PubMed

Int J Biol Macromol. 2024 Oct 14:136487. doi: 10.1016/j.ijbiomac.2024.136487. Online ahead of print.ABSTRACTFlammulina velutipes residues (FVR) are the waste culture medium derived from the collection of Flammulina velutipes fruiting bodies, with an annual output that remains largely unexplored. The characteristics of digestion and fermentation of Flammulina velutipes residues polysaccharide (FVRP) are still relatively unknown. This study investigated the structure of the gut microbiota through 16 s rDNA gene sequencing and analyzed changes in short-chain fatty acid (SCFA) content via targeted metabolome analysis. The aim was to explore the prebiotic activity of FVRP based on a simulated digestion model combined with an in vitro anaerobic fermentation model. The results demonstrated that FVRP did not exhibit significant changes during in vitro digestion and fermentation but did enhance antioxidant activity. Furthermore, FVRP was found to rapidly reduce the pH value and increase SCFA production in the fermentation broth from lactic acid bacteria and human feces. Notably, FVRP altered the gut microbiota structure, significantly increasing the relative abundance of Firmicutes and Bacteroidota. Thus, FVRP could be considered a promising prebiotic food and feed additive that promotes the generation of short-chain fatty acids by modulating gut microbiota.PMID:39414219 | DOI:10.1016/j.ijbiomac.2024.136487

Sci Total Environ. 2024 Oct 14:176858. doi: 10.1016/j.scitotenv.2024.176858. Online ahead of print.ABSTRACTPer- and polyfluoroalkyl substances (PFAS), especially long-chain perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), are increasingly acknowledged as a potential inflammatory bowel diseases (IBD) risk factor. Perfluorobutane sulfonate (PFBS), one kind of shorter chain alternative, has been reported to exhibit similar health hazards to those long-chain PFAS. However, the underlying mechanism underpinning PFBS-induced colonic inflammation has not been sufficiently elucidated. The T-helper-17 (Th17)/regulatory T (Treg) imbalance is a crucial event for the pathogenesis of colonic inflammation. In this study, we aimed to reveal whether and how perinatal PFBS exposure leads to the Th17/Treg imbalance and colonic inflammation in offspring. We firstly demonstrated in vivo that early-life PFBS exposure (0.5 mg/kg, 5 mg/kg) led to increased intestinal permeability and colonic inflammation accompanied by decreased expressions of tight junction protein 1 (Tjp1) and claudin-4 (Cldn4) and increased expressions of interleukin 17A (IL-17A) in colon of rat offspring. Further results indicated that PFBS exposure induces the Th17/Treg imbalance through upregulating the expression of retinoic acid receptor-related orphan receptor gamma t (Ror-γt) and transforming growth factor beta (TGF-β) and downregulating of forkhead box protein 3 (Foxp3) and IL-10 in colon. Moreover, metabolomics analyses indicated that bile secretion metabolism was significantly altered under PFBS exposure. The reduction of lithocholic acid and deoxycholic acid was closely related to the changes of TGF-β and IL-10 in colon, and may contribute to the perturbation of Th17/Treg balance and colonic inflammation. These results provide evidences for the immunotoxicity of PFBS and reveal the potential contribution to colonic inflammation, which raises concern on the health effects and risk assessment of short-chain PFAS.PMID:39414058 | DOI:10.1016/j.scitotenv.2024.176858

Biochim Biophys Acta Rev Cancer. 2024 Oct 14:189193. doi: 10.1016/j.bbcan.2024.189193. Online ahead of print.ABSTRACTCD8+ T-cell exhaustion has been identified as a significant contributor to immunosuppression and immune escape in triple-negative breast cancer (TNBC). Dysfunction due to cell exhaustion is characterized by reduced effector capacity and sustained expression of inhibitory receptors (IRs). The factors contributing to CD8+ T-cell exhaustion are multifaceted, encompassing external influences such as the upregulation of IRs, reduction of effector cytokines, and internal changes within the immune cell, including transcriptomic alterations, epigenetic landscape remodeling, and metabolomic shifts. The impact of the altered TNBC tumor microenvironment (TME) on Tex is also a critical consideration. The production of exhausted CD8+ T-cells (CD8+ Tex) is positively correlated with poor prognosis and reduced response rates to immunotherapy in TNBC patients, underscoring the urgent need for the development of novel TNBC immunotherapeutic strategies that target the mechanisms of CD8+ T-cell exhaustion. This review delineates the dynamic trajectory of CD8+ T-cell exhaustion development in TNBC, provides an update on the latest research advancements in understanding its pathogenesis, and offers insights into potential immunotherapeutic strategies.PMID:39413858 | DOI:10.1016/j.bbcan.2024.189193

Med. 2024 Oct 9:S2666-6340(24)00374-X. doi: 10.1016/j.medj.2024.09.007. Online ahead of print.ABSTRACTBACKGROUND: Viremic non-progressors (VNPs) represent an exceptional and uncommon subset of people with HIV-1, characterized by the remarkable preservation of normal CD4+ T cell counts despite uncontrolled viral replication-a trait reminiscent of natural hosts of simian immunodeficiency virus. The mechanisms orchestrating evasion from HIV-1 pathogenesis in human VNPs remain elusive, primarily due to the absence of integrative studies.METHODS: We implemented a novel single-cell and multiomics approach to comprehensively characterize viral, genomic, transcriptomic, and metabolomic factors driving this exceedingly rare disease phenotype in 16 VNPs and 29 HIV+ progressors.FINDINGS: Genetic predisposition to the VNP phenotype was evidenced by a higher prevalence of CCR5Δ32 heterozygosity, which was associated with lower levels of CCR5 expression and a lower frequency of infected cells in peripheral circulation. We also observed reduced levels of plasma markers of intestinal disruption and attenuated interferon responses in VNPs. These factors potentially drive the other phenotypic traits of immune preservation in this population, including the unaltered tryptophan metabolic profile, reduced activation of cytotoxic lymphocytes, and reduced bystander CD4+ T cell apoptosis.CONCLUSIONS: In summary, our comprehensive analysis identified intricate factors collectively associated with the unique immunovirological equilibrium in VNPs, shedding light on potential avenues for therapeutic exploration in managing HIV pathogenesis.FUNDING: The work was supported by funding from the Spanish Ministry of Science and Innovation and the National Institutes of Health (NIH).PMID:39413785 | DOI:10.1016/j.medj.2024.09.007

J Agric Food Chem. 2024 Oct 16. doi: 10.1021/acs.jafc.4c06888. Online ahead of print.ABSTRACTThe brown marmorated stink bug (Halyomorpha halys) poses a significant threat to hazelnut crops by affecting kernel development and causing quality defects, reducing the market value. While previous studies have identified bitter-tasting compounds in affected kernels, the impact of stink bug feeding on the hazelnut metabolome, particularly concerning aroma precursors, remains underexplored. This study aims to map the nonvolatile metabolome and volatilome of hazelnut samples obtained by caging H. halys on different cultivars in two locations to identify markers for diagnosing stink bug damage. Using a multiomic approach involving headspace solid-phase microextraction (HS-SPME), comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF MS), and liquid chromatography-high-resolution mass spectrometry (LC-HRMS), both raw and roasted hazelnuts are analyzed, with artificial intelligence (AI) and machine learning tools employed to explore data correlations. The study finds that the hazelnut metabolome and volatilome exhibit high chemical complexity with significant classes of compounds such as aldehydes, ketones, alcohols, and terpenes identified in both raw and roasted hazelnuts. Multivariate analysis indicates that the orchard location significantly impacts the metabolome, followed by damage type, with cultivar differences being less pronounced. Partial least-squares discriminant analysis (PLS-DA) models achieve high predictive accuracy for orchard location (99%) and damage type (≈80%), with the roasted volatilome showing the highest predictive accuracy. Correlation matrices reveal significant relationships between raw hazelnut metabolites and aroma compounds in roasted samples, suggesting potential markers for stink bug damage that could guide the quality assessment and mitigation strategies. Data fusion techniques further enhance classification performance, particularly in predicting damage type, underscoring the potential of integrating multiple data sets for comprehensive quality assessment.PMID:39413774 | DOI:10.1021/acs.jafc.4c06888

Poult Sci. 2024 Sep 28;103(12):104370. doi: 10.1016/j.psj.2024.104370. Online ahead of print.ABSTRACTThe hypothalamic-pituitary-gonadal (HPG) axis regulates egg laying through control hormones secretion in poultry. In this study, the serum hormones (12 samples per stage), serum biochemical indexes (12 samples per stage), and ovarian metabolites (8 samples per stage) of Muscovy breeder ducks were detected at prelaying stage (PT), start of laying stage (ST), high laying stage (HT), and the end of laying stage (ET). The serum hormones of Muscovy ducks were measured at 8:00, 13:00, 18:00, 23:00, and 4:00 within 1 d. The TG, TP, ALB, and GLB were significantly increased, while HDL-C was significantly decreased at ST as compared to PT (P < 0.05). Serum Na, Cl, Ca, P, and K showed significant rise at ST as compared to PT. Serum Na, Cl, Ca, and K were significantly declined, while P was significantly increased at ET as compared to HT (P < 0.05). Serum FSH, LH, PRL, E2, P4 levels peaked at ST (P < 0.05) with only FSH and LH fluctuated significantly within 1 ovulation cycle at ST (P < 0.05). Differential metabolites showed continued ovarian aging. The decline of nucleic acid metabolism occured in ST, the decline of sugar metabolism occurred in ET, and the decline of amino acid metabolism continued at all stages. Temporal expression patterns and correlation analyses indicated a high correlation between ovarian cAMP and serum reproductive hormone levels across different reproductive stages. In conclusion, this study revealed the changes in serum hormones, serum biochemical indicators, and ovarian metabolites, as well as the relationship between serum hormones and ovarian metabolites.PMID:39413699 | DOI:10.1016/j.psj.2024.104370

J Pharm Biomed Anal. 2024 Oct 10;252:116515. doi: 10.1016/j.jpba.2024.116515. Online ahead of print.ABSTRACTAcute lung injury is a significant global health issue, and its treatment is becoming a hot topic of the researchers. To investigate the feasibility of miRNA-150-5p tail vein injection in the treatment of SiO2-induced acute lung injury through the regulation of gut microbiota and serum metabolites based on multiomics technology. Twenty-four mice were randomly divided into the control, SiO2 and miRNA-150-5p intervention groups. The SiO2 and miRNA-150-5p intervention groups received a single intranasal dose of 100 µL 4 % SiO2 suspension. Meanwhile, the miRNA-150-5p intervention group was administered with two tail vein injections of miRNA-150-5p (15 nmol each per mouse) on the day of successful modelling and on the third day post modelling. Metagenomics and metabolomics techniques were used to measure gut microbiota and serum metabolites, respectively. Tail vein injection of miRNA-150-5p improved SiO2-induced acute lung injury and reduced the secretion of inflammatory factors interleukin (IL)-6, tumour necrosis factor-α and IL-1β. These conditions altered the structure of gut microbiota, which resulted in the notable modulation of eight species at the species level. In addition, tail vein injection of miRNA-150-5p considerably reduced the levels of substances, such as phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol, in the glycerophospholipid metabolism and glycosylphosphatidylinositol-anchor biosynthesis pathways. Tail vein injection of miRNA-150-5p can alleviate acute lung injury. Combined metagenomics and untargeted metabolomics revealed the miRNA-150-5p-mitigated SiO2-induced acute lung injury that occurred through the regulation of gut microbiota and serum metabolites.PMID:39413681 | DOI:10.1016/j.jpba.2024.116515

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Oct 11;52:101340. doi: 10.1016/j.cbd.2024.101340. Online ahead of print.ABSTRACTLow salinity environment is one of the key factors threatening the survival of aquatic organisms. Due to the strong adaptability of low salinity, Exopalaemon carinicauda is an ideal model to study the low salinity adaptation mechanism of crustaceans. In this study, E. carinicauda from the same family were divided into two groups, which were reared at salinity of 4 ‰ and 30 ‰, respectively. Integrated analysis of transcriptome and metabolome was used to uncover the mechanisms of E. carinicauda adaptation to chronic low salinity environment. Under the chronic low salinity stress, a total of 651 differentially expressed genes (DEGs) and 386 differential metabolites (DMs) were obtained, with the majority showing downregulation. These DEGs mainly involved MAPK signal transduction pathway and structural constituent of cuticle. Besides, chitin binding and chitin metabolism process were inhibited significantly. Among the DMs, lipids and lipid-like molecules, flavor amino acids and nucleotides were detected, which may be related to the adjustment of energy metabolism and flavor of muscle. In addition, ubiquinone and other terpenoid-quinone biosynthesis pathway and alanine, aspartate, and glutamate metabolic pathway were induced. These results will enrich our understanding of the molecular mechanism underlying the chronic low salinity tolerance in E. carinicauda, providing an important theoretical basis and practical guidance for the research and breeding, thereby promoting the sustainable development of aquaculture.PMID:39413659 | DOI:10.1016/j.cbd.2024.101340

Mar Pollut Bull. 2024 Oct 15;209(Pt A):117100. doi: 10.1016/j.marpolbul.2024.117100. Online ahead of print.ABSTRACTCadmium (Cd) is a typical heavy metal contaminant along China coasts. Clams Ruditapes philippinarum are widely distributed in multiple climatic zones. However, few research has been conducted on the different responses to Cd in clams from different climatic zones. In this study, the temperate zone Bohai Sea (BS) and tropical zone South China Sea (SCS) clams exhibited distinct background metabolome profiles, characterized by different strategies of osmotic regulation, energy metabolism, and anaerobiosis tendencies, suggesting different tolerance and enrichment capacities to Cd. After Cd treatments, the BS clams demonstrated quicker and higher accumulations of Cd than the SCS clams. Despite differences in their background metabolomes, both BS and SCS clams displayed similar metabolomic responses to Cd, such as anaerobiosis inhibition and increased energy demands. Overall, these findings suggested that the inconsistency of biological responses induced by geographic conditions should be considered in ecotoxicological studies. CAPSULE ABSTRACT: This study elucidated the biological differences in clams Ruditapes philippinarum from the Bohai Sea and South China Sea, and the metabolomic responses in these two clam populations after Cd (200 μg/L) treatments.PMID:39413473 | DOI:10.1016/j.marpolbul.2024.117100

Environ Sci Technol. 2024 Oct 16. doi: 10.1021/acs.est.4c07173. Online ahead of print.ABSTRACTDissolved organic matter (DOM) is an ultracomplex mixture that plays a central role in global biogeochemical cycles. Despite its importance, DOM remains poorly understood at the molecular level. Over the last decades, significant efforts have been made to decipher the chemical composition of DOM by high-resolution mass spectrometry (HR-MS) and liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS). Yet, the complexity and high degree of nonresolved isomers still hamper the full structural analysis of DOM. To address this challenge, we developed an offline two-dimensional (2D) LC approach using two reversed-phase dimensions with orthogonal pH levels, followed by MS/MS data acquisition and molecular networking. 2D-LC-MS/MS reduced the complexity of DOM, enhancing the quality of MS/MS spectra and increasing spectral annotation rates. Applying our approach to analyze coastal-surface DOM from Southern California (USA) and open-ocean DOM from the central North Pacific (Hawaii), we annotated in total more than 600 structures via MS/MS spectrum matching, which was up to 90% more than that in iterative 1D LC-MS/MS analysis with the same total run time. Our data offer unprecedented insights into the molecular composition of marine DOM and highlight the potential of 2D-LC-MS/MS approaches to decipher the chemical composition of ultracomplex samples.PMID:39413296 | DOI:10.1021/acs.est.4c07173

Cell Rep. 2024 Oct 15;43(10):114865. doi: 10.1016/j.celrep.2024.114865. Online ahead of print.ABSTRACTOrganisms integrate circadian and metabolic signals to optimize substrate selection to survive starvation, yet precisely how this occurs is unclear. Here, we show that hepatocyte Period1 (Per1) is selectively induced during fasting, and mice lacking hepatocyte Per1 fail to initiate autophagic flux, ketogenesis, and lipid accumulation. Transcriptomic analyses show failed induction of the fasting hepatokine Fgf21 in Per1-deficient mice, and single-nucleus multiome sequencing defines a putative responding hepatocyte subpopulation that fails to induce the chromatin accessibility near the Fgf21 locus. In vivo isotopic tracing and indirect calorimetry demonstrate that hepatocyte Per1-deficient mice fail to transit from oxidation of glucose to fat, which is completely reversible by exogenous FGF21 or by inhibiting pyruvate dehydrogenase. Strikingly, disturbing other core circadian genes does not perturb Per1 induction during fasting. We thus describe Per1 as an important mechanism by which hepatocytes integrate internal circadian rhythm and external nutrition signals to facilitate proper fuel utilization.PMID:39412985 | DOI:10.1016/j.celrep.2024.114865

J Agric Food Chem. 2024 Oct 16. doi: 10.1021/acs.jafc.4c05517. Online ahead of print.ABSTRACTThe peanut seed coat acts as a physical and biochemical barrier against Aspergillus flavus infection; however, the nature of the inhibitory chemicals in the peanut seed coat in general is not known. This study identified and characterized peanut seed coat metabolites that inhibit A. flavus growth and aflatoxin contamination. Selected peanut accessions grown under well-watered and water-deficit conditions were assayed for A. flavus resistance, and seed coats were metabolically profiled using liquid chromatography mass spectrometry. Kyoto Encyclopedia of Genes and Genome phenylpropanoid pathway reference analysis resulted in the identification of several seed coat metabolic compounds, and ten selected metabolites were tested for inhibition of A. flavus growth and aflatoxin contamination. Radial growth bioassay demonstrated that 2,5-dihydroxybenzaldehyde inhibited A. flavus growth (98.7%) and reduced the aflatoxin contamination estimate from 994 to 1 μg/kg. Scanning electron micrographs showed distorted hyphae and conidiophores in cultures of 2,5-dihydroxybenzaldehyde-treated A. flavus, indicating its potential use for field application as well as seed coat metabolic engineering.PMID:39412821 | DOI:10.1021/acs.jafc.4c05517

Anal Chem. 2024 Oct 16. doi: 10.1021/acs.analchem.4c05417. Online ahead of print.NO ABSTRACTPMID:39412394 | DOI:10.1021/acs.analchem.4c05417

J Sci Food Agric. 2024 Oct 16. doi: 10.1002/jsfa.13958. Online ahead of print.ABSTRACTBACKGROUND: Soybean reddening during storage and transportation has caused great concern due to the serious economic loss. However, the mechanism of reddening has not been clearly elucidated. In this study, metabolomics was employed to investigate the reasons for soybean reddening during storage.RESULTS: The results of multivariate statistical analysis showed that the metabolite level of red soybean was significantly different from that of normal soybean. The differentially expressed metabolites were mainly enriched by biosynthesis of secondary metabolites and amino acid metabolism. Metabolism analysis showed that the biosynthesis of cyanidin and betalains was enhanced in reddening soybean. In addition, it was found that phenolic and flavonoid compounds decreased, while quinones, furans and 5-hydroxymethylfurfural increased in reddening soybeans compared to normal soybeans.CONCLUSION: The upregulation of cyanidin and betalains was the main reason for soybean reddening. Besides, the oxidation of phenols and flavonoids, as well as Maillard reaction, also contributed to the color change. © 2024 Society of Chemical Industry.PMID:39412122 | DOI:10.1002/jsfa.13958

Anticancer Agents Med Chem. 2024 Oct 15. doi: 10.2174/0118715206327789241008162423. Online ahead of print.ABSTRACTBACKGROUND: Tender Coconut Water (TCW) is a nutrient-rich dietary supplement that contains in bioactive secondary metabolites and phytohormones with anti-oxidative and anti-inflammatory properties. Studies on TCW's anti-cancer properties are limited and the mechanism of its anti-cancer effects have not been defined.OBJECTIVE: In the present study, we investigate TCW for its anti-cancer properties and, using untargeted metabolomics, we identify components form TCW with potential anti-cancer activity.METHODOLOGY: Cell viability assay, BrdU incorporation assay, soft-agar assay, flow-cytometery, and Western blotting were used to analyze TCW's anticancer properties and to identify mechanism of action. Liquid chromatography- Tandem Mass Spectroscopy (LC-MS/MS) was used to identify TCW components.RESULTS: TCW decreased the viability and anchorage-independent growth of HepG2 hepatocellular carcinoma (HCC) cells and caused S-phase cell cycle arrest. TCW inhibited AKT and ERK phosphorylation leading to reduced ZEB1 protein, increased E-cadherin, and reduced N-cadherin protein expression in HepG2 cells, thus reversing the 'epithelial-to-mesenchymal' (EMT) transition. TCW also decreased the viability of Hep3B hepatoma, HCT-15 colon, MCF-7 and T47D luminal A breast cancer (BC) and MDA-MB-231 and MDA-MB-468 triplenegative BC cells. Importantly, TCW did not inhibit the viability of MCF-10A normal breast epithelial cells. Untargeted metabolomics analysis of TCW identified 271 metabolites, primarily lipids and lipid-like molecules, phenylpropanoids and polyketides, and organic oxygen compounds. We demonstrate that three components from TCW: 3-hydroxy-1-(4-hydroxyphenyl)propan-1-one, iondole-3-carbox aldehyde and caffeic acid inhibit the growth of cancer cells.CONCLUSION: TCW and its components exhibit anti-cancer effects. TCW inhibits the viability of HepG2 hepatocellular carcinoma cells by reversing the EMT process through inhibition of AKT and ERK signalling.PMID:39411967 | DOI:10.2174/0118715206327789241008162423

Plant Biotechnol J. 2024 Oct 16. doi: 10.1111/pbi.14447. Online ahead of print.ABSTRACTChickpea is the world's fourth largest grown legume crop, which significantly contributes to food security by providing calories and dietary protein globally. However, the increased frequency of drought stress has significantly reduced chickpea production in recent years. Here, we have performed a field experiment with 36 diverse chickpea genotypes to evaluate grain yield, photosynthetic activities and molecular traits related to drought stress. For metabolomics analysis, leaf tissue was collected at three time points representing different pod-filling stages. We identified L-threonic acid, fructose and sugar alcohols involved in chickpea adaptive drought response within the mid-pod-filling stage. A stress susceptibility index for each genotype was calculated to identify tolerance capacity under drought, distributing the 36 genotypes into four categories from best to worst performance. To understand how biochemical mechanisms control different traits for genetic improvement, we performed a differential Jacobian analysis, which unveiled the interplay between various metabolic pathways across three time points, including higher flux towards inositol interconversions, glycolysis for high-performing genotypes, fumarate to malate conversion, and carbon and nitrogen metabolism perturbations. Metabolic GWAS (mGWAS) analysis uncovered gene candidates involved in glycolysis and MEP pathway corroborating with the differential biochemical Jacobian results. Accordingly, this proposed data analysis strategy bridges the gap from pure statistical association to causal biochemical relations by exploiting natural variation. Our study offers new perspectives on the genetic and metabolic understanding of drought tolerance-associated diversity in the chickpea metabolome and led to the identification of metabolic control points that can be also tested in other legume crops.PMID:39411896 | DOI:10.1111/pbi.14447

Gut Microbes. 2024 Jan-Dec;16(1):2416517. doi: 10.1080/19490976.2024.2416517. Epub 2024 Oct 16.ABSTRACTInfecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed to prevent or treat various intestinal and extraintestinal diseases. However, full-scale clinical trials examining hookworm therapy are limited by the inability to scale-up the production of hookworm larvae to infect sufficient numbers of patients. With the aim of overcoming this challenge, this study infected four healthy individuals with hookworm larvae that had been reanimated from cryopreserved eggs to examine their viability and immunogenicity. We demonstrate that reanimated cryopreserved hookworm larvae establish a viable hookworm infection and elicit a similar immune response to larvae cultured from fresh stool. Furthermore, a refined understanding of the therapeutic mechanisms of hookworm is imperative to determine which diseases to target with hookworm therapy. To investigate potential therapeutic mechanisms, this study assessed changes in the immune cells, microbiome, and plasma metabolome in the four healthy individuals infected with cryopreserved hookworm larvae and another nine individuals infected with larvae cultured from freshly obtained stool. We identified potential immunoregulatory mechanisms by which hookworm may provide a beneficial effect on its host, including increased expression of CTLA-4 on regulatory T cells (Tregs) and upregulation of tryptophan metabolism. Furthermore, we found that a participant's baseline microbiome predicted the severity of symptoms and intestinal inflammation experienced during a controlled hookworm infection. In summary, our findings demonstrate the feasibility of full-scale clinical trials examining hookworm therapy by minimizing the reliance on human donors and optimizing the culturing process, thereby enabling viable hookworm larvae to be mass-produced and enabling on-demand inoculation of patients. Furthermore, this study provides insights into the complex interactions between helminths and their host, which could inform the development of novel therapeutic strategies.PMID:39411786 | DOI:10.1080/19490976.2024.2416517

Front Plant Sci. 2024 Oct 1;15:1378226. doi: 10.3389/fpls.2024.1378226. eCollection 2024.ABSTRACTMany soils face dual challenges of cadmium (Cd) contamination and salinization. However, the response of crops, especially wheat, to combined Cd and salinity stress is not understood. Here, wheat was grown in a hydroponic model for 14 days under single and combined Cd and NaCl stresses. Growth parameters, tissue Cd2+ and Na+ contents, and leaf chlorophyll (Chl), O2•-, and MDA levels were determined. Comparative transcriptomic and metabolomic analyses of the leaves were performed. The results showed that combined stress had a greater inhibitory effect on Chl contents and generated more O2•- and MDA, resulting in more severe wheat growth retardation than those under Cd or NaCl stress. Stress-induced decrease in Chl levels may be attributed to the inhibition of Chl biosynthesis, activation of Chl degradation, or a decline in glutamate content. Cd addition weakened the promotional effect of NaCl on SOS1 gene expression, thereby increasing the Na+ content. Contrastingly, NaCl supplementation downregulated the Nramp and ZIP gene expressions related to Cd uptake and transport, thereby impeding Cd2+ accumulation. All stresses enhanced tryptophan content via promoting tryptophan biosynthesis. Meanwhile, Cd and NaCl stresses activated phenylpropanoid biosynthesis and purine metabolism, respectively, thereby increasing the levels of caffeic acid, fumaric acid, and uric acid. Activating the TCA cycle was important in the wheat's response to combined stress. Additionally, NaCl and combined stresses affected starch and sucrose metabolism, resulting in sucrose and trehalose accumulation. Our findings provide a comprehensive understanding of the response of wheat to the combined Cd and salinity stress.PMID:39411653 | PMC:PMC11473431 | DOI:10.3389/fpls.2024.1378226

Front Vet Sci. 2024 Oct 1;11:1438717. doi: 10.3389/fvets.2024.1438717. eCollection 2024.ABSTRACTIn Holstein cows, β-casein, one of the most critical proteins in milk, exists in two main genotypes, A1 and A2. Herein, 45 Holstein cows [categorized into three groups based on β-casein A1A1, A1A2, and A2A2 genotypes (N = 15)] with the same feeding management and litter size were enrolled to explore differences in rumen microflora and metabolites across various β-casein genotypes. Rumen fluids were collected for metagenomics and metabolomics analyses. Metabolomics and weighted gene co-expression network analysis (WGCNA) revealed that arachidonic acid (AA), adrenic acid (AdA), glycocholic acid (GCA), and taurocholic acid (TCA) were significantly and positively correlated with milk fat % in dairy cows (p < 0.05). Furthermore, macro-genomics and Spearman's correlation analysis revealed significant positive correlations (p < 0.05) between the characteristic flora (g_Acetobacter, g_Pseudoxanthomonas, g_Streptococcus, and g_Pediococcus) and the five characteristic metabolites in the rumen of A2A2 dairy cows. Moreover, functional enrichment analysis revealed more genes enriched to the TRP channel's inflammatory mediator-regulated pathway and the mTOR signaling pathway in A2A2 genotyped cows. Additionally, the regulatory effects of AA on bovine mammary epithelial cells (BMECs) were examined using CCK-8, EdU, and qRT-PCR assays, revealing that AA promoted triglyceride (TG) synthesis and upregulated the milk fat marker genes including SREBF1, ACSS2, AGPAT6, and FASN. Overall, we identified characteristic microorganisms and metabolites in A2A2 Holstein cows and established that AA could be a biomarker for higher milk fat %.PMID:39411387 | PMC:PMC11475472 | DOI:10.3389/fvets.2024.1438717

Curr Pharm Biotechnol. 2024 Oct 9. doi: 10.2174/0113892010322778240927073617. Online ahead of print.ABSTRACTBACKGROUND: This study is the first report on the sequence of the transcriptome of Drimia indica, a non-model plant with medicinal properties found in a forest tribal belt, using the Illumina NovaSeq platform. The primary objectives of this study were to elucidate the gene expression profiles in different tissues, identify key regulatory genes and pathways involved in secondary metabolite biosynthesis, and explore the plant's potential pharmacological properties.METHODS: The study generated 670087 unigenes from both leaves and roots and identified putative homologs of annotated sequences against UniProt/Swiss-Prot and KEGG databases. The functional annotation of the identified unigenes revealed the secondary metabolite biosynthetic process as the most prominent pathway, with gene enrichment analysis predominantly accounting for secondary metabolite pathways, such as terpenoid, steroid, flavonoid, alkaloid, selenocompound, and cortisol synthesis. The study also identified regulatory genes NAC, Bhlh, WRKY, and C2H2 on the transcriptome dataset.RESULTS: The functionally annotated unigenes suggested phytocompounds in Drimia indica to have multi-potent properties, such as anti-cancer, anti-inflammatory, and anti-diabetic activities, which has been further validated by GC-MS-based metabolite profiling. Notably, we have identified two novel molecules, di-azo progesterone and 4H-pyran-4-one 2,3-dihydro-3,5-dihydroxy- 6-methyl, with potential BCL2 inhibitory anticancer properties, supported by stable binding interactions observed in molecular docking and dynamics simulations. Additionally, an abundance of mono-nucleotide SSR markers has been identified, useful for genetic diversity studies.CONCLUSION: This study provides a foundational understanding of the molecular mechanisms in Drimia indica, highlighting its potential as a source for novel therapeutic agents and contributing valuable insights for future pharmacological and agricultural applications. However, further in vivo studies are warranted to confirm these findings and validate their pharmacological efficacy and therapeutic potential. The SSR markers identified also offer valuable tools for molecular genetics, plant breeding, and sustainable drug development.PMID:39410890 | DOI:10.2174/0113892010322778240927073617