摘要:
Autophagy is a highly conserved catabolic process that mediates degradation of pernicious or dysfunctional cellular components, such as invasive pathogens, senescent proteins, and organelles. It can promote or suppress tumor development, so it is a “double-edged sword” in tumors that depends on the cell and tissue types and the stages of tumor. The epithelial-mesenchymal transition (EMT) is a complex biological trans-differentiation process that allows epithelial cells to transiently obtain mesenchymal features, including motility and metastatic potential. EMT is considered as an important contributor to the invasion and metastasis of cancers. Thus, clarifying the crosstalk between autophagy and EMT will provide novel targets for cancer therapy. It was reported that EMT-related signal pathways have an impact on autophagy; conversely, autophagy activation can suppress or strengthen EMT by regulating various signaling pathways. On one hand, autophagy activation provides energy and basic nutrients for EMT during metastatic spreading, which assists cells to survive in stressful environmental and intracellular conditions. On the other hand, autophagy, acting as a cancer-suppressive function, is inclined to hinder metastasis by selectively down-regulating critical transcription factors of EMT in the early phases. Therefore, the inhibition of EMT by autophagy inhibitors or activators might be a novel strategy that provides thought and enlightenment for the treatment of cancer. In this article, we discuss in detail the role of autophagy and EMT in the development of cancers, the regulatory mechanisms between autophagy and EMT, the effects of autophagy inhibition or activation on EMT, and the potential applications in anticancer therapy.
摘要:
Mitochondria are highly dynamic organelles beyond powerhouses of a cell. These components also play important roles in cell homeostasis by regulating cell function and phenotypic modulation. Atherosclerosis is the leading cause of morbidity and mortality in developed and developing countries. Mitochondrial dysfunction has been increasingly associated with the initiation and progression of atherosclerosis by elevating the production of reactive oxygen species and mitochondrial oxidative stress damage, mitochondrial dynamics dysfunction, and energy supply. In this review, we describe the progression of the link between mitochondrial dysfunction and atherosclerosis and its potential regulation mechanisms.
通讯机构:
[Li, Meixiang] U;Univ South China, Inst Clin Anat & Reprod Med, Dept Histol & Embryol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
Advanced glycosylation end products;Endocrine disrupting chemicals;Hyperandrogenemia;Insulin resistance;PCOS
摘要:
Polycystic ovary syndrome (PCOS) is one of the most common systemic reproductive endocrine diseases, which has a variety of effects on a woman's health. Because of the involvement of multiple pathways and the lack of common clues, PCOS demonstrates multifactorial properties and heterogeneity of symptoms. Recent studies have demonstrated that the core etiology and primary endocrine characteristics of PCOS are hyperandrogenemia (HA) and insulin resistance (IR). HA and IR are the main causes of PCOS and they can interplay each other in the occurrence and development of PCOS. Just because of this, the study about the effects of HA and IR on pathophysiology of various related symptoms of PCOS is very important to understand the pathogenesis of PCOS. This paper reviews the main symptoms of PCOS, including neuroendocrine disorders, reproductive processes, dyslipidemia, obesity, hypertension, nonalcoholic fatty liver disease (NAFLD), and sleep disordered breathing, which seriously affect the physical and mental health of PCOS women. The increasing knowledge of the development pattern of HA and IR in PCOS suggests that changes in diet and lifestyle, and the discovery of potential therapeutic agents may improve PCOS. However, further studies are needed to clarify the mutual influence and relation of HA and IR in development of PCOS. This review provides an overview of the current knowledge about the effects of HA and IR on PCOS.
期刊:
JOURNAL OF BREAST CANCER,2019年22(1):15-28 ISSN:1738-6756
通讯作者:
Zu, Xu-Yu
作者机构:
[Shen, Ying-Ying; Peng, Xiu-Da; Zhong, Jing; Zhong, Xiao-Lin; Xiao, Xiao; Ding, Wen-Jun; Chen, Ling; Zu, Xu-Yu; Liu, Jiang-Hua] Univ South China, Affiliated Hosp 1, Inst Clin Med, 69 Chuanshan Rd, Hengyang 421001, Peoples R China.;[Liao, Duan-Fang] Hunan Univ Chinese Med, Key Lab Qual Evaluat Bulk Herbs Hunan Prov, Div Stem Cell Regulat & Applicat, Changsha, Hunan, Peoples R China.;[Xiong, Wei] Cent S Univ, Canc Res Inst, Key Lab Carcinogenesis, Minist Hlth, Changsha, Hunan, Peoples R China.;[Xiong, Wei] Cent S Univ, Canc Res Inst, Key Lab Carcinogenesis & Canc Invas, Minist Educ, Changsha, Hunan, Peoples R China.
通讯机构:
[Zu, Xu-Yu] U;Univ South China, Affiliated Hosp 1, Inst Clin Med, 69 Chuanshan Rd, Hengyang 421001, Peoples R China.
关键词:
Breast neoplasms;Cell proliferation;Pokemon protein, human;SP1;Smad4 protein
摘要:
Purpose: Pokemon, also known as ZBTB7A, belongs to the POZ and Kruppel (POK) family of transcription repressors and is implicated in tumor progression as a key proto-oncogene. This present study aimed at determining the mechanism by which Pokemon inhibits transforming growth factor beta (TGFbeta)-Smad4 pathway-dependent proliferation arrest of breast cancer cells via specificity protein 1 (SP1). Methods: Over-expressing plasmid or small interfering RNA (siRNA) transfection was used to regulate Pokemon levels. The EdU incorporation assay, MTS assay, and clone formation were used to identify the inhibitory effect of Pokemon siRNA on cell proliferation. Quantitative real-time polymerase chain reaction assay confirmed that Pokemon deletion inhibited the expression of proliferation-associated genes. The dual-luciferase reporter assay, electrophoretic mobility shift assay, and co-immunoprecipitation assay were used to analyze binding between Pokemon, Smad4, and SP1. Results: Pokemon deletion induced proliferation arrest of breast cancer cells and inhibited the expression of proliferation-associated genes, especially Smad4. Pokemon bound with SP1 to interdict Smad4 promoter activity. Information on clinical samples was obtained from The Cancer Genome Atlas data, in which the Pokemon mRNA levels showed a negative correlation with Smad4 levels in different subtypes of breast cancer in two independent datasets. Conclusion: We demonstrated that Pokemon binds to SP1 to down-regulate Smad4 expression, thereby promoting proliferation of breast cancer cells. This suggests that Pokemon is a potential TGFbeta-signaling participant in breast cancer progression.
期刊:
DNA AND CELL BIOLOGY,2019年38(8):754-762 ISSN:1044-5498
通讯作者:
Wu, Peng;Mo, Zhongcheng
作者机构:
[Wu, Hongliang; Ou, Hanxiao; Chen, Zhuo; Wu, Peng; Mo, Zhongcheng] Univ South China, Hunan Prov Innovat Training Base Med Postgrad, YueYang Maternal Child Med Hlth Hosp, Yueyang 414000, Hunan, Peoples R China.;[Wu, Hongliang; Ou, Hanxiao; Chen, Zhuo; Wu, Peng; Mo, Zhongcheng] Yueyang Women & Childrens Med Ctr, Yueyang 414000, Hunan, Peoples R China.;[Ou, Hanxiao; Mo, Zhongcheng] Univ South China, Hengyang Med Sch, Clin Anat & Reprod Med Applicat Inst, Dept Histol & Embryol, Hengyang, Hunan, Peoples R China.;[Mo, Zhongcheng] Univ South China, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Wu, Peng; Mo, Zhongcheng] U;[Wu, Peng] Y;Univ South China, Hunan Prov Innovat Training Base Med Postgrad, YueYang Maternal Child Med Hlth Hosp, Yueyang 414000, Hunan, Peoples R China.;Yueyang Women & Childrens Med Ctr, Yueyang 414000, Hunan, Peoples R China.;Univ South China, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
摘要:
Polycystic ovary syndrome (PCOS) is the most typical metabolic syndrome in women of reproductive age, with a high prevalence and an increased risk of long-term complications. PCOS mainly manifests as hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovaries, in addition to being relevant to infertility, insulin resistance (IR), obesity, lipid abnormalities, and chronic low-grade inflammation. The etiology of this syndrome remains largely unknown. microRNAs (miRNAs), small, noncoding RNAs (nearly 22 nucleotides long), regulate gene expression at the posttranscriptional level. Abnormal miRNA levels are closely associated with the occurrence of diseases, such as diabetes, cancers, and atherosclerosis, and miRNAs can be used as predictors and diagnostic biomarkers for cancer. Interestingly, the roles of miRNAs in PCOS pathology have attracted considerable attention in recent years. Research has established that alterations in miRNA expression in women with PCOS compared with healthy women may act as noninvasive biomarkers and new therapeutic targets in PCOS. This article aims to summarize the latest research on the relationship between miRNAs and the clinical manifestations of PCOS while also providing a few mechanisms based on previous studies. Understanding the relationship between miRNAs and PCOS will provide guidance for researchers to further explore the complexity and heterogeneity of PCOS.
作者机构:
[Li, Tao; Chen, Zhongqing; Xu, Wei] Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China.;[Li, Tao; Li, Yunfeng; Dai, Xingui] Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China.;[Liu, Youtan; Liu, Ruimeng] Southern Med Univ, Shenzhen Hosp, Dept Anesthesiol, Shenzhen 518110, Peoples R China.;[Gao, Youguang] Fujian Med Univ, Affiliated Hosp 1, Dept Anesthesiol, Sch Clin Med 1, Fuzhou 350005, Fujian, Peoples R China.
通讯机构:
[Chen, Zhongqing] S;[Li, Yunfeng] U;Southern Med Univ, Sch Clin Med 1, Nanfang Hosp, Dept Crit Care Med, Guangzhou 510515, Guangdong, Peoples R China.;Univ South China, Peoples Hosp Chenzhou 1, Dept Crit Care Med, Inst Translat Med, Chenzhou 423000, Peoples R China.
摘要:
Mitophagy removes dysfunctional mitochondria and is known to play an important role in the pathogenesis of several diseases; however, the role of mitophagy in acute respiratory distress syndrome (ARDS) remains poorly understood. While we have previously demonstrated that polydatin (PD) improves lipopolysaccharide (LPS)-induced ARDS, the specific mechanism remains unclear. In present study, we aimed to determine whether PD activates Parkin-dependent mitophagy to protect against LPS-induced mitochondria-dependent apoptosis and lung injury. To establish the ARDS model, C57BL/6 mice were intratracheally injected with LPS (5 mg/kg) in vivo and Beas-2B cells were exposured to 0.5 mM LPS in vitro. Our results indicate that PD facilitates Parkin translocation to mitochondria and promotes mitophagy in ARDS-challenged mice and LPS-treated Beas-2B cells. However, PD-induced mitophagy was suppressed in Parkin-/- mice and Parkin siRNA transfected cells, indicating that PD activates Parkin-dependent mitophagy. Furthermore, the protective effects of PD against LPS-induced mitochondria-dependent apoptosis and lung injury were suppressed when Parkin was depleted both in vivo and in vitro. The inhibition of mitophagy with mitophagy inhibitor mitochondrial division inhibitor-1 in vivo and silencing of autophagy-related gene 7 in vitro also blocked the protective effects mediated by PD. Our data suggest that Parkin-dependent mitophagy induced by PD provides protection against mitochondria-dependent apoptosis in ARDS.
摘要:
Polycystic ovary syndrome (PCOS), one of the most common endocrine diseases that causes infertility in reproductive women, is characterized by hyperandrogenemia, chronic anovulation, and polycystic ovary morphology (PCOM), and most women with PCOS have metabolic abnormalities. A reduction in plasma sex hormone-binding globulin (SHBG), a transport carrier that binds estrogen and androgens and regulates their biological activities, is often used as an indicator of hyperandrogenism in women with PCOS. Low serum SHBG levels are considered a biomarker of abnormal metabolism and are related to insulin resistance (IR), compensatory hyperinsulinemia and abnormalities in glucose and lipid metabolism in PCOS patients. SHBG is also associated with the long-term prognosis of PCOS. SHBG gene polymorphism is correlated with the risk of PCOS. As SHBG plays a vital role in the occurrence and development of PCOS, knowledge regarding its role in PCOS is helpful for further understanding the molecular mechanism of SHBG in PCOS development and providing new ideas for the treatment of female infertility. Hepatocyte nuclear factor-4alpha (HNF-4alpha) is a vital transcription factor in the SHBG synthesis process. HNF-4alpha binds to the cis-type element DR1 in the SHBG promoter to initiate transcription and regulates hepatic SHBG levels by modulating glucose and lipid metabolism and inflammatory factors. However, it remains unclear whether HNF-4alpha is indirectly involved in the pathogenesis of PCOS via regulation of hepatic SHBG synthesis. Therefore, this review discusses the interaction between SHBG and the various complications of PCOS as well as the regulatory effect of HNF-4alpha on SHBG expression.
摘要:
Chlamydia psittaci is a zoonotic pathogen with multiple hosts, especially avian, and can be transmitted to humans, causing psittacosis or ornithosis. No effective vaccines have been developed. We therefore isolate and genotype avian C. psittaci strains and investigate the pathogenicity of isolates in the southern Hunan area of China. Among 200 suspicious avian specimens, eight were positive for the C. psittaci outer membrane protein A (ompA) gene (4%), and seven were successfully cultured in human epithelial type 2 and Vero cells (87.5%). Genotyping of the ompA gene of the eight PCR-positive samples revealed that all of the cultured strains, except for the E9 strain, belonged to genotype A. Pathologic changes in the mice infected with C. psittaci via intranasal inoculation showed severe pneumonia and intense infiltration of inflammatory cells in the lung in a dose-dependent manner, and immunohistochemical staining displayed different levels of infiltration of C. psittaci inclusions in the heart, liver, spleen, kidney, and, especially, lung. Our findings demonstrate that genotype A dominates all C. psittaci genotypes in the southern Hunan area and that the C. psittaci avian isolates in this region possess dose-dependent pathogenicity.
期刊:
INTERNATIONAL JOURNAL OF NANOMEDICINE,2019年14:6601-6613 ISSN:1178-2013
通讯作者:
Hu, SiHai
作者机构:
[Hu, SiHai; Li, Zhenyu; Hou, YongLi; Cao, Hui; Zheng, Kang; Liu, Peng; Deng, Qing] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, Hunan Prov Key Lab Special Pathogens Prevent & Co, Hengyang 421001, Peoples R China.;[Yan, Ting] Air Force Med Univ, Dept Hlth Serv, Xian 710032, Shaanxi, Peoples R China.;[Hu, SiHai] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[Hu, SiHai] U;Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
关键词:
hepatitis B core protein;Neisserial surface protein A;virus-like particles;recombinant protein vaccine;Neisseria meningitidis serogroup B
摘要:
Purpose: The primary goal of the present study was to explore and evaluate the highly conserved Neisserial surface protein A (NspA) molecule, fused with truncated HBV virus-like particles (VLPs), as a candidate vaccine against the virulent Neisseria meningitidis serogroup B (NMB). Methods: NspA was inserted into the major immunodominant region of the truncated hepatitis B virus core protein (HBc; amino acids 1-144). The chimeric protein, HBc-N144-NspA, was expressed from a prokaryotic vector and generated HBc-like particles, as determined by transmission electron microscopy. Further, the chimeric protein and control proteins were used to immunize mice and the resulting immune responses evaluated by flow cytometry, enzyme-linked immunosorbent assay, and analysis of serum bactericidal activity (SBA) titer. Results: Evaluation of the immunogenicity of the recombinant HBc-N144-NspA protein showed that it elicited the production of high levels of NspA-specific total IgG. The SBA titer of HBc-N144-NspA/F reached 1:16 2 weeks after the last immunization in BALB/c mice, when human serum complement was included in the vaccine. Immunization of HBc-N144-NspA, even without adjuvant, induced high levels of IL-4 and a high IgG1 to IgG2a ratio, confirming induction of an intense Th2 immune response. Levels of IL-17A increased rapidly in mice after the first immunization with HBc-N144-NspA, indicating the potential for this vaccine to induce a mucosal immune response. Meanwhile, the immunization of HBc-N144-NspA without adjuvant induced only mild inflammatory infiltration into the mouse muscle tissue. Conclusion: This study demonstrates that modification using HBc renders NspA a candidate vaccine, which can trigger protective immunity against NMB.
摘要:
BACKGROUND: During total aortic arch replacement surgery (TARS) for patients with acute type A aortic dissection, the organs in the lower body, such as the viscera and spinal cord, are at risk of ischemia even when antegrade cerebral perfusion (ACP) is performed. Combining ACP with retrograde inferior vena caval perfusion (RIVP) during TARS may improve outcomes by providing the lower body with oxygenated blood. METHODS: This study is designed as a multicenter, computer-generated, randomized controlled, assessor-blind, parallel-group study with a superiority framework in patients scheduled for TARS. A total of 636 patients will be randomized on a 1:1 basis to a moderate hypothermia circulatory arrest (MHCA) group, which will receive selective ACP with moderate hypothermia during TARS; or to an RIVP group, which will receive the combination of RIVP and selective ACP under moderate hypothermia during TARS. The primary outcome will be a composite of early mortality and major complications, including paraplegia, postoperative renal failure, severe liver dysfunction, and gastrointestinal complications. All patients will be analyzed according to the intention-to-treat protocol. DISCUSSION: This study aims to assess whether RIVP combined with ACP leads to superior outcomes than ACP alone for patients undergoing TARS under moderate hypothermia. This study seeks to provide high-quality evidence for RIVP to be used in patients with acute type A aortic dissection undergoing TARS. TRIAL REGISTRATION: Clinicaltrials.gov, ID: NCT03607786 . Registered on 30 July 2018.
期刊:
International Journal of Clinical and Experimental Medicine,2019年12(2):1535-1544 ISSN:1940-5901
通讯作者:
Xiao, Jianhua
作者机构:
[Li, Lifang; Xiao, Jianhua] Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 Changsheng Rd, Hengyang 421001, Peoples R China.;[Li, Lifang; Zou, Yan; Yan, Dewen; Lin, Guangfeng; Zhang, Tingji] Second Peoples Hosp Shenzhen, Shenzhen 518037, Peoples R China.
通讯机构:
[Xiao, Jianhua] U;Univ South China, Hengyang Med Coll, Inst Pathogen Biol, 28 Changsheng Rd, Hengyang 421001, Peoples R China.
关键词:
Type 2 diabetes mellitus;Baihu decoction;adipose tissue;chronic inflammation;CD14
摘要:
The incidence of Type 2 diabetes mellitus (T2DM) has increased worldwide. This study investigated the effect of a herbal extract, named as Baihu decoction (BHD), in treating T2DM by using mouse adipose cells and a mouse T2DM model. Mouse 3T3-L1 preadipocytes were cultured in DMEM culture medium and used for experiments when about 90% fat-differentiated cells were mature. The KM male mouse diabetes model was established by injecting streptozotocin. Thirty two KM T2DM mice were randomly divided into 4 groups, with 8 mice in each group. Enzyme-linked immunosorbent assays (ELISA) and Reverse Transcription-quantitative PCR (RT-real time-PCR) were performed to investigate the levels of inflammatory factors and adipokines related to diabetes and their mRNA levels. Western blot experiments were carried out to determine levels of a series of proteins. BHD reduced inflammatory responses induced by lipopolysaccharide in mouse adipose cells and repressed the activity of the CD14/TLR4-NF-kappa B signal pathway. Our siRNA experimental results demonstrated that decreased CD14 gene expression reduced the levels of inflammation significantly. The animal experimental results indicated that BHD has an effective effect on reduction of blood sugar level of T2DM mice. Furthermore, this anti-diabetic effect was due to inhibition of the activity of the CD14/TLR4-NF-kappa B signal pathway, especially CD14. BHD has anti-diabetic effect both in vitro and in vivo by down-regulating the activity of the CD14/TLR4-NF-kappa B signaling pathway, especially CD14.
作者机构:
[Zhang, Zi-xuan; You, Yong] Hainan Med Univ, Affiliated Hosp 2, Dept Neurol, Haikou 571199, Hainan, Peoples R China.;[Zhang, Zi-xuan] XiangTan Cent Hosp, Dept Neurol, Xiangtan 411100, Hunan, Peoples R China.;[Li, E.] Chinese Acad Sci, Inst Neurosci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai 200031, Peoples R China.;[Tian, Shao-Wen] Univ South China, Hengyang Med Coll, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.;[Shen, Pei; Fu, Wan; Yan, Jian-ping] Univ South China, Affiliated Hosp 1, Dept Neurol, Hengyang 421001, Hunan, Peoples R China.
通讯机构:
[You, Yong] H;[Tian, Shao-Wen] U;Hainan Med Univ, Affiliated Hosp 2, Dept Neurol, Haikou 571199, Hainan, Peoples R China.;Univ South China, Hengyang Med Coll, Dept Physiol, Hengyang 421001, Hunan, Peoples R China.
摘要:
Several experimental studies have proved that activation of neuroinflammation pathways may contribute to the development of depression, a neuropsychiatric disorder disease. Our previous studies have shown the antidepressant properties of apelin, but the mechanism was unkown. This study was performed to verify whether the antidepressant effect of apelin was related to its anti-inflammation effect in the central nervous system. To achieve our aim, we selected the co-treatment of chronic stress and LPS to induced an inflammatory process in rats. The effect of this co-treatment was evaluated through the expression of inflammatory markers and glial cell activation. LPS injection co-treated with unpredictable chronic mild stress resulted in the activation of microglial cell and astrocyte, expression of inflammatory markers and depressive behaviors. Treatment with apelin significantly attenuates the deleterious effects in these rats. Our results showed that apelin improved depressive phenotype and decreased the activation of glial cells in stress co-treatment group. The down-regulations of p-NF-kappaB and p-IKKbeta suggested that the effects are possibly mediated by inhibition of the NF-kappaB-mediated inflammatory response. These findings speculated that intracerebroventricular injection of apelin could be a therapeutic approach for the treatment of depression, and the antidepressant function of apelin may closely associated with its alleviation in neuroinflammation.
摘要:
Background: Chlamydia psittaci is a zoonotic bacteria closely associated with psittacosis/ornithosis. Vaccination has been recognized as the best way to inhibit the spread of C. psittaci due to the majority ignored of infections. The optimal Chlamydia vaccine was obstructed by the defect of single immunization route and the lack of availability of nontoxic and valid adjuvants. Methods: In this study, we developed a novel immunization strategy, simultaneous (SIM) intramuscular (IM) and intranasal (IN) administration of a C. psittaci antigens (Ags) adjuvanted with chitosan nanoparticles (CNPs). And SIM-CNPs-Ags were used to determine the different types of immune response and the protective role in vivo. Results: CNPs-Ags with zeta-potential values of 13.12 mV and of 276.1 nm showed excellent stability and optimal size for crossing the mucosal barrier with high 71.7% encapsulation efficiency. SIM-CPN-Ags mediated stronger humoral and mucosal responses by producing meaningfully high levels of IgG and secretory IgA (sIgA) antibodies. The SIM route also led to Ags-specific T-cell responses and increased IFN-gamma, IL-2, TNF-alpha and IL-17A in the splenocyte supernatants. Following respiratory infection with C. psittaci, we found that SIM immunization remarkably reduced bacterial load and the degree of inflammation in the infected lungs and made for a lower level of IFN-gamma, TNF-alpha and IL-6. Furthermore, SIM vaccination with CNPs-Ags had obviously inhibited C. psittaci disseminating to various organs in vivo. Conclusion: SIM immunization with CNPs-adjuvanted C. psittaci Ags may present a novel strategy for the development of a vaccine against the C. psittaci infection.