[Show abstract][Hide abstract] ABSTRACT: Citrate is commonly used as an anticoagulant in hemodialysis for chronic renal failure (CRF) and for the regulation of the immune dysfunction in CRF patients. The objective of this study was to investigate the effect of citrate on the balance of T helper 17 (Th17) and regulatory T (Treg) cells in CRF. The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were significantly increased in the CRF model group compared to the control group, and were decreased in the citrate-treated groups. Citrate treatment inhibited the viability of Th17 cells while elevating the viability of Treg cells in CRF rats. Moreover, Th17-related cytokines significantly decreased while the Treg-related cytokines significantly increased with citrate treatment. Moreover, citrate had a negative influence on the deviation of Th17/Treg cells in CRF rats. Therefore, our study suggests that citrate had an anti-inflammatory effect on CRF through the modulation of the Th17/Treg balance.
[Show abstract][Hide abstract] ABSTRACT: This study was to investigate whether sorafenib can inhibit the progression of renal fibrosis and to study the possible mechanisms of this effect.
Eight-week-old rats were subjected to unilateral ureteral obstruction (UUO) and were intragastrically administered sorafenib, while control and sham groups were administered vehicle for 14 or 21 days. NRK-52E cells were treated with TGF-β1 and sorafenib for 24 or 48 hours. HE and Masson staining were used to visualize fibrosis of the renal tissue in each group. The expression of α-SMA and E-cadherin in kidney tissue and NRK-52E cells were performed using immunohistochemistry and immunofluorescence. The apoptosis rate of NRK-52E cells was determined by flow cytometry analysis. The protein levels of Smad3 and p-Smad3 in kidney tissue and NRK-52E cells were detected by western blot analysis.
HE staining demonstrated that kidney interstitial fibrosis, tubular atrophy, and inflammatory cell infiltration in the sorafenib-treated-UUO groups were significantly decreased compared with the vehicle-treated-UUO group (p<0.05). Masson staining showed that the area of fibrosis was significantly decreased in the sorafenib-treated-UUO groups compared with vehicle-treated-UUO group (p<0.01). The size of the kidney did not significantly increase; the cortex of the kidney was thicker and had a richer blood supply in the middle-dose sorafenib group compared with the vehicle-treated-UUO group (p<0.05). Compared with the vehicle-treated-UUO and TGF-β-stimulated NRK-52E groups, the expression of a-SMA and E-cadherin decreased and increased, respectively, in the UUO kidneys and NRK-52E cells of the sorafenib-treated groups (p<0.05). The apoptotic rate of NRK-52E cells treated with sorafenib decreased for 24 hours in a dose-dependent manner (p<0.05). Compared with the vehicle-treated UUO and TGF-β-stimulated NRK-52E groups, the ratio of p-Smad3 to Smad3 decreased in the sorafenib-treated groups (p<0.05).
Our results suggest that sorafenib may useful for the treatment of renal fibrosis through the suppression of TGF-β/Smad3-induced EMT signaling.
[Show abstract][Hide abstract] ABSTRACT: T-2 toxin (T-2), one of the most important and toxic trichothecene mycotoxins, can cause many medical problems, such as diarrhea, nervous disorders, immunodepression and death, and is also believed as an etiological factor of Kashin-Beck disease, an endemic osteochondropathy prevailing in North China. However, the molecular mechanisms underlying T-2 effects on tissue damage remain elusive. We differentiated ATDC5 chondrogenic cells into hypertrophic chondrocytes, and found that T-2 reduced the expression of anabolic genes, and increased the expression of catabolic genes. To uncover the mechanism that T-2 influenced metabolic homeostasis of hypertrophic chondrocytes, we observed that T-2 increased the production of reactive oxygen species (ROS) and the degradation of IκB-α, and up-regulated the expression of hypoxia-induced factor-2α (HIF-2α). Bay11-7085 (an inhibitor of NF-κB pathway) inhibited the up-regulation of HIF-2α, and N-acetyl-l-cysteine (a ROS scavenger) inhibited both the decrease of IκB-α and the up-regulation of HIF-2α. Our results demonstrate that ROS-NF-κB-HIF-2α pathway participates in the effects of T-2 on hypertrophic chondrocytes, and HIF-2α plays an important role as a key mediator in this process.
No preview · Article · Jul 2012 · Toxicology in Vitro
[Show abstract][Hide abstract] ABSTRACT: Recently, two genome scan meta-analysis studies have found strong evidence for the association of loci on chromosome 8p with schizophrenia. The early growth response 3 (EGR3) gene located in chromosome 8p21.3 was also found to be involved in the etiology of schizophrenia. However, subsequent studies failed to replicate this finding. To investigate the genetic role of EGR3 in Chinese patients, we genotyped four SNPs (average interval ∼2.3 kb) in the chromosome region of EGR3 in 470 Chinese schizophrenia patients and 480 healthy control subjects. The SNP rs35201266 (located in intron 1 of EGR3) showed significant differences between cases and controls in both genotype frequency distribution (P = 0.016) and allele frequency distribution (P = 0.009). Analysis of the haplotype rs35201266-rs3750192 provided significant evidence for association with schizophrenia (P = 0.0012); a significant difference was found for the common haplotype AG (P = 0.0005). Furthermore, significant associations were also found in several other two-, and three-SNP tests of haplotype analyses. The meta-analysis revealed a statistically significant association between rs35201266 and schizophrenia (P = 0.0001). In summary, our study supports the association of EGR3 with schizophrenia in our Han Chinese sample, and further functional exploration of the EGR3 gene will contribute to the molecular basis for the complex network underlying schizophrenia pathogenesis.
[Show abstract][Hide abstract] ABSTRACT: Primary OA and Kashin-Beck disease (KBD) show similar pathological changes in articular cartilage. The objective was to screen differentially expressed genes between OA and normal cartilage, confirm the candidate gene expression among OA, KBD and normal cartilage, and then clarify its role in vitro.
Differentially expressed genes in OA cartilage were screened by suppression subtractive hybridization (SSH) and verified by real-time quantitative PCR (Q-PCR) analysis. Heparan sulphate 6-O-sulphotransferase 2 (HS6ST2) expression was identified by Q-PCR and immunohistochemistry. After suppressing HS6ST2 by RNA interference in C28/I2 human chondrocyte line, the effects were analysed through determining the cell viability by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), the aggrecan contents by toluidine blue staining and the mRNA expression levels of SRY-type high mobility group box 9 (SOX9), AGC1, MMP3, a disintegrin and metalloproteinase domain with thrombospondin motifs 4 (ADAMTS4) and ADAMTS5 by Q-PCR.
HS6ST2 in the reverse subtraction library was identified as a down-regulated gene in OA and KBD at both mRNA and protein levels. The percentage of safranion O staining area was correlated positively with the percentage of HS6ST2-positive chondrocytes in OA and KBD cartilage. After HS6ST2-specific short interfering RNA (siRNA) transfection to C28/I2 cells, the cell viability was inhibited significantly, and the mRNA expression levels of SOX9 and AGC1 were reduced markedly, while MMP3 expression was increased significantly. CONCLUSION; HS6ST2 down-regulation was identified in both OA and KBD cartilage. The findings first suggest that HS6ST2 may participate in the pathogenesis of OA and KBD by influencing aggrecan metabolism.
Full-text · Article · Dec 2011 · Rheumatology (Oxford, England)
[Show abstract][Hide abstract] ABSTRACT: To examine plasma levels of arthritis-related autoantibodies and inflammatory factors in Kashin-Beck disease (KBD) patients compared with rheumatoid arthritis (RA) patients, osteoarthritis (OA) patients, and healthy controls, the plasma levels of autoantibodies to types II, IX, and XI collagen and cyclic citrullinated peptide (CCP) and immunoglobulin (Ig)-G and IgM rheumatoid factors (IgG-RF and IgM-RF) from 45 KBD patients, 39 RA patients, 46 OA patients, and 30 healthy controls were determined by enzyme-linked immunosorbent assay. The plasma concentrations of nitric oxide (NO) and tumor necrosis factor-α (TNF-α) were measured using the Griess method and bioassay, respectively. Statistical analysis was performed using one-way analysis of variance followed by the least significant difference t test for differences among groups. Results indicated that the plasma levels of collagen IX antibodies, IgG-RF, and NO significantly increased in KBD patients compared with patients with RA and OA and the control group. The levels of collagen XI antibodies, CCP antibodies, and IgM-RF but not collagen II antibodies and TNF-α were significantly increased in the plasma of the KBD group compared with that of the control group. We conclude that autoimmunity and inflammation may be involved in the pathogenesis of KBD, in particular in the advanced stage.
No preview · Article · Jun 2011 · Human immunology