The Impact of Delirium after Radical Prostatectomy on Cognitive Function and Health Perception during the Recovery Period.

OBJECTIVE: This study aims to investigate the influence of delirium following radical prostatectomy on cognitive function and health perception during the recovery period. METHODS: Data were collected from patients who underwent radical prostatectomy at our institution between May 2020 and May 2022. Postoperative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), categorising patients into delirium and non-delirium groups. The Montreal Cognitive Assessment (MoCA) and the Brief Illness Perception Questionnaire (BIPQ) were employed to evaluate patients' mental health pre-and post-surgery. Comparative analyses were conducted between patients with and without delirium in the critical care unit, and correlation analyses were performed. RESULTS: The study revealed a delirium incidence rate of 19.13%. Patients in the delirium group exhibited significantly higher age and ICU length of stay compared to those without delirium (p < 0.05). No significant differences were observed in MoCA scores one day before surgery and seven days after surgery, as well as BIPQ scores one day before surgery, five days after surgery and seven days after surgery between the delirium and non-delirium groups (p > 0.05); However, the MoCA scores in the delirium group were significantly lower than those of the non-delirium group on the second and fifth days post-surgery. Additionally, the BIPQ scores in the delirium group were significantly higher than those in the non-delirium group two days after surgery (p < 0.001). A moderate negative correlation was observed between MoCA scores and CAM-ICU scores, and a moderate positive correlation was identified between BIPQ scores and CAM-ICU scores (p < 0.001). CONCLUSIONS: Patients experiencing delirium after radical prostatectomy are at a higher risk of cognitive function impairment and disease threat perception. A significant correlation exists between postoperative delirium and cognitive function as well as health perception.

The Impact of Delirium after Radical Prostatectomy on Cognitive Function and Health Perception during the Recovery Period

Objective: This study aims to investigate the influence of delirium following radical prostatectomy on cognitive function and health perception during the recovery period. Methods: Data were collected from patients who underwent radical prostatectomy at our institution between May 2020 and May 2022. Postoperative delirium was assessed using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), categorising patients into delirium and non-delirium groups. The Montreal Cognitive Assessment (MoCA) and the Brief Illness Perception Questionnaire (BIPQ) were employed to evaluate patients’ mental health pre-and post-surgery. Comparative analyses were conducted between patients with and without delirium in the critical care unit, and correlation analyses were performed. Results: The study revealed a delirium incidence rate of 19.13%. Patients in the delirium group exhibited significantly higher age and ICU length of stay compared to those without delirium (p < 0.05). No significant differences were observed in MoCA scores one day before surgery and seven days after surgery, as well as BIPQ scores one day before surgery, five days after surgery and seven days after surgery between the delirium and non-delirium groups (p > 0.05); However, the MoCA scores in the delirium group were significantly lower than those of the non-delirium group on the second and fifth days post-surgery. Additionally, the BIPQ scores in the delirium group were significantly higher than those in the non-delirium group two days after surgery (p < 0.001). A moderate negative correlation was observed between MoCA scores and CAM-ICU scores, and a moderate positive correlation was identified between BIPQ scores and CAM-ICU scores (p < 0.001). Conclusions: Patients experiencing delirium after radical prostatectomy are at a higher risk of cognitive function impairment and disease threat perception... (AU)

CD_99 G1 neutrophils modulate osteogenic differentiation of mesenchymal stem cells in the pathological process of ankylosing spondylitis.

OBJECTIVES: This study aimed to identify the types and heterogeneity of cells within the spinal enthesis and investigate the underlying mechanisms of osteogenesis. METHODS: Single-cell RNA sequencing was used to identify cell populations and their gene signatures in the spinal enthesis of five patients with ankylosing spondylitis (AS) and three healthy individuals. The transcriptomes of 40 065 single cells were profiled and divided into 7 clusters: neutrophils, monocytic cells, granulomonocytic progenitor_erythroblasts, T cells, B cells, plasma cells and stromal cells. Real-time quantitative PCR, immunofluorescence, flow cytometry, osteogenesis induction, alizarin red staining, immunohistochemistry, short hairpin RNA and H&E staining were applied to validate the bioinformatics analysis. RESULTS: Pseudo-time analysis showed two differentiation directions of stromal cells from the mesenchymal stem cell subpopulation MSC-C2 to two Cxcl12-abundant-reticular (CAR) cell subsets, Osteo-CAR and Adipo-CAR, within which three transcription factors, C-JUN, C-FOS and CAVIN1, were highly expressed in AS and regulated the osteogenesis of mesenchymal stem cells. A novel subcluster of early-stage neutrophils, CD99_G1, was elevated in AS. The proinflammatory characteristics of monocyte dendritic cell progenitor-recombinant adiponectin receptor 2 monocytic cells were explored. Interactions between Adipo-CAR cells, CD99_G1 neutrophils and other cell types were mapped by identifying ligand-receptor pairs, revealing the recruitment characteristics of CD99_G1 neutrophils by Adipo-CAR cells and the pathogenesis of osteogenesis induced in AS. CONCLUSIONS: Our results revealed the dynamics of cell subpopulations, gene expression and intercellular interactions during AS pathogenesis. These findings provide new insights into the cellular and molecular mechanisms of osteogenesis and will benefit the development of novel therapeutic strategies.

Diagnostic value of anti-Kaiso autoantibody in axial spondyloarthritis.

Objective: Axial spondyloarthritis (axSpA) is a chronic rheumatic disease predominantly characterized by inflammation and progressive structural damage. Patients are often diagnosed very late, which delays the optimal treatment period. Early diagnosis of axSpA, especially non-radiographic axSpA (nr-axSpA), remains a major challenge. This study aimed to investigate the diagnostic value of anti-Kaiso autoantibodies in axSpA and their correlation with clinical disease indicators. Methods: Two pooled serum samples (seven patients with nr-axSpA and seven healthy controls) were profiled using HuProt arrays to investigate the diagnostic value of autoantibodies in nr-axSpA. Levels of anti-Kaiso autoantibodies in patients with axSpA and controls were determined using the Meso Scale Discovery assay system. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic performance of anti-Kaiso autoantibodies in axSpA. Pearson's correlation was used to assess the correlation between anti-Kaiso autoantibodies and clinical parameters. Results: Seven candidate autoantibodies were present in the serum of patients with nr-axSpA. The levels of anti-Kaiso autoantibodies were significantly higher in the nr-axSpA group than in the other groups. It can differentiate nr-axSpA from ankylosing spondylitis (AS), healthy controls, and rheumatoid arthritis. The level of early-stage AS among patients with nr-axSpA decreased when they progressed to the late stage. Of all patients with axSpA, serum anti-Kaiso autoantibody levels were positively correlated with the C-reactive protein level and the Bath Ankylosing Spondylitis Disease Activity Index score and negatively correlated with disease duration. Conclusion: Anti-Kaiso autoantibody may be a valuable diagnostic biomarker for early-stage AS in the nr-axSpA period and may be a potential therapeutic target.

Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway.

Bone homeostasis is maintained by a dynamic balance between bone formation and bone resorption. The cellular activities of osteoblasts and osteoclasts are the primary factors that maintain this dynamic balance. The transcription factor Kaiso has been identified as a regulator of cell proliferation and differentiation in various cells. However, research into its role in bone homeostasis is currently lacking. In the present study, cell and animal experiments were conducted to investigate the role of Kaiso in bone homeostasis. The present study identified that Kaiso was downregulated during osteoblast differentiation in MC3T3­E1 cells. Gain­ and loss­of­function studies in MC3T3­E1 cells demonstrated that Kaiso served a critical role in osteoblast differentiation in vitro. The findings were further confirmed in vivo. The results of the sequence analysis indicated that Kaiso influenced osteoblast differentiation and mineralization by regulating the PI3K/AKT signaling pathway. Moreover, integrin subunit α10 (Itga10) was identified as a direct target of Kaiso via chromatin immunoprecipitation and luciferase reporter assays. Collectively, these findings suggested that Kaiso regulated the differentiation of osteoblasts via the Itga10/PI3K/AKT pathway, which represents a therapeutic target for bone formation or bone resorption­related diseases.

Punicalagin Exerts Protective Effects against Ankylosing Spondylitis by Regulating NF-κB-TH17/JAK2/STAT3 Signaling and Oxidative Stress.

BACKGROUND: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliitis and spinal rigidity of the axial joints. The role of oxidative stress and increased proinflammatory cytokines is well documented in AS pathogenesis. Punicalagin (2,3-hexahydroxydiphenoyl-gallagyl-D-glucose), an ellagitannin widely present in pomegranates, is found to exhibit potent anti-inflammatory, antiproliferative, and antioxidative effects. The present study was undertaken to investigate the effects of punicalagin in a rodent model of AS. METHODS: BALB/c mice induced spondylitis were sacrificed 24 h after the last injection of proteoglycan extract. Histological scoring was done to assess the degree of the disease. The expression of JAK2/STAT3 proteins and proteins of the nuclear factor-κB (NF-κB) pathway was determined by immunoblotting. Serum levels of inflammatory mediators-TNF-α, IL-1ß, IL-6, IL-17A, and IL-23-were assessed. Levels of lipid peroxidation and reactive oxygen species (ROS) were quantified. Antioxidant status as a measure of activities of antioxidant enzymes-catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD)-was determined. RESULTS: Punicalagin effectively improved antioxidant status and decreased lipid peroxidation, ROS production, and serum levels of inflammatory mediators. NF-κB pathway and JAK2/STAT3 signaling were significantly (p < 0.05) downregulated. Punicalagin effectively regulated the production of cytokines by the Th17 cells and the IL-17A/IL-23 axis. CONCLUSION: The observations suggest that punicalagin exerts a protective role in AS via reducing oxidative stress and regulating NF-κB/TH17/JAK2/STAT3 signal. Punicalagin thus could be explored further as a potent candidate compound in the treatment of AS.

PDGFRB as a potential therapeutic target of ankylosing spondylitis: validation following bioinformatics analysis.

Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disease that mainly affects the central axis joint. Although this disease has already been well documented and studied, its pathogenesis is still not well understood. This study aimed to screen and identify key candidate genes involved in the progression of AS. For this purpose, expression profiles of GSE39340 and GSE41038 were downloaded from the Gene Expression Omnibus and displayed in the form of volcano plots and heatmaps. Differentially expressed genes (DEGs) were identified by the Limma package in R and functional enrichment analyses were performed. Moreover, STRING and Cytoscape were utilized to construct protein-protein interaction (PPI) networks and screen significant modules. Immunohistochemistry (IHC) in tissue chips of AS and normal human synovial tissues was performed to confirm the major proteins associated with its development. Western blotting (WB) and alizarin red staining were applied to validate the expression level of platelet-derived growth factor receptor beta (PDGFRB) and function during osteogenesis differentiation of fibroblasts in AS. A total of 256 DEGs were screened, including 191 up-regulated genes and 65 down-regulated genes. The enriched functions of these identified genes mainly included adherens junction, focal adhesion, and cell-substrate adherens junction. The pathways most highly associated with the progression of AS were TGF-ß signaling pathway, the Hippo signaling pathway, and the AGE-RAGE signaling pathway. In addition, IHC showed that mitogen-activated protein kinase 1 (MAPK1), C-X-C motif chemokine receptor 4 (CXCR4), and PDGFRB were highly expressed in AS. PDGFRB was found upregulated during osteogenesis of fibroblasts and stimulates osteogenesis in AS. These findings may improve our understanding of the molecular mechanisms controlling AS. Pharmacological targeting of PDGFRB may initiate a possible suppression of bone formation in AS.

Cross-cultural adaption and validation of simplified Chinese version of the lower extremity function scale in patients with knee osteoarthritis.

INTRODUCTION: The lower extremity function scale (LEFS) is widely used to investigate patients' functional status due to musculoskeletal dysfunction of the lower extremity. The aims of this study were to translate and cross-culturally adapt the LEFS into simplified Chinese (SC-LEFS) and evaluate the psychometric properties in patients with knee osteoarthritis (OA). METHODS: The SC-LEFS was translated and cross-culturally adapted on the basis of guideline. Patients scheduled for knee arthroplasty (108) were invited in this study. The Cronbach's alpha coefficient was employed to assess the internal consistency. The test-retest reliability was determined by intra-class correlation coefficient (ICC). Pearson's correlation coefficient was detected to evaluate the criterion validity between the SC-LEFS and WOMAC/SF-36/range of motion (ROM). Construct validity was assessed by exploratory factorial analysis. Additionally, responsiveness analysis was conducted with effect size (ES) and standardized response mean (SRM). RESULTS: The results revealed good internal consistency (Cronbach's alpha = 0.975) and good test-retest reliability (ICC = 0.937). Strong correlations were observed between the SC-LEFS and WOMAC pain/function/total, physical component summary of SF-36, and ROM. We confirmed the SC-LEFS as a two-factor structure with factor 1 and factor 2 explaining 73.781% and 5.546% of the variance, respectively. The ES (1.74) and SRM (1.95) indicated a good responsiveness. CONCLUSIONS: The SC-LEFS has been nicely adapted into simplified Chinese. It was proved to be reliable and valid for knee OA patients from China mainland who are undergoing arthroplasty. Furthermore, additional research should be conducted to assess these findings in other dysfunctions of lower extremity in a larger sample size. Key Points • The present study firstly cross-culturally adapted the lower extremity function scale (LEFS) into simplified Chinese and applied for patients with knee osteoarthritis in China mainland. • The psychometric properties including reliability, validity, and responsiveness were evaluated in SC-LEFS. • The SC-LEFS turned out to be a reliable and valid tool for clinical physicians and researchers assessing patients with knee osteoarthritis.

Bibliometric analysis of research on the trends in autophagy.

BACKGROUND: Autophagy is an important mechanism to maintain homeostasis in cells. It has been linked with ageing and many currently incurable diseases, including heart disease, cancer, myopathies, neurodegeneration, and diabetes. Autophagy research is very important for identifying better treatments. This study aimed to explore the hotspots of autophagy research published from different countries, organizations, and authors. METHODS: Between 1962 and 2018, articles published about autophagy were identified in the Web of Science database. The total and annual number of articles, citations, impact factor, Hirsch (H)-index, number of article citations, productive authors, and involved journals were collected for quantitative and qualitative comparisons. RESULTS: From 1962 to 2018, 18,811 autophagy-related articles written in English were published. Most were from China (6,731). The United States dominated in citation frequency (391,030) and h-index (264). Among related journals, Autophagy published the most articles (1,388), followed by Plos One (585) and Oncotarget (392). Daniel Klionsky was the most productive author, with 171 publications. The article "LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing" was cited most frequently. The top-ranked keyword was "degradation" of macroautophagy. CONCLUSIONS: Publication of articles about autophagy has increased notably from 1962 to 2018, and has increased annually. The general quality of publications from China is still in need of improvement. Autophagy research has shifted gradually from basic studies to clinical studies in recent years.

Simplified Chinese version of hip and knee replacement expectations surveys in patients with osteoarthritis and ankylosing spondylitis: cross-cultural adaptation, validation and reliability.

BACKGROUND: The Hospital for Special Surgery Hip Replacement Expectations Survey (HSS-THRES) and Knee Replacement Expectations Survey (HSS-TKRES) are widely used tools developed to assess patients' preoperative expectations for total hip and knee arthroplasty. This study aimed to translate and adapt the HSS-THRES and HSS-TKRES into Chinese versions (SC-THRES/TKRES) and evaluate their psychometric properties in patients with osteoarthritis (OA) and ankylosing spondylitis (AS). METHODS: Patients scheduled for total hip (104 hip OA and 51 AS) or knee replacements (101 knee OA) were recruited in this study. Confirmatory Factor Analysis (CFA) was used to evaluate structural validity. The internal consistency was assessed by the Cronbach's α coefficient. The intraclass correlation coefficient (ICC) was used to assess test-retest reliability. The construct validity was analyzed by evaluating the correlations between SC-THRES/TKRES and the Expectation WOMAC. The correlations with the Expectation WOMAC were tested against our hypotheses. We additionally compared preoperative expectations of AS patients to those of hip OA patients. RESULTS: The results of CFA for the SC-THRES and SC-TKRES demonstrated good fit. The results for the SC-THRES/TKRES revealed good test-retest reliability and good internal consistency (AS: ICC = 0.893, Cronbach's α = 0.815; hip OA: ICC = 0.878, Cronbach's α = 0.814; knee OA: ICC = 0.806, Cronbach's α = 0.808). The correlations between the SC-THRES/TKRES and the Expectation WOMAC were moderate (0.541 for AS, 0.490 for hip OA and 0.465 for knee OA), which were consistent with the hypotheses. CONCLUSION: The SC-THRES/TKRES are reliable, valid for the evaluation of Chinese patients with OA and AS undergoing total hip and knee arthroplasty. The surveys can be used as part of preoperative assessments. Meanwhile, additional research is needed to replicate these findings and to assess the content validity in a larger sample.

Astaxanthin mitigates cobalt cytotoxicity in the MG-63 cells by modulating the oxidative stress.

BACKGROUND: With the re-popularity of metal-on-metal (MoM) bearing in recent years, the cobalt toxicity has been a cause for concern in the total hip replacement surgery by both physicians and patients. METHODS: MG-63 cell line was cultured in vitro and incubated with cobalt (II) chloride (CoCl2) and/or with astaxanthin (ASX) for 24 h. MTT assay was conducted to evaluate the cell viability after cobalt exposure and ASX treatment. Fluorescence-activated cell sorting (FACS) analysis was performed to examine the reactive oxygen species (ROS) level. Quantitative real-time polymerase chain reaction (PCR) was adopted to determine the mRNA levels of related targets. And western blot analysis was used to examine the protein expressions. One-way ANOVA with posttest Newman-Keuls multiple comparisons was adopted to analysis all the obtained data. RESULTS: In the current study, ASX exhibited significant protective effect against the Co(II)-induced cytotoxicity in MG-63 cell line. We also found that ASX protected the cells against Co-induced apoptosis by regulating the expression of Bcl-2 family proteins. Besides, heme oxygenase 1 (HO-1) could be activated by Co exposure; ASX treatment significantly inhibited HO-1 activation, suppressing the oxidative stress induced by Co exposure. Moreover, c-Jun N-terminal Kinase (JNK) phosphorylation was shown to participate in the signaling pathway of the protective effect of ASX. However, knockdown of JNK expression by siRNA transfection or JNK inhibitor SP600125 treatment did not affect the protective effect of ASX against cobalt cytotoxicity in MG-63 cells. CONCLUSIONS: ASX mitigated cobalt cytotoxicity in the MG-63 cells by modulating the oxidative stress. And ASX could be a promising therapy against cobalt toxicity in the hip articulation surgery.

Role of HLA-B27 in the pathogenesis of ankylosing spondylitis (Review).

The study of ankylosing spondylitis (AS) has made significant progress over the last decade. Genome-wide association studies have identified and further substantiated the role of susceptibility genes outside the major histocompatibility complex locus. However, human leukocyte antigen (HLA)­B27 has been suggested to be important in the pathogenesis of AS, contributing to ~20.1% of AS heritability. The current review will present the classical and non­classical forms of HLA-B27, as well as their pathogenic roles, and further discuss the hypotheses regarding the potential pathogenesis of AS. In addition, the association between the pathogenic role of HLA­B27 and inflammatory indexes, including the interleukin-23/­17 axis will be investigated to provide novel insights into the pathogenesis of AS. The aim of the present review is to provide an update of the current research into the pathogenesis of AS, and provide a comprehensive description of the pathogenic role of HLA-B27 in AS.

Differentially expressed mRNAs, lncRNAs, and miRNAs with associated co-expression and ceRNA networks in ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic autoimmune disease characterized by systemic inflammation and pathological osteogenesis. However, the genetic etiology of AS remains largely unknown. This study aimed to explore the potential role of coding and noncoding genes in the genetic mechanism of AS. Using microarray analyses, this study comprehensively compared lncRNA, microRNA, and mRNA profiles in hip joint ligament tissues from patients with AS and controls. A total of 661 lncRNAs, 574 mRNAs, and 22 microRNAs were differentially expressed in patients with AS compared with controls. Twenty-two of these genes were then validated using real-time polymerase chain reaction. Gene ontology and pathway analyses were performed to explore the principal functions of differentially expressed genes. The pathways were involved mainly in immune regulation, intercellular signaling, osteogenic differentiation, protein synthesis, and degradation. Gene signal transduction network, coding-noncoding co-expression network, and competing endogenous RNA expression network were constructed using bioinformatics methods. Then, two miRNAs, miR-17-5p and miR-27b-3p, that could increase the osteogenic differentiation potentials of ligament fibroblasts were identified. Finally, differentially expressed, five lncRNAs, four miRNAs, and five mRNAs were validated using quantitative real-time polymerase chain reaction. These results suggested that mRNAs, lncRNAs, and microRNAs were involved in AS pathogenesis. The findings might help characterize the pathogenesis of AS and provide novel therapeutic targets for patients with AS in the future.

The effect of total hip replacement on employment in patients with ankylosing spondylitis.

Although total hip replacement (THR) has been proven to be effective, the effect of THR on employment in ankylosing spondylitis (AS) in Chinese population is still unknown. We aimed to demonstrate whether or not patients with AS returned to work following THR and factors associated with the work ability after THR. We performed a retrospective study including a total number of 128 AS patients undergoing THR between 2009 and 2013. Presurgery and postsurgery data including disease state, work status, type of job, and time of resuming work were collected. Factors associated with early return to work were assessed through ordinal regression. Eighty-seven of 128 patients (68 %) were employed within 1 year before THR and 98 returned to work after surgery. Among them, 21, 46, and 31 resumed work by 3, 6, and 12 months postoperation, respectively. Multivariate ordinal regression showed that patients with unilateral THR, younger age, lower BASFI score, employed presurgery, and low or moderate physical demand were more likely to resume work earlier. Most individuals working presurgery returned to work after THR. For young AS patients with hip involvement, THR is an effective treatment for improving and maintaining work ability.

Comparison of Blood Loss After Total Hip Arthroplasty Between Ankylosing Spondylitis and Osteoarthritis.

BACKGROUND: This study was conducted to compare the blood loss during primary total hip arthroplasty (THA) between ankylosing spondylitis (AS) and hip osteoarthritis (OA). METHODS: We reviewed 120 THAs in 68 patients comprising 3 groups: AS with total bony ankylosis of the hips (ASB), AS with stiff hips (ASS), and OA. Demographics, perioperative laboratory values, intraoperative data, blood loss, transfusion rate, transfusion reactions, surgical complications, hospitalization cost, and length of stay (LOS) were collected and analyzed among ASB, ASS, and OA groups. RESULTS: The patients of the ASB and ASS groups were much younger and thinner than those of the OA group. There were no significant differences in the preoperative values of activated partial thromboplastin time, prothrombin time, and international normalized ratio among the 3 groups (all P > .05). The intraoperative blood loss, volume of drainage, hidden blood loss, transfusion rate, transfusion reactions, and hospitalization cost in the ASB group were significantly higher than in the other 2 groups, although not significantly different between the ASS and OA groups (P > .05). CONCLUSION: Both AS and OA can cause hyperosteogeny to the hips, but ASB patients have more serious symptoms in their affected hips. This may cause more blood loss in THA surgery because of bone surface bleeding. The reason that ASB patients suffered more blood loss may be related to the high difficulty and long duration of the operation.

Alterations of miR-132 are novel diagnostic biomarkers in peripheral blood of schizophrenia patients.

Alterations in microRNAs (miRNAs) have been considered to have diagnostic implications in most diseases, but few studies have reported dysregulated miRNAs in schizophrenia (SCZ). In order to observe an association between miRNAs and SCZ, this study was designed to investigate expression profiling of miRNAs in peripheral blood mononuclear cells (PBMCs). miRNA microarray technology was employed to compare the expression of miRNAs in PBMCs from SCZ patients (n=105) and normal controls (n=130), and real-time quantitative polymerase chain reaction (QPCR) was used to analyze the results. Several important miRNA levels were examined before and after antipsychotic treatment in first-onset SCZ patients. In addition, an SCZ-like rat model was established using dizocilpine (MK-801), and miR-132 expression in PBMCs and whole-brain tissue from SCZ-like rats was studied using QPCR. In humans, dysregulated miRNAs were observed before treatment and QPCR verified that miR-132, miR-134, miR-1271, miR-664(⁎), miR-200c and miR-432 levels were significantly decreased (P<0.01 for all) in PBMCs of SCZ patients compared with healthy controls. After antipsychotic treatment there was a marked increase in miR-132 (P<0.01), miR-664(⁎) (P<0.05) and miR-1271 (P<0.05) levels in SCZ patients compared with the levels before treatment. In the animal assays, miR-132 levels declined in PBMCs and whole-brain tissues (both P<0.05) of the SCZ-like rats compared to controls. For the first time, our results suggest that miR-132 is a potential and superior biomarker in peripheral blood that will allow discrimination of SCZ patients from healthy controls.

Tanshinone IIA blocks dexamethasone-induced apoptosis in osteoblasts through inhibiting Nox4-derived ROS production.

Apoptosis of osteoblasts caused by glucocorticoids has been identified as an important contributor to the development of osteoporosis. Tanshinone IIA (Tan), an active ingredient extracted from the rhizome of the Salvia miltiorrhiza Bunge (Danshen), has been reported to cast positive effects on osteoporosis. However, the precise mechanisms accounting this action remain elusive. In this study, by using osteoblastic MC3T3-E1 cells as a model, we confirmed the protective effects of Tan against dexamethasone (Dex)-induced cell apoptosis and further clarified its molecular mechanism of action. Our results showed that treatment with Dex caused cell injury, increased cytosol cytochrome c level and Nox expression, induced apoptosis in caspase-9-dependent manner, and enhanced reactive oxygen species (ROS) production. Tan attenuated these deleterious consequence triggered by Dex. Moreover, Dex-induced ROS production and cell injury were inhibited by antioxidant, NADPH oxidases inhibitors, Nox4 inhibitor, and Nox4 small interfering RNA (siRNA). Overexpression of Nox4 almost abolished the inhibitory effect of Tan on Dex-induced cell injury and apoptosis. The results also demonstrated significant involvement of Nox4 in the Dex-induced apoptosis. Nox4-derived ROS led to apoptosis through activation of intrinsic mitochondrial pathway. Additionally, we evidenced that Tan reversed Dex-induced apoptosis via inactivation of Nox4. The present findings suggest that inhibition of Nox4 may be a novel therapeutic approach of Tan to prevent against glucocorticoids-induced osteoblasts apoptosis and osteoporosis.