PubMed

J Trace Elem Med Biol. 2024 Nov 28;87:127571. doi: 10.1016/j.jtemb.2024.127571. Online ahead of print.ABSTRACTBACKGROUND: Cadmium (Cd) is a naturally occurring transition metal associated with oxidative stress in living organisms. Whereas Tetrapleura tetraptera (Tt), an ethnomedicinal plant is said to possess high antioxidant activity and used to treat various human diseases locally. Therefore, the study aimed to investigate the biological activity of the ethanolic pod extract of T. tetraptera in cadmium chloride-induced toxicity in Drosophila melanogaster.METHODS: Six groups of adults (1-3 days old) D. melanogaster as shown: Control, Tt 2.5 mg/10 g diet, Tt 5 mg/10 g diet, CdCl2, CdCl2+ Tt 2.5 mg/10 diet and CdCl2+Tt 5 mg/10 g diet were exposed via diet for 7 days consisting of 50 flies per vial and 5 replicate per group. Thereafter, we evaluated markers for free radical generation, antioxidant, non-antioxidant activities, and emergence rates of the flies. The active compounds of Tt extract were molecularly docked against glutathione-S-transferase II.RESULTS: The results indicated that CdCl2 significantly induced oxidative stress by increasing the levels of lipid peroxidation (LPO), hydrogen peroxide (H2O2), nitric oxide (NO) and decreasing the activity of GST without an effect on total thiol (T-SH) and non-protein thiols (NP-SHs) levels. However, co-treatment with T. tetraptera (2.5 mg/10 g diet) significantly decreased levels of LPO, H2O2, but increased GST activity. Also, co-treatment with T. tetraptera (5 mg/10 g diet) increased NPSH and T-SH levels by 18.6 % and 35.8 %. Furthermore, Co-treatment (5 mg/10 g diet) increased the rate of offspring emergence.CONCLUSION: T. tetraptera ameliorated cadmium chloride-induced oxidative stress in Drosophila melanogaster and increased offspring hatching rate. T. tetraptera may therefore serve as a good regimen for the treatment of oxidative stress-related diseases induced by cadmium.PMID:39637735 | DOI:10.1016/j.jtemb.2024.127571

Food Chem. 2024 Nov 29;467:142289. doi: 10.1016/j.foodchem.2024.142289. Online ahead of print.ABSTRACTLiupao tea is a post-fermented dark tea with bitterness and astringency as key sensory traits, though its chemical composition is not fully understood. Six Liupao tea samples with significant differences in bitterness and astringency were analyzed using non-targeted metabolomics and sensory evaluation. Thirty finished and five semi-finished Liupao tea samples were analyzed using UHPLC-MS-PRM for targeted quantification of bitter and astringent compounds. The results show that 477 non-volatile compounds were detected, including 18 potential bitter compounds and 22 potential astringent compounds. Six key bitter compounds (epigallocatechin gallate, catechin gallate, caffeine, quinic acid, neochlorogenic acid, and caffeic acid) and 11 key astringent compounds (e.g., epigallocatechin gallate, gallic acid, chlorogenic acid, ellagic acid) were identified. After fermentation, flavonoid glycosides and flavanols were reduced by 62.41 % to 97.46 %, while phenolic acids showed varied trends. Different rates of change in key compounds during fermentation resulted in variations in bitterness and astringency. This study offers insights for improving Liupao tea quality.PMID:39637669 | DOI:10.1016/j.foodchem.2024.142289

Food Chem. 2024 Nov 26;467:142244. doi: 10.1016/j.foodchem.2024.142244. Online ahead of print.ABSTRACTThe study aimed to distinguish between the role played by the structural properties of MFG from its chemical composition in modulating its interaction with pathogenic and commensal bacteria. MFG from mammary gland epithelial cells (MEC) or raw milk was tested. Small MFG from both sources promoted growth of B.subtilis while large MFG triggered biofilm formation. Metabolomic profiles supported these findings for MEC-derived MFG. In contrast, pathogenic bacteria like E. coli weren't affected by MFG size from both sources. Using lipid mixture formulated to mimic the chemical composition of small MFG did not induce growth of the bacteria. Results validate that (i) milk components secreted by MEC share some structural-functional properties with raw MFG and (ii) the structure of the MFG plays a pivotal role in modulating the interaction between milk fat and bacteria. Taken together, MFG size variations may provide a competitive advantage to commensal bacteria as a protective mechanism.PMID:39637660 | DOI:10.1016/j.foodchem.2024.142244

Sci Total Environ. 2024 Dec 4;958:177714. doi: 10.1016/j.scitotenv.2024.177714. Online ahead of print.ABSTRACTBisphenol A (BPA) is an endocrine disruptor that poses multiple risks to human health. In particular, the potential adverse effects of maternal exposure to BPA on offspring warrant further investigation. In this study, pregnant mice were exposed to BPA throughout gestation and the effects of BPA on placental function, fetal development, and health risks in adult offspring were assessed. The results showed that exposure to BPA during pregnancy led to abnormal fetal weight during the mid-to-late stages. Positron emission tomography (PET)/computed tomography (CT) and quantitative polymerase chain reaction (qPCR) were used to assess the expression of glucose transporters. The results showed that maternal BPA exposure altered glucose transport by upregulating Glut1. This alteration may significantly affect placental function and fetal development. Placental metabolomic analysis showed that BPA exposure led to downregulation of key intermediates in glucose metabolism, including UDP-d-glucose and D-glucosamine-6-phosphate. Additionally, the glycerophospholipid metabolite Dipalmitoylphosphatidylcholine (DPPC) was upregulated while CDP-choline and CDP-ethanolamine were downregulated. These disturbances in placental energy metabolism and alterations in glucose transport may be related to decreased fasting blood glucose levels and abnormal glucose tolerance in female offspring; however, these indices remained unaltered in male offspring. These findings provide preliminary insights into the potential pathological mechanisms underlying placental dysfunction and health risk caused by maternal BPA exposure in adult female offspring.PMID:39637470 | DOI:10.1016/j.scitotenv.2024.177714

J Breath Res. 2024 Dec 5. doi: 10.1088/1752-7163/ad9ac5. Online ahead of print.ABSTRACTThe ocean is facing many anthropogenic stressors caused from both pollution and climate change. These stressors are significantly impacting and changing the ocean's ecosystem, and as such, methods must continually be developed that can improve our ability to monitor the health of marine life. For cetaceans, the current practice for health assessments of individuals requires live capture and release, which is expensive, usually stressful, and for larger species impractical. In this study, we investigated the potential of exhaled breath condensate (EBC) samples to provide unique metabolomic profiles from healthy killer whales (Orcinus orca) of varying known age and sex. EBC collection is a non-invasive procedure that has potential for remote collection using unmanned aerial vehicles, thus improving our ability to understand physiologic parameters within wild populations while minimizing stress from collection procedures However, descriptions of the available metabolome within EBC and its clinical significance within animals of known health and age must be described before this technique can be considered diagnostically useful. We describe normal variations of the metabolome across age and sex and provide evidence for the potential of this breath analysis method to become a valuable adjunctive tool for assessing the health of managed-care and free-ranging killer whales.PMID:39637438 | DOI:10.1088/1752-7163/ad9ac5

Kardiologiia. 2024 Nov 30;64(11):106-116. doi: 10.18087/cardio.2024.11.n2794.ABSTRACTAim To identify metabolomic and structure and function markers of remote left ventricular (LV) remodeling in patients with chronic heart failure (CHF) of ischemic etiology and LV ejection fraction (EF) <50%.Material and methods This prospective study included 56 patients with 3-4 NYHA functional class CHF of ischemic etiology (mean age, 66±7 years) and 50 patients with ischemic heart disease (IHD) without signs of CHF (69 [64; 73.7] years). Concentration of 19 amino acids, 11 products of kynurenine catabolism of tryptophan, 30 acylcarnitines with different chain lengths were measured in all participants. The metabolites that showed statistical differences between the comparison groups were then used for the analysis. Echocardiography was used to assess LV cavity remodeling at the time of the CHF patient inclusion in the study and after 6 months of follow-up. Predictors of long-term LV cavity remodeling were assessed for this cohort taking into account statistically significant echocardiographic parameters and metabolites.Results Patients with CHF of ischemic etiology, predominantly (81%) had pathological calculated types of LV remodeling (concentric and eccentric hypertrophy, 46 and 35%, respectively). However, this classification had limitations in describing this cohort. In addition, in this group, the concentrations of alanine, proline, asparagine, glycine, arginine, histidine, lysine, valine, indolyl-3-acetic acid, indolyl-3-propionic acid, C16-1-OH, and C16-OH were significantly (p<0.05) lower, and the concentrations of most medium- and long-chain acylcarnitines were higher than in patients with IHD without signs of CHF. The long-term (6 months) reverse remodeling of the LV cavity in CHF of ischemic etiology was influenced by changes in the interventricular septum thickness (hazard ratio, HR, 19.07; 95% confidence interval, CI, 1.76-206.8; p=0.006) and concentrations of anthranilic acid (HR 19.8; 95% CI 1.01-387.8; p=0.019) and asparagine (HR 8.76; 95% CI 1.07-71.4; p=0.031).Conclusion The presence of an interventricular septum thickness of more than 13.5 mm, anthranilic acid concentrations of higher than 0.235 μM/l, or an asparagine concentration of less than 135.2 μM/l in patients with CHF of ischemic etiology after 6 months of follow-up affects their achievement of LV cavity reverse remodeling.PMID:39637396 | DOI:10.18087/cardio.2024.11.n2794

Pediatr Infect Dis J. 2024 Dec 3. doi: 10.1097/INF.0000000000004628. Online ahead of print.ABSTRACTBACKGROUND: We hypothesized that food sensitization in children could be linked to specific gut microbiota. The objective of this study is to assess a group of children with egg white sensitization (ES) from the microbiological and biochemical-metabolic standpoint, applying the microbiota and metabolomics approach to studying the intestinal contents of the feces.METHODS: Twenty-eight toddlers with ES (mean age 13.08 months) and 24 healthy controls (mean age 12.85 months) were recruited for feces collection, serum IgE measurement, gut microbiota and metabolomics analysis. Individual microbial diversity and composition were analyzed via targeting the 16S rRNA gene hypervariable V3-V5 regions. The metabolite profiles of human feces were explored by 1H nuclear magnetic resonance.RESULTS: Children with ES exhibited relatively high levels of Firmicutes at the phylum level and relatively low levels of Bacteroidetes. Moreover, children with ES exhibited significantly reduced overall gut microbiota diversity and richness compared with healthy children. At the family level, we observed significant increases in the numbers of Clostridiaceae, Lachnospiraceae, Pasteurellaceae and Ruminococcaceae in children with ES. Egg white sensitivity increases orotic acid, nicotinate, methyl succinate, urocanic acid, xanthine, amino acids (tyrosine, lysine, tryptophan, phenylalanine) and short-chain fatty acids (n-butyrate, valerate) levels according to the results of metabolomics analysis.CONCLUSIONS: In summary, some specific families and genera (dysbiosis) are enriched in the gut microbiota, and increases in the mean concentrations of organic compounds in the fecal metabolite profile are associated with ES in children. These findings may provide evidence of potential strategies to control the development of ES or other atopies by modifying the gut microbiota.PMID:39637305 | DOI:10.1097/INF.0000000000004628

PLoS One. 2024 Dec 5;19(12):e0314595. doi: 10.1371/journal.pone.0314595. eCollection 2024.ABSTRACTTea ranks among the top three most beloved non-alcoholic beverages worldwide and boasts significant economic and health benefits. In addition to Camellia sinensis (L.) O. Kuntze, and other Camellia plants in China are consumed by residents as tea drinks, which also have important economic value. The present study introduces one of the wild tea species, namely, Camellia tachangensis F. C. Zhang. We analyzed changes in metabolite abundance and gene expression patterns of C. tachangensis and C. sinensis using metabonomics and transcriptomics. We found 1056 metabolites, including 256 differential metabolites (67 upregulated and 189 downregulated). Additionally, transcriptome analysis revealed 8049 differentially expressed genes, with 4418 upregulated and 3631 downregulated genes. C. sinensis boasts a notable abundance of Amino acids, which can be attributed to its specific genetic makeup. In Theanine and Caffeine metabolic pathways, the levels of the majority of amino acids and caffeine tend to decrease. In Flavonoid biosynthesis, the levels of the Flavanone Fustin and Epicatechin are higher in C. tachangensis, while Epigallocatechin and Gallocatechin levels are higher in C. sinensis. This indicates that the metabolic components of C. sinensis and C. tachangensis are not identical, which may result in a unique flavor.PMID:39637125 | DOI:10.1371/journal.pone.0314595

Free Radic Res. 2024 Dec 5:1-15. doi: 10.1080/10715762.2024.2437640. Online ahead of print.ABSTRACTOxidative stress can be alleviated by antioxidants intakes. Taraxerol acetate (TA), a natural triterpenoid extracted from dandelions, may reduce the risk of metabolic disorders by regulating oxidative stress. In the study, we investigated the effects of TA in relieving oxidative stress in murine intestinal epithelial cells using multiomics techniques. Here, we found that TA activated the antioxidant defense system. Total antioxidant capacity (T-AOC) and Catalase (CAT) activity notably increased after TA treatment. Additionally, TA treatment effectively reduced the levels of lactate dehydrogenase (LDH) and malonaldehyde (MDA) and alleviated H2O2-induced oxidative stress. Furthermore, TA induced significant changes in the levels of 30 important metabolites. Specifically, it activated the complement and coagulation cascades, NF-κB and MAPK and glycerophospholipid pathways, resulting in altered transcript levels of related genes, such as Serpinb9e, SCD2, Hspa1b, and Hspa1a. Thus, the results demonstrated that TA potentially could promote health by alleviating H2O2-induced oxidative damage and provide valuable insights for its further development.PMID:39636737 | DOI:10.1080/10715762.2024.2437640

Plant J. 2024 Dec 5. doi: 10.1111/tpj.17188. Online ahead of print.ABSTRACTFlower color change, a common phenomenon that is important in pollination ecology, has intrigued scientists for decades. While previous flower color studies have mainly focused on color diversity among different plant species, our focus is on unraveling the mechanism of post-anthesis color change (PACC) and the molecular basis for its presence and absence, respectively, in two closely related species of Lotus, Lotus filicaulis and Lotus japonicus MG20. Metabolomic analysis reveals anthocyanins as the key metabolites responsible for the observed PACC. Differential expression of anthocyanin biosynthetic and transport genes causes the variation in PACC between the two Lotus species. Crucially, the significant upregulation of a functionally characterized MYB regulator, LfPAP1, is linked to the accumulation of anthocyanins and visible color alterations in L. filicaulis flowers. Notably, we uncover a nucleotide polymorphism in the initiation codon of LjPAP1. Although this mutation does not affect transcription, we show that it has a major effect in attenuating protein translation, reducing its capacity to activate anthocyanin biosynthesis, and leading to a failure of PACC in L. japonicus MG20. Our study sheds light on mechanisms of PACC phenomenon and highlights the potential for mutations in initiation sequences to generate phenotypic differences between species in evolution.PMID:39636691 | DOI:10.1111/tpj.17188

Plant Biotechnol J. 2024 Dec 5. doi: 10.1111/pbi.14534. Online ahead of print.ABSTRACTSalinity significantly inhibits plant growth and development. While the recretohalophyte Limonium bicolor can reduce its ion content by secreting salt, the metabolic pathways it employs to adapt to high salt stress remain unclear. This study aims to unravel this enigma through integrated transcriptomic and metabolomic analyses of L. bicolor under salt stress conditions. The results showed that compared to the control (S0), low salt treatment (S1) led to a significant increase in plant growth, photosynthesis efficiency and antioxidant enzyme activity but caused no significant changes in organic soluble substance and ROS contents. However, high salt treatments (S3 and S4) led to a significant decrease in plant growth, photosynthesis efficiency and antioxidant enzyme activity, accompanied by a significant increase in organic soluble substance and ROS contents. A significant increase in phenolic compounds, such as caffeoyl shikimic acid and coniferin, upon the treatments of S1, S3 and S4, and a decrease and increase in flavonoids upon the treatments of S1 and S3 were also observed, respectively. This study also demonstrated that the expression patterns of key genes responsible for the biosynthesis of these metabolites are consistent with the observed trends in their accumulation levels. These results suggest that under low salt stress conditions, the halophyte L. bicolor experiences minimal osmotic and oxidative stress. However, under high salt stress conditions, it suffers severe osmotic and oxidative stress, and the increase in organic soluble substances and flavonoids serves as a key response to these stresses and also represents a good strategy for the alleviation of them.PMID:39636615 | DOI:10.1111/pbi.14534

Metabolomics. 2024 Dec 4;21(1):1. doi: 10.1007/s11306-024-02201-3.ABSTRACTINTRODUCTION: Despite the well-established efficacy of thiazolidinediones (TZDs), including pioglitazone and rosiglitazone, in type II diabetes management, their potential contribution to heart failure risk remains a significant area of uncertainty. This incomplete understanding, which persists despite decades of clinical use of TZDs, has generated ongoing controversy and unanswered questions regarding their safety profiles, ultimately limiting their broader clinical application.OBJECTIVE AND METHODS: This study presented a multi-omics approach, integrating toxicoproteomics and toxicometabolomics data with the goal of uncovering novel mechanistic insights into TZD cardiotoxicity and identifying molecular signatures predictive of side effect progression.RESULTS: Network analysis of proteo-metabolomic data revealed a distinct fingerprint of disrupted biochemical pathways, which were primarily related to energy metabolism. Downregulation of oxidative phosphorylation and fatty acid synthesis was coupled with increased activity in anaerobic glycolysis, the pentose phosphate pathway, and amino acid and purine metabolism. This suggests a potential metabolic shift in AC16 cells from fatty acid oxidation towards anaerobic glycolysis, potentially contributing to observed cardiotoxicity. Additionally, the study identified a marked disruption in the glutathione system, indicating an imbalanced redox state triggered by TZD exposure. Importantly, our analysis identified key molecular signatures across omics datasets, including prominent signatures of amino acids like L-ornithine, L-tyrosine and glutamine, which are evidently associated with heart failure, supporting their potential use for the early prediction of cardiotoxicity progression.CONCLUSION: By uncovering a novel mechanistic explanation for TZD cardiotoxicity, this study simultaneously illuminates potential therapeutic interventions, opening avenues for future research to improve the safety profile of TZD agents. (250 words).PMID:39636558 | DOI:10.1007/s11306-024-02201-3

J Mol Histol. 2024 Dec 5;56(1):31. doi: 10.1007/s10735-024-10298-y.ABSTRACTBACKGROUND: Among couples, male factors account for approximately 50% of infertility cases, with nonobstructive azoospermia (NOA) representing one of the most clinically common and severe categories of male infertility, affecting approximately 10-15% of patients. Currently, L-carnitine is clinically used to improve spermatogenesis by regulating Sertoli cell function. Multiple clinical trials have described the efficacy of L-carnitine in treating NOA. Notably, Sertoli cells rely on organic carnitine transporter 2 (OCTN2) for carnitine transport. However, it remains unknown whether OCTN2 expression is involved in the pathological process of NOA.OBJECTIVE: To investigate the expression and function of OCTN2 in Sertoli cells from patients with NOA.MATERIALS AND METHODS: Ten testicular tissue samples were collected, including five from a healthy group and five from a group of patients with NOA. Immunohistochemistry and immunofluorescence were used to detect the expression of OCTN2 in testicular tissue. Additionally, an Octn2-KO TM4 cell line (a mouse testicular Sertoli cell line) was constructed to explore the function of OCTN2 expression in Sertoli cells through transcriptomic sequencing, cell proliferation experiments, metabolomic analysis, and Western blot analysis.RESULTS: Compared with those of the healthy group, the immunohistochemistry results revealed a significant decrease in OCTN2 expression in the Sertoli cells of the NOA group. Further investigation through cell proliferation experiments revealed a reduction in the proliferative capacity of the Octn2-KO TM4 cell line. Transcriptomic sequencing and metabolomic data analysis revealed a decrease in autophagy in the Octn2-KO TM4 cell line. Western blot analysis subsequently verified the expression levels of autophagy-related proteins.CONCLUSION: In the Sertoli cells of NOA patients, decreased OCTN2 protein expression leads to decreased cell proliferation and autophagy abnormalities, which may play a crucial role in the spermatogenic dysfunction observed in NOA patients.PMID:39636482 | DOI:10.1007/s10735-024-10298-y

Metabolomics. 2024 Dec 4;21(1):2. doi: 10.1007/s11306-024-02197-w.ABSTRACTINTRODUCTION: The knowledge of the mode of action of an antimicrobial is essential for drug development and helps to fight against bacterial resistance. Thus, it is crucial to use analytical techniques to study the mechanism of action of substances that have potential to act as antibacterial agents OBJECTIVE: To use NMR-based metabolomics combined with chemometrics and molecular docking to identify the metabolic responses of Staphylococcus aureus following exposure to commercial antibiotics and some synthesized ω-aminoalkoxylxanthones.METHODS: Intracellular metabolites of S. aureus were extracted after treatment with four commercial antibiotics and three synthesized ω-aminoalkoxylxanthones. NMR spectra were obtained and 1H NMR data was analyzed using both unsupervised and supervised algorithms (PCA and PLS-DA, respectively). Docking simulations on DNA topoisomerase IV protein were also performed for the ω-aminoalkoxylxanthones.RESULTS: Through chemometric analysis, we distinguished between the control group and antibiotics with extracellular (ampicillin) and intracellular targets (kanamycin, tetracycline, and ciprofloxacin). We identified 21 metabolites, including important metabolites that differentiate the groups, such as betaine, acetamide, glutamate, lysine, alanine, isoleucine/leucine, acetate, threonine, proline, and ethanol. Regarding the xanthone-type derivatives (S6, S7 and S8), we observed a greater similarity between S7 and ciprofloxacin, which targets bacterial DNA replication. The molecular docking analysis showed high affinity of the ω-aminoalkoxylxanthones with the topoisomerase IV enzyme, as well as ciprofloxacin.CONCLUSION: NMR-based metabolomics has shown to be an effective technique to assess the metabolic profile of S. aureus after treatment with certain antimicrobial compounds, helping the investigation of their mechanism of action.PMID:39636460 | DOI:10.1007/s11306-024-02197-w

Metabolomics. 2024 Dec 4;21(1):3. doi: 10.1007/s11306-024-02195-y.ABSTRACTINTRODUCTION: Coronavirus disease 2019 (COVID-19) has widely varying clinical severity. Currently, no single marker or panel of markers is considered standard of care for prediction of COVID-19 disease progression. The goal of this study is to gain mechanistic insights at the molecular level and to discover predictive biomarkers of severity of infection and outcomes among COVID-19 patients.METHOD: This cohort study (n = 76) included participants aged 16-78 years who tested positive for SARS-CoV-2 and enrolled in Memphis, TN between August 2020 to July 2022. Clinical outcomes were classified as Non-severe (n = 39) or Severe (n = 37). LC/HRMS-based untargeted metabolomics/lipidomics was conducted to examine the difference in plasma metabolome and lipidome between the two groups.RESULTS: Metabolomics data indicated that the kynurenine pathway was activated in Severe participants. Significant increases in short chain acylcarnitines, and short and medium chain acylcarnitines containing OH-FA chain in Severe vs. Non-severe group, which indicates that (1) the energy pathway switched to FA β-oxidation to maintain the host energy homeostasis and to provide energy for virus proliferation; (2) ROS status was aggravated in Severe vs. Non-severe group. Based on PLS-DA and correlation analysis to severity score, IL-6, and creatine, a biomarker panel containing glucose (pro-inflammation), ceramide and S1P (inflammation related), 4-hydroxybutyric acid (oxidative stress related), testosterone sulfate (immune related), and creatine (kidney function), was discovered. This novel biomarker panel plus IL-6 with an AUC of 0.945 provides a better indication of COVID-19 clinical outcomes than that of IL-6 alone or the three clinical biomarker panel (IL-6, glucose and creatine) with AUCs of 0.875 or 0.892.PMID:39636373 | DOI:10.1007/s11306-024-02195-y

FASEB J. 2024 Dec 15;38(23):e70226. doi: 10.1096/fj.202402088R.ABSTRACTMechano-induced keratinocyte hyperproliferation is reported to be associated with various skin diseases. Enhanced cell proliferation often requires the active metabolism of nutrients to produce energy. However, how keratinocytes adapt their cellular metabolism homeostasis to mechanical cues remains unclear. Here, we first found that mechanical stretched keratinocytes showed the accumulation of metabolic arachidonic acid by metabolomic analysis. Second, we found that mechanical stretch promoted keratinocyte proliferation through the activation of cytosolic calcium-dependent phospholipase A2 (cPLA2). Knockdown or inhibition of cPLA2 could reduce the release of arachidonic acid and inhibit the proliferation of stretched keratinocytes in vitro and in vivo. Third, by analyzing overlapping transcriptomes of stretched keratinocytes and arachidonic acid-stimulated keratinocytes, we identified the upregulation of hexokinase domain-containing protein 1 (HKDC1) expression, a novel gene involved in glucose metabolism, which was associated with arachidonic acid-induced keratinocyte proliferation during stretching. Our data reveal a metabolic regulation mechanism by which mechanical stretch induces keratinocyte proliferation, thereby coupling cellular metabolism to the mechanics of the cellular microenvironment. Strategies to change the metabolism process may lead to a new way to treat skin diseases that are related to biophysical forces.PMID:39636236 | DOI:10.1096/fj.202402088R

Elife. 2024 Dec 5;13:RP93004. doi: 10.7554/eLife.93004.ABSTRACTThe coordination of cell cycle progression and flagellar synthesis is a complex process in motile bacteria. In γ-proteobacteria, the localization of the flagellum to the cell pole is mediated by the SRP-type GTPase FlhF. However, the mechanism of action of FlhF, and its relationship with the cell pole landmark protein HubP remain unclear. In this study, we discovered a novel protein called FipA that is required for normal FlhF activity and function in polar flagellar synthesis. We demonstrated that membrane-localized FipA interacts with FlhF and is required for normal flagellar synthesis in Vibrio parahaemolyticus, Pseudomonas putida, and Shewanella putrefaciens, and it does so independently of the polar localization mediated by HubP. FipA exhibits a dynamic localization pattern and is present at the designated pole before flagellar synthesis begins, suggesting its role in licensing flagellar formation. This discovery provides insight into a new pathway for regulating flagellum synthesis and coordinating cellular organization in bacteria that rely on polar flagellation and FlhF-dependent localization.PMID:39636223 | DOI:10.7554/eLife.93004

Microbiol Spectr. 2024 Dec 5:e0122624. doi: 10.1128/spectrum.01226-24. Online ahead of print.ABSTRACTUnderstanding the extracellular electron transfer mechanisms of electroactive bacteria could help determine their potential in microbial fuel cells (MFCs) and their microbial syntrophy with redox-active minerals in natural environments. However, the mechanisms of extracellular electron transfer to electrodes by sulfate-reducing bacteria (SRB) remain underexplored. Here, we utilized double-chamber MFCs with carbon cloth electrodes to investigate the extracellular electron transfer mechanisms of Desulfovibrio vulgaris Hildenborough (DvH), a model SRB, under varying lactate and sulfate concentrations using different DvH mutants. Our MFC setup indicated that DvH can harvest electrons from lactate at the anode and transfer them to cathode, where DvH could further utilize these electrons. Patterns in current production compared with variations of electron donor/acceptor ratios in the anode and cathode suggested that attachment of DvH to the electrode and biofilm density were critical for effective electricity generation. Electron microscopy analysis of DvH biofilms indicated DvH utilized filaments that resemble pili to attach to electrodes and facilitate extracellular electron transfer from cell to cell and to the electrode. Proteomics profiling indicated that DvH adapted to electroactive respiration by presenting more pili- and flagellar-related proteins. The mutant with a deletion of the major pilus-producing gene yielded less voltage and far less attachment to both anodic and catholic electrodes, suggesting the importance of pili in extracellular electron transfer. The mutant with a deficiency in biofilm formation, however, did not eliminate current production indicating the existence of indirect extracellular electron transfer. Untargeted metabolomics profiling showed flavin-based metabolites, potential electron shuttles.IMPORTANCEWe explored the application of Desulfovibrio vulgaris Hildenborough in microbial fuel cells (MFCs) and investigated its potential extracellular electron transfer (EET) mechanism. We also conducted untargeted proteomics and metabolomics profiling, offering insights into how DvH adapts metabolically to different electron donors and acceptors. An understanding of the EET mechanism and metabolic flexibility of DvH holds promise for future uses including bioremediation or enhancing efficacy in MFCs for wastewater treatment applications.PMID:39636109 | DOI:10.1128/spectrum.01226-24

Front Pharmacol. 2024 Nov 20;15:1490892. doi: 10.3389/fphar.2024.1490892. eCollection 2024.ABSTRACTBACKGROUND: Pulmonary hypertension (PH) can lead to right ventricular hypertrophy, significantly increasing mortality rates. This study aims to clarify PH-specific metabolites and their impact on genomic and post-translational modifications (PTMs) in cancer, evaluating DHA and EPA's therapeutic potential to mitigate oxidative stress and inflammation.METHODS: Data from 289,365 individuals were analyzed using Mendelian randomization to examine 1,400 metabolites' causal roles in PH. Anti-inflammatory and antioxidative effects of DHA and EPA were tested in RAW 264.7 macrophages and cancer cell lines (A549, HCT116, HepG2, LNCaP). Genomic features like CNVs, DNA methylation, tumor mutation burden (TMB), and PTMs were analyzed. DHA and EPA's effects on ROS production and cancer cell proliferation were assessed.RESULTS: We identified 57 metabolites associated with PH risk and examined key tumor-related pathways through promoter methylation analysis. DHA and EPA significantly reduced ROS levels and inflammatory markers in macrophages, inhibited the proliferation of various cancer cell lines, and decreased nuclear translocation of SUMOylated proteins during oxidative stress and inflammatory responses. These findings suggest a potential anticancer role through the modulation of stress-related nuclear signaling, as well as a regulatory function on cellular PTMs.CONCLUSION: This study elucidates metabolic and PTM changes in PH and cancer, indicating DHA and EPA's role in reducing oxidative stress and inflammation. These findings support targeting these pathways for early biomarkers and therapies, potentially improving disease management and patient outcomes.PMID:39635438 | PMC:PMC11614602 | DOI:10.3389/fphar.2024.1490892

Front Pharmacol. 2024 Nov 20;15:1428604. doi: 10.3389/fphar.2024.1428604. eCollection 2024.ABSTRACTINTRODUCTION: Type 2 diabetes (T2D) is a metabolic disorder marked by disruptions in glucolipid metabolism, with numerous signaling pathways contributing to its progression. The liver, as the hub of glycolipid metabolism, plays a pivotal role in this context. Mulberry leaf (ML), a staple in traditional Chinese medicine, is widely utilized in the clinical management of T2D. Synthesizing existing literature with the outcomes of prior research, it has become evident that ML enhances glucose metabolism via multiple pathways.METHODS: In our study, we induced T2D in rats through a regimen of high-sugar and high-fat diet supplementation, coupled with intraperitoneal injections of streptozotocin. We subsequently administered the aqueous extract of ML to these rats and assessed its efficacy using fasting blood glucose levels and other diagnostic indicators. Further, we conducted a comprehensive analysis of the rats' liver tissues using metabolomics and proteomics to gain insights into the underlying mechanisms.RESULTS: Our findings indicate that ML not only significantly alleviated the symptoms in T2D rats but also demonstrated the capacity to lower blood glucose levels. This was achieved by modulating the glucose-lipid metabolism and amino-terminal pathways within the liver. ACSL5, Dlat, Pdhb, G6pc, Mdh2, Cs, and other key enzymes in metabolic pathways regulated by ML may be the core targets of ML treatment for T2D.DISCUSSION: Mulberry leaf ameliorate STZ induced diabetic rat by regulating hepatic glycometabolism and fatty acid β-oxidation.PMID:39635431 | PMC:PMC11614592 | DOI:10.3389/fphar.2024.1428604