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Photothermal therapy has been intensively investigated for treating cancer in recent years. However, the long-term therapeutic outcome remains unsatisfying due to the frequently occurred metastasis and recurrence. To address this challenge, immunotherapy has been combined with photothermal therapy to activate anti-tumor immunity and relieve the immunosuppressive microenvironment within tumor sites. Here, we engineered silica-based core‒shell nanoparticles (JQ-1@PSNs-R), in which silica cores were coated with the photothermal agent polydopamine, and a bromodomain-containing protein 4 (BRD4) inhibitor JQ-1 was loaded in the polydopamine layer to combine photothermal and immune therapy for tumor elimination. Importantly, to improve the therapeutic effect, we increased the surface roughness of the nanoparticles by hydrofluoric acid (HF) etching during the fabrication process, and found that the internalization of JQ-1@PSNs-R was significantly improved, leading to a strengthened photothermal killing effect as well as the increased intracellular delivery of JQ-1. In the animal studies, the multifunctional nanoparticles with rough surfaces effectively eradicated melanoma via photothermal therapy, successfully activated tumor-specific immune responses against residual tumor cells, and further prevented tumor metastasis and recurrence. Our results indicated that JQ-1@PSNs-R could serve as an innovative and effective strategy for combined cancer therapy.
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【Objective】 To study the effect of metformin (Met) hydrochloride on the expressions of inflammatory cytokines in Aβ1-42-induced BV-2 cells and its mechanisms. 【Methods】 BV-2 cells were induced by Aβ1-42 to mimic the neuroinflammatory cell model, and after treatment with Met, the contents of cytokines, including TNF-α, IL-1β, IL-6 and IL-18, in cell supernatant were examined by ELISA; the mRNA levels of TNF-α, IL-1β, IL-6 and IL-18 were examined by RT-PCR; and the expressions of NLRP3, ASC, pro-Caspase-1, Caspase-1, NF-κB, p-IκBα and IκBα were examined by Western blotting. 【Results】 Aβ1-42 at 1.25, 2.5 and 5 μmol/L could decrease the BV-2 cell viability in a dose-dependent manner, while Met at 0.5, 1 and 2 mmol/L could increase the cell viability in 5 μmol/L Aβ1-42-induced BV-2 cells. After treatment with Met, the transcription and secretion of TNF-α, IL-1β, IL-6 and IL-18, and the protein expressions of NLRP3, ASC, Caspase-1(p20), NF-κB and p-IκBα were significantly decreased in Aβ1-42-induced BV-2 cells. 【Conclusion】 Met attenuates inflammatory responses in Aβ1-42-induced BV-2 cells, which may be associated with the inhibition of NLRP3 inflammasome activation via NF-κB pathway.
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Objective To implement the harmonization of thyroid-stimulating hormone(TSH) of Mindray assay system by par-ticipating in harmonization research program of International Federation of Clinical Chemistry (IFCC)-Standardization of Thyroid Function Tests(C-STFT ) .Methods A total of three combinations of TSH reagents and calibrators were used to measure 20 serum samples of healthy human .Within-run precision and batch-to-batch variation were assessed .The concept of harmonization was dem-onstrated by comparing our test results with All Procedure Trimmed Mean (APTM ) provided by IFCC and recalibrating with Mater Calibrators .Results The within-run precision was 1 .96% ,batch-to-batch variation was 0 .47% - 1 .15% ,depending on the level of TSH analyte .There existed a positive bias compared to APTM values .After recalibration with Mater Calibrators and Passing &Bablok regression ,the slope of method comparison was 1 .0 ,and correlation coefficient was more than 0 .975 .Conclusion By using a panel of real human specimen and recalibration based on APTM ,the test results of Mindray assay system could be harmonized with mainstream manufacturers globally .
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<p><b>OBJECTIVE</b>This paper aims to study the effects of gossypol acetic acid (GAA) on proliferation and methylation level of human MutL homologue 1 (hMLH1) gene in human tongue cancer cell line Tca8113.</p><p><b>METHODS</b>The MTT assay was used to determine the effects of the acid on the proliferation inhibition in Tca8113 cells treated with different GAA concentrations. Nested methylation-specific polymerase chain reaction (nMSP) was used to detect the change in the methylation level of hMLH1 after 48 and 72 h with 30 and 15 micro mol L(-1) GAA treatment.</p><p><b>RESULTS</b>MTT assay results showed the growth and proliferation inhibition of Tca8113 cells in the experimental GAA group after 24 h to 72 h of GAA treatment. The nMSP results indicated that the average optical density of hMLH1 in the Tca8113 cells significantly changed after the GAA treatment (30 micro mol L(-1) GAA for 48 h and 15 micro mol L(-1) for 72 h) (P<0.05) compared with that of the control group.</p><p><b>CONCLUSION</b>GAA does not only inhibit Tca8113 proliferation but also has a demethylation effect on the hMLH1 gene. These phenomena may be part of an underlying tumor-suppression mechanism of GAA.</p>
Subject(s)
Humans , Cell Line , Cell Line, Tumor , Cell Proliferation , Gossypol , Methylation , Tongue NeoplasmsABSTRACT
Objective:To study the effects of gossypol acetic acid(GAA)on the methylation level and the mRNA expression of hM-LH1 in human tongue cancer Tca8113 cells.Methods:Tca8113 cells were treated by GAA at various doses for 24 h,48 h and 72 h respectively.MTT assay was used to detect the cell proliferation.Nested methylation specific PCR(nMSP)was used to detect methyl-ation level of hMLH1 .Real-time fluorescence quantitative PCR(RFQ-PCR)was applied to investigate the mRNA expression of hM-LH1 gene.Results:GAA inhibited the proliferation of Tca8113 cells dose-and-time dependently,decreased the DNA methylation level of hMLH1(P<0.05)and increased hMLH1 mRNA expression in Tca8113 cells(P<0.05).Conclusion:GAA can suppress proliferation of Tca8113 cells by demethylation of hMLH1 gene and increase of hMLH1 mRNA expression.
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Objective The purpose of this study was to investigate the effects of gossypol acetic acid (GAA) on protein and mRNA expressions of hMLH1 gene in human tongue carcinoma cell line Tca8113 in vitro in order to discuss the mechanism of tumor suppression of GAA. Methods (1) Western-blot was used to study the effects of GAA on protein expressions of hMLH1 gene in Tca8113 cell line treated by different concentrations of GAA for 48 h. (2) Real-time fluorescence quantitative PCR (RFQ-PCR) was used to investigate the effects on the mRNA expressions of hMLH1 gene in Tca8113 cell line treated by GAA for 48 h. Results (1) Compared with the control group, the results of Western-blot showed that the protein expression of hMLH1 gene was increased after treatment by GAA for 48 h ( <0.05) . (2) The results of RFQ-PCR indicated that the mRNA expression of hMLH1 gene was increased after GAA treatment for 48 h ( <0.05) . Conclusion GAA could up-regulate protein and mRNA expression of hMLH1 in Tca8113 cell line, which indicated that it may be one of the mechanisms of tumor suppression effect of GAA.
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Objective To investigate the expression of Notch1 and its ligand DLL4 in human gastric carcinoma tissues and its correlation with tumor angiogenic metastasis.Methods Immunohistochemical SP method was used to detect the expression of Notch1,DLL4 and VEGF in 45 gastric carcinoma tissues and paired adjacent normal gastric mucosa,and the relationship between them and clinico-pathological parameters were analyzed.Results The positive expression rate of Notch1,DLL4 and VEGF in gastric carcinoma were higher than that in normal gastric mucosa(P