PubMed

Metabolomics. 2023 Feb 24;19(3):14. doi: 10.1007/s11306-023-01978-z.ABSTRACTINTRODUCTION: In the advanced stage of chronic kidney disease (CKD), electrolytes, fluids, and metabolic wastes including various uremic toxins, accumulate at high concentrations in the patients' blood. Hemodialysis (HD) is the conventional procedure used worldwide to remove metabolic wastes. The creatinine and urea levels have been routinely monitored to estimate kidney function and effectiveness of the HD process. This study, first from in Indian perspective, aimed at the identification and quantification of major uremic toxins in CKD patients on maintenance HD (PRE-HD), and compared with the healthy controls (HC) as well as after HD (POST-HD).OBJECTIVES: The study mainly focused on the identification of major uremic toxins in Indian perspective and the quantitative analysis of indoxyl sulfate and p-cresol sulfate (routinely targeted uremic toxins), and phenyl sulfate, catechol sulfate, and guaiacol sulfate (targeted for the first time), apart from creatinine and urea in PRE-HD, POST-HD, and HC groups.METHODS: Blood samples were collected from 90 HD patients (both PRE-HD and POST-HD), and 74 HCs. The plasma samples were subjected to direct ESI-HRMS and LC/HRMS for untargeted metabolomics and LC-MS/MS for quantitative analysis.RESULTS: Various known uremic toxins, and a few new and unknown peaks were detected in PRE-HD patients. The p-cresol sulfate and indoxyl sulfate were dominant in PRE-HD, the concentrations of phenyl sulfate, catechol sulfate, and guaiacol sulfate were about 50% of that of indoxyl sulfate. Statistical evaluation on the levels of targeted uremic toxins in PRE-HD, POST-HD, and HC groups showed a significant difference among the three groups. The dialytic clearance of indoxyl sulfate and p-cresol sulfate was found to be < 35%, while that of the other three sulfates was 50-58%.CONCLUSION: LC-MS/MS method was developed and validated to evaluate five major uremic toxins in CKD patients on HD. The levels of the targeted uremic toxins could be used to assess kidney function and the effectiveness of HD.PMID:36826619 | DOI:10.1007/s11306-023-01978-z

Arch Toxicol. 2023 Feb 24. doi: 10.1007/s00204-023-03470-y. Online ahead of print.ABSTRACTDespite the high prevalence of alcoholic liver disease, its identification and characterization remain poor, especially in early stages such as alcoholic fatty liver disease and alcoholic steatohepatitis. This latter implies diagnostic difficulties, few therapeutic options and unclear mechanisms of action. To elucidate the metabolic alterations and pinpoint affected biochemical pathways, alcoholic steatohepatitis was simulated in vitro by exposing HepaRG cells to ethanol (IC10, 368 mM) and tumor necrosis factor alpha (TNF-α, 50 ng/mL) for 24 h. This combined exposure was compared to solely ethanol-exposed as well as -nonexposed cells. Four different metabolomics platforms were used combining liquid chromatography, high-resolution mass spectrometry and drift tube ion mobility to elucidate both intracellular and extracellular metabolic alterations. Some of the key findings include the influence of TNF-α in the upregulation of hepatic triglycerides and the downregulation of hepatic phosphatidylethanolamines and phosphatidylcholines. S-Adenosylmethionine showed to play a central role in the progression of alcoholic steatohepatitis. In addition, fatty acyl esters of hydroxy fatty acid (FAHFA)-containing triglycerides were detected for the first time in human hepatocytes and their alterations showed a potentially important role during the progression of alcoholic steatohepatitis. Ethoxylated phosphorylcholine was identified as a potential new biomarker of ethanol exposure.PMID:36826472 | DOI:10.1007/s00204-023-03470-y

Nucl Med Commun. 2023 Feb 27:e001671. doi: 10.1097/MNM.0000000000001671. Online ahead of print.ABSTRACTBACKGROUND: Sentinel lymph node (SLN) biopsy in cutaneous melanoma patients evaluates the regional draining basin for occult micrometastatic disease. Occasionally, nonidentification of SLN impairs the acquisition of this important prognostic factor.OBJECTIVES: To investigate the outcomes of melanoma patients with negative lymphoscintigraphic findings and patients who underwent SLN biopsy from 2004 to 2015 (n = 1200) were retrospectively reviewed for tumor characteristics and clinical outcomes.METHODS: Patients with nonvisualized lymph nodes (NV group) who underwent only preoperative lymphoscintigraphy were separated and compared with a cohort drawn from all melanoma patients who completed the surgical procedure within the same period (V group).RESULTS: A negative lymphoscintigraphic scan was observed in 38 cases (3.2% of all patients). The NV group showed a significantly older age (median 66.0 vs. 48.3 years; P < 0.0001). Head and neck melanomas were more frequent in the NV group compared to the control group (25.1 vs. 7.8%; P = 0.009). Tumor characteristics such as ulceration and Breslow thickness do not influence the lymphoscintigraphy result. No differences were found in overall survival (OS) and disease-free survival (DFS) between the groups.CONCLUSIONS: The nonvisualization of regional lymph nodes by lymphoscintigraphy is more frequent in older patients with head and neck melanomas. From the clinical point of view, no specific recommendation emerged for patients' management because the nonvisualization of the SLN did not show a significant influence on DFS and OS rates. However, lack of knowledge of lymph node status suggests performing a tighter follow-up eventually by ultrasound evaluation of all potential lymph node drainage basins.PMID:36826418 | DOI:10.1097/MNM.0000000000001671

Curr Issues Mol Biol. 2023 Jan 30;45(2):1086-1099. doi: 10.3390/cimb45020072.ABSTRACTThis experiment was conducted to define changes in metabolic pathways in response to mandibulate insect feeding and to provide a reference for further investigation of the molecular mechanisms underlying the development of conifer resistance. Chinese pine (Pinus tabuliformis Carr.) in good growth status in natural condition was chosen for stimulation by 10 pine caterpillars (Dendrolimus tabulaefomis Tsai et Liu) as feeding stimulation (FS), leaf clipping control (LCC) as mechanical damage, and CK group (with no treatment) (recorded as 0 h). The metabolome and total flavonoid content were measured in the needles at 0, 2, and 8 h after treatment. Plant hormones were measured with needles at 0, 0.5, 1, 1.5, 2, 4, 6, and 8 h after different treatments. The results show that a total of 30.8% flavonoids are identified by metabolomics analysis. Compared with leaf clipping control, feeding stimulation of Chinese pine caterpillars significantly induced the upregulation of metabolites in the flavonoid pathway in Chinese pine, and the plant hormones JA and IAA showed expression trends consistent with those of the metabolome. According to the biological processes of the four plant hormones involved, JA and SA are mostly involved in resistance formation, and in this study, both of them also have fluctuating expressions influenced by feeding stimulation, while the expressions of the growth-related hormones IAA and ABA have no significant changes at other time points except for 1 h after treatment. Thus, the flavonoid pathway is one of the main pathways involved in resistance formation in conifers, and JA and IAA are involved in the formation of resistance.PMID:36826017 | DOI:10.3390/cimb45020072

Curr Issues Mol Biol. 2023 Jan 20;45(2):990-1001. doi: 10.3390/cimb45020064.ABSTRACTTo understand differences in the quality of different conventional japonica rice varieties and variations in metabolites related to rice quality, the quality of three conventional japonica varieties was determined, and the metabolites of the milled rice were investigated using nontargeted metabolomics technology. The results showed that the taste value (TV) of Yangda 4Hao (YD4) was significantly higher than that of Yangda 3Hao (YD3) and Huaidao 5Hao (HD5). The protein content (PC) of HD5 was significantly higher than that of YD3 and YD4. PC was significantly negatively correlated with TV. Ninety-one differential metabolites (59 increased and 32 decreased) were identified between YD3 and HD5. A total of 144 differential metabolites (96 upregulated and 48 downregulated) were identified between YD4 and HD5. A total of 114 differential metabolites (40 increased and 74 decreased) were identified between YD3 and YD4. The metabolites with a high correlation to rice quality were mostly involved in the amino acid metabolism pathway. Amino acid metabolites play an important role in the formation of rice quality. The key metabolites in the synthesis and regulation of metabolic pathways are sucrose, levan, and amylose, which are carbohydrates, and L-glutamine, L-aspartic acid, and L-asparagine, which are amino acid metabolites. It can be seen from this study that the metabolites of sucrose, levan, amylose, L-glutamine, L-aspartic acid, and L-asparagine may be the key metabolites in the quality formation of high-quality rice varieties.PMID:36826009 | DOI:10.3390/cimb45020064

Curr Issues Mol Biol. 2023 Jan 18;45(2):838-851. doi: 10.3390/cimb45020055.ABSTRACTGlioblastoma (GBM) is the most common malignancy of the brain with a relatively short median survival and high mortality. Advanced age, high socioeconomic status, exposure to ionizing radiation, and other factors have been correlated with an increased incidence of GBM, while female sex hormones, history of allergies, and frequent use of specific drugs might exert protective effects against this disease. However, none of these explain the pathogenesis of GBM. The most recent WHO classification of CNS tumors classifies neoplasms based on their histopathological and molecular characteristics. Modern laboratory techniques, such as matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry, enable the comprehensive metabolic analysis of the tissue sample. MALDI imaging is able to characterize the spatial distribution of a wide array of biomolecules in a sample, in combination with histological features, without sacrificing the tissue integrity. In this review, we first provide an overview of GBM epidemiology, risk, and protective factors, as well as the recent WHO classification of CNS tumors. We then provide an overview of mass spectrometry workflow, with a focus on MALDI imaging, and recent advances in cancer research. Finally, we conclude the review with studies of GBM that utilized MALDI imaging and offer our perspective on future research.PMID:36826000 | DOI:10.3390/cimb45020055

Bioinformatics. 2023 Feb 24:btad096. doi: 10.1093/bioinformatics/btad096. Online ahead of print.ABSTRACTMOTIVATION: Untargeted metabolomics by mass spectrometry is the method of choice for unbiased analysis of molecules in complex samples of biological, clinical, or environmental relevance. The exceptional versatility and sensitivity of modern high-resolution instruments allows profiling of thousands of known and unknown molecules in parallel. Inter-batch differences constitute a common and unresolved problem in untargeted metabolomics, and hinder the analysis of multi-batch studies or the intercomparison of experiments.RESULTS: We present a new method, Regularized Adversarial Learning Preserving Similarity (RALPS), for the normalization of multi-batch untargeted metabolomics data. RALPS builds on deep adversarial learning with a three-term loss function that mitigates batch effects while preserving biological identity, spectral properties, and coefficients of variation. Using two large metabolomics datasets, we showcase the superior performance of RALPS as compared with six state-of-the-art methods for batch correction. Further, we demonstrate that RALPS scales well, is robust, deals with missing values, and can handle different experimental designs.AVAILABILITY: https://github.com/zamboni-lab/RALPS.SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online.PMID:36825815 | DOI:10.1093/bioinformatics/btad096

Pediatr Allergy Immunol. 2023 Feb;34(2):e13917. doi: 10.1111/pai.13917.ABSTRACTBACKGROUND: Evidence suggests maternal pregnancy dietary intake and nutrition in the early postnatal period to be of importance for the newborn child's health. However, studies investigating diet-related metabolites transferred from mother to child on disease risk in childhood are lacking. We sought to investigate the influence of vertically transferred metabolites on risk of atopic diseases and infections during preschool age.METHODS: In the Danish population-based COPSAC2010 mother-child cohort, information on 10 diet-related vertically transferred metabolites from metabolomics profiles of dried blood spots (DBS) at age 2-3 days was analyzed in relation to the risk of childhood asthma, allergy, eczema, and infections using principal component and single metabolite analyses.RESULTS: In 678 children with DBS measurements, a coffee-related metabolite profile reflected by principal component 1 was inversely associated with risk of asthma (odds ratio (95% CI) 0.78 (0.64; 0.95), p = .014) and eczema at age 6 years (0.79 (0.65; 0.97), p = .022). Furthermore, increasing stachydrine (fruit-related), 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (fish-related), and ergothioneine (fruit-, green vegetables-, and fish-related) levels were all significantly associated with reduced risks of infections at age 0-3 years (p < .05).CONCLUSION: This study demonstrates associations between pregnancy diet-related vertically transferred metabolites measured in children in early life and risk of atopic diseases and infections in childhood. The specific metabolites associated with a reduced disease risk in children may contribute to the characterization of a healthy nutritional profile in pregnancy using a metabolomics-based unbiased tool for predicting childhood health.PMID:36825739 | DOI:10.1111/pai.13917

J Appl Physiol (1985). 2023 Feb 24. doi: 10.1152/japplphysiol.00789.2022. Online ahead of print.ABSTRACTLow-load blood flow-restricted resistance exercise (BFRRE) constitute an effective means to produce skeletal muscle hypertrophy. Nonetheless, its applicability to counteract the age-related skeletal muscle decay at a cellular level, is not clear. Therefore, we investigated the effect of BFRRE on muscle fiber morphology, integrated muscle protein synthesis, muscle stem cells (MuSCs), myonuclear content and muscle functional capacity in healthy older individuals. Twenty-three participants with a mean age of 66 years (56-75 years) were randomized to six weeks of supervised BFRRE (3 sessions x week) or non-intervention control (CON). Biopsies were collected from vastus lateralis before and after the intervention. Immunofluorescent microscopy was utilized to assess muscle fiber type-specific cross-sectional area (CSA) as well as MuSC and myonuclear content. Deuterium oxide was orally administered throughout the intervention period, enabling assessment of integrated myofibrillar and connective tissue protein fractional synthesis rate (FSR). BFRRE produced uniform ~20% increases in the fiber CSA of both type I and type II fibers (p<0.05). This occurred concomitantly with improvements in both maximal strength and muscle strength-endurance, but in the absence of increased MuSC content and myonuclear addition. The observed muscle fiber hypertrophy was not mirrored by increases in either myofibrillar or connective tissue FSR. In conclusion, BFRRE proved effective in stimulating skeletal muscle growth and increased muscle function in older individuals, which advocates for the use of BFRRE as a countermeasure of age-related deterioration of skeletal muscle mass and function.PMID:36825645 | DOI:10.1152/japplphysiol.00789.2022

Front Microbiol. 2023 Feb 6;14:1096471. doi: 10.3389/fmicb.2023.1096471. eCollection 2023.ABSTRACTBACKGROUND AND OBJECTIVE: Impaired gut barrier contributes to the progression of type 2 diabetes mellitus (T2DM), and the gut microbiota and metabolome play an important role in it. Hemicellulose, a potential prebiotics, how its supplementation impacted the glucose level, the impaired gut barrier, and the gut microbiota and metabolome in T2DM remained unclear.METHODS: In this study, some mice were arranged randomly into four groups: db/db mice fed by a compositionally defined diet (CDD), db/db mice fed by a CDD with 10% and 20% hemicellulose supplementation, and control mice fed by a CDD. Body weight and fasting blood glucose levels were monitored weekly. The gut barrier was evaluated. Fresh stool samples were analyzed using metagenomic sequencing and liquid chromatography-mass spectrometry to detect gut microbiota and metabolome changes. Systemic and colonic inflammation were evaluated.RESULTS: Better glycemic control, restoration of the impaired gut barrier, and lowered systemic inflammation levels were observed in db/db mice with the supplementation of 10 or 20% hemicellulose. The gut microbiota showed significant differences in beta diversity among the four groups. Fifteen genera with differential relative abundances and 59 significantly different metabolites were found. In the db/db group, hemicellulose eliminated the redundant Faecalibaculum and Enterorhabdus. The increased succinate and ursodeoxycholic acid (UDCA) after hemicellulose treatment were negatively correlated with Bifidobacterium, Erysipelatoclostridium, and Faecalibaculum. In addition, hemicellulose reduced the colonic expressions of TLR2/4 and TNF-α in db/db mice.CONCLUSION: Hemicellulose may serve as a potential therapeutic intervention for T2DM by improving impaired intestinal mucosal barrier integrity, modulating gut microbiota composition, and altering the metabolic profile.PMID:36825092 | PMC:PMC9942597 | DOI:10.3389/fmicb.2023.1096471

Front Microbiol. 2023 Feb 7;14:1150175. doi: 10.3389/fmicb.2023.1150175. eCollection 2023.NO ABSTRACTPMID:36825090 | PMC:PMC9941732 | DOI:10.3389/fmicb.2023.1150175

bioRxiv. 2023 Feb 14:2023.02.13.528368. doi: 10.1101/2023.02.13.528368. Preprint.ABSTRACTDespite a wealth of exploratory plasma metabolomics studies in sickle cell disease (SCD), no study to date has evaluate a large and well phenotyped cohort to compare the primary erythrocyte metabolome of hemoglobin SS, SC and transfused AA red blood cells (RBCs) in vivo . The current study evaluates the RBC metabolome of 587 subjects with sickle cell sickle cell disease (SCD) from the WALK-PHaSST clinical cohort. The set includes hemoglobin SS, hemoglobin SC SCD patients, with variable levels of HbA related to RBC transfusion events, and HbF related to hydroxyurea therapy. Here we explore the modulating effects of genotype, age, sex, severity of hemolysis, and hydroxyurea and transfusion therapy on sickle RBC metabolism. Data - collated in an online portal - show that the Hb SS genotype is associated with significant alterations of RBC acylcarnitines, pyruvate, sphingosine 1-phosphate, creatinine, kynurenine and urate metabolism. Surprisingly, the RBC metabolism of SC RBCs is dramatically different from SS, with all glycolytic intermediates significantly elevated in SS RBCs, with the exception of pyruvate. This result suggests a metabolic blockade at the ATP-generating phosphoenolpyruvate to pyruvate step of glycolysis, which is catalyzed by redox-sensitive pyruvate kinase. Increasing in vivo concentrations of HbA improved glycolytic flux and normalized the HbS erythrocyte metabolome. An unexpectedly limited metabolic effect of hydroxyurea and HbF was observed, possibly related to the modest induction of HbF in this cohort. The metabolic signature of HbS RBCs correlated with the degree of steady state hemolytic anemia, cardiovascular and renal dysfunction and mortality.KEY POINTS: In vivo dysregulation of RBC metabolism by HbS is evaluated by metabolic profiling of 587 patients with variable HbA, HbC and HbF levels;RBC acyl-carnitines, urate, pyruvate metabolism, S1P, kynurenine relate to hemolysis and cardiorenal dysfunction, respond to transfusion.PMID:36824724 | PMC:PMC9948995 | DOI:10.1101/2023.02.13.528368

J Oncol. 2023 Feb 14;2023:3591758. doi: 10.1155/2023/3591758. eCollection 2023.ABSTRACTOBJECTIVES: Indoleamine 2,3-dioxygenase 1 (IDO1) acts as the key rate-limiting enzyme that converts tryptophan (Trp) to kynurenine (Kyn). Its activity was primarily induced by interferon-γ (IFN-γ), which was reported to play a role in the development of acute radiation-induced pneumonitis. In this study, we aimed to investigate the correlation between IDO1 activity and radiation-induced lung toxicity (RILT) in stage III nonsmall cell lung cancer (NSCLC) patients who were treated with chemoradiotherapy (CRT).MATERIALS AND METHODS: Systemic IDO1 activity was reflected by Kyn : Trp ratio. Plasma levels of Kyn and Trp in 113 stage III NSCLC patients were measured by high-performance liquid chromatography (HPLC) before the initiation of radiotherapy. Dynamic change of IDO1 activity was followed in 23 patients before, during, and after radiotherapy. We also used RNA sequencing (RNA-seq) data from the Cancer Genome Atlas Program (TCGA) database and performed gene set enrichment analysis (GSEA) to explore how IDO1 was involved in the development of RILT.RESULTS: 9.7% (11/113) of the whole group developed G3+ (greater than or equal to Grade 3) RILT. Preradiation IDO1 activity was significantly higher in patients who developed G3 + RILT than in nonG3 + RILT patients. (P = 0.029, AUC = 0.70). Univariate and multivariate analyses showed that high IDO1 activity was independently associated with the risk of G3 + RILT (P = 0.034). A predictive model combining both IDO1 activity and FEV1 was established for severe RILT and displayed a moderate predictive value (AUC = 0.83, P < 0.001). The incidence of G3 + RILT was 2.6% (1/38) in patients with an IDO activity ≤0.069 and FEV1 > 59.4%, and 50.0% (6/12) in those with an IDO activity >0.069 and FEV1 ≤ 59.4%. Of 23 patients with dynamic tracking, the IDO1 activity of postradiation was significantly lower than midradiation (P = 0.021), though no significant differences among the three time points were observed (P = 0.070). Bioinformatic analysis using RNA-seq data from 1014 NSCLC patients revealed that IDO mainly functioned in the inflammatory response instead of the late fibrosis process in NSCLC patients.CONCLUSION: High baseline IDO1 activity combined with unfavorable baseline FEV1 was predictive of severe RILT in unresectable stage III NSCLC patients. IDO1 might play a role in the acute inflammatory response. Finding effective interventions to alleviate RILT using IDO inhibitors is warranted in the future.PMID:36824664 | PMC:PMC9943611 | DOI:10.1155/2023/3591758

iScience. 2023 Jan 13;26(2):105965. doi: 10.1016/j.isci.2023.105965. eCollection 2023 Feb 17.ABSTRACTDespite the knowledge that protein translation and various metabolic reactions that create and sustain cellular life occur in the cytoplasm, the structural organization within the cytoplasm remains unclear. Recent models indicate that cytoplasm contains viscous fluid and elastic solid phases. We separated these viscous fluid and solid elastic compartments, which we call the cytosol and cytomatrix, respectively. The distinctive composition of the cytomatrix included structural proteins, ribosomes, and metabolome enzymes. High-throughput analysis revealed unique biosynthetic pathways within the cytomatrix. Enrichment of biosynthetic pathways in the cytomatrix indicated the presence of immobilized biocatalysis. Enzymatic immobilization and segregation can surmount spatial impediments, and the local pathway segregation may form cytoplasmic organelles. Protein translation was reprogrammed within the cytomatrix under the restriction of protein synthesis by drug treatment. The cytosol and cytomatrix are an elaborately interconnected network that promotes operational flexibility in healthy cells and the survival of malignant cells.PMID:36824274 | PMC:PMC9941065 | DOI:10.1016/j.isci.2023.105965

Front Nutr. 2023 Feb 7;10:1112497. doi: 10.3389/fnut.2023.1112497. eCollection 2023.ABSTRACTColored wheat has been recognized broadly for its nutritional value because of its natural content of the colorant anthocyanin. To investigate the reasons for the formation of the wheat grain color at maturity, metabolomic and transcriptomic analyses were performed on three different grain colors of wheat. Through metabolome analysis, 628 metabolites were identified. Of the 102 flavonoids, there are 9 kinds of anthocyanins related to color formation, mainly cyanidin and peonidin, and their metabolite content was the lowest in white-grain wheat. Among the genes associated with color formation, the structural gene TraesCS2D02G392900 in F3H with the bHLH transcription factor could elucidate the origin of wheat coloration. Multi-omics analysis showed that color formation is mainly influenced by the regulation of genes affecting anthocyanin and related synthesis. The results of this study may provide a theoretical basis for grain color formation at maturity and the nutritional and product development potential of colored wheat lines.PMID:36824168 | PMC:PMC9941320 | DOI:10.3389/fnut.2023.1112497

Allergy. 2023 Feb 23. doi: 10.1111/all.15690. Online ahead of print.ABSTRACTINTRODUCTION: Topical corticosteroids (TCS), used to treat atopic dermatitis (AD), have been associated with type 2 diabetes and osteoporosis in epidemiological studies, possibly explained by systemic absorption.OBJECTIVES: We examined whether intensive daily whole-body TCS treatment over two weeks followed by twice weekly application for four weeks could elicit insulin resistance and increase bone resorption in adults with AD.METHODS: A randomized parallel-group double-blind double-dummy non-corticosteroid-based active-comparator study design was completed in Copenhagen, Denmark. Thirty-six non-obese, non-diabetic adults with moderate-to-severe AD were randomized to whole-body treatment with betamethasone 17-valerate 0.1% plus a vehicle once daily or tacrolimus 0.1% twice daily after washout. Insulin sensitivity assessed by the hyperinsulinemic-euglycemic clamp combined with tracer infusions and biomarkers of bone formation (P1NP) and resorption (CTX) were evaluated at baseline, after two weeks of daily treatment and after further four weeks of twice-weekly maintenance treatment.RESULTS: AD severity improved with both treatments and systemic inflammation was reduced. After two weeks, we observed similar increase in peripheral insulin sensitivity with use of betamethasone (n=18) and tacrolimus (n=18). Bone resorption biomarker, CTX, was unchanged, while bone formation marker, P1NP, decreased after betamethasone treatment after both two and six weeks but remained unchanged in the tacrolimus arm.CONCLUSIONS: Whole-body treatment with TCS leads to systemic exposure but appears not to compromise glucose metabolism during short-term use, which may be a result of reduced systemic inflammatory activity. The negative impact on bone formation could be regarded an adverse effect of TCS.PMID:36824052 | DOI:10.1111/all.15690

BMC Cancer. 2023 Feb 23;23(1):183. doi: 10.1186/s12885-023-10656-1.ABSTRACTBACKGROUND: Breast cancer survivors face long-term sequelae compared to the general population, suggesting altered metabolic profiles after breast cancer. We used metabolomics approaches to investigate the metabolic differences between breast cancer patients and women in the general population, aiming to elaborate metabolic changes among breast cancer patients and identify potential targets for clinical interventions to mitigate long-term sequelae.METHODS: Serum samples were retrieved from 125 breast cancer cases recruited from the Chicago Multiethnic Epidemiologic Breast Cancer Cohort (ChiMEC), and 125 healthy controls selected from Chicago Multiethnic Prevention and Surveillance Study (COMPASS). We used liquid chromatography-high resolution mass spectrometry to obtain untargeted metabolic profiles and partial least squares discriminant analysis (PLS-DA) combined with fold change to select metabolic features associated with breast cancer. Pathway analyses were conducted using Mummichog to identify differentially enriched metabolic pathways among cancer patients. As potential confounders we included age, marital status, tobacco smoking, alcohol drinking, type 2 diabetes, and area deprivation index in our model. Random effects of residence for intercept was also included in the model. We further conducted subgroup analysis by treatment timing (chemotherapy/radiotherapy/surgery), lymph node status, and cancer stages.RESULTS: The entire study participants were African American. The average ages were 57.1 for cases and 58.0 for controls. We extracted 15,829 features in total, among which 507 features were eventually selected by our criteria. Pathway enrichment analysis of these 507 features identified three differentially enriched metabolic pathways related to prostaglandin, leukotriene, and glycerophospholipid. The three pathways demonstrated inconsistent patterns. Metabolic features in the prostaglandin and leukotriene pathways exhibited increased abundances among cancer patients. In contrast, metabolic intensity in the glycerolphospholipid pathway was deregulated among cancer patients. Subgroup analysis yielded consistent results. However, changes in these pathways were strengthened when only using cases with positive lymph nodes, and attenuated when only using cases with stage I disease.CONCLUSION: Breast cancer in African American women is associated with increase in serum metabolites involved in prostaglandin and leukotriene pathways, but with decrease in serum metabolites in glycerolphospholipid pathway. Positive lymph nodes and advanced cancer stage may strengthen changes in these pathways.PMID:36823587 | DOI:10.1186/s12885-023-10656-1

Arch Microbiol. 2023 Feb 24;205(3):97. doi: 10.1007/s00203-023-03439-6.ABSTRACTFor different breeds of dogs with acute diarrhea, the gut microbiota and metabolome profiles are unclear. This prospective observational study analyzed the gut microbiomes of poodles with acute diarrhea and Labrador retrievers with acute diarrhea based on 16S amplicon sequencing, with respective healthy dogs as controls. Fecal non-target metabolomics and metagenomics were performed on poodles with acute diarrhea. This study found that the diversity and structure of the microbial community differed significantly between the two breeds in cohorts of healthy dogs. Two breeds of dogs with acute diarrhea demonstrated different changes in microbial communities and metabolic functions. The metabolism of starch and sucrose was significantly decreased in dogs with acute diarrhea, which may be attributed to the reduced activity of dextran dextrinase. Non-targeted metabolomics identified 21 abnormal metabolic pathways exhibited by dogs with acute diarrhea, including starch, amino acid, bile acid metabolism, etc., and were closely related to specific intestinal flora. This study provided new insights into breed specificity and the development of dietary treatment strategy in canine gastrointestinal disease.PMID:36823480 | DOI:10.1007/s00203-023-03439-6

Environ Sci Pollut Res Int. 2023 Feb 24. doi: 10.1007/s11356-023-25965-y. Online ahead of print.ABSTRACTThe experiments were conducted in the Tibetan plateau environment, and the sewage treatment conditions were designed with ultraviolet (UV) irradiation for 5 min, 10 min, 30 min, and 180 min. The Illumina MiSeq high-throughput sequencing technology was used to analyze the microbiological and metabolomic patterns of the plateau sewage treatment at the experimental scale, and then the response mechanisms of microbial and nitrogen metabolism in sewage treatment were explored. The abundance of metabolism at the first level and global and overview maps at the second level were higher in the plateau environment than in other regions. The KEGG pathway shows the effect of UV on nitrogen metabolism and its aptitude to improving or inhibit it. The two main nitrogen removal processes are nitrification and dissimilatory nitrate reduction. This study reveals the response of activated sludge to UV radiation in a plateau environment from microbiological and metabolomic perspectives, providing ideas and perspectives for the study of water treatment system methods, as well as laying a valuable theoretical foundation for the enhancement of plateau sewage treatment capacity.PMID:36823464 | DOI:10.1007/s11356-023-25965-y

Nat Med. 2023 Feb 23. doi: 10.1038/s41591-023-02217-7. Online ahead of print.ABSTRACTFor decades, variability in clinical efficacy of the widely used inflammatory bowel disease (IBD) drug 5-aminosalicylic acid (5-ASA) has been attributed, in part, to its acetylation and inactivation by gut microbes. Identification of the responsible microbes and enzyme(s), however, has proved elusive. To uncover the source of this metabolism, we developed a multi-omics workflow combining gut microbiome metagenomics, metatranscriptomics and metabolomics from the longitudinal IBDMDB cohort of 132 controls and patients with IBD. This associated 12 previously uncharacterized microbial acetyltransferases with 5-ASA inactivation, belonging to two protein superfamilies: thiolases and acyl-CoA N-acyltransferases. In vitro characterization of representatives from both families confirmed the ability of these enzymes to acetylate 5-ASA. A cross-sectional analysis within the discovery cohort and subsequent prospective validation within the independent SPARC IBD cohort (n = 208) found three of these microbial thiolases and one acyl-CoA N-acyltransferase to be epidemiologically associated with an increased risk of treatment failure among 5-ASA users. Together, these data address a longstanding challenge in IBD management, outline a method for the discovery of previously uncharacterized gut microbial activities and advance the possibility of microbiome-based personalized medicine.PMID:36823301 | DOI:10.1038/s41591-023-02217-7