Objective To investigate the significance of sensory neuropeptides [calcitonin gene related peptide (CGRP) and substance P (SP)] in steroid-induced avascular necrosis of the femoral head (ANFH) by using a rabbit model. Methods Fifty-five adult female Japanese White rabbits (weighing 3 kg and aging 24 months) were randomly divided into experimental group (n=45) and control group (n=10). The rabbits in experimental group received a single intramuscularinjection of methylprednisolone at a dose of 4 mg/kg and then were sacrificed after 3 days (n=15), 1 week (n=15), and 2 weeks (n=15) of injection. The rabbits in control group were fed without any treatment. The necrosis of the femoral head was observed. And the expressions of the monoclonal antibodies CGRP and SP were observed with immunohistochemical staining. Also, the integrated absorbance (IA) value of the positive area was calculated. Results All rabbits survived to the end of the experiment. There was no necrosis of the bone or bone marrow in experimental group at 3 days; whereas ANFH was observed in 5 rabbits at 1 week (33%) and in 8 rabbits at 2 weeks (53%). There were significant differences in the rate of ANFH between 1 week, 2 weeks and 3 days (P lt; 0.05); but there was no significant difference between 1 week and 2 weeks (P gt; 0.05). The intensity of CGRP immunoreactivity increased and reached the peak at 1 week, and then decreased at 2 weeks in experimental group. The IA value of CGRP in experimental group at 1 week was significantly higher than that of control group and that of experimental group at 3 days (P lt; 0.05). The IA value of CGRP in experimental group at 2 weeks was significantly lower than those at 3 days and 1 week (P lt; 0.05). The intensity of SP immunoreactivity decreased and reached the lowest at 1 week, and then increased. The IA value of SP in experimental group at 1 week was significantly lower than that of control group and that of experimental group at 2 weeks (P lt; 0.05). Conclusion The sensory neuropeptides may be affected by the steroid, which may play a key role in the process of steroid-induced ANFH by imbalance of bone metabol ism, disturbance of the microcirculation of bone, and disorder of the protective pain-transmission.
ObjectiveTo investigate the effect and mechanism of sleeve gastrectomy (SG) on reducing blood glucose level. MethodsThirty GK rats were randomly divided into SG group, sham operation (SO) group, pair-fed (PF) group, and blank control (BC) group. The changes of weight, fasting blood glucose, glucose tolerance (oral glucose tolerance test, OGTT), insulin tolerance (insulin tolerance test, ITT), plasma insulin, ghrelin, and glucagon like peptide-1 (GLP-1) were monitored before and 24 weeks after operation respectively. ResultsFrom the 4th week after operation, weight gain in SG group and PF group began to decrease significantly compared with SO group (Plt;0.01). From the 2nd week after operation, fasting blood glucose level in SG group was lower than that in SO, PF, and BC groups (Plt;005), and the glucose tolerance in SG group obviously improved compared with preoperation and the other 3 groups (Plt;0.01). On the 6th week after operation, the insulin sensitivity in SG group obviously improved compared with SO group (Plt;0.05, Plt;0.01). There was no significant difference of insulin level between SG group and SO group (Pgt;0.05), ghrelin level significantly decreased (Plt;0.01) while GLP-1 level significantly increased (Plt;0.01) in SG group compared with SO group during 2-24 weeks after operation. ConclusionsThe effect of SG on reducing blood glucose is definite. SG can directly lower blood glucose independent with weight loss. Postoperative decreased ghrelin level and increased GLP-1 level may be its primary mechanism.
Objective To investigate the influence of Nogo extracellular peptide residues 1-40 (NEP1-40) gene modification on the survival and differentiation of the neural stem cells (NSCs) after transplantation. Methods NSCs were isolated from the cortex tissue of rat embryo at the age of 18 days and identified by Nestin immunofluorescence. The lentiviruses were transduced to NSCs to construct NEP1-40 gene modified NSCs. The spinal cords of 30 Sprague Dawley rats were hemisected at T9 level. The rats were randomly assigned to 3 groups: group B (spinal cord injury, SCI), group C (NSCs), and group D (NEP1-40 gene modified NSCs). Cell culture medium, NSCs, and NEP1-40 gene modified NSCs were transplanted into the lesion site in groups B, C, and D, respectively at 7 days after injury. An additional 10 rats served as sham-operation group (group A), which only received laminectomy. At 8 weeks of transplantation, the survival and differentiation of transplanted cells were detected with counting neurofilament 200 (NF-200), glial fibrillary acidic portein (GFAP), and myelin basic protein (MBP) positive cells via immunohistochemical method; the quantity of horseradish peroxidase (HRP) positive nerve fiber was detected via HRP neural tracer technology. Results At 8 weeks after transplantation, HRP nerve trace showed the number of HRP-positive nerve fibers of group A (85.17 ± 6.97) was significantly more than that of group D (59.25 ± 7.75), group C (33.58 ± 5.47), and group B (12.17 ± 2.79) (P lt; 0.01); the number of groups C and D were significantly higher than that of group B, and the number of group D was significantly higher than that of group C (P lt; 0.01). Immunofluorescent staining for Nestin showed no obvious fluorescence signal in group A, a few scattered fluorescent signal in group B, and b fluorescence signal in groups C and D. The number of NF-200-positive cells and MBP integral absorbance value from high to low can be arranged as an order of group A, group D, group C, and group B (P lt; 0.05); the order of GFAP-positive cells from high to low was group B, group D, group C, and group A (P lt; 0.05); no significant difference was found in the percentage of NF-200, MBP, and GFAP-positive cells between group C and group D (P gt; 0.05). Conclusion NEP1-40 gene modification can significantly improve the survival and differentiation of NSCs after transplantation, but has no induction on cell differentiation. It can provide a new idea and reliable experimental base for the study of NSCs transplantation for SCI.
Objective To investigate the effect of curcumin on calcitionin gene related peptide (CGRP) expression after spinal cord injury (SCI) in rats. Methods A total of 200 rats, weighing 250-300 g, were randomly divided into 4 groups (n=50): sham-operation group, normal saline (NS) group, low-dose curcumin group (30 mg/kg), and high-dose curcumin group (100 mg/kg). In sham-operation group, only vertebral lamina excision was performed without SCI; the SCI model was established in the other 3 groups. At immediate after modeling, 30 mg/kg and 100 mg/kg curcumin were injected intraperitoneally in 2 curcumin groups, equivalent NS was given in NS group (30 mg/kg), but no treatment in sham-operation group. At 1, 3, 7, 14, and 21 days after operation, the motor neural function was evaluated by the inclined plane test and Basso-Beattie-Bresnahan (BBB) scores; immunohistochemical staining and Western blot assay were used to observe CGRP expression. Results BBB score and inclined plane test score of NS group, low-dose curcumin group, and high-dose curcumin group were significantly lower than those of sham-operation group at each time point (P lt; 0.05). BBB score of low-dose curcumin group and high-dose curcumin group was significantly higher than that of NS group at 3, 7, 14, and 21 days after SCI (P lt; 0.05), and the score of high-dose group was significantly higher than that of low-dose curcumin group at 7, 14, and 21 days after SCI (P lt; 0.05). Inclined plane test score of low-dose curcumin group and high-dose curcumin group was significantly higher than that of NS group at 7, 14, and 21 days after SCI (P lt; 0.05), and the score of high-dose curcumin group was significantly higher than that of low-dose curcumin group at 7, 14, and 21 days after SCI (P lt; 0.05). Immunohistochemical staining results showed that the CGRP positive cells of sham-operation group was significantly more than those of the other 3 groups, and the CGRP positive cells of high-dose curcumin group were significantly more than those of low-dose curcumin group at each time point (P lt; 0.05); the CGRP positive cells of low- and high-dose curcumin groups were significantly more than those of NS group at 3, 7, 14, and 21 days after SCI (P lt; 0.05). Western blot assay results showed that the CGRP protein expressed at each time point after SCI in sham-operation group; the CGRP protein expression gradually decrease with time passing in NS group; but the CGRP protein expression gradually increased with time passing in low- and high-dose curcumin groups, and reached the peak at 14 days, then maintained a high level. Conclusion After SCI in rats, 30 mg/kg curcumin can improve rats’ motor function, and 100 mg/kg curcumin effect is more obvious, especially in promoting the expression of CGRP. That may be the mechanism of protection of the nervous system.
Objective To evaluate the diagnostic value of serum pro-gastrin-releasing peptide (Pro-GRP) in patients with small cell lung cancer. Methods We searched MEDLINE, EMBASE, The Cochrane Library and other databases (1966 to Sept 2009) to collect studies which evaluated the diagnostic value of Pro-GRP in patients with small cell lung cancer. The heterogeneity of the included studies was tested by the Cochrane Collaboration’s software RevMan 4.2. The Summary Receiver Operating Characteristic (SROC) curve and meta-analyses were performed by MetaDisc. Results A total of 256 relevant articles were retrieved and 19 were included in our review. Eleven studies involving 1 447 patients were included. Meta-analyses showed that the heterogeneity among studies was high (P﹤0.000 01, I2=69.3%), the pooled sensitivity was 0.717 and the pooled specificity was 0.963. Subgroup analyses indicated that 9 of the studies which used the LD (Limited diseases) SCLC group (P=0.003, I2=65.5%, SEN=0.637, SPE=0.968, SROC AUC=0.724 3) had heterogeneity and ED (Extensive diseases) SCLC group (P=0.2, I2=27.0%, SEN=0.766, SPE=0.968, SROC AUC=0.935 5) had no heterogeneity. And 15 of the studies of Pro-GRP which were determined by acmmercial sandwich ELISA (Japan) group (P=0.000 1, I2=68.5%) had heterogeneity. Three of the studies of Pro-GRP which were determined by ELISA (Germany) group (P=0.948 7, I2=0.001%) had no heterogeneity. Conclusion Pro-GRP could be regarded as one of the reference tests in patients with small cell lung cancer, but higher quality trials are required.
ObjectiveTo detect the expressions of signal peptide-CUB-EGF-like domain containing protein 3 (SCUBE3) and specificity protein 1 (SP1) in breast cancer tissues, and explore relations between their protein expressions and clinicopathologic features or prognosis.MethodsFrom February 2013 to October 2015, the breast cancer tissues and the corresponding adjacent normal breast tissues of 80 women patients with breast cancer in the Mianyang Central Hospital were selected, and the expressions of SCUBE3 and SP1 proteins in the tissues were detected by immunohistochemistry. The relations between the expressions of SCUBE3 and SP1 and clinicopathologic parameters of breast cancer were analyzed, the correlation between the SCUBE3 and SP1 was analyzed by Spearman rank correlation analysis. Kaplan-Meier method was used to analyze the survival of patients with breast cancer; and Cox proportional hazards regression model was used to analyze the risk factors of overall survival of patients with breast cancer.ResultsThe positive rates of SCUBE3 and SP1 proteins expressions in the breast cancer tissues were higher than those in the corresponding adjacent normal breast tissues (P<0.05). The positive rates of SCUBE3 and SP1 protein expressions were higher in the breast cancer tissues with lymph node metastasis and molecular subtypes of Luminal A or B (P<0.05), and the positive rates of SCUBE3 protein expression were higher in the breast cancer tissues with TNM stage Ⅱ–Ⅳ and high Ki67 (P<0.05). The retsult of Spearman rank correlation analysis showed that the positive rates of SCUBE3 and SP1 proteins expressions in the breast cancer tissues was positive correlation (χ2=7.979, rs=0.316, P=0.005). Kaplan-Meier curve showed that the overall survival of the patients with positive expression of SCUBE3 or SP1 protein was worse than that of the patients with negative expression (χ2=4.042, P=0.044; χ2=10.676, P=0.001). The Cox proportional hazards regression model multivariate analysis showed that the positive SCUBE3 (HR=6.020, P=0.016), positive SP1 (HR=4.077, P=0.018), lymph node metastasis (HR=3.518, P=0.017), and higher Ki67 expression (HR=7.989, P<0.001) were the independent risk factors of overall survival for the patients with breast cancer.ConclusionPositive rates of SCUBE3 and SP1 proteins expressions in breast cancer tissues are higher and there is a positive correlation between them, which are closely related to clinicopathologic parameters such as lymph node metastasis and molecular subtypes and prognosis of patients with breast cancer.
ObjectiveTo probe plasma calcitonin gene related peptide (CGRP) levels during thrombolytic therapy in patients with iliofemoral venous thrombosis in order to investigate its regularity of the alteration and its clinical significance.MethodsFifty patients with acute iliofemoral venous thrombosis and 30 patients with chronic iliofemoral venous thrombosis were given urokinase and prostaglandin E1 from veins for 15 days. The CGRP levels were determined by radioimmunoassay before treatment and on the 6th hour, 1st day, 3rd day, 7th day, 14th day, 30th day after treatment.ResultsThe plasma CGRP levels were increased in patients with acute iliofemoral venous thrombosis compared with the contrast ones. The CGRP levels in serious group was lower than those in mild group. However, the CGRP levels of 30 chronic patients and 12 patients who received the second course of thrombolysis as on effective were not different from those of contrast ones. The plasma CGRP levels were increased at the 6th hour,reached the peak at the 3th day and returned to normal at the 14th day after thrombolytic therapy in acute group which just consistent with the therapeutic effectiveness.ConclusionIt is helpful to judge whether the thrombolytic therapy is effective and the illness has come to chronic stage according to the levels of plasma CGRP in patients with iliofemoral venous thrombosis.
Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus. Severe diabetic macular edema or proliferative retinopathy may lead to impaired vision or even blindness in diabetic patients. The glucagon-like peptide-1 receptor agonist (GLP-1RA) is now commonly used as novel glucose-lowering agents in the clinical management of type 2 diabetes, but the rapid glycaemic changes associated with the use of the GLP-1RA may aggravate the risk of an increase in the occurrence of short-term potential DR. Potential effects and mechanisms of DR include oxidative stress, vascular endothelial growth factor, inflammation, retinal neurodegeneration, and other cytokines.Whether GLP-1RA leads to the increased risk of DR remains controversial. More basic and clinical studies are needed with the aim of further clarifying the correlation between GLP-1RA and DR risk.
ObjectiveTo investigate the effect and mechanism of gastric bypass surgery (GBP) on fasting bloo-glucose (FBG) in type 2 diabetic rats. MethodsThe models of type 2 diabetic rats were induced by stretozotocin and 20 diabetic rats were randomly divided into two groups: diabetes-operation group (DO group, n=10) and diabetes-control group (DC group, n=10). Another twenty normal rats were randomly divided into two groups: normaloperation group (NO group, n=10) and normal-control group (NC group, n=10). The rats underwent GBP in DO group and NO group and sham operation in DC group and NC group. The FBG levels, serum dipeptidyl peptidase Ⅳ (DPPⅣ), and glucagon-like peptide-1 (GLP-1) concentrations of rats in each group were detected before operation and at 72 h, on 1 week, 4 weeks, and 8 weeks after operation. ResultsThe FBG levels of rats before operation were not significantly different between DO group and DC group or between NO group and NCgroup (Pgt;0.05). After operation, the FBG levels of rats in DO group gradually declined, reached the bottom on 4 weeks after operation and rose slightly on 8 weeks; The FBG levels of rats in DO group were lower after operation than before operation (Plt;0.05); After operation the FBG levels of rats in DO group were higher than that in NO group and NC group at the same time point (Plt;0.05); In DC group, the difference of FBG levels of rats at different time point was not statistically significant (Pgt;0.05); The inter-group and intra-group difference of FPG levels of rats for NO group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum DPP-Ⅳ of rats before operation were not significantly different in each group (Pgt;0.05). After operation, the concentrations of serum DPP-Ⅳ of rats in DO group and NO group gradually decreased and markedly lower than that before operation, respectively (Plt;0.05). The concentrations of serum DPP-Ⅳ of rats after operation in DO group and NO group were significantly lower than that at the same time point in DC group and NC group, respectively (Plt;0.05); The intragroup difference of serum DPP-Ⅳ concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). The concentrations of serum GLP-1 of rats before operation were not significantly different between DO group and DC group or between NO group and NC group (Pgt;0.05). After operation, the concentrations of serum GLP-1 of rats in DO group and NO group gradually increased, reached the top on 4 weeks after operation and declined slightly on 8 weeks; The concentrations of serum GLP-1 of rats in DO group and NO group were higher after operation than before operation (Plt;0.05);After operation, the concentrations of serum GLP-1 of rats in NO group were higher than that in NC group (Plt;0.05), but the concentrations of serum GLP-1 of rats at different time point in NO group were not different (Pgt;0.05). The intragroup difference of serum GLP-1 concentrations of rats for DC group and NC group was not statistically significant (Pgt;0.05). ConclusionsThere is obvious hypoglycemic effect of GBP on FBG levels of type 2 diabetic rats other than normal rats, in which high secretion of GLP-1 and low secretion of DPP-Ⅳ may be play an important role.
【Abstract】Objective To introduce the current research status, value and development future of Arg-Gly-Asp (RGD) peptides in diagnosis and treatment of neoplasms. Methods The current literatures on advances about RGD peptides in diagnosis and treatment of neoplasms were reviewed. Results RGD peptides, specificly recognizing and combining with integrin receptors, exist in extracellular matrix (ECM) of many kinds of organisms. After combining with integrin receptors, extrinsic RGD peptides can prevent tumor cells from adhering to ECM and migrating as the competitive inhibitor of intrinsic RGD peptides, suppress agiogenesis and induce tumor cells apoptosis, showing potential value of tumor specific imaging by targetal labelling neoplasms and treating tumors combining with other methods.Conclusion RGD peptides may be a new drug for diagnosis and treatment of neoplasms.