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The present study aimed to investigate the expression and roles of interleukin (IL)-17 and tumor necrosis factor (TNF)-α in intervertebral disc degeneration (IDD) and to identify the association between the effects of IL-17 and TNF-α in IDD. This may increase understanding of the pathogenic mechanism underlying IDD, and aid the development of alternative therapies. The experimental group consisted of 40 samples of nucleus pulposus tissue obtained from the intervertebral discs (IVDs) of patients with IDD by surgical intervention, and was further divided into an annulus fibrosus disrupted group, comprising 18 patients in which the external annulus was ruptured, and an annulus fibrosus intact group comprising 22 patients. The control group consisted of 20 samples of nucleus pulposus tissue from the IVDs of patients with traumatic lumbar disc fractures. The mRNA and protein expression levels of IL-17 and TNF-α in the 50 tissue samples were detected by semi-quantitative reverse transcription polymerase chain reaction and immunohistochemical staining, respectively, and the results were statistically analyzed. The IL-17 and TNF-α protein and mRNA expression levels in the annulus fibrosus disrupted and annulus fibrosus intact groups were both higher compared with those in the control group. In addition, the expression levels of IL-17 and TNF-α in the annulus fibrosus disrupted group were significantly higher compared with those in the annulus fibrosus intact group (P<0.01). A positive correlation was identified between the mRNA and protein expression levels of IL-17 and TNF-α in the experimental group (r=0.957, P<0.01). IL-17 and TNF-α may therefore be involved in the progression of human IDD, and may have synergistic effects in the development of IDD. [ABSTRACT FROM AUTHOR]

The aim of the present study was to monitor long term antithyroid drug treatments and to identify prognostic factors for Graves' disease (GD). A total of 306 patients with GD who were referred to the Endocrinology Clinic at Weifang People's Hospital (Weifang, China) between August 2005 and June 2009 and treated with methimazole were included in the present study. Following treatment, patients were divided into non-remission, including recurrence and constant treatment subgroups, and remission groups. Various prognosis factors were analyzed and compared, including: Patient age, gender, size of thyroid prior to and following treatment, thyroid hormone levels, disease relapse, hypothyroidism and drug side-effects, and states of thyrotropin suppression were observed at 3, 6 and 12 months post-treatment. Sixty-five patients (21.2%) were male, and 241 patients (78.8%) were female. The mean age was 42±11 years, and the follow-up was 31.5±6.8 months. Following long-term treatment, 141 patients (46%) demonstrated remission of hyperthyroidism with a mean duration of 18.7±1.9 months. The average age at diagnosis was 45.6±10.3 years in the remission group, as compared with 36.4±8.8 years in the non-remission group (t=3.152; P=0.002). Free thyroxine (FT)3 levels were demonstrated to be 25.2±8.9 and 18.7±9.4 pmol/l in the non-remission and remission groups, respectively (t=3.326, P=0.001). The FT3/FT4 ratio and thyrotrophin receptor antibody (TRAb) levels were both significantly higher in the non-remission group (t=3.331, 3.389, P=0.001), as compared with the remission group. Logistic regression analysis demonstrated that elevated thyroid size, FT3/FT4 ratio and TRAb at diagnosis were associated with poor outcomes. The ratio of continued thyrotropin suppression in the recurrent subgroup was significantly increased, as compared with the remission group (P=0.001), as thyroid function reached euthyroid state at 3, 6 and 12 months post-treatment. Patients with GD exhibiting large thyroids, high pre-mediation TRAb levels and elevated FT3/FT4 ratios responded less markedly to antithyroid drug treatments, as compared with patients not exhibiting these prognostic factors. Furthermore, patients with large thyroids, post-medication ophthalmopathy and continued thyrotropin suppression demonstrated higher rates of recurrence. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by chronic inflammation affecting target tissues including the joints, bones, and synovial membrane. However, the etiology and pathogenesis of RA remains to be determined, and investigations into the treatment of RA are imperative. Vitamin D (Vit D) was previously found to be associated with the activity of RA and exerts therapeutic benefits. The aim of the present study was to investigate the effect of Vit D on the recurrence rate of RA. A total of 377 patients with RA at remission stage were divided into the normal Vit D group and the Vit D-deficient group according to their Vit D levels at baseline. The patients in the Vit D-deficient group were further randomly allocated to receive treatment with or without Vit D. The patients were followed up for 24 months, and the visual analogue scale, as well as the number of pain and swelling joints were recorded every 2-3 months. In addition, C-reactive protein and the blood sedimentation rate were measured every 2-3 months to assess the recurrence of RA based on disease activity score 28 (DAS28). The recurrence rate of RA was 16.7, 19.0 and 29.5% for the normal Vit D group (n=168), Vit D treatment subgroup (n=84), and non-Vit D treatment subgroup (n=88), respectively. The recurrence rate of the normal Vit D group was lower, compared to the non-Vit D treatment subgroup, and the difference was statistically significant. However, the difference was not statistically significant between the Vit D treatment subgroup and non-Vit D treatment subgroup. In conclusion, a decreased level of Vit D is a risk factor for the recurrence of RA. [ABSTRACT FROM AUTHOR]

Ischemic postconditioning (IPoC) involves a series of brief rapid intermittent ischemic episodes applied at the onset of reperfusion in the previously ischemic tissue or organ. Previous studies have demonstrated that IPoC attenuates tissue damage induced by ischemia and reperfusion (I/R) injury. The aim of the present study was to investigate whether IPoC has a beneficial effect on inflammation in a rat model of renal I/R injury. Wistar rats were subjected to 45 min of ischemia followed by 24, 72 or 120 h of reperfusion (I/R group). In the IPoC group, rats subjected to I/R were treated with six cycles of 10 sec reperfusion followed by a 10-sec ischemic episode. Blood samples were collected for the determination of blood urea nitrogen (BUN) and creatinine (Cr) levels. Furthermore, histological examination and immunohistochemical staining for the localization of nuclear factor-ΚB (NF-ΚB) were performed. In addition, quantitative polymerase chain reaction (qPCR) analysis was used to determine the expression levels of intercellular adhesion molecule-1 (ICAM-1), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), while western blot analysis was used to detect the protein expression levels of NF- ΚB. The results indicated that the BUN and Cr levels increased significantly in the I/R group, while the IPoC rats showed evidently reduced renal damage. Immunohistochemical analysis revealed that the expression levels of NF-ΚB were decreased by IPoC. In addition, the qPCR results revealed that IPoC significantly inhibited the increased mRNA expression levels of ICAM-1, IL-6 and TNF-α, induced by I/R injury. Western blot analysis indicated that the expression levels of NF-ΚB were upregulated in the I/R group, while IPoC was shown to inhibit the expression. In conclusion, IPoC was demonstrated to exhibit potent anti-inflammatory properties against renal I/R injury. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is characterized by progressive and inexorable β-cell dysfunction, leading to insulin deficiency. Novel strategies to preserve the remaining β-cells and restore β-cell function for the treatment of diabetes are urgently required. Mesenchymal stem cells (MSCs) have been exploited in a variety of clinical trials aimed at reducing the burden of immune-mediated disease. The aim of the present clinical trial was to assess the safety and efficacy of umbilical cord-derived MSC (UCMSC) transplantation for patients with T2D. The safety and efficacy of UCMSC application were evaluated in six patients with T2D during a minimum of a 24-month follow-up period. Following transplantation, the levels of fasting C-peptide, the peak value and the area under the C-peptide release curve increased significantly within one month and remained high during the follow-up period (P<0.05). Three of the six patients became insulin free for varying lengths of time between 25 and 43 months, while the additional three patients continued to require insulin injections, although with a reduced insulin requirement. Fasting plasma glucose and 2-h postprandial blood glucose levels were relatively stable in all the patients following transplantation. There was no immediate or delayed toxicity associated with the cell administration within the follow-up period. Therefore, the results indicated that transplantation of allogeneic UCMSCs may be an approach to improve islet function in patients with T2D. There were no safety issues observed during infusion and the long-term monitoring period. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of extract of Panax quinquefolius and Corydalis tuber (EPC) on platelet activation and the hypercoagulable state in rats with acute myocardial infarction (AMI). The MI model in Wistar rats was induced by coronary artery ligation. Sham surgery was performed as a control. The surviving rats that underwent MI surgery were divided into control (administered normal saline), metoprolol (9 mg/kg) and low-, moderate- and high-dose EPC groups (0.54, 1.08 g/kg and 2.16 g/kg, respectively). Saline, metoprolol and EPC were administered by gastrogavage for two consecutive weeks. The morphological changes of the myocardium were assessed by hematoxylin and eosin and nitroblue tetrazolium staining. Serum von Willebrand factor (vWF), D-dimer (DD), platelet membrane glycoproteins IIb-IIIa (GPIIb-IIIa) and CD62P levels were assessed using enzyme-linked immunosorbent assay. EPC attenuated the pathological changes of the myocardium. High-dose EPC decreased the serum concentration of vWF when compared with control group. Moderate and high doses of EPC decreased the DD and GPIIb-IIIa levels, and the CD62P level was gradually decreased with EPC dose escalation. The results therefore demonstrated that EPC protects the myocardium by inhibiting platelet activation and improving the hypercoagulable state in a rat model of AMI. [ABSTRACT FROM AUTHOR]

Picroside II possesses a wide range of pharmacological effects and has been demonstrated to ameliorate cerebral ischemia and reperfusion (I/R) injury. However, its effects on renal I/R injury remain unclear. In the present study, the role of picroside II in attenuating oxidative stress and the inflammatory response in a rat model of renal I/R injury was investigated. Sprague Dawley rats were subjected to 45 min of ischemia followed by 24 h of reperfusion. Prior to reperfusion, the rats were treated with picroside II or an equal volume of phosphate-buffered saline. Renal function and histological changes were compared and the relevant parameters of oxidative stress and inflammation were detected. The expression of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB; p65) were assessed by immunohistochemistry and western blotting. It was observed that renal function was significantly improved by treatment with picroside II. Morphological analysis indicated that picroside II clearly reduced tissue damage and the expression of TLR4 and NF-κB. Reverse transcription-quantitative polymerase chain reaction demonstrated that picroside II inhibited the increase of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and intercellular adhesion molecule (ICAM)-1 expression induced by I/R injury. Western blot analysis indicated that the expression levels of TLR4 and NF-κB were significantly downregulated in the picroside II group compared with those in the I/R group. These results indicate that picroside II treatment suppressed the TLR4/NF-κB signaling pathway, protecting renal tissue against I/R-induced oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]

Renal ischemia and reperfusion (I/R) injury, which commonly occurs in kidney transplantation, is the leading cause of acute kidney injury. Picroside II possesses a wide range of pharmacological effects, including anti-apoptosis effects. In the present study, the ability of picroside II to attenuate apoptosis in a rat model of renal I/R injury was investigated. Sprague-Dawley rats were subjected to 45 min of ischemia followed by 24 h of reperfusion. Prior to reperfusion, the rats were treated with picroside II or an equal volume of phosphate-buffered saline. It was observed that renal function was significantly improved by the treatment with picroside II. Morphological analysis indicated that picroside II markedly reduced tissue damage and the expression of cleaved caspase-3. Reverse transcription-quantitative polymerase chain reaction and western blotting revealed that the expression levels of Bax and poly(ADP-ribose) polymerase-1 (PARP-1) were upregulated in the I/R group, whereas those of Bcl-2 were downregulated. However, the treatment with picroside II inhibited these changes induced by renal I/R injury. In conclusion, picroside II has potent anti-apoptotic activity against renal I/R injury. [ABSTRACT FROM AUTHOR]

Ischemia and reperfusion injury (IRI) is a crucial contributor to the development of renal fibrosis. Ozone has been proposed as a novel medical therapy for various conditions, including organ IRI. The aim of this study was to investigate whether ozone oxidative preconditioning (OzoneOP) has a beneficial effect in preventing the development of renal fibrosis following IRI. Sprague Dawley rats were subjected to 45 min of ischemia followed by 8 weeks of reperfusion. Prior to surgery, rats in the OzoneOP group were treated with ozone and those in the IRI and Sham groups were untreated. Blood samples were collected for the detection of blood urea nitrogen (BUN) and creatinine (Cr) levels. To assess tissue fibrosis, Masson's trichrome staining was performed. Immunohistochemistry was also performed to determine the localization of α-smooth muscle actin (α-SMA). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to analyze the expression of transforming growth factor (TGF)-β1, α-SMA and Smad7. The levels of BUN and Cr did not significantly differ between groups. Rats pretreated with ozone showed markedly less interstitial fibrosis than untreated rats following IRI. In addition, immunohistochemistry revealed that α-SMA expression was attenuated in the OzoneOP group compared with the IRI group. RT-qPCR and western blot analysis showed that OzoneOP inhibited the IRI-induced increases in α-SMA and TGF-β1 expression levels, and that the IRI-induced reduction in the expression of Smad7 was inhibited in the OzoneOP group. The results indicate that OzoneOP has beneficial effects on ischemic renal fibrosis. OzoneOP may exert its protective effects by a mechanism involving modulation of the TGF-β1/Smad7 pathway. [ABSTRACT FROM AUTHOR]

Etanercept (ETN) has been widely applied in the treatment of ankylosing spondylitis (AS). As the use of ETN has increased, associated adverse effects have been reported frequently. Previous meta-analyses have focused on comparing the differences in clinical outcomes between ETN and placebo (PBO). The present meta-analysis evaluated randomised controlled trials (RCTs) to compare the effects of ETN and a PBO or sulfasalazine (SSZ) in patients with AS. The study population characteristics and the main results, including the Assessment in AS 20% response (ASAS 20), the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI), were extracted. The pooled odds ratios (ORs) or weighted mean differences (MDs) were calculated using a fixed or random effects model. Fifteen randomised controlled trials (RCTs) involving 2,194 subjects were included. Compared with a PBO, ETN significantly improved the ASAS 20 [P<0.00001; OR, 8.25; 95% confidence interval (CI), 5.92-11.50], BASDAI (P<0.00001; MD, -18.81; 95% CI, -24.47 to -13.15) and BASFI (P<0.00001; standard MD, -0.68; 95% CI, -0.85 to -0.50). In comparison with SSZ, ETN significantly decreased the BASDAI (P<0.00001; MD, -2.40; 95% CI, -2.89 to -1.90) and C-reactive protein (CRP) levels (P<0.0001; MD, -8.01; 95% CI, -11.73 to -4.29). The most common adverse effect of ETN was an injection site reaction. This meta-analysis shows that ETN monotherapy is effective in improving physical function and reducing disease activity in patients with AS. Compared with SSZ, ETN markedly decreased the BASDAI and CRP levels. However, the efficacy of ETN in treating AS requires further evaluation by more RCTs in a larger population of patients prior to recommending ETN as a substitute for synthetic disease-modifying antirheumatic drug (DMARD) monotherapy, or combinations of synthetic DMARDs. [ABSTRACT FROM AUTHOR]