PubMed

Elife. 2023 May 15;12:e85410. doi: 10.7554/eLife.85410. Online ahead of print.ABSTRACTFor at least two centuries, scientists have been enthralled by the 'zombie' behaviors induced by mind-controlling parasites. Despite this interest, the mechanistic bases of these uncanny processes have remained mostly a mystery. Here, we leverage the recently established Entomophthora muscae-Drosophila melanogaster 'zombie fly' system to reveal the molecular and cellular underpinnings of summit disease, a manipulated behavior evoked by many fungal parasites. Using a new, high-throughput behavior assay to measure summiting, we discovered that summiting behavior is characterized by a burst of locomotion and requires the host circadian and neurosecretory systems, specifically DN1p circadian neurons, pars intercerebralis to corpora allata projecting (PI-CA) neurons and corpora allata (CA), who are solely responsible for juvenile hormone (JH) synthesis and release. Summiting is a fleeting phenomenon, posing a challenge for physiological and biochemical experiments requiring tissue from summiting flies. We addressed this with a machine learning classifier to identify summiting animals in real time. PI-CA neurons and CA appear to be intact in summiting animals, despite E. muscae cells invading the host brain, particularly in the superior medial protocerebrum (SMP), the neuropil that contains DN1p axons and PI-CA dendrites. The blood-brain barrier of flies late in their infection was significantly permeabilized, suggesting that factors in the hemolymph may have greater access to the central nervous system during summiting. Metabolomic analysis of hemolymph from summiting flies revealed differential abundance of several compounds compared to non-summiting flies. Transfusing the hemolymph of summiting flies into non-summiting recipients induced a burst of locomotion, demonstrating that factor(s) in the hemolymph likely cause summiting behavior. Altogether, our work reveals a neuro-mechanistic model for summiting wherein fungal cells perturb the fly's hemolymph, activating the neurohormonal pathway linking clock neurons to juvenile hormone production in the CA, ultimately inducing locomotor activity in their host.PMID:37184212 | DOI:10.7554/eLife.85410

Aging Cell. 2023 May 15:e13868. doi: 10.1111/acel.13868. Online ahead of print.ABSTRACTIdentifying metabolic biomarkers of frailty, an age-related state of physiological decline, is important for understanding its metabolic underpinnings and developing preventive strategies. Here, we systematically examined 168 nuclear magnetic resonance-based metabolomic biomarkers and 32 clinical biomarkers for their associations with frailty. In up to 90,573 UK Biobank participants, we identified 59 biomarkers robustly and independently associated with the frailty index (FI). Of these, 34 associations were replicated in the Swedish TwinGene study (n = 11,025) and the Finnish Health 2000 Survey (n = 6073). Using two-sample Mendelian randomization, we showed that the genetically predicted level of glycoprotein acetyls, an inflammatory marker, was statistically significantly associated with an increased FI (β per SD increase = 0.37%, 95% confidence interval: 0.12-0.61). Creatinine and several lipoprotein lipids were also associated with increased FI, yet their effects were mostly driven by kidney and cardiometabolic diseases, respectively. Our findings provide new insights into the causal effects of metabolites on frailty and highlight the role of chronic inflammation underlying frailty development.PMID:37184129 | DOI:10.1111/acel.13868

J Am Heart Assoc. 2023 May 15:e026950. doi: 10.1161/JAHA.122.026950. Online ahead of print.ABSTRACTBackground Cardiac metabolic abnormalities are present in heart failure. Few studies have followed metabolic changes accompanying diastolic and systolic heart failure in the same model. We examined metabolic changes during the development of diastolic and severe systolic dysfunction in spontaneously hypertensive rats (SHR). Methods and Results We serially measured myocardial glucose uptake rates with dynamic 2-[18F] fluoro-2-deoxy-d-glucose positron emission tomography in vivo in 9-, 12-, and 18-month-old SHR and Wistar Kyoto rats. Cardiac magnetic resonance imaging determined systolic function (ejection fraction) and diastolic function (isovolumetric relaxation time) and left ventricular mass in the same rats. Cardiac metabolomics was performed at 12 and 18 months in separate rats. At 12 months, SHR hearts, compared with Wistar Kyoto hearts, demonstrated increased isovolumetric relaxation time and slightly reduced ejection fraction indicating diastolic and mild systolic dysfunction, respectively, and higher (versus 9-month-old SHR decreasing) 2-[18F] fluoro-2-deoxy-d-glucose uptake rates (Ki). At 18 months, only few SHR hearts maintained similar abnormalities as 12-month-old SHR, while most exhibited severe systolic dysfunction, worsening diastolic function, and markedly reduced 2-[18F] fluoro-2-deoxy-d-glucose uptake rates. Left ventricular mass normalized to body weight was elevated in SHR, more pronounced with severe systolic dysfunction. Cardiac metabolite changes differed between SHR hearts at 12 and 18 months, indicating progressive defects in fatty acid, glucose, branched chain amino acid, and ketone body metabolism. Conclusions Diastolic and severe systolic dysfunction in SHR are associated with decreasing cardiac glucose uptake, and progressive abnormalities in metabolite profiles. Whether and which metabolic changes trigger progressive heart failure needs to be established.PMID:37183873 | DOI:10.1161/JAHA.122.026950

Aging Cell. 2023 May 15:e13865. doi: 10.1111/acel.13865. Online ahead of print.ABSTRACTMitochondrial dysfunction is considered to be an important mediator of the pro-aging process in chronic kidney disease, which is continuously increasing worldwide. Although PTEN-induced kinase 1 (PINK1) regulates mitochondrial function, its role in renal aging remains unclear. We investigated the association between PINK1 and renal aging, especially through the cGAS-STING pathway, which is known to result in an inflammatory phenotype. Pink1 knockout (Pink1-/- ) C57BL/6 mice and senescence-induced renal tubular epithelial cells (HKC-8) treated with H2 O2 were used as the renal aging models. Extensive analyses at transcriptomic-metabolic levels have explored changes in mitochondrial function in PINK1 deficiency. To investigate whether PINK1 deficiency affects renal aging through the cGAS-STING pathway, we explored their expression levels in PINK1 knockout mice and senescence-induced HKC-8 cells. PINK1 deficiency enhances kidney fibrosis and tubular injury, and increases senescence and the senescence-associated secretory phenotype (SASP). These phenomena were most apparent in the 24-month-old Pink1-/- mice and HKC-8 cells treated with PINK1 siRNA and H2 O2 . Gene expression analysis using RNA sequencing showed that PINK1 deficiency is associated with increased inflammatory responses, and transcriptomic and metabolomic analyses suggested that PINK1 deficiency is related to mitochondrial metabolic dysregulation. Activation of cGAS-STING was prominent in the 24-month-old Pink1-/- mice. The expression of SASPs was most noticeable in senescence-induced HKC-8 cells and was attenuated by the STING inhibitor, H151. PINK1 is associated with renal aging, and mitochondrial dysregulation by PINK1 deficiency might stimulate the cGAS-STING pathway, eventually leading to senescence-related inflammatory responses.PMID:37183600 | DOI:10.1111/acel.13865

Aging Cell. 2023 May 14:e13862. doi: 10.1111/acel.13862. Online ahead of print.ABSTRACTSarcopenia, the age-related decline in muscle function, places a considerable burden on health-care systems. While the stereotypic hallmarks of sarcopenia are well characterized, their contribution to muscle wasting remains elusive, which is partly due to the limited availability of animal models. Here, we have performed cellular and molecular characterization of skeletal muscle from the African killifish-an extremely short-lived vertebrate-revealing that while many characteristics deteriorate with increasing age, supporting the use of killifish as a model for sarcopenia research, some features surprisingly reverse to an "early-life" state in the extremely old stages. This suggests that in extremely old animals, there may be mechanisms that prevent further deterioration of skeletal muscle, contributing to an extension of life span. In line with this, we report a reduction in mortality rates in extremely old killifish. To identify mechanisms for this phenomenon, we used a systems metabolomics approach, which revealed that during aging there is a striking depletion of triglycerides, mimicking a state of calorie restriction. This results in the activation of mitohormesis, increasing Sirt1 levels, which improves lipid metabolism and maintains nutrient homeostasis in extremely old animals. Pharmacological induction of Sirt1 in aged animals was sufficient to induce a late life-like metabolic profile, supporting its role in life span extension in vertebrate populations that are naturally long-lived. Collectively, our results demonstrate that killifish are not only a novel model to study the biological processes that govern sarcopenia, but they also provide a unique vertebrate system to dissect the regulation of longevity.PMID:37183563 | DOI:10.1111/acel.13862

CNS Neurosci Ther. 2023 May 14. doi: 10.1111/cns.14231. Online ahead of print.ABSTRACTINTRODUCTION: Spatial changes of amine metabolites and histopathology of the whole brain help to reveal the mechanism of traumatic brain injury (TBI) and treatment.METHODS: A newly developed liquid microjunction surface sampling-tandem mass tag-ultra performance liquid chromatography-mass spectrometry technique is applied to profile brain amine metabolites in five brain regions after impact-induced TBI at the subacute stage. H&E, Nissl, and immunofluorescence staining are performed to spatially correlate microscopical changes to metabolic alterations. Then, bioinformatics, molecular docking, ELISA, western blot, and immunofluorescence are integrated to uncover the mechanism of Xuefu Zhuyu decoction (XFZYD) against TBI.RESULTS: Besides the hippocampus and cortex, the thalamus, caudate-putamen, and fiber tracts also show differentiated metabolic changes between the Sham and TBI groups. Fourteen amine metabolites (including isomers such as L-leucine and L-isoleucine) are significantly altered in specific regions. The metabolic changes are well matched with the degree of neuronal damage, glia activation, and neurorestoration. XFZYD reverses the dysregulation of several amine metabolites, such as hippocampal Lys-Phe/Phe-Lys and dopamine. Also, XFZYD enhances post-TBI angiogenesis in the hippocampus and the thalamus.CONCLUSION: This study reveals the local amine-metabolite and histological changes in the subacute stage of TBI. XFZYD may promote TBI recovery by normalizing amine metabolites and spatially promoting dopamine production and angiogenesis.PMID:37183394 | DOI:10.1111/cns.14231

J Biosci Bioeng. 2023 May 12:S1389-1723(23)00115-9. doi: 10.1016/j.jbiosc.2023.04.004. Online ahead of print.ABSTRACTBiotin is an essential coenzyme that is bound to carboxylases and participates in fatty acid synthesis. The fact that sake yeast exhibit biotin prototrophy while almost all other Saccharomyces cerevisiae strains exhibit biotin auxotrophy, implies that biotin prototrophy is an important factor in sake brewing. In this study, we inserted a stop codon into the biotin biosynthetic BIO3 gene (cording for 7,8-diamino-pelargonic acid aminotransferase) of a haploid sake yeast strain using the marker-removable plasmid pAUR135 and investigated the fermentation profile of the resulting bio3 mutant. Ethanol production was not altered when the bio3 mutant was cultured in Yeast Malt (YM) medium containing 10% glucose at 15 °C and 30 °C. Interestingly, ethanol production was also not changed during the sake brewing process. On the other hand, the levels of organic acids in the bio3 mutant were altered after culturing in YM medium and during sake brewing. In addition, ethyl hexanoate and isoamyl acetate levels decreased in the bio3 mutant during sake brewing. Metabolome analysis revealed that the decreased levels of fatty acids in the bio3 mutant were attributed to the decreased levels of ethyl hexanoate. Further, the transcription level of genes related to the synthesis of ethyl hexanoate and isoamyl acetate were significantly reduced. The findings indicated that although the decrease in biotin biosynthesis did not affect ethanol production, it did affect the synthesis of components such as organic acids and aromatic compounds. Biotin biosynthesis ability is thus a key factor in sake brewing.PMID:37183145 | DOI:10.1016/j.jbiosc.2023.04.004

J Alzheimers Dis. 2023 May 5. doi: 10.3233/JAD-230061. Online ahead of print.ABSTRACTNumerous studies have demonstrated defects in multiple metabolic pathways in Alzheimer's disease (AD), detected in autopsy brains and in the cerebrospinal fluid in vivo. However, until the advent of techniques capable of measuring thousands of metabolites in a single sample, it has not been possible to rank the relative magnitude of these abnormalities. A recent study provides evidence that the abnormal turnover of the brain's most abundant phospholipids: phosphatidylcholine and phosphatidylethanolamine, constitutes a major metabolic pathology in AD. We place this observation in a historical context and discuss the implications of a central role for phospholipid metabolism in AD pathogenesis.PMID:37182883 | DOI:10.3233/JAD-230061

Toxicol Appl Pharmacol. 2023 May 12:116548. doi: 10.1016/j.taap.2023.116548. Online ahead of print.ABSTRACTNowadays, more and more new synthetic cannabinoids (SCs) appearing on the illicit market present challenges to analytical, forensic, and toxicology experts. For a better understanding of the physiological effect of SCs, the key issue is studying their metabolomic and psychoactive properties. In this study, our validated targeted reversed phase UHPLC-MS/MS method was used for determination of urinary concentration of 5F-MDMB-PICA, 4F-MDMB-BICA, and their primary metabolites. The liquid-liquid extraction procedure was applied for the enrichment of SCs.The pharmacological characterization of investigated SCs were studied by radioligand competition binding and ligand stimulated [35S]GTPγS binding assays. For 5F-MDMB-PICA and 4F-MDMB-BICA, the median urinary concentrations were 0.076 and 0.312 ng/mL. For primary metabolites, the concentration range was 0.029-881.02* ng/mL for 5F-MDMB-PICA-COOH, and 0.396-4579* ng/mL for 4F-MDMB-BICA-COOH. In the polydrug aspect, the 22 urine samples were verified to be abused with 6 illicit drugs. The affinity of the metabolites to CB1R significantly decreased compared to the parent ligands. In the GTPγS functional assay, both 5F-MDMB-PICA and 4F-MDMB-BICA were acting as full agonists, while the metabolites were found as weak inverse agonists. Additionally, the G-protein stimulatory effects of the full agonist 5F-MDMB-PICA and 4F-MDMB-BICA were reduced by metabolites. These results strongly indicate the dose-dependent CB1R-mediated weak inverse agonist effects of the two butanoic acid metabolites. The obtained high concentration of main urinary metabolites of 5F-MDMB-PICA and 4F-MDMB-BICA confirmed the relevance of their routine analysis in forensic and toxicological practices. Based on in vitro binding assays, the metabolites presumably might cause a lower psychoactive effect than parent compounds.PMID:37182749 | DOI:10.1016/j.taap.2023.116548

J Ethnopharmacol. 2023 May 12:116617. doi: 10.1016/j.jep.2023.116617. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Herb-induced liver injury is poorly described for African herbal remedies, such as Acokanthera oppositifolia. Although a commonly used treatment for pain, snake bites and anthrax, it is also a well-known arrow poison, thus toxicity is to be expected.AIM OF THE STUDY: The cytotoxicity and preliminary mechanisms of toxicity in HepG2 hepatocarcinoma cells were assessed.MATERIALS AND METHODS: The effect of hot water and methanol extracts were on cell density, oxidative status, mitochondrial membrane potential, fatty acids, caspase-3/7 activity, adenosine triphosphate levels, cell cycling and viability was assessed. Phytochemicals were tentatively identified using ultra-performance liquid chromatography.RESULTS: The hot water extract displayed an IC50 of 24.26 μg/mL, and reduced proliferation (S- and G2/M-phase arrest) and viability (by 30.71%) as early as 24 h after incubation. The methanol extract had a comparable IC50 of 26.16 μg/mL, and arrested cells in the G2/M-phase (by 18.87%) and induced necrosis (by 13.21%). The hot water and methanol extracts depolarised the mitochondrial membrane (up to 0.84- and 0.74-fold), though did not generate reactive oxygen species. The hot water and methanol extracts decreased glutathione (0.42- and 0.62-fold) and adenosine triphosphate (0.08- and 0.26-fold) levels, while fatty acids (2.00- and 4.61-fold) and caspase-3/7 activity (1.98- and 5.82-fold) were increased.CONCLUSION: Extracts were both cytostatic and cytotoxic in HepG2 cells. Mitochondrial toxicity was evident and contributed to reducing adenosine triphosphate production and fatty acid accumulation. Altered redox status perturbed proliferation and promoted necrosis. Extracts of A. oppositifolia may thus promote necrotic cell death, which poses a risk for inflammatory hepatotoxicity with associated steatosis.PMID:37182674 | DOI:10.1016/j.jep.2023.116617

Food Chem. 2023 May 6;423:136312. doi: 10.1016/j.foodchem.2023.136312. Online ahead of print.ABSTRACTThree genotypes each of bread wheat, durum wheat and tritordeum were grown in randomized replicated field trials in Andalusia (Spain) for two years and wholemeal flours analysed for a range of components to identify differences in composition. The contents of all components that were determined varied widely between grain samples of the individual species and in most cases also overlapped between the three species. Nevertheless, statistically significant differences between the compositions of the three species were observed. Notably, tritordeum had significantly higher contents of protein, some minerals (magnesium and iron), total phenolics and methyl donors. Tritordeum also had higher levels of total amino acids (but not asparagine) and total sugars, including raffinose. By contrast, bread wheat and tritordeum had similar contents of the two major dietary fibre components in white flour, arabinoxylan and β-glucan, with significantly lower contents in durum wheat.PMID:37182491 | DOI:10.1016/j.foodchem.2023.136312

iScience. 2023 Apr 19;26(5):106680. doi: 10.1016/j.isci.2023.106680. eCollection 2023 May 19.ABSTRACTAdaptation to host plants is of great significance in the ecology of xylophagous insects. The specific adaptation to woody tissues is made possible through microbial symbionts. We investigated the potential roles of detoxification, lignocellulose degradation, and nutrient supplementation of Monochamus saltuarius and its gut symbionts in host plant adaptation using metatranscriptome. The gut microbial community structure of M. saltuarius that fed on the two plant species were found to be different. Plant compound detoxification and lignocellulose degradation genes have been identified in both beetles and gut symbionts. Most differentially expressed genes associated with host plant adaptations were up-regulated in larvae fed on the less suitable host (Pinus tabuliformis) compared to larvae fed on the suitable host (Pinus koraiensis). Our findings indicated that M. saltuarius and its gut microbes respond to plant secondary substances through systematic transcriptome responses, allowing them to adapt to unsuitable host plants.PMID:37182102 | PMC:PMC10173737 | DOI:10.1016/j.isci.2023.106680

Front Psychiatry. 2023 Apr 20;14:1144873. doi: 10.3389/fpsyt.2023.1144873. eCollection 2023.ABSTRACTBACKGROUND: Risperidone is a commonly prescribed antipsychotic drug with a potential side effect of weight gain. However, the pathophysiological mechanism is still poorly understood. Here, we sought to identify potential biomarkers of risperidone-induced weight gain by using a targeted metabolomics approach.METHODS: We enrolled 30 subjects who received risperidone monotherapy for 8 weeks from a prospective longitudinal cohort study for drug-naïve schizophrenia patients. Plasma metabolites were measured by targeted metabolomics Biocrates MxP® Quant 500 Kit at baseline and 8-week follow-up.RESULTS: After 8 weeks of risperidone treatment, the levels of 48 differential metabolites were upregulated, including lysophosphatidylcholines (2), phosphatidylcholines (PC) (8), cholesteryl esters (CE) (3), and triglycerides (35), while 6 differential metabolites namely PC aa C38:6, methionine (Met), α-aminobutyric acid (AABA), TrpBetaine, CE (22:6), and Taurocholic acid (TCA) were downregulated. Interestingly, the reduction of PC aa C38:6, AABA and CE (22:6) was linearly related with increased BMI. Further multiple regression analysis showed that the changes of PC aa C38:6 and AABA were independent contributors of increased BMI. In addition, baseline levels of PC aa C36:5, CE (20:5) and AABA had positive relationships with the change of BMI.CONCLUSION: Our findings indicate phosphatidylcholines and amino acids may serve as biomarkers for risperidone-induced weight gain.PMID:37181896 | PMC:PMC10171109 | DOI:10.3389/fpsyt.2023.1144873

Drug Des Devel Ther. 2023 May 6;17:1371-1386. doi: 10.2147/DDDT.S407983. eCollection 2023.ABSTRACTPURPOSE: This study aimed to investigate the underlying treatment mechanism of Radix Astragali (RA) in hyperuricemia from the perspective of microbiota and metabolomics.METHODS: We used potassium oxyazinate (PO) to induce hyperuricemia mice, and we determined serum alanine aminotransferase/aspartate aminotransferase (ALT/AST), xanthine oxidase (XOD), creatinine (CRE), uric acid (UA), blood urea nitrogen (BUN) levels, liver XOD levels and assessed the kidney tissue histopathology. The therapeutic mechanism of RA in hyperuricemic mice was studied by 16S rRNA, metagenomic sequencing and metabolomics.RESULTS: Our research showed that RA has therapeutic effect in hyperuricemia mice, such as slow the weight loss, repair kidney damage, and downregulate serum UA, XOD, CRE, ALT/AST, BUN, and liver XOD levels. RA restored the disturbance structure of the microbiota in hyperuricemia mice by increasing the relative abundances of beneficial bacteria (Lactobacillaceae and Lactobacillus murine) but decreasing the relative abundances of pathogenic bacteria (Prevotellaceae, Rikenellaceae and Bacteroidaceae). Meanwhile, we found that RA directly regulated the metabolic pathway (such as linoleic acid metabolism and glycerophospholipid metabolism) and indirectly regulated bile acid metabolism by mediating microbiota to ameliorate metabolic disorders. Subsequently, there was a robust correlation between specific microbiota, metabolites and the disease index.CONCLUSION: The ability of RA to protect mice against hyperuricemia is strongly linked to the microbiome-metabolite axis, which would provide evidence for RA as a medicine to prevent or treat hyperuricemia.PMID:37181826 | PMC:PMC10171225 | DOI:10.2147/DDDT.S407983

Front Public Health. 2023 Apr 27;11:1100227. doi: 10.3389/fpubh.2023.1100227. eCollection 2023.ABSTRACTPURPOSE: To describe the study design, methodology, and cohort profile of the Eastern China Student Health and Wellbeing Cohort Study. The cohort baseline includes (1) targeted disease (myopia, obesity, elevated blood pressure, and mental health) and (2) exposures (individual behaviors, environment, metabolomics, and gene and epigenetics).PARTICIPANTS: Annual physical examination, questionnaire-based survey, and bio-sampling have been carried out in the study population. In the first stage (2019-2021), a total of 6,506 students in primary schools are enrolled in the cohort study.FINDINGS TO DATE: Of all the cohort participants, the ratio of male to female is 1.16 among a total of 6,506 student participants, of which 2,728 (41.9%) students are from developed regions and 3,778 (58.1%) students are from developing regions. The initial age of observation is 6-10 years, and they will be observed until they graduate from high school (>18 years of age). (1) Targeted diseases: The growth rates of myopia, obesity, and high blood pressure vary by regions, and for developed regions, the prevalence of myopia, obesity, and elevated blood pressure is 29.2%, 17.4%, and 12.6% in the first year, respectively. For developing regions, the prevalence of myopia, obesity, and elevated blood pressure is 22.3%, 20.7%, and 17.1% in the first year, respectively. The average score of CES-D is 12.9 ± 9.8 in developing regions/11.6 ± 9.0 in developed regions. (2) Exposures: ① The first aspect of individual behaviors: the questionnaire topics include diet, physical exercise, bullying, and family. ② The second aspect of environment and metabolomics: the average desk illumination is 430.78 (355.84-611.56) LX, and the average blackboard illumination is 365.33 (286.83-516.84) LX. Metabolomics like bisphenol A in the urine is 0.734 ng/ml. ③ The third aspect of gene and epigenetics: SNPs (rs524952, rs524952, rs2969180, rs2908972, rs10880855, rs1939008, rs9928731, rs72621438, rs9939609, rs8050136 and so on) are detected.FUTURE PLANS: Eastern China Student Health and Wellbeing Cohort Study is aiming to focus on the development of student-targeted diseases. For children with student common diseases, this study will focus on targeted disease-related indicators. For children without targeted disease, this study aims to explore the longitudinal relationship between exposure factors and outcomes, excluding baseline confounding factors. Exposure factors include three aspects: (1) individual behaviors, (2) environment and metabolomics, and (3) gene and epigenetics. The cohort study will continue until 2035.PMID:37181702 | PMC:PMC10173362 | DOI:10.3389/fpubh.2023.1100227

Food Sci Nutr. 2023 Mar 31;11(5):2277-2287. doi: 10.1002/fsn3.3168. eCollection 2023 May.ABSTRACTSulforaphane (SFN) is a promising phytochemical with a wide range of antitumor activities. A comprehensive understanding of the effects of SFN on breast cancer based on the metabolome and microbiome is limited. Thus, we treated MCF-7 cell-transplanted nude mice with 50 mg/kg SFN. SFN inhibits breast cancer cell proliferation. SFN increased the levels of sulfate-related metabolites and glutathione-related metabolites and decreased tryptophan metabolites and methyl-purine metabolites in urinary metabolic profile. SFN indirectly affected the activation of aryl hydrocarbon receptor by tryptophan metabolism. The ratio of SAM to methionine was decreased by SFN while the global DNA methylation was downregulated in tumor tissue. SFN decreased the sulfate-reducing bacterium Desulfovibrio, which is related to reduced methylation capacity, and increased the genus Lactobacillus related to tryptophan metabolites with antitumor activities. In conclusion, we provide a perspective on the metabolome and microbiome to elucidate the antitumor activities of SFN.PMID:37181316 | PMC:PMC10171519 | DOI:10.1002/fsn3.3168

Food Sci Nutr. 2023 Apr 7;11(5):2106-2117. doi: 10.1002/fsn3.2968. eCollection 2023 May.ABSTRACTThis study aimed to characterize the metabolic composition of four types of commercially available chicken breeds [village chicken, colored broiler (Hubbard), broiler (Cobb), and spent layers (Dekalb)] by 1H NMR coupling and discriminate them using multivariate analysis. Five chickens were collected for each chicken breed based on the marketing age from the respective commercial farms. The orthogonal partial least squares discriminant analysis (OPLS-DA) results showed an obvious separation of local village chickens from the other breeds based on the metabolites present in their serum and meat (pectoralis major). The cumulative values of Q 2, R 2 X, and R 2 Y of the OPLS-DA model for chicken serum were 0.722, 0.877, and 0.841. For the pectoralis major muscle, the cumulative values of Q 2, R 2 X, and R 2 Y of the OPLS-DA model were reported as 0.684, 0.781, and 0.786, respectively. The quality of both OPLS-DA models was accepted by the cumulative values of Q 2 ≥ 0.5 and R 2 ≥ 0.65. The 1H NMR result with multivariate analysis has successfully distinguished local village chicken from the other three commercial chicken breeds based on serum and pectoralis major muscle. Nonetheless, colored broiler (Hubbard) was not distinguished from broiler (Cobb) and spent layers (Dekalb) in serum and pectoralis major, respectively. The OPLS-DA assessment in this study identified 19 and 15 potential metabolites for discriminating different chicken breeds in serum and pectoralis major muscle, respectively. Some of the prominent metabolites identified include amino acids (betaine, glycine, glutamine, guanidoacetate, phenylalanine, and valine), nucleotides (IMP and NAD+), organic acids (lactate, malate, and succinate), peptide (anserine), and sugar alcohol (myo-inositol).PMID:37181311 | PMC:PMC10171504 | DOI:10.1002/fsn3.2968

J Pharm Anal. 2023 Apr;13(4):323-339. doi: 10.1016/j.jpha.2023.01.003. Epub 2023 Feb 6.ABSTRACTCapillary electrochromatography (CEC) plays a significant role in chiral separation via the double separation principle, partition coefficient difference between the two phases, and electroosmotic flow-driven separation. Given the distinct properties of the inner wall stationary phase (SP), the separation ability of each SP differs from one another. Particularly, it provides large room for promising applications of open tubular capillary electrochromatography (OT-CEC). We divided the OT-CEC SPs developed over the past four years into six types: ionic liquids, nanoparticle materials, microporous materials, biomaterials, non-nanopolymers, and others, to mainly introduce their characteristics in chiral drug separation. There also added a few classic SPs that occurred within ten years as supplements to enrich the features of each SP. Additionally, we discuss their applications in metabolomics, food, cosmetics, environment, and biology as analytes in addition to chiral drugs. OT-CEC plays an increasingly significant role in chiral separation and may promote the development of capillary electrophoresis (CE) combined with other instruments in recent years, such as CE with mass spectrometry (CE/MS) and CE with ultraviolet light detector (CE/UV).PMID:37181297 | PMC:PMC10173184 | DOI:10.1016/j.jpha.2023.01.003

Int J Chron Obstruct Pulmon Dis. 2023 May 5;18:785-795. doi: 10.2147/COPD.S405547. eCollection 2023.ABSTRACTBACKGROUND: Chronic obstructive pulmonary disease (COPD) has higher mortality when developing to acute exacerbation (AECOPD); hence, the early intervention of COPD is critical for preventing AECOPD. Exploring the serum metabolites associated with acute exacerbation in patients with COPD will contribute to the early intervention of COPD.METHODS: In the study, a non-targeted metabolomics strategy combined with multivariate statistical methods was performed to explore the metabolic profiling of COPD developing acute exacerbation, to screen the potential metabolites associated with AECOPD and to analyze the potential value of these metabolites in predicting the development of COPD.RESULTS: Serum lysine, glutamine, 3-hydroxybutyrate, pyruvate and glutamate levels were significantly higher, while 1-methylhistidine, isoleucine, choline, valine, alanine, histidine and leucine levels were significantly lower in AECOPD patients, compared with stable COPD patients after normalization based on the healthy controls. Moreover, eight metabolic pathways were significantly altered (P<0.05) in the serum of AECOPD patients compared with the stable COPD population, including purine metabolism, glutamine and glutamate metabolism, arginine biosynthesis, butyrate metabolism, ketone body synthesis and degradation, and linoleic acid metabolism. In addition, the correlation analysis between metabolites and AECOPD patients demonstrated that an M-score based on a weighted sum of concentrations of four metabolites including pyruvate, isoleucine, 1-methylhistidine and glutamine were significantly associated with the acute exacerbation of pulmonary ventilation function in COPD patients.CONCLUSION: Altogether, the metabolite score based on a weighted sum of concentrations of four serum metabolites was associated with an increased risk of COPD developing acute exacerbation, which will provide a new insight for the understanding of COPD development.PMID:37180750 | PMC:PMC10168002 | DOI:10.2147/COPD.S405547

Front Pharmacol. 2023 Apr 25;14:1084453. doi: 10.3389/fphar.2023.1084453. eCollection 2023.ABSTRACTZoledronic acid (ZOL) is a potent antiresorptive agent that increases bone mineral density (BMD) and reduces fracture risk in postmenopausal osteoporosis (PMOP). The anti-osteoporotic effect of ZOL is determined by annual BMD measurement. In most cases, bone turnover markers function as early indicators of therapeutic response, but they fail to reflect long-term effects. We used untargeted metabolomics to characterize time-dependent metabolic shifts in response to ZOL and to screen potential therapeutic markers. In addition, bone marrow RNA-seq was performed to support plasma metabolic profiling. Sixty rats were assigned to sham-operated group (SHAM, n = 21) and ovariectomy group (OVX, n = 39) and received sham operation or bilateral ovariectomy, respectively. After modeling and verification, rats in the OVX group were further divided into normal saline group (NS, n = 15) and ZOL group (ZA, n = 18). Three doses of 100 μg/kg ZOL were administrated to the ZA group every 2 weeks to simulate 3-year ZOL therapy in PMOP. An equal volume of saline was administered to the SHAM and NS groups. Plasma samples were collected at five time points for metabolic profiling. At the end of the study, selected rats were euthanatized for bone marrow RNA-seq. A total number of 163 compound were identified as differential metabolites between the ZA and NS groups, including mevalonate, a critical molecule in target pathway of ZOL. In addition, prolyl hydroxyproline (PHP), leucyl hydroxyproline (LHP), 4-vinylphenol sulfate (4-VPS) were identified as differential metabolites throughout the study. Moreover, 4-VPS negatively correlated with increased vertebral BMD after ZOL administration as time-series analysis revealed. Bone marrow RNA-seq showed that the PI3K-AKT signaling pathway was significantly associated with ZOL-mediated changes in expression (adjusted-p = 0.018). In conclusion, mevalonate, PHP, LHP, and 4-VPS are candidate therapeutic markers of ZOL. The pharmacological effect of ZOL likely occurs through inhibition of the PI3K-AKT signaling pathway.PMID:37180703 | PMC:PMC10166846 | DOI:10.3389/fphar.2023.1084453