RESUMO
The spontaneous changes in brain activity in patients with diabetic optic neuropathy using steady-state fMRI. The fractional amplitude of the low-frequency fluctuation method was applied to evaluate neural activity changes. The Hospital Anxiety and Depression Scale was used to assess the anxiety and depression status of participants. The independent sample t-test and chi-squared test were applied to analyze the demographics of diabetic optic neuropathy patients and healthy controls. Receiver operating characteristic curves were applied to analyze the variation in mean fractional amplitude of low-frequency fluctuation values between diabetic optic neuropathy patients and healthy controls. Pearson's correlation analysis analyzed the relationships between the fractional amplitude of low-frequency fluctuation values of brain regions and clinical behaviors in the diabetic optic neuropathy group. The fractional amplitude of low-frequency fluctuation value of diabetic optic neuropathy patients was significantly higher than healthy controls in the right precentral gyrus. However, the fractional amplitude of low-frequency fluctuation values in the right anterior cingulate gyrus and left middle cingulate gyrus were markedly decreased in diabetic optic neuropathy patients. The area under the curve of receiver operating characteristics for each brain region showed high accuracy. Pearson's correlation analysis showed that fractional amplitude of low-frequency fluctuation values of the right anterior cingulate gyrus and left middle cingulate gyrus was negatively correlated with Hospital Anxiety and Depression Scale scores. The fractional amplitude of low-frequency fluctuation values of the left middle cingulate gyrus was negatively correlated with diabetic optic neuropathy disease duration. In conclusion, we found abnormal spontaneous brain activities in regions related to cognitive and emotional dysfunction, eye movement disorder, and vision loss in patients with diabetic optic neuropathy. These results may indicate the underlying neuropathological mechanisms of diabetic optic neuropathy and show that fractional amplitude of low-frequency fluctuation may be an effective method to distinguish patients with diabetic optic neuropathy from healthy individuals.
Assuntos
Neuropatias Diabéticas/fisiopatologia , Neuroimagem Funcional , Giro do Cíngulo/fisiopatologia , Doenças do Nervo Óptico/fisiopatologia , Neuropatias Diabéticas/diagnóstico por imagem , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças do Nervo Óptico/diagnóstico por imagemRESUMO
OBJECTIVE: Neuroimaging studies have shown that patients with pain-related conditions have altered neuronal activity and structural functions. The purpose of this study was to investigate whether patients with classical trigeminal neuralgia (CTN) exhibit changes in corresponding neuronal activity via analysis of neuronal activity regional homogeneity (ReHo). METHODS: A total of 28 patients presenting with sore eyes (12 men and 16 women) were matched with 28 healthy controls (12 men and 16 women). All participants underwent functional magnetic resonance imaging (fMRI). This ReHo method was used to assess the consistency of changes in neural activity in various brain regions. The receiver operating characteristic (ROC) curve was applied to differentiate ReHo values of patients with CTN from ReHo values of healthy controls. Pearson's correlation analysis was applied to evaluate the correlation between ReHo values of different brain regions of patients with CTN and clinical manifestations. RESULTS: Compared with healthy controls, patients with CTN were found to have increased ReHo values in the inferior cerebellum bilaterally, right inferior temporal gyrus, right middle occipital gyrus, right fusiform gyrus, right superior frontal gyrus, and right precentral gyrus. ROC curve analysis of each brain region revealed near-perfect accuracy regarding the area under the curve. However, no correlation between ReHo values and clinical manifestations in patients with CTN was found. CONCLUSIONS: CTN is associated with altered neuronal networks in different areas of the brain. ReHo values all possess different degrees of change, implying that CTN has a certain impact on cerebral function.
Assuntos
Encéfalo/fisiopatologia , Neuralgia do Trigêmeo/fisiopatologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Curva ROCRESUMO
2-Substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole, a key structural moiety exiting in many bioactive molecules, has been shown to have excellent selective activity on COX-2. In the present study, the anti-inflammatory activity and the underlying molecular mechanism of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on skin inflammation were assessed by 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. Most of the compounds showed anti-inflammatory activity on TPA-induced skin inflammation. The anti-inflammatory activity of compound 4 showed higher anti-inflammatory activity than celecoxib (3.2-fold). Compound 4 pretreatment resulted in markedly suppression of TPA-induced IL-1ß, IL-6, TNF-α, and COX-2, respectively. Furthermore, the mechanical study indicated that the anti-inflammatory activity of compound 4 was associated with its ability to inhibit activation of factor kappa-κB (NF-κB) by blocking IκB kinase (IKK) activities. Accordingly, compound 4 could be used as a potential anti-inflammatory agent for skin inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Dermatite/prevenção & controle , Acetato de Tetradecanoilforbol/toxicidade , Animais , Ciclopentanos , Dermatite/etiologia , Camundongos , NF-kappa B/metabolismo , PirróisRESUMO
Background: CD276 is an emerging immune checkpoint molecule that has been implicated in various cancers. However, its specific role in hepatocellular carcinoma (HCC) remains unclear. This study examined the impact of CD276 on patient prognosis and the tumor microenvironment (TME). Methods: The Cancer Genome Atlas (TCGA) database was utilized to evaluate CD276 expression in HCC and the association between CD276 and immune indicators was also analyzed. The signaling pathways correlated with CD276 expression were identified by gene set enrichment analysis (GSEA). Different algorithms were used to assess immune cell infiltration. The effect of CD276 knockdown on HCC cell phenotypes and its relationship with macrophage polarization was examined using the cell counting kit 8 (CCK-8) assay and co-culture system. Results: CD276 was upregulated in HCC and associated with unfavorable clinical outcomes. Hgh CD276 expression was associated with enrichment of the G2/M checkpoint, E2F targets, and mitotic spindles. CD276 expression was correlated with the infiltration of immune cells, including high level of tumor-associated macrophages and low levels of CD8+ T cells. Knockdown of CD276 decreased HCC cell proliferation and increased apoptosis. CD276 silencing in HCC cells and co-culture with THP-1-derived macrophages had a regulatory effect on macrophage polarization and macrophage-mediated cell proliferation and migration. Conclusion: CD276 expression in HCC is associated with unfavorable clinical outcomes and may contribute to the development of an immunosuppressive microenvironment. Specifically, CD276 was associated with alterations in immune cell infiltration, immune marker expression, and macrophage polarization during HCC progression, suggesting its potential as a prognostic indicator and promising target for immunotherapeutic intervention in HCC.
RESUMO
Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39+Foxp3+CD4+ regulatory T cells (CD39+T-regs) and exhausted-like CD8+T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39+T-regs and CD39+PD-1+CD8+T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.
RESUMO
In the screening search for Hepatitis B virus inhibitory agents from medicinal plants, the ethanol extract of Piper longum Linn. was found to possess superior anti-HBV activity in vitro. Bioassay-guided fractionation coupled with repeated purification resulted in the isolation of four new compounds, involving two new glycosides longumosides A (1) and B (2) and two new amide alkaloids erythro-1-[1-oxo-9(3,4-methylenedioxyphenyl)-8,9-dihydroxy-2E-nonenyl]-piperidine (3), threo-1-[1-oxo-9(3,4-methylenedioxyphenyl)-8,9-dihydroxy-2E-nonenyl]-piperidine (4), as well as two compounds 3ß,4α-dihydroxy-2-piperidinone (5), 5,6-dihydro-2(1H)-pyridinone (6) from natural source for the first time. The structures of the four new compounds were determined by extensive analyses of the MS, IR, 1D and 2D NMR data. Besides, the compounds 2-6, together with the known compounds 7-11 obtained previously, were assayed for their anti-HBV activity by using Hep G 2.2.15 cell line in vitro. Results suggested the compound piperine (7) possessed remarkable inhibitory HBV activity, against the secretion of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg) with the Selectivity Index (SI) values of 15.7 and 16.8, respectively.
Assuntos
Antivirais/farmacologia , Vírus da Hepatite B/efeitos dos fármacos , Piper/química , Extratos Vegetais/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-AtividadeRESUMO
The diffuse-reflectance FTIR spectroscopy (DRIFTS) and attenuated total reflection FTIR (ATR-FTIR) were used to study polygonum multi florum Thumb and its extracts. The result shows that when acetone is used as extraction agent, the contents of extracts in polygonum multi florum Thunb's phloem are highest, those in polygonum multi florum Thunb's xylem are the lowest. Compared with DRIFTS and ATR-FTIR, it can be found that there are some differences between polygonum multi florum Thunb and its extracts. There are two gentle absorption peaks at 3 576 and 3 147 cm(-1) respectively for polygonum multi florum Thunb, while there is a strong absorption peak at 3 351 cm(-1) for its extracts, showing that there may be more OH... active ingredients in polygonum multi florum Thunb's extracts. Meanwhile, polygonum multiflorum Thunb has strong absorption peaks at 931, 859, 766 and 709 cm(-1) respectively, while its extracts have no resembling absorption peaks. It also shows that the extracts are active ingredients.
Assuntos
Medicamentos de Ervas Chinesas/análise , Extratos Vegetais/química , Polygonum/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
Growth arrest-specific gene 7 (Gas7) was involved in various cellular functions, although its specific roles and molecular mechanisms in hepatocellular carcinoma (HCC) remained unclear. So the current study was to investigate the role of Gas7 in HCC. Our findings revealed that Gas7 was downregulated in various HCC cell lines and low Gas7 expression was associated with decreased overall survival in patients with HCC. Additionally, our functional assays showed that Gas7 inhibited cell proliferation and migration, induced cell cycle arrest, apoptosis, and autophagy, and enhanced oxaliplatin sensitivity by inhibiting the PI3K/Akt signaling pathway. We also observed that transcription factorSp1 was responsible for inhibiting Gas7. These findings provide insights into the role and elucidated a potential mechanism of Gas7 in HCC progression and metastasis. It was also observed that the Sp1/Gas7/PI3K/Akt axis was critical for malignant phenotype and oxaliplatin sensitivity in HCC. Therefore, Gas7 can be considered as a prognostic predictor and therapeutic target for HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
Alzheimer's disease (AD) is a degenerative disease of the central nervous system. Numerous studies have shown that imbalances in cholesterol homeostasis in the brains of AD patients precede the onset of clinical symptoms. In addition, cholesterol deposition has been observed in the brains of AD patients even though peripheral cholesterol does not enter the brain through the bloodâbrain barrier (BBB). Studies have demonstrated that cholesterol metabolism in the brain is associated with many pathological conditions, such as amyloid beta (Aß) production, Tau protein phosphorylation, oxidative stress, and inflammation. In 2022, some scholars put forward a new hypothesis of AD: the disease involves lipid invasion and its exacerbation of the abnormal metabolism of cholesterol in the brain. In this review, by discussing the latest research progress, the causes and effects of cholesterol retention in the brains of AD patients are analyzed and discussed. Additionally, the possible mechanism through which AD may be improved by targeting cholesterol is described. Finally, we propose that improving the impairments in cholesterol removal observed in the brains of AD patients, instead of further reducing the already impaired cholesterol synthesis in the brain, may be the key to preventing cholesterol deposition and improving the corresponding pathological symptoms.
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Barreira Hematoencefálica/patologia , Colesterol/metabolismoRESUMO
In-situ attenuated total reflection FTIR (in situ ATR-FTIR) was used for the dynamic research on the residual of pesticide. The in-situ characterization of dichlorvos and orthene on the tomatoes' surface shows that the dichlorvos has obvious volatility and its degradation amount is 80% 20 minutes after spraying. Meanwhile, the ATR-FTIR shows that the strong absorption peak of dichlorvos at 1 734 cm(-1) turns to negative peaks and the absorption peaks at 3 073 cm(-1) significantly abate. The absorption peaks at 1 277 cm(-1) become weak and red shift (30 cm(-1)) shows that the dichlorvos may be hydrolyzed to some extent. While the absorption peaks of orthene show no change 120 minute after spraying. It shows that the orthene is relatively stable.
Assuntos
Resíduos de Praguicidas/análise , Solanum lycopersicum/química , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Diclorvós/análise , Compostos Organotiofosforados/análise , Fosforamidas , Propriedades de Superfície , VolatilizaçãoRESUMO
The poliovirus receptor (PVR) is a member of the immunoglobulin superfamily (Ig SF) and is essential for the promotion of cancer cell proliferation and invasion. However, the correlation between PVR expression and prognosis as well as immune infiltration in hepatocellular carcinoma (HCC) remains unclear. The expression level of PVR was quantified using the Tumor and Tumor Immunity Evaluation Resource (TIMER) and Sangerbox. The Gene Expression Omnibus (GEO) database was used to validate the PVR expression. The receiver operating characteristic (ROC) curve was used to evaluate the feasibility of using PVR as a differentiating factor according to the area under curve (AUC) score. A PVR binding protein network was built using the STRING tool. An enrichment analysis using the R package clusterProfiler was used to explore the potential function of PVR. Immune infiltration analysis was calculated with ESTIMATE algorithms. We also assessed the correlation between PVR expression and immune infiltration by the single-sample Gene Set Enrichment Analysis (ssGSEA) method from the R package GSVA and TIMER database. The results showed that PVR was commonly overexpressed in multiple types of tumors including HCC. The data of GSE64041 confirmed the same result. The ROC curve suggested that PVR could be a potential diagnostic biomarker. Additionally, high mRNA expression of PVR in HCC was significantly correlated with poor overall survival (OS) and relapse free survival (RFS). Results also indicated correlations between PVR mRNA expression with the level of infiltration immune cells including B cells, CD8+ T cells, cytotoxic cells, DCs, CD56dim NK cells, pDCs, and Th2 cells. Furthermore, the PVR level was significantly correlated with immune markers for immunosuppressive cells in HCC. In conclusion, PVR might be an important regulator of tumor immune cell infiltration and a valuable prognostic biomarker in HCC. However, additional work is needed to fully elucidate the underlying mechanisms.
RESUMO
ABSTRACT: The prognosis of patients with postmenopausal breast cancer (PBC) could be improved by the early detection of intraocular metastases (IOMs). However, serum biomarkers for IOMs in PBC remain elusive. In the current study, we investigated patients with PBC, and compared serum parameters in an IOM and a non-IOM group, and then differentiated the risk factors related to IOMs. A comparison between an IOM and a non-IOM (NIOM) group was performed using Student t-test and a Chi-Squared test. After constructing a Poisson regression model to identify risk factors, we plotted receiver operating characteristic curves to evaluate the predictive value of significant risk factors in detecting IOMs. The incidence of IOMs in PBC was 1.16%. The histopathology results were not significantly different between the 2 groups. The levels of serum carbohydrate antigen 125 (CA-125), carbohydrate antigen 15-3 (CA15-3) and alkaline phosphatase were significantly elevated in IOMs compared with NIOMs (P = .082, Pâ<â.001, and Pâ<â.001, respectively). Compared with NIOMs, age, carbohydrate antigen 19 to 9, hemoglobin, calcium, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A1 were remarkably lower in IOMs (P = .038, Pâ<â.001, Pâ<â.001, P = .032, P = .041, Pâ<â.001, and P = .001, respectively). Poisson regression suggested that CA-125, CA15-3 and LDL were contributing to IOMs in PBC as risk factors (OR = 1.003, 95% CI: 1.001-1.005; OR = 1.025, 95% CI: 1.019-1.033; OR = 0.238, 95% CI: 0.112-0.505, respectively). A receiver operating characteristic curve revealed that the cut-off values for CA-125, CA15-3 and LDL were 16.78 0âU/mL, 63.175âU/mL, and 2.415âmmol/L, respectively. The combination of CA-125 and CA15-3 showed significant diagnostic value (area under the curve [AUC] = 0.982, Pâ<â.001). Our investigation suggests that CA-125, CA15-3 and LDL remarkably predict IOMs in PBC as risk factors, and the combination of CA-125 and CA15-3 shows considerable diagnostic value.
Assuntos
Neoplasias da Mama/patologia , Antígeno Ca-125/sangue , Neoplasias Oculares/secundário , Lipoproteínas LDL/sangue , Mucina-1/sangue , Pós-Menopausa/fisiologia , Fatores Etários , Idoso , Biomarcadores Tumorais , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Curva ROCRESUMO
Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a secretory serine protease that plays multiple biological functions in the regulation of physiological and pathological processes. PCSK9 inhibitors decrease the circulating LDL-cholesterol level with well-known preventive and therapeutic effects on atherosclerosis (AS). Still, increasing evidence shows that the direct impact of PCSK9 on the vascular wall also plays an important role in atherosclerotic progression. Compared with other vascular cells, a large proportion of PCSK9 is originated from vascular smooth muscle cells (VSMC). Therefore, defining the effect of VSMC-derived PCSK9 on response changes, such as phenotypic switch, apoptosis, autophagy, inflammation, foam cell formation, and calcification of VSMC, helps us better understand the "pleiotropic" effects of VSMC on the atherosclerotic process. In addition, our understanding of the mechanisms of PCSK9 controlling VSMC functions in vivo is far from enough. This review aims to holistically evaluate and analyze the current state of our knowledge regarding PCSK9 actions affecting VSMC functions and its mechanism in atherosclerotic lesion development. A mechanistic understanding of PCSK9 effects on VSMC will further underpin the success of a new therapeutic strategy targeting AS.
Assuntos
Aterosclerose , Pró-Proteína Convertase 9 , Aterosclerose/tratamento farmacológico , LDL-Colesterol , Humanos , Músculo Liso VascularRESUMO
AIM: To assess changed spontaneous brain activity in hyperthyroid exophthalmos (HE) patients by the amplitude of the low-frequency fluctuation (ALFF) method, and to analyze the correlation between brain activity and ALFF values in these patients. METHODS: Totally 18 HE and 18 hyperthyroid non-exophthalmos (HNE) patients were enrolled. The participants were tested by resting-state functional magnetic resonance imaging, and receiver operating characteristic (ROC) curves were generated to classify the ALFF values of the study population. Pearson's correlation analysis was utilized to evaluate the relationship between the ALFF values obtained from different brain areas and clinical manifestations. RESULTS: Contrary to HNE patients, we observed lower ALFF values in the left calcarine fissure and surrounding cortex (LCFSC) in HE patients. In the ROC curve analysis of the LCFSC, the area under the curve reflected a high degree of accuracy. In addition, there was positive correlation between mean ALFF values of the LCFSC and the best-corrected visual acuity of the affected eyes. CONCLUSION: The study displays abnormal brain activity in LCFSC in patients with HE, which might suggest pathological mechanism of visual impairment of HE patients.
RESUMO
Microwave dielectric ceramics are vital for filters, dielectric resonators, and dielectric antennas in the 5G era. It was found that the (Cu1/3Nb2/3)4+ substitution can effectively adjust the TCF (temperature coefficient of resonant frequency) of Li2TiO3 and simultaneously increase its Q × f (Q and f denote the quality factor and the resonant frequency, respectively) value. Notably, excellent microwave dielectric properties (εr (permittivity) ≈ 18.3, Q × f ≈ 77,840 GHz, and TCF ≈ +9.8 ppm/°C) were achieved in the Li2Ti0.8(Cu1/3Nb2/3)0.2O3 (LTCN0.2) ceramic sintered at 1140 °C. Additionally, the sintering temperature of LTCN0.2 was reduced to 860 °C by the addition of 3 wt % H3BO3, exhibiting superior microwave dielectric properties (εr ≈ 21.0, Q × f ≈ 51,940 GHz, and TCF ≈ 1.4 ppm/°C) and being chemically compatible with silver. Moreover, LTCN0.2 + 3 wt % H3BO3 ceramics were designed as a patch antenna and a dielectric resonator antenna, both of which showed high simulated radiation efficiencies (88.4 and 93%) and gains (4.1 and 4.03 dBi) at the center frequencies (2.49 and 10.19 GHz). The LTCN0.2 + 3 wt % H3BO3 materials have promising future application for either 5G mobile communication devices and/or in low-temperature co-fired ceramic technology owing to their high Q, low sintering temperature, small density, and good temperature stability.
RESUMO
The purpose of this study was to detect clinical variations between lung adenocarcinoma patients with and without ocular metastasis (OM) to identify risk factors for OM and assess the diagnostic values. We included 1153 patients with lung adenocarcinoma in this study. Independent t-tests and chi-square tests were used to compare patients' clinical characteristics. Statistically significant parameters were analyzed by binary logistic regression to detect risk factors of OM. The results showed that the OM group had increased alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cytokeratin fragment 19 (CYFRA 21-1), carbohydrate antigen- (CA-) 125, CA-153, and total prostate-specific antigen (TPSA) compared with the NOM group. CYFRA21-1 is the most useful biomarker for detecting OM in this population.
Assuntos
Adenocarcinoma de Pulmão/patologia , Biomarcadores Tumorais/sangue , Neoplasias Oculares/secundário , Neoplasias Pulmonares/patologia , Adenocarcinoma de Pulmão/terapia , Antígenos de Neoplasias/sangue , Área Sob a Curva , Antígeno Ca-125/sangue , Neoplasias Oculares/sangue , Feminino , Humanos , Queratina-19/sangue , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de RiscoRESUMO
We propose a method for achieving THz ultra-broadband coherent absorption using the anti-reflection theory of metamaterials. The metamaterial absorber consists of a periodic array of electric ring resonators with a multilayered structure which form the desired refractive index dispersion and provide continuous anti-reflection over a wide frequency range. The destructive interference mechanism and resonance absorption of the absorber are determined by simulation analysis and numerical simulation. Simulation results show that the absorption bandwidth is almost 8.02 THz (absorption rate >90%) over the entire terahertz band (0.1 THz-10 THz). This design provides an effective and viable method for constructing broadband absorbers for stealth technology and the construction of enhanced transmittance devices.
RESUMO
Lung cancer is prone to metastasis to various organs. Although intraocular metastasis (IOM) occurs at a later stage than metastasis to other organs, it often adversely affects the quality of life and suggests a poor prognosis. In this study, we selected 1608 patients with lung cancer who had metastasis to at least one site and explored clinical differences between those with IOM and non-IOM (NIOM). An independent t test and chi-squared test were used to analyze the clinical features of the patients. The statistically significant parameters were analyzed by binary logistic regression to determine the risk factors for IOM. A receiver operating characteristic curve was constructed to assess their diagnostic value in IOM. The results showed that no significant differences were noted in age, gender, and pathological type between the IOM and NIOM groups. However, the IOM group had higher levels of alpha-fetoprotein, carcinoembryonic antigen, cancer antigen (CA)-125, CA-153, cytokeratin fragment 19 (CYFRA 21-1), and total prostate-specific antigen, compared with the NIOM group. Binary logistic regression indicated that CA-153 and CYFRA 21-1 were risk factors for IOM in patients with MLC (P < 0.05). Area under the curve of CA-153, CYFRA 21-1 and their combination were 0.791, 0.860, and 0.872 respectively. The cutoff values for CA-153 and CYFRA 21-1 were 22.2 U/mL and 6.785 ng/mL. In conclusion, both CA-153 and CYFRA 21-1 were independent risk factors for IOM in patients with metastatic lung cancer (MLC), whereas the combination of CA-153 and CYFRA 21-1 assessment yields the most value in the detection of IOM in patients with MLC.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Neoplasias Oculares/diagnóstico , Queratina-19/sangue , Neoplasias Pulmonares/patologia , Mucina-1/sangue , Adenocarcinoma de Pulmão/sangue , Adenocarcinoma de Pulmão/secundário , Neoplasias Oculares/sangue , Neoplasias Oculares/secundário , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Fatores de RiscoRESUMO
BACKGROUND: Combination drug therapy has become an effective strategy for inflammation control. The antiinflammatory capacities of silibinin and thymol have each been investigated on its own, but little is known about the synergistic anti-inflammatory effects of these two compounds. PURPOSE: This study aims to investigate the synergistic anti-inflammatory effects of silibinin and thymol when administered in combination to lipopolysaccharide (LPS)-induced RAW264.7 cells. METHODS: RAW264.7 cells were pre-treated with silibinin and thymol individually or in combination for 2 h before LPS stimulation. Cell viability was detected by the MTT assay. Nitric oxide (NO) production was measured by Griess reagent. Reactive oxygen species (ROS) was evaluated by 2',7'-dichlorofluorescein-diacetate. ELISA was used to detect tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Western blot was performed to analyse the protein expression of LPS-induced RAW264.7 cells. RESULTS: We observed a synergistic anti-inflammatory effect of silibinin and thymol when administered in combination to LPS-induced RAW264.7 cells. Silibinin combined with thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) had more potent effects on the inhibition of NO, TNF-α, and IL-6 than those exerted by individual administration of these compounds in LPS-induced RAW264.7 cells. The combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) strongly inhibited ROS and cyclooxygenase-2 (COX-2). More importantly, the combination of silibinin and thymol (40 µM and 120 µM respectively, with the molar ratio 1:3) was also successful in inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) activities. Our results suggest that the synergistic anti-inflammatory effects of silibinin with thymol were associated with the inhibition of NF-κB and MAPK signalling pathways. CONCLUSION: The combination of silibinin and thymol (40 µM and 120 µM, respectively, with the molar ratio 1:3) could inhibit inflammation by suppressing NF-κB and MAPK signalling pathways in LPS-induced RAW264.7 cells.