PubMed

Int Immunopharmacol. 2024 Nov 2;143(Pt 3):113535. doi: 10.1016/j.intimp.2024.113535. Online ahead of print.ABSTRACTColorectal cancer (CRC) ranks as China's second most common cancer and fifth top cancer death cause. The study highlights the role of Natural Killer (NK) cells in targeting cancer stem cells (CSCs) that evade immune responses in CRC. Colorectal cancer stem cells (CCSCs) were stem from HT-29 cells and co-cultured with NK cells under normoxic or hypoxic conditions. The impact of this co-culture was evaluated using CCK8 assays for NK cell viability, ELISA for cytokine level changes, and flow cytometry for assessing NK cell apoptosis and activation. Comprehensive metabolomic and transcriptomic analyses were also performed to identify key genes and metabolites involved in the interaction between CCSCs and NK cells Co-culture of CCSCs with NK cells under hypoxia reduced NK cytotoxicity, increased NK apoptosis, and altered cytokine secretion by decreasing IFN-γ and TNF-α levels while increasing IL-6. Transcriptomic and metabolomic analysis identified 4 genes (FADS1, ALDH3A2, GCSH, MTCL1) and 3 metabolites (glyoxylic acid, spermine, DDA) as significant. Interfering with FADS1 counteracted the suppression of IFN-γ and TNF-α induced by CSC cells. Curiously, this inhibition caused by si-FADS1 could be neutralized by the addition of exogenous DDA. Co-culturing with NK cells notably increased spermine levels. Exogenous spermine resulted in a significant reduction in HT-29 cell death rates at 32 µM, 64 µM, and 128 µM, compared to NK cells without spermine. Our research explored CCSCs employed the FADS1/DDA axis to evade NK cell-mediated immunosuppression after co-cultured with NK cells under hypoxia.PMID:39488917 | DOI:10.1016/j.intimp.2024.113535

J Pharm Biomed Anal. 2024 Oct 28;253:116551. doi: 10.1016/j.jpba.2024.116551. Online ahead of print.ABSTRACTOphiocordyceps sinensis is widely used to treat various diseases and as a health supplement. The present study comprehensively compared the metabolic differences between wild and cultivated O. sinensis through 2D 1H-13C HSQC-based metabolomics, and assessed their anti-lung cancer activity on A549 cells. To characterize the global metabolic profile, sample preparation was scrutinously optimized, and both polar (1:4 methanol-water) and non-polar (1:4 methanol-chloroform) extracts of O. sinensis were investigated. A total of 47 and 10 metabolites were identified in the polar and non-polar extracts, respectively. Principal Component Analysis (PCA) revealed greater differences between the two types of O. sinensis in the polar extracts than in the non-polar extracts. Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) together with univariate tests captured 23 and 19 differential spectral features (with 22 and 11 of them assigned) between wild and cultivated O. sinensis in the polar and non-polar extracts, respectively. Meanwhile, the anti-lung cancer activities of both polar and non-polar extracts of wild and cultivated O. sinensis were assessed by MTS assay on A549 cells, and the sterols found in non-polar extracts, such as ergosterol, ergosterol peroxide, and 9,11-dehydroergosterol peroxide, and β-sitosterol, are the active ingredients with potential anti-lung cancer properties. In this study, we introduced a comprehensive strategy integrating 2D NMR-based metabolomics with in vitro assays for comparing the chemical composition and assessing the pharmacological activity of wild and cultivated O. sinensis. Our results provided a scientific basis for the potential viability of cultivated O. sinensis as an alternative to the wild counterpart.PMID:39488908 | DOI:10.1016/j.jpba.2024.116551

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Oct 29;52:101346. doi: 10.1016/j.cbd.2024.101346. Online ahead of print.ABSTRACTGlobal warming has multi-dimensional and complex impacts on the Earth's system, among which changes in light intensities cannot be overlooked. Sea cucumbers are a marine biological resource with significant economic and ecological value. Their presence and activity help maintain the balance and stability of marine ecosystems. The variation in light intensities have important ecological effects on sea cucumbers. Light intensities can alter the synthesis and degradation of metabolic substances within the bodies of Apostichopus japonicus by changing their body color. Their changes affect the production of microorganisms in the environment, thereby achieving the goal of bioremediation. This study investigated metabolic variations in green, purple, and white sea cucumber Apostichopus japonicus under different light conditions (0 lx and 910 lx) with a 12-h light and 12-h dark photoperiod. The findings indicated that the sea cucumbers displayed more diverse metabolic alterations under 910 lx illumination compared to 0 lx. Specifically, these color morphs primarily responded to changes in light intensities through "tryptophan metabolism" and "biosynthesis of steroid hormones". Additionally, high light intensities environment exacerbated the consumption of fatty acids by sea cucumbers. Different color morphs of sea cucumbers have differences in key metabolites in response to changes in light intensities. Green and white sea cucumbers primarily adapt to environment through phospholipids, while purple sea cucumbers mainly utilize fatty acids. These results enhance our comprehension of how sea cucumbers adapt ecologically to varying light intensities, and they offer valuable insights for systematically uncovering the regulatory processes that marine animals employ in response to environmental changes.PMID:39488885 | DOI:10.1016/j.cbd.2024.101346

Phytomedicine. 2024 Oct 28;135:156184. doi: 10.1016/j.phymed.2024.156184. Online ahead of print.ABSTRACTBACKGROUND: Gui-Ling-Ji (GLJ) described in the ancient medical book 'Yunji Qijian' is a traditional Chinese medicine formula used to improve male fertility. It is now available for the treatment of oligoasthenoteratozoospermia (OAT). However, the active ingredients and mechanism of GLJ are not clear.PURPOSE: The aim of this study was to clarify the active ingredients and mechanism of GLJ in OAT.METHODS: Firstly, the cyclophosphamide-induced OAT rat model was established to evaluate the efficacy of GLJ. Secondly, serum/urine-based metabolomics and lipidomics and tissue-based transcriptomics were performed to discover the differential metabolites and genes in rats. Furthermore, network pharmacology was constructed to explore the associated mechanisms based on the results of multi-omics analysis. Finally, cellular experiment on testicular mesenchymal stromal cells (TM3) was used to validate the active ingredients and the key metabolic pathway.RESULTS: Rats were administered GLJ by gavage every day for 3 weeks. Testicular damage and weight loss caused by cyclophosphamide were restored in rats, the sperm count and motility were improved, and levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) secretion were also elevated. Compared to the metabolites of OAT rats, 51 and 37 differential metabolites regulated by GLJ were identified from serum and urine respectively, 54 lipid differential metabolites regulated by GLJ were identified by lipidomics. At the same time, 23 of the 258 differential genes were found to be regulated by OAT rats and then reverse-regulated by GLJ. Network pharmacology has identified 13 pathways (Steroid hormone biosynthesis, Taurine and hypotaurine metabolism, Primary bile acid biosynthesis, Linoleic acid metabolism, Retinol metabolism, Glycerophospholipid metabolism, Ether lipid metabolism, Sphingolipid metabolism, Arachidonic acid metabolism, Glutathione metabolism, Arginine biosynthesis, Arginine and proline metabolism, D-Arginine and D-ornithine metabolism), four metabolites (arachidonic acid, oestrone sulphate, phosphatidylglycerol choline and sphingomyelin) and 15 targets (ABCB11, ALDH18A1, CCL3, CD244, CIITA, CYP2C8, DLL1, ITGA4, ESR1, AR, ABCB1, ABCC1, ALB, PLA2G1B and NOS2). GLJ, psoralen, isopsoralen, liquiritin, isoliquiritin, liquiritigenin, and ginsenoside Ro could significantly promote T secretion from TM3 cells. Additionally, arachidonic acid metabolism particularly the cyclooxygenase pathway, is closely related to the promotion of testosterone secretion by GLJ in TM3.CONCLUSION: GLJ has a therapeutic efficacy in cyclophosphamide-induced OAT rats, which can modulate the disorders of lipid metabolism and amino acid metabolism. Arachidonic acid metabolism may be a key pathway, and six prototype compounds are potential key active ingredients for GLJ.PMID:39488872 | DOI:10.1016/j.phymed.2024.156184

STAR Protoc. 2024 Nov 2;5(4):103430. doi: 10.1016/j.xpro.2024.103430. Online ahead of print.ABSTRACTSingle-cell analysis of human peripheral blood cells provides insights into innate and adaptive immune systems. However, robust protocols are essential to ensuring single-cell sequencing data quality and cell viability. Here, we present a protocol for acquiring high-quality single-cell multi-omics data from human peripheral blood mononuclear cells (PBMCs). We describe steps for collecting human blood followed by single-cell sequencing, whole-genome sequencing, and metabolome and proteome analysis of PBMCs using modified multi-omics sample processing.PMID:39488839 | DOI:10.1016/j.xpro.2024.103430

Inflammopharmacology. 2024 Nov 3. doi: 10.1007/s10787-024-01594-w. Online ahead of print.ABSTRACTBACKGROUND: Osteoarthritis (OA) is a common age-related disease that causes pain and impaired mobility. Various blood metabolites are reportedly associated with bone health; however, their impact on OA remains unclear. Therefore, we conducted a metabolome-wide Mendelian randomization (MR) study to identify causal metabolites and therapeutic targets in OA.METHODS: Genetic associations of metabolites were derived from the largest genome-wide association study (GWAS) of the blood metabolome, which provided summary-level data on 1091 blood metabolites. Genetic associations with OA were obtained from four large-scale GWAS: McDonald's study (140,025 cases, 344,349 controls), Zengini's study (12,658 cases, 50,898 controls), Dönertaş's study (39,515 cases, 445,083 controls), and Tachmazidou's study (39,427 cases, 378,169 controls). MR and colocalization analyses were performed to validate the causal roles of the candidate metabolites. Further analyses were conducted using expression quantitative trait locus-based MR, single-cell sequencing data, protein-protein interaction networks, and druggability assessments. These analyses aimed to identify the differentially expressed genes and prioritize them as potential therapeutic targets.RESULTS: The genetically predicted levels of 10 metabolites were associated with OA. Elevated levels of five metabolites and reduced levels of another five metabolites were associated with an increased OA risk. Among these, five metabolites were prioritized based on the most compelling evidence. Seven genes were identified as potentially involved and could serve as novel therapeutic targets for OA.CONCLUSION: Several blood metabolites were associated with OA, providing new insights into the etiology of OA and highlighting promising therapeutic targets.PMID:39488818 | DOI:10.1007/s10787-024-01594-w

Allergy Asthma Clin Immunol. 2024 Nov 2;20(1):59. doi: 10.1186/s13223-024-00921-8.ABSTRACTBACKGROUND AND METHODS: The Zéro allergie research clinic (Saguenay, Canada) is a clinical and research initiative in oral immunotherapy (OIT) for managing IgE-mediated food allergy (FA). A total of 183 children with FA and 27 non-allergic siblings were recruited to date in the Zéro allergie cohort (ZAC) to better understand biological mechanisms underlying FA and OIT prognosis. The primary aims are to (a) better understand the genetic, epigenetic, transcriptomic, metabolomic, and microbial diversity associated with FA; (b) establish the multi-omics and microbial diversity profiles of children following OIT to identify predictive prognosis biomarkers, (c) make OIT more accessible to the population of the Saguenay-Lac-Saint-Jean region, and (d) build a biobank of data and biological material.RESULTS: The ZAC constitutes a unique and rich biobank of biological samples (blood, buccal swabs, microbiota samples [intestinal, buccal, nasal, and cutaneous]) combined with clinical data and more than 75 phenotypic characteristics.CONCLUSIONS: This represents an innovative interdisciplinary initiative by researchers, allergists, and paediatricians to make FA care accessible to a greater number of children with IgE-mediated FA. Ultimately, it will contribute to provide more accessible treatment options with greater chances of success through a better understanding of the biological nature of FA and OIT.PMID:39488713 | DOI:10.1186/s13223-024-00921-8

Microb Cell Fact. 2024 Nov 2;23(1):295. doi: 10.1186/s12934-024-02570-3.ABSTRACTBACKGROUND: Myceliophthora thermophila has been engineered as a significant cell factory for malic acid production, yet strategies to further enhance production remain unclear and lack rational guidance. 13C-MFA (13C metabolic flux analysis) offers a means to analyze cellular metabolic mechanisms and pinpoint critical nodes for improving product synthesis. Here, we employed 13C-MFA to investigate the metabolic flux distribution of a high-malic acid-producing strain of M. thermophila and attempted to decipher the crucial bottlenecks in the metabolic pathways.RESULTS: Compared with the wild-type strain, the high-Malic acid-producing strain M. thermophila JG207 exhibited greater glucose uptake and carbon dioxide evolution rates but lower oxygen uptake rates and biomass yields. Consistent with these phenotypes, the 13C-MFA results showed that JG207 displayed elevated flux through the EMP pathway and downstream TCA cycle, along with reduced oxidative phosphorylation flux, thereby providing more precursors and NADH for malic acid synthesis. Furthermore, based on the 13C-MFA results, we conducted oxygen-limited culture and nicotinamide nucleotide transhydrogenase (NNT) gene knockout experiments to increase the cytoplasmic NADH level, both of which were shown to be beneficial for malic acid accumulation.CONCLUSIONS: This work elucidates and validates the key node for achieving high malic acid production in M. thermophila. We propose effective fermentation strategies and genetic modifications for enhancing malic acid production. These findings offer valuable guidance for the rational design of future cell factories aimed at improving malic acid yields.PMID:39488710 | DOI:10.1186/s12934-024-02570-3

J Nanobiotechnology. 2024 Nov 2;22(1):671. doi: 10.1186/s12951-024-02952-0.ABSTRACTBladder cancer (BCa) exhibits the escalating incidence and mortality due to the untimely and inaccurate early diagnosis. Urinary exosome metabolites, carrying critical tumor cell information and directly related to bladder, emerge as promising non-invasive diagnostic biomarkers of BCa. Herein, the magnetic 3D ordered macroporous zeolitic imidazolate framework-8 (magMZIF-8) is synthesized and used for efficient urinary exosome isolation. Notably, beyond retaining the single crystals and micropores of conventional ZIF-8, MZIF-8 is further enhanced with highly oriented and ordered macropores (150 nm) and the large specific surface area (973 m2·g-1), which could enable the high purity and yield separation of exosomes via leveraging the combination of size exclusion, affinity, and electrostatic interactions between magMZIF-8 and the surfaces of exosome. Furthermore, the magnetic and hydrophilic properties of magMZIF-8 will further simplify the process and enhance the efficiency of separation. After conditional optimization, a 50 mL of urine is sufficient for exosome metabolomics analysis, and the time for isolating exosomes from 42 urine samples was 2 hours only. Incorporating machine learning algorithms with LC-MS/MS analysis of the metabolic patterns obtained from isolated exosomes, early-stage BCa patients were differentiated from healthy controls, with area under the curve (AUC) value of 0.844-0.9970 in the training set and 0.875-1.00 in the test set, signifying its potential as a reliable diagnostic tool. This study offers a promising approach for the non-invasive and efficient diagnosis of BCa on a large scale via exosome metabolomics.PMID:39488699 | DOI:10.1186/s12951-024-02952-0

Cardiovasc Diabetol. 2024 Nov 2;23(1):393. doi: 10.1186/s12933-024-02470-1.ABSTRACTBACKGROUND: Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations.METHODS: VITamin D and OmegA-3 TriaL (NCT01169259) was a randomized clinical trial testing vitamin D and n-3 FA for the prevention of CVD and cancer over a median of 5.3 years. Incident cases of T2D and CVD (including cardiovascular death, myocardial infarction, stroke, and coronary revascularization) were matched 1:1 on age, sex, and fasting status to controls. Conditional logistic regressions adjusted for demographic, clinical, and adiposity-related factors were used to assess the adjusted odds ratio (aOR) per-standard deviation (SD) and 95%CI of baseline insulin, C-peptide, HbA1c, and IRS (Insulin×0.0295 + C-peptide×0.00372) with risk of T2D, CVD, and coronary heart disease (CHD).RESULTS: We identified 218 T2D case-control pairs and 715 CVD case-control pairs including 423 with incident CHD. Each of the four biomarkers at baseline was separately associated with incident T2D, aOR (95%CI) per SD increment: insulin 1.46 (1.03, 2.06), C-peptide 2.04 (1.35, 3.09), IRS 1.72 (1.28, 2.31) and HbA1c 7.00 (3.76, 13.02), though only HbA1c remained statistically significant with mutual adjustments. For cardiovascular diseases, we only observed significant associations of HbA1c with CVD (1.19 [1.02, 1.39]), and IRS with CHD (1.25 [1.04, 1.50]), which persisted after mutual adjustment. Randomization to vitamin D and/or n-3 FA did not modify the association of these biomarkers with the endpoints.CONCLUSIONS: Each of insulin, C-peptide, IRS, and HbA1c were associated with incident T2D with the strongest association noted for HbA1c. While HbA1c was significantly associated with CVD risk, a novel IRS appears to be associated with CHD risk. Neither vitamin D nor n-3 FA modified the associations between these biomarkers and cardiometabolic outcomes.PMID:39488682 | DOI:10.1186/s12933-024-02470-1

Discov Oncol. 2024 Nov 2;15(1):614. doi: 10.1007/s12672-024-01467-2.ABSTRACTBACKGROUND: Gliomas are the most common malignant brain tumors characterized by angiogenesis and invasive growth. A detailed understanding of its molecular characteristics could provide potential therapeutic targets. In the present study, we sought to explore the key gene CXCL8 in methionine metabolism in gliomas and its potential role in angiogenesis.METHODS: U251 glioma cells were divided into control and methionine-restriction tolerant (constructed with 1/4 of the standard level of methionine in the culture medium) groups for transcriptome and metabolome analysis. To confirm the functions and mechanism of CXCL8 in glioma, heat map, volcano map, Go enrichment, gene set enrichment analysis (GSEA), protein-protein interaction network analysis, RT-PCR, western blotting assays, chicken embryo chorioallantoic membrane (CAM) test, chicken embryo yolk sac membrane (YSM) test and transplantation tumor nude mice model were performed. The TCGA database, CGGA database and clinical tissue samples were used to analyze CXCL8's significance on prognosis for patients with glioma.RESULTS: CXCL8 expression was significantly up-regulated in methionine-restricted tolerance cells, it also activated vascular system development and triggered angiogenesis. CXCL8 expression is negatively correlated with survival prognosis in gliomas.CONCLUSIONS: Glioma cells promote angiogenesis in methionine-restricted environments through the activation of CXCL8, compensating for nutrient deprivation, and possibly contributing to the failure of antiangiogenic therapy.PMID:39488622 | DOI:10.1007/s12672-024-01467-2

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