PubMed

Phytochem Anal. 2023 Oct 1. doi: 10.1002/pca.3289. Online ahead of print.ABSTRACTINTRODUCTION: Ophiocordyceps gracilis is an entomopathogenic fungus and a precious traditional Chinese medicine with similar medicinal properties to Ophiocordyceps sinensis. However, information on the metabolite profiles of natural O. gracilis and its cultures is lacking, which limits their utilization.OBJECTIVE: The metabolic variations and antioxidant activities of O. gracilis cultures and natural O. gracilis were analyzed to evaluate the nutritional and medicinal value of O. gracilis and its cultures.METHOD: The metabolite profiles of O. gracilis cultures (fruiting bodies and aerial mycelia), natural O. gracilis, and natural O. sinensis were compared by LC-MS/MS coupled with multivariate data analysis. Furthermore, their antioxidant activities were evaluated based on their DPPH• , ABTS•+ , and • OH scavenging abilities.RESULTS: A total of 612 metabolites were identified, and the metabolic compositions of the four Cordyceps samples were similar, with differences observed in the levels of some metabolites. There were 126 differential metabolites between natural O. gracilis and natural O. sinensis, among which fatty acids, carbohydrates, and secondary metabolites are predominant in natural O. gracilis. Furthermore, 116 differential metabolites between O. gracilis cultures and natural Cordyceps were identified, with generally higher levels in O. gracilis cultures than in natural Cordyceps. O. gracilis cultivated fruiting bodies exhibited the strongest antioxidant capacity among Cordyceps samples. Additionally, 46 primary and 24 secondary differential metabolites contribute to antioxidant activities.CONCLUSION: This study provides a reference for the application of natural O. gracilis and its cultures in functional food and medicine from the perspective of metabolites and antioxidant capacity.PMID:37779226 | DOI:10.1002/pca.3289

J Environ Sci (China). 2024 Jan;135:198-209. doi: 10.1016/j.jes.2022.11.007. Epub 2022 Nov 17.ABSTRACTQuaternary ammonium compounds (QACs) are commonly used in a variety of consumer and commercial products, typically as a component of disinfectants. During the COVID-19 pandemic, QACs became one of the primary agents utilized to inactivate the SARS-CoV-2 virus on surfaces. However, the ecotoxicological effects of QACs upon aquatic organisms have not been fully assessed. In this study, we examined the effects of a widely used QAC (benzalkonium chloride-C14, BAC-14) on two toxigenic Microcystis strains and one non-toxigenic freshwater Microcystis strain and carried out an analysis focused on primary, adaptive and compensatory stress responses at apical (growth and photosynthesis) and metabolic levels. This analysis revealed that the two toxic Microcystis strains were more tolerant than the non-toxic strain, with 96 hr-EC50 values of 0.70, 0.76, and 0.38 mg/L BAC-14 for toxigenic M. aeruginosa FACHB-905, toxigenic M. aeruginosa FACHB-469, and non-toxigenic M. wesenbergii FACHB-908, respectively. The photosynthetic activities of the Microcystis, assessed via Fv/Fm values, were significantly suppressed under 0.4 mg/L BAC-14. Furthermore, this analysis revealed that BAC-14 altered 14, 12, and 8 metabolic pathways in M. aeruginosa FACHB-905, M. aeruginosa FACHB-469, and M. wesenbergii FACHB-908, respectively. It is noteworthy that BAC-14 enhanced the level of extracellular microcystin production in the toxigenic Microcystis strains, although cell growth was not significantly affected. Collectively, these data show that BAC-14 disrupted the physiological and metabolic status of Microcystis cells and stimulated the production and release of microcystin, which could result in damage to aquatic systems.PMID:37778795 | DOI:10.1016/j.jes.2022.11.007

Cancer Sci. 2023 Oct 1. doi: 10.1111/cas.15983. Online ahead of print.ABSTRACTTo investigate the potential of the gut microbiome as a biomarker for predicting the early recurrence of HBV-related hepatocellular carcinoma (HCC), we enrolled 124 patients diagnosed with HBV-associated HCC and 82 HBV-related hepatitis, and 86 healthy volunteers in our study, collecting 292 stool samples for 16S rRNA sequencing and 35 tumor tissue samples for targeted metabolomics. We performed an integrated bioinformatics analysis of gut microbiome and tissue metabolome data to explore the gut microbial-liver metabolite axis associated with the early recurrence of HCC. We constructed a predictive model based on the gut microbiota and validated its efficacy in the temporal validation cohort. Dialister, Veillonella, the Eubacterium coprostanoligenes group, and Lactobacillus genera, as well as the Streptococcus pneumoniae and Bifidobacterium faecale species, were associated with an early recurrence of HCC. We also found that 23 metabolites, including acetic acid, glutamate, and arachidonic acid, were associated with the early recurrence of HCC. A comprehensive analysis of the gut microbiome and tissue metabolome revealed that the entry of gut microbe-derived acetic acid into the liver to supply energy for tumor growth and proliferation may be a potential mechanism for the recurrence of HCC mediated by gut microbe. We constructed a nomogram to predict early recurrence by combining differential microbial species and clinical indicators, achieving an AUC of 78.0%. Our study suggested that gut microbes may serve as effective biomarkers for predicting early recurrence of HCC, and the gut microbial-tumor metabolite axis may explain the potential mechanism by which gut microbes promote the early recurrence of HCC.PMID:37778742 | DOI:10.1111/cas.15983

Sci Total Environ. 2023 Sep 29:167446. doi: 10.1016/j.scitotenv.2023.167446. Online ahead of print.ABSTRACTMetabolomics is increasingly recognized as a useful approach to characterize environmental pollution gradients. While the performance of analytical procedures must be validated and documented, many studies only briefly describe sampling and sample storage. Here we advance our recent study on the influences of sampling delay and holding media on two contaminants of emerging concern in fish plasma by targeted analysis. We specifically examined the metabolome and exposome of common carp under three conditions: plasma sampled immediately after field collection (t = 0 h) and then after 3 h (t = 3 h) or 20 h (t = 20 h) of holding fish in lab water. Plasma samples were analyzed using reversed-phase and HILIC chromatography with mass spectrometric detection. 6143 of the 12,904 compounds (after clustering features) varied among the groups. We observed different metabolite variations patterns depending on the sample collection time. We also identified several xenobiotics (2-Ethylhexyl sulfate, 6-Chloro-5-methyl-1H-benzotriazole) at concentrations generally found at the highest levels in plasma sampled immediately after field collection (t = 0 h). Both the metabolome and the exposome changed rapidly in fish plasma with a time lag, which indicates that obtaining relevant results is complicated by fish-holding conditions. We further identified that non-lethal, relatively low-volume blood sample collection was sufficient with this species, which presents ethical and practical advantages.PMID:37778561 | DOI:10.1016/j.scitotenv.2023.167446

J Ethnopharmacol. 2023 Sep 29:117256. doi: 10.1016/j.jep.2023.117256. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) and traditional Korean medicine (TKM), Gwakhyangjeonggi-san (GJS) is an herbal decoction used to treat gastrointestinal disorders and allergic diseases. However, no randomized controlled trials have reported the efficacy and safety of GJS against atopic dermatitis (AD) or its comorbidities.AIM OF THE STUDY: This clinical trial investigated the clinical efficacy and safety of GJS for treating patients with AD who have gastrointestinal symptoms, using a multi-omics approach that included 16S rRNA sequencing and metabolomics.MATERIALS AND METHODS: This study was a randomized, double-blind, placebo-controlled, parallel-group clinical trial. Fifty-two patients with AD (age: 19-60) were randomly assigned to receive either the GJS (N = 27) or placebo (N = 25) granules thrice daily for 8 weeks. The primary outcome was measured as the change in the SCORing of Atopic Dermatitis index from baseline to 8 weeks. The secondary outcomes included the eczema area and severity index, dermatology life quality index, EuroQoL 5 dimensions 5 levels (EQ-5D-5L), immunological factors, gastrointestinal status, and safety evaluation. In addition, 16S rRNA sequencing on gut-microbiomes and non-targeted metabolomics approach using mass spectrometry on sera samples were applied to investigate the GJS therapeutic mechanism.RESULTS: After 8 weeks, AD symptoms were reduced in both the GJS and placebo groups without any serious adverse events, but the reduction was not significantly different between the two groups. However, the EQ-5D-5L scores and gastrointestinal symptom scores, such as bitter-tasting fluid presenting in the mouth, upper abdomen bloating, and nausea, only improved in the GJS group. To further elucidate the effect of GJS on patients with AD who have gastrointestinal symptoms, 16S rRNA sequencing and metabolomics were executed. The GJS group had lower gut microbiome diversity including observed OUT, Ace, Chao1 and Shannon index than the placebo group at enrollment time, while the difference in gut microbiome diversity between GJS and placebo group was eliminated by 8 weeks of treatment. Consistently, the metabolomics results showed that the gut microbiome-derived uremic toxins, including indoxyl sulfate and phenylacetylglutamine, significantly increased in the placebo group, while these in GJS group were maintained without any significant change.CONCLUSIONS: These results showed that the GJS had no significant effect on AD compared to the placebo but exerted a beneficial effect on improving the quality of life and gastrointestinal symptoms in patients with AD, and it acted by modulating gut microbiome diversity and gut microbiome-derived uremic toxins. Our findings support the use of GJS for AD comorbidities and also provide evidence that multi-omics approaches can be useful for understanding herbal decoctions in TCM and TKM comprehensively.PMID:37778520 | DOI:10.1016/j.jep.2023.117256

J Nutr. 2023 Sep 29:S0022-3166(23)72614-X. doi: 10.1016/j.tjnut.2023.09.019. Online ahead of print.ABSTRACTBACKGROUND: Palm oil (PO) is the most widely utilized plant oil for food production. Owing to great ecological problems associated with PO production, sustainably produced fats, such as insect fat, might be a suitable alternative.OBJECTIVE: The hypothesis was tested that fat from Hermetia illucens larvae (HF) compared with PO and soybean oil (SO) has no adverse effects on hepatic lipid metabolism, plasma metabolome and cecal microbiome in obese Zucker rats.METHODS: 30 male obese Zucker rats were randomly assigned to three groups (SO, PO, HF; n = 10 rats/group), and fed three different semisynthetic diets containing either SO, PO or HF as the main fat source for 4 weeks. The effects were evaluated by measurement of liver and plasma lipid concentrations, liver transcriptomics, targeted plasma metabolomics, and cecal microbiomics.RESULTS: Supplementation of HF reduced hepatic triglyceride (TG) concentration and mRNA levels of selected genes involved in fatty acid and TG synthesis in comparison to PO (P < 0.05). Pairwise comparison of Simpson index and Jaccard index showed a higher cecal microbial α- and β-diversity in rats fed the HF diet compared to rats fed the PO diet (P = 0.015 and P = 0.027, respectively), but no difference between rats fed the diets with SO or PO. Taxonomic analysis of the cecal microbial community revealed a lower abundance of Clostridium_sensu_stricto_1 and a higher abundance of Blautia, Mucispirillum, Anaerotruncus, Harryflintia and Peptococcus in rats supplemented with HF than in rats supplemented with PO (P < 0.05).CONCLUSIONS: HF compared with PO has liver lipid lowering effects in obese Zucker rats, which may be caused by a shift in the gut microbial community. Thus, HF might serve as a sustainably produced fat alternative to PO for food production.PMID:37778509 | DOI:10.1016/j.tjnut.2023.09.019

Toxicol Appl Pharmacol. 2023 Sep 29:116708. doi: 10.1016/j.taap.2023.116708. Online ahead of print.ABSTRACTPentachlorophenol (PCP) is a ubiquitous environmental toxicant with various adverse effects. Although its neurotoxicity has been reported, the underlying mechanism and subsequent detoxification remain unclear. In this study, embryos and adult zebrafish were exposed to PCP to determine its potential neurotoxic mechanism and protective indicators. The survival rate, heart rate, mobility time, active status and moving distance were significantly decreased in larvae after 30 μg/L PCP exposure. Likewise, the mobile time, latency to the first movement, velocity and moving distance of adult zebrafish were significantly reduced by PCP exposure. Untargeted metabolomics analysis of larvae revealed that arginine and proline metabolism was the primary pathway affected by PCP exposure, reflected by increased proline and decreased citrulline (CIT) contents, which were confirmed by quantitative data. PCP exposure suppressed the conversion from arginine to CIT in larvae by downregulating the expression of nos1 and nos2a. Ornithine content was increased in the brains and intestines of adult zebrafish after PCP exposure, which inhibited ornithine catabolism to CIT by downregulating otc, resulting in reduced CIT. Intriguingly, CIT supplementation significantly restored the neurobehavioral defects induced by PCP in larvae and adult zebrafish. CIT supplementation upregulated the expression of ef1α and tuba1 in larvae and inhibited the downregulation of ef1α in the brains of adult zebrafish. Taken together, these results indicated that CIT supplementation could protect against PCP-induced neurotoxicity by upregulating the expression of genes involved in neuronal development and function.PMID:37778480 | DOI:10.1016/j.taap.2023.116708

J Pharm Biomed Anal. 2023 Sep 21;236:115739. doi: 10.1016/j.jpba.2023.115739. Online ahead of print.ABSTRACTPseudomonas aeruginosa (PA) infection is commonly associated with hospital-acquired infections in patients with immune deficiency and/or severe lung diseases. Managing this bacterium is complex due to drug resistance and high adaptability. Fluorothiazinon (FT) is an anti-virulence drug developed to suppress the virulence of bacteria as opposed to bacterial death increasing host's immune response to infection and improving treatment to inhibit drug resistant bacteria. We aimed to evaluate FT pharmacokinetics, quorum sensing signal molecules profiling and tryptophan-related metabolomics in blood, liver, kidneys, and lungs of mice. Study comprised three groups: a group infected with PA that was treated with 400 mg/kg FT ("infected treated group"); a non-infected group, but also treated with the same single drug dose ("non-infected treated group"); and an infected group that received a vehicle ("infected non-treated group"). PA-mediated infection blood pharmacokinetics profiling was indicative of increased drug concentrations as shown by increased Cmax and AUCs. Tissue distribution in liver, kidneys, and lungs, showed that liver presented the most consistently higher concentrations of FT in the infected versus non-infected mice. FT showed that HHQ levels were decreased at 1 h after dosing in lungs while PQS levels were lower across time in lungs of infected treated mice in comparison to infected non-treated mice. Metabolomics profiling performed in lungs and blood of infected treated versus infected non-treated mice revealed drug-associated metabolite alterations, especially in the kynurenic and indole pathways.PMID:37778200 | DOI:10.1016/j.jpba.2023.115739

Atherosclerosis. 2023 Sep 9;382:117285. doi: 10.1016/j.atherosclerosis.2023.117285. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Plant-based dietary patterns have been associated with improved health outcomes. This study aims to describe the metabolomic fingerprints of plant-based diet indices (PDI) and examine their association with metabolic syndrome (MetS) and its components in a Danish population.METHODS: The MAX study comprised 676 participants (55% women, aged 18-67 y) from Copenhagen. Sociodemographic and dietary data were collected using questionnaires and three 24-h dietary recalls over one year (at baseline, and at 6 and 12 months). Mean dietary intakes were computed, as well as overall PDI, healthful (hPDI) and unhealthful (uPDI) scores, according to food groups for each plant-based index. Clinical variables were also collected at the same time points in a health examination that included complete blood tests. MetS was defined according to the International Diabetes Federation criteria. Plasma metabolites were measured using a targeted metabolomics approach. Metabolites associated with PDI were selected using random forest models and their relationships with PDIs and MetS were analyzed using generalized linear mixed models.RESULTS: The mean prevalence of MetS was 10.8%. High, compared to low, hPDI and uPDI scores were associated with a lower and higher odd of MetS, respectively [odds ratio (95%CI); hPDI: 0.56 (0.43-0.74); uPDI: 1.61 (1.26-2.05)]. Out of 411 quantified plasma metabolites, machine-learning metabolomics fingerprinting revealed 13 metabolites, including food and food-related microbial metabolites, like hypaphorine, indolepropionic acid and lignan-derived enterolactones. These metabolites were associated with all PDIs and were inversely correlated with MetS components (p < 0.05). Furthermore, they had an explainable contribution of 12% and 14% for the association between hPDI or uPDI, respectively, and MetS only among participants with overweight/obesity.CONCLUSIONS: Metabolites associated with PDIs were inversely associated with MetS and its components, and may partially explain the effects of plant-based diets on cardiometabolic risk factors.PMID:37778133 | DOI:10.1016/j.atherosclerosis.2023.117285

Biomed Chromatogr. 2023 Oct 1:e5750. doi: 10.1002/bmc.5750. Online ahead of print.ABSTRACTCisplatin-induced nephrotoxicity has been widely reported in numerous studies. The objective of this study is to assess the potential nephroprotective effects of Clinacanthus nutans (Burm. f.) Lindau (Acanthaceae) leaf extracts on human kidney cells (PCS-400-010) in vitro using an LCMS-based metabolomics approach. Orthogonal partial least square-discriminant analysis identified 16 significantly altered metabolites when comparing the control and pre-treated C. nutans cisplatin-induced groups. These metabolites were found to be associated with glycerophospholipid, purine, and amino acid metabolism, as well as the glycolysis pathway. Pre-treatment with C. nutans aqueous extract (125 μg/mL) for 24 h, followed by 48 h of cisplatin induction in PCS-400-010 cells, demonstrated a nephroprotective effect, particularly involving the regulation of amino acid metabolism.PMID:37778127 | DOI:10.1002/bmc.5750

Chin Med. 2023 Oct 1;18(1):127. doi: 10.1186/s13020-023-00835-4.ABSTRACTPolyphenols are the main component of Phyllanthus emblica (PE). However, polyphenols are so easy to transform that it is unknown that how drying methods driven by heating affect the anti-fatigue effect of PE. This manuscript investigated the effects of five drying methods on the chemical composition transformation and anti-fatigue of PE, and discussed the action mechanism. The results suggested that the anti-fatigue effect of PE with hot-air-dried at 100 °C was the best, which was as 1.63 times as that with freeze-drying. Ellagic acid (EA) may be a key component of PE in anti-fatigue, and its mechanism of action may be related to regulating intestinal microbiota, protecting mitochondria, and regulating energy metabolism. This study first revealed the thermal transformation of polyphenols in PE, found the most effective strategy for enhancing the anti-fatigue function, and explores its action mechanism.PMID:37779204 | DOI:10.1186/s13020-023-00835-4

Exp Mol Med. 2023 Oct 2. doi: 10.1038/s12276-023-01099-6. Online ahead of print.ABSTRACTThe interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.PMID:37779147 | DOI:10.1038/s12276-023-01099-6

Planta. 2023 Sep 30;258(5):91. doi: 10.1007/s00425-023-04242-9.ABSTRACTDue to harsh lifestyle changes, in the present era, nutritional security is needed along with food security so it is necessary to include underutilized cereal crops (UCCs) in our daily diet to counteract the rising danger of human metabolic illness. We can attain both the goal of zero hunger and nutritional security by developing improved UCCs using advanced pan-omics (genomics, transcriptomics, proteomics, metabolomics, nutrigenomics, phenomics and ionomics) practices. Plant sciences research progressed profoundly since the last few decades with the introduction of advanced technologies and approaches, addressing issues of food demand of the growing population, nutritional security challenges and climate change. However, throughout the expansion and popularization of commonly consumed major cereal crops such as wheat and rice, other cereal crops such as millet, rye, sorghum, and others were impeded, despite their potential medicinal and nutraceutical qualities. Undoubtedly neglected underutilized cereal crops (UCCs) also have the capability to withstand diverse climate change. To relieve the burden of major crops, it is necessary to introduce the new crops in our diet in the way of UCCs. Introgression of agronomically and nutritionally important traits by pan-omics approaches in UCCs could be a defining moment for the population's well-being on the globe. This review discusses the importance of underutilized cereal crops, as well as the application of contemporary omics techniques and advanced bioinformatics tools that could open up new avenues for future study and be valuable assets in the development and usage of UCCs in the perspective of green system biology. The increased and improved use of UCCs is dependent on number of factors that necessitate a concerted research effort in agricultural sciences. The emergence of functional genomics with molecular genetics might gear toward the reawakening of interest in underutilized cereals crops. The need of this era is to focus on potential UCCs in advanced agriculture and breeding programmes. Hence, targeting the UCCs, might provide a bright future for better health and scientific rationale for its use.PMID:37777666 | DOI:10.1007/s00425-023-04242-9

J Neurochem. 2023 Sep 30. doi: 10.1111/jnc.15960. Online ahead of print.ABSTRACTRett syndrome is an X-linked neurodevelopmental disorder caused by mutation of Mecp2 gene and primarily affects females. Glial cell dysfunction has been implicated in in Rett syndrome (RTT) both in patients and in mouse models of this disorder and can affect synaptogenesis, glial metabolism and inflammation. Here we assessed whether treatment of adult (5-6 months old) symptomatic Mecp2-heterozygous female mice with N-acetyl cysteine conjugated to dendrimer (D-NAC), which is known to target glia and modulate inflammation and oxidative injury, results in improved behavioral phenotype, sleep and glial inflammatory profile. We show that unbiased global metabolomic analysis of the hippocampus and striatum in adult Mecp2-heterozygous mice demonstrates significant differences in lipid metabolism associated with neuroinflammation, providing the rationale for targeting glial inflammation in this model. Our results demonstrate that treatment with D-NAC (10 mg/kg NAC) once weekly is more efficacious than equivalently dosed free NAC in improving the gross neurobehavioral phenotype in symptomatic Mecp2-heterozygous female mice. We also show that D-NAC therapy is significantly better than saline in ameliorating several aspects of the abnormal phenotype including paw clench, mobility, fear memory, REM sleep and epileptiform activity burden. Systemic D-NAC significantly improves microglial proinflammatory cytokine production and is associated with improvements in several aspects of the phenotype including paw clench, mobility, fear memory, and REM sleep, and epileptiform activity burden in comparison to saline-treated Mecp2-hetereozygous mice. Systemic glial-targeted delivery of D-NAC after symptom onset in an older clinically relevant Rett syndrome model shows promise in improving neurobehavioral impairments along with sleep pattern and epileptiform activity burden. These findings argue for the translational value of this approach for treatment of patients with Rett Syndrome.PMID:37777475 | DOI:10.1111/jnc.15960

Asian J Surg. 2023 Sep 28:S1015-9584(23)01455-0. doi: 10.1016/j.asjsur.2023.09.027. Online ahead of print.NO ABSTRACTPMID:37777406 | DOI:10.1016/j.asjsur.2023.09.027

Pharmacol Res. 2023 Sep 28:106943. doi: 10.1016/j.phrs.2023.106943. Online ahead of print.ABSTRACTBile acids (BAs), synthesized in the liver and modified by the gut microbiota, have been widely appreciated not only as simple lipid emulsifiers, but also as complex metabolic regulators and momentous signaling molecules, which play prominent roles in the complex interaction among several metabolic systems. Recent studies have drawn us eyes on the diverse physiological functions of BAs, to enlarge the knowledge about the "gut-bone" axis due to the participation about the gut microbiota-derived BAs to modulate bone homeostasis at physiological and pathological stations. In this review, we have summarized the metabolic processes of BAs and highlighted the crucial roles of BAs targeting bile acid-activated receptors (BARs), promoting the proliferation and differentiation of osteoblasts (OBs), inhibiting the activity of osteoclasts (OCs), as well as reducing articular cartilage degradation, thus facilitating bone repair. In addition, we have also focused on the bidirectional effects of BA signaling networks in coordinating the dynamic balance of bone matrix and demonstrated the promising effects of BAs on the development or treatment for pathological bone diseases. In a word, further clinical applications targeting BA metabolism or modulating gut metabolome and related derivatives may be developed as effective therapeutic strategies for bone destruction diseases.PMID:37777075 | DOI:10.1016/j.phrs.2023.106943

J Dairy Sci. 2023 Sep 28:S0022-0302(23)00707-5. doi: 10.3168/jds.2023-23841. Online ahead of print.ABSTRACTThe objective of this study was to characterize changes in the serum metabolome and various indicators of oxidative balance in dairy cows starting 2 wk before dry-off and continuing until wk 16 of lactation. Twelve Holstein dairy cows [body weight (BW) 745 ± 71 kg, body condition score 3.43 ± 0.66; mean ± SD] were housed in a tie-stall barn from 10 wk before to 16 wk after parturition. Cows were dried off 6 wk before the expected calving date (mean dry period length = 42 d). From 8 wk before calving to 16 wk after calving, blood samples were taken weekly to study redox metabolism by determining antioxidant capacity, measured as the ferric-reducing ability of plasma, reactive oxidative metabolites, oxidative stress index, oxidative damage of lipids, measured as thiobarbituric acid reactive substances, and glutathione peroxidase activity. According to these results, dairy cows had the lowest serum antioxidant capacity and greater levels of oxidative stress during the dry-off period and the early postpartum period. For metabolomics, a subset of serum samples including wk -7 (before dry-off), -5 (after dry-off), -1, 1, 5, 10, and 15 relative to calving were used. A targeted metabolomics approach was performed by liquid chromatography and flow injection with electrospray ionization triple quadrupole mass spectrometry using the MxP® Quant 500 kit. A total of 240 metabolites in serum were used in the final data analysis. Principal component analysis revealed a clear separation by days of sampling, indicating a remarkable shift in metabolic phenotype between the dry period and late and early lactation. Changes in many non-lipid metabolites associated with one-carbon metabolism, the tricarboxylic acid cycle, the urea cycle, and AA catabolism were observed in the study, with changes in AA serum concentrations likely related to factors such as energy and nitrogen balance, digestive efficiency, and changing diets. The study confirmed an extensive remodeling of the serum lipidome in peripartum dairy cows, highlighting the importance of changes in acylcarnitine (AcylCN), phosphatidylcholines (PC), and triacylglycerols (TG), as they play a crucial role in lipid metabolism. Results showed that short-chain AcylCN increased after dry-off and decreased thereafter, whereas lipid-derived AcylCN increased around parturition, suggesting that more fatty acids could enter mitochondria. Phospholipids and sphingolipids in serum showed changes during lactation. In particular, concentrations of sphingomyelins (SM), PC, and LysoPC decreased around calving but increased in mid- and late lactation. In contrast, concentrations of TG remained consistently low after parturition. The serum concentrations of bile acids fluctuated during the dry period and lactation, with glycocholic acid, cholic acid, glycodeoxycholic acid, and taurocholic acid showing the greatest concentrations. These changes are likely due to the interplay of diet, liver function, and the ability of the gut microbiota to convert primary to secondary bile acids. Overall, these descriptive results may aid in hypothesis generation, and the design and interpretation of future metabolite-based studies in dairy cows. Furthermore, they contribute to our understanding of the physiological ranges in serum metabolites relative to the lactation cycle of the dairy cow.PMID:37777004 | DOI:10.3168/jds.2023-23841

J Proteomics. 2023 Sep 28:105011. doi: 10.1016/j.jprot.2023.105011. Online ahead of print.ABSTRACTGallium has a long history as a chemotherapeutic agent. The mechanisms of action of Ga(III)-based anti-infectives are different from conventional antibiotics, which primarily result from the chemical similarities of Ga(III) with Fe(III) and substitution of gallium into iron-dependent biological pathways. However, more aspects of the molecular mechanisms of Ga(III) against human pathogens, especially its regulations on bacterial metabolic processes, remain to be understood. Herein, by using conventional quantitative proteomics approaches, we identified the protein changes of Pseudomonas aeruginosa (P. aeruginosa) in response to Ga(NO3)3 treatment. We show that Ga(III) exhibits bacteriostatic mode of action against P. aeruginosa through affecting the expressions of a number of key enzymes in the main metabolic pathways, including glycolysis, TCA cycle, amino acid metabolism, and protein and nucleic acid biosynthesis. In addition, decreased abundances of proteins associated with pathogenesis and virulence of P. aeruginosa were also identified. Moreover, the correlations between protein expressions and metabolome changes in P. aeruginosa upon Ga(III) treatment were identified and discussed. Our findings thus expand the understanding on the antimicrobial mechanisms of gallium that shed light on enhanced therapeutic strategies. BIOLOGICAL SIGNIFICANCE: Mounting evidence suggest that the efficacy and resistance of clinical antibiotics are closely related to the metabolic homeostasis in bacterial pathogens. Ga(III)-based compounds have been repurposed as antibacterial therapeutic candidates against antibiotics resistant pathogens, and represent a safe and promising treatment for clinical human infections, while more thorough understandings of how bacteria respond to Ga(III) treatment are needed. In the present study, we provide evidences at the proteome level to indicate Ga(III)-induced metabolic perturbations in P. aeruginosa. We identified and discussed the interference of Ga(III) on the expressions and activities of enzymes in the main metabolic pathways in P. aeruginosa. In view of our previous report that the antimicrobial efficacy of Ga(III) could be modulated according to Ga(III)-induced metabolome changes in P. aeruginosa, our current analyses may serve as theoretical basis for the development of efficient gallium-based therapies by exploiting bacterial metabolic mechanisms.PMID:37776994 | DOI:10.1016/j.jprot.2023.105011

Bioresour Technol. 2023 Sep 28:129812. doi: 10.1016/j.biortech.2023.129812. Online ahead of print.ABSTRACTIn practical engineering, nitrogen removal at low temperatures or low C/N ratios is difficult. Although strains can remove nitrogen well at low temperatures, there is no research on the performance and deep mechanism of strains under low C/N ratio stress. In this study, Pseudomonas sp. LW60 with superior nitrogen removal efficiency under low C/N ratio stress was isolated at 4 °C. With a C/N ratio of 2-10, the NH4+-N removal efficiency was 40.02 %-100 % at 4 °C. Furthermore, the resistance mechanism of Pseudomonas sp. LW60 to low C/N ratio stress was deeply investigated by multi-omics. The results of transcriptome, proteome, and metabolome revealed that the resistance of strain LW60 to low C/N ratio stress was attributed to enhanced central carbon metabolism, amino acid metabolism, and ABC transporters, rather than nitrogen removal pathways. This study isolated a strain with low C/N ratio tolerance and deeply explored its tolerance mechanism by multi-omics.PMID:37776911 | DOI:10.1016/j.biortech.2023.129812

Psychoneuroendocrinology. 2023 Sep 21;158:106395. doi: 10.1016/j.psyneuen.2023.106395. Online ahead of print.ABSTRACTBACKGROUND: During pregnancy, steroids enable physiological adaptations in response to many factors, including maternal stress or psychological functioning. While stress and psychological dysfunction can have endocrine-disrupting effects beyond cortisol disruption, associations between prenatal maternal stress or related psychological dysfunction and the broader steroid milieu remain understudied.AIM: To assess associations between independent and joint maternal stress and psychological functioning measures and steroid profiles in pregnancy (22-40 gestational weeks) in the Programming of Intergenerational Stress Mechanisms (PRISM) birth cohort (n = 334).METHODS: Serum metabolomics detected 42 steroids and their metabolites, which were grouped into five classes (pregnenolone, androgens, estrogens, progestin, and corticosteroids). The Perceived Stress Scale, Life Stressor Checklist-Revised, and Edinburgh Postnatal Depression Scale indexed lifetime traumatic/non-traumatic stressors, global prenatal stress appraisal, and depressive symptoms during pregnancy, respectively. Exposures were categorized as high-low using the corresponding 3rd quartiles. We assessed associations between both individual and joint stress exposures with steroid classes using linear mixed effect models and with individual steroids using linear regressions. We also examined fetal sex-specific effects.RESULTS: High prenatal perceived stress was independently associated with lower levels of androgens and estrogens in the overall sample [β (95%CI): androgens: -0.13 (-0.25;-0.01); estrogens: -0.16 (-0.31;-0.01)], particularly among women carrying males [androgens: -0.22 (-0.39;-0.05); estrogens: -0.28 (-0.50;-0.07)]. Results on estrogens were consistent when considering joint exposure to both greater lifetime stressors and higher prenatal perceived stress. We also found a single testosterone metabolite-5alpha-androstan-3alpha,17alpha-diol disulfate-negatively associated with both individual high perceived stress and joint exposure to high lifetime stressors and high perceived stress among women carrying males.CONCLUSIONS: Increased maternal perceived stress experienced in pregnancy was independently associated with lower maternal androgen and estrogen levels during pregnancy in the overall sample, particularly among women carrying males. Results on estrogens were consistent when we considered the joint exposure of increased lifetime stressors and higher prenatal perceived stress.PMID:37776732 | DOI:10.1016/j.psyneuen.2023.106395