目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分...目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分为3组,第1组为退行性腰椎滑脱组(DLS)10例;第2组为腰椎间盘突出症组(LDH)17例,第3组为正常对照组10例,其中7例取自腰椎骨折手术病人,3例取自意外死亡者。应用EnV is ion二步免疫组化的方法检测其TGF-1β、BM P-2和typeⅡco llagen的表达情况,普通光镜观察,计算出各标本的表达阳性率和表达强度,数据以x-±s标准差及表达强度表示,结果分别用Spss统计软件和R id it进行分析。结果TGF-1β、BM P-2和typeⅡco llagen的阳性表达产物见于成纤维细胞、成软骨细胞和软骨细胞中,而Ⅱ型胶原染色还可同时见于基质。TGF-1β、BM P-2和typeⅡco llagen在DLS组中的表达明显高于LDH组和正常组(P<0.01或P<0.05),Ⅱ型胶原基质染色明显深于LDH组和对照组。LDH组的TGF-1β和typeⅡco llagen的表达阳性率和表达强度与正常组之间差异无显著性(P>0.05),而BM P-2的表达阳性率和表达强度在LDH组与正常组之间具有统计学意义(P<0.01)。结论黄韧带所受到的异常机械牵张力可以增加TGF-1β在黄韧带细胞中的合成,而TGF-1β则促进退行性腰椎滑脱黄韧带中的Ⅱ型胶原合成,导致黄韧带的退变和肥厚。BM P-2在退变黄韧带中的表达异常增高,可能与黄韧带的软骨化倾向有关。展开更多
In this feeding trial rats were fed on diets of cereals from Kashin-Beck Disease (KBD) endemic area, Se-supplemented cereals from the above area, and cereals from Non-KBD endemic area. The purpose of this paper was to...In this feeding trial rats were fed on diets of cereals from Kashin-Beck Disease (KBD) endemic area, Se-supplemented cereals from the above area, and cereals from Non-KBD endemic area. The purpose of this paper was to investigate the effects of cereals from KBD endemic area and Se on the formation kinetics of cartilage type Ⅱ collagen fibril, the stability and ultrastructure of fibrils formed in vitro. The results indicated that low-selenium cereals from KBD endemic area resulted in a decelerated rate and extant of forming the type Ⅱ collagen fibril, the fibril stability reduced, fibril diameters diminished, and fibril banding periods increased or decreased in vitro. Sesupplemented cereals from KBD endemic area partially rectified the pathologic changes mentioned above. These data are important for further studying the etiology and pathology of KBD.展开更多
Objective: To explore the effect of radiofrequency hyperthermia on type Ⅱ collagen expression in a rabbit model of osteoarthri-tis (OA). Methods: Experimental model of knee OA was replicated in the right hind limbs o...Objective: To explore the effect of radiofrequency hyperthermia on type Ⅱ collagen expression in a rabbit model of osteoarthri-tis (OA). Methods: Experimental model of knee OA was replicated in the right hind limbs of 54 male rabbits by using modified Hulth modeling method. The rabbits were randomly divided into Model group, Lugua Polypeptide group and Radiofrequency Hyper-thermia group. After modeling, Lugua Polypeptide group was given intramuscular injection of Lugua polypeptide;Radiofre-quency Hyperthermia group was treated with radiofrequency hyperthermia;Model group was not given any special treatment. On the 7th, 13th and 19th day after radiofrequency hyperthermia, six experimental rabbits were chosen from each group and sacrificed to take out medial femoral condyle cartilages in the right hind limbs. Modified Mankins rating was applied to the morphological evaluation. Meanwhile, quantitative real-time PCR was used to detect the content of type Ⅱ collagen in cartilage tissues of medial femoral condyle. Results: At each time point after treatment, Mankins scores were decreased in all the 3 groups, with that of Model group sig-nificantly higher than those of the other two groups (Model group > Lugua Polypeptide group > Radiofrequency Hyperthermia group). The contents of type Ⅱ collagen in cartilage tissues were increased in all the 3 groups, with that of Radiofrequency Hyperthermia group significantly higher than those of the other two group (Model group < Lugua Polypeptide group < Ra-diofrequency Hyperthermia group). The difference between groups was of statistical significance (p < .05). For Radiofrequency Hyperthermia group, Mankins scores were decreased gradually as the treatment time went by, with the content of type Ⅱ colla-gen in cartilage tissues increased. The difference between time points was of statistical significance (p < .05). Conclusions: Radiofrequency hyperthermia is superior to Lugua polypeptide in the treatment of knee OA, at least in rabbits. Its therapeutic mechanism may be related to the significant increase in type Ⅱ collagen in cartilages.展开更多
Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous i...Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and safety.Herein,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal epithelium.After oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅡdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells activity.Surprisingly,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira.Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal epithelium.This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of liraglutide.In general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.展开更多
文摘目的研究TGF-1β、BM P-2和typeⅡco llagen在退行性腰椎滑脱(degenerative lum bar spondy lo listhes is,DLS)和腰椎间盘突出症(lum bar d isc hern iation,LDH)黄韧带中的表达及其意义。方法37例手术切除的腰椎椎板间部黄韧带标本分为3组,第1组为退行性腰椎滑脱组(DLS)10例;第2组为腰椎间盘突出症组(LDH)17例,第3组为正常对照组10例,其中7例取自腰椎骨折手术病人,3例取自意外死亡者。应用EnV is ion二步免疫组化的方法检测其TGF-1β、BM P-2和typeⅡco llagen的表达情况,普通光镜观察,计算出各标本的表达阳性率和表达强度,数据以x-±s标准差及表达强度表示,结果分别用Spss统计软件和R id it进行分析。结果TGF-1β、BM P-2和typeⅡco llagen的阳性表达产物见于成纤维细胞、成软骨细胞和软骨细胞中,而Ⅱ型胶原染色还可同时见于基质。TGF-1β、BM P-2和typeⅡco llagen在DLS组中的表达明显高于LDH组和正常组(P<0.01或P<0.05),Ⅱ型胶原基质染色明显深于LDH组和对照组。LDH组的TGF-1β和typeⅡco llagen的表达阳性率和表达强度与正常组之间差异无显著性(P>0.05),而BM P-2的表达阳性率和表达强度在LDH组与正常组之间具有统计学意义(P<0.01)。结论黄韧带所受到的异常机械牵张力可以增加TGF-1β在黄韧带细胞中的合成,而TGF-1β则促进退行性腰椎滑脱黄韧带中的Ⅱ型胶原合成,导致黄韧带的退变和肥厚。BM P-2在退变黄韧带中的表达异常增高,可能与黄韧带的软骨化倾向有关。
文摘In this feeding trial rats were fed on diets of cereals from Kashin-Beck Disease (KBD) endemic area, Se-supplemented cereals from the above area, and cereals from Non-KBD endemic area. The purpose of this paper was to investigate the effects of cereals from KBD endemic area and Se on the formation kinetics of cartilage type Ⅱ collagen fibril, the stability and ultrastructure of fibrils formed in vitro. The results indicated that low-selenium cereals from KBD endemic area resulted in a decelerated rate and extant of forming the type Ⅱ collagen fibril, the fibril stability reduced, fibril diameters diminished, and fibril banding periods increased or decreased in vitro. Sesupplemented cereals from KBD endemic area partially rectified the pathologic changes mentioned above. These data are important for further studying the etiology and pathology of KBD.
文摘Objective: To explore the effect of radiofrequency hyperthermia on type Ⅱ collagen expression in a rabbit model of osteoarthri-tis (OA). Methods: Experimental model of knee OA was replicated in the right hind limbs of 54 male rabbits by using modified Hulth modeling method. The rabbits were randomly divided into Model group, Lugua Polypeptide group and Radiofrequency Hyper-thermia group. After modeling, Lugua Polypeptide group was given intramuscular injection of Lugua polypeptide;Radiofre-quency Hyperthermia group was treated with radiofrequency hyperthermia;Model group was not given any special treatment. On the 7th, 13th and 19th day after radiofrequency hyperthermia, six experimental rabbits were chosen from each group and sacrificed to take out medial femoral condyle cartilages in the right hind limbs. Modified Mankins rating was applied to the morphological evaluation. Meanwhile, quantitative real-time PCR was used to detect the content of type Ⅱ collagen in cartilage tissues of medial femoral condyle. Results: At each time point after treatment, Mankins scores were decreased in all the 3 groups, with that of Model group sig-nificantly higher than those of the other two groups (Model group > Lugua Polypeptide group > Radiofrequency Hyperthermia group). The contents of type Ⅱ collagen in cartilage tissues were increased in all the 3 groups, with that of Radiofrequency Hyperthermia group significantly higher than those of the other two group (Model group < Lugua Polypeptide group < Ra-diofrequency Hyperthermia group). The difference between groups was of statistical significance (p < .05). For Radiofrequency Hyperthermia group, Mankins scores were decreased gradually as the treatment time went by, with the content of type Ⅱ colla-gen in cartilage tissues increased. The difference between time points was of statistical significance (p < .05). Conclusions: Radiofrequency hyperthermia is superior to Lugua polypeptide in the treatment of knee OA, at least in rabbits. Its therapeutic mechanism may be related to the significant increase in type Ⅱ collagen in cartilages.
基金financial support from National Natural Science Foundation of China (81872818)National Key R&D Program of China (2021YFE0115200)
文摘Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and safety.Herein,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal epithelium.After oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅡdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells activity.Surprisingly,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira.Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal epithelium.This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of liraglutide.In general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.
