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1.
Sci Total Environ ; 727: 138629, 2020 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-32330720

RESUMO

High concentrations of arsenic (As) occur in acid mine drainage (AMD), while the mechanisms governing its distribution along the flow of AMD are not fully understood. In this study, As species distribution was surveyed along the flow of an AMD in Jiaole coal mine in a typical kast area, in which length of creek is about 1100 m. AMD from the discharging source contained 1754.2 µg/L As (1570.0 µg/L in As (III)) and 644.1 mg/L Fe (all in Fe (II)) at pH 3.45. Both As and Fe concentrations decreased drastically to trace levels along the flow in the creek. As(III) oxidation to As(V) and Fe(II) oxidation to Fe(III) were discovered in a short distance from the discharging source. Lab experiments were performed to unveil the mechanisms governing As and Fe species distribution. Biological mechanism governed As(III) and Fe(II) oxidation in the AMD phase without contact with solid matrix, while different mechanisms governed the oxidation in the presence of solid matrix at different stages of AMD flow. At the beginning of AMD discharge, its contact with the soil matrix in rich of carbonate minerals in the karst area facilitated Fe(II) oxidation by O2 due to pH rise, which generated reactive oxidants for As(III) oxidation and iron oxyhydroxides for As adsorption or co-precipitation. Along the AMD flow, bacteria in the underlying sediments profoundly accelerated the biological oxidation of As(III) and Fe(II) as well as the co-precipitation into the sediments. Findings of this study deepen the understanding of As transport and transformation along the AMD flow, particularly in karst areas.

2.
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.

3.
Environ Sci Technol ; 54(8): 4942-4951, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32202769

RESUMO

Significance of reactive oxygen species (ROS) in subsurface has been increasingly documented in recent years, whereas the mechanisms controlling ROS production and distribution in subsurface remain poorly understood. Here we show that water table fluctuations regulate the dynamics of hydrogen peroxide (H2O2) production and distribution in unconfined aquifers. In one hydrological year, we measured the dynamics of H2O2 distribution in an unconfined aquifer impacted by a 14 m water level fluctuation in the adjacent Yangtze River. H2O2 concentrations in groundwater attained up to 123 nM at rising water table stage in summer, but were low or even below the detection limit at the other stages of stable and falling water table. Lab experiments and kinetic models revealed that abiotic reactions between dissolved O2 and reduced species (i.e., Fe(II) and organic matter) were responsible for H2O2 production in the aquifers. Both field observations and reactive transport models unveiled that a rising water table developed a thermodynamically unstable banded zone in the unconfined aquifer in which elevated coexisting dissolved O2 and reduced species favored abiotic H2O2 production. Our findings provide fundamentals for understanding and predicting ROS distribution in unconfined aquifers, and constrain the significance of ROS in aquifers to specific temporal and spatial domains.

4.
Int Immunopharmacol ; 83: 106428, 2020 Mar 24.
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.

5.
Cancer Nurs ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32132367

RESUMO

BACKGROUND: Despite tremendous progress in understanding the unmet needs of cancer survivors, our understanding of oncology nurses' perspectives and practices in the delivery of survivorship care is inadequate. OBJECTIVES: The aims of this study were to assess oncology nurses' perceptions about their responsibility and frequency of delivery of survivorship care to cancer patients and to examine the factors influencing such care. METHODS: A cross-sectional survey was administered to 81 nurses working in the oncology unit of hospitals in Hong Kong. Participants completed an investigator-developed questionnaire designed to assess oncology nurses' perceptions of responsibility, practices, and barriers regarding the provision of survivorship care for cancer patients. RESULTS: Results revealed discrepancies between oncology nurses' perceptions of responsibility and practices, with high levels of perceptions of various survivorship care as their responsibility but low levels in delivery of such care. Despite that discussing and managing pain was agreed by most oncology nurses as their responsibility (95.1%), 34.6% of them have never managed survivors' pain. Besides, 33.3% of nurses have never discussed and managed survivors' sexuality issues. Lack of time (79.0%), inadequate educational resources for family members (59.3%), and lack of knowledge and skills (54.4%) were major factors that impeded survivorship care provision. CONCLUSIONS: This study provides further evidence for inadequacies of oncology nurses in delivering survivorship care and their perceived barriers. Further studies are required to enhance our understanding of the strategies for improving the quality of cancer survivorship care. IMPLICATIONS FOR PRACTICE: Results underscore the need to develop educational resources and enhance training in survivorship care for oncology nurses.

6.
Environ Sci Technol ; 54(5): 2975-2984, 2020 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-32023045

RESUMO

It has been documented that contaminants could be degraded by hydroxyl radicals (•OH) produced upon oxygenation of Fe(II)-bearing sediments. However, the dependence of contaminant degradation on sediment characteristics, particularly Fe(II) species, remains elusive. Here we assessed the impact of the abundance of Fe(II) species in sediments on contaminant degradation by •OH during oxygenation. Three natural sediments with different Fe(II) contents and species were oxygenated. During 10 h oxygenation of 200 g/L sediment suspension, 2 mg/L phenol was negligibly degraded for sandbeach sediment (Fe(II): 9.11 mg/g), but was degraded by 41% and 52% for lakeshore (Fe(II): 9.81 mg/g) and farmland (Fe(II): 19.05 mg/g) sediments, respectively. •OH produced from Fe(II) oxygenation was the key reactive oxidant. Sequential extractions, X-ray diffraction, Mössbauer, and X-ray absorption spectroscopy suggest that surface-adsorbed Fe(II) and mineral structural Fe(II) contributed predominantly to •OH production and phenol degradation. Control experiments with specific Fe(II) species and coordination structure analysis collectively suggest the likely rule that Fe(II) oxidation rate and its competition for •OH increase with the increase in electron-donating ability of the atoms (i.e., O) complexed to Fe(II), while the •OH yield decreases accordingly. The Fe(II) species with a moderate oxidation rate and •OH yield is most favorable for contaminant degradation.


Assuntos
Radical Hidroxila , Minerais , Compostos Ferrosos , Oxirredução , Fenol
7.
J Hazard Mater ; 386: 121945, 2020 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-31893557

RESUMO

Clayed fractions in aquifers are generally deemed to be detrimental for in situ chemical oxidation (ISCO) treatments due to the difficulty of oxidant injection/transport and the retention/rebound of contaminants. Using a model clay mineral nontronite and a real sediment, here we show that the component of structural Fe(II) in clay minerals is particularly effective in activating hydrogen peroxide (H2O2) to hydroxyl radicals (OH) for contaminants degradation under pH-neutral conditions. Using reduced nontronite (Fe(II)/Fetotal : 40 %) as a model Fe(II)-bearing clay mineral, 2 mg/L trichloroethylene (TCE) was degraded by 82.0 % and 95.3 %at 2.5 min and 30 min, respectively, under the condition of 0.6 g/L reduced nontronite, 0.5 mM H2O2and pH 7.5. Reactive structural Fe(II) in nontronite was responsible for the initial quick reaction. The degradation was also efficient for phenol, benzoic, toluene and naphthalene, but exhibited higher efficiencies for those with stronger sorption to nontronite. With similar concentrations of H2O2 and Fe(II), nontronite-activated H2O2 at pH 7.5 led to similar efficiencies of TCE degradation and H2O2 utilization to classic homogeneous Fenton at pH 3. A real clayed sediment showed similar performance in activating H2O2 for contaminant degradation. Our findings implicate that clayed fractions in aquifers may probably contribute to contaminants degradation in H2O2-based ISCO treatments.

8.
Hepatology ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31680287

RESUMO

Embryonic stem cell related transcription factors are central to the establishment and maintenance of stemness and pluripotency; and their altered expression play key roles in tumors including hepatocellular carcinoma (HCC), a malignancy with no effective treatment. Here, we report the embryonic stem cell marker REX1 (also known as zinc finger protein 42, ZFP42) to be selectively down-regulated in HCC tumors. Deficiency of REX1 in HCC was attributed to a combination of hypermethylation at its promoter as well as histone modification by methylation and acetylation. Clinically, hypermethylation of REX1 was closely associated with neoplastic transition and advanced tumor stage in humans. Functionally, silencing of REX1 potentiated the tumor-initiating and metastasis potential of HCC cell lines and xenografted tumors. Lentivirus-mediated Rex1 ablation in liver of male immunocompetent mice with HCC induced by hydrodynamic tail vein injection of protooncogenes enhanced HCC development. Transcriptome profiling studies revealed REX1 deficiency in HCC cells to be enriched with genes implicated in focal adhesion and MAPK signaling. From this lead, we subsequently found REX1 to bind to the promoter region of MKK6, thereby obstructing its transcription, resulting in altered p38 MAPK signaling. Conclusion Our work describes a critical repressive function of REX1 in maintenance of HCC cells by regulating MKK6 binding and p38 MAPK signaling. REX1 deficiency induced enhancement of p38 MAPK signaling, leading to F-actin reorganization and activation of NRF2-mediated oxidative stress response, which collectively contributed to enhanced stemness and metastatic capabilities of HCC cells.

9.
Environ Sci Technol ; 53(23): 13767-13775, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31702131

RESUMO

Fe(II)-bearing clay minerals are important electron sources for Cr(VI) reduction in subsurface environments. However, it is not clear how iron (oxyhydr)oxides impact Cr(VI) reduction by Fe(II)-bearing clays as the two minerals can coexist in soil and sediment aggregates. This study investigated Cr(VI) reduction in the mixed suspensions of reduced nontronite NAu-2 (rNAu-2) and ferrihydrite (Fe(II)/Cr(VI) = 3:1). When the mineral premixing time increased from 0 to 72 h, Cr(VI) reduction was accelerated prominently in the initial stage, while Cr(VI) sorption was inhibited drastically. Mineral premixing led to electron transfer from structural Fe(II) in rNAu-2 to ferrihydrite with formation of reactive-surface-associated Fe(II), which catalyzed ferrihydrite transformation to lepidocrocite. Reactive-surface-associated Fe(II) accelerated Cr(VI) reduction initially, and ferrihydrite transformation to lepidocrocite was responsible for the inhibited sorption. When the reactive-surface-associated Fe(II) was consumed in the initial stage, the Cr(VI) reduction rate decreased dramatically due to the limitation of slow electron transfer from structural Fe(II) in rNAu-2 to surface-reactive sites. The main reduction sites shifted from rNAu-2 to ferrihydrite/lepidocrocite when rNAu-2 coexisted with ferrihydrite. Our findings demonstrate that electron transfer between minerals has important implications for Cr(VI) and other high-valence contaminant reduction by Fe(II)-bearing clay minerals in subsurface environments.


Assuntos
Compostos Férricos , Óxidos , Cromo , Argila , Compostos Ferrosos , Minerais , Oxirredução
10.
Hepatology ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610028

RESUMO

The survival benefit of sorafenib for hepatocellular carcinoma (HCC) patients is unsatisfactory due to the development of adaptive resistance. Increasing evidence has demonstrated that drug resistance can be acquired by cancer cells by activating a number of signaling pathways via receptor tyrosine kinases (RTKs), nevertheless the detailed mechanism for the activation of these alternative pathways is not fully understood. Given the physiological role of Src-homology 2 domain-containing phosphatase 2 (SHP2) as a downstream effector of many RTKs for activation various signaling cascades, we first found that SHP2 was markedly upregulated in our established sorafenib-resistant cell lines as well as patient-derived xenograft (PDTX). Upon sorafenib treatment, adaptive resistance was acquired in HCC cells via activation of RTKs including AXL, EGFR, EPHA2 and IGF1R, leading to RAS/MEK/ERK and AKT reactivation. We found that SHP2 inhibitor SHP099 abrogated sorafenib resistance in HCC cell lines and organoid culture in vitro by blocking this negative feedback mechanism. Interestingly, this sensitization effect was also mediated by induction of cellular senescence. SHP099 in combination with sorafenib was highly efficacious in the treatment of xenografts and genetically engineered models of HCC. In conclusion, SHP2 blockade by SHP099 in combination with sorafenib attenuated the adaptive resistance to sorafenib by impeding RTK-induced reactivation of the MEK/ERK and AKT signaling pathways. SHP099 in combination with sorafenib may be a novel and safe therapeutic strategy against HCC.

11.
Environ Sci Technol ; 53(21): 12629-12638, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31603317

RESUMO

Iron electrocoagulation (Fe EC) is normally considered as a separation process. Here, we found that Fe(II)-O2 interactions in Fe EC systems could produce reactive oxidants, mainly hydroxyl radicals (•OH), for refractory organic contaminant transformation. Production of reactive oxidants, probed by benzoate conversion to p-hydroxybenzoic acid (p-HBA), depended on dissolved oxygen (DO) concentration and Fe(II) speciation. Measurable levels of DO were required for significant p-HBA production. Fe precipitates evolved from lepidocrocite to magnetite when DO decreased to below the detection limit. Both experiments and kinetic modeling suggest that the main Fe(II) species contributing to reactive oxidants (mainly •OH) production changed from aqueous Fe(II) initially to lepidocrocite-sorbed Fe(II) with progressive precipitates formation. When DO was not measurable at high currents (≥50 mA or 100 mA/L), reactive oxidant production was ineffective because of pH rise and Fe(II) preservation in magnetite, but it could be enhanced drastically by aeration. The reactive oxidants produced at 30 mA (or 60 mA/L) could degrade about 47% of 10 µM aniline and 34% of sulfanilamide within 6 h of Fe EC treatment. Our findings highlight the importance of reactive oxidants for refractory organic contaminants oxidation in Fe EC systems.


Assuntos
Ferro , Oxidantes , Eletrocoagulação , Radical Hidroxila , Oxirredução
12.
J Glob Antimicrob Resist ; 20: 260-265, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31493529

RESUMO

OBJECTIVES: This study evaluated disc diffusion tests and agar screening for detecting mecA-mediated oxacillin resistance in Staphylococcus lugdunensis (S. lugdunensis). METHODS: Staphylococcus lugdunensis isolates (n = 179) from diverse sources in Hong Kong during 1998-2018 were investigated by disc diffusion tests (cefoxitin and oxacillin) and inoculation onto oxacillin (1 µg/mL and 2 µg/mL) and chromID methicillin-resistant Staphylococcus aureus (MRSA) agars. The results were compared with mecA PCR as the reference. Isolates with discordant results were further tested by MIC and penicillin-binding protein 2a (PBP2a) assays. RESULTS: Cefoxitin and oxacillin zone diameters were not distributed in ways that allowed reliable division of the mecA-positive (n = 52) and mecA-negative (n = 127) isolates. On applying the 2019 Clinical Laboratory Standards Institute (CLSI) M100 breakpoints for cefoxitin disc results, there was 88% categorical agreement (CA) and 40% very major error (VME). Screening using 2 µg/mL oxacillin agar reliably differentiated mecA-positive and mecA-negative isolates (100% CA) without any major error (ME) or VME results. The performance of screening using 1 µg/mL oxacillin agar or ChromID MRSA agar was variable (74-89% CA, 0-38% ME and 0-37% VME). The mecA-positive isolates (n = 21) that could not be detected by the cefoxitin disc test were further characterised. The cefoxitin MIC for all 21 isolates was ≤4 µg/mL. Twenty isolates had an oxacillin MIC of 1-2 µg/mL and one had an oxacillin MIC of 4 µg/mL. All had positive PBP2a results and were typed as clonal cluster 27/SCCmec V. CONCLUSIONS: These findings highlight the need to evaluate phenotypic methods using mecA-positive S. lugdunensis with different oxacillin resistance phenotypes.

13.
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
14.
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
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.
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.

17.
Asia Pac J Clin Oncol ; 15(5): e142-e146, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30761749

RESUMO

AIM: The aim of the study was to translate the Cancer Survivors' Unmet Needs (CaSUN) scale into Chinese, and then test its psychometric properties, for cancer survivors in Hong Kong. METHODS: The original questionnaire was translated from English into traditional Chinese (CaSUN-Chi), following standardized procedures. An expert panel was invited to assess the items' content validity, and pilot test on 15 patients to evaluate its readability. The sample for psychometric evaluation was drawn from a large multinational study assessing unmet needs of cancer survivors, with a convenience sample of 300 was recruited. Cronbach's α coefficient was used to assess the internal consistency of the scale, and confirmatory factor analysis to evaluate its construct validity. RESULTS: The CaSUN-Chi had good readability and high content validity (S-CVI 0.98). Cronbach's α for the entire scale was 0.93 and 0.71-0.91 for the five subscales. Confirmatory factor analysis indicated that the five-factor structure of the CaSUN-Chi was good fit to the data (CFI = 0.99, AGFI = 0.98, RMSEA = 0.054, SRMR = 0.071). CONCLUSION: The CaSUN-Chi showed desirable psychometric properties for assessing unmet needs of cancer survivors in Hong Kong. Using the newly translated scale to identify individual supportive care unmet needs can bridge the gap between patients' experiences and expectations, and improve healthcare provision and resource allocation.


Assuntos
Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Sobreviventes de Câncer/psicologia , Determinação de Necessidades de Cuidados de Saúde/normas , Psicometria/métodos , Qualidade de Vida , Traduções , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
18.
PLoS Negl Trop Dis ; 13(2): e0006855, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30789907

RESUMO

BACKGROUND: The highly variable tprK gene of Treponema pallidum has been acknowledged to be one of the mechanisms that causes persistent infection. Previous studies have mainly focused on the heterogeneity in tprK in propagated strains using a clone-based Sanger approach. Few studies have investigated tprK directly from clinical samples using deep sequencing. METHODS/PRINCIPAL FINDINGS: We conducted a comprehensive analysis of 14 primary syphilis clinical isolates of T. pallidum via next-generation sequencing to gain better insight into the profile of tprK in primary syphilis patients. Our results showed that there was a mixture of distinct sequences within each V region of tprK. Except for the predominant sequence for each V region as previously reported using the clone-based Sanger approach, there were many minor variants of all strains that were mainly observed at a frequency of 1-5%. Interestingly, the identified distinct sequences within the regions were variable in length and differed by only 3 bp or multiples of 3 bp. In addition, amino acid sequence consistency within each V region was found among the 14 strains. Among the regions, the sequence IASDGGAIKH in V1 and the sequence DVGHKKENAANVNGTVGA in V4 showed a high stability of inter-strain redundancy. CONCLUSIONS: The seven V regions of the tprK gene in primary syphilis infection demonstrated high diversity; they generally contained a high proportion sequence and numerous low-frequency minor variants, most of which are far below the detection limit of Sanger sequencing. The rampant variation in each V region was regulated by a strict gene conversion mechanism that maintained the length difference to 3 bp or multiples of 3 bp. The highly stable sequence of inter-strain redundancy may indicate that the sequences play a critical role in T. pallidum virulence. These highly stable peptides are also likely to be potential targets for vaccine development.


Assuntos
Proteínas da Membrana Bacteriana Externa/genética , DNA Bacteriano/genética , Técnicas de Amplificação de Ácido Nucleico , Sífilis/microbiologia , Treponema pallidum/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Eur Neurol ; 80(1-2): 82-86, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30343296

RESUMO

BACKGROUND: The differential diagnosis of general paresis (GP) and non-neurosyphilis (NS) dementia is not clearly defined. The present study examined the differences in clinical and laboratory features of GP and non-NS dementia. MATERIALS AND METHODS: We retrospectively examined clinical and laboratory features of 85 GP patients and 196 non-NS dementia patients. Data were collected from Zhongshan Hospital between June 2005 and June 2014. RESULTS: The GP group had a higher percentage of males (83.53%, 71/85) and younger median age ([52 [interquartile range 47.0-61.0] vs. 76 [68.3-82.0] years) than the non-NS dementia group. GP have higher Mini-Mental State Examination (MMSE; Z = -5.809; p = 0.000) than non-NS dementia. Distribution of CDR scores were significantly higher in the non-NS group than GP group (χ2 = 29.153; p = 0.000). The laboratory findings showed significantly different total cholesterol (CH), low-density lipoprotein CH and homocysteine levels between the 2 groups. Serologic testing for syphilis revealed that the GP group had higher seropositive rapid plasma reagin (RPR) and Treponema pallidum particle agglutination (TPPA) rates than the non-NS dementia group (96.47% [82/85] vs. 0.51% [1/196], Z = -2.663, p = 0.008; 100% [85/85] vs. 1.02% [2/196], Z = -2.663, p = 0.008). Interestingly, cerebrospinal fluid (CSF) biochemical indices, including pleocytosis rates, increased protein levels, and positive RPR and TPPA rates in the GP group were higher than that in the non-NS dementia group. CONCLUSIONS: Based on these preliminary data, patients with clinically evident symptoms of dementia, especially middle-aged males, should undergo blood tests for syphilis. All patients with positive serology results should undergo CSF examinations to diagnose GP dementia before further pharmaceutical and behavioral interventions.


Assuntos
Demência/diagnóstico , Neurossífilis/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Demência/sangue , Demência/líquido cefalorraquidiano , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Neurossífilis/sangue , Neurossífilis/líquido cefalorraquidiano , Estudos Retrospectivos , Testes Sorológicos , Treponema pallidum
20.
Front Microbiol ; 9: 2272, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30294321

RESUMO

The emergence of New Delhi metallo-ß-lactamase (NDM) in common enterobacterial species is a major concern for healthcare. Early reports have revealed that the spread of NDM involved diverse and heterogeneous plasmids. Recently, the involvement of a rare, IncX3 subtype plasmid has been increasingly recognized. Here, we studied the prevalence of IncX plasmid subtypes in 198 carbapenem-resistant Enterobacteriaceae, originating from a territory-wide active surveillance in Hong Kong in 2016. The complete sequences and biological features of the bla NDM-carrying plasmids were investigated. A total of 62 NDM-type, 21 OXA-48 type, 14 IMP-type, 8 KPC-type, 4 IMI-type producers, and 89 non-carbapenemase-producers were tested for presence of IncX subtypes. IncX3 (n = 60) was the most common subtype, followed by IncX4 (n = 6) and IncX1 (n = 2). The prevalence of IncX3 subtype in isolates producing NDM, other carbapenemase types and non-carbapenemase producers were 75.8, 21.3, and 3.4%, respectively (P < 0.001). An IncX3 plasmid (size ∼50 kb) was confirmed to carry bla NDM in 47 isolates of different enterobacterial species. Thirteen IncX3 plasmids originating from six healthcare regions in Hong Kong were completely sequenced. The results showed that the IncX3 plasmids carrying bla NDM share a high degree of sequence identity with a previously reported plasmid, pNDM-HN380 (GenBank accession JX104760), over the backbone and genetic load regions. A blast search further revealed the occurrence of identical or nearly identical IncX3 plasmids carrying bla NDM in other part of China, Korea, Myanmar, India, Oman, Kuwait, Italy, and Canada. Two IncX3 carrying bla NDM were investigated further. Conjugation experiments demonstrated that the IncX3 plasmids could be efficiently transferred to multiple enterobacterial species at frequencies that are comparable or higher than the epidemic IncFII plasmid carrying bla CTX-M (pHK01). In addition, efficient transfer of the NDM plasmids occurred over a range of temperatures. In conclusion, this study demonstrated the important role played by IncX3 in the dissemination of NDM and the occurrence of pNDM-HN380-like plasmids in geographically widespread areas. The high mobility of IncX3 plasmid across different enterobacterial species highlights the ability of this plasmid replicon to be an important vehicle in worldwide dissemination of NDM.

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