[Retracted] miR­486 suppresses the development of osteosarcoma by regulating PKC­Î´ pathway.

Following the publication of the above article, a concerned reader drew to the Editor's attention that, for the Transwell invasion and migration assay experiments shown in Figs. 5 and 6, there were multiple instances of apparently overlapping data panels, such that the data would have been derived from the same original sources where they were intended to show the results from differently performed experiments; moreover, certain of the data shown in Fig. 5B were strikingly similar to data that had appeared in Fig. 2 in a previously published paper written by different authors at different research institutes [Tian F, Ding D and Li D: Fangchinoline targets PI3K and suppresses PI3K/AKT signaling pathway in SGC7901 cells. Int J Oncol 46: 2355­2363, 2015]. In view of the fact that certain of the data in the above article had already appeared in a previously published paper, and given the large number of apparently overlapping data panels identified in the two referenced figures, the Editor of International Journal of Oncology has decided that this paper should be retracted from the publication. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Oncology 50: 1590­1600, 2017; DOI: 10.3892/ijo.2017.3928].

miR-197-3p Promotes Osteosarcoma Stemness and Chemoresistance by Inhibiting SPOPL.

First-line treatment for osteosarcoma includes chemotherapy and surgery. However, the five-year survival rate of refractory osteosarcoma remains unsatisfactory. Osteosarcoma cancer stem cells, possessing stemness and chemoresistance, are one of the critical causes of poor response to chemotherapy. Elucidating regulatory signaling pathways of osteosarcoma cancer stem cells may provide a rationale for improving regimens against chemoresistant osteosarcoma. Methotrexate (MTX)-resistant osteosarcoma cells were established. microRNA expression profiles were used for detecting differentially expressed microRNA in resistant clones and the parental cells. microRNA target databases were employed to predict potential microRNA and mRNA interactions. Flow cytometry was performed to measure stem cell marker Prominin-1 (CD133)-positive cells. Immunofluorescence staining was applied to detect CD133 expression. miR-197-3p mimic or anti-miR-197-3p stably transfected cells were used to generate xenograft models. In the study, we found that miR-197-3p was increased in MTX-resistant cell lines. Overexpression of miR-197-3p enhanced the expression of cancer stem cell markers CD133, Octamer-binding protein 4 (OCT4), Transcription factor SOX-2 (SOX2), and Homeobox protein NANOG (NANOG), as well as chemoresistance-associated genes ATP-dependent translocase ABCB1 (ABCB1) and Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2), whereas miR-197-3p knockdown inhibited stemness and recovered sensitivity to MTX. We also classified the tumor suppressor Speckle-type POZ protein-like (SPOPL) as a target of miR-197-3p. The miR-197-3p mutation that could not combine SPOPL promoter regions was unable to sustain stemness or chemoresistance. Collectively, we discovered miR-197-3p conferred osteosarcoma stemness and chemotherapy resistance by targeting SPOPL, prompting promising therapeutic candidates for refractory osteosarcoma treatment.

Automated identification of hip arthroplasty implants using artificial intelligence.

The purpose of this study was to develop and evaluate the performance of deep learning methods based on convolutional neural networks (CNN) to detect and identify specific hip arthroplasty models. In this study, we propose a novel deep learning-based approach to identify hip arthroplasty implants' design using anterior-posterior images of both the stem and the cup. We harness the pre-trained ResNet50 CNN model and employ transfer learning methods to adapt the model for the implants identification task using a total of 714 radiographs of 4 different hip arthroplasty implant designs. Performance was compared with the operative notes and crosschecked with implant sheets. We also evaluate the difference in performance of models trained with the images of the stem, the cup or both. The training and validation data sets were comprised of 357 stem images and 357 cup radiographs across 313 patients and included 4 hip arthroplasty implants from 4 leading implant manufacturers. After 1000 training epochs the model classified 4 implant models with very high accuracy. Our results showed that jointly using stem images and cup images did not improve the classification accuracy of the CNN model. CNN can accurately distinguish between specific hip arthroplasty designs. This technology could offer a useful adjunct to the surgeon in preoperative identification of the prior implant. Using stem images or cup images to train the CNN can both achieve effective identification accuracy, with the accuracy of the stem images being higher. Using stem images and cup images together is not more effective than using images from only one perspective.

Association of Depression, Antidepressants With Atrial Fibrillation Risk: A Systemic Review and Meta-Analysis.

Background: Depression is a possible influence factor for the increased risk of incident atrial fibrillation (AF). Although several investigations have assessed their association, the results are still controversial. Therefore, we conducted a meta-analysis to evaluate the association between depression or using antidepressants and AF. Methods: We systemically performed the literature retrieval from two electronic databases PubMed and EMBASE until March 2022 to extract relevant data. The hazard ratios (HRs) and odds ratios (OR) from included studies with 95% confidence intervals (CIs) were adjusted into the risk ratio (RR) and pooled by using the random-effects model. Results: Totally 9 studies about the associations between depression or antidepressants and incident AF risk were included in this meta-analysis. Among them, 5 studies specifically analyzed the impact of antidepressants on the risk of AF. The outcomes of our analysis indicated that depression or depressive symptoms could increase AF risk (RR = 1.15, 95% CI, 1.03-1.27, P < 0.01). In addition, the use of antidepressants can also increase AF risk (RR = 1.16, 95% CI, 1.07-1.25, P < 0.001). These results remained unchanged when we remove the source of heterogeneity or adjust the analysis model into the fixed-effects model. Conclusions: Based on existing investigations, both depression and the use of antidepressants are closely related to the increase of incident AF risk.

Identification of lncRNA NR_028138.1 as a biomarker and construction of a ceRNA network for bipolar disorder.

The pathogenesis of bipolar disorder (BD), a chronic mood disorder, is largely unknown. Noncoding RNAs play important roles in the pathogenesis of BD. However, little is known about the correlations of long noncoding RNAs (lncRNAs) with BD. Illumina high-throughput sequencing in BD patients and normal controls was used to identify differentially expressed (DE) genes. Two-step real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate DE-RNAs in the first cohort (50 BD and 50 control subjects). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and lncRNA-mRNA coexpression and lncRNA-microRNA (miRNA)-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network analyses were used to predict the functions of DE-RNAs. Receiver operating characteristic (ROC) curve analysis and logistic regression were applied to evaluate diagnostic performance in an additional testing group (80 BD and 66 control subjects). A total of 576 significantly DE-lncRNAs and 262 DE-mRNAs were identified in BD patients, and 95 lncRNA-miRNA-mRNA interactions were used to construct a ceRNA regulatory network. Analysis of the first cohort showed that six RNAs (NR_028138.1, TCONS_00018621, TCONS_00002186, TNF, PID1, and SDK1) were differentially expressed in the BD group (P < 0.01). NR_028138.1 was used to establish a BD diagnostic model (area under the ROC curve 0.923, P < 0.004, 95% CI: 0.830-0.999). Verification in the second cohort revealed uniformly significant differences in NR_028138.1 (P < 0.0001). This study constructed a ceRNA regulatory network and provided a hypothesis for the pathogenesis of BD. NR_028138.1 was identified as a central element involved in the transcriptional regulation in BD and a potential biomarker.

Bioinformatics Analysis of circRNA Expression and Construction of "circRNA-miRNA-mRNA" Competing Endogenous RNAs Networks in Bipolar Disorder Patients.

Bipolar disorder (BD) is a severe mood disorder disease in China, and its underlying pathogenesis remains unknown. Circular RNAs (circRNAs) have been reported to play a key role in mental disorders and can be used as competitive endogenous RNAs (ceRNAs). However, little is known about the correlation of circRNAs with BD. In this study, Deep RNA sequencing was used to identify differentially expressed circRNAs (DE-circRNAs) and differentially expressed mRNAs (DE-mRNAs) between BD patients and a control group. Real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to validate the differentially expressed RNAs (DE-RNAs). In all 9,593 circRNAs and 20,030 mRNAs were found in the two groups of specimens, among which 50 DE-circRNAs and 244 DE-mRNAs were significantly upregulated, and 44 DE-circRNAs and 294 DE-mRNAs were significantly downregulated. Based on the regulatory mechanism of ceRNAs, circRNAs can directly bind microRNAs (miRNAs) to affect mRNA expression, and the expression trends of circRNAs and mRNAs are consistent. According to this mechanism, we constructed two ceRNA networks by using the RNA sequencing data. The function of these DE-circRNAs was further elucidated by enrichment analysis. In summary, the present study showed that the circRNA expression profile of BD patients is altered, and a ceRNA regulatory network was constructed, which provided a hypothesis about the pathogenesis of BD.

Mediating effects of working memory on the relationship between chronic pain and overgeneral autobiographical memory.

This study is to explore the function of working memory (WM) and autobiographical memory (AM) in patients with chronic pain. Totally, 331 patients with chronic pain and 333 healthy controls were recruited. These subjects were subjected to assessment with Pain Assessment Protocol (PAP), Visual Analogue Scale (VAS), Working Memory Index (WMI) and Autobiographical Memory Test (AMT). Patients with chronic pain scored significantly lower in WMI and higher in overgeneral autobiographical memory (OGM) of AMT. Chronic pain was significantly negatively related with WM and positively related with OGM. The structural equation model indicated that WM mediated the relationship of chronic pain and OGM. These findings suggest that WM and AM are impaired in the patients with chronic pain,,chronic pain is closely related with OGM, and WM acts an important mediating role between chronic pain and OGM.

Diallyl thiosulfinate enhanced the anti-cancer activity of dexamethasone in the side population cells of multiple myeloma by promoting miR-127-3p and deactivating the PI3K/AKT signaling pathway.

BACKGROUND: Side population (SP) cells, which have similar features to those of cancer stem cells, show resistance to dexamethasone (Dex) treatment. Thus, new drugs that can be used in combination with Dex to reduce the population of SP cells in multiple myeloma (MM) are required. Diallyl thiosulfinate (DATS, allicin), a natural organosulfur compound derived from garlic, has been shown to inhibit the proliferation of SP cells in MM cell lines. Therefore, we investigated the effect of a combination of DATS and Dex (DAT + Dex) on MM SP cells. METHODS: SP cells were sorted from MM RPMI-8226 and NCI-H929 cell lines using Hoechst 33342-labeled fluorescence-activated cell sorting. The growth of SP cells was evaluated using the cell counting kit-8 assay. Cell cycle and apoptosis assays were conducted using a BD Calibur flow cytometer. miRNA expression was measured using quantitative reverse transcription-polymerase chain reaction. Phosphoinositide 3-kinase (PI3K), phosphorylated AKT (p-AKT), AKT, p-mechanistic target of rapamycin (mTOR), and mTOR levels were measured using western blot analysis. RESULTS: Our results showed that the combination of DATS+Dex inhibited sphere formation, colony formation, and proliferation of MM SP cells by inducing apoptosis and cell cycle arrest in the G1/S phase. In addition, the combination of DATS+Dex promoted miR-127-3p expression and inhibited PI3K, p-AKT, and p-mTOR expression in SP cells. Knockdown of miR-127-3p expression weakened the effect of DATS+Dex on cell proliferation, colony formation, apoptosis, and cell cycle of MM SP cells. Additionally, knockdown of miR-127-3p activated the PI3K/AKT/mTOR signaling pathway in MM SP cells cotreated with DATS+Dex. CONCLUSION: We demonstrated that cotreatment with DATS+Dex reduced cell proliferation, promoted apoptosis, and caused cell cycle arrest of MM SP cells by promoting miR-127-3p expression and deactivating the PI3K/AKT/mTOR signaling pathway.

The prevalence, risk factors, and prognostic value of venous thromboembolism in ovarian cancer patients receiving chemotherapy: a systematic review and meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) in ovarian cancer (OC) patients has been widely investigated, but our knowledge on the role of VTE in OC patients receiving chemotherapy is limited. The aim of our study was to investigate the prevalence, risk factors, and prognostic value of chemotherapy-associated VTE in OC. METHODS: Three databases (PubMed, Embase, and the Cochrane Library) were systematically searched from inception to October 14, 2020. The primary outcome was the prevalence of VTE in OC patients receiving chemotherapy. The risk factors and prognostic value of VTE were the secondary outcomes. The pooled prevalence of VTE was estimated using the generic inverse-variance method. The statistical heterogeneity was evaluated with Cochran's Q test and I2 statistic. Funnel plot, Begg's test, and Egger's test were used to assess the potential publication bias in the meta-analysis. RESULTS: A total of eleven observational studies with 4759 OC patients were included. The pooled prevalence of VTE was 9% (95% CI, 0.06-0.12) in OC patients receiving chemotherapy. The results of subgroup analysis and sensitivity analysis were basically consistent with the overall pooled estimate. Multiple significant risk factors associated with VTE were also identified including advanced age, D-dimer > 0.5 mg/mL, and tumor diameter > 10 cm. Only two included studies reported the prognostic value of VTE in OC patients receiving chemotherapy, but with inconsistent results. Funnel plot showed that there existed potential publication bias, which was further verified by statistical test, but the results of the trim-and-fill method showed the pooled estimate kept stable after adding two "missing" studies. CONCLUSIONS: This current study revealed that the pooled prevalence of chemotherapy-related VTE in OC was approximately 9% in OC patients. Risk factors for chemotherapy-related VTE were also identified which may contribute to targeting potentially preventative measures for VTE in OC.

Decreased Plasma Levels of Growth Differentiation Factor 11 in Patients With Schizophrenia: Correlation With Psychopathology and Cognition.

Schizophrenia is linked with abnormal neurodevelopment, on which growth differentiation factor 11 (GDF-11) has a great impact. However, a direct evidence linking GDF-11 to the pathophysiology of schizophrenia is still lacking. The current study aimed to investigate the relationship between plasma GDF-11 levels and both psychopathological symptoms and cognitive function in schizophrenia. Eighty-seven schizophrenia patients and 76 healthy controls were enrolled in the present study. The symptomatology of schizophrenia was evaluated using the Positive and Negative Syndrome Scale (PANSS). Cognitive function was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) including twelve neurocognitive tests in five aspects of cognitive function. Plasma GDF-11 levels were determined by enzyme-linked immunosorbent assay (ELISA). We found that plasma levels of GDF-11 were significantly lower in schizophrenia patients relative to healthy controls. Correlation analysis showed significant negative correlations between the GDF-11 levels and the PANSS total score, the positive symptoms score, the negative symptoms score or the general score. Additionally, positive associations were observed between plasma GDF-11 levels and the visuospatial/constructional, attention, immediate memory, or delayed memory in patients. Partial correlation analysis showed that these correlations were still significant after adjusting for age, gender, education years, body mass index, duration of illness, and age of onset except for the visuospatial/constructional and attention index. Multiple regression analysis revealed that GDF-11 was an independent contributor to the immediate memory, delayed memory and RBANS total score in patients. Collectively, the correlations between plasma GDF-11 and psychopathological and cognitive symptoms suggest that abnormal GDF-11 signaling might contribute to schizophrenic psychopathology and cognitive impairments and GDF-11 could be a potential and promising biomarker for schizophrenia.

ELFN1-AS1 accelerates cell proliferation, invasion and migration via regulating miR-497-3p/CLDN4 axis in ovarian cancer.

Previous studies indicated that long non-coding RNAs (LncRNAs) were involved in the progression of multiple cancers including ovarian cancer (OV). LncRNA ELFN1-AS1 functioned as an oncogene in many cancers, but its potential roles in OV were largely unclear. In the current study, we were aimed at clarifying the biological roles and molecular mechanisms of ELFN1-AS1 in OV. We found that ELFN1-AS1 was significantly upregulated in OV tissues and cell lines. High expression of ELFN1-AS1 was associated with poor prognosis in OV patients. Knockdown of ELFN1-AS1 inhibited the proliferation, migration and invasion of SKOV3 cell lines and repressed tumor growth in xenografted ovarian models. Mechanistically, ELFN1-AS1 promoted the proliferation, migration and invasion of SKOV3 cells by sponging miR-497-3p. Additionally, CLDN4 was verified to be the target of miR-497-3p. Rescue experiments revealed that miR-497-3p inhibition could partly reverse the inhibitory effect of ELFN1-AS1 silencing on proliferation, migration and invasion of SKOV3 cell lines. Taken together, our findings indicated that ELFN1-AS1 acted as an oncogene in ovarian cancer through regulating the expression of CLDN4 by directly interacting with miR-497-3p. The results suggested that ELFN1-AS1 might act as a promising therapeutic target for OV.

Relationship between psychological factors and atrial fibrillation: A meta-analysis and systematic review.

BACKGROUND: Although several studies have investigated the role of psychological factors in atrial fibrillation (AF), the results are still under debate. Therefore, we performed a meta-analysis to examine the relationship between psychological factors and the risk of incident AF. METHODS: We systematically searched the PubMed and EMBASE databases from inception to December 2019 to identify eligible studies. The hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled by using a random-effects model. RESULTS: A total of 11 cohort studies were included in this meta-analysis. There were 5, 2, 4, and 5 studies examining the association of anxiety, anger, depression, and psychological stress with AF, respectively. In the pooled analysis by a random-effects model, anxiety (HR = 1.10, 95%CI 0.97-1.24; P = .14), anger (HR = 1.08, 95%CI 0.95-1.23; P = .21), depression (HR = 1.15, 95%CI 0.98-1.35; P = .08), and work stress (HR = 1.14, 95%CI 0.98-1.34; P = .09) were not associated with the risk of AF. These results were not changed when we re-performed the analysis using a fixed-effects model. CONCLUSIONS: Based on current evidence, no associations were observed for anger, anxiety, and work stress with the risk of AF.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Peripheral Artery Disease: a Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with atrial fibrillation (AF) and peripheral artery disease (PAD) remain largely unknown. Therefore, we conducted a meta-analysis to explore the effects of NOACs versus warfarin in this population. METHODS: We systematically searched the PubMed and Embase databases, with no linguistic restrictions, until December 2019 for relevant randomized controlled trials (RCTs) and observational studies. A random-effects model using an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: A total of six studies (three post hoc analyses of RCTs and three cohort studies) were included in this meta-analysis. Among AF patients treated with NOACs and warfarin, individuals with PAD had increased rates of all-cause death (RR = 1.26, 95% CI 1.07-1.48) and cardiovascular death (RR = 1.32, 95% CI 1.06-1.64) compared with those without PAD. In AF patients with PAD, we observed a similar risk of thromboembolic events, bleeding, and death with NOACs as with warfarin. In addition, there were no interactions between PAD and non-PAD subgroups regarding any of the reported outcomes of NOACs versus warfarin in AF patients (all Pinteraction > 0.05). CONCLUSIONS: Based on current evidence, AF patients with PAD are at a higher risk of death than those without PAD. Efficacy and safety outcomes with NOACs are comparable to those with warfarin, suggesting that the use of NOACs has effects similar to warfarin in AF patients with concomitant PAD.

Effect of antidepressants on death in patients with heart failure: a systematic review and meta-analysis.

Depression is associated with an increased risk of death in patients with heart failure (HF); however, the association between the use of antidepressants and HF prognoses remains controversial. Therefore, this meta-analysis aimed to evaluate the effect of antidepressants on the risk of death in HF patients. We retrieved data from the PubMed and EMBASE databases until August 2019 for studies reporting the use of antidepressants in HF patients. Data were extracted from the eligible articles, and a random effects model was used to pool the effect estimates (risk ratios (RRs) and 95% confidence intervals (CIs)). A total of 8 studies were included in this meta-analysis. Overall, the use of antidepressants was associated with increased risks of all-cause death (RR = 1.27; 95% CI, 1.21-1.34) and cardiovascular death (RR = 1.14; 95% CI, 1.08-1.20) in HF patients with or without depression. Specifically, HF patients with depression taking antidepressants had increased risks of all-cause death (RR = 1.21; 95% CI, 1.16-1.27) and cardiovascular death (RR = 1.21; 95% CI, 1.13-1.30). Compared with nonusers, the use of selective serotonin reuptake inhibitors (SSRIs), tricyclics (TCAs), and selective serotonin reuptake inhibitors (SNRIs) significantly increased the rate of all-cause death (SSRIs (RR = 1.26; 95% CI, 1.19-1.32), TCAs (RR = 1.30; 95% CI, 1.16-1.46), and SNRIs (RR = 1.17; 95% CI, 1.08-1.26)) but not cardiovascular death (SSRIs (RR = 1.03; 95% CI, 0.84-1.26), TCAs (RR = 1.02; 95% CI, 0.86-1.21), and SNRIs (RR = 0.92; 95% CI, 0.48-1.78)). Based on current publications, the use of antidepressants could increase the risk of all-cause death in HF patients, regardless of whether they have depression or the type of antidepressants they use. Further study is needed to determine the relationship between antidepressant use and cardiovascular death.

Non-vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Liver Disease: A Meta-Analysis and Systematic Review.

BACKGROUND: The effect of non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF) and liver disease remains largely unresolved. Therefore, we performed a meta-analysis to compare the efficacy and safety of NOACs with warfarin in this population. METHODS: We systematically searched the Cochrane Library, PubMed, and Embase databases for studies reporting the comparisons of NOACs with warfarin in patients with AF and liver disease. A random-effects model was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: A total of six studies with 41,954 participants were included in this meta-analysis. In AF patients with liver disease, compared with warfarin use, the use of NOACs was associated with reduced risks of all-cause death (RR 0.78, 95% CI 0.66-0.93), major bleeding (RR 0.68, 95% CI 0.53-0.88), and intracranial hemorrhage (RR 0.49, 95% CI 0.41-0.59), but had comparable risks of stroke or system embolism (RR 0.80, 95% CI 0.57-1.12) and gastrointestinal bleeding (RR 0.90, 95% CI 0.61-1.34). In AF patients with cirrhosis, NOACs significantly reduced the risks of major bleeding (RR 0.53, 95% CI 0.37-0.76), gastrointestinal bleeding (RR 0.57, 95% CI 0.38-0.84), and intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.97) compared with warfarin. CONCLUSIONS: Based on current publications, the use of NOACs is at least non-inferior to warfarin in patients with AF and liver disease.

Oxymatrine suppresses the growth and invasion of MG63 cells by up-regulating PTEN and promoting its nuclear translocation.

Studies demonstrated that reduced PTEN levels are associated with poor prognoses of osteosarcoma. The nuclear localization of PTEN is important for its tumor suppressive function. Equally importantly, PTEN is the most significant negative regulator of PI3K/Akt signaling cascade, the constitutively activated pathway in osteosarcoma. In our study MG63 cells and U2OS cells were treated with the indicated concentrations of oxymatrine, in order to find the inhibition of oxymatrine to cells. We found the functions of oxymatrine on proliferation, apoptosis and invasion in cells. Oxymatrine could increase the expression of PTEN and promote its nuclear translocation in MG63 cells. In addition, oxymatrine could induce cell cycle arrest in G1 phase and apoptosis of MG63 cells. The migration and invasion potential of MG63 cells were also markedly inhibited by oxymatrine. Oxymatrine could suppress the growth and invasion of MG63 human osteosarcoma cells by up-regulating PTEN and promoting its nuclear translocation and inhibiting PI3K/Akt signaling pathway.

miR-486 suppresses the development of osteosarcoma by regulating PKC-δ pathway.

Osteosarcoma is one of the most highly malignant types of cancer in adolescents and young adults with a high mortality rate. Despite advances in surgery, radiation therapy and chemotherapy, the prognosis for patients with osteosarcoma has not significantly improved over the past several decades. It is necessary to find new indicators of prognosis and therapeutic targets of osteosarcoma. Through the analysis of 40 osteosarcoma tissues, we found that the expression of miR­486 was low and the expression of PKC­Î´ was high in osteosarcoma. Median survival of patients with low expression of miR-486 (30 months) was shorter than the patients with higher expression of miR­486 (40 months). We further found that miR-486 can inhibit the targeting of PKC­Î´ signaling pathways, and this inhibition can inhibit the growth and invasion of osteosarcoma cells. After transfection of miR­486 for 24 h, the proliferation of osteosarcoma cells was inhibited by ~20%, and the migration was inhibited by ~15%. In the present investigation, we demonstrated that miR­486 is negatively associated with the expression of PKC-δ and could regulate the development of osteosarcoma. miR-486 may be a potential target for the treatment of osteosarcoma.

miR-23a suppresses proliferation of osteosarcoma cells by targeting SATB1.

Accumulating evidence has shown that microRNAs are involved in multiple processes in cancer development and progression. Recent studies have shown that miR-23a functions as an oncogene in various human cancer types, but its role in osteosarcoma remains poorly understood. Here, we demonstrated that miR-23a is frequently downregulated in osteosarcoma specimens and cell lines compared with adjacent noncancerous tissues and cell line. Bioinformatics analysis further revealed SATB1 as a potential target of miR-23a. Data from luciferase reporter assays showed that miR-23a directly binds to the 3'UTR of SATB1 messenger RNA (mRNA). Furthermore, we found that expression patterns of miR-23a were inversely correlated with those of SATB1 in osteosarcoma tissues and cell lines, and overexpression of miR-23a suppressed SATB1 expression at both transcriptional and translational levels in osteosarcoma cell lines. In functional assays, miR-23a inhibited osteosarcoma cell proliferation, which could be reversed by overexpression of SATB1. Furthermore, knockdown of SATB1 reduced osteosarcoma cell proliferation, which resembled the inhibitory effects of miR-23a overexpression. Taken together, our data provide compelling evidence that miR-23a functions as a tumor suppressor in osteosarcoma, and its inhibitory effect on tumor are mediated chiefly through downregulation of SATB1.

Systemic treatment with vanadium absorbed by Coprinus comatus promotes femoral fracture healing in streptozotocin-diabetic rats.

The purpose of this study was to analyze the impact of vanadium absorbed by Coprinus comatus (VACC) on fracture healing in streptozotocin-diabetic rats. Forty-five male Wistar rats used were divided into three groups: normal rats (control), diabetic rats, and diabetic rats treated with VACC. A standardized fracture-healing model with a stable plate fixation was established for the rat femoral fracture. After a 4-week stable fixation, callus quality was assessed by microcomputerized tomography and histological and biomechanical examinations. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. Compared with the diabetic group, vanadium treatment significantly increased bone mineral content and biomechanical strength and improved microstructural properties of the callus. The ultimate load was increased by 29.1 % (P<0.05), and the total bone volume of callus enhanced by 11.2 % (P<0.05) at 4 weeks post fracture. Vanadium also promoted callus bone formation, which caused a 35.5 % increase in the total area of callus. However, VACC did not accelerate the fracture repair process in histological analysis. In conclusion, the current study suggests that systemic treatment with vanadium could promote fracture healing in streptozotocin-diabetic rats.