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Diffuse large B-cell lymphoma (DLBCL) is the most common pathological type of non-Hodgkin lymphoma, and is closely associated with hepatitis B virus (HBV) infection status and hepatitis B X (HBx) gene integration. This project investigated the cellular biological effects and molecular mechanisms responsible for lymphomagenesis and the progression of HBx integration in DLBCL. The data showed that clinical DLBCL cells demonstrated HBx integration, and the sequencing analysis of integrated sites validated HBx integration in the constructed HBx-transfected cells. Compared with control cells, HBx-transfected cells had a significantly reduced proportion of mitochondrial membrane potential, signals of chromosomal DNA breaks, and proportion of apoptotic cells. Further studies found that this decreased apoptosis level was associated with a significant reduction of cleaved Caspase-3 and downstream poly ADP-ribose polymerase (PARP) proteins, revealing the molecular mechanisms of HBx-associated apoptosis in DLBCL. Animal experiments also demonstrated that the protein expression of cleaved Caspase-3 and PARP was prominently reduced in HBx-transfected cells from subcutaneous tumors in mice. Furthermore, the HBx-integrated cells in clinical tissues had significantly lower cleaved PARP levels than the HBx-negative samples. Therefore, HBx integration inhibits cell apoptosis through the Caspase-3-PARP pathway in DLBCL indicating a potential biomarker and therapeutic target in HBV related DLBCL.
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Epithelial ovarian cancer (EOC) is one of the most common malignant gynecological tumors with rapid growth potential and poor prognosis, however, the molecular mechanism underlying its outgrowth remained elusive. Germ cell-specific gene 2 (GSG2) was previously reported to be highly expressed in ovarian cancer and was essential for the growth of EOC. In this study, GSG2-knockdown cells and GSG2-overexpress cells were established through lentivirus-mediated transfection with Human ovarian cancer cells HO8910 and SKOV3. Knockdown of GSG2 inhibited cell proliferation and induced G2/M phase arrest in EOC. Interestingly, the expression of p27, a well-known regulator of the cell cycle showed a most significant increase after GSG2 knockdown. Further phosphorylation-protein array demonstrated the phosphorylation of GSK3αSer21 decreased in GSG2-knockdown cells to the most extent. Notably, inhibiting GSK3α activity effectively rescued GSG2 knockdown's suppression on cell cycle as well as p27 expression in EOC. Our study substantiates that GSG2 is able to phosphorylate GSK3α at Ser21 and then leads to the reduction of p27 expression, resulting in cell cycle acceleration and cell proliferation promotion. Thus, GSG2 may have the potential to become a promising target in EOC.
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Carcinoma Epitelial do Ovário , Ciclo Celular , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p27 , Quinase 3 da Glicogênio Sintase , Peptídeos e Proteínas de Sinalização Intracelular , Neoplasias Ovarianas , Proteínas Serina-Treonina Quinases , Feminino , Humanos , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Carcinoma Epitelial do Ovário/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Quinase 3 da Glicogênio Sintase/metabolismo , Quinase 3 da Glicogênio Sintase/genética , Quinase 3 da Glicogênio Sintase/antagonistas & inibidores , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Fosforilação , Transdução de Sinais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismoRESUMO
To investigate the relationship between immune dynamic and graft-versus-host-disease (GVHD) risk, 111 initial diagnostic acute myeloid leukemia patients were reviewed. The flow cytometry data of 12 major lymphocyte subsets in bone marrow (BM) from 60 transplant patients at four different time points were analyzed. Additionally, 90 immune subsets in peripheral blood (PB) of 11 post-transplantation on day 100 were reviewed. Our results demonstrated that transplant patients had longer OS compared to non-transplant patients (Pâ <â 0.001). Among transplant patients, those who developed GVHD showed longer OS than those without GVHD (Pâ <â 0.05). URD donors and CMV-negative status donors were associated with improved OS in transplant patients (Pâ <â 0.05). Importantly, we observed a decreased Th/Tc ratio in BM at initial diagnostic in patients with GVHD compared to those without GVHD (Pâ =â 0.034). Receiver operating characteristic analysis indicated that a low Th/Tc ratio predicted an increased risk of GVHD with a sensitivity of 44.44% and specificity of 87.50%. Moreover, an increased T/NK ratio in BM of post-induction chemotherapy was found to be associated with GVHD, with a sensitivity of 75.76% and specificity of 65.22%. Additionally, we observed a decreased percentage of NK1 (CD56-CD16+NK) in PB on day 100 post-transplantation in the GVHD group (Pâ <â 0.05). These three indicators exhibit promising potential as specific and useful biomarkers for predicting GVHD. These findings provide valuable insights for the early identification and management of GVHD risk, thereby facilitating the possibility of improving patient outcomes.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante Homólogo , Estudos RetrospectivosRESUMO
BACKGROUND: Inflammation and immunity are two main characteristics of tumor microenvironment (TME). Interferon-gamma (IFN-γ) is generally considered as a pro-inflammatory cytokine which mediates anti-tumor immune response. Recently, IFN-γ was also reported to play a protumorigenic role. However, the mechanisms of tumor-promoting effect induced by IFN-γ remain unclear. METHODS: The expression of leukocyte antigen-E (HLA-E), IFN-γ, CD3 and CD56 in clinical samples of ovarian cancer was detected by mutiplexed immunohistochemistry. The mechanism to induce HLA-E overexpression by IFN-γ was explored using human ovarian cancer cell lines through western blot and flow cytometry. We further clarify the role of overexpressed-HLA-E on natural killer (NK)-mediated cell lysis. RESULTS: We found that IFN-γ could upregulate HLA-E protein expression through activating of JAK/STAT1 signaling pathway, and increase cell surface HLA-E level through enhancing proteasome activity. We also observed that only high levels of membrane HLA-E expression contributed to the inhibition of NK-mediated cytotoxicity. We showed that progression-free survival (PFS) of ovarian cancer patients was negatively correlated with IFN-γ expression in their tumor tissues, due to more tumor infiltrating NK cells compared with T lymphocytes. CONCLUSIONS: Our study revealed the protumorigenic role of IFN-γ by upregulation of HLA-E expression and rendering tumors less susceptible to immune attack. We also provided a novel insight into the relationship between tumor microenvironment and immune evasion.
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Interferon gama , Neoplasias Ovarianas , Humanos , Feminino , Microambiente Tumoral , Neoplasias Ovarianas/genética , Prognóstico , Antígenos HLA-ERESUMO
Polysaccharide-based QDs have attracted great attention in the field of biological imaging and diagnostics. How to get rid of the high heavy metal toxicity resulting from conventional Cd- and Pb-based QDs is now the main challenge. Herein, we offer a simple and environmentally friendly approach for the "direct" interaction of thiol-ending carboxymethyl chitosan (CMC-SH) with metal salt precursors, resulting in CuInS2 QDs based on polysaccharides. A nucleation-growth mechanism based on the LaMer model can explain how CMC-CuInS2 QDs are formed. As-prepared water-soluble CMC-CuInS2 QDs exhibit monodisperse particles with sizes of 5.5-6.5 nm. CMC-CuInS2 QDs emit the bright-green fluorescence at 530 nm when excited at 466 nm with the highest quantum yield of â¼18.0%. Meanwhile, the fluorescence intensity of CMC-CuInS2 QD aqueous solution is quenched with the addition of Pb2+ and the minimal limit of detection is as little as 0.4 nM. Furthermore, due to its noncytotoxicity, great biocompatibility, and strong biorecognition ability, CMC-CuInS2 QDs can be exploited as a possible cell membrane imaging reagent. The imaging studies also demonstrate that CMC-CuInS2 QDs are suitable for Pb2+ detection in live cells and living organisms (zebrafish). Thus, this work offers such an efficient, green, and practical method for creating low-toxicity and water-soluble QD nanosensors for a sensitive and selective detection of toxic metal ion in live cells and organisms.
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Quitosana , Pontos Quânticos , Animais , Pontos Quânticos/toxicidade , Chumbo/toxicidade , Peixe-Zebra , ÁguaRESUMO
Flame retardants (FRs) are ubiquitous in environment and biota and may pose harm to human health. In recent years, concern regarding legacy and alternative FRs has been intensified due to their widespread production and increasing contamination in environmental and human matrices. In this study, we developed and validated a novel analytical method for simultaneous determination of legacy and alternative FRs, including polychlorinated naphthalenes (PCNs), short- and middle-chain chlorinated paraffins (SCCPs and MCCPs), novel brominated flame retardants (NBFRs), and organophosphate esters (OPEs) in human serum. Serum samples were prepared by liquid-liquid extraction using ethyl acetate, and purified with Oasis® HLB cartridge and Florisil-silica gel columns. Instrumental analyses were carried out using gas chromatography-triple quadrupole mass spectrometry, high-resolution gas chromatography coupled with high-resolution mass spectrometry, and gas chromatography coupled with quadrupole time-of-flight mass spectrometry, respectively. The proposed method was validated for linearity, sensitivity, precision, accuracy, and matrix effects. Method detection limits for NBFRs, OPEs, PCNs, SCCPs, and MCCPs were 4.6 × 10-4-8.6 × 10-2, 4.3 × 10-3-1.3, 1.1 × 10-5-1.0 × 10-4, 1.5, and 9.0 × 10-1 ng/mL, respectively. Matrix spike recoveries ranged from 73%-122%, 71%-124%, 75%-129%, 92%-126%, and 94%-126% for NBFRs, OPEs, PCNs, SCCPs, and MCCPs, respectively. The analytical method was applied for detection of real human serum. CPs were the dominant FRs in serum, indicating CPs were widely presented in human serum and should be pay more attention for their health risk.
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Monitoramento Biológico , Retardadores de Chama , Humanos , Biota , Cromatografia Gasosa-Espectrometria de Massas , Espectrometria de Massas , NaftalenosRESUMO
Glyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the "direct" reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0-4.0 nm. They exhibited well-separated dual emission in the visible region (500-590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from - 23.9 to - 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.
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Nanopartículas , Pontos Quânticos , Humanos , Diagnóstico por Imagem , Células HeLa , ÁguaRESUMO
Fluorescent non-conjugated nanoparticles without any π-aromatic building blocks are of great interest in biological applications due to their low cytotoxicity and biocompatibility. Herein, the non-conjugated AIE-active polymer nanoparticles bearing ß-cyclodextrin (ß-CD-PNs) were obtained through self-assembly of amphiphilic poly(isobutylene-alt-maleic anhydride)-g-ß-CD (PIMA-g-ß-CD). Unexpectedly, ß-CD-PNs without conventional AIE fluorophores showed strong fluorescence emission in the aggregated state, excellent photostability and water-solubility. More interestingly, ß-CD-PNs showed excellent biocompatibility and low biotoxicity after being co-incubated with HeLa cells and passaged several times. As a result, the strong blue fluorescence signals could still be detected in HeLa cells after up to 15 generations of passages and showed complete cell morphology. Furthermore, ß-CD-PNs could also be used in zebrafish for bioimaging. The results indicated that ß-CD-PNs was a good choice as a tracer for long-term cell tracking and in vivo imaging agent. Our research provided an effective strategy for developing low-toxicity bioprobes based on ß-CD.
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Nanopartículas , Polímeros , Animais , Rastreamento de Células , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Iodeto de Potássio , Peixe-ZebraRESUMO
Owing to various chemical structures and different basicity of amines, a fluorescent probe that could distinguish aromatic and aliphatic amines is highly desirable for practical applications. Herein, an olefin-based, fluorescent COF (COF-Py-AN) with unique π-electron deficient groups was synthesized, which was a functionalized platform to realize sensing of π electron-rich aromatic amines. COF-Py-AN displayed fluorescence quenching in the presence of aromatic amines like aniline, with excellent selectivity against a variety of aromatic molecules, and the detection limit of COF-Py-AN toward aniline was as low as 1.29â µM. More importantly, COF-Py-AN could realize discriminating between aromatic and aliphatic amines. Furthermore, density functional theory calculations showed that the photoinduced electron transfer mechanism contributes to fluorescence sensing. This is the first example of olefin-based fluorescent COF materials for selective sensing of aromatic amines.
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Estruturas Metalorgânicas , Alcenos , Aminas/química , Compostos de Anilina , Corantes Fluorescentes/química , Estruturas Metalorgânicas/químicaRESUMO
Breast cancer is one of the leading causes of mortality among women. Triple-negative breast cancer (TNBC) is responsible for a large percentage of all breast cancer deaths in women. This study demonstrated the function of Myb-like, SWIRM, and MPN domains 1 (MYSM1), an H2A deubiquitinase (DUB), in TNBC. MYSM1 expression was drastically decreased in breast cancer, especially in TNBC, suggesting a potential anticancer effect. Overexpressing and suppressing MYSM1 expression in TNBC cell lines led to significant biological changes in cell proliferation. Furthermore, MYSM1 overexpression increased cisplatin-induced apoptosis, which might be attributed to RSK3 inactivation and the subsequently decreased phosphorylation of Bcl-2 antagonist of cell death (BAD) (Ser 112). The findings suggest that MYSM1 is a potential target for regulating cell apoptosis and suppressing resistance to cisplatin in TNBC.
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Exploring effective electrocatalysts for oxygen evolution reaction (OER) is a crucial requirement of many energy storage and transformation systems, involving fuel cells, water electrolysis, and metal-air batteries. Transition-metal oxides (TMOs) have attracted much attention to OER catalysts because of their earth abundance, tunable electronic properties, and so forth. Defect engineering is a general and the most important strategy to tune the electronic structure and control size, and thus improve their intrinsic activities. Herein, OER performance on spinel CuCo2O4 was greatly enhanced through cation substitution and size reduction. Ce-substituted spinel CuCeδCo2-δOx (δ = 0.45, 0.5 and 0.55) nanoparticles in the quantum dot scale (2-8 nm) were synthesized using a simple and facile phase-transfer coprecipitation strategy. The as-prepared samples were highly dispersed and have displayed a low overpotential of 294 mV at 10 mA·cm-2 and a Tafel slope of 57.5 mV·dec-1, which outperform commercial RuO2 and the most high-performance analogous catalysts reported. The experimental and calculated results all confirm that Ce substitution with an appropriate content can produce rich oxygen vacancies, tune intermediate absorption, consequently lower the energy barrier of the determining step, and greatly enhance the OER activity of the catalysts. This work not only provides advanced OER catalysts but also opens a general avenue to understand the structure-activity relationship of pristine TMO catalysts deeply in the quantum dot scale and the rational design of more efficient OER catalysts.
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BACKGROUND: Drug resistance and recurrence are main contributors to the poor prognosis of ovarian cancer. Cisplatin is a platinum compound which is widely used in the treatment of various solid tumors including ovarian cancer. Up to now, the mechanism of cisplatin resistance in ovarian cancer is unclear. Threonine and tyrosine kinase (TTK), an integral part of the spindle assembly checkpoint, may be a potential new target associated with chemotherapy sensitivity. RESULTS: TTK was up-regulated in the cisplatin-resistant ovarian cancer cell line. Down-regulation of TTK could recover the sensitivity of cisplatin-resistant ovarian cancer cells to cisplatin treatment. Mechanistically, the PI3K/AKT signaling pathway was activated in cisplatin-resistant cells, and this pathway would be affected by TTK expression. Furthermore, TTK was highly expressed in the tissues of ovarian cancer patients, especially those acquired resistance to cisplatin. CONCLUSIONS: Our study revealed that TTK may be a promising therapeutic target for cisplatin-resistant ovarian cancer.
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Proteínas de Ciclo Celular/metabolismo , Cisplatino/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Cisplatino/farmacologia , Feminino , HumanosRESUMO
Serous ovarian cancer (SOC) is the most common women cancer and the leading cause of cancer-related mortality among the gynaecological malignancies. Although effective chemotherapeutics combined with surgery are developed for the treatment, the five-year survival rate is unsatisfactory due to chemoresistance. To overcome this shortcoming of chemotherapy, we established taxol and carboplatin resistant SOC cell lines for the understandings of the molecular and cellular mechanisms of chemoresistance. Here, we found that these chemoresistant cell lines showed less viability and proliferation, due to more cells arrested at G0/G1 phase. Glutathione-S-transferases-theta1 (GSTT1) was significantly upregulated in these chemoresistant cells, along with other chemoresistant genes. Meanwhile, GSTT1 expression was also significantly upregulated in the SOC patient tissues after taxol treatment, indicating this upregulation was physiologically relevant to chemotherapy. Further, suppression of GSTT1 expression by shRNA in SOC cell lines led to more sensitivity to drug treatment, through increasing divided cells and promoting cell death. Moreover, the expression of DNA topoisomerase 1 (Topo I) was in synergy with that of GSTT1 in the chemoresistant cells, and GSTT1 can bind to Topo I in vitro, which suggested GSTT1 could function through DNA repair mechanism during chemoresistance. In summary, our data imply that GSTT1 may be a potential biomarker or indicator of drug resistance in serous ovarian cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/metabolismo , Cistadenocarcinoma Seroso/tratamento farmacológico , Cistadenocarcinoma Seroso/metabolismo , Glutationa Transferase/metabolismo , Carboplatina/administração & dosagem , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Regulação para CimaRESUMO
Clear cell renal cell carcinomas (ccRCC) reprogram carbon metabolism responses to hypoxia, thereby promoting utilization of glutamine. Recently, sirtuin 4 (SIRT4), a novel molecular has turned out to be related to alternating glutamine metabolism and modulating the tumor microenvironment. However, the role of SIRT4 in ccRCC remains poorly understood. Here, we illustrated that the expression of SIRT4 is markedly reduced in cancerous tissues, and closely associated with malignancy stage, grade, and prognosis. In ccRCC cells, SIRT4 exerted its proapoptotic activity through enhancing intracellular reactive oxygen species (ROS). Heme oxygenase-1 (HO-1) is part of an endogenous defense system against oxidative stress. Nevertheless, overexpression of SIRT4 hindered the upregulation of HO-1 in von Hippel-Lindau (VHL)-proficient cells and repressed its expression in VHL-deficient cells. This discrepancy indicated that competent VHL withstands the inhibitory role of SIRT4 on HIF-1α/HO-1. Functionally, overexpression of HO-1 counteracted the promotional effects of SIRT4 on ROS accumulation and apoptosis. Mechanistically, SIRT4 modulates ROS and HO-1 expression via accommodating p38-MAPK phosphorylation. By contrast, downregulation of p38-MAPK by SB203580 decreased intracellular ROS level and enhanced the expression of HO-1. Collectively, this work revealed a potential role for SIRT4 in the stimulation of ROS and the modulation of apoptosis. SIRT4/HO-1 may act as a potential therapeutic target, especially in VHL-deficient ccRCCs.
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Carcinoma de Células Renais/enzimologia , Heme Oxigenase-1/metabolismo , Neoplasias Renais/enzimologia , Proteínas Mitocondriais/metabolismo , Estresse Oxidativo , Sirtuínas/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Apoptose , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glutamina/deficiência , Heme Oxigenase-1/genética , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Proteínas Mitocondriais/genética , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Sirtuínas/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Caldesmon gene (CALD1) plays an important role in many cellular functions. Some researchers have found the correlation between CALD1 expression and prognosis of gastrointestinal cancer (GI), but the association with tumor-infiltrating lymphocytes (TILs) still unclear. METHODS: The expression of CALD1 in different human tumor was analyzed by Oncomine and Tumor Immune Estimation Resource (TIMER) databases. The correlations between CALD1 and prognosis in types cancer were explored by Kaplan-Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) databases. The association between CALD1 expression and tumor immune cell infiltration was further analyzed via TIMER and GEPIA databases. RESULTS: The CALD1 expressions in types cancer between tumor tissues and adjacent normal tissues were significantly different. The high expression of CALD1 was related with poor overall survival (OS) of patients with gastric cancer, especially in gastric cancer patients at N1, N2 and N3 stages. The expression of CALD1 was positively associated with immune-infiltrated, such as CD8+T cells, CD4+T cells, macrophages, neutrophils, and dendritic cells (DCs) in gastric cancer. CONCLUSIONS: CALD1 was considerably a key role in prognosis of patients with gastric cancer. The expression level of CALD1 is significantly associated with immune-infiltrated in gastric cancer. Furthermore, CALD1 expression may be involved in regulating tumor-associated macrophages (TAMs), dendritic cells, exhausted T cells and regulatory T cells in gastric cancer. These findings suggest that CALD1 could be utilized as a marker of prognosis and immune infiltration in gastric cancer.
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AIM: To investigate the clinical significance of detecting several biomarkers collectively in the diagnosis of rheumatoid arthritis (RA). METHODS: 128 RA patients, 174 non-RA patients and 80 healthy controls were enrolled. HLA-DR4 and HLA-DR53 were detected by the PCR-SSP method, 14-3-3η protein, anti-CCP and anti-Sa were detected by ELISA and DD was detected by latex immunoturbidimetric assay. RESULTS: The positive rates of HLA-DR4, HLA-DR53, 14-3-3η protein, anti-CCP and anti-Sa were obviously higher in the RA group (43.8, 38.3, 51.6, 80 and 40.6%, respectively); anti-CCP was of highest sensitivity (79.68%), highest specificity (97.5%) and Youden index (0.77). The AUC of 14-3-3η protein, DD, anti-CCP, anti-Sa were 0.813, 0.859, 0.930, 0.861, respectively. CONCLUSION: All biomarkers were strongly correlated risk factors for RA; the combination of multiple biomarkers might be of help for diagnostic and therapeutic strategies in RA of recent onset.
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Proteínas 14-3-3/sangue , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Antígenos HLA-DR/sangue , Antígeno HLA-DR4/sangue , Cadeias HLA-DRB4/sangue , Adulto , Anticorpos Antiproteína Citrulinada/sangue , Artrite Reumatoide/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To research the diagnostic performance of clinical potential bone turnover indexes in rheumatoid arthritis (RA) complicated with osteoporosis (OP). METHODS: This study involved 87 RA patients, 48 with OP, and 39 without OP, and 204 non-RA control patients, including those with systemic lupus erythematosus, ankylosing spondylitis, primary Sjogren's syndrome, systemic sclerosis, and healthy patients. The levels of 25-hydroxyvitamin D [25(OH)D], ß-crosslaps (ß-CROSSL), parathyroid hormone (PTH) were measured by electrochemiluminescence (ECLIA), and the level of bone alkaline phosphatase (BALP) was measured by lectin affinity method. RESULTS: The serum concentration of 25(OH)D in the RA with OP group was significantly lower than the control group (P<0.01), while the levels of ß-CROSSL, BALP in the RA with OP group considerably exceeded those found in the control group (P<0.01). The levels of ß-CROSSL and PTH were significantly higher in RA patients with OP than without OP (P<0.01), while the level of 25(OH)D was statistically lower than without OP (P<0.01). An unconditional logistical regression analysis proved an association with low 25(OH)D and elevated ß-CROSSL in RA with OP, with 25(OH)D demonstrating greatest diagnostic potential according to the ROC curve. CONCLUSION: The significantly reduced levels of 25(OH)D and excessive ß-CROSSL may indicate a high risk of the secondary osteoporosis in RA patients.
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Artrite Reumatoide , Osso e Ossos/metabolismo , Osteoporose/complicações , Osteoporose/patologia , Vitamina D/análogos & derivados , Absorciometria de Fóton , Adulto , Idoso , Fosfatase Alcalina/metabolismo , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/etiologia , Artrite Reumatoide/patologia , Densidade Óssea , Colágeno/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Curva ROC , Estudos Retrospectivos , Vitamina D/metabolismoRESUMO
OBJECTIVE: To investigate the value of serum levels of IgG4 and CA19-9, and autoantibodies in the diagnosis of IgG4-related sclerosing cholangitis (IgG4-SC). METHODS: We detected the serum IgG4 and CA19-9 of 45 IgG4-SC patients, 173 non-IgG4-SC patients and 48 healthy controls by immunoassay and chemiluminescence, respectively, with antinuclear antibody (ANA), anti-neutrophil antibody (ANCA), anti-smooth muscle antibody (SMA) and anti-mitochondrial antibody (AMA) level detected by indirect immunofluorescence. Then analyze the detection results. RESULTS: (1) The positive rates of ANA, ANCA, SMA and AMA in patients with IgG4-SC were 40%, 6.67%, 0 and 2.22%. Among them, the positive rate of ANA was significantly higher than that of the healthy control group (p < .01), and the positive rate of ANA, ANCA, SMA and AMA were significantly different from that of the non-IgG4-SC group (p < .05). (2) Serum levels of IgG4 and CA19-9 increased significantly in patients with IgG4-SC compared with the healthy controls (p < .01). The areas under the ROC curve (AUC) of IgG4 and CA19-9 were 0.9750 and 0.6498, respectively (p < .05). CONCLUSION: The high levels of serum IgG4 and CA19-9, and autoantibodies detections are of great important clinical value in diagnosis and differential diagnosis of IgG4-SC.
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Antígenos Glicosídicos Associados a Tumores/sangue , Autoanticorpos/sangue , Colangite Esclerosante/diagnóstico , Imunoglobulina G/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , China , Colangite Esclerosante/sangue , Diagnóstico Diferencial , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Using environment-friendly materials for sensing toxic metal ions has drawn significant attention in recent research. Herein, we present an aqueous synthesis of stable CdS quantum dots (QDs) using thiol-functionalized poly(vinyl alcohol) (PVA) as the unique capping ligand for the detection of trace Hg(2+) in environmental water samples. The CdS QDs with an average size of 3.3 nm had good water-solubility and favorable fluorescence with a quantum yield of 32.8% and a longer luminescence lifetime of 31.9 ns. The fluorescence intensity of QDs aqueous solution in the 520 nm wavelength was quenched upon the addition of Hg(2+). Under the optimal conditions, the ratio of the blank fluorescence intensity to the quenched fluorescence intensity was linearly proportional to the Hg(2+) concentration from 2 to 4000 nM with a detection limit of 1 nM. Also, many co-existing metal ions were not interfered with the detection of Hg(2+). This nanomaterial was successfully applied to the measurement of Hg(2+) in water samples.
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Naringin is a flavonoid showing variable pharmacological properties and is distributed ubiquitously in plant foods. There is a paucity of reported data regarding its safety profile. In the present study, chronic toxicity studies of naringin was designed and conducted by oral gavage at doses of 0, 50, 250 and 1250 mg/kg in Sprague-Dawley (SD) rats for six months followed by 1-month recovery period. During the 6-month treatment period and one month recovery period, no mortality and toxicologically significant changes in clinical signs, opthalmoscopic examination, hematology, clinical biochemistry, serumsexhormone, macroscopic findings, organ weights and histopathological examination were noted and attributed to naringin administration. Although consecutive and/or isolated periods of significant body weights and food consumption decreases were relevant to naringin administration, they were not considered toxicologically significant. In addition, slight, non-pathological and reversible hair loss was noted during the 6-month treatment period and considered as a kind of change possibly relevant to naringin administration; however, it was not considered adverse change and to be of toxicological significance. Based on the results of this study, the no-observed-adverse-effect-level (NOAEL) of naringin in rats is greater than 1250 mg/kg/day when administered orally for 6 consecutive months.