of unknown origin. To distinguish this from other types of encephalopathy, such as acute necrotizing encephalopathy, exome sequencing was performed, and four novel heterozygous variations, namely, c.169G>A (p.Ala57Thr), c.383C>T (p.Ala128Val), c.76G>A (p.Gly26Arg), and c.745T>A (p.Phe249Ile), were identified in SLC25A19. All variants were confirmed using Sanger sequencing. To determine the pathogenicity of these variants, functional studies were performed. We found that mitochondrial TPP levels were significantly decreased in the presence of SLC25A19 variants, indicating that TPP transport activities of mutated SLC25A19 proteins were impaired. Thus, combining clinical phenotype, genetic analysis, and functional studies, these variants were deemed as likely pathogenic.ConclusionsExome sequencing analysis enables molecular diagnosis as well as provides potential etiology. Further studies will enable the elucidation of SLC25A19 protein function. Our investigation supplied key molecular evidence for the precise diagnosis of and clinical decision-making for a rare disease.

Molecular mechanism of locus coeruleus involved in acupuncture anti-myocardial ischemia based on transcriptome sequencing

To explore the molecular mechanism of locus coeruleus（LC） involved in electroacupuncture (EA) anti myocardial ischemia. Twenty-four SD rats were randomly divided into sham-operation, model, EA and EA +lesion groups, with 6 rats in each group. The acute myocardial ischemia (AMI) model was established by ligation of the left anterior descending branch of coronary artery. EA (2 Hz/15 Hz, 1 mA) was applied to bilateral "Shenmen" (HT7) -"Tongli" (HT5) and the middle-point between HT7 and HT5 for 30 min, once daily for 3 days. For rats of the EA +lesion group, the virus (300 nL) was injected into bilateral LC before EA treatment. Serum aspartate aminotransferase (AST) was detected by ELISA. The gene expression profiles of rat heart were detected by transcriptome sequencing, the differentially expressed genes were screened, and Gene Ontology (GO) functional classification and Kyoto Encyclopedia of genes and genomes (KEGG) metabolic pathway enrichment analysis were performed. Compared with the sham-operation group, serum AST content was significantly increased in the model group (P<0.01). Following the intervention, serum AST was significantly reduced in the EA group (P<0.01), while the serum AST in the EA + lesion group was significantly higher compared with the EA group (P<0.05). Differential expression analysis showed that 1 138 differentially expressed genes were screened out between the model group and the sham-operation group, 1 330 differentially expressed genes between model and EA group, and 804 differentially expressed genes between EA and EA + lesion group. Among them, 218 differential genes were involved in the regulation of EA anti-myocardial ischemia in LC. GO functional classification analysis showed that these differentially expressed genes mainly involved in cell processes, metabolic processes and biological regulation in biological processes. KEGG pathway analysis showed that these differentially expressed genes were enriched in sulfur relay system, thiamine metabolism, glutathione metabolism, C5 branch dicarboxylic acid metabolism, cell adhesion molecules and Th1 and Th2 cell differentiation. EA intervention has a positive effect in anti-myocardial ischemia, which may be related to the sulfur relay system, thiamine metabolism, glutathione metabolism, C5 branch dicarboxylic acid metabolism, cell adhesion molecules and Th1 and Th2 cell differentiation involved in LC.

Estimation of thiamine hydrochloride and sulphite using charge transfer complex reaction

A new spectrophotometric method is used for estimating Thiamine hydrochloride in its pure form and pharmaceutical formulations, the present method depends on the reaction between Thiamine hydrochloride and chrome azurol S to form a red complex which exhibit maximum absorption at 510 nm, the addition of Sulphite to the resulted red complex is bleaching it and this step was used for the determination of Sulphite which is considered an attacker of Thiamine hydrochloride, therefore, this method was developed for determination of Thiamine hydrochloride in presence of Sulphite. The linearity of the proposed method was obeyed Beer’s law from 2 to 48 and 0.04 to 2.4 ppm for Thiamine hydrochloride and Sulphite respectively. Also, the method sensitivity was measured by molar absorptivity values 5.9×104 l.mol-1.cm-1 and 1.68×104 l.mol-1.cm-1 for Thiamine hydrochloride and Sulphite respectively. The present method accuracy (average recovery) 100.06% and 100.04% the precision (RSD) of the method is ±0.98 - ±1.27% and ±0.76 - ±1.47 of Thiamine hydrochloride and Sulphite respectively. This method was applied for the estimation of B1 and SO32- in pharmaceutical preparations and various water samples respectively.

Aromatic amino acids play a harmonizing role in prostate cancer: A metabolomics-based cross-sectional study.

BackgroundProstate cancer (PCa) is a common health problem worldwide. The rate of this disease is likely to grow by 2021. PCa is a heterogeneous disorder, and various biochemical factors contribute to the development of this disease. The metabolome is the complete set of metabolites in a cell or biological sample and represents the downstream end product of the omics. Hence, to model PCa by computational systems biology, a preliminary metabolomics-based study was used to compare the metabolome profile pattern between healthy and PCa men.ObjectiveThis study was carried out to highlight energy metabolism modification and assist the prognosis and treatment of disease with unique biomarkers.Materials and MethodsIn this cross-sectional research, 26 men diagnosed with stage-III PCa and 26 healthy men with normal PSA levels were enrolled. Urine was analyzed with proton nuclear magnetic resonance (H-NMR) spectroscopy, accompanied by the MetaboAnalyst web-based platform tool for metabolomics data analysis. Partial least squares regression discriminant analysis was applied to clarify the separation between the two groups. Outliers were documented and metabolites determined, followed by identifying biochemical pathways.ResultsOur findings reveal that modifications in aromatic amino acid metabolism and some of their metabolites have a high potential for use as urinary PCa biomarkers. Tryptophan metabolism (p 0.001), tyrosine metabolism (p 0.001), phenylalanine, tyrosine and tryptophan biosynthesis (p 0.001), phenylalanine metabolism (p = 0.01), ubiquinone and other terpenoid-quinone biosynthesis (p = 0.19), nitrogen metabolism (p = 0.21), and thiamine metabolism (p = 0.41) with Q (0.198) and R (0.583) were significantly altered.ConclusionThe discriminated metabolites and their pathways play an essential role in PCa causes and harmony.

Thiamine additive engineering enables improved film formation towards high efficiency and moisture stability in perovskite solar cells

Perovskite solar cells (PSCs) attract widespread research interest due to their exceptional properties. However, the instability of the perovskite layer, especially the moisture instability, and existing defects seriously restrict the performance and limit the development of PSCs towards commercialization. Herein, we fabricate moisture-stable and efficient PSCs by incorporating a thiamine (THM) additive into a lead iodide (PbI2) precursor using a two-step spin-coating method. This strategy enables a better interaction between the THM additive and PbI2. Then, a higher energy barrier is produced when the material reacts with A-site cations to form perovskite crystals, resulting in larger grains and better-quality perovskite films. Through optimization of the concentration of the THM additive, the optimal perovskite achieves improved moisture stability and decreased trap states; thus, the corresponding unencapsulated devices achieve a remarkable power conversion efficiency (PCE) of 21.40% and maintain >92% of their initial PCE after 180 h in ambient air (∼50% humidity). The excellent performance is mainly attributed to the fact that THM promotes crystal growth and passivates defects in perovskite films.

Assessment of elementary derivatives of 1,5-benzodiazepine as anticancer agents with synergy potential

Herein, we designed and synthesized 1,5-benzodiazepines as a lead molecule for anticancer activity and as potent synergistic activity with drug Methotrexate. Working under the framework of green chemistry principles, series of 1,5-benzodiazepine derivatives (3a-3a1) were synthesized using biocatalyst i.e. thiamine hydrochloride under solvent free neat heat conditions. These compounds were screened for in vitro anti cancer activity against couple of cancer cell lines (HeLa and HEPG2) and normal human cell line HEK-293 via MTT assay. The IC50 values for the compounds were in the range 0.067 to 0.35 µM, better than Paclitaxel and compatible with the drug Methotrexate. Compound 3x was found to be influential against both the cell lines with IC50 values of 0.067 ± 0.002 µM against HeLa and 0.087 ± 0.003 µM against HEPG2 cell line, having activity as compatible to the standard drug Methotrexate. Bioinformatic analysis showed that these compounds are good tyrosine kinase inhibitors which was then proved using enzyme inhibition assay. The studies of apoptosis revealed late apoptotic mode of cell death for the compounds against HEPG2 cancer cell line using flow cytometry method. Synergistic studies of compound 3x and drug Methotrexate showed that the combination was highly active against cancer HeLa and HEPG2 cell line with IC50 value 0.046 ± 0.002 µM and 0.057 ± 0.002 µM respectively, which was well supported by apoptosis pathway. Further the compounds proved its scope as DNA intercalating agents, as its molecular docking and DNA binding studies revealed that the compounds would fit well into the DNA strands.

Historical Features Regarding the Neuropathic Outbreaks in Brazilian Troops in the Paraguayan War.

During the Paraguayan War, Brazilian army and navy officers attributed outbreaks of combatant limb weakness with particular features such as tingling to palustrian causes. A dietary basis was not fully suspected at the time, and the popular name beriberi had not been coined. During wartime, there was a shortage in the food supply in addition to poor environmental conditions and diarrheal diseases, and many reports of "palustrian cachexia" were made. There are also reports of the use of native flora to feed troops, as well as alcoholism. There are also accounts of the death of horses with symptoms similar to those of combatants. It was reported that black soldiers were more resistant to "palustrian cachexia." This article presents the disease ecology and clinical manifestations of beriberi at wartime, linked to starvation and consumption of pickled food and native flora. These military explorations and operations in the Paraguayan War happened more than 150 y ago and present some aspects of wilderness medicine in the past.

Pharmacokinetics of thiamine (vitamin B1) in adult horses after administration of three single intravenous doses.

Thiamine is a vital co-factor for several anti-inflammatory and antioxidant processes that are critical for mitigation of sepsis-associated inflammation, but pharmacokinetic (PK) analysis has not been reported in horses. We hypothesized that IV thiamine hydrochloride (TH) at increasing dosages would result in corresponding increases in plasma thiamine concentrations without causing adverse effects. A randomized cross-over study was performed in 9 healthy horses that each received TH at 5, 10, and 20mg/kg IV. Blood was collected immediately prior to drug administration and at several time points thereafter. High-performance liquid chromatography with mass spectrometry was used to quantify thiamine concentrations at each time point. Non-compartmental PK methods showed that IV TH resulted in supraphysiologic plasma concentrations with a short half-life (0.77-1.12h) and no adverse clinical signs were observed. The terminal rate constant decreased as the dosage increased (p<.0001) and clearance significantly decreased at the 20mg/kg dosage (p=.0011). The area under the curve (AUC) increased in a non-linear fashion. These findings suggest that thiamine follows non-linear elimination kinetics in horses, which is likely due to saturation of renal elimination. Future studies are needed to identify therapeutic plasma concentrations and develop thiamine dosing recommendations for horses.

Thiamine deficiency in rats affects thiamine metabolism possibly through the formation of oxidized thiamine pyrophosphate

BackgroundThiamine deficiency (TD) has a number of features in common with the neurodegenerative diseases development and close relationship between TD and oxidative stress (OS) has been repeatedly reported in the literature. The aim of this study is to understand how alimentary TD, accompanied by OS, affects the expression and level of two thiamine metabolism proteins in rat brain, namely, thiamine transporter 1 (THTR1) and thiamine pyrophosphokinase (TPK1), and what factors are responsible for the observed changes. MethodsThe effects of OS caused by TD on the THTR1and TPK1 expression in rat cortex, cerebellum and hippocampus were examined. The levels of active and oxidized forms of ThDP (enzymatically measured) in the blood and brain, ROS and SH-groups in the brain were also analyzed. ResultsTD increased the expression of THTR1 and protein level in all studied regions. In contrast, expression of TPK1 was depressed. TD-induced OS led to the accumulation of ThDP oxidized inactive form (ThDPox) in the blood and brain. In vitro reduction of ThDPox by dithiothreitol regenerates active ThDP suggesting that ThDPox is in disulfide form. A single high-dose thiamine administration to TD animals had no effect on THTR1 expression, partly raised TPK1 mRNA and protein levels, but is unable to normalize TPK1 enzyme activity. Brain and blood ThDP levels were increased in these conditions, but ThDPox was not decreased. General significanceIt is likely, that the accumulation of ThDPox in tissue could be seen as a potential marker of neurocellular dysfunction and thiamine metabolic state.

Determination of Thiamine Hydrochloride in Commonly used food Materials-Rice by UV-Spectrophotometric Methods

Vitamins and their coenzymes roles are indispensable for normal functioning of biochemical metabolic pathways. The water soluble vitamin thiamine plays an important role in energy metabolism and its continuous intake is very essential. The source of vitamins can be obtained from many foods like milk, legumes, peas and rice and which is depends on availability, cost. Although most part of the south Indians especially in Tamilnadu the people predominantly depends on rice as a major source of food. So in order to identify the recommended dietary allowance of thiamine the following rice samples were collected from provisional store in Chennai. The collected five rice samples were Deluxe, Bapatla, Karnataka, Rupali ponni rice and Basmati rice. The concentration of thiamine present in the rice was estimated by UV Spectrophotometrically at 246 nm using 0.1M hydrochloride as blank. In order to measure the actual content the high heat and pressure not used and washing is not used. Among the tested 10gm of rice samples, Rupali ponni rice has127 µg which is very less quantity and Bapatla, Deluxe, Karnataka ponni rice has 420 to 430 µg. The high content of was present in Basmati rice-983 µg. Anyhow normal consuming rice quantity is more sufficient to meet Recommended Daily Allowance- RDA level but more washing of rice, prolong boiling will reduce the amount of thiamine content in rice during usage.

Non-alcoholic Wernicke’s encephalopathy in a kidney transplant recipient

Background. Non-alcoholic Wernicke’s encephalopathy occurs in various somatic conditions with thiamine deficiency, excessive excretion of thiamine, or impaired thiamine metabolism. Very few cases of this pathology have been described in chronic kidney disease (CKD). We present a unique case of non-alcoholic Wernicke’s encephalopathy in a patient with a kidney transplant is presented.Past medical history. The patient underwent kidney transplantation in 2008. Outpatient follow-up by a nephrologist was irregular. Renal graft function remained relatively stable: blood creatinine 200–240 μmol/L, estimated glomerular filtration rate 40–30 mL/min, tacrolimus plasma concentrations tended to increase (5.7–7.6–8.4–10.4 ng/mL); repeated graft biopsy (in 2015 and in 2017) determined the chronic toxicity of calcineurin inhibitors. The patient’s condition worsened in late January 2020: body temperature increased to 38°C, nausea, vomiting, loose, watery stools for up to 5 times per day, 8 kg weight loss, decreased diuresis. A few days later, double vision, shaky gait and then immobility appeared. Biochemical examination results: potassium 3.8 mmol/L, sodium 139 mmol/L, alpha-amylase 159 units/L (norm 0–100 units/L), creatinine 242 mmol/L, urea 13.2 mmol/L; ultrasound signs of pancreatitis. Magnetic resonance imaging (MRI) of the brain: bilateral diffuse lesions of the midbrain, thalamus, and cerebellum. Based on the clinical picture and on brain MRI results, Wernicke’s encephalopathy was diagnosed. Parenteral administration of thiamine had a good effect.Conclusion. Possible mechanisms of the development of Wernicke’s encephalopathy in a patient were discussed. Vigilance is required regarding this disease when metabolic disorders occur in patients with CKD.

Investigations on volumetric, compressibility and viscometric properties of L-ascorbic acid and thiamine hydrochloride in aqueous 1-ethyl-3-methylimidazolium hydrogen sulfate solutions at different temperatures

A comprehensive study on volumetric, compressibility, and viscometric properties of two vitamins namely L-ascorbic acid and thiamine hydrochloride in aqueous and (0.05, 0.10, and 0.15 mol kg−1) binary aqueous 1-ethyl-3-methylimidazolium hydrogen sulfate media has been done. The physical properties like density, speed of sound, and viscosity have been estimated at six discrete temperatures (293.15–318.15) K and ambient pressure (0.1 MPa). The thermophysical parameters like apparent molar volume (Vϕ), partial molar volume (Voϕ), partial molar expansivity (Eϕo), Hepler’s constant ∂Eϕo∂TP, apparent molar isentropic compressibility (Kϕ,s), partial molar isentropic compressibility (Kϕ,so), acoustic and volumetric interaction coefficients (KAB, KABB, VAB, VABB), Jones-dole coefficients (A and B) etc are deliberated. Cosphere overlap model was employed for the understanding of various types of molecular interactions that are established in the studied systems. Also, the structure breaking ability of both vitamins have been examined through the positive sign of dBdT values and negative sign of ∂Eϕo∂TP values. Moreover, this study provides the crucial data imperative for the designing of several industrial processes.

The impact of thiamine deficiency and benfotiamine treatment on Nod-like receptor protein-3 inflammasome in microglia.

Thiamine-dependent processes are critical in cerebral glucose metabolism, it is abnormity induces oxidative stress, inflammation and neurodegeneration. Nod-like receptor protein-3 (NLRP3) inflammasome-mediated inflammation is closely related to neurologic diseases and can be activated by oxidative stress. However, the impact of thiamine deficiency on NLRP3 inflammasome activation remains unknown. In this study, we found that NLRP3 inflammasomes were significantly activated in the microglia of thiamine deficiency mice model. In contrast, benfotiamine dampened inflammation NLRP3 mediated in BV2 cells stimulated with LPS and ATP through reducing mitochondrial reactive oxygen species levels and mitigating autophagy flux defect. These data identify an important role of thiamine metabolism in NLRP3 inflammasome activation, and correcting thiamine metabolism through benfotiamine provides a new therapeutic strategy for NLRP3 inflammasome related neurological, metabolic, and inflammatory diseases.

Report of the Largest Chinese Cohort With SLC19A3 Gene Defect and Literature Review.

Thiamine metabolism dysfunction syndrome 2 (THMD2) is a rare metabolic disorder caused by SLC19A3 mutations, inherited in autosomal recessive pattern. As a treatable disease, early diagnosis and therapy with vitamin supplementation is important to improve the prognosis. So far, the reported cases were mainly from Saudi Arab regions, and presented with relatively simple clinical course because of the hot spot mutation (T422A). Rare Chinese cases were described until now. In this study, we investigated 18 Chinese THMD2 patients with variable phenotypes, and identified 23 novel SLC19A3 mutations, which expanded the genetic and clinical spectrum of the disorder. Meanwhile, we reviewed all 146 reported patients from different countries. Approximately 2/3 of patients presented with classical BTBGD, while 1/3 of patients manifested as much earlier onset and poor prognosis, including infantile Leigh-like syndrome, infantile spasms, neonatal lactic acidosis and infantile BTBGD. Literature review showed that elevated lactate in blood and CSF, as well as abnormal OXPHOS activities of muscle or skin usually correlated with infantile phenotypes, which indicated poor outcome. Brainstem involvement on MRI was more common in deceased cases. Thiamine supplementation is indispensable in the treatment of THMD2, whereas combination of biotin and thiamine is not superior to thiamine alone. But biotin supplementation does work in some patients. Genotypic-phenotypic correlation remains unclear which needs further investigation, and biallelic truncated mutations usually led to more severe phenotype.

ITRAQ-based quantitative proteomic analysis of the hepatopancreas in Scylla paramamosain during the molting cycle

The hepatopancreas is the key organ involved in energy storage, immune response, and metabolism during crustacean molting, yet the underlying molecular mechanisms in the hepatopancreas that regulate molting remain unknown. In the present study, we conducted a comprehensive proteomic analysis in the hepatopancreas and quantified 1527 proteins, of which 193 changed significantly in abundance among three molting stages (pre-molt: PrM, post-molt: PoM, and inter-molt: InM) of Scylla paramamosain using iTRAQ-coupled LC-MS/MS. Ten exoskeleton and cuticle reconstruction proteins, such as chitinase, cuticle protein and myosin heavy chain, were found change significantly in abundance between PoM and PrM. Six energy metabolism proteins such as mitochondrial cytochrome c oxidase, cytochrome b-c1 and cAMP-dependent protein kinase with positive loadings showed a higher abundance in InM than PoM. In addition, all differentially abundance proteins (DAPs) were annotated for GO function and KEGG pathway analysis. GO analysis demonstrated function subcategories mainly including thiamine metabolism, complement and coagulation cascades, endocrine, shigellosis, salmonella infection, and other factor-regulated calcium reabsorption. The KEGG pathway enrichment analysis indicated that the DAPs were mainly involved in reconstruction of the exoskeleton and cuticle, energy reserves, metabolism, and immune response during the molting process. The results for the proteins and key pathways involved in the molting process provide fundamental molecular evidence that will improve our understanding of morphological and metabolism variation in the molting cycle and will serve as a potential blueprint for future study on molecular mechanism of molting in crustaceans.