Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Work-family conflict and its related factors among emergency department physicians in China: A national cross-sectional study

Thu, 06/04/2023 - 12:00
Front Public Health. 2023 Mar 20;11:1092025. doi: 10.3389/fpubh.2023.1092025. eCollection 2023.ABSTRACTBACKGROUND: Work-family conflict is common among emergency department physicians. Identifying the factors associated with work-family conflict is key to reducing its negative impact on mental health and work attitudes. However, the work-family conflict of Chinese emergency department physicians and the related factors have been scarcely studied.OBJECTIVE: This study aimed to investigate the current status and related factors of work-family conflict among Chinese emergency department physicians.METHODS: A national cross-sectional study was conducted among emergency department physicians in China from June 2018 to August 2018. A standard questionnaire was used to investigate the demographic characteristics, work-related factors, and work-family conflict of emergency department physicians. The generalized linear regression analysis was used to identify the related factors of work-family conflict.RESULTS: A total of 10,457 licensed emergency department physicians participated in the study. The average score of work-family conflict among the enrolled emergency department physicians was 19.27 ± 3.94, and the prevalence of high levels of work-family conflict was 69.19%. The multivariable regression analysis showed that emergency physicians who were female (linear regression coefficient, -0.25; SE, 0.08; P = 0.002), older than 40 years (linear regression coefficient,-0.53; SE, 0.14; P < 0.001), and earning more than 4,000 CNY per month (e.g., 4,001~6,000 vs. ≤4,000 CNY: linear regression coefficient, -0.17; SE, 0.09; P = 0.04) had lower work-family conflicts. However, emergency department physicians who were married (linear regression coefficient, 0.37; SE, 0.11; P < 0.001), highly educated (linear regression coefficient, 0.46; SE, 0.10; P < 0.001), had a high technical title (e.g., intermediate vs. junior technical title: linear regression coefficient, 0.61; SE, 0.09; P < 0.001), worked in a high-grade hospital (e.g., tertiary hospital vs. emergency center: linear regression coefficient, 0.38; SE, 0.11; P < 0.001), had a higher frequency of night shifts (e.g., 6~10 night shifts per month vs. 0~5 night shifts per month: linear regression coefficient, 0.43; SE, 0.10; P < 0.001), self-perceived shortage of physicians in the department (linear regression coefficient, 2.22; SE, 0.08; P < 0.001), and experienced verbal abuse (linear regression coefficient, 1.48; SE, 0.10; P < 0.001) and physical violence (linear regression coefficient, 0.84; SE, 0.08; P < 0.001) in the workplace had higher work-family conflict scores.CONCLUSION: Most emergency department physicians in China experience a high-level work-family conflict. Hospital administrations are recommended to develop family-friendly workplace policies, establish a scientific shift system, and keep the number of emergency department physicians to meet the demand to reduce work-family conflict.PMID:37020815 | PMC:PMC10067613 | DOI:10.3389/fpubh.2023.1092025

Role of human milk oligosaccharide metabolizing bacteria in the development of atopic dermatitis/eczema

Thu, 06/04/2023 - 12:00
Front Pediatr. 2023 Mar 20;11:1090048. doi: 10.3389/fped.2023.1090048. eCollection 2023.ABSTRACTDespite affecting up to 20% of infants in the United States, there is no cure for atopic dermatitis (AD), also known as eczema. Atopy usually manifests during the first six months of an infant's life and is one predictor of later allergic health problems. A diet of human milk may offer protection against developing atopic dermatitis. One milk component, human milk oligosaccharides (HMOs), plays an important role as a prebiotic in establishing the infant gut microbiome and has immunomodulatory effects on the infant immune system. The purpose of this review is to summarize the available information about bacterial members of the intestinal microbiota capable of metabolizing HMOs, the bacterial genes or metabolic products present in the intestinal tract during early life, and the relationship of these genes and metabolic products to the development of AD/eczema in infants. We find that specific HMO metabolism gene sets and the metabolites produced by HMO metabolizing bacteria may enable the protective role of human milk against the development of atopy because of interactions with the immune system. We also identify areas for additional research to further elucidate the relationship between the human milk metabolizing bacteria and atopy. Detailed metagenomic studies of the infant gut microbiota and its associated metabolomes are essential for characterizing the potential impact of human milk-feeding on the development of atopic dermatitis.PMID:37020647 | PMC:PMC10069630 | DOI:10.3389/fped.2023.1090048

Circulating metabolic signatures of heart failure in precision cardiology

Thu, 06/04/2023 - 12:00
Precis Clin Med. 2023 Mar 14;6(1):pbad005. doi: 10.1093/pcmedi/pbad005. eCollection 2023 Mar.ABSTRACTPrecision cardiology aims to implement personalized health care and precise medical decisions based on the specific characteristics of individuals. Metabolic remodeling plays a causal role in the pathogenesis of heart failure (HF). Changes in metabolic pathways such as substrate preference, high-energy phosphate metabolism and amino acid metabolism, are involved in pathological structural remodeling and functional impairment. These metabolic alterations are usually not restricted in the cardiac tissue, but also manifest in circulation. In clinical practice, blood sample is routinely used for HF screening. Metabolomics is an emerging omics technology that provides an efficient way to acquire dynamic metabolic profiles in circulation. An increasing number of metabolic biomarkers have been implicated in disease progression, making it possible to fight HF in a more effective and precise way. This review summarizes the modern analytical techniques in metabolomics as well as emerging circulating metabolites during the pathogenesis of HF, aiming to provide new insights into the prevention, diagnosis and treatment of HF in the era of precision medicine.PMID:37020642 | PMC:PMC10068425 | DOI:10.1093/pcmedi/pbad005

Insights into the role of nucleotide methylation in metabolic-associated fatty liver disease

Thu, 06/04/2023 - 12:00
Front Immunol. 2023 Mar 20;14:1148722. doi: 10.3389/fimmu.2023.1148722. eCollection 2023.ABSTRACTMetabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by fatty infiltration of the liver. In recent years, the MAFLD incidence rate has risen and emerged as a serious public health concern. MAFLD typically progresses from the initial hepatocyte steatosis to steatohepatitis and then gradually advances to liver fibrosis, which may ultimately lead to cirrhosis and carcinogenesis. However, the potential evolutionary mechanisms still need to be clarified. Recent studies have shown that nucleotide methylation, which was directly associated with MAFLD's inflammatory grading, lipid synthesis, and oxidative stress, plays a crucial role in the occurrence and progression of MAFLD. In this review, we highlight the regulatory function and associated mechanisms of nucleotide methylation modification in the progress of MAFLD, with a particular emphasis on its regulatory role in the inflammation of MAFLD, including the regulation of inflammation-related immune and metabolic microenvironment. Additionally, we summarize the potential value of nucleotide methylation in the diagnosis and treatment of MAFLD, intending to provide references for the future investigation of MAFLD.PMID:37020540 | PMC:PMC10067741 | DOI:10.3389/fimmu.2023.1148722

Endogenous neural stem cells characterization using omics approaches: Current knowledge in health and disease

Wed, 05/04/2023 - 12:00
Front Cell Neurosci. 2023 Apr 5;17:1125785. doi: 10.3389/fncel.2023.1125785. eCollection 2023.ABSTRACTNeural stem cells (NSCs), an invaluable source of neuronal and glial progeny, have been widely interrogated in the last twenty years, mainly to understand their therapeutic potential. Most of the studies were performed with cells derived from pluripotent stem cells of either rodents or humans, and have mainly focused on their potential in regenerative medicine. High-throughput omics technologies, such as transcriptomics, epigenetics, proteomics, and metabolomics, which exploded in the past decade, represent a powerful tool to investigate the molecular mechanisms characterizing the heterogeneity of endogenous NSCs. The transition from bulk studies to single cell approaches brought significant insights by revealing complex system phenotypes, from the molecular to the organism level. Here, we will discuss the current literature that has been greatly enriched in the "omics era", successfully exploring the nature and function of endogenous NSCs and the process of neurogenesis. Overall, the information obtained from omics studies of endogenous NSCs provides a sharper picture of NSCs function during neurodevelopment in healthy and in perturbed environments.PMID:37091923 | PMC:PMC10113633 | DOI:10.3389/fncel.2023.1125785

Clinical efficacy of Yiqi Yangxue formula on knee osteoarthritis and unraveling therapeutic mechanism through plasma metabolites in rats

Wed, 05/04/2023 - 12:00
Front Genet. 2023 Apr 5;14:1096616. doi: 10.3389/fgene.2023.1096616. eCollection 2023.ABSTRACTObjective: To observe the clinical efficacy and safety of Yiqi Yangxue formula (YQYXF) on knee osteoarthritis (KOA), and to explore the underlying therapeutic mechanism of YQYXF through endogenous differential metabolites and their related metabolic pathways. Methods: A total of 61 KOA patients were recruited and divided into the treatment group (YQYXF, 30 cases) and the control group (celecoxib, Cxb, 31 cases). Effects of these two drugs on joint pain, swelling, erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) were observed, and their safety and adverse reactions were investigated. In animal experiments, 63 SD rats were randomly divided into normal control (NC) group, sham operation (sham) group, model (KOA) group, Cxb group, as well as low-dose (YL), medium-dose (YM), and high-dose groups of YQYXF (YH). The KOA rat model was established using a modified Hulth method. Ultra-high-performance liquid chromatography/Q Exactive HF-X Hybrid Quadrupole-Orbitrap Mass (UHPLC-QE-MS)-based metabolomics technology was used to analyze the changes of metabolites in plasma samples of rats. Comprehensive (VIP) >1 and t-test p < 0.05 conditions were used to screen the disease biomarkers of KOA, and the underlying mechanisms of YQYXF were explored through metabolic pathway enrichment analysis. The related markers of YQYXF were further verified by ELISA (enzyme-linked immunosorbent assay). Results: YQYXF can improve joint pain, swelling, range of motion, joint function, Michel Lequesen index of severity for osteoarthritis (ISOA) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, ESR, and CRP. No apparent adverse reactions were reported. In addition, YQYXF can improve cartilage damage in KOA rats, reverse the abnormal changes of 16 different metabolites, and exert an anti-KOA effect mainly through five metabolic pathways. The levels of reactive oxygen species (ROS) and glutathione (GSH) were significantly decreased after the treatment of YQYXF. Conclusion: YQYXF can significantly improve the clinical symptoms of KOA patients without obvious adverse reactions. It mainly improved KOA through modulating lipid metabolism-related biomarkers, reducing lipid peroxidation and oxidative stress.PMID:37091797 | PMC:PMC10113924 | DOI:10.3389/fgene.2023.1096616

Chronic alcohol administration alters metabolomic profile of murine bone marrow

Wed, 05/04/2023 - 12:00
Front Immunol. 2023 Apr 5;14:1128352. doi: 10.3389/fimmu.2023.1128352. eCollection 2023.ABSTRACTINTRODUCTION: People with hazardous alcohol use are more susceptible to viral, bacterial, and fungal infections due to the effect of alcohol on immune system cell function. Metabolized ethanol reduces NAD+ to NADH, affecting critical metabolic pathways. Here, our aim was to investigate whether alcohol is metabolized by bone marrow cells and if it impacts the metabolic pathways of leukocyte progenitor cells. This is said to lead to a qualitative and quantitative alteration of key metabolites which may be related to the immune response.METHODS: We addressed this aim by using C57BL/6 mice under chronic ethanol administration and evaluating the metabolomic profile of bone marrow total cells by gas chromatography-coupled mass spectrometry (GC-MS).RESULTS: We identified 19 metabolites. Our data demonstrated that chronic ethanol administration alters the metabolomic profile in the bone marrow, resulting in a statistically diminished abundance of five metabolites in ethanol-treated animals: uracil, succinate, proline, nicotinamide, and tyrosine.DISCUSSION: Our results demonstrate for the first time in the literature the effects of alcohol consumption on the metabolome content of hematopoietic tissue and open a wide range of further studies to investigate mechanisms by which alcohol compromises the cellular function of the immune system.PMID:37090737 | PMC:PMC10113543 | DOI:10.3389/fimmu.2023.1128352

Corrigendum: Protective effects of Mefunidone on ischemia-reperfusion injury/folic acid-induced acute kidney injury

Wed, 05/04/2023 - 12:00
Front Pharmacol. 2023 Apr 5;14:1188615. doi: 10.3389/fphar.2023.1188615. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fphar.2022.1043945.].PMID:37089951 | PMC:PMC10115130 | DOI:10.3389/fphar.2023.1188615

Vitamin C and vitamin D<sub>3</sub> alleviate metabolic-associated fatty liver disease by regulating the gut microbiota and bile acid metabolism <em>via</em> the gut-liver axis

Wed, 05/04/2023 - 12:00
Front Pharmacol. 2023 Apr 5;14:1163694. doi: 10.3389/fphar.2023.1163694. eCollection 2023.ABSTRACTBackground: Previous studies have demonstrated that both vitamin C (VC) and vitamin D3 (VD3) have therapeutic potential against metabolic disorders, including obesity, diabetes, and metabolic-associated fatty liver disease (MAFLD). However, it is unclear whether VC supplementation is associated with improving the intestinal flora and regulating the metabolism of bile acids via the gut-liver axis in MAFLD. There is still no direct comparison or combination study of these two vitamins on these effects. Methods: In this study, we employed biochemical, histological, 16S rDNA-based microbiological, non-targeted liver metabolomic, and quantitative real-time polymerase chain reaction analyses to explore the intervening effect and mechanism of VC and VD3 on MAFLD by using a high-fat diet (HFD)-induced obese mouse model. Results: Treatment of mice with VC and VD3 efficiently reversed the characteristics of MAFLD, such as obesity, dyslipidemia, insulin resistance, hepatic steatosis, and inflammation. VC and VD3 showed similar beneficial effects as mentioned above in HFD-induced obese mice. Interestingly, VC and VD3 reshaped the gut microbiota composition; improved gut barrier integrity; ameliorated oxidative stress and inflammation in the gut-liver axis; inhibited bile acid salt reflux-related ASBT; activated bile acid synthesis-related CYP7A1, bile acid receptor FXR, and bile acid transportation-related BSEP in the gut-liver axis; and improved bile secretion, thus decreasing the expression of FAS in the liver and efficiently ameliorating MAFLD in mice. Conclusion: Together, the results indicate that the anti-MAFLD activities of VC and VD3 are linked to improved gut-liver interactions via regulation of the gut microbiota and bile acid metabolism, and they may therefore prove useful in treating MAFLD clinically.PMID:37089915 | PMC:PMC10113476 | DOI:10.3389/fphar.2023.1163694

Corrigendum: Research progress and trends in metabolomics of fruit trees

Wed, 05/04/2023 - 12:00
Front Plant Sci. 2023 Apr 5;14:1192425. doi: 10.3389/fpls.2023.1192425. eCollection 2023.ABSTRACT[This corrects the article DOI: 10.3389/fpls.2022.881856.].PMID:37089659 | PMC:PMC10113609 | DOI:10.3389/fpls.2023.1192425

Assessment of transcriptional reprogramming of lettuce roots in response to chitin soil amendment

Wed, 05/04/2023 - 12:00
Front Plant Sci. 2023 Apr 5;14:1158068. doi: 10.3389/fpls.2023.1158068. eCollection 2023.ABSTRACTChitin soil amendment is known to improve soil quality, plant growth and stress resilience, but the underlying mechanisms are not well understood. In this study, we monitored chitin's effect on lettuce physiology every two weeks through an eight-week growth period, analyzed the early transcriptional reprogramming and related metabolomic changes of lettuce, in response to crab chitin treatment in peat-based potting soil. In commercial growth conditions, chitin amendment still promoted lettuce growth, increased chlorophyll content, the number of leaves and crop head weight from week six. The flavonoid content in lettuce leaves was altered as well, showing an increase at week two but a decrease from week six. Transcriptomic analysis showed that over 300 genes in lettuce root were significantly differentially expressed after chitin soil treatment. Gene Ontology-term (GO) enrichment analysis revealed statistical overrepresentation of GO terms linked to photosynthesis, pigment metabolic process and phenylpropanoid metabolic process. Further analysis of the differentially expressed genes (DEGs) showed that the flavonoid pathway was mostly upregulated whereas the bifurcation of upstream phenylpropanoid pathway towards lignin biosynthesis was mostly downregulated. Metabolomic analysis revealed the upregulation of salicylic acid, chlorogenic acid, ferulic acid, and p-coumaric acid in chitin-treated lettuce seedlings. These phenolic compounds (PCs) mainly influence the phenylpropanoid biosynthesis pathway and may play important roles in plant defense reactions. Our results suggest that chitin soil amendments might activate induced resistance by priming lettuce plants and promote lettuce growth via transcriptional changes.PMID:37089656 | PMC:PMC10115174 | DOI:10.3389/fpls.2023.1158068

The structure of biodegradable surfactants shaped the microbial community, antimicrobial resistance, and potential for horizontal gene transfer

Wed, 05/04/2023 - 12:00
Water Res. 2023 Apr 5;236:119944. doi: 10.1016/j.watres.2023.119944. Online ahead of print.ABSTRACTWhile most household surfactants are biodegradable in aerobic conditions, their biodegradability may obscure their environmental risks. The presence of surfactants in a biological treatment process can lead to the proliferation of antimicrobial-resistance genes (ARG) in the biomass. Surfactants can be cationic, anionic, or zwitterionic, and these different classes may have different effects on the proliferation ARG. Cationic hexadecyltrimethyl-ammonium (CTAB), anionic sodium dodecyl sulfate (SDS), and zwitterionic 3-(decyldimethylammonio)-propanesulfonate inner salt (DAPS) were used to represent the three classes of surfactants in domestic household clean-up products. This study focused on the removal of these surfactants by the O2-based Membrane Biofilm Reactor (O2-MBfR) for hotspot scenarios (∼1 mM) and how the three classes of surfactants affected the microbial community's structure and ARG. Given sufficient O2 delivery, the MBfR provided at least 98% surfactant removal. The presence and biodegradation for each surfactant uniquely shaped the biofilms' microbial communities and the presence of ARG. CTAB had by far the strongest impact and the higher ARG abundance. In particular, Pseudomonas and Stenotrophomonas, the two main genera in the biofilm treating CTAB, were highly correlated to the abundance of ARG for efflux pumps and antibiotic inactivation. CTAB also led to more functional genes relevant to the Type-IV secretion system and protection against oxidative stress, which also could encourage horizontal gene transfer. Our findings highlight that the biodegradation of quaternary ammonium surfactants, while beneficial, can pose public health concerns from its ability to promote the proliferation of ARG.PMID:37087920 | DOI:10.1016/j.watres.2023.119944

Effect of pentobarbital as a euthanasia agent on equine in vitro embryo production

Wed, 05/04/2023 - 12:00
Theriogenology. 2023 Apr 5;205:1-8. doi: 10.1016/j.theriogenology.2023.04.002. Online ahead of print.ABSTRACTPostmortem and pre-euthanasia oocyte retrieval provides the last opportunity to preserve the genetic material in mares. Pentobarbital (PB) is the most common euthanasia agent; however, its effect on the developmental competence of oocytes has not been determined. Here, we evaluated the concentration of PB in equine follicular fluid (FF) and investigated its effect on the developmental competence of oocytes using a bovine IVF model to overcome the low availability of equine oocytes. The concentration of PB was measured by gas-chromatography/mass-spectrometry in FF collected from mare ovaries immediately after euthanasia (n = 10), 24 h post-euthanasia (n = 10), and from the ovaries collected by ovariectomy (negative control; n = 10). The serum concentration of PB was also evaluated as a positive control. PB was detected in all FF samples with an average concentration of 56.5 μg/ml. Next, bovine cumulus-oocyte complexes (COC) were held in holding media with PB for 6 h at 60 μg/ml (H60, n = 196), 164 μg/ml (H164, n = 215) or without PB (control; n = 212). After holding, the oocytes were matured and fertilized in vitro, followed by in vitro culture to the blastocyst stage. The cumulus expansion grade, cleavage rate, blastocyst rate, embryo kinetic rate and the blastocyst cell numbers were compared among the experimental groups of bovine COC. Higher rates of Grade 1 cumulus expansion were found in controls (54%, 32-76%; median, min-max) in comparison to H60 and H164 (24%,11-33% and 13%, 8-44%; P < 0.001). The cleavage rate was higher in the controls than in H164 (64% vs. 44%; P < 0.01). Blastocyst rates (blastocyst/cleaved oocytes) and total cell number were not different among the groups (control 29%, H60 25%, and H164 24%). In a preliminary study, equine oocytes (n = 28) were exposed to PB in vitro for 6 h followed by intracytoplasmic sperm injection (ICSI) and in vitro embryo production. Exposed oocytes showed a numerically lower maturation rate (43% Vs 52%; P > 0.05) in comparison to the laboratory-established rate during the same timepoints. Overall, we showed that PB reaches the FF immediately after euthanasia, exposing oocytes to this drug. This exposure affected cumulus expansion and cleavage rates in a bovine model, suggesting initial damage caused by PB that may not completely impede the formation of embryos, although lower overall embryo numbers might be obtained.PMID:37084499 | DOI:10.1016/j.theriogenology.2023.04.002

LncRNA RP11-620J15.3 promotes HCC cell proliferation and metastasis by targeting miR-326/GPI to enhance glycolysis

Wed, 05/04/2023 - 12:00
Biol Direct. 2023 Apr 5;18(1):15. doi: 10.1186/s13062-023-00370-0.ABSTRACTBACKGROUND: Accumulating studies have demonstrated that the Warburg effect plays a central role in the occurrence and development of hepatocellular carcinoma (HCC), albeit the role of non-coding RNA (lncRNA) in its association remains unclear.METHODS: The Zhengzhou University People's Hospital kindly provided 80 pairs of HCC tissues and their matched paracancerous tissues for this study. Bioinformatics analysis, real-time quantitative polymerase chain reaction, Western blotting, and oncology functional assays were performed to determine the contribution of RP11-620J15.3 to the development of HCC. The mechanism of co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how RP11-620J15.3 interacts with important molecular targets.RESULTS: Our results revealed that a lncRNA termed RP11-620J15.3 was overexpressed in HCC and was substantially associated with the tumor size. A high expression of RP11-620J15.3 mRNA was found to be significantly associated with worsening prognosis in HCC patients. We discovered that RP11-620J15.3 stimulated the glycolytic pathway in HCC cells by RNA-sequencing (RNA-seq) and metabolomics analyses. Mechanistically, RP11-620J15.3 acted as a competitive endogenous RNA to regulate the GPI expression by sponging miR-326 in HCC. In addition, TBP acted as a transcription factor for RP11-620J15.3, which contributed to the high expression of RP11-620J15.3 in HCC cells.CONCLUSION: Based on our findings, lncRNA RP11-620J15.3 is a novel LncRNA that positively regulates tumor progression. Specifically, RP11-620J15.3/miR-326/GPI pathway promotes HCC malignant progression by regulating glycolysis, thereby providing novel targets for HCC treatment and drug development.PMID:37020316 | DOI:10.1186/s13062-023-00370-0

Exploring the aging process of cognitively healthy adults by analyzing cerebrospinal fluid metabolomics using liquid chromatography-tandem mass spectrometry

Wed, 05/04/2023 - 12:00
BMC Geriatr. 2023 Apr 5;23(1):217. doi: 10.1186/s12877-023-03939-6.ABSTRACTBACKGROUND: During biological aging, significant metabolic dysregulation in the central nervous system may lead to cognitive decline and neurodegeneration. However, the metabolomics of the aging process in cerebrospinal fluid (CSF) has not been thoroughly explored.METHODS: In this cohort study of CSF metabolomics using liquid chromatography-mass spectrometry (LC-MS), fasting CSF samples collected from 92 cognitively unimpaired adults aged 20-87 years without obesity or diabetes were analyzed.RESULTS: We identified 37 metabolites in these CSF samples with significant positive correlations with aging, including cysteine, pantothenic acid, 5-hydroxyindoleacetic acid (5-HIAA), aspartic acid, and glutamate; and two metabolites with negative correlations, asparagine and glycerophosphocholine. The combined alterations of asparagine, cysteine, glycerophosphocholine, pantothenic acid, sucrose, and 5-HIAA showed a superior correlation with aging (AUC = 0.982). These age-correlated changes in CSF metabolites might reflect blood-brain barrier breakdown, neuroinflammation, and mitochondrial dysfunction in the aging brain. We also found sex differences in CSF metabolites with higher levels of taurine and 5-HIAA in women using propensity-matched comparison.CONCLUSIONS: Our LC-MS metabolomics of the aging process in a Taiwanese population revealed several significantly altered CSF metabolites during aging and between the sexes. These metabolic alterations in CSF might provide clues for healthy brain aging and deserve further exploration.PMID:37020298 | DOI:10.1186/s12877-023-03939-6

Exploring the association of physical activity with the plasma and urine metabolome in adolescents and young adults

Wed, 05/04/2023 - 12:00
Nutr Metab (Lond). 2023 Apr 5;20(1):23. doi: 10.1186/s12986-023-00742-3.ABSTRACTBACKGROUND: Regular physical activity elicits many health benefits. However, the underlying molecular mechanisms through which physical activity influences overall health are less understood. Untargeted metabolomics enables system-wide mapping of molecular perturbations which may lend insights into physiological responses to regular physical activity. In this study, we investigated the associations of habitual physical activity with plasma and urine metabolome in adolescents and young adults.METHODS: This cross-sectional study included participants from the DONALD (DOrtmund Nutritional and Anthropometric Longitudinally Designed) study with plasma samples n = 365 (median age: 18.4 (18.1, 25.0) years, 58% females) and 24 h urine samples n = 215 (median age: 18.1 (17.1, 18.2) years, 51% females). Habitual physical activity was assessed using a validated Adolescent Physical Activity Recall Questionnaire. Plasma and urine metabolite concentrations were determined using ultra-high-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) methods. In a sex-stratified analysis, we conducted principal component analysis (PCA) to reduce the dimensionality of metabolite data and to create metabolite patterns. Multivariable linear regression models were then applied to assess the associations between self-reported physical activity (metabolic equivalent of task (MET)-hours per week) with single metabolites and metabolite patterns, adjusted for potential confounders and controlling the false discovery rate (FDR) at 5% for each set of regressions.RESULTS: Habitual physical activity was positively associated with the "lipid, amino acids and xenometabolite" pattern in the plasma samples of male participants only (β = 1.02; 95% CI: 1.01, 1.04, p = 0.001, adjusted p = 0.042). In both sexes, no association of physical activity with single metabolites in plasma and urine and metabolite patterns in urine was found (all adjusted p > 0.05).CONCLUSIONS: Our explorative study suggests that habitual physical activity is associated with alterations of a group of metabolites reflected in the plasma metabolite pattern in males. These perturbations may lend insights into some of underlying mechanisms that modulate effects of physical activity.PMID:37020289 | DOI:10.1186/s12986-023-00742-3

Isha yoga practices, vegan diet, and participation in Samyama meditation retreat: impact on the gut microbiome &amp; metabolome - a non-randomized trial

Wed, 05/04/2023 - 12:00
BMC Complement Med Ther. 2023 Apr 5;23(1):107. doi: 10.1186/s12906-023-03935-8.ABSTRACTBACKGROUND: Growing evidence suggests a role for gut bacteria and their metabolites in host-signaling responses along the gut-brain axis which may impact mental health. Meditation is increasingly utilized to combat stress, anxiety, and depression symptoms. However, its impact on the microbiome remains unclear. This study observes the effects of preparation and participation in an advanced meditation program (Samyama) implemented with a vegan diet including 50% raw foods, on gut microbiome and metabolites profiles.METHODS: There were 288 subjects for this study. Stool samples were collected at 3-time points for meditators and household controls. Meditators prepared for 2 months for the Samyama, incorporating daily yoga and meditation practices with a vegan diet including 50% raw foods. Subjects were requested to submit stool samples for 3 time points - 2 months before Samyama (T1), right before Samyama (T2), and 3 months following Samyama (T3). 16 s rRNA sequencing was used to study participants' microbiome. Alpha and beta diversities along with short-chain fatty acid (SCFA) were assessed. Metabolomics were performed on a mass spectrometer coupled to a UHLPC system and analyzed by El-MAVEN software.RESULTS: Alpha diversity showed no significant differences between meditators and controls, while beta diversity showed significant changes (padj = 0.001) after Samyama in meditators' microbiota composition. After the preparation phase, changes in branched short-chain fatty acids, higher levels of iso-valerate (padj = 0.02) and iso-buytrate (padj = 0.019) were observed at T2 in meditators. Other metabolites were also observed to have changed in meditators at timepoint T2.CONCLUSION: This study examined the impact of an advanced meditation program combined with a vegan diet on the gut microbiome. There was an increase in beneficial bacteria even three months after the completion of the Samyama program. Further study is warranted to validate current observations and investigate the significance and mechanisms of action related to diet, meditation, and microbial composition and function, on psychological processes, including mood.TRIAL REGISTRATION: Registration number: NCT04366544 ; Registered on 29/04/2020.PMID:37020274 | DOI:10.1186/s12906-023-03935-8

Author Correction: Uncovering mechanisms of global ocean change effects on the Dungeness crab (Cancer magister) through metabolomics analysis

Wed, 05/04/2023 - 12:00
Sci Rep. 2023 Apr 5;13(1):5569. doi: 10.1038/s41598-023-30370-z.NO ABSTRACTPMID:37019945 | DOI:10.1038/s41598-023-30370-z

Counteracting gemcitabine+nab-paclitaxel induced dysbiosis in KRAS wild type and KRAS<sup>G12D</sup> mutated pancreatic cancer in vivo model

Wed, 05/04/2023 - 12:00
Cell Death Discov. 2023 Apr 5;9(1):116. doi: 10.1038/s41420-023-01397-y.ABSTRACTPancreatic cancer (PC) has a very low survival rate mainly due to late diagnosis and refractoriness to therapies. The latter also cause adverse effects negatively affecting the patients' quality of life, often requiring dose reduction or discontinuation of scheduled treatments, compromising the chances of cure. We explored the effects of a specific probiotic blend on PC mice xenografted with KRAS wild-type or KRASG12D mutated cell lines alone or together with gemcitabine+nab-paclitaxel treatment to then assess tumor volume and clinical pathological variables. Beside a semi-quantitative histopathological evaluation of murine tumor and large intestine samples, histochemical and immunohistochemical analyses were carried out to evaluate collagen deposition, proliferation index Ki67, immunological microenvironment tumor-associated, DNA damage markers and also mucin production. Blood cellular and biochemical parameters and serum metabolomics were further analyzed. 16S sequencing was performed to analyze the composition of fecal microbiota. Gemcitabine+nab-paclitaxel treatment impaired gut microbial profile in KRAS wild-type and KRASG12D mice. Counteracting gemcitabine+nab-paclitaxel- induced dysbiosis through the administration of probiotics ameliorated chemotherapy side effects and decreased cancer-associated stromatogenesis. Milder intestinal damage and improved blood count were also observed upon probiotics treatment as well as a positive effect on fecal microbiota, yielding an increase in species richness and in short chain fatty acids producing- bacteria. Mice' serum metabolomic profiles revealed significant drops in many amino acids upon probiotics administration in KRAS wild-type mice while in animals transplanted with PANC-1 KRASG12D mutated all treated groups showed a sharp decline in serum levels of bile acids with respect to control mice. These results suggest that counteracting gemcitabine+nab-paclitaxel-induced dysbiosis ameliorates chemotherapy side effects by restoring a favorable microbiota composition. Relieving adverse effects of the chemotherapy through microbiota manipulation could be a desirable strategy in order to improve pancreatic cancer patients' quality of life and to increase the chance of cure.PMID:37019893 | DOI:10.1038/s41420-023-01397-y

Impact of nanopesticide CuO-NPs and nanofertilizer CeO<sub>2</sub>-NPs on wheat Triticum aestivum under global warming scenarios

Wed, 05/04/2023 - 12:00
Chemosphere. 2023 Apr 3:138576. doi: 10.1016/j.chemosphere.2023.138576. Online ahead of print.ABSTRACTConcurrent effect of nanomaterials (NMs) and warming on plant performance remains largely unexplored. In this study, the effects of nanopesticide CuO and nanofertilizer CeO2 on wheat (Triticum aestivum) under optimal (22 °C) and suboptimal (30 °C) temperatures were evaluated. CuO-NPs exerted a stronger negative effect on plant root systems than CeO2-NPs at tested exposure levels. The toxicity of both NMs could be attributed to altered nutrient uptake, induced membrane damage, and raised disturbance of antioxidative related biological pathways. Warming significantly inhibited root growth, which was mainly linked to the disturbance of energy metabolism relevant biological pathways. The toxicity of NMs was enhanced upon warming, with a stronger inhibition of root growth and Fe and Mn uptake. Increasing temperature increased the accumulation of Ce upon CeO2-NP exposure, while the accumulation of Cu was not affected. The relative contribution of NMs and warming to their combined effects was evaluated by comparing disturbed biological pathways under single and multiple stressors. CuO-NPs was the dominant factor inducing toxic effects, while both CeO2-NPs and warming contributed to the mixed effect. Our study revealed the importance of carefully considering global warming as a factor in risk assessment of agricultural applications of NMs.PMID:37019396 | DOI:10.1016/j.chemosphere.2023.138576

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