1.Therapeutic Effect of Heat-clearing and Dampness-removing Therapy Combined with Bifico for Ulcerative Colitis and Its Influence on Tumor Necrosis Factor Alpha and Interleukin-10 in Rats
Jing WANG ; Yuxiang KUANG ; Haiyan ZHANG ; Shijuan LUO ; Suiping HUANG ; Xinge FU
Journal of Guangzhou University of Traditional Chinese Medicine 2014;(5):756-761,845
Objective To observe the therapeutic effect of heat-clearing and dampness-removing therapy combined with Bifico for ulcerative colitis ( UC) induced by trinitrobenzene sulfonic acid ( TNBS), and to explore its influence on tumor necrosis factor alpha ( TNF-α) and interleukin-10 ( IL-10) in rats. Methods Forty female adult Sprague-Dawley rats were evenly randomized into five groups, namely normal control group, model group, Bifico (175 mg/kg) group, Chinese medicine group(enema with Changdiqing 3.6/kg and oral use of Changyanling Recipe l) , and Chinese medicine plus Bifico group. After treatment, the damage of colonic mucous membrane was evaluated, and expression levels of IL-10 and TNF-α in colonic mucosa were observed through immunohistochemical assay. Results The degree of colonic mucosal injury was severer and the inflammation was more obvious in the model group than those in the normal control groups ( P<0.01) , and the above changes were relieved to various degrees in the medication group ( P<0.01 compared with those in the model group) . Chinese medicine plus Bifico group had better effect on reducing colonic mucosa damage index ( CMDI) and inflammation, and on promoting the healing of colonic mucosa than Bifico group and Chinese medicine group (P<0.05 ) . The expression level of TNF-α in the colonic mucosa was markedly increased while that of IL-10 was markedly decreased in the model group ( P<0.01 compared with those in the normal control group) . The medication groups could counteract the above changes in the colonic mucosa ( P<0.01 compared with those in the model group) . The combination group and Chinese medicine group had better effect on decreasing TNF-α expression level and on increasing IL-10 expression level than Bifico group ( P<0.05) . Conclusion IL-10 and TNF-α play an important role in the pathogenesis and development of ulcerative colitis. Chinese medicine combined with Bifico has satisfactory therapeutic effect on UC rats, and its mechanism may be related with the increase of IL-10 expression level and with the decrease of TNF-α expression level.
2.Effects of fasudil hydrochloride on ROCK2 protein and ferroptosis in hippocampus during early brain injury in rats with subarachnoid hemorrhage
Linlin SUN ; Zhiying LI ; Xingxiang ZHANG ; Zehong XU ; Baiqiang WU ; Tiantian WANG ; Xinge XU ; Aijun FU
Chinese Journal of Behavioral Medicine and Brain Science 2023;32(1):9-14
Objective:To investigate the effects of fasudil hydrochloride(FH) on Rho-associated kinase 2(ROCK2) protein and ferroptosis in hippocampal area during early brain injury in rats with subarachnoid hemorrhage(SAH).Methods:Total 36 SPF grade Sprague-Dawley rats were divided into 3 groups by random number table method: Sham group, SAH group and SAH+ FH (a ROCK2 protein inhibitor) group (FH goup) with 12 rats in each group.SAH animal model was established by internal carotid artery perforation.The rats in FH group were injected intraperitoneally with FH(15 mg/kg) 30 minutes after successful modeling, and rats in Sham group and SAH group were injected intraperitoneally with the same volume of 0.9% sodium chloride solution.Twenty-four hours after the intervention, shuttle box test was used to observe the learning and memory ability of rats.The Fe 2+ content in rat hippocampus tissue was detected by colorimetry, and the protein levels of ROCK2 and ferroptosis-related long-chain acyl-CoA synthetase 4(ACSL4) and glutathione peroxidase 4(GPX4) in hippocampus were detected by immunohistochemistry and Western blot.Statistical analysis was performed by SPSS 20.0 software.One-way ANOVA was used for multigroup comparison, and LSD test was used for further pairwise comparison. Results:(1)In the shuttle box test, there were statistically significant differences in the number of avoidance reactions and avoidance reaction time of rats among the three groups( F=20.348, 22.316, both P<0.05). The number of avoidance reaction in SAH group was less than that in Sham group ((17.92±2.94) times, (27.13±3.48) times, P<0.05), the time of avoidance reaction in SAH group was longer than that in Sham group ((9.15±2.87) s, (3.68±1.09) s, P<0.05), while the number of avoidance reaction in FH group ((21.63±4.11) times) was more than that in SAH group, and the time of avoidance reaction ((6.08±1.76) s) was shorter than that in SAH group (both P<0.05). (2) The colorimetry results showed that there was a statistically significant difference in the content of Fe 2+ in hippocampus of rats among the three groups( F=7.965, P<0.05). The Fe 2+ content in SAH group was significantly higher than that of Sham group((0.091±0.032) nmol/mg, (0.038±0.024) nmol/mg, P<0.05), and the Fe 2+ content in the FH group ((0.065±0.021) nmol/mg) was lower than that of SAH group ( P<0.05). (3) There were significant differences in the number of ROCK2, ACSL4 and GPX4 positive cells in hippocampus of rats among the three groups in immunohistochemistry ( F=7.602, 14.171, 36.077, all P<0.05). The positive cells of ROCK2 and ACSL4 in SAH group ((21.63±4.72), (55.13±19.41)) were significantly higher than those of Sham group ((11.63±3.62), (23.38±3.74)) (both P<0.05), and the positive cells of ROCK2 and ACSL4 in FH group ((15.88±6.64), (44.75±8.29)) were both lower than those of SAH group(both P<0.05), while the number of GPX4 positive cells in SAH group (25.38±6.30) was significantly lower than that of Sham group (60.25±10.36) ( P<0.05), and the number of GPX4 positive cells in FH group (45.13±7.51) was higher than that of SAH group( P<0.05). (4)The results of Western blot showed that there were significant differences in the expression levels of ROCK2, ACSL4 and GPX4 proteins in the hippocampus of rats among the three groups( F=4.812, 12.573, 10.849, all P<0.05). The protein expression levels of ROCK2 and ACSL4 in SAH group were significantly higher than those in Sham group(both P<0.05), and the protein expression levels of ROCK2 and ACSL4 in FH group were lower than those in SAH group (both P<0.05), while the expression level of GPX4 protein in SAH group (0.27±0.09) was significantly lower than that in Sham group( P<0.05), and the expression level of GPX4 protein in FH group was higher than that of SAH group ( P<0.05). Conclusion:FH can inhibit ferroptosis in the hippocampus and improve the learning and memory ability of rats, and the mechanism may be related with down-regulation of ROCK2 protein.
3.The Prognostic Significance of Notch1 and Fatty Acid Binding Protein 7 (FABP7) Expression in Resected Tracheobronchial Adenoid Cystic Carcinoma: A Multicenter Retrospective Study.
Mian XIE ; Xiaojun WU ; Jinjun ZHANG ; Chaosheng HE ; Shenhai WEI ; Junyao HUANG ; Xinge FU ; Yingying GU
Cancer Research and Treatment 2018;50(4):1064-1073
PURPOSE: Adenoid cystic carcinoma (ACC) of the trachea and bronchus is a rare tumor. Although MYB-NFIB oncogene fusion and Notch1 mutation have been identified in ACC, little is known about the expression and clinical significance of Notch1 and its target gene fatty acid binding protein 7 (FABP7) in tracheobronchial ACC. MATERIALS AND METHODS: Primary tracheobronchial ACC that were resected between 1998 and 2014 were identified through the pathology and oncology database from five thoracic oncology centers in China. A tissue array was constructed from the patients’ samples and the expressions of Notch1 and FABP7 were evaluated by immunohistochemistry. The association between the expression of both markers and survival was determined. RESULTS: Overexpression of Notch1 and FABP7, detected in 37.8% and 38.3% of 368 patients with tracheobronchial ACC, respectively, was an independent prognostic indicator for recurrencefree survival (RFS) by multivariable Cox proportional hazard model (p=0.032 and p=0.048, respectively). Overexpression of Notch1, but not of FABP7, predicted overall survival (OS) (p=0.018). When categorized into four groups according to coexpression of Notch1 and FABP7, patients with overexpression of both Notch1 and FABP7 belonged to the group with the shortest RFS and OS (p=0.01 and p=0.048, respectively). CONCLUSION: Expression of Notch1 and FABP7, and coexpression of Notch1 and FABP7, is strongly associated with poor survival in resected tracheobronchial ACC. These data are consistent with the hypothesis that poor differentiation of tracheobronchial ACC correlates with the activation of Notch signaling.
Adenoids*
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Bronchi
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Carcinoma, Adenoid Cystic*
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Carrier Proteins*
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China
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Humans
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Immunohistochemistry
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Oncogene Fusion
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Pathology
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Prognosis
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Proportional Hazards Models
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Retrospective Studies*
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Trachea