ABSTRACT
Noise-induced hearing loss (NIHL) is a complex disease caused by interactions between environmental and genetic factors. This study investigated whether genetic variability in protocadherin related 15 (PCDH15) underlies an increased susceptibility to the development of NIHL in a Chinese population. The results showed that compared with the TT genotype of rs11004085, CT/CC genotypes were associated with an increased risk of NIHL [adjusted odds ratio (OR) = 2.64; 95% confidence interval (CI): 1.14-6.11, P = 0.024]. Additionally, significant interactions between the rs11004085 and rs978842 genetic variations and noise exposure were observed in the high-level exposure groups (P < 0.05). Furthermore, the risk haplotype TAGCC was observed when combined with higher levels of noise exposure (P < 0.05). Thus, our study confirms that genetic variations in PCDH15 modify the susceptibility to NIHL development in humans.
Subject(s)
Humans , Cadherins , Genetics , China , Genetic Predisposition to Disease , Genetic Variation , Hearing Loss, Noise-Induced , Epidemiology , Genetics , Risk FactorsABSTRACT
<p><b>OBJECTIVE</b>To explore the anti-tumor mechanism of the combination of cisplatin with DC vaccine in tumor-bearing mice.</p><p><b>METHODS</b>B16 melanoma cells were treated with cisplatin at the final concentration of 20 µg/ml in vitro for 24 h. The expression of HMGB1, Hsp70 and TGF-β were detected by Western blot. B16 tumor-bearing mouse models were generated. The therapeutic effect of the combination of cisplatin (100 µg/mouse i.p., for sequential 3 days) and intratumoral injection of DC cells (3×10(6)/mouse, twice with a 7-day interval) in the tumor-bearing mouse models was evaluated. Expression of MHC II, ICAM-1 and CD86 was analyzed by flow cytometry. The mice were sacrificed at 28 days after tumor cell inoculation. The tumors were removed and weighed, and tissue samples were taken for pathological examination. Tumor infiltrating lymphocytes (TIL) were isolated by discontinuous gradient centrifugation. The distribution of T-reg and CD8(+) T cells in the TIL was analyzed by flow cytometry, and the ratio of CD8(+) T/T-reg was determined. The activity of cytotoxic lymphocytes (CTL) was determined by microcytotoxicity assay.</p><p><b>RESULTS</b>Cisplatin enhanced both the B16 cell apoptosis and HMGB1 expression. After loading with cisplatin-treated cell lysate, the expression of MHC II, ICAM-1 and CD86 on DC cells were (47.5 ± 8.8)%, (35.5 ± 8.3)% and (36.2 ± 9.2)%, respectively. At 28 days after tumor cell inoculation, the tumor weight of the control group was (2.1 ± 0.6) g, that of the cisplatin group was (0.3 ± 0.2) g and that of cisplatin + DC vaccine group was (0.5 ± 0.2) g, showing a significant inhibition of tumor growth (P < 0.01). Furthermore, the CD8(+) T/T-reg ratio and CTL activity in TIL were also significantly enhanced in the tumor-bearing mice treated with cisplatin + DC vaccine. When the effector-to-target ratio was 20:1, 10:1 and 5:1, the CTL activity in the cisplatin + DC vaccine treated mice was (25.0 ± 5.0)%, (22.0 ± 6.0)% and (14.0 ± 4.0)%, respectively, significantly higher than (8.2 ± 3.6)%, (6.7 ± 1.8)% and (3.6 ± 1.9)%, respectively, in the control group (all P < 0.01).</p><p><b>CONCLUSION</b>Cisplatin promotes the anti-tumor effect of DC vaccine by down-regulating T-reg cells and enhancing the CTL activity in tumors.</p>
Subject(s)
Animals , Female , Mice , Antineoplastic Agents , Pharmacology , Apoptosis , B7-2 Antigen , Metabolism , CD8-Positive T-Lymphocytes , Pathology , Cancer Vaccines , Pharmacology , Cell Line, Tumor , Cisplatin , Pharmacology , Dendritic Cells , Allergy and Immunology , Metabolism , Genes, MHC Class II , HMGB1 Protein , Metabolism , Intercellular Adhesion Molecule-1 , Metabolism , Melanoma, Experimental , Pathology , Mice, Inbred C57BL , Neoplasm Transplantation , T-Lymphocytes, Cytotoxic , Allergy and Immunology , T-Lymphocytes, Regulatory , Pathology , Tumor BurdenABSTRACT
<p><b>OBJECTIVE</b>To study the anticancerous effect of Fuganchun 6 (FGC-6) and its immunoregulatory effect on tumor-bearing mice.</p><p><b>METHOD</b>The mice inoculated by H22 cells were divided into 5 groups: model group, 5-Fu group and FGC-6 in high dose, medium dose, and low dose groups. The normal mice were also observed. These mice were treated for 10 days. The weight of tumor mass and mouse were examined. The target-cell-killing activity of NK cells. The proliferation activity of lymphocyte and the production of IL-2 of murine splenocytes were detected respectively. The serum containing FGC-6 was prepared and its inhibition effect on H22 cells was examined by MTT assay and growth curve in vitro.</p><p><b>RESULT</b>Growth of tumor was inhibited markedly by FGC-6 high dose. The inhibition of serum containing FGC-6 on the proliferation of H22 cells in vitro was observerd in a dose and time-dependent manner. The target-cell-killing activity of NK cells and the production of IL-2 of murine splenocytes of model group were lower than those of normal group (P < 0.05). When compared with model group, FGC-6 in high dose elevated the two indexes above-mentioned, and also enhanced the proliferation activity of lymphocyte markedly (P < 0.05). The production of IL-2 of murine splenocytes was also improved when treated by FGC-6 in medium dose (P < 0.05).</p><p><b>CONCLUSION</b>FGC-6 can inhibite the growth of H22 cells markedly and also can strengthen the immunity of H22 transplanted mouse.</p>
Subject(s)
Animals , Humans , Male , Mice , Antineoplastic Agents, Phytogenic , Pharmacology , Cell Line , Cell Proliferation , Drug Combinations , Drugs, Chinese Herbal , Pharmacology , Interleukin-2 , Metabolism , Killer Cells, Natural , Allergy and Immunology , Liver Neoplasms, Experimental , Allergy and Immunology , Pathology , Lymphocytes , Pathology , Plants, Medicinal , Chemistry , Spleen , Cell Biology , MetabolismABSTRACT
The mainly antigenic sites for the adenovirus neutraliation are present on Loop1 and Loop2 of hexon.Majority research were focus in the human adenovirus.Little was known on infectious canine hepatitis virus (ICHV), which was also called canine adenovirus typeⅠ.Here,ICHV (the isolated strain) DNA was isolated and purified from the cultured MDCK cells.The Loop1 and Loop2 fragments were amplified by polymerase chain reaction(PCR) method,and then was connected by ligase T4.The target fragment was then connected with vector pET28a.The nucleotide sequence ecoding Loop1 and Loop2 was determined.The nucleotide sequence identity of Loop1 region between the isolated strain and CLL, RI261 and Toronto A26/61 strains is 100%, 100% and 83.8%, and the nucleotide sequence identity of Loop2 region between the isolated strain and CLL, RI261 and Toronto A26/61 strains is 88.1% , 88.1% and 99.3%, and amino acid identity is 93.6%, 93.6% and 98.6%.The recombinant Loop protein was expressed in E.coli and was approximately 36kDa in size,and then was purified. Then BALB/c mice were injected subcutaneously in the back and armpit with the recombinant Loop protein.The anti-ICHV antibody titers of immunized serum was tested by indirect ELISA and the titers were up to 1:320.Western blot demonstrated that immunized sera could specifically combine with ICHV. The research laid a foundation for creating new genetic engineering products of infectious canine hepatitis virus.
ABSTRACT
The aim of this research is to refine the protocol of purification of SA and identify the character of SA. By utilizing the cold-denaturing method, most of other kinds of protein were screened out and SA was purified from the fermentation broth of L-183 by using the refined affinity chromatography method. The rate of recollection was checked to be 75%～85%. By identification, it is indicated that the molecular weight of self-made SA was 74.5kD, the biotin-combining number 3.2, the activity 11.2u/mg, the pI around 7.4. So, the essential characters of SA are same as described by documents.