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1.
Eur J Oral Sci ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31786813

RESUMO

Mediator of DNA damage checkpoint protein 1 (MDC1) is involved in DNA damage repair and has been linked to tumor invasion, metastasis, and prognosis. This study investigated the effects of MDC1 in oral squamous cell carcinoma (OSCC) in vitro and in vivo. RNA interference-mediated knockdown of MDC1 was performed in two OSCC cell lines (Tca-8113 and KB). Real-time PCR and western blotting were performed to determine expression of mRNA and protein, respectively, of MDC1. Cell viability was assessed using the MTT assay. Colony-formation assays were performed by staining with 0.5% crystal violet. Cell migration and invasion were detected by Transwell assays. The role of MDC1 in OSCC was examined in vivo via injection of Tca-8113 cells transfected with MDC1 small interfering (si)RNA or negative-control siRNA into a mouse xenograft model of OSCC. Our results showed that MDC1 knockdown decreased cell proliferation. Inhibition of MDC1 decreased colony formation of Tca-8113 and KB cells by 62% and 68%, respectively, and MDC1 knockdown reduced the number of migratory and invasive cells compared with the control group. Moreover, the xenograft mouse model of MDC1 knockdown showed reduced tumor growth. Our study suggests that MDC1 plays a role in tumorigenesis and might be a potential target for the treatment of patients with OSCC.

2.
J Agric Food Chem ; 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31789033

RESUMO

Pentagalloyl glucose (PGG) has been studied for its valuable biological activities. However, the functional role of PGG in lipid metabolism in vivo is unclear. Here, we investigated the effects of PGG on lipid metabolism and its underlying mechanism in Caenorhabditis elegans (C. elegans). PGG decreased the accumulation of ROS at 800 µM and remarkably increased activities of antioxidant enzymes. PGG decreased significantly fat accumulation in wild-type worms (39.7±5.7% in the normal group and 19.9±4.5% in the high-fat group by Oil Red O; 21.2±2.7% in the high-fat group by Nile red; p<0.001), but fat reduction by PGG was eliminated in skn-1 mutant. The amount and size of lipid droplets in ZXW618 mutant were decreased by PGG. The proportions of unsaturated fatty acids in both conditions were increased by PGG. In addition, the expression levels of fat metabolism genes were significantly changed in both conditions by PGG, which including mdt-15, pod-2, elo-2, fat-6, and fat-7 genes modulated fat synthesis, aak-2 and nhr-49 genes participated in fat consumption and tub-1 gene regulated fat storage. However, fat-5 and acs-2 were downregulated in high-fat worms only, and vit-2 and lipl-4 were downregulated in normal worms only. Our study provided new insights into the role of PGG in alleviating fat accumulation and its underlying mechanism of action in C. elegans.

3.
Biomol Ther (Seoul) ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31791116

RESUMO

The present research work primarily investigated whether spinosin has the potential of improving the pathogenesis of Alzheimer's disease (AD) driven by ß-amyloid (Aß) overproduction through impacting the procession of amyloid precursor protein (APP). Wild type mouse Neuro-2a cells (N2a/WT) and N2a stably expressing human APP695 (N2a/APP695) cells were treated with spinosin for 24 h. The levels of APP protein and secreted enzymes closely related to APP procession were examined by western blot analysis. Oxidative stress related proteins, such as nuclear factor-erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were detected by immunofluorescence assay and western blot analysis, respectively. The intracellular reactive oxygen species (ROS) level was analyzed by flow cytometry, the levels of Aß1-42 were determined by ELISA kit, and Thioflavin T (ThT) assay was used to detect the effect of spinosin on Aß1-42 aggregation. The results showed that ROS induced the expression of ADAM10 and reduced the expression of BACE1, while spinosin inhibited ROS production by activating Nrf2 and up-regulating the expression of HO-1. Additionally, spinosin reduced Aß1-42 production by impacting the procession of APP. In addition, spinosin inhibited the aggregation of Aß1-42. In conclusion, spinosin reduced Aß1-42 production by activating the Nrf2/HO-1 pathway in N2a/WT and N2a/ APP695 cells. Therefore, spinosin is expected to be a promising treatment of AD.

4.
Biosci Rep ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31803920

RESUMO

BACKGROUND: MicroRNA-135(miR-135) is a well-known non-coding RNA that has been demonstrated to participate in tumorigenesis and cancer development; however, the clinical prognostic value of microRNA-135 in digestive system cancers remains controversial. This meta-analysis aims to explore the potential value of microRNA-135 as a prognostic marker for digestive system cancers. METHODS: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible articles published before August 31, 2019. Stata 12.0 software was used to analyze the overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) rates to access the prognostic value of microRNA-135 in digestive system cancers. We then used TCGA datasets to validate the meta-analysis results. Results A total of 1,470 patients from 17 studies were included in this meta-analysis. The pooled results showed that enhanced microRNA-135 expression was significantly associated with poor OR (HR: 1.790; 95%CI: 1.577-2.031; P=0.000), DFS (HR: 1.482; 95%CI: 0.914-2.403; P=0.110), and RFS (HR: 3.994; 95%CI: 1.363-11.697; P=0.012) in digestive system cancers. A sensitivity analysis confirmed the reliability of our findings, and no significant publication bias was observed. CONCLUSION: MicroRNA-135 can be used as a novel biomarker for patients with digestive system cancers. We look forward to future large-scale clinical studies that will investigate the prognostic value of microRNA-135.

5.
Int J Biol Macromol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31758991

RESUMO

Edible and medicinal fungi are one of the major sources for extraction and identification of polysaccharides, which are important biological response modifiers with notable antitumor, hepatoprotective effect and other pharmacological activities. This study aimed to evaluate the hepatoprotective effect of isolated Phellinus linteus polysaccharide (PL-N1) against acetaminophen (APAP) induced liver injury in mice. Mice were treated intragastrical with PL-N1 (10, 50 and 100 mg/kg) and APAP (300 mg/kg) injection. APAP alone caused increased serum aminotransferase levels and changes in hepatic histopathology, promoted oxidative stress by increasing lipid peroxidation and decreasing anti-oxidant enzyme activities, leading to hepatocellular necrosis and reduced liver function. PL-N1 decreased cytochrome P450 2E1 (CYP2E1) expression and hepatic release of cytokines to enhance the level of phase II enzymes. Also, PL-N1 obviously accelerates the metabolism of APAP in the rat model. Molecular docking analysis revealed the α-d-glucopyranosyl exhibit maximum interaction (-8.099) against CYP2E1 as comparably less than standard drug silibinin (-13.767). PL-N1 could be a promising natural substance for ameliorating acute APAP-induced oxidative stress and hepatic injury.

6.
J Cardiothorac Surg ; 14(1): 193, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711516

RESUMO

BACKGROUND: For low risk patients undergoing median sternotomies, no midterm follow-up studies involving sternal healing have been conducted. In this study we evaluated sternal healing in low risk patients by chest CT scan and the risk factors associated with poor healing were analyzed. METHODS: Patients who underwent sternal median incision heart surgery from September 2014 to March 2015 were recruited. The clinical information of these patients during hospitalization was collected, and the CT scan data were submitted to the two chief physicians of the Radiology Department for radiographical sternal healing score determination. Based on the method of wound closure, the patients were divided into sternum plate (Plates) and wire groups (Wires). RESULTS: Forty-four patients were recruited. The mean CT examination time was 17.27 ± 2.30 months postoperatively. Twenty-nine (65.9%) patients met the criteria for radiographic sternal healing. Three segments, including the aortopulmonary window, the main pulmonary artery, and the aortic root, had healed less in comparison to the manubrium segment. Compared to patients in whom 6-7 metal wires were used for sternal closure, healing of the lower sternum was worse in patients in whom five wires were used, but the difference in healing was not statistically significant. Univariate analysis of sternal healing showed that patient age was a risk factor for sternal non-healing. When the patient age was > 45 years, the predicted risk of radiographic sternal non-union was 1.833 (95% CI: 1.343-2.503). CONCLUSIONS: At the mid-term follow-up, 65.9% of patients undergoing median sternotomies demonstrated radiographic sternal healing. Age, but not closure device, was a risk factor for sternal non-healing in low risk patients. Use of more wires had a positive impact on sternal healing. TRIAL REGISTRATION: researchregistry4918, registered 28 May 2019, retrospectively registered.

7.
J Neuroinflammation ; 16(1): 230, 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31747905

RESUMO

BACKGROUND: It is widely accepted that mitochondria have a direct impact on neuronal function and survival. Oxidative stress caused by mitochondrial abnormalities play an important role in the pathophysiology of lipopolysaccharide (LPS)-induced memory impairment. Elamipretide (SS-31) is a novel mitochondrion-targeted antioxidant. However, the impact of elamipretide on the cognitive sequelae of inflammatory and oxidative stress is unknown. METHODS: We utilized MWM and contextual fear conditioning test to assess hippocampus-related learning and memory performance. Molecular biology techniques and ELISA were used to examine mitochondrial function, oxidative stress, and the inflammatory response. TUNEL and Golgi-staining was used to detect neural cell apoptosis and the density of dendritic spines in the mouse hippocampus. RESULTS: Mice treated with LPS exhibited mitochondrial dysfunction, oxidative stress, an inflammatory response, neural cell apoptosis, and loss of dendritic spines in the hippocampus, leading to impaired hippocampus-related learning and memory performance in the MWM and contextual fear conditioning test. Treatment with elamipretide significantly ameliorated LPS-induced learning and memory impairment during behavioral tests. Notably, elamipretide not only provided protective effects against mitochondrial dysfunction and oxidative stress but also facilitated the regulation of brain-derived neurotrophic factor (BDNF) signaling, including the reversal of important synaptic-signaling proteins and increased synaptic structural complexity. CONCLUSION: These findings indicate that LPS-induced memory impairment can be attenuated by the mitochondrion-targeted antioxidant elamipretide. Consequently, elamipretide may have a therapeutic potential in preventing damage from the oxidative stress and neuroinflammation that contribute to perioperative neurocognitive disorders (PND), which makes mitochondria a potential target for treatment strategies for PND.

8.
Future Oncol ; 15(34): 3945-3961, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31746646

RESUMO

Aim: To characterize the epidemiology of appendiceal mucinous adenocarcinoma. Methods: Prognostic factors were evaluated with univariate and multivariate analyses. The results were used to generate a nomogram. Results: The incidence of appendiceal mucinous adenocarcinoma showed a significant upward trend. Multivariate Cox analysis identified 11 independent prognostic factors. The nomogram was based on independent risk factors that were significant in multivariate Cox analysis, and the concordance-index for overall survival and cancer-specific survival were 0.76 (95% CI: 0.71-0.79) and 0.74 (95% CI: 0.70-0.79), respectively. Conclusion: Advanced age, single relationship status, male sex, black race, the presence of distant and regional lymph node metastases, poor differentiation or lack of differentiation, advanced SEER extent of disease, cancer-directed surgery and chemotherapy were independently associated with prognosis.

9.
Medicine (Baltimore) ; 98(48): e18024, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770215

RESUMO

BACKGROUND: The family of tripartite motif (TRIM) proteins, which includes 80 known TRIM protein genes in humans, play a key role in cellular processes. TRIM59, a member of the TRIM family of proteins, has been reported to be involved in the carcinogenesis of multiple types of tumors. However, the prognostic value of TRIM59 in the survival of tumor patients remains controversial. We therefore conducted a meta-analysis to assess the prognostic significance of TRIM59 in cancer patients. MATERIALS AND METHODS: PubMed, Embase, VIP, CNKI and Wanfang Data were searched for eligible reports published before September 30, 2018. The hazard ratio (HR) and 95% confidence intervals (CIs) were adopted to estimate the association between TRIM59 and overall survival (OS). RESULTS: Six studies with 1584 patients were included to assess the effect. The results showed that high levels of TRIM59 were significantly associated with poor OS in cancer patients (HR = 1.43, 95%CI: 1.24-1.66, P < .001), indicating that higher TRIM59 expression could be an independent prognostic factor for poor survival in cancer patients. CONCLUSION: Our meta-analysis suggests that higher TRIM59 expression predicts poor prognosis in cancer patients, and it may therefore serve as a promising prognostic factor.

10.
Biomol Ther (Seoul) ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31649209

RESUMO

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic ß-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic ß-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic ß-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin- induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic ß-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 µM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic ß-cells through regulation of ERα expression.

11.
Dalton Trans ; 48(39): 14678-14686, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31536090

RESUMO

5,10,15,20-Tetrakis (4-aminophenyl) Mn-porphyrin and 2,4,6-trihydroxy-1,3,5-benzenetricarbaldehyde were combined into a new mesoporous organic framework by a Schiff-base-type reaction. Sn(OH)x helped in improving the yield of this Mn-COF. Further, S-containing dimethyl sulfoxide solvent molecules were tripped in the pores of Mn-COFs. Such heteroatoms-enriched Mn-COFs could be used to fabricate Mn-S-N-doped carbons (Mn-S-N-Cs) with abundant mesopores. In particular, Mn-Nx sites could be partly maintained and highly dispersed on the surface of Mn-S-N-Cs; impressively, Mn-N-S-C-800 could be catalyzed for oxygen electroreduction in both alkaline and acidic media. Its half-wave potential reached 0.86 V in 0.1 M KOH, with a very low yield of HO2- (4.02%) and better durability. The thermal conversion of the synthesized mesoporous porphyrinic Mn-COFs provided an efficient strategy for fabricating high-dispersion Mn-Nx sites on mesoporous S and N codoped carbons.

12.
Glob Chang Biol ; 2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31495039

RESUMO

Recycling of livestock manure to agricultural land may reduce the use of synthetic fertilizer and thereby enhance the sustainability of food production. However, the effects of substitution of fertilizer by manure on crop yield, nitrogen use efficiency (NUE), and emissions of ammonia (NH3 ), nitrous oxide (N2 O) and methane (CH4 ) as function of soil and manure properties, experimental duration and application strategies have not been quantified systematically and convincingly yet. Here, we present a meta-analysis of these effects using results of 143 published studies in China. Results indicate that the partial substitution of synthetic fertilizers by manure significantly increased the yield by 6.6% and 3.3% for upland crop and paddy rice, respectively, but full substitution significantly decreased yields (by 9.6% and 4.1%). The response of crop yields to manure substitution varied with soil pH and experimental durations, with relatively large positive responses in acidic soils and long-term experiments. NUE increased significantly at a moderate ratio (<40%) of substitution. NH3 emissions were significantly lower with full substitution (62%-77%), but not with partial substitution. Emissions of CH4 from paddy rice significantly increased with substitution ratio (SR), and varied by application rates and manure types, but N2 O emissions decreased. The SR did not significantly influence N2 O emissions from upland soils, and a relative scarcity of data on certain manure characteristic was found to hamper identification of the mechanisms. We derived overall mean N2 O emission factors (EF) of 0.56% and 0.17%, as well as NH3 EFs of 11.1% and 6.5% for the manure N applied to upland and paddy soils, respectively. Our study shows that partial substitution of fertilizer by manure can increase crop yields, and decrease emissions of NH3 and N2 O, but depending on site-specific conditions. Manure addition to paddy rice soils is recommended only if abatement strategies for CH4 emissions are also implemented.

13.
Psychol Health Med ; : 1-8, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31532238

RESUMO

Breast and cervical cancer screening are associated with dramatically reduced cancer mortality. Mental illnesses have been demonstrated to influence preventative behaviours. This study aims to explore whether anxiety or depressive symptoms is associated with breast and cervical cancer screening. We analyzed data (n = 3104) from the 2013 Brazos Valley Community Health Assessment. The GAD-7 Scale was used to assess the anxiety level, and PHQ-2 was used to assess the depressive symptoms. Stata 15.0 statistical software was used to perform descriptive and logistic regression analysis. Overall, 80.61% of women in each sample met breast cancer or cervical cancer screening guidelines, respectfully. Anxiety was associated with missing breast and cervical cancer screening, but the association was only significant for cervical cancer (OR = 1.430, CI = 1.009, 2.026), not for breast cancer (OR = 1.406, CI = .952, 2.078). Depressive symptom was significantly associated with missing breast (OR = 1.502, CI = 1.051, 2.149) and cervical (OR = 1.689, CI = 1.208, 2.362) cancer screening after controlling for demographics. Women with depressive symptoms and anxiety had higher odds of missing breast and cervical cancer screening. Health promotion programs should consider targeting individuals with anxiety and depression to improve cancer-screening rates..

15.
Ann Rheum Dis ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537547

RESUMO

OBJECTIVES: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. METHODS: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. RESULTS: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. CONCLUSIONS: Low-dose IL-2 might be effective and tolerated in treatment of SLE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137).

16.
Food Funct ; 10(9): 5827-5842, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31463498

RESUMO

In this study, we aim to assess possible impacts of essential oil (SEO) from Schisandra chinensis (Turcz.) Baill. (S. chinensis) on mice with cognition impairment. Our data showed that SEO improved the cognitive ability of mice with Aß1-42 or lipopolysaccharides (LPS)-induced Alzheimer's disease (AD) and suppressed the production of tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) in the hippocampus. Furthermore, SEO inhibited p38 activation, but had little effect on other signaling proteins in the MAPK family, such as extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun N-terminal kinase 1/2 (JNK). The SEO and BV-2 microglia co-culture was performed to further confirm the anti-inflammatory activity of SEO. The data showed that SEO decreased nitric oxide (NO) levels in LPS-stimulated BV-2 microglia and significantly blocked LPS-induced MAPKs activation. Taken together, these findings suggested that SEO produces anti-AD effects on AD mice partly by modulating neuroinflammation through the NF-κB/MAPK signaling pathway.

17.
Environ Sci Pollut Res Int ; 26(29): 29736-29747, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31402438

RESUMO

Developing low cost and efficient method for the treatment of electroplating wastewater containing heavy metals complexed with chelating agent has attracted increasing attention in industrial wastewater treatment. This study involved a system combining Fenton oxidation (FO) and recycled ferrite (RF) process for treating synthetic solution containing Ni(II)-EDTA at ambient temperature. In this system, the FO reaction can produce hydroxyl radicals with high redox potential to decomplex the metal-organic complexes and degrade the organics, thereby enhancing the removal efficiency of heavy metals. The RF process is to incorporate the non-iron metal into the spinel ferrites at room temperature, and stabilize the sludge. As a result, the toxicity characteristic leaching procedure can fulfill the relevant standards. Furthermore, the ferrous ions in Fenton reaction could be used as the source of irons in RF process. After treatment by the combined process, the effluent water fulfills the relevant standard in China. In comparison with conventional alkaline precipitation, the sludge sedimentation velocity of FO-RF is 2.16 times faster than that of conventional alkaline precipitation and the volume of sludge is reduced by half, which strongly demonstrated the advantages of the presented FO-RF system and indicated the huge potential for the treatment of EDTA-chelated nickel.

18.
Environ Sci Pollut Res Int ; 26(29): 29789-29798, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407258

RESUMO

In this study, environment-friendly inorganic basalt fiber (BF) was used as bio-carrier for wastewater treatment. To enhance the bio-affinity, raw BF was modified by grafting the diethylamino functional groups to make the surface more hydrophilic and electro-positive. Contact angle and zeta potential of modified basalt fiber (MBF) were characterized. The capacity of MBF bio-carriers was evaluated by microorganism immobilization tests. To explain the mechanism of capacity enhancement by modification, the profiles of total interaction energy barrier between raw BF (or MBF) and bacteria (Escherichia coli, E. coli) were discussed based on the extended Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. The results showed the contact angle of fiber decreased from 89.71° to 63.08° after modification, and zeta potential increased from - 18.53 to +10.58 mV. The microorganism immobilization tests showed that the surface modification accelerated the initial bacterial adhesion on fiber. The total interaction energy barrier between MBF and E. coli disappeared as a result of electrostatic and hydrophilic attractive forces, and enhanced the irreversible adhesion. MBF bio-carrier medium provides a promising alternative to conventional bio-carrier materials for wastewater treatment. Graphical abstract.

19.
J Mater Chem B ; 7(30): 4620-4629, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31364679

RESUMO

A novel probe, 3-benzyl-2-(N-ethylcarbazole-3-vinyl)-benzothiazolium bromide (L), was synthesized and utilized for the specific detection of cyanide ions in neutral aqueous solution (HEPES buffer, pH 7.4). This probe displays a fast response through visible colorimetric and fluorogenic changes toward CN-, allowing for ratiometric sensing of cyanide in aqueous media. The ratiometric response is due to the breaking of the extensive π-conjugation and the intramolecular charge transfer (ICT) by the nucleophilic conjugation addition of cyanide to L, which is ascertained by NMR and ESI-MS analysis as well as density functional theory (DFT) calculations. The detection limit of CN- (3.39 × 10-7 M) is well below the limit recommended in the World Health Organization (WHO) guidelines for drinking water. Moreover, fluorescence co-localization studies demonstrate that L is a specific mitochondria-targeting fluorescent probe. As far as we are aware, compound L is the first mitochondria-targeting probe for cyanide detection and can be used for sensing CN- in living cells with dual channel ratiometric fluorescence imaging.

20.
PLoS One ; 14(7): e0218990, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31310631

RESUMO

Abdominal aortic aneurysm (AAA) is a life-threatening immunological disease responsible for 1 to 2% of all deaths in 65 year old or older individuals. Although mononuclear cell infiltrates have been demonstrated in AAA lesions and autoimmunity may be responsible for the initiation and account for the propagation of the disease, the information available about the pathogenesis of AAA is limited. To examine whether AAA lesions from patients with AAA contain clonally expanded α-chain TCR transcripts, we amplified by the non-palindromic adaptor-PCR (NPA-PCR)/Vα-specific PCR and/or the Vα-specific PCR these α-chain TCR transcripts. The amplified transcripts were cloned and sequenced. Substantial proportions of identical α-chain TCR transcripts were identified in AAA lesions of 4 of 5 patients, demonstrating that clonally expanded T cells are present in these AAA lesions. These results were statistically significant by the bimodal distribution. Three of 5 of these patients were typed by DNA-based HLA-typing and all three expressed DRB1 alleles containing the DRßGln70 amino acid residue that has been demonstrated to be associated with AAA. All three patients exhibited clonally expanded T cells in AAA lesions. Four of the 5 patients with AAA who exhibited clonal expansions of α-chain TCR transcripts, also exhibited clonal expansions of ß-chain TCR transcripts in AAA lesions, as we have demonstrated previously (J Immunol 192:4897, 2014). αß TCR-expressing T cells infiltrating AAA lesions contain T-cell clones which have undergone proliferation and clonal expansion in vivo in response to as yet unidentified specific antigens that may be self or nonself. These results provide additional evidence supporting the hypothesis that AAA is a specific antigen-driven T-cell autoimmune disease.

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