AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats...AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCh and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol （v/v）. EGb-protected group was treated with EGb （0.5 g/kg body weight per day） for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor β1 （TGF-β1） a-smooth muscle actin （α-SMA） and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS： The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and albumin （AIb） in EGb-protected group were notably improved as compared with the CCL4-treated group （P 〈 0.01）. The contents of serum hyaluronic acid （HA）, type III procollagen （PCⅢ）, type IV collagen （CIV） and the expression of hepatic tissue TGF-β1, α-SMA and type I collagen in EGb-protected group were significantly lower than those in CCL4-treated groups （P 〈 0.05, P 〈 0.01）. The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups （6.58 ±1.25 vs 9.52 ± 2.06, P 〈 0.05）. Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase （Se-GSH-Px）, superoxide dismutase （SOD） and malondialdehyde （MDA） were strikingly improved also in EGb-protected group （P 〈 0.05, P 〈 0.01）. CONCLUSION： EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4.展开更多
Melittin is a basic 26-amino-acid polypeptide that constitutes 40-60% of dry honeybee（Apis mellifera）venom.Although much is known about its strong surface activity on lipid membranes,less is known about its painprod...Melittin is a basic 26-amino-acid polypeptide that constitutes 40-60% of dry honeybee（Apis mellifera）venom.Although much is known about its strong surface activity on lipid membranes,less is known about its painproducing effects in the nervous system.In this review,we provide lines of accumulating evidence to support the hypothesis that melittin is the major pain-producing substance of bee venom.At the psychophysical and behavioral levels,subcutaneous injection of melittin causes tonic pain sensation and pain-related behaviors in both humans and animals.At the cellular level,melittin activates primary nociceptor cells through direct and indirect effects.On one hand,melittin can selectively open thermal nociceptor transient receptor potential vanilloid receptor channels via phospholipase A2-lipoxygenase/cyclooxygenase metabolites,leading to depolarization of primary nociceptor cells.On the other hand,algogens and inflammatory/proinflammatory mediators released from the tissue matrix by melittin＇s pore-forming effects can activate primary nociceptor cells through both ligand-gated receptor channels and the G-protein-coupled receptor-mediated opening of transient receptor potential canonical channels.Moreover,subcutaneous melittin up-regulates Nav1.8 and Nav1.9subunits,resulting in the enhancement of tetrodotoxinresistant Na~＋currents and the generation of long-term action potential firing.These nociceptive responses in the periphery finally activate and sensitize the spinal dorsal horn pain-signaling neurons,resulting in spontaneous nociceptive paw flinches and pain hypersensitivity to thermal and mechanical stimuli.Taken together,it is concluded that melittin is the major pain-producing substance of bee venom,by which peripheral persistent pain and hyperalgesia（or allodynia）,primary nociceptive neuronal sensitization,and CNS synaptic plasticity（or metaplasticity） can be readily induced and the molecular and cellular mechanisms underlying naturally-occurring venomous biotoxins can be experimentally unraveled.展开更多
Intractable central post-stroke pain（CPSP） is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and cha...Intractable central post-stroke pain（CPSP） is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV（ITC） injection. Then, we evaluated the efficacy of gabapentin（GBP）, an anticonvulsant that binds the voltage-gated Ca2＋ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration（1, 10, or 100 mg/kg） on day 7 post-ITC, with significant effects lasting at least 5 hfor the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness（drug tolerance） at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.展开更多
The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive...The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotrans- mitter release. We previously showed that GBP has an anti- allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated adminis- tration in a rat model of central post-stroke pain （CPSP） hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the c^2g-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor ~2^-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.展开更多
BACKGROUND Natural killer(NK)/T cell lymphoma is a rare and highly aggressive malignant tumor,and is a special form of non-Hodgkin's lymphoma.Although extranodal involvement is frequently found in tissues such as ...BACKGROUND Natural killer(NK)/T cell lymphoma is a rare and highly aggressive malignant tumor,and is a special form of non-Hodgkin's lymphoma.Although extranodal involvement is frequently found in tissues such as the skin,testicular and gastrointestinal tract etc,its presence in skeletal muscle has scarcely been reported in the literature.CASE SUMMARY We report a case of extranodal NK/T cell lymphoma with muscle swelling as the first clinical manifestation.A 42-year-old man,who initially presented with localized swelling in the double lower extremities,demonstrated gradual facial and eyelid swelling,and his imaging results showed multiple sites of muscle damage throughout the body.The final pathological results suggested NK/T cell lymphoma,and immunohistochemistry showed CD20(-),CD3(+),CD30(+),CD56(-),EBER(+),Ki67(60%),TIA-1(+)and CD68(±)staining.The muscle swelling significantly improved after treatment with chemotherapy regimens.CONCLUSION This disease is difficult to diagnose and highly invasive,and should be included in the differential diagnosis of unexplained muscle swelling.展开更多
文摘AIM： To study the effects of extract from Ginkgo biloba （EGb） containing 22% flavonoid and 5% terpenoid on chronic liver injury and liver fibrosis of rats induced by carbon tetrachloride （CCh）. METHODS： All rats were randomly divided into control group, CCl4-treated group, colchicine-treated group and EGb-protected group. Chronic liver injury was induced in experimental groups by subcutaneous injection of CCh and fed with chows premixed with 79.5% corn powder, 20% lard and 0.5% cholesterol （v/v）. EGb-protected group was treated with EGb （0.5 g/kg body weight per day） for 7 wk. At the end of wk 8, all the rats were killed. Liver function, liver fibrosis, oxidative stress and expression of transforming growth factor β1 （TGF-β1） a-smooth muscle actin （α-SMA） and type I collagens in liver were determined. In addition, pathology changes of liver tissue were observed under light microscope. RESULTS： The levels of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and albumin （AIb） in EGb-protected group were notably improved as compared with the CCL4-treated group （P 〈 0.01）. The contents of serum hyaluronic acid （HA）, type III procollagen （PCⅢ）, type IV collagen （CIV） and the expression of hepatic tissue TGF-β1, α-SMA and type I collagen in EGb-protected group were significantly lower than those in CCL4-treated groups （P 〈 0.05, P 〈 0.01）. The degrees of liver fibrosis in EGb-protected groups were lower than those in CCL4-treated groups （6.58 ±1.25 vs 9.52 ± 2.06, P 〈 0.05）. Compared to the CCL4-treated group, the levels of plasma glutathoine peroxidase （Se-GSH-Px）, superoxide dismutase （SOD） and malondialdehyde （MDA） were strikingly improved also in EGb-protected group （P 〈 0.05, P 〈 0.01）. CONCLUSION： EGb resists oxidative stress and thereby reduces chronic liver injury and liver fibrosis in rats with liver injury induced by CCl4.
基金supported by grants from the National Basic Research Development Program of China (2013CB 835100)the National Natural Science Foundation of China (81171049,31300919,and 31400948)+1 种基金the National Key Technology R&D Program,China (2013BAI04B04)the Twelfth Five-Year Project of China (AWS12J004)
文摘Melittin is a basic 26-amino-acid polypeptide that constitutes 40-60% of dry honeybee（Apis mellifera）venom.Although much is known about its strong surface activity on lipid membranes,less is known about its painproducing effects in the nervous system.In this review,we provide lines of accumulating evidence to support the hypothesis that melittin is the major pain-producing substance of bee venom.At the psychophysical and behavioral levels,subcutaneous injection of melittin causes tonic pain sensation and pain-related behaviors in both humans and animals.At the cellular level,melittin activates primary nociceptor cells through direct and indirect effects.On one hand,melittin can selectively open thermal nociceptor transient receptor potential vanilloid receptor channels via phospholipase A2-lipoxygenase/cyclooxygenase metabolites,leading to depolarization of primary nociceptor cells.On the other hand,algogens and inflammatory/proinflammatory mediators released from the tissue matrix by melittin＇s pore-forming effects can activate primary nociceptor cells through both ligand-gated receptor channels and the G-protein-coupled receptor-mediated opening of transient receptor potential canonical channels.Moreover,subcutaneous melittin up-regulates Nav1.8 and Nav1.9subunits,resulting in the enhancement of tetrodotoxinresistant Na~＋currents and the generation of long-term action potential firing.These nociceptive responses in the periphery finally activate and sensitize the spinal dorsal horn pain-signaling neurons,resulting in spontaneous nociceptive paw flinches and pain hypersensitivity to thermal and mechanical stimuli.Taken together,it is concluded that melittin is the major pain-producing substance of bee venom,by which peripheral persistent pain and hyperalgesia（or allodynia）,primary nociceptive neuronal sensitization,and CNS synaptic plasticity（or metaplasticity） can be readily induced and the molecular and cellular mechanisms underlying naturally-occurring venomous biotoxins can be experimentally unraveled.
基金supported by grants from the National Natural Science Foundation of China (81171049)the National Basic Research Development Program of China (2011CB504100,2013CB835100 and 2013BAI04B04)
文摘Intractable central post-stroke pain（CPSP） is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV（ITC） injection. Then, we evaluated the efficacy of gabapentin（GBP）, an anticonvulsant that binds the voltage-gated Ca2＋ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration（1, 10, or 100 mg/kg） on day 7 post-ITC, with significant effects lasting at least 5 hfor the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness（drug tolerance） at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.
基金supported by the National Natural Science Foundation of China(81171049)the National Basic Research Development Program of China(2011CB504100 and2013CB835100)+1 种基金the National Key Technology R&D Program of China(2013BAI04B04)the Twelfth Five-Year Project of China(AWS12J004)
文摘The α2δ-1 subunit of the voltage-gated Ca2＋ channel （VGCC） is a molecular target of gabapentin （GBP）, which has been used as a first-line drug for the relief of neuropathic pain. GBP exerts its anti-nociceptive effects by disrupting trafficking of the α2δ-1 subunit to the presynaptic membrane, resulting in decreased neurotrans- mitter release. We previously showed that GBP has an anti- allodynic effect in the first two weeks; but this is followed by insensitivity in the later stage after repeated adminis- tration in a rat model of central post-stroke pain （CPSP） hypersensitivity induced by intra-thalamic hemorrhage. To explore the mechanisms underlying GBP insensitivity, the cellular localization and time-course of expression of the α2δ-1 subunit in both the thalamus and spinal dorsal horn were studied in the same model. We found that the α2δ-1 subunit was mostly localized in neurons, but not astrocytes and microglia. The level of α2δ-1 protein increased in the first two weeks after injury but then decreased in the third week, when GBP insensitivity occurred. Furthermore, the c^2g-1 down-regulation was likely caused by later neuronal loss in the injured thalamus through a mechanism other than apoptosis. In summary, the present results suggest that the GBP receptor ~2^-1 is mainly expressed in thalamic neurons in which it is up-regulated in the early stage of CPSP but this is followed by dramatic down-regulation, which is likely associated with GBP insensitivity after long-term use.
基金Supported by the National Natural Science Foundation of China,No.81400978
文摘BACKGROUND Natural killer(NK)/T cell lymphoma is a rare and highly aggressive malignant tumor,and is a special form of non-Hodgkin's lymphoma.Although extranodal involvement is frequently found in tissues such as the skin,testicular and gastrointestinal tract etc,its presence in skeletal muscle has scarcely been reported in the literature.CASE SUMMARY We report a case of extranodal NK/T cell lymphoma with muscle swelling as the first clinical manifestation.A 42-year-old man,who initially presented with localized swelling in the double lower extremities,demonstrated gradual facial and eyelid swelling,and his imaging results showed multiple sites of muscle damage throughout the body.The final pathological results suggested NK/T cell lymphoma,and immunohistochemistry showed CD20(-),CD3(+),CD30(+),CD56(-),EBER(+),Ki67(60%),TIA-1(+)and CD68(±)staining.The muscle swelling significantly improved after treatment with chemotherapy regimens.CONCLUSION This disease is difficult to diagnose and highly invasive,and should be included in the differential diagnosis of unexplained muscle swelling.
