通讯机构:
[Qu, Xiaowang] U;Univ South China, Peoples Hosp Chenzhou 1, Translat Med Inst, 102 Luojiajing, Chenzhou 423000, Hunan, Peoples R China.
关键词:
T follicular helper cell;coinfection;hepatitis B virus;hepatitis C virus;neutralizing antibody response
摘要:
Hepatitis C virus (HCV) and hepatitis B virus (HBV) coinfection reciprocally influences viral replication and host defence responses. This study aimed to investigate the impact of HBV coinfection on circulating T follicular helper cell (cTfh) distribution and the HCV neutralizing antibody (nAb) response. HCV neutralizing antibody responses were measured in individuals with HCV monoinfection (n = 83) and HBV/HCV coinfection (n = 78) using the HCV pseudoparticle neutralization assay. The frequencies of cTfh cells and their subsets in HCV monoinfection (n = 34) and HBV/HCV coinfection (n = 30) were analysed by flow cytometry. The correlations of clinical parameters, cTfh cells and neutralizing antibody responses were analysed. Compared with HCV monoinfection, the HBV coinfection group showed significantly lower HCV neutralizing antibody responses (P < 0.001) and a decreased frequency of circulating Th1-like Tfh cells (Tfh1) (P = 0.004). In HCV monoinfection, the frequency of the Tfh1 subset was positively correlated with HCV neutralizing antibody responses (R = 0.378, P = 0.03), but this correlation was lost under HBV/HCV coinfection (R = 0.115, P = 0.551). In contrast, the frequency of circulating Th2-like Tfh cells (Tfh2) was negatively correlated with the HCV neutralizing antibody responses (R = 0.404, P = 0.003). Further analysis showed that HBV coinfection enhanced the Tfh2 subset composition within cTfh cells (P < 0.001), which was associated with serum HBsAg in HBV/HCV coinfection (R = 0.521, P = 0.003). As expected, HBsAg also exhibited an inverse association with HCV neutralizing antibody responses in HBV/HCV coinfection (R = 0.59, P < 0.001). In contrast to HCV monoinfection, HBV/HCV coinfection leads to altered cTfh cell distribution and impaired HCV neutralizing antibody responses, which are associated with HBsAg. These findings will be helpful for better understanding the immunopathogenesis of HBV/HCV coinfection.
期刊:
American Journal of Human Genetics,2019年105(1):166-176 ISSN:0002-9297
通讯作者:
Shen, Lu;Jin, Peng
作者机构:
[Tian, Yun; Sun, Qi-Ying; Yi, Fang; Tang, Bei-Sha; Zhou, Ya-Fang; Xu, Hong-Wei] Cent S Univ, Xiangya Hosp, Dept Geriatr, Changsha 410008, Hunan, Peoples R China.;[Zeng, Sheng; Jiao, Bin; Liu, Zhen; Chen, Zhao; Jiang, Hong; Zhou, Chao-Jun; Yan, Xin-Xiang; Hou, Xuan; Guo, Ji-Feng; Tang, Bei-Sha; Long, Hong-Yu; Wang, Jun-Ling; Shen, Lu] Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;[Tian, Yun; Tang, Bei-Sha; Shen, Lu] Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;[Xia, Kun; Hu, Zheng-Mao; Huang, Wen; Duan, Ran-Hui] Cent S Univ, Sch Life Sci, Ctr Med Genet, Changsha 410008, Hunan, Peoples R China.;[Kong, Ha Eun; Li, Yujing; Shafik, Andrew Mark; Allen, Emily G.; Jin, Peng] Emory Univ, Sch Med, Dept Human Genet, Whitehead Res Bldg,Room 305A,615 Michael St, Atlanta, GA 30322 USA.
通讯机构:
[Shen, Lu] C;[Jin, Peng] E;Cent S Univ, Xiangya Hosp, Dept Neurol, Changsha 410008, Hunan, Peoples R China.;Cent S Univ, Xiangya Hosp, Natl Clin Res Ctr Geriatr Disorders, Changsha 410008, Hunan, Peoples R China.;Emory Univ, Sch Med, Dept Human Genet, Whitehead Res Bldg,Room 305A,615 Michael St, Atlanta, GA 30322 USA.
摘要:
Neuronal intranuclear inclusion disease (NIID) is a slowly progressing neurodegenerative disease characterized by eosinophilic intranuclear inclusions in the nervous system and multiple visceral organs. The clinical manifestation of NIID varies widely, and both familial and sporadic cases have been reported. Here we have performed genetic linkage analysis and mapped the disease locus to 1p13.3-q23.1; however, whole-exome sequencing revealed no potential disease-causing mutations. We then performed long-read genome sequencing and identified a large GGC repeat expansion within human-specific NOTCH2NLC. Expanded GGC repeats as the cause of NIID was further confirmed in an additional three NIID-affected families as well as five sporadic NIID-affected case subjects. Moreover, given the clinical heterogeneity of NIID, we examined the size of the GGC repeat among 456 families with a variety of neurological conditions with the known pathogenic genes excluded. Surprisingly, GGC repeat expansion was observed in two Alzheimer disease (AD)-affected families and three parkinsonism-affected families, implicating that the GGC repeat expansions in NOTCH2NLC could also contribute to the pathogenesis of both AD and PD. Therefore, we suggest defining a term NIID-related disorders (NIIDRD), which will include NIID and other related neurodegenerative diseases caused by the expanded GGC repeat within human-specific NOTCH2NLC.
作者机构:
[Wang, Siyang; Liu, Zhigang; Liu, Qiaodan; Yao, Jijin] Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Cent S Univ, Xiangya Sch Med, Affiliated Canc Hosp, Dept Radiat Oncol,Hunan Canc Hosp, Changsha 410000, Hunan, Peoples R China.;[Zhou, Jiao; Liu, Guiyun; Xu, Chenyang; Liu, Fengzin; Jiang, Rong] Univ South China, Dept Clin Med, Hengyang 421000, Peoples R China.;[Jiang, Wen] Univ Texas Southwestern Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA.
通讯机构:
[Liu, Zhigang] S;Sun Yat Sen Univ, Phase 1 Clin Trial Ward, Dept Head & Neck Oncol, Canc Ctr,Affiliated Hosp 5, Zhuhai 519001, Peoples R China.
摘要:
Nasopharyngeal carcinoma (NPC) is endemic in southern China. Due to the unique anatomical and biological properties of NPCs, radiotherapy or combined modality based on radiotherapy is an effective treatment option. Helical tomotherapy (HT) is an emerging intensity modulated radiotherapy technology. The advantages of dose homogeneity, steepness of dose gradient, and protection of normal organs are reflected in the treatment of head and neck cancers. We present the preliminary (2-year) clinical outcomes of HT in 85 patients with locally advanced NPC (LA-NPC). Of these patients, 3 patients (3.5%) experienced treatment interruption due to severe pulmonary infection, and 82 (96.5%) completed radiation treatments. The 2-year estimate of progression-free survival, local relapse-free survival, nodal relapse-free survival, distant metastases-free survival, and overall survival rate were 90%, 96.3%, 98.8%, 96.3%, and 96.3%, respectively. Among the three patients that died, one had stage III disease and died from fatal nasopharyngeal bleeding after radiotherapy, while the other two patients succumbed to local recurrence. Our experience suggests that HT can achieve promising disease control and survival in the treatment of LA-NPC patients with mild acute and late toxicity profiles.
摘要:
Worldwide, gastric cancer (GC) is one of the deadliest malignant tumors of the digestive system. Moreover, microRNAs (miRNAs) of exosomes harbored within cancer cells have been determined to induce inflammatory conditions that accelerate tumor growth and metastasis. Interestingly, the oncogenic role of bone marrow mesenchymal stem cells (BM-MSCs) in the modulation of immunosuppression, tumor invasion, and metastasis was discovered to be partly mediated through the secretion of exosomes. In this article, high expression of miRNA-221 (miR-221) in exosomes of the peripheral blood was determined to be positively correlated with the poor clinical prognosis of GC, especially with respect to tumor, node, and metastases stage. Therefore, the expression of miR-221 in exosomes of the peripheral blood may be an important detection index for GC. Proliferation, migration, invasion, and adhesion to the matrix of GC BGC-823 and SGC-7901 cells were significantly enhanced by exosomes that originated from BM-MSCs that were transfected with miR-221 mimics. In conclusion, extracted exosomes from BM-MSCs transfected with miR-221 oligonucleotides can act as high-efficiency nanocarriers, which can provide sufficient miR-221 oligonucleotides to influence the tumor microenvironment and tumor aggressiveness effectively. Notably, the use of a miR-221 inhibitor with an excellent restraining effect in exosomes provides therapeutic potential for GC in future clinical medicine.
通讯机构:
[Yimou Wu] I;Institution of Pathogenic Biology, Medical College, University of South China, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China
摘要:
Treponema pallidum subsp. pallidum membrane proteins are considered as potent inducers in the initiation and development of inflammation. In the present study, the mechanism that leads to the production of interleukin 6 (IL-6), one of the key proinflammatory cytokines, by human monocytic THP-1 cells when these cells are treated with T. pallidum flagellin FlaA2 was investigated. Stimulation with flagellin FlaA2 can induce IL-6 expression in human monocytes and augment the phosphorylation of ERK, p38, and NF-κB, but has no effect on the phosphorylation of JNK. Likewise, FlaA2-induced IL-6 production was found to be attenuated by inhibitors for ERK, p38, and NF-κB, but not by JNK inhibitor. Immunofluorescence analysis showed that flagellin FlaA2 could stimulate the translocation of IκBα from the cytosol to the nucleus, and this phenomenon could be inhibited by the specific inhibitor BAY11-7082. FlaA2–induced IL-6 expression was also proved to be abrogated by transfection with dominant negative (DN) plasmid of MyD88. We further demonstrated that transfection with DN-TLR2 was sufficient to attenuate IL-6 expression and the phosphorylation of ERK, p38, and IκBα. These results suggest that flagellin FlaA2 induces IL-6 production via signaling pathways involving TLR2, MyD88, ERK, p38, and NF-κB in monocytes, which could contribute to the pathogenesis of T. pallidum.
期刊:
Pathogens and Disease,2017年75(9) ISSN:2049-632X
通讯作者:
Chen, Lili
作者机构:
[Bai, Qinqin; Zeng, Xindian; Chen, Lili; Zhou, Pufan; Liu, Ziqing; Zhou, Peng; Sun, Yuanbin] Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Shenghua] Univ South China, Med Coll, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wu, Haiying] Univ South China, Affiliated Hosp 2, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Hu, Chunsheng] Hunan Prov Ctr Dis Control & Provent, Outpatient Dept, Changsha 421000, Hunan, Peoples R China.;[Chen, Yuyu] Cent S Univ, Xiangya Sch Med, Hunan Canc Hosp, Changsha 421000, Hunan, Peoples R China.
通讯机构:
[Chen, Lili] U;Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
摘要:
The publisher apologizes that this article was originally published under an incorrect DOI (10.1093/femsle/ftx088). The correct DOI is now displayed.
期刊:
Pathogens and Disease,2017年75(7):188-188 ISSN:2049-632X
通讯作者:
Chen, Lili
作者机构:
[Bai, Qinqin; Zeng, Xindian; Chen, Lili; Zhou, Pufan; Liu, Ziqing; Zhou, Peng; Sun, Yuanbin] Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Shenghua] Univ South China, Med Coll, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wu, Haiying] Univ South China, Affiliated Hosp 2, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Hu, Chunsheng] Hunan Prov Ctr Dis Control & Provent, Outpatient Dept, Changsha 421000, Hunan, Peoples R China.;[Chen, Yuyu] Cent S Univ, Hunan Canc Hosp, Changsha 421000, Hunan, Peoples R China.
通讯机构:
[Chen, Lili] U;Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
会议名称:
2017年第二届全国特殊病原体学术会议
会议时间:
2017-08-13
会议地点:
南京
会议论文集名称:
2017年第二届全国特殊病原体学术会议论文集
关键词:
Chlamydia psittaci;STAT3;apoptosis;Bax/Bcl-2
摘要:
The Janus kinase-signal transducer and activator of transcription-3 (JAK-STAT3) signaling pathway is a key regulator of cell growth, motility, migration, invasion and apoptosis in mammalian cells. Infection with intracellular pathogens of the genus Chlamydia can inhibit host cell apoptosis, and here we asked whether the JAK-STAT3 pathway participates in chlamydial anti-apoptotic activity. We found that, compared with uninfected cells, levels of JAK1 and STAT3 mRNA as well as total and phosphorylated JAK1 and STAT3 protein were significantly increased in Chlamydia psittaci-infected HeLa cells. Moreover, the apoptosis rate of infected cells was higher after treatment with the tyrosine kinase inhibitor AG-490 (2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide). Immunoblotting of apoptosis-related proteins showed that C. psittaci infection reduces Bax, but increases Bcl-2, protein levels, resulting in reduced activation of caspase-3, caspase-7, caspase-9 and PARP; AG490 attenuates these effects. Together, our data suggest that the JAK/STAT3 signaling pathway facilitates the anti-apoptotic effect of C. psittaci infection by reducing the Bax/Bcl-2 apoptotic switch ratio, and by inhibiting the intracellular activation of key pro-apoptotic enzymes.
通讯机构:
[Zhuang, T; Wang, H; Zhu, J] X;[Mu, Kun] S;[Zhu, Jian] U;Xinxiang Med Univ, Sch Lab Med, Res Ctr Immunol, Xinxiang, Henan, Peoples R China.;Xinxiang Med Univ, Henan Collaborat Innovat Ctr Mol Diag & Lab Med, Xinxiang, Henan, Peoples R China.
关键词:
ER alpha;SHARPIN;breast cancer;protein stability;ubiquitination
摘要:
Estrogen receptor a is expressed in the majority of breast cancers and promotes estrogen-dependent cancer progression. In our study, we identified the novel E3 ubiquitin ligase SHARPIN function to facilitate ER alpha signaling. SHARPIN is highly expressed in human breast cancer and correlates with ER alpha protein level by immunohistochemistry. SHARPIN expression level correlates with poor prognosis in ER alpha positive breast cancer patients. SHARPIN depletion based RNA-sequence data shows that ER alpha signaling is a potential SHARPIN target. SHARPIN depletion significantly decreases ER alpha protein level, ER alpha target genes expression and estrogen response element activity in breast cancer cells, while SHARPIN overexpression could reverse these effects. SHARPIN depletion significantly decreases estrogen stimulated cell proliferation in breast cancer cells, which effect could be further rescued by ER alpha overexpression. Further mechanistic study reveals that SHARPIN mainly localizes in the cytosol and interacts with ER alpha both in the cytosol and the nuclear. SHARPIN regulates ER alpha signaling through protein stability, not through gene expression. SHARPIN stabilizes ER alpha protein via prohibiting ER alpha protein poly-ubiquitination. Further study shows that SHARPIN could facilitate the mono-ubiquitinaiton of ER alpha at K302/303 sites and facilitate ERE luciferase activity. Together, our findings propose a novel ER alpha modulation mechanism in supporting breast cancer cell growth, in which SHARPIN could be one suitable target for development of novel therapy for ER alpha positive breast cancer.
摘要:
Asthma is a complicated systemic disease of the airways, which is characterized by variable symptoms, including bronchial hyper-responsive-ness, inflammation and airflow obstruction. The prevalence of asthma has increased 2-3-fold over recent decades in developed countries; however, the molecular mechanism of asthma remains unclear. In the current study, the expression of recombinant protein Dermatophagoides farinaeI (Derf I) was induced by isopropyl beta-D-1-thiogalactoside (IPTG) and purified using Ni-NTA. Derf I, an important antigen of asthma, was used to establish the animal model of asthma. Airway hyper-responsiveness was mea-sured using unrestrained whole-body plethysmography with a four-chamber system. Immunoglobulin (Ig) E, IgG and IgG2a were analyzed using indirect enzyme-linked immunosorbent assay (ELISA). Proteomic technology was applied to detect the difference between the normal lung tissue and asthma lung tissue samples of the asthma model. Cytokines in bronchoalveolar lavage fluid and the splenocyte culture medium were measured by ELISA and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to detect the mRNA expression of ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide (ATP5b). In addition, cell growth of arterial smooth muscle cells (ASMCs) was evaluated by MTT assay. In the current study, Derf I was successfully used to construct the animal model of asthma. Out of 23 proteins that exhibit 3-fold upregulation or downregulation, ATP5b was chosen for further investigation. The data indicated that ATP5b was overexpressed in the asthma lung tissue when compared with the normal lung tissue. However, when ATP5b was knocked down, cell growth decreased. Therefore, overexpressed ATP5b leads to airway smooth muscle cell (ASMC) proliferation and finally to ASM thickening. Thus, to the best of our knowledge, this is the first study to report that the expression level of ATP5b was markedly increased in lung tissue samples of an asthma model compared with the tissue samples from normal lungs, which promoted ASMC proliferation and contributed to airway remodeling.