Vitamin D levels in idiopathic inflammatory myopathy patients: a meta-analysis.

PURPOSE: This meta-analysis aimed to explore correlations between vitamin D and idiopathic inflammatory myopathy (IIM). METHODS: A comprehensive database search was conducted on 13 October 2020. Mean differences (MDs) and aggregated risk ratios (RR) with 95% confidence intervals (CIs) were used to determine the correlation between vitamin D deficiency (VDD) and IIM. Statistical analysis was performed with RevMan 5.4 and Stata15, statistical significance was set at p < 0.05. RESULTS: Search revealed five studies with 286 IIM patients and 480 healthy controls. Results with random-effects modeling indicated that serum vitamin D levels were significantly lower in IIM patients than in healthy controls (MD = -13.10 ng/mL; 95% CI: -16.51 to -9.68; p < 0.00001). No differences were found between patients with IIM and other autoimmune diseases on vitamin D levels (MD =-2.65 ng/mL; 95% CI: -11.31-6.01; p = 0.55). In two studies with 185 IIM patients, those with low vitamin D levels exhibited higher creatine kinase levels (MD = 85.20 IU/L; 95% CI: 72.67-97.73; p < 0.00001) than those with normal vitamin D levels. VDD was correlated with an increased risk of IIM (RR = 3.24, 95% CI: 1.81-5.79; p < 0.0001). CONCLUSION: This meta-analysis showed correlations between vitamin D level and IIM. The results indicated, VDD may be a risk factor for IIM, a determinant of immune dysregulation in IIM, or a consequence of IIM. Also, it implied further research to determine whether vitamin D supplementation is beneficial for patients with IIM.

Quantum Correlation Swapping between Two Werner States Undergoing Local and Nonlocal Unitary Operations.

In this paper, quantum correlation (QC) swapping between two Werner-like states, which are transformed from Werner states undergoing local and nonlocal unitary operations, are studied. Bell states measures are performed in the middle node to realize the QC swapping and correspondingly final correlated sates are obtained. Two different QC quantifiers, i.e., measurement-induced disturbance (MID) and ameliorated MID, are employed to characterize and quantify all the concerned QCs in the swapping process. All QCs in the concerned states are evaluated analytically and numerically. Correspondingly, their characteristics and properties are exposed in detail. It is exposed that, through the QC swapping process, one can obtain the long-distance QC indeed. Moreover, the similarities of monotony features of MID and AMID between the initial states and final states are exposed and analyzed.

Increasing Quantum Correlations Based on Measurement-Induced Disturbance via a Swapping Procedure with Two-Qubit Mixed States.

In this paper, quantum correlation (QC) swapping for certain separable two-qubit mixed states is treated. A QC quantifier, measurement-induced disturbance (MID) (Luo in Phys Rev A 77:022301, 2008), is employed to characterize and quantify QCs in the relevant states. Properties of all QCs in the swapping process are revealed. Particularly, it is found that MID can be increased through QC swapping for certain separable two-qubit mixed states.

Analytic Expression of Quantum Discords in Werner States under LQCC.

In this paper, quantum discords in a special kind of states, i.e., Werner states by local quantum operations and classical communication (LQCC) protocols (WLQCC states), are studied. Nineteen parameters to quantify the quantum discords are reduced to four parameters in terms of properties of Werner states and quantum discord. In the case of orthogonal projective measures, analytic expression of quantum discords in WLQCC states is analytically worked out. Some properties of the quantum discord in the WLQCC states are obtained, especially the variation relations between the quantum discords and the parameters characterizing the WLQCC states. By virtue of numerical computations, quantum discords in a Werner state before and after LQCC protocols are compared. It is found that quantum discord in any WLQCC state cannot exceed that in the original Werner state.

Ginkgolide B attenuates collagen-induced rheumatoid arthritis and regulates fibroblast-like synoviocytes-mediated apoptosis and inflammation.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic disease characterized by chronic synovial infiltration and proliferation, cartilage destruction, and joint injury. Ginkgolide B (GB) is an extract of the leaves of Ginkgo biloba, and pharmacological studies have shown that it has anti-inflammatory and anti-apoptotic activities. The purpose of this study was to investigate the anti-RA properties of GB. METHODS: In vivo, we established a collagen II-induced arthritis (CIA) mouse model. Mice were divided into five groups (n=10): sham, CIA, GB (10 µM), GB (20 µM), and GB (40 µM). We measured arthritis score, synovial histopathological change, and peripheral blood cytokine levels. In vitro, we used lipopolysaccharide (LPS)-induced-fibroblast-like synoviocytes (RA-FLSs) as the study subject. Cell viability, apoptosis, and inflammatory cytokines levels were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, flow cytometry, and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), respectively. Finally, the protein expression of wingless-type family member 5A (Wnt5a), c-Jun N-terminal kinase (JNK), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65 were detected by Western blot. RESULTS: Arthritis scores, synovial hyperplasia, and cartilage and bone destruction were significantly ameliorated by GB. Additionally, GB decreased the serum levels of interleukin (IL)-1ß, IL-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α), matrix metalloproteinase (MMP)-3 and MMP-13, and increased IL-10. In vitro, we found that GB remarkably inhibited RA-FLSs viability at 24 or 48 h in a concentration-dependent manner. The apoptotic ratio was reduced by GB, and it increased the expression of cleaved-Caspase-3 and Bax while decreasing Bcl-2 expression in RA-FLSs. Furthermore, GB attenuated the progression of inflammation by mediating inflammatory cytokine release and MMPs gene expression. Meanwhile, GB inactivated the expression levels of Wnt5a, phosphorylated (p)-JNK, and p-P65 in the synovial tissues and RA-FLSs. CONCLUSIONS: This study was the first to demonstrate that the anti-RA effect of GB is related to reducing articular cartilage and bone destruction, inducing RA-FLSs apoptosis, and regulating inflammatory cytokine release and the Wnt5a/JNK/NF-κB axis. All the findings highlight that GB might provide a novel treatment approach for RA.

Triptolide suppresses human synoviocyte MH7A cells mobility and maintains redox balance by inhibiting autophagy.

Triptolide (TPL), the main active ingredient in Tripterygium glycosides, has been reported to exert anti-inflammation and anti-tumor effects. The present study was designed to investigate the effects of TPL on rheumatoid arthritis (RA) and explore the underlying mechanisms. By using human synoviocyte MH7A cells, TPL was proven to significantly impede migration and invasion of MH7A cells, and also inhibited MMP-2 and MMP-9 expression. Moreover, TPL was found to increase SOD, CAT, GSH-Px activities while decrease MDA activity, indicating that TPL maintained redox balance in MH7A cells. TPL could down-regulate the number of LC3+ puncta, Beclin1 expression and LC3 II/I ratio in a concentration-dependent manner, indicating that TPL inhibited autophagy in MH7A cells. Activation of autophagy was found to counteract the effects of TPL on MH7A cells while inhibition of autophagy had the opposite effects. Our data demonstrated that TPL suppressed cell mobility and maintained redox balance through inhibiting autophagy in MH7A cells. Finally, our data revealed that TPL increased p-AKT/AKT ratio significantly and inhibition of PI3K/AKT signaling pathway activated autophagy in MH7A cells, suggesting that TPL suppressed autophagy through activating AKT signaling pathway in MH7A cells. Taken together, our present study revealed that TPL inhibited cell mobility and maintained redox balance in human synoviocyte MH7A cells through autophagy inhibition. Our findings suggested the potential clinical application of TPL on RA treatment.

Up-regulation of miR-383-5p suppresses proliferation and enhances chemosensitivity in ovarian cancer cells by targeting TRIM27.

MicroRNAs are small non-coding RNAs which play important roles in tumor progression. MiR-383-5p has been characterized as a cancer suppressor in several cancers. The aim of theses present study was to explore the role of miR-383-5p in the proliferation and chemosensitivity of ovarian cancer cells. MiR-383-5p expression was down-regulated while the expression of TRIM27 was up-regulated in ovarian cancer tissues and cell lines. We came up with the hypothesis that miR-383-5p might be involved in the tumor progression and chemoresistance of ovarian cancer through targeting TRIM27. Bioinformatics study and Luciferase reporter assay indicated that TRIM27 was a target of miR-383-5p and negatively regulated by miR-383-5p in ovarian cancer cells. Up-regulation of miR-383-5p was found to suppress cell proliferation and decrease Ki67 and PCNA expression in ovarian cancer cells (OVCAR3, A2780), suggesting that overexpressed miR-383-5p inhibited cell proliferation of ovarian cancer cells. In addition, up-regulation of miR-383-5p decreased the IC50 value of ovarian cancer cells to paclitaxel and increased cell apoptosis rate under the treatment of paclitaxel, indicating that overexpressed miR-383-5p enhanced chemosensitivity in ovarian cancer cells. However, overexpressed TRIM27 by pcDNA3.1-TRIM27 transfection counteracted the inhibitory effect of miR-383-5p on cell proliferation and chemoresistance in ovarian cancer cells. In vivo experiments also revealed that tumor growth could be inhibited by miR-383-5p mimic. Taken together, this present study found that miR-383-5p was lowly expressed while TRIM27 was highly expressed in ovarian cancer. Up-regulation of miR-383-5p inhibited cell proliferation, tumor growth and enhanced chemosensitivity of ovarian cancer cells through suppressing TRIM27 expression. Therefore, miR-383-5p/TRIM27 axis may be the potential target for the treatment of ovarian cancer.

[Effect of acetazolamide on AQP1 and AQP3 expressions in fibroblast-like synoviocytes of rheumatoid arthritis].

OBJECTIVE: To observe the effect of acetazolamide (AZ) on the expressions of aquaporin 1 (AQP1) and AQP3 in fibroblast-like synoviocytes of rheumatoid arthritis (RAFLSs) and explore the roles of AQP1 and AQP3 in the development of rheumatoid arthritis (RA). METHODS: The study included 12 RA with knee hydrarthrosis and 10 osteoarthritis (OA) with knee hydrarthrosis and collected their synovia. From the synovia, FLSs were separated and cultured in vitro. RAFLSs were treated with different concentrations of acetazolamide (10(-4), 10(-6), 10(-8) mol/L) for different time (24, 48, 72 hours). The expressions of AQP1 mRNA and AQP3 mRNA in RAFLSs and OAFLSs were measured by RT-PCR; the expression of AQP1 protein was detected by immunofluorescence in RAFLSs and OAFLSs treated with the same concentration of acetazolamide (10(-4) mol/L) for different time (24, 48, 72 hours). RESULTS: AQP1 mRNA and AQP3 mRNA were both expressed in RAFLSs. The level of AQP1 mRNA in RAFLSs was significantly higher than that in OAFLSs (P<0.05). Different concentrations of acetazolamide (10(-4), 10(-6), 10(-8) mol/L) were able to significantly decrease the expression level of AQP1 mRNA in RAFLSs (P<0.05) in a time- and dose-dependent manner. There was no significant difference in transcription level of AQP3 mRNA between RAFLSs and OAFLSs (P>0.05); Immunofluorescence showed that AQP1 protein was significantly distributed on cell membrane. AQP1 protein expression was very apparent without acetazolamide treatment, whereas the expression was significantly attenuated by acetazolamide in a time-dependent manner. CONCLUSION: Up-regulation of AQP1 expression in RA synovial membrane may be the one of mechanisms of arthroedema. Acetazolamide can reduce the expression of AQP1 rather than AQP3 in RAFLSs.

[The association of vitamin D receptor gene ApaI and BsmI polymorphism with systemic lupus erythematosus].

OBJECTIVE: To determine the distribution of vitamin D receptor (VDR) gene ApaI and BsmI polymorphism in systemic lupus erythematosus (SLE) and the association with SLE in Chinese Han patients. METHODS: Genomic DNA from 244 Chinese SLE patients and 162 sex and ethnically matched controls were typed for VDR ApaI and BsmI polymorphism combination by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Clinical characteristics were analyzed between different ApaI and BsmI genotypes. RESULTS: There was no significant difference between the distribution frequencies of allelic gene A and a in SLE patients and the controls, but the distribution frequency of genotypes heterozygote Aa in SLE patients was higher than that in the controls (38.9% vs 22.2%, χ(2) = 12.442, P = 0.000). There was no significant difference between the distribution frequency of allelic gene and genotypes of BsmI in SLE patients and the controls (P > 0.05). However, there was significant difference between the distribution frequencies of ApaI and BsmI genotypes combination in SLE patients and the controls (χ(2) = 18.226, P = 0.006). The distribution frequency of genotypes Aa-bb in SLE patients was higher than that in the controls (32.4% vs 17.9%, χ(2) = 10.449 P = 0.001), while the distribution frequency of genotypes Aa-bb in SLE patients was lower than that in the controls (30.3% vs 42.0%, χ(2) = 5.808, P = 0.016). Furthermore, analyzing the effect of VDR ApaI and BsmI polymorphism combination to the symptoms of SLE, significant difference was observed in SLE patients carrying Aa-bb genotypes involved in serositis (P = 0.003), hematological system disorder (P = 0.021), and anti-Sm antibodies (P = 0.01) compared with other genotypes. CONCLUSION: There is significant association between ApaI and BsmI gene polymorphism Aa-bb genotypes and the incidence of SLE in the Han population of China, and genotype Aa-bb is more involved in serositis, hematological system disorder and has a positive effect on production of antibodies.

Expression of FLICE-inhibitory protein in synovial tissue and its association with synovial inflammation in juvenile idiopathic arthritis.

OBJECTIVE: To examine the expression of FLICE-inhibitory protein (FLIP) in juvenile idiopathic arthritis (JIA) and analyze its correlation with synovial inflammation. METHODS: The expression of FLIP was assessed in 11 JIA and 3 normal synovial tissue samples by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The cell types expressing FLIP were further characterized, and the correlation of FLIP expression with the degree of synovial inflammation, as well as the activity of caspase 8 was then analyzed. RESULTS: RT-PCR revealed the expression of FLIP mRNA in all 11 JIA samples, but not in 3 normal synovial tissues. In JIA, FLIP expression could be found in both the lining and sublining layers, mainly in the macrophage-like cells. Moreover, the expression of FLIP in JIA synovial tissues was positively correlated with the degree of synovial inflammation (r = 0.563, P < 0.05). CONCLUSION: The expression of antiapoptotic FLIP in JIA synovial tissue and its correlation to accumulation of inflammatory cells in synovial tissue suggests that FLIP potentially extends the lifespan of synovial cells and thus contributes to the progression of joint destruction.

Expression of CC chemokine ligand 5 in patients with rheumatoid arthritis and its correlation with disease activity and medication.

OBJECTIVE: To determine the levels of CC chemokine ligand 5 (CCL5) in serum and synovial fluid (SF) from patients with rheumatoid arthritis (RA) and their relations with disease activity and medication. METHODS: CCL5 in serum and SF was quantified by enzyme-linked immunosorbent assay (ELISA) in 28 RA patients and 21 osteoarthritis (OA) patients. In RA patients, the correlations of CCL5 levels in serum and SF with disease activity were analyzed. Meanwhile, the serum CCL5 levels among RA patients treated with disease-modifying antirheumatic drugs (DMARDs), Tripterygium Glucosides, and other Chinese herbs without disease-modifying effects were also compared. RESULTS: CCL5 levels in both serum and SF of RA patients were significantly higher than those of OA patients (P < 0.05). Moreover, the level of CCL5 was higher in SF than that in serum of RA patients (P < 0.01). Serum CCL5 level was correlated significantly with the number of swollen joints (r = 0.3329, P < 0.05), erythrocyte sedimentation rate (r = 0.4001, P < 0.05), and C reactive protein (r = 0.3735, P < 0.01). In addition, the level of CCL5 had a trend of lower in patients treated with DMARDs or Tripterygium Glucosides than those treated with other Chinese herbs, although the difference was not significant among those patients due to the small number of patients in each group. CONCLUSIONS: In RA patients, the expression of CCL5 increases and correlates with some clinical and laboratory parameters of RA, which indicate that CCL5 plays an important role in RA and may serve as a useful marker of disease activity. DMARDs and Tripterygium Glucosides might exert their clinical effects through reducing CCL5 production in RA.