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Objective To determine the risk and time trends of hospitalized heart failure (HF) in individuals with newly diagnosed polymyositis (PM) and dermatomyositis (DM) at the general population level. Methods We conducted a retrospective cohort study using a nationwide insurance database in Taiwan. Patients with incident PM/DM and without previous histories of HF were selected between 2000 and 2013. Unmatched and propensity score-matched cohorts were established separately. Multivariable Cox proportional hazard regression model was used to estimate adjusted hazard ratios (HRs) in the unmatched population. In the propensity-matched cohort, controls were selected and matched to the PM/DM group at a 1:1 ratio based on propensity scores, which accounted for confounding factors: sex, age, year of index date, comorbidities, and medication exposure. The cumulative HF incidence was estimated with Kaplan-Meier method. A stratified Cox model was used to calculate HR for HF events in the matched cohort. Results There were 2025 PM/DM patients and 196,109 controls in the unmatched cohort. Multivariable Cox regression model adjusted for age, sex, comorbidities, and medication use revealed a greater risk of hospitalized HF in the PM/DM than in the control groups (adjusted HR: 3.29, 95% confidence interval [CI]: 2.60-4.18). After propensity score matching, a total of 1997 pairs of PM/DM patients and controls were identified. The cumulative HF incidence at 3, 5, and 10 years in patients with PM/DM were 3.3%, 4.4%, and 7.4%, respectively. The absolute risk difference in the PM/DM group versus controls were 1.8% at 3 years, 2.1% at 5 years and 3.0% at 10 years. Compared with non-PM/DM individuals, PM/DM patients exhibited an augmented HF risk (HR: 2.06, 95% CI: 1.36-3.12]. The stratified analysis according to follow-up period revealed that the increased risk of HF persisted for up to 10 years after the PM/DM diagnosis. Conclusions Our results indicated an increased risk of hospitalized HF in patients with PM/DM throughout the study period, supporting the need for increased vigilance and monitoring patients with PM/DM for this potential lethal complication.

Ischemic stroke is a major cause of disability and mortality globally. Although thrombolytic therapy is routinely adopted in cases of ischemic stroke, various alternative natural neuroprotectants are also used as effective adjuvant therapies to recover neurofunction following ischemic stroke. Raffinee, a natural fermented product with strong antioxidant and neuroprotective activities, has antiatherogenic effects in animals and has exhibited neuroprotective effects in a clinical trial by recovering motor and sensory function following spinal cord lesion. This study reveals the advantageous effects of Raffinee on PC12 cells by decreasing hypoxia-induced apoptosis in mice with permanent middle cerebral artery occlusion (pMCAO) by increasing the levels of neurotrophic factors such as S100β, reducing serum inflammatory factors such as matrix metalloproteinases (MMP)-9/MMP-2 ratio, tumor necrosis factor-α, and interleukin (IL)-6 level, and increasing IL-10 levels. Significantly reduced brain infarct volume along with a favorable survival ratio was observed for pMCAO mice that received Raffinee, suggesting a neuroprotective potential of Raffinee in cases of acute ischemic stroke by suppressing apoptosis.

Liver cancer is a leading cause of cancer-related mortality globally. Since hepatitis virus infections have been strongly associated with the incidence of liver cancer, studies concerning the effects of antiviral drugs on liver cancer have attracted great attention in recent years. The present study investigated the effects of two anti-hepatitis virus drugs, lamivudine and ribavirin, and one anti-influenza virus drug, oseltamivir, on liver cancer cells to assess alternative methods for treating liver cancer. MTT assays, wound healing assays, Transwell assays, flow cytometry, immunoblotting, ELISA, immunofluorescence staining and a xenograft animal model were adopted to verify the effects of lamivudine, ribavirin and oseltamivir on liver cancer cells. Treatment with ribavirin and oseltamivir for 24 and 48 h significantly decreased the viability of both Huh-7 and HepG2 cells compared with that of THLE-3 cells in a dose-dependent manner. The subsequent investigations focused on oseltamivir, considering the more serious clinical adverse effects of ribavirin than those of oseltamivir. Significantly decreased migration and invasion were observed in both Huh-7 and HepG2 cells that were treated with oseltamivir for 24 and 48 h. In addition, oseltamivir significantly increased autophagy in Huh-7 cells, as revealed by the significantly higher ratios of LC3-II/LC3-I, increased expression of Beclin-1, and decreased expression of p62, whereas no significant increases in the expression of apoptosis-related proteins, including Apaf-1, cleaved caspase-3, and cleaved PARP-1, were detected. Notably, apoptosis and autophagy were significantly increased in HepG2 cells in the presence of oseltamivir, as revealed by the significant increases in the expression of Apaf-1, cleaved caspase-3, and cleaved PARP-1, the higher ratios of LC3-II/LC3-I, the increased expression of Beclin-1, and the decreased expression of p62. Additionally, significant inhibitory effects of oseltamivir on xenografted Huh-7 cells in athymic nude mice were observed. The present study, for the first time to the best of our knowledge, reported the differential effects of oseltamivir on inducing liver cancer cell death both in vitro and in vivo and may provide an alternative approach for treating liver cancer.

A unique region of human parvovirus B19 virus‑VP1 (B19V‑VP1u) has been linked to a variety of cardiac disorders. However, the precise role of B19V‑VP1u in inducing cardiac injury remains unknown. The present study investigated the effects of B19V‑VP1u and different regions of B19V‑VP1u, including B19V‑VP1uA (residues 1‑60), B19V‑VP1uB (residues 61‑129), B19V‑VP1uC (residues 130‑195) and B19V‑VP1uD (residues 196‑227), on inducing cardiac injury in naive mice by zymography, immunoblotting, H&E staining and cytokine immunoassay. A significantly higher MMP‑9/MMP‑2 ratio and increased levels of inflammatory cytokines, including IL‑6 and IL‑1β, were detected in the left ventricles of the mice injected with B19V‑non‑structural protein 1 (B19V‑NS1) and B19V‑VP1u, accompanied by increased expression levels of phosphorylated (p‑)ERK and p‑P38. Significantly upregulated expression levels of atrial natriuretic peptide (ANP), heart‑type fatty acid‑binding protein (H‑FABP) and creatine kinase isoenzyme‑MB (CK‑MB), which are well‑known cardiac injury markers, as well as increased infiltration of lymphocytes, were detected in the left ventricles of the mice injected with B19V‑VP1, B19V‑NS1 and B19V‑VP1u. Moreover, a significantly higher MMP‑9/MMP‑2 ratio and increased levels of IL‑6 and IL‑1β were observed in the left ventricles of the mice injected with B19V‑VP1u, B19V‑VP1u‑A, B19V‑VP1u‑B and B19V‑VP1u‑C, accompanied by upregulated p‑ERK and p‑P38 expression. Notably, significantly lower levels of IL‑6 and IL‑1β were observed in the left ventricles of the mice injected with B19V‑VP1uD. Furthermore, significantly increased ANP, H‑FABP and CK‑MB expression levels were detected in the left ventricles of the mice injected with B19V‑VP1u, B19V‑VP1u‑A and B19V‑VP1u‑B, along with enhanced infiltration of lymphocytes. Significantly higher serum IL‑1β, IL‑6, TNF‑α and IFN‑γ levels were also detected in the mice injected with B19V‑VP1u, B19V‑VP1u‑A and B19V‑VP1u‑B. To the best of our knowledge, the findings of the present study were the first to demonstrate that the N‑terminal region (residues 1‑129) of B19V‑VP1u induces an increase in the levels of cardiac injury markers, thus providing evidence for understanding the possible functional regions within B19V‑VP1u.

Background A variety of chronic inflammatory diseases are linked to ischemic heart disease (IHD); however, this association is less well studied in patients with Behçet’s syndrome (BS). The primary objective of this study was to examine the impact of BS on the risk of IHD. The secondary objective was to estimate the long-term mortality risk in patients with BS. Methods Using a retrospective cohort design based on the Taiwan National Health Insurance Database, patients diagnosed with BS between 2000 and 2013, without prior history of IHD, were compared to non-BS individuals. The BS and non-BS cohorts were matched with a 1:2 ratio by propensity score, accounting for the following confounders: age, sex, year of index date, comorbidities, and drug exposure. Cox proportional hazard regression was used to derive the hazard ratio (HR) for IHD and mortality. The long-term survival rate was estimated using the Kaplan-Meier method. Results After propensity score matching, a total of 1554 patients newly diagnosed with BS and 3108 control subjects were identified. The incidence rate of IHD in the BS and control groups was 2.7 and 2.9 per 1000 person-years, respectively. The risk of IHD was comparable between BS and control cohorts [adjusted HR, 1.03; 95% confidence interval (CI), 0.66 to 1.62]. The 5- and 10-year survival rate of BS patients was 96.8% and 95.0%, respectively. Patients with BS exhibited a significantly higher risk of mortality than the sex- and age-matched general population (adjusted HR, 1.73; 95% CI, 1.30 to 2.32). Conclusion Unlike other chronic systemic autoimmune disorders, BS does not appear to be associated with an excess risk of IHD.

Attention deficit hyperactivity disorder (ADHD) is a most common mental illness in both children and adults. Our recent studies revealed that high-dose taurine improves hyperactivity in SHR rats by reducing mALFF signal and striatal dopamine uptake. This study further revealed the association between immune factors and hyperactivity in SHR rats fed with high-dose taurine. A positive correlation was detected between systolic blood pressure (SBP) and horizontal locomotion in SHR rats fed with high-dose taurine. Significantly higher striatal Hsp27 and galectin-3 were detected in SHR rats fed with high-dose taurine. Significantly lower IL-2 and IL-6 were detected in SHR rats fed with high-dose taurine, whereas significantly higher IL-10 was detected. Significantly increased splenic CD4+CD25+Foxp3+ regulatory T cells was detected in SHR rats fed with high-dose taurine with a negative correlation. These findings suggest that high-dose taurine reduce hyperactive behavior in SHR rats probably via multifactorial modulation on immune system.

Background No population-based study has investigated the cumulative incidence of pulmonary arterial hypertension (PAH) in patients with newly diagnosed systemic lupus erythematosus (SLE) or the survival impact of PAH in this population. Method We used a nationwide database in Taiwan and enrolled incident SLE patients between January 1, 2000, and December 31, 2013. The cumulative incidence of PAH in the SLE patients and the survival of these patients were estimated by the Kaplan-Meier method. Potential predictors of the development of PAH were determined using a Cox proportional hazards regression model. Results Of 15,783 SLE patients, 336 (2.13%) developed PAH. The average interval from SLE diagnosis to PAH diagnosis was 3.66 years (standard deviation [SD] 3.36, range 0.1 to 13.0 years). Seventy percent of the patients developed PAH within 5 years after SLE onset. The 3- and 5-year cumulative incidence of PAH were 1.2% and 1.8%, respectively. Systemic hypertension was an independent predictor of PAH occurrence among the SLE patients (adjusted hazard ratio 2.27, 95% confidence interval 1.59–2.97). The 1-, 3-, and 5-year survival rates of SLE patients following the diagnosis of PAH were 87.7%, 76.8%, and 70.1%, respectively. Conclusions PAH is a rare complication of SLE and the majority of PAH cases occur within the first 5 years following SLE diagnosis. Systemic hypertension may be a risk factor for PAH development in the SLE population. The overall 5-year survival rate after PAH diagnosis was 70.1%.

Warts are a common skin problem and are caused by infection with a virus. Warts are currently mainly treated by therapies involving ablating tissue or interrupting cellular division. However, all these existing treatments are either invasive or cause skin pain and tissue destruction. Imiquimod is a synthetic compound that belongs to the imidazoquinolinone family. It has been successfully used as a topical drug to treat external anogenital warts. However, topical imiquimod cream for warts is restricted by low skin permeability, and several side effects such as itching, pain, and erosions occur most frequently following topical treatment. Microneedle technology, a minimally invasive drug delivery system, has the potential to overcome the barrier of the stratum corneum. This technique would also offer a painless treatment choice and provide personalized therapies. In the study, we loaded imiquimod within dissolving microneedles using the molding method. Gelatin was used as a structural material for microneedle formation without adding a crosslinker. To our knowledge, this is the first study of using dissolving microneedles and exploring their utilization with imiquimod for the treatment of warts. First, we added fluorescent dye and trypan blue into the microneedles to evaluate the status of drugs in the microneedles and the degradation property of microneedles made of gelatin, respectively. Here we also prove the strength of the imiquimod microneedles and study their capability to penetrate the skin. The results show no apparent differences in mechanical failure after an additional imiquimod-loaded. Besides, we provide evidence that imiquimod microneedles induce secreted embryonic alkaline phosphatase (SEAP) in the RAW 264.7 macrophages. Gelatin does not affect the imiquimod in microneedles; a similar immune response was affected by the imiquimod alone or imiquimod complexed with gelatin. Our research demonstrates a proof of concept of using imiquimod microneedles for future warts treatment.

Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. Methods: We used data from Taiwan&rsquo, s National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25&ndash, 0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.

Background Hepatocellular carcinoma (HCC) is the second leading cancer-related cause of mortality worldwide. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), are commonly used worldwide. Available evidence investigating the association between SSRIs use and HCC risk is limited. Objective The present study aimed to investigate if the effect of all kinds of SSRIs on HCC was the same or not using population-based study. Methods The nationwide population-based study herein using Taiwan's National Health Insurance Research Database included a total of 59 859 cases with HCC and 285 124 matched controls. Conditional logistic regression analyses were adjusted for confounding variables. Results All common kinds of SSRIs including fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine were associated with lower HCC risk, and the findings were dose-dependent (eg, fluoxetine: 1-28 DDD [defined daily dose]: adjusted odds ratio [aOR]: 0.81, 95% confidence interval [CI], 0.73-0.89; 29-365 DDD: aOR: 0.71, 95% CI, 0.64-0.79; and ≥366 DDD: aOR: 0.55, 95% CI, 0.45-0.67) (P for trend

Probiotics are known to regulate host immunity by interacting with systemic and mucosal immune cells as well as intestinal epithelial cells. Supplementation with certain probiotics has been reported to be effective against various disorders, including immune-related diseases. However, little is known about the effectiveness of Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263) in the management of autoimmune diseases, especially systemic lupus erythematosus (SLE). NZB/W F1 mice, which are a lupus-prone animal model, were orally gavaged with GMNL-32, GMNL-89 or GMNL-263 to investigate the effects of these Lactobacillus strains on liver injuries in NZB/W F1 mice. The results thus obtained reveal that supplementary GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice ameliorates hepatic apoptosis and inflammatory indicators, such as matrix metalloproteinase-9 activity and C-reactive protein and inducible nitric oxide synthase expressions. In addition, supplementation with GMNL-32, GMNL-89 or GMNL-263 in NZB/W F1 mice reduced the expressions of hepatic IL-1β, IL-6 and TNF-α proteins by suppressing the mitogen-activated protein kinase and NF-κB signalling pathways. These findings, presented here for the first time, reveal that GMNL-32, GMNL-89 and GMNL-263 mitigate hepatic inflammation and apoptosis in lupus-prone mice and may support an alternative remedy for liver disorders in cases of SLE.

Ferulic acid (FA) derivatives have applied in American clinical trials for preventing and treating auditory dysfunctions. However, the effects of FA on neomycin-mediated sensorineural hearing loss are still unknown. We developed a transgenic zebrafish ( pvalb3b:TagGFP ) expressing green-colored hair cells in the inner ear and lateral line neuromasts by Tol2 system. Then, we determined the effects of FA on neomycin-induced ototoxicity in 4 dpf transgenic larvae. FA conferred significant protection against hair cell loss across a wide range of neomycin concentrations. In addition, FA significantly decreased intracellular ROS production and TUNAL reactions in larvae pretreated with FA prior to neomycin exposure. These findings suggest that FA has antioxidant effects and can attenuate neomycin-induced hair cell death in neuromasts. The green hair cells of transgenic zebrafish lateral line may provide a useful basis on which to investigate the cellular pathways related to the hair cell death and survival imparted by FA.

The nonstructural protein NS1 of human parvovirus B19 (B19) is known to exacerbate disease activity in systemic lupus erythematosus (SLE). However, no specific medicine for B19 infection is available. The roots of Gentiana macrophylla Pall. (GM), the traditional Chinese medicine "Qinjiao," have been used for centuries to treat rheumatic disease, including SLE. Herein, we aimed to investigate the effects of GM root extract (100 and 300 mg/kg body weight) on B19-NS1-exacerbated liver injury in NZB/W F1 mice; liver tissues were assessed by hematoxylin-eosin staining and immunoblotting. The GM root extract significantly decreased B19-NS1-exacerbated liver inflammation by suppressing the expressions of hepatic inducible nitric oxide synthase, cyclooxygenase type 2 (COX-2), interleukin (IL)-1β proteins, values of serum asparate transaminase (AST) and alanine transaminase (ALT), and lymphocyte infiltration (P .05). It also significantly reduced the B19-NS1-exacerbated hepatic matrix metalloproteinase-9 (MMP-9) and urokinase plasminogen activator (uPA) expressions by downregulating tumor necrosis factor (TNF)-α/NF-κB (p65) signaling. These findings suggest a therapeutic potential of GM root extract against B19-NS1-exacerbated liver inflammation in SLE.

Objective To estimate and compare the burdens of opportunistic infections and herpes zoster in real-world practice among patients with various systemic rheumatic diseases. Methods This 13-year cohort study used national health insurance data to compare the incidence rates (IRs) of nine opportunistic infections among patients with five rheumatic diseases. The analyses were stratified according to follow-up duration using Poisson regression, and Cox models were used to compare the risk of first opportunistic infection. Results During 2000–2013, we identified 76,966 patients who had polymyositis/dermatomyositis (PM/DM, 2270 cases), systemic lupus erythematosus (SLE, 15,961 cases), systemic sclerosis (SSc, 2071 cases), rheumatoid arthritis (RA, 38,355 cases), or primary Sjögren’s syndrome (pSS, 18,309 cases). The IR of opportunistic infections was highest for PM/DM cases (61.3/1000 person-years, 95% confidence interval [CI] 56.6–66.2), followed by SLE cases (43.1/1000 person-years, 95% CI 41.7–44.5), SSc cases (31.6/1000 person-years, 95% CI 28.3–35.1), RA cases (25.0/1000 person-years, 95% CI 24.4–25.7), and pSS cases (24.1/1000 person-years, 95% CI 23.1–25.2). Multivariable Cox analysis revealed that, relative to SLE, PM/DM was associated with a significantly higher risk of opportunistic infections (hazard ratio 1.18, 95% CI 1.08–1.29). The risk of opportunistic infections was highest during the first year after the diagnosis of all five rheumatic diseases. Conclusions The risk of opportunistic infection was highest for PM/DM, followed by SLE, SSc, RA, and pSS. Careful observation and preventive therapy for opportunistic infections may be warranted in selected PM/DM patients, especially during the first year after the diagnosis.

Evidence has indicated that viral infection increases the risk of developing asthma. Although the association of human parvovirus B19 (B19V) or human bocavirus (HBoV) with respiratory diseases has been reported, little is known about the influence of the B19V-VP1u and HBoV-VP1u proteins on the symptoms of asthma. Herein, we investigated the systemic influence of subcutaneously injected B19V-VP1u and HBoV-VP1u recombinant proteins in an OVA-sensitized asthmatic mouse model. A significantly higher Penh ratio and IgE level were detected in the serum, bronchoalveolar lavage fluid (BALF) and the supernatant of a lymphocyte culture from mice treated with HBoV-VP1u or B19V-VP1u than in a lymphocyte culture from OVA-sensitized mice. Significantly higher levels of serum and BALF IgE, total IgG, IgG1, OVA-specific IgE and OVA-specific IgG1 were detected in mice treated with HBoV-VP1u or B19V-VP1u than in OVA-sensitized mice. Conversely, a significantly lower IgG2a level was detected in mice from the HBoV-VP1u or B19V-VP1u groups than in mice from the OVA group. The mice treated with HBoV-VP1u or B19V-VP1u exhibited more significant lung inflammatory indices, including elevated serum and BALF IL-4, IL-5, IL-10 and IL-13 levels; BALF lymphocyte, neutrophil and eosinophil counts, MMP-9 and MMP-2 activity; and the amount of lymphocyte infiltration, relative to those in the control mice or in those sensitized with OVA. These findings demonstrate that the subcutaneous injection of HBoV-VP1u or B19V-VP1u proteins in OVA-sensitized mice result in elevated asthmatic indices and suggest that human parvoviruses may increase the risk of developing airway inflammation in a mouse model of asthma.

Introduction: Glioblastoma multiforme (GBM) is the most aggressive glioma, and its diffuse nature makes resection of it difficult. Moreover, even with the administration of postoperative radiotherapy and chemotherapy, prolonged remission is often not achieved. Hence, innovative or alternative treatments for GBM are urgently required. Traditional Chinese herbs and their functional components have long been used in the treatment of various cancers, including GBM. The current study investigated the antitumor activity of Wedelia chinensis and its major functional components, luteolin and apigenin, on GBM. Materials and Methods: MTT assay, Transwell migration assay, and flow cytometry analysis were adopted to assess the cell viability, invasive capability, and cell cycle. Immunofluorescence staining and Western blotting were used to detect the expressions of apoptotic and autophagy-related signaling molecules. Results: The W. chinensis extract (WCE) significantly inhibited the proliferation and invasive ability of both GBM8401 and U-87MG cells in a dose-dependent manner. Moreover, differential effects of WCE on GBM8401 and U-87MG cells were observed: WCE induced apoptosis in GBM8401 cells and autophagy in U-87MG cells. Notably, WCE had significant effects in reducing the cell survival and invasive capability of both GBM8401 and U-87MG cells than the combination of luteolin and apigenin. Conclusions: Taken together, these findings indicate the potential of using WCE and the combination of luteolin and apigenin for GBM treatment. However, further investigations are warranted before considering recommending the clinical use of WCE or the combination of luteolin and apigenin as the standard for GBM treatment.

Human parvovirus B19 (B19V) is a human pathogen known to be associated with many non-erythroid diseases, including hepatitis. Although B19V VP1-unique region (B19-VP1u) has crucial roles in the pathogenesis of B19V infection, the influence of B19-VP1u proteins on hepatic injury is still obscure. This study investigated the effect and possible inflammatory signaling of B19-VP1u in livers from BALB/c mice that were subcutaneously inoculated with VP1u-expressing COS-7 cells. The in vivo effects of B19-VP1u were analyzed by using live animal imaging system (IVIS), Haematoxylin-Eosin staining, gel zymography, and immunoblotting after inoculation. Markedly hepatocyte disarray and lymphocyte infiltration, enhanced matrix metalloproteinase (MMP)-9 activity and increased phosphorylation of p38, ERK, IKK-α, IκB and NF-κB (p-p65) proteins were observed in livers from BALB/c mice receiving COS-7 cells expressing B19-VP1u as well as the significantly increased CRP, IL-1β and IL-6. Notably, IFN-γ and phosphorylated STAT1, but not STAT3, were also significantly increased in the livers of BALB/c mice that were subcutaneously inoculated with VP1u-expressing COS-7 cells. These findings revealed the effects of B19-VP1u on liver injury and suggested that B19-VP1u may have a role as mediators of inflammation in B19V infection.

Accumulating evidence indicates that overconsumption of ethanol contributes in many ways to the pathogenesis of hepatic injury. Although studies indicate that taurine decreases lipogenesis, oxidative stress, and inflammatory cytokines, the protective effect of taurine against alcohol-induced liver injury is still unclear. To clarify the precise signaling involved in the beneficial effect of taurine on alcohol-induced liver injury, rats were randomly divided into four treatment groups: (1) control (Ctl), (2) alcohol (Alc), (3) Alc+taurine (Tau), and (4) Alc+silymarin (Sil). The Tau and Sil groups had lower lymphocyte infiltration and significantly lower TLR-4/MyD88 and IκB/NFκB compared to the Alc group. The inducible nitric oxide synthase (iNOS), C-reactive protein (CRP), tumor necrosis factors (TNF)-α, interleukin (IL)-6, and IL-1β were also significantly lower in the Tau and Sil groups than in the Alc group. The experimental results indicated that hepatoprotection against alcohol-induced inflammation may be mediated by decreased TLR-4/MyD88 signaling.

It has been encouraged to use large existing data like insurance claims data to investigate the new indications of old drugs. New strategies of research are warranted to identify feasible drugs. We conducted a dual research model with a population-based case-control study using Taiwan's National Health Insurance Research Database and an in vitro study to investigate the association between atypical antipsychotic and Hepatocellular carcinoma (HCC) risk. The study herein consists of two components. The first is a population-based case-control study using existing data from the Taiwan National Health Insurance Research Database. The second component was an in vitro study in which HCC cell lines (Huh7 and Hep G2) were treated with risperidone, quetiapine and clozapine. after treatment of the foregoing antipsychotics, the HCC cell lines were assessed for cell proliferation, invasion and apoptosis. Multivariate conditional logistic regression analysis revealed that antipsychotic use was independently and inversely associated with HCC risk (adjusted odds-ratio [aOR]:0.85, 95% CI: 0.81-0.89). The protective effect was dose-dependent: compared to the low cumulative defined daily dose (cDDD) group (0-29 cDDD), the 30-89 cDDD and ≥90 cDDD groups were associated with significantly reduced risk for HCC (aOR: 0.56, 95% CI: 0.41-0.76; aOR: 0.37, 95% CI: 0.27-0.50, respectively). In vitro study results indicated that risperidone, quetiapine and clozapine significantly inhibited cell proliferation, invasion and induced apoptosis in human HCC cell lines. Our results herein suggested that antipsychotic use might reduce the risk of HCC and may provide evidence for new uses of old drugs.

Human parvovirus B19 (B19) and human bocavirus 1 (HBoV) are the only known pathogenic parvoviruses, and are responsible for a variety of diseases in human beings. Mounting evidence indicates a strong association between B19 infection and cardiac disorders including myocarditis, dilated cardiomyopathy and heart failure. However, very limited information about the role of HBoV in cardiac disorders is known. To elucidate the effects of B19 and HBoV on cardiac disorders, we expressed EGFP‑conjugate constructs of B19‑VP1 unique region (VP1u) and HBoV‑VP1u, along with the mutants EGFP‑B19‑VP1uD175A and EGFP‑HBoV‑VP1uV12A, in H9c2 cells by stable transfection. The protein expression levels of EGFP, EGFP‑B19‑VP1u, EGFP‑B19‑VP1uD175A, EGFP‑HBoV‑VP1u and EGFP‑HBoV‑VP1uV12A in H9c2 cells were observed under a fluorescence microscope and confirmed by western blotting. Secreted phospholipase A2 (sPLA2) activity was detected in B19‑VP1u and HBoV‑VP1u but not B19‑VP1uD175A and HBoV‑VP1uV12A recombinant proteins. Significantly higher expression levels of MCP2 and IP‑10 mRNA were detected in H9c2 cells that were transfected with pEGFP‑B19‑VP1u, compared with in those cells transfected with pEGFP‑HBoV‑VP1u, pEGFP‑B19‑VP1uD175A or pEGFP‑HBoV‑VP1uV12A. Significantly higher protein levels of IL‑1β and IL‑6 were detected in H9c2 cells transfected with pEGFP‑B19‑VP1u or pEGFP‑HBoV‑VP1u, compared with in those cells transfected with pEGFP‑B19‑VP1uD175A or pEGFP‑HBoV‑VP1uV12A. Notably, significantly higher expression of both TNF‑α and NF‑κB was observed only in H9c2 cells transfected with pEGFP‑B19‑VP1u, but not in those cells transfected with pEGFP‑HBoV‑VP1u, pEGFP‑B19‑VP1uD175A or pEGFP‑HBoV‑VP1uV12A. These findings, to our knowledge for the first time, reveal the difference between B19‑VP1u and HBoV‑VP1u in H9c2 cells and provide insight into the roles of B19‑VP1u and HBoV‑VP1u in the pathogenesis of cardiac inflammation.

Glioblastoma multiforme (GBM) is recognized as a most aggressive brain cancer with the worst prognosis and survival time. Owing to the anatomic location of gliomas, surgically removing the tumour is very difficult and avoiding damage to vital brain regions during radiotherapy is impossible. Therefore, therapeutic strategies for malignant glioma must urgently be improved. Recent studies have demonstrated that selective serotonin reuptake inhibitors (SSRIs) have cytotoxic effect on certain cancers. Considering as a more superior SSRI, escitalopram oxalate exhibits favourable tolerability and causes generally mild and temporary adverse events. However, limited information is revealed about the influence of escitalopram oxalate on GBM. Therefore, an attempt was made herein to explore the effects of escitalopram oxalate on GBM. The experimental results revealed that escitalopram oxalate significantly inhibits the proliferation and invasive ability of U‐87MG cells and significantly reduced the expressions of cell cycle inhibitors such as Skp2, P57, P21 and P27. Notably, escitalopram oxalate also induced significant apoptotic cascades in U‐87MG cells and autophagy in GBM8401 cells. An animal study indicated that escitalopram oxalate inhibits the proliferation of xenografted glioblastoma in BALB/c nude mice. These findings implied that escitalopram oxalate may have potential in treatment of glioblastomas.

Systemic lupus erythematosus (SLE) is an autoimmune disease that is characterised by a dysregulation of the immune system, which causes inflammation responses, excessive oxidative stress and a reduction in the number of cluster of differentiation (CD)4+CD25+forkhead box P3 (FoxP3)+ T cells. Supplementation with certain Lactobacillus strains has been suggested to be beneficial in the comprehensive treatment of SLE. However, little is known about the effect and mechanism of certain Lactobacillus strains on SLE. To investigate the effects of Lactobacillus on SLE, NZB/W F1 mice were orally gavaged with Lactobacillus paracasei GMNL-32 (GMNL-32), Lactobacillus reuteri GMNL-89 (GMNL-89) and L. reuteri GMNL-263 (GMNL-263). Supplementation with GMNL-32, GMNL-89 and GMNL-263 significantly increased antioxidant activity, reduced IL-6 and TNF-α levels and significantly decreased the toll-like receptors/myeloid differentiation primary response gene 88 signalling in NZB/W F1 mice. Notably, supplementation with GMNL-263, but not GMNL-32 and GMNL-89, in NZB/W F1 mice significantly increased the differentiation of CD4+CD25+FoxP3+ T cells. These findings reveal beneficial effects of GMNL-32, GMNL-89 and GMNL-263 on NZB/W F1 mice and suggest that these specific Lactobacillus strains can be used as part of a comprehensive treatment of SLE patients.

Attention deficit hyperactivity disorder (ADHD) is a global behavior illness among children and adults. To investigate the effects of taurine on resting-state fMRI activity in ADHD, a spontaneously hypertensive rat (SHR) animal model was adopted. Significantly decreased serum C-reactive protein (CRP) was detected in rats of Wistar Kyoto (WKY) high-taurine group and significantly decreased interleukin (IL)-1β and CRP were detected in rats of SHR low-taurine and high-taurine groups. Moreover, significantly higher horizontal locomotion was detected in rats of WKY low-taurine and SHR low-taurine groups than in those of controls. In contrast, significantly lower horizontal locomotion was detected in rats of the SHR high-taurine group than in those of the SHR control group. Additionally, significantly lower functional connectivity (FC) and mean amplitude of low-frequency fluctuation (mALFF) in the bilateral hippocampus in rats of WKY high-taurine and SHR high-taurine groups was detected. Notably, the mALFF in rats of the SHR low-taurine and high-taurine groups was significantly lower than in those of the SHR control group. These findings suggest that the administration of a high-dose taurine probably improves hyperactive behavior in SHR rats by ameliorating the inflammatory cytokines and modulating brain functional signals in SHR rats.

Dysregulation of inflammasomes serves a pathogenic role in autoinflammatory diseases (AIDs) and adult-onset Still's disease (AOSD) has been categorized as an AID. The present study investigated the expression of NLR family pyrin domain containing proteins (NLRPs) inflammasome in patients with AOSD, the effect of inflammasome inhibitors on NLRP3 signaling and whether human parvovirus B19‑associated antigens can activate NLRP3 in patients with AOSD. mRNA expression levels of NLRPs in peripheral blood mononuclear cells (PBMCs) from 34 patients with AOSD and 14 healthy individuals were determined using reverse transcription‑quantitative polymerase chain reaction. Protein expression of NLRP3 was evaluated by western blotting. Supernatant cytokine levels were measured by ELISA. Among the NLRPs investigated in the present study, NLRP3 transcripts were markedly elevated and expression of NLRP2, NLRP7 and NLRP12 was decreased in patients with AOSD compared with the controls. Treatment with NLRP3 inhibitors significantly reduced downstream NLRP3 signaling in PBMCs form patients with AOSD. B19‑nonstructural protein (NS)1 stimulation of PBMCs from patients with AOSD induced significant upregulation of transcript levels of NLRP3, caspase‑1 and interleukin (IL)‑1β compared with PBMCs from healthy controls. B19‑NS1 stimulation of PBMCs from patients with AOSD induced significant increase in supernatant levels of IL‑1β and protein expression of NLRP3, caspase‑1, IL‑1β, and IL‑18 compared with healthy controls. Elevated expression of NLRP3 and its downstream inflammasome signaling components in patients with AOSD indicated a potential pathogenic role of B19‑NS1. Thus, B19‑NS1 may induce expression of IL‑1β and IL‑18 through activation of caspase‑1‑associated NLRP3‑inflammasome in AOSD.

Attenuated antioxidant activities, irregular cytokines expressions and reduced regulatory T cells, are strongly associated with the pathogenesis of systemic lupus erythematosus (SLE). Despite the well-established beneficial effects of cystamine on lupus-prone mice, the extent to which cystamine contributes to antioxidant activity and the reduction of regulatory T cells has seldom been investigated. Therefore, this study elucidates how cystamine affects anti-oxidant activities in NZB/W F1 mice by performing assays of Glutathione (GSH), 1,1-diphenyl-2- picryl-hydrazyl (DPPH) and malondialdehyde thiobarbituric acid (MDA). In addition, investigations of the effects of cystamine on CD4(+) /CD25(+) regulatory T cells and interleukin-6 (IL6)/STAT-3 signalling were performed with flow cytometry and immunoblots. Experimental results reveal more significantly reduced MDA and increased GSH and DPPH in NZB/W F1 mice receiving cystamine than in those mice receiving PBS. Meanwhile, CD4(+) /CD25(+) regulatory T cells more significantly increase in NZB/W F1 mice receiving cystamine than in those mice receiving PBS, accompanied by significantly reduced IL-6/phosphorylated STAT-3 expression. The above findings suggest the beneficial effects of cystamine in terms of increasing antioxidant activities and CD4(+) /CD25(+) regulatory T cells in lupus-prone mice by suppressing IL-6/STAT3 signalling.

The aim of this study is to investigate the protective effects of cystamine on lupus-associated cardiac hypertrophy.Balb/c and lupus-prone NZB/W-F1 mice were individually randomized into sham group (saline, n=16) and cystamine group (n=16). Mice received saline or cystamine (100 mmol in 100 μL saline) by daily intraperitoneal injection for 2 consecutive weeks. Morphological, histological, and biochemical alterations were investigated.Cystamine decreased both left ventricular (LV) mass and LV mass/tissue-to-blood ratio (TBR) in NZB/W-F1 mice (p0.05), whereas slight effects were observed in Balb/c mice. Moreover, cystamine reduced levels of atrial natriuretic peptide (ANP), C-reactive protein (CRP), heart type-fatty acid binding protein (h-FABP), creatine kinase-MB (CK-MB) and IL-6 in LV tissues of NZB/W-F1 mice (p0.05). Additionally, in LV tissues of NZB/W-F1 mice, suppression of hypertrophic signaling mediated by IL-6 in response to administration of cystamine was revealed, including phosphorylation of MEK5, ERK5, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38) (p0.05).Cystamine alleviated LV hypertrophy in NZB/W-F1 mice as a result of decrease in hypertrophic mediators and suppression of IL-6 mediated hypertrophic signaling.

Human parvovirus B19 (B19) infection has been postulated to both myocardial injury and development of systemic lupus erythematosus (SLE). However, the influence of anti-B19-VP1u antibodies on cardiac disorders in SLE is still obscure. To elucidate the effects of anti-B19-VP1u IgG in SLE, passive transfer of PBS, normal rabbit IgG or rabbit anti-B19-VP1u IgG was injected intravenously into NZB/W F1 mice, respectively. Significant expression of IL-1β, IL-6 and TNF-α were detected in NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Markedly cardiomyocyte disarray and lymphocyte infiltration were observed in left ventricle of hearts from NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Additionally, significant increases of matrix metalloproteinase-9 (MMP9) activity and protein expression were detected in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. Accordingly, significant increase of phosphorylated p-38 and NF-κB proteins were observed in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. However, no significant variation of cardiac atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), heart-type fatty acid-binding protein (h-FABP) and creatine kinase MB (CK-MB) were detected among all experimental groups. These findings firstly demonstrated the aggravated effects of anti-B19 VP1u IgG on cardiac injury by induction of inflammatory but not myocardial infarction-associated proteins through activation of phosphorylated p-38 and NF-κB signaling.

Our recent studies indicated that electrodialysed deep-sea water (ED-DSW) revealed the cardiovascular health effects, such as hindrances of the dietary-induced evaluation of total cholesterol (TC), triglyceride (TG) and nonhigh-density-lipoprotein cholesterol (HDL-C), as well as improvement of HDL-C/non-HDL-C ratio and blood pressure. In the current study, we further revealed the beneficial effects of ED-DSW on high-cholesterol dietary mice by reducing abnormal cardiac architecture, apoptosis and enhancing insulin-like growth factor-1 receptor (IGF-1R) cardiac survival signaling compared with those mice that were treated with distilled water, reverse osmosis (RO)-DSW or 10% (v/v) dilution with ddH2O (10% DSW). These findings further clarified the possible mechanisms of cardiac protective effects of ED-DSW and might suggest ED-DSW as an ingredient of cardiovascular health food in some niche markets. PRACTICAL APPLICATIONS Deep-sea water (DSW) has been applied on several fields including aquaculture, agriculture, food processing, cosmetics and medicine. Recently, we have indicated that high-cholesterol dietary mice drinking electrodialysed DSW (ED-DSW) showed decreased serum lipids, blood pressure and improving blood cholesterol profile. In this study, we further demonstrated the beneficial effects of ED-DSW on high-cholesterol dietary mice by reducing abnormal cardiac architecture, apoptosis in left ventricle and increasing cardiac survival signaling, such as insulin-like growth factor-1 receptor, phosphoinositide-3-kinases and p-AKT/AKT ratio. Altogether, these findings indicated that ED-DSW revealed the cardiac protective effects and might be suggested as an ingredient of cardiovascular health food in a variety of niche markets.

Numerous studies have implicated a connection between schizophrenia and autoimmune disorders. However, the precise relationship and underlying mechanism are still obscure. To further identify the association between autoimmune disorders and schizophrenia, the mRNA expressions of various cytokines and Toll-like receptors (TLRs) in monocytes are examined by using RT-PCR. Additionally, ELISA and zymography were performed to determine the anti-cardiolipin antibody (aCL) and MMP9 activity in serum form schizophrenic patients. Notably, significantly increased interleukin (IL)-6 and IL-10 mRNA were observed in schizophrenic patients, whereas significant reductions of TLR-3 and TLR-5 mRNA were detected. Moreover, significantly increased levels of aCL antibody and a higher frequency of positive-MMP9 activity were detected in serum from patients with schizophrenia. Meanwhile, no significant association was found between each of the medications and aCL activity. These findings demonstrated autoimmune-related phenomena in schizophrenic patients and further suggested a connection between schizophrenia and autoimmune disorders.

Background Human parvovirus B19 (B19) infection has been identified as a trigger of antiphospholipid syndrome (APS). However, the precise role of B19-VP1 unique region (VP1u) in patients with antiphospholipid syndrome remains unclear. Methods IgM and IgG against B19-VP, and serum levels of antibodies directed against cardiolipin (CL), beta2-glycoprotein-I (β2GPI) and phospholipid (PhL) were determined using ELISA in 45 APS patients. Humoral responses of anti-B19-VP1u were assessed by Western blot and B19 DNA was detected by nested PCR. Absorption experiments were performed using B19-VP1u protein to determine the binding specificity of antiphospholipid antibodies (aPL). Results One and 18 of 45 APS patients had detectable levels of anti-B19-VP IgM and anti-B19-VP IgG, indicating recent and past infection respectively. All serum samples from APS patients with diagnostic pattern DNA−/IgM−/IgG+ had anti-B19-VP1u activity. APS patients with anti-B19-VP1u antibody had a 4-fold increased risk for recurrent vascular thrombosis compared with those without anti-B19-VP1u antibody. The binding inhibition of CL, β2GPI, and PhL by absorption with B19-VP1u ranged from 31.4% to 91.1%, 0.8% to 59.8% and 20.2% to 72.1% respectively. Significantly higher inhibition to β2GPI by B19-VP1u absorption was observed in APS patients with anti-B19-VP1u antibody than in those without anti-B19-VP1u antibody. Conclusions We show a close association of B19 infection with aPL production and suggest B19-VP1u may be of pathogenetic importance in some patients with APS.

Increased macrophage vulnerability is associated with progression of systemic lupus erythematosus. Our previous studies have shown that cystamine, an inhibitor of transglutaminase 2 (TG2), alleviated the apoptosis of hepatocyte and brain cell in lupus-prone mice NZB/W-F1. In present study, we further investigated the effects of cystamine on apoptosis-prone macrophages (APMs) in the lupus mice. Using two-dimensional gel electrophoresis (2-DE) analysis, we found that cystamine induced a differential protein expression pattern of APM as comparing to the PBS control. The protein spots presenting differential level between cystamine and PBS treatment were then identified by peptide-mass fingerprinting (PMF). After bioinformatic analysis, these identified proteins were found involved in mitochondrial apoptotic pathway, oxidative stress, and mitogen-activated protein (MAP) kinase-mediated pathway. Further investigation revealed that cystamine significantly decreased the levels of apoptotic Bax and Apaf-1 and the activity of caspase-3, and increased the levels of anti-apoptotic Bcl-2 in APM. We also found that these apoptotic mediators were up-regulated in a correlation with the progression of lupus severity in NZB/W-F1, which were little affected in BALB/c mice. We also found that the reduced serum glutathione was restored by cystamine in NZB/W-F1. Interestingly, the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in APM and the phagocytic ability was diminished in presence of cystamine. In conclusion, our findings indicate that cystamine significantly inhibited mitochondrial pathway, induced antioxidant proteins, and diminished phosphorylation of extracellular ERK1/2, which may alleviate the apoptosis and the phagocytic ability of APM.

A hypercholesterolemic diet has been associated with the hepatic abnormalities and the pathological processes of systemic lupus erythematosus (SLE). To investigate the effects of taurine on the hepatic abnormality in SLE, NZB/W F1 mice were used as an animal model by receiving control, cholesterol, or cholesterol + taurine diets, respectively. Reductions (P < 0.05) of liver-to-body weight ratio, lipid deposit, mean arterial pressure, serum total cholesterol (TC), triacylglycerol (TAG), AST, ALT and hepatic CRP levels were detected in the cholesterol + taurine group as compared to those of the cholesterol group. In addition, stress-related molecules in livers, including HSP70, HSP90, MMP9 and iNOS, were also lower (P < 0.05) in the cholesterol + taurine group compared to the cholesterol group. These findings demonstrated the protective effects of taurine on the hepatic abnormality in NZB/W F1 mice fed a hypercholesterolemic diet and may suggest taurine as a dietary supplementation for SLE patients.

Antibodies against the proliferating cell nuclear antigen (PCNA) was first discovered in the sera of systemic lupus erythematosus (SLE) patients. However, the reactivity and specificity of anti-PCNA autoantibodies are still unclear. To investigate the property of anti-PCNA autoantibodies, we conducted an ELISA screening of the anti-PCNA autoantibodies in sera of SLE patients. Eighteen out of 191 SLE sera were found to be positive for anti-PCNA antibodies giving a frequency of nearly 10%. Among the positive sera, a sample with the highest titer of anti-PCNA autoantibody preferentially recognizes the wild-type PCNA as compared to the Y114A mutation which contains a single amino acid substitution at 114 and fails to form the toroidal structure. Moreover, the autoantibody purified from this serum identifies only the free PCNA in crude mammalian cell extracts but not other associated cellular components. This finding raises a possibility that immunostaining with the human anti-PCNA autoantibodies in previous studies might have only partially PCNAs in tissues.

A significantly higher prevalence of cardiovascular disease (CVD) is reported in patients with systemic lupus erythematosus (SLE) as compared with the general population and accounts for approximately 30% of deaths in SLE patients. However, the mechanism of and treatments for CVD in patients with SLE are still unclear. To explore the effects of taurine on cardiac abnormality in SLE, NZB/W F1 mice were used as the experimental model by receiving control, cholesterol, or cholesterol/taurine diets, respectively. Improved cardiac histopathological changes were observed in left ventricle tissues from the cholesterol/taurine group as compared to the control or cholesterol group. Significant reductions of TUNEL-positive cells, Fas death receptor-related components, mitochondrial-dependent apoptosis, cardiac fibrosis, and fibrotic signaling components were detected in the left ventricle tissues from the cholesterol/taurine group as compared to the control or cholesterol group. Additionally, cardiac IGR1R survival signaling components were significantly increased in the left ventricle tissues from the cholesterol/taurine group as compared to the control or cholesterol group. These findings revealed the protective effects of taurine against the cardiac abnormalities in NZB/W F1 mice and may suggest the potential for clinical application of taurine in treatment of CVD in SLE.

Evidence have indicated the impairment of central nervous system (CNS) and neuropsychiatric disorder in patients with systemic lupus erythematosus (SLE). However, little is known to improve the brain abnormality in SLE. To investigate the effect of cystamine on brain abnormality in SLE, NZB/W F1 mice were used as the animal model. Notably, significantly reduced neural Nitric Oxide Synthase (nNOS), inducible Nitric Oxide Synthase (iNOS), p53, p21WAF1/CIP1, and heat shock protein (HSP)-90 proteins were detected in the brain of NZB/W F1 mice that were treated with cystamine. In contrast, no variation was observed between the brain samples of BALB/c mice that were treated with PBS or cystamine. Moreover, significantly reduced Toll-like receptors- (TLR-) 4, 5 and 7 were detected in the brain samples of NZB/W F1 mice that were treated with cystamine whereas no variation of TLR-4, TLR-5, TLR-7, and TLR-9 was observed in BALB/c mice that were treated with PBS or cystamine. These findings demonstrated the beneficial effects of cystamine on brain abnormality in NZB/W F1 mice and probably suggested the potential of cystamine on treating patients with neuropsychiatric SLE.

Cholesterol-rich diets are known to cause hepatic apoptosis, which has been associated with the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanisms and treatments for hepatic apoptosis in SLE are poorly understood. To clarify the effects of taurine on hepatic apoptosis in SLE, NZB/W F1 mice received control, cholesterol, and cholesterol/taurine diets. Significant reductions of caspase-3 activity, TUNEL-positive cells, and Fas- and mitochondrial- dependent apoptosis were detected in liver from the cholesterol/taurine group as compared to the cholesterol group. Moreover, significant increases of phosphorylated AKT, NF-kappaB (p65), and ERK1/2 proteins were detected in liver from the cholesterol/taurine group as compared to the cholesterol group. In contrast, a significant reduction of phosphorylated p38 protein was observed in the cholesterol/taurine group. These experimental results demonstrated positive effects of taurine against hepatic apoptosis in NZB/W F1 mice fed a high-cholesterol diet and suggested the therapeutic potential of taurine in SLE.

Background Human parvovirus B19 infection has been frequently described as a cause or trigger of various autoimmune diseases. In previous studies, we have postulated the association among human parvovirus B19 (B19)-VP1 unique region (VP1u), production of anti-beta2-glycoprotein I (anti-β2GPI) antibody and anti-phospholipid syndrome (APS)-like autoimmunity. However, the precise role of B19-VP1u in induction of APS is still obscure. Methods To further elucidate the pathogenic roles of VP1u in B19 infection and autoimmunity, we examined the effect of anti-B19-VP1u IgG antibodies on endothelial cells that is recognized to play crucial roles in APS. Human vascular endothelial cells, ECV-304, were incubated with various preparations of purified human or rabbit IgG. The activation of endothelial cells and production of cytokines were assessed by flow cytometry and ELISA, respectively. Results Purified IgG from rabbits immunized with recombinant B19-VP1u proteins can up-regulate ICAM-1 (CD54), VCAM-1 (CD106), E-selectin (CD62E), MHC class II (HLA-DR, DP, DQ) molecule expression, and TNF-α production in endothelial cells as compared to those endothelial cells cultured with control IgG. Additionally, significantly increased phosphorylated-P38 mitogen-activated protein kinase (P38 MAPK) and iNOS were observed in both human anti-β2GPI IgG and rabbit anti-B19-VP1u IgG treated-ECV-304 cells, respectively. Conclusions These experimental results imply that antibodies against B19-VP1u play important roles in the immunopathological processes as well as human anti-β2GPI IgG that leads to development of APS by involving p38 phosphorylation and iNOS activation. It could provide a clue in understanding the role of anti-B19-VP1u antibodies in APS manifestations.

Objectives Matrix metalloproteinases (MMPs) are suggested to play important roles in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). This study is to examine the MMPs expressions and activities in Taiwanese RA and SLE patients. Design and methods Levels and activities of plasma MMP-2 and MMP-9 were investigated by enzyme-linked immunosorbent assay and zymography, respectively. Results MMP-2 levels in control subjects, RA and SLE patients were 146.1 ± 34.2, 194.0 ± 24.2 and 208.9 ± 75.9 ng/mL respectively, and for MMP-9 were 51.4 ± 57.1, 567.7 ± 313.1 and 208.7 ± 105.5 ng/mL respectively. Both MMP-2 and MMP-9 levels and activities from all patients were significantly higher than that from control subjects. Conclusions MMP-2 levels in both patients groups were approximately 1.3–1.4 folds higher than that in control subjects, notably, MMP-9 levels were 11- and 4-folds significantly higher, respectively, in RA and SLE patients. The results which MMP-2 and MMP-9 levels and activities are significantly elevated support the involvement of MMPs proteins in these autoimmune disorders.

Lyme arthritis and rheumatoid arthritis share common clinical features and synovial histology. It is unclear whether they also share similar pathogenesis. Previous studies have shown that the severity and duration of Lyme arthritis correlate directly with serum concentrations of antibody against outer surface protein A (OspA) of the causative pathogen Borrelia burgdorferi . We tested the sera of 68 subjects with rheumatoid arthritis, 147 subjects with other autoimmune diseases, and 44 healthy subjects who had never had Lyme disease, as well as sera of 16 patients who had Lyme disease, for reactivity against the B. burgdorferi OspA protein. The sera of about a quarter of the rheumatoid arthritis patients and a 10th of the autoimmune disease and Lyme disease patients reacted against OspA antigen. Of 50 rheumatoid arthritis patients who could be evaluated for disease severity, a 28-joint count disease activity score of >2.6 was noted for 11 of 15 (73%) patients whose sera reacted against OspA antigen and 13 of 35 (37%; P < 0.05) whose sera were nonreactive. Serum reactivity against OspA antigen is associated with the pathogenesis of rheumatoid arthritis.

Background Previous studies have postulated a connection between human parvovirus B19 (B19) infection and anti-phospholipid antibodies (APhL). B19 infection and anti-phospholipid syndrome (APS) exhibit congruent symptoms. Recently, phospholipase A2 (PLA2)-like activity has been linked to the VP1 unique region (VP1u) of B19. However, the precise role of B19-VP1u in pathogenesis of autoimmunity is still obscure. Methods To elucidate the roles of VP1u in B19 infection and autoimmunity, the reactivity of B19-VP1u proteins with various autoantibodies were evaluated by ELISA and immunoblotting. Rabbits were immunized with purified recombinant B19-VP1u protein to generate anti-sera. Absorption experiments were conducted to determine the binding specificity of rabbit anti-sera against B19-VP1u, cardiolipin (CL) and β-2-glycoprotein I (β2GPI). Moreover, the effects of passive transfer of polyclonal rabbit anti-B19-VP1u IgG antibodies on platelets, activated partial thromboplastin time (aPTT), and autoantibodies were assessed. Results Autoantibodies against CL, β2GPI, and phospholipid (PhL) in sera from patients with B19 infection, were cross-reactive with B19-VP1u. Consistently, sera from rabbits immunized with recombinant B19-VP1u protein displayed raised detectable immunoglobulins against B19-VP1u, CL, β2GPI and PhL. Additionally, the mice immunized with anti-B19-VP1u IgG developed thrombocytopenia, prolongation of aPTT, and autoantibody against β2GPI and PhL. Conclusions These experimental results suggested the association between B19-VP1u and production of anti-β2GPI antibodies, APhL, and APS-like autoimmunity. Altogether, it may provide a clue in understanding the role of B19-VP1u in inducing autoantibodies and B19-associated APS manifestations.