[Show abstract][Hide abstract] ABSTRACT: : In previous studies, both 17β-estradiol (E2) and resveratrol (RES) were reported to protect intervertebral disc cells against aberrant apoptosis. Given that E2 has a better anti-apoptotic effect with more cancer risk and RES has an anti-apoptotic effect with less cancer risk, the combined use of E2 with RES is promising in developing clinical therapies to treat apoptosis-related diseases such as intervertebral disc degeneration in the future.
: The purpose of this study was to explore the combined effect of E2 with RES on rat nucleus pulposus cells and the underlying mechanisms.
: TUNEL assay and FACS analysis were used to determine apoptotic incidence of nucleus pulposus cells. MTS assay was used to determine cell viability, and cellular binding assay was used to determine cell-ECM (extracellular matrix) ability. Real-time quantitative RT-PCR was to determine mRNA level of target genes. And Western blot was used to determine the protein level.
: Both E2 and RES decreased apoptotic incidence when used singly; interestingly, they decreased apoptosis more efficiently when used combinedly. Meanwhile, E2 and RES combined together against the decrease of cell viability and binding ability resulting from IL-1β cytotoxicity. As well, activated caspase-3 was suppressed by the combined effect. Furthermore, IL-1β downregulated expression level of type II collagen and aggrecan (standing for anabolism), while upregulated MMP-3 and MMP-13 (standing for catabolism). However, the combined use of E2 with RES effectively abolished the above negative effects caused by IL-1β, better than either single use. Finally, it turned out to be that E2 and RES combined together against apoptosis via the activation of PI3K/Akt/caspase-3 pathway.
: This study presented that IL-1β induced aberrant apoptosis, which was efficiently resisted by the combined use of E2 with RES via PI3K/Akt/caspase-3 pathway.
[Show abstract][Hide abstract] ABSTRACT: This cross-sectional study was designed to obtain the current prevalence of deep vein thrombosis (DVT) and analyze related risk factors in patients undergoing lumbar interbody fusion.Medical record data were collected from Department of Spinal Surgery, The Third Hospital of Hebei Medical University, between July 2014 and March 2015. Both univariate analysis and binary logistic regression analysis were performed to determine risk factors for DVT.A total of 995 patients were admitted into this study, including 484 men and 511 women, aged from 14 to 89 years old (median 50, IQR 19). The detection rate of lower limb DVT by ultrasonography was 22.4% (223/995) in patients undergoing lumbar interbody fusion. Notably, average VAS (visual analog scale) score in the first 3 days after surgery in the DVT group was more than that in the non-DVT group (Z = -21.69, P < 0.001). The logistic regression model was established as logit P = -13.257 + 0.056*X1 - 0.243*X8 + 2.085*X10 + 0.001*X12, (X1 = age; X8 = HDL; X10 = VAS; X12 = blood transfusion; x = 677.763, P < 0.001).In conclusion, advanced age, high postoperative VAS scores, and blood transfusion were risk factors for postoperative lower limb DVT. As well, the logistic regression model may contribute to an early evaluation postoperatively to ascertain the risk of lower limb DVT in patients undergoing lumbar interbody fusion surgery.
[Show abstract][Hide abstract] ABSTRACT: Tribbles 3, whose expression is up-regulated by insulin resistance, was confirmed to be involved in diabetic cardiomyopathy in our previous study. However, it is not known whether Tribbles 3 has a role on conduit arteries such as the aorta in diabetes. Type 2 diabetic rat model was induced by high-fat diet and low-dose streptozotocin. We evaluated the characteristics of diabetic rats by serial ultrasonography and histopathologic analyses of aortic wall architecture. Diabetic rats displayed increased aortic medial thickness, excessive collagen deposition, diminished elastic fibres and reduced vascular compliance together with Tribbles 3 overexpression. To further investigate the role of Tribbles 3 in aortic remodelling, we used Tribbles 3 gene silencing in vivo 12 weeks after onset of diabetes. Silence of Tribbles 3 significantly reversed pathological aortic remodelling without blood pressure modification. In Tribbles 3-small interfering RNA group, medial thickness and perivascular fibrosis were markedly decreased; moreover, there were prominent reductions in collagen content and collagen/elastin ratio, resulting in an improved arterial compliance. Additionally, with Tribbles 3 silencing, the diminished phosphorylation of PI3K/Akt was restored, and increased activation of MKK4/JNK was decreased. Silence of Tribbles 3 is potent in mediating reversal of aortic remodelling, implicating that Tribbles 3 is proposed to be a potential therapeutic target for vascular complication in diabetes.
No preview · Article · Sep 2015 · Diabetes & Vascular Disease Research
[Show abstract][Hide abstract] ABSTRACT: Background:
Vascular remodeling is an important feature of diabetic macrovascular complications. The prostaglandin F2α receptor (FP), the expression of which is upregulated by insulin resistance and diabetes, is reportedly involved in myocardial remodeling. In this study, we aimed to investigate whether the FP receptor is implicated in diabetes-induced vascular remodeling.
A type 2 diabetic rat model was induced through a high-fat diet and low-dose streptozotocin (STZ). Thirty-two rats were randomized into four groups: control, diabetes, diabetes treated with empty virus and diabetes treated with FP receptor-shRNA. Then, we evaluated the metabolic index, FP receptor expression and vascular remodeling. We used FP receptor gene silencing in vivo to investigate the role that the FP receptor plays in the pathophysiologic features of vascular remodeling.
Diabetic rats displayed increased levels of blood glucose, cholesterol, and triglycerides, as well as severe insulin resistance and FP receptor overexpression. In addition, increased medial thickness, excessive collagen deposition and diminished elastic fibers were observed in the diabetic rats, resulting in vascular remodeling. In the FP receptor-shRNA group, the medial thickness, collagen content, elastin/collagen ratio, and collagen I/collagen III content ratio were markedly decreased. Additionally, with FP receptor gene silencing, the JNK phosphorylation level was markedly decreased.
Silencing of the FP receptor exerts a protective effect on diabetes-induced vascular remodeling, thereby suggesting a new therapeutic target for vascular remodeling in diabetes.
No preview · Article · Sep 2015 · Experimental and Molecular Pathology
[Show abstract][Hide abstract] ABSTRACT: Deep vein thrombosis (DVT) is common seen in patients undergoing spine surgery. However, its prevalence and associated risk factors have not been well understood yet. This retrospective case-cohort study was designed to investigate risk factors for postoperative DVT using retrospectively collected data from department of spine surgery between 07/2013 and 07/2014. Univariate analysis and binary logistic regression analysis were used to determine risk factors for DVT. A total of 861 patients were admitted into DVT-associated analyses, including 410 males and 451 females, aged from 15 to 87 years old (median 54, IQR 18). Of them, 147 cases (17%) sustained postoperative DVT. DVT incidence was 15.9% in patients undergoing lumbar interbody fusion, 13.5% in patients treated by low-molecular-weight heparin (LMWH), while only 8.1% in patients without LMWH. However, it revealed no significant difference between LMWH group and non-LMWH group (χ(2) = 1.933, p = 0.164). Logistic regression equation was logit P = -4.09 + 0.05*X1 - 0.55*X2 + 0.41*X3 + 1.41*X7, (X1 = age; X2 = regions; X3 = hypertension; X7 = D-dimer). In this study, LMWH prophylaxis after spine surgery proved ineffective. Advanced age, D-dimer and hypertension have proved to be the risk factors for postoperative DVT in patients undergoing spine surgery.
No preview · Article · Jul 2015 · Scientific Reports
[Show abstract][Hide abstract] ABSTRACT: Recent studies suggested an increased risk of fractures with interaction between bisphosphonates (BPs) and proton pump inhibitors (PPIs). We performed a meta-analysis of fractures between patients taking BPs/PPIs and those taking BPs only.
We conducted a PubMed database and Ovid database search, as well as Cochrane Library search (up to July 2014) for studies assessing the association between fractures and BPs or/and PPIs. We performed random effects meta-analysis of odds ratios (OR) according to fracture type and conducted subgroup analyses by race and BP subtypes. Heterogeneity was assessed using Q statistics and I(2) statistic.
After study selection, 4 unique studies (5 comparisons) including 57259 patients were available for this meta-analysis. Pooled analysis of overall fracture risk of BP+PPI group versus BP group showed a significant increase in risk of fractures (OR = 1.52, P = 0.025), with substantial heterogeneity. However, heterogeneity was drastically reduced in subgroup of Asian (I(2) = 24% and P = 0.251), and fracture risk showed a significant increase (OR = 1.75, P = 0.026). In contrast, heterogeneity was little eliminated in subgroup of European, and fracture risk was no statistical difference (OR = 1.42, P = 0.068). Three studies including 4 comparisons reported on spine fracture were included in the pooled analysis demonstrating an increased spine fracture risk associated with BP/PPI interaction (OR = 1.60, 95% CI 1.13-2.26, P = 0.008, I(2) = 58.6%).
This meta-analysis suggests that there is an interaction associated with increased fracture risk (particularly for spine and Asian race) between BP and PPI use. Clinicians should carefully evaluate such risk factors for osteoporosis in patients taking BPs, before routinely prescribing PPIs, and make a careful judgment as to whether PPIs may be safe for patients at high risk of fractures.
No preview · Article · Jul 2015 · International Journal of Clinical and Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: Severe thoracolumbar kyphotic deformity caused by old compressive vertebrae fracture remains a big challenge for spine surgeons. When symptoms related to significant deformities cannot be adequately managed conservatively, posterior vertebral column resection (PVCR) is required, but with long operating time and severe blood loss. We develop a UPVCR technique, which is done through a unilateral approach instead of a bilateral approach, vertebral body resection advancing to cross the midline in an abrasive way from an extreme oblique orientation enable the resection of most contralateral vertebral body. In the present study, the effects of UPVCR for severe thoracolumbar kyphotic deformity were investigated. We did find that satisfactory correction of sagittal deformity, functional improvement and pain relief can be achieved by UPVCR, and it has the advantage of shortening surgery time, reducing blood loss and incidence of nerve root impingement over PVCR.
No preview · Article · May 2015 · International Journal of Clinical and Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: Upper lumbar disc herniation (ULDH) is easy to be misdiagnosed due to its special anatomical and atypical clinical features. Few studies have identified the relationship between ULDH and adjacent wedge-shaped vertebrae (WSV).
WSV may have some indicative relations withULDH.
Between January 2003 and October 2013, 47 patients (27 males and 20 females; mean age, 41.2 years) with single-level ULDH (as study group) and 47 sex- and age-matched healthy volunteers (as control group) were studied by radiograph. The two groups were compared with respect to age, sexual proportion, body mass index (BMI), kyphotic angle, and the proportion of WSV. Also, correlative analyses were conducted in the study group to investigate the relation between the kyphotic angle of target vertebrae and other factors including age, BMI, Cobb angle, JOA score and bone mineral density (BMD).
The average kyphotic angle in the study group was 11° (4°-22°), while the average kyphotic angle in the control group was 2° (0°-7°). Obviously, the mean kyphotic angle in the study group was statistically larger than that in the control group (t=13.797, P<0.001). The proportion of WSV in the study group was significantly larger than that in the control group (x(2)=36.380, P<0.0001). The correlations between kyphotic angles and other items (i.e., age, BMI, BMD, Cobb angle and JOA score) in the study group and the control group were low or uncorrelated.
WSV are indicatively associated with adjacent ULDH. Thus, ULDH should be alerted when WSV are first found in radiograph and accompanied by clinical symptoms.
No preview · Article · Jan 2015 · International Journal of Clinical and Experimental Medicine
[Show abstract][Hide abstract] ABSTRACT: In our previous study, 17β-estradiol was proved to protect rat annulus fibrosus cells against apoptosis induced by interleukin-1β (IL-1β). However, whether 17β-estradiol has protective effect on rat nucleus pulposus cells remains unclear. The purpose of this study was to further explore the effects of 17β-estradiol on rat nucleus pulposus cells based on IL-1β-induced apoptosis. TUNEL assay and Annexin V/PI double staining were used to detect apoptosis and revealed that IL-1β induced notable apoptosis, which was reversed by 17β-estradiol. Meanwhile, cell viability and binding ability were decreased by IL-1β, but activated caspase-3 was increased. However, all of the detected effects of IL-1β were eliminated by 17β-estradiol. Furthermore, real-time quantitative RT-PCR was used to further find that IL-1β downregulated expression level of type II collagen, aggrecan, tissue inhibitor of matrix metalloproteinase (TIMP)-1, while upregulated matrix metalloproteinase (MMP)-3, MMP-13 and Bcl-2, which was further confirmed by western blot. Finally, 17β-estradiol was proved to abolish the above negative effects of IL-1β. In summary, this work presented that IL-1β maybe induced apoptosis of rat nucleus pulposus cells, which was resisted by 17β-estradiol by down-regulating MMP-3 and MMP-13 via a mitochondrial pathway. This research provides a novel insight into the anti-apoptotic effect of 17β-estradiol on IL-1β-induced cytotoxicity, and may potentially lead to a better understanding of the clinical effects of 17β-estradiol, especially in terms of intervertebral disc degeneration.
[Show abstract][Hide abstract] ABSTRACT: Background
Fluoroquinolones are in wide clinical use as safe and effective antibiotics. Articular cartilage, tendons, and epiphyseal growth plates have been recognized as targets of fluoroquinolone-induced connective tissue toxicity. However, the effects of fluoroquinolones on annulus fibrosus (AF) cells are still unknown.
The main objective of this study was to investigate the effects of levofloxacin, a typical fluoroquinolone antibiotic drug, on rat AF cells in vitro. Rat annulus fibrosus (RAF) cells were treated with levofloxacin at different concentrations (0, 10, 20, 30, 40, 60, 80, and 90 μg/ml) and were assessed to determine the possible cytotoxic effects of levofloxacin. Inverted phase-contrast microscopy was used to accomplish the morphological observation of apoptosis of treated cells. Western blot and real-time quantitative RT-PCR (qPCR) was used to explore the expression of active caspase-3 and MMP-3. Flow cytometry was used to measure the apoptotic incidences.
Our study showed that levofloxacin, with concentrations at 30, 60, and 90 μg/ml, induced dose-dependent RAF cell apoptosis and higher expression of caspase-3 and MMP-3. More apoptotic cells were observed by inverted phase-contrast microscopy. Moreover, levofloxacin increased the activity of caspase-3, and it also reduced cell viability with different concentrations ranging from 10 to 80 μg/ml.
Our study results suggest that levofloxacin has cytotoxic effects on RAF cells, characterized by enhancing apoptosis and reducing cell viability, and indicate a potential toxic effect of fluoroquinolones on RAF cells.
Preview · Article · Nov 2014 · Medical science monitor: international medical journal of experimental and clinical research
[Show abstract][Hide abstract] ABSTRACT: Abstract Levofloxacin, a fluoroquinolone, is a widely-used and effective antibiotic. However, various adverse side effects are associated with levofloxacin. The purpose of this study was to further explore the effects of levofloxacin on rat nucleus pulposus cells. Inverted phase-contrast microscopy, flow cytometry, and caspase-3 activity assays were used, and revealed that serum deprivation induced apoptosis, which was markedly increased by levofloxacin in a dose-dependent manner. Simultaneously, levofloxacin decreased cell binding to type II collagen. Thus, levofloxacin-induced apoptosis exhibits characteristics of anoikis, the process by which cell death is triggered by separation from the extracellular matrix, which contains type II collagen. Furthermore, real-time quantitative RT-PCR was used to further confirm that levofloxacin downregulates type II collagen expression in a dose-dependent manner. At last, western blot was used to find that levofloxacin increased the ratio of Bax/Bcl-2 and active caspase-3 in a dose-dependent manner. Levofloxacin therefore increases the effects of serum deprivation on anoikis by downregulating type II collagen in rat nucleus pulposus cells in vitro via Bax/Bcl-2/caspase-3 pathway. This research provides a novel insight into the mechanisms of levofloxacin-induced toxicity, and may potentially lead to a better understanding of the clinical effects of levofloxacin, especially in terms of intervertebral disc degeneration.
No preview · Article · Sep 2014 · Toxicology mechanisms and methods
[Show abstract][Hide abstract] ABSTRACT: Background and objective:
Cervical spondylotic amyotrophy (CSA) is a relatively rare disorder. This study was conducted to elucidate the prognosis of proximal-type CSA after anterior decompressive surgery by evaluating clinical factors and imaging findings.
Anterior decompressive surgery was performed in 40 patients with proximal-type CSA between March 2000 and December 2011. Patients were classified into 2 categories based on axial T2-weighted magnetic resonance imaging (MRI) findings: "nerve root compression (NRC)", with nerve root compressed at the intervertebral foramen, and "spinal cord compression (SCC)" with spinal cord compressed at the medial or paramedial site of spinal canal. Manual muscle testing (MMT) was used to evaluate the surgical effect. Scapular, deltoid, and biceps brachii muscles of the affected side were tested and the sum scores were calculated. Clinical factors and imaging findings, such as age, duration of disease, preoperative MMT grade, number of affected levels and signal intensity changes of spinal cord, were collected to analyze prognostic factors.
After anterior decompressive surgery, 30 patients (75%) showed an improvement. NRC was observed in 6 patients and SCC in the rest 34 patients based on MRI findings. All patients (100%) with NRC had an improvement, while only 24 patients (70.6%) with SCC improved. In patients with SCC, there was a significant difference in duration of disease between patients who had an improvement and those who had not (P< 0.01).
Anterior decompressive surgery is effective in the treatment of most patients with CSA. NRC on MRI may indicate a good surgical outcome. In patients with SCC, a long duration of disease is a risk factor for poor prognosis.
No preview · Article · Aug 2014 · Journal of Back and Musculoskeletal Rehabilitation
[Show abstract][Hide abstract] ABSTRACT: The causal relationship between vertebroplasty and new-onset vertebral fractures remains unproved. We undertook a systematic review and meta-analysis of randomized controlled trials to assess whether vertebroplasty increases the incidence of new vertebral fractures and adjacent vertebral fractures. A systematic literature search of PubMed, EMBASE and Cochrane Library databases up to April 2013 was conducted. Eligible studies were randomized controlled trials of osteoporotic vertebral fracture patients receiving vertebroplasty. Risk ratios (RR) and 95% confidence intervals (CI) were calculated and heterogeneity was assessed with both the chi-squared test and the I(2) test. Four studies with a total of 454 patients met the inclusion criteria. All four studies described the incidence of new vertebral fractures and three studies described adjacent vertebral fractures. The pooled results revealed that vertebroplasty was not associated with a significant increase in the incidence of new vertebral fractures (RR 1.12, 95% CI 0.75-1.67; p=0.59) or adjacent vertebral fractures (RR 2.31, 95% CI 0.36-15.06; p=0.38). Based on available evidence, it cannot be concluded that vertebroplasty can significantly increase the postoperative rate of new vertebral fractures and adjacent vertebral fractures. However, due to some limitations, the results of this meta-analysis should be cautiously accepted, but further studies are needed.
No preview · Article · Jun 2014 · Journal of Clinical Neuroscience
[Show abstract][Hide abstract] ABSTRACT: Study Design: A retrospective study. Objective: This study was aimed to analyze the changes in spinopelvic parameters after surgical correction of degenerative spondylolisthesis and to determine which deformity is most responsible for changes in sagittal spinopelvic alignment. Summary of Background Data: The basic deformities of degenerative spondylolisthesis are forward slippage of the vertebral body, segmental kyphotic angle, and loss of disc height. Correction of those deformities during surgery will subsequently affect the spinopelvic parameters. A few studies have reported the changes of sagittal spinopelvic alignment after surgical treatment of isthmic spondylolisthesis. However, there appears to be relatively little information regarding degenerative spondylolisthesis. Methods: Fifty-three patients with L4-L5 degenerative spondylolisthesis were included. All patients underwent posterior lumbar interbody fusion and posterior instrumentation. Back pain, as the clinical outcome, was evaluated by visual analogue scale (VAS). The pre- and postoperative spinopelvic parameters, including sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL), and L1 axis S1 distance (LASD) were measured, and then the correlations between spinopelvic parameters and local deformity parameters such as slip degree (SD), slip angle (SA), and height of the intervertebral disc (HOD) were evaluated. Results: After surgical correction of local deformity, all spinopelvic parameters changed subsequently: PT and LASD had a decrease, SS and LL had an increase. VAS score decreased from 6.1+/-2.3 before surgery to 2.4+/-1.7 at the final follow-up assessment. Patients with VAS score changes >=3 showed significantly higher SS and LL, and lower PT compared with those with VAS score changes <3. Among deformity parameters, restoration of the SA revealed significant correlation with improvement of LL (r=0.32, P=0.02), increase of SS (r=0.29, P=0.03), and decrease of PT (r=-0.29, P=0.03). Conclusions: Surgical correction of degenerative spondylolisthesis with posterior lumbar interbody fusion and posterior instrumentation resulted in relief of back pain, which may be associated with improvement of sagittal spinopelvic alignment. Surgeons should consider deformity parameters, especially the SA, in the surgical treatment of degenerative spondylolisthesis.
No preview · Article · Jun 2014 · Journal of Spinal Disorders & Techniques
[Show abstract][Hide abstract] ABSTRACT: Prostaglandin F2α-F-prostanoid (PGF2α-FP) receptor is closely related to insulin resistance, which plays a causal role in the pathogenesis of diabetic cardiomyopathy (DCM). We sought to reveal whether PGF2α-FP receptor plays an important part in modulating DCM and the mechanisms involved. We established the type 2 diabetes rat model by high-fat diet and low-dose streptozotocin (STZ) and then evaluated its characteristics by metabolite tests, Western blot analysis for FP-receptor expression, histopathologic analyses of cardiomyocyte density and fibrosis area. Next, we used gene silencing to investigate the role of FP receptor in the pathophysiologic features of DCM. Our study showed elevated cholesterol, triglyceride, glucose, and insulin levels, severe insulin resistance, and FP-receptor overexpression in diabetic rats. The collagen volume fraction (CVF) and perivascular collagen area/luminal area (PVCA/LA) were higher in the diabetic group than the control group (CVF% 10.99 ± 0.99 vs 1.59 ± 0.18, P < 0.05; PVCA/LA% 17.07 ± 2.61 vs 2.86 ± 0.69, P < 0.05). We found that the silencing of FP receptor decreased cholesterol, triglyceride, glucose, and insulin levels and ameliorated insulin resistance. The CVF and PVCF/LA were significantly downregulated in FP-receptor short hairpin RNA (shRNA) treatment group (FP-receptor shRNA group vs vehicle group: CVF% 5.59 ± 0.92 vs 10.97 ± 1.33, P < 0.05, PVCA/LA% 4.74 ± 1.57 vs 14.79 ± 2.22, P < 0.05; FP-receptor shRNA + PGF2α group vs vehicle group : CVF% 5.19 ± 0.79 vs 10.97 ± 1.33, P < 0.05, PVCA/LA% 5.96 ± 1.15 vs 14.79 ± 2.22, P < 0.05, respectively). Furthermore, with FP-receptor gene silencing, the activated protein kinase C (PKC) and Rho kinase were significantly decreased, and the blunted phosphorylation of Akt was restored. FP-receptor gene silencing may exert a protective effect on DCM by improving myocardial fibrosis, suggesting a new therapeutic approach for human DCM.
FP-receptor gene silencing improves glucose tolerance and insulin resistance in type 2 diabetes (T2D). FP-receptor gene silencing modulates the activities of PKC/Rho and Akt signaling pathways in T2D. FP-receptor gene silencing decreases collagen expression and ameliorates myocardial fibrosis in T2D. FP-receptor gene silencing protects from diabetic cardiomyopathy in T2D.
No preview · Article · Feb 2014 · Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Our research aims to evaluate the function of the STAMP2 gene, an important trigger in insulin resistance (IR), and explore its role in macrophage apoptosis in diabetic atherosclerotic vulnerable plaques. The characteristics of diabetic mice were measured by serial metabolite and pathology tests. The level of STAMP2 was measured by RT-PCR and Western blot. The plaque area, lipid and collagen content of brachiocephalic artery plaques were measured by histopathological analyses, and the macrophage apoptosis was measured by TUNEL. Correlation of STAMP2/Akt signaling pathway and macrophage apoptosis was validated by Ad-STAMP2 transfection and STAMP2 siRNA inhibition. The diabetic mice showed typical features of IR, hyperglycaemia. Overexpression of STAMP2 ameliorated IR and decreased serum glucose level. In brachiocephalic lesions, lipid content, macrophage quantity and the vulnerability index were significantly decreased by overexpression of STAMP2. Moreover, the numbers of apoptotic cells and macrophages in lesions were both significantly decreased. In vitro, both mRNA and protein expressions of STAMP2 were increased under high glucose treatment. P-Akt was highly expressed and caspase-3 was decreased after overexpression of STAMP2. However, expression of p-Akt protein was decreased and caspase-3 was increased when STAMP2 was inhibited by siRNA. STAMP2 overexpression could exert a protective effect on diabetic atherosclerosis by reducing IR and diminishing macrophage apoptosis.
Full-text · Article · Jan 2014 · Journal of Cellular and Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: Levofloxacin has been reported to have cytotoxicity to chondrocytes in vitro. And 17β-estradiol has been widely studied for its protective effects against cell apoptosis. Based on apoptotic cell model induced by levofloxacin, the purpose of this study was to explore the mechanism by which 17β-estradiol protects rat nucleus pulposus cells from apoptosis. Inverted phase-contrast microscopy, flow cytometry, and caspase-3 activity assay were used to find that levofloxacin induced marked apoptosis, which was abolished by 17β-estradiol. Interestingly, estrogen receptor antagonist, ICI182780, and functional blocking antibody to α2β1 integrin, both prohibited the effect of 17β-estradiol. Simultaneously, levofloxacin decreased cellular binding ability to type II collagen, which was also reversed by 17β-estradiol. Furthermore, western blot and real-time quantitative PCR were used to find that integrin α2β1 was responsible for estrogen-dependent anti-apoptosis, which was time-response and dose-response effect. 17β-estradiol was proved for the first time to protect rat nucleus pulposus cells against levofloxacin-induced apoptosis by upregulating integrin α2β1 signal pathway.
[Show abstract][Hide abstract] ABSTRACT: The causal relationship between vertebroplasty and new-onset vertebral fractures remains unproved. We undertook a systematic review and meta-analysis of randomized controlled trials to assess whether vertebroplasty increases the incidence of new vertebral fractures and adjacent vertebral fractures. A systematic literature search of PubMed, EMBASE and Cochrane Library databases up to April 2013 was conducted. Eligible studies were randomized controlled trials of osteoporotic vertebral fracture patients receiving vertebroplasty. Risk ratios (RR) and 95% confidence intervals (CI) were calculated and heterogeneity was assessed with both the chi-squared test and the I2 test. Four studies with a total of 454 patients met the inclusion criteria. All four studies described the incidence of new vertebral fractures and three studies described adjacent vertebral fractures. The pooled results revealed that vertebroplasty was not associated with a significant increase in the incidence of new vertebral fractures (RR 1.12, 95% CI 0.75–1.67; p = 0.59) or adjacent vertebral fractures (RR 2.31, 95% CI 0.36–15.06; p = 0.38). Based on available evidence, it cannot be concluded that vertebroplasty can significantly increase the postoperative rate of new vertebral fractures and adjacent vertebral fractures. However, due to some limitations, the results of this meta-analysis should be cautiously accepted, but further studies are needed.
[Show abstract][Hide abstract] ABSTRACT: STAMP2 is a counterregulator of inflammation and insulin resistance. The aim of this study is to investigate whether activation of STAMP2 improves insulin resistance by regulating macrophage polarization in adipose tissues. The diabetic ApoE(-/-)/LDLR(-/-) mouse model was induced by high-fat diet and low-dose streptozotocin. Samples were obtained from epididymal, subcutaneous and brown adipose tissues. Infiltration of M1/M2 macrophages and inflammatory cytokines were investigated by immunohistochemistry. We then used gene overexpression to investigate the effect of STAMP2 on macrophages infiltration and polarization and inflammatory cytokines expression. Our results showed that infiltration of macrophages, the ratio of M1/M2 macrophages and the expression of pro-inflammatory cytokines were enhanced and STAMP2 was downregulated in adipose tissues of diabetic ApoE(-/-)/LDLR(-/-) mice compared with control mice. STAMP2 gene overexpression could significantly reduce macrophages infiltration, the ratio of M1/M2 macrophages and the expression of pro-inflammatory cytokines in epididymal and brown adipose tissues, improving insulin resistance. Our results suggested that STAMP2 gene overexpression may improve insulin resistance via regulating macrophage polarization in visceral and brown adipose tissues.
[Show abstract][Hide abstract] ABSTRACT: Renal fibrosis is thought to be the common pathway in most cases of chronic kidney disease. Recently, TRIB3 was found to play an important role in progression of cardiac fibrosis in an insulin-resistant state. We investigated whether TRIB3 might participate in the pathogenesis of renal fibrosis in insulin-resistant rats.
We randomly separated 40 male Sprague-Dawley into 4 groups for treatment (n=10 each): control and high-fat diet (HFD) with TRIB3 siRNA adenovirus transfection, vehicle transfection or HFD alone. Insulin resistance markers were measured. Renal tissues were stained with hematoxylin and eosin, Masson's trichrome and periodic acid-Schiff.
Rats with HFD showed insulin resistance and TRIB3 overexpression. Upregulated TRIB3 expression could induce renal fibrosis accompanied by increased phosphorylation of extracellular signal-regulated kinase (ERK). Also, TRIB3 siRNA knockdown could ameliorate renal fibrosis, which was accompanied by decreased phosphorylation of ERK.
TRIB3 gene silencing can attenuate renal fibrosis for beneficial effect on the development of renal fibrosis in chronic kidney disease in rat.
Full-text · Article · Dec 2013 · Experimental and Molecular Pathology