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1.
Clin Chim Acta ; 523: 196-200, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34592307

RESUMO

BACKGROUND: Serofast status is challenging to interpret in clinical work, and distinguishing active syphilis in serofast patients can provide a reference for clinical diagnosis and treatment. However, effective serologic markers for active syphilis are still lacking. OBJECTIVES: We aimed to explore the possibility of nontreponemal IgM antibodies in distinguishing active syphilis in serofast patients. METHODS: A total of 1501 clinical serum samples were collected from 301 serofast patients, and nontreponemal IgM antibodies were detected by chemiluminescence immunoassay. RESULTS: The results showed that a total of 29 samples (9.63%) of 301 serofast patients were positive for nontreponemal IgM antibodies, and our limited follow-up data showed that 66.67% (2/3) of the serofast patients progressed to neurosyphilis and cardiovascular syphilis. CONCLUSION: These findings demonstrate that most serofast patients with positive nontreponemal IgM antibodies have evidence of progressive syphilis, and nontreponemal IgM antibodies can be used as a new serologic marker for the activity of syphilis. Nontreponemal IgM antibodies may play a role in the management of serofast patients.

2.
Future Microbiol ; 16: 1041-1051, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34493087

RESUMO

Aim: To screen novel biomarkers in serum of syphilis patients using a mass spectrometry-based method. Materials & methods: Sera were collected from 18 syphilis patients and divided into three groups. Every six serum samples (before and after treatment) in each group were pooled and detected by mass spectrometry. Results: Twenty-five unique peptides corresponding to 15 Treponema pallidum proteins were discovered. Among them, Tp0369 was discovered as a promising biomarker candidate in this study. Tp0524 and Tp0984 levels decreased 0.38-fold and 0.51-fold after BPG treatment, respectively, which may be related to disease outcomes of syphilis. Conclusion: These findings confirmed the presence of detectable T. pallidum protein in patients' serum, which could promote the development of syphilis diagnostics.

3.
Epigenomics ; 13(15): 1187-1203, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34382410

RESUMO

Aim: Neurosyphilis patients exhibited significant expression of long noncoding RNA (lncRNA) in peripheral blood T lymphocytes. In this study, we further clarified the role of lncRNA-ENST00000421645 in the pathogenic mechanism of neurosyphilis. Methods: lncRNA-ENST00000421645 was transfected into Jurkat-E6-1 cells, namely lentivirus (Lv)-1645 cells. RNA pull-down assay, flow cytometry, RT-qPCR, ELISA (Neobioscience Technology Co Ltd, Shenzhen, China) and RNA immunoprecipitation chip assay were used to analyze the function of lncRNA-ENST00000421645. Results: The expression of IFN-γ in Lv-1645 cells was significantly increased compared to that in Jurkat-E6-1 cells stimulated by phorbol-12-myristate-13-acetate (PMA). Then, it was suggested that lncRNA-ENST00000421645 interacts with PCM1 protein. Silencing PCM1 significantly increased the level of IFN-γ in Lv-1645 cells stimulated by PMA. Conclusion: This study revealed that lncRNA-ENST00000421645 mediates the production of IFN-γ by sponging PCM1 protein after PMA stimulation.

4.
Inorg Chem ; 60(10): 6986-6990, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33913715

RESUMO

Multifunctional lanthanide coordination polymers (CPs) have the advantages of acting in two or more fields simultaneously. Herein, two single lanthanide CPs, formulated as LnL(D/L-Hlac)(H2O)2·0.5H2O (Ln = Eu (1), Tb (2); H2L = 4,4'-(pyridine-3,5-diyl)dibenzoic acid) and their doped lanthanide analogue Tb0.9373Eu0.0627L(D/L-Hlac)(H2O)2·0.5H2O (3) were prepared through hydrothermal methods. Luminescence measurements reveal that 1 displays red photoluminescence and its Commission International ed'Eclairage (CIE) coordinates are almost invariant in the temperature range from 80 to 300 K, while the emission color of 2 changes from yellow to green and its CIE coordinates change from (0.36132, 0.56365) at 80 K to (0.30448, 0.45566) at 300 K. Significantly, 3 not only displays white-light emission with CIE coordinates of (0.32999, 0.33406) but also exhibits a thermal sensitivity of 2.27% K-1 at 230-300 K. The obviously larger thermal sensitivity in 3 in comparison to that of 1.07% K-1 for 2 demonstrates that lanthanide CPs with both a heat-sensitive fluorescent thermometer and high-efficiency white-light emission can be expected by doping Eu(III) ions into Tb(III)-based CPs.

5.
Inorg Chem ; 60(10): 6981-6985, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33913721

RESUMO

Four pairs of chiral 3D coordination polymers (CPs), [Zn2(BDC)(lac)(DMF)]·guest (2) (H2BDC = benzene dicarboxylic acid; H2lac = lactic acid; guest = 1.5DMF + i-PrOH), [Co2(BDC)(lac)(DMF)]·guest (3) (guest = DMF + 2H2O), [Fe4(BDC)3(lac)2(DMF)2](CO3)·guest (4) (guest = DMF + 2H2O), and {Zn11(BPDC)6(lac)6[NH2(CH3)2]2}·guest (H2BPDC = 3,3'-biphenyldicarboxylic acid; guest = 6DMF + 18H2O) (5), are prepared through the reactions of racemic lactic acid (rac-H2lac) with different metal ions and auxiliary ligands. Structural analyses and DFT calculations reveal that forming more and stronger coordination bonds between the auxiliary ligand and metal ions is more conducive to the spontaneous resolution of enantiomers in 3D CPs than simply increasing the entropy of the auxiliary ligand itself.

7.
Sex Transm Infect ; 97(2): 120-125, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33214321

RESUMO

OBJECTIVES: A novel tp0548 sequence-type was identified in one clinical isolate (X-4) from a patient diagnosed with primary syphilis in Xiamen, China. To precisely define and characterise a new clinical isolate, we performed further genome-scale molecular analysis. METHODS: The pooled segment genome sequencing method followed by Illumina sequencing was performed. RESULTS: This novel sequence-type contained a unique nucleotide substitution 'T' at position 167 and belonged to the SS14-like clade of TPA strains, as determined by phylogenetic analysis. Multi-locus sequence analysis of nine chromosomal loci demonstrated that the X-4 isolate was clustered within a monophyletic group of TPA strains. Whole-genome phylogenetic analysis subsequently corroborated the TPA strain classification of the X-4 isolate and revealed that the isolate was closely related to the SS14 strain, with 42 single-nucleotide variations and 12 insertions/deletions. In addition, high intrastrain heterogeneity in the length of the poly G/C tracts was found in the TPAChi_0347 locus, which might indicate that this gene of the X-4 isolate is likely involved in phase variation events. The length heterogeneity of the poly A/T tracts was lower than the genetic variability of the poly G/C tracts, and all the observed intrastrain variations fell within coding regions. CONCLUSION: The novel tp0548 sequence-type was determined to belong to a new TPA isolate, X-4. The identification of variable length in homopolymetic tracts (G/C and A/T) could provide a snapshot of the genes that potentially involved in genotype-phenotype variations. These findings provide an unequivocal characterisation for better understanding the molecular variation of this emerging isolate.


Assuntos
Sífilis/microbiologia , Treponema pallidum/genética , Treponema pallidum/isolamento & purificação , Adulto , Técnicas de Tipagem Bacteriana , China , Variação Genética , Genoma Bacteriano/genética , Humanos , Masculino , Tipagem de Sequências Multilocus , Filogenia , Análise de Sequência de DNA , Sífilis/diagnóstico , Treponema pallidum/classificação
8.
Front Cell Infect Microbiol ; 10: 592864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33282751

RESUMO

Monocytes are widely involved in the body's defense response, and abnormally regulated monocyte subsets are closely related to the pathogenesis of various diseases. It is unclear whether Treponema pallidum (Tp) dysregulates monocyte subsets and impacts the functions of monocytes. This study aims to analyze the distribution of monocyte subsets in syphilis patients and the effect of Tp on monocyte functions to explore the pathogenesis of syphilis. Flow cytometry was employed to detect monocyte subsets. With or without pre-treatment with rapamycin, THP-1 cell migration stimulated by Tp was investigated by a Transwell migration assay, and THP-1 cell phagocytosis was studied using fluorescent microspheres. IL-1ß and TNF-α expression was quantified by PCR and flow cytometry, while LC3 and mTOR were investigated in Tp-exposed THP-1 cells using western blotting. Tp infection led to an increase in the proportion of CD14++CD16+ monocytes and a decrease in the proportion of CD14++CD16- monocytes. In addition, Tp promoted monocyte (THP-1) CD14 and CD16 expression in vitro, induced the expression of IL-1ß and TNF-α in a dose-dependent manner and promoted the migration and autophagy of monocytes. Furthermore, mTOR phosphorylation on monocytes was stimulated by Tp, and the levels peaked at 30 min. Pre-treatment with rapamycin (mTOR inhibitor) attenuated the expression of IL-1ß and migration in Tp-exposed THP-1 cells. Tp abnormally regulates monocyte subsets and promotes migration, autophagy, and the expression of IL-1ß and TNF-α in THP-1 cells. Meanwhile, the mTOR affected the expression of IL-1ß and migration in Tp-exposed THP-1 cells. This study is important as it sheds light on the mechanism by which monocytes interact with Tp during infection.


Assuntos
Monócitos , Transdução de Sinais , Humanos , Interleucina-1beta , Receptores de Lipopolissacarídeos , Monócitos/metabolismo , Células THP-1 , Serina-Treonina Quinases TOR/metabolismo , Treponema pallidum/metabolismo
9.
Dalton Trans ; 49(46): 16745-16761, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33146650

RESUMO

A new tetradentate chelating ligand appending a stilbene derivative, E-N',N'-bis(pyridin-2-ylmethyl)-4-styrylbenzohydrazide (HL) was synthesized, together with two ß-diketonates (4,4,4-trifluoro-1-phenylbutane-1,3-dionate, tfd), with or without the trifluoroacetate anion present as a ligand for coordination with lanthanide(iii) ions to form [Ln(tfd)2(HL)(CF3CO2)] (LnC49H36F9N4O7, Ln = La (1), Nd (2), Eu (3), Gd (4)) and [Yb(tfd)2(L)] (YbC47H35F6N4O5 (5), L = deprotonated HL). All five complexes were structurally characterized, and five crystals were obtained and analyzed by single-crystal X-ray diffraction. The quantum yield of trans-to-cis photoisomerization of the stilbene group in gadolinium complex 4 was enhanced about five-fold compared with that of HL itself. Other complexes showed slightly enhanced or depressed photoisomerization. The total luminescence quantum yield/sensitization efficiency of europium complex 3 in the solid state and acetonitrile solution were 22.1%/96.7% and 19.3%/97.9%, respectively. The transfer of ligand energy to the Eu3+ ion was highly efficient. This enhanced photoisomerization and luminescence of the stilbene group within complexes was found to be related to the energy level of lanthanide ions and whether a ligand-to-metal center or ligand-to-ligand charge transfer process was present. The interpretation of experimental results is rationally supported by time-dependent density-functional theory calculations. In complex 4, except for the intramolecular absorption transition of HL ligand itself (IL, πHL-π*HL), the presence of the ligand-to-ligand charge transfer transition from tfd to HL (LLCT, πtfd-π*HL) and the triplet state energy of HL being unable to transfer to the higher 6P7/2 excited energy level of the Gd3+ ion would facilitate HL photoisomerization. For complex 3, this was due to reversed ligand-to-ligand charge transfer transition from HL to tfd (LLCT, πHL-π*tfd) and its energy transfer to the metal center. Although the observed radiative lifetimes of NIR luminescent complexes 2 and 5 were around 10 µs, these systems contained only two diketone ligands, indicating that HL still had a certain promoting effect compared with tris(diketonate) lanthanide complexes. These results offer an important route for the design of new lanthanide-based molecular switching materials.

10.
Exp Cell Res ; 396(1): 112289, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32950474

RESUMO

Lesion healing without treatment is a unique clinical characteristic of the early stages of syphilis infection. Angiogenesis, which involves endothelial cell migration, is an important process in wound healing. Tp0136, an outer membrane protein of T. pallidum, has the ability to bind host fibronectin-producing cells, which plays a crucial role in the pathogenesis of syphilis. In this research, we purposed to analyze the role of Tp0136 in the migration of human microvascular endothelial (HMEC-1) cells and to explore the related mechanism. First, Tp0136 significantly promoted HMEC-1 cell migration. Furthermore, the levels of C-C motif ligand 2 (CCL2) mRNA and protein expression rose with the concentration and time increasing of Tp0136. The migration of HMEC-1 cells was significantly suppressed by an anti-CCL2 antibody and a CCR2 (the CCL2 receptor) inhibitor. Further study revealed that, in cells pretreated with anti-fibronectin antibody, anti-integrin ß1 antibody or RGD (Arg-Gly-Asp), the expression levels of CCL2 induced by Tp0136 were notably decreased. Additionally, after pretreatment with an anti-fibronectin antibody, an anti-integrin ß1 antibody or RGD, the migration of HMEC-1 cells treated with Tp0136 was obviously suppressed. These results show that Tp0136 promots the migration of HMEC-1 cells by inducing CCL2 expression via the interaction of the fibronectin RGD domain with integrin ß1 and the CCL2/CCR2 signaling pathway, and these interactions may contribute to the mechanisms that increase the capacity for self-healing syphilis infection.


Assuntos
Proteínas de Bactérias/farmacologia , Movimento Celular/efeitos dos fármacos , Fibronectinas/genética , Integrina beta1/genética , Treponema pallidum/metabolismo , Anticorpos Neutralizantes/farmacologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Linhagem Celular , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Clonagem Molecular , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Escherichia coli/genética , Escherichia coli/metabolismo , Fibronectinas/antagonistas & inibidores , Fibronectinas/metabolismo , Expressão Gênica , Regulação da Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Interações Hospedeiro-Patógeno/genética , Humanos , Integrina beta1/metabolismo , Oligopeptídeos/farmacologia , Ligação Proteica , Receptores CCR2/genética , Receptores CCR2/metabolismo , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais , Treponema pallidum/química
11.
Int Immunopharmacol ; 82: 106344, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32151957

RESUMO

It is unclear whether P2X7 receptor (P2X7R) mediates NOD-like receptor family protein 3 (NLRP3)-dependent IL-1ß secretion and spirochete phagocytosis in syphilis. This study was conducted to investigate the role of P2X7R in modifying NLRP3-dependent IL-1ß secretion and regulating phagocytosis by Treponema pallidum (T. pallidum)-induced macrophages. Macrophages derived from a human acute monocytic leukemia cell line were cultured with T. pallidum. The activation of P2X7R in T. pallidum-treated macrophages occurred in a dose- and time-dependent manner. The P2X7R silencing group showed significantly decreased NLRP3 mRNA and protein levels (vs. the Tp group, P < 0.001). Similar results were observed for IL-1ß secretion using ELISA (vs. the Tp group, P < 0.001). Furthermore, P2X7R siRNA transfection significantly decreased the percentage of spirochete-positive macrophages (29.73% vs. 70.83%, P < 0.001) and spirochete internalization (mean fluorescence intensity (MFI), 9.20 vs. 19.39, P < 0.001). This finding revealed that P2X7R played a role in the induction of NLRP3-dependent IL-1ß secretion by T. pallidum-induced macrophages. Furthermore, we found that P2X7R plays an important role in IL-1ß secretion and in the promotion of T. pallidum phagocytosis by macrophages. These results may not only contribute to our understanding of the immune mechanism that is active during T. pallidum infection but may also lay the groundwork for strategies to combat syphilis.

12.
Int Immunopharmacol ; 83: 106428, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217461

RESUMO

The effect of anti-TP0136 antibodies on the progression of syphilis is poorly understood. This study aimed to investigate the effect of anti-TP0136 antibodies on the progression of lesions in an infected rabbit model. Intramuscular injection of rTP0136 into rabbits in the immunized group (n = 4) elicited high titers of anti-TP0136 antibodies, and rabbits were then challenged with 105T. pallidum per site along their back. Lesion development was observed, and the injection sites were biopsied for tp0574 mRNA and histological analyses every week until the wound healed. The rabbits in the control group were injected with normal saline instead of rTP0136. Viable T. pallidum in the challenged rabbits was assessed with rabbit infectivity tests. The lesions in the immunized group took longer to heal than those in the control group (42 d vs. 28 d, P < 0.001) and had markedly higher levels of total cellular infiltrates. The mRNA level of tp0574 in the immunized group was significantly higher than that in the control group (P < 0.05). Viable T. pallidum was detected in rabbit lymph nodes in both the immunized and control groups. Our study showed that high titers of anti-TP0136 antibodies promoted the infiltration of inflammatory cells into local lesions and intensified tissue damage, thus delaying wound healing, and had no protective effect on the occurrence of syphilis in the rabbit model.


Assuntos
Adesinas Bacterianas/imunologia , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Sífilis/imunologia , Sífilis/prevenção & controle , Treponema pallidum/imunologia , Cicatrização/imunologia , Adesinas Bacterianas/administração & dosagem , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Vacinas Bacterianas , Modelos Animais de Doenças , Masculino , Coelhos , Soroconversão , Sífilis/microbiologia , Sorodiagnóstico da Sífilis , Ferimentos e Lesões/genética , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/metabolismo , Ferimentos e Lesões/patologia
13.
Front Cell Infect Microbiol ; 10: 618747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33680984

RESUMO

In total, 49 clinical samples were analyzed using two typing schemes, Enhanced Centers for Disease Control and Prevention (ECDC) and multilocus sequence typing (MLST), to describe the molecular characteristics of circulating Treponema pallidum isolates in Xiamen between 2016 and 2017. In addition, genetic mutations potentially related to antibiotic resistance of T. pallidum were also analyzed. Forty five samples were fully typed by ECDC, and 14 different subtypes were detected. The most common subtype was 16d/f (24.4%), followed by 14d/f (20.0%). All forty nine samples were successfully typed by MLST, while only four allelic profiles were identified, including three SS14-like profiles and one Nichols-like profile. Among them, the major allelic profile was 1.1.8 (85.7%). Interestingly, the allelic profile 1.3.1 widespread in Europe and North America was not detected in this region. Additionally, A2058G mutation in 23S rRNA was found in all detectable samples (38/38), and no mutation in 16S rRNA was observed (36/36). Four non-synonymous single-nucleotide polymorphisms in penicillin-binding protein genes were found in the 35 samples eligible for Sanger sequencing. Among them, the variant in tp0500 (P564I) can only be found in the SS14-like isolates. Homoplastic changes in tp0760 (I415F/I415M) and tp0705 (A506V/A506T) were found. Moreover, the variant tp0705 A506V and the variant tp0705 A506T separately appeared in the SS14-like isolates and Nichols-like isolates, respectively. This study showed that the genotypes of T. pallidum isolates in Xiamen between 2016 and 2017 were different from those in other geographic areas. The resistance-related variants of T. pallidum isolates identified in this study could provide awareness for clinicians in the treatment of syphilis.


Assuntos
Tipagem de Sequências Multilocus , China , Resistência Microbiana a Medicamentos , Europa (Continente) , Tipagem Molecular , América do Norte , RNA Ribossômico 16S , Treponema
14.
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.


Assuntos
Infecções do Sistema Nervoso Central/complicações , Diabetes Mellitus/epidemiologia , Dislipidemias/epidemiologia , Hipertensão/epidemiologia , Neurossífilis/complicações , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
15.
ACS Omega ; 4(13): 15530-15538, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31572854

RESUMO

The ligand, bis-ß-diketone with an azobenzene bridge (4,4'-(4,4,4-trifluoro-1,3-butanedione)azobenzene, H 2 L), was prepared for the synthesis of a series of dinuclear lanthanide complexes with the formula [Ln 2 L 3 (DMSO) 4 ] (Ln = Eu3+, Gd3+, Tb3+, and DMSO = dimethyl sulfoxide). X-ray crystallographic analysis reveals that the three complexes are triple-stranded dinuclear structures formed by three bis-ß-diketonate ligands with two lanthanide ions (Ln3+). The trans-to-cis photoisomerization rates of the azobenzene group of the three [Ln 2 L 3 (DMSO) 4 ] complexes in ethanol and acetonitrile solutions are similar to those of the pure H 2 L ligand and other azobenzene-containing mononuclear lanthanide complexes, but the trans-to-cis quantum yields (Φt→c = 10-3) are 1 order of magnitude smaller. The first-order rate constant for the cis-to-trans thermal isomerization at 50 °C of the H 2 L ligand is similar to those of azobenzene derivatives, while those for the [Ln 2 L 3 (DMSO) 4 ] complexes (k iso = 10-4 s-1) are higher than those of the mononuclear azobenzene-containing lanthanide complexes. Furthermore, as the lanthanide ionic radius becomes smaller from Eu3+ to Gd3+ to Tb3+, the thermal isomerization rate constant decreases and the half-life increases. All these results are proposed to arise from the rigidity at both ends of the azo group by coordination to the dinuclear lanthanide ions and the different isomerization mechanisms. These are the first examples of bis-ß-diketonate dinuclear lanthanide complexes with an azobenzene bridge and help illustrate the mechanism of azobenzene isomerization.

16.
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.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , Variação Genética , Sífilis/microbiologia , Treponema pallidum/genética , Adulto , Feminino , Genes Bacterianos , Humanos , Masculino
17.
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.


Assuntos
Monócitos/fisiologia , Treponema pallidum , Movimento Celular , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Células THP-1 , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidor Tecidual de Metaloproteinase-2/genética
18.
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.


Assuntos
Secreções Corporais , Adesão Celular , Movimento Celular , Citocinas/metabolismo , Células THP-1 , Treponema pallidum/metabolismo , Anticorpos Neutralizantes , Quimiocina CCL2/metabolismo , Humanos , Molécula 1 de Adesão Intercelular , Interleucina-6/metabolismo , Miócitos de Músculo Liso , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Sífilis/imunologia , Treponema pallidum/patogenicidade
19.
Exp Cell Res ; 381(1): 150-162, 2019 08 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.


Assuntos
Músculo Liso Vascular/metabolismo , Sífilis/microbiologia , Treponema pallidum/fisiologia , beta-Lactamases/fisiologia , Adesão Celular , Movimento Celular , Células Cultivadas , Quimiocina CCL2/metabolismo , Derme/metabolismo , Derme/patologia , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Músculo Liso Vascular/patologia , NF-kappa B/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Recombinantes , Transdução de Sinais , Sífilis/metabolismo , Sífilis/patologia , Células THP-1 , beta-Lactamases/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
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
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