PubMed

J Ethnopharmacol. 2023 Dec 29:117670. doi: 10.1016/j.jep.2023.117670. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Shen Bai formula (SBF) is a proven effective traditional Chinese medicine for treating viral myocarditis (VMC) sequelae in clinic, and myocardial injury is the pathological basis of VMC sequelae. However, the pharmacological action and mechanism of SBF have not been systematically elucidated.AIM OF THE STUDY: In present research, the doxorubicin-induced myocardial injury rat model was used to evaluate the efficacy of SBF, and energy metabolism and metabolomics approaches were applied to elucidate the effects of SBF on myocardial injury.MATERIALS AND METHODS: Through energy metabolism measurement system and UPLC-Q-TOF-MS/MS oriented blood metabolomics, directly reflected the therapeutic effect of SBF at a macro level, and identified biomarkers of myocardial injury in microcosmic, revealing its metabolomic mechanism.RESULTS: Results showed that SBF significantly improved the electrocardiogram (ECG), heart rate (HR), extent of myocardial tissue lesion, and ratio of heart and spleen. In addition, the serum levels of AST, CK, LDH, α-HBDH, cTnI, BNP, and MDA decreased, whereas SOD and ATP activity and content increased. Moreover, SBF increased locomotor activity and basic daily metabolism in rats with myocardial injury, restoring their usual level of energy metabolism. A total of 45 potential metabolomic biomarkers were identified. Among them, 44 biomarkers were significantly recalled by SBF, including representative biomarkers arachidonic acid (AA), 12-HETE, prostaglandin J2 (PGJ2), 15-deoxy-Δ-12,14-PGJ2, 15-keto-PGE2, 15(S)-HPETE, 15(S)-HETE, 8,11,14-eicosatrienoic acid and 9(S)-HODE, which involved AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism.CONCLUSION: We successfully replicated a myocardial injury rat model with the intraperitoneal injection of doxorubicin, and elucidated the mechanism of SBF in treating myocardial injury. This key mechanism may be achieved by targeting action on COX, Alox, CYP, and 15-PGDH to increase or decrease the level of myocardial injury biomarker, and then emphatically interven in AA metabolism, biosynthesis of unsaturated fatty acids and linoleic acid metabolism, and participate in regulating purine metabolism, sphingolipid metabolism, primary bile acid biosynthesis, and steroid hormone synthesis.PMID:38160867 | DOI:10.1016/j.jep.2023.117670

J Ethnopharmacol. 2023 Dec 29:117658. doi: 10.1016/j.jep.2023.117658. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus, diabetes belongs to the category of "emaciation-thirst disease" in traditional Chinese medicine (TCM). Bushen Huoxue Prescription (BHP) is composed of traditional Chinese materia medica, which has therapeutic effects on DR and early diabetic retinal edema (EDRE). However, the therapeutic mechanism is unclear.AIM OF THE STUDY: Exploring the mechanism of BHP against EDRE.METHODS: Feeding Sprague Dawley (SD) rats a high-fat, high-sugar diet as well as providing intraperitoneal injections of streptozotocin (STZ) to promote inner blood-retinal barrier (iBRB) damage that can trigger EDRE, evaluating the therapeutic effect of BHP by the level of expressiveness of TJ proteins (ZO-1,Occludin) of the iBRB and the leakage of rhodamine B isothiocyanate (RITC) in the retina. The combination of network pharmacology and metabolomics was employed to study the mechanism of BHP in preventing of EDRE, then four proteins which were closely to the damage of iBRB were chosen for the validation by employing Western Blot (WB).RESULTS: Research of network pharmacology had shown that BHP had efficacy against EDRE by regulating targets such as AKT1, ALB, TNF, PPARG, etc, its potential pathways mainly involving signaling pathways such as HIF-1. In untargeted metabolomics analysis of serum, 15 differential metabolites were identified, with the metabolic pathways focusing on ketone body metabolism and synthesis, sphingolipid metabolism and phenylalanine metabolism. The conclusions of metabolomics and network pharmacology revealed that BHP can treat EDRE by alleviating hypoxia and oxidative stress and exerting protection of the iBRB. Finally, BHP's protection behavior of the iBRB was validated by WB experiments.CONCLUSION: Through integrating pharmacodynamics, network pharmacology and metabolomics, BHP was discovered to have a crucial function in EDRE therapy by preserving the integrity of iBRB. This comprehensive strategy also provided a reasonable way to reveal the multi-components, multi-targets, multi-pathways mechanism of TCM.PMID:38160865 | DOI:10.1016/j.jep.2023.117658

Am J Clin Nutr. 2023 Dec 29:S0002-9165(23)66357-9. doi: 10.1016/j.ajcnut.2023.12.024. Online ahead of print.ABSTRACTBACKGROUND: Identifying lipidomic markers of diet quality is needed to inform the development of biomarkers of diet, and to understand the mechanisms driving the diet- coronary heart disease (CHD) association.OBJECTIVE: To identify lipidomic markers of diet quality and examine whether these lipids are associated with incident CHD.METHODS: Using LC-MS, we measured 1,542 lipid species from 1,694 American Indian adults (aged 18-75, 62% female) in the Strong Heart Family Study. Participants were followed for development of CHD through 2020. Information on past year diet was collected using the Block Food Frequency Questionnaire, and diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI). Mixed-effects linear regression was used to identify individual lipids cross-sectionally associated with AHEI. In prospective analysis, Cox frailty model was used to estimate the hazard ratio (HR) of each AHEI-related lipid for incident CHD. All models adjusted for age, sex, center, education, BMI, smoking, alcohol drinking, level of physical activity, energy intake, diabetes, hypertension, and use of lipid-lowering drugs. Multiple testing was controlled at false discovery rate <0.05.RESULTS: Among 1,542 lipid species measured, 71 lipid species (23 known) including acylcarnitine, cholesterol esters, glycerophospholipids, sphingomyelins and triacylglycerols, were associated with AHEI. Most of the identified lipids were associated with consumption of ω-3 fatty acids. In total, 147 participants developed CHD during a mean follow-up of 17.8 years. Among the diet-related lipids, 10 lipids (5 known, including CE(22:5)B, PC(p-14:0/22:1)/PC(o-14:0/22:1), PC(p-38:3)/PC(o-38:4)B, PE(p-18:0/20:4)/PE(o-18:0/20:4), and SM(d36:2)A) were associated with incident CHD. On average, each standard deviation increase in the baseline level of these 5 lipids was associated with 17%-23% increased risk of CHD [HR (95%CI) ranged from 1.17 (1, 1.36) to 1.23 (1.05, 1.43)].CONCLUSION: We identified lipidomic markers of diet quality in American Indian adults. Some diet-related lipids are associated with risk of CHD beyond established risk factors.PMID:38160800 | DOI:10.1016/j.ajcnut.2023.12.024

J Lipid Res. 2023 Dec 29:100494. doi: 10.1016/j.jlr.2023.100494. Online ahead of print.ABSTRACTHDL particles vary in lipidome and proteome, which dictate their individual physicochemical properties, metabolism, and biological activities. HDL dysmetabolism in non-diabetic hypertriglyceridemia (HTG) involves subnormal HDL-cholesterol and apoAI levels. Metabolic anomalies may impact the qualitative features of both the HDL lipidome and proteome. Whether particle content of bioactive lipids and proteins may differentiate HDL subclasses (HDL2b, 2a, 3a, 3b and 3c) in HTG is unknown. Moreover, little is known of the effect of statin treatment on the proteolipidome of hypertriglyceridemic HDL and its subclasses. Non-diabetic, obese, HTG males (n=12) received pitavastatin calcium (4mg/day) for 180 days in a single-phase, unblinded study. ApoB-containing lipoproteins were normalized post-statin. Individual proteolipidomes of density-defined HDL subclasses were characterized pre- and post-statin. At baseline, dense HDL3c was distinguished by marked protein diversity and peak abundance of surface lysophospholipids, amphipathic DAG and dhCer, and core CE and TAG, (normalized to mol PC), whereas light HDL2b showed peak abundance of COH, SM, glycosphingolipids (MHC, DHC, THC and anionic GM3), thereby arguing for differential lipid transport and metabolism between subclasses. Post-statin, bioactive lysophospholipid (LPC, LPC(O), LPE and LPI) cargo was preferentially depleted in HDL3c. By contrast, baseline lipidomic profiles of ceramide, dhCer and related glycosphingolipids and GM3/PC were maintained across particle subclasses. All subclasses were depleted in TAG and DAG/PC. The abundance of apolipoproteins CI, CII, CIV and M diminished in the HDL proteome. Statin treatment principally impacts metabolic remodeling of the abnormal lipidome of HDL particle subclasses in non-diabetic HTG, with lesser effects on the proteome.PMID:38160756 | DOI:10.1016/j.jlr.2023.100494

Curr Opin Pharmacol. 2023 Dec 29;74:102424. doi: 10.1016/j.coph.2023.102424. Online ahead of print.ABSTRACTRecent advancements in prostaglandin analogs (PGAs) have reinforced their role in managing intraocular pressure (IOP). Latanoprost excels in 24-h IOP control, while various PGAs offer similar effectiveness and side effects, generic PGAs perform as well as branded ones, and a notable IOP rise observed upon PGA discontinuation. Formulations with or without preservatives show comparable IOP reduction and adherence, often surpassing benzalkonium chloride (BAK)-preserved options. Emergent PGAs, such as latanoprostene bunod, fixed-dose netarsudil combined with latanoprost, and omidenepag Isopropyl, offer enhanced or non-inferior IOP reduction. The bimatoprost implant introduces a novel administration method with effective IOP reduction. These developments underscore ongoing progress in PGA-focused ophthalmological research. This article offers a comprehensive review of available prostanoid analogs and explores new developments.PMID:38160646 | DOI:10.1016/j.coph.2023.102424

Br J Cancer. 2023 Dec 30. doi: 10.1038/s41416-023-02553-y. Online ahead of print.ABSTRACTBACKGROUND: Lung cancer is the most lethal cancer, and 85% of cases are classified as non-small cell lung cancer (NSCLC). Metabolic rewiring is a cancer hallmark that causes treatment resistance, and lacks insights into serine/glycine pathway adaptations upon radiotherapy.METHODS: We analyzed radiotherapy responses using mass-spectrometry-based metabolomics in NSCLC patient's plasma and cell lines. Efficacy of serine/glycine conversion inhibitor sertraline with radiotherapy was investigated by proliferation, clonogenic and spheroid assays, and in vivo using a serine/glycine dependent NSCLC mouse model by assessment of tumor growth, metabolite and cytokine levels, and immune signatures.RESULTS: Serine/glycine pathway metabolites were significantly consumed in response to radiotherapy in NSCLC patients and cell models. Combining sertraline with radiotherapy impaired NSCLC proliferation, clonogenicity and stem cell self-renewal capacity. In vivo, NSCLC tumor growth was reduced solely in the sertraline plus radiotherapy combination treatment group. Tumor weights linked to systemic serine/glycine pathway metabolite levels, and were inhibited in the combination therapy group. Interestingly, combination therapy reshaped the tumor microenvironment via cytokines associated with natural killer cells, supported by eradication of immune checkpoint galectin-1 and elevated granzyme B levels.CONCLUSION: Our findings highlight that targeting serine/glycine metabolism using sertraline restricts cancer cell recovery from radiotherapy and provides tumor control through immunomodulation in NSCLC.PMID:38160212 | DOI:10.1038/s41416-023-02553-y

Acupunct Med. 2023 Dec 30:9645284231207871. doi: 10.1177/09645284231207871. Online ahead of print.ABSTRACTOBJECTIVE: To investigate the effects of electroacupuncture (EA) at ST36 on intestinal microflora and plasma metabolites in a mouse model of type 2 diabetes mellitus (T2DM), to provide a theoretical basis and guidance for the clinical treatment of T2DM by traditional Chinese medicine (TCM).METHODS: Sixteen T2DM db/db mice were randomly divided into treatment (T, n = 8) and model (M, n = 8) groups, and a further eight normal db/m+ mice reared under the same conditions served as a non-diabetic control group (C, n = 8). The general conditions of mice were observed weekly. After obtaining blood and stool samples, the mice were euthanized. Fasting blood glucose (FBG) was measured using a glucometer and fasting insulin (FINS) was measured in plasma by enzyme-linked immunosorbent assay (ELISA). Liver and colon tissues were embedded in paraffin and subjected to hematoxylin-eosin (HE) staining to observe pathological changes in these tissues. In addition, 16S ribosomal RNA (rRNA) sequencing was performed to analyze changes in the intestinal flora and metabolomics was employed to assess changes in metabolites in the blood.RESULTS: EA significantly reduced FBG and FINS levels and alleviated pathological damage to the liver and colon. Furthermore, EA increased intestinal community richness and diversity by decreasing the relative abundance of Clostridium and incresasing the relative abundance of Lactobacillus. EA also reduced D-fructose levels in T2DM mice according to plasma metabolomics.CONCLUSION: EA has a positive regulatory effect on the intestinal flora and can regulate blood glucose and improve insulin resistance in T2DM model mice.PMID:38160204 | DOI:10.1177/09645284231207871

J Biol Chem. 2023 Dec 28:105598. doi: 10.1016/j.jbc.2023.105598. Online ahead of print.ABSTRACTCofactor imbalance obstructs the productivities of metabolically engineered cells. Herein, we employed a minimally perturbing system, xylose reductase and lactose (XR/lactose), to increase levels of a pool of sugar-phosphates which are connected to the biosynthesis of NAD(P)H, FAD, FMN and ATP in Escherichia coli. The XR/lactose system could increase the amounts of the precursors of these cofactors and was tested with three different metabolically engineered cell systems (fatty alcohol biosynthesis, bioluminescence light generation and alkane biosynthesis) with different cofactor demands. Productivities of these cells were increased 2-4-fold by the XR/lactose system. Untargeted metabolomic analysis revealed different metabolite patterns among these cells; demonstrating that only metabolites involved in relevant cofactor biosynthesis were altered. The results were also confirmed by transcriptomic analysis. Another sugar reducing system (glucose dehydrogenase, GDH) could also be used to increase fatty alcohol production but resulted in less yield enhancement than XR. This work demonstrates that the approach of increasing cellular sugar phosphates can be a generic tool to increase in vivo cofactor generation upon cellular demand for synthetic biology.PMID:38159859 | DOI:10.1016/j.jbc.2023.105598

Sci Total Environ. 2023 Dec 28:169606. doi: 10.1016/j.scitotenv.2023.169606. Online ahead of print.ABSTRACTNanoplastic particles are pervasive environmental contaminants with potential health risks, while mouse intestinal organoids provide accurate in vitro models for studying these interactions. Metabolomics, especially through LC-MS, enables detailed cellular response studies, and there's a novel interest in comparing metabolic changes across nanoparticle species using gut organoids. This study used a mouse intestinal organoid combined with cell model to explore the differences in metabolites and toxicity mechanisms induced by exposure to three nanoplastics (PS, PTFE, and PMMA). The results showed that PS, PTFE, and PMMA exposure reduced mitochondrial membrane potential, intracellular ROS accumulation and oxidative stress, and inhibited the AKT/mTOR signaling pathway. Non-targeted metabolomics results confirmed that three types of nanoplastic particles regulate cellular status by regulating fatty acid metabolism, nucleotide metabolism, necroptosis and autophagy pathways. More importantly, these representative metabolites were further validated in model groups after mouse intestinal organoids and HCT116 cells were exposed to the respective NPs, indicating that organoid metabolomics results can be used to effectively predict toxicity. Untargeted metabolomics is sensitive enough to detect subtle metabolomic changes when functional cellular analysis shows no significant differences. Overall, our study reveals the underlying metabolic mechanism of NPs-induced intestinal organoid toxicity and provides new insights into the possible adverse consequences of NPs.PMID:38159744 | DOI:10.1016/j.scitotenv.2023.169606

Environ Pollut. 2023 Dec 28:123238. doi: 10.1016/j.envpol.2023.123238. Online ahead of print.ABSTRACTExposure to pesticides has been associated with several cardiovascular complications in animal models. Neonicotinoids are now the most widely used insecticide globally, while the impact of neonicotinoids on cardiovascular function and the role of mitochondrial dynamics in neonicotinoids-induced cardiotoxicity is unclear. In the present study, Xenopus laevis tadpoles were exposed to environmental related concentrations (0, 5, and 50 μg/L) of typical neonicotinoid dinotefuran, with two enantiomers, for 21 days. We evaluated the changes in heart rate and cardiomyocyte apoptosis in exposed tadpoles. Then, we performed the transcriptome, metabolomics, transmission electron microscopy (TEM), and protein immunoblot to investigate the potential adverse impact of two enantiomers of dinotefuran on cardiotoxicity associated with mitochondrial dynamics. We observed changes in heart rate and increased cardiomyocyte apoptosis in exposed tadpoles, indicating that dinotefuran had a cardiotoxic effect. We further found that the cardiac contractile function pathway was significantly enriched, while the glucose metabolism-related pathways were also disturbed significantly. TEM observation revealed that the mitochondrial morphology of cardiomyocytes in exposed tadpoles was swollen, and mitophagy was increased. Mitochondria fusion was excessively manifested in the enhanced mitochondrial fusion protein. The mitochondrial respiratory chain was also disturbed, which led to an increase in ROS production and a decrease in ATP content. Therefore, our results suggested that dinotefuran exposure can induce cardiac disease associated mitochondrial disorders by interfering with the functionality and dynamics of mitochondria. In addition, both two enantiomers of dinotefuran have certain toxicity to tadpole cardiomyocytes, while R-dinotefuran exhibited higher toxicity than S-enantiomer, which may be attributed to disparities in the activation capacities of the respiratory chain.PMID:38159629 | DOI:10.1016/j.envpol.2023.123238

Environ Pollut. 2023 Dec 28;343:123261. doi: 10.1016/j.envpol.2023.123261. Online ahead of print.ABSTRACTMonoaromatic hydrocarbons (MAHs) and polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants from industry, with multiple adverse effects on respiratory system. However, the underlying mechanisms of their mixture to induce asthma is still unclear. Here, we examined mixture of 8 MAHs, mixture of 16 PAHs and a total mixture (MIX) on human bronchial epithelial (16-HBE) cells. Exposure to MIX resulted in increased expressions of asthma alarm cytokines (TSLP, IL-25 and IL-33), indicating potential asthma risk. Exposure to MIX led to significant upregulation of transcriptional level of oxidative stress and inflammation biomarkers through aryl hydrocarbon receptor activation, including SOD-2, NQO-1, IL-1β, IL-6 and IL-8 with 3.1, 19.9, 3.5, 23.4, 18.7, 28.1-fold change, indicated asthma related epithelial cell lesions. A total of 25, 49 and 59 differential metabolites were identified in cells response to MAH, PAH and MIX exposure, respectively, and enrichment analysis demonstrated MIX exposure disturbing alanine, aspartate and glutamate metabolism, glutathione metabolism, methionine metabolism and sphingolipid metabolism, involved in antioxidative defense and inflammation response. Combined exposure of MAHs and PAHs may result in increased toxic risks, and provide evidence to asthma onset and deterioration.PMID:38159626 | DOI:10.1016/j.envpol.2023.123261

Plant Physiol Biochem. 2023 Dec 27;206:108304. doi: 10.1016/j.plaphy.2023.108304. Online ahead of print.ABSTRACTBlindness is a physiopathy characterized by apical abortion that particularly affects the Brassica family. The occurrence of blindness has been related to exposure to low temperatures during early developmental stages. However, the causes of this selective sensitivity and how they affect the correct development remain unknown. In this study, we investigated the mechanisms involved in the occurrence of blindness in broccoli plants. The analysis of RNAseq, focused on membrane transporters and the synthesis pathways of glucosinolates and phenolics, was related with physiological changes in nutrient and water uptake, gas exchange, and metabolism. Comparative gene expression analysis between control and blindness-affected broccoli plants revealed distinct regulation patterns in roots and shoots, leading to reduced synthesis of glucosinolates and phenolics. Additionally, the expression levels of aquaporins and potassium transporters were found to be associated with mineral and water transport. In this way, our results revealed the causes of blindness by identifying differentially expressed genes, highlighting those related to secondary metabolism, as well as genes involved in water and nutrient uptake and transport as the crucial involved in the physiopathy appearance.PMID:38159550 | DOI:10.1016/j.plaphy.2023.108304

Plant Physiol Biochem. 2023 Dec 26;206:108318. doi: 10.1016/j.plaphy.2023.108318. Online ahead of print.ABSTRACTWe used manganese (Mn)-tolerant 'Xuegan' (Citrus sinensis) seedlings as materials and examined the characterization of Mn uptake and Mn-activated-release of root exudates under hydroponic conditions. We observed that root and shoot Mn bioaccumulation factor (BCF) reduced with the increase of Mn supply, and that Mn transfer factor (Tf) reduced greatly as Mn supply increased from 0 to 500 μM, beyond which Tf slightly increased with increasing Mn supply, suggesting that Mn supply reduced the ability to absorb and accumulate Mn in roots and shoots, as well as root-to-shoot Mn translocation. Without Mn, roots alkalized the solution pH from 5.0 to above 6.2, while Mn supply reduced root-induced alkalization. As Mn supply increased from 0 to 2000 μM, the secretion of root total phenolics (TPs) increased, while the solution pH decreased. Mn supply did not alter the secretion of root total free amino acids, total soluble sugars, malate, and citrate. Mn-activated-release of TPs was inhibited by low temperature and anion channel inhibitors, but not by protein biosynthesis inhibitor. Using widely targeted metabolome, we detected 48 upregulated [35 upregulated phenolic compounds + 13 other secondary metabolites (SMs)] and three downregulated SMs, and 39 upregulated and eight downregulated primary metabolites (PMs). These findings suggested that reduced ability to absorb and accumulate Mn in roots and shoots and less root-to-shoot Mn translocation in Mn-toxic seedlings, rhizosphere alkalization, and Mn-activated-release of root exudates (especially phenolic compounds) contributed to the high Mn tolerance of C. sinensis seedlings.PMID:38159548 | DOI:10.1016/j.plaphy.2023.108318

J Hazard Mater. 2023 Dec 27;465:133376. doi: 10.1016/j.jhazmat.2023.133376. Online ahead of print.ABSTRACTDeoxynivalenol contamination in feed and food, pervasive from growth, storage, and processing, poses a significant risk to dairy cows, particularly when exposed to a high-starch diet; however, whether a high-starch diet exacerbates these negative effects remains unclear. Therefore, we investigated the combined impact of deoxynivalenol and dietary starch on the production performance, rumen function, and health of dairy cows using metabolomics and 16 S rRNA sequencing. Our findings suggested that both high- and low-starch diets contaminated with deoxynivalenol significantly reduced the concentration of propionate, isobutyrate, valerate, total volatile fatty acids (TVFA), and microbial crude protein (MCP) concentrations, accompanied by a noteworthy increase in NH3-N concentration in vitro and in vivo (P < 0.05). Deoxynivalenol altered the abundance of microbial communities in vivo, notably affecting Oscillospiraceae, Lachnospiraceae, Desulfovibrionaceae, and Selenomonadaceae. Additionally, it significantly downregulated lecithin, arachidonic acid, valine, leucine, isoleucine, arginine, and proline metabolism (P < 0.05). Furthermore, deoxynivalenol triggered oxidative stress, inflammation, and dysregulation in immune system linkage, ultimately compromising the overall health of dairy cows. Collectively, both high- and low-starch diets contaminated with deoxynivalenol could have detrimental effects on rumen function, posing a potential threat to production performance and the overall health of cows. Notably, the negative effects of deoxynivalenol are more pronounced with a high-starch diet than a low-starch diet.PMID:38159518 | DOI:10.1016/j.jhazmat.2023.133376

Cell Rep. 2023 Dec 28;43(1):113615. doi: 10.1016/j.celrep.2023.113615. Online ahead of print.ABSTRACTThe integrated stress response (ISR) is critical for cell survival under stress. In response to diverse environmental cues, eIF2α becomes phosphorylated, engendering a dramatic change in mRNA translation. The activation of ISR plays a pivotal role in the early embryogenesis, but the eIF2-dependent translational landscape in pluripotent embryonic stem cells (ESCs) is largely unexplored. We employ a multi-omics approach consisting of ribosome profiling, proteomics, and metabolomics in wild-type (eIF2α+/+) and phosphorylation-deficient mutant eIF2α (eIF2αA/A) mouse ESCs (mESCs) to investigate phosphorylated (p)-eIF2α-dependent translational control of naive pluripotency. We show a transient increase in p-eIF2α in the naive epiblast layer of E4.5 embryos. Absence of eIF2α phosphorylation engenders an exit from naive pluripotency following 2i (two chemical inhibitors of MEK1/2 and GSK3α/β) withdrawal. p-eIF2α controls translation of mRNAs encoding proteins that govern pluripotency, chromatin organization, and glutathione synthesis. Thus, p-eIF2α acts as a key regulator of the naive pluripotency gene regulatory network.PMID:38159280 | DOI:10.1016/j.celrep.2023.113615

J Exp Bot. 2023 Dec 30:erad508. doi: 10.1093/jxb/erad508. Online ahead of print.ABSTRACTPhotosynthesis plays a vital role in acclimating to and mitigating climate change, providing food and energy security for a population that is constantly growing, and achieving an economy with zero carbon emissions. A thorough comprehension of the dynamics of photosynthesis, including its molecular regulatory network and limitations, is essential for utilizing it as a tool to boost plant growth, enhance crop yields, and support the production of plant biomass for carbon storage. Photorespiration constrains photosynthetic efficiency and contributes significantly to carbon loss. Therefore, modulating or circumventing photorespiration presents opportunities to enhance photosynthetic efficiency. Over the past eight decades substantial progress has been made in elucidating the molecular basis of photosynthesis, photorespiration, and the key regulatory mechanisms involved, beginning with the discovery of the canonical Calvin-Benson-Bassham cycle. Advanced chromatographic and mass spectrometric technologies have allowed a comprehensive analysis of the metabolite patterns associated with photosynthesis, contributing to a deeper understanding of its regulation. In this review, we summarize of the results of metabolomics studies that shed light on the molecular intricacies of photosynthetic metabolism. We also discuss the methodological requirements essential for effective analysis of photosynthetic metabolism, highlighting the value of this technology in supporting strategies aimed at enhancing photosynthesis.PMID:38158893 | DOI:10.1093/jxb/erad508

Chem Biodivers. 2023 Dec 29:e202301653. doi: 10.1002/cbdv.202301653. Online ahead of print.ABSTRACTRheumatoid arthritis (RA) is an autoimmune disease characterized by aggressive cartilage and bone erosion. This work aimed to evaluate the metabolomic profile of Medicago sativa L. (MS) seeds and explore its therapeutic impact against RA in rats. Arthritis was induced by complete Freund's adjuvant (CFA) and its severity was assessed by the arthritis index. Treatment with MS seeds butanol fraction and interlukin-1 receptor antagonist (IL-1RA) were evaluated through measuring interlukin-1 receptor (IL-1R) type 1 gene expression, interlukin-1 beta (IL-1β), oxidative stress markers, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), caspase-3 (Cas-3), intracellular adhesion molecule-1 (ICAM-1), DNA fragmentation, and chromosomal damage. Total phenolics/ flavonoids content in the ethyl acetate, butanol fraction and crude extract of MS seeds were estimated. The major identified compounds were Quercetin, Trans-taxifolin, gallic acid, 7,4'-Dihydroxyflavone, Cinnamic acid, Kudzusaponin SA4, Isorhamnetin 3-O-beta-D-2'',3'',4''-triacetylglucopyranoside, Apigenin, 5,7,4'-Trihydroxy-3'-methoxyflavone, Desmethylxanthohumol, Pantothenic acid, Soyasapogenol E, Malvidin, Helilandin B, Stigmasterol, and Wairol. Treatment with MS seeds butanol fraction and IL-1RA enhanced all the biochemical parameters and the histopathological features of the ankle joint. In conclusion, Trans-taxifolin was isolated for the first time from the genus Medicago. MS butanol fraction seeds extract and IL-1 RA were considered as anti-rheumatic agents.PMID:38158718 | DOI:10.1002/cbdv.202301653

J Extracell Vesicles. 2024 Jan;13(1):e12397. doi: 10.1002/jev2.12397.ABSTRACTCerebrospinal fluid (CSF) is a clear, transparent fluid derived from blood plasma that protects the brain and spinal cord against mechanical shock, provides buoyancy, clears metabolic waste and transports extracellular components to remote sites in the brain. Given its contact with the brain and the spinal cord, CSF is the most informative biofluid for studies of the central nervous system (CNS). In addition to other components, CSF contains extracellular vesicles (EVs) that carry bioactive cargoes (e.g., lipids, nucleic acids, proteins), and that can have biological functions within and beyond the CNS. Thus, CSF EVs likely serve as both mediators of and contributors to communication in the CNS. Accordingly, their potential as biomarkers for CNS diseases has stimulated much excitement for and attention to CSF EV research. However, studies on CSF EVs present unique challenges relative to EV studies in other biofluids, including the invasive nature of CSF collection, limited CSF volumes and the low numbers of EVs in CSF as compared to plasma. Here, the objectives of the International Society for Extracellular Vesicles CSF Task Force are to promote the reproducibility of CSF EV studies by providing current reporting and best practices, and recommendations and reporting guidelines, for CSF EV studies. To accomplish this, we created and distributed a world-wide survey to ISEV members to assess methods considered 'best practices' for CSF EVs, then performed a detailed literature review for CSF EV publications that was used to curate methods and resources. Based on responses to the survey and curated information from publications, the CSF Task Force herein provides recommendations and reporting guidelines to promote the reproducibility of CSF EV studies in seven domains: (i) CSF Collection, Processing, and Storage; (ii) CSF EV Separation/Concentration; (iii) CSF EV Size and Number Measurements; (iv) CSF EV Protein Studies; (v) CSF EV RNA Studies; (vi) CSF EV Omics Studies and (vii) CSF EV Functional Studies.PMID:38158550 | DOI:10.1002/jev2.12397

Environ Sci Pollut Res Int. 2023 Dec 30. doi: 10.1007/s11356-023-31561-x. Online ahead of print.ABSTRACTThe honey bee is an important pollinator insect susceptible to environmental contaminants. We investigated the effects of a waste fire event on elemental content, oxidative stress, and metabolic response in bees fed different nutrients (probiotics, Quassia amara, and placebo). The level of the elements was also investigated in honey and beeswax. Our data show a general increase in elemental concentrations in all bee groups after the event; however, the administration of probiotics and Quassia amara help fight oxidative stress in bees. Significantly lower concentrations of Ni, S, and U for honey in the probiotic group and a general and significant decrease in elemental concentrations for beeswax in the probiotic group and Li in the Quassia amara group were observed after the fire waste event. The comparison of the metabolic profiles through pre- and post-event PCA analyses showed that bees treated with different feeds react differently to the environmental event. The greatest differences in metabolic profiles are observed between the placebo-fed bees compared to the others. This study can help to understand how some stress factors can affect the health of bees and to take measures to protect these precious insects.PMID:38158534 | DOI:10.1007/s11356-023-31561-x

Pigment Cell Melanoma Res. 2023 Dec 29. doi: 10.1111/pcmr.13158. Online ahead of print.ABSTRACTIntercellular communication is a cell-type and stimulus-dependent event driven not only by soluble factors but also by extracellular vesicles (EVs). EVs include vesicles of different size and origin that contain a myriad of molecules. Among them, small EVs (sEV; <200 nm) have been shown to modulate not just regional cell responses but also distant organ behavior. In cancer, distant organ modulation by sEVs has been associated to disease dissemination, which is one of the main concerns in melanoma. Description of broadly conserved alterations in sEV-contained molecules represents a strategy to identify key modifications in cellular communication as well as new disease biomarkers. Here, we characterize proteomes of cutaneous melanocyte and melanoma-derived sEVs to deepen on the landscape of normal and disease-related cell communication. Results reveal the presence of unique protein signatures for melanocytes and melanoma cells that reflect cellular transformation-related profound modifications. Melanocyte-derived sEVs are enriched in oxidative metabolism (e.g., aconitase 2, ACO2) or pigmentation (e.g., tyrosinase, TYR) related proteins while melanoma-derived sEVs reflect a generalized decrease in mature melanocytic markers (e.g., melanoma antigen recognized by T-cells 1, MART-1, also known as MLANA) and an increase in epithelial to mesenchymal transition (EMT)-related adhesion molecules such as tenascin C (TNC).PMID:38158521 | DOI:10.1111/pcmr.13158