Circ_0008146 Exacerbates Ferroptosis via Regulating the miR-342-5p/ACSL4 Axis After Cerebral Ischemic/Reperfusion.

Purpose: Acute ischemic stroke (AIS) has seriously threatened people's health worldwide and there is an urge need for early diagnosis and effective treatment of AIS. This research intended to clarify the regulatory role of circ_0008146/miR-342-5p/ACSL4 axis in AIS. Methods: High-throughput small RNA sequencing analysis was adapted to identify differentially expressed miRNAs between the AIS and control group. The circ_0008146, miR-342-5p, and ACSL4 levels were detected by qRT-PCR. Middle cerebral artery occlusion/reperfusion (MCAO/R) models were constructed in C57BL/6J mice. Assay kits were used to determine Fe2+ levels and a battery of oxidative stress and lipid peroxidation indicators, including ROS, MDA, LPO, SOD and GSH/GSSG ratio. The protein levels of ACSL4 were measured by Western blot. The behavioral function was assessed using neurobehavioral tests. TTC staining was employed to visualize infarction size. Nissl staining was adapted to detect histopathological changes. Receiver operating characteristic curve and correlation analysis were applied to investigate the clinical value and association of miR-342-5p and ACSL4. Results: A total of 44 AIS patients and 49 healthy controls were enrolled in our study. The small RNA sequencing unveiled a significant decrease in miR-342-5p levels in AIS patients. MiR-342-5p inhibited oxidative stress and RSL3-induced ferroptosis after cerebral ischemic/reperfusion injury in vivo by targeting ferroptosis-related gene ACSL4. Circ_0008146 acted as a sponge of miR-342-5p, and overexpression of circ_0008146 increased neurological deficits and brain injury in mice. Circ_0008146 contributed to ferroptosis in cerebral infarction via sponging miR-342-5p to regulate ACSL4. Plasma miR-342-5p and ACSL4 demonstrated significant correlation and good diagnostic value for AIS patients. Conclusion: This study provides the first in vivo evidence to show that circ_0008146 exacerbates neuronal ferroptosis after AIS via the miR-342-5p/ACSL4 axis. Furthermore, miR-342-5p/ACSL4 axis holds promise as a viable therapeutic target and practical biomarkers for AIS patients.

Clinical evolution of antisynthetase syndrome-associated interstitial lung disease after COVID-19 in a man with Klinefelter syndrome: A case report.

BACKGROUND: This study presents a case of rapidly developing respiratory failure due to antisynthetase syndrome (AS) following coronavirus disease 2019 (COVID-19) in a 33-year-old man diagnosed with Klinefelter syndrome (KS). CASE SUMMARY: A 33-year-old man with a diagnosis of KS was admitted to the Department of Pulmonary and Critical Care Medicine of a tertiary hospital in China for fever and shortness of breath 2 wk after the onset of COVID-19. Computed tomography of both lungs revealed diffuse multiple patchy heightened shadows in both lungs, accompanied by signs of partial bronchial inflation. Metagenomic next-generation sequencing of the bronchoalveolar lavage fluid suggested absence of pathogen. A biopsy specimen revealed organizing pneumonia with alveolar septal thickening. Additionally, extensive auto-antibody tests showed strong positivity for anti-SSA, anti-SSB, anti-Jo-1, and anti-Ro-52. Following multidisciplinary discussions, the patient received a final diagnosis of AS, leading to rapidly progressing respiratory failure. CONCLUSION: This study underscores the clinical progression of AS-associated interstitial lung disease subsequent to viral infections such as COVID-19 in patients diagnosed with KS.

Shared and distinct prefrontal cortex alterations of implicit emotion regulation in depression and anxiety: An fNIRS investigation.

BACKGROUND: Emotion regulation deficits, particularly in cognitive reappraisal, are crucial in depression and anxiety. However, research on the neural mechanisms of implicit emotion regulation is lacking, and it remains unclear whether these mechanisms are shared or distinct between the two disorders. METHODS: We investigated the neural mechanisms of implicit cognitive reappraisal in 28 individuals with major depressive disorder (MDD), 25 with generalized anxiety disorder (GAD), and 30 healthy controls (HC) using functional near-infrared spectroscopy (fNIRS). Participants completed an implicit cognitive reappraisal task and underwent neuropsychological and clinical assessments. RESULTS: We found that MDD patients reported higher levels of rumination and lower utilization of cognitive reappraisal, while GAD patients reported reduced use of perspective-taking. Notably, both MDD and GAD patients exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) and orbitofrontal cortex (OFC) compared to HC participants during implicit cognitive reappraisal. Specifically, inadequate OFC activation was observed in MDD patients, while GAD patients demonstrated OFC deactivation during the task. Furthermore, DLPFC activation showed a negative correlation with depression severity in MDD patients, while OFC activation was positively correlated with perspective-taking in GAD patients. LIMITATIONS: fNIRS has limited depth and spatial resolution. CONCLUSION: Our fNIRS study is the first to reveal shared and distinct neurobiological profiles of depression and anxiety in implicit emotion regulation. These findings underscore the significance of reduced DLPFC/OFC activation in emotion regulation impairment and highlight unique OFC activation patterns in these disorders. These insights have potential implications for developing cognitive-behavioral therapy and transcranial magnetic stimulation as treatment approaches.

Resting-state cortico-limbic functional connectivity pattern in panic disorder: Relationships with emotion regulation strategy use and symptom severity.

Cognitive reappraisal is an effective emotion regulation strategy involving prefrontal cortex (PFC) control of the amygdala. Its aberrant functioning is closely associated with panic disorder (PD). However, the resting-state functional connectivity (rsFC) between the PFC, implicated in cognitive reappraisal, and the amygdala in PD has not been studied. Thus, this study aims to investigate the rsFC patterns and their association with cognitive reappraisal and PD. This study involved 51 participants, including 26 untreated patients with PD and 25 healthy controls (HC). We evaluated the habit of cognitive reappraisal assessment and the severity of PD using neuropsychological and clinical measures. Resting-state fMRI was utilized to evaluate the rsFC pattern between the PFC, engaged in cognitive reappraisal, and the amygdala. Mediation analysis was performed to explore the role of this rsFC in the relationship between cognitive reappraisal and PD severity. PD patients showed reduced rsFC between the PFC and the amygdala compared to HC. This weakened rsFC was associated with the severity of PD symptoms. Moreover, cognitive reappraisal was negatively correlated with PD severity, and mediation analysis indicated that the rsFC of the PFC-amygdala played a mediating role in this association. Abnormal PFC-amygdala rsFC may play a pivotal role in PD development and/or manifestation and mediate the association between cognitive reappraisal and PD severity, potentially serving as a clinical indicator for monitoring and intervention.

Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol.

As one of the key components of clinical trials, blinding, if successfully implemented, can help to mitigate the risks of implementation bias and measurement bias, consequently improving the validity and reliability of the trial results. However, successful blinding in clinical trials of traditional Chinese medicine (TCM) is hard to achieve, and the evaluation of blinding success through blinding assessment lacks established guidelines. Taking into account the challenges associated with blinding in the TCM field, here we present a framework for assessing blinding. Further, this study proposes a blinding assessment protocol for TCM clinical trials, building upon the framework and the existing methods. An assessment report checklist and an approach for evaluating the assessment results are presented based on the proposed protocol. It is anticipated that these improvements to blinding assessment will generate greater awareness among researchers, facilitate the standardization of blinding, and augment the blinding effectiveness. The use of this blinding assessment may further advance the quality and precision of TCM clinical trials and improve the accuracy of the trial results. The blinding assessment protocol will undergo continued optimization and refinement, drawing upon expert consensus and experience derived from clinical trials. Please cite this article as: Wang XC, Liu XY, Shi KL, Meng QG, Yu YF, Wang SY, Wang J, Qu C, Lei C, Yu XP. Blinding assessment in clinical trials of traditional Chinese medicine: Exploratory principles and protocol. J Integr Med. 2023; 21(6): 528-536.

Probiotics Can Boost the Antitumor Immunity of CD8+T Cells in BALB/c Mice and Patients with Colorectal Carcinoma.

BACKGROUND: The drug resistance and the immune suppression in the tumor microenvironment are important factors affecting tumor progression. Reversing drug resistance and changing tumor suppression microenvironment are ideal ways to inhibit tumor progression. OBJECTIVE: The aim of the study is to verify antitumor immune response of probiotics in patients with colorectal carcinoma and to explore its mechanism. METHODS: To detect the tumor samples of 122 patients with colorectal carcinoma after surgery, analyze the effect of probiotics on enhancing tumor-infiltrating CD8+T cells to inhibit colorectal carcinoma, and further verify the mechanism of probiotics on enhancing the antitumor immune response of CD8+T cells through animal experiments. RESULTS: The results of immunohistochemistry showed that the proportion of CD8+T cells in the patients treated with probiotics before surgery was increased significantly than that in other patients (P = 0.033). The results of flow cytometry also showed that the proportion of CD8+T cells in the probiotics group was higher than that in the nonprobiotics group (P = 0.029). Kaplan-Meier survival estimates also showed that the CD8+T cells, TNM stage, pathology grade, lymphatic metastasis, and probiotic treatment were significantly associated with the progression-free survival (PFS) (χ 2 = 9.684, P = 0.002 for CD8+T cells; χ 2 = 5.878, P = 0.015 for TNM stage; χ 2 = 7.398, P = 0.004 for pathology grade; χ 2 = 8.847, P = 0.003 for Lymphatic metastasis; and χ 2 = 4.622, P = 0.032 for the group (group A was treated with probiotics before surgery; group B was not treated with probiotics)). The experimental results in mice showed that probiotics could inhibit tumor growth and increase the proportion of CD8+T cells in mice; the difference was statistically significant (P = 0.037). It was also found that probiotic feeding could upregulate the expression of T-cell immunoglobulin mucin receptor 1(TIM-1) in CD8+T cells of mice and also found that probiotic feeding could downregulate the expression of programmed cell death protein 1 (PD-1) in CD8+T cells of mice, compared with the nonfeeding group; the difference was statistically significant (P = 0.045 for TIM-1 and P = 0.02 for PD-1, respectively). In order to further understand the functional status of CD8+T cells, we analyzed interferon-gamma (IFN-γ)+ T cells and tumor necrosis factor-α (TNF-α)+CD8+T cells by flow cytometry. The results showed that the proportion of IFN-γ + T cells and TNF-α +CD8+T cells significantly increased after probiotic treatment, compared with the nonprobiotic treatment group; the difference was statistically significant (P = 0.040 for IFN-γ + T cells and P = 0.014 for TNF-α +CD8+T, respectively). CONCLUSIONS: Probiotics can enhance the antitumor immune response of CD8+T cells. It can play a synergistic antitumor role. On the one hand, its mechanism is through regulating intestinal flora, and on the other hand, through regulating the antitumor immune function of CD8+T cells.

Prognostic value of carbohydrate antigen125 and carcino embryonic antigen expression in patients with colorectal carcinoma and its guiding significance for chemotherapy.

The aim of this study is to evaluate the predictive value of carbohydrate antigen125 (CA125) and carcino embryonic antigen (CEA) expression and its guiding role of choosing chemotherapy regimen in post-operation patients with colorectal carcinoma.The clinical data of all patients, including laboratory data and pathological data, were collected from the electronic medical records. Kaplan-Meier Log rank test, COX regression model and subgroup analyses were employed to assess the correlation between the expression of CA125 and CEA in patients with colorectal carcinoma and the survival, and the effect on chemotherapy efficacy.Kaplan-Meier showed that CA125 expression is negatively related to the progression-free survival (PFS) of the post-operative patients, Median PFS was 1140 days in the patients with high expression, and Median PFS was 1387 days in the patients with low expression (χ = 4.715, P = .030); CEA expression is also negatively associated with the PFS of the post-operative patients, Median PFS was 1197 days in the patients with high expression, and Median PFS was 1424 days in the patients with low expression (χ = 4.992, P = .025). Subgroup analysis also showed that the patients with normal CA125 and CEA had better prognosis, median PFS was 1505 days, and the patients with CA125 and (or) CEA high expression had poor prognosis and median PFS was 1162 days (χ = 13.346, P = .001), and found that there was no statistical difference in patients with oxaliplatin plus capecitabine (XELOX) and oxaliplatin, 5-fluorouracil and Calcium folinate (FOLFOX) chemotherapy in patients with CA125 and CEA low expression. However, in these patients with CA125 or (and) CEA high expression, the median PFS of patients treated with XELOX was 1082 days, and the median PFS of patients treated with FOLFOX chemotherapy was 1335 (χ = 4.547, P = .033).Expression of CA125 and CEA associated with the survival of patients, and have some guiding significance for chemotherapy in patients with colorectal cancer after operation; Compared with XELOX, FOLFOX chemotherapy is more effective for CA125 or (and) CEA high expression patients with colorectal carcinoma.

Activity of fibroblast-like synoviocytes in rheumatoid arthritis was impaired by dickkopf-1 targeting siRNA.

BACKGROUND: Fibroblast-like synoviocytes (FLSs), resident mesenchymal cells of synovial joints, play an important role in the pathogenesis of rheumatoid arthritis (RA). Dickkopf-1 (DKK-1) has been proposed to be a master regulator of bone remodeling in inflammatory arthritis. Here, potential impairation on the activity of FLSs derived from RA to small interfering RNAs (siRNAs) targeting DKK-1 was investigated. METHODS: siRNAs targeting DKK-1 were transfected into FLSs of patients with RA. Interleukin (IL)-1ß, IL-6, IL-8, matrix metalloproteinase (MMP) 2, MMP3, MMP9, transforming growth factor (TGF)-ß1, TGF-ß2 and monocyte chemoattractant protein (MCP)-1 levels in the cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). Invasion assay and H incorporation assay were utilized to investigate the effects of siRNAs targeting DKK-1 on FLSs invasion and cell proliferation, respectively. Western blotting was performed to analyze the expression of nuclear factor (NF)-κB, interleukin-1 receptor-associated kinase (IRAK)1, extracellular regulated protein kinases (ERK)1, Jun N-terminal kinase (JNK) and ß-catenin in FLSs. RESULTS: DKK-1 targeting siRNAs inhibited the expression of DKK-1 in FLSs (P < 0.01). siRNAs induced a significant reduction of the levels of IL-6, IL-8, MMP2, MMP3 and MMP9 in FLSs compared to the control group (P < 0.05). DKK-1 targeting siRNAs inhibited the proliferation and invasion of FLSs (P < 0.05). Important molecules of pro-inflammatory signaling in FLSs, including IRAK1 and ERK1, were decreased by the inhibition of DKK-1 in FLSs. In contrast, ß-catenin, a pivotal downstream molecule of the Wnt signaling pathway was increased. CONCLUSIONS: By inhibiting DKK-1, we were able to inhibit the proliferation, invasion and pro-inflammatory cytokine secretion of FLSs derived from RA, which was mediated by the ERK or the IRAK-1 signaling pathway. These data indicate the application of DKK-1 silencing could be a potential therapeutic approach to RA.

Pmma-XO (X = C, Si, Ge) monolayer as promising anchoring materials for lithium-sulfur battery: a first-principles study.

Lithium-sulfur (Li-S) batteries hold great promise for the next-generation lithium-ion energy storage devices. A key issue in the Li-S batteries is, however, the dissolving and migrating of the soluble polysulfides during the charge and discharge processes and introducing anchoring materials (AM) in the batteries effectively prevent the problem and improve the cycling stability of the Li-S batteries. Herein, Pmma-XO (X = C, Si, Ge, Sn) monolayers are introduced as AM to confine the lithium polysulfides and their anchoring properties are studied with the density functional theory methods. Particularly, Pmma-SiO and GeO monolayers are studied for the first time, and our calculations show that these two materials are stable semiconductive monolayers with direct-band-gaps and moderate binding with lithium polysulfides Li2S n (n = 8, 6, 4, 2 and 1). The Pmma-SiO and GeO trap Li2S n species on their surfaces and keep them intact during the charge and discharge, and the adsorption of Li2S n species leads to the enhanced conductivity of Pmma-SiO and GeO monolayers. Our study suggests that the Pmma-SiO and GeO monolayers are the promising AM for highly efficient Li-S batteries.

Isoliquiritigenin inhibits proliferation and metastasis of MKN28 gastric cancer cells by suppressing the PI3K/AKT/mTOR signaling pathway.

Isoliquiritigenin (ISL) is a flavonoid extracted from licorice root, which is known to serve important antitumor roles in numerous types of cancers; however, its effect on gastric cancer remains to be elucidated. The present study aimed to explore the roles and underlying mechanisms of ISL in MKN28 gastric cancer cells. MKN28 cell proliferation was measured using the Cell Counting Kit­8 (CCK8) assay. A Transwell assay was used to determine the effects of ISL on the migration and invasion of MKN28 cells. Apoptosis was assessed by flow cytometry, and the expression levels of apoptosis­, autophagy­ and signaling pathway­related proteins were detected by western blot analysis. The results of the CCK8 assay demonstrated that ISL significantly inhibited the proliferation of MKN28 cells (P<0.05). Transwell assays demonstrated that the migration and invasion of MKN28 cells were significantly inhibited following treatment with ISL (P<0.05). Flow cytometric analysis indicated that ISL induced apoptosis of MKN28 cells. In addition, western blot analysis revealed that the ratio of microtubule­associated proteins 1A/1B light chain 3B (LC3)II/LC3I was upregulated, as was Beclin 1 expression; however, p62 was downregulated following ISL pretreatment, thus suggesting that ISL triggered autophagy in MKN28 cells. In addition, the phosphorylation levels of protein kinase B (AKT) and mammalian target of rapamycin (mTOR) were significantly reduced following ISL treatment. These results indicated that ISL may influence apoptosis and autophagy in MKN28 cells by suppressing the phosphoinositide 3­kinase/AKT/mTOR signaling pathway. In conclusion, the findings of the present study suggested that ISL may inhibit MKN28 cell proliferation, migration and invasion by inducing apoptosis and autophagy, implying potential as a therapeutic agent for gastric cancer.

Treatment efficacy and safety of low-dose azathioprine in chronic active ulcerative colitis patients: A meta-analysis and systemic review.

OBJECTIVE: To evaluate the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active ulcerative colitis (UC). METHODS: A literature search of Medline, Embase, the Cochrane Library, Web of Science, Wanfang Database, CNKI, SinoMed, VIP Chinese Science and the Technology Journals Database was conducted to identify eligible studies that evaluated the efficacy and safety of low-dose azathioprine (AZA) in treating patients with chronic active UC published up to 15 July 2015. Data were extracted from the studies, including clinical efficacy (response rate, adverse drug reaction [ADR] rate, steroid withdrawal rate and relapse rate) and endoscopic improvement (endoscopic remission rate and mucosal healing rate). RESULTS: Six studies with 211 patients were eligible for the analysis. The overall response rates after 6 and 12 months of treatment were 78.0% (95% confidence interval [CI] 71.0-85.0%) and 88.0% (95% CI 80.0-96.0%), respectively. The overall ADR rate was 25.0% (95% CI 18.0-31.0%). Endoscopic response rate was around 85.0%, while the endoscopic remission rates and mucosal healing rates after 6 and 12 months of treatment were above 60.0% and 70.0%, respectively. The steroid withdrawal rate and relapse rate were in moderate to high heterogeneity. Egger's test indicated that there was no publication bias for studies regarding the 6-month response rate and ADR rate. CONCLUSIONS: Low-dose AZA is effective and safe in the treatment of chronic active UC patients. However, randomized controlled trials with large sample sizes are needed to draw definitive conclusions.

[Clinical research of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma].

This study was purposed to explore the efficacy and feasibility of reduced-intensity allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of multiple myeloma (MM). Three patients with MM from January 2011 to January 2012 in General Hospital of Beijing Military Area were treated by reduced-intensity allo-HSCT. All donors are compatriots and affinity HLA identical. Donors were mobilized with granulocyte colony-stimulating factor (G-CSF), the MM patients were given combined transplantation of bone marrow and peripheral blood stem cells. Preconditioning regimen consisted of fludarabine combined with melphalan and anti-human thymocyte globulin, and the classic cyclosporin A (CsA) combined with methotrexate (MTX) was used to prevent graft-versus-host disease (GVHD). The preventive donor peripheral blood stem cell infusion in dose 0.2×10(8)/kg mononuclear cells (MNC) was applied after 3 months of transplantation, then the toxicity, GVHD and disease-free survival (DFS) in patients were observed after transplantation. The results showed that 3 patients got hematopoietic reconstitution, the average time of neutrophils ≥ 0.5×10(9)/L and platelets ≥ 20×10(9)/L was 14.3 d and 15.3 d respectively, the detection of implanting efficacy displayed 100% complete donor hematopoiesis. Follow-up to January 2013, the median follow-up time was 13 months (12 to 15 months), As a result, none of the patients got GVHD, infection and other serious complications, all patients are still in complete remission (CR), the longest DFS time has reached to 15 months. It is concluded that the reduced-intensity allogeneic hematopoietic stem cell transplantation is the effective method for MM, this method has the high safety and efficacy, as well as high complete remission rate in early transplantation, the MM patients may get a long-term survival. This method can be used as a key technology in clinic for treating MM.

Epidemiology of eight common rheumatic diseases in China: a large-scale cross-sectional survey in Beijing.

OBJECTIVE: To investigate the prevalence of eight common rheumatic diseases in a large Chinese population. METHODS: A population-based epidemiological investigation of the prevalence of eight common rheumatic diseases in a suburb of Beijing was conducted in 14 642 individuals. A community-based survey was carried out using a screening questionnaire. Positive responders were included in a clinical and laboratory examination. Diagnosis was based on the criteria of ACR or those used widely in literature. RESULTS: A total of 10 556 inhabitants were interviewed. Forty-three cases of RA were identified with an age-adjusted prevalence of 0.28% (95% CI 0.19%, 0.41%). Gout was diagnosed with a crude prevalence of 0.09% (95% CI 0.05%, 0.17%). Psoriasis was reported in 28 individuals with a prevalence of 0.27% (95% CI 0.18%, 0.38%). This included two cases diagnosed with PsA, resulting in a prevalence of 7.14% (95% CI 0.88%, 23.5%) in psoriasis patients and 0.02% (95% CI 0%, 0.07%) in the general population. Three individuals were identified with SLE, with a prevalence of 0.03% (95% CI 0%, 0.06%). One individual was identified with SSc and the calculated prevalence was 0.01% (95% CI 0%, 0.05%). One case of Behçet's disease was identified, giving a prevalence of 0.01% (95% CI 0%, 0.05%). CONCLUSION: This large-scale epidemiological survey provides an estimate of the burden of rheumatic diseases in China.

Circulating Dickkopf-1 is correlated with bone erosion and inflammation in rheumatoid arthritis.

OBJECTIVE: To explore the potential role of Dickkopf-1 (DKK-1) in rheumatoid arthritis (RA) and to evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (infliximab) and an interleukin 1 receptor antagonist (IL-1Ra; anakinra) on DKK-1 secretion in patients with RA. METHODS: Serum samples were collected from 100 patients with RA, 100 patients with other rheumatic diseases (e.g., osteoarthritis and ankylosing spondylitis), and 40 healthy controls. DKK-1 and osteoprotegerin (OPG) levels in serum were detected by ELISA. Serum C-reactive protein (CRP) levels, erythrocyte sedimentation rates (ESR), rheumatoid factor (RF) titers, and anti-cyclic citrullinated peptide antibody were also measured in patients with RA. RESULTS: The serum level of DKK-1 was significantly higher in patients with RA than in healthy controls and those with other rheumatic diseases (p < 0.01); the serum DKK-1 level was correlated with levels of CRP (r = 0.488, p = 0.003) and ESR (r = 0.458, p = 2.4 x 10(-4)) and the Sharp score of radiologic change (r = 0.449, p = 0.001) in RA. In contrast to the increasing level of OPG, DKK-1 was significantly decreased in RA patients treated with TNF-α inhibitor (p < 0.01). DKK-1 was significantly decreased in RA patients treated with IL-1Ra (p < 0.01). CONCLUSION: DKK-1, as an important mediator, was correlated with bone erosion and inflammation in RA. The change of DKK-1 level may serve as a biomarker of disease activity and bone erosion.

Circulating Dickkopf-1 and osteoprotegerin in patients with early and longstanding rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by inflammation of the synovial membrane, leading to invasion of synovial tissue into the adjacent cartilage matrix with degradation of articular cartilage and bone as a consequence. Dickkopf-1 (DKK-1) and osteoprotegerin (OPG) have been demonstrated to be key molecules involved in bone erosion and bone remodeling. The aim of this study was to explore the potential role of DKK-1 and OPG in different stage of RA. METHODS: The protein levels of DKK-1 and OPG were detected by ELISA. The serum samples were collected from 300 patients with RA and 60 healthy controls. Of which, 150 RA patients were defined as early RA (disease duration < or = 1 year), and other 150 RA patients were defined as longlasting RA (disease duration > or = 5 years). At the time of serum sampling, various clinical and laboratory parameters were assessed. The correlations of DKK-1 or OPG and clinical/laboratory parameters were analyzed. RESULTS: The serum level of DKK-1 was elevated in patients with longstanding RA compared with healthy controls, while no significant difference was observed between the two groups in the level of OPG. In contrast, in early RA patients, the circulating OPG was elevated, while there was no significant difference between the two groups in expression of DKK-1. The serum DKK-1 was correlated with Sharp score and DAS28 in longstanding RA patients. In early RA, age was the only parameter that was significantly related to serum OPG. CONCLUSIONS: There was a cross-talk between DKK-1 and OPG, which involved in bone destruction in RA. In different stage of RA, DKK-1 and OPG may play different roles in the pathogenesis of RA.

[Mechanisms of juvenile neuronal ceroid lipofuscinosis (JNCL)].

Juvenile neuronal ceroid lipofuscinosis (JNCL) is one type of the neuronal ceroid lipofuscinosis (NCLs), which is a group of pediatric neurodegenerative disorders. The symptoms of JNCL are retinal degeneration (rd), seizures, cognitive, and motor decline. The pathogenesis, summarized in this review, include apoptosis, autophagy, dysfunction in the structure associated with plasmalemma, oxidative stress and disruption of nitric oxide signaling, dysfunction of the mitochondrial and lysosome, unbalanced intracellular pH, and other relative mechanisms. Among them, only apoptosis and autophagy are well known. In apoptosis, the defects in CLN3 result in ceramide accumulation and upstream of mitochondrial membrane per-meabilization, which eventually induce caspase-dependent and caspase-independent cell death. Autophagy exists but is disrupted because the immaturity of autophagic vacuoles leads to the failure of autophagy circulation. Understanding of the pathogenesis, especially the pathways of cell death in JNCL, is helpful to explore the mechanism of neurodegenerative dis-orders, such as JNCL.

Inhibitory effect of activin A on activation of lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells.

Activin A is a member of transforming growth factor beta (TGF-beta) superfamily, which is also named restrictin-P, and can inhibit the secretion of nitric oxide (NO) and interleukin-1beta (IL-1beta) from LPS-activated mouse macrophages. In this study, the regulation effect and possible mechanism of activin A as an anti-inflammatory factor on lipopolysaccharide (LPS)-activated macrophages were investigated in vitro. It was observed that activin A could not only decrease the secretion of IL-1beta and NO, as well as the mRNA expressions of IL-1beta and iNOS, but also suppress the pinocytosis of mouse macrophage cell line RAW264.7 cells induced by LPS. In addition, activin A could obviously reduce the expressions of CD68 and CD14, as well as Toll-like receptor 4 (TLR4) on RAW264.7 cells induced by LPS, but could not influence the proliferation of RAW264.7 cells. These findings suggest that activin A may play an important down-regulation role in inflammatory factor production and phagocytosis of the activated macrophages via suppressing the maturation of LPS-induced macrophages or LPS-TLR4 signal transduction.