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Aim To investigate the role of TGF-β/Smad signaling pathway in rheumatoid arthritis (RA) - associated postinterstitial pulmonary fibrosis in mice. Methods The mouse model of RA was constructed by subcutaneous administration of complete Freund's adjuvant (CFA) and chicken II collagen (Col-II) to the tail root of mice. The blank group was given the same amount of distilled water, and the control group was given the same amount of glacial acetic acid (solvent). The degree of toe swelling (joint swelling degree and arthritis index) was monitored to evaluate the mouse modeling. The pathological changes of mouse lung tissues were observed by HE and Masson staining. The expression of TGF-β in lung tissues were observed by immunohistochemical staining. The level of hydroxyproline in lung tissues was measured by chemiluminescence method. The expressions of Smad2, Smad3 and phosphorylated p-Smad2 and phosphorylated p-Smad3 in lung tissues were detected by Western blot. Results Compared with blank group and solvent group, the joint swelling and arthritis index of model group significantly increased. Twenty-one days after administration, HE staining showed inflammatory changes in lung interstitium of the model group, Masson staining showed collagen fiber deposition and obvious fibrosis in lung interstitium of the model group, and immunohistochemical staining showed that the expression of TGF-β in cytoplasm of lung interstitial cells of the model group increased, which was brown and yellow. Meanwhile, hydroxyproline was significantly raised in lung tissue homogenate of the model group. Further WB analysis showed that compared with blank group and solvent group, the expression of p-Smad2 and pSmad3 in lung tissues of the model group was significantly up-regulated (P < 0. 05, P < 0. 01). Conclusions RA can give rise to pulmonary fibrosis, and the expressions of p-Smad2 and p-Smad3 are up-regulated, which is be pivotal in pulmonary fibrosis and RA-related post-interstitial pulmonary fibrosis.
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Objective@#To investigate the characteristics of histogram analysis and differences of apparent diffusion coefficient (ADC) for normal pancreas with different diffusion gradients of diffusion weighted imaging (DWI) at 3.0T.@*Methods@#Three unidirectional diffusion gradients (X, Y or Z direction) and three orthogonal diffusion gradient DWI data of 21 volunteers with normal pancreas were retrospectively analyzed. The histogram parameters of mean ADC, percentile, skewness, peak and the like were measured based on home-made DWI post-processing software, and the differences on histogram parameters obtained from 4 different diffusion gradients were compared by using Kruskal Wallis test.@*Results@#There was no significant difference on the mean ADC, skewness, percentile and the like for normal pancreas among 3 unidirectional diffusion gradients and tri-orthogonal diffusion gradient DWIs, but there was significant difference on the mean kurtosis value (X: 3.16±1.44, Y: 4.72±2.26, Z: 4.47±2.1, tri-orthogonal: 3.69±1.82; χ2 =-9.84, P=0.02). Further analyses results showed that the ADC kurtosis of normal pancreas obtained from X-directional diffusion gradient DWI was significantly smaller than that of the direction of Y or Z, and the difference was statistically significant (P<0.05).@*Conclusions@#The ADC kurtosis of normal pancreas is related to the direction of diffusion gradient in DWI, and the ADC kurtosis of normal pancreas obtained by X-direction diffusion gradient is the smallest.
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Objective To investigate the ability of quantitative radiomic method based on highresolution magnetic resonance imaging (HR-MRI) to distinguish between culprit plaques and non-culprit plaques of intracranial atherosclerosis.Methods Patients with middle cerebral artery and basilar artery stenosis underwent HR-MRI in Changhai Hospital Affiliated to the Naval Medical University from September 2013 to October 2016 were analyzed retrospectively.The minimum lumen area,plaque burden,severity of luminal stenosis,intraplaque hemorrhage (IPH),enhancement rate,and 109quantitative radiomic characteristics of the culprit and non-culprit plaques were measured.For clinical features and traditional plaque morphology,multivariate logistic regression models were used to determine independent risk factors for culprit plaque.A random forest-supervised machine learning method was used to determine the radiomic characteristics of distinguishing between symptomatic plaques and asymptomatic plaques.The receiver operating characteristic (ROC) curve was constructed,and the diagnostic efficacy was described by the area under the curve (AUC).Results During the study,158 subjects were enrolled,and they aged (59.42± 11.62) years.The plaques of 75 patients were located in middle cerebral artery,and the plaques of 83 patients were located in basilar artery.There were 111 symptomatic patients and 47 asymptomatic patients.Multivariate logistic regression analysis showed that smoking (odds ratio [OR] 2.724,95％ confidence interval [CI] 1.200-6.183),IPH (OR 11.340,95％ CI 1.441-89.221),and enhancement rate (OR 6.865,95％ CI 1.052-44.802) were the independent risk factors for culprit plaques.The AUC of these three characteristics for predicting symptomatic plaques were 0.605,0.584,and 0.590,respectively.The combination of the three cloud improve the test efficacy for the intracranial atherosclerotic culprit plaques,AUC could reached 0.714.Radiomic analysis showed that 22 radiomic characteristics extracted from T-2 weighted imaging,T1 weighted imaging,and contrast-enhanced T1 weighted imaging were associated with the culprit plaques.Their AUCs were 0.801,0.835,and 0.846,respectively.After the combination of all morphological and radiomic characteristics,AUC could reach 0.976,the accuracy rate was 87.4％.However,the difference was not statistically significant compared to the combined AUC of all radiomic characteristics (0.953) (P=0.275).Conclusion Radiomic analysis could accurately distinguish between the culprit plaques and non-culprit plaques of intracranial atherosclerosis,and is superior to the traditional morphological methods.
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Objective To investigate the characteristics of histogram analysis and differences of apparent diffusion coefficient ( ADC) for normal pancreas with different diffusion gradients of diffusion weighted imaging (DWI) at 3. 0T. Methods Three unidirectional diffusion gradients (X, Y or Z direction) and three orthogonal diffusion gradient DWI data of 21 volunteers with normal pancreas were retrospectively analyzed. The histogram parameters of mean ADC, percentile, skewness, peak and the like were measured based on home-made DWI post-processing software, and the differences on histogram parameters obtained from 4 different diffusion gradients were compared by using Kruskal Wallis test. Results There was no significant difference on the mean ADC, skewness, percentile and the like for normal pancreas among 3 unidirectional diffusion gradients and tri-orthogonal diffusion gradient DWIs, but there was significant difference on the mean kurtosis value ( X:3. 16 ± 1. 44, Y:4. 72 ± 2. 26, Z:4. 47 ± 2. 1, tri-orthogonal:3. 69 ± 1. 82; χ2 = -9. 84, P=0. 02). Further analyses results showed that the ADC kurtosis of normal pancreas obtained from X-directional diffusion gradient DWI was significantly smaller than that of the direction of Y or Z, and the difference was statistically significant (P<0.05). Conclusions The ADC kurtosis of normal pancreas is related to the direction of diffusion gradient in DWI, and the ADC kurtosis of normal pancreas obtained by X-direction diffusion gradient is the smallest.
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Objective: To determine the role of intensity of plum-blossom needle tapping in treating alopecia areata.Methods: The BALB/c mice were randomized into a normal group, a control group, a roller-needle (RN) group, a mild plum-blossom needle (MP) group, and a heavy plum-blossom needle (HP) group. An area of hair was removed by external application of 8% sodium sulfide on BALB/c mice. The hair regrowth, hair follicle changes, and local inflammatory factor changes after cutaneous acupuncture were observed.Results: After treated with sodium sulfide, the hair was completely removed, the local hair follicles reached the catagen phase, and the expressions of interleukin (IL)-1α, IL-1β, IL-2, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and IL-17 were increased. Mice intervened by RN achieved the same hair growth rating as the controls but with thicker hair shafts; mice in the MP group had incomplete and uneven hair growth but thicker hair shafts; mice in the HP group didn't show hair growth. Pathological analysis revealed significant inflammatory infiltration into the local follicle bulbs and increased catagen-phase follicles in the control group, while RN and MP groups showed significantly increased anagen-phase follicles, coarser individual hairs, and obvious hair shafts. Meanwhile, most of the hair follicles in the HP group were in telogen phase and showed obvious surrounding inflammatory infiltration. RN, MP, and HP significantly down-regulated the increased IL-2, IL-1α, IL-1β, TNF-α, and IFN-γ levels (P0.05).Conclusion: Cutaneous acupuncture with heavy stimulation intensity can inhibit hair growth in hair removal mice, while RN, with the lightest stimulation intensity, is unlikely to affect hair growth but may make hair shafts thicker and follicles larger.
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The aim of this study was to investigate the effect of proteasome inhibitor bortezomib on the expression of ERK, JNK, and P38 in daunorubicin (DNR)-resistant K562 cells and its mechanism. MTT method was used to determine the drug-resistant K562 cells and the cellular toxicity of bortezomib; Western blot was used to detect the expression of protein ERK, JNK and P38 in K562 cells after treatment with 100 nmol/L DNR alone or combined with 1 nmol/L and 10 nmol/L bortezomib for 36 hours. Flow cytometry assay was used to detect the apoptosis rate in each group cells. The results indicated that the expression of ERK and P38 were significantly suppressed (p < 0.05) and the expression of JNK was significantly enhanced (p < 0.05) in the cells treated by DNR combined with bortezomib. It is concluded that bortezomib can decrease the expressions of protein ERK and P38 and enhance the expression of JNK, the bortezomib reverses the cellular drug-resistance and promote cell apoptosis through MAPK pathway.
Subject(s)
Humans , Antineoplastic Agents , Pharmacology , Boronic Acids , Pharmacology , Bortezomib , Drug Resistance, Neoplasm , JNK Mitogen-Activated Protein Kinases , Metabolism , K562 Cells , Protease Inhibitors , Pharmacology , Pyrazines , Pharmacology , p38 Mitogen-Activated Protein Kinases , MetabolismABSTRACT
The study was aimed to investigate the effects of bortezomib (BTZ) on the expression of ERK, JNK and P38 in daunorubicin (DNR)-resistant K562 cells (K562/DNR) and to clarify the molecular mechanism of BTZ in reversing the drug-resistance in leukemic cells. The K562/DNR cells and the cellular toxicity of BTZ was determined by MTT, then 4 µg/L of BTZ was chosen to do the experiment. The expression of ERK, JNK, p38 and P-gp of K562/DNR cells treated with DNR only or DNR combined with BTZ for 12, 24 and 36 hours was detected by Western blot. The apoptosis rate in each group was assayed by flow cytometry. The results showed that as compared with DNR group, the expression of P-ERK, P-P38 and P-gp was significantly suppressed (p < 0.05) and the expression of P-JNK was significantly enhanced (p < 0.05) in the cells treated with DNR combined with BTZ. There was no change in the expression of total ERK, P38 and JNK. The effect increased with the prolonging of time. Meanwhile, the apoptosis rate in cells treated with DNR combined with BTZ increased compared with DNR only. It is concluded that the BTZ can reverse the drug resistance in K562/DNR cells by MAPK signaling pathway and increase the apoptosis of leukemic cells. The effect shows the characteristics of time-dependent manner.