PubMed

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

Front Immunol. 2023 May 31;14:1190607. doi: 10.3389/fimmu.2023.1190607. eCollection 2023.ABSTRACTAs a chronic progressive autoimmune disease, rheumatoid arthritis (RA) is characterized by mainly damaging the synovium of peripheral joints and causing joint destruction and early disability. RA is also associated with a high incidence rate and mortality of cardiovascular disease. Recently, the relationship between lipid metabolism and RA has gradually attracted attention. Plasma lipid changes in RA patients are often detected in clinical tests, the systemic inflammatory status and drug treatment of RA patients can interact with the metabolic level of the body. With the development of lipid metabolomics, the changes of lipid small molecules and potential metabolic pathways have been gradually discovered, which makes the lipid metabolism of RA patients or the systemic changes of lipid metabolism after treatment more and more comprehensive. This article reviews the lipid level of RA patients, as well as the relationship between inflammation, joint destruction, cardiovascular disease, and lipid level. In addition, this review describes the effect of anti-rheumatic drugs or dietary intervention on the lipid profile of RA patients to better understand RA.PMID:37325667 | PMC:PMC10264672 | DOI:10.3389/fimmu.2023.1190607

Front Immunol. 2023 May 30;14:1172938. doi: 10.3389/fimmu.2023.1172938. eCollection 2023.ABSTRACTINTRODUCTION: Human immunodeficiency virus type 1 (HIV-1) causes a chronic, incurable infection leading to immune activation and chronic inflammation in people with HIV-1 (PWH), even with virologic suppression on antiretroviral therapy (ART). The role of lymphoid structures as reservoirs for viral latency and immune activation has been implicated in chronic inflammation mechanisms. Still, the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue remain unexplored.METHODS: In this study, we utilized human tonsil explants from healthy human donors and infected them with HIV-1 ex vivo. We performed single-cell RNA sequencing (scRNA-seq) to analyze the cell types represented in the tissue and to investigate the impact of infection on gene expression profiles and inflammatory signaling pathways.RESULTS: Our analysis revealed that infected CD4+ T cells exhibited upregulation of genes associated with oxidative phosphorylation. Furthermore, macrophages exposed to the virus but uninfected showed increased expression of genes associated with the NLRP3 inflammasome pathway.DISCUSSION: These findings provide valuable insights into the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue. The activation of oxidative phosphorylation in infected CD4+ T cells and the proinflammatory response in macrophages may contribute to the chronic inflammation observed in PWH despite ART. Understanding these mechanisms is crucial for developing targeted therapeutic strategies to eradicate HIV-1 infection in PWH.PMID:37325659 | PMC:PMC10266353 | DOI:10.3389/fimmu.2023.1172938

Front Cell Infect Microbiol. 2023 May 30;13:1196967. doi: 10.3389/fcimb.2023.1196967. eCollection 2023.ABSTRACTBACKGROUND AND AIMS: Gastrointestinal microbial metabolomics is closely related to the state of the organism and has significant interaction with the pathogenesis of many diseases. Based on the publications in Web of Science Core Collection(WoSCC) from 2004 to 2022, this study conducted a bibliometric analysis of this field, aiming to understand its development trend and frontier, and provide basic information and potential points for in-depth exploration of this field.METHODS: All articles on gastrointestinal flora and metabolism published from 2004 to 2022 were collected and identified in WoCSS. CiteSpace v.6.1 and VOSviewer v.1.6.15.0 were used to calculate bibliometric indicators, including number of publications and citations, study categories, countries/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords. A map was drawn to visualize the data based on the analysis results for a more intuitive view.RESULTS: There were 3811 articles in WoSCC that met our criteria. Analysis results show that the number of publications and citations in this field are increasing year by year. China is the country with the highest number of publications and USA owns the highest total link strength and citations. Chinese Acad Sci rank first for the number of institutional publications and total link strength. Journal of Proteome Research has the most publications. Nicholson, Jeremy K. is one of the most important scholars in this field. The most cited reference is "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease". Burst detection indicates that Urine, spectroscopy, metabonomic and gut microflora are long-standing hot topics in this field, while autism spectrum disorder and omics are likely to be at the forefront of research. The study of related metabolic small molecules and the application of gastrointestinal microbiome metabolomics in various diseases are currently emerging research directions and frontier in this field.CONCLUSION: This study is the first to make a bibliometric analysis of the studies related to gastrointestinal microbial metabolomics and reveal the development trends and current research hotspots in this field. This can contribute to the development of the field by providing relevant scholars with valuable and effective information about the current state of the field.PMID:37325519 | PMC:PMC10266355 | DOI:10.3389/fcimb.2023.1196967

Food Sci Nutr. 2023 Apr 5;11(6):3516-3534. doi: 10.1002/fsn3.3340. eCollection 2023 Jun.ABSTRACTPalm kernel meal (PKM) has been shown to be a high-quality protein source in ruminant feeds. This study focused on the effects of feed, supplemented with different amounts of PKM (ZL-0 as blank group, and ZL-15, ZL-18, and ZL-21 as treatment group), on the quality and flavor profile of Tibetan sheep meat. Furthermore, the deposition of beneficial metabolites in Tibetan sheep and the composition of rumen microorganisms on underlying regulatory mechanisms of meat quality were studied based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry as well as 16S rDNA sequencing. The results of the study showed that Tibetan sheep in the ZL-18 group exhibited superior eating quality and flavor profile while depositing more protein and fat relative to the other groups. The ZL-18 group also changed significantly in terms of the concentration and metabolic pathways of meat metabolites, as revealed by metabolomics. Metabolomics and correlation analyses finally showed that PKM feed mainly affected carbohydrate metabolism in muscle, which in turn affects meat pH, tenderness, and flavor. In addition, 18% of PKM increased the abundance of Christensenellaceae R-7 group, Ruminococcaceae UCG-013, Lachnospiraceae UCG-002, and Family XIII AD3011 group in the rumen but decreased the abundance of Prevotella 1; the above bacteria groups regulate meat quality by regulating rumen metabolites (succinic acid, DL-glutamic acid, etc.). Overall, the addition of PKM may improve the quality and flavor of the meat by affecting muscle metabolism and microorganisms in the rumen.PMID:37324863 | PMC:PMC10261763 | DOI:10.1002/fsn3.3340

Front Plant Sci. 2023 May 30;14:1024981. doi: 10.3389/fpls.2023.1024981. eCollection 2023.ABSTRACTCyanobacteria are a promising platform for the production of the triterpene squalene (C30), a precursor for all plant and animal sterols, and a highly attractive intermediate towards triterpenoids, a large group of secondary plant metabolites. Synechocystis sp. PCC 6803 natively produces squalene from CO2 through the MEP pathway. Based on the predictions of a constraint-based metabolic model, we took a systematic overexpression approach to quantify native Synechocystis gene's impact on squalene production in a squalene-hopene cyclase gene knock-out strain (Δshc). Our in silico analysis revealed an increased flux through the Calvin-Benson-Bassham cycle in the Δshc mutant compared to the wildtype, including the pentose phosphate pathway, as well as lower glycolysis, while the tricarboxylic acid cycle predicted to be downregulated. Further, all enzymes of the MEP pathway and terpenoid synthesis, as well as enzymes from the central carbon metabolism, Gap2, Tpi and PyrK, were predicted to positively contribute to squalene production upon their overexpression. Each identified target gene was integrated into the genome of Synechocystis Δshc under the control of the rhamnose-inducible promoter Prha. Squalene production was increased in an inducer concentration dependent manner through the overexpression of most predicted genes, which are genes of the MEP pathway, ispH, ispE, and idi, leading to the greatest improvements. Moreover, we were able to overexpress the native squalene synthase gene (sqs) in Synechocystis Δshc, which reached the highest production titer of 13.72 mg l-1 reported for squalene in Synechocystis sp. PCC 6803 so far, thereby providing a promising and sustainable platform for triterpene production.PMID:37324717 | PMC:PMC10266222 | DOI:10.3389/fpls.2023.1024981

Front Plant Sci. 2023 May 30;14:1181680. doi: 10.3389/fpls.2023.1181680. eCollection 2023.ABSTRACTRed and blue light-emitting diodes (LEDs) affect the quality of sweet potato leaves and their nutritional profile. Vines cultivated under blue LEDs had higher soluble protein contents, total phenolic compounds, flavonoids, and total antioxidant activity. Conversely, chlorophyll, soluble sugar, protein, and vitamin C contents were higher in leaves grown under red LEDs. Red and blue light increased the accumulation of 77 and 18 metabolites, respectively. Alpha-linoleic and linolenic acid metabolism were the most significantly enriched pathways based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 615 genes were differentially expressed between sweet potato leaves exposed to red and blue LEDs. Among these, 510 differentially expressed genes were upregulated in leaves grown under blue light compared with those grown under red light, while the remaining 105 genes were expressed at higher levels in the latter than in the former. Among the KEGG enrichment pathways, blue light significantly induced anthocyanin and carotenoid biosynthesis structural genes. This study provides a scientific reference basis for using light to alter metabolites to improve the quality of edible sweet potato leaves.PMID:37324670 | PMC:PMC10266350 | DOI:10.3389/fpls.2023.1181680

Biomed Rep. 2023 May 29;19(1):43. doi: 10.3892/br.2023.1626. eCollection 2023 Jul.ABSTRACTEndometriosis is characterized by the presence of endometrial-like tissue outside the uterus and is associated with an inflammatory immune response. The gut and reproductive tract microbiota constitute a protective barrier against infection by pathogens and regulate inflammatory and immune functions. This review summarizes microbiota imbalance (i.e., dysbiosis) in endometriosis and discusses how dysbiosis influences disease development. The literature was searched for studies published from inception to March 2022 in the PubMed and Google Scholar databases using a combination of specific terms. An altered gut and reproductive tract microbiome has been reported in numerous conditions, such as inflammatory bowel disease, allergies, autoimmunity, cancer and reproductive disorders (e.g., endometriosis). Furthermore, microbial dysbiosis is a hallmark of endometriosis and is characterized by a decrease in beneficial probiotics and an increase in pathogenic microbes, which leads to a series of estrobolomic and metabolomic changes. Gut or reproductive tract microbiome dysbiosis was reported in mice, nonhuman primates, and females with endometriosis. Animal models of endometriosis demonstrated the effects of the gut microbiome on lesion growth and vice versa. The immune system mediated by the microbiota-gut-reproductive tract axis triggers an inflammatory response that damages reproductive tract tissue, which possibly leads to endometriosis. However, whether the alteration of eubiosis (a balanced microbiota) to dysbiosis is a cause or a result of endometriosis is unclear. In conclusion, this review provides an overview of the relationship between the gut and reproductive tract microbiome and endometriosis, focusing on the mechanisms by which dysbiosis may increase the risk of disease.PMID:37324168 | PMC:PMC10265574 | DOI:10.3892/br.2023.1626

J Thorac Dis. 2023 May 30;15(5):2668-2679. doi: 10.21037/jtd-23-250. Epub 2023 May 24.ABSTRACTBACKGROUND: Invasive puncture biopsy is currently the main method of identifying benign and malignant pulmonary nodules (PNs). This study aimed to investigate the application effect of chest computed tomography (CT) images, tumor markers (TMs), and metabolomics in the identification of benign and malignant PNs (MPNs).METHODS: A total of 110 patients with PNs who were hospitalized in Dongtai Hospital of Traditional Chinese Medicine from March 2021 to March 2022 were selected as the study cohort. A retrospective analysis study of chest CT imaging, serum TMs testing, and plasma fatty acid (FA) metabolomics was performed on all participants.RESULTS: According to the pathological results, participants were divided into a MPN group (n=72) and a benign PN (BPN) group (n=38). The morphological signs of CT images, the levels and positive rate of serum TMs, and the plasma FA indicator were compared between groups. There were significant differences between the MPN group and the BPN group in the CT morphological signs, including location of PN and the number of patients with or without lobulation sign, spicule sign, and vessel convergence sign (P<0.05). Serum carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA 21-1), neuron-specific enolase (NSE), and squamous cell carcinoma antigen (SCC-Ag) were not significantly different between the 2 groups. The serum contents of CEA and CYFRA 21-1 in the MPN group were remarkably higher than those in the BPN group (P<0.05). The plasma levels of palmitic acid, total omega-3 polyunsaturated FA (W3), nervonic acid, stearic acid, docosatetraenoic acid, linolenic acid, eicosapentaenoic acid, total saturated FA, and total FA were much higher in the MPN group than the BPN group (P<0.05).CONCLUSIONS: In conclusion, chest CT images and TMs, combined with metabolomics, has a good application effect in the diagnosis of BPNs and MPNs, and is worthy of further promotion.PMID:37324101 | PMC:PMC10267948 | DOI:10.21037/jtd-23-250

J Thorac Dis. 2023 May 30;15(5):2544-2558. doi: 10.21037/jtd-22-1731. Epub 2023 May 22.ABSTRACTBACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common chronic lung disease and its incidence is steadily increasing. COPD patients and mouse models of COPD share some similarities in lung pathology and physiology. We performed this study to explore the potential metabolic pathways involved in the pathogenesis of COPD and to discover the COPD-associated biomarkers. Furthermore, we aimed to examine how much the mouse model of COPD was similar and different to human COPD in terms of the altered metabolites and pathways.METHODS: Twenty human lung tissue samples (ten COPD and ten controls) and twelve mice lung tissue samples (six COPD and six controls) were analyzed by targeted HM350 metabolomics, and multivariate and pathway analysis were performed by Kyoto Encyclopedia of Genes and Genomes (KEGG) database.RESULTS: The counts of many metabolites such as amino acids, carbohydrates and carnitines were changed in both COPD patients and mice compared to controls, respectively. While lipid metabolism was changed only in COPD mice. After KEGG analysis, we found these altered metabolites involved in COPD through aging, apoptosis, oxidative stress and inflammation pathways.CONCLUSIONS: The expressions of metabolites changed in both COPD patients and cigarette smoke exposed (CS-exposed) mice. And there were also some differences between COPD patients and mouse models due to the differences between species. Our study suggested the dysregulation in amino acid metabolism, energy production pathway and perhaps lipid metabolism may be significantly related to the pathogenesis of COPD.PMID:37324094 | PMC:PMC10267913 | DOI:10.21037/jtd-22-1731

Front Microbiol. 2023 May 30;14:1222594. doi: 10.3389/fmicb.2023.1222594. eCollection 2023.NO ABSTRACTPMID:37323916 | PMC:PMC10265112 | DOI:10.3389/fmicb.2023.1222594

ACS Omega. 2023 Jun 1;8(23):20755-20766. doi: 10.1021/acsomega.3c01370. eCollection 2023 Jun 13.ABSTRACTBiofluid metabolomics is a very appealing tool to increase the knowledge associated with pathophysiological mechanisms leading to better and new therapies and biomarkers for disease diagnosis and prognosis. However, due to the complex process of metabolome analysis, including the metabolome isolation method and the platform used to analyze it, there are diverse factors that affect metabolomics output. In the present work, the impact of two protocols to extract the serum metabolome, one using methanol and another using a mixture of methanol, acetonitrile, and water, was evaluated. The metabolome was analyzed by ultraperformance liquid chromatography associated with tandem mass spectrometry (UPLC-MS/MS), based on reverse-phase and hydrophobic chromatographic separations, and Fourier transform infrared (FTIR) spectroscopy. The two extraction protocols of the metabolome were compared over the analytical platforms (UPLC-MS/MS and FTIR spectroscopy) concerning the number of features, the type of features, common features, and the reproducibility of extraction replicas and analytical replicas. The ability of the extraction protocols to predict the survivability of critically ill patients hospitalized at an intensive care unit was also evaluated. The FTIR spectroscopy platform was compared to the UPLC-MS/MS platform and, despite not identifying metabolites and consequently not contributing as much as UPLC-MS/MS in terms of information concerning metabolic information, it enabled the comparison of the two extraction protocols as well as the development of very good predictive models of patient's survivability, such as the UPLC-MS/MS platform. Furthermore, FTIR spectroscopy is based on much simpler procedures and is rapid, economic, and applicable in the high-throughput mode, i.e., enabling the simultaneous analysis of hundreds of samples in the microliter range in a couple of hours. Therefore, FTIR spectroscopy represents a very interesting complementary technique not only to optimize processes as the metabolome isolation but also for obtaining biomarkers such as those for disease prognosis.PMID:37323376 | PMC:PMC10237515 | DOI:10.1021/acsomega.3c01370

Ther Adv Med Oncol. 2023 Jun 5;15:17588359231177021. doi: 10.1177/17588359231177021. eCollection 2023.ABSTRACTBACKGROUND: The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor (EGFR) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses.OBJECTIVES: We report details of the clinical portion prior to omics analyses.DESIGN: A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed.METHODS: Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated.RESULTS: A total of 103 patients (median age 70 years, range 42-88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 (n = 27), 30 (n = 23), and 20 mg/day (n = 35), and 20 mg every other day (n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did (n = 25) and did not (n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively (p = 0.654).CONCLUSIONS: As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib.TRIAL REGISTRATION: UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688.PMID:37323187 | PMC:PMC10262622 | DOI:10.1177/17588359231177021

Pharm Biol. 2023 Dec;61(1):927-937. doi: 10.1080/13880209.2023.2222755.ABSTRACTCONTEXT: Qingyi granules can be used to effectively treat patients with severe acute pancreatitis (SAP).OBJECTIVE: To elucidate the role of gut microbiota-mediated metabolism in the therapeutic effects of Qingyi granules.MATERIALS AND METHODS: Sprague-Dawley rats were grouped into the sham operation, SAP model, Qingyi granule intervention (Q, 1.8 g/kg) and emodin intervention (E, 50 mg/kg) groups and observed for 24 h. H&E staining and ELISA were used for histopathological analysis and serum enzyme and cytokine assays. 16S rDNA sequencing and UHPLC-HRMS were used for gut microbiota analysis and untargeted metabolomics.RESULTS: In SAP rats, Qingyi granules decreased the pancreatic pathological score (Q, 7.4 ± 1.14; SAP, 11.6 ± 1.14, p < 0.01); serum amylase (Q, 121.2 ± 6.7; SAP, 144.3 ± 8.86, p < 0.05), lipase (Q, 566 ± 20.34; SAP, 656.7 ± 29.32, p < 0.01), and diamineoxidase (Q, 492.8 ± 26.08; SAP, 566.1 ± 26.83, p < 0.05) activities; and IL-1β (Q, 29.48 ± 0.88; SAP, 36.17 ± 1.88, p < 0.01), IL-6 (Q, 112.2 ± 3.57; SAP, 128.9 ± 9.09, p < 0.05) and TNF-α (Q, 215.3 ± 8.67; SAP, 266.4 ± 28.03, p < 0.05) levels. SAP induced Helicobacter and Lactobacillus overgrowth and suppressed Romboutsia and Allobaculum growth and caused aberrations in bacterial metabolites, which were partly reversed by Qingyi granules.DISCUSSION AND CONCLUSIONS: Qingyi granules can modulate the gut microbiota and metabolic abnormalities to ameliorate SAP. Multi-omics approaches allow systematic study of the pharmacological mechanisms of compound prescriptions for critical illnesses.PMID:37323024 | DOI:10.1080/13880209.2023.2222755

Carbohydr Polym. 2023 Sep 15;316:121039. doi: 10.1016/j.carbpol.2023.121039. Epub 2023 May 25.ABSTRACTDietary fibers are known to modulate microbiome composition, but it is unclear to what extent minor fiber structural differences impact community assembly, microbial division of labor, and organismal metabolic responses. To test the hypothesis that fine linkage variations afford different ecological niches for distinct communities and metabolism, we employed a 7-day in vitro sequential batch fecal fermentation with four fecal inocula and measured responses using an integrated multi-omics approach. Two sorghum arabinoxylans (SAXs) were fermented, with one (RSAX) having slightly more complex branch linkages than the other (WSAX). Although there were minor glycoysl linkage differences, consortia on RSAX retained much higher species diversity (42 members) than on WSAX (18-23 members) with distinct species-level genomes and metabolic outcomes (e.g., higher short chain fatty acid production from RSAX and more lactic acid produced from WSAX). The major SAX-selected members were from genera of Bacteroides and Bifidobacterium and family Lachnospiraceae. Carbohydrate active enzyme (CAZyme) genes in metagenomes revealed broad AX-related hydrolytic potentials among key members; however, CAZyme genes enriched in different consortia displayed various catabolic domain fusions with diverse accessory motifs that differ among the two SAX types. These results suggest that fine polysaccharide structure exerts deterministic selection effect for distinct fermenting consortia.PMID:37321733 | DOI:10.1016/j.carbpol.2023.121039

Sci Total Environ. 2023 Jun 13:164857. doi: 10.1016/j.scitotenv.2023.164857. Online ahead of print.ABSTRACTSulfonamide antibiotics (SAs) are ubiquitous in surface water and soil environments, raising considerable concerns about their risk and removal. However, the impacts of various bromide ion (Br-) concentrations on the phytotoxicity, uptake and fate of SAs in plant growth and physiological metabolism of plants have not been well understood. Our research demonstrated that low concentrations of Br- (0.1, 0.5 mM) promoted the uptake and degradation of sulfadiazine (SDZ) in wheat and attenuated the phytotoxicity of SDZ. Additionally, we proposed a degradation pathway and identified the brominated product of SDZ (SDZBr), which attenuated the dihydrofolate synthesis inhibition by SDZ. The primary mechanism was that Br- reduced the level of reactive oxygen radicals (ROS) and alleviated oxidative damage. The production of SDZBr and the high consumption of H2O2 suggest the potential generation of reactive bromine species, contributing to the degradation of the electron-rich SDZ and thus reducing its toxicity. Moreover, metabolome analysis of wheat roots indicated that low concentrations of Br- stimulated the production of indoleacetic acid under SDZ stress, promoting growth and enhancing the uptake and degradation of SDZ. Conversely, high Br- (1 mM) concentration produced a deleterious effect. These findings provide valuable insights into the mechanisms of antibiotic removal, suggesting a potentially novel approach to plant-based antibiotic remediation.PMID:37321499 | DOI:10.1016/j.scitotenv.2023.164857

J Ethnopharmacol. 2023 Jun 13:116782. doi: 10.1016/j.jep.2023.116782. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium wilfordii polyglycosides (TWP), extracted from the traditional Chinese herb Tripterygium wilfordii, has been widely used in the treatment of rheumatoid arthritis (RA). However, the toxicity of TWP to a variety of organs such as liver, kidney and testis greatly limits its clinical application. Salvia miltiorrhiza Bunge is often used in the treatment of RA due to its blood circulation promoting, stasis resolving, and anti-inflammatory effects. Salvia miltiorrhiza Bunge has also been reported to possess multiple organ protective effects.AIM OF THE STUDY: To investigate the influences of two main components of Salviorrhiza miltiorrhiza Bunge, hydrophilic salvianolic acids (SA) and lipophilic tanshinones (Tan), on the efficacy and toxicity of TWP in treating RA and to explore the underlying mechanisms.MATERIALS AND METHODS: SA and Tan were extracted from Salvia miltiorrhiza Bunge and the extracts were quantitated by HPLC and identified by UPLC-Q/TOF-MS. Then, a collagen-induced arthritis (CIA) rat model was established using bovine type II collagen (CII) and incomplete Freund's adjuvant (IFA). CIA rats were treated with TWP and/or SA/Tan. After 21 days of continuous treatment, arthritis symptoms and organs toxicity were evaluated. Meanwhile, serum metabolomics were investigated by the UPLC-Q/TOF-MS to understand the underlying mechanism.RESULTS: SA and Tan extracts could significantly alleviate arthritis symptoms in CIA rats and decrease the serum levels of inflammatory factors TNF-α, IL-1β and IL-6 when combined with TWP. Meanwhile, both extracts alleviated injury of liver, kidney and testis caused by TWP, and the hydrophilic extract SA was superior. Moreover, a total of 38 endogenous differential metabolites were identified between the CIA model group and the TWP group, among which 33 metabolites were significantly recovered after the combination of SA or Tan. Metabolic pathway analysis showed that SA and Tan can affect metabolic pathways including linoleic acid metabolism, glycerophospholipid metabolism, sphingolipid metabolism and steroid biosynthesis metabolism pathway.CONCLUSIONS: Our findings indicated for the first time that two Salviorrhiza miltiorrhiza Bunge extracts could improve the efficacy and reduce the toxicity of TWP in the treatment of RA by adjusting metabolic pathways, and the hydrophilic extract SA was superior.PMID:37321427 | DOI:10.1016/j.jep.2023.116782