RESUMO
Dry eye syndrome (DES) is a growing public health concern with a high global prevalence; however, the fundamental processes involved in its pathogenic mechanisms remain poorly understood. In the present study, we applied nanoscale liquid chromatography and quadrupole time-of-flight tandem mass spectrometry (nanoLC/Q-TOF-MS/MS) and ultraperformance LC/Q-TOF-MS/MS technologies on tear samples obtained from 18 dry eye patients and 19 healthy controls for integrated proteomic and metabolomic analyses. Overall, 1031 tear proteins were detected, while 190 proteins were determined to be significantly expressed in dry eye patients. Further functional analysis suggested that various biological processes were highly expressed and involved in the pathogenesis of DES, especially immune and inflammatory processes. In total, 156 named metabolites were identified, among which 34 were found to be significantly changed in dry eye patients. The results highlighted the key elements, especially inflammatory-related proteins and metabolites that played important roles in the development of DES. Further, the regulatory roles of primary pathways, including complement and coagulation cascades, glycolysis/gluconeogenesis, and amino acid metabolism, were also identified as processes involved in DES. Collectively, our work not only provided insight into the potential biomarkers of DES for diagnostic and prognostic purposes but extended our knowledge of the physiopathology of this syndrome.
Assuntos
Proteínas do Sistema Complemento/genética , Síndromes do Olho Seco/genética , Proteínas do Olho/genética , Metaboloma , Proteoma/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/metabolismo , Estudos de Casos e Controles , Cromatografia Líquida , Proteínas do Sistema Complemento/classificação , Proteínas do Sistema Complemento/metabolismo , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/fisiopatologia , Proteínas do Olho/classificação , Proteínas do Olho/metabolismo , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Gluconeogênese/genética , Glicólise/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mapeamento de Interação de Proteínas , Proteoma/classificação , Proteoma/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Lágrimas/químicaRESUMO
Fungi are key decomposers of deadwood, but the impact of anthropogenic changes in nutrients and temperature on fungal community and its consequences for wood microbial respiration are not well understood. Here, we examined how nitrogen and phosphorus additions (field experiment) and warming (laboratory experiment) together influence fungal composition and microbial respiration from decomposing wood of angiosperms and gymnosperms in a subtropical forest. Nutrient additions significantly increased wood microbial respiration via fungal composition, but effects varied with nutrient types and taxonomic groups. Specifically, phosphorus addition significantly increased wood microbial respiration (65%) through decreased acid phosphatase activity and increased abundance of fast-decaying fungi (e.g., white rot), while nitrogen addition marginally increased it (30%). Phosphorus addition caused a greater increase in microbial respiration in gymnosperms than in angiosperms (83.3% vs. 46.9%), which was associated with an increase in Basidiomycota:Ascomycota operational taxonomic unit abundance in gymnosperms but a decrease in angiosperms. The temperature dependencies of microbial respiration were remarkably constant across nutrient levels, consistent with metabolic scaling theory hypotheses. This is because there was no significant interaction between temperature and wood phosphorus availability or fungal composition, or the interaction among the three factors. Our results highlight the key role of tree identity in regulating nutrient response of wood microbial respiration through controlling fungal composition. Given that the range of angiosperm species may expand under climate warming and forest management, our data suggest that expansion will decrease nutrient effects on forest carbon cycling in forests previously dominated by gymnosperm species.
Assuntos
Fungos , Árvores , Madeira , Fungos/fisiologia , Madeira/microbiologia , Árvores/microbiologia , Fósforo/metabolismo , Nitrogênio/metabolismo , Magnoliopsida/fisiologiaRESUMO
Colorectal cancer (CRC) is a growing public health concern due to its high mortality rate. Currently, there is a lack of valid diagnostic biomarkers and few therapeutic strategies are available for CRC treatment, especially for advanced CRC whose underlying pathogenic mechanisms remain poorly understood. In the present study, we investigated the serum samples from 20 patients with stage III or IV advanced CRC using data-independent acquisition (DIA)-based proteomics and ultra-performance liquid chromatography coupled to time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS) metabolomics techniques. Overall, 551 proteins and 719 metabolites were identified. Hierarchical clustering analysis revealed that the serum proteomes of advanced CRC are more diversified than the metabolomes. Ten biochemical pathways associated with cancer cell metabolism were enriched in the detected proteins and metabolites, including glycolysis/gluconeogenesis, biosynthesis of amino acids, glutathione metabolism, and arachidonic acid metabolism, etc. A protein-protein interaction network in advanced CRC serum was constructed with 80 proteins and 21 related metabolites. Correlation analysis revealed conserved roles of lipids and lipid-like molecules in a regulatory network of advanced CRC. Three metabolites (hydroquinone, leucenol and sphingomyelin) and two proteins (coagulation factor XIII A chain and plasma kallikrein) were selected to be potential biomarkers for advanced CRC, which are positively and significantly correlated with CEA and/or CA 19-9. Altogether, the results expanded our understanding of the physiopathology of advanced CRC and discovered novel potential biomarkers for further validation and application to improve the diagnosis and monitoring of advanced CRC.
RESUMO
Esophageal cancer is a deadly disease in the esophagus with a poor prognosis. Over 90 % of esophageal cancer is esophageal squamous cell carcinoma (ESCC) and its pathogenic mechanisms remain unclear. Epidemiology study found a strong gender difference with a sex ratio of 8-9:1 in favor of males, but the molecular mechanisms for so striking gender difference are poorly understood so far. In the present study, we demonstrated the expression of estrogen receptors in human ESCC cells. 17ß-E2 but not 17α-E2 was found to dose-dependently suppress the cell proliferation of human ESCC cells, which was attenuated by estrogen receptor antagonist ICI1 82,780. Furthermore, 17ß -E2 but not 17α-E2 10 nM markedly induced both intracellular Ca2+ release and extracellular Ca2+ entry into ESCC cells, which was again attenuated by estrogen receptor antagonist ICI182,780. Taken together, our data clearly demonstrate that estrogen exerts anti-proliferative action on human ESCC cells likely through estrogen receptor-Ca2+ signaling pathway, which may provide a reasonable explanation on the striking male predominance of ESCC.
Assuntos
Cálcio/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células/fisiologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Receptores de Estrogênio/metabolismo , Linhagem Celular Tumoral , Carcinoma de Células Escamosas do Esôfago , Esôfago/metabolismo , Esôfago/patologia , Estrogênios/metabolismo , Feminino , Humanos , Masculino , Transdução de Sinais/fisiologiaRESUMO
Peiminine, a compound extracted from the bulbs of Fritillaria thunbergii and traditionally used as a medication in China and other Asian countries, was reported to inhibit colorectal cancer cell proliferation and tumor growth by inducing autophagic cell death. However, its mechanism of anticancer action is not well understood, especially at the metabolic level, which was thought to primarily account for peiminine's efficacy against cancer. Using an established metabolomic profiling platform combining ultra-performance liquid chromatography/tandem mass spectrometry with gas chromatography/mass spectrometry, we identified metabolic alterations in colorectal cancer cell line HCT-116 after peiminine treatment. Among the identified 236 metabolites, the levels of 57 of them were significantly (p < 0.05) different between peiminine-treated and -untreated cells in which 45 metabolites were increased and the other 12 metabolites were decreased. Several of the affected metabolites, including glucose, glutamine, oleate (18:1n9), and lignocerate (24:0), may be involved in regulation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway and in the oxidative stress response upon peiminine exposure. Peiminine predominantly modulated the pathways responsible for metabolism of amino acids, carbohydrates, and lipids. Collectively, these results provide new insights into the mechanisms by which peiminine modulates metabolic pathways to inhibit colorectal cancer cell growth, supporting further exploration of peiminine as a potential new strategy for treating colorectal cancer.