PubMed

Toxicon. 2024 Oct 21:108137. doi: 10.1016/j.toxicon.2024.108137. Online ahead of print.ABSTRACTSome of the most commonly identified freshwater toxins are anatoxin-a (ATX-a), cylindrospermopsin (CYN), and microcystin-LR (MC-LR). The aim of this paper was to compare different methods of extracting and concentrating these cyanotoxins and check the impact of selected physical factors on the accumulation of biomass of Dolichospermum flos-aquae, Microcystis aeruginosa, and Raphidiopsis raciborskii. The effect of different cyanobacteria cultivation conditions on the amount of cyanotoxins synthesized showed no significant changes over time in the average concentration of all tested toxins in the medium compared to the control. Mixing cultures increases the intracellular content of ATX-a. Aerating also positively affects the concentration of MC-LR intracellularly. In order to optimize the solid phase extraction (SPE) process of toxins, the C18 phase or activated carbon was used. In general, higher toxin recoveries were achieved when using the C18 phase. The best result was achieved for ATX-a, 94% recovery with elution using methanol with 0.1% trifluoroacetic acid (TFA). For MC-LR, the best recovery was 59%, and for CYN 22%. The study evaluated the various methods to release cyanotoxins from cyanobacteria showed that: the highest ATX-a concentration (0.60 μg/mg d.w) was obtained using MilliQ water and microwave treatment for 10 to 15 seconds. For MC-LR, the highest extracted amount (6.73 μg/mg d.w) resulted from methanol treatment and boiling at 100°C for 15 minutes. CYN extraction was the most effective by using MilliQ water and alternative freezing/thawing (1.54 μg/mg d.w). In conclusion, changing the optimal parameters of cyanobacterial cultivation, only slightly affects the increase in biomass accumulation and synthesis of cyanobacterial toxins. In the case of ATX, the key is the use of the TFA additive in the SPE process. No single method has been identified as the ideal approach for isolating various intracellular cyanotoxins.PMID:39442567 | DOI:10.1016/j.toxicon.2024.108137

Cell Metab. 2024 Oct 18:S1550-4131(24)00395-4. doi: 10.1016/j.cmet.2024.09.013. Online ahead of print.ABSTRACTObesity is a major risk factor for poor breast cancer outcomes, but the impact of obesity-induced tumor microenvironment (TME) metabolites on breast cancer growth and metastasis remains unclear. Here, we performed TME metabolomic analysis in high-fat diet (HFD) mouse models and found that glutathione (GSH) levels were elevated in the TME of obesity-accelerated breast cancer. The deletion of glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme in GSH biosynthesis, in adipocytes but not tumor cells reduced obesity-related tumor progression. Mechanistically, we identified that GSH entered tumor cells and directly bound to lysosomal integral membrane protein-2 (scavenger receptor class B, member 2 [SCARB2]), interfering with the interaction between its N and C termini. This, in turn, recruited mTORC1 to lysosomes through ARF1, leading to the activation of mTOR signaling. Overall, we demonstrated that GSH links obesity and breast cancer progression by acting as an activator of mTOR signaling. Targeting the GSH/SCARB2/mTOR axis could benefit breast cancer patients with obesity.PMID:39442522 | DOI:10.1016/j.cmet.2024.09.013

Am J Hum Genet. 2024 Oct 21:S0002-9297(24)00368-9. doi: 10.1016/j.ajhg.2024.09.008. Online ahead of print.ABSTRACTBalancing the tradeoff between quantity and quality of phenotypic data is critical in omics studies. Measurements below the limit of quantification (BLQ) are often tagged in quality control fields, but these flags are currently underutilized in human genetics studies. Extreme phenotype sampling is advantageous for mapping rare variant effects. We hypothesize that genetic drivers, along with environmental and technical factors, contribute to the presence of BLQ flags. Here, we introduce "hypometric genetics" (hMG) analysis and uncover a genetic basis for BLQ flags, indicating an additional source of genetic signal for genetic discovery, especially from phenotypic extremes. Applying our hMG approach to n = 227,469 UK Biobank individuals with metabolomic profiles, we reveal more than 5% heritability for BLQ flags and report biologically relevant associations, for example, at APOC3, APOA5, and PDE3B loci. For common variants, polygenic scores trained only for BLQ flags predict the corresponding quantitative traits with 91% accuracy, validating the genetic basis. For rare coding variant associations, we find an asymmetric 65.4% higher enrichment of metabolite-lowering associations for BLQ flags, highlighting the impact of putative loss-of-function variants with large effects on phenotypic extremes. Joint analysis of binarized BLQ flags and the corresponding quantitative metabolite measurements improves power in Bayesian rare variant aggregation tests, resulting in an average of 181% more prioritized genes. Our approach is broadly applicable to omics profiling. Overall, our results underscore the benefit of integrating quality control flags and quantitative measurements and highlight the advantage of joint analysis of population-based samples and phenotypic extremes in human genetics studies.PMID:39442521 | DOI:10.1016/j.ajhg.2024.09.008

J Pharm Biomed Anal. 2024 Oct 17;253:116521. doi: 10.1016/j.jpba.2024.116521. Online ahead of print.ABSTRACTMetastasis is the leading cause of mortality in cervical cancer (CC), with a particular prevalence of lymph node and lung metastases. Patients with CC who have developed distant metastases typically face a poor prognosis, and there is a scarcity of non-invasive strategies for predicting CC metastasis. In this study, we utilized label-free proteomics and untargeted metabolomics to analyze plasma samples from 25 non-metastatic, 14 with lung metastasis, and 15 with lymph node metastasis CC patients. Pathway enrichment analysis revealed a shared inflammatory process between the two metastatic groups, while the central carbon metabolism in cancer showed distinct features in the lung metastasis cohort. Additionally, cholesterol metabolism, hypoxia-inducible factor 1, and ferroptosis signaling pathways were specifically altered in the lymph node metastasis group. Utilizing the receiver operating characteristic curve analysis and Random Forest algorithm, we identified two distinct biomarker panels for the prediction of lung metastasis and lymph node metastasis, respectively. The lung metastasis panel includes properdin, neural cell adhesion molecule 1, and keratin 6 A, whereas the lymph node metastasis panel consists of quiescin sulfhydryl oxidase 1, paraoxonase 1, and keratin 6 A. Each panel exhibited significant diagnostic potential, with high area under the curve (AUC) values for lung metastasis (training set: 0.989, testing set: 0.789) and lymph node metastasis (training set: 0.973, testing set: 0.900). This study conducted an integrated proteomic and metabolomic analysis to clarify the factors contributing to lung and lymph node metastases in CC and has successfully established two biomarker panels for their prediction.PMID:39442446 | DOI:10.1016/j.jpba.2024.116521

Animal. 2024 Sep 24;18(11):101343. doi: 10.1016/j.animal.2024.101343. Online ahead of print.ABSTRACTLaying ducks in cage environments face various stressors, including the fear of novelty, which negatively affects their behaviour and performance. The reasons behind the variation in behaviour under identical stress conditions are not well understood. This study investigated how different behaviours affect production performance, immune response, antioxidant capabilities, adrenal gene expression, and serum metabolite profiles in caged laying ducks subjected to the same stressor. Overall, 42-week-old laying ducks (N = 300) were selected, fed for 60 days, and simultaneously underwent behavioural tests. Based on their behavioural responses, 24 ducks were chosen and categorised into two groups: high-active avoidance (HAA) and low-active avoidance (LAA). The study utilised phenotypic, genetic, and metabolomic analyses, coupled with bioinformatics, to identify crucial biological processes, genes, and metabolites. The results indicated that ΔW (BW gain) and average daily egg weight (ADEW) were significantly lower in the HAA group compared to the LAA group (P < 0.05). By contrast, the feed-to-egg ratio was higher in the HAA group than in the LAA group (P < 0.05). Levels of serum immunoglobulin A, total antioxidant capacity, and the activities of enzymes like superoxide dismutase and catalase (CAT) were significantly lower in the HAA than in the LAA group (P < 0.05), whereas serum ACTH levels were significantly higher in HAA than in the LAA group (P < 0.05). The adrenal transcriptome analysis revealed 148 differentially expressed genes in the HAA group, with 97 up-regulated and 51 down-regulated. Moreover, enrichment analysis highlighted significant differences in two metabolic pathways: neuroactive ligand-receptor interaction and oxidative phosphorylation (P < 0.05). Serum metabolomics identified 11 differentially accumulated metabolites between the groups, with variations in up and down-regulation. Integrative analysis of phenotype, transcriptome, and metabolome data showed a strong correlation between the exosome component 3 (EXOSC3) gene, phenotypic traits, and differential metabolites. Thus, we deduced that the differences in average daily egg weight among ducks could be linked to variations in gabapentin and EXOSC3 gene expressions, affecting serum CAT levels.PMID:39442284 | DOI:10.1016/j.animal.2024.101343

Phytomedicine. 2024 Oct 9;135:156128. doi: 10.1016/j.phymed.2024.156128. Online ahead of print.ABSTRACTBACKGROUND: Cisplatin-induced acute kidney injury (AKI) is a complex and serious clinical issue, representing a major cause of hospital-acquired AKI. Alkaloids are the main active constituents of Aconitum carmichaelii Debx, which exhibit protective effects in several kidney disease models and against other acute organ injuries. However, its activity and mechanism of action in AKI treatment remain unclear.PURPOSE: This study aimed to elucidate the effect of Aconitum carmichaelii Debx (ACA) in a model of cisplain-induced AKI and comprehensively investigate its underlying mechanisms.METHODS: The major alkaloids in ACA were analyzed using high-performance liquid chromatography. Blood urea nitrogen (BUN) and serum creatine levels were measured using automated biochemical instruments. 16S rRNA sequencing, short-chain fatty acid (SCFA) analysis, fecal microbiota transplantation (FMT), non-targeted metabolomics, and transcriptomics were performed to systematically identify prospective biomarkers after ACA treatment. Anti-inflammatory and anti-oxidative stress activities were monitored using ELISA and western blotting.RESULTS: Four main compounds (fuziline, neoline, talatisamine, and songorine) were identified in ACA. ACA significantly alleviated cisplatin-induced AKI by reducing (BUN) and serum creatine levels and improving histopathological scores. Moreover, ACA balanced cisplatin-mediated confoundments in microbial composition and function, including decreasing the levels of Escherichia-Shigella, Clostridium, and Ruminococcus, as well as increasing Ligilactobacillus, Anaerotruncus, Bacteroides and Desulfovibrio levels, accompanied by uremic toxin reduction, and augmenting serum SCFAs. The FMT experiments further confirmed that ACA exerts anti-AKI effects by affecting gut microbiota. A multi-omics study has shown that ACA regulates glutathione and tryptophan metabolism and mediates pathways that trigger inflammatory responses. Finally, ACA reduced serum levels of inflammatory factors (IL-1β, IL-6, and TNF-α), restored enzymes of the antioxidative system (SOD and CAT) and GSH values, and decreased monoester diterpene alkaloid levels in the kidney by inhibiting the expression of NF-κB pathway-related proteins and increasing Nrf2/HO-1 pathway-related protein expression.CONCLUSION: ACA protects against cisplatin-induced AKI through its anti-inflammatory and antioxidant functions, which may be associated with the restoration of gut microbiota metabolism. ACA is a potential drug for AKI and other forms of organ damage related to the disruption of the gut microbiota.PMID:39442279 | DOI:10.1016/j.phymed.2024.156128

Food Chem. 2024 Oct 19;464(Pt 2):141728. doi: 10.1016/j.foodchem.2024.141728. Online ahead of print.ABSTRACTTo illustrate the mechnism of the better flavor and color in combined fermented sausages than single fermentation with L. sakei, the growth behavior, pH, and metabolomics of L. sakei in single fermentation and in combination with S. carnosus at 0, 3, 6, 12, 24, and 48 h were studied, and the sensory evaluation of fermented beef sausage was conducted. Through KEGG topology analysis found that L. sakei is related to caffeine metabolism and citrate cycle, L. sakei and S. carnosus are related to metabolism of purine metabolism, caffeine metabolism, and alanine, aspartate and glutamate metabolism. Compared with L. sakei fermentation alone, the compound fermentation with S. carnosus increased the content of asparagine. The content of the bitter substance tyrosine decreased during the compound fermentation. As starter cultures for the L. sakei applied to provide a basis for the fermented beef sausage.PMID:39442216 | DOI:10.1016/j.foodchem.2024.141728

J Agric Food Chem. 2024 Oct 23. doi: 10.1021/acs.jafc.4c07127. Online ahead of print.ABSTRACTTerpenoids are important secondary metabolites in Rubus. Rubusoside is a relatively specific diterpenoid bioactive component in the leaves of Chinese Sweet Tea (Rubus suavissimus). However, the terpenoid anabolic pathway of Rubus and the molecular mechanism underlying the specific accumulation of rubusoside in R. suavissimus remain unclear. Here, metabolomics and transcriptomics analyses were performed on differences in terpenoid metabolism levels between R. suavissimus (sweet leaves) and Rubus chingii (bitter leaves). Steviol glycosides and goshonosides primarily accumulated in R. suavissimus and R. chingii, respectively. Three pairs of highly homologous glycosyltransferase genes (UGT85A57, UGT75L20, and UGT75T4) associated with rubusoside biosynthesis in the two Rubus species were identified. The three pairs of UGT proteins in both species could glycosylate steviol. Thus, the transcriptional regulation of UGTs in R. suavissimus appears to play a pivotal role in rubusoside accumulation. Our findings provide insights into the differences in terpenoid metabolism between R. suavissimus and R. chingii and reveal the molecular mechanism of rubusoside accumulation in R. suavissimus.PMID:39442010 | DOI:10.1021/acs.jafc.4c07127

Blood. 2024 Oct 23:blood.2024025366. doi: 10.1182/blood.2024025366. Online ahead of print.ABSTRACTAntibiotic-induced microbiome dysbiosis is widespread in oncology, adversely affecting outcomes and side effects of various cancer treatments, including immune checkpoint inhibitors and chimeric antigen receptor T (CAR-T) cell therapies. In this study, we observed that prior exposure to broad-spectrum ABX with extended anaerobic coverage like piperacillin-tazobactam and meropenem was associated with worsened anti-CD19 CAR-T therapy survival outcomes in large B-cell lymphoma patients (n=422), compared to other ABX classes. In a discovery subset of these patients (n=67), we found that the use of these ABX was in turn associated with substantial dysbiosis of gut microbiome function, resulting in significant alterations of the gut and blood metabolome, including microbial effectors such as short-chain fatty acids (SCFAs) and other anionic metabolites, findings that were largely reproduced in an external validation cohort (n=58). Broader evaluation of circulating microbial metabolites revealed reductions in indole and cresol derivatives, as well as trimethylamine N-oxide, in patients who received ABX treatment (discovery n=40, validation n=28). These findings were recapitulated in an immune-competent CAR-T mouse model, where meropenem-induced dysbiosis led to a systemic dysmetabolome and decreased murine anti-CD19 CAR-T efficacy. Furthermore, we demonstrate that SCFAs can enhance the metabolic fitness of CAR-T cells, leading to improved tumor killing capacity. Together, these results suggest that broad-spectrum ABX deplete metabolically active commensals whose metabolites are essential for enhancing CAR-T efficacy, shedding light on the intricate relationship between ABX exposure, microbiome function and their impact on CAR-T cell efficacy. This highlights the potential for modulating the microbiome to augment CAR-T immunotherapy.PMID:39441941 | DOI:10.1182/blood.2024025366

J Cancer Res Clin Oncol. 2024 Oct 23;150(10):471. doi: 10.1007/s00432-024-05990-1.ABSTRACTThe incidence of brain tumors among children is second only to acute lymphoblastic leukemia, but the mortality rate of brain tumors has exceeded that of leukemia, making it the most common cause of death among children. Medulloblastoma (MB) is the most common type of brain tumor among children. Malignant brain tumors have strong invasion and metastasis capabilities, can spread through cerebrospinal fluid, and have a high mortality rate. In 2010, the World Health Organization first divided MB into four molecular subtypes based on molecular markers: WNT, Sonic hedgehog (SHH), Group 3, and Group 4. MB is a highly heterogeneous tumor. Different molecular subtypes of MB have significantly different clinical, pathological, and molecular characteristics. The prognosis of MB varies significantly among patients with different subtypes of this cancer. Thus, it is needed to study new diagnostic and therapeutic strategies. Metabolomics is an advanced analytical technology that uses various spectroscopic, electrochemical, and data analysis technologies to study and analyze the body's metabolites. By detecting changes in metabolite types and quantities in different types of samples, it can sensitively discover the physiological and pathological changes in the body. It has great potential for clinical application and personalized medicine. It is promising and can help develop personalized treatment strategies based on the metabolic profiles of individuals. It can unravel the unique metabolic profiles of MB, which may revolutionize our understanding of the disease and improve patients' outcomes.PMID:39441459 | DOI:10.1007/s00432-024-05990-1

Funct Integr Genomics. 2024 Oct 23;24(6):194. doi: 10.1007/s10142-024-01481-1.ABSTRACTExtreme anthropogenic activities and current farming techniques exacerbate the effects of water and soil impurity by hazardous heavy metals (HMs), severely reducing agricultural output and threatening food safety. In the upcoming years, plants that undergo exposure to HM might cause a considerable decline in the development as well as production. Hence, plants have developed sophisticated defensive systems to evade or withstand the harmful consequences of HM. These mechanisms comprise the uptake as well as storage of HMs in organelles, their immobilization via chemical formation by organic chelates, and their removal using many ion channels, transporters, signaling networks, and TFs, amid other approaches. Among various cutting-edge methodologies, omics, most notably genomics, transcriptomics, proteomics, metabolomics, miRNAomics, phenomics, and epigenomics have become game-changing approaches, revealing information about the genes, proteins, critical metabolites as well as microRNAs that govern HM responses and resistance systems. With the help of integrated omics approaches, we will be able to fully understand the molecular processes behind plant defense, enabling the development of more effective crop protection techniques in the face of climate change. Therefore, this review comprehensively presented omics advancements that will allow resilient and sustainable crop plants to flourish in areas contaminated with HMs.PMID:39441418 | DOI:10.1007/s10142-024-01481-1

Arch Toxicol. 2024 Oct 23. doi: 10.1007/s00204-024-03876-2. Online ahead of print.ABSTRACTMulti-omics data integration has been repeatedly discussed as the way forward to more comprehensively cover the molecular responses of cells or organisms to chemical exposure in systems toxicology and regulatory risk assessment. In Canzler et al. (Arch Toxicol 94(2):371-388. https://doi.org/10.1007/s00204-020-02656-y ), we reviewed the state of the art in applying multi-omics approaches in toxicological research and chemical risk assessment. We developed best practices for the experimental design of multi-omics studies, omics data acquisition, and subsequent omics data integration. We found that multi-omics data sets for toxicological research questions were generally rare, with no data sets comprising more than two omics layers adhering to these best practices. Due to these limitations, we could not fully assess the benefits of different data integration approaches or quantitatively evaluate the contribution of various omics layers for toxicological research questions. Here, we report on a multi-omics study on thyroid toxicity that we conducted in compliance with these best practices. We induced direct and indirect thyroid toxicity through Propylthiouracil (PTU) and Phenytoin, respectively, in a 28-day plus 14-day recovery oral rat toxicity study. We collected clinical and histopathological data and six omics layers, including the long and short transcriptome, proteome, phosphoproteome, and metabolome from plasma, thyroid, and liver. We demonstrate that the multi-omics approach is superior to single-omics in detecting responses at the regulatory pathway level. We also show how combining omics data with clinical and histopathological parameters facilitates the interpretation of the data. Furthermore, we illustrate how multi-omics integration can hint at the involvement of non-coding RNAs in post-transcriptional regulation. Also, we show that multi-omics facilitates grouping, and we assess how much information individual and combinations of omics layers contribute to this approach.PMID:39441382 | DOI:10.1007/s00204-024-03876-2

Probiotics Antimicrob Proteins. 2024 Oct 23. doi: 10.1007/s12602-024-10379-0. Online ahead of print.ABSTRACTWe previously observed that supplementation with antimicrobial peptides facilitated the average daily weight gain, net meat, and carcass weights of Holstein bulls. To expand our knowledge of the possible impact of antimicrobial peptides on cecum microbiota, further investigations were conducted. In this study, 18 castrated Holstein bulls with insignificant weight differences and 10 months of age were split randomly into two groups. The control group (CK) was fed a basic diet, whereas the antimicrobial peptide group (AP) was supplemented with 8 g of antimicrobial peptides for 270 days. After slaughter, metagenomic and metabolomic sequencing analyses were performed on the cecum contents. The results showed significantly higher levels of amylase, cellulase, protease, and lipase in the CK than in the AP group (P ≤ 0.05). The levels of β-glucosidase and xylanase (P ≤ 0.05), and acetic and propionic acids (P ≤ 0.01), were considerably elevated in the AP than in the CK group. The metagenome showed variations between the two groups only at the bacterial level, and 3258 bacteria with differences were annotated. A total of 138 differential abundant genes (P < 0.05) were identified in the CAZyme map, with 65 genes more abundant in the cecum of the AP group and 48 genes more abundant in the cecum of the CK group. Metabolomic analysis identified 68 differentially expressed metabolites. Conjoint analysis of microorganisms and metabolites revealed that Lactobacillus had the greatest impact on metabolites in the AP group and Brumimicrobium in the CK group. The advantageous strains of the AP group Firmicutes bacterium CAG:110 exhibited a strong symbiotic relationship with urodeoxycholic acid and hyodeoxycholic acid. This study identified the classification characteristics, functions, metabolites, and interactions of cecal microbiota with metabolites that contribute to host growth performance. Antimicrobial peptides affect the cecal microorganisms, making the use of nutrients more efficient. The utilization of hemicellulose in the cecum of ruminants may contribute more than cellulose to their production performance.PMID:39441337 | DOI:10.1007/s12602-024-10379-0

ACS Chem Neurosci. 2024 Oct 23. doi: 10.1021/acschemneuro.4c00345. Online ahead of print.ABSTRACTThe occurrence and development of depression are closely related to disorders of the brain and peripheral substances. Abnormal metabolites in the blood affect the signal regulation function of the nerve center, which is one of the key factors for depression episodes. This study was focused on metabolites in serum and the mechanism of its antidepressant in the hippocampus. In the present study, serum metabolites in patients with depression were screened by metabolomic techniques. Various depressive mouse models and behavioral tests were used to assess its antidepressant effects. The expressions of inflammatory signaling were detected by using Western blot, ELISA, and immunofluorescence. We found that the metabolite hypoxanthine in the serum of patients with depression was significantly reduced, and the same result was also found in two mouse models of depression such as chronic unpredictable mild stress (CUMS) and social defeat stress (SD). By administering different doses of hypoxanthine (5, 10, 15 mg/kg), we found that only 15 mg/kg was able to significantly reduce the latency and increase food consumption in the novelty suppressed-feeding test (NSF), which was also able to reverse the depressive phenotypes of mice in the CUMS model after a single administration at 2 h later. Hypoxanthine obviously reduced the expressions of inflammation in serum and downregulated the expressions of MAPK and NLRP3-related pathways in the hippocampus in CUMS mice. Moreover, hypoxanthine also suppressed the activations of glial cells including GFAP and IBA-1 in hippocampal CA1, CA3, and dentate gyrus (DG). To sum up, hypoxanthine exerted antidepressant effect relying on the inhibition of peripheral and hippocampal inflammations by regulating MAPK, NLRP3-related pathways, and glial cells. This was the first time that we have found a disordered metabolite in patients with depression and further systematically demonstrated its efficacy and potential mechanism of antidepressants, providing new ideas for antidepressant drug development.PMID:39441118 | DOI:10.1021/acschemneuro.4c00345

J Agric Food Chem. 2024 Oct 23. doi: 10.1021/acs.jafc.4c04989. Online ahead of print.ABSTRACTStreptomyces species can form beneficial relationships with hosts as endophytes, including the phytopathogen-inhibiting strain, Streptomyces griseoaurantiacusMH191, isolated from wheat plants. Using genomic characterization and untargeted metabolomics, we explored the capacity of strain MH191 to inhibit a range of fungal phytopathogens through the production of secondary metabolites. Complete genome assembly of strain MH191 predicted 24 biosynthetic gene clusters. Secondary metabolite production was assessed following culture on six different media, with the detection of 205 putative compounds. Members of the manumycin family, undecylprodigiosin, and desferrioxamine were identified as the predominant metabolites. Antifungal activity was validated for undecylprodigiosin and manumycin. These compounds were produced from different BGCs, which showed similarity to asukamycin, undecylprodigiosin, and FW0622 gene clusters, respectively. The growth of strain MH191 on different media illustrated the metabolic regulation of these gene clusters and the strain's extended chemical potential, with the asukamycin gene cluster alone, producing a variety of antifungal metabolites. The study highlights the extended chemical capability of strain MH191, which could be exploited as a biological control agent for designing future crop protection solutions.PMID:39440812 | DOI:10.1021/acs.jafc.4c04989

J Clin Transl Hepatol. 2024 Oct 28;12(10):865-877. doi: 10.14218/JCTH.2024.00203. Epub 2024 Sep 19.ABSTRACTLiver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function, triggered by factors both within and outside the liver. While the definition of acute-on-chronic liver failure (ACLF) may vary by region, it is universally recognized for its association with multiorgan failure, a robust inflammatory response, and high short-term mortality rates. Recent advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ACLF. Additionally, immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell functions. Therefore, understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for ACLF. This review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions, offering novel perspectives for immune regulation and therapeutic management of liver failure.PMID:39440217 | PMC:PMC11491507 | DOI:10.14218/JCTH.2024.00203

Front Immunol. 2024 Oct 8;15:1445769. doi: 10.3389/fimmu.2024.1445769. eCollection 2024.ABSTRACTINTRODUCTION: Elevated blood eosinophil levels in patients with chronic obstructive pulmonary disease (COPD) with or without asthma are linked to increased exacerbations and the effectiveness of inhaled corticosteroid treatment. This study aimed to delineate the inflammatory cellular properties of eosinophils in patients with asthma-COPD overlap (ACO) and eosinophilic COPD (eCOPD).METHODS: Eosinophils were isolated from the peripheral blood of healthy volunteers, patients with non-eCOPD, and those with ACO/eCOPD. Multi-omics analysis involving transcriptomics, proteomics, and lipidomics was performed, followed by bioinformatic data analyses. In vitro experiments using eosinophils from healthy volunteers were conducted to investigate the molecular mechanisms underlying cellular alterations in eosinophils.RESULTS: Proteomics and transcriptomics analyses revealed cellular characteristics in overall COPD patients represented by viral infection (elevated expression of sterol regulatory element-binding protein-1) and inflammatory responses (elevated levels of IL1 receptor-like 1, Fc epsilon receptor Ig, and transmembrane protein 176B). Cholesterol metabolism enzymes were identified as ACO/eCOPD-related factors. Gene Ontology and pathway enrichment analyses demonstrated the key roles of antiviral responses, cholesterol metabolism, and inflammatory molecules-related signaling pathways in ACO/eCOPD. Lipidomics showed the impaired synthesis of cyclooxygenase-derived mediators including prostaglandin E2 (PGE2) in ACO/eCOPD. In vitro assessment confirmed that IL-33 or TNF-α stimulation combined with IL-5 and IFN-γ stimulation induced cellular signatures in eosinophils in ACO/eCOPD. Atorvastatin, dexamethasone, and PGE2 differentially modulated these inflammatory changes.DISCUSSION: ACO/eCOPD is associated with viral infection and an inflammatory milieu. Therapeutic strategies using statins and inhaled corticosteroids are recommended to control these pathogenic changes.PMID:39439801 | PMC:PMC11493663 | DOI:10.3389/fimmu.2024.1445769

Br J Nutr. 2024 Oct 23:1-35. doi: 10.1017/S0007114524002526. Online ahead of print.ABSTRACTThe increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre "Western diets". Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast β-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinemia and insulin resistance in a murine model. Here we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2.5g/day of maltodextrin (placebo) or yeast β-1,3/1,6-D-glucan (treatment). Yeast β-glucan (Wellmune) lowered insulin resistance (HOMA-IR) compared to the placebo maltodextrin after 8 weeks of consumption. TNFα was significantly lower after 4 weeks of β-glucan supplementation. Significantly higher faecal concentrations of several bile acids were detected in the treatment group when compared to the placebo after 8 weeks. These included tauroursodeoxycholic acid (TUDCA) which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast β-glucan was independent of any changes in faecal microbiota composition or short-chain fatty acid (SCFA) levels. Our findings highlight the potential of yeast β-glucan to lower insulin resistance in patients with T2DM.PMID:39439317 | DOI:10.1017/S0007114524002526

Alzheimers Dement. 2024 Oct 22. doi: 10.1002/alz.14249. Online ahead of print.ABSTRACTBACKGROUND: Metabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). Although metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic comparison of the diseases has not yet been performed.METHODS: We analyzed 342 postmortem brain samples from the Mayo Clinic Brain Bank and examined 658 metabolites in the cerebellar cortex and the temporal cortex between the two tauopathies.RESULTS: Our findings indicate that both diseases display oxidative stress associated with lipid metabolism, mitochondrial dysfunction linked to lysine metabolism, and an indication of tau-induced polyamine stress response. However, specific to AD, we detected glutathione-related neuroinflammation, deregulations of enzymes tied to purines, and cognitive deficits associated with vitamin B.DISCUSSION: Our findings underscore vast alterations in the brain's metabolome, illuminating shared neurodegenerative pathways and disease-specific traits in AD and PSP.HIGHLIGHTS: First high-throughput metabolic comparison of Alzheimer's diesease (AD) versus progressive supranuclear palsy (PSP) in brain tissue. Cerebellar cortex (CER) shows substantial AD-related metabolic changes, despite limited proteinopathy. AD impacts both CER and temporal cortex (TCX); PSP's changes are primarily in CER. AD and PSP share metabolic alterations despite major pathological differences.PMID:39439201 | DOI:10.1002/alz.14249

J Agric Food Chem. 2024 Oct 22. doi: 10.1021/acs.jafc.4c06793. Online ahead of print.ABSTRACTThis work was designed for the in-depth characterization and holistic comparison of up to 12 ginseng varieties, which can benefit the development of functional foods and ensure their authenticity in the food industry. An online comprehensive two-dimensional liquid chromatography/quadrupole time-of-flight mass spectrometry (2D-LC/QTOF-MS) approach was established by configurating the XCharge C18 and HSS Cyano columns. Under the optimal conditions, we characterized a total of 1146 ginsenosides (including 876 potentially new compounds) from 12 ginseng varieties by reference to an in-house library of 573 known ginsenosides and 70 reference compounds. The online 2D-LC/QTOF-MS-based untargeted metabolomics workflows were developed, by which 126 potential ginsenoside markers were unveiled and utilized to establish the key identification points for each ginseng species. Compared with the conventional liquid chromatography/mass spectrometry metabolomics, our multidimensional chromatography approach performed better in discriminating multiple ginseng varieties. This work demonstrates a potent and practical methodology to identify easily confused functional plants.PMID:39439127 | DOI:10.1021/acs.jafc.4c06793