Discovery of biomarkers related to abnormal lipid metabolism in liver and serum and intervention mechanism of ginsenoside Rb_1 in hyperlipidemia rats based on non-targeted metabolomics / 中国中药杂志

Through the non-targeted metabolomics study of endogenous substances in the liver and serum of hyperlipidemia rats, the biomarkers related to abnormal lipid metabolism in hyperlipidemia rats were found, and the target of ginsenoside Rb_1 in improving hyperlipidemia was explored and its mechanism was elucidated. The content of serum biochemical indexes of rats in each group was detected by the automatic biochemical analyzer. The metabolite profiles of liver tissues and serum of rats were analyzed by HPLC-MS. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to compare and analyze the metabolic data in the normal group, the hyperlipidemia group, and the ginsenoside Rb_1 group, and screen potential biomar-kers. The related metabolic pathways were further constructed by KEGG database analysis. The results showed that hyperlipemia induced dyslipidemia in rats, which was alleviated by ginsenoside Rb_1. The non-targeted metabolomics results showed that there were 297 differential metabolites in the liver tissues of hyperlipidemia rats, 294 differential metabolites in the serum samples, and 560 diffe-rential metabolites in the hyperlipidemia rats treated by ginsenoside Rb_1. Perillic acid and N-ornithyl-L-taurine were common metabolites in the liver and serum samples, which could be used as potential biomarkers for ginsenoside Rb_1 in the improvement of hyperlipidemia. As revealed by pathway enrichment in the liver and serum, ginsenoside Rb_1 could participate in the metabolic pathway of choline in both the liver and serum. In addition, ginsenoside Rb_1 also participated in the ABC transporter, alanine, aspartic acid, and glutamate metabolism, protein digestion and absorption, β-alanine metabolism, taurine and hypotaurine metabolism, caffeine metabolism, valine, leucine, and isoleucine biosynthesis, arachidonic acid metabolism, and methionine and cysteine metabolism to improve dyslipidemia in rats.

Mechanism of Learning and Memory Impairment in Rats Exposed to Arsenic and/or Fluoride Based on Microbiome and Metabolome / 生物医学与环境科学（英文）

OBJECTIVE@#Arsenic (As) and fluoride (F) are two of the most common elements contaminating groundwater resources. A growing number of studies have found that As and F can cause neurotoxicity in infants and children, leading to cognitive, learning, and memory impairments. However, early biomarkers of learning and memory impairment induced by As and/or F remain unclear. In the present study, the mechanisms by which As and/or F cause learning memory impairment are explored at the multi-omics level (microbiome and metabolome).@*METHODS@#We stablished an SD rats model exposed to arsenic and/or fluoride from intrauterine to adult period.@*RESULTS@#Arsenic and/fluoride exposed groups showed reduced neurobehavioral performance and lesions in the hippocampal CA1 region. 16S rRNA gene sequencing revealed that As and/or F exposure significantly altered the composition and diversity of the gut microbiome，featuring the Lachnospiraceae_NK4A136_group, Ruminococcus_1, Prevotellaceae_NK3B31_group, [Eubacterium]_xylanophilum_group. Metabolome analysis showed that As and/or F-induced learning and memory impairment may be related to tryptophan, lipoic acid, glutamate, gamma-aminobutyric acidergic (GABAergic) synapse, and arachidonic acid (AA) metabolism. The gut microbiota, metabolites, and learning memory indicators were significantly correlated.@*CONCLUSION@#Learning memory impairment triggered by As and/or F exposure may be mediated by different gut microbes and their associated metabolites.

Impacto de la cuarentena por COVID-19 en el perfil metabólico de personas con infección por VIH en Argentina / Impact of COVID-19 related lockdown on the metabolic profile of people with HIV infection in Argentina

INTRODUCCIÓN: Para mitigar la propagación del SARS-CoV-2 se requirió de un confinamiento generalizado. Las autoridades argentinas impusieron aislamiento social preventivo durante 234 días (20 de marzo al 9 de noviembre de 2020), modificando el estilo de vida de la población. OBJETIVOS: Examinar la influencia de las medidas de bloqueo en el perfil metabólico de pacientes infectados por VIH en Argentina. PACIENTES Y MÉTODOS: Estudio de cohorte retrospectivo de 10.239 pacientes en seguimiento en una clínica de atención privada de personas con infección por VIH. Se incluyeron pacientes adultos con terapia antirretroviral (TARV) en curso que tuvieran una determinación de glucemia, colesterol total, colesterol HDL y trigliceridemia antes de la cuarentena (Pre-C: segundo semestre 2019) y una segunda determinación durante la misma (Intra-C: mayo 2020). Se excluyeron los pacientes con cambios en la TARV con impacto metabólico, los que iniciaron o suspendieron hipolipemiantes o hipoglucemiantes y mujeres embarazadas. Las variables categóricas se compararon mediante la prueba de la χ2 o la prueba exacta de Fisher y las continuas mediante la prueba t o la prueba de Mann-Whitney según correspondiera. Se consideró significativo un valor de p a dos colas < 0,05. RESULTADOS: Se incluyeron 540 individuos. La mediana de edad fue de 47 años y 74,6% fueron de sexo masculino. La mediana de índice de masa corporal fue 26,1 y 94,6% tenían bajo riesgo cardiovascular. Hubo un aumento significativo en el porcentaje de pacientes con hiperglucemia (Pre-C 5,2% vs Intra-C 8,5%, p 0,04), hipertrigliceridemia (Pre-C 33,9% vs Intra-C 40,7%, p 0,02) e hipercolesterolemia LDL (Pre-C 12,6% vs Intra-C 17,2%, p 0,04). CONCLUSIÓN: Nuestros resultados sugieren que la cuarentena, al menos en sus fases iniciales, puede tener un impacto negativo en el perfil metabólico de esta población.

BACKGROUND: The spread of SARS-CoV-2 required widespread lockdown to mitigate the pandemic. Argentine authorities imposed preventive social isolation for 234 days (March 20th to November 9th 2020). This measure led to major changes in the population's lifestyle. AIM: To examine the influence of COVID-19 lockdown measures on the metabolic profile of HIV-infected patients in Argentina. METHODS: Retrospective cohort study of 10,239 HIV-infected patients under follow up in a private clinic for HIV care. Adult patients with ongoing antiretroviral therapy (ART) and a baseline determination of blood glucose, total cholesterol, HDL-cholesterol and triglycerides done before lockdown (BL: second semester of 2019) and a second determination during lockdown (DL: May 2020) were included. Patients with recent changes in ART that may have metabolic impact, those starting lipid/glucose lowering agents and pregnant women were excluded. Categorical variables were compared using the χ2 test or Fisher's exact test, and continuous variables using the t-test or the Mann-Whitney test. A two-tailed value of p < 0.05 was considered significant. RESULTS: 540 individuals were included, median of age was 47 years and 74.6% were male. Median body mass index was 26.1 and 94.6% had low cardiovascular risk. There was a significant increase in the percentage of patients that met criteria for hyperglycemia (BL 4.8% and DL 8.5%, p < 0.001). We also observed significant (p < 0.001) increase in median (IQR) BL vs DL values in LDL-cholesterol [109 (90-128) vs 118 (97-139) mg/dL]; and triglycerides [120 (87-172) vs. 132 mg/dL (96-184)]. The proportion of patients with hyper-LDL cholesterolemia according to individual cardiovascular risk increased from 12.6 to 17.2% (p = 0.04). CONCLUSION: Our results suggest that quarantine, at least in its initial phases, may have a negative impact on the metabolic profile of this population.

Viscumalbum L. homeopathic mother tinctures: metabolome and antitumor activity

Viscum album L. is a semi-parasitic plant with antitumor activity attributed to theaqueous extracts. However, European V. album ethanolic extracts (VAE) have also demonstrated invitro activity in tumor models. Aims: Evaluate the metabolic profiles of fifty VAE harvested duringsummer and winter seasons and their antitumor activity through 2D and 3D models. Methodology:VAEwerepreparedbymacerationfrom:V.albumsubsp.albumgrowingonMalus domestica,Quercus sp.and Ulmus sp.; V. album subsp. austriacum from Pinus sylvestris; V. album subsp. abietis from Abies alba.Chemical analyses were performed through liquid chromatography coupled with high resolutionmass spectrometry and Partial Least Squares Discriminant Analysis (PLS-DA) was performed in theMetaboanalyst 4.0. The antitumor potential of the selected VAE was evaluated in 2D and 3D models(MDA-MB-231 cancer cells) by MTT, crystal violet and glycolytic pathway analysis. Results anddiscussion:Thefirst3principalcomponentsinPLS-DAexplained60%and40%ofdatavariationin positive andnegativemodesrespectively.Threegroupswereformedandshowedchemicalsimilarityamong V. album subspecies. The compounds responsible for group separation were tentativelyidentifiedas:pinobankasinornaringenin hexoside;isorhamnetin-3-hexoside,meglutolanddifferent aminoacids.ThesummerVAEat0.5%v/vinducedhighercytotoxicdamagethanthewinterpreparations, and Abies alba and Quercus sp. VAE promoted 49% and 42% reduction of tumorviability in 3D model (72h incubation), respectively. MDA-MB-231 glycolytic pathway in 2D modelshowed a decrease in the glucose consumption and extracellular lactate production. Also, PFK (6-phosphofructo-1-kinase)andPK(Pyruvatekinase)activitieswereinhibitedbyAbiesalbaandQuercus sp. VAE at 48h of incubation. Conclusion: VAE extracts showed different metabolomes andthe glycolytic pathway should be an important target involved in the inhibition of tumor growth bytheseextracts

Preliminary exploration of the metabolic profile and metabolic pathways in newly diagnosed multiple myeloma / 中华肿瘤杂志

Objective: To explore the metabolite profile and metabolic pathways of newly diagnosed multiple myeloma (MM). Methods: Gas chromatography-mass spectrometry (GC-MS) was employed for the high-throughput detection and identification of serum samples from 55 patients with MM and 37 healthy controls matched for age and sex from 2016 to 2017 collected at the First Affiliated Hospital of Soochow University. The relative standard deviation (RSD) of quality control (QC) samples was employed to validate the reproducibility of GC-MS approach. The differential metabolites between patients with MM and healthy controls were detected by partial least squares discrimination analysis (PLS-DA), and t-test with false discovery rate (FDR) correction. Metabolomics pathway analysis (MetPA) was employed to construct metabolic pathways. Results: There were 55 MM patients, including 34 males and 21 females. The median age was 60 years old (42-73 years old). There were 30 cases of IgG type, 9 cases of IgA type, 1 case of IgM type, 2 cases of non-secreted type, 1 case of double clone type and 12 cases of light chain type, including 3 cases of kappa light chain type and 9 cases of lambda light chain type. The result of QC sample test showed that the proportion of compounds with the RSD of the relative content of metabolites < 15% was 70.21% obtained by the reproducibility of GC-MS experimental data, which implied that the experimental data were reliable. A total of 17 metabolites were screened differently with the healthy control group, including myristic acid, hydroxyproline, cysteine, palmitic acid, L-leucine, stearic acid, methionine, phenylalanine, glycerin, serine, isoleucine, tyrosine, valine, citric acid, inositol, threonine, and oxalic acid (VIP>1, P<0.05). Metabolic pathway analysis suggested that metabolic disorders in MM patients comprised mainly phenylalanine metabolism, glyoxylic acid and dicarboxylic acid metabolism, phosphoinositide metabolism, cysteine and methionine metabolism, glycerolipid metabolism, glycine, serine, and threonine metabolism. Conclusion: Compared with normal people, patients with newly diagnosed MM have obvious differences in metabolic profiles and metabolic pathways.

Metabolomics approach: Interpretation of changes in rat plasma metabolites after solifenacin treatment

Abstract Changes in metabolite levels of patients using the long-term drug can be comprehensively demonstrated by pharmacometabolomic studies. In this study, biological alterations induced by the administration of solifenacin succinate were investigated with a pharmacometabolomics approach on rat metabolism. Plasma samples obtained from rats were analyzed by LC-Q- TOF/MS/MS. METLIN and HMDB databases were used to identify metabolites. Data were processed and classified with MATLAB 2017b. 53 m/z values were found to be significantly different between the drug and control groups (p ≤ 0.01 and fold analysis > 1.5) and identified by comparing METLIN and HMDB databases. According to multivariate data analysis, changes in arachidonic acid, thromboxane A2, palmitic acid, choline, calcitriol, histamine phosphate, retinyl ester, l-cysteine, l-leucine, beta-alanine, l-histidine levels were found to be statistically significant compare to the control group. Differences in the biosynthesis of phenylalanine, aminoacyl-tRNA, tyrosine, tryptophan, metabolism of glycerophospholipid, cysteine, methionine, histidine, arachidonic metabolism have been successfully demonstrated by the metabolomics approach. Our study provides important information to explain the efficacy and toxicity of chronic administration of solifenacin succinate

Metaboloma use in ophthalmology / Uso de metaboloma em oftalmologia: uma revisão narrativa

ABSTRACT It is part of the omic sciences to search for an understanding of how the cellular system of organisms works as well as studying their biological changes. As part of the omic sciences, we can highlight the genomics whose function is the study of genes, the transcriptomics that studies the changes in the transcripts, the proteomics responsible for understanding the changes that occur in proteins, and the metabolomics that studies all the metabolic changes that occur in a certain system when it is submitted to different types of stimuli. Metabolomics is the science that studies the endogenous and exogenous metabolites in biological systems, which aims to provide comparative quantitative or semi-quantitative information about all metabolites in the system. This review aims to describe the main applications of metabolomics science in ophthalmolog. We searched the literature on main applications of metabolomics science in ophthalmology, using the MEDLINE and LILACS databases, with the keywords "metabolomics" and "ophthalmology", from January 1, 2009, to April 5, 2021. We retrieved 216 references, of which 58 were considered eligible for intensive review and critical analysis. The study of the metabolome allows a better understanding of the metabolism of ocular tissues. The results are important to aid diagnosis and as predictors of the progression of many eye and systemic diseases.

RESUMO Faz parte das ciências ômicas buscar entender como funciona o sistema celular dos organismos e estudar suas alterações biológicas. Como parte das ciências ômicas, destacam-se a genômica, cuja função é o estudo dos genes; a transcriptômica, que estuda as mudanças nos transcritos; a proteômica, responsável por entender as mudanças que ocorrem nas proteínas, e a metabolômica, que estuda todo o metabolismo das alterações que ocorrem em um determinado sistema quando ele é submetido a diferentes tipos de estímulos. A metabolômica é a ciência que estuda os metabólitos endógenos e exógenos em sistemas biológicos, visando fornecer informações comparativas quantitativas ou semiquantitativas sobre todos os metabólitos do sistema. Esta revisão teve como objetivo descrever as principais aplicações da ciência metabolômica na oftalmologia. Trata-se de revisão narrativa desenvolvida por um grupo de pesquisa da Universidade Federal de São Paulo, em São Paulo (SP). Buscaram-se, na literatura, as principais aplicações da ciência metabolômica em oftalmologia, utilizando as bases de dados Medline® e Lilacs, com as palavras-chave "metabolomics" e "oftalmologia", de 1º de janeiro de 2009 a 5 de abril de 2021. Foram recuperadas 216 referências, das quais 58 foram consideradas elegíveis para revisão intensiva e análise crítica. O estudo do metaboloma permite um melhor entendimento do metabolismo dos tecidos oculares. Os resultados são importantes para auxiliar no diagnóstico e como preditores da progressão de muitas doenças oculares e sistêmicas.

Metabolomics Changes of Serum and Tissues in Mice Died of Acute Tetracaine Poisoning / 法医学杂志

Objective To study the changes of metabolites in serum and tissues （kidney, liver and heart） of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Orbitrap HRMS）. Multivariate statistical principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.

Research Progress on the Omics of Methamphetamine Toxic Damage and Addiction / 法医学杂志

The mechanism of methamphetamine toxicity and addiction is the key research direction of forensic toxicology, and the development of omics technology provides a new platform for further study of this direction. METH toxic damage and addiction are reflected differently in genes, ribonucleic acid (RNA) transcription, protein and metabolism. This article summarizes the achievements and shortcomings of multi-omics technologies such as genome, transcriptome, metabolome and proteome in the study of METH damage and addiction, and discusses the strategies and advantages of multi-omics combined analysis in the study of METH toxic damage and addiction mechanism, in order to provide more useful reference information for forensic toxicology of METH.

Application of UPLC-QTOF-MS in Analysis of Non-targeted Urine Metabolomics in Rats with Yunaconitine Poisoning / 法医学杂志

OBJECTIVES@#To explore the possible mechanism of Yunaconitine poisoning by studying the changes of urine metabolic profile in rats chronically poisoned by Yunaconitine via non-targeted metabolomics.@*METHODS@#A rat model of Yunaconitine poisoning was established, and a metabolomics method based on UPLC-QTOF-MS technology was used to obtain the urine metabolic profile. Principal component analysis (PCA), orthogonal projections to latent structures-discriminant analysis (OPLS-DA), variable importance in projection (VIP) value greater than 1, fold change (FC) value greater than 3 or less than 0.33 and P value less than 0.05 were used to screen potential biomarkers related to the toxicity of Yunaconitine. The metabolic pathway analysis was performed through the MetaboAnalyst website and pathological changes of related tissues were observed.@*RESULTS@#Sixteen potential biomarkers including L-isoleucine were screened, which mainly involved six metabolic pathways including the biosynthesis and degradation of valine, leucine and isoleucine, pentose and glucuronate interconversions, and propanoate metabolism, alanine, aspartate and glutamate metabolism, tyrosine metabolism. Pathological studies showed that rat toxic change in nervous system, liver and cardiac caused by Yunaconitine.@*CONCLUSIONS@#Yunaconitine may cause neurotoxicity, hepatotoxicity and cardiotoxicity by affecting amino acid and glucose metabolism.

Metabolic profile during pregnancy in BRISA birth cohorts of Ribeirão Preto and São Luís, Brazil

During pregnancy, metabolic changes that develop in women may increase the risk of diseases and conditions that may also harm the life of the growing fetus. The aim of the present study was to identify and compare the metabolic profile (MP) during pregnancy in two birth cohorts in 2010 in the cities of Ribeirão Preto (RP) and São Luís (SL), Brazil. Pregnant women (1393 in RP and 1413 in SL) were studied; information was obtained through questionnaires in addition to anthropometric, biochemical, and blood pressure measurements. Data are presented as means and proportions. To compare the characteristics of pregnant women in both cities, chi-squared and Student's t-tests were applied, with 5% significance level. Ribeirão Preto presented higher mean values than SL for pre-gestational body mass index (24.5 vs 23 kg/m2, P<0.001), systolic (108.4 vs 102.8 mmHg, P<0.001) and diastolic (65.9 vs 61.8 mmHg, P<0.001) blood pressure, total cholesterol (226.3 vs 213.7 mg/dL, P<0.001) and fractions, and glycemia (84.5 vs 80.2 mg/dL, P<0.001), except for triglycerides (P=0.135). Women from RP also showed higher rates of pre-gestational overweight and obesity compared with SL (40.1 vs 25.8%). In the present study, pregnant women in RP had a worse gestational metabolic profile than those in SL, with higher pre-gestational excess weight, indicating that nutritional transition was more advanced in the more developed city.

Avaliação do perfil metabólico dos pacientes transplantados do coração no Hospital de Messejana / Evaluation of the metabolic profile of heart transplant patients at the Hospital de Messejana

Objetivo: Este estudo visa avaliar o perfil metabólico de pacientes que foram submetidos a TxC em um centro de referência do estado do Ceará. Métodos: Trata-se de um estudo transversal, quantitativo, em que se avaliaram 110 pacientes receptores de TxC no Hospital de Messejana de Fortaleza, no período de 2011 a 2018, por meio de uma ficha clínica. Resultados: observou-se que a maioria dos pacientes era do gênero masculino (76,5%), e a média de idade foi de 46,26 ± 12,73 anos. Entre os pacientes, observou-se que previamente à cirurgia, 42,5% tinham histórico familiar de doença cardíaca, 40,1% estavam com sobrepeso e 15% eram diabéticos. A classe de medicação mais utilizada para as doenças de bases foram os diuréticos, inibidores da enzima conversora da angiotensina e bloqueadores de receptores da angiotensina. A principal etiologia que levou à necessidade do TxC foi a miocardiopatia isquêmica. Conclusões: Nesta amostra, a doença de base com maior prevalência que levou ao transplante foi a miocardiopatia isquêmica. A maioria dos pacientes apresentou rejeição ao enxerto em algum momento do período estudado. Todos os pacientes que apresentaram descompensação glicêmica fizeram uso de insulina.

Objective: This study aims to assess the metabolic profile of patients who underwent HT at a referral center in the state of Ceará. Methods: This is a cross-sectional, quantitative study, in which 110 patients receiving HT were evaluated at the Hospital de Messejana in Fortaleza, from 2011 to 2018, through a clinical form. Results: It was observed that the majority of patients were male (76.5%) and the mean age was 46.26 ± 12.73 years. Among the patients, it was observed that prior to surgery, 42.5% had a family history of heart disease, 40.1% were overweight, and 15% were diabetic. The most used class of medication for underlying diseases were diuretics, angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers. The main etiology leading to the need for HT was ischemic cardiomyopathy. Conclusions: In this sample, the most prevalent underlying disease leading to transplantation was ischemic cardiomyopathy. Most patients presented graft rejection at some point during the study period. All patients who presented glycemic decompensation used insulin.

Untargeted Metabolomic Profiling of Liver and Serum in Mouse during Normal Aging / 中国医学科学院学报

Objective To obtain the metabolome profiles in liver and serum of mice during normal aging. Methods The liver and serum samples of ten 2-month-old mice and ten 18-month-old C57BL/6J mice under physiological conditions were collected.Metabolites were identified and quantified by liquid chromatography-tandem mass spectrometry.The overall assessment,differential screening,and functional analysis were performed with the filtered high-quality data. Results In the negative-ion mode and positive-ion mode,242 and 399 metabolites were identified in the liver and 265 and 230 in serum,respectively.The difference of metabolome between young and old mice was moderate.The upregulated metabolites identified in aging liver were related to the metabolism of riboflavin,glucose,and arachidonic acid,while the downregulated ones were associated with the metabolism of pyrimidine,purine,glycerophospholipid,glutathione,and nicotinamide.Altered metabolites in serum during aging were involved in a variety of nucleic acid metabolism-related pathways,such as pyrimidine metabolism,purine metabolism,one carbon pool by folate,and amino sugar and nucleotide sugar metabolism. Conclusions The metabolome profiles of mouse liver and serum both revealed dysregulated nucleic acid metabolism pathways during normal aging.This study provides metabolome data for further research on aging-associated mechanism and may support the discovery of intervention methods for aging.

Analysis of apple postharment damage under high CO₂ concentration by transcriptome combined with metabolome / 生物工程学报

The environmental gas concentration affects the storage period and quality of fruits and vegetables. High concentration CO₂ treating for a long time will cause damage to fruits, However, the specific molecular mechanism is unclear. To analyze the mechanism of CO₂ injury in apple, high-throughput sequencing technology of Illumina Hiseq 4000 and non-targeted metabolism technology were used to analyze the transcriptome sequencing and metabolomics analysis of browning flesh tissue of damage fruit and normal pulp tissue of the control group. A total of 6 332 differentially expressed genes were obtained, including 4 187 up-regulated genes and 2 145 down regulated genes. Functional analysis of the differentially expressed genes confirmed that the occurrence of CO₂ injury in apple was related to redox process, lipid metabolism, hormone signal transduction process and energy metabolism process. Twenty candidate browning genes were successfully screened, among which grxcr1 (md14g1137800) and gpx (md06g1081300) participated in the reactive oxygen species scavenging process, and pld1_ 2 (md15g1125000) and plcd (md07g1221900) participated in phospholipid acid synthesis and affected membrane metabolism. mdh1 (md05g1238800) participated in TCA cycle and affected energy metabolism. A total of 77 differential metabolites were obtained by metabolomic analysis, mainly organic acids, lipids, sugars and polyketones, including 35 metabolites related to browning. The metabolism of flavonoids was involved in the browning process of apple. Compared with the control tissue, the content of flavonoids such as catechin and quercetin decreased significantly in the damaged apple tissue, the antioxidant capacity of cells decreased, the redox state was unbalanced, and the cell structure was destroyed, resulting in browning. The results of this study further enrich the theoretical basis of CO₂ damage, and provide reference for the practical application of high concentration CO₂ preservation technology.

Transcriptome sequencing and metabolome analysis reveal the mechanism of Shuanghua Baihe Tablet in the treatment of oral mucositis / 中国天然药物

Oral mucositis (OM) caused by cancer therapy is the most common adverse reaction in the radiotherapy of head and neck tumors. In severe cases, it can lead to the interruption of treatment, which affects the control of the disease and the quality of life. Shuanghua Baihe Tablet (SBT) is a traditional Chinese medicine (TCM) formula, which is administerd to treat OM in China. It has been clinically effective for more than 30 years, but the underlying mechanism is not completely understood. With the development of multiple omics, it is possible to explore the mechanism of Chinese herbal compound prescriptions. Based on transcriptomics and metabolomics, we explored the underlying mechanism of SBT in the treatment of OM. An OM model of rats was established by 5-FU induction, and SBT was orally administered at dosages of 0.75 and 3 g·kg

Analysis of metabolic profile and genetic variants for newborns with primary carnitine deficiency from Guangxi / 中华医学遗传学杂志

OBJECTIVE@#To analyze the metabolic profile and genetic variants for newborns with primary carnitine deficiency (PCD) from Guangxi, China.@*METHODS@#From January 2014 to December 2019, 400 575 newborns from the jurisdiction of Guangxi Zhuang Autonomous Region Newborn Screening Center were subjected to tandem mass spectrometry (MS/MS) analysis. Newborns with positive results for PCD and their mothers were recalled for retesting. Those who were still positive were subjected to sequencing of the SLC22A5 gene.@*RESULTS@#Twenty-two newborns and 9 mothers were diagnosed with PCD, which gave a prevalence rate of 1/18 208. Sequencing of 18 newborns and 4 mothers have identified 14 types of SLC22A5 gene variants, with the common ones including c.51C>G (10/44, 22.7%), c.1195C>T (9/44, 20.5%) and c.1400C>G (7/44, 15.9%), The c.517delC(p.L173Cfs*3) and c.1031C>T(p.T344I) were unreported previously and predicted to be pathogenic (PVS1+PM2_supporting+PM3+PP4) and likely pathogenic (PM1+PM2_supporting+PM3+PP3+PP4) based on the American College of Medical Genetics and Genomics standards and guidelines.@*CONCLUSION@#c.51C>G, c.1195C>T and c.1400C>G are the most common variants underlying PCD in Guangxi.

Does Cystatin C have a role as metabolic surrogate in peritoneal dialysis beyond its association with residual renal function? / Teria a Cistatina C um papel como substituto metabólico na diálise peritoneal além de sua associação com a função renal residual?

ABSTRACT Introduction: It has been suggested that cystatin C levels are modified by obesity and inflammation. Furthermore, cystatin C has been associated with cardiovascular events and mortality outcomes. Aim: To study the association of cystatin C with the metabolic profile and cardiovascular disease of peritoneal dialysis patients. Methods: Data collected included clinical, laboratorial, and multifrequency bioimpedance assessment of 52 stable peritoneal dialysis patients. Minimal residual renal function was defined as > 2mL/min/1.73m2. Results: Serum cystatin C was not significantly associated with peritoneal or urinary cystatin C excretion. Negative correlation of cystatin C with normalized protein catabolic rate (rho -0.33, p = 0.02) and a trend towards positive correlation with relative body fat (rho 0.27, p = 0.05) were not independent from residual renal function. Cystatin C was not significantly associated with cardiovascular disease (p = 0.28), nor with glycated hemoglobin (p = 0.19) or c-reactive protein (p = 0.56). In the multivariate model, both age and diabetes were the strongest predictors of cardiovascular disease (odds ratio 1.09, p = 0.029 and odds ratio 29.95, p = 0.016, respectively), while relative body fat was negatively associated with cardiovascular disease (p = 0.038); neither cystatin C (p = 0.096) nor minimal residual renal function (p = 0.756) reached a significant association with cardiovascular disease. Conclusions: In this group of peritoneal dialysis patients, cystatin C did not correlate with the metabolic or inflammatory status, nor cardiovascular disease, after adjustment for residual renal function.

RESUMO Introdução: Tem sido sugerido que os níveis de cistatina C são modificados pela obesidade e inflamação. Além disso, a cistatina C tem sido associada a eventos cardiovasculares e desfechos de mortalidade. Objetivo: Estudar a associação da cistatina C com o perfil metabólico e doença cardiovascular de pacientes em diálise peritoneal. Métodos: Os dados coletados incluíram avaliação clínica, laboratorial e de bioimpedância múltipla de 52 pacientes estáveis em diálise peritoneal. A função renal residual mínima foi definida como > 2mL/min/1,73m2. Resultados: A cistatina C sérica não esteve significativamente associada à excreção peritoneal ou urinária. A correlação negativa da cistatina C com a taxa catabólica protéica normalizada (rho -0,33, p = 0,02) e uma tendência de correlação positiva com a gordura corporal relativa (rho 0,27, p = 0,05) não foram independentes da função renal residual. A cistatina C não se associou significativamente à doença cardiovascular (p = 0,28), nem com hemoglobina glicada (p = 0,19) ou proteína C reativa (p = 0,56). No modelo multivariado, idade e diabetes foram os mais fortes preditores de doença cardiovascular (razões de probabilidade 1,09, p = 0,029 e 29,95, p = 0,016, respectivamente) enquanto a gordura corporal relativa se associou negativamente à doença cardiovascular (p = 0,038). A cistatina C não se associou significativamente com doença cardiovascular (p = 0,096), tampouco a função residual mínima (p = 0,756). Conclusão: Neste grupo de pacientes em diálise peritoneal, a cistatina C não se correlacionou com o estado metabólico ou inflamatório, nem com doença cardiovascular, após ajuste para função renal residual.

Expressão e atividade de sistemas de dois componentes (TCS) de Salmonella enterica sorovar Typhimurium no contexto do metaboloma intestinal humano / Expression and activity of two-component systems of Salmonella enterica sorovar Typhimurium in the context of the human intestinal metabolome

A interação entre membros do microbioma intestinal humano, células hospedeiras e patógenos invasores pode ocorrer de diversas formas, sendo uma delas através de pequenas moléculas chamadas metabólitos. A percepção e resposta efetiva de um microrganismo às diferentes condições encontradas em seu ambiente, incluindo metabólitos produzidos por outros microrganismos, são fatores importantes para sua adaptação, sobrevivência e disseminação. Os sistemas de dois componentes (TCS) permitem a percepção e resposta a mudanças ambientais, regulando a expressão de genes específicos. Nosso grupo mostrou anteriormente que um extrato orgânico de fezes humanas (EF), bem como o ácido 3,4-dimetilbenzoico (3,4-DMB), encontrado no EF, inibe a capacidade de Salmonella enterica sorovar Typhimurium de invadir células hospedeiras. O presente trabalho propôs investigar o impacto do microbioma intestinal humano, bem como de pequenas moléculas produzidas por Clostridium citroniae (membro deste microbioma) na expressão e atividade dos genes de TCS de Salmonella. Os metabólitos de EF e de culturas puras de C. citroniae foram extraídos com acetato de etila e adicionados a meio de cultura. O pH do meio foi ajustado (~ 7,4) e a solução foi esterilizada por filtragem. Salmonella foi cultivada na presença ou ausência do EF e do extrato de C. citroniae, bem como do ácido 3,4-DMB, em condições aeróbias e anaeróbias, até alcançar o meio da fase logarítmica de crescimento. O RNA foi extraído para a realização de PCR em Tempo Real utilizando iniciadores direcionados a quase todos os TCS de Salmonella. Nossos resultados mostraram que vários genes de TCS envolvidos na virulência de Salmonella (SsrAB, EnvZ-OmpR, QseCB, PhoQP, TorSR, TtrRS) foram regulados diferencialmente por esses metabólitos, tanto em condições aeróbias quanto anaeróbias. EnvZ-OmpR, PhoPQ e SsrAB estão diretamente envolvidos na regulação das Ilhas de Patogenicidade 1 e 2 de Salmonella. QseCB é crucial para a detecção de quorum em Salmonella, de hormônios hospedeiros e para a regulação da motilidade (swimming). Vários outros TCS também foram regulados, incluindo TorSR e TtrRS, envolvidos na regulação da respiração anaeróbica de N-óxido de trimetilamina (TMAO) e tetrationato, respectivamente. Esses compostos são importantes para a sobrevivência de Salmonella no ambiente anaeróbico do intestino humano. Nossos resultados de avaliação de expressão gênica global de Salmonella cultivada na presença de ácido 3,4-DMB (aerobiose e anaerobiose) bem como na presença do EF em anaerobiose, mostraram que genes condificados em SPI-1 e SPI-2, SPI-4 e alguns genes do TCS foram reprimidos, enquanto genes marR, marB e marA foram ativadas nessas condições. Adicionalmente, comparamos nossos resultados de RNAseq, de Salmonella cultivada na presença do ácido 3,4-DMB em aerobiose, com resultados disponíveis da base de dados Salmonella Compendium. Ainda, a capacidade de Salmonella de adentrar e sobreviver dentro de células fagocíticas (macrófagos RAW 264.7) parece ser afetada pelas três condições testadas neste trabalho. Nossos resultados mostram que importantes vias de sinalização da virulência de Salmonella podem ser moduladas pelos metabólitos presentes no microbioma intestinal humano e abrem caminhos para novas pesquisas sobre a sinalização intercelular microbioma-patógeno no ambiente intestinal.

The interaction between members of the human gut microbiome, host cells and invading pathogens often occurs through small molecules, also called metabolites. The perception and effective response of a microorganism to the different conditions found in its environment, including metabolites produced by other microbes, is important for its adaptation, survival and dissemination. Two-component systems (TCS) allow the perception and response to environmental changes by regulating the expression of specific genes. Our group previously showed that organic extracts of human feces (EF) as well as the specific metabolite 3,4-dimethylbenzoic acid (3,4-DMB) found within the EF, inhibit the ability of Salmonella enterica sorovar Typhimurium to invade host cells. In the present work, we investigated the impact of the human gut microbiome as well as small molecules produced by Clostridium citroniae (a member of this microbiome) on the expression and activity of Salmonella TCS genes. Metabolites (from feces or C. citroniae cultures) were extracted using ethyl acetate and added to culture medium. The pH of the medium was adjusted (~7.4), and the solution was filter sterilized. Salmonella was grown in the presence or absence of the organic extracts as well as 3,4-DMB acid under aerobic and anaerobic conditions until it reached mid-log growth. RNA was then extracted for Real-time PCR using primers targeting almost all Salmonella TCS. Our results showed that several TCS involved in Salmonella virulence (SsrAB, EnvZ-OmpR, QseCB, PhoQP, TorSR, TtrRS) were differentially regulated by these metabolites both in aerobic and anaerobic conditions. EnvZ-OmpR, PhoPQ, and SsrAB are directly involved in the regulation of Salmonella Pathogenicity Islands 1 and 2. QseCB is crucial for Salmonella =quorum sensing, sensing of host hormones and regulation of swimming motility. Several other TCS were also regulated, including TorSR and TtrRS, which are involved in the anaerobic respiration of trimethylamine N-oxide (TMAO) and tetrathionate, respectively. These compounds are important for Salmonella survival in the anaerobic environment of the human gut. Our results of the evaluation of global Salmonella gene expression grown in the presence of 3,4-DMB acid (aerobiosis and anaerobiosis) as well as in the presence of EF in anaerobiosis, showed that genes encoded in SPI-1 and SPI-2, SPI-4 and some TCS genes have been repressed, while multiple drug resistance genes, as well marR, marB and marA genes have been activated under these conditions. Besides, we compared our results of RNAseq, Salmonella was grown in the presence of 3,4-DMB acid in aerobiosis, with results available from the Salmonella Compendium database. Also, Salmonella's ability to enter and survive within phagocytic cells (macrophages RAW 264.7) appears to be affected by the three conditions tested in this work. Our results show that important Salmonella virulence signalling pathways can be modulated by the metabolites present in the human intestinal microbiome and open the way for further research on the microbiome-pathogen intercellular signalling in the intestinal environment.

Serum Metabolomic Indicates Potential Biomarkers and Metabolic Pathways of Pediatric Kashin-Beck Disease / 生物医学与环境科学（英文）

Objective@#To explore potential serum biomarkers of children with Kashin-Beck Disease (KBD) and the metabolic pathways to which the biomarkers belong.@*Methods@#A two-stage metabolomic study was employed. The discovery cohort included 56 patients, 51 internal controls, and 50 external controls. The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases (HMDB) and Metlin databases. MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to analyze the metabolic pathways of the candidate metabolites. The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients, 41 internal controls, and 50 external controls.@*Results@#Eight candidate metabolites were identified out in the discovery study, namely kynurenic acid, N-α-acetylarginine, 6-hydroxymelatonin, sphinganine, ceramide, sphingosine-1P, spermidine, and glycine. These metabolites exist in sphingolipid, glutathione, and tryptophan metabolic pathways. In the second-stage study, five candidate metabolites were validated, including kynurenic acid, N-α-acetylarginine, sphinganine, spermidine, and sphingosine-1P. Except for spermidine, all substances exhibited low expression in the case group compared with the external control group, and the difference in levels of sphinganine, spermidine, and sphingosine-1P was statistically significant.@*Conclusion@#The direction of change of levels of sphinganine, spermidine, and sphingosine-1P in the two-stage study cohorts was completely consistent, and the differences were statistically significant. Therefore, these substances can be used as potential biomarkers of KBD. Furthermore, these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.

Blood lipid metabolic profile of overweight/obese boys aged 9-12 years / 中国当代儿科杂志

OBJECTIVE@#To study the features of blood lipid metabolic profile in overweight/obese boys aged 9-12 years and the possible mechanism of overweight/obesity in children.@*METHODS@#According to body mass index (BMI), 72 boys, aged 9-12 years, were divided into a control group with 42 boys and an overweight/obesity group with 30 boys. Fasting venous blood samples were collected early in the morning. BMI, waist-hip ratio, body composition, and blood lipids were measured. Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technique was used to analyze the serum lipid compounds. A statistical analysis and visualization of the data were performed.@*RESULTS@#Compared with the control group, the overweight/obesity group had significantly higher waist-hip ratio, body fat percentage, and triglyceride level (P<0.05) and a significantly lower level of high-density lipoprotein cholesterol (P<0.05). The metabolomic analysis identified 150 differentially expressed lipid compounds between the two groups, mainly glycerolipids (40.7%), glycerophospholipids (24.7%), fatty acyls (10.7%), and sphingolipids (7.3%). The levels of most of glycerolipids were significantly upregulated in the overweight/obesity group, while those of most of glycerophospholipids and sphingolipids were downregulated in this group. Key lipids with differential expression were enriched into two KEGG metabolic pathways, i.e., ether lipid metabolism pathway and terpenoid backbone biosynthesis pathway (P<0.05), and might further affected the biosynthesis and metabolism of downstream coenzyme Q and other terpenoids (P=0.06).@*CONCLUSIONS@#Disordered lipid metabolic profile is observed in overweight/obese boys aged 9-12 years, with increases in most glycerolipids and reductions in glycerophospholipids and sphingolipids. Overweight/obese boys may have disorders in ether lipid metabolism and biosynthesis of terpenoid and even coenzyme Q.