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Carbon material has widely been utilized in the synthesis of efficient carbon-supported Pt (Pt/C) catalysts, in which the structural properties greatly influence the electrocatalytic performances of Pt/C catalysts. However, the effects of intrinsic defects in carbon supports on the performance of the alkaline hydrogen evolution reaction (HER) have not been systematically investigated. Herein, porous carbon supports with different degrees of intrinsic defects were prepared by a simple template-assisted strategy, and the resulting samples were systematically studied by various analytical methods. The results suggested that the presence of abundant intrinsic defects (vacancy and topological defects) in the carbon support was advantageous in terms of favoring the dispersion and anchoring of Pt species, promoting electron transfer between Pt atoms and the carbon support, and tuning the electronic states of Pt species. These features improved the HER performance of Pt/C catalysts. Compared to the nontemplate-assisted carbon-supported Pt catalyst (Pt/NTC) with an overpotential of 178 mV, the optimized template-assisted carbon-supported Pt catalyst (Pt/TC) exhibited a lower overpotential of 58 mV at 10 mA cm-2. Besides, the Pt/TC catalyst displayed better HER durability than the Pt/NTC catalyst owing to its strong metal-support interaction. The DFT calculations confirmed the important role played by intrinsic defects (vacancy and topological defects) in stabilizing Pt atoms, with Pt-C3 coordination identified as the most favorable structure for improving the HER performance of Pt. Overall, novel insights on the significant contribution of intrinsic defects in porous carbon supports on the HER performances of Pt/C catalysts were provided, useful for future design and fabrication of advanced carbon-supported catalysts or other carbon-based electrode materials.
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Shallow landslides of expensive soil slopes occur from time to time, and most engineering geological problems are directly or indirectly caused by soil structure cracks. The existence of tensile cracks can significantly affect the hydro-mechanical properties of soils. In this paper, the mechanism of expansive soil landslide formation is explored, and swelling pressures, and drying and wetting cycles are introduced into the discrete element method (DEM), and the landslide process of expansive soils is studied by the numerical simulation mothed. The relationship between the crack development and the instability of expansive soil slopes was investigated. The results show that under the condition of seasonal dry and wet alternation, the cracks of the expansive soil slope gradually develop, the rainwater infiltrates rapidly, the mechanical properties gradually deteriorate, and under the effect of such adverse cycle, the soil gradually softens and the stability decreases. Under the influence of human activities, vehicle loads and other factors, the slope body slides. These findings are helpful for the design and construction of expansive soil slopes and foundations.
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BACKGROUND: The objective of the current study was to investigate the safety and feasibility of mediastinoscopy-assisted esophagectomy (MAE). METHODS: A meta-analysis was conducted between MAE and traditional transthoracic esophagectomy (TTE). For a comparative analysis of MAE and TTE, we searched PubMed, the Cochrane Library, Embase, and Web of Science databases. We identified the relevant literature and extracted the relevant data. Finally, RevMan 5.3 software was applied to conduct a meta-analysis of the data. RESULTS: A total of 1256 people were enrolled in 16 studies, comprising 575 patients with MAE and 681 with TTE. The findings revealed that the pulmonary complications, cardiac complications, and postoperative hospital stay in the MAE group were significantly better than those in the TTE group. No significant differences were found between the 2 groups in postoperative chylothorax, anastomotic fistula, and postoperative mortality. But the incidence of recurrent laryngeal nerve injury in the MAE group was higher than that in the TTE group (odds ratio=1.64, 95% CI, 1.15 to 2.35, P =0.006). The MAE group had less lymph node dissection than the TTE group (mean difference=-4.62, 95% CI, -5.97 to 3.45, P <0.00001). CONCLUSIONS: This meta-analysis presented that MAE was safe and feasible, reduced postoperative pulmonary and cardiac complications, and shortened hospital stay, but lymph node dissection was less, recurrent laryngeal nerve injury was higher, and the impact of long-term survival prognosis required more randomized controlled trials.
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Neoplasias Esofágicas , Traumatismos do Nervo Laríngeo Recorrente , Humanos , Mediastinoscopia/efeitos adversos , Esofagectomia/efeitos adversos , Estudos de Viabilidade , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/patologia , Excisão de Linfonodo , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgiaRESUMO
The oxygen functionalization of carbon materials has widely been employed to improve the catalytic performance of carbon-supported Pt (Pt/C) catalysts. Hydrochloric acid (HCl) has often been employed to clean carbons during the preparation of carbon materials. However, the effect of oxygen functionalization through a HCl treatment of porous carbon (PC) supports on the performance of the alkaline hydrogen evolution reaction (HER) has rarely been investigated. Herein, the impact of HCl combined with the heat treatment of PC supports on the HER performance of Pt/C catalysts has been comprehensively investigated. The structural characterizations revealed similar structures of pristine and modified PC. Nevertheless, the HCl treatment resulted in abundant hydroxyl and carboxyl groups and the further heat treatment formed thermally stable carbonyl and ether groups. Among the catalysts, Pt loading on the HCl-treated PC followed by a heat treatment at 700 °C (Pt/PC-H-700) exhibited elevated HER activity with a lower overpotential of 50 mV at 10 mA cm-2 when compared to the unmodified Pt/PC (89 mV). Pt/PC-H-700 also exhibited better durability than the Pt/PC. Overall, novel insights into the impact of the surface chemistry properties of porous carbon supports on the HER performance of Pt/C catalysts were provided, which were useful for highlighting the feasible improvement of HER performances by regulating the surface oxygen species of porous carbon supports.
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New and old subgrade stability is a crucial problem for widening projects in soft soil foundations because uncoordinated deformations can cause serious engineering accidents, even disasters. In order to ensure the stability of a widening expressway project near a pond in the Qinbei section, a series of on-site investigations, lab tests, and numerical analyses was performed. The settlement and displacement of on-site monitoring were carried out during the construction period to verify the analyzed results. It was found that the uneven settlement caused heavy settlement and displacement of the embankment; thus, net cracks and longitudinal cracks occurred in the expressway. The new embankment was also affected by the weak foundation; therefore, the foundation should be reinforced before the construction of the widening part. Considering the economy and effectiveness of the widening project, the replacement method was recommended for the weak foundation reinforcement based on the numerical analysis and on-site motoring results. Water pumping had a significant effect on the settlement of the embankment. Water pumping caused seepage in the foundation and increased the effective stress of the soil, making the foundation more consolidated. The pond slope should be reinforced before the construction of the embankment because it was not confined by the surrounding soil. Therefore, the slope soil could not provide sufficient passive soil pressure and easily slide.
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Transverse cracking is a serious problem for semi-rigid base asphalt pavement. The shrinkage of the base course and the surface course, as well as reflective cracks, are key factors for transverse cracking in asphalt pavement. Crack spacing can directly reflect the degree of transverse cracking in pavements. Therefore, this study aims to calculate the transverse crack spacing and discuss its affecting factors. To this end, a calculation model of transverse crack spacing for the semi-rigid base asphalt pavement was first established. Then, the transverse crack spacings of different composite structures were calculated, and the influences of the shrinkage coefficient, the structural layer thickness, and the pavement tensile strength on transverse crack spacing were expounded. Finally, the transverse crack spacing of the pavement after the appearance of the reflective was calculated. The results show that the lower lime and fly ash content and skeleton gap gradation can be adopted during the design of the base course. Meanwhile, the lower lime and fly ash content in the macadam base, the skeleton gap gradation and asphalt concrete with a larger particle size in the surface layer can be used during the design of surface layer. In addition, the transverse crack spacing of the semi-rigid base asphalt pavement could be increased by reducing the shrinkage coefficient, increasing the thicknesses of the surface course and the base course, and improving the tensile strength of the pavement. After the appearance of reflective cracks, the transverse crack spacing of the surface layer ranged between 32.8 m and 66.5 m. 15fp-AC25, 15fp-AC20, 15df-AC25, and 17fp-AC25 were found to be the best semi-rigid base asphalt pavement structures to reduce transverse cracking. Finally, transverse cracking in pavement composite structures under different bonding conditions needs to be analyzed in the follow-up work.
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In order to explore the effect of the foaming agent type on the properties of foamed mixture lightweight soil mixed with bauxite tailings (FMLSB), low-density (437.5 kg/m3 and 670 kg/m3) and high-density (902.5 kg/m3 and 1170 kg/m3) FMLSB were prepared using protein-based and synthetic-based foaming agents (AF and SF, respectively). The foam stability, micro characteristics, compressive strength, fluidity, and volume of water absorption of the FMLSB were investigated. The results showed that the foam made from AF had better strength and stability compared to SF. The internal pore sizes of both AF- and SF-FMLSB at low density were large, but at high density the internal pore sizes and area porosity of AF-FMLSB were smaller than those of SF-FMLSB. In terms of compressive strength, the compressive strength of AF-FMLSB was improved by 17.5% to 43.2% compared to SF-FMLSB. At low density, the fluidity of AF- and SF-FMLSB is similar, while at high density the fluidity of AF-FMLSB is much higher than that of SF-FMLSB. In addition, the stable volume of water absorption of SF-FMLSB is smaller than that of AF-FMLSB at low density, and the corresponding water resistance is better, but the situation is reversed at high density.
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The single light oil regenerating agent has certain limitations on the performance recovery of aged asphalt. In this study, tung oil, dioctyl phthalate (DOP), C9 petroleum resin, and organic montmorillonite (OMMT) were used to prepare the composite regenerating agent, and its optimal mix proportion was determined by the orthogonal experimental design. The rheological properties and anti-aging performance of reclaimed asphalt were studied by the dynamic shear rheometer (DSR) and bending beam rheometer (BBR); and the Fourier transform infrared (FTIR) spectrometer, gel permeation chromatography (GPC), and scanning electron microscope (SEM) were adopted to explore its microstructure, morphology, and mechanism of action. The results show that with the addition of tung oil composite regenerating agent, the rheological properties of aged asphalt can be effectively recovered, even better than that of base asphalt. By using the complex modulus aging index (CMAI) and phase angle aging index (PMAI) it is found that the anti-aging performance of reclaimed asphalt is better than that of base asphalt. With the optimal content of the tung oil composite regenerating agent, the contents of characteristic functional groups and macromolecular asphaltenes in the aged asphalt can be reduced, indicating that the composite regenerating agent is beneficial to the dispersion and dissolution of polar substances in the aged asphalt. After aging, a large number of wrinkles appear on the surface of the asphalt. However, the addition of the tung oil composite regenerating agent can make the asphalt surface smooth, which indicates that the tung oil composite regenerating agent can restore the microstructure and morphology of aged asphalt to a certain extent.
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Electroreduction of N2 to NH3 at ambient conditions using renewable electricity is promising, but developing efficient electrocatalysts is still challenging due to the inertness of N≡N bonds. Layer double hydroxides (LDHs) composed of first-row transition metals with empty d-orbitals are theoretically promising for N2 electroreduction (NRR) but rarely reported. Herein, hollow NiCo-LDH nanocages with different Ni/Co ratios were prepared, and their electronic structures and atomic arrangements were critical. The synergetic mechanisms of Ni and Co ions were revealed, and the optimized catalytic sites were proposed. Besides, in-situ Raman spectroscopy and 15 N2 isotopic labeling studies were applied to detect reaction intermediates and confirm the origin of NH3 . As a result, high NH3 yield of 52.8â µg h-1 mgcat -1 and faradaic efficiency of 11.5 % were obtained at -0.7â V, which are top-ranking among Co/Ni-based NRR electrocatalysts. This work elucidates the structure-activity relationship between LDHs and NRR and is instructive for rational design of LDH-based electrocatalysts.
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Renal interstitial fibrosis is a final pathway that is observed in various types of kidney diseases, including diabetic kidney disease (DKD). The present study investigated the effect of tranilast on renal interstitial fibrosis and the association between its role and mast cell infiltration in a rat model of DKD. A total of 30 healthy 6weekold male SpragueDawley rats were randomly divided into the following four groups: Normal control group; DKD model group; lowdose tranilast group (200 mg/kg/day); and highdose tranilast group (400 mg/kg/day). The morphological alterations of tubulointerstitial fibrosis were evaluated by Masson's trichrome staining, while mast cell infiltration into the renal tubular interstitium was measured by toluidine blue staining and complement C3a receptor 1 (C3aR) immunohistochemical staining (IHC). The expression of fibronectin (FN), collagen I (ColI), stem cell factor (SCF) and protooncogene ckit (ckit) was detected by IHC, western blotting and reverse transcriptionquantitativepolymerase chain reaction. The results demonstrated that tubulointerstitial fibrosis and mast cell infiltration were observed in DKD model rats, and this was improved dosedependently in the tranilast treatment groups. The expression of FN, ColI, SCF and ckit mRNA and protein was upregulated in the tubulointerstitium of DKD model rats compared with the normal control rats, and tranilast inhibited the upregulated expression of these markers. Furthermore, the degree of SCF and ckit expression demonstrated a significant positive correlation with C3aRpositive mast cells and the markers of renal interstitial fibrosis. The results of the present study indicate that mast cell infiltration may promote renal interstitial fibrosis via the SCF/ckit signaling pathway. Tranilast may prevent renal interstitial fibrosis through inhibition of mast cell infiltration mediated through the SCF/c-kit signaling pathway.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Rim/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , ortoaminobenzoatos/uso terapêutico , Animais , Colágeno/análise , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Fibronectinas/análise , Fibrose , Rim/patologia , Masculino , Mastócitos/patologia , Ratos Sprague-DawleyRESUMO
This research aims to explore the dynamic characteristics and settlement prediction of soft soil. Accordingly, the dynamic shear modulus formula considering the vibration frequency was utilized and the dynamic triaxial test conducted to verify the validity of the formula. Subsequently, the formula was applied to the dynamic creep strain function, with the factors influencing the improved dynamic creep strain curve of soft soil being analyzed. Meanwhile, the variation law of dynamic stress with sampling depth was obtained through the finite element simulation of subway foundation. Furthermore, the improved dynamic creep strain curve of soil layer was determined based on the dynamic stress. Thereafter, it could to estimate the long-term settlement under subway vibration loading by norms. The results revealed that the dynamic shear modulus formula is straightforward and practical in terms of its application to the vibration frequency. The values predicted using the improved dynamic creep strain formula closed to the experimental values, whilst the estimating settlement closed to the measured values obtained in the field test.
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OBJECTIVE: To determine the role and mechanism of tranilast preventing the progression of tubulointerstilial fibrosis in diabetic kidney disease (DKD). METHODS: Sprague-Dawley rats were randomly divided into a control group (n=6), DKD model group (n=8), low dose tranilast group [200 mg/(kg.d), n=8], and high dose tranilast group [400 mg/(kg.d), n=8]. Tranilast was administered daily after the model was built. Rats were sacrificed at day 56, 24 hour urine was collected to measure 24-hour urine albumin excretion, and blood was collected to determine the renal function and serum albumin. Then the kidneys were harvested and subjected to studies. The expression of C3aR, E-cadherin, α-SMA, fibronectin(FN), collagen I (Col I), stem cell factor (SCF) and c-kit were detected by immunohistochemical staining respectively. The expression of E-cadherin, α-SMA, FN, Col I, SCF and c-kit protein was analyzed by Western blot, and the expression of FN, Col I, SCF and c-kit mRNA was examined by RT-PCR. RESULTS: Tranilast can inhibit the infiltration of mast cells in the kidneys of DKD rats. The expression of α-SMA in the kidneys of DKD rats inereased significantly (P<0.05), while the expression of E-cadherin decreased (P<0.05). Tranilast increased the expression of E-cadherin and decreased the expression of α-SMA in the prophase of DKD dose dependently. The expressions of FN and Col I were increased in the tubulointerstitial fields in DKD model rats (P<0.05). After the tranilast treatment, these changes were relieved to a certein degree (P<0.05). The expression of SCF and c-kit in the tubular and interstitial tissue was slight. The increased expressions of SCF and c-kit protein and mRNA in DKD model rats were downregulated by tranilat (P<0.05). The expressions of SCF and c-kit were positively correlated with the infiltration degree of mast cells and the expressions of FN, Col I. CONCLUSION: Mast cells participate in and aggravate the renal tubulointerstitial fibrosis in DKD rats. Tranilast can reverse the EMT of renal tubular cells and inhibit the tubulointersitial fibrosis of DKD by blocking the infiltration of mast cells induced by SCF/c-kit pathway.
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Nefropatias Diabéticas/tratamento farmacológico , ortoaminobenzoatos/farmacologia , Animais , Caderinas , Progressão da Doença , Fibronectinas , Fibrose , Rim/patologia , Mastócitos , Proteínas Proto-Oncogênicas c-kit , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Fator de Células-TroncoRESUMO
OBJECTIVE: To observe the effect of norcantharidin (NCTD) on the expression of mRNA and protein of fibronectin (FN), collagen IV(Col IV) and transforming growth factor-ß1(TGF-ß1) in human kidney proximal tubular epithelial (HK)-2 cells induced by high glucose. METHODS: HK-2 cells were incubated with serum-free DMEM for 24 h to synchronize cell growth, and then the cells were divided into 4 groups: Group C (5.5 mmol/L D-glucose), Group M (5.5 mmol/L D-glucose + 24.5 mmol/L-mannitol), Group HG (30 mmol/L D-glucose), and Group HG + NCTD (30 mmol/L D-glucose + 0.5-40 mg/L NCTD). Cytotoxicity of HK-2 cells induced by high glucose of NCTD was detected by Trypan blue dye exclusive assay. The effect of NCTD on the proliferation of HK-2 cells in high glucose was determined by MTT. The cells were collected to extract total RNA and protein at 6, 24 and 48 h after the incubation. The expression of FN, Col IV and TGF-ß1 mRNA was examined by RT-PCR, and FN, Col IV and TGF-ß1 protein was analyzed by Western blot. RESULTS: Trypan blue dye exclusive assay showed NCTD concentrations over 5 mg/L were rather toxic in HK-2 cells. The proliferation of HK-2 cells in high glucose was interrupted by interfered with 5 mg/L NCTD as measured by MTT (P<0.05). NCTD at 5 mg/L had a stronger inhibitory effect than NCTD at 2.5 mg/L. Real-time PCR and Western blot showed that the mRNA and protein expression of FN, collagen IV and TGF-ß1 increased in HK-2 cells treated with high glucose (P<0.05), while that in cells treated by NCTD was dramatically inhibited (P<0.05). No change in these parameters was detected in the 30 mmol/L D-mannitol control group (P>0.05). CONCLUSION: NCTD can downregulate FN, collagen IV and TGF-ß1 mRNA and protein expression in HK-2 cells stimulated by 30 mmol/L D-glucose.
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Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Colágeno Tipo IV/metabolismo , Fibronectinas/metabolismo , Túbulos Renais Proximais/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Linhagem Celular , Colágeno Tipo IV/genética , Regulação para Baixo/efeitos dos fármacos , Células Epiteliais/citologia , Fibronectinas/genética , Glucose/farmacologia , Humanos , Túbulos Renais Proximais/citologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta1/genéticaRESUMO
Norcantharidin (NCTD) was shown in our previous studies to attenuate renal tubulointerstitial fibrosis in rat models with diabetic nephropathy (DN). The aim of this study was to determine the effects of NCTD on the expression of extracellular matrix (ECM) and TGF-ß1 in HK-2 cells stimulated by high glucose and on calcineurin (CaN)/NFAT pathway. Whether or not the antifibrotic effect of NCTD on renal interstitium was dependent on its inhibition of CaN pathway was also investigated. Experimental concentrations of NCTD were verified by cytotoxic test and MTT assay. HK-2 cells were transfected with CaN small interference RNA (siRNA). The mRNA and protein expressions of FN, ColIV, TGF-ß1, and CaN in HK-2 cells were detected by real-time PCR and western blot. The CaN/NFAT pathway was examined by indirect immunofluorescence and western blot. Our study revealed that NCTD concentrations over 5 mg/l had overt cytotoxicity on HK-2 cells. Meanwhile, both 2.5 and 5 mg/l NCTD inhibited HK-2 cell proliferation (P < 0.05). NCTD inhibited the upregulation of FN, ColIV, and TGF-ß1 of HK-2 cells stimulated by high glucose (P < 0.05), and also significantly downregulated the expression of CaN mRNA and protein in HK-2 cells (P < 0.05). In addition, not only was the nuclear translocation of NFATc inhibited, but its protein level in the nucleus was also reduced. Following CaN siRNA transfection, CaN mRNA and protein expression were significantly decreased. In contrast, the protein levels of FN, ColIV, and TGF-ß1 increased in HK-2 cells stimulated by high glucose (P < 0.05). However, NCTD treatment downregulated their expression. These results indicated that NCTD could decrease the expression of ECM and TGF-ß1 in HK-2 cells stimulated by high glucose, downregulate CaN expression, and block the CaN/NFAT signaling pathway. However, the effect of NCTD on inhibition of the expression of ECM and TGF-ß1 was not associated with its inhibition of the CaN/NFAT pathway.
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Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Calcineurina/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Matriz Extracelular/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo IV/metabolismo , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Avaliação Pré-Clínica de Medicamentos , Células Epiteliais/efeitos dos fármacos , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Glucose/efeitos adversos , Humanos , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the effects of norcantharidin (NCTD) on tubulointerstitial fibrosis of diabetic nephropathy (DN) in streptozotocin-induced rat model. METHODS: Sprague-Dawley rats were randomly divided into control group, model group, low-dose NCTD (0.05 mg/kg/day) group, and high-dose NCTD (0.1 mg/kg/day) group. The model group was induced by injection intraperitoneally with 30 mg/kg streptozotocin in 0.1 mol/L sodium citrate solution (pH 4.5), after high-calorie foods were given for 2 months. NCTD was administered daily after the DN rat model was built. Rats were sacrificed at the end of the third and the eighth week; renal fibrosis and the expression of FN, collagen IV, TGF-ß1, and calcineurin (CaN) were detected by Masson and immunohistochemistry staining, respectively. RESULTS: Tubulointerstitial fibrosis was observed in DN rats, this kind of pathological changes was ameliorated in NCTD treatment group (p < 0.05). The expressions of FN, collagen IV, and TGF-ß1 protein increased in the tubulointerstitial field of DN rats compared with the rats in control group. NCTD treatment could dose-dependently decrease their expression and reverse the fibrotic degree (p < 0.05). Meanwhile, the expression of CaN was detected in tubular fields of normal kidney and increased in the tubulointerstitial field in DN rats. However, NCTD downregulated its expression in a dose-dependent manner (p < 0.05). CONCLUSIONS: NCTD could downregulate FN, collagen IV, and TGF-ß1 expression in tubulointerstitial fields and attenuate tubulointerstitial fibrosis in the early stage of DN rats. NCTD also alleviated the expression of CaN in tubules in DN. The relationship between the role of NCTD's anti-tubulointerstitial fibrosis and its inhibition to CaN expression remains to be further elucidated.
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Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Nefrite Intersticial/tratamento farmacológico , Animais , Calcineurina/metabolismo , Colágeno Tipo IV/metabolismo , Creatinina/sangue , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Avaliação Pré-Clínica de Medicamentos , Fibronectinas/metabolismo , Fibrose , Rim/metabolismo , Rim/patologia , Masculino , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/metabolismo , Nefrite Intersticial/patologia , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: p75NTR has been used to isolate esophageal and corneal epithelial stem cells. In the present study, we investigated the expression of p75NTR in esophageal squamous cell carcinoma (ESCC) and explored the biological properties of p75NTR+ cells. METHODS: p75NTR expression in ESCC was assessed by immunohistochemistry. p75NTR+ and p75NTR- cells of 4 ESCC cell lines were separated by fluorescence-activated cell sorting. Differentially expressed genes between p75NTR+ and p75NTR- cells were determined by real-time quantitative reverse transcription-PCR. Sphere formation assay, DDP sensitivity assay, 64copper accumulation assay and tumorigenicity analysis were performed to determine the capacity of self-renewal, chemotherapy resistance and tumorigenicity of p75NTR+ cells. RESULTS: In ESCC specimens, p75NTR was found mainly confined to immature cells and absent in cells undergoing terminal differentiation. The percentage of p75NTR+ cells was 1.6%-3.7% in Eca109 and 3 newly established ESCC cell lines. The expression of Bmi-1, which is associated with self-renewal of stem cells, was significantly higher in p75NTR+ cells. p63, a marker identified in keratinocyte stem cells, was confined mainly to p75NTR+ cells. The expression of CTR1, which is associated with cisplatin (DDP)-resistance, was significantly decreased in p75NTR+ cells. Expression levels of differentiation markers, such as involucrin, cytokeratin 13, beta1-integrin and beta4-integrin, were lower in p75NTR+ cells. In addition, p75NTR+ cells generated both p75NTR+ and p75NTR- cells, and formed nonadherent spherical clusters in serum-free medium supplemented with growth factors. Furthermore, p75NTR+ cells were found to be more resistant to DDP and exhibited lower 64copper accumulation than p75NTR- cells. CONCLUSION: Our results demonstrated that p75NTR+ cells possess some characteristics of CSCs, namely, self-renewal and chemotherapy resistance. Chemotherapy resistance of p75NTR+ cells may probably be attributable to decreased expression of CTR1.