PubMed

Plant Cell Environ. 2024 Oct 17. doi: 10.1111/pce.15210. Online ahead of print.ABSTRACTPeach Leaf Curl Disease, caused by Taphrina deformans, is characterized by reddish hypertrophic and hyperplasic leaf areas. To comprehend the biochemical imbalances caused by the fungus, dissected symptomatic (C) and asymptomatic areas (N) from leaves with increasing disease extension were analyzed by an integrated approach including metabolomics, lipidomics, proteomics, and complementary biochemical techniques. Drastic metabolic differences were identified in C areas with respect to either N areas or healthy leaves, including altered chloroplastic functioning and composition, which differs from the typical senescence process. In C areas, alteration in redox-homoeostasis proteins and in triacylglycerols content, peroxidation and double bond index were observed. Proteomic data revealed induction of host enzymes involved in auxin and jasmonate biosynthesis and an upregulation of phenylpropanoid and mevalonate pathways and downregulation of the plastidic methylerythritol phosphate route. Amino acid pools were affected, with upregulation of proteins involved in asparagine synthesis. Curled areas exhibited a metabolic shift towards functioning as a sink tissue importing sugars, probably from N areas, and producing energy through fermentation and respiration and reductive power via the pentose phosphate route. Identifying the metabolic disturbances leading to disease symptoms is a key step in designing strategies to prevent or delay the progression of the disease.PMID:39420723 | DOI:10.1111/pce.15210

Mol Nutr Food Res. 2024 Oct 17:e2300672. doi: 10.1002/mnfr.202300672. Online ahead of print.ABSTRACTSCOPE: The gut microbiota plays a role in fat accumulation and energy homeostasis. Therefore, probiotic supplementation may improve metabolic parameters and control body weight.METHODS AND RESULTS: In this study, mice are fed either a high-fat diet (HFD) or an HFD supplemented with oral gavage of a mixture of three probiotic strains, Bifidobacterium lactis Lafti B94, Lactobacillus plantarum HA-119, and Lactobacillus helveticus Lafti L10 for 7 weeks. It finds that probiotic supplementation modulates body weight gain, food energy efficiency, and fat accumulation caused by the HFD. This probiotic mix prevents liver damage and lipid metabolic disorders in HFD-fed obese mice. The probiotic supplementation significantly downregulates the expression of the proinflammatory cytokines interleukin-1β, tumor necrosis factor-α, and malondialdehyde (MDA) in the liver and upregulated catalase (CAT), superoxide dismutase (SOD), and nuclear respiratory factor 1 (Nrf1) expression. Mice supplemented with the probiotic mix also show different microbiota compositions, with an increase in Clostridia_UCG-014 and Lachnospiraceae_nk4a136_group and a decrease in the Dubosiella genus compared with those in mice fed only an HFD. Finally, the amounts of fecal pentanoic acid and the three bile acid species increase in mice with probiotic supplementation.CONCLUSION: Treatment with a combination of a mixture of three probiotic strains, B. lactis Lafti B94, L. plantarum HA-119, and L. helveticus Lafti L10 for 7 weeks, ameliorates the effects of HFD induced obesity in mice.PMID:39420712 | DOI:10.1002/mnfr.202300672

Nat Prod Res. 2024 Oct 17:1-5. doi: 10.1080/14786419.2024.2417371. Online ahead of print.ABSTRACTSolanum violaceum Ortega is a perennial tropical shrub traditionally used as conventional medicine for the treatment of various ailments. The present study aims to validate the use of S. violaceum Ortega leaf (SVLE) and fruit extracts (SVFE) in traditional medicine through untargeted metabolomics and assessment of its biological and phytochemical properties. GC-MS-based untargeted metabolomics identified derivatives of 59 and 50 metabolites in SVLE and SVFE, respectively. The study authenticated the presence of several bioactive compounds including Diosgenin, n-Hexadecanoic acid and Stigmasterol in SVLE and Ricinoleic acid, 9,12-Octadecadienoic acid and Oleic acid in SVFE, thus corroborating the use of the plant in traditional medicine as an anti-inflammatory and antioxidant agent. Both SVFE and SVLE demonstrated potent antioxidant, protease and anticoagulant properties with partial inhibitory effects on the physiological function of Factor Xa. This study provides insight into the phytochemical and pharmacological properties of S. violaceum and its potential ethnomedicinal relevance.PMID:39420624 | DOI:10.1080/14786419.2024.2417371

Nurs Res. 2024 Oct 10. doi: 10.1097/NNR.0000000000000783. Online ahead of print.ABSTRACTBACKGROUND: In the U.S., Black adults have the highest prevalence of obesity and hypertension, increasing their risk of morbidity and mortality. Caregivers of persons with dementia are also at increased risk of morbidity and mortality due to the demands of providing care. Thus, Black caregivers-who are the second largest group of caregivers of persons with dementia in the U.S.-have the highest risks for poor health outcomes among all caregivers. However, the physiologic changes associated with multiple chronic conditions in Black caregivers are poorly understood.OBJECTIVES: In this study, metabolomics were compared to the metabolic profiles of Black caregivers with obesity, with or without hypertension. Our goal was to identify metabolites and metabolic pathways that could be targeted to reduce obesity and hypertension rates in this group.METHODS: High-resolution, untargeted metabolomic assays were performed on plasma samples from 26 self-identified Black caregivers with obesity, 18 of whom had hypertension. Logistic regression and pathway analyses were employed to identify metabolites and metabolic pathways differentiating caregivers with obesity only and caregivers with both obesity and hypertension.RESULTS: Key metabolic pathways discriminating caregivers with obesity only and caregivers with obesity and hypertension were butanoate and glutamate metabolism, fatty acid activation/biosynthesis, and the carnitine shuttle pathway. Metabolites related to glutamate metabolism in the butanoate metabolism pathway were more abundant in caregivers with hypertension, while metabolites identified as butyric acid/butanoate and R-(3)-hydroxybutanoate were less abundant. Caregivers with hypertension also had lower levels of several unsaturated fatty acids.DISCUSSION: In Black caregivers with obesity, multiple metabolic features and pathways differentiated among caregivers with and without hypertension. If confirmed in future studies, these findings would support ongoing clinical monitoring and culturally tailored interventions focused on nutrition (particularly polyunsaturated fats and animal protein), exercise, and stress management to reduce the risk of hypertension in Black caregivers with obesity.PMID:39420455 | DOI:10.1097/NNR.0000000000000783

Biol Sex Differ. 2024 Oct 17;15(1):80. doi: 10.1186/s13293-024-00652-w.ABSTRACTBACKGROUND: Placental macrophages, Hofbauer cells (HBC) are the only fetal immune cell population within the stroma of healthy placenta along pregnancy. They are central players in maintaining immune tolerance during pregnancy. Immunometabolism emerged a few years ago as a new field that integrates cellular metabolism with immune responses, however, the immunometabolism of HBC has not been explored yet. Here we studied the sex-specific differences in the phenotypic, functional and immunometabolic profile of HBC.METHODS: HBC were isolated from human term placentas (N = 31, 16 from male and 15 female neonates). Ex vivo assays were carried out to assess active metabolic and endoplasmic reticulum stress pathways by flow cytometry, confocal microscopy, gene expression and in silico approaches.RESULTS: HBC from female placentas displayed a stronger M2 phenotype accompanied by high rates of efferocytosis majorly sustained on lipid metabolism. On the other hand, male HBC expressed a weaker M2 phenotype with higher glycolytic metabolism. LPS stimulation reinforced the glycolytic metabolism in male but not in female HBC. Physiological endoplasmic reticulum stress activates IRE-1 differently, since its pharmacological inhibition increased lipid mobilization, accumulation and efferocytosis only in female HBC. Moreover, differential sex-associated pathways accompanying the phenotypic and functional profiles of HBC appeared related to the placental villi environment.CONCLUSIONS: These results support sex-associated effects on the immunometabolism of the HBC and adds another layer of complexity to the intricate maternal-fetal immune interaction.PMID:39420346 | DOI:10.1186/s13293-024-00652-w

Mol Cancer. 2024 Oct 17;23(1):231. doi: 10.1186/s12943-024-02152-2.NO ABSTRACTPMID:39420364 | DOI:10.1186/s12943-024-02152-2

Lipids Health Dis. 2024 Oct 17;23(1):339. doi: 10.1186/s12944-024-02317-4.ABSTRACTBACKGROUND: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles.METHODS: This is a cross-sectional analysis of a prospectively enrolled multicenter cohort. PWH without alcohol abuse or known liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Lipidomic and metabolomic profiling was undertaken with nuclear magnetic resonance (NMR) spectroscopy. Hepatic steatosis was defined as CAP ≥ 263 dB/m and clinically significant fibrosis (CSF) as LSM ≥ 8 kPa. Logistic regression models assessed associations between MASLD, CSF and lipidomic and metabolic parameters.RESULTS: Of 190 participants (71% cisgender male, 96% on antiretroviral therapy), 58% had MASLD and 12% CSF. Mean (SD) age was 48.9 (12.1) years and body mass index (BMI) 29.9 (6.4) kg/m2. Compared to PWH without MASLD (controls), PWH with MASLD had lower HDL-C but higher total triglyceride, VLDL-C, branched-chain amino acids, GlycA, trimethylamine N-oxide levels, Lipoprotein-Insulin Resistance and Diabetes Risk Indices. There were no significant differences in these parameters between participants with MASLD with or without CSF. In a multivariable regression analysis, MASLD was independently associated with changes in most of these parameters after adjustment for age, gender, race/ethnicity, type 2 diabetes mellitus, BMI, and lipid lowering medications use.CONCLUSIONS: MASLD in PWH is independently associated with altered advanced lipoprotein and targeted metabolic profiles, indicating a higher CVD risk in this population.PMID:39420356 | DOI:10.1186/s12944-024-02317-4

J Transl Med. 2024 Oct 17;22(1):945. doi: 10.1186/s12967-024-05757-9.ABSTRACTBACKGROUND: Although numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA).METHODS: Demographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors.RESULTS: LSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p < 0.05). Moreover, serum metabolite levels were significantly altered, revealing intergroup differences in 229 metabolites mapped to 72 metabolic pathways (p < 0.05, VIP > 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p < 0.05). Furthermore, pairwise correlations were detected between gut microbiota and serum metabolites (p < 0.05). Functional neuroimaging analysis revealed that LSG increased functional connectivity in cognitive-related frontotemporal networks (FPN, p < 0.01). Additionally, normalization of the default mode network (DMN) and salience network (SN) connectivity was observed after LSG (p < 0.001). Further canonical correlation and correlation analysis suggested that the cognitive-related brain network changes induced by LSG were associated with key gut microbiota species (Akkermansia, Blautia, Collinsella, Phascolarctobacterium, and Ruminococcus, p < 0.05) and neuroactive metabolites (Glycine, L-Serine, DL-Dopa, SM (d18:1/24:1(15Z), p < 0.05).CONCLUSION: These findings indicate the pathophysiological role of the microbiota-gut-brain axis in enhancing cognitive function after bariatric surgery, and the study provides a basis for clinical dietary adjustments, probiotic supplementation, and guidance for bariatric surgery, but further research is still needed.TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100049403. Registered 02 August 2021, https://www.chictr.org.cn/ .PMID:39420319 | DOI:10.1186/s12967-024-05757-9

BMC Plant Biol. 2024 Oct 18;24(1):980. doi: 10.1186/s12870-024-05663-8.ABSTRACTBACKGROUND: Drought stress is a significant abiotic stressor that hinders growth, development, and crop yield in soybeans. Strigolactones (SLs) positively regulate plant resistance to drought stress. However, the impact of foliar application of SLs having different concentrations on soybean growth and metabolic pathways related to osmoregulation remains unknown. Therefore, to clarify the impact of SLs on soybean root growth and cellular osmoregulation under drought stress, we initially identified optimal concentrations and assessed key leaf and root indices. Furthermore, we conducted transcriptomic and metabolic analyses to identify differential metabolites and up-regulated genes.RESULTS: The results demonstrated that drought stress had a significant impact on soybean biomass, root length, root surface area, water content and photosynthetic parameters. However, when SLs were applied through foliar application at appropriate concentrations, the accumulation of ABA and soluble protein increased, which enhanced drought tolerance of soybean seedlings by regulating osmotic balance, protecting membrane integrity, photosynthesis and activating ROS scavenging system. This also led to an increase in soybean root length, lateral root number and root surface area. Furthermore, the effects of different concentrations of SLs on soybean leaves and roots were found to be time-sensitive. However, the application of 0.5 µM SLs had the greatest beneficial impact on soybean growth and root morphogenesis under drought stress. A total of 368 differential metabolites were screened in drought and drought plus SLs treatments. The up-regulated genes were mainly involved in nitrogen compound utilization, and the down-regulated metabolic pathways were mainly involved in maintaining cellular osmoregulation and antioxidant defenses.CONCLUSIONS: SLs enhance osmoregulation in soybean plants under drought stress by regulating key metabolic pathways including Arachidonic acid metabolism, Glycerophospholipid metabolism, Linoleic acid metabolism, and Flavone and flavonol biosynthesis. This study contributes to the theoretical understanding of improving soybean adaptability and survival in response to drought stress.PMID:39420293 | DOI:10.1186/s12870-024-05663-8

Nat Commun. 2024 Oct 17;15(1):8965. doi: 10.1038/s41467-024-53353-8.ABSTRACTInfection is a devastating post-surgical complication, often requiring additional procedures and prolonged antibiotic therapy. This is especially relevant for craniotomy and prosthetic joint infections (PJI), both of which are characterized by biofilm formation on the bone or implant surface, respectively, with S. aureus representing a primary cause. The local tissue microenvironment likely has profound effects on immune attributes that can influence treatment efficacy, which becomes critical to consider when developing therapeutics for biofilm infections. However, the extent to which distinct tissue niches influence immune function during biofilm development remains relatively unknown. To address this, we compare the metabolomic, transcriptomic, and functional attributes of leukocytes in mouse models of S. aureus craniotomy and PJI complemented with patient samples from both infection modalities, which reveals profound tissue niche-dependent differences in nucleic acid, amino acid, and lipid metabolism with links to immune modulation. These signatures are both spatially and temporally distinct, differing not only between infection sites but evolving over time within a single model. Collectively, this demonstrates that biofilms elicit unique immune and metabolic responses that are heavily influenced by the local tissue microenvironment, which will likely have important implications when designing therapeutic approaches targeting these infections.PMID:39420209 | DOI:10.1038/s41467-024-53353-8

EMBO J. 2024 Oct 17. doi: 10.1038/s44318-024-00271-6. Online ahead of print.ABSTRACTTriple-negative breast cancer (TNBC) metabolism and cell growth uniquely rely on glutamine uptake by the transporter ASCT2. Despite previous data reporting cell growth inhibition after ASCT2 knockdown, we here show that ASCT2 CRISPR knockout is tolerated by TNBC cell lines. Despite the loss of a glutamine transporter and low rate of glutamine uptake, intracellular glutamine steady-state levels were increased in ASCT2 knockout compared to control cells. Proteomics analysis revealed upregulation of macropinocytosis, reduction in glutamine efflux and increased glutamine synthesis in ASCT2 knockout cells. Deletion of ASCT2 in the TNBC cell line HCC1806 induced a strong increase in macropinocytosis across five ASCT2 knockout clones, compared to a modest increase in ASCT2 knockdown. In contrast, ASCT2 knockout impaired cell proliferation in the non-macropinocytic HCC1569 breast cancer cells. These data identify macropinocytosis as a critical secondary glutamine acquisition pathway in TNBC and a novel resistance mechanism to strategies targeting glutamine uptake alone. Despite this adaptation, TNBC cells continue to rely on glutamine metabolism for their growth, providing a rationale for targeting of more downstream glutamine metabolism components.PMID:39420093 | DOI:10.1038/s44318-024-00271-6

Nat Commun. 2024 Oct 17;15(1):8983. doi: 10.1038/s41467-024-52973-4.ABSTRACTH3K27M diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPG), exhibit cellular heterogeneity comprising less-differentiated oligodendrocyte precursors (OPC)-like stem cells and more differentiated astrocyte (AC)-like cells. Here, we establish in vitro models that recapitulate DMG-OPC-like and AC-like phenotypes and perform transcriptomics, metabolomics, and bioenergetic profiling to identify metabolic programs in the different cellular states. We then define strategies to target metabolic vulnerabilities within specific tumor populations. We show that AC-like cells exhibit a mesenchymal phenotype and are sensitized to ferroptotic cell death. In contrast, OPC-like cells upregulate cholesterol biosynthesis, have diminished mitochondrial oxidative phosphorylation (OXPHOS), and are accordingly more sensitive to statins and OXPHOS inhibitors. Additionally, statins and OXPHOS inhibitors show efficacy and extend survival in preclinical orthotopic models established with stem-like H3K27M DMG cells. Together, this study demonstrates that cellular subtypes within DMGs harbor distinct metabolic vulnerabilities that can be uniquely and selectively targeted for therapeutic gain.PMID:39419964 | DOI:10.1038/s41467-024-52973-4

Antonie Van Leeuwenhoek. 2024 Oct 17;118(1):21. doi: 10.1007/s10482-024-02028-x.ABSTRACTMicroalgae are significantly influenced by light quality and quantity, whether in their natural habitats or under laboratory and industrial culture conditions. The present study examines the adaptive responses of the marine microalga Tetraselmis chuii to different light regimes, using a cost-effective filtering method and a multi-omics approach. Microalgal growth rates were negatively affected by all filtered light regimes. After six days of cultivation, growth rate for cultures exposed to blue and green filtered light was 67%, while for red filter was 83%, compared to control cultures. Transcriptomic analysis revealed that the usage of green filters resulted in upregulation of transcripts involved in ribosome biogenesis or coding for elongation factors, exemplified by a 2.3-fold increase of TEF3. On the other hand, a 2.7-fold downregulation was observed in photosynthesis-related petJ. Exposure to blue filtered light led to the upregulation of transcripts associated with pyruvate metabolism, while photosynthesis was negatively impacted. In contrast, application of red filter induced minor transcriptomic alterations. Regarding metabolomic analysis, sugars, amino acids, and organic acids exhibited significant changes under different light regimes. For instance, under blue filtered light sucrose accumulated over 6-fold, while aspartic acid content decreased by 4.3-fold. Lipidomics analysis showed significant accumulation of heptadecanoic and linoleic acids under green and red light filters. Together, our findings indicate that filter light can be used for targeted metabolic manipulation.PMID:39419938 | DOI:10.1007/s10482-024-02028-x

Planta. 2024 Oct 17;260(5):118. doi: 10.1007/s00425-024-04544-6.ABSTRACTHeat stress reduces strawberry growth and fruit quality by impairing photosynthesis, disrupting hormone regulation, and altering mineral nutrition. Multi-omics studies show extensive transcriptional, post-transcriptional, proteomic and metabolomic under high temperatures. Garden strawberry is a globally cultivated, economically important fruit crop highly susceptible to episodic heat waves and chronically rising temperatures associated with climate change. Heat stress negatively affects the growth, development, and quality of strawberries. Elevated temperatures affect photosynthesis, respiration, water balance, hormone signaling, and carbohydrate metabolism in strawberries. Heat stress reduces the size and number of leaves, the number of crowns, the differentiation of flower buds, and the viability of pollen and fruit set, ultimately leading to a lower yield. On a physiological level, heat stress reduces membrane stability, increases the production of reactive oxygen species, and reduces the antioxidant capacity of strawberries. Heat-tolerant varieties have better physiological and biochemical adaptation mechanisms compared to heat-sensitive varieties. Breeding heat-tolerant strawberry cultivars involves selection for traits such as increased leaf temperature, membrane thermostability, and chlorophyll content. Multi-omics studies show extensive transcriptional, post-transcriptional, proteomic, metabolomic, and ionomic reprogramming at high temperatures. Integrative-omics approaches combine multiple omics datasets to obtain a systemic understanding of the responses to heat stress in strawberries. This article summarizes the deciphering of strawberry responses to heat stress using physiological, biochemical, and molecular approaches that will enable the development of resilient adaptation strategies that sustain strawberry production under global climate change.PMID:39419853 | DOI:10.1007/s00425-024-04544-6

J Appl Microbiol. 2024 Oct 17:lxae269. doi: 10.1093/jambio/lxae269. Online ahead of print.ABSTRACTAIMS: Vulvovaginal candidiasis (VVC) is a prevalent condition affecting a significant proportion of women worldwide, with recurrent episodes leading to detrimental effects on quality of life. While treatment with clotrimazole is common, the specific alterations it evokes in the vaginal bacteriome and metabolome were previously underexplored.METHODS AND RESULTS: In this prospective study, we enrolled reproductive-age women diagnosed with single VVC and conducted comprehensive analyses of vaginal fungi, bacteriome, and metabolome before and after local clotrimazole treatment. We observed a significant reduction in Candida albicans and notable improvements in vaginal cleanliness. Advanced sequencing revealed substantial shifts in the vaginal bacteriome, with an increase in Lactobacillus-dominant communities post-treatment. Our findings identified 17 differentially abundant bacterial species, including notable decreases in pathogenic anaerobes such as Gardnerella vaginalis, Dialister micraerophilus, and Aerococcus christensenii, suggesting a restoration of a healthier microbial balance. Furthermore, metabolomic analysis revealed significant changes in 230 metabolites, particularly within lipid metabolism pathways, with marked downregulation of lipid-related compounds linked to inflammation. Correlation studies indicated a strong interplay between lipid metabolites and specific bacterial species, emphasizing the influence of clotrimazole treatment on microbial and metabolic interactions. Importantly, predictive models using microbiota and metabolite signatures demonstrated high accuracy in distinguishing pre- and post-treatment states.CONCLUSIONS: This research highlights clotrimazole's dual role in effectively clearing Candida infection and promoting a healthier vaginal microenvironment, paving the way for novel microbial and metabolomic-based diagnostic approaches to enhance VVC management and understand its underlying mechanisms.PMID:39419780 | DOI:10.1093/jambio/lxae269

Autophagy. 2024 Oct 17:1-3. doi: 10.1080/15548627.2024.2411854. Online ahead of print.ABSTRACTThe plasma concentration of the macroautophagy/autophagy inhibitor DBI/ACBP (diazepam binding inhibitor, acyl-CoA binding protein) increases with aging and body mass index (BMI). Both advanced age and obesity are among the most important risk factors for the development of cancer. We observed that patients with cancer predisposition syndromes due to mutations in BRCA1, BRCA2 and TP53 exhibit abnormally high plasma DBI/ACBP levels. Additionally, patients without known cancer predisposition syndromes also manifest higher DBI/ACBP levels before imminent cancer diagnosis (within 0-3 years) as compared to age and BMI-matched controls who remain cancer-free. Thus, supranormal plasma DBI/ACBP constitutes a risk factor for later cancer development. Mouse experimentation revealed that genetic or antibody-mediated DBI/ACBP inhibition can delay the development or progression of cancers. In the context of chemoimmunotherapy, DBI/ACBP neutralization enhances tumor infiltration by non-exhausted effector T cells but reduces infiltration by regulatory T cells. This resulted in better cancer control in models of breast cancer, non-small cell lung cancer and sarcoma. We conclude that DBI/ACBP constitutes an actionable autophagy checkpoint for improving cancer immunosurveillance. Abbreviation: BMI, body mass index; CTL, cytotoxic T lymphocyte; DBI, diazepam binding inhibitor, acyl-CoA binding protein; mAb, monoclonal antibody; NSCLC, non-small cell lung cancer; PDCD1/PD-1, programmed cell death 1; scRNA-seq, single-cell RNA sequencing; Treg, regulatory T cell.PMID:39419485 | DOI:10.1080/15548627.2024.2411854

Bioresour Technol. 2024 Oct 15:131644. doi: 10.1016/j.biortech.2024.131644. Online ahead of print.ABSTRACTThe fixation of carbon dioxide (CO2) using microalgae is a promising CO2 capture and utilization technology. Microalgae have also been suggested as a potential treatment for biogas slurry (BS). This study screened microalgae capable of tolerating both high CO2 concentrations and BS, assessed their CO2 fixation and pollutant removal capabilities, and evaluated the potential use of the resulting algal biomass. Chlamydopodium sp. HS01, which showed the highest tolerance to 15% CO2 and BS, was selected due to its strong growth, CO2 fixation, and ammonia nitrogen removal abilities. The generated biomass also demonstrated significant potential for bioenergy production. Metabolomics analysis revealed that the lipid composition of HS01 underwent substantial changes under 15% CO2 alone and in combination with BS, likely as a stress adaptation strategy. Overall, HS01 presents high potential for resource utilization of CO2 coupled with actual BS.PMID:39419404 | DOI:10.1016/j.biortech.2024.131644

Chemosphere. 2024 Oct 15:143541. doi: 10.1016/j.chemosphere.2024.143541. Online ahead of print.ABSTRACTAlthough the hazards of environmental microplastics (MPs) are well known, it is unclear which of their characteristics have the greatest effects on organism. We investigated the toxic effects of oral administration according to physical properties, including the shape of fragmented polyethylene terephthalate (PET) (FrPET) and fibrous PET (FiPET) MPs. After 72 h of exposure, apoptosis and phagocytic activity varied significantly among juvenile rockfish (Sebastes schlegeli) exposed to both FrPET and FiPET. The levels of immune-related genes and hepatic metabolic activity also increased after exposure to both shapes of MPs, but the variation in responses was greater in fish exposed to FiPET compared with those exposed to FrPET. The transcriptomic and metabolomics analysis results indicated that the maintenance and homeostasis of immune system was affected by oral exposure to FrPET and FiPET. The amino acid metabolic processes were identified in rockfish exposed to FrPET, but the notch signaling pathway were evident in the FiPET exposure group. Metabolomics analysis revealed that oral ingestion of MP fibers led to a stronger inflammatory response and greater oxidative stress in juvenile rockfish. These results can be used to understand environmentally dominant MP toxic effects such as type, size, shapes, as well as to prioritize ecotoxicological management.PMID:39419335 | DOI:10.1016/j.chemosphere.2024.143541

Clin Chim Acta. 2024 Oct 15:120004. doi: 10.1016/j.cca.2024.120004. Online ahead of print.ABSTRACTAs a large and structurally diverse family of small molecules, bile acids play a crucial role in regulating lipid, glucose, and energy metabolism. In the human body, bile acids share a similar chemical structure with many isomers, exhibit little difference in polarity, and possess various physiological activities. The types and contents of bile acids present in different diseases vary significantly. Therefore, comprehensive and accurate detection of the content of various types of bile acids in different biological samples can not only provide new insights into the pathogenesis of diseases but also facilitate the exploration of novel strategies for disease diagnosis, treatment, and prognosis. The detection of disease-induced changes in bile acid profiles has emerged as a prominent research focus in recent years. Concurrently, targeted metabolomics methods utilizing high-performance liquid chromatography-mass spectrometry (HPLC-MS) have progressively established themselves as the predominant technology for the separation and detection of bile acids. Bile acid profiles will increasingly play an important role in diagnosis and guidance in the future as the relationship between disease and changes in bile acid profiles becomes clearer. This highlights the growing diagnostic value of bile acid profiles and their potential to guide clinical decision-making. This review aims to explore the significance of bile acid profiles in clinical diagnosis from four perspectives: the synthesis and metabolism of bile acids, techniques for detecting bile acid profiles, changes in bile acid profiles associated with diseases, and the challenges and future prospects of applying bile acid profiles in clinical settings.PMID:39419312 | DOI:10.1016/j.cca.2024.120004

J Ethnopharmacol. 2024 Oct 15:118950. doi: 10.1016/j.jep.2024.118950. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The Cissus gongylodes has traditionally been used in the diet of indigenous people in Brazil and in traditional medicine for kidney stone removal and inflammatory diseases. The active compounds responsible for these pharmacological activities are unknown.AIM OF THE STUDY: This study aims to isolate, for the first time, the compounds in the decoction of C. gongylodes leaves responsible for their anti-inflammatory and anti-urolithiatic ethnopharmacological properties.MATERIALS AND METHODS: The most active fractions of the C. gongylodes leaf decoction were fractionated using SPE-C18 and the compounds were purified through HPLC-UV-DAD. The decoction fractions and isolated compounds were evaluated for their anti-inflammatory and anti-urolithiatic activities. The anti-inflammatory activity was assessed using an ex vivo assay in human blood induced by LPS and calcium ionophore, measuring inflammatory mediators, PGE2 and LTB4. The anti-urolithiatic activity was evaluated using an in vitro experimental model with human urine to determine the dissolution of the most recurrent calcium oxalate (CaOx) crystals. Additionally, the decoction was chemically characterized through metabolomic analysis using UHPLC-ESI-HRMS.RESULTS: The isolated compounds from the decoction of C. gongylodes, including rutin, eriodictyol 3'-O-glycoside, and isoquercetin, have demonstrated significant multi-target actions. These components act as anti-inflammatory agents by inhibiting the release of main inflammatory mediators, PGE2 and LTB4. Additionally, they exhibit anti-urolithiatic properties, promoting the dissolution of calcium oxalate (CaOx) crystals. Furthermore, the characterization of the decoction by UHPLC-ESI-HRMS revealed a high content of flavonoids, mainly glycosylated flavonoids.CONCLUSIONS: The results support the traditional use of C. gongylodes decoction, identifying the compounds responsible for its anti-inflammatory and anti-urolithiatic effects. The decoction fractions and isolated compounds exhibited dual anti-inflammatory activity, effectively inhibiting key inflammatory pathways and potentially presenting fewer adverse effects while also promoting the dissolution of CaOx crystals associated with urolithiasis. The multi-target action displayed by C. gongylodes is particularly desirable in the treatment of urolithiasis, as inflammation and PGE2 production precede and contribute to the formation of CaOx crystals in the kidneys. Based on these actions, C. gongylodes emerges as a potent source of active compounds for the development of new treatments for urolithiasis.PMID:39419303 | DOI:10.1016/j.jep.2024.118950