RESUMEN
BACKGROUND: Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas. METHODS: Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM). RESULTS: Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05-3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients. CONCLUSIONS: High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Encefálicas , Glioma , Microglobulina beta-2 , Humanos , Microglobulina beta-2/sangre , Femenino , Masculino , Persona de Mediana Edad , Pronóstico , Biomarcadores de Tumor/sangre , Glioma/sangre , Glioma/mortalidad , Glioma/patología , Glioma/diagnóstico , Estudios Retrospectivos , Adulto , Neoplasias Encefálicas/sangre , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/diagnóstico , Anciano , Curva ROC , Estimación de Kaplan-Meier , Índice de Severidad de la EnfermedadRESUMEN
Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).
Asunto(s)
Enfermedades del Sistema Nervioso Central , Microglobulina beta-2 , Humanos , Microglobulina beta-2/metabolismo , Enfermedades del Sistema Nervioso Central/metabolismo , Enfermedades del Sistema Nervioso Central/patología , AnimalesRESUMEN
OBJECTIVE TERT: is the most frequently mutated gene in adult glioblastomas (GBMs) defined by the 2021 World Health Organization classification system. The present study aims to explore differences in clinical characteristics and immune microenvironment between TERT mutant and wild-type GBM. METHODS: Three GBM-related cohorts consisting of 205 GBM patients in our cohort, 463 GBM patients without immune checkpoint inhibitor(ICI) therapy and 1465 tumour patients (including 92 GBM cases) receiving ICI treatment in the MSK cohort were included. Retrospective analysis and immunohistochemistry assay were used for investigating the local (including tumour cells, local immune cells, and seizures) and systemic (including circulating immune cells, coagulation-related functions, and prognosis) effects of TERT mutations. Besides, differences in genetic alterations and immunotherapy responses between TERT mutant and wild-type GBMs were also explored. RESULTS: We found that TERT mutant and wild-type GBMs possessed similar initial clinic symptoms, circulating immune microenvironment and immunotherapy response. With respect to that in TERT wild-type GBMs, mutations in TERT resulted in higher levels of tumour-infiltrating neutrophils, prolonged coagulation time, worse chemotherapy response and poorer overall survival. CONCLUSION: Mutations in TERT alter the local immune environment and decrease the sensitivity of GBM to chemotherapy.
RESUMEN
BACKGROUND: Glioma is the most common and aggressive tumor in the adult brain. Recent studies have indicated that Zinc finger DHHC-type palmitoyltransferases (ZDHHCs) play vital roles in regulating the progression of glioma. ZDHHC15, a member of the ZDHHCs family, participates in various physiological activities in the brain. However, the biological functions and related mechanisms of ZDHHC15 in glioma remain poorly understood. METHODS: Data from multiple glioma-associated datasets were used to investigate the expression profiles and potential biological functions of ZDHHC15 in glioma. Expression of ZDHHC15 and its association with clinicopathological characteristics in glioma were validated by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemical experiments. GO enrichment analysis, KEGG analysis, GSEA analysis, CCK-8, EdU, transwell, and western blotting assays were performed to confirm the functions and mechanism of ZDHHC15 in glioma. Moreover, we performed Kaplan-Meier analysis and Cox progression analysis to explore the prognostic significance of ZDHHC15 in glioma patients. RESULTS: ZDHHC15 expression was significantly up-regulated in glioma and positively associated with malignant phenotypes. Results from the GO and KEGG enrichment analysis revealed that ZDHHC15 was involved in regulating cell cycle and migration. Knockdown of ZDHHC15 inhibited glioma cell proliferation and migration, while overexpression of ZDHHC15 presented opposite effects on glioma cells. Besides, results from GSEA analysis suggested that ZDHHC15 was enriched in STAT3 signaling pathway. Knockdown or overexpression of ZDHHC15 indeed affected the activation of STAT3 signaling pathway. Additionally, we identified ZDHHC15 as an independent prognostic biomarker in glioma, and higher expression of ZDHHC15 predicted a poorer prognosis in glioma patients. CONCLUSION: Our findings suggest that ZDHHC15 promotes glioma malignancy and can serve as a novel prognostic biomarker for glioma patients. Targeting ZDHHC15 may be a promising therapeutic strategy for glioma.
Asunto(s)
Glioma , Humanos , Pronóstico , Glioma/genética , Western Blotting , Encéfalo , Biomarcadores , Proteínas de Unión al ADNRESUMEN
Adult gliomas are divided into isocitrate dehydrogenase (IDH) wild-type and IDH mutant subtypes according to the new 2021 World Health Organization classification system. However, the local and systemic effects of IDH mutations on primary glioma patients are not well illustrated. Retrospective analysis, immune-cell infiltration analysis, meta-analysis, and immunohistochemistry assay were applied in the present study. The results from our cohort showed that IDH mutant gliomas own a lower proliferating rate compared to that in wild-type gliomas. Patients with mutant IDH exhibited a higher frequency of seizures in both our cohort and the cohort from the meta-analysis. Mutations in IDH result in lower levels of intra-tumour but higher levels of circulating CD4+ and CD8+ T lymphocytes. Levels of neutrophils in both intra-tumour and circulating blood were lower in IDH mutant gliomas. Moreover, IDH mutant glioma patients receiving radiotherapy in combination with chemotherapy exhibited better overall survival with respect to radiotherapy alone. Mutations in IDH alters the local and circulating immune microenvironment, and increases the sensitivity of tumour cell to chemotherapy.
Asunto(s)
Neoplasias Encefálicas , Glioma , Adulto , Humanos , Isocitrato Deshidrogenasa/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Estudios Retrospectivos , Glioma/genética , Glioma/patología , Mutación , Microambiente Tumoral/genéticaRESUMEN
Here, we investigated the effects of straw returning combined with biochar application on summer maize yield and soil nitrous oxide (N2O) emissions, based on a field location trial in the Guanzhong Plain from 2019 to 2020. The soil N2O emission rates were monitored using the static chamber-chromatography method. A comprehensive analysis of summer maize yields, soil N2O emissions, and soil labile nitrogen components was conducted to clarify the effects of straw returning combined with biochar application on improving soil fertility, increasing summer maize yield, and reducing greenhouse gas emissions. The three treatments were no straw returning (S0), straw returning (S), and straw returning combined with biochar application (SB). The results showed that the peak of N2O emissions from each treatment occurred 10 d after the straw return, and the rate of soil N2O emissions remained at a low level after 30 d of straw return. The rate of soil N2O emissions showed highly significant positive correlations (P<0.05) with ammonium nitrogen (NH4+-N), inorganic nitrogen (SIN), microbial nitrogen (MBN), and dissolved organic nitrogen (DON) contents. S significantly increased summer maize yield, cumulative N2O emissions, yield-scaled N2O intensity, and total nitrogen (TN) content by 7.4%-13%, 65.8%-132.2%, 54.6%-103%, and 27.8%-33%, respectively, compared to those in S0. Although the trend for SB to increase summer maize yield (2.5%-3.3%) compared to that in S was not significant (P>0.05), SB significantly reduced cumulative N2O emissions and yield-scaled N2O intensity by 24.0%-27.3% and 26.4%-29.2%, respectively, compared to that in S. SB significantly reduced the rate of soil N2O emissions by 45.1%-69.6% at the peak of N2O emissions compared to that in S. Biochar application mitigated soil N2O emissions induced by straw return and had a peak-shaving effect. SB significantly increased soil total N by 9.1%-12.2% compared to that in S. Combining summer maize yield, soil N2O emissions, and TN content, SB not only improved soil fertility and summer maize yield but also reduced yield-scaled N2O intensity, making it a suitable management practice that can be replicated to balance crop yield and environmental friendliness.
Asunto(s)
Suelo , Zea mays , Agricultura/métodos , Carbón Orgánico , China , Fertilizantes/análisis , Nitrógeno/análisis , Óxido Nitroso/análisis , Suelo/química , TriticumRESUMEN
Elaborate architectural manipulation of nanohybrids with multi-components into controllable 3D hierarchical structures is of great significance for both fundamental scientific interest and realization of various functionalities, yet remains a great challenge because different materials with distinct physical/chemical properties could hardly be incorporated simultaneously into the synthesis process. Here, we develop a novel one-pot cyanogel-bridged synthetic approach for the generation of 3D flower-like metal/Prussian blue analogue nanohybrids, namely PdCo/Pd-hexacyanocobaltate for the first time. The judicious introduction of polyethylene glycol (PEG) and the formation of cyanogel are prerequisite for the successful fabrication of such fascinating hierarchical nanostructures. Due to the unique 3D hierarchical structure and the synergistic effect between hybrid components, the as-prepared hybrid nanoflowers exhibit a remarkable catalytic activity and durability toward the reduction of Rhodamine B (RhB) by NaBH4. We expect that the obtained hybrid nanoflowers may hold great promises in water remediation field and beyond. Furthermore, the facile synthetic strategy presented here for synthesizing functional hybrid materials can be extendable for the synthesis of various functional hybrid nanomaterials owing to its versatility and feasibility.
RESUMEN
Since 1949, 3 large-range resource investigation of Chinese medical classical have been carried out and Union Catalog for Chinese Medical Books, National Union Catalog for Chinese Medical Books, and General Catalog for Chinese Medical Classical in China have been compiled. Among them, the last one was the all-around catalog and 13,455 ancient literature were included. During its compilation, some problems in former two catalogs were revised, including the classification of literature, title, complete date, author, publish date and edition etc. However, during the use of General Catalog for Chinese Medical Classical in China, some shortcomings were still needed to be noticed, like classification, title, volume. living dynasty of author, complete date and edition etc.
Asunto(s)
Libros/historia , Catálogos como Asunto , Medicina Tradicional China , China , Historia del Siglo XVI , Historia del Siglo XVII , Historia del Siglo XVIII , Historia del Siglo XIX , Historia del Siglo XX , Historia del Siglo XXIRESUMEN
OBJECTIVE: To observe the expression pattern of albumin during the hepatocyte differentiation by human bone marrow stem cells in vitro. METHODS: Human bone marrow cells were harvested and cultured in the presence of hepatocyte growth factor (HGF), fibroblast growth factor (FGF) and lymphocyte inhibitory factor (LIF). Cells were stained immunohistochemically by albumin specific antibody and examined under a confocal microscope. Supernatant albumin level was measured biochemically on a serial time points of the culture. RESULTS: By this condition, the attached cells became mature morphologically in 1 week of culture. Hepatocyte-specific albumin could be detected in mature cells. The albumin level revealed a time-dependent change during a 4-week culture. CONCLUSION: Human bone marrow cells could be induced to differentiate to mature hepatocytes that produce and secret albumin in vitro. These cells may contribute to a stable source of hepatocytes for clinical hepatocyte transplantation and artificial liver support system.
Asunto(s)
Albúminas/biosíntesis , Células de la Médula Ósea/citología , Hepatocitos/citología , Células Madre Mesenquimatosas/citología , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Medios de Cultivo Condicionados/farmacología , Factores de Crecimiento de Fibroblastos/farmacología , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Células Madre Mesenquimatosas/fisiologíaRESUMEN
OBJECTIVE: To report a family of familial dysalbuminaemic hyperthyroxinaemia(FDH). METHODS: Four members, including the female proband, mother, daughter and brother, went through the measurement of thyroid hormone and thyroid-stimulating hormone (TSH). Electrophoretic analysis of the patient's serum proteins was carried out after the patient's serum being incubated with fluorescein isothiocyanate (FITC) labeled thyroxine(T4), The point mutation of Alb gene was determined in all members. RESULTS: The measurements of thyroid hormane and TSH showed that in three members (the proband, her mother and her daughter), the total thyroxine(TT4) serum level was high, the total triiodothyronine(TT3), FT4, FT3 and TSH serum levels were normal. And the enhanced albumin binding of fluorescenced T4 by electrophoresis showed a mutation transition 653 G-->A on DNA coding region of albumin. But in the proband's brother, the thyroid function and the results of electrophoresis of thyroxine-binding protein and determination of albumin gene were normal. CONCLUSION: A family with FDH in China is firstly reported here, a mutation at albumin gene DNA coding region 653G-->A causing enhanced albumin binding of T4 results in high T4 level.