PubMed

Respir Res. 2024 Jul 30;25(1):288. doi: 10.1186/s12931-024-02916-w.ABSTRACTBACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for pulmonary hypertension (PH), a complication that adversely affects patient prognosis. However, the mechanisms underlying this association remain poorly understood. A major obstacle to progress in this field is the lack of a reliable animal model replicating CKD-PH.METHODS: This study aimed to establish a stable rat model of CKD-PH. We employed a combined approach, inducing CKD through a 5/6 nephrectomy and concurrently exposing the rats to a high-salt diet. The model's hemodynamics were evaluated dynamically, alongside a comprehensive assessment of pathological changes in multiple organs. Lung tissues and serum samples were collected from the CKD-PH rats to analyze the expression of angiotensin-converting enzyme 2 (ACE2), evaluate the activity of key vascular components within the renin-angiotensin-aldosterone system (RAAS), and characterize alterations in the serum metabolic profile.RESULTS: At 14 weeks post-surgery, the CKD-PH rats displayed significant changes in hemodynamic parameters indicative of pulmonary arterial hypertension. Additionally, right ventricular hypertrophy was observed. Notably, no evidence of pulmonary vascular remodeling was found. Further analysis revealed RAAS dysregulation and downregulated ACE2 expression within the pulmonary vascular endothelium of CKD-PH rats. Moreover, the serum metabolic profile of these animals differed markedly from the sham surgery group.CONCLUSIONS: Our findings suggest that the development of pulmonary arterial hypertension in CKD-PH rats is likely a consequence of a combined effect: RAAS dysregulation, decreased ACE2 expression in pulmonary vascular endothelial cells, and metabolic disturbances.PMID:39080603 | DOI:10.1186/s12931-024-02916-w

BMC Plant Biol. 2024 Jul 30;24(1):727. doi: 10.1186/s12870-024-05342-8.ABSTRACTBACKGROUND: Fusarium circinatum is the causal agent of pine pitch canker disease, which affects Pinus species worldwide, causing significant economic and ecological losses. In Spain, two Pinus species are most affected by the pathogen; Pinus radiata is highly susceptible, while Pinus pinaster has shown moderate resistance. In F. circinatum-Pinus interactions, phytohormones are known to play a crucial role in plant defense. By comparing species with different degrees of susceptibility, we aimed to elucidate the fundamental mechanisms underlying resistance to the pathogen. For this purpose, we used an integrative approach by combining gene expression and metabolomic phytohormone analyses at 5 and 10 days post inoculation.RESULTS: Gene expression and metabolite phytohormone contents suggested that the moderate resistance of P. pinaster to F. circinatum is determined by the induction of phytohormone signaling and hormone rearrangement beginning at 5 dpi, when symptoms are still not visible. Jasmonic acid was the hormone that showed the greatest increase by 5 dpi, together with the active gibberellic acid 4 and the cytokinin dehydrozeatin; there was also an increase in abscisic acid and salicylic acid by 10 dpi. In contrast, P. radiata hormonal changes were delayed until 10 dpi, when symptoms were already visible; however, this increase was not as high as that in P. pinaster. Indeed, in P. radiata, no differences in jasmonic acid or salicylic acid production were found. Gene expression analysis supported the hormonal data, since the activation of genes related to phytohormone synthesis was observed earlier in P. pinaster than in the susceptible P. radiata.CONCLUSIONS: We determine that the moderate resistance of P. pinaster to F. circinatum is in part a result of early and strong activation of plant phytohormone-based defense responses before symptoms become visible. We suggest that jasmonic acid signaling and production are strongly associated with F. circinatum resistance. In contrast, P. radiata susceptibility was attributed to a delayed response to the fungus at the moment when symptoms were visible. Our results contribute to a better understanding of the phytohormone-based defense mechanism involved in the Pinus-F. circinatum interactions and provide insight into the development of new strategies for disease mitigation.PMID:39080528 | DOI:10.1186/s12870-024-05342-8

BMC Plant Biol. 2024 Jul 30;24(1):726. doi: 10.1186/s12870-024-05455-0.ABSTRACTBACKGROUND: Pb stress, a toxic abiotic stress, critically affects maize production and food security. Although some progress has been made in understanding the damage caused by Pb stress and plant response strategies, the regulatory mechanisms and resistance genes involved in the response to lead stress in crops are largely unknown.RESULTS: In this study, to uncover the response mechanism of maize to Pb stress phenotype, physiological and biochemical indexes, the transcriptome, and the metabolome under different concentrations of Pb stress were combined for comprehensive analysis. As a result, the development of seedlings and antioxidant system were significantly inhibited under Pb stress, especially under relatively high Pb concentrations. Transcriptome analysis revealed 3559 co-differentially expressed genes(co-DEG) under the four Pb concentration treatments (500 mg/L, 1000 mg/L, 2000 mg/L, and 3000 mg/L Pb(NO3)2), which were enriched mainly in the GO terms related to DNA-binding transcription factor activity, response to stress, response to reactive oxygen species, cell death, the plasma membrane and root epidermal cell differentiation. Metabolome analysis revealed 72 and 107 differentially expressed metabolites (DEMs) under T500 and T2000, respectively, and 36 co-DEMs. KEGG analysis of the DEMs and DEGs revealed a common metabolic pathway, namely, flavonoid biosynthesis. An association study between the flavonoid biosynthesis-related DEMs and DEGs revealed 20 genes associated with flavonoid-related metabolites, including 3 for genistin and 17 for calycosin.CONCLUSION: In summary, the study reveals that flavonoid metabolism plays an important role in response to Pb stress in maize, which not only provides genetic resources for the genetic improvement of maize Pb tolerance in the future but also enriches the theoretical basis of the maize Pb stress response.PMID:39080516 | DOI:10.1186/s12870-024-05455-0

Sci Rep. 2024 Jul 30;14(1):17617. doi: 10.1038/s41598-024-68722-y.ABSTRACTA recent systematic review indicated that gut-microbiota-brain axis contributes to growth and rupture of intracranial aneurysms. However, gaps were detected in the role of intestinal microbiome in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). This is the first pilot study aiming to test study feasibility and identify differences in gut microbiota between subjects with and without CVS following aSAH. A prospective nested case-control pilot study with 1:1 matching was conducted recruiting subjects with aSAH: cases with CVS; and controls without CVS based on the clinical picture and structured bedside transcranial Doppler (TCD). Fecal samples for microbiota analyses by means of 16S rRNA gene amplicon sequencing were collected within the first 96 h after ictus. Operational taxonomic unit tables were constructed, diversity metrics calculated, phylogenetic trees built, and differential abundance analysis (DAA) performed. At baseline, the groups did not differ significantly in basic demographic and aneurysm-related characteristics (p > 0.05). Alpha-diversity (richness and Shannon Index) was significantly reduced in cases of middle cerebral artery (MCA) vasospasm (p < 0.05). In DAA, relative abundance of genus Acidaminococcus was associated with MCA vasospasm (p = 0.00013). Two butyrate-producing genera, Intestinimonas and Butyricimonas, as well as [Clostridium] innocuum group had the strongest negative correlation with the mean blood flow velocity in anterior cerebral arteries (p < 0.01; rho = - 0.63; - 0.57, and - 0.57, respectively). In total, 16 gut microbial genera were identified to correlate with TCD parameters, and two intestinal genera correlated with outcome upon discharge. In this pilot study, we prove study feasibility and present the first preliminary evidence of gut microbiome signature associating with CVS as a significant cause of stroke in subjects with aSAH.PMID:39080476 | DOI:10.1038/s41598-024-68722-y

Sci Rep. 2024 Jul 30;14(1):17477. doi: 10.1038/s41598-024-67104-8.ABSTRACTThe combination of multi-omic techniques, such as genomics, transcriptomics, proteomics, metabolomics and epigenomics, has revolutionised studies in medical research. These techniques are employed to support biomarker discovery, better understand molecular pathways and identify novel drug targets. Despite concerted efforts in integrating omic datasets, there is an absence of protocols that integrate all four biomolecules in a single extraction process. Here, we demonstrate for the first time a minimally destructive integrated protocol for the simultaneous extraction of artificially degraded DNA, proteins, lipids and metabolites from pig brain samples. We used an MTBE-based approach to separate lipids and metabolites, followed by subsequent isolation of DNA and proteins. We have validated this protocol against standalone extraction protocols and show comparable or higher yields of all four biomolecules. This integrated protocol is key to facilitating the preservation of irreplaceable samples while promoting downstream analyses and successful data integration by removing bias from univariate dataset noise and varied distribution characteristics.PMID:39080329 | DOI:10.1038/s41598-024-67104-8

Sci Rep. 2024 Jul 29;14(1):17472. doi: 10.1038/s41598-024-67170-y.ABSTRACTChronic pruritus of unknown origin (CPUO) is characterized by chronic itch for 6 weeks or greater without an identifiable primary cause. Studies are needed to investigate circulating blood biomarkers to elucidate disease pathogenesis. The objective of this study was to investigate changes in circulating blood metabolites in CPUO patients and to identify potential therapeutic targets. Our cross-sectional study collected plasma from 11 CPUO patients and 11 matched control patients for mass-spectrometry based metabolite data analysis. 15 metabolites differed significantly in the blood of CPUO patients compared to controls, including nine amino acids (isoleucine, L-tyrosine, threonine, DL-tryptophan, L-valine, methionine, glycine, lysine, and L-phenylalanine), four amino acid derivatives (creatinine, DL-carnitine, acetyl-L-carnitine, and indole-3-acrylic acid), and two aromatic and fatty acid derivatives (2-hydroxycinnamic acid and oleamide). These metabolites were also correlated with itch severity. Metabolic set enrichment analysis (MSEA) identified downregulation of several pathways in CPUO: phenylalanine, tyrosine, tryptophan biosynthesis; catecholamine biosynthesis; and glycine, serine, and threonine metabolism. Our study identified decreases in several circulating plasma metabolites in CPUO patients and downregulation of pathways related to catecholamine biosynthesis and tryptophan biosynthesis, providing insight into the pathogenesis of CPUO.PMID:39080299 | DOI:10.1038/s41598-024-67170-y

Cell Death Dis. 2024 Jul 30;15(7):541. doi: 10.1038/s41419-024-06933-x.ABSTRACTEsophageal squamous cell carcinoma (ESCC) possesses a poor prognosis and treatment outcome. Dysregulated metabolism contributes to unrestricted growth of multiple cancers. However, abnormal metabolism, such as highly activated pentose phosphate pathway (PPP) in the progression of ESCC remains largely unknown. Herein, we report that high-mobility group AT-hook 1 (HMGA1), a structural transcriptional factor involved in chromatin remodeling, promoted the development of ESCC by upregulating the PPP. We found that HMGA1 was highly expressed in ESCC. Elevated HMGA1 promoted the malignant phenotype of ESCC cells. Conditional knockout of HMGA1 markedly reduced 4-nitroquinoline-1-oxide (4NQO)-induced esophageal tumorigenesis in mice. Through the metabolomic analysis and the validation assay, we found that HMGA1 upregulated the non-oxidative PPP. With the transcriptome sequencing, we identified that HMGA1 upregulated the expression of transketolase (TKT), which catalyzes the reversible reaction in non-oxidative PPP to exchange metabolites with glycolytic pathway. HMGA1 knockdown suppressed the PPP by downregulating TKT, resulting in the reduction of nucleotides in ESCC cells. Overexpression of HMGA1 upregulated PPP and promoted the survival of ESCC cells by activating TKT. We further characterized that HMGA1 promoted the transcription of TKT by interacting with and enhancing the binding of transcription factor SP1 to the promoter of TKT. Therapeutics targeting TKT with an inhibitor, oxythiamine, reduced HMGA1-induced ESCC cell proliferation and tumor growth. Together, in this study, we identified a new role of HMGA1 in ESCCs by upregulating TKT-mediated activation of PPP. Our results provided a new insight into the role of HMGA1/TKT/PPP in ESCC tumorigenesis and targeted therapy.PMID:39080260 | DOI:10.1038/s41419-024-06933-x

Plant Cell Rep. 2024 Jul 30;43(8):203. doi: 10.1007/s00299-024-03292-x.ABSTRACTMultiple regulatory pathways of Zostera japonica to salt stress were identified through growth, physiological, transcriptomic and metabolomic analyses. Seagrasses are marine higher submerged plants that evolved from terrestrial monocotyledons and have fully adapted to the high saline seawater environment during the long evolutionary process. As one of the seagrasses growing in the intertidal zone, Zostera japonica not only has the ability to quickly adapt to short-term salt stress but can also survive at salinities ranging from the lower salinity of the Yellow River estuary to the higher salinity of the bay, making it a good natural model for studying the mechanism underlying the adaptation of plants to salt stress. In this work, we screened the growth, physiological, metabolomic, and transcriptomic changes of Z. japonica after a 5-day exposure to different salinities. We found that high salinity treatment impeded the growth of Z. japonica, hindered its photosynthesis, and elicited oxidative damage, while Z. japonica increased antioxidant enzyme activity. At the transcriptomic level, hypersaline stress greatly reduced the expression levels of photosynthesis-related genes while increasing the expression of genes associated with flavonoid biosynthesis. Meanwhile, the expression of candidate genes involved in ion transport and cell wall remodeling was dramatically changed under hypersaline stress. Moreover, transcription factors signaling pathways such as mitogen-activated protein kinase (MAPK) were also significantly influenced by salt stress. At the metabolomic level, Z. japonica displayed an accumulation of osmolytes and TCA mediators under hypersaline stress. In conclusion, our results revealed a complex regulatory mechanism in Z. japonica under salt stress, and the findings will provide important guidance for improving salt resistance in crops.PMID:39080075 | DOI:10.1007/s00299-024-03292-x

Support Care Cancer. 2024 Jul 31;32(8):558. doi: 10.1007/s00520-024-08752-4.ABSTRACTAdvances in the treatment of cancer have significantly improved mortality rates; however, this has come at a cost, with many treatments still limited by their toxic side effects. Mucositis in both the mouth and gastrointestinal tract is common following many anti-cancer agents, manifesting as ulcerative lesions and associated symptoms throughout the alimentary tract. The pathogenesis of mucositis was first defined in 2004 by Sonis, and almost 20 years on, the model continues to be updated reflecting ongoing research initiatives and more sophisticated analytical techniques. The most recent update, published by the Multinational Association for Supportive Care in Cancer and the International Society for Oral Oncology (MASCC/ISOO), highlights the numerous co-occurring events that underpin mucositis development. Most notably, a role for the ecosystem of microorganisms that reside throughout the alimentary tract (the oral and gut microbiota) was explored, building on initial concepts proposed by Sonis. However, many questions remain regarding the true causal contribution of the microbiota and associated metabolome. This review aims to provide an overview of this rapidly evolving area, synthesizing current evidence on the microbiota's contribution to mucositis development and progression, highlighting (i) components of the 5-phase model where the microbiome may be involved, (ii) methodological challenges that have hindered advances in this area, and (iii) opportunities for intervention.PMID:39080025 | DOI:10.1007/s00520-024-08752-4

Cancer Chemother Pharmacol. 2024 Jul 30. doi: 10.1007/s00280-024-04703-2. Online ahead of print.ABSTRACTPURPOSE: 4-hydroxycyclophosphamide (4HCY) is the principal precursor to the cytotoxic metabolite of cyclophosphamide (CY), which is often used as first-line treatment of children with cancer. There is conflicting data regarding the relationship between CY efficacy, toxicity, and pharmacokinetics with the genes encoding proteins involved in 4HCY pharmacokinetics, specifically its formation and elimination.METHODS: We evaluated germline pharmacogenetics in children with various malignancies receiving their first CY dose. Using linear regression, we analyzed the associations between two pharmacokinetic outcomes - how fast a child cleared CY (i.e., CY clearance) and the ratio of the 4HCY/CY exposure, specifically area under the plasma concentration-time curve (AUC), and 372 single nucleotide polymorphisms (SNP) in 14 drug-metabolizing transporters or enzymes involved in 4HCY formation or elimination.RESULTS: Age was associated with the ratio of 4HCY/CY AUC (P = 0.004); Chemotherapy regimen was associated with CY clearance (P = 0.003). No SNPs were associated with CY clearance or the ratio of 4HCY/CY AUC after controlling for a false discovery rate.CONCLUSION: Age and chemotherapy regimen, but not germline pharmacogenomics, were associated with CY clearance or the ratio of 4HCY/CY AUC. Other methods, such as metabolomics or lipidomics, should be explored.PMID:39080017 | DOI:10.1007/s00280-024-04703-2

Anal Bioanal Chem. 2024 Jul 30. doi: 10.1007/s00216-024-05448-w. Online ahead of print.ABSTRACTThe complete characterization of selenium-enriched yeast in terms of selenium species has been the goal of extensive research for the last three decades. This contribution addresses the two outstanding questions: the mass balance of the identified and reported selenium species and the possible presence of inorganic selenium. For this purpose, four procedures have been designed combining, in diverse order, the principal steps of selenium speciation analysis in Se-rich yeast: extraction of the Se-metabolome, derivatization of cysteine and Se-cysteine (SeCys) residues, proteolysis, and definitive Se recovery using SDS extraction, followed by mineralization. The recovery of selenium in each step and its speciation were controlled by ICP MS and by reversed-phase HPLC-ICP MS, respectively. The study, carried out for the SELM-1 reference material, demonstrated the presence of about 10% of inorganic selenium and a serious risk of losses of SeCys during derivatization and proteolysis. As result of our work, we postulate the following values for SELM-1: Se-metabolome fraction (SeMF) 14.8 ± 0.7%; total selenomethionine (SeMet) 66.2 ± 2.7% (including ca. 1.5% SeMet present in the SeMF); total SeCys 12.5 ± 1.5% (including 2% of SeCys present in the Se-MF); total inorganic selenium 9.7 ± 1.7%, accounting for > 99.8% of the selenium.PMID:39079983 | DOI:10.1007/s00216-024-05448-w

Sci Rep. 2024 Jul 30;14(1):17551. doi: 10.1038/s41598-024-68387-7.ABSTRACTManuka honey (MH) has garnered much attention due to its remarkable antimicrobial, anticancer, immunomodulatory and wound-healing properties. This study compared the antiproliferative effects of raw and powdered MH (pMH) on various human and murine cancer cell lines. A detailed metabolomics analysis was also carried out using untargeted ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) to compare the constituents in raw MH and pMH. The results of the viability studies showed that both raw MH and pMH caused a dose-dependent inhibition of tumor cell growth at concentrations of > 1% w/v (equivalent to ~ 10 mg/ml). A differential susceptibility to MH was observed among the cell lines with the human MDA-MB-231 and A549 cells and murine B16.F10 cells being relatively resistant to MH while the murine MC38 colorectal adeno-carcinoma cells showing the most sensitivity. The effect of raw MH and pMH on cell viability was validated using 2 indepndent assays. Metabolomics analysis detected 2440 compounds, out of which 833 were successfully identified. Among these, 90 phytochemical compounds, predominantly comprising terpenoids, flavonoids, coumarins and derivatives, and phenylpropanoic acids, and 79 lipids were identifiable. Significant differences in 5 metabolite classes, including flavonoids, phenols, terpenoids, carbohydrates, and organic acids were observed between the raw and pMH. Moreover, several altered metabolic pathways were identified in pMH compared to raw MH, such as energy metabolism, amino acid metabolism, and various other pathways that collectively influence biological functions associated with cellular growth, signaling, and stress response.PMID:39079967 | DOI:10.1038/s41598-024-68387-7

Sci Rep. 2024 Jul 30;14(1):17574. doi: 10.1038/s41598-024-68261-6.ABSTRACTThe changes in tongue coating metabolites in patients with chronic gastritis (CG) under different gastroscopy indicators were analyzed, and these metabolites were screened for potential non-invasive biomarkers to assist in the diagnosis of chronic gastritis. The technology of gas chromatography and liquid chromatography combined with mass spectrometry has been used to more comprehensively detect tongue coating metabolites of 350 CG patients. Spearman correlation analysis and random forest algorithm were used to screen metabolites that can serve as potential biomarkers. Compared with healthy individuals, CG group showed significant changes in the content of 101 metabolites, with an increase in the content of 54 metabolites and a decrease in the content of 47 metabolites. These differential metabolites are mainly composed of 47 lipids and lipid like substances. 1 metabolite was associated with bile reflux, 1 metabolite was associated with gastric mucosal erosion, 10 metabolites were associated with atrophy, 10 metabolites were associated with intestinal metaplasia, and 3 metabolites were associated with Helicobacter pylori infection. The ROC model composed of 5 metabolites can distinguish between CG group and healthy individuals, with an accuracy of 95.4%. The ROC model composed of 5,6-Dihydroxyindole can distinguish between chronic superficial gastritis group and chronic atrophic gastritis group, with an accuracy of 75.3%. The lipids and lipid like metabolites were the main abnormal metabolites in patients with chronic gastritis. It was worth noting that the content of Sphinganine 1-phase, 4-Ipomenol, and Nervonic acid in tongue coating increased, and the content of 1-Methyladenosine and 3-Hydroxycapric acid decreased, which helped to identify CG patients. The decrease in the content of 5,6-dihydroxyindole reminded patients that the development trend of CG was shifting from superficial to atrophic or even intestinal metaplasia. The detection of these metabolic markers of tongue coating was expected to be developed as a non-invasive and convenient technology in the future to assist us in monitoring and diagnosing the occurrence and development of CG.PMID:39079952 | DOI:10.1038/s41598-024-68261-6

Commun Chem. 2024 Jul 31;7(1):167. doi: 10.1038/s42004-024-01251-x.ABSTRACTMetabolomics plays a crucial role in understanding metabolic processes within biological systems. Using specific pulse sequences, NMR-based metabolomics detects small and macromolecular metabolites that are altered in blood samples. Here we proposed a method called spectral editing neural network, which can effectively edit and separate the spectral signals of small and macromolecules in 1H NMR spectra of serum and plasma based on the linewidth of the peaks. We applied the model to process the 1H NMR spectra of plasma and serum. The extracted small and macromolecular spectra were then compared with experimentally obtained relaxation-edited and diffusion-edited spectra. Correlation analysis demonstrated the quantitative capability of the model in the extracted small molecule signals from 1H NMR spectra. The principal component analysis showed that the spectra extracted by the model and those obtained by NMR spectral editing methods reveal similar group information, demonstrating the effectiveness of the model in signal extraction.PMID:39079950 | DOI:10.1038/s42004-024-01251-x

Nat Chem. 2024 Jul 30. doi: 10.1038/s41557-024-01577-y. Online ahead of print.ABSTRACTThe identification of readers, an important class of proteins that recognize modified residues at specific sites, is essential to uncover the biological roles of post-translational modifications. Photoreactive crosslinkers are powerful tools for investigating readers. However, existing methods usually employ synthetically challenging photoreactive warheads, and their high-energy intermediates generated upon irradiation, such as nitrene and carbene, may cause substantial non-specific crosslinking. Here we report dimethylsulfonium as a methyllysine mimic that binds to specific readers and subsequently crosslinks to a conserved tryptophan inside the binding pocket through single-electron transfer under ultraviolet irradiation. The crosslinking relies on a protein-templated σ-π electron donor-acceptor interaction between sulfonium and indole, ensuring excellent site selectivity for tryptophan in the active site and orthogonality to other methyllysine readers. This method could escalate the discovery of methyllysine readers from complex cell samples. Furthermore, this photo crosslinking strategy could be extended to develop other types of microenvironment-dependent conjugations to site-specific tryptophan.PMID:39079947 | DOI:10.1038/s41557-024-01577-y

Phytother Res. 2024 Jul 30. doi: 10.1002/ptr.8271. Online ahead of print.ABSTRACTMagnoflorine (Mag), a natural alkaloid component originating from the Ranunculaceae Juss. Family, has a various of pharmacological activities. This study aimed to investigate the therapeutic effects and potential mechanism of Mag on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) based on comprehensive approaches. Therapeutic effects of Mag on 3% DSS-induced UC mice were analyzed. UHPLC-Q-TOF/MS was performed to investigate the potential metabolites and signaling pathway of Mag on DSS-induced UC. Furthermore, the predicted mRNA and protein levels of JAK2/STAT3 signaling pathway in colon tissue were verified and assessed by qRT-PCR and Western Blotting, respectively. Therapeutic effects of Mag on UC mice were presented in down-regulation serum biochemical indices, alleviating histological damage of colon tissue. Serum untargeted metabolomics analysis showed that the potential mechanism of Mag on UC is mainly associated with the regulation of six biomarkers and 11 pathways, which may be responsible for the therapeutic efficacy of UC. The "component-metabolites-targets" interactive network indicated that Mag exerts its anti-UC effect by regulating PTGS1 and PTGS2, thereby regulating arachidonic acid. Moreover, the results of qRT-PCR showed that Mag could substantially decrease the relative mRNA expression level of Hub genes. In addition, it was found that Mag could inhibit the relative mRNA and protein expression of JAK2/STAT3 signaling pathway. The present results highlighted the role of Mag ameliorated colon injury in DSS-induced UC mice by inhibiting the JAK2/STAT3 signaling pathway. These results suggest that Mag may be an effective agent for the treatment of UC.PMID:39079890 | DOI:10.1002/ptr.8271

Free Radic Res. 2024 Jul 30:1-16. doi: 10.1080/10715762.2024.2386457. Online ahead of print.ABSTRACTOvarian cancer, marked by high rate of recurrence, novel therapeutic strategies are needed to improve patient outcome. One of the potential strategies is inducing ferroptosis in ovarian cancer cells. Ferroptosis is an iron-dependent, lipid peroxidation-driven mode of cell death primarily occurring on the cell membrane. PTRF, an integral component of the caveolae structures located on the cell membrane, is involved in a multitude of physiological processes, including but not limited to, endocytosis, signal transduction, and lipid metabolism. This study elucidates the relationship between PTRF and ferroptosis in ovarian cancer, offering a fresh perspective for the development of new therapeutic strategies. We knocked down PTRF employing siRNA in the ovarian cancer cell lines HEY and SKOV3, following which we stimulated ferroptosis with Erastin (Era). Our research indicates that the lack of PTRF sensitizes cancer cell to ferroptosis, likely by altering membrane stability and tension, thereby affecting signal pathways related to ferroptosis, such as lipid and atherosclerosis, fluid shear stress and atherosclerosis. Our findings provide new insights for developing new treatments for ovarian cancer.PMID:39079051 | DOI:10.1080/10715762.2024.2386457

J Proteome Res. 2024 Jul 30. doi: 10.1021/acs.jproteome.4c00138. Online ahead of print.ABSTRACTAcute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.PMID:39078945 | DOI:10.1021/acs.jproteome.4c00138

Anal Chem. 2024 Jul 30. doi: 10.1021/acs.analchem.3c04979. Online ahead of print.ABSTRACTMetabolomics commonly relies on using one-dimensional (1D) 1H NMR spectroscopy or liquid chromatography-mass spectrometry (LC-MS) to derive scientific insights from large collections of biological samples. NMR and MS approaches to metabolomics require, among other issues, a data processing pipeline. Quantitative assessment of the performance of these software platforms is challenged by a lack of standardized data sets with "known" outcomes. To resolve this issue, we created a novel simulated LC-MS data set with known peak locations and intensities, defined metabolite differences between groups (i.e., fold change > 2, coefficient of variation ≤ 25%), and different amounts of added Gaussian noise (0, 5, or 10%) and missing features (0, 10, or 20%). This data set was developed to improve benchmarking of existing LC-MS metabolomics software and to validate the updated version of our MVAPACK software, which added gas chromatography-MS and LC-MS functionality to its existing 1D and two-dimensional NMR data processing capabilities. We also included two experimental LC-MS data sets acquired from a standard mixture andMycobacterium smegmatiscell lysates since a simulated data set alone may not capture all the unique characteristics and variability of real spectra needed to assess software performance properly. Our simulated and experimental LC-MS data sets were processed with the MS-DIAL and XCMSOnline software packages and our MVAPACK toolkit to showcase the utility of our data sets to benchmark MVAPACK against community standards. Our results demonstrate the enhanced objectivity and clarity of software assessment that can be achieved when both simulated and experimental data are employed since distinctly different software performances were observed with the simulated and experimental LC-MS data sets. We also demonstrate that the performance of MVAPACK is equivalent to or exceeds existing LC-MS software programs while providing a single platform for processing and analyzing both NMR and MS data sets.PMID:39078713 | DOI:10.1021/acs.analchem.3c04979

J Robot Surg. 2024 Jul 30;18(1):301. doi: 10.1007/s11701-024-02037-y.ABSTRACTThis investigation sought to conduct a comprehensive meta-analysis to assess the comparative effectiveness and safety of percutaneous ablation (PCA) versus robotic-assisted partial nephrectomy (RAPN) among individuals diagnosed with cT1 renal tumors. This study rigorously followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to conduct a systematic review and meta-analysis. A systematic search was carried out in the PubMed, Embase, Web of Science, and Cochrane Library databases, focusing on studies published in English through February 2024. We focused on evaluating primary outcomes, specifically perioperative outcomes, functional outcomes, and oncological outcomes. In this analysis, data from 1534 patients across 13 studies were evaluated. PCA was found to have advantageous outcomes in comparison to RAPN regarding hospital stay durations, with a Weighted Mean Difference (WMD) of - 2.03 days (95% Confidence Interval [CI]: -3.78 to - 0.27; p = 0.02), operative times (WMD: -106.75 min; 95% CI: - 170.78 to - 42.72; p = 0.001), and overall complication rates (Odds Ratio [OR]: 0.61; 95% CI: 0.42 to 0.89; p = 0.01). Conversely, PCA showed a higher incidence of local recurrence compared to RAPN, with an OR of 3.20 (95% CI: 1.91 to 5.35; p < 0.00001). Moreover, there were no statistically significant differences between the two treatments in terms of major complications, declines in estimated glomerular filtration rates (eGFR), variations in creatinine levels, overall survival rates, and recurrence-free survival. While PCA exhibits higher local recurrence rates than RAPN, it also presents significant advantages, such as shorter hospital stays, decreased operative durations, and lower complication rates. This juxtaposition underscores the urgent need for further, more rigorous research to substantiate these findings.PMID:39078530 | DOI:10.1007/s11701-024-02037-y