摘要：
Syphilis is a chronic bacterial infection caused by Treponema pallidum (T pallidum) and the pathogenesis that T pallidum infection induces immunopathological damages in skin and other tissues remains unclear. We have previously reported that recombinant flagellins of T pallidum can elicit IL-6 and IL-8 transcriptions via TLR5 pathway. To identify the domains which induced the pro-inflammatory activity and the importance of the interactions between TLR5 and domains, homology-based modelling and comparative structural analyses revealed that Tpflagellins can combine with TLR5 directly. Deletion mutations showed that the ND1 domain binding to TLR5 is required but not sufficient in TLR5 activation. Moreover, site-directed mutagenesis analysis indicated that the arginine residue (Tpflagellins R89) of the ND1 domain and its adjacent residues (Tpflagellins L93 and E113) constitute a hot spot that elicits IL-6, IL-8 transcriptions and TLR5 activation, and affects the binding of Tpflagellins to TLR5. Taken together, these results give insight into the pathogenesis of T pallidum and may contribute to the future design of Tpflagellins-based therapeutics and syphilis vaccine.
摘要：
Chlamydia psittaci is an obligate intracellular pathogen with a biphasic developmental life cycle. It is auxotrophic for a variety of essential metabolites and obtains amino acids from eukaryotic host cells. Chlamydia can develop inside host cells within chlamydial inclusions. A pathway secreting proteins from inclusions into the host cellular cytoplasm is the type III secretion system (T3SS). The T3SS is universal among several Gram-negative bacteria. Here, we show that CPSIT_0959 of C. psittaci is expressed midcycle and secreted into the infected cellular cytoplasm via the T3SS. Recombinant CPSIT_0959 possesses cysteine desulfurase and PLP-binding activity, which removes sulfur from cysteine to produce alanine, and helps chlamydial replication. Our study shows that CPSIT_0959 improve the infectivity of offspring elementary bodies and seems to promote the replication by its product. This phenomenon has inhibited by the PLP-dependent enzymes inhibitor. Moreover, CPSIT_0959 increased expression of Bim and tBid, and decreased the mitochondrial membrane potential of host mitochondria to induce apoptosis in the latecycle for release of offspring. These results demonstrate that CPSIT_0959 has cysteine desulfurase and PLP-binding activity and is likely to contribute to apoptosis of the infected cells via a mitochondria-mediated pathway to improve the infectivity of progeny.
作者机构：
[Li, Junyu] Canc Hosp Jiangxi Prov, Dept Radiotherapy, Nanchang 330029, Jiangxi, Peoples R China.;[Li, Yuehua; Wu, Xiaoping] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang 421001, Hunan, Peoples R China.;[Li, Ying] Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Li, Ying] H;Hubei Canc Hosp, Dept Radiat Oncol, 116 Zhuodaoquan South Rd, Wuhan 430079, Hubei, Peoples R China.
关键词：
biomarker;head and neck squamous cell carcinoma;long non-coding RNA;signature;survival
摘要：
Long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer and their aberrant expression has been associated with cancer diagnosis and prognosis, which suggests that they may be promising molecular biomarkers. However, understanding of the expression pattern of lncRNAs and their prognostic roles in head and neck squamous cell carcinoma (HNSCC) is relatively limited. In the current study, the prognostic value of lncRNA expression profiles in predicting the OS of patients with HNSCC was investigated by integrating clinical and profiling data from The Cancer Genome Atlas. A total of ten lncRNAs closely associated with the prognosis of patients with HNSCC were identified and may serve as novel biomarkers. This 10-lncRNA signature was used to classify patients into 2 groups with significantly different overall survival (OS) times (median OS time, 1.65 vs. 13.04 years; P<0.0001). This lncRNA signature was validated in an independent testing cohort. The results of multivariable Cox regression and stratification analyses revealed that the prognostic value of the 10-lncRNA signature was independent of other clinical and pathological factors for the survival of patients with HNSCC. Functional analysis demonstrated that lncRNA expression-based risk scoring may reflect the basic status of the immune response in the tumor microenvironment. The presented study demonstrated the value of a lncRNA signature as a potential biomarker to improve the clinical prognosis of patients with HNSCC.
摘要：
A biosorbent, 4-sulfonylcalix[6]arene modified Fe(3)O(4)@Aspergillus Niger (MFSC), was successfully prepared through a two-step route for the effective removal of uranium (U(VI)) from aqueous solutions with high selectivity. The structure of MFSC was characterized by FT-IR, SEM, XRD, TGA and VSM, respectively. The impacts of various experimental parameters were investigated in detail. The results indicated that the biosorption of U(VI) on MFSC was mainly attributed to the electrostatic attraction (91% within 8 hours for U(VI)). The adsorption kinetics and adsorption isotherm of U(VI) were found to follow the pseudo second-order model and to be fitted by the Langmuir model, respectively. The thermodynamic parameters revealed that the adsorption process was spontaneous and endothermic. The findings herein highlight the MFSC with high ability for removal of U(VI) from aqueous solutions.
作者机构：
[Peng Qiu; Gan Run-Liang] Univ South China, Canc Res Inst, Hengyang 421001, Peoples R China.;[Liu Liang-Zhuan] Univ South China, Expt Ctr Med Res, Hengyang 421001, Peoples R China.
通讯机构：
[Gan Run-Liang] U;Univ South China, Canc Res Inst, Hengyang 421001, Peoples R China.
摘要：
Neuropathic pain represents one of the most common complications associated with diabetes mellitus (DM) that impacts quality of life. Accumulating studies have highlighted the involvement of miRNAs in DM. Thus, the current study aimed to investigate the roles of miR-155 in diabetic peripheral neuropathy (DPN). In vitro DPN models were established using rat Schwann cells (SCs) by treatment with 5.5 mM glucose. Gain- or loss-of-function studies were conducted to determine the effect of miR-155 on Nrf2, cellular function, reactive oxygen species and inflammation. Rat DNP models were established by streptozotocin injection and damage of sciatic nerve. Next, miR-155 antagomir or agomir was employed to investigate the effects associated with miR-155 on motor and sciatic nerve conduction velocity (MNCV, SNCV), angiogenesis and inflammatory response in vivo. Nrf2 was identified to be a target of miR-155 by dual-luciferase reporter gene assay. Silencing of miR-155 or restoration of Nrf2 promoted cell proliferation, inhibited apoptosis and alleviated inflammation in vitro. miR-155 antagomir-induced inhibition increased MNCV and SNCV, strengthened angiogenesis and alleviated inflammation in DPN rats. Additionally, the effects exerted by miR-155 were reversed when Nrf2 was restored both in vitro and in vivo. Taken together, the key findings of our study provide evidence indicating that miR-155 targeted and suppressed Nrf2 in DPN. miR-155 silencing was found to alleviate sciatic nerve injury in DPN, highlighting its potential as a therapeutic target for DPN.
期刊：
Frontiers in Physiology,2019年10(MAR):165 ISSN：1664-042X
通讯作者：
Tang, Ya-Ling;Liao, Duan-Fang
作者机构：
[Gu, Hong-Feng; Xu, Zhao-Qian; Chen, Ru-Meng; Tang, Ya-Ling; Li, Na; Hu, Lu; Li, Hui; Zhang, Rong-Jie; Liao, Duan-Fang; Tang, YL; Liao, DF] Univ South China, Dept Physiol, Hengyang, Peoples R China.;[Gu, Hong-Feng; Xu, Zhao-Qian; Chen, Ru-Meng; Tang, Ya-Ling; Li, Na; Hu, Lu; Li, Hui; Zhang, Rong-Jie; Liao, Duan-Fang; Tang, YL; Liao, DF] Univ South China, Inst Neurosci, Hengyang, Peoples R China.;[Zheng, Xi-Long; Liao, Duan-Fang] Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
通讯机构：
[Tang, YL; Liao, DF] U;[Liao, Duan-Fang] H;Univ South China, Dept Physiol, Hengyang, Peoples R China.;Univ South China, Inst Neurosci, Hengyang, Peoples R China.;Hunan Univ Chinese Med, Div Stem Cell Regulat & Applicat, State Key Lab Chinese Med Powder & Med Innovat Hu, Changsha, Hunan, Peoples R China.
摘要：
Overlap extension polymerase chain reaction (PCR) is a powerful technology for DNA assembly. Based on this technology, we synthesized DNA templates, which were transcribed into sgRNA in vitro, and further detected their efficiency of purified sgRNAs with Cas9 nuclease. The sgRNAs synthesized by this approach can effectively cleave the DNA fragments of interest in vitro and in vivo. Compared with the conventional method for generating sgRNA, it does not require construction of recombinant plasmids and design of primers to amplify sgRNA core fragment. Only several short primers with overlapped sequences are needed to assemble a DNA fragment as the template of sgRNA. This modified and simplified method is highly applicable and less time-consuming.
通讯机构：
[Yin, WD; Tang, CK] U;Univ South China, Med Res Expt Ctr, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Inst Cardiovasc Dis,Key Lab Arteriosclerol Hunan, Hengyang 421001, Hunan, Peoples R China.
关键词：
AS;CCDC80;DNA methylation;LPL;TET2
摘要：
Recent studies showed that coiled-coil domain-containing 80 (CCDC80) has a positive link with atherosclerosis and that plasma CCDC80 levels are positively correlated with the levels of fasting plasma triglycerides (TG) in obese individuals. The underlying mechanisms, however, are unclear. Using Hematoxylin-eosin (H&E) and Oil Red O staining, we found that CCDC80 overexpression in vivo significantly increased plasma lipid contents, decreased the expression and activity of lipoprotein lipase (LPL), and accelerated the development of atherosclerosis. Conversely, knockdown of CCDC80 decreased plaque lesions area. In vitro, qRT-PCR and western blot results showed that CCDC80 overexpression significantly decreased, while CCDC80 knockdown increased, LPL expression in cultured vascular smooth muscle cells (VSMCs). Further, we found that CCDC80 reduced LPL expression via inhibiting the phosphorylation of extracellular regulated protein kinase 1/2 (ERK1/2) and also increased the methylation of LPL promoter via down-regulating Tet methylcytosine dioxygenase 2 (TET2). Our results also revealed that CCDC80 significantly down-regulated TET2 expression through decreasing the phosphorylation of ERK1/2. In addition, we found that CCDC80 decreased binding of TET2 to forkhead box O3 (FOXO3a) but had no effect on FOXO3a expression. On the other hand, and that FOXO3a was partially involved in TET2-regulated LPL expression. CCDC80 down-regulated ERK1/2 phosphorylation and decreased expression of TET2 and its interaction with FOXO3a, leading to a reduction of LPL expression and acceleration of atherosclerosis.
作者机构：
[Li, Jie; Tian, Shao-Wen; Chen, Fang-Ling] Univ South China, Dept Physiol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;[Wang, Bo] Univ South China, Affiliated Hosp 1, Dept Anesthesiol, Hengyang 421001, Hunan, Peoples R China.;[Tian, Shao-Wen] Guilin Med Univ, Guangxi Key Lab Brain & Cognit Neurosci, Guilin 541000, Guangxi, Peoples R China.;[Long, Chen] Cent S Univ, Xiangya Hosp 2, Dept Minimally Invas Surg, Changsha 410011, Hunan, Peoples R China.
通讯机构：
[Tian, Shao-Wen] U;[Long, Chen] C;Univ South China, Dept Physiol, Hengyang Med Coll, Hengyang 421001, Hunan, Peoples R China.;Cent S Univ, Xiangya Hosp 2, Dept Minimally Invas Surg, Changsha 410011, Hunan, Peoples R China.
关键词：
Apelin-13;Fear extinction;Memory;PTSD;Rats
摘要：
Fear extinction is considered as a new learning process that is valid to model features of post-traumatic stress disorder (PTSD). The neuropeptide apelin, such as apelin-13, apelin-17 and apelin-36, are endogenous ligands of the G-protein coupled receptor APJ. Apelin and its receptor APJ are widely distributed in the central nervous system. Accumulating evidence suggests the critical role of apelin-13 in modulation of learning and memory, however, its specific role in fear extinction remains unclear. In the present study, we investigated the effect of apelin-13 administration on contextual fear extinction in rats. The behavioral procedure included four sessions: habitation, conditioning, extinction training and extinction recall. Rats received intracerebroventricular infusion of apelin-13 (3 or 6 mu g) 0.5 h prior to the extinction training. Percentage of freezing was utilized to assess the conditioned fear response. Results showed that apelin-13, with the dose of 6 but not 3 mu g, significantly decreased freezing response during both extinction training and extinction recall test sessions. Furthermore, apelin-13 did not affect the levels of baseline freezing, locomotor activity and anxiety. The results suggest that apelin-13 dose-dependently enhances contextual fear extinction, and may function as a novel target for treatment of PTSD.
摘要：
Exposure to Mycoplasma pneumoniae leads to lung inflammation through a host defense pathway. Increasing evidence has indicated that the mycoplasma-derived membrane lipoprotein, or its analogue macrophage-activating lipopeptide-2 (MALP-2), excretes LPS as an immune system-stimulating substance and plays a crucial role in pathological injury during M. pneumoniae infection. It has been established that Sulforaphane confers anti-inflammatory properties. However, the underlying mechanism responsible for the inhibitory actions of Sulforaphane in the context of mycoplasmal pneumoniae are poorly understood. Here, we report that Sulforaphane is an inducer of heme oxygenase (HO)-1, a cytoprotective enzyme that catalyzes the degradation of heme through signaling pathways in human monocytes. Sulforaphane stimulated NF-E2-related factor 2 (Nrf2) translocation from the cytosol to the nucleus, and small interfering RNA-mediated knock-down of Nrf2 significantly inhibited Sulforaphane-induced HO-1 expression. Additionally, PI3K/Akt and ROS were also involved in Sulforaphane-induced Nrf2 activation and HO-1 expression, as revealed by the pharmacological inhibitors LY294002 and NAC. Moreover, Sulforaphane treatment inhibited MALP-2-induced pro-inflammatory cytokine secretion and pulmonary inflammation in mice, as well as MALP-2-triggered NF-kappaB activation. Furthermore, SnPP, a selective inhibitor of HO-1, reversed the inhibitory actions of Sulforaphane, while a carbon monoxide-releasing molecule, CORM-2, caused a significant decrease in MALP-2-induced cytokine secretion. Collectively, these results suggest that Sulforaphane functions as a suppressor of the MALP-2-induced inflammatory response, not only by inhibiting the expression of cytokines and the induction of HO-1 but also by diminishing NF-kappaB activation in cultured monocytes and the lungs of mice.
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.
关键词：
apoptosis;atherosclerosis;inflammation;macrophage;nuclear factor-kappaB;protein kinase B;tumor necrosis factor-alpha-induced protein 8-like 2
摘要：
Macrophage apoptosis and inflammation serve pivotal roles in the occurrence of atherosclerosis. However, the detailed underlying mechanism of macrophage action during atherosclerosis is poorly understood. Tumor necrosis factor-alpha-induced protein 8-like 2 (TIPE2) is a well-known negative regulator of the immune response. The current study assessed the association between TIPE2 and apoptosis-associated molecules in macrophages during atherosclerosis, as well as the role of TIPE2 in macrophage inflammation. RAW264.7 macrophages were subsequently transfected with a TIPE2 expression plasmid. Following oxidized low-density lipoprotein (oxLDL) induction (100 microg/m1) for 48 h, macrophage apoptosis was assessed via Annexin V/propidium iodide dual staining. The apoptosis-associated factors and Akt signaling pathway-associated factors were also evaluated via western blot analysis. The expression of inflammatory factors was determined via a reverse transcription-quantitative polymerase chain reaction assay and western blotting. Furthermore, a transwell assay was performed to test cell invasion ability. NF-kappaB phosphorylation and nuclear translocation were also assessed via western blotting. The results demonstrated that TIPE2 overexpression may promote oxLDL-induced RAW264.7 macrophage apoptosis by inhibiting the protein kinase B (Akt) signaling pathway. Furthermore, it was demonstrated that TIPE2 significantly reduced oxLDL-induced tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemoattractant protein 1 expression (MCP-1), and increased IL-10 expression by suppressing NF-kappaB phosphorylation and nuclear translocation in RAW264.7 macrophages. These results indicated that TIPE2 serves a protective role in oxLDL-induced RAW264.7 macrophages, and its mechanism may partly be exerted via the inhibition of the PI3K/Akt signaling pathway and the reduction of the macrophage inflammatory response achieved via the suppression of NF-kappaB signal activation.
