PubMed
Microplastics meet invasive plants: Unraveling the ecological hazards to agroecosystems
Sci Total Environ. 2023 Oct 11:167756. doi: 10.1016/j.scitotenv.2023.167756. Online ahead of print.ABSTRACTThe objective of this study was to assess the combined impact of environmental microplastic pollution and biological invasion which represent critical global eco-environmental challenges. The invasion of Solidago canadensis L. and soil microplastic contamination in the agroecosystem pose severe hazards to soil and plant ecology and human health. Oryza sativa L. (rice) was examined after individual and combined exposure to Solidago canadensis L. invasion (SI) and soil polyethylene microplastic contamination (MPc). Comparing the individual and combination treatments to the control, leaf biomass decreased, with varying changes in carbon, nitrogen, and phosphorus. Antioxidant enzyme activity and reactive oxygen species levels were significantly reduced following SI exposure and increased following the combined treatment (SI × MP). In contrast, ascorbate peroxidase and catalase activities were reduced after the combined treatment. Due to the confluence of various abiotic stressors, the combined treatment had a higher impact on leaf metabolites than the singular SI and MPc treatments. However, in comparison, the combined treatment significantly influenced the metabolic profile. In conclusion, the interaction between SI and MPc resulted in significant metabolic alterations. These changes were characterized by shifts in metabolite pools influenced by antioxidant enzyme activities and nutrient content, ultimately enhancing defense mechanisms within rice crops. Consequently, these stressors threaten the food safety, sustainability, and agricultural output of crops. The co-exposure of invasive plants and microplastics sheds light on the bio-ecological risks associated with microplastics in staple foods and offers valuable insights into the phytotoxicity of invasive plants in the presence of polyethylene microplastics.PMID:37832681 | DOI:10.1016/j.scitotenv.2023.167756
Efficacy evaluation and metabolomics analysis of raw and salt-processed Achyranthes bidentata Radix in zebrafish larvae for osteoporosis treatment
J Pharm Biomed Anal. 2023 Oct 10;237:115774. doi: 10.1016/j.jpba.2023.115774. Online ahead of print.ABSTRACTOsteoporosis, characterized by reduced bone density and the deterioration of bone tissue, poses a significant health challenge. The mechanisms underlying the protective effects of both raw and salt-processed Achyranthes bidentata Radix in osteoporosis remains unclear. This study endeavors to unravel and analyze the therapeutic mechanisms of these two forms of Achyranthes bidentata Radix in osteoporotic zebrafish larvae, utilizing GC/MS-based metabolomics. Zebrafish larvae were categorized into five groups: blank control, model, positive control, and groups treated with raw and salt-processed Achyranthes bidentata Radix. Following drug administration, notable enhancements were observed in both mineralized bone area and cumulative optical density. Various data mining techniques were employed, encompassing principal component analysis, orthogonal projections to latent structures discriminant analysis, and metabolic pathway analysis. These analyses unveiled 26 differential endogenous metabolites with significant biological implications in the zebrafish osteoporosis model. Among these metabolites, 12 (including acetamide, L-lactic acid, threonine, glycerol, rhamnose, azelaic acid, palmitic acid, inositol, stearic acid, hexadecane, sucrose, and glyceryl monostearate) were validated using standard compounds, exhibiting strong linear correlation coefficients (R2) ranging from 0.9917 to 0.9999. Furthermore, the method demonstrated excellent repeatability, as evidenced by relative standard deviation (RSD) values below 7.37%. The average spiked recoveries of the standard compounds fell within the range of ± 15%, ranging from 85.45% to 114.28%. Additionally, the stability of the standard compounds was confirmed after three freeze-thaw cycles, with RSD values remaining below 14.40%. Collectively, the metabolomic analysis unearthed potential biomarkers that could serve as indicators of the therapeutic effects of raw and salt-processed Achyranthes bidentata Radix on osteoporosis. This research offers valuable insights into the potential utilization of these herbal remedies as natural interventions for osteoporosis.PMID:37832477 | DOI:10.1016/j.jpba.2023.115774
Co-exposure to UV-aged microplastics and cadmium induces intestinal toxicity and metabolic responses in earthworms
J Hazard Mater. 2023 Oct 6;462:132737. doi: 10.1016/j.jhazmat.2023.132737. Online ahead of print.ABSTRACTAged microplastics (MPs) alter the interaction with heavy metals due to changes in surface properties. However, the combined toxicological effects of aged MPs on heavy metals in soil remain poorly understood. In this study, earthworms were employed as model animals to investigate the effects of aged MPs on the biotoxicity of cadmium (Cd) by simulating the exposure patterns of original and UV-aged MPs (polylactic acid (PLA) and polyethylene (PE)) with Cd. The results showed that UV-aging decreased the zeta potential and increased the specific surface area of the MPs, which enhanced the bioaccumulation of Cd and caused more severe oxidative stress to earthworms. Meanwhile, the earthworm intestines exhibited increased tissue damage, including chloragogenous tissue congestion lesions, and typhlosole damage. Furthermore, the combined exposure to UV-aged MPs and Cd enhanced the complexity of the microbial network in the earthworm gut and interfered with endocrine disruption, membrane structure, and energy metabolic pathways in earthworms. The results emphasized the need to consider the degradation of MPs in the environment. Hence, we recommend that future toxicological studies use aged MPs that are more representative of the actual environmental conditions, with the results being important for the risk assessment and management of MPs.PMID:37832442 | DOI:10.1016/j.jhazmat.2023.132737
Age-related influence on DNA damage, proteomic inflammatory markers and oxidative stress in hospitalized COVID-19 patients compared to healthy controls
Redox Biol. 2023 Oct 3;67:102914. doi: 10.1016/j.redox.2023.102914. Online ahead of print.ABSTRACTCOVID-19 infections are accompanied by adverse changes in inflammatory pathways that are also partly influenced by increased oxidative stress and might result in elevated DNA damage. The aim of this case-control study was to examine whether COVID-19 patients show differences in oxidative stress-related markers, unconjugated bilirubin (UCB), an inflammation panel and DNA damage compared to healthy, age-and sex-matched controls. The Comet assay with and without the treatment of formamidopyrimidine DNA glycosylase (FPG) and H2O2 challenge was used to detect DNA damage in whole blood. qPCR was applied for gene expression, UCB was analyzed via HPLC, targeted proteomics were applied using Olink® inflammation panel and various oxidative stress as well as clinical biochemistry markers were analyzed in plasma. Hospitalized COVID-19 patients (n = 48) demonstrated higher serum levels of 55 inflammatory proteins (p < 0.001), including hs-C-reactive protein levels (p < 0.05), compared to healthy controls (n = 48). Interestingly, significantly increased age-related DNA damage (%-DNA in tail) after formamidopyrimidine DNA glycosylase (FPG) treatment was measured in younger (n = 24, average age 55.7 years; p < 0.05) but not in older COVID-19 patients (n = 24, average age 83.5 years; p > 0.05). Although various oxidative stress markers were not altered (e.g., FRAP, malondialdehyde, p > 0.05), a significant increased ratio of oxidized to reduced glutathione was detected in COVID-19 patients compared to healthy controls (p < 0.05). UCB levels were significantly lower in individuals with COVID-19, especially in younger COVID-19 patients (p < 0.05). These results suggest that COVID-19 infections exert effects on DNA damage related to age in hospitalized COVID-19 patients that might be driven by changes in inflammatory pathways but are not altered by oxidative stress parameters.PMID:37832397 | DOI:10.1016/j.redox.2023.102914
Plasma levels of per- and polyfluoroalkyl substances (PFAS) and cardiovascular disease - Results from two independent population-based cohorts and a meta-analysis
Environ Int. 2023 Oct 5;181:108250. doi: 10.1016/j.envint.2023.108250. Online ahead of print.ABSTRACTBACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent chemicals that have been linked to increased cholesterol levels and thus may have a role in the development of cardiovascular disease (CVD).OBJECTIVES: To investigate associations between PFAS exposure and incident CVD (a combined CVD end-point consisting of myocardial infarction, ischemic stroke, or heart failure) in two independent population-based cohorts in Sweden. In addition, we performed a meta-analysis also including results from previous studies.METHODS: In 2,278 subjects aged 45-75 years from the EpiHealth study, the risk of incident CVD in relation to relative plasma levels of perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) was investigated. Associations between plasma levels of six PFAS and incident CVD were also examined in the PIVUS-study (n = 1,016, all aged 70 years). In addition, a meta-analysis was performed including three previous prospective studies, together with the results from the present study.RESULTS: There were no overall statistically significant associations between levels of the different PFAS and incident CVD, neither in EpiHealth nor in PIVUS. However, there was a significant sex interaction for PFOS in EpiHealth (p = 0.008), and an inverse association could be seen only in men (Men, HR: 0.68, 95 % CI: 0.52, 0.89) (Women, HR: 1.13, 95 % CI: 0.82, 1.55). A meta-analysis of five independent studies regarding PFOA and incident CVD showed a risk ratio (RR) of 0.80 (CI: 0.66, 0.94) when high levels were compared to low levels.CONCLUSIONS: This longitudinal study using data from two population-based cohort studies in Sweden did not indicate any increased risk of incident CVD for moderately elevated PFAS levels. A meta-analysis of five independent cohort studies rather indicated a modest inverse association between PFOA levels and incident CVD, further supporting that increasing PFAS levels are not linked to an increased risk of CVD.PMID:37832261 | DOI:10.1016/j.envint.2023.108250
Aberrant colon metabolome and the sudden infant death syndrome
Pediatr Res. 2023 Oct 13. doi: 10.1038/s41390-023-02847-0. Online ahead of print.ABSTRACTBACKGROUND: The Sudden Infant Death Syndrome (SIDS) has been associated with increased peripheral serotonin and an abnormal colonic microbiome, suggesting the colonic metabolome may also be abnormal. This study addresses this potential correlation by comparing colonic autopsy tissue from SIDS to age-matched non-SIDS controls.METHODS: Untargeted metabolomic analysis by mass spectrometry is used to assess human colonic metabolomic differences including serotonin. Expression of genes associated with colonic serotonin synthesis and transport (TPH1, TPH2, DDC, SCL6A4) is measured by qRT-PCR. Microbiome analysis is performed to compare the SIDS and non-SIDS colonic microbiome.RESULTS: Unsupervised hierarchical cluster and principal component analyses of metabolomic data shows increased variability in the SIDS cohort and separation of SIDS cases from the non-SIDS controls. There is a trend toward increased serotonin in the SIDS cohort but there is no significant difference in expression of the serotonin synthesis and transport genes between SIDS and non-SIDS control cohorts. Microbiome analysis shows no significant difference between the SIDS and non-SIDS control cohorts.CONCLUSIONS: This study demonstrates increased variability in the colonic metabolome and a trend towards increased colonic serotonin in SIDS. The underlying cause of colon metabolomic variability, and its potential role in SIDS pathogenesis, warrants further investigation.IMPACT STATEMENT: The key message of this article is that SIDS is associated with an aberrant colonic metabolome. This is a novel observation suggesting another component in the pathophysiology underlying SIDS. Investigation of why the colonic metabolome is aberrant may offer new insights to SIDS pathogenesis and new strategies to reduce risk.PMID:37833530 | DOI:10.1038/s41390-023-02847-0
Unusual concurrence of P-solubilizing and biocontrol traits under P-limitation in plant-beneficial Pseudomonas aeruginosa P4: insights from in vitro metabolic and gene expression analysis
Arch Microbiol. 2023 Oct 13;205(11):355. doi: 10.1007/s00203-023-03692-9.ABSTRACTPlant-beneficial fluorescent Pseudomonas species with concurrent P-solubilizing and biocontrol traits could have improved rhizospheric survival and efficacy; this rare ability being subject to diverse environmental and endogenous regulations. This study correlates growth patterns, time-course analysis of selected metabolites, non-targeted metabolomics of exometabolites and selected gene expression analysis to elucidate P-limitation-induced physiological shifts enabling co-production of metabolites implied in P-solubilization and biocontrol by P. aeruginosa P4 (P4). P-limited culture supernatants showed enhanced production of selected biocontrol metabolites such as pyocyanin, pyoverdine and pyochelin and IAA while maintaining biomass yield despite reduced growth rate and glucose consumption. Non-targeted exometabolomics further indicated that P-limitation positively impacted pentose phosphate pathway as well as pyruvate, C5-branched dibasic acid and amino acid metabolism. Its correlation with unusually reduced aroC expression and growth phase-dependent changes in the expression of key biosynthetic genes pchA, pchE, pchG, pvdQ and phzM implied a probable regulation of biosynthesis of chorismate-derived secondary metabolites, not neglecting the possibility of multiple factors influencing the gene expression profiles. Similar increase in biocontrol metabolite production was also observed in Artificial Root Exudates (ARE)-grown P4 cultures. While such metabolic flexibility could impart physiological advantage in sustaining P-starvation stress, it manifests as unique coexistence of P-solubilizing and biocontrol abilities.PMID:37833514 | DOI:10.1007/s00203-023-03692-9
The cancer-immune dialogue in the context of stress
Nat Rev Immunol. 2023 Oct 13. doi: 10.1038/s41577-023-00949-8. Online ahead of print.ABSTRACTAlthough there is little direct evidence supporting that stress affects cancer incidence, it does influence the evolution, dissemination and therapeutic outcomes of neoplasia, as shown in human epidemiological analyses and mouse models. The experience of and response to physiological and psychological stressors can trigger neurological and endocrine alterations, which subsequently influence malignant (stem) cells, stromal cells and immune cells in the tumour microenvironment, as well as systemic factors in the tumour macroenvironment. Importantly, stress-induced neuroendocrine changes that can regulate immune responses have been gradually uncovered. Numerous stress-associated immunomodulatory molecules (SAIMs) can reshape natural or therapy-induced antitumour responses by engaging their corresponding receptors on immune cells. Moreover, stress can cause systemic or local metabolic reprogramming and change the composition of the gastrointestinal microbiota which can indirectly modulate antitumour immunity. Here, we explore the complex circuitries that link stress to perturbations in the cancer-immune dialogue and their implications for therapeutic approaches to cancer.PMID:37833492 | DOI:10.1038/s41577-023-00949-8
Comparative metabolomics analysis investigating the impact of melatonin-enriched diet on energy metabolism in the crayfish, Cherax destructor
J Comp Physiol B. 2023 Oct 13. doi: 10.1007/s00360-023-01518-0. Online ahead of print.ABSTRACTMelatonin is a multifunctional bioactive molecule present in almost all organisms and has been gradually used in the aquaculture industry in recent years. Energy metabolism is an essential process for individuals to maintain their life activities; however, the process through which melatonin regulates energy metabolism in aquatic animals remains unclear. The present study aimed to conduct a comprehensive analysis of the regulatory mechanism of melatonin for energy metabolism in Cherax destructor by combining metabolomics analysis with the detection of the key substance content, enzymatic activity, and gene expression levels in the energy metabolism process after culturing with dietary melatonin supplementation for 8 weeks. Our results showed that dietary melatonin increased the content of glycogen, triglycerides, and free fatty acids; decreased lactate levels; and promoted the enzymatic activity of pyruvate kinase (PK), malate dehydrogenase (MDH), and acetyl-CoA carboxylase. The results of gene expression analysis showed that dietary melatonin also increased the expression levels of hexokinase, PK, MDH, lactate dehydrogenase, lipase, and fatty acid synthase genes. The results of metabolomics analysis showed that differentially expressed metabolites were significantly enriched in lysine degradation and glycerophospholipid metabolism. In conclusion, our study demonstrates that dietary melatonin increased oxidative phosphorylation, improved glucose utilization, and promoted storage of glycogen and lipids in C. destructor. These lipids are used not only for energy storage but also to maintain the structure and function of cell membranes. Our results further add to the understanding of the mechanisms of energy regulation by melatonin in crustaceans.PMID:37833417 | DOI:10.1007/s00360-023-01518-0
Trace impurities in sodium phosphate influences the physiological activity of Escherichia coli in M9 minimal medium
Sci Rep. 2023 Oct 13;13(1):17396. doi: 10.1038/s41598-023-44526-4.ABSTRACTIn the field of applied microbiology, reproducibility and experimental variability are important factors that influence both basic research as well as process development for industrial applications. Experimental reproducibility and accuracy depend not only on culture conditions such as temperature and aeration but also on raw materials and procedures used for media preparation. The M9 minimal medium is one of the most common synthetic media for culturing Escherichia coli and other bacteria. This synthetic medium can be used to observe and evaluate the physiological activity of microbes under minimal nutritional requirements and determine the limiting factor for the desired phenotype. Although one of the advantages using the M9 medium is that its composition can be modulated, it is difficult to control presence of trace components and impurities from the reagents for preparing this medium. Herein, we showed that trace ingredients present in the reagents used for M9 media preparation affect the bacterial physiological activities (e.g., cell growth, substrate consumption, and byproduct formation). Additionally, we systematically identified the trace ingredient that influenced phenotypic differences. Our results showed that the selection of reagents and accuracy during reagent preparation is important for experimental reproducibility in the field of bio-engineering and systems biology focused on the systematic and continuous development of biomolecular systems (e.g., biorefinery, metabolic engineering, and synthetic biology).PMID:37833342 | DOI:10.1038/s41598-023-44526-4
The many paths to artemisinin resistance in Plasmodium falciparum
Trends Parasitol. 2023 Oct 11:S1471-4922(23)00232-5. doi: 10.1016/j.pt.2023.09.011. Online ahead of print.ABSTRACTEmerging resistance against artemisinin (ART) poses a major challenge in controlling malaria. Parasites with mutations in PfKelch13, the major marker for ART resistance, are known to reduce hemoglobin endocytosis, induce unfolded protein response (UPR), elevate phosphatidylinositol-3-phosphate (PI3P) levels, and stimulate autophagy. Nonetheless, PfKelch13-independent resistance is also reported, indicating extensive complementation by reconfiguration in the parasite metabolome and transcriptome. These findings implicate that there may not be a single 'universal identifier' of ART resistance. This review sheds light on the molecular, transcriptional, and metabolic pathways associated with ART resistance, while also highlighting the interplay between cellular heterogeneity, environmental stress, and ART sensitivity.PMID:37833166 | DOI:10.1016/j.pt.2023.09.011
Study on the performance of Anerinibacillus sp. in degrading cyanide wastewater and its metabolic mechanism
Chemosphere. 2023 Oct 11:140354. doi: 10.1016/j.chemosphere.2023.140354. Online ahead of print.ABSTRACTCyanide extraction dominates the gold smelting industry, which leads to the generation of large amounts of cyanide-containing wastewater. In this study, Aneurinibacillus tyrosinisolvens strain named JK-1 was used for cyanide wastewater biodegradation. First, we tested the performance of JK-1 in degrading cyanide under different conditions. Then, we screened metabolic compounds and pathways associated with cyanide degradation by JK-1. Finally, we explored the potential JK-1-mediated cyanide degradation pathway. Our results showed that the optimal pH and temperature for cyanide biodegradation were 7.0 and 30 °C, respectively; under these conditions, a degradation rate of >98% was achieved within 48 h. Untargeted metabolomics results showed that increased cyanide concentration decreased the abundance of metabolic compounds by 71.1% but upregulated 32 metabolic pathways. The Kyoto Encyclopedia of Genes and Genomes enrichment results revealed significant changes in amino acid metabolism pathways during cyanide degradation by JK-1, including cyanoamino acid metabolism, β-alanine metabolism, and glutamate metabolism. Differential metabolic compounds included acetyl-CoA, l-asparagine, l-glutamic acid, l-phenylalanine, and l-glutamine. These results confirmed that cyanide degradation by JK-1 occurs through amino acid assimilation. This study provides new insights into the mechanism of cyanide biodegradation, which can be applied in the treatment of cyanide wastewater or tailings.PMID:37832879 | DOI:10.1016/j.chemosphere.2023.140354
Identification of Blood Metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with Type 2 Diabetes Mellitus
J Peripher Nerv Syst. 2023 Oct 13. doi: 10.1111/jns.12600. Online ahead of print.ABSTRACTBACKGROUND: Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN.METHODS: A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 non-diabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose were analyzed.RESULTS: A total of 16 plasma metabolites and 3 cholesterol-related laboratory parameters were found to have variable importance in the projection score > 1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, 5 serum metabolites including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630) are potential biomarkers (all p<0.05) in distinguishing T2DM with DSPN from those without (AUC = 0.720).CONCLUSIONS: In this cross-sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted. This article is protected by copyright. All rights reserved.PMID:37831393 | DOI:10.1111/jns.12600
Dendrobium huoshanense polysaccharide improves high-fat diet induced liver injury by regulating the gut-liver axis
Chem Biodivers. 2023 Oct 13:e202300980. doi: 10.1002/cbdv.202300980. Online ahead of print.ABSTRACTDendrobium huoshanense is an important Traditional Chinese medicine that thickens the stomach and intestines. Its active ingredient Dendrobium huoshanense polysaccharide (DHP), was revealed to relieve the symptoms of liver injury. However, its mechanism of action remains poorly understood. This study aimed to investigate the mechanism of DHP in protecting the liver. The effects of DHP on lipid levels, liver function, and intestinal barrier function were investigated in mice with high-fat diet-induced liver damage. Changes in the gut flora and their metabolites were analyzed using 16S rRNA sequencing and metabolomics. The results showed that DHP reduced lipid levels, liver injury, and intestinal permeability. DHP altered the intestinal flora structure and increased the relative abundance of Bifidobacterium animalis and Clostridium disporicum. Furthermore, fecal metabolomics revealed that DHP altered fecal metabolites and significantly increased levels of gut-derived metabolites, spermidine, and indole, which have been reported to inhibit liver injury and improve lipid metabolism and the intestinal barrier. Correlation analysis showed that spermidine and indole levels were significantly negatively correlated with liver injury-related parameters and positively correlated with the intestinal species B. animalis enriched by DHP. Overall, this study confirmed that DHP prevented liver injury by regulating intestinal microbiota dysbiosis and fecal metabolites.PMID:37831331 | DOI:10.1002/cbdv.202300980
Comparative metabolomics reveal key pathways associated with the synergistic activities of aztreonam and clavulanate combination against multidrug-resistant <em>Escherichia coli</em>
mSystems. 2023 Oct 13:e0075823. doi: 10.1128/msystems.00758-23. Online ahead of print.ABSTRACTThe use of combination antibiotics has been useful in the treatment of multidrug-resistant bacterial infections. The synergistic effect of amoxicillin/clavulanate and aztreonam combination against Escherichia coli carrying New Delhi metallo-β-lactamase (NDM) was primarily due to clavulanate inhibiting aztreonam degradation. In the present study, we employed metabolomic analysis to investigate the downstream changes in E. coli after treatment with aztreonam and clavulanate. E. coli metabolomes were compared at 1 and 24 h following treatments with clavulanate (4 µg/mL) and aztreonam (4 µg/mL) alone and in combination. Excluding false positives, 198 metabolites were identified to be affected by antibiotic treatment. Aztreonam/clavulanate combination inhibited cell wall synthesis more aggressively at 1 h and 24 h than aztreonam alone. The purine and pyrimidine metabolism, the central carbon metabolism, and the amino acid metabolism were also disrupted resulting in a prolonged bactericidal effect. This study reveals the synergistic killing mechanism of clavulanate and aztreonam combination against E. coli harboring NDM and provides a theoretical basis for the combined use of aztreonam/clavulanate in the treatment of multidrug-resistant E. coli infection. IMPORTANCE Multidrug-resistant Escherichia coli is a major threat to the health care system and is associated with poor outcomes in infected patients. The combined use of antibiotics has become an important treatment method for multidrug-resistant bacteria. However, the mechanism for their synergism has yet to be explored.PMID:37830827 | DOI:10.1128/msystems.00758-23
Normalization of the ATP1A1 Signalosome Rescinds Epigenetic Modifications and Induces Cell Autophagy in Hepatocellular Carcinoma
Cells. 2023 Sep 27;12(19):2367. doi: 10.3390/cells12192367.ABSTRACTHepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In metabolic dysfunction-associated steatohepatitis (MASH)-related HCC, cellular redox imbalance from metabolic disturbances leads to dysregulation of the α1-subunit of the Na/K-ATPase (ATP1A1) signalosome. We have recently reported that the normalization of this pathway exhibited tumor suppressor activity in MASH-HCC. We hypothesized that dysregulated signaling from the ATP1A1, mediated by cellular metabolic stress, promotes aberrant epigenetic modifications including abnormal post-translational histone modifications and dysfunctional autophagic activity, leading to HCC development and progression. Increased H3K9 acetylation (H3K9ac) and H3K9 tri-methylation (H3K9me3) were observed in human HCC cell lines, HCC-xenograft and MASH-HCC mouse models, and epigenetic changes were associated with decreased cell autophagy in HCC cell lines. Inhibition of the pro-autophagic transcription factor FoxO1 was associated with elevated protein carbonylation and decreased levels of reduced glutathione (GSH). In contrast, normalization of the ATP1A1 signaling significantly decreased H3K9ac and H3K9me3, in vitro and in vivo, with concomitant nuclear localization of FoxO1, heightening cell autophagy and cancer-cell apoptotic activities in treated HCC cell lines. Our results showed the critical role of the ATP1A1 signalosome in HCC development and progression through epigenetic modifications and impaired cell autophagy activity, highlighting the importance of the ATP1A1 pathway as a potential therapeutic target for HCC.PMID:37830582 | DOI:10.3390/cells12192367
An overview of metabolomic and proteomic profiling in bipolar disorder and its clinical value
Expert Rev Proteomics. 2023 Oct 13. doi: 10.1080/14789450.2023.2267756. Online ahead of print.ABSTRACTINTRODUCTION: Bipolar disorder (BD) is a complex psychiatric disease characterized by alternating mood episodes. As for any other psychiatric illness, currently there is no biochemical test that is able to support diagnosis or therapeutic decisions for BD. In this context, the discovery and validation of biomarkers are interesting strategies that can be achieved through proteomics and metabolomics.AREAS COVERED: In this descriptive review, a literature search including original articles and systematic reviews published in the last decade was performed with the objective to discuss the results of BD proteomic and metabolomic profiling analyses and indicate proteins and metabolites (or metabolic pathways) with potential clinical value.EXPERT OPINION: A large number of proteins and metabolites have been reported as potential BD biomarkers; however, most studies do not reach biomarker validation stages. An effort from the scientific community should be directed toward the validation of biomarkers and the development of simplified bioanalytical techniques or protocols to determine them in biological samples, in order to translate proteomics and metabolomics findings into clinical routine assays.PMID:37830362 | DOI:10.1080/14789450.2023.2267756
Global and Spatial Metabolomics of Individual Cells Using a Tapered Pneumatically Assisted nano-DESI Probe
J Am Soc Mass Spectrom. 2023 Oct 13. doi: 10.1021/jasms.3c00239. Online ahead of print.ABSTRACTSingle-cell metabolomics has the potential to reveal unique insights into intracellular mechanisms and biological processes. However, the detection of metabolites from individual cells is challenging due to their versatile chemical properties and concentrations. Here, we demonstrate a tapered probe for pneumatically assisted nanospray desorption electrospray ionization (PA nano-DESI) mass spectrometry that enables both chemical imaging of larger cells and global metabolomics of smaller 15 μm cells. Additionally, by depositing cells in predefined arrays, we show successful metabolomics from three individual INS-1 cells per minute, which enabled the acquisition of data from 479 individual cells. Several cells were used to optimize analytical conditions, and 93 or 97 cells were used to monitor metabolome alterations in INS-1 cells after exposure to a low or high glucose concentration, respectively. Our analytical approach offers insights into cellular heterogeneity and provides valuable information about cellular processes and responses in individual cells.PMID:37830184 | DOI:10.1021/jasms.3c00239
Feasibility of NAD(P)/NAD(P)H as redox agents in enzymatic plasmonic gold nanostar assays for galactose quantification
R Soc Open Sci. 2023 Oct 11;10(10):230825. doi: 10.1098/rsos.230825. eCollection 2023 Oct.ABSTRACTPlasmonic colorimetric sensors have emerged as powerful analytical tools in biochemistry due to their localized surface plasmon resonance extinction in the visible range. Here, we describe the feasibility of NAD(P)/NAD(P)H as redox agents in enzymatic plasmonic gold nanostar (AuNS) assays for galactose quantification using three model enzymes, GalDH, AR and GalOx, immobilized separately on polyvinylpyrrolidone-capped AuNS scaffolds. These highly specific, sensitive and selective bioassays induce the transformation of AuNS into quasi-spherical nanoparticles during the biorecognition of galactose in water and synthetic blood matrices. As a result, using our inexpensive and simple AuNS plasmon bioassays, the presence of galactose may be detected spectrophotometrically and by the naked eye.PMID:37830025 | PMC:PMC10565372 | DOI:10.1098/rsos.230825
Evaluation of the biological responses of silver nanoparticles synthesized using <em>Pelargonium</em> x <em>hortorum</em> extract
RSC Adv. 2023 Oct 11;13(42):29784-29800. doi: 10.1039/d3ra00201b. eCollection 2023 Oct 4.ABSTRACTSilver nanoparticles (AgNPs) are one of the widely studied nanomaterials for diverse biomedical applications, in particular, as antimicrobial agents to kill bacteria, fungi, and viruses. In this report, AgNPs were synthesized using a geranium (Pelargonium x hortorum) leaves extract and tested for their antimicrobial and cytotoxic activity and reactive oxygen species (ROS) production. Using green biosynthesis, the leaves extract was employed as a reducing and stabilizing agent. Synthesis parameters like reaction time and precursor (silver nitrate AgNO3) volume final were modified, and the products were tested against Streptococcus mutans. For the first time, the metabolomic analysis of extract, we have identified more than 50 metabolites. The UV-Vis analysis showed a peak ranging from 410-430 nm, and TEM confirmed their nearly spherical morphology for all NPs. The antimicrobial activity of the NPs revealed a minimum inhibitory concentration (MIC) of 10 μg mL-1. Concerning cytotoxicity, a dose-time-dependent effect was observed with a 50% cellular cytotoxicity concentration (CC50) of 4.51 μg mL-1 at 24 h. Interestingly, the cell nuclei were visualized using fluorescence microscopy, and no significant changes were observed. These results suggest that synthesized spherical AgNPs are promising potential candidates for medical applications.PMID:37829709 | PMC:PMC10565737 | DOI:10.1039/d3ra00201b