PubMed

Plant Physiol Biochem. 2024 Oct 30;217:109253. doi: 10.1016/j.plaphy.2024.109253. Online ahead of print.ABSTRACTFoxtail millet is a C4 crop rich in folate (FA). This study explores the roles of the 4-amino-4-deoxychorismate lyase (ADCL) - a member of the transaminase IV group of enzymes - in FA metabolism and conferred phenotypes. Phylogenetic comparisons identified diversity in the transaminase IV/ADCL gene family in the foxtail millet genome which was associated with genomic duplications. Molecular docking studies suggested that SiADCL1 bound most strongly to aminodeoxychorismate (ADC) and most likely had the highest catalytic activities. SiADCL1 which was highly expressed in roots, peduncles and flag leaves. Over-expression of SiADCL1 in Arabidopsis significantly increased total FA content (1.14-1.84 fold) and this was linked to a delayed flowering time. Metabolomic and transcriptomic characterization of the derived over-expression lines, found that FA promotes the change of methylation-related genes, ethylene synthesis, amino acid metabolism and flowering-related genes. This study revealed a potential gene coexpression network linked with FA and targeted key genes that could be exploited in foxtail millet breeding programs.PMID:39488163 | DOI:10.1016/j.plaphy.2024.109253

Phytomedicine. 2024 Oct 28;135:156182. doi: 10.1016/j.phymed.2024.156182. Online ahead of print.ABSTRACTBACKGROUND: Numerous experiments and clinical practices have demonstrated the effectiveness of Qishen Yiqi dripping pills (QSYQ) on myocardial ischemia (MI). However, the bioactive ingredients and mechanisms remain unclear, leading to huge gaps between quality control and biological effect of QSYQ. Discovering quality markers (Q-markers) based on effective components is crucial for ensuring stable quality and clinical effectiveness of QSYQ.PURPOSE: To explore Q-markers of QSYQ against MI by a stepwise strategy integrating serum pharmacochemistry, network pharmacology, metabolomics, quantitative analysis, and cell experiments.METHODS: Firstly, liquid/gas chromatography-mass spectrometry was applied to characterize chemical profiles of QSYQ in vitro and in vivo. Based on the serum migrating constituents, a component-target-MI interaction network was constructed. Subsequently, pharmacodynamics and metabolomics were conducted to evaluate cardioprotective effect and potential mechanism of QSYQ. Next, conjoint analysis of network pharmacology and metabolomics was performed to screen candidate Q-markers. Finally, the measurability and bioactivity were validated to justify their usage as Q-markers.RESULTS: A total of 97 components were identified in QSYQ, 24 prototypes of which were detected in serum. The "component-target-disease" interaction network was constructed based on serum migrating constituents. Pharmacodynamic results showed that QSYQ effectively improved cardiac function, attenuated inflammatory cell infiltration, alleviated myocardial fibrosis, and reduced the levels of myocardial enzymes and oxidative stress in MI rats. Metabolomics study demonstrated that 59 metabolites were markedly altered in MI rats, 25 of which were significantly reversely regulated by QSYQ. After integrative analysis of network pharmacology and metabolomics, 12 components were selected as candidate Q-markers of QSYQ, and the contents were quantified. These candidate Q-markers displayed synergistic protective effects against H2O2-induced injury in H9c2 cells. Taken together, 12 components with properties of transitivity and traceability, effectiveness, measurability, and compatibility contribution were defined as representative Q-markers of QSYQ, including Astragaloside IV, Ononin, Calycosin, Formononetin, Rosmarinic acid, Cryptotanshinone, Salvianolic acid A, Tanshinol, Ginsenoside Rb1, Ginsenoside Rg1, Nerolidol, and Santalol.CONCLUSION: In this study, a novel stepwise integrated strategy was presented for discovering Q-markers related to therapeutic effects of traditional Chinese medicine prescriptions. Twelve comprehensive and representative Q-markers of QSYQ were identified for the first time to improve its quality control.PMID:39488103 | DOI:10.1016/j.phymed.2024.156182

Phytomedicine. 2024 Oct 28;135:156174. doi: 10.1016/j.phymed.2024.156174. Online ahead of print.ABSTRACTBACKGROUND: Gastric intestinal metaplasia (GIM) is a crucial stage in the progression of gastric cancer. Huangqi Jianzhong decoction (HQJZ) has emerged as a leading therapeutic strategy for treating GIM patients with cold intolerance in traditional Chinese medicine clinics, but the detailed mechanism remains poorly understood.OBJECTIVE: The present study aimed to elucidate the molecular mechanism by which HQJZ alleviates GIM in a rat model on the basis of the gut microbiota‒thyroid axis.METHODS: A GIM rat model was established by administering cold salicylic acid and sodium deoxycholate (SDC) for 12 weeks, followed by gavage treatment with HQJZ for an additional four weeks. Lianpu Yin (LPY) was used as a comparison formula. The cold tolerance characteristics of GIM rats were evaluated using cold tolerance and temperature‒tropism experiment experiments. Thyroid pathological changes were evaluated with HE staining, and thyroid function was measured via quantification of T3 and T4 levels with ELISA. The gut microbiota was analyzed using 16S rRNA gene sequencing, and fecal butyric acid and serum metabolites were quantified utilizing metabolomics. The key molecular mechanism was verified in the Nthy-ori 3-1 cell model.RESULTS: HQJZ, but not LPY, significantly improved gastric mucosa and thyroid tissue lesions in GIM rats, increased the serum levels of the thyroid hormones T3 and T4, and enhanced cold tolerance. HQJZ treatment promoted the enrichment of fecal butyrate-producing bacteria, specifically the bacteria Allobaculum and Bifidobacterium, resulting in a marked increase in fecal butyric acid concentrations. HQJZ treatment significantly diminished the levels of mitochondrial damage-related serum metabolites, including p-cresol sulfate and indoxyl sulfate. Mechanistically, in vivo investigations further demonstrated that butyric acid not only improved thyroid tissue lesions but also restored the fecal microbiota structure, as well as low-temperature tropism, in GIM rats. Furthermore, butyrate diminished the mitochondrial damage induced by SDC in these cells, as evidenced by decreased reactive oxygen species levels and increased ATP production and mitochondrial membrane potential. Importantly, in vitro studies revealed that butyrate protected against SDC-induced injury in Nthy-ori 3-1 cells through the upregulation of TG, TPO, and TSHR expression.CONCLUSIONS: HQJZ promotes cold tolerance and improves thyroid function in GIM rats by enriching gut butyrate-producing bacteria.PMID:39488101 | DOI:10.1016/j.phymed.2024.156174

Phytomedicine. 2024 Oct 28;135:156181. doi: 10.1016/j.phymed.2024.156181. Online ahead of print.ABSTRACTBACKGROUND: Alcohol dependence (AD) is a common psychiatric disorder, often accompanied by anxiety and depression. These comorbidities are linked to disturbances in serotonin (5-HT) metabolism and gut microbiota dysbiosis. Clinical studies suggest that inulin, a prebiotic, can alleviate anxiety and depression in AD patients by affecting the gut microbiota, although the mechanisms remain unclear.PURPOSE: The purpose of this study is to investigate the potential mechanisms by which inulin, a prebiotic, improves anxiety and depression-like behaviors in AD withdrawal mice. This research is based on the drug and food homology and intestinal treatment of encephalopathy, with the goal of developing new clinical strategies for AD treatment.STUDY DESIGN: For this purpose, fecal samples from AD patients were analyzed to identify microorganisms associated with AD. An AD withdrawal mouse model was created, with inulin as the intervention and fluvoxamine maleate as the control. Techniques such as 16S microbiome sequencing and UPLC-TQMS-targeted metabolomics were used to assess gut microbiota, short-chain fatty acids (SCFAs) levels, and 5-HT metabolism.METHODS: The AD withdrawal model was built using the "Drinking-in-the-dark" protocol over 6 weeks. Inulin (2 g/kg/day) and fluvoxamine maleate (30 mg/kg/day) were administered for 4 weeks. The open field test, forced swim test, and tail suspension test were used to evaluate anxiety and depression-like behaviors in mice. ELISA and qRT-PCR assessed 5-HT metabolism in the colon, blood, and prefrontal cortex, while 16S microbiome sequencing analyzed changes in gut microbiota and UPLC-TQMS examined SCFAs levels. Immunohistochemistry was used to study intestinal barrier integrity.RESULTS: AD patients showed reduced SCFA-producing bacteria such as Faecalibacterium and Roseburia. In mice, AD withdrawal led to anxiety and depression-like behaviors, disrupted 5-HT metabolism, and gut microbiota dysbiosis. Inulin supplementation alleviated these behaviors, increased 5-HT and 5-hydroxytryptophan (5-HTP) levels, upregulated colonic tryptophan hydroxylase 1 (TPH1) expression, and promoted the growth of beneficial bacteria such as Faecalibacterium and Roseburia, while also increasing SCFAs levels.CONCLUSION: Inulin increases the abundance of Faecalibacterium and Roseburia, enhances SCFAs production, and regulates 5-HT metabolism, improving anxiety and depression-like behaviors in AD withdrawal mice. These findings suggest that inulin may serve as a nutritional intervention for mental health in AD patients by targeting the microbiome-gut-brain axis.PMID:39488100 | DOI:10.1016/j.phymed.2024.156181

J Cutan Med Surg. 2024 Nov 2:12034754241293138. doi: 10.1177/12034754241293138. Online ahead of print.ABSTRACTHidradenitis suppurativa (HS) is recognized as a systemic immune-mediated disease (IMID), sharing genetic and environmental risk factors with other IMIDs such as inflammatory bowel disease and psoriasis. Over time, correlating clinical findings with genetic, proteomic, and metabolomic results has been challenging due to diverse sampling methods, analysis techniques, and the use of variable clinical phenotype descriptions across studies. This review aims to summarize the results from various omics fields to explore the etiopathology of HS. Genetic studies highlight defects in Notch and γ-secretase signaling and inflammasome function. Syndromic HS involves specific mutations in autoinflammatory syndromes such as pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) and pyoderma gangrenosum, acne, and HS (PASH). Proteomic analyses reveal key inflammatory pathways indicating activation of both innate and adaptive immunity. Additionally, microbiome studies show an increased presence of anaerobes like Prevotella in HS lesions and a decreased presence of commensals such as Staphylococcus epidermidis. Gut microbiota dysbiosis, particularly involving Ruminococcus gnavus and Clostridium ramosum, is associated with HS. Moreover, metabolomic profiling indicates dysregulated tryptophan catabolism and lipid metabolism, with increased 5-lipoxygenase-derived metabolites and odd-chain fatty acids suggesting bacterial involvement. In summary, despite advances, robust associations between genetics, proteomics, microbiome, and metabolomics in HS are still lacking. Integrating these datasets could identify new clinical phenotypes, genetic predispositions, microbial signatures, and therapeutic targets, enhancing personalized treatment strategies and biomarker discovery for HS classification, prognosis, and treatment response.PMID:39487752 | DOI:10.1177/12034754241293138

J Sep Sci. 2024 Nov;47(21):e70003. doi: 10.1002/jssc.70003.ABSTRACTIn the last decade, the instrumentation improvements in supercritical fluid chromatography (SFC) and the hyphenation to mass spectrometry (MS), have increased the SFC acceptance between scientists, becoming today a valuable tool in analytical chemistry. The unique selectivity, short analysis times, low consumption of organic solvents, and the greener mobile phase, have contributed to expanding its applicability which has led to an increase in the number of publications especially in the bioanalysis area. This work reviews the advantages and main applications of SFC in bioanalysis during the last 5 years. Fundamental aspects concerning mobile phase composition, stationary phase, hyphenation to MS as well as matrix effect have been discussed. Finally, the most relevant applications have been summarized.PMID:39487700 | DOI:10.1002/jssc.70003

Dev Med Child Neurol. 2024 Nov 2. doi: 10.1111/dmcn.16164. Online ahead of print.NO ABSTRACTPMID:39487678 | DOI:10.1111/dmcn.16164

Mol Plant Pathol. 2024 Nov;25(11):e70007. doi: 10.1111/mpp.70007.ABSTRACTPathogens must efficiently acquire nutrients from host tissue to proliferate, and strategies to block pathogen access therefore hold promise for disease control. In this study, we investigated whether heme biosynthesis is an effective target for ablating the virulence of the phytopathogenic fungus Ustilago maydis on maize plants. We first constructed conditional heme auxotrophs of the fungus by placing the heme biosynthesis gene hem12 encoding uroporphyrinogen decarboxylase (Urod) under the control of nitrogen or carbon source-regulated promoters. These strains were heme auxotrophs under non-permissive conditions and unable to cause disease in maize seedlings, thus demonstrating the inability of the fungus to acquire sufficient heme from host tissue to support proliferation. Subsequent experiments characterized the role of endocytosis in heme uptake, the susceptibility of the fungus to heme toxicity as well as the transcriptional response to exogenous heme. The latter RNA-seq experiments identified a candidate ABC transporter with a role in the response to heme and xenobiotics. Given the importance of heme biosynthesis for U. maydis pathogenesis, we tested the ability of the well-characterized herbicide BroadStar to influence disease. This herbicide contains the active ingredient flumioxazin, an inhibitor of Hem14 in the heme biosynthesis pathway, and we found that it was an effective antifungal agent for blocking disease in maize. Thus, repurposing herbicides for which resistant plants are available may be an effective strategy to control pathogens and achieve crop protection.PMID:39487654 | DOI:10.1111/mpp.70007

J Anim Sci Biotechnol. 2024 Nov 2;15(1):144. doi: 10.1186/s40104-024-01105-5.ABSTRACTBACKGROUND: Necrotic enteritis (NE) is an economically important disease of broiler chickens caused by Clostridium perfringens (CP). The pathogenesis, or disease process, of NE is still not clear. This study aimed to identify the alterations of metabolites and metabolic pathways associated with subclinical or clinical NE in CP infected birds and to investigate the possible variations in the metabolic profile of birds infected with different isolates of CP.METHODOLOGY: Using a well-established NE model, the protein content of feed was changed abruptly before exposing birds to CP isolates with different toxin genes combinations (cpa, cpb2, netB, tpeL; cpa, cpb2, netB; or cpa, cpb2). Metabolomics analysis of jejunal contents was performed by a targeted, fully quantitative LC-MS/MS based assay.RESULTS: This study detected statistically significant differential expression of 34 metabolites including organic acids, amino acids, fatty acids, and biogenic amines, including elevation of butyric acid at onset of NE in broiler chickens. Subsequent analysis of broilers infected with CP isolates with different toxin gene combinations confirmed an elevation of butyric acid consistently among 21 differentially expressed metabolites including organic acids, amino acids, and biogenic amines, underscoring its potential role during the development of NE. Furthermore, protein-metabolite network analysis revealed significant alterations in butyric acid and arginine-proline metabolisms.CONCLUSION: This study indicates a significant metabolic difference between CP-infected and non-infected broiler chickens. Among all the metabolites, butyric acid increased significantly in CP-infected birds compared to non-infected healthy broilers. Logistic regression analysis revealed a positive association between butyric acid (coefficient: 1.23, P < 0.01) and CP infection, while showing a negative association with amino acid metabolism. These findings suggest that butyric acid could be a crucial metabolite linked to the occurrence of NE in broiler chickens and may serve as an early indicator of the disease at the farm level. Further metabolomic experiments using different NE animal models and field studies are needed to determine the specificity and to validate metabolites associated with NE, regardless of predisposing factors.PMID:39487547 | DOI:10.1186/s40104-024-01105-5

J Transl Med. 2024 Nov 1;22(1):989. doi: 10.1186/s12967-024-05801-8.ABSTRACTBACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.METHODS: To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP).RESULTS: Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression.CONCLUSIONS: Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.PMID:39487546 | DOI:10.1186/s12967-024-05801-8

BMC Microbiol. 2024 Nov 1;24(1):445. doi: 10.1186/s12866-024-03560-6.ABSTRACTBACKGROUND: Sponge-associated microorganisms are promising resources for the production of bioactive compounds with cytotoxic potential. The main goal of our study is to isolate the fungal endophytes from the Red Sea sponge Hyrtios sp. followed by investigating their cytotoxicity against number of cell lines.RESULTS: The fungal strain UR3 was isolated from the Red Sea sponge using Sabouraud dextrose agar media. It was identified based on partial 18 S rRNA gene and ITS sequence analyses as Cladosporium sp. UR3. The in vitro cytotoxic potential of the ethyl acetate extract of the fungal isolate was evaluated using MTT assay against three cancer cell lines: CACO2, MCF7, and HEPG2. Metabolomics profiling of the obtained ethyl acetate extract using LC-HR-ESI-MS, along with molecular docking and pharmacological network studies for the dereplicated compounds were performed to explore its chemical profile and the possible cytotoxic mechanism of the sponge-associated fungi.CONCLUSION: These results highlighted the role of sponge-associated fungi as a fruitful resource for the discovery of cytotoxic metabolites.PMID:39487417 | DOI:10.1186/s12866-024-03560-6

Metabolomics. 2024 Nov 2;20(6):122. doi: 10.1007/s11306-024-02192-1.ABSTRACTINTRODUCTION AND OBJECTIVES: Since the use of a bio stimulant should provide a response to a problem that depends on the production system implemented (crops, plant model, soil, climate, the farmer's practices…), the agricultural sector is facing concomitant challenges of choosing the best bio stimulant that suits their needs. Thus, understanding bio stimulant-plant interactions, at molecular level, using metabolomics approaches is a prerequisite, for the development of a bio stimulant, leading to an effective exploration and application of formulations in agriculture. AGRO-K®, is commercialized as a plant-based bio stimulant that improve vigor and enhance resistance to lodging in cereal crops. A recent previous untargeted metabolomics study has demonstrated the ability of this bio stimulant to improve wheat resistance to lodging, in real open-field conditions. However, the reproducibility of the impact of this bio stimulant in other filed crops is not yet investigated.METHODS: Therefore, the present study aimed to assess the changes in primary and secondary metabolites in the roots, stems, and leaves of fiber flax (Linum usitatissimum L), treated with the bio stimulant, using NMR and LC-MS-based untargeted metabolomics approach.RESULTS AND CONCLUSIONS: In addition to the previous result conducted in wheat, the present analysis seemed to show that this bio stimulant led to a similar pathway enhancement in flax. The pathways which seem to be reproducibly impacted are hydroxycinnamic acid amides (HCAAs), phenylpropanoids and flavonoids. Impacting these pathways enhance root growth and elongation and cell wall lignification, which can aid in preventing crop lodging. These results confirm that HCAAs, flavonoids, and phenylpropanoids could serve as signatory biomarkers of the impact of AGRO-K® on improving lodging resistance across various plant species.PMID:39487363 | DOI:10.1007/s11306-024-02192-1

Metabolomics. 2024 Nov 2;20(6):121. doi: 10.1007/s11306-024-02188-x.ABSTRACTBACKGROUND: Chronic kidney disease (CKD) is common in patients with diabetes mellitus (DM). Volatile organic compounds (VOCs) are widespread pollutants that may impact DM development.OBJECTIVE: This study aims to explore the association between urinary VOC metabolites and CKD in patients with DM.METHODS: Adult National Health and Nutrition Examination Survey (NHANES) 2011 to 2018 participants with DM were included in this study. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g. Multivariable regression models were used to analyze the associations between urinary VOC metabolites and CKD.RESULTS: A total of 1,295 participants with DM and a mean age of 59 years were included. After adjustment for demographic and clinical characteristics, elevated levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) (tertile 2: adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI): 1.15-2.85, p = 0.012), N-acetyl-S-(N-methylcarbamoyl)-L-cysteine (AMCC) (tertile 2: aOR = 1.84, 95% CI: 1.10-3.08, p = 0.021), DHBMA (tertile 3: aOR = 1.93, 95% CI: 1.12-3.35, p = 0.020), and phenylglyoxylic acid (PGA) (tertile 3: aOR = 1.71, 95% CI: 1.11-2.63, p = 0.017) were significantly associated with increased likelihood of CKD.CONCLUSION: Specific urinary VOC metabolite levels are positively associated with an increased risk of CKD in patients with DM. These findings suggest that monitoring urinary VOC metabolites could be important for the prevention and management of CKD in this population. Future longitudinal studies should focus on establishing causality and elucidating the underlying mechanisms of these associations.PMID:39487359 | DOI:10.1007/s11306-024-02188-x

Metabolomics. 2024 Nov 2;20(6):123. doi: 10.1007/s11306-024-02191-2.ABSTRACTINTRODUCTION: Breast Cancer (BC) is one of the most diagnosed malignancies among women and the second leading cause of cancer related death in North America. Triple Negative BC (TNBC), one of the most severe subtypes of BC, is extremely aggressive and has a higher chance of occurrence in women under 50 years of age. Due to a lack of regular mammographic testing in women under 50, many individuals with TNBC are diagnosed late which can decrease their survival rate. Currently, liquid biopsy is being investigated as a potentially less-invasive alternative to traditional breast tissue biopsy, but this approach is not completely reliable. Blood contains extracellular vesicles (EVs), which carry biomolecular cargo and play a role in BC progression and metastasis. Examination of small EVs could potentially yield metabolite biomarkers for early BC diagnosis.OBJECTIVE: We aim to study metabolites in small EVs to find biomarkers for BC diagnosis.METHODS: In this work, an untargeted nano-LC MS/MS metabolomics approach was used to analyze metabolites from small EVs derived from metastatic MDA-MB-231 and compare it with a non-cancerous MCF10A cell line.RESULTS: Two metabolites, LysoPC 22:6/0:0 and N-acetyl-L-Phenylalanine, unique to sEVs of MDA-MB-231, were identified, validated, and proposed as potential BC biomarkers.CONCLUSION: Metabolites from sEVs may be used for BC diagnosis.PMID:39487276 | DOI:10.1007/s11306-024-02191-2

Sci Rep. 2024 Nov 1;14(1):26290. doi: 10.1038/s41598-024-76637-x.ABSTRACTStuccoes are very delicate decorative elements of Roman age. Very few of them survived almost intact to present days and, for this reason, they are of great interest to restorers and conservators. In this study, we combined metabarcoding and untargeted metabolomics to characterise the taxonomic and metabolic profiles of the microorganisms forming biofilms on the stuccoes located on the ceiling of the laconicum, a small thermal environment in the archaeological park of Baia (southern Italy). We found that some samples were dominated by bacteria while others by eukaryotes. Additionally, we observed high heterogeneity in the type and abundance of bacterial taxa, while the eukaryotic communities, except in one sample (at prevalence of fungi), were dominated by green algae. The metabolic profiles were comparable across samples, with lipids, lipid-like molecules and carbohydrates accounting for roughly the 50% of metabolites. In vitro and in vivo tests to remove biofilms on stuccoes using essential oils blends were successful at a 50% dilution for one hour and half. This integrative study advanced our knowledge on taxonomic and metabolic profiles of biofilms on ancient stuccoes and highlighted the potential impacts of these techniques in the field of cultural heritage conservation.PMID:39487240 | DOI:10.1038/s41598-024-76637-x

Sci Rep. 2024 Nov 1;14(1):26291. doi: 10.1038/s41598-024-77909-2.ABSTRACTPorphyromonas gingivalis (P. gingivalis), the main pathogen responsible for periodontitis, is linked to systemic disorders via the oral-gut axis. Short-chain fatty acids (SCFAs) are vital for gut health, but their role in P. gingivalis-induced gut disorders remains unclear. This study utilized metabolomics and 16 S rRNA sequencing to explore gut microbiota and SCFAs levels in P. gingivalis-induced periodontitis mouse models. Significant changes were observed in gut, including a reduction in SCFAs-producing bacteria, such as Lactobacillus, Ligilactobacillus, Allobucalum, and a notable decrease in Firmicutes and Actinobacteriota. The intestinal permeability tests and histological analyses revealed that periodontitis led to epithelial inflammation, reduced mucin secretion, and compromised gut barrier integrity. In vitro experiments with Caco-2 cells co-cultured with P. gingivalis showed that the bacterium disrupted cellular junctions by impairing autophagy, specifically through the ATG5-LC3 pathway, leading to decreased expression of tight junction proteins and reduced SCFA absorption. Remarkably, rapamycin treatment both in vitro and in vivo restored gut barrier function by enhancing autophagy, increasing tight junction protein expression, and promoting SCFAs absorption via MCT1 and SMCT1, alongside GPR43/GPR109a pathway activation. These findings reveal autophagy's novel role in regulating SCFAs metabolism in P. gingivalis-induced gut dysbiosis, offering insights for preventing and treating periodontitis-related systemic diseases.PMID:39487211 | DOI:10.1038/s41598-024-77909-2

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Oct 24;1248:124342. doi: 10.1016/j.jchromb.2024.124342. Online ahead of print.ABSTRACTThis study has developed a new targeted methodology for the separation, detection, and quantification of metabolites from the wider energy metabolome of industrially important microorganisms such as Saccharomyces cerevisiae in a single analytical sample. This has been achieved using UHPLC-MS technology in HILIC mode. Absolute concentrations of metabolites nicotinamide adenine dinucleotide (NAD), nicotinamide adenine dinucleotide reduced (NADH), nicotinamide adenine dinucleotide phosphate (NADP), nicotinamide adenine dinucleotide phosphate reduced (NADPH), flavin adenine dinucleotide (FAD), adenosine-monophosphate (AMP), adenosine-diphosphate (ADP), and adenosine-triphosphate (ATP) were determined in a single extraction and analytical methodology. This study demonstrated the development of a rapid, statistically robust, and reproducible methodology through regression calibrations of standard samples from 0.1 to 100 µMol providing a correlation value of r2 = >0.98 for all metabolites. Sample preparation, extraction and analytical methodologies used showed high accuracy, sensitivity, and recovery. With an LOD and LOQ for the targeted analysis of metabolites from the wider energy metabolism in a single sample and analytical run with the lowest LOD of 0.055 nMol (±0.002) and lowest LOQ of 0.167 nMol (±0.006). This method was then applied to Saccharomyces cerevisiae cell culture to evaluate the methodology in industrially used microbial cultures. Results obtained have been statistically determined to be robust and reproducible through recovery analysis using deuterated and isotopically labelled internal standards AMP-15N, ADP-15N and ATP-d14.PMID:39486264 | DOI:10.1016/j.jchromb.2024.124342

Environ Int. 2024 Oct 22;193:109092. doi: 10.1016/j.envint.2024.109092. Online ahead of print.ABSTRACTFluorotelomer sulfonates (FTSs) are widely used as novel substitutes for perfluorooctane sulfonate, inevitably leading to FTSs accumulation in various environmental media and subsequent exposure to humans. This accumulation eventually poses environmental hazards and health risks. However, their toxicity mechanisms remain unclear. Herein, the mechanisms of two FTSs (6:2 and 8:2 FTS) induced toxicity in human hepatocellular carcinoma cells were investigated via non-targeted metabolomics and lipidomics based on liquid chromatography-high resolution mass spectrometry. Our results revealed that amino acid, purine, acylcarnitine and lipid levels were significantly perturbed by 6:2 and 8:2 FTS exposure. The effects of 8:2 FTS exposure were largely characterized by up-regulation of pyruvate metabolism pathway and down-regulation of purine metabolism pathway, whereas the opposite trends were induced by 6:2 FTS exposure. The opposite trends were confirmed by the mRNA expression levels of four key genes (glyoxalase 1, adenylosuccinate lyase, inosine monophosphate dehydrogenase 1 (IMPDH1) and IMPDH2) determined by real-time PCR. Common lipid perturbations included significantly increased ceramide/sphingomyelin ratios, and obvious accumulation of hexosylceramides and lysoglycerophospholipids. 6:2 FTS exposure induced sharp accumulation of glycerides, including monoglycerides, diglycerides and triglycerides. 8:2 FTS exposure induced decreased levels of acylcarnitines and fatty acids. Both of 6:2 and 8:2 FTS exposure induced increased levels of intracellular reactive oxygen species, an imbalance in energy metabolism homeostasis, and mitochondrial dysfunction. The results of integrated omics analysis are expected to serve as valuable information for the health risk assessment of 6:2 FTS and 8:2 FTS.PMID:39486253 | DOI:10.1016/j.envint.2024.109092

Mar Pollut Bull. 2024 Oct 31;209(Pt B):117197. doi: 10.1016/j.marpolbul.2024.117197. Online ahead of print.ABSTRACTThe neurotoxin β-N-methylamino-L-alanine (BMAA) produced by marine diatoms has been implicated in some neurological disorders, and there is a need to elucidate the biological processes involved in the production of BMAA-containing proteins. In this study, growth of seven diatoms was suppressed under nitrogen limitation, however the production of BMAA-containing proteins was significantly increased in six of them, up to 5.22-fold increase in Thalassiosira andamanica. These variations were associated with reduced concentration of dissolved inorganic nitrogen (DIN) and changes in photosynthetic efficiency. Analytical results of non-targeted metabolomics showed that the obvious changes in amino acids, lipids and sugars may help diatoms to adjust growth and physiological parameters. Combined with previous transcriptomic data, a decrease in N-acetyl-D-glucosamine (GlcNAc) leads to an increase in N-glycan terminal modifications, which in turn increases protein misfolding. In addition, the reduced efficiency of vesicular transport in the COPII system may have exacerbated the accumulation of BMAA-containing proteins.PMID:39486208 | DOI:10.1016/j.marpolbul.2024.117197

Org Lett. 2024 Nov 1. doi: 10.1021/acs.orglett.4c03470. Online ahead of print.ABSTRACTMoon snails (family: Naticidae) lay egg masses that are rich in bacterial species distinct from the surrounding environment. We hypothesized that this microbiome chemically defends the moon snail eggs from predation and pathogens. Herein, we report the discovery of bokeelamides, new lipopeptides from the egg mass-associated bacterium, Ectopseudomonas khazarica, which were discovered using mass spectrometry (MS)-based metabolomics. The structures of the bokeelamides were elucidated using two-dimensional (2D) nuclear magnetic resonance (NMR), tandem MS, Marfey's, and genomic analyses.PMID:39486159 | DOI:10.1021/acs.orglett.4c03470