scholarly journals Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells

2000 ◽  
Vol 30 (12) ◽  
pp. 3468-3477 ◽  
Author(s):  
Franca M. Spada ◽  
Frank Borriello ◽  
Masahiko Sugita ◽  
Gerald F. M. Watts ◽  
Yasuhiko Koezuka ◽  
...  
2019 ◽  
Vol 57 (1) ◽  
pp. 105-112 ◽  
Author(s):  
Li-Hsin Huang ◽  
Hao-Yeh Lin ◽  
Ying-Tzu Lyu ◽  
Chiau-Ling Gung ◽  
Ching-Tsan Huang

Orally administered fungal vaccines show promise for the prevention of infectious diseases. Edible mushrooms are deemed appropriate hosts to produce oral vaccines due to their low production cost and low risk of gene contamination. However, their low expression level of antigens has limited the potential development of oral vaccines using mushrooms. The low expression level might result from impurity of the transgenic mycelia since dikaryotic mycelia are commonly used as transformation materials. In this study, stable transgenic hepatitis B virus surface antigen (HBsAg) in Flammulina velutipes transformants was obtained by Agrobacterium-mediated transformation, followed by fruiting and basidiospore mating. The formation of HBsAg was detected by western blot analysis. The expression levels of HBsAg in transgenic F. velutipes fruiting bodies were (129.3±15.1), (110.9±1.7) and (161.1±8.5) ng/g total soluble protein. However, the values may be underestimated due to incomplete protein extraction. Two of the four pigs in the experimental group produced positive anti-HBsAg-specific IgG after being fed the HBsAg transgenic F. velutipes fruiting bodies for 20 weeks, while no anti-HBsAg antibody was detected in the control group. One of the positive pigs had HBsAg titres of 5.36 and 14.9 mIU/mL in weeks 10 and 14, respectively, but expression faded thereafter. The other positive pig displayed HBsAg titres of 9.75, 17.86 and 39.87 mIU/mL in weeks 14, 18 and 20, respectively. The successful immunogenicity in pigs fed transgenic F. velutipes fruiting bodies demonstrated the potential of using the fungus as an oral vaccine.


2018 ◽  
Vol 33 (4) ◽  
pp. 500-506 ◽  
Author(s):  
Yaser Mansoori ◽  
Mohammad Bagher Tabei ◽  
Alireza Askari ◽  
Pantea Izadi ◽  
Abdolreza Daraei ◽  
...  

Background: Epidemiological and experimental literature indicates that the risk of breast cancer incidence is strongly linked to hormone-dependent factors, including reproductive history and obesity. However, the molecular mechanisms underlying the association between these factors and breast cancer risk are poorly understood. The aim of this study, therefore, was to determine whether obesity and reproductive history are associated with expression levels of two breast cancer-related long non-coding RNAs (lncRNAs), namely ZFAS1 and SRA1 in cancer-free breast tissues of women. Methods: In the current research, 145 healthy women were recruited, and the quantitative expression levels of the two lncRNAs were determined through qPCR assay after gathering the mammoplasty breast tissue samples. Results: It was found that women with body mass index (BMI)≥30 kg/m2 and BMI 25–29 kg/m2 show a low expression of ZFAS1 compared to the BMI<25 kg/m2 ( P=0.031 and P=0.027, respectively). Then, the correlation analysis disclosed a negative correlation of ZFAS1 low expression with increasing BMI (r=−0.194, P=0.019). Interestingly, this analysis demonstrated a negative correlation between low expression of the ZFAS1 and high BMI in women with menarche age below 14 (r=−221; P=0.028). Lastly, it was also revealed that there was a negative association of the low expression level of ZFAS1 with increasing BMI in women through regression models (B=−0.048, P=0.019). Conclusions: These findings suggest interesting clues about the links between high BMI and the expression levels of ZFAS1 in non-diseased breasts that may help us better understand the underlying mechanisms through which obesity contributes to breast carcinogenesis. However, such results need more validations in future research.


2020 ◽  
Author(s):  
Zhao Hongcan ◽  
Yang Hongjian ◽  
Zhang Xiping

Abstract Background: To analyze and screen the miRNAs associated with lymph node metastasis of breast cancer (BC), and to explore the roles of these miRNAs in the proliferation, invasion and prognosis of BC. Methods: MicroRNAs associated with lymph node metastasis in Her-2 positive BC was screened by TCGA database. The qRT-PCR was used to verify theses 5 miRNAs in 30 cases of Her-2 positive BC with lymph node metastasis of different degree. The tumor tissue samples were divided into non-lymph node metastasis group, ≤ 3 lymph node metastasis group and > 3 lymph node metastasis group. In addition, 10 cases of paracancerous tissues were considered as paracancerous control group. Pearson correlation analysis was used to analysis the relationship of 5 miRNAs and MALAT1 with Her-2 positive BC patients' clinicopathological characteristics and prognosis. CCK8 and Transwell experiments were used to detect the effects of miR-143 and miR-455 on the proliferation and invasion of Her-2 positive BC cells (MDA-MB-453). Results: Five kinds of miRNA (miR-143, miR-196a, miR-455, miR-9 and miR-92a) related with Her-2 positive BC with lymph node metastasis were screened by TCGA database. The detecting results of qRT-PCR showed that the levels of miR-143, miR-196a, miR-9 and MALAT1 increased with the increased number of lymph nodes. The expression level of miR-143 in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly higher than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly higher than that in the group of ≤ 3 lymph nodes metastasis (P<0.001). The expression level of miR-196a in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly higher than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly higher than that in the group of ≤ 3 lymph nodes metastasis (P<0.001). The expression level of miR-455 in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly lower than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly lower than that in the group of ≤ 3 lymph nodes metastasis (P<0.001). The expression level of MALAT1 in the group of ≤ 3 lymph nodes metastasis and > 3 lymph nodes metastasis was significantly higher than that in the group of non-lymph nodes metastasis (P<0.001), and that in the group of > 3 lymph nodes metastasis was significantly higher than that in the group of ≤ 3 lymph nodes metastasis (P<0.01). Pearson correlation analysis showed that the expression levels of miR-455-5p, miR-196a-5p and MALAT1 were negatively correlated, positively correlated and positively correlated with the pathological stages of Her-2 positive BC, respectively. The results of survival analysis showed that RFS of patients with high expression of miR-196a, miR-92a and MALAT1 was significantly lower than that of patients with low expression (P<0.05), and OS and RFS of patients with high expression of miR-9 were significantly lower than those of patients with low expression, while OS and RFS of patients with high expression of miR-455 were significantly higher than those of patients with low expression (P<0.05). Cytological experiments showed that up regulation of miR-455 significantly inhibited the proliferation and invasion of BC cells, while down regulation of miR-143 significantly inhibited the proliferation and invasion of BC cells and the expression of MALAT1 (P<0.05). Conclusion: High expression of miR-143, miR-9, miR-196a, MALAT1 and low expression of miR-455 are related to the degree of lymph node metastasis of Her-2-positive BC patients, indicating poor prognosis. Down-regulation of miR-455 and up-regulation of miR-143 and MALAT1 can promote the cell proliferation and invasion of Her-2-positive BC.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 530-530 ◽  
Author(s):  
Shinichiro Yamada ◽  
Mitsuo Shimada ◽  
Toru Utsunomiya ◽  
Satoru Imura ◽  
Yuji Morine ◽  
...  

530 Background: It has recently been suggested that the SDF-1/CXCR4 axis is involved in tumor progression, angiogenesis, metastasis, and survival in various cancer. In this study, we investigate the possible role of SDF-1/CXCR4 axis in colorectal liver metastasis. Methods: Both primary colorectal tumors and liver metastatic tumors were obtained from 12 patients with colorectal liver metastasis. Expression levels of CXCR4 and SDF-1 were determined using RT-PCR. In 4 patients with benign liver disease, the expression level of SDF-1 in normal liver tissues was also determined. We divided the 12 patients into two groups; high expression group (n=6) and low expression group (n=6) according to each expression level of SDF-1 and CXCR4, and compared the clinicopathological factors between the two groups. Results: 1. CXCR4 expression levels in primary tumor: The frequency of the peritoneal dissemination in the CXCR4 high expression group was higher than in the low expression group (p=0.07). Moreover, overall survival rate in the CXCR4 high expression group was significantly lower than that in the low expression group (3 year-survival rate: 67% vs. 100%, p<0.05). 2. CXCR4 in metastatic tumor tissues and SDF-1 in non-tumor liver tissues: The expression level of SDF-1 in non-tumor liver tissues was significantly higher than that in normal liver tissues (p<0.01). A significant correlation between the CXCR4 expression levels in metastatic tumor tissues and SDF-1 expression levels of non-tumor liver tissues (p<0.05). The number of metastatic liver tumors in the SDF-1 high expression group tended to be larger than that in the low expression group (p=0.12). Conclusions: The present data suggest that there is a significant association of the SDF-1/CXCR4 axis with enhanced liver metastasis and poor prognosis of the patients with colorectal liver metastasis. Furthermore, an enhanced expression of SDF-1 in non-tumor liver tissues may have an important role in the formation of liver metastasis.


2021 ◽  
Author(s):  
Ni Gao ◽  
Jing Hu ◽  
Haibo Zhou ◽  
Hui Yang

Abstract Detection of genetic information in the natural context is essential to understand the biological principles. However, the ability to sense the activity of endogenous genes is limited for conventional tools. Here, we developed a highly programmable sgRNA switch system (Ents) that enables detection of endogenous genes and lncRNAs, even with very low expression level. This protocol is related to the publication “Endogenous promoter-driven sgRNA for monitoring the expression of low-abundant genes and lncRNAs” in Nature Cell Biology.


2021 ◽  
Vol 11 (12) ◽  
pp. 2375-2380
Author(s):  
Hui Zhang ◽  
Wei Chen ◽  
Shenmiao Chen ◽  
Junrong Wang ◽  
Shunfen Mao

In order to investigate the expression and clinical significance of MMPs (Matrix Metalloproteinase) (MPP-2 and MPP-9), Wnt5a as well as β-catenin in placental tissues of preeclampsia (PE) patients, 36 PE patients (PE group) and 25 pregnant women (control group) with normal pregnancy were selected for cesarean delivery. The expression and localization of MPP-2, MPP-9, Wnt5a as well as β-catenin proteins in placental tissue were detected by Western blot method and immunohistochemistry method. The correlation between the poor prognosis of mother and child and the expression level of MMPs, Wnt5a as well as β-catenin is analyzed. The results showed that Western blot results showed that MPP-2, MPP-9, Wnt5a as well as β-catenin proteins were expressed in placental tissue, and the expression level of them of placental tissue in PE group was significantly lower than that in control group (P < 0.01). Immunohistochemistry showed that MMPs, Wnt5a, as well as β-catenin proteins were expressed in the cytotrophoblast cell (CTB) and syncytiotrophoblast cell (STB) of placental tissue, among which Wnt5a proteins as well as β-catenin proteins were mainly expressed in the cytoplasm of STB and CTB respectively. MMPs proteins were mainly expressed in the cytoplasm of these two types of cells. Low expression of MPPs, Wnt5a, β-catenin proteins may be related to blood pressure as well as 24 h urine protein of pregnant women at admission. In conclusion, Low expression of MPPs, Wnt5a, β-catenin proteins may be involved in the PE pathogenesis.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2814-2814
Author(s):  
Masayuki Shiseki ◽  
Mayuko Ishii ◽  
Kenjiro Mitsuhashi ◽  
Norina Tanaka ◽  
Kentaro Yoshinaga ◽  
...  

Abstract The preferentially expressed antigen of the melanoma (PRAME) gene was first identified in melanoma tissue as a tumour-associated antigen recognized by autologous cytotoxic T cells against a melanoma surface antigen. While expression level of PRAME is quite low in most of normal tissues of human, including bone marrow normal CD34+ cells, except for testis, PRAME overexpression is observed in various human cancers, including hematological malignant disorders. Although clinical and biological significance of PRAME expression in human cancers has not been fully elucidated, it has been demonstrated that high PRAME expression is associated poor clinical outcomes in a number of solid cancers. Association between PRAME expression and clinical outcomes in hematological malignancies has not been clarified. In acute myeloid leukemia, high expression of PRAME was shown to be associated with worse progression-free survival or overall survival by some research groups but not by other groups. Our previous study demonstrated that inhibition of PRAME expression in leukemic cells results in cell cycle arrest and induction of apoptosis, suggesting oncogenic function of PRAME expression in leukemogenesis. Clinical significance of PRAME expression in myelodysplastic syndromes (MDS) also has not been fully elucidated. In the present study, we examined PRAME expression of bone marrow cells in MDS patients to clarify clinical significance of PRAME expression. Bone marrow samples of MDS patients were used for analysis. Samples were taken at the time of diagnosis with written informed consent from patients. Total RNA extraction, cDNA synthesis and quantitative real-time RT-PCR by the TaqMan probe method using an ABI 7500 real-time PCR system (Applied Biosystems) with co-amplification of the endogenous control gene, human GAPDH (Applied Biosystems), were performed. Expression levels were obtained using the standard curve method in each experiment, after normalization with the GAPDH gene for each sample in duplicate wells. The human PRAME primer-probe sets were from Applied Biosystems (assay ID: Hs00196132_m1). Data including patients’ demographic, disease status, medical history, clinical and laboratory findings, and outcome, were collected from medical records and laboratory data base. A total of 111 MDS patients, 68 males and 43 females with median age of 69 years (range: 20-91 years) were included in the present study. They were classified as RCUD (n=15), RCMD (n=61), RARS (n=8), RAEB-1 (n=15), and RAEB-2 (n=12) according to WHO classification. Based on the IPSS, they were categorized in four risk groups, low risk (n=29), intermediate-1 risk (n=55), intermediate-2 risk (n=23), and high risk(n=4). Expression level of PRAME was varied among the MDS patients analyzed. Median value of relative PRAME expression level of 111 MDS patients and that of 19 control subjects were 0.073 and 0.07, and there was no significant difference in distribution of expression level of PRAME. However, when we compared expression patterns of PRAME among five WHO-subtypes, statistical difference was observed (P=0.0116). Relative PRAME expression level in WHO-subtypes with high blast counts (RAEB-1 and RAEB-2) was significantly higher than that in WHO-subtypes with less blast counts (RCUD, RCMD, RARS) (median value: 0.44 vs. 0.05, P=0.0012). To investigate prognostic implication of PRAME expression in MDS, we analyzed impact of PRAME expression on overall survival (OS). Based on PRAME expression level, 111 patients were divided into two categories, ‘high expression group’ (above median value) and ‘low expression group’ (below median value). Kaplan-Meier analysis demonstrated that high expression group showed significantly poorer overall survival than low expression group (P=0.0165). The estimated 5-year OS rates in high expression group and low expression group were 63.5% and 78.4%, respectively. The present study demonstrated that high PRAME expression is associated with poorer clinical outcome, indicating that PRAME expression could be a useful prognostic marker in MDS. Biological significance of PRAME expression in MDS is unclear. Expression level of PRAME was higher in WHO-subtypes with high blasts counts, suggesting that PRAME may play role in disease progression in MDS. Further studies should be necessary to clarify clinicopathological and biological significance of PRAME expression in MDS. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Mei Li Pei ◽  
Zong Xia Zhao ◽  
Ting Shuang

Abstract Aim This study aimed to explore whether the dysregulation of lnc-small nucleolar RNA host gene 1 (SNHG1) and miR-216b-5p correlated with chemoresistance and indicated poor prognosis of serous epithelial ovarian cancer (EOC). Methods and results The expression of lnc-SNHG1 was upregulated, while miR-216b-5p showed low expression in patients with chemoresistant EOC compared with patients with chemosensitive EOC. The multivariate Cox regression analysis showed that the expression of miR-216b-5p and FIGO stage were independent prognostic factors for the overall survival (OS) of patients with serous EOC. Kaplan–Meier curves revealed a significant association of the increased expression level of lnc-SNHG1 with shorter OS and disease-free survival (DFS). Patients with a low expression level of miR-216b-5p also had shorter OS and DFS. The biological functions were tested using CCK-8 assay, colony formation assay, wound healing assay, and cell apoptosis. The knockdown of SNHG1 and the overexpression of miR-216b-5p stimulated paclitaxel sensitivity in A2780/Taxol cells through inhibiting cell growth and migration and promoting apoptosis. The inhibition of miR-216b-5p could rescue the effect of lnc-SNHG1 inhibition on the sensitivity of A2780/Taxol cells to paclitaxel. Luciferase reporter assay, RNA Binding Protein Immunoprecipitation Assay (RIP), and quantitative reverse transcription–polymerase chain reaction (qRT-PCR) indicated that lnc-SNHG1 acted as a sponge of miR-216b-5p in A2780/Taxol cells. Conclusions This study showed that the overexpression of lnc-SNHG1 and decreased expression level of miR-216b-5p correlated with the chemoresistance of patients with serous EOC and indicated shorter OS and DFS. Lnc-SNHG1 functioned as a ceRNA with miR-216b-5p, which was critical in modulating the paclitaxel sensitivity of ovarian cancer cells.


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