RESUMO
BACKGROUND: Aspergillosis is a common cause of morbidity and mortality in immunocompromised populations. PU.1 is critical for innate immunity against Aspergillus fumigatus (AF) in macrophages. However, the molecular mechanism underlying PU.1 mediating immunity against AF infection in human alveolar macrophages (AMs) is still unclear. METHODS: In this study, we detected the expressions of PU.1, CD23, p-ERK, CCL20 and IL-8 and key inflammatory markers IL-1ß, IL-6, TNF-α and IL-12 in human THP-1-derived macrophages (HTMs) or PU.1/CD23-overexpressed immunodeficient mice with AF infection. Moreover, we examined these expressions in PU.1-overexpressed/interfered HTMs. Additionally, we detected the phagocytosis of macrophages against AF infection with altered PU.1 expression. Dual luciferase, ChIP and EMSAs were performed to detect the interaction of PU.1 and CD23. And we invested the histological changes in mouse lung tissues transfected with PU.1/CD23-expressing adenoviruses in AF infection. RESULTS: The results showed that the expressions of PU.1, CD23, p-ERK, CCL20, IL-8, IL-1ß, IL-6, TNF-α and IL-12 increased significantly with AF infection, and PU.1 regulated the later 8 gene expressions in HTMs. Moreover, CD23 was directly activated by PU.1, and overexpression of CD23 in PU.1-interfered HTMs upregulated IL-1ß, IL-6, TNF-α and IL-12 levels which were downregulated by PU.1 interference. PU.1 overexpression strengthened the phagocytosis of the HTMs against AF. And injection of PU.1/CD23-expressing adenoviruses attenuated pathological defects in immunodeficient mouse lung tissues with AF infection. Adenovirus (Ad)-PU.1 increased the CD23, p-ERK, CCL20, IL-8 levels. CONCLUSIONS: Our study concluded that PU.1-CD23 signaling mediates innate immunity against AF in lungs through regulating inflammatory response. Therefore, PU.1-CD23 may be a new anti-aspergillosis therapeutic for the treatment of invasive aspergillosis with the deepening of gene therapy and its wide application in the clinic.
Assuntos
Aspergilose , Aspergillus fumigatus , Humanos , Animais , Camundongos , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6 , Interleucina-8 , Pulmão , Imunidade Inata/genética , Interleucina-12RESUMO
The role of step sites on nanocatalysts in the electrocatalytic dechlorination reaction (ECDR) was studied using 3 Pd nanocatalysts with different densities of step sites, which decreased in the order of: tetrahexahedral Pd{310} nanocrystals (THH Pd{310} NCs) > commercial Pd nanoparticles (Pd black) > cubic Pd{100} NCs. The two well-defined Pd NCs served as model catalysts and were prepared through the electrochemical square-wave potential (SWP) method. The toxic herbicide alachlor was first employed in this study as an objective probe to determine the dechlorination performance, which was quantified by the alachlor removal (Rala), the current efficiency (CEala), and the dechlorination selectivity (Sdes). The experimental results demonstrated that the THH Pd{310} NCs with abundant step sites exhibited much higher electrocatalytic performance compared to the cubic Pd{100} NCs with terrace sites. The combination of cyclic voltammetry studies, electrochemical in situ FTIR analysis, and density functional theory (DFT) calculations revealed that the adsorbed CîO bond and generated on the step sites could lower the C-Cl bond splitting barrier, leading to a high ECDR efficiency. Other chlorinated organics with an activated carbon atom were also investigated, which revealed that the superiority of the step sites toward Cl-C bond breaking was particular to the compounds with CîO bonds. This study provides a deep understanding of high actvitiy of step sites on Pd NCs in EHDC and a strategy to improve this important environmental electrocatalysis process.
RESUMO
The electrocatalytic activity of bismuth considered as a low-cost and green electrode material was studied in reductive dechlorination processes. Cyclic voltammetry analyses showed that the Bi electrode exhibited a high catalytic activity to reduce alachlor, a chlorinated herbicide, in the aqueous medium at different pH values. Bulk electrolyses were performed at different potentials and pH values. Alachlor was reduced in deschloroalachlor, its dechlorinated derivative, with a high selectivity (96%) and a current efficiency of 48%. The reductive dechlorination of other chlorinated compounds with an activated carbon atom was then studied, showing that the bismuth electrode catalyzed the electroreduction of chloroacetamides, α-halocarbonyl, and α-haloallyl pollutants. Cyclic voltammetry experiments allowed us to propose a mechanism explaining the high catalytic activity of bismuth to reduce these families of compounds.
Assuntos
Bismuto , Poluentes Ambientais , Eletrodos , Eletrólise , HalogenaçãoRESUMO
Ammonia (NH3) is a highly important industrial chemical used as fuel and fertilizer. The industrial synthesis of NH3 relies heavily on the Haber-Bosch route, which accounts for roughly 1.2% of global annual CO2 emissions. As an alternative route, the electrosynthesis of NH3 from nitrate anion (NO3-) reduction (NO3-RR) has drawn increasing attention, since NO3-RR from wastewater to produce NH3 can not only recycle waste into treasure but also alleviate the adverse effects of excessive NO3- contamination in the environment. This review presents contemporary views on the state of the art in electrocatalytic NO3- reduction over Cu-based nanostructured materials, discusses the merits of electrocatalytic performance, and summarizes current advances in the exploration of this technology using different strategies for nanostructured-material modification. The electrocatalytic mechanism of nitrate reduction is also reviewed here, especially with regard to copper-based catalysts.
RESUMO
The development of electrocatalysts capable of efficient reduction of nitrate (NO3-) to ammonia (NH3) is drawing increasing interest for the sake of low carbon emission and environmental protection. Herein, we present a CuCo bimetallic catalyst able to imitate the bifunctional nature of copper-type nitrite reductase, which could easily remove NO2- via the collaboration of two active centers. Indeed, Co acts as an electron/proton donating center, while Cu facilitates NOx- adsorption/association. The bio-inspired CuCo nanosheet electrocatalyst delivers a 100 ± 1% Faradaic efficiency at an ampere-level current density of 1035 mA cm-2 at -0.2 V vs. Reversible Hydrogen Electrode. The NH3 production rate reaches a high activity of 4.8 mmol cm-2 h-1 (960 mmol gcat-1 h-1). A mechanistic study, using electrochemical in situ Fourier transform infrared spectroscopy and shell-isolated nanoparticle enhanced Raman spectroscopy, reveals a strong synergy between Cu and Co, with Co sites promoting the hydrogenation of NO3- to NH3 via adsorbed *H species. The well-modulated coverage of adsorbed *H and *NO3 led simultaneously to high NH3 selectivity and yield.
Assuntos
Amônia , Carbono , Hidrogenação , Adsorção , Nitrito RedutasesRESUMO
PURPOSE: The prognostic efficiency of clinical grading and staging in patients with confined or moderately differentiated prostate cancer (PCa) has been markedly improved, which underscores the importance of new prognostic markers. Extracellular matrix metalloproteinase inducer (EMMPRIN) has been demonstrated to be involved in cancerangiogenesis, metastasis and invasion. EMMPRIN expression was evaluated by measuring mRNA and protein levels in a large cohort of patients with PCa following prostatectomy and the findings were compared with clinico-pathological parameters, including prostate-specific antigen (PSA) relapse time. METHODS: EMMPRIN mRNA levels in 20 pairs of normal and cancerous prostate tissues were determined by quantitative real-time PCR. Protein expression in paraffin-embedded specimens of prostates gathered from 300 patients with PCa was detected by immunohistochemistry using a monoclonal antibody against EMMPRIN. The associations of EMMPRIN protein expression with the clinico-pathological parameters and PSA relapse-free time after radical prostatectomy were subsequently assessed. RESULTS: Both EMMPRIN mRNA and protein levels were higher in PCa tissue, compared with adjacent normal tissue. In addition, the positive expression rates of EMMPRIN in PCa tissues were significantly associated with preoperative PSA levels (p=0.008), AJCC stage (p=0.006) and Gleason Score (p < 0.001), Risk classification (p < 0.001), lymph node status post-surgery (p < 0.001) and surgical margin status (p < 0.001) were also determined. Multivariate analysis, using the Cox proportional hazards model, revealed that positive EMMPRIN expression was an independent prognostic factor for an increased risk of PSA relapse. CONCLUSION: Over-expression of EMMPRIN correlated with the aggressiveness of PCa, and the PSA relapse-free time, and may be a novel and useful biomarker for follow-up and treatment decisions for PCa.
Assuntos
Basigina/metabolismo , Antígeno Prostático Específico/metabolismo , Prostatectomia/métodos , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/cirurgia , Idoso , Basigina/genética , Indução Enzimática , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/genética , Neoplasias da Próstata/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Background: Birt-Hogg-Dubé (BHD) syndrome and congenital contractural arachnodactyly (CCA) or Beals-Hecht syndrome are clinically rare autosomal dominant genetic diseases. In this study, we describe an extremely rare family with BHD syndrome and CCA. Objective: To investigate the clinical and genetic characteristics of a family with BHD syndrome and CCA. Methods: We describe the clinical characteristics, family history, and clinical manifestations of the patient's family members. The patient underwent a blood test, computed tomography (CT) of the chest, color Doppler ultrasound of the abdomen and heart, and digital radiography of the hands. Whole exome sequencing was performed on his family members. Results: Two years ago, the male proband developed chest tightness and shortness of breath that was accompanied by an irritating cough as well as repeated (four times) spontaneous pneumothorax. The chest CT indicated spontaneous pneumothorax on the right side and cyst and bullae in both lungs. He had no kidney tumors or skin lesions. His son had a history of pulmonary bullae and experienced spontaneous pneumothorax twice. The proband, his mother, and his son were all born with a hand deformity. The sequencing results demonstrated that both the proband and his son had heterozygous variations of the folliculin (FLCN) gene c.1015C > T (p. Gln339Ter) and fibrillin-2 (FBN2) gene c.3485G > A (p. Cys1162Tyr), which are associated with BHD syndrome and CCA, respectively. Conclusion: For patients with chest tightness, shortness of breath, recurrent spontaneous pneumothorax, and congenital hand deformity without inducement, genetic testing should be carried out as soon as possible to make a clear diagnosis, which can then guide treatment and genetic counseling.
RESUMO
OBJECTIVE: To investigate the factors of long-turn survival of liver cancer after surgical treatment. METHODS: Five hundred and twenty-two cases of liver cancer that received surgical treatment in 14 years were analyzed retrospectively. RESULTS: Comparison between the small liver cancer (< 5 cm) and the greater one (> 10 cm) revealed that the small liver cancer had a higher survival rates than the greater one [3 year (61.25 +/- 4.41)% versus (45.90 +/- 6.98)%; 5 year (53.84 +/- 5.68)% versus (30.21 +/- 10.23)%]. There were same results between single-nodule and two or more than two nodule [3 year (61.86 +/- 3.69)% versus (38.31 +/- 4.97)%; 5 year (55.40 +/- 4.91)% versus (28.01 +/- 6.31)%], between child I and child II or more than II [3 year (60.68 +/- 3.68)% versus (49.88 +/- 4.13)%; 5 year (50.99 +/- 5.10)% versus (36.39 +/- 7.58)%], and between single segmentectomy of the liver and two or more than two segmentectomy [3 year (68.65 +/- 4.95)% versus (49.88 +/- 4.13)%; 5 year (65.38 +/- 5.69)% versus (37.98 +/- 5.70)%]. CONCLUSIONS: Small liver cancer, single-nodule, good hepatic function and minor resection were important factors to prolong survival further.
Assuntos
Neoplasias Hepáticas/cirurgia , Adolescente , Adulto , Idoso , Criança , Feminino , Seguimentos , Hepatectomia/métodos , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Troxerutin, a natural bioflavonoid, has been reported to have many benefits and medicinal properties. In this study, we evaluated the protective effect of troxerutin against D-gal-induced oxidative DNA damage in mouse kidney, and explored the potential mechanism of its action. Our data showed that troxerutin significantly decreased levels of urea, uric acid and creatinine in serum and the renal histological injury in D-gal-treated mice. Troxerutin markedly restored Cu/Zn-SOD, CAT and GPx activities in the kidney of D-gal-treated mouse. Furthermore, the increase of 8-hydroxydeoxyguanosine (a marker of oxidative DNA damage) induced by d-gal was effectively suppressed by troxerutin. Internucleosomal DNA ladder fragmentation and the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labeling (TUNEL)-positive cells in D-gal-treated mice were inhibited by troxerutin, which might be attributed to its antioxidant property by decreasing activities of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and levels of reactive oxygen species (ROS). In conclusion, these results suggested that troxerutin could protect the mouse kidney against D-gal-induced injury by improving renal function, attenuating histopathologic changes, reducing ROS production, renewing the activities of antioxidant enzymes and decreasing DNA oxidative damage. This study provided novel insights into the protective mechanisms of troxerutin in D-gal-induced kidney injury.