PubMed

Cancer Med. 2023 Jun 17. doi: 10.1002/cam4.6248. Online ahead of print.ABSTRACTBACKGROUND: Trials of tyrosine kinase inhibitors (TKI) have not demonstrated dramatic benefits in advanced colorectal cancer (CRC), and this may be a function of poor patient selection. TKI-induced hypertension is reportedly a surrogate marker for treatment benefit for some tumor types. Our objective was to determine whether hypertension was associated with benefit in the context of CRC treatment, and also to gain insight on the pathogenesis of TKI-induced hypertension by monitoring associated changes in the circulating metabolome.PATIENTS AND METHODS: Clinical data were acquired from clinical trial patients with metastatic CRC randomized to cetuximab ± the TKI brivanib (N = 750). Outcomes were evaluated as a function of treatment-induced hypertension. For metabolomic studies, plasma samples were taken at baseline, as well as at 1, 4, and 12 weeks after treatment initiation. Samples were submitted to gas chromatography-mass spectrometry to identify treatment-related metabolomic changes associated with TKI-induced hypertension, compared to pre-treatment baseline. A model based on changes in metabolite concentrations was generated using orthogonal partial least squares discriminant analysis (OPLS-DA).RESULTS: In the brivanib treated group, 95 patients had treatment-related hypertension within 12 weeks of initiating treatment. TKI-induced hypertension was not associated with a significantly higher response rate, nor was it associated with improved progression-free or overall survival. In metabolomic studies, 386 metabolites were identified. There were 29 metabolites that changed with treatment and distinguished patients with and without TKI-induced hypertension. The OPLS-DA model for brivanib-induced hypertension was significant and robust (R2 Y score = 0.89, Q2 Y score = 0.70, CV-ANOVA = 2.01 e-7). Notable metabolomic features previously reported in pre-eclampsia and associated with vasoconstriction were found.CONCLUSION: TKI-induced hypertension was not associated with clinical benefit in metastatic CRC. We have identified changes in the metabolome that are associated with the development of worsening brivanib-induced hypertension that may be useful in future efforts of characterizing this toxicity.PMID:37329221 | DOI:10.1002/cam4.6248

Plant J. 2023 Jun 17. doi: 10.1111/tpj.16357. Online ahead of print.ABSTRACTCassava's storage roots represent one of the most important sources of nutritional carbohydrates worldwide. Particularly, smallholder farmers in Sub-Saharan Africa depend on this crop plant, where resilient and yield-improved varieties are of vital importance to support steadily increasing populations. Aided by a growing understanding of the plant's metabolism and physiology, targeted improvement concepts already led to visible gains in recent years. To expand our knowledge and to contribute to these successes, we investigated storage roots of eight cassava genotypes with differential dry matter content from three successive field trials for their proteomic and metabolic profiles. At large, the metabolic focus in storage roots transitioned from cellular growth processes towards carbohydrate and nitrogen storage with increasing dry matter content. This is reflected in higher abundance of proteins related to nucleotide synthesis, protein turnover and vacuolar energization in low starch genotypes, while proteins involved in sugar conversion and glycolysis were more prevalent in high dry matter genotypes. This shift in metabolic orientation was underlined by a clear transition from oxidative- to substrate-level phosphorylation in high dry matter genotypes. Our analyses highlight metabolic patterns that are consistently and quantitatively associated with high dry matter accumulation in cassava storage roots, providing fundamental understandings of cassava's metabolism as well as a data resource for targeted genetic improvement.PMID:37329210 | DOI:10.1111/tpj.16357

Proteomics Clin Appl. 2023 Jun 17:e2300008. doi: 10.1002/prca.202300008. Online ahead of print.ABSTRACTPURPOSE: Our main goal is to identify the alterations in the amniotic fluid (AF) metabolome in Zika virus (ZIKV)-infected patients and their relation to congenital Zika syndrome (CZS) progression.EXPERIMENTAL DESIGN: We applied an untargeted metabolomics strategy to analyze seven AF of pregnant women: healthy women and ZIKV-infected women bearing non-microcephalic and microcephalic fetuses.RESULTS: Infected patients were characterized by glycerophospholipid metabolism impairment, which is accentuated in microcephalic phenotypes. Glycerophospholipid decreased concentration in AF can be a consequence of intracellular transport of lipids to the placental or fetal tissues under development. The increased intracellular concentration of lipids can lead to mitochondrial dysfunction and neurodegeneration caused by lipid droplet accumulation. Furthermore, the dysregulation of amino acid metabolism was a molecular fingerprint of microcephalic phenotypes, specifically serine, and proline metabolisms. Both amino acid deficiencies were related to neurodegenerative disorders, intrauterine growth retardation, and placental abnormalities.CONCLUSIONS AND CLINICAL RELEVANCE: This study enhances our understanding of the development of CZS pathology and sheds light on dysregulated pathways that could be relevant for future studies.PMID:37329193 | DOI:10.1002/prca.202300008

Cardiovasc Diabetol. 2023 Jun 16;22(1):141. doi: 10.1186/s12933-023-01862-z.ABSTRACTBACKGROUND: Metabolic Syndrome (MetS) is characterized by risk factors such as abdominal obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol (HDL-C), hypertension, and hyperglycemia, which contribute to the development of cardiovascular disease and type 2 diabetes. Here, we aim to identify candidate metabolite biomarkers of MetS and its associated risk factors to better understand the complex interplay of underlying signaling pathways.METHODS: We quantified serum samples of the KORA F4 study participants (N = 2815) and analyzed 121 metabolites. Multiple regression models adjusted for clinical and lifestyle covariates were used to identify metabolites that were Bonferroni significantly associated with MetS. These findings were replicated in the SHIP-TREND-0 study (N = 988) and further analyzed for the association of replicated metabolites with the five components of MetS. Database-driven networks of the identified metabolites and their interacting enzymes were also constructed.RESULTS: We identified and replicated 56 MetS-specific metabolites: 13 were positively associated (e.g., Val, Leu/Ile, Phe, and Tyr), and 43 were negatively associated (e.g., Gly, Ser, and 40 lipids). Moreover, the majority (89%) and minority (23%) of MetS-specific metabolites were associated with low HDL-C and hypertension, respectively. One lipid, lysoPC a C18:2, was negatively associated with MetS and all of its five components, indicating that individuals with MetS and each of the risk factors had lower concentrations of lysoPC a C18:2 compared to corresponding controls. Our metabolic networks elucidated these observations by revealing impaired catabolism of branched-chain and aromatic amino acids, as well as accelerated Gly catabolism.CONCLUSION: Our identified candidate metabolite biomarkers are associated with the pathophysiology of MetS and its risk factors. They could facilitate the development of therapeutic strategies to prevent type 2 diabetes and cardiovascular disease. For instance, elevated levels of lysoPC a C18:2 may protect MetS and its five risk components. More in-depth studies are necessary to determine the mechanism of key metabolites in the MetS pathophysiology.PMID:37328862 | DOI:10.1186/s12933-023-01862-z

Mol Neurobiol. 2023 Jun 16. doi: 10.1007/s12035-023-03403-x. Online ahead of print.ABSTRACTOptimizing the metabolic phenotype to improve cerebral function is critical for treatment of cerebral ischemia-reperfusion (I/R) injury. Guhong injection (GHI), which comprised safflower extract and aceglutamide, is widely prescribed in Chinese medicine for the treatment of cerebrovascular diseases. In this study, a combination of LC-QQQ-MS and MALDI-MSI were utilized to explore tissue-specific metabolic alterations in the brain of I/R, as well as to evaluate the therapeutic effect of GHI. Pharmacological evaluation demonstrated that GHI can significantly improve infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. Based on LC-QQQ-MS, 23 energy metabolites were found to be significantly altered in the I/R group compared to the sham group (P < 0.05). After GHI treatment, 12 metabolites, including G6P, TPP, NAD, citrate, succinate, malate, ATP, GTP, GDP, ADP, NADP, and FMN showed a significant tendency of returning to baseline values (P < 0.05). Based on MALDI-MSI, 4 metabolites in glycolysis and TCA, 4 metabolites in nucleic acid metabolism, 4 amino acid metabolites, and 6 metabolites were discovered and compared between the different groups in the four special regions of cortex, hippocampus, hypothalamus, and striatum. Parts of these were found to have significant changes after I/R in the special brain region, and were regulated by GHI. The study provides comprehensive and detailed information for specific metabolic reprogramming of brain tissue in rats with I/R, and the therapeutic effect of GHI. Schema describing the discovery strategies of integrated LC-MS and MALDI-MSI to identify cerebral ischemia reperfusion metabolic reprogramming and GHI therapeutic effects.PMID:37328677 | DOI:10.1007/s12035-023-03403-x

Amino Acids. 2023 Jun 17. doi: 10.1007/s00726-023-03293-2. Online ahead of print.ABSTRACTSome individuals are susceptible to accelerated biological ageing, resulting in premature alterations in arterial structure and function. Identifying early-onset vascular ageing characterised by arterial stiffening is vital for intervention and preventive strategies. We stratified and phenotyped healthy children (5-9 yrs) and young adults (20-30 yrs) into their vascular ageing extremes established by carotid-femoral pulse wave velocity (cfPWV) percentiles (i.e., healthy vascular ageing (HVA) and early vascular ageing (EVA)). We compared anthropometric, cardiovascular, and metabolomic profiles and explored associations between cfPWV and urinary metabolites. Children and adults in the EVA groups displayed higher levels of adiposity, cardiovascular, and lifestyle risk factors (adults only) (all p ≤ 0.018). In adults, several urinary metabolites were lower in the EVA group (all q ≤ 0.039) when compared to the HVA group, with no differences observed in children. In multiple regression analysis (adults only), we found inverse associations between cfPWV with histidine (adj. R2 = 0.038; β = -0.192; p = 0.013) and beta-alanine (adj. R2 = 0.034; β = -0.181; p = 0.019) in the EVA group, but with arginine (adj. R2 = 0.021; β = -0.160; p = 0.024) in the HVA group. The inverse associations of beta-alanine and histidine with cfPWV in the EVA group is suggestive that asymptomatic young adults who present with an altered metabolomic and less desired cardiovascular profile in combination with unfavourable lifestyle behaviours may be predisposed to early-onset vascular ageing. Taken together, screening on both a phenotypic and metabolic level may prove important in the early detection, prevention, and intervention of advanced biological ageing.PMID:37328631 | DOI:10.1007/s00726-023-03293-2

Sci Rep. 2023 Jun 16;13(1):9802. doi: 10.1038/s41598-023-36874-y.ABSTRACTBladder cancer (BC) is a common urological malignancy with a high probability of death and recurrence. Cystoscopy is used as a routine examination for diagnosis and following patient monitoring for recurrence. Repeated costly and intrusive treatments may discourage patients from having frequent follow-up screenings. Hence, exploring novel non-invasive ways to help identify recurrent and/or primary BC is critical. In this work, 200 human urine samples were profiled using ultra-high-performance liquid chromatography and ultra-high-resolution mass spectrometry (UHPLC-UHRMS) to uncover molecular markers differentiating BC from non-cancer controls (NCs). Univariate and multivariate statistical analyses with external validation identified metabolites that distinguish BC patients from NCs disease. More detailed divisions for the stage, grade, age, and gender are also discussed. Findings indicate that monitoring urine metabolites may provide a non-invasive and more straightforward diagnostic method for identifying BC and treating recurrent diseases.PMID:37328580 | DOI:10.1038/s41598-023-36874-y

Environ Pollut. 2023 Jun 14:122040. doi: 10.1016/j.envpol.2023.122040. Online ahead of print.ABSTRACTDespite the growing concerns about arsenic (As) toxicity, information on wheat adaptability in such an aggravating environment is limited. Thus, the present investigation based on an iono-metabolomic approach is aimed to decipher the response of wheat genotypes towards As toxicity. Wheat genotypes procured from natural conditions were characterized as high As-contaminated (Shri ram-303 and HD-2967) and low As-contaminated (Malviya-234 and DBW-17) based on ICP-MS As accumulation analysis. Reduced chlorophyll fluorescence attributes, grain yield and quality traits, and low grain nutrient status were accompanied by remarkable grain As accumulation in high As-contaminated genotypes, thus imposing a higher potential cancer risk and hazard quotient. Contrarily, in low As-contaminated genotypes, the richness of Zn, N, Fe, Mn, Na, K, Mg, and Ca could probably have supported less grain As accumulation, imparting better agronomic and grain quality traits. Additionally, from metabolomic analysis (LC-MS/MS and UHPLC), abundances of alanine, aspartate, glutamate, quercetin, isoliquiritigenin, trans-ferrulic, cinnamic, caffeic, and syringic bestow Malviya-234 as the best edible wheat genotype. Further, the multivariate statistical analysis (HCA, PCA, and PLS-DA) revealed certain other key metabolites (rutin, nobletin, myricetin, catechin, and naringenin) based genotypic discrimination that imparts strength to genotypes for better adaptation in harsh conditions. Out of the 5 metabolic pathways ascertained through topological analysis, the two main pathways vital for plant's metabolic adjustments in an As-induced environment were: 1. The alanine, aspartate and glutamate metabolism pathway, and 2. The flavonoid biosynthesis pathway. This is also evident from network analysis, which stipulates amino acid metabolism as a prominent As regulatory factor closely associated with flavonoids and phenolics. Therefore, the present findings are useful for wheat breeding programs to develop As adaptive genotypes that are beneficial for crop improvement and human health.PMID:37328127 | DOI:10.1016/j.envpol.2023.122040

J Ethnopharmacol. 2023 Jun 14:116765. doi: 10.1016/j.jep.2023.116765. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Liver cancer is a worldwide malignant tumor, and currently lacks effective treatments. Clinical studies have shown that epimedium (YYH) has therapeutic effects on liver cancer, and some of its prenylflavonoids have demonstrated anti-liver cancer activity through multiple mechanisms. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of YYH.AIM OF THE STUDY: This study aimed to screen the anti-cancer material basis of YYH via integrating spectrum-effect analysis with serum pharmacochemistry, and explore the multi-target mechanisms of YYH against liver cancer by combining network pharmacology with metabolomics.MATERIALS AND METHODS: The anti-cancer effect of the extract of YYH (E-YYH) was first evaluated in mice with xenotransplantation H22 tumor cells burden and cultured hepatic cells. Then, the interaction between E-YYH compounds and the cytotoxic effects was revealed through spectrum-effect relationship analysis. And the cytotoxic effects of screened compounds were verified in hepatic cells. Next, UHPLC-Q-TOF-MS/MS was employed to identify the absorbed components of E-YYH in rat plasma to distinguish anti-cancer components. Subsequently, network pharmacology based on anti-cancer materials and metabolomics were used to discover the potential anti-tumor mechanisms of YYH. Key targets and biomarkers were identified and pathway enrichment analysis was performed.RESULTS: The anti-cancer effect of E-YYH was verified through in vitro and in vivo experiments. Six anti-cancer compounds in plasma (icariin, baohuoside Ⅰ, epimedin C, 2″-O-rhamnosyl icariside Ⅱ, epimedin B and sagittatoside B) were screened out by spectrum-effect analysis. Forty-five liver-cancer-related targets were connected with these compounds. Among these targets, PTGS2, TNF, NOS3 and PPARG were considered to be the potential key targets preliminarily verified by molecular docking. Meanwhile, PI3K/AKT signaling pathway and arachidonic acid metabolism were found to be associated with E-YYH's efficacy in network pharmacology and metabolomics analysis.CONCLUSIONS: Our research revealed the characteristics of multi-component, multi-target and multi-pathway mechanism of E-YYH. This study also provided an experimental basis and scientific evidence for the clinical application and rational development of YYH.PMID:37328080 | DOI:10.1016/j.jep.2023.116765

Cell Host Microbe. 2023 Jun 7:S1931-3128(23)00215-9. doi: 10.1016/j.chom.2023.05.022. Online ahead of print.ABSTRACTThe microbiomes of cesarean-born infants differ from vaginally delivered infants and are associated with increased disease risks. Vaginal microbiota transfer (VMT) to newborns may reverse C-section-related microbiome disturbances. Here, we evaluated the effect of VMT by exposing newborns to maternal vaginal fluids and assessing neurodevelopment, as well as the fecal microbiota and metabolome. Sixty-eight cesarean-delivered infants were randomly assigned a VMT or saline gauze intervention immediately after delivery in a triple-blind manner (ChiCTR2000031326). Adverse events were not significantly different between the two groups. Infant neurodevelopment, as measured by the Ages and Stages Questionnaire (ASQ-3) score at 6 months, was significantly higher with VMT than saline. VMT significantly accelerated gut microbiota maturation and regulated levels of certain fecal metabolites and metabolic functions, including carbohydrate, energy, and amino acid metabolisms, within 42 days after birth. Overall, VMT is likely safe and may partially normalize neurodevelopment and the fecal microbiome in cesarean-delivered infants.PMID:37327780 | DOI:10.1016/j.chom.2023.05.022

Mar Pollut Bull. 2023 Jun 14;193:115153. doi: 10.1016/j.marpolbul.2023.115153. Online ahead of print.ABSTRACTMicroplastics (MPs) pollution and salinity variation are two environmental stressors, but their combined effects on marine mollusks are rarely known. Oysters (Crassostrea gigas) were exposed to 1 × 104 particles L-1 spherical polystyrene MPs (PS-MPs) of different sizes (small polystyrene MPs (SPS-MPs): 6 μm, large polystyrene MPs (LPS-MPs): 50-60 μm) under three salinity levels (21, 26, and 31 psu) for 14 days. Results demonstrated that low salinity reduced PS-MPs uptake in oysters. Antagonistic interactions between PS-MPs and low salinity mainly occurred, and partial synergistic effects were mainly induced by SPS-MPs. SPS-MPs induced higher lipid peroxidation (LPO) levels than LPS-MPs. In digestive glands, low salinity decreased LPO levels and glycometabolism-related gene expression, which was related to salinity levels. Low salinity instead of MPs mainly affected metabolomics profiles of gills through energy metabolism and osmotic adjustment pathway. In conclusion, oysters can adapt to combined stressors through energy and antioxidative regulation.PMID:37327720 | DOI:10.1016/j.marpolbul.2023.115153

J Chromatogr B Analyt Technol Biomed Life Sci. 2023 Jun 10;1226:123787. doi: 10.1016/j.jchromb.2023.123787. Online ahead of print.ABSTRACTMetabolomics studies in human dermal fibroblasts can elucidate the biological mechanisms associated with some diseases, but several methodological issues that increase variability have been identified. We aimed to quantify the amino acid levels in cultured fibroblasts and to apply different sample-based normalization approaches. Forty-four skin biopsies from control subjects were collected. Amino acids were measured in fibroblasts supernatants by UPLC-MS/MS. Statistical supervised and unsupervised studies were used. Spearman's test showed that phenylalanine displayed the second highest correlation with the remaining amino acids (mean r = 0.8), whereas the total protein concentration from the cell pellet showed a mean of r = 0.67. The lowest percentage of variation was obtained when amino acids were normalized by phenylalanine values, with a mean of 42% vs 57% when normalized by total protein values. When amino acid levels were normalized by phenylalanine, Principal Component Analysis and clustering analyses identified different fibroblasts groups. In conclusion, phenylalanine may be a suitable biomarker to estimate cellular content in cultured fibroblasts.PMID:37327517 | DOI:10.1016/j.jchromb.2023.123787

PLoS One. 2023 Jun 16;18(6):e0287331. doi: 10.1371/journal.pone.0287331. eCollection 2023.ABSTRACTOphiocordyceps sinensis is a fungus with medicinal value in treating lung diseases, but no study has reported how to prevent acute lung injury using this fungus. The mice were divided into normal, model, positive control, and O. sinensis groups to observe lung histopathological sections and transmission electron microscopy, along with liquid chromatography-mass spectrometry and hematoxylin and eosin (H&E) staining to closely identify structural differences resulting from destruction between the groups. The results of the H&E staining showed that, compared with the normal group, the model group showed alveolar collapse. Compared with the model group, the infiltration of inflammatory cells in the alveolar cavity of the O. sinensis group was significantly reduced. Mitochondrial plate-like cristae were observed in type II alveolar cells of the normal group, with normal coloration of the mitochondrial matrix. Type II alveolar cells in the model group showed obvious edema. The statuses of type II alveolar cells in the O. sinensis and positive groups were similar to that in the normal group. Twenty-nine biomarkers and 10 related metabolic pathways were identified by serum metabolomics screening. The results showed that O. sinensis mycelia had a significant effect on the prevention of lipopolysaccharide-induced inflammation.PMID:37327224 | DOI:10.1371/journal.pone.0287331

Curr Med Sci. 2023 Jun 16. doi: 10.1007/s11596-023-2747-0. Online ahead of print.ABSTRACTOBJECTIVE: Metabolic disorders are regarded as hallmarks of multiple myeloma (MM) and are responsible for rapid cancer cell proliferation and tumor growth. However, the exact biological roles of metabolites in MM cells have not been fully explored. This study aimed to explore the feasibility and clinical significance of lactate for MM and investigate the molecular mechanism of lactic acid (Lac) in the proliferation of myeloma cells and cell sensitivity to bortezomib (BTZ).METHODS: Metabolomic analysis of the serum was carried out to obtain metabolites expression and clinical characteristics in MM patients. The CCK8 assay and flow cytometry were used to detect cell proliferation, apoptosis, and cell cycle changes. Western blotting was used to detect the potential mechanism and apoptosis- and cycle-related protein changes.RESULTS: Lactate was highly expressed in both the peripheral blood and bone marrow of MM patients. It was significantly correlated with Durie-Salmon Staging (DS Staging) and the International Staging System (ISS Staging) and the serum and urinary involved/uninvolved free light chain ratios. Patients with relatively high lactate levels had a poor treatment response. Moreover, in vitro experiments showed that Lac could promote the proliferation of tumor cells and decrease the proportion of G0/G1-phase cells, which was accompanied by an increased proportion of S-phase cells. In addition, Lac could decrease tumor sensitivity to BTZ by disrupting the expression of nuclear factor kappa B subunit 2 (NFkB2) and RelB.CONCLUSION: Metabolic changes are important in MM cell proliferation and treatment response; lactate could be used as a biomarker in MM and as a therapeutic target to overcome cell resistance to BTZ.PMID:37326888 | DOI:10.1007/s11596-023-2747-0

Cell Oncol (Dordr). 2023 Jun 16. doi: 10.1007/s13402-023-00823-8. Online ahead of print.ABSTRACTPURPOSE: Serine metabolism is frequently dysregulated in many types of cancers and the tumor suppressor p53 is recently emerging as a key regulator of serine metabolism. However, the detailed mechanism remains unknown. Here, we investigate the role and underlying mechanisms of how p53 regulates the serine synthesis pathway (SSP) in bladder cancer (BLCA).METHODS: Two BLCA cell lines RT-4 (WT p53) and RT-112 (p53 R248Q) were manipulated by applying CRISPR/Cas9 to examine metabolic differences under WT and mutant p53 status. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and non-targeted metabolomics analysis were adopted to identify metabolomes changes between WT and p53 mutant BLCA cells. Bioinformatics analysis using the cancer genome atlas and Gene Expression Omnibus datasets and immunohistochemistry (IHC) staining was used to investigate PHGDH expression. Loss-of-function of PHGDH and subcutaneous xenograft model was adopted to investigate the function of PHGDH in mice BLCA. Chromatin immunoprecipitation (Ch-IP) assay was performed to analyze the relationships between YY1, p53, SIRT1 and PHGDH expression.RESULTS: SSP is one of the most prominent dysregulated metabolic pathways by comparing the metabolomes changes between wild-type (WT) p53 and mutant p53 of BLCA cells. TP53 gene mutation shows a positive correlation with PHGDH expression in TCGA-BLCA database. PHGDH depletion disturbs the reactive oxygen species homeostasis and attenuates the xenograft growth in the mouse model. Further, we demonstrate WT p53 inhibits PHGDH expression by recruiting SIRT1 to the PHGDH promoter. Interestingly, the DNA binding motifs of YY1 and p53 in the PHGDH promoter are partially overlapped which causes competition between the two transcription factors. This competitive regulation of PHGDH is functionally linked to the xenograft growth in mice.CONCLUSION: YY1 drives PHGDH expression in the context of mutant p53 and promotes bladder tumorigenesis, which preliminarily explains the relationship between high-frequency mutations of p53 and dysfunctional serine metabolism in bladder cancer.PMID:37326803 | DOI:10.1007/s13402-023-00823-8

Mol Biol Rep. 2023 Jun 16. doi: 10.1007/s11033-023-08551-w. Online ahead of print.ABSTRACTGenetic improvement of sesame (Sesamum indicum L.), one of the most important oilseed crops providing edible oil, proteins, minerals, and vitamins, is important to ensure a balanced diet for the growing world population. Increasing yield, seed protein, oil, minerals, and vitamins is urgently needed to meet the global demand. The production and productivity of sesame is very low due to various biotic and abiotic stresses. Therefore, various efforts have been made to combat these constraints and increase the production and productivity of sesame through conventional breeding. However, less attention has been paid to the genetic improvement of the crop through modern biotechnological methods, leaving it lagging behind other oilseed crops. Recently, however, the scenario has changed as sesame research has entered the era of "omics" and has made significant progress. Therefore, the purpose of this paper is to provide an overview of the progress made by omics research in improving sesame. This review presents a number of efforts that have been made over past decade using omics technologies to improve various traits of sesame, including seed composition, yield, and biotic and abiotic resistant varieties. It summarizes the advances in genetic improvement of sesame using omics technologies, such as germplasm development (web-based functional databases and germplasm resources), gene discovery (molecular markers and genetic linkage map construction), proteomics, transcriptomics, and metabolomics that have been carried out in the last decade. In conclusion, this review highlights future directions that may be important for omics-assisted breeding in sesame genetic improvement.PMID:37326753 | DOI:10.1007/s11033-023-08551-w

Pain. 2023 Jun 15. doi: 10.1097/j.pain.0000000000002938. Online ahead of print.ABSTRACTChronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generated by A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps.PMID:37326643 | DOI:10.1097/j.pain.0000000000002938

Free Radic Res. 2023 Jun 16:1-15. doi: 10.1080/10715762.2023.2226315. Online ahead of print.ABSTRACTBACKGROUND/AIMS: In recent years, many metabolites specific to nonalcoholic fatty liver disease (NAFLD) have been identified thanks to the application of metabolomics techniques. This study aimed to investigate the candidate targets and potential molecular pathways involved in NAFLD in the presence of iron overload.METHODS: Male Sprague Dawley rats were fed with control or high-fat diet with or without excess iron. After 8,16,20 weeks of treatment, urine samples of rats were collected for metabolomics analysis using ultra-performance liquid chromatography/mass spectrometry (UPLC-MS). Blood and liver samples were also collected.RESULTS: High-fat, high-iron diet resulted in increased triglyceride accumulation and increased oxidative damage. A total of 13 metabolites and four potential pathways were identified. Compared to the control group, the intensities of adenine, cAMP, hippuric acid, kynurenic acid, xanthurenic acid, uric acid, and citric acid were significantly lower (P < 0.05) and the concentration of other metabolites was significantly higher in the high-fat diet group. In the high-fat, high-iron group, the differences in the intensities of the above metabolites were amplified.CONCLUSION: Our findings suggest that NAFLD rats have impaired antioxidant system and liver function, lipid disorders, abnormal energy, and glucose metabolism, and that iron overload may further exacerbate these disorders.PMID:37326040 | DOI:10.1080/10715762.2023.2226315

Food Funct. 2023 Jun 16. doi: 10.1039/d3fo01097j. Online ahead of print.ABSTRACTA carotenoid production strain Rhodosporidium toruloides NP11 and its mutant strain R. toruloides A1-15 were studied under chemostat nitrogen-limited cultivation. Multi-omics analysis (metabolomics, lipidomics and transcriptomics) was used to investigate the different mechanisms of torularhodin accumulation between NP11 and A1-15. The results showed that the carotenoid synthesis pathway was significantly enhanced in A1-15 compared to NP11 under nitrogen limitation, due to the significant increase of torularhodin. Under nitrogen-limited conditions, higher levels of β-oxidation were present in A1-15 compared to those in NP11, which provided sufficient precursors for carotenoid synthesis. In addition, ROS stress accelerated the intracellular transport of iron ions, promoted the expression of CRTI and CRTY genes, and reduced the transcript levels of FNTB1 and FNTB2 in the bypass pathway, and these factors may be responsible for the regulation of high torularhodin production in A1-15. This study provided insights into the selective production of torularhodin.PMID:37325941 | DOI:10.1039/d3fo01097j

Phenomics. 2023 Mar 2;3(3):268-284. doi: 10.1007/s43657-023-00095-0. eCollection 2023 Jun.ABSTRACTThe gut microbiota refers to the gross collection of microorganisms, estimated trillions of them, which reside within the gut and play crucial roles in the absorption and digestion of dietary nutrients. In the past decades, the new generation 'omics' (metagenomics, transcriptomics, proteomics, and metabolomics) technologies made it possible to precisely identify microbiota and metabolites and describe their variability between individuals, populations and even different time points within the same subjects. With massive efforts made, it is now generally accepted that the gut microbiota is a dynamically changing population, whose composition is influenced by the hosts' health conditions and lifestyles. Diet is one of the major contributors to shaping the gut microbiota. The components in the diets vary in different countries, religions, and populations. Some special diets have been adopted by people for hundreds of years aiming for better health, while the underlying mechanisms remain largely unknown. Recent studies based on volunteers or diet-treated animals demonstrated that diets can greatly and rapidly change the gut microbiota. The unique pattern of the nutrients from the diets and their metabolites produced by the gut microbiota has been linked with the occurrence of diseases, including obesity, diabetes, nonalcoholic fatty liver disease, cardiovascular disease, neural diseases, and more. This review will summarize the recent progress and current understanding of the effects of different dietary patterns on the composition of gut microbiota, bacterial metabolites, and their effects on the host's metabolism.PMID:37325710 | PMC:PMC10260722 | DOI:10.1007/s43657-023-00095-0