Ballistic transport spectroscopy of spin-orbit-coupled bands in monolayer graphene on WSe2.

Van der Waals interactions with transition metal dichalcogenides were shown to induce strong spin-orbit coupling (SOC) in graphene, offering great promises to combine large experimental flexibility of graphene with unique tuning capabilities of the SOC. Here, we probe SOC-driven band splitting and electron dynamics in graphene on WSe2 by measuring ballistic transverse magnetic focusing. We found a clear splitting in the first focusing peak whose evolution in charge density and magnetic field is well reproduced by calculations using the SOC strength of ~ 13 meV, and no splitting in the second peak that indicates stronger Rashba SOC. Possible suppression of electron-electron scatterings was found in temperature dependence measurement. Further, we found that Shubnikov-de Haas oscillations exhibit a weaker band splitting, suggesting that it probes different electron dynamics, calling for a new theory. Our study demonstrates an interesting possibility to exploit ballistic electron motion pronounced in graphene for emerging spin-orbitronics.

Caregiver burden and associated factors among primary caregivers of patients with ALS in home care: a cross-sectional survey study.

OBJECTIVES: This study aims to understand the caregiver burden experienced by the primary caregivers of patients with amyotrophic lateral sclerosis (ALS), and to explore the factors influencing caregiver burden. DESIGN: A cross-sectional survey design was used. SETTING: This study was conducted with ALS inpatients and follow-up outpatients at the neurology department of a tertiary general hospital in Taiyuan, Shanxi, China and their caregivers. PARTICIPANTS: Patients with ALS and their caregivers (N=120 pairs) participated in a face-to-face interview. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures included the Zarit Burden Interview scores and personal/role burden scores. There were no secondary outcomes. RESULTS: Multiple linear and logistic regression analyses were performed to examine the factors influencing burden in ALS patient's caregivers. Multiple linear regression showed that caregivers with higher Anxiety Index (AI) experienced greater personal (ß=0.089, p<0.001), role (ß=0.065, p<0.001) and overall (ß=0.200, p<0.001) burden. Logistic regression analysis showed that AI (p=0.025; OR 1.351, 95% CI 1.038 to 1.759) and disease knowledge level (p=0.033; OR 0.305, 95% CI 0.107 to 0.593) are the influencing factors of ALS load classification. CONCLUSIONS: Higher AI scores were associated with greater caregiver burden. Caregiver burden of caregivers who had no knowledge of the patient's disease was 0.305 times that of those who had good knowledge. The level of disease knowledge and AI score can serve as key predictors of caregiver burden in ALS.

Enhancement of Rashba spin-orbit coupling by electron confinement at the LaAlO3/SrTiO3 interface.

Electrical transport property is closely related to the dimensionality of carriers' distribution. In this work, we succeed in tuning the carriers' distribution and the Rashba spin-orbit coupling at LaAlO3/SrTiO3 interface by varying the oxygen pressure (c-P O2) adopted in crystalline LaAlO3 growth. Measurements of the in-plane anisotropic magnetoresistance and the conducting-layer thickness indicate that the carriers' distribution changes from three to two dimensions with c-P O2 increasing, i.e. the electron confinement gets stronger. Importantly, by measuring the low-temperature out-of-plane magnetoresistance and analyzing the weak localization/weak anti-localization, we find that the strength of Rashba spin-orbit coupling can be enhanced by electron confinement. The electron confinement is a manifestation of breaking of spatial inversion symmetry. Therefore, our work reveals the intimate relationship between spatial inversion symmetry breaking and Rashba spin-orbit coupling at the LaAlO3/SrTiO3 interface, and provides a new method to tune the Rashba spin-orbit coupling, which is valuable in the application of oxide-spintronics.

Design and Evaluation of a Novel Laminectomy Auxiliary Device Based on Rats.

Most types of spinal cord injury (SCI) observed in humans can be replicated in adult rat models, which are widely used for laboratory studies of SCI rehabilitation. To ensure the effectiveness and efficiency of an SCI rat model, the minimal time spent performing the laminectomy procedure and the damage caused to the body are of great importance. We describe and evaluate the effectiveness and advantages of a laminectomy auxiliary device (LAD) for removing the rat vertebral lamina without injuring the spinal cord. The incision size, success rate, operation duration, body weight, BBB score, step detection, latency and amplitude of transcranial electrical motor-evoked potentials (tceMEPs), and serum MDA and SOD levels were recorded in 8 normal rats, 8 rats treated with traditional laminectomy and 8 rats treated with LAD laminectomy. Compared with traditional laminectomy, in our LAD, the surgical incision was smaller (approximately 2.2 and 1.3 cm, respectively), the success rate was higher (88.89% and 100%, respectively) and the duration shorter (14.644±1.617 and 4.821±0.668 minutes, respectively). Compared with normal rats, those treated with either laminectomy using LAD or the traditional method showed slower body weight gain and temporarily increased oxidative stress levels. However, there were no significant differences between these two groups. Our results show that laminectomy using this LAD provides three main advantages in rats: a high success rate, time savings, small incisions and reduced trauma. We believe this LAD can be used as an effective assistant tool for rodent laminectomy.

Planar Hall effect induced by anisotropic orbital magnetoresistance in type-II Dirac semimetal PdTe2.

We measure planar Hall effect (PHE) and longitudinal anisotropic magnetoresistance (AMR) with a magnetic field rotating in the a-b plane in the type-II Dirac semimetal PdTe2. The measured PHE and AMR curves can be fitted by the theoretical equations; however, a detailed analysis of the extracted data demonstrates that the parameter related to PHE and AMR has no relationship with the chiral anomaly due to the absence of negative longitudinal magnetoresistance (MR) when the electric and magnetic fields are parallel to each other. Meanwhile, we prove that the origin of PHE in PdTe2 is the anisotropic orbital MR. Our work suggests that negative longitudinal MR is necessary to identify chiral anomaly, and we cannot in general use PHE as a signal for the presence of the chiral anomaly in Dirac/Weyl semimetals.

Naltrexone (NTX) relieves inflammation in the collagen-induced- arthritis (CIA) rat models through regulating TLR4/NFκB signaling pathway.

OBJECTIVE: Our aim was to study the efficacy and mechanism by which NTX alleviate arthritis in CIA rat models in vivo. METHODS: Female Wistar rats were randomly divided into 6 groups, their weights were observed and the severity of arthritis and pathological changes were evaluated by HE staining. T lymphocyte subsets were detected by flow cytometry. The expression of cytokines was detected in peripheral serum by ELISA. Real time PCR, immunohistochemical staining and western blot analysis were utilized to detect the mRNA and protein expression of opioid receptors, TLR4, RANKL and /NF-κB in synovial tissue and the spleen. RESULTS: The weight of the rats in the 10 mg/kg NTX group decreased the least, and had the least severe arthritis. CD4+ T cells, Th1 cells and Treg cells increased, and CD8+T cells, Th1 cells and Th17 cells decreased in the splenic lymphocytes. The expression of proinflammatory cytokines decreased, and the expression of anti-inflammatory cytokines increased. MOR and DOR were strongly expressed in the spleen, whereas KOR and DOR were strongly expressed in synovial tissue. The expression of TLR4, NF-κB and RANKL was reduced in the spleen and synovium in the NTX group. CONCLUSIONS: NTX relieved the severity of arthritis in the CIA rat models at a concentration of 10 mg/kg by regulating T lymphocyte subsets and the expression of cytokines. NTX affected opioid receptors to inhibit the TLR4/NF-κB signaling pathway, regulating the systemic immune response and decreasing osteoclast differentiation, thereby alleviating inflammation and the erosion of articular cartilage along with bone tissue.

Decreased Serum Lipid Levels and Ratios Correlate with Low Prevalence of Coronary Heart Disease in Patients with Parkinson's Disease.

BACKGROUND: Patients with Parkinson's disease (PD) are at a lower risk of suffering cardiovascular events, but the underlying factors for this decreased risk remain unclear. Serum triglycerides (TG) and total cholesterol (TC), and their expression relative to high-density lipoprotein cholesterol (TG/HDL-C and TC/HDL-C), are independent predictors of cardiovascular events. This study aimed to determine if PD patients have decreased lipid levels and lipid ratios, which may underlie the decreased risk of coronary heart disease (CHD). METHODS: This retrospective study included 92 PD patients (PD group), 450 control subjects with no CHD (OD group), and 450 CHD patients (CHD group). We analyzed serum lipid levels and lipid ratios in each group. RESULTS: There were significant differences in TC (F = 10.459, p < 0.0001), TG (F = 46.856, p < 0.0001), low density lipoprotein cholesterol (LDL-C) (F = 6.910, p = 0.001), high density lipoprotein cholesterol HDL-C (F = 30.694, p < 0.0001), TC/HDL-C (F = 32.675, p < 0.0001), and TG/HDL-C (F = 45.554, p < 0.0001) between all three groups; TC/LDL-C (F = 2.518, p = 0.081) was not significantly different between groups. Compared to the CHD group, PD patients had lower TC (p < 0.0001), TG (p < 0.0001), LDL-C (p = 0.001), TG/HDL-C (p < 0.0001), and TC/HDL-C (p < 0.0001); TC/LDL-C (p = 0.563) and HDL-C (p = 0.196) were not significantly different. TC and LDL-C levels were positively correlated within individual groups (all p < 0.0001). In addition, TG and HDL-C were negatively correlated in the OD and CHD groups (p < 0.0001); no significant negative association was observed in the PD group (p = 0.077). TG/HDL and LDL-C levels were inversely correlated in the CHD group (p < 0.0001) and weakly positively correlated in the PD (p = 0.159) and OD (p = 0.199) groups. CONCLUSIONS: TC/HDL and TG/HDL ratios were significantly lower in PD patients compared to CHD patients, suggesting there is a strong correlation between lipid ratios and incidence of CHD in PD patients.

Interaction between in-gap states and carriers at the conductive interface between perovskite oxides.

The 2D electron systems of SrTiO3/NdGaO3 (STO/NGO) and amorphous-LaAlO3/SrTiO3/NdGaO3 (a-LAO/STO/NGO) heterojunctions were explored. An obvious interaction between in-gap states (IGSs) and carriers was found. The IGSs can trap a large number of carriers and enhance carrier scattering. As a result of the high density of IGSs in STO, the conductivity of STO/NGO was severely weakened. However, for a-LAO/STO/NGO heterojunctions, the high carrier density can reduce the effect of IGSs through the electrostatic screening effect. The competition between IGSs and the screening effect of carriers results in an insulator-metal transition and a strange temperature dependence of carrier density. We also explored the interaction between IGSs and carriers theoretically. A mathematical description was proposed and the calculated results showed good agreement with experimental findings.

Formation of Two-dimensional Electron Gas at Amorphous/Crystalline Oxide Interfaces.

Experimentally, we found the percentage of low valence cations, the ionization energy of cations in film, and the band gap of substrates to be decisive for the formation of two-dimensional electron gas at the interface of amorphous/crystalline oxide (a-2DEG). Considering these findings, we inferred that the charge transfer from the film to the interface should be the main mechanism of a-2DEG formation. This charge transfer is induced by oxygen defects in film and can be eliminated by the electron-absorbing process of cations in the film. Based on this, we propose a simple dipole model that successfully explains the origin of a-2DEG, our experimental findings, and some important properties of a-2DEG.

Influence of In-Gap States on the Formation of Two-Dimensional Election Gas at ABO3/SrTiO3 Interfaces.

We explored in-gap states (IGSs) in perovskite oxide heterojunction films. We report that IGSs in these films play a crucial role in determining the formation and properties of interfacial two-dimensional electron gas (2DEG). We report that electron trapping by IGSs opposes charge transfer from the film to the interface. The IGS in films yielded insulating interfaces with polar discontinuity and explained low interface carrier density of conducting interfaces. An ion trapping model was proposed to explain the physics of the IGSs and some experimental findings, such as the unexpected formation of 2DEG at the initially insulating LaCrO3/SrTiO3 interface and the influence of substitution layers on 2DEG.

Associations of perceived social support and positive psychological resources with fatigue symptom in patients with rheumatoid arthritis.

OBJECTIVE: This study aimed to assess the association between perceived social support (PSS) and fatigue and the roles of hope, optimism, general self-efficacy and resilience as mediators or moderators on PSS-fatigue association among Rheumatoid Arthritis (RA) patients in China. METHODS: A multi-center, cross-sectional study was conducted withinpatients diagnosed with RA in northeast China, in which 305 eligible inpatients were enrolled. The Multidimensional Fatigue Inventory, Multidimensional Scale of Perceived Social Support, Herth Hope Index, Life Orientation Test Revised, General Self-Efficacy Scale and Ego-Resiliency Scale were completed. The associations of PSS, hope, optimism, general self-efficacy and resilience with fatigue and the moderating roles of these positive psychological constructs were tested by hierarchical linear regression. Asymptotic and resampling strategies were utilized to assess the mediating roles of hope, optimism, general self-efficacy and resilience. RESULTS: The mean score of the MFI was 57.88 (SD = 9.50). PSS, hope, optimism and resilience were negatively associated with RA-related fatigue, whereas DAS28-CRP was positively associated. Only resilience positively moderated the PSS-fatigue association (B = 0.03, ß = 0.13, P<0.01). Hope, optimism and resilience may act as partial mediators in the association between PSS and fatigue symptoms (hope: a*b = -0.16, BCa 95%CI: -0.27, -0.03; optimism: a*b = -0.20, BCa 95%CI: -0.30, -0.10; resilience: a*b = -0.12, BCa 95%CI: -0.21-0.04). CONCLUSIONS: Fatigue is a severe symptom among RA patients. Resilience may positively moderate the PSS-fatigue association. Hope, optimism and resilience may act as partial mediators in the association. PSS, hope, optimism and resilience may contribute as effective recourses to alleviate fatigue, upon which PSS probably has the greatest effect.

Astragalus polysaccharides attenuate PCV2 infection by inhibiting endoplasmic reticulum stress in vivo and in vitro.

This study explored the effects of Astragalus polysaccharide (APS) on porcine circovirus type 2 (PCV2) infections and its mechanism in vivo and vitro. First, fifty 2-week-old mice were randomly divided into five groups: a group without PCV2 infection and groups with PCV2 infections at 0, 100, 200 or 400 mg/kg APS treatments. The trial lasted for 28 days. The results showed that APS treatments at 200 and 400 mg/kg reduced the pathological injury of tissues, inhibited PCV2 infection and decreased glucose-regulated protein 78 (GRP78) and GADD153/CHOP gene mRNA and protein expression significantly (P < 0.05). Second, a study on endoplasmic reticulum stress mechanism was carried out in PK15 cells. APS treatments at 15 and 45 µg/mL significantly reduced PCV2 infection and GRP78 mRNA and protein expression (P < 0.05). Tunicamycin supplementation increased GRP78 mRNA and protein expression and significantly attenuated the APS-induced inhibition of PCV2 infection (P < 0.05). Tauroursodeoxycholic acid supplementation decreased GRP78 mRNA and protein expression and significantly inhibited PCV2 infection (P < 0.05). In addition, fifty 2-week-old mice were randomly divided into five groups: Con, PCV2, APS + PCV2, TM + PCV2 and TM + APS + PCV2. The results were similar to those in PK15 cells. Taken together, it could be concluded that APS suppresses PCV2 infection by inhibiting endoplasmic reticulum stress.

Overexpression of pig selenoprotein S blocks OTA-induced promotion of PCV2 replication by inhibiting oxidative stress and p38 phosphorylation in PK15 cells.

Porcine circovirus type 2 (PCV2) is the primary cause of porcine circovirus disease, and ochratoxin A (OTA)-induced oxidative stress promotes PCV2 replication. In humans, selenoprotein S (SelS) has antioxidant ability, but it is unclear whether SelS affects viral infection. Here, we stably transfected PK15 cells with pig pCDNA3.1-SelS to overexpress SelS. Selenium (Se) at 2 or 4 µM and SelS overexpression blocked the OTA-induced increases of PCV2 DNA copy number and infected cell numbers. SelS overexpression also increased glutathione (GSH), NF-E2-related factor 2 (Nrf2) mRNA, and γ-glutamyl-cysteine synthetase mRNA levels; decreased reactive oxygen species (ROS) levels; and inhibited p38 phosphorylation in PCV2-infected PK15 cells, regardless of OTA treatment. Buthionine sulfoximine reversed all of the above SelS-induced changes. siRNA-mediated SelS knockdown decreased Nrf2 mRNA and GSH levels, increased ROS levels, and promoted PCV2 replication in OTA-treated PK15 cells. These data indicate that pig SelS blocks OTA-induced promotion of PCV2 replication by inhibiting the oxidative stress and p38 phosphorylation in PK15 cells.

Nephropathy and hepatopathy in weaned piglets provoked by natural ochratoxin A and involved mechanisms.

Ochratoxin A (OTA) contamination is a worldwide problem in pig industry. The objectives of the present study were to investigate the toxicity of natural OTA in weaned piglets and to further explore the underlying mechanisms. Totally, 36 crossbred ([Landrace × Yorkshire] × Duroc) piglets were randomly divided into 3 groups (three replicates per group, 4 piglets per replicate), and fed a basal diet (Con group) and basal diets added with 0.4 mg (OTA-L group) or 0.8 mg OTA/kg (OTA-H group), respectively for 42 days. The results showed that growth performance was significantly decreased (P<0.05) in OTA added groups compared with Con group. OTA concentration was relatively high in serum and OTA concentration in kidney was higher than in liver, respectively. AST, creatinine and urea in serum of OTA added groups were significantly increased (P<0.05), while glucose, total protein, albumin and globulin in serum of OTA added groups were significantly decreased (P<0.05) compared with Con group. Degenerative changes were observed in the epithelial cells of proximal tubules and in hepatocytes of OTA added groups. Antioxidant capacities in blood of OTA added groups and in kidney of OTA-H group were significantly decreased (P<0.05) compared with Con group. The mRNA expressions of bcl-2 were up-regulated, mRNA expressions of bax were down-regulated and the ratio of bcl-2 and bax was increased in kidney and liver of OTA added groups compared with Con group. In conclusion, OTA could reduce antioxidant capacity and suppress apoptosis in tissues and cause degenerative changes in the epithelial cells in proximal tubules and hepatic cells, which may have a negative effect on the growth performance of piglets.

Astragalus polysaccharides inhibits PCV2 replication by inhibiting oxidative stress and blocking NF-κB pathway.

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated disease (PCVAD). Astragalus polysaccharide (APS), as one kind of biological macromolecule extracted from Astragalus, has antiviral activities. This study was undertaken to explore the effect of APS on PCV2 replication in vitro and the underlying mechanisms. Our results showed that adding APS before PCV2 infection decreased significantly PCV2 DNA copies, the number of infected cells, MDA level, ROS level and NF-κB activation in PK15 cells and increased significantly GSH contents and SOD activity compared to control without APS. Oxidative stress induced by BSO could eliminate the effect of PCV2 replication inhibition by APS. LPS, as a NF-κB activator, could attenuate the effect of PCV2 replication inhibition by APS. BAY 11-7082, as a NF-κB inhibitor, could increase the effect of PCV2 replication inhibition by APS. In conclusion, APS inhibits PCV2 replication by decreasing oxidative stress and the activation of NF-κB signaling pathway, which suggests that APS might be employed for the prevention of PCV2 infection.

High-dose thalidomide increases the risk of peripheral neuropathy in the treatment of ankylosing spondylitis.

Thalidomide is an effective drug for the treatment of ankylosing spondylitis but might induce peripheral neuropathy. This major adverse reaction has attracted much concern. The current study aimed to observe the incidence of thalidomide-induced peripheral neuropathy among ankylosing spondylitis patients for 1 year after treatment. In this study, 207 ankylosing spondylitis cases received thalidomide treatment, while 116 ankylosing spondylitis cases received other treatments. Results showed that the incidence of thalidomide-induced peripheral neuropathy in the thalidomide group was higher than that in the non-thalidomide group. There was no significant difference in the incidence of neuropathy between the < 6 months medication and ≥ 6 months medication groups. There were no differences in the mean age, gender, or daily dose between the two groups. The incidence of peripheral neuropathy among patients receiving 25, 50, 75, or 100 mg thalidomide per day was 4.6%, 8.5%, 17.1%, 21.7%, respectively. The incidence was significantly different between the groups receiving 25 mg and 100 mg thalidomide. In conclusion, thalidomide can induce peripheral neuropathy within 1 year after treatment of ankylosing spondylitis; however, age and gender have no obvious impact on the incidence of peripheral neuropathy. The incidence of peripheral neuropathy is associated with increasing daily doses of thalidomide.

Selenium alleviates porcine nephrotoxicity of ochratoxin A by improving selenoenzyme expression in vitro.

Ochratoxin A (OTA), a mycotoxin, is a potent nephrotoxin in humans and animals. Selenium (Se) is an essential micronutrient for humans and animals, and plays a key role in antioxidant defense. To date, little is known about the effect of Se on OTA-induced nephrotoxicity. In this study, the protective effects of selenomethionine against OTA-induced nephrotoxicity were investigated using the porcine kidney 15 (PK15) cells as a model. The results showed that OTA induced nephrotoxicity in a dose-dependent manner. Se at 0.5, 1, 2 and 4 µM had significant protective effects against OTA-induced nephrotoxicity. Furthermore, selenomethionine enhanced the activity and mRNA and protein expression of glutathione peroxidase 1 (GPx1), mRNA expression of GPx4, and mRNA expression of thioredoxin reductase 1 in the presence and absence of OTA. Among them, promoting effect of selenomethionine on GPx1 was maximal. Knock-down of GPx1 by using a GPx1-specific siRNA eliminated the protective effects of selenomethionine against OTA-induced nephrotoxicity. The results suggest that selenomethionine alleviates OTA-induced nephrotoxicity by improving selenoenzyme expression in PK15 cells. Therefore, selenomethionine supplementation may be an attractive strategy for protecting humans and animals from the risk of kidney damage induced by OTA.

Ochratoxin A promotes porcine circovirus type 2 replication in vitro and in vivo.

Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin in animals and humans. Porcine circovirus-associated disease (PCVAD), including porcine dermatitis and nephropathy syndrome, is a worldwide swine disease. To date, little is known concerning the relationship between OTA and porcine circovirus type 2 (PCV2), the primary causative agent of PCVAD. The effects of OTA on PCV2 replication and their mechanisms were investigated in vitro and in vivo. The results in vitro showed that low doses of OTA significantly increased PCV2 DNA copies and the number of infected cells. Maximum effects were observed at 0.05 µg/ml OTA. The results in vivo showed that PCV2 replication was significantly increased in serum and tissues of pigs fed 75 µg/kg OTA compared with the control group and pigs fed 150 µg/kg OTA. In addition, low doses of OTA significantly depleted reduced glutathione and mRNA expression of NF-E2-related factor 2 and γ-glutamylcysteine synthetase; increased reactive oxygen species, oxidants, and malondialdehyde; and induced p38 and ERK1/2 phosphorylation in PK15 cells. Adding N-acetyl-L-cysteine reversed the changes induced by OTA. Knockdown of p38 and ERK1/2 by their respective specific siRNAs or inhibition of p38 and ERK1/2 phosphorylation by their respective inhibitors (SB203580 and U0126) eliminated the increase in PCV2 replication induced by OTA. These data indicate that low doses of OTA promoted PCV2 replication in vitro and in vivo via the oxidative stress-mediated p38/ERK1/2 MAPK signaling pathway. This suggests that low doses of OTA are potentially harmful to animals, as they enhance virus replication, and partly explains why the morbidity and severity of PCVAD vary significantly in different pig farms.

Expression of peptidylarginine deiminase 4 and protein tyrosine phosphatase nonreceptor type 22 in the synovium of collagen-induced arthritis rats.

OBJECTIVE: To study the expression level of peptidylarginine deiminase 4 (PADI4) and protein tyrosine phosphatase nonreceptor type 22 (PTPN22) in the synovium of rat model of collagen-induced arthritis, and to explore their possible therapeutic role in rheumatoid arthritis. METHODS: Thirty-two female Wistar rats weighing 100±20 g were randomly assigned into 3-week collagen-induced arthritis (CIA) model group (n=8), 4-week CIA model group (n=8), 6-week CIA model group (n=8), and the control group (n=8). The body weight changes of each group were recorded. The expression levels of PADI4 and PTPN22 were detected and compared by the methods of immunohistochemical staining and Western blot. RESULTS: Arthritis of rat began to form 14 days after sensitization and the joint swelling reached peak at 28 days. The weights of the rats slowly grew both in CIA model groups and the control group. Immunohistochemical staining results showed that the positive expression of PADI4 and PTPN22 was mainly located in cartilage peripheral mononuclear cells, the cytoplasm of infiltrated cells, and bone marrow cavity. There were significant differences in the optical density of PADI4 and PTPN22 among CIA model groups and the control group (PADI4, 0.2898±0.012, 0.2982±0.022, 0.2974±0.031, 0.2530±0.013 in 3-week CIA model, 4-week CIA model, 6-week CIA model and control groups; PTPN22, 0.2723±0.004, 0.2781±0.010, 0.2767±0.008, 0.2422±0.019; all P <0.05). The expression bands of PADI4 were observed in Western blot 3 weeks after initial immunization, the thickest in the 4th week, and decreased in the 6th week. The expression bands of PTPN2 were observed at all the time points, with no obvious time-dependent trend. CONCLUSIONS: PADI4 and PTPN22 are obviously correlated with CIA in rat model. PADI4 is expressed at early stage of the disease, while the expression of PTPN22 sustains throughout the course.

Effect of local viral transfer of interleukin 10 gene on a rabbit arthritis model induced by interleukin 1beta.

BACKGROUND: Interleukin 1beta (IL-1beta) is the principal mediator in the pathogenesis of rheumatoid arthritis. Continuous injection of interleukin 1beta (IL-1beta) into the knee articular cavities of animals can induce models that resemble rheumatoid arthritis. The objective of this study was to evaluate the feasibility of local recombinant retrovirus viral interleukin 10 (rRV-vIL-10) gene transfer treatment of a rabbit model of arthritis induced by IL-1beta. METHODS: An hIL-1beta-induced rabbit rheumatoid arthritis model was established using the MFG-hIL-1beta-neo-HIG-82 cell line, which is capable of continuous secretion of hIL-1beta. After transfecting the rabbit synovial fibroblast cell line (MFG-hIL-1beta-neo-HIG-82) with rRV-vIL-10, G418 was then added to identify the positive clone. The rRV-vIL-10 positive clone was injected into the established rabbit rheumatoid arthritis model through intra-articular injection. Successful gene transfer was determined by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. The levels of IL-1beta before and after treatment were determined by enzyme- linked immunosorbent assay. RESULTS: Retrovirus vector was an effective vector both to synoviocytes in vitro and synovium tissue in vivo as confirmed by RT-PCR and immunohistochemistry. The rabbit arthritis model treated with rRV-vIL-10 showed a dramatic remission of arthritis and a decline in the level of cytokines such as IL-1beta. CONCLUSIONS: Retrovirus-mediated transfection of vIL-10 successfully transferred the gene into rabbit synovium ex vivo and was able to suppress intra-articular inflammation response to IL-1beta.