PubMed

Front Genet. 2023 Sep 15;14:1184661. doi: 10.3389/fgene.2023.1184661. eCollection 2023.ABSTRACTIntroduction: Metabolic syndrome (MetS) increases the risk of cardiovascular disease and death. Previous '-omics' studies have identified dysregulated serum metabolites and aberrant DNA methylation in the setting of MetS. However, the relationship between the metabolome and epigenome have not been elucidated. In this study, we identified serum metabolites associated with MetS and DNA methylation, and we conducted bidirectional Mendelian randomization (MR) to assess causal relationships between metabolites and methylation. Methods: We leveraged metabolomic and genomic data from a national United States cohort of older adults (REGARDS), as well as metabolomic, epigenomic, and genomic data from a family-based study of hypertension (HyperGEN). We conducted metabolite profiling for MetS in REGARDS using weighted logistic regression models and validated them in HyperGEN. Validated metabolites were selected for methylation studies which fit linear mixed models between metabolites and six CpG sites previously linked to MetS. Statistically significant metabolite-CpG pairs were selected for two-sample, bidirectional MR. Results: Forward MR indicated that glucose and serine metabolites were causal on CpG methylation near CPT1A [B(SE): -0.003 (0.002), p = 0.028 and B(SE): 0.029 (0.011), p = 0.030, respectively] and that serine metabolites were causal on ABCG1 [B(SE): -0.008(0.003), p = 0.006] and SREBF1 [B(SE): -0.009(0.004), p = 0.018] methylation, which suggested a protective effect of serine. Reverse MR showed a bidirectional relationship between cg06500161 (ABCG1) and serine [B(SE): -1.534 (0.668), p = 0.023]. Discussion: The metabolome may contribute to the relationship between MetS and epigenetic modifications.PMID:37779905 | PMC:PMC10540781 | DOI:10.3389/fgene.2023.1184661

Cureus. 2023 Aug 30;15(8):e44359. doi: 10.7759/cureus.44359. eCollection 2023 Aug.ABSTRACTArtificial intelligence (AI) has transformed pharmacological research through machine learning, deep learning, and natural language processing. These advancements have greatly influenced drug discovery, development, and precision medicine. AI algorithms analyze vast biomedical data identifying potential drug targets, predicting efficacy, and optimizing lead compounds. AI has diverse applications in pharmacological research, including target identification, drug repurposing, virtual screening, de novo drug design, toxicity prediction, and personalized medicine. AI improves patient selection, trial design, and real-time data analysis in clinical trials, leading to enhanced safety and efficacy outcomes. Post-marketing surveillance utilizes AI-based systems to monitor adverse events, detect drug interactions, and support pharmacovigilance efforts. Machine learning models extract patterns from complex datasets, enabling accurate predictions and informed decision-making, thus accelerating drug discovery. Deep learning, specifically convolutional neural networks (CNN), excels in image analysis, aiding biomarker identification and optimizing drug formulation. Natural language processing facilitates the mining and analysis of scientific literature, unlocking valuable insights and information. However, the adoption of AI in pharmacological research raises ethical considerations. Ensuring data privacy and security, addressing algorithm bias and transparency, obtaining informed consent, and maintaining human oversight in decision-making are crucial ethical concerns. The responsible deployment of AI necessitates robust frameworks and regulations. The future of AI in pharmacological research is promising, with integration with emerging technologies like genomics, proteomics, and metabolomics offering the potential for personalized medicine and targeted therapies. Collaboration among academia, industry, and regulatory bodies is essential for the ethical implementation of AI in drug discovery and development. Continuous research and development in AI techniques and comprehensive training programs will empower scientists and healthcare professionals to fully exploit AI's potential, leading to improved patient outcomes and innovative pharmacological interventions.PMID:37779744 | PMC:PMC10539991 | DOI:10.7759/cureus.44359

Front Microbiol. 2023 Sep 13;14:1264602. doi: 10.3389/fmicb.2023.1264602. eCollection 2023.ABSTRACTAlthough cellular metabolic states have been shown to modulate bacterial susceptibility to antibiotics, the interaction between glutamate (Glu) and chloramphenicol (CAP) resistance remains unclear because of the specificity of antibiotics and bacteria. We found that the level of Glu was upregulated in the CAP-resistant strain of Edwardsiella tarda according to a comparative metabolomics approach based on LC-MS/MS. Furthermore, we verified that exogenous metabolites related to Glu, the tricarboxylic acid (TCA) cycle, and glutathione (GSH) metabolism could promote CAP resistance in survival assays. If GSH metabolism or the TCA cycle is inhibited by L-buthionine sulfoximine or propanedioic acid, the promotion of CAP resistance by Glu in the corresponding pathway disappears. According to metabolomic analysis, exogenous Glu could change pantothenate metabolism, affecting GSH biosynthesis and the TCA cycle. These results showed that the glutamate-pantothenate pathway could promote CAP resistance by being involved in the synthesis of GSH, entering the TCA cycle by direct deamination, or indirectly affecting the metabolism of the two pathways by pantothenate. These results extend our knowledge of the effect of Glu on antibiotic resistance and suggest that the potential effect, which may aggravate antibiotic resistance, should be considered before Glu and GSH administration in the clinic.PMID:37779691 | PMC:PMC10533917 | DOI:10.3389/fmicb.2023.1264602

Food Funct. 2023 Oct 2. doi: 10.1039/d3fo02653a. Online ahead of print.ABSTRACTNonalcoholic fatty liver disease (NAFLD), as the commonest chronic liver disease, is accompanied by liver oxidative stress and inflammatory responses. Herein, the extract obtained from Rubus corchorifolius fruits was purified and characterized for its polyphenol composition. The liver protective effect of the purified R. corchorifolius fruit extract (RCE) on mice with high-fat-diet (HFD)-induced NAFLD were investigated, and the potential mechanisms were explored through the integration of transcriptomics and metabolomics. Results showed that the polyphenolic compounds in RCE mainly included (-)-epigallocatechin, procyanidin B2, keracyanin, vanillin, dihydromyricetin, and ellagic acid. In addition, RCE intervention ameliorated liver and mitochondrial damage, which was evidenced by decreased indices of oxidative stress, liver function markers, and lipid profile levels. The liver metabonomics research revealed that RCE intervention affected the metabolic pathways of metabolites, including linoleic acid metabolism, galactose metabolism, alanine, aspartate and glutamate metabolism, retinol metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, aminoacyl-tRNA biosynthesis, riboflavin metabolism, starch and sucrose metabolism, and arachidonic acid metabolism. Additionally, liver transcriptomics research indicated that pathways like fatty acid degradation, circadian rhythm, valine, leucine and isoleucine degradation, primary bile acid biosynthesis, cytokine-cytokine receptor interaction, adipocytokine signaling pathway, glutathione metabolism, lipid and atherosclerosis were significantly enriched. The transcriptomics and metabolomics analysis demonstrated that RCE intervention had significant modulatory effects on the metabolic pathways associated with glycolipid metabolism. Moreover, RT-PCR results verified that RCE intervention regulated liver mRNA levels associated with the inflammatory response. Therefore, our findings suggest that the intake of RCE might be an effective strategy to alleviate liver damage.PMID:37779461 | DOI:10.1039/d3fo02653a

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