PubMed

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

J Lipid Res. 2023 Jan 10:100329. doi: 10.1016/j.jlr.2023.100329. Online ahead of print.ABSTRACTCoordinated lipid metabolism contributes to maintaining skin homeostasis by regulating skin barrier formation, immune reactions, thermogenesis, and perception. Several reports have documented the changes in lipid composition in dermatitis, including in atopic dermatitis (AD); however, the specific mechanism by which these lipid profiles are altered during AD pathogenesis remains unknown. Here, we performed untargeted and targeted lipidomic analyses of an AD-like dermatitis model resulting from constitutive activation of Jak1 (Spade mice) to capture the comprehensive lipidome profile during dermatitis onset and progression. We successfully annotated over 700 skin lipids, including glycerophospholipids, ceramides, neutral lipids, and fatty acids, many of which were found to be present at significantly changed levels after dermatitis onset, as determined by the pruritus and erythema. Among them, we found the levels of ceramides composed of non-hydroxy fatty acids and dihydrosphingosines (Cer[NDS]) containing very long-chain (C22 or more) fatty acids were significantly downregulated before AD onset. Furthermore, in vitro enzyme assays using the skin of Spade mice demonstrated the enhancement of ceramide desaturation. Finally, we reveal topical application of Cer[NDS] before AD onset effectively ameliorated the progression of AD symptoms in Spade mice. Our results suggest that the disruption in epidermal ceramide composition is caused by boosting ceramide desaturation in the initiation phase of AD, which regulates AD pathogenesis.PMID:36639058 | DOI:10.1016/j.jlr.2023.100329

J Adv Res. 2023 Jan 10:S2090-1232(23)00021-8. doi: 10.1016/j.jare.2023.01.008. Online ahead of print.ABSTRACTINTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea.OBJECTIVES: This in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored.METHODS: The histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota.RESULTS: TB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota.CONCLUSION: We find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.PMID:36639024 | DOI:10.1016/j.jare.2023.01.008

Biochem Pharmacol. 2023 Jan 10:115411. doi: 10.1016/j.bcp.2023.115411. Online ahead of print.ABSTRACTNervonic acid (NA) is one of the long-chain fatty acids with significant biological activity that has been widely studied in recent years. It is believed that NA may play a crucial role in the recovery of human cognitive disorders. Although many literatures have shown that NA has some neuroprotective effect in experimental animal models, the detailed neuroprotective mechanism of NA is still poorly understood. In this study, we applied behavioral, transcriptomic and metabolomic approaches to analyze the neuroprotective effect of NA and its molecular mechanism in AD (Alzheimer's disease) model mice. We demonstrated that NA improved motor skills and learning and memory abilities of mice at the behavioral level. To further understand the specific pathways involved in this protective effect, we applied the metabolomics and transcriptomics profilings and focused on the expression patterns of genes that NA might alter, particularly those related to the accumulation of metabolites in the brain. According to the results, pathways related to neuroinflammation were significantly increased in LPS (lipopolysaccharide)-induced AD mice compared with the normal control, and pathways related to neuronal growth and synaptic plasticity were significantly downregulated. When NA was used for protection, these signaling pathways induced by LPS were partially reversed. At the same time, compared with the AD model group, upregulation of arachidonic acid metabolism, purine metabolism, and primary bile acid biosynthesis and downregulation of amino acid metabolic pathways were particularly pronounced in the NA treatment group. We also verified the enzymes of some metabolic pathways were consistent with transcriptome result. In summary, our results show that NA can significantly ameliorate LPS-induced neuroinflammation and deterioration of learning and memory, and exerts a neuroprotective function through regulation of multiple gene transcription and metabolism pathways. In particular, the arachidonic acid metabolism which related to inflammation and the amino acids metabolism which related to the synthesis of neurotransmitters were most significant response to NA treatment. Our results provided the first preliminary evidences for molecular mechanism investigation of NA from a combined transcriptome and metabolome perspective.PMID:36639003 | DOI:10.1016/j.bcp.2023.115411

Eur J Pharm Sci. 2023 Jan 10:106378. doi: 10.1016/j.ejps.2023.106378. Online ahead of print.ABSTRACTColorectal cancer (CRC) is the most frequent form of gastrointestinal cancer and one of the major causes of human mortality worldwide. Many of the current CRC therapies have limitations due to multidrug resistance and/or severe side effects. Quinazoline derivatives are promising lead compounds with a wide range of pharmacological actions. In this study, the effect of seven synthesized 2,3-dihydroquinazolin-4(1H)-one analogues as potential anticancer agents against two CRC cell lines (HCT116 and SW480) was investigated using cell viability proliferation, migration, adhesion and invasion assays. A liquid chromatography-mass spectrometry (LC-MS/MS) metabolomics approach was used to identify the underlying biochemical pathways disturbed in treated-HCT116 cells. Cell viability proliferation assay revealed that four compounds (C2, C3, C5, and C7) had IC50 < 10 µM with C5 displaying the most potent cytotoxic effect (IC50 1.4 and 0.3 µM against HCT116 and SW480, respectively). Additionally, the compounds showed suppression of wound closure after 72 hr, and both C2 and C5 significantly decreased the number of adherent cells and suppressed HCT116 cells invasion. Metabolomics study revealed that C5 induced significant perturbations in the level of several metabolites including spermine, polyamines, glutamine, creatine and carnitine, and altered biochemical processes essential for cell proliferation and progression such as amino acids biosynthesis and metabolism, redox homeostasis, energy related processes (e.g., fatty acid oxidation, second Warburg like effect) and one-carbon metabolism. Our findings indicate that 2,3-dihydroquinazolin-4(1H)-one analogues, particularly C5, have promising anticancer properties, and shed light on the role of metabolomics in identifying new therapeutic targets and providing better understanding of the pathways altered in treated cancer cells.PMID:36638899 | DOI:10.1016/j.ejps.2023.106378

Transl Res. 2023 Jan 10:S1931-5244(23)00001-4. doi: 10.1016/j.trsl.2023.01.001. Online ahead of print.ABSTRACTPost-operative atrial fibrillation (POAF) is a common complication of coronary artery bypass grafting (CABG) procedures. However, the molecular mechanism of POAF remains poorly understood, hence the absence of effective prevention strategies. Here we used targeted metabolomics on pericardial fluid and serum samples from CABG patients to investigate POAF-associated metabolic alterations and related risk prediction of new-onset AF. Nine differential metabolites in various metabolic pathways were found in both pericardial fluid and serum samples from patients with POAF and without POAF. By using machine learning algorithms and regression models, a four-metabolite (aceglutamide, ornithine, methionine, and arginine) risk prediction model was constructed and showed accurate performance in predicting POAF in both discovery and validation sets. This work extends the metabolic insights of the cardiac microenvironment and blood in patients with POAF and paves the way for the use of targeted metabolomics for predicting POAF in patients with CABG surgery.PMID:36638862 | DOI:10.1016/j.trsl.2023.01.001

Microb Pathog. 2023 Jan 10:105985. doi: 10.1016/j.micpath.2023.105985. Online ahead of print.ABSTRACTTalaromycosis is a fatal mycosis caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). The pathogenic mechanisms of talaromycosis are still poorly understood. This work combined metabolomics, transcriptomics, and verification experiments in vivo and in vitro to detect metabolic profiles and differentially expressed genes (DEGs) in T. marneffei infected and uninfected macrophages to explore possible pathogenesis and underlying mechanisms. A total of 256 differential metabolites (117 up-regulated and 148 down-regulated) and 1320 DEGs (1286 up-regulated and 34 down-regulated) were identified between the two groups. Integrative metabolomics and transcriptomics analysis showed sphingolipid signaling pathway is the most influential. Verification experiments showed that compared with the control group, the production of sphingosine-1-phosphate (S1P) and the expression of the S1PR1, S1PR2, phosphor-PI3K, and phosphor-Akt genes involved in the sphingolipid signaling pathway have significantly increased in the T. marneffei infection group (p < 0.05). T. marneffei activates the S1PR2/PI3K/Akt pathways in J774A.1 macrophage, regulation of the S1P singling might serve as a promising therapeutic strategy for talaromycosis.PMID:36638850 | DOI:10.1016/j.micpath.2023.105985

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Jan 6;1216:123594. doi: 10.1016/j.jchromb.2023.123594. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is a rheumatic disease that easily causes synovial hyperplasia and joint damage. Comprehensive metabolomic profiling of synovial tissue can reveal local pathological changes during RA and identify metabolites as candidate biomarkers. Detecting metabolites in synovial tissue can more directly reflect the pathological state and disease activity associated with it. stir-fried Xanthii Fructus has demonstrated efficacy in treating RA, but its pharmacodynamic property and mechanism of action are unclear. In this study, the molecular composition of the extract of stir-fried Xanthium Fructus was determined through HPLC. The major components that exert anti-inflammatory and analgesic effects were speculated to be phenolic acids. Next, the effect of stir-fried Xanthii Fructus extracts in RA treatment was comprehensively evaluated using rat body weight, foot volume, inflammatory factors, and histopathological sections of the ankle joint as evaluation indicators. The results showed that the extract of stir-fried Xanthii Fructus could significantly reduce the inflammatory response and improve the degree of joint swelling and the imbalance between pro-inflammatory and anti-inflammatory in adjuvant arthritis rats. Finally, non-targeted metabolomics based on UPLC-Q-TOF/MS and multivariate statistical analysis were used to explore the changes of endogenous metabolites in synovium tissues and to search for potential biomarkers and related metabolic pathways in stir-fried Xanthii Fructus extract-treated AA rats. The results showed that stir-fried Xanthii Fructus mainly treated RA by regulating energy metabolism, hormone metabolism, amino acid metabolism and oxidative stress response in adjuvant arthritis rats. This study provides a theoretical basis for the mechanism of action of stir-fried Xanthii Fructus extract in treating RA.PMID:36638684 | DOI:10.1016/j.jchromb.2023.123594

Biomed Pharmacother. 2023 Jan 11;159:114244. doi: 10.1016/j.biopha.2023.114244. Online ahead of print.ABSTRACTObesity is a disorder with an increasing prevalence, which impairs the life quality of patients and intensifies societal health care costs. The development of safe and innovative prevention strategies and therapeutic approaches is thus of great importance. The complex pathophysiology of obesity involves multiple signaling pathways that influence energy metabolism in different tissues. The phosphatidylinositol 3-kinases (PI3K)/protein kinase B (AKT) pathway is critical for the metabolic homeostasis and its function in insulin-sensitive tissues is described in the context of health, obesity and obesity-related complications. The PI3K family participates in the regulation of diverse physiological processes including but not limited to cell growth, survival, differentiation, autophagy, chemotaxis, and metabolism depending on the cellular context. AKT is downstream of PI3K in the insulin signaling pathway, and promotes multiple cellular processes by targeting a plethora of regulatory proteins that control glucose and lipid metabolism. Natural products are essential for prevention and treatment of many human diseases, including obesity. Anti-obesity natural compounds effect multiple pathophysiological mechanisms involved in obesity development. Numerous recent preclinical studies reveal the advances in using plant secondary metabolites to target the PI3K/AKT signaling pathway for obesity management. In this paper the druggability of PI3K as a target for compounds with anti-obesity potential is evaluated. Perspectives on the strategies and limitations for clinical implementation of obesity management using natural compounds modulating the PI3K/AKT pathway are suggested.PMID:36638594 | DOI:10.1016/j.biopha.2023.114244

Ecotoxicol Environ Saf. 2023 Jan 11;251:114523. doi: 10.1016/j.ecoenv.2023.114523. Online ahead of print.ABSTRACTSaline-alkalinity is one of the important ecological parameter that has an impact function on the physiological metabolism, osmoregulation, survival, growth, development and distribution of teleost fish. Oreochromis mossambicus, a species of euryhaline that can withstand a wide variety of salinities, may be used as a research model animal in environmental studies. In order to detect the metabolism responses and mechanisms of different osmotic stresses tolerance in the gills of O. mossambicus, in present study, the metabolic responses of O. mossambicus subjected to salinity (25 g/L, S_S), alkalinity (4 g/L, A_S) and saline-alkalinity stress (salinity: 25 g/L, alkalinity: 4 g/L; SA_S) with the control environment (freshwater, C_S) were investigated by LC-MS/MS-based metabolomics. The metabolism results indicated that numerous metabolites were identified between the stress groups and the control group. In addition, under three osmotic stresses, the amino acid and carbohydrate metabolism, levels of amino acids, osmolytes and energy substances, such as L-lysine, arachidonic acid, docosahexaenoic acids, creatine and taurine, were significantly affected and changed in the metabolism of the gills of O. mossambicus. The metabolism data indicated that signal transduction and regulation pathways, including FoxO signaling pathway, mTOR signaling pathway and prolactin signaling pathway, were enriched in the gill during adaptation to high salinity, alkalinity and saline-alkalinity stress. The results of this study provide more comprehensive and reliable data for the osmotic pressure regulation mechanism and biological response of euryhaline teleost, and provide reliable scientific basis for the breeding and research of high salinity tolerance population, and further promote the development and utilization of saline-alkalinity water resources.PMID:36638565 | DOI:10.1016/j.ecoenv.2023.114523

Blood. 2023 Jan 13:blood.2022017514. doi: 10.1182/blood.2022017514. Online ahead of print.ABSTRACTHematopoietic stem cell (HSC) aging is accompanied by hematopoietic reconstitution dysfunction, including loss of regenerative and engraftment ability, myeloid differentiation bias and elevated risks of hematopoietic malignancies. Gut microbiota, a key regulator of host health and immunity, has been recently reported to impact hematopoiesis. However, there is currently limited empirical evidence elucidating the direct impact of gut microbiome on aging hematopoiesis. In this study, we performed fecal microbiota transplantation (FMT) from young mice to aged mice and observed significant increment in lymphoid differentiation and decrease in myeloid differentiation in aged recipient mice. Further, FMT from young mice rejuvenated aged HSCs with enhanced short-term and long-term hematopoietic repopulation capacity. Mechanistically, single-cell RNA sequencing deciphered that FMT from young mice mitigated inflammatory signals, upregulated FoxO signaling pathway and promoted lymphoid differentiation of HSCs during aging. Finally, integrated microbiome and metabolome analyses uncovered that FMT reshaped gut microbiota construction and metabolite landscape, and Lachnospiraceae and tryptophan-associated metabolites promoted the recovery of hematopoiesis and rejuvenated aged HSCs. Together, our study highlights the paramount importance of the gut microbiota in HSC aging and provides insights into therapeutic strategies for aging-related hematologic disorders.PMID:36638348 | DOI:10.1182/blood.2022017514

J Anim Sci. 2023 Jan 3;101:skac376. doi: 10.1093/jas/skac376.ABSTRACTPrevious studies investigated the biochemical basis of dark-cutting conditions at elevated muscle pH (above 6), but the molecular basis at slightly above normal pH (between 5.6 and 5.8) is still unclear. The objective was to determine protein and metabolite profiles to elucidate postmortem muscle darkening at slightly elevated pH. Loins were selected based on the criteria established in our laboratory before sample collections, such as pH less than 5.8, L* values (muscle lightness) less than 38, and not discounted by the grader (high-pH beef with dark color are discounted and not sold in retail stores). Six bright red loins (longissimus lumborum) at normal-pH (average pH = 5.57) and six dark-colored strip loins at slightly elevated pH (average pH = 5.70) from A maturity carcasses were obtained within 72-h postmortem from a commercial beef purveyor. Surface color, oxygen consumption, metmyoglobin reducing activity, protein, and metabolite profiles were determined on normal-pH and dark-colored steaks at slightly elevated pH. Enzymes related to glycogen metabolism and glycolytic pathways were more differently abundant than metabolites associated with these pathways. The results indicated that oxygen consumption and metmyoglobin reducing activity were greater (P < 0.05) in darker steaks than normal-pH steaks. Enzymes involved with glycogen catabolic pathways and glycogen storage disease showed lower abundance in dark beef. The tricarboxylic acid metabolite, aconitic acid, was overabundant in darker-colored beef than normal-pH beef, but glucose derivative metabolites were less abundant. The majority of glycogenolytic proteins and metabolites reported as overabundant in the previous dark-cutting studies at high pH (>6.4) also did not show significant differences in the current study. Therefore, our data suggest enzymes involved in glycogen metabolism, in part, create a threshold for muscle darkening than metabolites.PMID:36638080 | DOI:10.1093/jas/skac376

Biol Res Nurs. 2023 Jan 13:10998004221149959. doi: 10.1177/10998004221149959. Online ahead of print.ABSTRACTElectronic cigarette use is highest among adults of child-bearing age. Many parents that use electronic cigarettes believe that secondhand exposure of electronic cigarette vapors for their children is not dangerous and is less harmful than secondhand exposure to traditional cigarette smoke. These beliefs may prompt excessive secondhand exposure to electronic cigarette vapors for their children. Little research has been done to document exposure in children. The traditional biological method of exposure detection is through a blood draw, which is difficult and undesirable in children. The purpose of this study was to assess the feasibility of using saliva and exhaled breath condensate as non-invasive biomatrices for detecting secondhand electronic cigarette vapor exposure in children. In this cross-sectionally designed study, we recruited 22 children exposed to electronic cigarette vapors and 26 non-exposed between the ages of 4-12 years. We compared metabolic features across three biomatrices, blood, saliva, and exhaled breath condensate. We noted moderate to strong pairwise, sample-specific, and feature-specific adjusted correlations. Annotated features associated with direct and secondhand electronic cigarette exposure were noted. These results demonstrate that less invasive biomatrices may be used to detect features associated with secondhand electronic cigarette vapor exposure in children.PMID:36637872 | DOI:10.1177/10998004221149959