PubMed

Front Microbiol. 2022 Dec 20;13:908244. doi: 10.3389/fmicb.2022.908244. eCollection 2022.ABSTRACTThis study investigated the effects of active dry yeast (ADY) and yeast culture (YC) supplementation on rumen bacteria and metabolites in finishing bulls fed high-concentrate diets using the full-length 16S rDNA gene sequencing and liquid chromatography-mass spectrometry. Supplementation with ADY improved the alpha diversity and relative abundance of rumen bacteria, while YC only affected relative abundance of rumen bacteria at the genus level. Sixty-three differential metabolites were identified in rumen fluid after ADY supplementation, and 17 after YC. PICRUSt2 functional prediction showed that ADY supplementation improved the capacity of amino acid metabolism, lipid metabolism, carbohydrate metabolism, metabolism of terpenoids and polyketides, and energy metabolism in rumen bacteria (all P < 0.05). Correlation analysis showed that the rumen differential metabolites following ADY supplementation were mainly related to Oligosphaera, Verruc, Mycoplasma, and Anaeroplasma. Supplementation with ADY was more effective than YC in remodeling the rumen bacterial flora structure and metabolite composition under high-concentrate diets.PMID:36605509 | PMC:PMC9810264 | DOI:10.3389/fmicb.2022.908244

Curr Res Food Sci. 2022 Dec 27;6:100430. doi: 10.1016/j.crfs.2022.100430. eCollection 2023.ABSTRACTEdible fungus is a large fungus distributed all over the world and used as food and medicine. But people's understanding of edible fungi is not as much as that of ordinary crops, so people have started a number of research on edible fungi in recent years. With the development of science and technology, omics technology has gradually walked into people's vision. Omics technology has high sensitivity and wide application range, which is favored by researchers. The application of omics technology to edible fungus research is a major breakthrough, which has transferred edible fungus research from artificial cultivation to basic research. Now omics technology in edible fungi has been flexibly combined with other research methods, involving multiple studies of edible fungus, such as genetic breeding, growth and development, stress resistance, and the use of special components in edible fungus as pharmaceutical additives. It is believed that in the future, the research of edible fungi will also be brought to a deeper level with the help of omics technology. This paper introduces the application progress of modern omics technology to the study on edible fungi and mentions the application prospect of edible fungi research with the constant development of omics technology, thereby providing ideas for the follow-up in-depth research on edible fungi.PMID:36605463 | PMC:PMC9807862 | DOI:10.1016/j.crfs.2022.100430

Front Immunol. 2022 Dec 20;13:982746. doi: 10.3389/fimmu.2022.982746. eCollection 2022.ABSTRACTBACKGROUND: Even during long-term combination antiretroviral therapy (cART), people living with HIV (PLHIV) have a dysregulated immune system, characterized by persistent immune activation, accelerated immune ageing and increased risk of non-AIDS comorbidities. A multi-omics approach is applied to a large cohort of PLHIV to understand pathways underlying these dysregulations in order to identify new biomarkers and novel genetically validated therapeutic drugs targets.METHODS: The 2000HIV study is a prospective longitudinal cohort study of PLHIV on cART. In addition, untreated HIV spontaneous controllers were recruited. In-depth multi-omics characterization will be performed, including genomics, epigenomics, transcriptomics, proteomics, metabolomics and metagenomics, functional immunological assays and extensive immunophenotyping. Furthermore, the latent viral reservoir will be assessed through cell associated HIV-1 RNA and DNA, and full-length individual proviral sequencing on a subset. Clinical measurements include an ECG, carotid intima-media thickness and plaque measurement, hepatic steatosis and fibrosis measurement as well as psychological symptoms and recreational drug questionnaires. Additionally, considering the developing pandemic, COVID-19 history and vaccination was recorded. Participants return for a two-year follow-up visit. The 2000HIV study consists of a discovery and validation cohort collected at separate sites to immediately validate any finding in an independent cohort.RESULTS: Overall, 1895 PLHIV from four sites were included for analysis, 1559 in the discovery and 336 in the validation cohort. The study population was representative of a Western European HIV population, including 288 (15.2%) cis-women, 463 (24.4%) non-whites, and 1360 (71.8%) MSM (Men who have Sex with Men). Extreme phenotypes included 114 spontaneous controllers, 81 rapid progressors and 162 immunological non-responders. According to the Framingham score 321 (16.9%) had a cardiovascular risk of >20% in the next 10 years. COVID-19 infection was documented in 234 (12.3%) participants and 474 (25.0%) individuals had received a COVID-19 vaccine.CONCLUSION: The 2000HIV study established a cohort of 1895 PLHIV that employs multi-omics to discover new biological pathways and biomarkers to unravel non-AIDS comorbidities, extreme phenotypes and the latent viral reservoir that impact the health of PLHIV. The ultimate goal is to contribute to a more personalized approach to the best standard of care and a potential cure for PLHIV.PMID:36605197 | PMC:PMC9809279 | DOI:10.3389/fimmu.2022.982746

Endocrinol Metab (Seoul). 2022 Dec;37(6):891-900. doi: 10.3803/EnM.2022.1590. Epub 2022 Dec 26.ABSTRACTBACKGRUOUND: An excess of thyroid hormones in Graves' disease (GD) has profound effects on systemic energy metabolism that are currently partially understood. In this study, we aimed to provide a comprehensive understanding of the metabolite changes that occur when patients with GD transition from hyperthyroidism to euthyroidism with methimazole treatment.METHODS: Eighteen patients (mean age, 38.6±14.7 years; 66.7% female) with newly diagnosed or relapsed GD attending the endocrinology outpatient clinics in a single institution were recruited between January 2019 and July 2020. All subjects were treated with methimazole to achieve euthyroidism. We explored metabolomics by performing liquid chromatography-mass spectrometry analysis of plasma samples of these patients and then performed multivariate statistical analysis of the metabolomics data.RESULTS: Two hundred metabolites were measured before and after 12 weeks of methimazole treatment in patients with GD. The levels of 61 metabolites, including palmitic acid (C16:0) and oleic acid (C18:1), were elevated in methimazole-naïve patients with GD, and these levels were decreased by methimazole treatment. The levels of another 15 metabolites, including glycine and creatinine, were increased after recovery of euthyroidism upon methimazole treatment in patients with GD. Pathway analysis of metabolomics data showed that hyperthyroidism was closely related to aminoacyl-transfer ribonucleic acid biosynthesis and branched-chain amino acid biosynthesis pathways.CONCLUSION: In this study, significant variations of plasma metabolomic patterns that occur during the transition from hyperthyroidism to euthyroidism were detected in patients with GD via untargeted metabolomics analysis.PMID:36604959 | DOI:10.3803/EnM.2022.1590

Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(24):6780-6793. doi: 10.19540/j.cnki.cjcmm.20220614.501.ABSTRACTThis study aims to explore the anti-asthma components and mechanism of Kechuanting acupoint application therapy(KAAT) based on serum metabolomics and network pharmacology. A total of 60 asthma patients who had used low-dose inhaled corticosteroids-formoterol(ICS-formoterol) for a long time were randomized into the western medicine group(low-dose ICS-formoterol) and western medicine+Kechuanting group(KAAT+low-dose ICS-Formoterol), 30 in either group. In addition, 30 healthy people were included as the control(no intervention). The asthma control test(ACT) score, forced expiratory volume in 1 second(FEV1), and peak expiratory flow(PEF) were measured in the western medicine group and western medicine+Kechuanting group before and after treatment. The potential biomarkers of KAAT in the treatment of asthma were screened by gas chromatography-mass spectrometry combined with multivariate analysis, and the related metabolic pathways were further analyzed. UPLC/LTQ-Orbitrap-MS, together with network pharmacology, was employed to construct the component-target-pathway network. Thereby, the effective components and me-chanism of KAAT in the treatment of asthma were clarified. According to the ACT score, FEV1, and PEF, KAAT was effective in the treatment of asthma. A total of 10 endogenous biomarkers of KAAT in the treatment of asthma were screened by serum metabolomics, and the pathways of the metabolism of glycine, serine and threonine, and the metabolism of glyoxylic acid and dicarboxylic acid were obtained. UPLC/LTQ-Orbitrap-MS identified 51 chemical components of KAAT: 24 flavonoids, 11 alkaloids, 8 phenols, 2 diterpenoids, 2 triterpenoids, 2 glycosides, and 2 aldehydes. Network pharmacology analysis suggested that KAAT mainly acted on serum crea-tinine(SRC), matrix metalloproteinase 9(MMP-9), and other target proteins. The treatment was closely related to metabolic pathway, phosphatidylinositol 3-kinase-protein kinase B(PI3 K-Akt), mitogen-activated protein kinase(MAPK), and calcium signaling pathway. Sinapine thiocyanate, corydaline, dihydroberberine, stylopine, leonticine, N-methyl tetrahydroberberine, kaempferide, erio-dictyol, quercetin, catechin, 6-gingerol, 6-shogaol, ingenol, and luteolin may be potential effective compounds of KAAT in the treatment of asthma. This study preliminarily revealed that the effective components and mechanism of KAAT in treatment of asthma based on serum metabolomics and network pharmacology. It lays a theoretical foundation for in-depth study of the mechanism and clinical development and application.PMID:36604927 | DOI:10.19540/j.cnki.cjcmm.20220614.501

Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(24):6741-6752. doi: 10.19540/j.cnki.cjcmm.20220902.701.ABSTRACTTo explore the mechanism of Suanzaoren Decoction(SZRD) in improving the insomnia rat model induced by DL-4-chlorophenylalanine(PCPA). The insomnia model was established by single intraperitoneal injection with PCPA(400 mg·kg~(-1)), UPLC-Q-TOF-MS/MS was used to analyze the profile of metabolites in rat hippocampus samples, combined with multivariate statistical analysis and screening of differential metabolites, and related metabolic pathways were constructed with MetaboAnalyst 5.0. The high-throughput sequencing of V3-V4 regions of 16 S rRNA gene was used to predict the structure and relative abundance of intestinal flora by LEfSe, OPLS-DA and PICRUSt2. A total of 22 differential hippocampus metabolites were identified by metabolomics analysis, including amino acids, fatty acids, nucleosides, organic acids, vitamins, and others. Pathway analysis showed that alanine, aspartate and glutamic metabolism, D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis were the main pathways. 16 S rRNA gene sequencing showed that Ruminococcus and Eubacterium were the differences between SZRD group and model group. Ruminococcus might be the sign of SZRD improving PCPA insomnia on analysis of PICRUSt2 and LEfSe. Furthermore Spearman correlation analysis showed that the differential metabolites 2-oxo-4-methylthiobutyric acid and palmitic acid intervened by SZRD were significantly positively correlated with the differential flora. In conclusion, SZRD indirectly improves insomnia by affecting metabolic pathways such as amino acids metabolic pathways and regulating the structure of flora. The results of this study provide a new mechanism and new idea for elucidating the mechanism of classic famous prescription SZRD in improving insomnia from the perspective of intestinal flora.PMID:36604924 | DOI:10.19540/j.cnki.cjcmm.20220902.701

Zhongguo Zhong Yao Za Zhi. 2022 Dec;47(24):6679-6686. doi: 10.19540/j.cnki.cjcmm.20220728.401.ABSTRACTNon-targeted metabonomics was used to investigate the metabolite changes in the glioblastoma orthotopic tumor-bearing mice after timosaponin AⅢ(TIA) intervention to explore the metabolic relevant mechanism of glioblastoma and TIA intervention. The mice were randomly divided into a blank group, a model group, and a TIA group. HPLC-LTQ-Orbitrap Elite liquid chromatography-mass spectrometry was used to detect the metabolite changes in the serum of rats in the three groups after treatment for 4 weeks. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were performed on the metabolites, and the differential metabolites were selected based on VIP values and P values(P&lt;0.05). The results showed that TIA significantly inhibited the in vivo glioblastoma growth, but it had limited influence on body weight. Serum samples were clearly distinguishable among groups. As compared with the blank group, six metabolites including ceramide, succinic acid, α-ketoglutarate acid(αKG), citric acid, indophenol sulfate, and 3 a, 6 b, 7 b-trihydroxy-5 b-cholic acid in the model group significantly decreased. As compared with the model group, five metabolites except phenol sulfate, PC[20:4(5Z,7E,11Z,14Z)-OH(9)/diMe(9,3)], o-palmitoyl carnitine, α-ketoglutarate acid, and citric acid in the TIA group significantly increased. According to the MetaboAnalyst enrichment analysis, the metabolic pathways were enriched in the tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism. These results show that during the glioblastoma growth process, the metabolites including αKG and citric acid are down-regulated, and TIA exerts the anti-glioblastoma growth effect through the regulation of tricarboxylic acid cycle, and alanine, aspartic acid, and glutamate metabolism to elevate the levels of αKG, citric acid, and other metabolites.PMID:36604918 | DOI:10.19540/j.cnki.cjcmm.20220728.401

Cancer Cell Int. 2023 Jan 5;23(1):2. doi: 10.1186/s12935-022-02845-y.ABSTRACTBACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cancer. The molecules (proteins, metabolites) secreted by tumors affect their extracellular milieu to support cancer progression. If secreted in amounts detectable in plasma, these molecules can also serve as useful, minimal invasive biomarkers. The knowledge of ccRCC tumor microenvironment is fragmentary. In particular, the links between ccRCC transcriptome and the composition of extracellular milieu are weakly understood. In this study, we hypothesized that ccRCC transcriptome is reprogrammed to support alterations in tumor microenvironment. Therefore, we comprehensively analyzed ccRCC extracellular proteomes and metabolomes as well as transcriptomes of ccRCC cells to find molecules contributing to renal tumor microenvironment.METHODS: Proteomic and metabolomics analysis of conditioned media isolated from normal kidney cells as well as five ccRCC cell lines was performed using mass spectrometry, with the following ELISA validation. Transcriptomic analysis was done using microarray analysis and validated using real-time PCR. Independent transcriptomic and proteomic datasets of ccRCC tumors were used for the analysis of gene and protein expression as well as the level of the immune infiltration.RESULTS: Renal cancer secretome contained 85 proteins detectable in human plasma, consistently altered in all five tested ccRCC cell lines. The top upregulated extracellular proteins included SPARC, STC2, SERPINE1, TGFBI, while downregulated included transferrin and DPP7. The most affected extracellular metabolites were increased 4-hydroxy-proline, succinic acid, cysteine, lactic acid and downregulated glutamine. These changes were associated with altered expression of genes encoding the secreted proteins (SPARC, SERPINE1, STC2, DPP7), membrane transporters (SLC16A4, SLC6A20, ABCA12), and genes involved in protein trafficking and secretion (KIF20A, ANXA3, MIA2, PCSK5, SLC9A3R1, SYTL3, and WNTA7). Analogous expression changes were found in ccRCC tumors. The expression of SPARC predicted the infiltration of ccRCC tumors with endothelial cells. Analysis of the expression of the 85 secretome genes in > 12,000 tumors revealed that SPARC is a PanCancer indicator of cancer-associated fibroblasts' infiltration.CONCLUSIONS: Transcriptomic reprogramming of ccRCC supports the changes in an extracellular milieu which are associated with immune infiltration. The proteins identified in our study represent valuable cancer biomarkers detectable in plasma.PMID:36604669 | DOI:10.1186/s12935-022-02845-y

Nat Microbiol. 2023 Jan;8(1):91-106. doi: 10.1038/s41564-022-01279-6. Epub 2023 Jan 5.ABSTRACTSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease caused by a phlebovirus in the Bunyaviridae family. Infection can result in systemic inflammatory response syndrome with a high fatality rate, and there are currently no treatments or vaccines available. The microbiota has been implicated in host susceptibility to systemic viral infection and disease outcomes, but whether the gut microbiota is implicated in severe fever with thrombocytopenia syndrome virus (SFTSV) infection is unknown. Here, we analysed faecal and serum samples from patients with SFTS using 16S ribosomal RNA-sequencing and untargeted metabolomics, respectively. We found that the gut commensal Akkermansia muciniphila increased in relative abundance over the course of infection and was reduced in samples from deceased patients. Using germ-free or oral antibiotic-treated mice, we found that A. muciniphila produces the β-carboline alkaloid harmaline, which protects against SFTSV infection by suppressing NF-κB-mediated systemic inflammation. Harmaline indirectly modulated the virus-induced inflammatory response by specifically enhancing bile acid-CoA: amino acid N-acyltransferase expression in hepatic cells to increase conjugated primary bile acids, glycochenodeoxycholic acid and taurochenodeoxycholic acid. These bile acids induced transmembrane G-protein coupled receptor-5-dependent anti-inflammatory responses. These results indicate the probiotic potential of A. muciniphila in mitigating SFTSV infection.PMID:36604506 | DOI:10.1038/s41564-022-01279-6

Sci Rep. 2023 Jan 5;13(1):186. doi: 10.1038/s41598-022-26515-1.ABSTRACTPosition within the social group has consequences on individual lifespans in diverse taxa. This is especially obvious in eusocial insects, where workers differ in both the tasks they perform and their aging rates. However, in eusocial wasps, bees and ants, the performed task usually depends strongly on age. As such, untangling the effects of social role and age on worker physiology is a key step towards understanding the coevolution of sociality and aging. We performed an experimental protocol that allowed a separate analysis of these two factors using four groups of black garden ant (Lasius niger) workers: young foragers, old foragers, young nest workers, and old nest workers. We highlighted age-related differences in the proteome and metabolome of workers that were primarily related to worker subcaste and only secondarily to age. The relative abundance of proteins and metabolites suggests an improved xenobiotic detoxification, and a fuel metabolism based more on lipid use than carbohydrate use in young ants, regardless of their social role. Regardless of age, proteins related to the digestive function were more abundant in nest workers than in foragers. Old foragers were mostly characterized by weak abundances of molecules with an antibiotic activity or involved in chemical communication. Finally, our results suggest that even in tiny insects, extended lifespan may require to mitigate cancer risks. This is consistent with results found in eusocial rodents and thus opens up the discussion of shared mechanisms among distant taxa and the influence of sociality on life history traits such as longevity.PMID:36604491 | DOI:10.1038/s41598-022-26515-1

Sci Rep. 2023 Jan 5;13(1):203. doi: 10.1038/s41598-022-26816-5.ABSTRACTCrohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract. A clear gap in our existing CD diagnostics and current disease management approaches is the lack of highly specific biomarkers that can be used to streamline or personalize disease management. Comprehensive profiling of metabolites holds promise; however, these high-dimensional profiles need to be reduced to have relevance in the context of CD. Machine learning approaches are optimally suited to bridge this gap in knowledge by contextualizing the metabolic alterations in CD using genome-scale metabolic network reconstructions. Our work presents a framework for studying altered metabolic reactions between patients with CD and controls using publicly available transcriptomic data and existing gene-driven metabolic network reconstructions. Additionally, we apply the same methods to patient-derived ileal enteroids to explore the utility of using this experimental in vitro platform for studying CD. Furthermore, we have piloted an untargeted metabolomics approach as a proof-of-concept validation strategy in human ileal mucosal tissue. These findings suggest that in silico metabolic modeling can potentially identify pathways of clinical relevance in CD, paving the way for the future discovery of novel diagnostic biomarkers and therapeutic targets.PMID:36604447 | DOI:10.1038/s41598-022-26816-5

Amino Acids. 2023 Jan 5. doi: 10.1007/s00726-022-03231-8. Online ahead of print.ABSTRACTDoxorubicin (DOX) is a cornerstone of chemotherapy for solid tumors and leukemias. DOX-induced cognitive impairment, termed chemo brain, has been reported in cancer survivors, whereas its mechanism remains poorly understood. Here we initially evaluated the cognitive impairments of mice treated with clinically relevant, long-term, low-dosage of DOX. Using HILIC-MS/MS-based targeted metabolomics, we presented the changes of 21 amino acids across six anatomical brain regions of mice with DOX-induced chemo brain. By mapping the altered amino acids to the human metabolic network, we constructed an amino acid-based network module for each brain region. We identified phenylalanine, tyrosine, methionine, and γ-aminobutyric acid as putative signatures of three regions (hippocampus, prefrontal cortex, and neocortex) highly associated with cognition. Relying on the reported mouse brain metabolome atlas, we found that DOX might perturb the amino acid homeostasis in multiple brain regions, similar to the changes in the aging brain. Correlation analysis suggested the possible indirect neurotoxicity of DOX that altered the brain levels of phenylalanine, tyrosine, and methionine by causing metabolic disorders in the liver and kidney. In summary, we revealed the region-specific amino acid signatures as actionable targets for DOX-induced chemo brain, which might provide safer treatment and improve the quality of life among cancer survivors.PMID:36604337 | DOI:10.1007/s00726-022-03231-8

Acta Biochim Biophys Sin (Shanghai). 2022 Nov 25;54(11):1599-1609. doi: 10.3724/abbs.2022162.ABSTRACTPancreatic neuroendocrine tumor (pNET) is the second most common malignant tumors of the pancreas. Multiple endocrine neoplasia 1 ( MEN1) is the most frequently mutated gene in pNETs and MEN1-encoded protein, menin, is a scaffold protein that interacts with transcription factors and chromatin-modifying proteins to regulate various signaling pathways. However, the role of MEN1 in lipid metabolism has not been studied in pNETs. In this study, we perform targeted metabolomics analysis and find that MEN1 promotes the generation and oxidation of polyunsaturated fat acids (PUFAs). Meanwhile lipid peroxidation is a hallmark of ferroptosis, and we confirm that MEN1 promotes ferroptosis by inhibiting the activation of mTOR signaling which is the central hub of metabolism. We show that stearoyl-coA desaturase (SCD1) is the downstream of MEN1-mTOR signaling and oleic acid (OA), a metabolite of SCD1, recues the lipid peroxidation caused by MEN1 overexpression. The negative correlation between MEN1 and SCD1 is further verified in clinical specimens. Furthermore, we find that BON-1 and QGP-1 cells with MEN1 overexpression are more sensitive to everolimus, a widely used drug in pNETs that targets mTOR signaling. In addition, combined use everolimus with ferroptosis inducer, RSL3, possesses a more powerful ability to kill cells, which may provide a new strategy for the comprehensive therapy of pNETs.PMID:36604142 | DOI:10.3724/abbs.2022162

Gut. 2023 Jan 5:gutjnl-2022-327756. doi: 10.1136/gutjnl-2022-327756. Online ahead of print.ABSTRACTOBJECTIVE: Gut microbiota dysbiosis is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify potential probiotic gut microbes that can ameliorate the development of RA.DESIGN: Microbiota profiling in patients with RA and healthy individuals was investigated via 16S rDNA bacterial gene sequencing and shotgun metagenomics. Collagen-induced arthritic mice and TNF-α transgenic mice were used to evaluate the roles of the gut commensal Parabacteroides distasonis in RA. The effects of P. distasonis-derived microbial metabolites on the differentiation of CD4+ T cells and macrophage polarisation were also investigated.RESULTS: The relative abundance of P. distasonis in new-onset patients with RA and patients with RA with history of the disease was downregulated and this decrease was negatively correlated with Disease Activity Score-28 (DAS28). Oral treatment of arthritic mice with live P. distasonis (LPD) considerably ameliorated RA pathogenesis. LPD-derived lithocholic acid (LCA), deoxycholic acid (DCA), isolithocholic acid (isoLCA) and 3-oxolithocholic acid (3-oxoLCA) had similar and synergistic effects on the treatment of RA. In addition to directly inhibiting the differentiation of Th17 cells, 3-oxoLCA and isoLCA were identified as TGR5 agonists that promoted the M2 polarisation of macrophages. A specific synthetic inhibitor of bile salt hydrolase attenuated the antiarthritic effects of LPD by reducing the production of these four bile acids. The natural product ginsenoside Rg2 exhibited its anti-RA effects by promoting the growth of P. distasonis.CONCLUSIONS: P. distasonis and ginsenoside Rg2 might represent probiotic and prebiotic agents in the treatment of RA.PMID:36604114 | DOI:10.1136/gutjnl-2022-327756

Carbohydr Polym. 2023 Feb 15;302:120395. doi: 10.1016/j.carbpol.2022.120395. Epub 2022 Nov 30.ABSTRACTIn cancer microenvironment, aberrant glycosylation events of ECM proteins and cell surface receptors occur. We developed a protocol to generate 3D bioprinted models of colorectal cancer (CRC) crosslinking hyaluronic acid and gelatin functionalized with three signalling glycans characterized in CRC, 3'-Sialylgalactose, 6'-Sialylgalactose and 2'-Fucosylgalactose. The crosslinking, performed exploiting azide functionalized gelatin and hyaluronic acid and 4arm-PEG-dibenzocyclooctyne, resulted in biocompatible hydrogels that were 3D bioprinted with commercial CRC cells HT-29 and patient derived CRC tumoroids. The glycosylated hydrogels showed good 3D printability, biocompatibility and stability over the time. SEM and synchrotron radiation SAXS/WAXS analysis revealed the influence of glycosylation in the construct morphology, whereas MALDI-MS imaging showed that protein profiles of tumoroid cells vary with glycosylation, indicating that sialylation and fucosylation of ECM proteins induce diverse alterations to the proteome of the tumoroid and surrounding cells.PMID:36604073 | DOI:10.1016/j.carbpol.2022.120395

J Ethnopharmacol. 2023 Jan 2:116116. doi: 10.1016/j.jep.2022.116116. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Hypertension coincides with the category of "vertigo" and/or "headache" on the basis clinical manifestations and traditional Chinese medicine (TCM) theory. Chai-Gui Decoction (CGD), which is in usage for relieving "vertigo" and/or "headache", had been demonstrated to be useful in ameliorating hypertension.AIM OF STUDY: This study was planned to investigate the mechanism of CGD and its components in hypertension by using spontaneous hypertension rat (SHR).MATERIALS AND METHODS: CGD extract and its classification component samples (compounds in plasma, CP; compounds in gut, CG; compounds in plasma and gut, CPG) were prepared for animal experiment. SHR rats were induced with CGD extract (3 g/kg/d BW, 5 g/kg/d BW, 15 g/kg/d BW) and CGD-component classes (CP = 19.501 mg/kg/d, CG = 5.240 mg/kg/d, CPG = 24.741 mg/kg/d) for 4 weeks. Blood pressure (BP) and indexes of renin-angiotensin-aldosterone system (RAAS system) were measured. Histopathology was carried out to assess the efficacy of CGD and its components on aorta tissues. Untargeted metabolomics of lipid from rat serum samples were applied by Ultra-High performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) and chemometric analysis to explore the relationship between metabolic pathways and hypertension. 16S rRNA gene sequencing of rat colon content and bioinformatics analysis were used to characterize the effects of CGD and its components on the gut microbiota composition of SHR rats.RESULTS: CGD and its component mixtures showed antihypertensive effect on SHR rats, decreased the blood pressure and reduced the aortic wall thickness in SHR rats. CGD and its component mixtures could improve the RAAS in SHR rats, including increase the percentage of angiotensin 1-7 (Ang 1-7), decrease the percentage of angiotensin II (Ang II), and decrease the Ang Ⅱ/Ang 1-7 ratio. CGD and its component mixtures could regulate the metabolome in SHR rats, mainly as decreasing the higher serum levels of Lysophosphatidylcholine (LPC) 16: 0, LPC 20: 4, and LPC 22: 6. In addition, bacteria from family S24-7 were negatively correlated with levels of LPE 16:0, LPE 18:0, LPE 18:1, and LPE 18:2.CONCLUSION: CGD and its component mixtures exhibited antihypertensive effect on SHR rats. The underlying mechanism could be related to modulation on RAAS, LPC metabolism and the bacterial abundance of family S24-7 in gut.PMID:36603783 | DOI:10.1016/j.jep.2022.116116

Biochem Pharmacol. 2023 Jan 2:115405. doi: 10.1016/j.bcp.2022.115405. Online ahead of print.ABSTRACTMitochondria and mitochondrial proteins represent a group of promising pharmacological-target candidates in the search of new molecular targets and drugs to counteract the onset of hypertension and more in general cardiovascular diseases (CVDs). Indeed, several mitochondrial pathways result impaired in CVDs, showing ATP depletion and ROS production as common traits of cardiac tissue degeneration. Thus, targeting mitochondrial dysfunction in cardiomyocytes can represent a successful strategy to prevent heart failure. In this context, the identification of new pharmacological targets among mitochondrial proteins paves the way for the design of new selective drugs. Thanks to the advances in omics approaches, to a greater availability of mitochondrial crystallized protein structures and to the development of new computational approaches for protein 3D-modelling and drug-design, it is now possible to investigate in detail impaired mitochondrial pathways in CVDs. Furthermore, it is possible to design new powerful drugs able to hit the selected pharmacological targets in a highly selective way to rescue mitochondrial dysfunction and prevent cardiac tissue degeneration. The role of mitochondrial dysfunction in the onset of CVDs appears increasingly evident, as reflected by the impairment of proteins involved in lipid peroxidation, mitochondrial dynamics, respiratory chain complexes, and membrane polarization maintenance in CVD patients. Conversely, little is known about proteins responsible for the cross-talk between mitochondria and cytoplasm in cardiomyocytes. Mitochondrial transporters of the SLC25A family, in particular, are responsible for the translocation of nucleotides (e.g., ATP), amino acids (e.g., aspartate, glutamate, ornithine), organic acids (e.g. malate and 2-oxoglutarate), and other cofactors (e.g., inorganic phosphate, NAD+, FAD, carnitine, CoA derivatives) between the mitochondrial and cytosolic compartments. Thus, mitochondrial transporters play a key role in the mitochondria-cytosol cross-talk by leading metabolic pathways such as the malate/aspartate shuttle, the carnitine shuttle, the ATP export from mitochondria, and the regulation of permeability transition pore opening. Since all these pathways are crucial for maintaining healthy cardiomyocytes, mitochondrial carriers emerge as an interesting class of new possible pharmacological targets for CVD treatments.PMID:36603686 | DOI:10.1016/j.bcp.2022.115405

Sci Total Environ. 2023 Jan 2:161247. doi: 10.1016/j.scitotenv.2022.161247. Online ahead of print.ABSTRACTPolystyrene nanoplastics (PSNPs, <100nm), an artificial pollutant that is widespread in the environment, can be assimilated by plants to alter plant gene expression and its metabolic pathway; thus, interfering with physiological homeostasis and growth of plants. Recently, the biosafety and potential environmental risks of PSNPs have attracted enormous attention. However, the knowledge regarding the uptake and phytotoxicity of atmosphere PSNPs subsiding to plant leaves is still limited. Here, we separately applied 50 mg/L and 100 mg/L PSNPs on cucumber leaves to simulate the plant response to the atmosphere PSNPs. We found that the PSNPs can be accumulated on the surface of cucumber leaves and are also able to be uptake by cucumber leaf stomata. The repertoires of metabolomics and transcriptomics from cucumber leaves upon PSNPs treatment demonstrated that the deposition of PSNPs on leaves alters the biosynthesis of various metabolites and the expression of a variety of genes. The leaves exposure to low concentration (50 mg/L) of PSNPs impact the genes involved in carbohydrate metabolism and the biosynthesis of metabolites related to membrane stability maintenance, thereby, probably enhancing plant tolerance to the stress caused by PSNPs. Whereas, exposure to high concentration (100 mg/L) of PSNPs, both nitrogen and carbohydrate metabolism in cucumber leaves are affected, as well as that the photosynthetic capacity was decreased, leading to the threat to plant health. Combined omics technologies, our findings advance our understanding about how the PSNPs released to ecological environment influence the terrestrial plant growth and provide phytotoxic mechanism.PMID:36603646 | DOI:10.1016/j.scitotenv.2022.161247

Sci Total Environ. 2023 Jan 2:161330. doi: 10.1016/j.scitotenv.2022.161330. Online ahead of print.ABSTRACTIn order to understand the mechanism that allows modified biochar (BC) to enhance the salt tolerance and growth of crops in saline-alkali soil, we tested the effects of ordinary BC, nanoparticle-size BC, acidified BC (HBC), and acidified nanoparticle-size BC on winter wheat growth and the soil properties by combining microbiological and metabolomics analyses. The results showed that compared with the control with no BC, the plant height increased by 17.33 % under HBC and the proportion of large soil aggregates increased by 1.25-2.83 times. HBC increased the relative abundances of some dominant genera of bacteria (e.g., Streptococcus) and fungi (e.g., Mycothermus), as well as functions such as bacterial metabolic genetic information processing and cellular processes, and reduced the abundance of pathotrophic fungi. Metabolomics analysis showed that HBC upregulated various metabolites (including amino acids and their derivatives, lipids, flavonoids, and organic acids) and five main metabolic pathways. Among the KEGG pathways, the pyrimidine metabolism pathway was significantly upregulated, as well as crop leaf metabolism, β-alanine metabolism, and valine, leucine, and isoleucine metabolism, and the antioxidant levels and resistance to salt-alkali stress were enhanced in winter wheat leaves. Partial least squares-path modeling suggested that HBC affected the growth of winter wheat by significantly changing the soil physicochemical properties and microbial structure (path coefficients of 0.566 and 0.512, respectively).PMID:36603639 | DOI:10.1016/j.scitotenv.2022.161330

Biochem Biophys Res Commun. 2022 Dec 28;643:129-138. doi: 10.1016/j.bbrc.2022.12.078. Online ahead of print.ABSTRACTThere is an alarming increase in incidence of fatty liver disease worldwide. The fatty liver disease spectrum disease ranges from simple steatosis (NAFL) to steatohepatitis (NASH) which culminates in cirrhosis and cancer. Altered metabolism is a hallmark feature associated with fatty liver disease and palmitic acid is the most abundant saturated fatty acid, therefore, the aim of this study was to compare metabolic profiles altered in hepatocytes treated with palmitic acid and also the differentially expressed plasma metabolites in spectrum of nonalcoholic fatty liver. The metabolites were analyzed by liquid chromatography-mass spectrometry (LC-MS) platform. Hepatocyte cell lines PH5CH8 and HepG2 cells when treated with 400 μM dose of palmitic acid showed typical features of steatosis. Metabolomic analysis of lipid treated hepatocyte cell lines showed differential changes in phenylalanine and tyrosine pathways, fatty acid metabolism and bile acids. The key metabolites tryptophan, kynurenine and carnitine differed significantly between subjects with NAFL, NASH and those with cirrhosis. As the tryptophan-kynurenine axis is also involved in denovo synthesis of NAD+, we found significant alterations in the NAD+ related metabolites in both palmitic acid treated and also fatty liver disease with cirrhosis. The study underscores the importance of amino acid and NAD+supplementation as promising strategies in fatty liver disorder.PMID:36603530 | DOI:10.1016/j.bbrc.2022.12.078