Hydrophilic Metabolites Research Articles

Metabolic impact of low dose IL-2 therapy for primary Sjögren's Syndrome in a double-blind, randomized clinical trial.

Low-dose interleukin 2 (Ld-IL2) is increasingly being explored as an immune-modulating treatment for autoimmune diseases which mainly affect T cell subsets. This study investigates the metabolic effects of Ld-IL2 therapy in patients with primary Sjögren's syndrome (pSS). A total of 60 patients were recruited to conduct a double-blind, randomized clinical trial. Of these patients, 50% (30/60) received Ld-IL2 therapy along with standard treatment for 12 weeks, followed by 12 weeks of follow-up. The effectiveness was evaluated by Sjögren's Tool for Assessing Response (STAR). An untargeted analysis was performed to profile hydrophilic metabolites. Metabolic profiling revealed significant alterations post-treatment, notably in metabolites like acetyl-CoA, ascorbic acid, and glutathione, which are beneficial in managing autoimmune diseases. In addition, the levels of metabolite accumulation were correlated with variations in immune cell subsets (p< 0.05), particularly Tregs. Moreover, patients exhibiting a specific metabolic profile, including lower serum levels of isoleucine, ADP, Thymidine 5'-triphosphate, and other metabolites, had a high response rate (91.7%-98.6%), as indicated by the receiver operating characteristic (ROC) curve. These findings suggest that Ld-IL2 therapy influences metabolic pathways in pSS, offering insights into the systemic effects of Ld-IL2 therapy beyond immune modulation. ClinicalTrials.gov number, NCT02464319. Key Points •Metabolic alteration in pSS is significantly associated with Ld-IL2 therapy. •Metabolic changes correlate with variations in immune cell subsets, particularly Tregs. •Metabolic profiling could be a valuable tool in guiding Ld-IL2 therapy choices for pSS patients.

Serum metabolomics after exercise in ambulatory individuals with cerebral palsy.

To evaluate whether serum metabolomics differ between ambulatory individuals with cerebral palsy (CP) compared with individuals with typical development and whether functional capacity is associated with metabolite abundance. Thirty-eight adolescents and young adults were enrolled (CP: n = 19; typical development: n = 19). After functional capacity testing (10-meter walk, sit-to-stand, and peak knee flexion/extension torques), blood was drawn. Targeted serum metabolomics on hydrophilic metabolites were performed by high-performance liquid chromatography coupled with high-resolution and tandem mass spectrometry. Metabolite dimensionality reduction, pathway analysis, fold change, and t-tests evaluated changes in metabolite abundance. Associations were tested between functional measures and metabolite abundance. Individuals with CP had a significant increase in the abundance of essential amino acids, catabolic products of protein metabolism, and tricarboxylic acid cycle substrates, such as valine, tryptophan, kynurenic acid, and pyruvate (p < 0.05). Importantly, the abundance of numerous metabolites was only highly associated with functional capacity in individuals with CP such that greater abundance was associated with greater capacity, but not in those with typical development. Our findings show clear increases in serum metabolites in individuals with CP, which are associated with functional capacity for movement. The altered metabolite profile measured after exercise might reflect increased energy production needed for movement. Appropriate nutritional intake during exercise might be needed given increased energy requirements.

Combining metabolomics and machine learning to discover biomarkers for early-stage breast cancer diagnosis.

There is an urgent need for better biomarkers for the detection of early-stage breast cancer. Utilizing untargeted metabolomics and lipidomics in conjunction with advanced data mining approaches for metabolism-centric biomarker discovery and validation may enhance the identification and validation of novel biomarkers for breast cancer screening. In this study, we employed a multimodal omics approach to identify and validate potential biomarkers capable of differentiating between patients with breast cancer and those with benign tumors. Our findings indicated that ether-linked phosphatidylcholine exhibited a significant difference between invasive ductal carcinoma and benign tumors, including cases with inconsistent mammography results. We observed alterations in numerous lipid species, including sphingomyelin, triacylglycerol, and free fatty acids, in the breast cancer group. Furthermore, we identified several dysregulated hydrophilic metabolites in breast cancer, such as glutamate, glycochenodeoxycholate, and dimethyluric acid. Through robust multivariate receiver operating characteristic analysis utilizing machine learning models, either linear support vector machines or random forest models, we successfully distinguished between cancerous and benign cases with promising outcomes. These results emphasize the potential of metabolic biomarkers to complement other criteria in breast cancer screening. Future studies are essential to further validate the metabolic biomarkers identified in our study and to develop assays for clinical applications.

Assessing plant pigmentation impacts: A novel approach integrating UAV and multispectral data to analyze atrazine metabolite effects from soil contamination

The objective of this study was to evaluate the levels of desethylatrazine (DEA), a hydrophilic metabolite of atrazine, and its impact on plant health. This was achieved by utilizing multispectral imagery captured by Unmanned Aerial Vehicles (UAVs) in combination with ground-measured data to assess photosynthetic pigment levels in Green Cos lettuce following atrazine application in agricultural soil. Strong correlations were found between DEA levels and chlorophyll a, chlorophyll b, and anthocyanin levels in lettuce (R² > 0.70), while the correlation with carotenoid levels was weaker (R² = 0.55). This disruption to the pigments could interfere with photosynthesis, potentially hindering the plant's growth and development, and ultimately leading to a reduction in yield. The Anthocyanin Reflectance Index (ARI) demonstrated a robust positive correlation with DEA, whereas the Normalized Difference Red Edge (NDRE), Leaf Chlorophyll Index (LCI), and Normalized Difference Vegetation Index (NDVI) displayed pronounced negative correlations. Incorporating ARI, LCI, and NDRE, with or without NDVI, provided the most accurate prediction of DEA levels, with an R² exceeding 0.96. NDRE emerged as the most efficient index for forecasting chlorophyll a and chlorophyll b levels. Modified Chlorophyll Absorption in Reflectance Index (MCARI) demonstrated the best fit for carotenoids, while ARI performed exceptionally well in describing actual measurements of anthocyanins (R² = 0.90). The best-performing VI models, developed from the selection of effective single variables, exhibited the best fit to actual pigment measurements (R² > 0.83). These findings underscore the role of UAV-derived multispectral imagery in assessing DEA levels and improving environmental monitoring, aiding in better planning for agriculture and environmental remediation to enhance ecosystem health and resilience.

Stage-Specific Plasma Metabolomic Profiles in Colorectal Cancer.

Background/Objectives: The objective of this study was to investigate the metabolomic profiles of patients with colorectal cancer (CRC) across various stages of the disease. Methods: The plasma samples were obtained from 255 subjects, including patients with CRC in stages I-IV, polyps, and controls. We employed capillary electrophoresis time-of-flight mass spectrometry and liquid chromatography triple quadrupole mass spectrometry to analyze hydrophilic metabolites comprehensively. The data were randomly divided into two groups, and consistent differences observed in both groups were analyzed. Results: Acetylated polyamines, such as N1-acetylspermine and N1, N12-diacetylspermine, consistently showed elevated concentrations in stage IV compared to stages I-III. Non-acetylated polyamines, including spermine and spermidine, exhibited increasing trends from polyp to stage IV. Other metabolites, such as histidine and o-acetylcarnitine, showed decreasing trends across stages. While acetylated polyamines have been reported as CRC detection markers, our findings suggest that they also possess diagnostic potential for distinguishing stage IV from other stages. Conclusions: This study showed stage-specific changes in metabolic profiles, including polyamines, of colorectal cancer.

Lipophilic and Hydrophilic Metabolites as Descriptors of Different Coffee Beverages.

Coffee is a widely consumed beverage rich in bioactive phytochemicals. This study investigated the effect of brewing method on the profile of potential bioactive compounds in different coffee beverages using metabolomics and lipidomics based on UHPLC-MS/QTOF. The oil contents of the espresso coffee (EC), pot coffee (PC), instant coffee (IC), and filter coffee (FC) beverages studied were 0.13% ± 0.002, 0.12% ± 0.001, 0.04% ± 0.002, and 0.03% ± 0.003, respectively. Univariate analysis indicated significant differences (P < 0.001) in oil content when EC and PC beverages were compared with IC and FC beverages. Principal component analysis revealed similarities in the lipid profiles of FC and EC beverages and the hydrophilic profiles of PC and FC beverages. The EC beverage had the highest intensity of hydrophilic compounds such as adenine, theobromine, chlorogenic acid, and caffeine. The PC beverage was the most abundant in triglycerides, phosphatidylcholine, and diterpenes. Cafestol and kahweol esters, but not their free forms, were the most abundant diterpenes in the PC beverage. This work provides information on the differences in the profile of potentially bioactive compounds in four commonly consumed coffee beverage types and, thus, on the possible differences in the health effects of these coffee beverage types.

Isotope dilution with isotopically labeled biomass: An effective alternative for quantitative metabolomics

BackgroundState-of-the-art quantitative metabolomics relies on isotope dilution using internal standards (IS) derived from fully 13C labeled biomass. By spiking samples and external standards with known amounts of IS, the spike characterization demands are kept to a minimum. In fact, it is sufficient to experimentally assess the isotopic enrichment of the IS. This study develops the yeast derived IS toolbox further, (1) by characterizing the concentration levels of hydrophilic metabolites in a yeast fermentation batch and (2) by exploring the analytical figures of merit of one-point IS versus multipoint external calibration using IS, the established gold-standard for quantitative metabolomics. ResultsIndependent reverse isotope dilution experiments using different chromatographic methods over a period of several months, delivered a list of 83 13C-labeled metabolites with fully characterized concentration and their uncertainty, covering 5 orders of magnitude, from the nanomolar to the low millimolar range. The 13C-labeled yeast-derived IS showed excellent intermediate stability with 92 % of molecules showing inter-method RSDs ≤30 % (75 % of molecules showed RSDs ≤15 %) over a timeframe of five months. One-point internal standardization with the characterized labeled biomass achieved figures of merit equivalent to multipoint calibrations for the majority of metabolites. SignificanceThe proposed calibration workflow rationalizes time and standard expenditure and is particularly beneficial for laboratories dealing with wide-target assays and small analysis batches. The present assessment serves as a seminal study for further developments of the concept towards absolute quantification from archive high-resolution MS data of U13C-biomass-spiked samples and the implementation of quick biomass recalibration with each experiment, promising seamless transition between internal standards derived from different fermentation batches.

Efficacy of novel bacterial consortia in degrading fipronil and thiobencarb in paddy soil: a survey for community structure and metabolic pathways.

Fipronil (FIP) and thiobencarb (THIO) represent widely utilized pesticides in paddy fields, presenting environmental challenges that necessitate effective remediation approaches. Despite the recognized need, exploring bacterial consortia efficiently degrading FIP and THIO remains limited. This study isolated three unique bacterial consortia-FD, TD, and MD-demonstrating the capability to degrade FIP, THIO, and an FIP + THIO mixture within a 10-day timeframe. Furthermore, the bioaugmentation abilities of the selected consortia were evaluated in paddy soils under various conditions. Sequencing results shed light on the consortia's composition, revealing a diverse bacterial population prominently featuring Azospirillum, Ochrobactrum, Sphingobium, and Sphingomonas genera. All consortia efficiently degraded pesticides at 800 µg/mL concentrations, primarily through oxidative and hydrolytic processes. This metabolic activity yields more hydrophilic metabolites, including 4-(Trifluoromethyl)-phenol and 1,4-Benzenediol, 2-methyl-, for FIP, and carbamothioic acid, diethyl-, S-ethyl ester, and Benzenecarbothioic acid, S-methyl ester for THIO. Soil bioaugmentation tests highlight the consortia's effectiveness, showcasing accelerated degradation of FIP and THIO-individually or in a mixture-by 1.3 to 13-fold. These assessments encompass diverse soil moisture levels (20 and 100% v/v), pesticide concentrations (15 and 150 µg/g), and sterile conditions (sterile and non-sterile soils). This study offers an understanding of bacterial communities adept at degrading FIP and THIO, introducing FD, TD, and MD consortia as promising contenders for bioremediation endeavors.

A Scoping Review on Carotenoid Profiling in Passiflora spp.: A Vast Avenue for Expanding the Knowledge on the Species.

The Passiflora genus is recognised for its ethnopharmacological, sensorial, and nutritional significance. Yet, the screening of its dietary and bioactive molecules has mainly targeted hydrophilic metabolites. Following the PRISMA-P protocol, this review assessed the current knowledge on carotenoid composition and analysis within Passiflora, examining 968 records from seven databases and including 17 studies focusing on carotenoid separation and identification in plant parts. Those publications originated in America and Asia. P. edulis was the most frequently examined species of a total of ten, while pulp was the most studied plant part (16 studies). Carotenoid analysis involved primarily high-performance liquid chromatography separation on C18 columns and detection using diode array detectors (64.71%). Most studies identified the provitamin A β-carotene and xanthophylls lutein and zeaxanthin, with their geometric configuration often neglected. Only one study described carotenoid esters. Besides the methodology's insufficient description, the lack of use of more accurate techniques and practices led to a high risk of bias in the carotenoid assignment in 17.65% of the articles. This review highlights the opportunity to broaden carotenoid studies to other species and parts within the diverse Passiflora genus, especially to wild, locally available fruits, which may have a strategic role in enhancing food diversity and security amidst climatic changes. Additionally, it urges the use of more accurate and efficient analytical methods based on green chemistry to better identify Passiflora carotenoids.

Multiomics analysis to explore blood metabolite biomarkers in an Alzheimer’s Disease Neuroimaging Initiative cohort

Alzheimer's disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD within two years using the baseline metabolome. Patients with lower ergothioneine levels had a 12% higher rate of AD progression with the significance of P = 0.012 (Wald test). Furthermore, an increase in ganglioside (GM3) and decrease in plasmalogen lipids, many of which are associated with apolipoprotein E polymorphism, were confirmed in AD patients, and the higher levels of lysophosphatidylcholine (18:1) and GM3 d18:1/20:0 showed 19% and 17% higher rates of AD progression, respectively (Wald test: P = 3.9 × 10–8 and 4.3 × 10–7). Palmitoleamide, oleamide, diacylglycerols, and ether lipids were also identified as significantly altered metabolites at baseline in patients with pMCI. The integrated analysis of metabolites and genomics data showed that combining information on metabolites and genotypes enhances the predictive performance of AD progression, suggesting that metabolomics is essential to complement genomic data. In conclusion, the reanalysis of multiomics data provides new insights to detect early development of AD pathology and to partially understand metabolic changes in age-related onset of AD.

The Hydrophilic Metabolite UMP Alleviates Obesity Traits through a HIF2α-ACER2-Ceramide Signaling Axis.

Metabolic abnormalities contribute to the pathogenesis of obesity and its complications. Yet, the understanding of the interactions between critical metabolic pathways that underlie obesity remains to be improved, in part owing to the lack of comprehensive metabolomics studies that reconcile data from both hydrophilic and lipophilic metabolome analyses that can lead to the identification and characterization of key signaling networks. Here, the study conducts a comprehensive metabolomics analysis, surveying lipids and hydrophilic metabolites of the plasma and omental adipose tissue of obese individuals and the plasma and epididymal adipose tissue of mice. Through these approaches, it is found that a significant accumulation of ceramide due to inhibited sphingolipid catabolism, while a significant reduction in the levels of uridine monophosphate (UMP), is critical to pyrimidine biosynthesis. Further, it is found that UMP administration restores sphingolipid homeostasis and can reduce obesity in mice by reversing obesity-induced inhibition of adipocyte hypoxia inducible factor 2a (Hif2α) and its target gene alkaline ceramidase 2 (Acer2), so as to promote ceramide catabolism and alleviate its accumulation within cells. Using adipose tissue Hif2α-specific knockout mice, the study further demonstrates that the presence of UMP can alleviate obesity through a HIF2α-ACER2-ceramide pathway, which can be a new signaling axis for obesity improvement.

Targeted Metabolite Fingerprints of Thirteen Gambierdiscus, Five Coolia and Two Fukuyoa Species.

The genus Gambierdiscus produces an array of bioactive hydrophilic and lipophilic secondary metabolites that range in mode of action and toxicity. In this study, the metabolite fingerprint was mapped for thirteen Gambierdiscus, five Coolia and two Fukuyoa species (34 isolates) by assessing the production of 56 characterised secondary metabolites. Gambierdiscus polynesiensis was the only species to produce Pacific-ciguatoxin-3B (P-CTX3B), P-CTX3C, iso-P-CTX3B/C, P-CTX4A, P-CTX4B and iso-P-CTX4A/B. G. australes produced maitotoxin-1 (MTX-1) and MTX-5, G. cheloniae produced MTX-6 and G. honu produced MTX-7. Ubiquitous production of 44-methylgambierone was observed amongst all the Gambierdiscus isolates, with nine species also producing gambierone. Additional gambierone analogues, including anhydrogambierone (tentatively described herein), were also detected in all Gambierdiscus species, two Coolia and two Fukuyoa species. Gambieroxide was detected in G. lewisii and G. pacificus and gambieric acid A was detected in ten Gambierdiscus species, with G. australes (CAWD381) being the only isolate to produce gambieric acids A-D. This study has demonstrated that the isolates tested to date produce the known CTXs or MTXs, but not both, and highlighted several species that produced 'unknown' compounds displaying characteristics of cyclic polyethers, which will be the focus of future compound discovery efforts.

Salivary metabolomic biomarkers for non-invasive lung cancer detection.

Identifying novel biomarkers for early detection of lung cancer is crucial. Non-invasively available saliva is an ideal biofluid for biomarker exploration; however, the rationale underlying biomarker detection from organs distal to the oral cavity in saliva requires clarification. Therefore, we analyzed metabolomic profiles of cancer tissues compared with those of adjacent non-cancerous tissues, as well as plasma and saliva samples collected from patients with lung cancer (n = 109 pairs). Additionally, we analyzed plasma and saliva samples collected from control participants (n = 83 and 71, respectively). Capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry were performed to comprehensively quantify hydrophilic metabolites. Paired tissues were compared, revealing 53 significantly different metabolites. Plasma and saliva showed 44 and 40 significantly different metabolites, respectively, between patients and controls. Of these, 12 metabolites exhibited significant differences in all three comparisons and primarily belonged to the polyamine and amino acid pathways; N1-acetylspermidine exhibited the highest discrimination ability. A combination of 12 salivary metabolites was evaluated using a machine learning method to differentiate patients with lung cancer from controls. Salivary data were randomly split into training and validation datasets. Areas under the receiver operating characteristic curve were 0.744 for cross-validation using training data and 0.792 for validation data. This model exhibited a higher discrimination ability for N1-acetylspermidine than that for other metabolites. The probability of lung cancer calculated using this model was independent of most patient characteristics. These results suggest that consistently different salivary biomarkers in both plasma and lung tissues might facilitate non-invasive lung cancer screening.

Comparison of Amine-Modified Polymeric Stationary Phases for Polar Metabolomic Analysis Based on Unified-Hydrophilic Interaction/Anion Exchange Liquid Chromatography/High-Resolution Mass Spectrometry (Unified-HILIC/AEX/HRMS).

In metabolomic analysis, one of the most commonly used techniques to support the detection sensitivity and quantitation of mass spectrometry is combining it with liquid chromatography. Recently, we developed a method that enables comprehensive single-run measurement of hydrophilic metabolites using unified-hydrophilic interaction/anion exchange liquid chromatography/high-resolution mass spectrometry (unified-HILIC/AEX/HRMS) with a polymer-based mixed amines column (Gelpack GL-HilicAex). However, the importance of stationary phase functional groups and mobile phase conditions for the separation mechanisms and sensitive detection in unified-HILIC/AEX/HRMS is not yet fully understood. This study aimed to understand the importance of the mobile and stationary phases in unified-HILIC/AEX/HRMS. Two different alkali-resistant polymer-based amines-modified columns (Gelpack GL-HilicAex, primary, secondary, tertiary, and quaternary amine-modified polyglycerol dimethacrylate gel; Asahipak NH2P-50 2D, secondary amine-modified polyvinyl alcohol gel) and two eluents (acetonitrile and ammonium bicarbonate solution, pH 9.8) were used for comparative validation. A comparison of mobile phase conditions using both columns confirmed that the two-step separation from HILIC to AEX characteristic of unified-HILIC/AEX requires a linear gradient condition from acetonitrile to nearly 50% water and AEX with up to 40 mM bicarbonate ions. We found that when alkali-resistant hydrophilic polymer packing materials are modified with amines, unified-HILIC/AEX separation can be reproduced if at least one secondary amine associated with the amine series is present in the stationary phase. Furthermore, the difference in sensitivity in the HILIC and AEX modes owing to the different columns indicates the need for further improvements in the mobile phase composition and stationary phase.

Predicting Retention Time in Unified-Hydrophilic-Interaction/Anion-Exchange Liquid Chromatography High-Resolution Tandem Mass Spectrometry (Unified-HILIC/AEX/HRMS/MS) for Comprehensive Structural Annotation of Polar Metabolome.

The accuracy of the structural annotation of unidentified peaks obtained in metabolomic analysis using liquid chromatography/tandem mass spectrometry (LC/MS/MS) can be enhanced using retention time (RT) information as well as precursor and product ions. Unified-hydrophilic-interaction/anion-exchange liquid chromatography high-resolution tandem mass spectrometry (unified-HILIC/AEX/HRMS/MS) has been recently developed as an innovative method ideal for nontargeted polar metabolomics. However, the RT prediction for unified-HILIC/AEX has not been developed because of the complex separation mechanism characterized by the continuous transition of the separation modes from HILIC to AEX. In this study, we propose an RT prediction model of unified-HILIC/AEX/HRMS/MS, which enables the comprehensive structural annotation of polar metabolites. With training data for 203 polar metabolites, we ranked the feature importance using a random forest among 12,420 molecular descriptors (MDs) and constructed an RT prediction model with 26 selected MDs. The accuracy of the RT model was evaluated using test data for 51 polar metabolites, and 86.3% of the ΔRTs (difference between measured and predicted RTs) were within ±1.50 min, with a mean absolute error of 0.80 min, indicating high RT prediction accuracy. Nontargeted metabolomic data from the NIST SRM 1950-Metabolites in frozen human plasma were analyzed using the developed RT model and in silico MS/MS prediction, resulting in a successful structural estimation of 216 polar metabolites, in addition to the 62 identified based on standards. The proposed model can help accelerate the structural annotation of unknown hydrophilic metabolites, which is a key issue in metabolomic research.

A very-low carbohydrate content in a high-fat diet modifies the plasma metabolome and impacts systemic inflammation and experimental atherosclerosis

Ketogenic diets (KDs) are very high-fat low-carbohydrate diets that promote nutritional ketosis and are widely used for weight loss, although concerns about potential adverse cardiovascular effects remain. We investigated a very high-fat KD's vascular impact and plasma metabolic signature compared to a non-ketogenic high-fat diet (HFD). Apolipoprotein E deficient (ApoE −/−) mice were fed a KD (%kcal:81:1:18, fat/carbohydrate/protein), a non-ketogenic high-fat diet with half of the fat content (HFD) (%kcal:40:42:18, fat/carbohydrate/protein) for 12 weeks. Plasma samples were used to quantify the major ketone body beta−hydroxybutyrate (BHB) and several pro-inflammatory cytokines (IL-6, MCP-1, MIP-1alpha, and TNF alpha), and to targeted metabolomic profiling by mass spectrometry. In addition, aortic atherosclerotic lesions were quantified ex-vivo by magnetic resonance imaging (MRI) on a 14-tesla system. KD was atherogenic when compared to the control diet, but KD mice, when compared to the HFD group (1) had markedly higher levels of BHB and lower levels of cytokines, confirming the presence of ketosis that alleviated the well-established fat-induced systemic inflammation; (2) displayed significant changes in the plasma metabolome that included a decrease in lipophilic metabolites and an increase in hydrophilic metabolites; (3) had significantly lower levels of several atherogenic lipid metabolites, including phosphatidylcholines, cholesterol esters, sphingomyelins, and ceramides; and (4) presented significantly lower aortic plaque burden. KD was atherogenic and was associated with specific metabolic changes but alleviated the fat-induced inflammation and lessened the progression of atherosclerosis when compared to the HFD.

Review: Cytohistophysiological Aspects of Blood Organ/Tissue Barriers

General physiology is the basis of basic and applied aspects of life processes and moleculo-biochemical aspects that ensures the survival of species efficiently. There is a need to maintain specific amount and numbers of metabolites in the body fluid and the fluid present in the organs. This needs a specific check on the body fluid that provides the required metabolites and removes unwanted ones. For this scrutiny, there is something like a ‘check post’ and it is referred to as ‘blood organ/tissue barrier’. Further, this ensures the restoration of appropriate ambient environment for the ongoing physiological processes in an organism. Structural, biochemical and molecular aspects of blood organ barriers have potential to illustrate on the survival mechanisms. Further, biotechnological research, artificial mode of physiological techniques and the technological advancement help to understand the intricacies of various physiological mechanisms occurring in the life activities and the remedial aspects in cases of pathogenesis. For normal physiological functioning a suitable physiological homeostasis is an important basis. The respective balanced biochemical and molecular interactions depend on processes like paracellular diffusion of metabolites, activated transport of hydrophobic and hydrophilic metabolites and drugs from the circulating blood stream. There is a specific need of an effective drug therapy along with appropriate drug delivery system that can regulate the correct dose of drug at the site to meet the remedial parameters while dealing with pathogenesis and dysfunctioning of the organ. The investigations relating blood barrier are significant while investigation the toxicological and pathological aspects of a given organ.

Integrated Metabolomics and Transcriptomics Analyses Reveal the Candidate Genes Regulating the Meat Quality Change by Castration in Yudong Black Goats (Capra hircus).

Yudong black goats (YDGs) are a local breed in southwest China that possess unique meat qualities and produce a high meat yield, making them ideal models for studying goat meat quality. Castration may decrease off-odors, significantly change metabolites and improve meat quality. Using multi-omics techniques, this study focused on Yudong black goat wethers (YDW, n = 4) and Yudong black bucks (YDB, n = 4). The findings revealed that 33 differentially expressed genes (DEGs) and 279 significantly changed metabolites (SCMs) influenced goat meat quality by affecting fat accumulation and lipolysis regulatory processes. Herein, several candidate genes (IGF1, TNNT2, PPP2R2C, MAPK10 and VNN1, etc.) were identified that play a role in regulating meat quality, non-castrated and castrated, alongside a series of metabolites that may serve as potential meat quality biomarkers. Lipids (triglycerides, oxidized lipids_5-iso PGF2VI, ceramide (t18:1/36:2(2OH)) and Carnitine C20:5, etc.) were significantly higher in the castrated goats. These results revealed that lipids and hydrophilic metabolites were affected by castration, which might be beneficial in terms of goat meat quality. This study aimed to investigate the differences in meat quality between uncastrated and castrated male goats and the possible molecular regulatory mechanisms.

Exploring the metabolomic landscape: Perilla frutescens as a promising enhancer of production, flavor, and nutrition in Tan lamb meat

Addressing health-related concerns linked to the metabolite profile of lamb meat has become paramount, in line with the growing demand for enhanced flavor and taste. We examined the impact of Perilla frutescens seeds on Tan lamb growth, carcass traits, and metabolite profiles. Three diets were employed: a low-concentrate group (LC), a high-concentrate group (HC), and a PFS group (the LC diet supplemented with 3% Perilla frutescens seeds) on a dry matter basis. Forty-five male Tan-lambs (approximately six months) with similar body weights (25.1 kg ± 1.12 SD) were randomly assigned to one of these three groups for 84-day feeding, including an initial 14-day adjustment phase. The supplementation of PFS resulted in increased average daily gain (P < 0.01) and improved carcass quality and meat color (P < 0.05). Additionally, it led to an enhancement in omega-3 polyunsaturated fatty acids (P < 0.05) and a reduction in the omega-6/omega-3 ratio (P < 0.05). Using gas chromatography–mass spectrometry, 369 volatile compounds were identified with enhanced levels of acetaldehyde and 1,2,4-trimethyl-benzene associated with PFS (P < 0.05). Among the 807 compounds identified by ultra-high performance liquid chromatography-mass spectrometry, there were 66 significantly differential compounds (P < 0.05), including 43 hydrophilic metabolites and 23 lipids. PFS supplementation led to significant alterations in 66 metabolites, with three metabolites including 2,5-diisopropyl-3-methylphenol, 3-hydroxydecanoic acid, and lysophosphatidylcholine (15:0) emerging as potential PFS-related biomarkers. The study indicates that PFS supplementation can enhance Tan-lamb growth, feed efficiency, and meat quality, potentially providing lamb meat with improved flavor and nutritional characteristics.

Acute exposure to PM2.5 promotes arterial stiffening by down-regulating serine and trans-4-hydroxyproline dependent pathways - results from an Asutralian cohort metabolomic study

Abstract Background Exposure to air pollution is known to have both acute and chronic adverse effects on the cardiovascular system, but the pathophysiology of cardiac complications associated with air pollutants remains poorly understood; however, utilizing high-throughput omic studies can provide a better understanding of involved biomarkers, which may ultimately help identify, prevent, and discover drugs for high-risk populations. Purpose Utilising the targeted metabolomics in the BioHEART Discovery cohort we set to identify metabolites implicated in cardiovascular diseases in relation to acute exposure to air pollution. Method We included 1002 clinically stable study participants who were referred for a clinically indicated CT coronary angiogram (CTCA) between November 2015 and March 2020. Coronary artery disease (CAD) burden was assessed using coronary artery calcium scores (CACS) and the Gensini scores. We performed targeted metabolomic analysis of hydrophilic metabolites in positive and negative ionisation using Liquid chromatography–mass spectrometry (LC-MS). Acute air pollution exposure was defined as the daily average and maximum climatic (temperature and humidity) and particulate matter levels on the day of and up to 3 days prior to enrollment, based on the patient's postcode. Using K-means clustering, we grouped the population based on their overall maximum PM2.5 exposure. We also used PCA and sPLS-DA to cluster and perform variable importance selection. Results PCA demonstrated good separation between the high vs normal PM2.5 exposure groups in PC1-PC2 dimensions, with scores of 29.5% and 8.5% respectively [Figure 1]. All of the top five metabolites detected by sPLS-DA, including Trans-4-Hydroxyproline and Serine, demonstrated down-regulation in the high exposure cohort.Trans-4-Hydroxyproline is involved in the urea cycle and arginine and proline metabolism, while Serine is a marker of glycine, serine, and threonine metabolism. Previous studies [1] have shown that these metabolites have an inverse correlation with carotid-femoral pulse-wave velocity (PWV), an indirect measure of arterial stiffness and an indication of increased risk of all-cause mortality and cardiac morbidity [2]. Conclusion Here we have demonstrated that acute exposure to PM2.5 can potentially result in a shift in metabolimic signature that is associated with vascular dysfunction.PCA clusters demonstrating a good separaComparing Trans-4-HYP and Serine