Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ rec...Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ receptor(IGF-IR),and cytoplasmic downstream effectors such as insulin-receptor substrates(IRS)contribute to proliferation,anti-apoptosis,and invasive behavior. This review focuses on the relevant alterations in this signaling pathway and independent in vivo models that support the central role IGF-Ⅱsignaling during HCC development and progression.Since this pathway has become the center of interest as a target for potential anti-cancer therapy in many types of malignancies,various experimental strategies have been developed,including neutralizing antibodies and selective receptor kinase inhibitors,with respect to the specific and efficient reduction of oncogenic IGF-Ⅱ/IGF-IR-signaling.展开更多
Objective Chinese allergic subjects have high levels of sensitization to house dust mite （HDM） and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samp...Objective Chinese allergic subjects have high levels of sensitization to house dust mite （HDM） and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samples were collected from nine cities. Major allergens Der p 1 and Der f I from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.Results HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from 〈0.006 to 9.2 μg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.Conclusion HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.展开更多
Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory...Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting se展开更多
Background Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response.Interleukin-10 （IL-10） plays a crucial role in inducing allergen-specific tolerance.However t...Background Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response.Interleukin-10 （IL-10） plays a crucial role in inducing allergen-specific tolerance.However the reports of the changes of IL-10 in house dust mite （HDM）-specific immunotherapy were varied.The aim of this study was to evaluate the function of IL-10-secreting regulatory T cells in asthma children successfully treated with HDM immunotherapy.Methods Peripheral blood mononuclear cells （PBMCs） were isolated from 27 patients following 1.5--2 years of HDM-specific immunotherapy （SIT, SIT group） and from 27 matched treated asthmatic children allergic to HDM （asthmagroup）.After 48 hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T cells were measured by four colour flow cytometry.Sera were tested for allergen-specific IgG4 and IgE using the Immuno CAP 100 assay.Results PBMCs from children undergoing immunotherapy following HDM extracts stimuli produced significantly more IL-10 compared with the asthma group.The frequency of iTreg cells and aTreg cells increased in SIT group after HDM stimulation, while it was not affected in the asthma group.Among the iTreg cells and aTreg cells, the frequency of CD4＋CD25-Foxp3-IL-10＋ Treg cells increased the most which was 2 times higher than that in unstimulated cultures in SIT group.The levels of HDM-specific IgG4 of SIT group was significiently higher compared with asthma group, but there was no correlation of the levels of HDM-specific IgG4 and IL-10 secreting Treg cells.Conclusions HDM-specific immunotherapy can successfully upregulate the frequency of IL-10-secreting Treg cells.CD4＋CD25-Foxp3-IL-10＋ Treg cells may play a key role in inducing the immune tolerance in HDM-specific immunotherapy.展开更多
The large-sized rammed-earth building foundations on the Panlongcheng site at Huangpi are remains of early Shang period palace complex. The No. 1 Panlongcheng palace consists of four rooms with wooden-framed walls. Th...The large-sized rammed-earth building foundations on the Panlongcheng site at Huangpi are remains of early Shang period palace complex. The No. 1 Panlongcheng palace consists of four rooms with wooden-framed walls. The two rooms in the middle each have two doors on the northern and southern sides respectively；while the two end rooms have only southern doors. So the No. 1 palace must have been in the center of the whole building complex. The roof supported by peripheral columns and wooden-framed walls can be reconstructed to be hipped and single- or double- eaved. The hypothesis that the No. 1 palace may have had projecting-eaves columns has not been confirmed. The No. 2 palace is an open hall without peripheral walls and room division； its roof is supported by peripheral columns only. The idea of reconstructing it as a building with pilasters and multiple rooms seems to lack archaeological evidence. The remaining vestiges show that there were side corridors in the two flanks of the main hall of the No. 2 palace. Referring to the Shang period palace material unearthed from the Shang city-site at Yanshi and other localities, it can be inferred that either of the Nos. 1 and 2 palaces must have had an eastern corridor and a western one, and, in addition, the No. 2 palace must have had a southern corridor with a gate house. The Nos. 1--3 palaces of the Panlongcheng site formed three compounds located one behind another, and belonged to the type of court-and-living building complex. Among them the No. 2 palace was the outer court for holding great ceremonies, the No. 1 palace was the inner court for handling daily administrative affairs, and the No. 3 palace was the king and queen's living place. To the southeast of the No. 2 palace remains a group of rammed-earth house-foundations, which must have been left over from another type of palace building, possibly an ancestral temple. The remaining city-walls at Panlongcheng must have belonged to the peripheral city-walls. The palace area is in the northeast of the encl展开更多
文摘Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ receptor(IGF-IR),and cytoplasmic downstream effectors such as insulin-receptor substrates(IRS)contribute to proliferation,anti-apoptosis,and invasive behavior. This review focuses on the relevant alterations in this signaling pathway and independent in vivo models that support the central role IGF-Ⅱsignaling during HCC development and progression.Since this pathway has become the center of interest as a target for potential anti-cancer therapy in many types of malignancies,various experimental strategies have been developed,including neutralizing antibodies and selective receptor kinase inhibitors,with respect to the specific and efficient reduction of oncogenic IGF-Ⅱ/IGF-IR-signaling.
文摘Objective Chinese allergic subjects have high levels of sensitization to house dust mite （HDM） and other indoor allergens. This study quantifies common indoor allergen levels in Chinese households. Methods Dust samples were collected from nine cities. Major allergens Der p 1 and Der f I from Dermatophagoides pteronyssinus and D. farinae, and specific antigens of Blomia tropicalis, Tyrophagus putrescentiae, Acarus siro, and cockroach species Blattella germanica and Periplaneta americana were measured by ELISA.Results HDM allergens were found in dust samples from bedding in 95% of the Chinese households. The median levels varied from 〈0.006 to 9.2 μg/g of dust, depending on the city. The percentages of households having HDM allergen levels associated with the risk of developing allergy sensitization and asthma were 65% and 25%, respectively. Specific antigens of the storage mite and cockroach were only found in samples from the southern and tropical regions of China. Levels of mite allergens were generally higher in samples from bedding compared to samples from the living room, even for storage mites, whereas levels of cockroach antigens were higher in the living room samples.Conclusion HDM allergens are present in bedding dust samples from most Chinese households. Cities in southern and central China have relatively high levels of HDM major allergens compared to cities in northern and western China. Antigens of storage mites and cockroaches are not as common as HDM allergens.
基金supported by grants awarded to YY by the National Natural Science Foundation of China (81870019, 82170029)the Guangdong Provincial Natural Science Foundation (2018A030313554)+3 种基金the Innovation Research Team for Basic and Clinical Studies on Chronic Liver Diseases of 2018 High-Level Health Teams of ZhuhaiYKQ by the National Natural Science Foundation of China (82002612)the Chinese Postdoctoral Science Foundation (2019M660211)ZGC by the Science and Technology Program of Guangzhou,China (201704020179)。
文摘Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting se
文摘Background Subcutaneous specific immunotherapy has been demonstrated to be capable of inducing T-cell regulatory response.Interleukin-10 （IL-10） plays a crucial role in inducing allergen-specific tolerance.However the reports of the changes of IL-10 in house dust mite （HDM）-specific immunotherapy were varied.The aim of this study was to evaluate the function of IL-10-secreting regulatory T cells in asthma children successfully treated with HDM immunotherapy.Methods Peripheral blood mononuclear cells （PBMCs） were isolated from 27 patients following 1.5--2 years of HDM-specific immunotherapy （SIT, SIT group） and from 27 matched treated asthmatic children allergic to HDM （asthmagroup）.After 48 hours of in vitro stimulation with HDM extracts, IL-10-secreting regulatory T cells were measured by four colour flow cytometry.Sera were tested for allergen-specific IgG4 and IgE using the Immuno CAP 100 assay.Results PBMCs from children undergoing immunotherapy following HDM extracts stimuli produced significantly more IL-10 compared with the asthma group.The frequency of iTreg cells and aTreg cells increased in SIT group after HDM stimulation, while it was not affected in the asthma group.Among the iTreg cells and aTreg cells, the frequency of CD4＋CD25-Foxp3-IL-10＋ Treg cells increased the most which was 2 times higher than that in unstimulated cultures in SIT group.The levels of HDM-specific IgG4 of SIT group was significiently higher compared with asthma group, but there was no correlation of the levels of HDM-specific IgG4 and IL-10 secreting Treg cells.Conclusions HDM-specific immunotherapy can successfully upregulate the frequency of IL-10-secreting Treg cells.CD4＋CD25-Foxp3-IL-10＋ Treg cells may play a key role in inducing the immune tolerance in HDM-specific immunotherapy.
文摘The large-sized rammed-earth building foundations on the Panlongcheng site at Huangpi are remains of early Shang period palace complex. The No. 1 Panlongcheng palace consists of four rooms with wooden-framed walls. The two rooms in the middle each have two doors on the northern and southern sides respectively；while the two end rooms have only southern doors. So the No. 1 palace must have been in the center of the whole building complex. The roof supported by peripheral columns and wooden-framed walls can be reconstructed to be hipped and single- or double- eaved. The hypothesis that the No. 1 palace may have had projecting-eaves columns has not been confirmed. The No. 2 palace is an open hall without peripheral walls and room division； its roof is supported by peripheral columns only. The idea of reconstructing it as a building with pilasters and multiple rooms seems to lack archaeological evidence. The remaining vestiges show that there were side corridors in the two flanks of the main hall of the No. 2 palace. Referring to the Shang period palace material unearthed from the Shang city-site at Yanshi and other localities, it can be inferred that either of the Nos. 1 and 2 palaces must have had an eastern corridor and a western one, and, in addition, the No. 2 palace must have had a southern corridor with a gate house. The Nos. 1--3 palaces of the Panlongcheng site formed three compounds located one behind another, and belonged to the type of court-and-living building complex. Among them the No. 2 palace was the outer court for holding great ceremonies, the No. 1 palace was the inner court for handling daily administrative affairs, and the No. 3 palace was the king and queen's living place. To the southeast of the No. 2 palace remains a group of rammed-earth house-foundations, which must have been left over from another type of palace building, possibly an ancestral temple. The remaining city-walls at Panlongcheng must have belonged to the peripheral city-walls. The palace area is in the northeast of the encl
