Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of is...Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of ischemia.The hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or apoptosis.Cyclosporine(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and injury.NIM-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the mPTP.In this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.Materials and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/kg.Thereafter,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after reperfusion.Serum alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.Results:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(P<0.001,0.007,and 0.031,respectively).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,<0.001,0.003,and 0.043,respectively)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,and<0.001,respectively).Levels of the pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control mice.Conclusions:Premedication with CsA or NIM-811 miti展开更多
Summary： This study examined the inhibitory effect of topical cyclosporine （CsA） treatment on conjunctiva epithelial apoptosis in a murine model of xerophthalamia. Dry eye was induced in 3 groups of C57BL6 mice by ...Summary： This study examined the inhibitory effect of topical cyclosporine （CsA） treatment on conjunctiva epithelial apoptosis in a murine model of xerophthalamia. Dry eye was induced in 3 groups of C57BL6 mice by subcutaneous injection of scopolamine （t.i.d） and exposure to an air draft and low-humidity environment for 16 h each day for 12 days. The dry eye control group received no topical treatment; another group received 1 μL of 0.05 % CsA topically （t.i.d, dry eye＋CsA）; and the third group received 1 μL of the castor oil vehicle of CsA topically （t.i.d, dry eye ＋ vehicle）. Normal mice were used as untreated controls. Twelve days later, the mice were killed, and their conjunctivas were excised. The number of the conjunctival goblet cells was counted in tissue sections stained with periodic acid Schiff （PAS） reagent. Their conjunctiva epithelium had been investigated by immuno-histochemical staining to detect the goblet cells and the expression of Caspase-3, Bax and bcl-2 Our results showed that compared with dry eye control and dry eye mice ＋ vehicle groups, the number of conjunctival epithelial goblet cells was significantly greater in the untreated controls and dry eye mice receiving CsA （P 〈 0.01 for both groups）. There was no significant difference in the number of conjunctival epithelial goblet cells between the dry eye control and dry eye＋vehicle group. It was also true of the number of conjunctival epithelial goblet cells when comparison was made between the normal group and the dry eye＋CsA group. Expressions of Caspas-3 and Bax were increased and ex-pression of bcl-2 was decreased in conjunctival epithelial cells in dry eye control and dry eye mice＋vehicle groups. There was a significant positive correlation between goblet cell number and the number of cells that expressed bcl-2, and a negative correlation between goblet cells and Caspase-3 and Bax expression. It is concluded that the topical use of CsA could significantly reduce conjuncti-val epithelial apopt展开更多
Hypertrichosis is one of the most common side effects of systemic cyclosporine A therapy.It has been previously shown that cyclosporine A induces anagen and inhibits catagen development in mice.In the present study,to...Hypertrichosis is one of the most common side effects of systemic cyclosporine A therapy.It has been previously shown that cyclosporine A induces anagen and inhibits catagen development in mice.In the present study,to explore the mechanisms of cyclosporine A,we investigated the effects of cyclosporine A on hair shaft elongation,hair follicle cell proliferation,apoptosis,and mRNA expression of selected growth factors using an organ culture model of mouse vibrissae.In this model,cyclosporine A stimulated hair growth of normal mouse vibrissae follicles by inhibiting catagen-like development and promoting matrix cell proliferation.In addition,cyclosporine A caused an increase in the expression of vascular endothelial growth factor（VEGF）,hepatocyte growth factor（HGF）,and nerve growth factor（NGF）,and inhibited follistatin expression.Our findings provide an explanation for the clinically observed effects of cyclosporine A on hair growth.The mouse vibrissae organ culture offers an attractive model for identifying factors involved in the modulation of hair growth.展开更多
文摘Background and aim:The liver is susceptible to ischemia-reperfusion injury(IRI)during hepatic surgery,when the vessels are compressed to control bleeding,or liver transplantation,when there is an obligate period of ischemia.The hallmark of IRI comprises mitochondrial dysfunction,which generates reactive oxygen species,and cell death through necrosis or apoptosis.Cyclosporine(CsA),which is a well-known immunosuppressive agent that inhibits calcineurin,has the additional effect of inhibiting the mito-chondrial permeability transition pore(mPTP),thereby,preventing mitochondrial swelling and injury.NIM-811,which is the nonimmunosuppressive analog of CsA,has a similar effect on the mPTP.In this study,we tested the effect of both agents on mitigating warm hepatic IRI in a murine model.Materials and methods:Before ischemic insult,the mice were administered with intraperitoneal normal saline(control);CsA at 2.5,10,or 25 mg/kg;or NIM-811 at 10 mg/kg.Thereafter,the mice were subjected to partial warm hepatic ischemia by selective pedicle clamping for 60 min,followed by 6 h of recovery after reperfusion.Serum alanine transaminase(ALT)was measured,and the liver tissue was examined histologically for the presence of apoptosis and the levels of inflammatory cytokines.Results:Compared with the control mice,the mice treated with 10 and 25 mg/kg of CsA and NIM-811 had significantly lower ALT levels(P<0.001,0.007,and 0.031,respectively).Moreover,the liver tissue showed reduced histological injury scores after treatment with CsA at 2.5,10,and 25 mg/kg and NIM-811(P=0.041,<0.001,0.003,and 0.043,respectively)and significant decrease in apoptosis after treatment with CsA at all doses(P=0.012,0.007,and<0.001,respectively).Levels of the pro-inflammatory cyto-kines,particularly interleukin(IL)-1β,IL-2,IL-4,IL-10,and keratinocyte chemoattractant/human growth-regulated oncogene significantly decreased in the mice treated with the highest dose of CsA(25 mg/kg)than those in the control mice.Conclusions:Premedication with CsA or NIM-811 miti
文摘Summary： This study examined the inhibitory effect of topical cyclosporine （CsA） treatment on conjunctiva epithelial apoptosis in a murine model of xerophthalamia. Dry eye was induced in 3 groups of C57BL6 mice by subcutaneous injection of scopolamine （t.i.d） and exposure to an air draft and low-humidity environment for 16 h each day for 12 days. The dry eye control group received no topical treatment; another group received 1 μL of 0.05 % CsA topically （t.i.d, dry eye＋CsA）; and the third group received 1 μL of the castor oil vehicle of CsA topically （t.i.d, dry eye ＋ vehicle）. Normal mice were used as untreated controls. Twelve days later, the mice were killed, and their conjunctivas were excised. The number of the conjunctival goblet cells was counted in tissue sections stained with periodic acid Schiff （PAS） reagent. Their conjunctiva epithelium had been investigated by immuno-histochemical staining to detect the goblet cells and the expression of Caspase-3, Bax and bcl-2 Our results showed that compared with dry eye control and dry eye mice ＋ vehicle groups, the number of conjunctival epithelial goblet cells was significantly greater in the untreated controls and dry eye mice receiving CsA （P 〈 0.01 for both groups）. There was no significant difference in the number of conjunctival epithelial goblet cells between the dry eye control and dry eye＋vehicle group. It was also true of the number of conjunctival epithelial goblet cells when comparison was made between the normal group and the dry eye＋CsA group. Expressions of Caspas-3 and Bax were increased and ex-pression of bcl-2 was decreased in conjunctival epithelial cells in dry eye control and dry eye mice＋vehicle groups. There was a significant positive correlation between goblet cell number and the number of cells that expressed bcl-2, and a negative correlation between goblet cells and Caspase-3 and Bax expression. It is concluded that the topical use of CsA could significantly reduce conjuncti-val epithelial apopt
基金supported by grants from the National Natural Science Foundation of China(No.30571678 and No.30771947)the Natural Science Foundation of Jiangsu Province(No.BK2007248)
文摘Hypertrichosis is one of the most common side effects of systemic cyclosporine A therapy.It has been previously shown that cyclosporine A induces anagen and inhibits catagen development in mice.In the present study,to explore the mechanisms of cyclosporine A,we investigated the effects of cyclosporine A on hair shaft elongation,hair follicle cell proliferation,apoptosis,and mRNA expression of selected growth factors using an organ culture model of mouse vibrissae.In this model,cyclosporine A stimulated hair growth of normal mouse vibrissae follicles by inhibiting catagen-like development and promoting matrix cell proliferation.In addition,cyclosporine A caused an increase in the expression of vascular endothelial growth factor（VEGF）,hepatocyte growth factor（HGF）,and nerve growth factor（NGF）,and inhibited follistatin expression.Our findings provide an explanation for the clinically observed effects of cyclosporine A on hair growth.The mouse vibrissae organ culture offers an attractive model for identifying factors involved in the modulation of hair growth.
