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Analyze interleukin-1β,interleukin-6,and tumor necrosis factor-αlevels in dry eye and the therapeutic effect of cyclosporine a

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World Journal of Clinical Cases 2024年第25期12卷 5665-5672页

作者： Juan Wu Gui-Jun Li Jie Niu Fei Wen Li Han Department of Ophthalmology The First People’s Hospital of XiningXining 810000Qinghai ProvinceChina

BACKGROUND Dry eye is a common eye *** tears supplements are widely used for the treatment of dry ***,multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears,which may affect the therapeutic *** To analyze the characteristics of interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor-alpha(TNF-α)levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine *** A total of 124 dry eye patients treated at The First People’s Hospital of Xining from April 2020 to April 2022 were selected as the observation group,while 20 healthy individuals served as the control group during the same *** of inflammatory markers,including IL-1β,IL-6,and TNF-α,were *** observation group was further divided into a study group and a control group,each consisting of 62 *** control group received artificial tears,whereas the study group received a combination of artificial tears and cyclosporine *** markers,Schirmer’s test(SIT),tear break-up time(TBUT),corneal fluorescein staining(CFS),National Eye Institute Visual Function Questionnaire-25(NEI-VFQ-25)scores,and adverse events(AEs)were compared between the two *** The observation group exhibited significantly elevated serum levels of IL-1β,IL-6,and TNF-αin comparison to the healthy *** treatment,the study group demonstrated substantial reductions in IL-1β,IL-6,and TNF-αlevels relative to the control ***,after treatment,the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control ***,significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia,foreign body sensation,fatigue,red eye,and burning sensation within the study ***,post-treatment NEI-VFQ-25 scores across all d

关键词： Artificial tears Dry eye syndrome cyclosporine Eye inflammation Interleukin-1β Interleukin-6 Tumor necrosis factor-α cyclosporine a

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cyclosporine a, FK-506, 40-0-[2-hydroxyethyl]rapamycin and mycophenolate mofetil inhibit proliferation of human intrahepatic biliary epithelial cells in vitro

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World Journal of Gastroenterology 2005年第48期11卷 7602-7606页

作者： Chao Liu Thomas Schreiter Andrea Frilling Uta Dahmen Christoph E Broelsch Guido Gerken Ulrich Treichel Department of Gastroenterology and Hepatology University Hospital Essen Germany Department of General Surgery and Transplantation University Hospital Essen Germany

AIM： To investigate the effect of cyclosporine a （CsA）, FK-506, and mycophenolate mofetil （MMF） and 40-0-[2- hydroxyethyl]rapamycin （RAD） on proliferation of human intrahepatic biliary epithelial cells （BECs） in ***： BECs were isolated from six human liver tissuespecimens with the immunomagnetic separation method and treated with different concentrations of CsA, FK-S06, RAD, and MMF in vitro. Proliferation of the cells was measured by MTT assay at 24 and 48 h after treatment, respectively. One-way analysis of variance was used to analyze the results. Expression of CK 19 in BECs was monitored by flow cytometry and Western ***： Six lines of BECs were established. They survived for 4-18 wk in vitro. Flow cytometry analysis showed that these cells always expressed CK19. CsA, FK-506, RAD, and MMF inhibited proliferation of BECs in a dose-dependent manner. The lowest concentration of CsA, FK-506, RAD, and MMF to inhibit proliferation of BECs （P〈0.05） was 500, 100, 0.25, and 100 pg/L, respectively. However, the expression of CK19 by BECs was not ***： CsA, FK-506, RAD, and MMF have an antiproliferative effect on human intrahepatic BECs in vitro, while RAD has the strongest growth-inhibitory effect. Their possible effects on liver regeneration and bile duct injury in transplant patients should be further investigated.

关键词： cyclosporine a FK-506, Rapamycin Mycophenolate mofetil Biliary epithelial cells

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Co-administration of cyclosporine a alleviates thioacetamide-induced liver injury

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World Journal of Gastroenterology 2005年第10期11卷 1411-1419页

作者： Sabrina Fan Ching-Feng Weng Institute of Biotechnology

AIM: To investigate the effects of cyclosporine a (CsA)on thioacetamide (TAA)-induced liver ***: CsA was co-administrated (7.5 μg/kg body weight per day, i.p.) into rat to investigate the role of CsA on TAA-(200 mg/kg body weight per 3 d for 30 d, i.p.)induced liver ***: The data show that TAA caused liver fibrosis in rat after 30 d of treatment. CsA alleviates the morphological changes of TAA-induced fibrosis in rat liver. The blood glutamyl oxaloacetic transaminase (GOT)/glutamyl pyruvic transaminase (GPT) in the TAA-injury group is elevated compared to that of the normal rat. Compared with the TAA-injury group, the blood GOT/GPT and TGFβ1 (by RT-PCR analysis) are reduced in the CsA plus TAA-treated rat. The level of the transforming growth factor receptor I (TGFβ-R1) in the CsA plus TAA-treated group shows higher than that in the TAA only group, but shows a lower level of the fibroblast growth factor receptor 4 (FGFR4)in the CsA plus TAA-treated group, when using the Western blot analysis. After immunostaining of the frozen section,TGFβ-R1 and FGFR4 are more concentrated in rat liver after CsA plus TAA ***: This result suggests that CsA has an alleviated effect on TAA-induced liver injury by increasing the multidrug resistance P-glycoprotein and could be through the regulation of TGFβ-R1 and FGFR4.

关键词： cyclosporine a Thioacetamide Liver injury P-glycoprotein TGFβ1 TGFβ-R1 FGFR4

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Evaluation of hepatitis B virus replication and proteomic analysis of HepG2.2.15 cell line after cyclosporine a treatment

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Acta Pharmacologica Sinica 2007年第7期28卷 975-984页

作者： Hai-yang XIE,Wei-liang XIA,Chun-chao ZHANG,Li-ming WU,Hao-feng JI,Yu CHENG,Shu-sen ZHENG~2Department of Hepatobiliary Pancreatic Surgery,Key Laboratory of Multiple Organ Transplantation,Ministry of Public Health,Key Labo-ratory of Organ Transplantation Zhejiang Province,First Affiliated Hospital,School of Medicine,Zhejiang University,Hangzhou 310003,China Department of Hepatobiliary Pancreatic Surgery Key Laboratory of Multiple Organ Transplantation Ministry of Public Health Key Laboratory of Organ Transplantation Zhejiang Province First Affiliated Hospital School of Medicine Zhejiang University Hangzhou China

Aim:The effect of cyclosporine a (CsA) on hepatitis B virus (HBV) replicationwas investigated,and proteomics expression differentiation after CsA treatmentwas studied in order to provide clues to explore the effect of CsA on ***:Methyl thiazolyl tetrazolium (MTT) assay was used toevaluate the cytotoxicity of *** HBV replication level in the HBV genomicDNA transfected HepG2.2.15 cell line was determined by an ELISA analysis ofhepatitis B surface antigens (HBsAg) and Hepatitis B e antigens (HBeAg) inculture supernatant,while the intracellular HBV DNA replication level was ana-lyzed by slot blot ***-dimensional electrophoresis was used toinvestigate the alteration of protein expression in HepG2.2.15 after CsA treatmentin *** differentially-expressed proteins were identified by Matrix-assistedlaser desorption/ionization-time of flight mass spectrometry combined with anonline database ***:CsA was able to inhibit the expression of HBsAg,HBeAg,and HBV DNA replication in vitro in a dose-dependent *** analysis indicated that the expression of 17 proteins changed signifi-cantly in the CsA treatment group compared to the control *** of the 17proteins were identified,including the overexpression of eukaryotic translationinitiation factors (eIF) 3k,otubain 1,14.3.3 protein,eIF2-α,eIF5A,and thetyrosine 3/tryptophan 5-mono-oxygenase activation protein in CsA-treatedHepG2.2.15 *** downregulation of the ferritin light subunit,erythrocytecytosolic protein of 51 kDa (ECP-51),stathmin 1/oncoprotein,adeninephosphoribosyl-transferase,and the position of a tumor protein,translationally-controlled 1,was shifted,suggesting it had undergone ***:Our study identified the inhibitory effect of CsA onHBV replication,and found that a group of proteins may be responsible for thisinhibitory effect.

关键词： hepatitis B virus cyclosporine a replication proteomics

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Treatment of ocular rosacea: comparative study of topical cyclosporine and oral doxycycline

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International Journal of Ophthalmology(English edition) 2015年第3期8卷 544-549页

作者： Aysegul Arman Duriye Deniz Demirseren Tamer Takmaz Ophthalmology Clinic Ankara Ataturk Training and Research Hospital Dermatology Clinic Ankara Ataturk Training and Research Hospital

AIM: To compare the effectiveness of topical cyclosporine a emulsion with that of oral doxycycline for rosacea associated ocular changes and dry eye ***: One hundred and ten patients with rosacea were screened. Thirty-eight patients having rosacea associated eyelid and ocular surface changes and dry eye complaints were included in the study. Patients were randomly divided into two groups: nineteen patients were given topical cyclosporine twice daily and nineteen patients were given oral doxycycline 100 mg twice daily for the first month and once daily for the following two months. Symptom and sign scores, ocular surface disease index questionnarie and tear function tests were evaluated at baseline and monthly for 3mo. Three months after results were compared with that of ***: Mean values of symptom, eyelid sign and corneal/conjunctival sign scores of each treatment group at baseline and 3mo after treatments were compared and both drugs were found to be effective on rosacea associated ocular changes(P cyclosporine was more effective in symptomatic relief and in the treatment of eyelid signs(P =0.01). There was statistically significant increase in the mean Schirmer score with anesthesia and tear break up time scores in the cyclosporine treatment group compared to the doxycycline treatment group(P cyclosporine as a topical drug can be used in the treatment of rosacea associated ocular complications because it is more effective than doxycycline. In addition ocular rosacea as a chronic disease requires long term treatment and doxycycline has various side effects limiting its long term usage.

关键词： cyclosporine a doxycycline rosacea

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Discovery of the anti-influenza A virus activity of SB216763 and cyclosporine a by mining infected cells and compound cellular signatures

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Chinese Chemical Letters 2022年第5期33卷 2541-2544页

作者： Ke Tang You Wu Shubing Chen Yijing Xin Ying Guo State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Department of Pharmacology Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

In this study,SB216763 and cyclosporine a were identified as anti-influenza A virus(IAV)agents by tran-scriptome signature reversion(TSR)analysis through deep mining of the cellular transcriptome of hu-man airway and lung cell lines infected with 3 strains of IAV and the chemical perturbations library.A synergistic effect of SB216763 and cyclosporine a against influenza A was disclosed by quantification of the network-based relationship,which was validated in *** with burgeoning omics approaches,transcriptome-based drug development is flourishing,which provides a novel insight into antivirals dis-covery with comprehensive cellular transcriptional information of disease and chemical perturbations in multicomponent *** strategy can be applied as a new approach in discovering multitar-get antiviral agents from approved drugs,clinical compounds,natural products or other known bioactive compounds.

关键词： Chemical perturbagen signature Host factor Transcriptome signature reversion Influenza A virus SB216763 cyclosporine a Drug combination

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Structure-guided manipulation of the regioselectivity of the cyclosporine a hydroxylase CYP-sb21 from Sebekia benihana

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Synthetic and Systems Biotechnology 2020年第3期5卷 236-243页

作者： Fengwei Li Li Ma Xingwang Zhang Jingfei Chen Feifei Qi Yinyue Huang Zepeng Qu Lishan Yao Wei Zhang Eung-Soo Kim Shengying Li State Key Laboratory of Microbial Technology Shandong UniversityQingdaoShandong266237China Shandong Provincial Key Laboratory of Synthetic Biology CAS Key Laboratory of BiofuelsQingdao Institute of Bioenergy and Bioprocess TechnologyChinese Academy of SciencesQingdaoShandong266101China Department of Biological Engineering Inha UniversityIncheon22212South Korea Laboratory for Marine Biology and Biotechnology Qingdao National Laboratory for Marine Science and TechnologyQingdaoShandong266237China

The cytochrome P450 enzyme CYP-sb21 from the rare actinomycete Sebekia benihana is capable of hydroxylating the immunosuppressive drug molecule cyclosporine a(CsA)primarily at the 4th N-methyl leucine(MeLeu4),giving rise toγ-hydroxy-N-methyl-L-Leu4-CsA(CsA-4-OH).This oxidative modification of CsA leads to dramatically reduced immunosuppressive activity while retaining the hair growth-promoting side-effect,thus demonstrating great application potential in both pharmaceutical and cosmetic ***,this P450 enzyme also hydroxylates CsA at the unwanted position of the 9th N-methyl leucine(MeLeu9),indicating that the regioselectivity needs to be improved for the development of CsA-4-OH into a commercial hair growth ***,we report the crystal structure of CYP-sb21 in its substrate-free form at 1.85Å.Together with sequence and 3D structure comparisons,Autodock-based substrate docking,molecular dynamics(MD)simulation,and site-directed mutagenesis,we identified a number of key residues including R294,E264,and M179 that can improve catalytic efficiency or change the regioselectivity of CYP-sb21 towards CsA,setting the stage for better enzymatic preparation of *** study also provides new insights into the substrate recognition and binding mechanism of P450 enzymes that accommodate bulky substrates.

关键词： Cytochrome P450 monooxygenase Crystal structure cyclosporine a Regioselectivity Hair growth stimulator

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Inhibitory effect of tea polyphenals on transforming growth factor-β1 expression in rat with cyclosporine a-induced chronic nephrotoxicity

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Acta Pharmacologica Sinica 2004年第1期 100-105页

作者： Shao-hua SHI, Shu-sen ZHENG, Chang-ku JIA, You-fa ZHU, Hai-yang XIEDepartment of Hepatobiliary Surgery, the First Affiliated Hospital, Medical College, Zhejiang University Department of Pathology, Medical College, Zhejiang University Institute of Surgery, Zhejiang University, Hangzhou 310003, China

AIM: To investigate the inhibitory effect of tea polyphenols (TP)on the transforming growth factor-pi (TGF-β1) expression in rat model of cyclosporine a (CsA)-induced chronic nephrotoxicity. METHODS: The rat model of CsA-induced chronic nephrotoxicity was used, 4 groups of rats were respectively treated with vehicle (0.1 mL·lg-1-d-1 sc), TP (80 mg·kg-1·d-1 ig), CsA (15 mg·2kg-1·d-1sc) and TP plus CsA (CsA 15 mg·kg-1·d-1 sc+TP 80 mg·kg-1·d-1 ig). At the end of day 28 of treatment, serum and urine are analyzed for creatinine clearance, kidney tissue for pathologic analysis. The TGF-β1 mRNA and its protein expression were detected by RT-PCR, immunohistochemistry, and Western blot. RESULTS: CsA-treated rats had increased renal expression of TGF-pl mRNA and its protein, compared with the vehicle- or TP- treated

关键词： tea cyclosporine a transforming growth factor-β kidney polymerase chain reaction immunohistochemistry Western blotting

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Treatment of gingival hyperplasia induced by cyclosporine a

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Frontiers of Medicine 2008年第3期2卷 290-294页

作者： Jingzhi MA Ming LI Yingguang CAO Center of Stomatological Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

The clinical therapy for cyclosporine a(CsA)-induced gingival hyperplasia(GH)and the pathological changes in hyperplastic gingival tissues were *** cases of CsA-induced GH after renal transplantation were subjected to periodontal non-surgical treatment and surgical treatment and were followed *** index(GI),dental plaque index(PLI)and GH degree(GHD)at different time points were *** light and elec-tron microscopy,the pathological changes in hyperplastic gingival tissues were *** CsA concentrations in gingival tissues and blood were determined by using fluor-escence polarization immunoassay with TDxFLx monoclo-nal *** results showed that GI,PLI and GHD in patients with GH declined after periodontal *** patients suffered from different degrees of GH during the 6 months to 54 months *** trans-mission electron microscopy,fibroblasts in the hyperplastic gingival tissues were enlarged,cytoplasmic rough endoplas-mic reticula were abundant and expanded slightly,and a few fibroblasts with early apoptotic changes were *** concentrations of CsA in hyperplastic gingival tissues were from 351.00 to 1345.47 ng/mL,which were significantly higher than in the blood of the same patients taken at the same time *** was concluded that GI and PLI declined after periodontal treatment in combination with surgical treatment in patients taking CsA for a long time,but in some patients,GH *** fact that the con-centration of CsA in hyperplastic gingival tissues is higher than in blood awaits further studies.

关键词： cyclosporine a renal transplantation gin-gival hyperplasia

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The effects of diltiazem in renal transplantation patients treated with cyclosporine a

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The Journal of Biomedical Research 2010年第4期24卷 317-323页

作者： Wujun Xue Yong Song Puxun Tian Xiaoming Ding Xiaoming Pan Hang Yan Jun Hou Xinshun Feng Heli Xiang Xiaohui Tian Department of Renal Transplant Center of Nephropathy the First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 Shaanxi Province China

Objective： To investigate the effects of diltiazem and cyclosporine a （CsA） combination therapy on protecting the kidney, promoting graft functioning and improving post-transplanted kidney recovery. Methods： The blood con- centrations of CsA, the condition of the post-transplant kidney, the rate of acute rejection （AR）, as well as hepatic and renal toxicity in 636 cases of renal transplant recipients were determined after being treated by CsA, with or without diltiazem. Results： Compared with the control group which received CsA, mycophenolate mofetil （MMF） and prednisolone （Pred） but lacked diltiazem, the group receiving these agents together with diltiazem required reduced dosage of CsA （P 〈 0.01）, while blood concentrations of CsA were significantly increased （P 〈 0.01）; the recovery time of graft function was reduced from （6.2± 1.5） d to （3.9± 1.4） d （P 〈 0.01）, and the rate of AR was decreased from 13.2% to 7.9% （P 〈 0.01）. Conclusion： In renal transplantation patients treated with CsA and diltiazem, blood concentrations of CsA were increased while the dosage was decreased. This efficient combination therapy reduced patients economic burden, at the same time retained kidney function, promoted graft function recovery and decreased hepatic and renal toxicity and the rate of AR.

关键词： transplant/kidney diltiazem cyclosporine a

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