PubMed

J Ethnopharmacol. 2024 Jun 27:118465. doi: 10.1016/j.jep.2024.118465. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease.AIM OF THE STUDY: To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS.MATERIALS AND METHODS: This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia.RESULTS: PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe2+ efflux and regulating mitochondrial Fe2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer).CONCLUSIONS: This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.PMID:38944360 | DOI:10.1016/j.jep.2024.118465

J Ethnopharmacol. 2024 Jun 27:118500. doi: 10.1016/j.jep.2024.118500. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use.AIM OF THE STUDY: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium.MATERIALS AND METHODS: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound.RESULTS: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc26230 in both log phase growth and metabolically downshifted hypoxic cultures.CONCLUSIONS: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.PMID:38944359 | DOI:10.1016/j.jep.2024.118500

Genomics. 2024 Jun 27:110893. doi: 10.1016/j.ygeno.2024.110893. Online ahead of print.ABSTRACTUnderstanding phytohormonal signaling is crucial for elucidating plant defense mechanisms against environmental stressors. However, knowledge regarding phytohormone-mediated tolerance pathways under salt stress in Elymus sibiricus, an important species for forage and ecological restoration, remains limited. In this study, transcriptomic and metabolomic approaches uncover the dynamics of phytohormonal signaling in Elymus sibiricus under salt stress. Notably, four hours after exposure to salt, significant activity was observed in the ABA, JA, IAA, and CTK pathways, with ABA, JA, JA-L-Ile, and IAA identified as key mediators in the response of Elymus sibiricus' to salinity. Moreover, SAPK3, Os04g0167900-like, CAT1, MKK2, and MPK12 were identified as potential central regulators within these pathways. The complex interactions between phytohormones and DEGs are crucial for facilitating the adaptation of Elymus sibiricus to saline environments. These findings enhance our understanding of the salt tolerance mechanisms in Elymus sibiricus and provide a foundation for breeding salt-resistant varieties.PMID:38944355 | DOI:10.1016/j.ygeno.2024.110893

Environ Pollut. 2024 Jun 27:124466. doi: 10.1016/j.envpol.2024.124466. Online ahead of print.ABSTRACTOxidative stress is a universal interpretation for the toxicity mechanism of nanoplastics to microalgae. However, there is a lack of deeper insight into the regulation mechanism in microalgae response to oxidative stress, thus affecting the prevention and control for nanoplastics hazard. The integrated analysis of transcriptomics and metabolomics was employed to investigate the mechanism for the oxidative stress response of Chlorella pyrenoidosa to nanoplastics and subsequently lock the according core pathways and driver genes induced. Results indicated that the linoleic acid metabolism, glycine (Gly)-serine (Ser)-threonine (Thr) metabolism, and arginine and proline metabolism pathways of C. pyrenoidosa were collectively involved in oxidative stress. The analysis of linoleic acid metabolism suggested that nanoplastics prompted algal cells to secrete more allelochemicals, thereby leading to destroy the immune system of cells. Gly-Ser-Thr metabolism and arginine and proline metabolism pathways were core pathways involved in algal regulation of cell membrane function and antioxidant system. Key genes, such as LOX2.3, SHM1, TRPA1, and proC1, are drivers of regulating the oxidative stress of algae cells. This investigation lays the foundation for future applications of gene editing technology to limit the hazards of nanoplastics on aquatic organism.PMID:38944181 | DOI:10.1016/j.envpol.2024.124466

Ecotoxicol Environ Saf. 2024 Jun 28;281:116662. doi: 10.1016/j.ecoenv.2024.116662. Online ahead of print.ABSTRACTOBJECTIVE: This study aimed to investigate the mechanism that Lactobacillus murinus (L. murinus) alleviated lung inflammation induced by polycyclic aromatic hydrocarbons (PAHs) exposure based on metabolomics.METHODS: Female mice were administrated with PAHs mix, L. murinus and indoleacrylic acid (IA) or indolealdehyde (IAId). Microbial diversity in feces was detected by 16 S rRNA gene sequencing. Non-targeted metabolomics analysis in urine samples and targeted analysis of tryptophan metabolites in serum by UPLC-Orbitrap-MS and short-chain fatty acids (SCFA) in feces by GC-MS were performed, respectively. Flow cytometry was used to determine T helper immune cell differentiation in gut and lung tissues. The levels of IgE, IL-4 and IL-17A in the bronchoalveolar lavage fluid (BALF) or serum were detected by ELISA. The expressions of aryl hydrocarbon receptor (Ahr), cytochrome P450 1A1 (Cyp1a1) and forkheadbox protein 3 (Foxp3) genes and the histone deacetylation activity were detected by qPCR and by ELISA in lung tissues, respectively.RESULTS: PAHs exposure induced lung inflammation and microbial composition shifts and tryptophan metabolism disturbance in mice. L. murinus alleviated PAHs-induced lung inflammation and inhibited T helper cell 17 (Th17) cell differentiation and promoted regulatory T cells (Treg) cell differentiation. L. murinus increased the levels of IA and IAId in the serum and regulated Th17/Treg imbalance by activating AhR. Additionally, L. murinus restored PAHs-induced decrease of butyric acid and valeric acid which can reduce the histone deacetylase (HDAC) level in the lung tissues, enhancing the expression of the Foxp3 gene and promoting Treg cell differentiation.CONCLUSION: our study illustrated that L. murinus alleviated PAHs-induced lung inflammation and regulated Th17/Treg cell differentiation by regulating host tryptophan metabolism and SCFA levels. The study provided new insights into the reciprocal influence between gut microbiota, host metabolism and the immune system, suggesting that L. murinus might have the potential as a novel therapeutic strategy for lung diseases caused by environmental pollution in the future.PMID:38944008 | DOI:10.1016/j.ecoenv.2024.116662

Biomed Pharmacother. 2024 Jun 28;177:117067. doi: 10.1016/j.biopha.2024.117067. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Drugs resolving steatotic liver disease (SLD) could prevent the evolution of metabolic dysfunction associated SLD (MASLD) to more aggressive forms but must show not only efficacy, but also a high safety profile. Repurposing of drugs in clinical use, such as pemafibrate and mirabegron, could facilitate the finding of an effective and safe drug-treatment for SLD.APPROACH AND RESULTS: The SLD High Fat High Fructose (HFHFr) rat model develops steatosis without the influence of other metabolic disturbances, such as obesity, inflammation, or type 2 diabetes. Further, liver fatty acids are provided, as in human pathology, both from dietary origin and de novo lipid synthesis. We used the HFHFr model to evaluate the efficacy of pemafibrate and mirabegron, alone or in combination, in the resolution of SLD, analyzing zoometric, biochemical, histological, transcriptomic, fecal metabolomic and microbiome data. We provide evidence showing that pemafibrate, but not mirabegron, completely reverted liver steatosis, due to a direct effect on liver PPARα-driven fatty acid catabolism, without changes in total energy consumption, subcutaneous, perigonadal and brown fat, blood lipids and body weight. Moreover, pemafibrate treatment showed a neutral effect on whole-body glucose metabolism, but deeply modified fecal bile acid composition and microbiota.CONCLUSIONS: Pemafibrate administration reverts liver steatosis in the HFHFr dietary rat SLD model without altering parameters related to metabolic or organ toxicity. Our results strongly support further clinical research to reposition pemafibrate for the treatment of SLD/MASLD.PMID:38943989 | DOI:10.1016/j.biopha.2024.117067

Food Chem. 2024 Jun 25;458:140226. doi: 10.1016/j.foodchem.2024.140226. Online ahead of print.ABSTRACTShaking constitutes a pivotal technique for enhancing black tea quality; nevertheless, its impact on the transformation mechanism of non-volatile metabolites (NVMs) in black tea remains obscure. The present study aimed to investigate the impact of shaking-withering methods (SWM) and traditional-withering methods (TWM) on black tea quality and NVMs conversion. A total of 57 NVMs and 14 objective quantitative indicators were obtained. SWM enhanced sweetness and umami taste, as well as appearance and liquor color brightness of black tea. Eight key differential NVMs were identified by multivariate statistical and dose over threshold value analysis. Metabolic pathway and evolution law analysis revealed that SWM enhanced the oxidation of catechins and flavonol glycosides, promoted the decarboxylation of glutamic acid, then facilitated the formation of theaflavin-3,3'-digallate, finally enhanced the taste and color quality of black tea. This study offers theoretical guidance and technical support for the targeted processing of high-quality black tea.PMID:38943961 | DOI:10.1016/j.foodchem.2024.140226

Food Chem. 2024 Jun 24;458:140207. doi: 10.1016/j.foodchem.2024.140207. Online ahead of print.ABSTRACTFalse flax (Camelina sativa L.), known as camelina, is an ancient oil plant that has gathered renewed interest. In this study, a comprehensive analysis encompassing nontargeted volatilomics and targeted, quantitative metabolomics performed for cold-pressed oil and press cake and was integrated with sensory analysis of cold-pressed camelina oil and the effect of seed roasting was evaluated. Roasting in general resulted in the formation of 22 new volatile organic compounds (VOCs) in oil, while roasting at 140 and 180 °C resulted in the formation of 12 and 124 unique VOCs, respectively. Roasting notably influenced the profile of primary and secondary metabolites in both oil and press cakes, as well as volatilome and aroma of cold-pressed camelina oil. Many VOCs can be attributed to thermal degradation of primary and secondary metabolites. Roasting intensified the flavour of cold-pressed camelina oil, enhancing the perception of notes formed through the Maillard reaction.PMID:38943959 | DOI:10.1016/j.foodchem.2024.140207

Food Chem. 2024 Jun 16;457:140130. doi: 10.1016/j.foodchem.2024.140130. Online ahead of print.ABSTRACTComparative proteomics and non-target metabolomics, together with physiological and microstructural analyses of wheat grains (at 15, 20, 25, and 30 days after anthesis) from two different quality wheat varieties (Gaoyou 5766 (strong-gluten) and Zhoumai 18) were performed to illustrate the grain filling material dynamics and to search for quality control genes. The differential expressions of 1541 proteins and 406 metabolites were found. They were mostly engaged in protein metabolism, stress/defense, energy metabolism, and amino acid metabolism, and the metabolism of stored proteins and carbohydrates was the major focus of the latter stages. The core proteins and metabolites in the growth process were identified, and the candidate genes for quality differences were screened. In conclusion, this study offers a molecular explanation for the establishment of wheat quality, and it aids in our understanding of the intricate metabolic network between different qualities of wheat at the filling stage.PMID:38943917 | DOI:10.1016/j.foodchem.2024.140130

J Trace Elem Med Biol. 2024 Jun 21;85:127491. doi: 10.1016/j.jtemb.2024.127491. Online ahead of print.ABSTRACTBACKGROUND: Chronic kidney disease (CKD) is a global public health problem, resulting in end-stage kidney disease, cardiovascular disease, and premature death.AIM: The aim of the study was to determine the profile of essential and toxic trace elements in erythrocytes of patients with end-stage renal disease (ESRD) and their relationship with selected anthropometric and biochemical parameters.METHODS: The present study compared the profiles of trace elements, including toxic sub-stances, in the erythrocytes of 80 hemodialysis patients with CKD with 40 healthy subjects. All patients had stage 5 CKD. The levels of Cd and Pb were determined by graphite furnace atomic absorption spectrometry and levels of Fe, Mn, Zn, Cu Cr, Ni, and Li by inductively coupled plasma atomic emission spectrometry.RESULTS: The ESRD patients demonstrated significantly lower Fe and Zn concentrations and significantly higher Mn and Li and toxic Pb and Cd concentrations in erythrocytes compared to those of the healthy controls. Negative correlations were observed, among others, between the concentrations of Cu, Li, and creatinine; Cu and phosphates; Mn, Pb, and transferrin saturation while positive correlations were noted between Cu, Cr, and transferrin and Pb, Cr, and the normalized protein catabolism rate.CONCLUSIONS: The higher concentrations of toxic elements present in the erythrocytes of CKD patients might have resulted from the reduced ability of the kidneys to excrete them. Moreover, differences in the concentrations of essential elements (Fe, Mn, Zn) between the two groups indicated that their resorption in the kidneys of CKD patients was impaired. Patients with CKD might benefit from interventions intended to reduce high, toxic concentrations of Pb and Cd and Li and Mn as an alternative supportive treatment. Iron and zinc supplementation should be a component for the treatment of anemia in CKD patients.PMID:38943837 | DOI:10.1016/j.jtemb.2024.127491

J Pharm Biomed Anal. 2024 Jun 26;248:116328. doi: 10.1016/j.jpba.2024.116328. Online ahead of print.ABSTRACTOxylipins are important low abundant signaling molecules in living organisms. In platelets they play a primary role in platelet activation and aggregation in the course of thrombotic events. In vivo, they are enzymatically synthesized by cyclooxygenases, lipoxygenases, or cytochrome P450 isoenzmes, resulting in diverse polyunsaturated fatty acid (FA) metabolites including hydroxy-, epoxy-, oxo-FAs, and endoperoxides with pro-thrombotic or anti-thrombotic effects. In a recent study, it was reported that hemin induces platelet death which was accompanied by enhanced reactive oxygen species (ROS) production (measured by flow cytometry) and lipid peroxidation (as determined by proxy using flow cytometry with BODIPY-C11 as sensor). Lipidomic studies further indicated significant changes of the platelet lipidome upon ex vivo hemin treatment, amongst others oxylipins were increased. The effect could be (at least partly) reversed by riociguat/diethylamine NONOate diethylammonium salt (DEA/NO) which modulates the soluble guanylate cyclase(sGC)-cGMP-cGMP-dependent protein kinase I(cGKI) signaling axis. In the original work, oxylipins were measured by a non-enantioselective UHPLC-tandem-MS assay which may not give the full picture whether oxylipin elevation is due to ROS or by enzymatic processes. We present here the study of the stereochemical disposition of hemin-induced platelet lipidome alterations using Chiralpak IA-U column with amylose tris(3,5-dimethylphenylcarbamate) chiral selector immobilized on 1.6 µm silica particles. It was found that the major platelet oxylipins 12-HETE, 12-HEPE and 14-HDoHE (from 12-LOX) and 12-HHT (from COX-1) were present in S-configuration indicating their enzymatic formation. On the other hand, both R and S enantiomers of 9- and 13-HODE, 11- and 15-HETE were detected, possibly due to enzyme promiscuity rather than non-specific oxidation (by ROS or autoxidation), as confirmed by multi-loop based two-dimensional LC-MS using selective comprehensive mode with achiral RPLC in the 1st dimension and chiral LC in the 2nd using a multiple heart-cutting interface. For 12-HETrE, a peak at the retention time of the R-enantiomer was ruled out as isobaric interference by 2D-LC-MS. In particular, arachidonic acid derivates 12(S)-HHT, 11(R)-HETE and 15(S)-HETE were found to be sensitive to hemin and cGMP modulation.PMID:38943819 | DOI:10.1016/j.jpba.2024.116328

J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Jun 25;1243:124219. doi: 10.1016/j.jchromb.2024.124219. Online ahead of print.ABSTRACTThe variation of qualitative information among different types of mainstream hyphenated instruments of ultra-performance liquid chromatography coupled to high-resolution mass spectrometry (UPLC-HRMS) makes data sharing and standardization, and further comparison of results consistency in metabolite annotation not easy to attain. In this work, a quantitative study of correlation and difference was first achieved to systematically investigate the variation of retention time (tR), precursor ion (MS1), and product fragment ions (MS2) generated by three typical UPLC-HRMS instruments commonly used in metabolomics area. In terms of the findings of systematic and correlated variation of tR, MS1, and MS2 between different instruments, a computational strategy for integrated metabolite annotation was proposed to reduce the influence of differential ions, which made full use of the characteristic (common) and non-common fragments for scoring assessment. The regular variations of MS2 among three instruments under four collision energy voltages of high, medium, low, and hybrid levels were respectively inspected with three technical replicates at each level. These discoveries could improve general metabolite annotation with a known database and similarity comparison. It should provide the potential for metabolite annotation to generalize qualitative information obtained under different experimental conditions or using instruments from various manufacturers, which is still a big headache in untargeted metabolomics. The mixture of standard compounds and serum samples with the addition of standards were applied to demonstrate the principle and performance of the proposed method. The results showed that it could be an optional strategy for general use in HRMS-based metabolomics to offset the difference in metabolite annotation. It has some potential in untargeted metabolomics.PMID:38943690 | DOI:10.1016/j.jchromb.2024.124219

Plant J. 2024 Jun 29. doi: 10.1111/tpj.16896. Online ahead of print.ABSTRACTCold and saline-alkali stress are frequently encountered by plants, and they often occur simultaneously in saline-alkali soils at mid to high latitudes, constraining forage crop distribution and production. However, the mechanisms by which forage crops respond to the combination of cold and saline-alkali stress remain unknown. Alfalfa (Medicago sativa L.) is one of the most essential forage grasses in the world. In this study, we analyzed the complex response mechanisms of two alfalfa species (Zhaodong [ZD] and Blue Moon [BM]) to combined cold and saline-alkali stress using multi-omics. The results revealed that ZD had a greater ability to tolerate combined stress than BM. The tricarboxylic acid cycles of the two varieties responded positively to the combined stress, with ZD accumulating more sugars, amino acids, and jasmonic acid. The gene expression and flavonoid content of the flavonoid biosynthesis pathway were significantly different between the two varieties. Weighted gene co-expression network analysis and co-expression network analysis based on RNA-Seq data suggested that the MsMYB12 gene may respond to combined stress by regulating the flavonoid biosynthesis pathway. MsMYB12 can directly bind to the promoter of MsFLS13 and promote its expression. Moreover, MsFLS13 overexpression can enhance flavonol accumulation and antioxidant capacity, which can improve combined stress tolerance. These findings provide new insights into improving alfalfa resistance to combined cold and saline-alkali stress, showing that flavonoids are essential for plant resistance to combined stresses, and provide theoretical guidance for future breeding programs.PMID:38943631 | DOI:10.1111/tpj.16896

J Proteome Res. 2024 Jun 29. doi: 10.1021/acs.jproteome.4c00035. Online ahead of print.ABSTRACTTumor necrosis factor (TNF) has well-established roles in neuroinflammatory disorders, but the effect of TNF on the biochemistry of brain cells remains poorly understood. Here, we microinjected TNF into the brain to study its impact on glial and neuronal metabolism (glycolysis, pentose phosphate pathway, citric acid cycle, pyruvate dehydrogenase, and pyruvate carboxylase pathways) using 13C NMR spectroscopy on brain extracts following intravenous [1,2-13C]-glucose (to probe glia and neuron metabolism), [2-13C]-acetate (probing astrocyte-specific metabolites), or [3-13C]-lactate. An increase in [4,5-13C]-glutamine and [2,3-13C]-lactate coupled with a decrease in [4,5-13C]-glutamate was observed in the [1,2-13C]-glucose-infused animals treated with TNF. As glutamine is produced from glutamate by astrocyte-specific glutamine synthetase the increase in [4,5-13C]-glutamine reflects increased production of glutamine by astrocytes. This was confirmed by infusion with astrocyte substrate [2-13C]-acetate. As lactate is metabolized in the brain to produce glutamate, the simultaneous increase in [2,3-13C]-lactate and decrease in [4,5-13C]-glutamate suggests decreased lactate utilization, which was confirmed using [3-13C]-lactate as a metabolic precursor. These results suggest that TNF rearranges the metabolic network, disrupting the energy supply chain perturbing the glutamine-glutamate shuttle between astrocytes and the neurons. These insights pave the way for developing astrocyte-targeted therapeutic strategies aimed at modulating effects of TNF to restore metabolic homeostasis in neuroinflammatory disorders.PMID:38943617 | DOI:10.1021/acs.jproteome.4c00035

Plant J. 2024 Jun 29. doi: 10.1111/tpj.16905. Online ahead of print.ABSTRACTWhile it is known that increased dissolved CO2 concentrations and rising sea surface temperature (ocean warming) can act interactively on marine phytoplankton, the ultimate molecular mechanisms underlying this interaction on a long-term evolutionary scale are relatively unexplored. Here, we performed transcriptomics and quantitative metabolomics analyses, along with a physiological trait analysis, on the marine diatom Thalassiosira weissflogii adapted for approximately 3.5 years to warming and/or high CO2 conditions. We show that long-term warming has more pronounced impacts than elevated CO2 on gene expression, resulting in a greater number of differentially expressed genes (DEGs). The largest number of DEGs was observed in populations adapted to warming + high CO2, indicating a potential synergistic interaction between these factors. We further identified the metabolic pathways in which the DEGs function and the metabolites with significantly changed abundances. We found that ribosome biosynthesis-related pathways were upregulated to meet the increased material and energy demands after warming or warming in combination with high CO2. This resulted in the upregulation of energy metabolism pathways such as glycolysis, photorespiration, the tricarboxylic acid cycle, and the oxidative pentose phosphate pathway, as well as the associated metabolites. These metabolic changes help compensate for reduced photochemical efficiency and photosynthesis. Our study emphasizes that the upregulation of ribosome biosynthesis plays an essential role in facilitating the adaptation of phytoplankton to global ocean changes and elucidates the interactive effects of warming and high CO2 on the adaptation of marine phytoplankton in the context of global change.PMID:38943614 | DOI:10.1111/tpj.16905

Expert Opin Ther Targets. 2024 Jun 29. doi: 10.1080/14728222.2024.2375372. Online ahead of print.ABSTRACTINTRODUCTION: Systemic Lupus Erythematosus (SLE) is a multi-dimensional autoimmune disease involving numerous tissues throughout the body. The chromatin accessibility landscapes in immune cells play a pivotal role in governing their activation, function, and differentiation. Aberrant modulation of chromatin accessibility in immune cells is intimately associated with the onset and progression of SLE.AREAS COVERED: In this review, we described the chromatin accessibility landscapes in immune cells, summarized the recent evidence of chromatin accessibility related to the pathogenesis of SLE, and discussed the potential of chromatin accessibility as a valuable option to identify novel therapeutic targets for this disease.EXPERT OPINION: Dynamic changes in chromatin accessibility are intimately related to the pathogenesis of SLE and have emerged as a new direction for exploring its epigenetic mechanisms. The differently accessible chromatin regions in immune cells often contain binding sites for transcription factors (TFs) and cis-regulatory elements such as enhancers and promoters, which may be potential therapeutic targets for SLE. Larger scale cohort studies and integrating epigenomic, transcriptomic, and metabolomic data can provide deeper insights into SLE chromatin biology in the future.PMID:38943564 | DOI:10.1080/14728222.2024.2375372

Bratisl Lek Listy. 2024;125(7):457-462. doi: 10.4149/BLL_2024_70.ABSTRACTIncreased serum lactate dehydrogenase (LDH) activity is considered as a marker of cellular necrosis and serves as a metabolomic diagnostic marker in several types of cancer including head and neck squamous cell carcinoma (HNSCC). LDH, an enzyme involved in the glycolytic cycle, is correlated not only with the activation of oncogenes such as HIF-α and Myc, but also with effects such as tumor proliferation and metastasis. Serum alkaline phosphatase (ALP) is a marker of cell differentiation and tumor induction. Albumin-to-alkaline phosphatase ratio (AAPR) could be an advantageous biomarker due to its easily accessible dynamics and cost-effectiveness. Elevated values of AAPR could be associated with longer overall survival (OS) in cases with solid tumors. Diabetes mellitus (DM) could influence the outcome of patients with HNSCC by contributing to insulin resistance and chronic inflammation, and by being involved in various aspects of carcinogenesis, disease progression and metastasis. However, the use of antihyperglycemic medications (metformin) can have beneficial effects by inhibiting tumor metabolic pathways. The biomarker role of LDH and AAPR in HNSCC patients with DM has been less evaluated. The purpose of the study was to assess the prognostic value of pretreatment serum lactate dehydrogenase (LDH) and albumin-to-alkaline phosphatase ratio (AAPR) in predicting the duration of non-surgical oncological treatment and glycemic control in cases of head and neck cancers patients with DM, including cases selected from the database of the oncology clinic and oncology outpatient clinic of the Craiova County Hospital. Both LDH and AAPR can be used as pre-treatment biomarkers predictive of treatment response, or prognostic tools included in complex multi-parametric models in HNC associated with DM. However, given the impact of short-term glycemic control on the LDH level, it is necessary to evaluate these biomarkers after assessing and controlling for DM, and with the recommended cut-off value set around 0.5. Due to the limited number of cases, it is necessary to validate the results in multicentric trials with a larger number of patients (Tab. 5, Ref. 50). Keywords: diabetes mellitus, HNC, LDH, AAPR, biomarkers, predictive, head and neck cancers, lactate dehydrogenase, albumin-to-alkaline phosphatase ratio.PMID:38943508 | DOI:10.4149/BLL_2024_70

Anim Microbiome. 2024 Jun 28;6(1):37. doi: 10.1186/s42523-024-00325-4.ABSTRACTBACKGROUND: Pinus koraiensis cone essential oil (PEO) contains functional compounds such as monoterpene hydrocarbons, and the administration of PEO reduced methane (CH4) emissions during growing phase of goats. However, the mode of action of PEO driven CH4 reduction is not known, especially how the administration of PEO can affect rumen microbiota and host metabolism in goats during the fattening phase. This study aimed to elucidate the potential microbial and host responses PEO supplementation in goats using metataxonomics (prokaryotes and protozoa) and metabolomics (rumen fluid and serum).RESULTS: Ten fattening Korean native goats were divided into two dietary groups: control (CON; basal diet without additives) and PEO (basal diet + 1.5 g/d of PEO) with a 2 × 2 crossover design and the treatment lasted for 11 weeks. Administration of PEO reduced CH4 concentrations in the exhaled gas from eructation by 12.0-13.6% (P < 0.05). Although the microbial composition of prokaryotes (bacteria and archaea) and protozoa in the rumen was not altered after PEO administration. MaAsLin2 analysis revealed that the abundance of Selenomonas, Christensenellaceae R-7 group, and Anaerovibrio were enriched in the rumen of PEO supplemented goats (Q < 0.1). Co-occurrence network analysis revealed that Lachnospiraceae AC2044 group and Anaerovibrio were the keystone taxa in the CON and PEO groups, respectively. Methane metabolism (P < 0.05) was enriched in the CON group, whereas metabolism of sulfur (P < 0.001) and propionate (P < 0.1) were enriched in the PEO group based on microbial predicted functions. After PEO administration, the abundance of 11 rumen and 4 serum metabolites increased, whereas that of 25 rumen and 14 serum metabolites decreased (P < 0.1). Random forest analysis identified eight ruminal metabolites that were altered after PEO administration, among which four were associated with propionate production, with predictive accuracy ranging from 0.75 to 0.88. Additionally, we found that serum sarcosine (serum metabolite) was positively correlated with CH4 emission parameters and abundance of Methanobrevibacter in the rumen (|r|≥ 0.5, P < 0.05).CONCLUSIONS: This study revealed that PEO administration reduced CH4 emission from of fattening goats with altered microbial interactions and metabolites in the rumen and host. Importantly, PEO administration affected utilizes various mechanisms such as formate, sulfur, methylated amines metabolism, and propionate production, collectively leading to CH4 reduction. The knowledge is important for future management strategies to maintain animal production and health while mitigate CH4 emission.PMID:38943213 | DOI:10.1186/s42523-024-00325-4

Int Breastfeed J. 2024 Jun 28;19(1):45. doi: 10.1186/s13006-024-00652-x.ABSTRACTBACKGROUND: Despite global public health organizations endorsing breastfeeding or human milk (HM) as the optimal source of nutrition for infants, detailed knowledge of how HM composition influences infant growth is lacking. In this commentary we summarize and interpret the key findings of a large systematic review on HM components and child growth (N = 141 articles included). We highlight the most consistent associations, discuss study quality issues, explore socio-economic and time trends in this body of research, and identify gaps and future research directions.KEY FINDINGS OF SYSTEMATIC REVIEW: We grouped HM components into three categories: micronutrients (28 articles), macronutrients (57 articles), and bioactives (75 articles). Overall, we struggled to find consistent associations between HM components and infant growth. The majority of studies (85%) were of moderate or low-quality, with inconsistent HM collection and analysis strategies being identified as the most substantial quality concerns. Additional quality issues included failing to account for potential confounding by factors such as breastfeeding exclusivity and maternal body mass index.CONSIDERATIONS FOR FUTURE HUMAN MILK RESEARCH: Many opportunities exist for the future of HM research. Using untargeted metabolomics will expand our understanding of HM components beyond previously defined and well-understood components. Machine learning will allow researchers to investigate HM as an integrated system, rather than a collection of individual components. Future research on HM composition should incorporate evidence-based HM sampling strategies to encompass circadian variation as well as infant consumption. Additionally, researchers need to focus on developing high quality growth data using consistent growth metrics and definitions. Building multidisciplinary research teams will help to ensure that outcomes are meaningful and clinically relevant.CONCLUSION: Despite a large body of literature, there is limited quality evidence on the relationship between HM composition and infant growth. Future research should engage in more accurate collection of breastfeeding data, use standardized HM collection strategies and employ assays that are validated for HM. By systematically evaluating the existing literature and identifying gaps in existing research methods and practice, we hope to inspire standardized methods and reporting guidelines to support robust strategies for examining relationships between HM composition and child growth.PMID:38943170 | DOI:10.1186/s13006-024-00652-x

Cardiovasc Diabetol. 2024 Jun 28;23(1):223. doi: 10.1186/s12933-024-02298-9.ABSTRACTBACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure.METHODS: 26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed.RESULTS: SGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects.CONCLUSIONS: Our results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.PMID:38943140 | DOI:10.1186/s12933-024-02298-9