Prognostic model on pregnancy outcomes for women with recurrent spontaneous abortions treated with cyclosporin A: A single-institution experience

Abstract Background: This study aimed to identify prognostic factors for pregnancy outcomes and construct a prognostic model for pregnancy outcomes in women with Recurrent Spontaneous Abortions (RSA) treated with cyclosporin A. Methods: A total of 154 RSA patients treated with cyclosporin A between October 2016 and October 2018 were retrospectively recruited. Multivariate logistic regression was applied to identify the prognostic factors for pregnancy success in RSA women treated with cyclosporin A. The Receiver Operating Characteristic (ROC) curve was applied to construct prognostic value, and the prognostic performance was assessed using area under the ROC. Results: After adjusting potential confounding factors, the authors noted increased age (OR = 0.771; 95 % CI 0.693‒0.858; p < 0.001) and positive antinuclear antibodies (OR = 0.204; 95 % CI 0.079‒0.526; p = 0.001) were associated with a reduced incidence of pregnancy success, while positive anti-β2 glycoprotein-I-antibody (OR = 21.941; 95 % CI 1.176‒409.281; p = 0.039) was associated with an increased incidence of pregnancy success after treated with cyclosporin A. The AUC of combining these variables for predicting pregnancy failure was 0.809 (95 % CI 0.735‒0.880). Conclusion: This study systematically identified the prognostic factors for pregnancy success in women treated with cyclosporin A, and the constructed prognostic model based on these factors with relatively higher prognostic value. Further large-scale prospective studies should be performed to validate the prognostic value of the constructed model.

Research progress of CYPA in malignant tumors / 国际生物医学工程杂志

Cyclosporin A (CYPA) is an important member of the cyclophilin family, encoded by the peptidyl prolyl isomerase A gene, and has a variety of important biological functions, mainly involved in inflammation, immunity, and other pathophysiological processes. In addition, CYPA plays a regulatory role in tumor cell proliferation, invasion, apoptosis, metastasis, angiogenesis, and epithelial-mesenchymal transition through various molecular mechanisms, among which the specific binding of CYPA to CD147 has received wide attention. In this review, the mechanism of CYPA in various malignant tumors was mainly reviewed, and its regulatory mechanism and potential interventions in malignant tumors were analyzed, with the aim that CYPA will play an important role in the early diagnosis and precise treatment of tumors in the future.

Therapeutic drug monitoring in the individualized administration of cyclosporin A: Application and research progress / 中国临床药理学与治疗学

Cyclosporine A (CsA) is a kind of cellular immunosuppressant, which is widely used in organ transplantation, blood diseases and autoimmune diseases. Because of its poor oral bioavailability, individual differences and prone to adverse reactions, so clinical therapeutic drug monitoring (TDM) and individual administration of CsA can ensure its safety and effectiveness. However, the treatment window of CsA is narrow, and its blood concentration is affected by age, sex, diet, drug factors, genetic factors and so on. Therefore, combined with the literature reports at home and abroad, this paper reviews the research on the application of TDM and individual drug administration of CsA, in order to provide more valuable reference for clinical safe and rational drug use.

Evaluation of the Efficacy of Cyclosporin A Combined with Recombined Human Erythropoietin in the Treatment of Patients with Chronic Aplastic Anemia / 中国医学科学院学报

Objective To compare the efficacy and safety of cyclosporin A(CsA)and CsA combined with recombined human erythropoietin(rhEPO)in the treatment of patients with chronic aplastic anemia(CAA).Methods Data of 79 patients with CAA treated at Department of Hematology,PUMC Hospital between January 2016 and June 2018 were collected for retrospective analysis.Forty-five patients were treated with CsA+rhEPO,and the other 34 patients with CsA alone.All the enrolled patients were treated for at least 1.5-2.0 years and followed for at least 1.0 year.The efficacy,side effects,long-term outcomes were compared between the two groups,and factors that may influence the efficacy were analyzed.Results The patients treated with CsA+rhEPO included 14 males and 31 females,with a median age of 43(19,73)years old.The median treatment duration of CsA and rhEPO was 26(12,38)and 4(3,6)months,respectively,and the median followed-up time was 24(12,42)months.The patients treated with CsA alone included 16 males and 18 females,with a median age of 36(16,85)years old.The median CsA treatment duration was 24(12,40)months and the median follow-up time was 25(12,40)months.There was no statistical difference in baseline characteristics between the two groups(all

Clinical and laboratory analysis of 17 patients with γδT-cell large granular lymphocyte leukemia / 中华血液学杂志

Objective: To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αβ T-cell large granular lymphocyte leukemia (αβT-LGLL) . Methods: The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αβT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed. Results: The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αβT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4(-)/CD8(-) phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%. Conclusion: γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αβT-LGLL. γδT-LGLL predominantly expressed a CD4(-)/CD8(-) phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.

Role of cyclophilin A during coronavirus replication and the antiviral activities of its inhibitors / 生物工程学报

Cyclophilin A (CypA) is a widely distributed and highly conserved protein in organisms. It has peptidyl-prolyl cis/trans isomerase activity and is a receptor for cyclosporin A (CsA). Coronaviruses are enveloped, single-stranded, positive-sense RNA viruses. Seven types of coronaviruses are currently known to infect humans, among which SARS-CoV, MERS-CoV, and SARS-CoV-2 are fatal for humans. It is well established that CypA is essential for the replication of various coronaviruses such as SARS-CoV, CoV-229E, CoV-NL63, and FCoV. Additionally, CsA and its derivatives (ALV, NIM811, etc.) have obvious inhibitory effects on a variety of coronaviruses. These results suggest that CypA is a potential antiviral target and the existing drug CsA might be used as an anti-coronavirus drug. At the end of 2019, SARS-CoV-2 raged in China, which seriously theatern human health and causes huge economic lases. In view of this, we describe the effects of CypA on the replication of coronaviruses and the antiviral activities of its inhibitors, which will provide the scientific basis and ideas for the development of antiviral drugs for SARS-CoV-2.

Clinical and laboratory analysis of 17 patients with γδT-cell large granular lymphocyte leukemia / 中华血液学杂志

Objective@#To compare the difference of the clinical and laboratory characteristics between γδ T-cell large granular lymphocyte leukemia (γδT-LGLL) and αβ T-cell large granular lymphocyte leukemia (αβT-LGLL) .@*Methods@#The clinical and laboratory characteristics of 17 patients with γδT-LGLL and 91 patients with αβT-LGLL in the department of therapeutic center of anemia of enrolled in our hospital from January 2009 to January 2019 were retrospectively analyzed.@*Results@#The median age of the 17 patients with γδT-LGLL was 54 years (range, 25-73 years) , the most common presenting symptom was anemia. In comparison with αβT-LGLL patients, splenomegaly was common (41% and 44%, respectively) , whereas hepatomegaly (12% and 5%, respectively) and lymphadenopathy (6% and 8%, respectively) were rare. The positive rates of antinuclear antibody (59% and 45%, respectively) were high, whereas the positive rates of rheumatoid factor (6% and 10%, respectively) were rare for both groups. There were no differences on peripheral blood counts between the two groups. However, γδT-LGLL patients were found to be predominantly expressed a CD4−/CD8− phenotype. Steroid therapy with prednisone was used alone as first-line therapy for 1 patient. Cyclosporin A (CsA) was used alone as first-line therapy for 3 patients. CsA in combination with steroids were administered in 13 patients. After 4 months treatment, 2 patients acquired complete response, 4 patients acquired partial response, the overall response was 35%.@*Conclusion@#γδT-LGLL is a rare mature T-lymphocyte proliferative disease. Clinical and laboratory characteristics were quite similar for γδT-LGLL in compare with αβT-LGLL. γδT-LGLL predominantly expressed a CD4−/CD8− phenotype. The data presented here indicate the CsA is an effective option for the first-line treatment of γδT-LGLL.

Effect of cyclosporine A combined with glucocorticoid in the treatment of corneal ulcer / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the effect of cyclosporine A combined with glucocorticoid in the treatment of corneal ulcer.<p>METHODS: From May 2015 to May 2018, 200 patients with corneal ulcer were selected and divided into combined group and glucocorticoid group according to different treatment methods, 100 cases each. In the combined group, cyclosporine A was given on the basis of the glucocorticoid group. C-reactive protein(CRP)and interleukin-6(IL-6)were measured to evaluate the quality of life, clinical symptoms, treatment efficiency, recurrence rate and incidence of adverse reactions.<p>RESULTS: After treatment, the levels of CRP and IL-6 in the two groups were lower than that before treatment, and the quality of life was higher than that before treatment(<i>P</i><0.05). The level of CRP and IL-6 in the combined group was lower than that in the glucocorticoid group, and the quality of life was higher than that in the glucocorticoid group(<i>P</i><0.05). The time of conjunctival hyperemia, ophthalmalgia and ulcer healing in the combined group were lower than those in the glucocorticoid group(<i>P</i><0.05). The effective rate of combined group was higher than that of glucocorticoid group, and the recurrence rate of combined group was lower than that of glucocorticoid group(<i>P</i><0.05).<p>CONCLUSION: Cyclosporine a combined with hormone is effective in the treatment of corneal ulcer, which can improve the clinical symptoms, reduce the inflammation, improve the quality of life and reduce the recurrence.

The protective effects of cyclosporin A on vascular permeability in sepsis rats / 药学学报

The protective effects of cyclosporin A (CsA), an inhibitor of mitochondrial permeability transition pore (MPTP), on vascular permeability in sepsis rats were investigated. Cecal ligation and puncture (CLP)-induced sepsis rats were used for in vivo studies, and the effects of CsA (1 and 5 mg·kg-1) on vascular permeability of lung, kidney, and intestine, mitochondrial respiratory control ratio, and the survival of the sepsis rats were observed. Lipopolysaccharide (LPS) was used for stimulating vascular endothelial cells (VECs) in vitro, and the effects of CsA on leakage of microvascular, immunofluorescence of zonula occludes-1 (ZO-1), and transendothelial electrical resistance (TER) were observed. All the animal welfare and experimental procedures are in accordance with the regulations of the Animal Ethics Committee of the Army Medical University. Compared with sham-operated group, the vascular permeability of lung, kidney, and intestine in sepsis rats increased significantly (P<0.05). Compared with conventional treatment group, CsA could significantly decrease the vascular permeability of lung, kidney, and intestine (P<0.05 or P<0.01), and prolong the survival period. The results of microcirculation also showed that CsA could significantly reduce the permeability of mesenteric venules in sepsis rats. At the cellular level, LPS stimulation significantly increased the permeability of vascular endothelial cells, including the decrease of transmembrane resistance and protein expression of ZO-1 (P<0.05). CsA can significantly reduce the increase of permeability of vascular endothelial cells induced by LPS stimulation (P<0.01). The function of mitochondria in the kidneys and intestines of sepsis rats was obviously impaired, and the respiratory control ratio of mitochondria was decreased. LPS significantly increased MPTP opening of VECs, while CsA significantly inhibited MPTP opening and improved mitochondrial function. CsA may protect mitochondrial function by inhibiting the opening of MPTP and play a protective role in the vascular permeability of sepsis rats. This study will provide an insight for the treatment of sepsis vascular leakage.

<i>In vitro</i> interactions between antifungals and Cyclosporin A against Fusarium solani / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the<i> in vitro</i> interaction between antifungals and tacrolimus acting alone or in combination against Fusarium solani.<p>METHODS: According to Clinical and Laboratory Standards Institute(CLSI)M27-Ed4 and M38-A3, 22 strains of Fusarium solani were used to perform drug sensitivity tests with chessboard microdilution method by cyclosporin A combined with 4 kinds of antifungal drugs <i>in vitro</i>.<p>RESULTS: The MIC ranges of natamycin, voriconazole, amphotericin B and fluconazole against 22 strains of Fusarium solani were 2-8, 1-8, 1-8 and 8-512μg/mL respectively. When combined with tacrolimus <i>in vitro</i>, the synergistic effects of fluconazole and Amphotericin B were observed in 64% and 41% strains respectively. There were no antagonistic effects observed in all combined drug tests. With the combination, the sensitivity of Fusarium to amphotericin B was significantly increased from 4.5% to 68.2%(<i>P</i><0.001).<p>CONCLUSION: Fusarium solani is sensitive to natamycin <i>in vitro</i> and is partially sensitive to voriconazole. When combined with cyclosporine A, it can produce synergistic effects with fluconazole and amphotericin B, and significantly increase the sensitivity of Fusarium solani to amphotericin B drugs.

Agrandamiento gingival generalizado en un paciente con trasplante renal / Generalized gingival enlargement in a patient with renal transplant

Introducción: El agrandamiento gingival es el aumento exagerado y desfigurante del volumen de la encía. Su aparición se asocia a fármacos, entre los que se encuentran los inmunosupresores y los bloqueadores de los canales de calcio como la ciclosporina A y amlodipino. Objetivo: Describir un caso clínico de agrandamiento gingival asociado a ciclosporina A y amlodipino, con periodontitis crónica subyacente, su tratamiento y prevención de recidiva. Presentación del caso: Paciente masculino, de 50 años de edad, antecedentes de hipertensión arterial, asma bronquial y hepatitis C, además de presentar insuficiencia renal crónica para la cual se le realizó un trasplante renal. Recibe tratamiento con ciclosporina A y amlodipino. Al examen clínico se observaron aumento de volumen generalizado en la encía, que cubría completamente la corona de los dientes, bolsas periodontales de 5 a 8 mm, sangramiento gingival y movilidad dentaria. Principales comentarios: El proceso diagnóstico permitió comprobar que además del agrandamiento gingival generalizado existía una periodontitis crónica generalizada. Conclusiones: La ingestión de un inmunosupresor como la ciclosporina A con el uso de un bloqueador de los canales de calcio, el amlodipino, y la influencia de factores de connotación local, parecen ser los responsables de la aparición combinada del agrandamiento gingival generalizado y la periodontitis crónica concomitante. La fase higiénica contribuyó considerablemente a mejorar el estado periodontal, cuya solución definitiva se alcanzó con la cirugía periodontal convencional. Se corrobora la importancia del examen periodontal en pacientes candidatos a trasplantes de órganos(AU)

Introduction: Gingival enlargement is an exaggerated and disfiguring increase in gum volume, associating its appearance with drugs like immunosuppressants and calcium channel's blockers such as cyclosporine A and Amlodipine. Objective: To describe a clinical case of gingival enlargement associated to cyclosporine A and amlodipine, presenting chronic underlying periodontitis, its treatment and prevention in case of recurrence. Case Presentation: Male patient, 50 years old with a history of arterial hypertension, bronchial asthma and hepatitis C, and presenting chronic renal failure leading renal transplant. The patient was treated with cyclosporine A and amlodipine. In the clinical examination was observed an increased volume in the gum, which completely covered the crown of the teeth, also periodontal bags of 5 to 8 mm, gingival bleeding and dental mobility. Main Comments: The diagnostic process allowed to verify that in addition to the generalized gingival enlargement there was a generalized chronic periodontitis. Conclusions: The ingestion of an immunosuppressant such as Cyclosporin A with the use of a calcium channel's blocker, amlodipine, and the influence of local connotation factors seem to be responsible for the combined appearance of generalized gingival enlargement and concomitant chronic periodontitis. The hygienic phase contributed considerably to improve the periodontal state, whose definitive solution was achieved with conventional periodontal surgery. The importance of periodontal examination in patients who are candidates for organ transplants is corroborated(AU)

Assessment of The Potential Role of Parsley (Petroselinum Crispum) Leaves Extract in Ameliorating Cyclosporin A- Induced Nephrotoxicity in Rats

In this study, a potentiometric titration method by Calvin-Bjerrum and Irwing-Rosotti was used to investigate binarycomplexes of ibandronate sodium, a nitrogen-containing bisphosphonate, with Ca(II), Mg(II) and Sr(II). Dissociationconstants (pKa) of ibandronate sodium were measured and the stability constants of the complexes formed in aqueoussolutions at 22 oC (I = 0.11 M NaClO4) were determined. The stoichiometry of ibandronate sodium/metal complexes wasfound as 1/1 for each metal ion.

Performance Evaluation of the ARCHITECT i2000 for the Determination of Whole Blood Cyclosporin A and Tacrolimus

Maintaining immunosuppressant concentrations within the therapeutic range in organ recipients requires regular monitoring. The blood concentrations of immunosuppressants are routinely measured using one of several automated immunoassays, such as chemiluminescence immunoassays (CLIAs) and liquid chromatography-tandem mass spectrometry (LC-TMS). The ARCHITECT i2000 immunoassay analyzer (Abbott Diagnostics, USA) was developed as an automated CLIA analyzer for the measurement of cyclosporin A and tacrolimus in whole blood. Here, the precision and linearity of the ARCHITECT i2000 analyzer for the detection of cyclosporin A and tacrolimus in whole blood were evaluated according to Clinical and Laboratory Standards Institute guidelines and were compared with those of an LC-TMS detection method. The total coefficient of variation for the two drugs was less than 10%, and they showed linearity values of 0.97 or more, which was within the manufacturer's range. The measurements of both immunosuppressants by the ARCHITECT i2000 were closely correlated with measurements determined by LC-TMS. However, most measurements were lower with LC-TMS than with the ARCHITECT i2000. Measurement of cyclosporin A and tacrolimus in whole blood using the ARCHITECT i2000 showed very satisfactory performance in terms of precision and linearity as well as good correlation with the comparative method.

Identification of the related substances of cyclosporin A by LC-MS techniques / 中国药科大学学报

@#To identify the related substances of cyclosporin A by LC-MS techniques, the separation of cyclosporin A and its related substances was carried out on a Hypersil BDS C18(100 mm×4. 6 mm, 2. 4 μm)column with isocratic elution by a mixture of acetonitrile-water-MTBE and formic acid(430 ∶520 ∶50 ∶1)as the mobile phase. Cyclosporin A and its 29 related substances(9 process related and 20 degradants)were well separated under the established conditions. Among them, 13 were listed in EP and the rest 16 were unknown products having not been reported before. Electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of parent ions of all the components, and triple quadrupoles tandem mass was employed for the product mass spectra determination. Thence, the structures of all the 29 detected substances were successfully characterized through spectra elucidation and the fragmentation pathways analysis. The established LC-MS method was successfully employed for the separation and identification of the related substances of cyclosporin A and it is useful for its fermentation processes and quality control.

Efficacy and Safety of Ciclosporin Combined with Glucocorticoid versus Cyclophosphamide Combined with Glucocorticoid in the Treatment of Membranous Nephropathy ：a Meta-analysis / 中国药房

OBJECTIVE： To systematically evaluate the efficacy and safety of cyclosporin combined with glucocorticoid versus cyclophosphamide combined with glucocorticoid in the treatment of membranous nephropathy （MN）. METHODS： Retrieved from Embase， Medline， CNKI， VIP and Wanfang database， RCTs about cyclosporin combined with glucocorticoid （trial group） versus cyclophosphamide combined with glucocorticoid （control group） in the treatment of MN were collected. Meta-analysis was conducted by using Rev Man 5.3 statistical software after literature screening， data extraction and quality evaluation with Jadad scale. RESULTS： Totally 6 RCTs were included， involving 312 patients in total. Results of Meta-analysis showed that remission rate 3 months after treatment [OR＝3.42，95％CI（2.05，5.71），P＜0.000 01] and relapse rate [OR＝3.12，95％CI（1.45，6.70），P＝0.004]， leukocyte count 12 months after treatment [MD＝1.77，95％CI（0.96，2.58），P＜0.000 1] in trial group were significantly higher than control group. There was no statistical significance in remission rate 6 months after treatment [OR＝2.06，95％CI（0.80，5.30），P＝0.13] and remission rate 12 months after treatment [OR＝1.30，95％CI（0.68，2.48），P＝0.42]， blood creatinine level 3 months after treatment [MD＝－1.55，95％CI（－6.72，3.62），P＝0.56] and blood creatinine level 6 months after treatment [MD＝－1.21，95％CI（－5.96，3.54），P＝0.62]， cholesterol level 12 months after treatment [MD＝－0.77，   95％CI（－1.81，0.28），P＝0.15] or ALT level[MD＝－0.40，95％CI（－4.38，3.58），P＝0.98] between 2 groups. ADR were reported in 5 RCTs， but their results were different. CONCLUSIONS： Long-term efficacy of cyclosporine combined with corticosteroid is similar to that of cyclophosphamide combined with corticosteroid in the treatment of MN. Cyclosporin combined with glucocorticoid has a faster effect， but a higher relapse rate.

Simvasatin plus cyclosporin A inhibits obliterative bronchiolitis in a murine heterotopic tracheal transplant model / 中华器官移植杂志

Objective@#To explore the effect of simvastatin combined with cyclosporin A treatment on the development of obliterative bronchiolitis in a murine heterotopic tracheal transplantation model.@*Methods@#Murine tracheals were heterotopically transplanted from BALB/c donors into C57BL/6 recipients. Transplanted animals received either control chow, chow containing simvastatin, chow containing cyclosporine A, or chow containing simvastatin and cyclosporine A. beginning immediately after transplantation. Epithelial loss and luminal obstruction were analyzed by morphometry. Immunohistochemistry assay was used for quantifying inflammatory cell infiltration and expression of chemokine in tracheal allografts. collagen deposition was studied by picro sirius red staining.Group t test was used to calculate the difference between groups.@*Results@#simvastatin combined with cyclosporin A treatment reduced chemokine(MCP-1, RANTES)release, inhibited CD4+ and CD8+ T cells and macrophages accumulation in tracheal allografts, resulting in limited bronchial inflammation and diminished epithelial loss. simvastatin plus cyclosporin A treatment also inhibited proliferation of myofibroblast cells, reduced MMP-2 release and decreased the amounts of type I and III collagen deposition, resulting in preserved luminal patency and inhibited development of OB compared with those of controls.@*Conclusions@#When simvastatin was used in combination with CsA, the development of OB was significantly inhibited.

Simvasatin plus cyclosporin A inhibits obliterative bronchiolitis in a murine heterotopic tracheal transplant model / 中华器官移植杂志

Objective To explore the effect of simvastatin combined with cyclosporin A treatment on the development of obliterative bronchiolitis in a murine heterotopic tracheal transplantation model .Methods Murine tracheals were heterotopically transplanted from BALB/c donors into C57BL/6 recipients .Transplanted animals received either control chow ,chow containing simvastatin ,chow containing cyclosporine A ,or chow containing simvastatin and cyclosporine A . beginning immediately after transplantation .Epithelial loss and luminal obstruction were analyzed by morphometry .Immunohistochemistry assay was used for quantifying inflammatory cell infiltration and expression of chemokine in tracheal allografts .collagen deposition was studied by picro sirius red staining .Group t test was used to calculate the difference between groups .Results simvastatin combined with cyclosporin A treatment reduced chemokine (MCP-1 , RANTES ) release , inhibited CD4+ and CD8+ T cells and macrophages accumulation in tracheal allografts ,resulting in limited bronchial inflammation and diminished epithelial loss .simvastatin plus cyclosporin A treatment also inhibited proliferation of myofibroblast cells ,reduced M M P-2 release and decreased the amounts of type I and III collagen deposition ,resulting in preserved luminal patency and inhibited development of OB compared with those of controls .Conclusions When simvastatin was used in combination with CsA ,the development of OB was significantly inhibited .

Molecular Pathway of Psoralidin-Induced Apoptosis in HepG2 Cell Line / 中国结合医学杂志

OBJECTIVE@#To test the role of psoralidin in human liver cancer HepG2 cells in vitro.@*METHODS@#Cell viability was assessed by methylthiazolyldiphenyl-tetrazolum bromide assay and apoptotic cells were labeled by annexin V then sorted by flow cytometry. Protein expressions of caspase-3, caspase-8, caspase-9, Bax, Bid, Bcl-2, Bcl-xL and p53 were examined by western blot while activity of caspase-3, -8 and -9 were also determined.@*RESULTS@#Psoralidin reduces cell viability greatly in a time dependent manner (64%, 40%, 21%, 12% at 2, 6, 24 and 48 h treatment with 64 μmol/L psoralidin respectively) and up-regulates activities of caspase-3, -8 and -9 in a concentration dependent manner (between 4 to 64 μmol/L). Psoralidin also increases the expression of pro-apoptosis genes Bax, Bid and p53 while decreases the expression of pro-survival genes Bcl-2 and Bcl-xL, both in a concentration dependent manner between 4 and 64 μmol/L (P<0.05 at 16 and 64 μmol/L). Caspase-3 inhibitor (Ac-DEVD-CHO at concentrations between 10 to 20 μmol/L), p53 inhibitor (pifithrin-α at 5 μmol/L) and cyclosporin A can attenuate the apoptotic effect of psoralidin.@*CONCLUSION@#The cytotoxic role of psoralidin might work through both intrinsic and extrinsic apoptotic pathway.

Cyclosporin A aggravates hydrogen peroxide-induced cell death in kidney proximal tubule epithelial cells / 대한해부학회지

Cyclosporin A (CsA) does not only exert a toxic effect on kidney parenchymal cells, but also protects them against necrotic cell death by inhibiting opening of mitochondrial permeability transition pore. However, whether CsA plays a role in hydrogen peroxide-induced kidney proximal tubular cell death is currently unclear. In the present study, treatment with CsA further increased apoptosis and necrosis in HK-2 human kidney proximal tubule epithelial cells during exposure to hydrogen peroxide. In addition, hydrogen peroxide-induced p53 activation and BH3 interacting-domain death agonist (BID) expression were higher in CsA-treated cells than those in non-treated cells, whereas hydrogen peroxide-induced activation of mitogen-activated protein kinases including p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase and activation of protein kinase B were not significantly altered by treatment with CsA. In oxidant-antioxidant system, reactive oxygen species (ROS) production induced by hydrogen peroxide was further enhanced by treatment with CsA. However, expression levels of antioxidant enzymes including manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase were not altered by treatment with hydrogen peroxide or CsA. Treatment with CsA further enhanced mitochondrial membrane potential induced by exposure to hydrogen peroxide, although it did not alter endoplasmic reticulum stress based on expression of glucose-regulated protein 78 and 94. Taken together, these data suggest that CsA can aggravate hydrogen peroxide-induced cell death through p53 activation, BID expression, and ROS production.

Cyclosporin for treatment of subcutaneous panniculitis-like T-cell lymphoma: report of one case and review of literature / 白血病·淋巴瘤

Objective@#To investigate the effect of cyclosporin (CsA) on initial, relapsed or refractory subcutaneous panniculitis-like T-cell lymphoma (SPTCL).@*Methods@#The clinical data of one case with long-survival SPTCL in China-Japan Friendship Hospital was retrospectively analyzed, and the literature was reviewed.@*Results@#After CsA treatment as the initial therapy, the patient obtained rapid response and complete remission (CR). Lymphoma occurred relapse several times, but the use of CsA could got rapid remission. CR sustained from 1 to 6 years after drug withdrawal. However, CsA did not bring remission after the recent relapse. Then CHOP-like regimen was carried out, and partial remission could be reached. The patient achieved CR and 22 years survival time with CsA maintenance therapy until now.@*Conclusion@#CsA has a favorable effect on initial, relapsed or refractory SPTCL.