PubMed

Phytomedicine. 2023 Jan 11;111:154653. doi: 10.1016/j.phymed.2023.154653. Online ahead of print.ABSTRACTBACKGROUND: Xingpi Capsule (XP), a commercially available over-the-counter herbal medicine in China, plays a prominent role in treating diarrhea-predominant irritable bowel syndrome (IBS-D). Nevertheless, the potential mechanisms remain unclear.PURPOSE: This study aimed to investigate XP efficacy in IBS-D and elucidate the underlying molecular mechanisms.METHODS: A rat IBS-D model was established by senna decoction gavage combined with restraint stress and swimming exhaustion. The changes in rat body weight and stool were recorded daily. Colon pathological changes and the number of colonic goblet cells of rats were observed by hematoxylin-eosin (HE) staining and Alcian blue plus periodic acid-Schiff (AB-PAS) staining, respectively. The expression of Occludin, a tight-junction-associated protein, was examined via immunohistochemistry. Images of colonic microvilli were obtained by TEM. Western blotting (WB) was used to analyze the protein expression of the ASK1/P38 MAPK pathway. The composition of the rat intestinal microbiota was detected by 16S rRNA sequencing. Changes in colonic metabolites were evaluated by liquid chromatography-mass spectrometry (LC-MS). Changes in colon RNA expression were assessed by RNA sequencing (RNA-Seq). The nontoxic range of hypoxanthine (HPX) was screened by Cell Counting Kit-8 (CCK8), the cell model of human colonic epithelial cells (NCM460) induced by lipopolysaccharide (LPS) was established, and the effective concentration of HPX was screened by CCK8. After transfection of pcDNA3.1-MAP3K5, Hoechst 33,342 staining, flow cytometry to detect cell apoptosis, and immunofluorescence to detect the fluorescence changes of ASK1 and ZO-1. WB detection of ASK1/P38 MAPK pathway protein expression changes.RESULTS: XP increased the body weight of IBS-D patients and reduced the loose stool rate, loose stool index, and Bristo score. In addition, XP mitigated colon lesions, increased the number of goblet cells and the expression of Occludin, and prevented severe distortion and effacement of the microvillous structure. Specifically, 16S rRNA gene sequence analysis showed that XP decreased the abundance of Desulfurium and Prevotella 9 at the phylum and genus levels while increasing the abundance of Bacteroides at the genus level. RNA-Seq combined with WB validation showed that XP exerted antidiarrheal effects by inhibiting the ASK1/P38 MAPK signaling pathway. Additionally, XP also increased the relative expression level of the metabolite HPX, as revealed by untargeted metabolomics analysis. Impressively, the correlation analysis between 16S rRNA sequencing and LC-MS suggested that HPX and Prevotella 9 are negatively correlated, which indicated that XP might increase the content of HPX by reducing the abundance of Prevotella 9. Meanwhile, a negative correlation between HPX and ASK1 was indicated through RNA-Seq and LC-MS, which suggested that the inhibition of ASK1 (Map3k5) may be ascribed to the increase in HPX after XP treatment. In vitro experiments have proven that HPX can alleviate LPS-induced NCM460 damage, specifically manifested as enhancing cell viability, reducing cell apoptosis, increasing ZO-1 expression, reducing the fluorescence intensity of MAP3K5 in the model group, and inhibiting the expression of ASK1/P38 MAPK pathway proteins. The protective effect of HPX was reversed after transfection with pcDNA 3.1-MAP3K5, which fully demonstrated that the protective mechanism of HPX was achieved by inhibiting MAP3K5 and its downstream pathways.CONCLUSION: XP displayed multifaceted protection against IBS-D in rats by regulating the intestinal microbiota, increasing the relative expression level of HPX, a metabolite of the microbiota, and inhibiting the ASK1/P38 MAPK signaling pathway.PMID:36641976 | DOI:10.1016/j.phymed.2023.154653

Food Chem. 2023 Jan 10;410:135444. doi: 10.1016/j.foodchem.2023.135444. Online ahead of print.ABSTRACTAscorbic acid (AsA) inhibits wound healing in fresh-cut potatoes (FCP); however, the comprehensive regulatory mechanisms of the chemical during wound healing remain unclear. Here, physiobiochemical, transcriptomic, and metabolomic analyses were performed. In total, 685 differentially expressed genes (DEGs) and 1921 differentially accumulated metabolites (DAMs) were identified between control and AsA-treated samples. The level of the majority of DEGs expression and DAMs abundance in AsA-treated samples were similar to data of newly cut samples. The collective data indicated that the AsA treatment inhibited wound healing in FCPs by regulating glutathione metabolism, enhancing starch metabolism, and inhibiting phenylalanine metabolism, sucrose degradation, and fatty acid synthesis. Major genes and metabolites affected by AsA treatment included StGST, StPAL, StPHO1 and StLOX5, and starch, sucrose, and linoleic acid. AsA treatment increased starch content and amylase and lipoxygenase activity and decreased free fatty acid level. Our research provides fundamental insights into wound healing mechanisms in FCP.PMID:36641908 | DOI:10.1016/j.foodchem.2023.135444

J Gastroenterol Hepatol. 2023 Jan;38(1):5-6. doi: 10.1111/jgh.16098.NO ABSTRACTPMID:36641630 | DOI:10.1111/jgh.16098

Anal Chim Acta. 2023 Feb 1;1240:340741. doi: 10.1016/j.aca.2022.340741. Epub 2022 Dec 23.ABSTRACTSupercritical Fluid Chromatography (SFC), a high-throughput separation technique, has been widely applied as a promising routine method in pharmaceutical, pesticides, and metabolome analysis in the same way as conventional liquid chromatography and gas chromatography. Unified chromatography (UC), an advanced version of SFC, which applied gradient elution with mobile phase changing continuously from supercritical to subcritical and to liquid states, can further extend the SFC applications. UC mostly applying the popular mobile phase of 95%:5%/Methanol:Water with additives allows to analyze many hydrophilic compounds. However, many of phosphorylated metabolites or multi carboxylic acids show very poor peak shapes or even can't be eluted under UC conditions, thus hampering the UC's metabolome coverage. In this study, we proposed the first proof-of-concept of UC/HILIC, a novel strategy to extend the current UC metabolome coverage by employing an aqueous gradient right after the UC gradient on a single packed column in a single measurement. The proposed method showed significant improvement regarding the chromatographic performance and metabolome coverage, while still maintaining the precision and high throughput in comparison with conventional UC methods.PMID:36641155 | DOI:10.1016/j.aca.2022.340741

Gene. 2023 Jan 11:147195. doi: 10.1016/j.gene.2023.147195. Online ahead of print.ABSTRACTThe gamma amino butyric acid (GABA) is a chemical messenger and is essential for the health of the brain and muscles. Some lactic acid bacteria (LAB) have the potential to function as psychobiotic cultures because they can produce significant amounts of neuroactive compounds like GABA. Psychobiotics are known to alter bidirectional communication between the gastrointestinal tract and the central nervous system. In the present study, the Limosilactobacillus reuteri (L. reuteri) strain, isolated from human breast milk, was used to detect the GABA-producing glutamic acid decarboxylase (gad) gene and GABA production. PCR, HPLC and UHPLCQ-TOF- MS2 approaches were applied to identify the gad gene, GABA content, and bioactive compounds produced by the bacterial strain, respectively. Additionally, the whole genome was sequenced to better understand the strain's psychobiotic and technological genomic properties. The gadB and gadC genes were confirmed in plasmid 1 of the whole genome. The complete genome sequence of L. reuteri comprises the genome length of 2,087,202 bp with 51.6 percent of G+C content. The results indicate that L. reuteri can be used as a starter culture for the production of GABA-enriched functional foods as well as psychobiotics for health benefits.PMID:36641079 | DOI:10.1016/j.gene.2023.147195

Toxicol Appl Pharmacol. 2023 Jan 11:116378. doi: 10.1016/j.taap.2023.116378. Online ahead of print.ABSTRACTGinsenosides are the main bioactive constituents of Panax ginseng, which have been broadly studied in cancer treatment. Our previous studies have demonstrated that 3β-O-Glc-DM (C3DM), a biosynthetic ginsenoside, exhibited antitumor effects in several cancer cell lines with anti-colon cancer activity superior to ginsenoside 20(R)-Rg3 in vivo. However, the efficacy of C3DM on glioma has not been proved yet. In this study, the antitumor activities and underlying mechanisms of C3DM on glioma were investigated in vitro and in vivo. Cell viability, apoptosis, migration, FCM, IHC, RT-qPCR, quantitative proteomics, and western blotting were conducted to evaluate the effect of C3DM on glioma cells. ADP-Glo™ kinase assay was used to validate the interaction between C3DM and EGFR. Co-cultured assays, lactic acid kit, and spatially resolved metabolomics were performed to study the function of C3DM in regulating glioma microenvironment. Both subcutaneously transplanted syngeneic models and orthotopic models of glioma were used to determine the effect of C3DM on tumor growth in vivo. We found that C3DM dose-dependently induced apoptosis, and inhibited the proliferation, migration and angiogenesis of glioma cells. C3DM significantly inhibited tumor growth in both subcutaneous and orthotopic mouse glioma models. Moreover, C3DM attenuated the acidified glioma microenvironment and enhanced T-cell function. Additionally, C3DM inhibited the kinase activity of EGFR and influenced the EGFR/PI3K/AKT/mTOR signaling pathway in glioma. Overall, C3DM might be a promising candidate for glioma prevention and treatment.PMID:36641037 | DOI:10.1016/j.taap.2023.116378

Chemosphere. 2023 Jan 11:137830. doi: 10.1016/j.chemosphere.2023.137830. Online ahead of print.ABSTRACTUrinary biomonitoring delivers the most accurate environmental phenols exposure assessment. However, environmental phenol exposure-related biomarkers are required to improve risk assessment to understand the internal processes perturbed, which may link exposure to specific health outcomes. This study aimed to investigate the association between environmental phenols exposure and the metabolome of young adult females from India. Urinary metabolomics was performed using liquid chromatography-mass spectrometry. Environmental phenols-related metabolic biomarkers were investigated by comparing the low and high exposure of environmental phenols. Seven potential biomarkers, namely histidine, cysteine-s-sulfate, 12-KETE, malonic acid, p-hydroxybenzoic acid, PE (36:2), and PS (36:0), were identified, revealing that environmental phenol exposure altered the metabolic pathways such as histidine metabolism, beta-Alanine metabolism, glycerophospholipid metabolism, and other pathways. This study also conceived an innovative strategy for the early prediction of diseases by combining urinary metabolomics with machine learning (ML) algorithms. The differential metabolites' predictive accuracy by ML models was>80%. This is the first mass spectrometry-based metabolomics study on young adult females from India with environmental phenols exposure. The study is valuable in demonstrating multiple urine metabolic changes linked to environmental phenol exposure and a better understanding of the mechanisms behind environmental phenol-induced effects in young female adults.PMID:36640981 | DOI:10.1016/j.chemosphere.2023.137830

Sci Total Environ. 2023 Jan 11:161549. doi: 10.1016/j.scitotenv.2023.161549. Online ahead of print.ABSTRACTDue to the rising usage of plastics, plastic debris are present throughout marine ecosystems and detrimentally affects marine biota. Additionally, plastics likely result in elusive toxicity effects due to addition of plasticizers. The aim of the present study was to reveal the potential effects and mechanism of microplastics (MPs), di-(2-ethylhexyl) phthalate (DEHP) and copollution of MPs and DEHP (MPs-DEHP) on Peneaus vannamei (P. vannamei) juveniles regarding oxidative stress, transcriptomics and metabolomics. MPs, DEHP and MPs-DEHP significantly induced the activities of superoxide dismutase (SOD) and catalase (CAT); MPs and DEHP have an antagonistic effect for malondialdehyde (MDA); suggesting that disorders of the antioxidant defence systems. 13, 133 and 58 differentially expressed genes and 21, 82 and 39 differentially expressed metabolites were responsible for the distinction of MPs, DEHP and MPs-DEHP groups, respectively. The combination of transcriptomic and metabolomic analyses showed that MPs, DEHP and MPs-DEHP exposure disturbed amino acid and lipid metabolism, and further induced inflammatory responses and dysfunction of purine metabolism. Furthermore, the presence of MPs might alleviate the biotoxicity of DEHP in P. vannamei. These findings provide new insights into the single and combined toxicological effects of MPs and additives for marine biota.PMID:36640892 | DOI:10.1016/j.scitotenv.2023.161549

Bioresour Technol. 2023 Jan 11:128617. doi: 10.1016/j.biortech.2023.128617. Online ahead of print.ABSTRACTThe aim of this work was to assess the efficiency of freshwater green microalga, Chlorella sorokiniana for diclofenac sodium (DFS) removal, and metabolic response of alga to comprehend the metabolic pathways involved/affected during DFS decontamination. Results showed 91.51% removal of DFS could be achieved within 9 days of algal treatment along with recovery of enhanced value-added bioresources i.e. chlorophyll, carotenoids, and lipids from the spent biomass. DFS also had an effect on enzyme activity including superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (MDA). Furthermore, metabolomics profiling provided an in-depth insight into changes in the metabolic response of C. sorokiniana wherein DFS induced 32 metabolites in microalgae compared to unexposed-control. This study offers microalgae as a green option for DFS removal, and the metabolomics study complemented with DFS could be an approach to understand the stress-induced strategies of C. sorokiniana for concomitant value-added products recovery in presence of DFS.PMID:36640815 | DOI:10.1016/j.biortech.2023.128617

Ecotoxicol Environ Saf. 2023 Jan 12;251:114518. doi: 10.1016/j.ecoenv.2023.114518. Online ahead of print.ABSTRACTDental fluorosis (DF) is a widely prevalent disease caused by excessive fluoride with limited awareness of its underlying pathogenesis. Here, a pilot population study was conducted to explore the pathogenesis of DF from the perspective of intestinal microbiome changes, and verified it in animal experiments combining intestinal microbiome and metabolomics. A total of 23 children were recruited in 2017 in China and divided into DF (n = 9) and control (n = 14) groups (DFG and CG, respectively). The SD rat model was established by drinking water containing sodium fluoride (NaF). Gut microbiome profiles of children and rats were analyzed by16S rDNA V3-V4 sequencing, and the intestinal metabolomics analysis of rats was performed by LC-MS methods. The 16 S rDNA sequencing revealed that the gut microbiome composition was significantly perturbed in children in DFG compared to that in CG. Acidobacteria and Thermi were specifically observed in DFG and CG, respectively. Besides, 15 fecal microbiotas were significantly altered at the genus level in DFG. Furthermore, only the expression of annotated genes for pentose and glucuronate interconversion pathway was significant lower in DFG than that in CG (P = 0.04). Notably, in NaF-treated rats, we also observed the changes of some key components of pentose and glucuronate interconversion pathway at the level of microorganisms and metabolites. Our findings suggested that the occurrence of DF is closely related to the alteration of intestinal microorganisms and metabolites annotated in the pentose and glucuronate interconversion pathway.PMID:36640576 | DOI:10.1016/j.ecoenv.2023.114518

Cell Rep. 2022 Dec 30;42(1):111928. doi: 10.1016/j.celrep.2022.111928. Online ahead of print.ABSTRACTThe human population is aging, and the need for interventions to slow progression of age-related diseases (geroprotective interventions) is growing. Repurposing compounds already used clinically, usually at modified doses, allows rapid implementation of geroprotective pharmaceuticals. Here we find the anti-retroviral nucleoside reverse transcriptase inhibitor (NRTI) zidovudine robustly extends lifespan and health span in C. elegans, independent of electron transport chain impairment or ROS accumulation. Rather, zidovudine treatment modifies pyrimidine metabolism and transcripts related to proteostasis. Testing regulators of mitochondrial stress and proteostasis shows that lifespan extension is dependent on activating transcription factor 4 (ATF-4). ATF-4 regulates longevity induced by mitochondrial stress, specifically communication between mitochondrial and cytosolic translation. Translation is reduced in zidovudine-treated worms, also dependent on ATF-4. Finally, we show ATF-4-dependent lifespan extension induced by didanosine, another NRTI. Altogether, our work elucidates the geroprotective effects of NRTIs such as zidovudine in vivo, via reduction of translation and ATF-4.PMID:36640360 | DOI:10.1016/j.celrep.2022.111928

J Diabetes Investig. 2023 Jan 14. doi: 10.1111/jdi.13970. Online ahead of print.ABSTRACTType 2 diabetes results from a complex interaction between genetic and environmental factors. Precision medicine for type 2 diabetes using genetic data is expected to predict the risk of developing diabetes and complications and to predict the effects of medications and life-style intervention more accurately for individuals. Genome-wide association studies (GWAS) have been conducted in European and Asian populations and new genetic loci have been identified that modulate the risk of developing type 2 diabetes. Novel loci were discovered by GWAS in diabetic complications with increasing sample sizes. Large-scale genome-wide association analysis and polygenic risk scores using biobank information is making it possible to predict the development of type 2 diabetes. In the ADVANCE clinical trial of type 2 diabetes, a multi-polygenic risk score was useful to predict diabetic complications and their response to treatment. Proteomics and metabolomics studies have been conducted and have revealed the associations between type 2 diabetes and inflammatory signals and amino acid synthesis. Using multi-omics analysis, comprehensive molecular mechanisms have been elucidated to guide the development of targeted therapy for type 2 diabetes and diabetic complications.PMID:36639962 | DOI:10.1111/jdi.13970

Biotechnol Bioeng. 2023 Jan 13. doi: 10.1002/bit.28332. Online ahead of print.ABSTRACTAstaxanthin (AX) is a carotenoid pigment with antioxidant properties widely used as a feed supplement. Wild-type strains of Phaffia rhodozyma naturally produce low AX yields, but we increased AX yields 50-fold in previous research using random mutagenesis of P. rhodozyma CBS6938 and fermentation optimisation. On that study, genome changes were linked with phenotype, but relevant metabolic changes were not resolved. In this study, the wild-type and the superior P. rhodozyma mutant strains were grown in chemically defined media and instrumented fermenters. Differential kinetic, metabolomics, and transcriptomics data were collected. Our results suggest that carotenoid production was mainly associated with cell growth and had a positive regulation of central carbon metabolism metabolites, amino acids, and fatty acids. In the stationary phase, amino acids associated with the TCA cycle increased, but most of the fatty acids and central carbon metabolism metabolites decreased. TCA cycle metabolites were in abundance and media supplementation of citrate, malate, α-ketoglutarate, succinate, or fumarate increased AX production in the mutant strain. Transcriptomic data correlated with the metabolic and genomic data and found a positive regulation of genes associated with the electron transport chain suggesting this to be the main driver for improved AX production in the mutant strain. This article is protected by copyright. All rights reserved.PMID:36639843 | DOI:10.1002/bit.28332

Microbiome. 2023 Jan 13;11(1):9. doi: 10.1186/s40168-022-01429-2.ABSTRACTBACKGROUND: Celiac disease (CD) is an autoimmune disorder triggered by gluten consumption. Almost all CD patients possess human leukocyte antigen (HLA) DQ2/DQ8 haplotypes; however, only a small subset of individuals carrying these alleles develop CD, indicating the role of environmental factors in CD pathogenesis. The main objective of this study was to determine the contributory role of gut microbiota and microbial metabolites in CD onset. To this end, we obtained fecal samples from a prospective cohort study (ABIS) at ages 2.5 and 5 years. Samples were collected from children who developed CD after the final sample collection (CD progressors) and healthy children matched by age, HLA genotype, breastfeeding duration, and gluten-exposure time (n=15-16). We first used 16S sequencing and immunoglobulin-A sequencing (IgA-seq) using fecal samples obtained from the same children (i) 16 controls and 15 CD progressors at age 2.5 and (ii) 13 controls and 9 CD progressors at age 5. We completed the cytokine profiling, and plasma metabolomics using plasma samples obtained at age 5 (n=7-9). We also determined the effects of one microbiota-derived metabolite, taurodeoxycholic acid (TDCA), on the small intestines and immune cell composition in vivo.RESULTS: CD progressors have a distinct gut microbiota composition, an increased IgA response, and unique IgA targets compared to healthy subjects. Notably, 26 plasma metabolites, five cytokines, and one chemokine were significantly altered in CD progressors at age 5. Among 26 metabolites, we identified a 2-fold increase in TDCA. TDCA treatment alone caused villous atrophy, increased CD4+ T cells, Natural Killer cells, and two important immunoregulatory proteins, Qa-1 and NKG2D expression on T cells while decreasing T-regulatory cells in intraepithelial lymphocytes (IELs) in C57BL/6J mice.CONCLUSIONS: Pediatric CD progressors have a distinct gut microbiota composition, plasma metabolome, and cytokine profile before diagnosis. Furthermore, CD progressors have more IgA-coated bacteria and unique targets of IgA in their gut microbiota. TDCA feeding alone stimulates an inflammatory immune response in the small intestines of C57BJ/6 mice and causes villous atrophy, the hallmark of CD. Thus, a microbiota-derived metabolite, TDCA, enriched in CD progressors' plasma, has the potential to drive inflammation in the small intestines and enhance CD pathogenesis. Video Abstract.PMID:36639805 | DOI:10.1186/s40168-022-01429-2

Respir Res. 2023 Jan 13;24(1):15. doi: 10.1186/s12931-022-02297-y.ABSTRACTBACKGROUND: Chronic respiratory diseases are disorders of the airways and other structures of the lung, and include chronic obstructive pulmonary disease (COPD), lung cancer, asthma, bronchiectasis, interstitial lung diseases, occupational lung diseases and pulmonary hypertension. Through this article we take a broad view of chronic lung disease while highlighting (1) the complex interactions of lung diseases with environmental factors (e.g. climate change, smoking and vaping) and multimorbidity and (2) proposed areas to strengthen for better global patient outcomes.CONCLUSION: We suggest new directions for the research agenda in high-priority populations and those experiencing health disparities. We call for lung disease to be made a research priority with greater funding allocation globally.PMID:36639661 | DOI:10.1186/s12931-022-02297-y

Basic Res Cardiol. 2023 Jan 13;118(1):3. doi: 10.1007/s00395-022-00976-x.ABSTRACTRecent studies demonstrated that mitochondrial antioxidant MnSOD that reduces mitochondrial (mito) reactive oxygen species (ROS) helps maintain an optimal balance between sub-cellular ROS levels in coronary vascular endothelial cells (ECs). However, it is not known whether EC-specific mito-ROS modulation provides resilience to coronary ECs after a non-reperfused acute myocardial infarction (MI). This study examined whether a reduction in endothelium-specific mito-ROS improves the survival and proliferation of coronary ECs in vivo. We generated a novel conditional binary transgenic animal model that overexpresses (OE) mitochondrial antioxidant MnSOD in an EC-specific manner (MnSOD-OE). EC-specific MnSOD-OE was validated in heart sections and mouse heart ECs (MHECs). Mitosox and mito-roGFP assays demonstrated that MnSOD-OE resulted in a 50% reduction in mito-ROS in MHEC. Control and MnSOD-OE mice were subject to non-reperfusion MI surgery, echocardiography, and heart harvest. In post-MI hearts, MnSOD-OE promoted EC proliferation (by 2.4 ± 0.9 fold) and coronary angiogenesis (by 3.4 ± 0.9 fold), reduced myocardial infarct size (by 27%), and improved left ventricle ejection fraction (by 16%) and fractional shortening (by 20%). Interestingly, proteomic and Western blot analyses demonstrated upregulation in mitochondrial complex I and oxidative phosphorylation (OXPHOS) proteins in MnSOD-OE MHECs. These MHECs also showed increased mitochondrial oxygen consumption rate (OCR) and membrane potential. These findings suggest that mito-ROS reduction in EC improves coronary angiogenesis and cardiac function in non-reperfused MI, which are associated with increased activation of OXPHOS in EC-mitochondria. Activation of an energy-efficient mechanism in EC may be a novel mechanism to confer resilience to coronary EC during MI.PMID:36639609 | DOI:10.1007/s00395-022-00976-x

Sci Rep. 2023 Jan 13;13(1):696. doi: 10.1038/s41598-023-27401-0.ABSTRACTMetabolomics is a modern tool that aids in our understanding of the molecular changes in organisms. Archaeological science is a branch of archaeology that explores different archaeological materials using modern analytical tools. Human osteoarchaeological material are a frequent finding in archaeological contexts and have the potential to offer information about previous human populations, which can be illuminating about our current condition. Using a set of samples comprising different skeletal elements and bone structures, here we explore for the first time the possibility of extracting metabolites from osteoarchaeological material. Here, a protocol for extraction and measurement of extracted polar and less-polar/apolar metabolites by ultra-high performance liquid chromatography hyphenated to high resolution mass spectrometry is presented to measure the molecules separated after a reversed phase and hydrophilic interaction liquid chromatography column. Molecular information was obtained, showing that osteoarchaeological material is a viable source of molecular information for metabolomic studies.PMID:36639564 | DOI:10.1038/s41598-023-27401-0

J Cancer Res Clin Oncol. 2023 Jan 13. doi: 10.1007/s00432-023-04576-7. Online ahead of print.ABSTRACTBacteria have been found in tumors for over 100 years, but the irreproducibility of experiments on bacteria, the limitations of science and technology, and the contamination of the host environment have severely hampered most research into the role of bacteria in carcinogenesis and cancer treatment. With the development of molecular tools and techniques (e.g., macrogenomics, metabolomics, lipidomics, and macrotranscriptomics), the complex relationships between hosts and different microorganisms are gradually being deciphered. In the past, attention has been focused on the impact of the gut microbiota, the site where the body's microbes gather most, on tumors. However, little is known about the role of microbes from other sites, particularly the intratumor microbiota, in cancer. In recent years, an increasing number of studies have identified the presence of symbiotic microbiota within a large number of tumors, bringing the intratumor microbiota into the limelight. In this review, we aim to provide a better understanding of the role of the intratumor microbiota in cancer, to provide direction for future experimental and translational research, and to offer new approaches to the treatment of cancer and the improvement of patient prognosis.PMID:36639531 | DOI:10.1007/s00432-023-04576-7

Nat Commun. 2023 Jan 13;14(1):218. doi: 10.1038/s41467-023-35787-8.ABSTRACTFamilial dysautonomia (FD) is a rare genetic neurologic disorder caused by impaired neuronal development and progressive degeneration of both the peripheral and central nervous systems. FD is monogenic, with >99.4% of patients sharing an identical point mutation in the elongator acetyltransferase complex subunit 1 (ELP1) gene, providing a relatively simple genetic background in which to identify modifiable factors that influence pathology. Gastrointestinal symptoms and metabolic deficits are common among FD patients, which supports the hypothesis that the gut microbiome and metabolome are altered and dysfunctional compared to healthy individuals. Here we show significant differences in gut microbiome composition (16 S rRNA gene sequencing of stool samples) and NMR-based stool and serum metabolomes between a cohort of FD patients (~14% of patients worldwide) and their cohabitating, healthy relatives. We show that key observations in human subjects are recapitulated in a neuron-specific Elp1-deficient mouse model, and that cohousing mutant and littermate control mice ameliorates gut microbiome dysbiosis, improves deficits in gut transit, and reduces disease severity. Our results provide evidence that neurologic deficits in FD alter the structure and function of the gut microbiome, which shifts overall host metabolism to perpetuate further neurodegeneration.PMID:36639365 | DOI:10.1038/s41467-023-35787-8

J Dermatol Sci. 2023 Jan 7:S0923-1811(23)00001-4. doi: 10.1016/j.jdermsci.2023.01.001. Online ahead of print.ABSTRACTBACKGROUND: Radiation-induced skin injury is a serious concern during radiotherapy and accidental exposure to radiation.OBJECTIVE: This study aims to investigate the molecular events in early response to ionizing radiation of skin tissues and underlying mechanism.METHODS: Mice and rats were irradiated with an electron beam. Skin tissues were used for liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, mRNA-Seq and single-cell RNA sequencing (scRNA-Seq). Human keratinocytes (HaCaT) and skin fibroblasts (WS1) were used for functional studies.RESULTS: The integrated analysis of metabolomics and transcriptomics showed that 6 key fatty acid-associated metabolites, 9 key fatty acid-associated genes and multiple fatty acid-associated pathways were most obviously enriched and increased in the irradiated skins. Among them, acyl-CoA dehydrogenase very long chain (ACADVL) was investigated in greater detail due to its most obvious expression difference and significance in fatty acid metabolism. ScRNA-Seq of rat skin from irradiated individuals revealed that ACADVL was expressed in all subpopulations of skin tissues, with variations at different timepoints after radiation. Immunohistochemistry confirmed an increased ACADVL expression in the epidermis from human sample and various animal models, including monkeys, rats and mice. The knockdown of ACADVL increased the radiosensitivity of human keratinocytes and human skin fibroblasts. Silencing of ACADVL facilitated the expression of apoptosis and pyroptosis-related proteins following ionizing radiation.CONCLUSION: This study illustrated that cutaneous fatty acid metabolism was altered in the early response of ionizing radiation, and fatty acid metabolism-associated ACADVL is involved in radiation-induced cell death.PMID:36639278 | DOI:10.1016/j.jdermsci.2023.01.001