Pipecolinic Acid Research Articles

Physiological and biochemical attributes of the association host-parasite Tamarix aphylla-Plicosepalus acacia

Parasitic plants have been viewed as pests since they are able to damage agricultural crops and forest trees. They establish vasculature connections with the hosts and withdraw the required nutritive resources. This study aimed to explore the physiological and biochemical effects of the parasitic plant Plicosepalus acacia on the host Tamarix aphylla. It was conducted on young fully expanded leaves from the uninfected and infected trees and the parasitic plant ‘in situ’. The parasite had higher net photosynthetic assimilation rate (A), transpiration rate (E) and stomatal conductance (gs) compared to the host. Equally, it had two-fold greater water potential (Ψ) and osmotic potential (Ψs). It accumulated high amount of K, while it avoided accumulation of the most trace and ultratrace elements. Otherwise, parasitism seemed to increase A, WUE, water uptake and accumulation of the most major, trace and ultra-trace elements, however it reduced the accumulation of osmolytes at the infected plants. Based on UPLC-MS approach, P. acacia seemed to use a group of composites to interact with the host, including oleamide as a protector metabolite against host's defense system, carvone to establish vasculature connections with the host, cuminaldehyde to weaken growth and proliferation of the host, and caprolactam to weaken the distal part of the host. In contrast, the host T. aphylla could be used pipecolinic acid and nicotinamide to regulate systemic resistance and to defense against the parasite infection. Finally, despite the defense molecular interactions between the two partners, the parasitic plant exhibited several beneficial effects on the host.

Characterizing the metabolic divide: distinctive metabolites differentiating CAD-T2DM from CAD patients

ObjectiveTo delineate the metabolomic differences in plasma samples between patients with coronary artery disease (CAD) and those with concomitant CAD and type 2 diabetes mellitus (T2DM), and to pinpoint distinctive metabolites indicative of T2DM risk.MethodPlasma samples from CAD and CAD-T2DM patients across three centers underwent comprehensive metabolomic and lipidomic analyses. Multivariate logistic regression was employed to discern the relationship between the identified metabolites and T2DM risk. Characteristic metabolites' metabolic impacts were further probed through hepatocyte cellular experiments. Subsequent transcriptomic analyses elucidated the potential target sites explaining the metabolic actions of these metabolites.ResultsMetabolomic analysis revealed 192 and 95 significantly altered profiles in the discovery (FDR < 0.05) and validation (P < 0.05) cohorts, respectively, that were associated with T2DM risk in univariate logistic regression. Further multivariate regression analyses identified 22 characteristic metabolites consistently associated with T2DM risk in both cohorts. Notably, pipecolinic acid and L-pipecolic acid, lysine derivatives, exhibited negative association with CAD-T2DM and influenced cellular glucose metabolism in hepatocytes. Transcriptomic insights shed light on potential metabolic action sites of these metabolites.ConclusionsThis research underscores the metabolic disparities between CAD and CAD-T2DM patients, spotlighting the protective attributes of pipecolinic acid and L-pipecolic acid. The comprehensive metabolomic and transcriptomic findings provide novel insights into the mechanism research, prophylaxis and treatment of comorbidity of CAD and T2DM.

TMET-18. METABOLOMIC APPROACH TO IDENTIFICATION OF PROGNOSTIC BIOMARKERS OF GLIOBLASTOMA

Abstract Glioblastoma, the most common malignant primary brain tumor, is associated with poor prognosis despite aggressive treatment. Alterations in cellular metabolism driven by acquired mutations contribute to tumor progression and recurrence. Metabolic changes in plasma can serve as potential biomarkers, offering insights into treatment response and prognostic value. In this prospective study, we enrolled 36 patients with isocitrate dehydrogenase (IDH) wild type glioblastoma (18 MGMT methylated, 16 MGMT unmethylated, 2 MGMT unknown) and performed untargeted metabolomics on patient plasma before and after surgery, as well as before and after concurrent chemoradiation. Our analysis focused on examining changes in 157 metabolites throughout each stage of treatment. We conducted correlations between metabolite levels and treatment stages, as well as associations between metabolite levels and disease progression or overall survival to identify clinically relevant biomarkers. Preliminary results demonstrate positive correlation between specific metabolite levels at the time of diagnosis and eventual overall survival. Notably, metabolites such as trans-4-hydroxyproline, ribose, pipecolinic acid, phenol, kynurenine, inositol-4-monophosphate, indole-3-propionic acid, glucose, arachidonic acid, 5-methoxytryptamine, and 3-aminopiperidine-2,6-dione show significant positive correlations (p&amp;lt; 0.05) with overall survival. However, no metabolites exhibited negative associations with overall survival. Ongoing analysis will further explore the relationship between metabolite levels at different treatment stages and survival outcomes. By future planned machine learning techniques integration to our study, we aim to enhance our understanding of the metabolomic changes associated with treatment response and prognosis. This study represents a step toward unraveling the metabolomic alterations in glioblastoma patients throughout treatment. Although the underlying metabolic pathways and potential shared mechanisms are not yet fully understood, the identified metabolites associated with overall survival hold promise as potential biomarkers for prognosis. Furthermore, the integration of machine learning techniques will provide a more comprehensive understanding of the complex metabolic changes in glioblastoma.

Faecal metabolome responses to an altered dietary protein:carbohydrate ratio in adult dogs

High-protein diets may aid weight loss and weight maintenance programs in both humans and dogs, although the effect of dietary protein levels on gut metabolism and functionality has not been studied in depth. The current study aimed to investigate the effect of an altered dietary protein:carbohydrate ratio on gut function in adult dogs by means of faecal metabolomic fingerprinting. More specifically, functional metabolic differences in dogs fed a high-protein/low-carbohydrate (HPLC) vs. low-protein/high-carbohydrate (LPHC) diet were studied by equally allocating twelve clinically healthy (6 lean and 6 obese) Beagles into two groups in a cross-over design, with each group receiving two isocaloric diets for four weeks. The faecal metabolome revealed that different protein:carbohydrate ratio can influence host and/or gut microbiome metabolism and function, while no effect was observed on the body condition. Targeted analysis demonstrated that the HPLC diet significantly increased the concentration of indole, spermidine, and pipecolinic acid and decreased the concentration of azelaic acid, D-fructose, mannose, and galactose (p < 0.05). Multivariate modelling (OPLS-DA) of the untargeted faecal metabolome revealed distinctly different metabolomic profiles following the HPLC vs. LPHC diet, with 18 altered pathways. The HPLC diet influenced amino acid and lipid metabolism, potentially promoting weight loss and immune function, whereas the LPHC diet affected carbohydrate fermentation and may promote anti-oxidative function.

Aspertides A-E: Antimicrobial Pentadepsipeptides with a Unique p-Methoxycinnamoyl Amide Group from the Marine Isolates Aspergillus tamarii MA-21 and Aspergillus insuetus SD-512.

Marine fungus-derived natural products are an important source of antimicrobial compounds against marine aquatic pathogens. Here, we describe the isolation and characterization of five new pentadepsipeptides, aspertides A-E (1-5), containing a unique p-methoxycinnamoyl amide group, from the marine fungi Aspergillus tamarii MA-21 and Aspergillus insuetus SD-512. Among them, aspertides B-E (2-5) also possessed uncommon amino acid residues, such as 3-hydroxyproline, 2,3-dihydroxyproline, or pipecolinic acid. The structures of these compounds were elucidated on the basis of NMR and mass spectroscopic analyses. The absolute configurations of them were established by chiral HPLC analyses of the acidic hydrolysates and NMR calculations with DP4+ probability analysis. In bio-activity assays, compounds 4 and 5 exhibited antibacterial activities against aquatic-pathogenic bacteria, including Edwardsiella tarda, Vibrio alginolyticus, Vibrio anguillarum, Vibrio vulnificus, and Staphylococcus aureus, with MIC values of 8-32 μg/mL.

Extraction of Faloak Stem Bark (Sterculia quadrifida R. Br) Using Microwave-Assisted Extraction Method And LC-HRMS Profiling of the Extract

The extraction of bioactive plants is an essential step in isolating the targeted bioactive compounds. Microwave-assisted extraction (MAE) offers a green technology extraction that can minimize energy, time, and solvent and is a suitable method for extracting thermolabile plant bioactive compounds. The study aims to find out the optimal time and temperature for isolating the total phenolic content (TPC), total flavonoid (TF), and antioxidant activity (AO) of faloak stem bark (FSB) (Sterculia quadrifida R. Br) and to profile the phytochemicals in the FSB extract using sophisticated of LC-HRMS (Liquid Chromatography High-Resolution Mass Spectrometry). The research used the Randomized Block Design (RBD) method with two factors. The factors were the extraction time (5, 15, and 25 min) and temperature variation (50, 60, and 70°C). The data of observed parameters were calculated using Analysis of Variance (ANOVA) and followed by a further test with a 95% confidence interval. The results showed an interaction between temperature and time of extraction on TPC, TF, and AO activity. The best MAE condition for extracting FSB was achieved at 60°C for 25 min. The FSB extract had a TPC of 81.2 mg GAE/g, TF of 70.30 mg QE/g, and AO activity of 67.8%. LC-HRMS revealed the newly identified phenolic compounds such as methyl cinnamate, vanillin, apocynin, scopoletin, L(-)-pipecolinic acid, arecoline, δ-valerolactam, 3,4-dihydroxybenzaldehyde, 4-hydroxybenzaldehyde; flavonoids such as epicatechin and rutin and some fatty acids and its derivatives. Future research could focus on developing new therapies for promoting human health using extract FSB.

New pattern of Pd-Catalyzed electrochemical hydrodechlorination in conversion of chlorinated aromatic pollutants to Value-Added chemicals

Pd-catalyzed electrochemical hydrodechlorination (HDC), as a key process before discharge and biological treatment, is an effective strategy for the in-situ conversion of low concentration chlorinated aromatic pollutants (CAPs) in wastewater or polluted water. However, its application has been greatly hindered by the low Pd utilization and operation efficiency. Herein, we developed an electrocatalytic HDC method using Pd nanoparticles modified nickel foam (Pd NPs/Ni) as cathode and alkaline aqueous solution as catholyte, and applied it to convert high concentration CAPs to value-added chemicals. The results showed that the reaction efficiency and selectivity of the developed HDC method mainly depend on the cathode material, pH and cathode potential. The HDC method can convert CAPs (4 categories) with various high concentrations (0.05 ∼ 1 M) into a single value-added chemical (picolinic acid, phenoxyacetic acid, benzoic acid or phenol) with very high yield (>95 %) and chemo-selectivity (>97 %). Compared with the conventional Pd-catalyzed HDC methods, the new patterned one can greatly improve Pd utilization and operation efficiency (The Pd mass activity and the area activity of cathode increased by 16 ∼ 685 times). In addition, the underlying reaction pathway and catalytic mechanism of the developed HDC system has also been studied using 3,6-dichloropicolinic acid (3,6-D) as the model CAPs. The HDC of 3,6-D on the Pd NPs/Ni in a stepwise fashion with 3-chloropicolinic acid (3-ClPA) as the main intermediate product is suggested, and it follows the indirect HDC mechanism with electrochemically adsorbed H as the reductant. The end product (picolinic acid) of the HDC could be further reduced to pipecolinic acid at very negative potentials following direct hydrogenation mechanism, which would significantly lower the selectivity of HDC.

Enantio- and Diastereoselective De Novo Synthesis of 3-Substituted Proline Derivatives via Cooperative Photoredox/Brønsted Acid Catalysis and Epimerization.

Herein, a novel strategy for the catalytic asymmetric synthesis of enantioenriched 3-cis- and 3-trans-substituted prolines has been successfully established via an unprecedented cascade radical addition/cyclization enabled by synergistic photoredox/Brønsted acid catalysis and subsequent base-assisted epimerization. The current protocol provides a unique de novo access to all four stereoisomers of 3-substituted prolines which are not readily achieved via currently established methods. This methodology could be further extended to the asymmetric synthesis of the full complement of stereoisomers of 3-substituted pipecolinic acids.

Regioselective synthesis of enantiopure 1,2- and 1,3-dispirooxindoles along with a DFT study.

In the present study, a library of important enantiopure dispirooxindole [indolizidine, pyrrolizidine, and pyrrolidine] derivatives with three or four contiguous and two quaternary stereogenic centers using different amino acids (pipecolic acid, sarcosine, proline and hydroxyproline) were synthesized in high yields (up to 96%) through a regio- and diastereoselective (up to 99 : 1) multicomponent 1,3-dipolar cycloaddition strategy. Based on the results, the alteration of amino acids led to a change in the regioselectivity and unusual regioisomers (pyrrolizidine versus indolizidine/pyrrolidine) were obtained to construct a novel enantiopure 1,3-dispirooxindole skeleton. The stereochemical outcome of the cycloaddition was determined by single crystal X-ray diffraction analysis and the self-disproportionation of enantiomers (SDE) test confirmed the enantiomeric purity of the desired products. The mechanism and differences in the regioselectivity of the 1,3-dipolar cycloaddition reactions between the stable azomethane ylides obtained from ninhydrin, pipecolinic acid, and proline with (E)-2-oxoindolin-3-ylideneacetyl sultam were theoretically studied through DFT calculations at the M06-2X/6-31G(d,p) level in methanol.

Molecular Mechanisms Underlying Flax (Linum usitatissimum L.) Tolerance to Cadmium: A Case Study of Proteome and Metabolome of Four Different Flax Genotypes.

Cadmium is one of the most toxic heavy metal pollutants, and its accumulation in the soil is harmful to agriculture. Plants have a higher cadmium tolerance than animals, and some species can be used for phytoremediation. Flax (Linum usitatissimum L.) can accumulate high amounts of cadmium, but the molecular mechanism behind its tolerance is unknown. Here, we employed four genotypes representing two fiber cultivars, an oilseed breeding line, and a transgenic line overexpressing the metallothionein domain for improved cadmium tolerance. We analyzed the proteome of suspensions and the proteome and metabolome of seedling roots in response to cadmium. We identified more than 1400 differentially abundant proteins representing putative mechanisms in cadmium tolerance, including metal-binding proteins and transporters, enzymes of flavonoid, jasmonate, polyamine, glutathione metabolism, and HSP70 proteins. Our data indicated the role of the phytohormone cytokinin in the observed responses. The metabolome profiling found that pipecolinic acid could be a part of the cadmium accumulation mechanism, and the observed accumulation of putrescine, coumaric acid, cinnamic acid, and coutaric acid confirmed the role of polyamines and flavonoids in tolerance to cadmium. In conclusion, our data provide new insight into cadmium tolerance and prospective targets for improving cadmium tolerance in other plants.

Research progress of Shenling Baizhu San and predictive analysis on its quality markers

Shenling Baizhu San is a classic prescription for replenishing Qi to invigorate the spleen and dispelling dampness to check diarrhea, which mainly treats the syndrome of spleen deficiency and heavy dampness. With the pharmacological effects of regulating immune system, improving lung function and gastrointestinal function, and resisting oxygen, tumor, and inflammation, Shenling Baizhu San is commonly used in modern clinical practice to treat chronic obstructive pulmonary disease, pulmonary fibrosis, bronchial asthma, irritable bowel syndrome, ulcerative colitis, chronic diarrhea, and diabetic, etc. This paper summarized the chemical constituents, pharmacological effects, and clinical application of Shenling Baizhu San in recent years, and predictively analyzed the quality markers of Shenling Baizhu San according to the &quot;five principles&quot; of Q-marker. The Q-markers of Shenling Baizhu San involved ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, pachymic acid, dehydrotumulosic acid, batatasin Ⅰ, batatasin Ⅲ, diosgenin, liensinine, neferine, luteolin, quercetin, glycerol trioleate, β-sitosterol, platycodin D, glycyrrhizic acid, glycyrrhetinic acid, liquiritin, pipecolinic acid, atractylenolide Ⅰ, atractylenolide Ⅲ, and bornyl acetate, which provided references for the quality control and follow-up research of Shenling Baizhu San.

Total synthesis and antimicrobial evaluation of xylapeptide A

AbstractXylapeptide A is a cyclopentapeptide, [cyclo‐D‐Ala‐L‐Val‐N‐Me‐L‐Phe‐L‐Pip‐L‐Leu], first isolated from Xylaria sp. × Sophora tonkinensis, together with its analogue, xylapeptide B, which differ by only one residue, proline in xylapeptide B is replaced by pipecolinic acid (Pip) in xylapeptide A. Both xylapeptides A and B possess antimicrobial properties against several bacteria and fungi. Herein, we describe the first total synthesis and antimicrobial evaluation of xylapeptide A containing two non‐proteinogenic residues, N‐Me‐phenylalanine and pipecolinic acid. The synthesis of xylapeptide A was achieved by a combination of solid‐ and solution‐phase methods that were applied for the synthesis of xylapeptide B. Interestingly, the cyclization of linear xylapeptide A was more straightforward yielding 22% compared to 8.9% for xylapeptide B, suggesting that the presence of pipecolinic acid in the linear precursor affected the cyclization process. NMR analysis of synthetic xylapeptide A revealed that the chemical shifts of all protons and carbons of xylapeptide A are highly similar to the natural product. The synthetic xylapeptide A, together with xylapeptide B, were evaluated for their antimicrobial properties, showing that synthetic xylapeptide A has moderate antimicrobial activity and better antimicrobial properties compared to synthetic xylapeptide B. The presence of pipecolinic acid in xylapeptide A is an important requirement for antimicrobial activity.

Blood metabolic and physiological profiles of Bama miniature pigs at different growth stages

BackgroundBama miniature pigs aged between six (6 M) and twelve months (12 M) are usually used in human medical research as laboratory pigs. However, the difference in serum metabolic profiles from 6 to 12 M-old pigs remains unclear. This study aimed to identify the metabolic and physiological profiles present in the blood to further explain changes in Bama miniature pig growth. We collected blood samples from 6 M-, eight-month- (8 M-), ten-month- (10 M-), and 12 M-old healthy Guangxi Bama miniature pigs. A total of 20 blood physiological indices (BPIs) were measured: seven for white blood cells, eight for red blood cells, and five for platelet indices. Liquid chromatography and mass spectrometry-based non-targeted metabolomic approaches were used to analyze the difference in metabolites. The associations between the differences were calculated using Spearman correlations with Benjamini–Hochberg adjustment. The 100 most abundant differential metabolites were selected for analysis of their metabolic profiles.ResultsThere were no significant differences in BPIs at different ages, but the mid cell ratio and red blood cell number increased with age. Seven BPIs in Bama miniature pigs were closer to human BPIs than to mouse BPIs. A total of 14 and 25 significant differential metabolites were identified in 6 M vs. 12 M and 8 M vs. 12 M, respectively. In total, 9 and 18 amino acids and their derivatives showed significantly lower concentrations in 6 M- and 8 M-old pigs than in 12 M-old pigs. They were identified as the core significantly different metabolites between the age groups 6 M vs. 12 M and 8 M vs. 12 M. Half of the enriched pathways were the amino acids metabolism pathways. The concentration of six amino acids (dl-tryptophan, phenylacetylglycine, muramic acid, N-acetylornithine, l(−)-pipecolinic acid, and creatine) and their derivatives increased with age. A total of 61 of the top 100 most abundant metabolites were annotated. The metabolic profiles contained 14 amino acids and derivatives, six bile acids and derivatives, 19 fatty acids and derivatives, and 22 others. The concentrations of fatty acids and derivatives were found to be inversely proportional to those of amino acids and derivatives.ConclusionThese findings suggest high levels of MID cell ratio, red blood count, and amino acids in 12 M-old pigs as indicators for improved body function over time in Bama miniature pigs, similar to those in human development. This makes the pig a more suitable medical model organism than the mouse. The results of this study are limited to the characteristics of blood metabolism in the inbred Bama miniature pigs, and the effects of impacting factors such as breed, age, sex, health status and nutritional level should be considered when studying other pig populations.

Metabolic adaptation of diatoms to hypersalinity

Microalgae are important primary producers and form the basis for the marine food web. As global climate changes, so do salinity levels that algae are exposed to. A metabolic response of algal cells partly alleviates the resulting osmotic stress. Some metabolites involved in the response are well studied, but the full metabolic implications of adaptation remain unclear. Improved analytical methodology provides an opportunity for additional insight. We can now follow responses to stress in major parts of the metabolome and derive comprehensive charts of the resulting metabolic re-wiring. In this study, we subjected three species of diatoms to high salinity conditions and compared their metabolome to controls in an untargeted manner. The three well-investigated species with sequenced genomes Phaeodactylum tricornutum, Thalassiosira pseudonana, and Skeletonema marinoi were selected for our survey. The microalgae react to salinity stress with common adaptations in the metabolome by amino acid up-regulation, production of saccharides, and inositols. But also species-specific dysregulation of metabolites is common. Several metabolites previously not connected with osmotic stress reactions are identified, including 4-hydroxyproline, pipecolinic acid, myo-inositol, threonic acid, and acylcarnitines. This expands our knowledge about osmoadaptation and calls for further functional characterization of metabolites and pathways in algal stress physiology.

Nontargeted serum metabolomics analysis and potential biomarkers for systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a multisystem chronic autoimmune disease characterized by specific clinical and serological changes. Currently, the pathogenesis of SLE remains unclear. This study aimed to identify potential diagnostic biomarkers for SLE and discover the metabolic pathways associated with the disease. We collected serum samples from 260 subjects, including patients with SLE and healthy controls (HCs). Metabolite profiles were analyzed using a nontargeted gas chromatography-mass spectrometry (GC–MS) serum metabolomics method, and differentially altered metabolites were screened and assessed using univariate and multivariate analyses. In this study, patients with SLE and HCs were distinguished by 14 significant metabolites. The levels of pipecolinic acid, glutamine, creatine, stearic acid, asparagine and uric acid were increased in serum samples from patients with SLE, whereas levels of allo-inositol, trans-4-hydroxy-L-proline, glycerol-1-phosphate, N-acetyl-L-aspartic acid, malic acid, phosphate, arabitol and ribose were decreased. Arabitol, asparagine and stearic acid were identified as potential biomarkers, and their diagnostic performance was evaluated by performing a receiver operating characteristic (ROC) curve analysis. Significantly altered pathways included aspartate metabolism, glycine and serine metabolism, cardiolipin biosynthesis, riboflavin metabolism, plasmalogen synthesis, mitochondrial beta-oxidation of long-chain saturated fatty acids, ammonia recycling, pentose phosphate pathway, arginine and proline metabolism and purine metabolism. By identifying serum biomarkers and analyzing metabolic pathways, our study contributes to a better understanding of the pathogenesis of SLE.

Metabolome-Genome-Wide Association Study (mGWAS) Reveals Novel Metabolites Associated with Future Type 2 Diabetes Risk and Susceptibility Loci in a Case-Control Study in a Chinese Prospective Cohort.

In a Chinese prospective cohort, 500 patients with new‐onset type 2 diabetes (T2D) within 4.61 years and 500 matched healthy participants are selected as case and control groups, and randomized into discovery and validation sets to discover the metabolite changes before T2D onset and the related diabetogenic loci. A serum metabolomics analysis reveals that 81 metabolites changed significantly before T2D onset. Based on binary logistic regression, eight metabolites are defined as a biomarker panel for T2D prediction. Pipecolinic acid, carnitine C14:0, epinephrine and phosphatidylethanolamine 34:2 are first found associated with future T2D. The addition of the biomarker panel to the clinical markers (BMI, triglycerides, and fasting glucose) significantly improves the predictive ability in the discovery and validation sets, respectively. By associating metabolomics with genomics, a significant correlation (p < 5.0 × 10−8) between eicosatetraenoic acid and the FADS1 (rs174559) gene is observed, and suggestive correlations (p < 5.0 × 10−6) between pipecolinic acid and CHRM3 (rs535514), and leucine/isoleucine and WWOX (rs72487966) are discovered. Elevated leucine/isoleucine levels increased the risk of T2D. In conclusion, multiple metabolic dysregulations are observed to occur before T2D onset, and the new biomarker panel can help to predict T2D risk.

Gut Microbiota and Host Cometabolism Are Altered by Patiromer-Induced Changes in Serum and Stool Potassium

Gut Microbiota and Host Cometabolism Are Altered by Patiromer-Induced Changes in Serum and Stool Potassium

Dl-Piperidinium-2-carboxyl-ate bis-(hydrogen peroxide): unusual hydrogen-bonded peroxide chains.

The title compound, C6H11NO2·2H2O2, is the richest (by molar ratio) in hydrogen peroxide among the peroxosolvates of aliphatic α-amino acids. The asymmetric unit contains a zwitterionic pipecolinic acid mol-ecule and two hydrogen peroxide mol-ecules. The two crystallographically independent hydrogen peroxide mol-ecules form a different number of hydrogen bonds: one forms two as donor and two as acceptor ([2,2] mode) and the other forms two as donor and one as acceptor ([2,1] mode). The latter hydrogen peroxide mol-ecule forms infinite hydrogen-bonded hydro-peroxo chains running along the c-axis direction, which is unusual for aliphatic α-amino acid peroxosolvates.

Widely targeted metabolomic analyses unveil the metabolic variations after stable knock-down of NME4 in esophageal squamous cell carcinoma cells.

NME4, also designated nm23-H4 or NDPK-D, has been known for years for its well-established roles in the synthesis of nucleoside triphosphates, though; little has been known regarding the differential metabolites involved as well as the biological roles NME4 plays in proliferation and invasion of esophageal squamous cell carcinoma (ESCC) cells. To understand the biological roles of NME4 in ESCC cells, lentiviral-based short hairpin RNA interference (shRNA) vectors were constructed and used to stably knock down NME4. Then, the proliferative and invasive variations were assessed using MTT, Colony formation and Transwell assays. To understand the metabolites involved after silencing of NME4 in ESCC cells, widely targeted metabolomic screening was taken. It was discovered that silencing of NME4 can profoundly suppress the proliferation and invasion in ESCC cells in vitro. Metabolically, a total of 11 differential metabolites were screened. KEGG analyses revealed that Tryptophan, Riboflavin, Purine, Nicotinate, lysine degradation, and Linoleic acid metabolism were also involved in addition to the well-established nucleotides metabolism. Some of these differential metabolites, say, 2-Picolinic Acid, Nicotinic Acid and Pipecolinic Acid were suggested to be associated with tumor immunomodulation. The data we described here support the idea that metabolisms occurred in mitochondrial was closely related to tumor immunity.

A Metabolomic Analysis of the Hispanic Paradox

INTRODUCTIONObesity has increased in prevalence among Latinos in the United States over the last several decades and continues to trend upward. The current obesity rate for this population is 34.4%, which is significantly higher than that of the general American population (28.7%). However, increased body fat and excessive weight are not necessarily associated with an increase in premature mortality.METHODSIn this cross‐sectional analysis, we used a metabolomic analysis to look at the mechanisms behind the Hispanic Paradox. To do this, we examined the role dietary intake, body mass index (BMI; kg/m2), and generational level (GL) played on serum metabolomic fingerprints in 70 Mexican Americans (26 male, 44 female). Metabolomic phenotypes of plasma were measured using liquid chromatography tandem‐mass spectrometry (LC‐MS).RESULTSThere was no significant metabolic separation among BMI groups (normal weight = BMI &lt; 25; overweight = 25 £ BMI &lt; 30; obese = BMI ³ 30), suggesting that the metabolome remains unchanged despite an increase in BMI. When stratified for caloric intake (&lt; 2200 kcal/d vs &gt; 2200 kcal/d), a log‐transformed OPLS‐DA model showed clear separation in men, while females remained relatively unchanged. Only one metabolite, pipecolinic acid (P = .009; fold change = 3.43), was significantly greater among obese women relative to their non‐obese counterparts, whereas no metabolites were significantly different among men with different BMI status. A log‐transformed PLS‐DA model found similar results between GLs 1, 2, and 3–5 Mexican Americans, potentially signifying the resistance to alteration of the female metabolome. A significant metabolite between the female generation levels was N‐acetylethanolamine, an anti‐inflammatory, analgesic, and satiety producing compound. Additionally, a pathway analysis of significant metabolites between men and women revealed significant alterations in branched‐chain amino acid (BCAA) and aromatic amino acid (AAA) profiles and mechanisms, both prevalent in obesity and type 2 diabetes (T2DM).CONCLUSIONWhile Mexican American males demonstrated variance in metabolic profiles when examined for caloric intake and generational level, the metabolome of female participants showed resilience and largely remained unaffected. Further research is needed to better understand how significant pathways associated with comorbidities may not affect the relatively consistent metabolome of Mexican Americans.