PubMed

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Front Microbiol. 2023 Sep 27;14:1214845. doi: 10.3389/fmicb.2023.1214845. eCollection 2023.ABSTRACTThe present crisis at hand revolves around the need to enhance plant resilience to various environmental stresses, including abiotic and biotic stresses, to ensure sustainable agriculture and mitigate the impact of climate change on crop production. One such promising approach is the utilization of plant growth-promoting rhizobacteria (PGPR) to mediate plant resilience to these stresses. Plants are constantly exposed to various stress factors, such as drought, salinity, pathogens, and nutrient deficiencies, which can significantly reduce crop yield and quality. The PGPR are beneficial microbes that reside in the rhizosphere of plants and have been shown to positively influence plant growth and stress tolerance through various mechanisms, including nutrient solubilization, phytohormone production, and induction of systemic resistance. The review comprehensively examines the various mechanisms through which PGPR promotes plant resilience, including nutrient acquisition, hormonal regulation, and defense induction, focusing on recent research findings. The advancements made in the field of PGPR-mediated resilience through multi-omics approaches (viz., genomics, transcriptomics, proteomics, and metabolomics) to unravel the intricate interactions between PGPR and plants have been discussed including their molecular pathways involved in stress tolerance. Besides, the review also emphasizes the importance of continued research and implementation of PGPR-based strategies to address the pressing challenges facing global food security including commercialization of PGPR-based bio-formulations for sustainable agricultural.PMID:37829451 | PMC:PMC10565232 | DOI:10.3389/fmicb.2023.1214845

Front Pharmacol. 2023 Sep 27;14:1275832. doi: 10.3389/fphar.2023.1275832. eCollection 2023.ABSTRACTMale infertility occurs approximately in about 50% of all infertility cases and represents a serious concern worldwide. Traditional semen analysis alone is insufficient to diagnose male infertility. Over the past two decades, advances in omics technologies have led to the widespread application of metabolomics profiling as a valuable diagnostic tool for various diseases and disorders. Seminal plasma represents a rich and easily accessible source of metabolites surrounding spermatozoa, a milieu that provides several indispensable nutrients to sustain sperm motility and fertilization. Changes of metabolic profiles in seminal plasma reflect male reproductive tract disorders. Here, we performed seminal plasma metabolomics and lipidomics profiling to identify a new pattern of biomarkers of male infertility. Seminal plasma samples from unfertile subjects (n = 31) and fertile controls (n = 19) were analyzed using an untargeted metabolomics/lipidomics integrated approach, based on Ultra-High-Pressure Liquid Chromatography-tandem Mass Spectrometry. Partial Least Squares-Discriminant Analysis showed a distinct separation between healthy fertile men and infertile subjects. Among the 15 selected candidate biomarkers based on Variable Importance in Projection scores, phosphatidylethanolamine (PE) (18:1; 18:1) resulted with the highest score. In total, 40 molecular species showed statistically significant variations between fertile and infertile men. Heat-map and volcano plot analysis indicated that acylcarnitines, phosphatidylserine (PS) (40:2) and lactate were decreased, while PE (18:1; 18:1), Phosphatidic acid (PA) (O-19:2; 18:1), Lysophosphatidylethanolamine (LPE) (O-16:1) and Phosphatidylcholine (PC) (O-16:2; 18:1)-CH3 were increased in the infertile group. The present study is the first one to analyze the metabolomics/lipidomics dysregulation in seminal plasma between fertile and infertile individuals regardless of sub-infertility condition. Association of several metabolites/lipids dysregulation with male infertility reinforced data of previous studies performed with different approaches. In particular, we confirmed significantly decreased levels of PS and carnitines in infertile patients as well as the positive correlation with sperm motility and morphology. If validated on a larger prospective cohort, the metabolite biomarkers of infertility in seminal plasma we identified in the present study might inform novel strategies for diagnosis and interventions to overcome male infertility.PMID:37829298 | PMC:PMC10565040 | DOI:10.3389/fphar.2023.1275832

Front Immunol. 2023 Sep 27;14:1254155. doi: 10.3389/fimmu.2023.1254155. eCollection 2023.ABSTRACTBACKGROUND: Chronic metabolic changes relevant to human immunodeficiency virus type 1 (HIV-1) infection and in response to antiretroviral therapy (ART) remain undetermined. Moreover, links between metabolic dysfunction caused by HIV and immunological inflammation in long-term treated individuals have been poorly studied.METHODS: Untargeted metabolomics and inflammatory cytokine levels were assessed in 47 HIV-infected individuals including 22 immunological responders (IRs) and 25 non-responders (INRs) before and after ART. The IRs and INRs were matched by age, gender, baseline viral load, and baseline CD4+T cell counts. Another 25 age-matched uninfected healthy individuals were also included as controls.RESULTS: Among the 770 plasma compounds detected in the current study, significant changes were identified in lipids, nucleotides, and biogenic amino acids between HIV-infected patients and healthy controls. Principal Component Analysis (PCA) and the Random Forest (RF) model suggested that levels of selected metabolites could differentiate HIV-infected patients clearly from healthy controls. However, the metabolite profiles identified in our patients were similar, and only three metabolites, maltotetraose, N, N-dimethyl-5-aminovalerate, and decadienedioic acid (C10:2-DC), were different between IRs and INRs following long-term ART. The pathway enrichment analysis results revealed that disturbances in pyrimidine metabolism, sphingolipid metabolism, and purine metabolism after HIV infection and these changes did not recover to normal levels in healthy controls even with suppressive ART. Correlation analysis of the metabolism-immune network indicated that interleukin (IL)-10, D-dimer, vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), and TNF-RII were positively correlated with most of the significantly changed lipid and amino acid metabolites but negatively correlated with metabolites in nucleotide metabolism.CONCLUSIONS: Significant changes in many metabolites were observed in HIV-infected individuals before and after ART regardless of their immunological recovery status. The disturbed metabolic profiles of lipids and nucleotides in HIV infection did not recover to normal levels even after long-term ART. These changes are correlated with modified cytokines and biomarkers of chronic non-AIDS events, warranting tryout of interventions other than ART.PMID:37828979 | PMC:PMC10565217 | DOI:10.3389/fimmu.2023.1254155