Colloidal mesoporous silica nanoparticles functionalized with carboxy-terminated polyethylene glycol(CMS-PEG-COOH) were successfully synthesized by covalently grafting dicarboxy-terminated polyethylene glycol(HOOC-PEG...Colloidal mesoporous silica nanoparticles functionalized with carboxy-terminated polyethylene glycol(CMS-PEG-COOH) were successfully synthesized by covalently grafting dicarboxy-terminated polyethylene glycol(HOOC-PEG-COOH) on the surface of the amino functionalized CMS nanoparticles with amide bond as a cross linker. Moreover, the structural and particle properties of CMS-PEG-COOH were characterized by nuclear magnetic resonance spectroscopy(1 H-NMR), transmission electron microscopy(TEM), dynamic light scattering(DLS), nitrogen adsorption-desorption measurements, X-ray diffraction(XRD), and Fourier transform infrared spectroscopy(FT-IR). The nanomaterials presented a relatively uniform spherical shape morphology with diameters of about 120 nm,and favorable dispersibility in weak acid solution. The CMSPEG-COOH exhibited no changes in the state of amorphous, while the mesopores sizes of 5.25 nm might provide the nanomaterials with large capacity for the loading and releasing of drugs. So the results indicated that CMSPEG-COOH might be a critical nanomaterial for drug delivery system in the future.展开更多
Background Pain has a substantial impact on patients＇ activities and overall quality of life, but current conventional drugs have debilitating side effects, including gastrointestinal disorders. Thus there is a press...Background Pain has a substantial impact on patients＇ activities and overall quality of life, but current conventional drugs have debilitating side effects, including gastrointestinal disorders. Thus there is a pressing need for new therapies with fewer side effects to alleviate cancer pain. We recently developed a topical herbal formula Xiaotan Tongluo analgesic gel （X＇I-IL gel） based on the principles of traditional Chinese herbalism, and we have received positive feedback from bone cancer pain patients. The aim of this study was to determine the analgesic effects and explore the mechanisms of XTI-L gel in a rat model of bone cancer pain. Methods The rat model of bone cancer pain was established by inoculating Walker-256 rat carcinoma cells directly into the right tibial medullary cavity of Wistar rats. The rats were randomly assigned to three groups （n=-10 per group）： （1） sham bone cancer control （sham group）： vehicle （PBS） inoculation without carcinoma cells plus topical administration of blank gel; （2） Sham treatment control （vehicle group）： Walker-256 cell inoculation plus topical administration of blank gel; （3） XTTL gel treatment （treatment group）： Walker-256 cell inoculation plus topical administration of XTTL gel. XTTL gel treatments were applied daily for 7 days starting on day 14 following inoculation. Outcomes were assessed 21 days after inoculation by mechanical allodynia, histological staining, and by measuring concentrations of type I collagen carboxy-terminal telopeptide （ICTP） and bone-specific alkaline phosphatase （BAP） in serum. Results Fourteen days after cancer cell incubation, significant mechanical allodynia in the ipsilateral hind paw and tumor growth in proximal end of the tibia were observed in the vehicle and treatment groups but not in the sham group. At day 21, mechanical withdrawal thresholds in treatment group rats were significantly higher （（4.8557±0.8336） g） compared with those of the vehicle group （（1.8630±1.4展开更多
Cardiotrophin-1 （CT-1） activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expres- sion pattern of sarcomeric...Cardiotrophin-1 （CT-1） activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expres- sion pattern of sarcomeric contractile protein α-actin, specialized eytoskeletal protein α-actinin and mitochondrial uncoupling protein-2 （UCP2） in myocardial remodeling induced by chronic exposure to CT-1. Kunming mice were intraperitoneally injected with carboxy-terminal polypeptide （CP） of CT-1 （CT-1-CP, 500 μg·kg-1·day^-1） for 1, 2, 3 and 4 week （s）, respectively （4 groups obtained according to the injection time, n=10 each, with 5 males and 5 females in each group）, Those injected with physiological saline for 4 weeks served as controls （n=10, with 5 males and 5 females）. The heart tissues of mice were harvested at 1, 2, 3 or 4 week （s）. Immunohistochemistry （IHC） and Western blotting （WB） were used to detect the distribution and expression of sarcomeric α-actin, α-aetinin and mitoehondrial UCP2 in myocardial tissues. IHC showed that α-actin was mainly distributed around the nuclei of cardiomyo- cytes, α-actinin concentrated around the striae and UCP2 scattered rather evenly in the plasma. The ex- pression of α-actin was slightly greater than that of α-actinin and UCP2 in the control group （IHC： χ^2=6.125; WB： F=0.249, P〉0.05） and it gradually decreased after exposure to CT-1-CP. There was no significant difference in the expression of α-actin between the control group and the CT-1-CP-treated groups （χ^2=7.386, P〉0.05）. But Western blotting revealed significant difference in the expression of α-actin between the control group and the 4-week CT-1-CP-treated group （F=2.912; q=4.203, P〈0.05）. Moreover, it was found that the expression of α-actinin increased stepwise with the exposure time in CT-1-CP-treated groups and differed significantly between CT-1-CP-treated groups and the control group （ICH： χ^2=21.977; WB： F=50.388; P〈0.01）. The e展开更多
AIM: To investigate the relationship between clinicopathological features and bone turnover markers in castration-resistant prostate cancer(CRPC) patients treated with docetaxel.METHODS: Thirty-three patients were enr...AIM: To investigate the relationship between clinicopathological features and bone turnover markers in castration-resistant prostate cancer(CRPC) patients treated with docetaxel.METHODS: Thirty-three patients were enrolled in this study. Serum levels of carboxyterminal cross-linked telopeptide of type 1 collagen generated by metalloproteinases(1CTP) and alkaline phosphatase(ALP) were measured at the start of docetaxel chemotherapy. We examined the relationship between clinicopathological features and serum levels of 1CTP and ALP levels in CRPC patients treated with docetaxel.RESULTS: For the total patient group, the mean ± standard deviation(SD) values for docetaxel chemotherapy dose, dose intensity, dosage interval, and num-ber of cycles were 59.3 ± 10.6 mg/m2, 13.9 ± 5.2 mg/m2 per week, 4.7 ± 1.2 wk, and 11.2 ± 7.4, respectively. Fourteen patients died from prostate cancer. Patients were divided into two groups according to mean + SD of serum 1CTP(8.2 ng/m L) and ALP(538.2 IU/L) levels at the start of docetaxel chemotherapy. Patients with lower levels of serum 1CTP and ALP had significantly better survivals than those with higher serum levels(P < 0.05).CONCLUSION: Serum levels of 1CTP and ALP are predictors of survival in patients with CRPC who are treated with docetaxel.展开更多
BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-termin...BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-terminal hydrolase L1(UCH-L1)and glial fibrillary acidic protein(GFAP)levels in patients with glioma pre-and postoperatively.METHODS Between June 2018 and June 2021,91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group.Sixty healthy volunteers were included in the control group.Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery.UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery.The patients were followed-up until February 2022.Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels,which could assist in predicting postoperative glioma recurrence.RESULTS UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy(P<0.05).However,UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery(P<0.05).There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex,age,pathological type,tumor location,or number of lesions(P>0.05).Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with gradeⅢ-IV tumors(P<0.05).Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter≤5 cm than in those with diameter>5 cm,in which the differences were statistically significant(P<0.05).Glioma recurred in 22 patients.The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group(P<0.05).Receiver operating characteristic curv展开更多
To study the expression of the carboxy-ter-minal PSD-95/DLG/ZO-1 ligand of nNOS(CAPON)and Dexras1 mRNA during development in the spinal cord of rats,real-time polymerase chain reaction(Real-time PCR),as a quantitative...To study the expression of the carboxy-ter-minal PSD-95/DLG/ZO-1 ligand of nNOS(CAPON)and Dexras1 mRNA during development in the spinal cord of rats,real-time polymerase chain reaction(Real-time PCR),as a quantitative method,was used to study the developmental expression of CAPON and Dexras1 mRNA level in the spinal cord.The spatial expression of CAPON and Dexras1 mRNA was examined by a com-bination of in situ hybridization(ISH)and immunofluor-escence.During the development of the spinal cord,CAPON mRNA was expressed in low levels from embryo day 14 to day 18.At postnatal day 1,it reached the peak and was expressed in the part which will become the dor-sal horn when mature.It then decreased gradually until postnatal week 12,when it presented in the ventral horn.At embryo day 14,Dexras1 mRNA was expressed at low levels,increased during embryo day 16 to day 18 and peaked at postnatal day 1.Spatiotemporal expression of Dexras1 mRNA was similar to CAPON as confirmed by correlation analysis and colocalization.CAPON and neuronal nitric oxide synthase(nNOS)was expressed within the same cells of the dorsal horn at postnatal day 1 but had different subcellular localizations.Co-express-ion of CAPON and Dexras1 mRNA in myeloid tissue during development process of rat indicates that the adaptor protein,CAPON may play a probable role in differentiation of neurons,synaptic plasticity and synap-togenesis by regulating nNOS to activate Dexras1.展开更多
目的通过观察不同血液净化方式的联合应用对血液透析患者血清中骨代谢指标及骨质疏松患病率的影响,来评价血液透析方式的不同组合对血液透析患者矿物质和骨异常(mineral and bone disorder,MBD)的影响。方法维持性血液透析患者90例,随...目的通过观察不同血液净化方式的联合应用对血液透析患者血清中骨代谢指标及骨质疏松患病率的影响,来评价血液透析方式的不同组合对血液透析患者矿物质和骨异常(mineral and bone disorder,MBD)的影响。方法维持性血液透析患者90例,随机分为血液透析组(对照组或HD组)、血液透析加血液透析滤过组(HD+HDF组)、血液透析加血液灌流组(HD+HP组),每组30例,观察6个月,比较组内及组间6个月前后血钙、血磷、全段甲状旁腺激素(intact parathyroid hormone,iPTH)、成纤维生长因子23(fibroblast growth factor23,FGF-23)、β-I型胶原羧基末端肽(β-Type I collagen carboxy-terminal peptide,β-CTX)、I型前胶原氨基末端肽(Type I procollagen amino-terminal peptide,PINP)、骨质疏松患病率等指标的变化来评价不同透析方式的组合对血液透析患者MBD的影响。结果组内自身前后比较:HD组血磷[(2.21±0.55)mmol/l vs.(2.64±1.04)mmol/l,t=2.047、P=0.049]、iPTH[(427.7±44.00)pg/ml vs.(452.1±43.00)pg/ml,t=2.140,P=0.038]变化有统计学差异;HD+HDF组的iPTH下降有统计学差异[(465.3±43.02)pg/ml vs.(431.0±37.39)pg/ml,t=3.298,P=0.007];HD+HP组的iPTH[(457.4±60.01)pg/mlvs.(389.1±29.89)pg/ml,t=5.598,P=0.001)、β-CTX[(2.73±1.16)ng/ml vs.(2.13±1.51)ng/ml,t=2.142,P=0.045];PINP[(157.92±31.16)ng/mlvs.(140.76±36.13)ng/ml,t=2.106,P=0.047];FGF-23[(461.16±101.69)ng/ml vs.(397.30±63.18)ng/ml,t=2.922,P=0.011]下降均有统计学意义。组间比较6个月后,HD+HDF组PINP为(147.33±40.72)ng/ml,HD组PINP为(165.32±43.11)ng/ml,二者比较有统计学差异(t=1.969,P=0.048);HD+HDF组FGF-23(465.38±101.36)ng/ml,HD组FGF-23(403.56±96.81)ng/ml,二者比较HD+HDF组更低,有统计学差异(t=2.415,P=0.019);组间比较6个月后,HD+HP组与HD组比较,血磷[(2.02±0.81)mmol/L vs.(2.64±1.04)mmol/L,t=3.221,P=0.003]、iPTH[(389.1±29.89)pg/ml vs.(452.1±43.0)pg/ml,t=6.661,P=0.005]、β-CTX[(2.13±1.51)ng/ml vs.(2.95±1.28)ng/ml,t=2.278,P=0.031]、PINP[(140.76±36展开更多
基金Funded by the National Natural Science Foundation of China(No.81201197)
文摘Colloidal mesoporous silica nanoparticles functionalized with carboxy-terminated polyethylene glycol(CMS-PEG-COOH) were successfully synthesized by covalently grafting dicarboxy-terminated polyethylene glycol(HOOC-PEG-COOH) on the surface of the amino functionalized CMS nanoparticles with amide bond as a cross linker. Moreover, the structural and particle properties of CMS-PEG-COOH were characterized by nuclear magnetic resonance spectroscopy(1 H-NMR), transmission electron microscopy(TEM), dynamic light scattering(DLS), nitrogen adsorption-desorption measurements, X-ray diffraction(XRD), and Fourier transform infrared spectroscopy(FT-IR). The nanomaterials presented a relatively uniform spherical shape morphology with diameters of about 120 nm,and favorable dispersibility in weak acid solution. The CMSPEG-COOH exhibited no changes in the state of amorphous, while the mesopores sizes of 5.25 nm might provide the nanomaterials with large capacity for the loading and releasing of drugs. So the results indicated that CMSPEG-COOH might be a critical nanomaterial for drug delivery system in the future.
文摘Background Pain has a substantial impact on patients＇ activities and overall quality of life, but current conventional drugs have debilitating side effects, including gastrointestinal disorders. Thus there is a pressing need for new therapies with fewer side effects to alleviate cancer pain. We recently developed a topical herbal formula Xiaotan Tongluo analgesic gel （X＇I-IL gel） based on the principles of traditional Chinese herbalism, and we have received positive feedback from bone cancer pain patients. The aim of this study was to determine the analgesic effects and explore the mechanisms of XTI-L gel in a rat model of bone cancer pain. Methods The rat model of bone cancer pain was established by inoculating Walker-256 rat carcinoma cells directly into the right tibial medullary cavity of Wistar rats. The rats were randomly assigned to three groups （n=-10 per group）： （1） sham bone cancer control （sham group）： vehicle （PBS） inoculation without carcinoma cells plus topical administration of blank gel; （2） Sham treatment control （vehicle group）： Walker-256 cell inoculation plus topical administration of blank gel; （3） XTTL gel treatment （treatment group）： Walker-256 cell inoculation plus topical administration of XTTL gel. XTTL gel treatments were applied daily for 7 days starting on day 14 following inoculation. Outcomes were assessed 21 days after inoculation by mechanical allodynia, histological staining, and by measuring concentrations of type I collagen carboxy-terminal telopeptide （ICTP） and bone-specific alkaline phosphatase （BAP） in serum. Results Fourteen days after cancer cell incubation, significant mechanical allodynia in the ipsilateral hind paw and tumor growth in proximal end of the tibia were observed in the vehicle and treatment groups but not in the sham group. At day 21, mechanical withdrawal thresholds in treatment group rats were significantly higher （（4.8557±0.8336） g） compared with those of the vehicle group （（1.8630±1.4
文摘Cardiotrophin-1 （CT-1） activates a distinct form of cardiac muscle cell hypertrophy in which the sarcomeric units are assembled in series. The aim of the study was to determine the expres- sion pattern of sarcomeric contractile protein α-actin, specialized eytoskeletal protein α-actinin and mitochondrial uncoupling protein-2 （UCP2） in myocardial remodeling induced by chronic exposure to CT-1. Kunming mice were intraperitoneally injected with carboxy-terminal polypeptide （CP） of CT-1 （CT-1-CP, 500 μg·kg-1·day^-1） for 1, 2, 3 and 4 week （s）, respectively （4 groups obtained according to the injection time, n=10 each, with 5 males and 5 females in each group）, Those injected with physiological saline for 4 weeks served as controls （n=10, with 5 males and 5 females）. The heart tissues of mice were harvested at 1, 2, 3 or 4 week （s）. Immunohistochemistry （IHC） and Western blotting （WB） were used to detect the distribution and expression of sarcomeric α-actin, α-aetinin and mitoehondrial UCP2 in myocardial tissues. IHC showed that α-actin was mainly distributed around the nuclei of cardiomyo- cytes, α-actinin concentrated around the striae and UCP2 scattered rather evenly in the plasma. The ex- pression of α-actin was slightly greater than that of α-actinin and UCP2 in the control group （IHC： χ^2=6.125; WB： F=0.249, P〉0.05） and it gradually decreased after exposure to CT-1-CP. There was no significant difference in the expression of α-actin between the control group and the CT-1-CP-treated groups （χ^2=7.386, P〉0.05）. But Western blotting revealed significant difference in the expression of α-actin between the control group and the 4-week CT-1-CP-treated group （F=2.912; q=4.203, P〈0.05）. Moreover, it was found that the expression of α-actinin increased stepwise with the exposure time in CT-1-CP-treated groups and differed significantly between CT-1-CP-treated groups and the control group （ICH： χ^2=21.977; WB： F=50.388; P〈0.01）. The e
基金Supported by Grants-in-Aid from the Ministry of Education,Culture,Sports,Science and Technology,Tokyo,Japan,No.22591761,No.23791792
文摘AIM: To investigate the relationship between clinicopathological features and bone turnover markers in castration-resistant prostate cancer(CRPC) patients treated with docetaxel.METHODS: Thirty-three patients were enrolled in this study. Serum levels of carboxyterminal cross-linked telopeptide of type 1 collagen generated by metalloproteinases(1CTP) and alkaline phosphatase(ALP) were measured at the start of docetaxel chemotherapy. We examined the relationship between clinicopathological features and serum levels of 1CTP and ALP levels in CRPC patients treated with docetaxel.RESULTS: For the total patient group, the mean ± standard deviation(SD) values for docetaxel chemotherapy dose, dose intensity, dosage interval, and num-ber of cycles were 59.3 ± 10.6 mg/m2, 13.9 ± 5.2 mg/m2 per week, 4.7 ± 1.2 wk, and 11.2 ± 7.4, respectively. Fourteen patients died from prostate cancer. Patients were divided into two groups according to mean + SD of serum 1CTP(8.2 ng/m L) and ALP(538.2 IU/L) levels at the start of docetaxel chemotherapy. Patients with lower levels of serum 1CTP and ALP had significantly better survivals than those with higher serum levels(P < 0.05).CONCLUSION: Serum levels of 1CTP and ALP are predictors of survival in patients with CRPC who are treated with docetaxel.
基金Supported by Hebei Medical Science Research Project,No.20220648。
文摘BACKGROUND Brain gliomas are malignant tumors with high postoperative recurrence rates.Early prediction of prognosis using specific indicators is of great significance.AIM To assess changes in ubiquitin carboxy-terminal hydrolase L1(UCH-L1)and glial fibrillary acidic protein(GFAP)levels in patients with glioma pre-and postoperatively.METHODS Between June 2018 and June 2021,91 patients with gliomas who underwent surgery at our hospital were enrolled in the glioma group.Sixty healthy volunteers were included in the control group.Serum UCH-L1 and GFAP levels were measured in peripheral blood collected from patients with glioma before and 3 d after surgery.UCH-L1 and GFAP levels in patients with glioma with different clinicopathological characteristics were compared before and after surgery.The patients were followed-up until February 2022.Postoperative glioma recurrence was recorded to determine the serum UCH-L1 and GFAP levels,which could assist in predicting postoperative glioma recurrence.RESULTS UCH-L1 and GFAP levels in patients with glioma decreased significantly 3 d after surgery compared to those before therapy(P<0.05).However,UCH-L1 and GFAP levels in the glioma group were significantly higher than those in the control group before and after surgery(P<0.05).There were no statistically significant differences in preoperative serum UCH-L1 and GFAP levels among patients with glioma according to sex,age,pathological type,tumor location,or number of lesions(P>0.05).Serum UCH-L1 and GFAP levels were significantly lower in the patients with WHO grade I-II tumors than in those with gradeⅢ-IV tumors(P<0.05).Serum UCH-L1 and GFAP levels were lower in the patients with tumor diameter≤5 cm than in those with diameter>5 cm,in which the differences were statistically significant(P<0.05).Glioma recurred in 22 patients.The preoperative and 3-d postoperative serum UCH-L1 and GFAP levels were significantly higher in the recurrence group than these in the non-recurrence group(P<0.05).Receiver operating characteristic curv
基金This work was supported by the National Natural Science Foundation of China(Grant No.30300099,Grant No.30770488)Natural Science Foundation of Jiangsu Province(No.BK2003035,No.BK2006547)and"Six Talent Peak"Foundation of Jiangsu Province.
文摘To study the expression of the carboxy-ter-minal PSD-95/DLG/ZO-1 ligand of nNOS(CAPON)and Dexras1 mRNA during development in the spinal cord of rats,real-time polymerase chain reaction(Real-time PCR),as a quantitative method,was used to study the developmental expression of CAPON and Dexras1 mRNA level in the spinal cord.The spatial expression of CAPON and Dexras1 mRNA was examined by a com-bination of in situ hybridization(ISH)and immunofluor-escence.During the development of the spinal cord,CAPON mRNA was expressed in low levels from embryo day 14 to day 18.At postnatal day 1,it reached the peak and was expressed in the part which will become the dor-sal horn when mature.It then decreased gradually until postnatal week 12,when it presented in the ventral horn.At embryo day 14,Dexras1 mRNA was expressed at low levels,increased during embryo day 16 to day 18 and peaked at postnatal day 1.Spatiotemporal expression of Dexras1 mRNA was similar to CAPON as confirmed by correlation analysis and colocalization.CAPON and neuronal nitric oxide synthase(nNOS)was expressed within the same cells of the dorsal horn at postnatal day 1 but had different subcellular localizations.Co-express-ion of CAPON and Dexras1 mRNA in myeloid tissue during development process of rat indicates that the adaptor protein,CAPON may play a probable role in differentiation of neurons,synaptic plasticity and synap-togenesis by regulating nNOS to activate Dexras1.
