PubMed

J Agric Food Chem. 2023 Sep 8. doi: 10.1021/acs.jafc.3c04637. Online ahead of print.ABSTRACTWhile molybdenum (Mo) application can improve phosphorus (P) availability to plants by changing P speciation in the rhizosphere, the mechanistic basis of this process remains unclear. This work investigated the impact of various combinations of Mo and P treatments on root morphology, P and Mo uptake, and root transcriptome and metabolome. Mo application significantly increased soybean biomass and the number of lateral roots at both low (5 μmol) or normal (500 μmol) P levels and significantly improved P concentration and accumulation in Normal P treatment. Compared with the Normal P treatment, Low P significantly increased the number of roots, root surface area, and root acid phosphatase secretion. A total of 6811 Mo-responsive differentially expressed genes and 135 differential metabolites were identified at two P levels. At Low P, transcriptional changes significantly increased root synthesis and secretion of succinic acid, methylmalonic acid, and other organic acids as well as acid phosphatase, thereby increasing the conversion of soil aluminum-bound P and organic P into available P. At Normal P, Mo application increased P uptake mainly by increasing the number of lateral roots. Thus, Mo helps crops adapt to different P levels by regulating root anatomy and transcriptional and metabolic profiles of their roots.PMID:37682241 | DOI:10.1021/acs.jafc.3c04637

Medicine (Baltimore). 2023 Sep 8;102(36):e34768. doi: 10.1097/MD.0000000000034768.ABSTRACTBACKGROUND: The objective of this study was to determine the efficacy of acupuncture on the outcome of in vitro fertilization (IVF) in elderly infertile patients with kidney qi deficiency, and to explore its possible mechanism from the perspective of pseudo-targeted metabolomics of follicular fluid.METHODS: Sixty cases of elderly women undergoing IVF were sampled and randomly divided into 2 equal groups: the treatment and the elderly control (HA) group. In the treatment group, routine ovulation induction combined with acupuncture treatment was used. Routine ovulation induction combined with sham acupuncture was used in the HA group. Reproductive outcomes of the 2 groups were compared. The follicular fluid of patients obtained on the day of oocyte retrieval was analyzed by the ultra-high-performance liquid chromatography-mass spectrometry analysis system.RESULTS: Compared with the HA group, the score of kidney qi deficiency syndrome in the treatment group was significantly decreased, and the 2 PN fertilization rate, high-quality embryo rate and cumulative pregnancy rate were significantly increased (P < .05). Through the identification of target metabolites, 3 metabolic pathways were found to be closely related to the developmental potential of oocytes, namely: Retinol metabolism pathway; Glycine, serine, and threonine metabolism pathway; Glycerophospholipid metabolism pathway.CONCLUSION: From our findings, acupuncture can improve the quality of oocytes thus bettering the outcome of IVF-assisted pregnancy in elderly patients with kidney qi deficiency.TRIAL REGISTRATION: ChiCTR1800018329.PMID:37682195 | DOI:10.1097/MD.0000000000034768

Cells. 2023 Aug 30;12(17):2179. doi: 10.3390/cells12172179.ABSTRACTOsteosarcoma is a primary malignant bone tumor affecting adolescents and young adults. This study aimed to identify proteomic signatures that distinguish between different osteosarcoma subtypes, providing insights into their molecular heterogeneity and potential implications for personalized treatment approaches. Using advanced proteomic techniques, we analyzed FFPE tumor samples from a cohort of pediatric osteosarcoma patients representing four various subtypes. Differential expression analysis revealed a significant proteomic signature that discriminated between these subtypes, highlighting distinct molecular profiles associated with different tumor characteristics. In contrast, clinical determinants did not correlate with the proteome signature of pediatric osteosarcoma. The identified proteomics signature encompassed a diverse array of proteins involved in focal adhesion, ECM-receptor interaction, PI3K-Akt signaling pathways, and proteoglycans in cancer, among the top enriched pathways. These findings underscore the importance of considering the molecular heterogeneity of osteosarcoma during diagnosis or even when developing personalized treatment strategies. By identifying subtype-specific proteomics signatures, clinicians may be able to tailor therapy regimens to individual patients, optimizing treatment efficacy and minimizing adverse effects.PMID:37681913 | DOI:10.3390/cells12172179

Cells. 2023 Aug 30;12(17):2180. doi: 10.3390/cells12172180.ABSTRACTThere is an increasing interest in biomarkers of nitric oxide dysregulation and oxidative stress to guide management and identify new therapeutic targets in patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis of the association between circulating metabolites within the arginine (arginine, citrulline, ornithine, asymmetric, ADMA, and symmetric, SDMA dimethylarginine), transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6, and vitamin B12) metabolic pathways and COPD. We searched electronic databases from inception to 30 June 2023 and assessed the risk of bias and the certainty of evidence. In 21 eligible studies, compared to healthy controls, patients with stable COPD had significantly lower methionine (standardized mean difference, SMD = -0.50, 95% CI -0.95 to -0.05, p = 0.029) and folic acid (SMD = -0.37, 95% CI -0.65 to -0.09, p = 0.009), and higher homocysteine (SMD = 0.78, 95% CI 0.48 to 1.07, p < 0.001) and cysteine concentrations (SMD = 0.34, 95% CI 0.02 to 0.66, p = 0.038). Additionally, COPD was associated with significantly higher ADMA (SMD = 1.27, 95% CI 0.08 to 2.46, p = 0.037), SDMA (SMD = 3.94, 95% CI 0.79 to 7.08, p = 0.014), and ornithine concentrations (SMD = 0.67, 95% CI 0.13 to 1.22, p = 0.015). In subgroup analysis, the SMD of homocysteine was significantly associated with the biological matrix assessed and the forced expiratory volume in the first second to forced vital capacity ratio, but not with age, study location, or analytical method used. Our study suggests that the presence of significant alterations in metabolites within the arginine, transsulfuration, and folic acid pathways can be useful for assessing nitric oxide dysregulation and oxidative stress and identifying novel treatment targets in COPD. (PROSPERO registration number: CRD42023448036.).PMID:37681911 | DOI:10.3390/cells12172180

Cells. 2023 Aug 23;12(17):2132. doi: 10.3390/cells12172132.ABSTRACTThe course of pathophysiological mechanisms involved in fragile X-associated tremor/ataxia syndrome (FXTAS) remains largely unknown. Previous proteomics and metabolomics studies conducted in blood samples collected from FMR1 premutation carriers with FXTAS reported abnormalities in energy metabolism, and precursors of gluconeogenesis showed significant changes in plasma expression levels in FMR1 premutation carriers who developed FXTAS. We conducted an analysis of postmortem human brain tissues from 44 donors, 25 brains with FXTAS, and 19 matched controls. We quantified the metabolite relative abundance in the inferior temporal gyrus and the cerebellum using untargeted mass spectrometry (MS)-based metabolomics. We investigated how the metabolite type and abundance relate to the number of cytosine-guanine-guanine (CGG) repeats, to markers of neurodegeneration, and to the symptoms of FXTAS. A metabolomic analysis identified 191 primary metabolites, the data were log-transformed and normalized prior to the analysis, and the relative abundance was compared between the groups. The changes in the relative abundance of a set of metabolites were region-specific with some overlapping results; 22 metabolites showed alterations in the inferior temporal gyrus, while 21 showed differences in the cerebellum. The relative abundance of cytidine was decreased in the inferior temporal gyrus, and a lower abundance was found in the cases with larger CGG expansions; oleamide was significantly decreased in the cerebellum. The abundance of 11 metabolites was influenced by changes in the CGG repeat number. A histological evaluation found an association between the presence of microhemorrhages in the inferior temporal gyrus and a lower abundance of 2,5-dihydroxypyrazine. Our study identified alterations in the metabolites involved in the oxidative-stress response and bioenergetics in the brains of individuals with FXTAS. Significant changes in the abundance of cytidine and oleamide suggest their potential as biomarkers and therapeutic targets for FXTAS.PMID:37681866 | DOI:10.3390/cells12172132

Cells. 2023 Aug 22;12(17):2123. doi: 10.3390/cells12172123.ABSTRACTMolecular subtype (MS) is one of the most used classifications of breast cancer (BC). Four MSs are widely accepted according to receptor expression of estrogen, progesterone, and HER2. The impact of adipose tissue on BC MS metabolic impairment is still unclear. The present work aims to elucidate the metabolic alterations in breast cancer cell lines representing different MSs subjected to adipocyte associated factors. Preadipocytes isolated from human subcutaneous adipose tissue were differentiated into mature adipocytes. MS representative cell lines were exposed to mature adipocyte secretome. Extracellular medium was collected for metabolomics and RNA was extracted to evaluate enzymatic expression by RT-PCR. Adipocyte secretome exposure resulted in a decrease in the Warburg effect rate and an increase in cholesterol release. HER2+ cell lines (BT-474 and SK-BR-3) exhibited a similar metabolic pattern, in contrast to luminal A (MCF-7) and triple negative (TN) (MDA-MB-231), both presenting identical metabolisms. Anaplerosis was found in luminal A and TN representative cells, whereas cataplerotic reactions were likely to occur in HER2+ cell lines. Our results indicate that adipocyte secretome affects the central metabolism distinctly in each BC MS representative cell line.PMID:37681855 | DOI:10.3390/cells12172123

Environ Toxicol. 2023 Sep 8. doi: 10.1002/tox.23967. Online ahead of print.ABSTRACTInflammatory response and oxidative stress are considered to be important mechanisms of lung injury induced by lunar dust. However, the pulmonary toxicological mechanism remains unclear. In the present study, Wistar rats were exposed to CLDS-i 7 days/week, 4 h/day, for 4 weeks in the mouth and nose. Lung tissue samples were collected for histopathological analysis and ultra-performance liquid chromatography-mass spectrometry analysis. Enzyme activities and expression levels of key metabolic enzymes were detected by biochemical analysis and real-time PCR. The pathological features of lung tissue showed that CLDS-i caused congestion and inflammation in the lungs, and the lung structure was severely damaged. Metabolomics analysis showed that 141 metabolites were significantly changed in the lung tissue of the CLDS-i group compared with the control group. Combined with Kegg pathway analysis, it was found that the changes of amino acid metabolites were involved in these pathways, indicating that the simulated lunar dust exposure had the most obvious effect on amino acid metabolism in the lung tissue of rats. Real-time PCR analysis showed that the mRNA expression of six key enzymes related to amino acid metabolism was changed, and the enzyme activities of these key enzymes were also changed, which were consistent with the results of qPCR. These results suggest that changes in amino acid metabolism may be closely related to the pathogenesis of lung injury induced by lunar dust, and amino acid metabolism may be a potential biomarker of lung diseases related to lunar dust exposure.PMID:37681755 | DOI:10.1002/tox.23967

Anal Chem. 2023 Sep 8. doi: 10.1021/acs.analchem.3c00029. Online ahead of print.ABSTRACTTraditionally, a relatively big urine volume (e.g., 500 μL) is used in nuclear magnetic resonance (NMR)-based human metabolomics, which is not feasible for studies with limited/precious samples. Although urine may be diluted before conventional high-throughput metabolomics analysis, the comprehensive effect of urine dilution on metabolic profiles is unknown. Here, for the first time, we systematically investigated the effect of urine dilution on 1H NMR metabolic profiles, by evaluating signal detectability, integration, signal-to-noise ratio (SNR), chemical shift (δ) and its variation, and signal overlapping of 47 metabolites in 10 volunteers. We observed significant linear changes along with increased dilution, including decreased integration and SNR, altered δ, decreased intersample variation of δ, and increased separation between overlapped signals, e.g., lactate and threonine, β-d-glucose and an unassigned signal, and histidine and 3-methylhistidine. We further tested the 40% dilution level (i.e., employing 300 μL urine) in an epidemiological study containing 1018 pregnant women from the Tongji-Shuangliu Birth Cohort, showing acceptable detectability and chemical shift variability for most of the 47 metabolites profiled. It indicated that mild (e.g., 40%) dilution of human urine can largely preserve the high-abundance metabolites profiled, reduce intersample chemical shift variations, and increase separations of overlapped signals, which is an improvement of routine sample preparation methods in NMR-based metabolomics and is applicable for studies with limited urine volumes, including large-scale epidemiological studies.PMID:37681715 | DOI:10.1021/acs.analchem.3c00029

Biotechniques. 2023 Sep 8. doi: 10.2144/btn-2023-0023. Online ahead of print.ABSTRACTTechnological advancements in genome sequencing, assembly and annotation platforms and algorithms that resulted in several genomic studies have created an opportunity to further our understanding of the biology of phytopathogens, including Armillaria species. Most Armillaria species are facultative necrotrophs that cause root- and stem-rot, usually on woody plants, significantly impacting agriculture and forestry worldwide. Genome sequencing, assembly and annotation in terms of samples used and methods applied in Armillaria genome projects are evaluated in this review. Infographic guidelines and a database of resources to facilitate future Armillaria genome projects were developed. Knowledge gained from genomic studies of Armillaria species is summarized and prospects for further research are provided. This guide can be applied to other diploid and dikaryotic fungal genomics.PMID:37681497 | DOI:10.2144/btn-2023-0023

RSC Adv. 2023 Sep 6;13(38):26630-26639. doi: 10.1039/d3ra03992g. eCollection 2023 Sep 4.ABSTRACTChemodynamic therapy (CDT) has received more and more attention as an emerging therapeutic strategy, especially transition metals with Fenton or Fenton-like activity have good effects in CDT research, manganese dioxide nanosheets (MnO2 NSs) and their complexes have become one of the most favored nanomaterials in CDT of tumors. CDT is mainly based on the role of reactive oxygen species (ROS) in tumor treatment, which have clear chemical properties and produce clear chemical reactions. However, their mechanism of interaction with cells has not been fully elucidated. Here, we performed CDT on mouse breast cancer cells (4T1) based on MnO2 NSs, extracted the metabolites from the 4T1 cells during the treatment, and analyzed the differences in metabolites by using high-resolution liquid chromatography-mass spectrometry (LC-MS). Untargeted metabolomics studies were conducted using the relevant data. This study mainly explored the changes in MnO2 NSs on the metabolite profile of 4T1 cells and their potential impact on tumor therapy, in order to determine the mechanism of action of MnO2 NSs in the treatment of breast cancer. The results of the study showed the presence of 11 different metabolites in MnO2 NSs CDT for 4T1 tumor cells, including phosphoserine, sphingine, phosphocholine, and stearoylcarnitine. These findings provide a deeper understanding of breast cancer treatment, and are beneficial for the further research and clinical application of CDT.PMID:37681048 | PMC:PMC10481133 | DOI:10.1039/d3ra03992g

Front Physiol. 2023 Aug 23;14:1254992. doi: 10.3389/fphys.2023.1254992. eCollection 2023.ABSTRACTTo understand the effects of vitamin A on lipid deposition in rice field eels, integrated liver transcriptome and metabolome were conducted and the changes in the genes and metabolites were assessed. Three groups of rice field eel were fed with 0, 200, and 16,000 IU/kg vitamin A supplementations in their diets for 70 days. The total lipid content in the whole body of the rice field eels was significantly increased with the vitamin A supplementations (p < 0.05). Comparative transcriptome analysis revealed 14 pathways and 46 differentially expressed genes involved in lipid metabolism. Sphingolipid metabolism, glycerolipid metabolism, primary bile acid biosynthesis and steroid hormone biosynthesis were significantly enriched pathways. In these pathways, three differential genes phospholipid phosphatase 1a (PLPP1a), phospholipid phosphatase 2b (PLPP2b), cytochrome P450 21a2 (CYP21a2) were consistent with the change trend of lipid content, and the other three differential genes aldo-keto reductase family 1 member D1 (AKR1D1), uridine diphosphate glucuronic acid transferase 1a1 (UGT1a1), cytochrome P450 1a (CYP1a) were opposite. Metabolomic analysis revealed that primary bile acid biosynthesis, sphingolipid metabolism, steroid hormone biosynthesis and biosynthesis of unsaturated fatty acids were all critical for rice field eel metabolic changes in response to vitamin A. Six important differential metabolites (eicosapentaenoic acid, sphinganine, 11-beta-hydroxyprogesterone, hydroxyeicosatetraenoic acid, cholic acid, and glycochenodeoxycholate) were identified and have provided new insights into how vitamin A regulates lipid deposition. Integrated transcriptome and metabolome analyses revealed that primary bile acid biosynthesis was the only remarkably enriched pathway in both the transcriptome and metabolome while that sphingosine was the main metabolite. Based on the above results, we have concluded that vitamin A promotes lipid deposition in the rice field eel through the primary bile acid synthesis pathway, and lipid deposits are widely stored in cell membranes, mainly in the form of sphingosine. These results will provide reference data to help improve our understanding of how vitamin A regulates lipid metabolism.PMID:37680772 | PMC:PMC10482098 | DOI:10.3389/fphys.2023.1254992

Front Immunol. 2023 Aug 23;14:1204338. doi: 10.3389/fimmu.2023.1204338. eCollection 2023.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored.METHODS: Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied.RESULTS: Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells.CONCLUSION: We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.PMID:37680641 | PMC:PMC10482091 | DOI:10.3389/fimmu.2023.1204338

Conserv Physiol. 2023 Sep 5;11(1):coad074. doi: 10.1093/conphys/coad074. eCollection 2023.ABSTRACTBiologists monitoring freshwater mussel (order Unionida) populations rely on behavioral, often subjective, signs to identify moribund ("sick") or stressed mussels, such as gaping valves and slow response to probing, and they lack clinical indicators to support a diagnosis. As part of a multi-year study to investigate causes of reoccurring mortality of pheasantshell (Ortmanniana pectorosa; synonym Actinonaias pectorosa) in the Clinch River, Virginia and Tennessee, USA, we analyzed the hemolymph metabolome of a subset of mussels from the 2018 sampling period. Mussels at the mortality sites were diagnosed in the field as affected (case) or unaffected (control) based on behavioral and physical signs. Hemolymph was collected in the field by non-lethal methods from the anterior adductor muscle for analysis. We used ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectroscopy to detect targeted and untargeted metabolites in hemolymph and compared metabolomic profiles by field assessment of clinical status. Targeted biomarker analysis found 13 metabolites associated with field assessments of clinical status. Of these, increased gamma-linolenic acid and N-methyl-l-alanine were most indicative of case mussels, while adenine and inosine were the best indicators of control mussels. Five pathways in the targeted analysis differed by clinical status; two of these, purine metabolism and glycerophospholipid metabolism, were also indicated in the untargeted analysis. In the untargeted nalysis, 22 metabolic pathways were associated with clinical status. Many of the impacted pathways in the case group were catabolic processes, such as degradation of amino acids and fatty acids. Hierarchical clustering analysis matched clinical status in 72% (18 of 25) of mussels, with control mussels more frequently (5 of 16) not matching clinical status. Our study demonstrated that metabolomic analysis of hemolymph is suitable for assessing mussel condition and complements field-based indicators of health.PMID:37680611 | PMC:PMC10482074 | DOI:10.1093/conphys/coad074

Front Microbiol. 2023 Aug 23;14:1225643. doi: 10.3389/fmicb.2023.1225643. eCollection 2023.ABSTRACTThis study used Silibinin as an additive to conduct fermentation experiments, wherein its effects on rumen gas production, fermentation, metabolites, and microbiome were analyzed in vitro. The silibinin inclusion level were 0 g/L (control group), 0.075 g/L, 0.15 g/L, 0.30 g/L, and 0.60 g/L (experimental group). Fermentation parameters, total gas production, carbon dioxide (CO2), methane (CH4), hydrogen (H2), and their percentages were determined. Further analysis of the rumen microbiome's relative abundance and α/β diversity was performed on the Illumina NovaSeq sequencing platform. Qualitative and quantitative metabolomics analyses were performed to analyze the differential metabolites and metabolic pathways based on non-targeted metabolomics. The result indicated that with an increasing dose of silibinin, there was a linear reduction in total gas production, CO2, CH4, H2 and their respective percentages, and the acetic acid to propionic acid ratio. Concurrent with a linear increase in pH, when silibinin was added at 0.15 g/L and above, the total volatile fatty acid concentration decreased, the acetic acid molar ratio decreased, the propionic acid molar ratio increased, and dry matter digestibility decreased. At the same time, the relative abundance of Prevotella, Isotricha, Ophryoscolex, unclassified_Rotifera, Methanosphaera, Orpinomyces, and Neocallimastix in the rumen decreased after adding 0.60 g/L of silibinin. Simultaneously, the relative abundance of Succiniclasticum, NK4A214_group, Candidatus_Saccharimonas, and unclassified_Lachnospiraceae increased, altering the rumen species composition, community, and structure. Furthermore, it upregulated the ruminal metabolites, such as 2-Phenylacetamide, Phlorizin, Dalspinin, N6-(1,2-Dicarboxyethyl)-AMP, 5,6,7,8-Tetrahydromethanopterin, Flavin mononucleotide adenine dinucleotide reduced form (FMNH), Pyridoxine 5'-phosphate, Silibinin, and Beta-D-Fructose 6-phosphate, affecting phenylalanine metabolism, flavonoid biosynthesis, and folate biosynthesis pathways. In summary, adding silibinin can alter the rumen fermentation parameters and mitigate enteric methane production by regulating rumen microbiota and metabolites, which is important for developing novel rumen methane inhibitors.PMID:37680535 | PMC:PMC10481870 | DOI:10.3389/fmicb.2023.1225643

Front Plant Sci. 2023 Aug 23;14:1220507. doi: 10.3389/fpls.2023.1220507. eCollection 2023.ABSTRACTINTRODUCTION: Dendrobium nobile L. is a rare orchid plant with high medicinal and ornamentalvalue, and extremely few genetic species resources are remaining in nature. In the normal purple flower population, a type of population material with a white flower variation phenotype has been discovered, and through pigment component determination, flavonoids were preliminarily found to be the main reason for the variation.METHODS: This study mainly explored the different genes and metabolites at different flowering stages and analysed the flower color variation mechanism through transcriptome- and flavonoid-targeted metabolomics. The experimental materials consisted of two different flower color phenotypes, purple flower (PF) and white flower (WF), observed during three different periods.RESULTS AND DISCUSSION: The results identified 1382, 2421 and 989 differentially expressed genes (DEGs) in the white flower variety compared with the purple flower variety at S1 (bud stage), S2 (chromogenic stage) and S3 (flowering stage), respectively. Among these, 27 genes enriched in the ko00941, ko00942, ko00943 and ko00944 pathways were screened as potential functional genes affecting flavonoid synthesis and flower color. Further analysis revealed that 15 genes are potential functional genes that lead to flavonoid changes and flower color variations. The metabolomics results at S3 found 129 differentially accumulated metabolites (DAMs), which included 8 anthocyanin metabolites, all of which (with the exception of delphinidin-3-o-(2'''-o-malonyl) sophoroside-5-o-glucoside) were found at lower amounts in the WF variety compared with the PF variety, indicating that a decrease in the anthocyanin content was the main reason for the inability to form purple flowers. Therefore, the changes in 19 flavone and 62 flavonol metabolites were considered the main reasons for the formation of white flowers. In this study, valuable materials responsible for flower color variation in D. nobile were identified and further analyzed the main pathways and potential genes affecting changes in flavonoids and the flower color. This study provides a material basis and theoretical support for the hybridization and molecular-assisted breeding of D. nobile.PMID:37680360 | PMC:PMC10481954 | DOI:10.3389/fpls.2023.1220507

Front Bioeng Biotechnol. 2023 Aug 23;11:1230422. doi: 10.3389/fbioe.2023.1230422. eCollection 2023.ABSTRACTS-Sulfocysteine (SSC), a bioavailable L-cysteine derivative (Cys), is known to be taken up and metabolized in Chinese hamster ovary (CHO) cells used to produce novel therapeutic biological entities. To gain a deeper mechanistic insight into the SSC biological activity and metabolization, a multi-omics study was performed on industrially relevant CHO-K1 GS cells throughout a fed-batch process, including metabolomic and proteomic profiling combined with multivariate data and pathway analyses. Multi-layered data and enzymatical assays revealed an intracellular SSC/glutathione mixed disulfide formation and glutaredoxin-mediated reduction, releasing Cys and sulfur species. Increased Cys availability was directed towards glutathione and taurine synthesis, while other Cys catabolic pathways were likewise affected, indicating that cells strive to maintain Cys homeostasis and cellular functions.PMID:37680342 | PMC:PMC10482334 | DOI:10.3389/fbioe.2023.1230422

J Tradit Chin Med. 2023 Oct;43(5):1026-1033. doi: 10.19852/j.cnki.jtcm.2023.05.006.ABSTRACTOBJECTIVE: To investigate the effect of - Xiaoyi Yusi decoction (XYYSD, ), a Traditional Chinese Medicine (TCM), on fertilization and embryo transfer (IVF-ET) in patients with endometriosis, and to study the mechanism underpinning the action.METHODS: Women who underwent IVF-ET were divided into three groups by simple randomization: the treatment ( 32; with TCM treatment), patient (28; with endometriosis alone), and control (33; with male factor alone) groups. The luteal phase short-acting gonadotropin-releasing hormone agonist prolonged protocol was used in all three groups. To compare the changes in TCM scores and reproductive outcomes before and after TCM intervention in patients with endometriosis, partial least-squares discriminant analysis was used to analyze the follicular fluid samples of each group and screen and compare metabolites using the MetaboAnalyst software.RESULTS: The clinical data indicated that following TCM intervention, kidney deficiency and blood stasis symptom patterns improved dramatically in patients with endometriosis and that their clinical pregnancy rate increased significantly (71.9% 57.1%, 0.05). Metabolomics showed that the two groups of samples were separated before and after TCM intervention. After TCM intervention, the intervention group was close to the control group, indicating that the TCM had a certain effect. Pathway analysis revealed that after TCM intervention, the metabolism of glycerin phospholipid, pyruvate, and citric acid was regulated.CONCLUSIONS: Through the pyruvate and glycerophospholipid metabolism pathways and tricarboxylic acid cycle, the TCM XYYSD successfully improved kidney deficiency and blood stasis symptom pattern, as well as the clinical reproductive outcomes of patients with endometriosis-related infertility.PMID:37679991 | DOI:10.19852/j.cnki.jtcm.2023.05.006

J Neuroinflammation. 2023 Sep 7;20(1):204. doi: 10.1186/s12974-023-02889-5.ABSTRACTBACKGROUND: 17β-Estradiol (E2) is generally considered neuroprotective in humans. However, the current clinical use of estrogen replacement therapy (ERT) is based on the physiological dose of E2 to treat menopausal syndrome and has limited therapeutic efficacy. The efficacy and potential toxicity of superphysiological doses of ERT for menopausal neurodegeneration are unknown.METHODS: In this study, we investigated the effect of E2 with a supraphysiologic dose (0.5 mg/kg, sE2) on the treatment of menopausal mouse models established by ovariectomy. We performed the open field, Y-maze spontaneous alternation, forced swim tests, and sucrose preference test to investigate behavioral alterations. Subsequently, the status of microglia and neurons was detected by immunohistochemistry, HE staining, and Nissl staining, respectively. Real-time PCR was used to detect neuroinflammatory cytokines in the hippocampus and cerebral cortex. Using mass spectrometry proteomics platform and LC-MS/ MS-based metabolomics platform, proteins and metabolites in brain tissues were extracted and analyzed. BV2 and HT22 cell lines and primary neurons and microglia were used to explore the underlying molecular mechanisms in vitro.RESULTS: sE2 aggravated depression-like behavior in ovariectomized mice, caused microglia response, and increased proinflammatory cytokines in the cerebral cortex and hippocampus, as well as neuronal damage and glycerophospholipid metabolism imbalance. Subsequently, we demonstrated that sE2 induced the pro-inflammatory phenotype of microglia through ERα/NF-κB signaling pathway and downregulated the expression of cannabinoid receptor 1 in neuronal cells, which were important in the pathogenesis of depression.CONCLUSION: These data suggest that sE2 may be nonhelpful or even detrimental to menopause-related depression, at least partly, by regulating microglial responses and glycerophospholipid metabolism.PMID:37679787 | DOI:10.1186/s12974-023-02889-5

BMC Med. 2023 Sep 8;21(1):347. doi: 10.1186/s12916-023-03027-x.ABSTRACTBACKGROUND: T2D is of high prevalence in the middle east and thus studying its mechanisms is of a significant importance. Using 1026 Qatar BioBank samples, epigenetics, whole genome sequencing and metabolomics were combined to further elucidate the biological mechanisms of T2D in a population with a high prevalence of T2D.METHODS: An epigenome-wide association study (EWAS) with T2D was performed using the Infinium 850K EPIC array, followed by whole genome-wide sequencing SNP-CpG association analysis (> 5.5 million SNPs) and a methylome-metabolome (CpG-metabolite) analysis of the identified T2D sites.RESULTS: A total of 66 T2D-CpG associations were identified, including 63 novel sites in pathways of fructose and mannose metabolism, insulin signaling, galactose, starch and sucrose metabolism, and carbohydrate absorption and digestion. Whole genome SNP associations with the 66 CpGs resulted in 688 significant CpG-SNP associations comprising 22 unique CpGs (33% of the 66 CPGs) and included 181 novel pairs or pairs in novel loci. Fourteen of the loci overlapped published GWAS loci for diabetes related traits and were used to identify causal associations of HK1 and PFKFB2 with HbA1c. Methylome-metabolome analysis identified 66 significant CpG-metabolite pairs among which 61 pairs were novel. Using the identified methylome-metabolome associations, methylation QTLs, and metabolic networks, a multi-omics network was constructed which suggested a number of metabolic mechanisms underlying T2D methylated genes. 1-palmitoyl-2-oleoyl-GPE (16:0/18:1) - a triglyceride-associated metabolite, shared a common network with 13 methylated CpGs, including TXNIP, PFKFB2, OCIAD1, and BLCAP. Mannonate - a food component/plant shared a common network with 6 methylated genes, including TXNIP, BLCAP, THBS4 and PEF1, pointing to a common possible cause of methylation in those genes. A subnetwork with alanine, glutamine, urea cycle (citrulline, arginine), and 1-carboxyethylvaline linked to PFKFB2 and TXNIP revealed associations with kidney function, hypertension and triglyceride metabolism. The pathway containing STYXL1-POR was associated with a sphingosine-ceramides subnetwork associated with HDL-C and LDL-C and point to steroid perturbations in T2D.CONCLUSIONS: This study revealed several novel methylated genes in T2D, with their genomic variants and associated metabolic pathways with several implications for future clinical use of multi-omics associations in disease and for studying therapeutic targets.PMID:37679740 | DOI:10.1186/s12916-023-03027-x

BMC Med. 2023 Sep 8;21(1):349. doi: 10.1186/s12916-023-03054-8.ABSTRACTBACKGROUND: Placental dysfunction, a root cause of common syndromes affecting human pregnancy, such as preeclampsia (PE), fetal growth restriction (FGR), and spontaneous preterm delivery (sPTD), remains poorly defined. These common, yet clinically disparate obstetrical syndromes share similar placental histopathologic patterns, while individuals within each syndrome present distinct molecular changes, challenging our understanding and hindering our ability to prevent and treat these syndromes.METHODS: Using our extensive biobank, we identified women with severe PE (n = 75), FGR (n = 40), FGR with a hypertensive disorder (FGR + HDP; n = 33), sPTD (n = 72), and two uncomplicated control groups, term (n = 113), and preterm without PE, FGR, or sPTD (n = 16). We used placental biopsies for transcriptomics, proteomics, metabolomics data, and histological evaluation. After conventional pairwise comparison, we deployed an unbiased, AI-based similarity network fusion (SNF) to integrate the datatypes and identify omics-defined placental clusters. We used Bayesian model selection to compare the association between the histopathological features and disease conditions vs SNF clusters.RESULTS: Pairwise, disease-based comparisons exhibited relatively few differences, likely reflecting the heterogeneity of the clinical syndromes. Therefore, we deployed the unbiased, omics-based SNF method. Our analysis resulted in four distinct clusters, which were mostly dominated by a specific syndrome. Notably, the cluster dominated by early-onset PE exhibited strong placental dysfunction patterns, with weaker injury patterns in the cluster dominated by sPTD. The SNF-defined clusters exhibited better correlation with the histopathology than the predefined disease groups.CONCLUSIONS: Our results demonstrate that integrated omics-based SNF distinctively reclassifies placental dysfunction patterns underlying the common obstetrical syndromes, improves our understanding of the pathological processes, and could promote a search for more personalized interventions.PMID:37679695 | DOI:10.1186/s12916-023-03054-8