ABSTRACT
Osteoporosis (OP) is a systemic skeletal disease that primarily affects the elderly population, which greatly increases the risk of fractures. Here we report that Kindlin-2 expression in adipose tissue increases during aging and high-fat diet fed and is accompanied by decreased bone mass. Kindlin-2 specific deletion (K2KO) controlled by Adipoq-Cre mice or adipose tissue-targeting AAV (AAV-Rec2-CasRx-sgK2) significantly increases bone mass. Mechanistically, Kindlin-2 promotes peroxisome proliferator-activated receptor gamma (PPARγ) activation and downstream fatty acid binding protein 4 (FABP4) expression through stabilizing fatty acid synthase (FAS), and increased FABP4 inhibits insulin expression and decreases bone mass. Kindlin-2 inhibition results in accelerated FAS degradation, decreased PPARγ activation and FABP4 expression, and therefore increased insulin expression and bone mass. Interestingly, we find that FABP4 is increased while insulin is decreased in serum of OP patients. Increased FABP4 expression through PPARγ activation by rosiglitazone reverses the high bone mass phenotype of K2KO mice. Inhibition of FAS by C75 phenocopies the high bone mass phenotype of K2KO mice. Collectively, our study establishes a novel Kindlin-2/FAS/PPARγ/FABP4/insulin axis in adipose tissue modulating bone mass and strongly indicates that FAS and Kindlin-2 are new potential targets and C75 or AAV-Rec2-CasRx-sgK2 treatment are potential strategies for OP treatment.
ABSTRACT
The ubiquitin-proteasome system (UPS) dedicates to degrade intracellular proteins to modulate demic homeostasis and functions of organisms. These enzymatic cascades mark and modifies target proteins diversly through covalently binding ubiquitin molecules. In the UPS, E3 ubiquitin ligases are the crucial constituents by the advantage of recognizing and presenting proteins to proteasomes for proteolysis. As the major regulators of protein homeostasis, E3 ligases are indispensable to proper cell manners in diverse systems, and they are well described in physiological bone growth and bone metabolism. Pathologically, classic bone-related diseases such as metabolic bone diseases, arthritis, bone neoplasms and bone metastasis of the tumor, etc., were also depicted in a UPS-dependent manner. Therefore, skeletal system is versatilely regulated by UPS and it is worthy to summarize the underlying mechanism. Furthermore, based on the current status of treatment, normal or pathological osteogenesis and tumorigenesis elaborated in this review highlight the clinical significance of UPS research. As a strategy possibly remedies the limitations of UPS treatment, emerging PROTAC was described comprehensively to illustrate its potential in clinical application. Altogether, the purpose of this review aims to provide more evidence for exploiting novel therapeutic strategies based on UPS for bone associated diseases.
ABSTRACT
With the increasing incidence of osteoporosis, osteoporotic vertebral compression fracture (OVCF) has become a common disease in the elderly. Relevant researches have indicated that percutaneous vertebroplasty (PVP) has become the main treatment for painful osteoporotic vertebral compression fractures. In aspect of perioperative nursing care for PVP, both domestic and foreign scholars have published a large number of research reports, indicating that perioperative nursing intervention can alleviate the pain, reduce the incidence of complications, improve the quality of life of patients, and promote rehabilitation. This article aims to make a comprehensive review about the perioperative nursing care for patients with osteoporotic vertebral compression fractures who are receiving PVP so as to provide reference for clinical nursing staff in the implementation of nursing intervention. (J Intervent Radiol, 2018, 27:290-293)
ABSTRACT
Objective To discuss the perioperative nursing measures for patients with osteoporotic vertebral compression fractures who are receiving percutaneous vertebroplasty (PVP) treatment by using high viscosity bone cement.Methods A total of 30 patients with osteoporotic vertebral compression fractures were included in this study.All patients were treated with PVP by using high viscosity bone cement.Preoperative routine nursing,psychological intervention,dietary intervention,postoperative guidance of rehabilitation exercise of limbs,close observation of bone cement leakage were strictly implemented,and the corresponding nursing measures were promptly taken when needed.Results Through strict implement of the nursing intervention all 30 patients could actively cooperate with PVP treatment,and after PVP the pain was significantly relieved in all patients.Conclusion Adequate preoperative preparation,proper postoperative guidance,careful observation and effective nursing can help the patients resume their daily life activities as soon as possible,relieve the pain,and improve the quality of life as well.(J Intervent Radiol,2017,26:274-276)
ABSTRACT
Objective To investigate the feasibility of green fluorescent protein (GFP) as a marker to trace the transplanted um-bilical cord mesenchymal stem cells (ucMSCs) in rats with cerebral ischemia-reperfusion .Methods ucMSCs were transfected by GFP-adenovirus .The rats were subjected to left middle cerebral artery occlusion using suture method .1 × 106 GFP-ucMSCs were transplanted with cerebral stereotaxic technique .Frozen sections of brain tissue were made at 7 d after cerebral ischemia .The ex-pression of GFP was observed by fluorescence microscope .Results In vitro ,the morphology of GFP in ucMSCs was fibrous ,and when fused ,the clusters were arranged in a radial or whirlpool shape ,The morphological feature of transfected ucMSCs was similar to that un-transfected ucMSCs .Under the fluorescence microscope ,the positive rate of GFP was more than 80% .In addition ,GFP could spread to the whole cells and show the completed form .No rejection was observed in the rats after transplantation ,and the GFP was found near the site of transplantation after 7 d ,and the fluorescence was not attenuated .Conclusion GFP is an effective tracer maker for ucMSCs transplantation in the treatment of ischemia-reperfusion ,which could provide experimental method for fur-ther study .
ABSTRACT
Objective To investigate the feasibility of green fluorescent protein (GFP) as a marker to trace the transplanted um-bilical cord mesenchymal stem cells (ucMSCs) in rats with cerebral ischemia-reperfusion .Methods ucMSCs were transfected by GFP-adenovirus .The rats were subjected to left middle cerebral artery occlusion using suture method .1 × 106 GFP-ucMSCs were transplanted with cerebral stereotaxic technique .Frozen sections of brain tissue were made at 7 d after cerebral ischemia .The ex-pression of GFP was observed by fluorescence microscope .Results In vitro ,the morphology of GFP in ucMSCs was fibrous ,and when fused ,the clusters were arranged in a radial or whirlpool shape ,The morphological feature of transfected ucMSCs was similar to that un-transfected ucMSCs .Under the fluorescence microscope ,the positive rate of GFP was more than 80% .In addition ,GFP could spread to the whole cells and show the completed form .No rejection was observed in the rats after transplantation ,and the GFP was found near the site of transplantation after 7 d ,and the fluorescence was not attenuated .Conclusion GFP is an effective tracer maker for ucMSCs transplantation in the treatment of ischemia-reperfusion ,which could provide experimental method for fur-ther study .
ABSTRACT
Objective To compare the transfection efficiency of cationic polyethylenimine(PEI)with Lipofectamine 2000TM by using the plasmid DNA encoding vascular endothelial cell growth factor (VEGF165 )gene in human embryonic kidney cell line 293T.Methods PEI of different N/P ratio and Lipofectamine 2000TM were used to deliver the vector containing VEGF165 to 293T cells,respectively.Green fluorescent protein(GFP)gene was inserted into the vector as a report gene.Evaluation of cytoactive was performed by CCK-8 assay 24 h after transfection.The cells were observed by fluorescent microscope and the presence of VEGF165 in cell supernatant was detected by ELISA 48 h after transfection.The transfection efficiency was calculated and com-pared.Results Similar cytoactive and best transfection efficiency could be obtained when N/P ratio was 9,the transfection efficien-cy was around 70%.Furthermore,the presence of VEGF165 increased significantly after transfection(P <0.05),but there was no significant difference between the two groups in which different transfection methods were adopted.Conclusion PEI as a novel oli-gofectamine reagent could mediate more efficient transfection compared with lipofectamine.It also has low cell-toxicity and low price and could be an ideal vector in gene delivery technology.
ABSTRACT
Objective Class 1 integrase(intI 1),qacE△1-sul1 and sul2 genes were detected in trimethoprim-sulfamethoxazole resistant Stenotrophomonas maltophilia by PCR to assess the relationship between the antibiotic resistance mechanism for trimethoprim-sulfamethoxazole (TMP-SMZ)and these genes distribution.Methods S.maltophilia isolates were collected from patients treated in Affilitated hospital of Nanjing University of TCM during January to May in 2013,DNA was ab-stracted by boiling method and genes were detected by polymerase chain reaction.Results intI 1 genes were observed posi-tive in 25 of 28 strains resistant for TMP-SMZ,qacE△1-sul1 genes were positive in 21 while sul2 genes positive in 15,the positive rates of intI 1,qacE△1-sul1 and sul2 genes were 89.29%,75% and 53.57%;in 18 trimethoprim-sulfamethoxazole sensitive strains,5 were intI 1 positive,4 were qacE△1-sul1 positive while sul2 were none,the positive rates of intI1 and qacE△1-sul1 were 27.78% and 22.22%.Conclusion Most of stenotrophomonas maltophilia resisted trimethoprim-sulfa-methoxazole had intI 1,qacEΔ1-sul 1 and sul2 genes.
ABSTRACT
Objective To investigate the effects of 2.45 GHz microwave on the apoptosis of HeLa cells and explore the underlying mechanism.Methods HeLa cells were divided into five groups randomly:control group,sham-irradiation group,and three irradiation groups exposed with 10,15 and 20 mW/cm2 2.45 GHz microwave for 10 min.Cell survival was tested by MTT assay,cell nucleus fashion was observed by a laser scanning confocal microscope,cell cycle distribution was measured by flow cytometry,and cell protein expressions were detected by Western blot.Results The cell survival in control group,shamirradiation group and low dose irradiation group had no difference but it became lower in the middle and high dose irradiated group(t =-16.47,-14.23,P ＜ 0.05).The abnormal rates of nuclear fashion in the low,middle and high dose irradiation groups were obviously higher compared with control group (t =9.37,11.25,8.47,P ＜ 0.05),while high dose irradiation group was higher than the low and middle dose group (t =15.32,10.25,P ＜0.05).The rate of HeLa cells in sub-G1 in the irradiation groups were higher than that in control group (t =15.24,22.31,10.69,P ＜ 0.05).The results of immunohistochemistry showed that the expression of Bax and Caspase-3 in irradiation groups was significantly increased,and the expression of Bcl-2 was decreased.Conclusions 2.45 GHz microwave can induce HeLa cells apoptosis with a positive correlation with microwave dose.
ABSTRACT
Objective To investigate the effects of propofol on lipopolysaccharide (LPS)-induced brain injury in rats.Methods Fifty-four pathogen-free SD rats of both sexes, aged 6 weeks, weighing 200-250 g, were randomly divided into 3 groups: control group (group C, n = 6) ; LPS group (group L, n = 24) ; propofol group (group P, n = 24) . Brain injury was produced by injection of LPS 1 mg/kg via the left internal carotid artery in L and P groups. Propofol 100 mg/kg was injected intraperitonealry immediately after the LPS administration in group P, while the equal volume of normal saline was given instead of propofol in group L. The equal volume of normal saline was given instead of LPS and propofol in group C. Six rats in each group were sacrificed and the brain tissues were immediately removed at 24 h after intraperitoneal administration in group C, and at 6, 24, 48 and 72 h after intraperitoneal administration in L and P groups for determination of brain water content, high-mobility group box 1 ( HMGB1) expression and NF-κB activity, and microscopic examination. Results The brain water content and NF-kB activity were significantly increased, and HMGB1 expression was up-regulated in group L as compared to group C (P ＜ 0.05) . The brain water content, expression of HMGB1 and NF-kB activity were significantly lower in group P than in group L ( P ＜ 0.05) . The microscopic examination showed that brain injury was attenuated in group P compared with group L. The brain water content was positively correlated with the HMGB1 expression and NF- κB activity (r = 0.692 and 0.769 respectively, P ＜ 0.05). Conclusion Propofol can reduce the LPS- induced brain injury by reducing inflammatory response of the brain tissues.
ABSTRACT
Objective To examine the expression of Cath D,SP-A and GLUT-1 in patients with bronchiogenic carcinoma.Methods A total of 41 patients were included in the study,10 of whom received the histological diagnosis of small cell lung cancer(SCLC).The other 28 were squamous cell carcinoma(SC) and 3 were inflammation.And all the samples were taken from the patients′ tunica mucosa bronchiorum through bronchofibroscope,then we detected the cathepsin D,SP-A and GLUT-1 following SP immunohistochemistry.Results ①Cath D: 6 samples(60%) in group SCLC were negtive expression(-6),4(40%)were moderately positive(++4),4(14%) were negative(-4),2(7%) were positive(+2),8(28%) were moderately positive(++8) and 14(50%) were intensive positive(+++14) in the other group.SCLC was significant different from SC in expressing cathepsin D(P
ABSTRACT
To investigate the effect of P53 protein accumulation and p53 gene mutation in the pathogenesis of glioma and to study the role of MDM2, P53 and P16 protein in glioma formation and progression and their relationship with each other, LSAB immunohistochemical staining method and non-isotopic PCR-SSCP techniques were used to detect the expression of MDM2, P53 and P16 pro tein and p53 gene mutation in 48 cases of gliomas. The results showed that the positive expression rate of MDM2, P53 and the negative rate of P16 was 22.9 %, 41.7 % and 60.4 %, respectively.The latter two in high grade (grade Ⅲ , Ⅳ) gliomas had a significantly higher rate than in the low grade (grade Ⅱ ) gliomas. Moreover, the co-expression of MDM2 and P53 protein was confirmed in only 1 of 48 cases. No significant difference was found in the rate of the expression of MDM2 between high grade and low grade gliomas (P＞0.1) . PCR SSCP results showed that mutation of 5-8 exons of p53 gene was detected in 17 out of 48 cases (35.42 %) . Mutation was detected in 16of 20 cases of positive p53 expression, and another one was detected in 28 cases of negative expression cases. The correlation between p53 mutation and p53 immunopositivity was observed in 89.6% of the cases. P53 gene mutation and the level of MDM2, P53 and P16 protein were not related to age, gender of the patients, tumor location and size. It is concluded that the mutation of p53 and deletion of p16 might play important roles in the tumorigenesis of gliomas and it was significantly associated with the grade of tumor differentiation. P53 protein accumulation can indirectly reflect p53 mutation. MDM2 amplification and overexpression might be an early event in the growth of human gliomas.
ABSTRACT
Objective To explore the changes of serum leptin level in patients with diabetic microangiopathy.Methods A total of 90 subjects were assigned to three groups which included 30 healthy controls,30 diabetic patients without microangiopathy and 30 patients with diabetic microangiopathy.The studing groups were matched for sex and BMI.The level of serum leptin ,ⅣC,insulin and glucose of these patients were measured,and the correlation between serum leptin level and other indexes was analyzed.Results The level of serum leptin in controls,diabetic patients without microangiopathy and patients with diabetic microangiopathy were (7.20?2.11) ?g/L, (7.95?3.78)?g/L and (10.26?4.37)?g/L respectively .The patients with diabetic microangiopathy had higher serum leptin levels than in the diabetic patients without microangiopathy( t =2.18, P
ABSTRACT
Objective To study the expression and significance of CEA in occult micrometastasis ofcolorectal carcinoma. Methods 287 cases without metastatic lymph nodes were observed in 54 cases ofcolorectal carcinoma by immunohistochemical (LSAB) method. Results 15 cases of lymph nodes werefound with occult micrometastasis in 8 patients. All micrometastasis was positive in detection of CEA.Conclusion Detection of CEA was conducive to detect micrometastasis of lymphnode. It is significant forDukes staging,prognostic determination and treatment.
ABSTRACT
0.05). As compared with Qingkailing group, the body temperature at the 5th day of treatment and WBC at the 3rd day of treatment were significantly decreased (P