PubMed

Plant Physiol Biochem. 2024 Jun 5;213:108798. doi: 10.1016/j.plaphy.2024.108798. Online ahead of print.ABSTRACTTerpene synthases (TPSs) are enzymes responsible for catalyzing the production of diverse terpenes, the largest class of secondary metabolites in plants. Here, we identified 107 TPS gene loci encompassing 92 full-length TPS genes in upland cotton (Gossypium hirsutum L.). Phylogenetic analysis showed they were divided into six subfamilies. Segmental duplication and tandem duplication events contributed greatly to the expansion of TPS gene family, particularly the TPS-a and TPS-b subfamilies. Expression profile analysis screened out that GhTPSs may mediate the interaction between cotton and Verticillium dahliae. Three-dimensional structures and subcellular localizations of the two selected GhTPSs, GhTPS6 and GhTPS47, which belong to the TPS-a subfamily, demonstrated similarity in protein structures and nucleus and cytoplasm localization. Virus-induced gene silencing (VIGS) of the two GhTPSs yielded plants characterized by increased wilting and chlorosis, more severe vascular browning, and higher disease index than control plants. Additionally, knockdown of GhTPS6 and GhTPS47 led to the down-regulation of cotton terpene synthesis following V. dahliae infection, indicating that these two genes may positively regulate resistance to V. dahliae through the modulation of disease-resistant terpene biosynthesis. Overall, our study represents a comprehensive analysis of the G. hirsutum TPS gene family, revealing their potential roles in defense responses against Verticillium wilt.PMID:38852238 | DOI:10.1016/j.plaphy.2024.108798

Oral Dis. 2024 Jun 9. doi: 10.1111/odi.15034. Online ahead of print.ABSTRACTOBJECTIVE: This study focused on the metabolic characteristics of tongue coating in patients with intra-oral halitosis (IOH) to investigate potential diagnostic biomarkers for IOH.METHODS: Oral healthy participants were enrolled in this study. Halitosis was evaluated with an organoleptic assessment, a Halimeter®, and an OralChroma™. Tongue coating samples were collected from 18 halitosis patients and 18 healthy controls. Liquid chromatography-mass spectrometry was conducted to reveal the IOH-related metabolic variations in tongue coating.RESULTS: A total of 2214 metabolites were obtained. Most metabolites were shared between the two groups. A total of 274 upregulated metabolites, such as paramethasone acetate and indole-3-acetic acid, and 43 downregulated metabolites, including deoxyadenosine and valyl-arginine, were detected in the halitosis group. Functional analysis indicated that several metabolic pathways, including arginine biosynthesis, arginine and proline metabolism, histidine metabolism, and lysine degradation were significantly enriched in the IOH group. The least absolute shrinkage and selection operator logistic regression analysis revealed that paramethasone acetate, {1-[2-(4-carbamimidoyl-benzoylamino)-propionyl]-piperidin-4-yloxy}-acetic acid, indole-3-acetic acid, and valyl-arginine were remarkably associated with IOH.CONCLUSIONS: This study revealed the metabolites present in tongue coating and identified effective biomarkers, providing essential insights into the prediction, pathogenesis, and diagnosis of IOH.PMID:38852162 | DOI:10.1111/odi.15034

Best Pract Res Clin Rheumatol. 2024 Jun 7:101961. doi: 10.1016/j.berh.2024.101961. Online ahead of print.ABSTRACTThe gut microbiota plays a pivotal role in regulating host immunity, and dysregulation of this interaction is implicated in autoimmune and inflammatory diseases, including spondyloarthritis (SpA). This review explores microbial dysbiosis and altered metabolic function observed in various forms of SpA, such as ankylosing spondylitis (AS), psoriatic arthritis (PsA), acute anterior uveitis (AAU), and SpA-associated gut inflammation. Studies on animal models and clinical samples highlight the association between gut microbial dysbiosis, metabolic perturbations and immune dysregulation in SpA pathogenesis. These studies have received impetus through next-generation sequencing methods, which have enabled the characterization of gut microbial composition and function, and host gene expression. Microbial/metabolomic studies have revealed potential biomarkers and therapeutic targets, such as short-chain fatty acids, and tryptophan metabolites, offering insights into disease mechanisms and treatment approaches. Further studies on microbial function and its modulation of the immune response have uncovered molecular mechanisms underlying various SpA. Understanding the complex interplay between microbial community structure and function holds promise for improved diagnosis and management of SpA and other autoimmune disorders.PMID:38851970 | DOI:10.1016/j.berh.2024.101961

Sci Rep. 2024 Jun 8;14(1):13207. doi: 10.1038/s41598-024-63837-8.ABSTRACTFemoral head necrosis (FHN) is a serious complication after femoral neck fractures (FNF), often linked to sclerosis around screw paths. Our study aimed to uncover the proteomic and metabolomic underpinnings of FHN and sclerosis using integrated proteomics and metabolomics analyses. We identified differentially expressed proteins (DEPs) and metabolites (DEMs) among three groups: patients with FNF (Group A), sclerosis (Group B), and FHN (Group C). Using the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analyses, we examined the roles of these proteins and metabolites. Our findings highlight the significant differences across the groups, with 218 DEPs and 44 DEMs identified between the sclerosis and FNF groups, 247 DEPs and 31 DEMs between the FHN and sclerosis groups, and a stark 682 DEPs and 94 DEMs between the FHN and FNF groups. Activities related to carbonate dehydratase and hydrolase were similar in the FHN and sclerosis groups, whereas extracellular region and lysosome were prevalent in the FHN and FNF groups. Our study also emphasized the involvement of the PI3K-Akt pathway in sclerosis and FHN. Moreover, the key metabolic pathways were implicated in glycerophospholipid metabolism and retrograde endocannabinoid signaling. Using western blotting, we confirmed the pivotal role of specific genes/proteins such as ITGB5, TNXB, CA II, and CA III in sclerosis and acid phosphatase 5 and cathepsin K in FHN. This comprehensive analyses elucidates the molecular mechanisms behind sclerosis and FHN and suggests potential biomarkers and therapeutic targets, paving the way for improved treatment strategies. Further validation of the findings is necessary to strengthen the robustness and reliability of the results.PMID:38851808 | DOI:10.1038/s41598-024-63837-8

Orphanet J Rare Dis. 2024 Jun 8;19(1):228. doi: 10.1186/s13023-024-03230-w.ABSTRACTBACKGROUND: Developmental dysplasia of the hip (DDH) is a common childhood health complaint, whose etiology is multifactorial. The incidence of DDH is variable and higher in Tibet plateau. Here, we collected plasma samples and studied the metabolomics signatures of DDH.METHODS: Fifty babies were enrolled: 25 with DDH and 25 age-matched non-DDH healthy controls (HC group). We collected plasma samples, laboratory parameters and conducted untargeted metabolomics profiling.RESULTS: There are many differential metabolites among patients with DDH, including 4-β-hydroxymethyl-4-α-methyl-5-α-cholest-7-en-3-beta-ol, β-cryptoxanthin, α-tocopherol, taurocholic acid, glycocholic acid, 2-(3,4-dihydroxybenzoyloxy)-4,6-dihydroxybenzoate, arabinosylhypoxanthine, leucyl-hydroxyproline, hypoxanthine. The main differential metabolic pathways focused on primary bile acid biosynthesis, arginine and proline metabolism, phenylalanine metabolism, histidine metabolism, purine metabolism.CONCLUSIONS: To our knowledge, this is the first report of metabolomics profile in babies with DHH. By combining the α-tocopherol and taurocholic acid, we could achieve the differential diagnosis of DDH.PMID:38851765 | DOI:10.1186/s13023-024-03230-w

BMC Plant Biol. 2024 Jun 8;24(1):519. doi: 10.1186/s12870-024-05255-6.ABSTRACTRice seeds of different varieties exhibited distinct metabolic profiles in our study. We analyzed the metabolites in seeds of six rice varieties (CH, HM, NX, YX, HY, and MX) using non-targeted GC-MS. Our findings revealed that amino acids, sugars, and organic acids were predominant in all varieties, with significant differences observed in CH compared to the others. Specifically phenylalanine and glycine content differed notably in NX and YX, respectively. Additionally, 1,5-anhydroglucitol content in NX, and glutamate, aspartate, and lactulose in NX, YX, HM, HY, and MX were up-regulated. Due to the biological functions of these amino acids and sugars, these indicated that compared to CH, rice of NX were more conducive to metabolism of carbohydrate and fat, and healthy growth maintenance in the human body, but mightThese variations suggest that NX rice may be more beneficial for carbohydrate and fat metabolism and overall health maintenance compared to CH. However, it may not be suitable for diabetic patients. YX rice may not be an ideal glycine supplement, rice ofwhile HM, HY, and MX rice could serve as potential lactulose sources. Furthermore, NX and YX rice exhibited higher levels of main storage proteins compared to CH. This study offers valuable insights into the metabolic differences among various rice varieties.PMID:38851682 | DOI:10.1186/s12870-024-05255-6

Am J Clin Nutr. 2024 Jun 6:S0002-9165(24)00521-5. doi: 10.1016/j.ajcnut.2024.05.027. Online ahead of print.ABSTRACTBACKGROUND: We previously showed that dietary intervention effects on cardiometabolic health were driven by tissue-specific insulin resistance (IR) phenotype: individuals with predominant muscle IR (MIR) benefitted more from a low-fat, high-protein, high-fiber diet (LFHP), while individuals with predominant liver IR (LIR) benefitted more from a diet rich in mono-unsaturated fat (HMUFA).OBJECTIVE: To further characterize the effects of LFHP and HMUFA diets and their interaction with tissue-specific IR, we investigated dietary intervention effects on fasting and postprandial plasma metabolite profile.METHODS: Adults with MIR or LIR (40-75 years, BMI 25-40 kg/m2) were randomized to a 12-week HMUFA or LFHP diet (n=242). After exclusion of statin use, 214 participants were included in this pre-specified secondary analysis. Plasma samples were collected before (T=0) and after (T=30, 60, 120, 240 min) a high-fat mixed meal for quantification of 247 metabolite measures using nuclear magnetic resonance spectroscopy.RESULTS: A larger reduction in fasting VLDL-TAG and VLDL particle size was observed in individuals with MIR following the LFHP diet and those with LIR following the HMUFA diet, although no longer statistically significant after false discovery rate (FDR) adjustment. No IR phenotype-diet interactions were found for postprandial plasma metabolites assessed as total area under the curve (tAUC). Irrespective of IR phenotype, the LFHP diet induced greater reductions in postprandial plasma tAUC of the larger VLDL particles and small HDL particles, and TAG content in most VLDL subclasses and the smaller LDL and HDL subclasses (e.g. VLDL-TAG tAUC standardized mean change [95% CI] LFHP = -0.29 [-0.43, -0.16] compared to HMUFA = -0.04 [-0.16, 0.09]; FDR-adjusted P for Diet x Time = 0.041).CONCLUSIONS: Diet effects on plasma metabolite profiles were more pronounced than phenotype-diet interactions. A LFHP diet may be more effective than a HMUFA diet for reducing cardiometabolic risk in individuals with tissue-specific IR, irrespective of IR phenotype.GOV REGISTRATION: NCT03708419, https://clinicaltrials.gov/study/NCT03708419?term=NCT03708419&rank=1 CCMO REGISTRATION: NL63768.068.17, https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=3969AABCD9BA27FEC12587F1001BCC65.PMID:38851634 | DOI:10.1016/j.ajcnut.2024.05.027

Eur J Pharmacol. 2024 Jun 6:176724. doi: 10.1016/j.ejphar.2024.176724. Online ahead of print.ABSTRACTINTRODUCTION: Mangiferin is a Chinese herbal extract with multiple biological activities. Mangiferin can penetrate the blood‒brain barrier and has potential in the treatment of nervous system diseases. These findings suggest that mangiferin protects the neurological function in ischemic stroke rats by targeting multiple signaling pathways. However, little is known about the effect and mechanism of mangiferin in alleviating poststroke cognitive impairment.METHODS: Cerebral ischemia/reperfusion (I/R) rats were generated via middle cerebral artery occlusion. Laser speckle imaging was used to monitor the cerebral blood flow. The I/R rats were intraperitoneally (i.p.) injected with 40 mg/kg mangiferin for 7 consecutive days. Neurological scoring, and TTC staining were performed to evaluate neurological function. Behavioral experiments, including the open field test, elevated plus maze, sucrose preference test, and novel object recognition test, were performed to evaluate cognitive function. Metabolomic data from brain tissue with multivariate statistics were analyzed by gas chromatography‒mass spectrometry and liquid chromatography‒mass spectrometry.RESULTS: Mangiferin markedly decreased neurological scores, and reduced infarct areas. Mangiferin significantly attenuated anxiety-like and depression-like behaviors and enhanced learning and memory in I/R rats. According to the metabolomics results, 13 metabolites were identified to be potentially regulated by mangiferin, and the differentially abundant metabolites were mainly involved in lipid metabolism.CONCLUSIONS: Mangiferin protected neurological function and relieved poststroke cognitive impairment by improving lipid metabolism abnormalities in I/R rats.PMID:38851559 | DOI:10.1016/j.ejphar.2024.176724

Biochim Biophys Acta Gene Regul Mech. 2024 Jun 6:195045. doi: 10.1016/j.bbagrm.2024.195045. Online ahead of print.ABSTRACTThe histone acetyltransferase HBO1, also known as KAT7, is a major chromatin modifying enzyme responsible for H3 and H4 acetylation. It is found within two distinct tetrameric complexes, the JADE subunit-containing complex and BRPF subunit-containing complex. The HBO1-JADE complex acetylates lysine 5, 8 and 12 of histone H4, and the HBO1-BRPF complex acetylates lysine 14 of histone H3. HBO1 regulates gene transcription, DNA replication, DNA damage repair, and centromere function. It is involved in diverse signaling pathways and plays crucial roles in development and stem cell biology. Recent work has established a strong relationship of HBO1 with the histone methyltransferase MLL/KMT2A in acute myeloid leukemia. Here, we discuss functional and pathological links of HBO1 to cancer, highlighting the underlying mechanisms that may pave the way to the development of novel anti-cancer therapies.PMID:38851533 | DOI:10.1016/j.bbagrm.2024.195045

Gene. 2024 Jun 6:148650. doi: 10.1016/j.gene.2024.148650. Online ahead of print.ABSTRACTBACKGROUND: Acute kidney injury (AKI) is frequently caused by renal ischemia-reperfusion injury (IRI). Identifying potential renal IRI disease biomarkers would be useful for evaluating AKI severity.OBJECTIVE: We used proteomics and metabolomics to investigate the differences in renal venous blood between ischemic and healthy kidneys in an animal model by identifying differentially expressed proteins (DEPs) and differentially expressed protein metabolites (DEMs).METHODS: Nine pairs of renal venous blood samples were collected before and at 20, 40, and 60 min post ischemia. The ischemia time of Group A, B and C was 20,40 and 60 min. The proteome and metabolome of renal venous blood were evaluated to establish the differences between renal venous blood before and after ischemia.RESULTS: We identified 79 common DEPs in all samples of Group A, 80 in Group B, and 131 in Group C. Further common DEPs among all three groups were Tyrosineprotein kinase, GPR15LG, KAZALD1, ADH1B. We also identified 81, 64, and 83 common DEMs in each group respectively, in which 30 DEMs were further common to all groups. Bioinformatic analysis of the DEPs and DEMs was conducted.CONCLUSION: This study demonstrated that different pathological processes occur during short- and long-term renal IRI. Tyrosine protein kinase, GPR15LG, Kazal-type serine peptidase inhibitor domain 1, and all-trans-retinol dehydrogenase are potential biomarkers of renal IRI.PMID:38851364 | DOI:10.1016/j.gene.2024.148650

Sci Total Environ. 2024 Jun 6:173697. doi: 10.1016/j.scitotenv.2024.173697. Online ahead of print.ABSTRACTSurfactants as synergistic agents are necessary to improve the stability and utilization of pesticides, while their use is often accompanied by unexpected release into the environment. However, there are no efficient strategies available for screening low-toxicity surfactants, and traditional toxicity studies rely on extensive experimentation which are not predictive. Herein, a commonly used agricultural adjuvant Triton X (TX) series was selected to study the function of amphipathic structure to their toxicity in zebrafish. Molecular dynamics (MD) simulations, transcriptomics, metabolomics and machine learning (ML) were used to study the toxic effects and predict the toxicity of various TX. The results showed that TX with a relatively short hydrophilic chain was highly toxic to zebrafish with LC50 of 1.526 mg/L. However, TX with a longer hydrophilic chain was more likely to damage the heart, liver and gonads of zebrafish through the arachidonic acid metabolic network, suggesting that the effect of surfactants on membrane permeability is the key to determine toxic results. Moreover, biomarkers were screened through machine learning, and other hydrophilic chain lengths were predicted to affect zebrafish heart health potentially. Our study provides an advanced adjuvants screening method to improve the bioavailability of pesticides while reducing environmental impacts.PMID:38851350 | DOI:10.1016/j.scitotenv.2024.173697

Sci Total Environ. 2024 Jun 6:173733. doi: 10.1016/j.scitotenv.2024.173733. Online ahead of print.ABSTRACTSymbiotic nitrogen fixation can reduce the impact of agriculture on the environment by reducing fertilizer input. The rapid development of nanomaterials in agriculture provides a new prospect for us to improve the biological nitrogen fixation ability of leguminous crops. Molybdenum is an important component of nitrogenase, and the potential application of MoO3NPs in agriculture is largely unexplored. In this study, on the basis of verifying that MoO3NPs can improve the nitrogen fixation ability of soybean, the effects of MoO3NPs on the symbiotic nitrogen fixation process of soybean were investigated by using dynamic transcriptome and targeted metabolome techniques. Here we showed that compared with conventional molybdenum fertilizer, minute concentrations of MoO3NPs (0.01-0.1 mg kg-1) could promote soybean growth and nitrogen fixation efficiency. The nodules number, fresh nodule weight and nitrogenase activity of 0.1 mg kg-1 were increased by 17 %, 14 % and 27 %, and plant nitrogen accumulation increased by 17 %. Compared with conventional molybdenum fertilizer, MoO3NPs had a greater effect on apigenin, kaempferol and other flavonoid, and the expression of nodulation related genes such as ENOD93, F3'H. Based on WGCNA analysis, we identified a core gene GmCHS9 that was positively responsive to molybdenum and was highly expressed during MoO3NPs induced nodulation. MoO3NPs could improve the nitrogen fixation ability of soybean by promoting the secretion of flavonoids and the expression of key genes. This study provided a new perspective for the nano-strengthening strategy of nodules development and flavonoid biosynthesis by molybdenum.PMID:38851347 | DOI:10.1016/j.scitotenv.2024.173733

Sci Total Environ. 2024 Jun 6:173835. doi: 10.1016/j.scitotenv.2024.173835. Online ahead of print.ABSTRACTOBJECTIVE: Chronic exposure to cold temperature is known to elevate blood pressure, leading to a condition known as cold-induced hypertension (CIH). Our previous research suggested correlations between alterations in gut microbiota, decrease in butyrate level, and the onset and progression of CIH. However, the role of butyrate in CIH and the underlying mechanisms need further investigation.METHODS: We exposed Specific Pathogen Free (SPF) rats to continuous cold temperature (4 ± 1 °C) for 6 weeks to establish a CIH rat model. Rats were divided into different groups by dose and duration, and the rats under cold were administered butyrate (0.5 or 1 g/kg/day) daily. We assessed hypertension-associated phenotypes, pathological morphological changes, and endocrine-related phenotypes of brown adipose tissue (BAT). The effects of butyrate on gut microbiota and intestinal content metabolism were evaluated by 16s RNA sequencing and non-targeted metabolomics, respectively.RESULTS: The systolic blood pressure (SBP) of rats exposed to cold after supplemented with butyrate were significantly lower than that of the Cold group. Butyrate may increase the species, abundance, and diversity of gut microbiota in rats. Specifically, butyrate intervention enriched beneficial bacterial genera, such as Lactobacillaceae, and decreased the levels of harmful bacteria genera, such as Actinobacteriota and Erysipeiotrichaceae. Cold exposure significantly increased BAT cells and the number of mitochondria. After butyrate supplementation, the levels of peroxisome proliferator-activated receptor gamma coactivator 1a and fibroblast growth factor 21 in BAT were significantly elevated (P < 0.05), and the volume and number of lipid droplets increased. The levels of ANG II and high-density lipoprotein were elevated in the Cold group but decreased after butyrate supplementation.CONCLUSION: Butyrate may reduce blood pressure in CIH by promoting the growth of beneficial bacteria and the secretion of beneficial derived factors produced by BAT, thus alleviating the elevation of blood pressure induced by cold. This study demonstrates the anti-hypertensive effects of butyrate and its potential therapeutic mechanisms, offering novel insights into the prevention and treatment of CIH in populations living or working in cold environments.PMID:38851345 | DOI:10.1016/j.scitotenv.2024.173835

Sci Total Environ. 2024 Jun 6:173795. doi: 10.1016/j.scitotenv.2024.173795. Online ahead of print.ABSTRACTBile acids (BAs) are amphipathic steroid acids whose production and diversity depend on both host and microbial metabolism. Nitrate (NO3-) is a widespread pollutant in aquatic ecosystems, which can cause rapid changes in microbial community structure and function. However, the effect of gut microbiota reshaped by nitrate‑nitrogen (NO3-N) on BAs profiles remains unclarified. To test this, intestinal targeted BAs metabolomics and fecal metagenomic sequencing were performed on Bufo gargarizans tadpoles treated with different concentrations of NO3-N. NO3-N exposure induced a reduction in the abundance of microbiota with bile acid-inducible enzymes (BAIs) and/or hydroxysteroid dehydrogenases (HSDHs), thus inhibiting the conversion of primary BAs to secondary BAs. Inhibition of BAs biotransformation decreased protective hydrophilic BAs (UDCA) and increased toxic hydrophobic BAs (CA and CDCA), which may contribute to intestinal histopathological damage. Moreover, we found that NO3-N treatment increased microbial virulence factors and decreased Glycoside hydrolases, further highlighting the deleterious risk of NO3-N. Overall, this study shed light on the complex interactions of NO3-N, gut microbiota, and BAs, and emphasized the hazardous effects of NO3-N pollution on the health of amphibians.PMID:38851338 | DOI:10.1016/j.scitotenv.2024.173795

Phytomedicine. 2024 Jun 1;131:155782. doi: 10.1016/j.phymed.2024.155782. Online ahead of print.ABSTRACTBACKGROUND: Asthma is a complex disease with mechanisms involving multiple factors, and there is still a lack of highly effective and low-side-effect drugs. Traditional Chinese medicine Fagopyrum Dibotrys Rhizoma (FDR) has been applied for the treatment of acute and chronic bronchitis as well as bronchial asthma due to its favorable pharmacological activity. However, the exact mechanism of FDR remains unclear.OBJECTIVE: A mouse model of asthma was created using OVA and HDM. To investigate the mechanism of FDR in asthma treatment, a combination of network pharmacology, lipidomics, and molecular biology approaches was employed.METHODS: To evaluate the therapeutic effects of FDR on asthma, we established two distinct models of asthma in C57BL/6 J mice using OVA and HDM, respectively. We then employed LC-MS to analyze the major chemical constituents in FDR. Next, the network pharmacology approach was used to predict the potential targets and mechanisms of FDR in asthma treatment. Additionally, lipidomics analysis of mouse serum was conducted using LC-MS. Finally, the impact of FDR on the ERK -cPLA2 signaling pathway was investigated through Western Blotting assay.RESULTS: FDR treatment has been shown to improve histomorphological changes, lung function and inflammation in models of OVA and HDM-induced asthma. Using UPLC/LTQ-Orbitrap-MS, we were able to identify 12 potential active components. Network pharmacology analysis revealed that FDR shares 75 targets with asthma. Further analysis using GO and KEGG pathways demonstrated the involvement of key pathways such as PI3K-Akt, TNF, and MAPK. Additionally, lipidomics analysis of the serum from OVA and HDM induced asthma mice showed disturbances in lipid metabolism, which were effectively ameliorated by FDR treatment. Mechanistically, FDR inhibits ERK1/2-cPLA2, leading to a reduction in lysophospholipids and restoration of lipid balance, thereby aiding in the treatment of asthma.CONCLUSION: FDR has been shown to improve lipid metabolism disorder in the serum of asthmatic mice, thereby potentially serving as a treatment for asthma. This can be achieved by regulating the activation levels of ERK1/2 and p38MAPK. Consequently, the production of lysophosphatide is reduced, thereby alleviating the disorder of lipid metabolism and achieving the desired therapeutic effect in asthma treatment.PMID:38851102 | DOI:10.1016/j.phymed.2024.155782

Phytomedicine. 2024 May 28;131:155787. doi: 10.1016/j.phymed.2024.155787. Online ahead of print.ABSTRACTBACKGROUND: The gut microbiota is crucial in human health and diseases. Traditional Chinese Medicine Constitution (TCMC) divides people into those with a balanced constitution (Ping-he [PH]) and those with an unbalanced constitution. Dampness-heat constitution (Shi-re [SR]) is a common unbalanced constitution in the Chinese population and is susceptible to diseases. However, unbalanced constitutions can be regulated by Chinese medicine and lifestyle interventions in clinical practice. Ermiao Pill (EMP) is a Chinese medicine known for clearing heat and draining dampness and improving SR. However, the efficacy and mechanism of EMP are unclear.HYPOTHESIS/PURPOSE: To determine alterations in the gut microbiota and metabolome in SR and any changes after EMP treatment combined with lifestyle intervention.STUDY DESIGN: Randomized clinical trial.METHODS: We enrolled 112 healthy SR individuals and evaluated the efficacy of EMP along with lifestyle interventions. We further assessed serum cytokine levels, serum and urinary metabolomes, and the gut microbiota by 16S rRNA gene sequencing analysis before and after the EMP and lifestyle interventions.RESULTS: 107 SR individuals (55 in the intervention group and 52 in the control group) completed the 1-month-intervention and 1-year-follow-up. The intervention group significantly improved their health status within 1 month, with a reduced SR symptom score, and the efficacy lasted to the 1-year follow-up. The control group needed a further 6 months to reduce the SR symptom score. The gut microbiota of PH individuals was more diverse and had significantly higher proportions of many bacterial species than the SR. Microbiota co-occurrence network analysis showed that SR enriches metabolites correlating with microbial community structure, consistent with traits of healthy SR-enriched microbiota.CONCLUSION: EMP combined with lifestyle intervention produced health benefits in SR individuals. Our study indicates a pivotal role of gut microbiota and metabolome alterations in distinguishing between healthy SR and PH. Furthermore, the study reveals structural changes of gut microbiota and metabolites induced by EMP and lifestyle intervention. The treatment enriched the number of beneficial bacteria, such as Akkermansia muciniphila and Lactobacillus in the gut. Our findings provide a strong indication that several metabolite factors are associated with the gut microbiota. Moreover, the gut microbiome and metabolome might be powerful tools for TCMC diagnosis and personalized therapy.PMID:38851100 | DOI:10.1016/j.phymed.2024.155787

Phytomedicine. 2024 Jun 3;131:155800. doi: 10.1016/j.phymed.2024.155800. Online ahead of print.ABSTRACTBACKGROUND: The incidence of gouty arthritis (GA) has gradually increased, and modern drug therapies have obvious side effects. Guizhi Shaoyao Zhimu Decoction (GSZD), a classic prescription in Traditional Chinese Medicine for treating various osteoarthritis, has shown significant advantages in curing GA.PURPOSE: To verify the therapeutic effect of GSZD on GA and investigate its potential pharmacological mechanism via integrated analysis of the gut microbiota and serum metabolites for the first time.METHODS: The chemical composition of GSZD was determined using UPLC-MS. The GA rat model was established by the induction of a high-purine diet combined with local injection. We examined the effects and mechanisms of GSZD after 21 d using enzyme-linked immunosorbent assays, 16S rRNA, and non-targeted metabolomics. Finally, correlation analysis and validation experiment were performed to explore the association among the gut microbiota, serum metabolites, and GA-related clinical indices.RESULTS: In total, 19 compounds were identified as GSZD. High-purine feedstuff with local injection-induced arthroceles were significantly attenuated after GSZD treatment. GSZD improved bone erosion and reduced the serum levels of inflammatory factors (lipopolysaccharide, tumor cell necrosis factor-α, and interleukin) and key indicators of GA (uric acid). 16S rRNA analysis indicated that GSZD-treated GA rats exhibited differences in the composition of the gut microbiota. The abundance of flora involved in uric acid transport, including Lactobacillus, Ruminococcaceae, and Turicibacter, was elevated to various degrees, whereas the abundance of bacteria involved in inflammatory responses, such as Blautia, was markedly reduced after treatment. Moreover, serum metabolite profiles revealed 27 different metabolites associated with the amelioration of GA, which primarily included fatty acids, glycerophospholipids, purine metabolism, amino acids, and bile acids, as well as primary metabolic pathways, such as glycerophospholipid metabolism and alanine. Finally, correlation analysis of the heat maps and validation experiment demonstrated a close relationship among inflammatory cytokines, gut microbial phylotypes, and metabolic parameters.CONCLUSION: This study demonstrated that GSZD could modulate the gut microbiota and serum metabolic homeostasis to treat GA. In addition, the application of gut microbiota and serum metabolomics correlation analyses sheds light on the mechanism of Traditional Chinese Medicine compounds in the treatment of bone diseases.PMID:38851098 | DOI:10.1016/j.phymed.2024.155800

J Hazard Mater. 2024 Jun 3;474:134800. doi: 10.1016/j.jhazmat.2024.134800. Online ahead of print.ABSTRACTMicroplastics have emerged as a prominent global environmental contaminant, and they have been found in both human placenta and breast milk. However, the potential effects and mechanisms of maternal exposure to microplastics at various gestational stages on offspring neurodevelopment remain poorly understood. This investigation delves into the potential neurodevelopmental ramifications of maternal exposure to polystyrene nanoplastics (PS-NPs) during distinct phases of pregnancy and lactation. Targeted metabolomics shows that co-exposure during both pregnancy and lactation primarily engendered alterations in monoamine neurotransmitters within the cortex and amino acid neurotransmitters within the hippocampus. After prenatal exposure to PS-NPs, fetal rats showed appreciably diminished cortical thickness and heightened cortical cell proliferation. However, this exposure did not affect the neurodifferentiation of radial glial cells and intermediate progenitor cells. In addition, offspring are accompanied by disordered neocortical migration, typified by escalated superficial layer neurons proliferation and reduced deep layer neurons populations. Moreover, the hippocampal synapses showed significantly widened synaptic clefts and diminished postsynaptic density. Consequently, PS-NPs culminated in deficits in anxiolytic-like behaviors and spatial memory in adolescent offspring, aligning with concurrent neurotransmitter and synaptic alterations. In conclusion, this study elucidates the sensitive windows of early-life nanoplastic exposure and the consequential impact on offspring neurodevelopment.PMID:38850955 | DOI:10.1016/j.jhazmat.2024.134800

J Hazard Mater. 2024 Jun 4;474:134807. doi: 10.1016/j.jhazmat.2024.134807. Online ahead of print.ABSTRACTNanocrop protectants have attracted much attention as sustainable platforms for controlling pests and diseases and improving crop nutrition. Here, we reported the fungicidal activity and disease inhibition potential of pectin-coated metal-iron organic framework nanoparticles (Fe-MOF-PT NPs) against rice stripe blight (RSB). An in vitro bacterial inhibition assay showed that Fe-MOF-PT NPs (80 mg/L) significantly inhibited mycelial growth and nucleus formation. The Fe-MOF-PT NPs adsorbed to the surface of mycelia and induced toxicity by disrupting cell membranes, mitochondria, and DNA. The results of a nontargeted metabolomics analysis showed that the metabolites of amino acids and their metabolites, heterocyclic compounds, fatty acids, and nucleotides and their metabolites were significantly downregulated after treatment with 80 mg/L NPs. The difference in metabolite abundance between the CK and Fe-MOF-PT NPs (80 mg/L) treatment groups was mainly related to nucleotide metabolism, pyrimidine metabolism, purine metabolism, fatty acid metabolism, and amino acid metabolism. The results of the greenhouse experiment showed that Fe-MOF-PT NPs improved rice resistance to R. solani by inhibiting mycelial invasion, enhancing antioxidant enzyme activities, activating the jasmonic acid signaling pathway, and enhancing photosynthesis. These findings indicate the great potential of Fe-MOF-PT NPs as a new RSB disease management strategy and provide new insights into plant fungal disease management.PMID:38850939 | DOI:10.1016/j.jhazmat.2024.134807

J Hazard Mater. 2024 Jun 4;474:134816. doi: 10.1016/j.jhazmat.2024.134816. Online ahead of print.ABSTRACTPolyethylene microplastics (PE MPs) are the main MPs in agricultural soils and undergo oxidation upon environmental exposure. However, the influence of MP oxidation on phytotoxicity (especially for crop fruit) is still limited. This study aimed to explore the effect of PE MP oxidation on crop toxicity. Herein, a combination of plant phenotyping, metabolomic, and transcriptomic approaches was used to evaluate the effects of low-oxidation PE (LOPE) and high-oxidation PE (HOPE) on wheat growth, grain quality, and related molecular mechanisms using pot experiments. The results showed that HOPE induced a stronger inhibition of wheat growth and reduction in protein content and mineral elements than LOPE. This was accompanied by root ultrastructural damage and downregulation of carbohydrate metabolism, translation, nutrient reservoir activity, and metal ion binding gene expression. Compared with HOPE, LOPE activated a stronger plant defense response by reducing the starch content by 22.87 %, increasing soluble sugar content by 44.93 %, and upregulating antioxidant enzyme genes and crucial metabolic pathways (e.g., starch and sucrose, linoleic acid, and phenylalanine metabolism). The presence of PE MPs in the environment exacerbates crop growth inhibition and fruit quality deterioration, highlighting the need to consider the environmental and food safety implications of MPs in agricultural soils.PMID:38850928 | DOI:10.1016/j.jhazmat.2024.134816