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1.
Artigo em Inglês | MEDLINE | ID: mdl-31856347

RESUMO

BACKGROUND: Chancre self-healing is an important clinical feature in the early stages of syphilis infection. Wound healing may involve an important mechanism by the migration of fibroblasts filling the injured lesion. However, the specific mechanism underlying this process is still unknown. OBJECTIVE: We aimed to analyse the role of Tp0136 in the migration of fibroblasts and the related mechanism. METHODS: The migration ability of fibroblasts was detected by a wound-healing assay. RT-PCR and ELISA detected the expression of MCP-1, IL-6 and MMP-9. TLR4 expression was detected by RT-PCR. The protein levels of CCR2 and relevant signalling pathway molecules were measured by western blotting. RESULTS: Tp0136 significantly promoted fibroblast migration. Subsequently, the levels of MCP-1 and its receptor CCR2 were increased in this process. The migration of fibroblasts was significantly inhibited by an anti-MCP-1 neutralizing antibody or CCR2 inhibitors. Furthermore, studies demonstrated that Tp0136 could activate the ERK/JNK/PI3K/NF-κB signalling pathways through TLR4 activity and that signalling pathways inhibitors could weaken MCP-1 secretion and fibroblast migration. CONCLUSION: These findings demonstrate that Tp0136 promotes the migration of fibroblasts by inducing MCP-1/CCR2 expression through signalling involving the TLR4, ERK, JNK, PI3K and NF-κB signalling pathways, which could contribute to the mechanism of chancre self-healing in syphilis.

3.
Parasit Vectors ; 12(1): 592, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852494

RESUMO

BACKGROUND: Eimeria tenella is a highly pathogenic coccidian that causes avian coccidiosis. Both nitromezuril (NZL) and ethanamizuril (EZL) are novel triazine compounds with high anticoccidial activity, but the mechanisms of their action are still unclear. This study explored the response of E. tenella to NZL and EZL by the study of changes in protein composition of the second-generation merozoites. METHODS: Label-free quantification (LFQ) proteomics of the second-generation merozoites of E. tenella following NZL and EZL treatment were studied by LC-MS/MS to explore the mechanisms of action. The identified proteins were annotated and analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and protein-protein interaction (PPI) networks analysis. RESULTS: A total of 1430 proteins were identified by LC-MS/MS, of which 375 were considered as differential proteins in response to drug treatment (DPs). There were 26 only found in the NZL treatment group (N-group), 63 exclusive to the EZL treatment group (E-group), and 80 proteins were present in both drug groups. In addition, among the DPs, the abundant proteins with significantly altered expression in response to drug treatment (SDPs) were found compared with the C-group, of which 49 were upregulated and 51 were downregulated in the N-group, and 66 upregulated and 79 downregulated in the E-group. Many upregulated proteins after drug treatment were involved in transcription and protein metabolism, and surface antigen proteins (SAGs) were among the largest proportion of the downregulated SDPs. Results showed the top two enriched GO terms and the top one enriched pathway treated with EZL and NZL were related, which indicated that these two compounds had similar modes of action. CONCLUSIONS: LFQ proteomic analysis is a feasible method for screening drug-related proteins. Drug treatment affected transcription and protein metabolism, and SAGs were also affected significantly. This study provided new insights into the effects of triazine anticoccidials against E. tenella.

4.
Huan Jing Ke Xue ; 40(12): 5570-5580, 2019 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854630

RESUMO

Preventing the environmental risks linked to contaminated sites and guaranteeing the safety of human settlements are some of the challenges and tasks involved in the construction of world-class city clusters in the Guangdong-Hong Kong-Macao Greater Bay Area. Due to differences in the political systems and land property rights between Guangdong, Hong Kong, and Macao, as well as in the levels of urbanization, industrial structures, and environmental management capabilities of the nine cities in the Pearl River Delta, the risk management and control mode of contaminated sites varies considerably within the Greater Bay Area. In this context, an analysis of the features of risk management and control in the contaminated sites of typical cities can help strengthening technical communication and cooperation, optimizing risk management and control systems. This article briefly describes the risk management and control systems adopted for polluted sites in China; in particular it elaborates on the features of these systems in Guangzhou, Shenzhen, Dongguan, Hong Kong, and Macao, which have been subjected to monitoring, contamination assessments, and renovation procedures. During our study, the risk management and control systems adopted in different cities have been analyzed and compared; moreover, we elaborated thoughts and suggestions for land planning, policy feedback, information disclosure, and alliance mechanisms. We conclude that, overall, Hong Kong and several cities of the Pearl River Delta have established effective risk management and control systems for the polluted sites, which take into account certain local characteristics. However, with the further development and reuse of contaminated sites, the building of a world-class urban agglomeration in the Guangdong-Hong Kong-Macao Greater Bay Area will require safer, more refined, and more efficient risk management and control strategies. We highlight the need to exchange information among researchers in order to promote technical exchange and cooperation. This is particularly important for the risk management and control of polluted sites distributed within the two regions and nine cities of the Guangdong-Hong Kong-Macao Greater Bay Area, sine it would allow their safe reuse and efficient development.


Assuntos
Monitoramento Ambiental , Poluentes Ambientais , Gestão de Riscos , China , Cidades , Hong Kong , Humanos , Macau
5.
Mol Oncol ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670863

RESUMO

Hepatocellular carcinoma (HCC), with its ineffective therapeutic options and poor prognosis, represents a global threat. In the present study, we show that RAD52 motif 1 (RDM1), a key regulator of DNA double-strand break repair and recombination, is downregulated in HCC tissues and suppresses tumor growth. In clinical HCC samples, low expression of RDM1 correlates with larger tumor size, poor tumor differentiation and unfavorable survival. In vitro and in vivo data demonstrate that knockdown of RDM1 increases HCC cell proliferation, colony formation and cell population at G2/M phase, whereas RDM1 overexpression results in the opposite phenotypes. Mechanistically, RDM1 binds to the tumor suppressor p53 and enhances its protein stability. In the presence of p53, RDM1 suppresses the phosphorylation of Raf and ERK. Overexpression of p53 or treatment with ERK inhibitor significantly abolishes cell proliferation induced by the depletion of RDM1. In addition, overexpression of methyltransferase-like 3 (METTL3) markedly induces N6-methyladenosine (m6 A) modification of RDM1 mRNA and represses its expression. Taken together, our study indicates that RDM1 functions as a tumor suppressor and may be a potential prognostic and therapeutic factor for HCC.

7.
Cancer Manag Res ; 11: 8359-8370, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571992

RESUMO

Background: Growing evidence suggests that the ubiquitin-proteasome system is involved in the pathogenesis and recurrence of hepatocellular carcinoma (HCC); yet, little is known about the role of ubiquitin-conjugating enzyme E2T (UBE2T) in HCC. Materials and methods: UBE2T levels were detected in HCC tissues and hepatoma cell lines using quantitative reserve transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after UBE2T knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of UBE2T in HCC was tested using ex vivo and in vivo methods. Results: In the present study, we reported that UBE2T mRNA and protein levels were significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Additionally, suppression of UBE2T expression inhibited proliferation, colony formation, tumorigenesis, migration, and invasion of hepatoma cells, whereas UBE2T overexpression led to the opposite outcomes. Moreover, suppression of UBE2T expression resulted in an increase in G2/M phase and a decrease in the percentage of cells in G1 phase, which indicated a cell cycle arrest at the G2/M phase. In contrast, the percentage of cells in G2/M phase decreased following UBE2T overexpression. Further study indicated that UBE2T regulated the G2/M transition by modulating cyclin B1 and cyclin-dependent kinase 1. Conclusion: Taken together, the findings of the present study uncover biological functions of UBE2T in hepatoma cells, and delineate preliminary molecular mechanisms of UBE2T in modulating HCC development and progression.

8.
Eur Neurol ; 81(5-6): 270-277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618750

RESUMO

INTRODUCTION: Recently, neurosyphilis was found to be associated with diabetes mellitus (DM). Whether the association was specific to neurosyphilis among central nervous system (CNS) infections, and whether neurosyphilis is associated with other prevalent metabolic disorders deserves further study. METHODS: An in-depth cross-sectional study was conducted with 74 neurosyphilis patients and 74 sex- and age-matched patients with other CNS infections. DM-, hypertension-, and dyslipidemia-related factors were compared between patients with neurosyphilis and those with other CNS infections. RESULTS: The prevalence rates of hypertension and hyperlipidemia in neurosyphilis patients were 45.9 and 21.4%, respectively, which were higher than those in patients with other CNS infections (45.9 vs. 28.4%, p = 0.027; 21.4 vs. 8.3%, p = 0.028). In addition, neurosyphilis patients had significantly higher systolic blood pressure (BP; median 139 mm Hg; interquartile range [IQR] 121-151 mm Hg), -diastolic BP (median 83 mm Hg; IQR 76-89 mm Hg), total cholesterol (median 4.86 mmol/L; IQR 3.80-5.51 mmol/L), low-density lipoprotein (median 3.39 mmol/L; IQR 2.52-3.95 mmol/L), and apolipoprotein A1 (apoA1; median 1.31 g/L; IQR 1.06-1.52 g/L) levels and lower apoB/A1 ratios (median 0.67; IQR 0.49-0.99) than patients with other CNS infections (p< 0.05). There were no differences in the DM-related factors between patients with neurosyphilis and those with other CNS infections (p> 0.05). CONCLUSION: Potential association between neurosyphilis and metabolic disorders was found among CNS infections. The results could have important implications for clinical practice, alerting more clinicians to this issue.

9.
Int J Mol Med ; 44(5): 1844-1854, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31485608

RESUMO

Long non­coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA­miRNA­mRNA co­expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor­free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor­free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA­mRNA­miRNA co­expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan­Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc­HACE1­6:1 and lnc­ICOSLG­11:1, are significantly upregulated in HCC tissues compared with adjacent tumor­free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.

10.
PLoS Negl Trop Dis ; 13(7): e0007621, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31329597

RESUMO

BACKGROUND: Although the tprK gene of Treponema pallidum are thought to play a critical role in the pathogenesis of syphilis, the profile of variations in tprK during the development of human syphilis infection have remained unclear. METHODS/PRINCIPAL FINDINGS: Through next-generation sequencing, we compared the tprK gene of 14 secondary syphilis patients with that of 14 primary syphilis patients, and the results showed an increased number of variants within the seven V regions of the tprK gene in the secondary syphilis samples. The length of the sequences within each V region also presented a 3-bp changing pattern. Interestingly, the frequencies of predominant sequences within the V regions in the secondary syphilis samples were generally decreased compared with those found in the primary syphilis samples, particularly in the V7 region, where a frequency below 60% was found in up to 57% (8/14) of all secondary samples compared with 7% (1/14) of all primary samples. Moreover, the number of minor variants distributed between frequencies of 10 and 49.9% was increased. The alignment of all amino acid sequences within each V region of the primary and secondary syphilis samples revealed that some amino acid sequences, particularly the amino acid sequences IASDGGAIKH and IASEDGSAGNLKH in V1, were highly stable. Additionally, the amino acid sequences in V6 also exhibited notable intrastrain heterogeneity and were likely to form a strain-specific pattern at the interstrain level. CONCLUSIONS: The identification of different profiles of the tprK gene in primary and secondary syphilis patients indicated that the tprK gene of T. pallidum undergoes constant variation to result in the best adaptation to the host. The highly stable peptides found in V1 are likely promising potential vaccine components. The highly heterogenetic regions (e.g., V6) could help to understand the role of tprK in immune evasion.

11.
Int Immunopharmacol ; 75: 105744, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31319358

RESUMO

Although the infiltration of monocytes into local lesions is an obvious pathological manifestation in the pathogenesis of syphilis, little is known about the role of metalloproteinase (MMP)/tissue inhibitor of metalloproteinases (TIMP) imbalance in the migration/invasion of THP-1 cells induced by Treponema pallidum (T. pallidum). The influence of T. pallidum on the invasion and migration of THP-1 cells was evaluated. Changes in the MMP/TIMP balance and the mechanisms underlying the involvement of the MAPK and NF-κB signaling pathways in this process were explored. T. pallidum induced the migration/invasion of THP-1 cells and the mRNA and protein expression of MMP-1, MMP-9 and TIMP-1. The mRNA expression of TIMP-2 was reduced, and the protein expression of TIMP-2 was not changed. The MMP-1/TIMP-1, MMP-1/TIMP-2, MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios were increased. Inhibition of JNK, MEK/ERK, p38 MAPK and NF-κB significantly decreased the MMP/TIMP ratio and ultimately suppressed the migration/invasion of THP-1 cells. These findings revealed that MMP/TIMP imbalances induced by T. pallidum enhanced THP-1 cell migration and invasion via MAPK and NF-κB signaling pathway activation, which revealed a novel step in syphilis pathophysiology.

12.
Hepatol Int ; 13(5): 560-572, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273618

RESUMO

BACKGROUND AND AIMS: Liver stiffness measurement (LSM) by transient elastography (TE) has been assessed for the evaluation of clinically relevant outcomes in patients with chronic liver diseases (CLDs) while with variable results. This systematic review and meta-analysis aims to investigate the relationship between baseline LSM by TE and the development of clinically relevant outcomes. METHODS: The systematic review identified eligible cohorts reporting the association between baseline LSM by TE and risk of hepatic carcinoma (HCC), hepatic decompensation (HD), all-cause and/or liver-related mortality and liver-related events (LREs) in CLD patients. Summary relative risks (RRs) with 95% confidence intervals (CIs) were estimated using a random-effect model. The dose-response association was evaluated by generalized least squares trend (Glst) estimation and restricted cubic splines. Commands of GLST, MKSPLINE, MVMETA were applied for statistical analysis. RESULTS: 62 cohort studies were finally included, reporting on 43,817 participants. For one kPa (kilopascal) increment in baseline liver stiffness (LS), the pooled RR (95% CI) was 1.08 (1.05-1.11) for HCC, 1.08 (1.06-1.11) for all-cause mortality, 1.11 (1.05-1.17) for liver-related mortality, 1.08 (1.06-1.10) for HD and 1.07 (1.04-1.09) for LREs. Furthermore, the nonlinear dose-response analysis indicated that the significant increase in the risk of corresponding clinically relevant outcomes turned to a stable increase or a slight decrease with increasing baseline LS changing primarily in the magnitude of effect rather than the direction. CONCLUSIONS: The dose-response meta-analysis presents a combination between the levels of baseline LS and RRs for each clinically relevant outcome. TE, which is noninvasive, might be a novel strategy for risk stratification and identification of patients at high risk of developing these outcomes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31293985

RESUMO

The pathological features of syphilis, a disease caused by Treponema pallidum (T. pallidum), are characterized by vascular involvement with endarteritis and periarteritis. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. In the present study, we demonstrated that stimulation of HDVSMCs with T. pallidum resulted in the upregulated gene transcription and protein expression of interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) in a dose- and time-dependent manner. Moreover, the migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that T. pallidum activated the NF-κB signaling pathway in HDVSMCs. Inhibition of NF-κB suppressed T. pallidum-induced IL-6, MCP-1, and ICAM-1 expression. In addition, the migration and adhesion of THP-1 cells to T. pallidum-treated HDVSMCs were significantly decreased by pretreatment with an NF-κB inhibitor. These findings demonstrate that T. pallidum induces the production of IL-6, MCP-1, and ICAM-1 in HDVSMCs and promotes the adherence and migration of THP-1 cells to HDVSMCs through the NF-κB signaling pathway, which may provide new insight into the pathogenesis of T. pallidum infection.

14.
Int Immunopharmacol ; 74: 105566, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31177015

RESUMO

BACKGROUND: Tp47 can induce immune cells to produce numerous inflammatory factors, some of which can trigger autophagy. Increased autophagy has a dual effect on cell survival. However, whether Tp47 induces autophagy in microglia is unknown. OBJECTIVE: To evaluate the potential role of Tp47 in microglia. METHODS: After treatment with Tp47, autophagy-related proteins were assessed in HMO6 human microglial cells by flow cytometry, Western blotting and immunofluorescence. Cell death was assessed by flow cytometry and trypan blue staining. Changes in mTOR pathway proteins were explored by using Western blotting. RESULTS: After treatment with Tp47, a gradual increase in total LC3 expression was observed as a dose- and time-dependent accumulation of its active form, LC3-II (P < 0.05), but P62 expression was downregulated (P < 0.05). Moreover, microglial mortality gradually increased in a dose- and time-dependent manner. 3-Methyladenine (3-MA), a specific inhibitor of PI3KC3, reversed autophagy and cell death. The mortality rate of HMO6 microglial cells treated with Tp47 was approximately 13.7 ±â€¯2%, and the basal expression of p-mTOR, p-p70s6k and p-S6 in these cells was significantly downregulated by Tp47. Moreover, the mortality rate of microglia was significantly reduced after mTOR agonist intervention. CONCLUSION: In human microglial HMO6 cells, Tp47 induces autophagy- and mTOR pathway-dependent cell death.

15.
Exp Cell Res ; 381(1): 150-162, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075255

RESUMO

Vascular inflammation is a complex and multifactorial pathophysiological process that plays a crucial role in all stages of syphilis and is responsible for tissue damage. Little is known about the interactions of infiltrating immunocytes with human dermal vascular smooth muscle cells (HDVSMCs) in arterioles during the immunopathogenesis of syphilis. The Treponema pallidum subsp. pallidum membrane protein Tp47 is considered a major inducer of inflammation initiation and development. In this study, we demonstrated that Tp47 promoted the migration and adhesion of THP-1 cells to HDVSMCs. Furthermore, Tp47 increased monocyte chemoattractant protein-1 (MCP-1) and intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels in a dose- and time-dependent manner. The migration and adhesion of THP-1 cells to HDVSMCs were significantly suppressed by anti-MCP-1 and anti-ICAM-1 neutralizing antibodies, respectively. Further studies revealed that treatment of HDVSMCs with Tp47 activated the PI3K/Akt, p38 MAPK and NF-κB signalling pathways. Inhibition of PI3K/Akt, p38 MAPK and NF-κB suppressed the MCP-1 and ICAM-1 expression induced by Tp47. In addition, the migration and adhesion of THP-1 cells to Tp47-treated HDVSMCs were significantly decreased by pretreatment with PI3K/Akt, p38 MAPK and NF-κB inhibitors. These findings demonstrate that Tp47 promotes the migration and adherence of THP-1 cells to HDVSMCs by inducing MCP-1 and ICAM-1 expression, which is mediated by activation of the PI3K/Akt, p38 MAPK and NF-κB pathways. This study provides a novel potential therapeutic strategy for controlling the vascular inflammatory response in syphilis patients.

16.
Stem Cells Int ; 2019: 8108576, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31001342

RESUMO

MicroRNAs (miRNAs) are potential therapeutic targets in endometrial cancer, but the difficulties associated with their delivery to tumor target cells have hampered their applications. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a well-recognized tumor-homing ability, emphasizing the capacity of tumor-targeted delivery of extracellular vesicles. hUCMSCs release extracellular vesicles rich in miRNAs, which play a vital role in intercellular communication. The purpose of this study was to verify a potential tumor suppressor microRNA, miR-302a, and engineered hUCMSC extracellular vesicles enriched with miR-302a for therapy of endometrial cancer. Here, we observed that miR-302a was significantly downregulated in endometrial cancer tissues when compared with adjacent tissues. Overexpression of miR-302a in endometrial cancer cells robustly suppressed cell proliferation and migration. Meanwhile, the proliferation and migration were significantly inhibited in endometrial cancer cells when cultured with miR-302a-loaded extracellular vesicles derived from hUCMSCs. Importantly, our data showed that engineered extracellular vesicles rich in miR-302 significantly inhibited the expression of cyclin D1 and suppressed AKT signaling pathway in endometrial cancer cells. These results suggested that exogenous miR-302a delivered by hUCMSC-derived extracellular vesicles has exciting potential as an effective anticancer therapy.

17.
Microb Pathog ; 130: 213-218, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30862559

RESUMO

OBJECTIVES: The host immune response could be an imperative factor in the pathogenesis of neurosyphilis, but the role of T lymphocyte subsets remains unclear. In the present study, we assessed the CD4+ T and CD8+ T cell subsets in the peripheral blood of patients with HIV-negative symptomatic neurosyphilis and then explored the clinical application value of neurosyphilis. METHODS: In total, 24 patients with HIV-negative symptomatic neurosyphilis and 22 patients with syphilis/non-neurosyphilis were included in this study and cerebrospinal fluid (CSF) and blood samples were obtained. Th1, Th2, Th17, Th9, CD8+IFN-γ+, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells were identified by flow cytometry. RESULTS: The levels of CD8+IFN-γ+ were significantly increased in the peripheral blood of neurosyphilis patients compared to that in syphilis/non-neurosyphilis patients, but it was opposite to Th2, Th9, CD8+IL-4+, CD8+IL-9+, and CD8+IL-17 + cells. Dendritic cells (DCs) of neurosyphilis matured by T. pallidum induced the development of a combination of IFN-γ-producing Th1 cells. The number of CD8+IL-17 + cells was significantly correlated with the CSF RPR and CSF TPPA levels. ROC curve analysis revealed that the number of CD8+IFN-γ+ cells could be a potential biomarker for neurosyphilis from non-neurosyphilis/syphilis. CONCLUSIONS: High expression of CD8+IFN-γ+ cells and low expression of CD8+IL-17 + cells in patients with symptomatic neurosyphilis, which explains the pathogenesis of symptomatic neurosyphilis, meanwhile CD8+IFN-γ+ cells may be a better indicator in classifying symptomatic neurosyphilis from non-neurosyphilis/syphilis among patients without HIV infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Neurossífilis/patologia , Subpopulações de Linfócitos T/imunologia , Adulto , Idoso , Células Sanguíneas , Líquido Cefalorraquidiano/citologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade
18.
Front Neurosci ; 13: 150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863278

RESUMO

The mechanism underlying the stealth property of neurosyphilis is still unclear. Global metabolomics analysis can provide substantial information on energy metabolism, physiology and possible diagnostic biomarkers and intervention strategies for pathogens. To gain better understanding of the metabolic mechanism of neurosyphilis, we conducted an untargeted metabolomics analysis of cerebrospinal fluid (CSF) from 18 neurosyphilis patients and an identical number of syphilis/non-neurosyphilis patients and syphilis-free patients using the Agilent, 1290 Infinity LC system. The raw data were normalized and subjected to subsequent statistical analysis by MetaboAnalyst 4.0. Metabolites with a variable importance in projection (VIP) greater than one were validated by Student's T-test. A total of 1,808 molecular features were extracted from each sample using XCMS software, and the peak intensity of each feature was obtained. Partial-least squares discrimination analysis provided satisfactory separation by comparing neurosyphilis, syphilis/non-neurosyphilis and syphilis-free patients. A similar trend was obtained in the hierarchical clustering analysis. Furthermore, several metabolites were identified as significantly different by Student's T-test, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, hypoxanthine, and S-methyl-5'-thioadenosine. Notably, 87.369-fold and 7.492-fold changes of N-acetyl-L-tyrosine were observed in neurosyphilis patients compared with syphilis/non-neurosyphilis patients and syphilis-free patients. These differential metabolites are involved in overlapping pathways, including fructose and mannose metabolism, lysosomes, ABC transporters, and galactose metabolism. Several significantly expressed metabolites were identified in CSF from neurosyphilis patients, including L-gulono-gamma-lactone, D-mannose, N-acetyl-L-tyrosine, and hypoxanthine. These differential metabolites could potentially improve neurosyphilis diagnostics in the future. The role of these differential metabolites in the development of neurosyphilis deserves further exploration.

19.
Oncol Rep ; 41(4): 2379-2388, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30816507

RESUMO

Lung cancer is the most common malignant tumor in China. It often metastasizes to bone, thereby significantly shortening the lives of patients, and reducing their quality of life. However, the efficacy of treatment for bone metastasis of lung cancer at this stage is very limited. The development and clinical application of molecular­targeted drugs for the effective targeted therapy of bone metastasis of lung cancer are urgently required. The growth differentiation factor 15 (GDF15) gene which may be associated with bone metastasis of lung cancer, was screened out by whole­genome sequencing. In the present study, we used a recombinant GDF15 lentivirus technique to upregulate the expression of GDF15 in lung adenocarcinoma A549 cells, and the results revealed that GDF15 could inhibit the proliferation, migration and invasion, while promoting apoptosis of A549 cells. In addition, GDF15 significantly decreased the number and sites of lung metastases and bone metastases in vivo compared to the control group. Finally, it was revealed that Smad2 and phospho­Smad2 protein expression was lower in the GDF15­overexpressing A549 cells. This result indicated that the tumor suppressive effect of GDF15 may be related to the TGF­ß/Smad signaling pathway, although more studies are still required for confirmation. In summary, GDF15 inhibited the growth and bone metastasis of lung adenocarcinoma A549 cells, and this effect may be achieved through the TGF­ß/Smad signaling pathway.


Assuntos
Adenocarcinoma de Pulmão/patologia , Neoplasias Ósseas/patologia , Fator 15 de Diferenciação de Crescimento/metabolismo , Neoplasias Pulmonares/patologia , Células A549 , Adenocarcinoma de Pulmão/secundário , Animais , Neoplasias Ósseas/secundário , Movimento Celular , Proliferação de Células , Feminino , Humanos , Camundongos , Proteínas Recombinantes/metabolismo , Transdução de Sinais , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Int J Cardiol ; 283: 9-16, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30808602

RESUMO

PURPOSE: The present study aimed to investigate the relationship between serum levels of secretory vimentin and coronary artery disease (CAD). The biological effect of secretory vimentin was ascertained by experiments. METHODS: We analysed serum levels of secretory vimentin in CAD patients (n = 288) and non-CAD controls (n = 195) by ELISA. To evaluate the pro-inflammatory effects of secreted vimentin, the human aortic endothelial cells (HAECs) and human peripheral blood mononuclear cells (PBMCs) were treated with recombinant vimentin or saline. Intraperitoneal injection of vimentin (1 µg/each) or saline was performed every other day for 12 weeks in ApoE-/- mice for assessment of atherogenic effect. RESULTS: Serum levels of secretory vimentin were significantly increased in CAD patients than in health controls (p < 0.05), and correlated with the number of diseased coronary arteries, Syntax and Gensini score (for all comparison, p < 0.01). Logistic regression analysis showed that vimentin level is an independent determinant of CAD. In experiments, recombinant vimentin protein enhanced the expression of adhesion molecules and inflammatory cytokines in both endothelial cells and macrophages. This protein also promoted macrophage-endothelial cells adhesion in vitro and the recruitment of leukocytes to mesenteric venules in C57BL/6 mice. Compared with saline, intraperitoneal injection of recombinant vimentin (1 µg/each) every other day induced atherogenesis in ApoE-/- mice at 12-weeks, with significant increase of inflammatory cytokine and adhesion molecules expression in aortic tissue (p < 0.05). CONCLUSION: Serum vimentin levels are associated with the presence and the severity of CAD. Vimentin protein promotes atherogenesis in ApoE-/- mice.

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