Multi-Label Action Anticipation for Real-World Videos With Scene Understanding.

With human action anticipation becoming an essential tool for many practical applications, there has been an increasing trend in developing more accurate anticipation models in recent years. Most of the existing methods target standard action anticipation datasets, in which they could produce promising results by learning action-level contextual patterns. However, the over-simplified scenarios of standard datasets often do not hold in reality, which hinders them from being applied to real-world applications. To address this, we propose a scene-graph-based novel model SEAD that learns the action anticipation at the high semantic level rather than focusing on the action level. The proposed model is composed of two main modules, 1) the scene prediction module, which predicts future scene graphs using a grammar dictionary, and 2) the action anticipation module, which is responsible for predicting future actions with an LSTM network by taking as input the observed and predicted scene graphs. We evaluate our model on two real-world video datasets (Charades and Home Action Genome) as well as a standard action anticipation dataset (CAD-120) to verify its efficacy. The experimental results show that SEAD is able to outperform existing methods by large margins on the two real-world datasets and can also yield stable predictions on the standard dataset at the same time. In particular, our proposed model surpasses the state-of-the-art methods with mean average precision improvements consistently higher than 65% on the Charades dataset and an average improvement of 40.6% on the Home Action Genome dataset.

Multiple programmed cell death patterns and immune landscapes in bladder cancer: Evidence based on machine learning and multi-cohorts.

BACKGROUND: Bladder cancer (BLCA) is the most prevalent malignant neoplasm of the urinary tract, and ranks seventh as the most frequent systemic neoplasm in males. Dysregulation of programmed cell death (PCD) has been implicated in various stages of cancer progression, including tumorigenesis, invasion, and metastasis. However, the correlation between multiple PCD modes and BLCA is lacking. Thus, a risk prediction model was built based on 12 models of PCD to predict prognosis and immunotherapy response in patients with BLCA. METHODS: The RNA sequencing transcriptome data of BLCA were collected from the Cancer Genome Atlas Program (TCGA) and GEO datasets. Univariate Cox and LASSO regression analyzes were performed to identify PCD-related genes (PCDRGs) significant for prognosis. Multivariate Cox regression analysis was used to develop a prognostic model for PCD. Survival analysis and chi-squared test were employed to analyze the survival variations between different risk groups. Univariate and multivariate Cox analyses were performed to evaluate the model as an independent prognostic predictor. A nomogram was formulated using both clinical data and the model to predict the survival rates of BLCA patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were performed to analyze and elucidate the molecular mechanisms and pathways operating within different risk score groups. Furthermore, the immune landscape was investigated and the efficacy of various anti-tumor drugs was evaluated for BLCA. Finally, consensus clustering analysis was adopted to explore the association between different PCD clusters and clinical characteristics. RESULTS: Assessment of the public datasets and multivariate Cox analysis yielded 1254 PCDRGs, of which 10 PCDRGs for BLCA were identified. Based on the PCDRGs, a prognostic model was built for BLCA patient prognosis. Compared with the low-risk group, the high-risk group had a poorer prognosis. The model predicted area under the curve (AUC) values of 0.751, 0.753, and 0.763, respectively, for 1-, 3-, and 5-year survival of BLCA patients. The nomogram further demonstrated the credibility of the prognosis model. The low-risk group patients exhibited lower TIDE scores and higher TMB scores, implying better response of the low-risk group to immunotherapy. The consensus clustering analysis indicated that compared with PCD cluster A, PCD cluster B was significantly more expressed in PCDRGs, suggesting a closer relation of PCD cluster B to PCDRGs. Patients in PCD cluster B had lower risk scores. CONCLUSION: To summarize, the effects of 12 PCD patterns on BLCA were synthesized and the correlation between PCD and BLCA was explored. These findings provide new and convincing evidence for individualized treatment of BLCA, and help guide the treatment strategy and improve the prognosis of BLCA patients.

A New Time-Window Prediction Model For Traumatic Hemorrhagic Shock Based on Interpretable Machine Learning.

ABSTRACT: Early warning prediction of traumatic hemorrhagic shock (THS) can greatly reduce patient mortality and morbidity. We aimed to develop and validate models with different stepped feature sets to predict THS in advance. From the PLA General Hospital Emergency Rescue Database and Medical Information Mart for Intensive Care III, we identified 604 and 1,614 patients, respectively. Two popular machine learning algorithms (i.e., extreme gradient boosting [XGBoost] and logistic regression) were applied. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of the models. By analyzing the feature importance based on XGBoost, we found that features in vital signs (VS), routine blood (RB), and blood gas analysis (BG) were the most relevant to THS (0.292, 0.249, and 0.225, respectively). Thus, the stepped relationships existing in them were revealed. Furthermore, the three stepped feature sets (i.e., VS, VS + RB, and VS + RB + sBG) were passed to the two machine learning algorithms to predict THS in the subsequent T hours (where T = 3, 2, 1, or 0.5), respectively. Results showed that the XGBoost model performance was significantly better than the logistic regression. The model using vital signs alone achieved good performance at the half-hour time window (AUROC = 0.935), and the performance was increased when laboratory results were added, especially when the time window was 1 h (AUROC = 0.950 and 0.968, respectively). These good-performing interpretable models demonstrated acceptable generalization ability in external validation, which could flexibly and rollingly predict THS T hours (where T = 0.5, 1) prior to clinical recognition. A prospective study is necessary to determine the clinical utility of the proposed THS prediction models.

Elasticity evaluation of the plantar fascia: A shear wave elastography study involving 33 early-stage plantar fasciopathy subjects.

Background: Plantar fasciopathy, the most common foot condition seen in elderly and athletic populations, can be diagnosed and differentially diagnosed with imaging modalities such as ultrasound shear wave elastography (SWE). However, standard guidelines for ultrasound elastography of the plantar fascia are lacking. The purpose of this study was to determine the impact of the region of interest (ROI) on the evaluation of the plantar fascia elasticity and confirm the screening accuracy of SWE in the early-stage of plantar fasciopathy. Methods: This was an observational case‒control study involving 50 feet of 33 early-stage plantar fasciopathy subjects (the plantar fasciopathy group) and 96 asymptomatic feet of 48 healthy volunteers (the non-pain group). Clinical information, including age, gender, height, weight, visual analogue scale (VAS) score, American Orthopaedic Foot and Ankle Scale score (AOFAS), and the symptom duration, were recorded. All participants underwent both conventional ultrasound and SWE evaluation. The plantar fascia elastic parameters included SWEsingle-point, calculated with a single-point ROI set at the greatest thickness of the plantar fascia, and SWEmulti-point, calculated by multipoint ROIs set continuously from the origin at the calcaneus to about 2 cm from the calcaneal origin. Results: The plantar fasciopathy group presented a higher VAS score (median [IQR), 4.00 (3.00) vs. 0.00 (0.00), p < 0.001] and lower AOFAS score [median (IQR), 79.50 (3.00) vs. 100.00 (10.00), p < 0.001] than the non-pain group. The median plantar fascia thickness of the plantar fasciopathy group was significantly greater than that of the non-pain group [median (IQR), 3.95 (1.37) mm vs 2.40 (0.60) mm, p < 0.001]. Abnormal ultrasound features, including echogenicity, border irregularities, and blood flow signals, were more prominent in the plantar fasciopathy group than in the non-pain group (29% vs. 0%, p < 0.001; 26% vs. 1%, p < 0.001; 12% vs. 0%, p < 0.001, respectively). Quantitative analysis of the plantar fascia elasticity revealed that the difference between the value of SWEsingle-point and SWEmultipoint was significant [median (IQR), 65.76 (58.58) vs. 57.42 (35.52) kPa, p = 0.02). There was a moderate and significant correlation between the value of SWEsingle-point and heel pain. However, there was no correlation between the value of SWEmultipoint and heel pain. Finally, we utilized the results of SWEsingle-point as the best elastic parameter reflecting clinical heel pain and found that SWEsingle-point could provide additional value in screening early-stage plantar fasciopathy, with an increase in sensitivity from 76% to 92% over conventional ultrasound alone. Additionally, compared with conventional ultrasound and SWE, the use of both improved the accuracy of screening for plantar fasciopathy. Although there were no significant differences in the negative predictive value of conventional ultrasound, SWE, and their combination, the positive predictive value when using both (90.20%) was significantly greater than that when using conventional ultrasound (74.50%) or SWE alone (76.50%). Conclusion: The plantar fascia elastic parameter calculated with single-point ROIs set at the greatest thickness of the plantar fascia is positively correlated with fascia feel pain. Single-point analysis is sufficient for the screening of the early-stage plantar fasciopathy using SWE. SWEsingle-point may provide additional valuable information for assessing the severity of plantar fasciopathy.

An interpretable machine learning model based on a quick pre-screening system enables accurate deterioration risk prediction for COVID-19.

A high-performing interpretable model is proposed to predict the risk of deterioration in coronavirus disease 2019 (COVID-19) patients. The model was developed using a cohort of 3028 patients diagnosed with COVID-19 and exhibiting common clinical symptoms that were internally verified (AUC 0.8517, 95% CI 0.8433, 0.8601). A total of 15 high risk factors for deterioration and their approximate warning ranges were identified. This included prothrombin time (PT), prothrombin activity, lactate dehydrogenase, international normalized ratio, heart rate, body-mass index (BMI), D-dimer, creatine kinase, hematocrit, urine specific gravity, magnesium, globulin, activated partial thromboplastin time, lymphocyte count (L%), and platelet count. Four of these indicators (PT, heart rate, BMI, HCT) and comorbidities were selected for a streamlined combination of indicators to produce faster results. The resulting model showed good predictive performance (AUC 0.7941 95% CI 0.7926, 0.8151). A website for quick pre-screening online was also developed as part of the study.

The Relationship Between Hematologic Parameters and Erectile Dysfunction.

INTRODUCTION: Certain hematologic parameters related to blood cells, known as the biomarkers that predict cardiovascular disease, might be potential predictors of erectile dysfunction (ED) due to the shared pathophysiology between ED and cardiovascular disease . AIM: To investigate the relationship between ED and these hematologic parameters and the clinical significance of hematologic parameters for the diagnosis of ED. METHODS: A total of 113 male patients diagnosed with ED were included in this study. Blood samples were collected before 10:00 AM for blood cells examination, biochemical tests, and sex hormone analysis. Another 212 healthy controls without ED from the health management center was included as the control group. The relationship between hematologic parameters and ED was assessed by comparing differences in body mass index (BMI), biochemical indexes and hematologic parameters between the 2 groups, and the diagnostic value of hematologic parameters for ED was also examined and compared. MAIN OUTCOME MEASURES: International Index of Erectile Function, hematologic parameters RESULTS: The neutrophil count (NC), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) in ED patients were significantly higher than those in healthy controls, whereas the lymphocyte count (LC) was significantly lower than that in healthy controls. After adjusting for age, BMI, uric acid (UA), fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), increases in the NC, NLR, and PLR and a decrease in the LC were shown to be independent risk factors for ED. Receiver operating characteristic (ROC) curve analysis showed that the NLR exhibited better diagnostic performance for ED than the other parameters. CONCLUSION: Increases in the NC, NLR, and PLR and a decrease in the LC significantly increased the risk of ED. The NC, LC, NLR and PLR could contribute to the diagnosis and assessment of ED. Zhangcheng L, Yuxin T, Xiucheng L and Dongjie L, et al. The Relationship Between Hematologic Parameters and Erectile Dysfunction. Sex Med 2021;9:100401.

Galangin suppresses RANKL-induced osteoclastogenesis via inhibiting MAPK and NF-κB signalling pathways.

Osteoclasts play a critical role in osteoporosis; thus, inhibiting osteoclastogenesis is a therapeutic strategy for osteoporosis. Galangin, a natural bioflavonoid extracted from a traditional Chinese herb, possesses a variety of biological activities, including anti-inflammation and anti-oxidation. However, its effects on osteoporosis have not been elucidated. In this study, we found that galangin treatment dose-dependently decreased osteoclastogenesis in bone marrow-derived macrophages (BMMs). Moreover, during osteoclastogenesis, osteoclast-specific genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CtsK), ATPase, H + transporting, lysosomal V0 subunit D2 (V-ATPase d2) and dendritic cell-specific transmembrane protein (DC-STAMP), were down-regulated by galangin treatment. Furthermore, the results of the pit formation assay and F-actin ring staining revealed impaired osteoclastic bone resorption in the galangin-treated group compared with that in the control group. Additionally, galangin treatment also inhibited the phosphorylation of p38 and ERK of MAPK signalling pathway, as well as downstream factors of NFATc1, C-Jun and C-Fos. Consistent with our in vitro results, galangin suppressed lipopolysaccharide (LPS)-induced bone resorption via inhibition of osteoclastogenesis. Taken together, our findings provide evidence that galangin is a promising natural compound for the treatment of osteoporosis and may be associated with the inhibition of MAPK and NF-κB signalling pathways.

The Suggestive Effect of Apo A, Apo B, and Apo A/Apo B on Erectile Dysfunction.

BACKGROUND: Erectile dysfunction (ED) is closely related to coronary heart disease (CHD). Apolipoprotein (Apo) A1, Apo B, and Apo A/Apo B are known to be predictive factors for CHD. They are not yet a definite laboratory marker for the diagnosis of ED in cardiology. Therefore, we investigated the association between Apo A1, Apo B, and Apo A/Apo B, and ED. AIM: To investigate the association between Apo A, Apo B, and Apo A/Apo B and the severity of ED. METHODS: A total of 152 ED patients and 39 healthy control participants underwent a fasting blood draw to test for Apo A, Apo B, and Apo A/Apo B and a detailed laboratory examination. The International Erectile Function Index (IIEF-5) was used to determine the severity of ED. Receiver operating characteristic (ROC) curve analysis was performed to identify the cutoff values for Apo A, Apo B, and Apo A/Apo B. Each questionnaire was completed before any diagnosis was made or treatment performed. OUTCOMES: Several lipid profile indicators (Apo A, Apo B, Apo A/Apo B, lipoprotein (a), free fatty acids, and total cholesterol) were studied, along with several questionnaires. RESULTS: In our study, the number of patients with no ED, mild ED, mild-to-moderate ED, and moderate-to-severe ED were 39 (20.4%), 58 (30.4%), 36 (18.8%), and 58 (30.4%), respectively. Apo A and Apo A/Apo B were significantly reduced in patients with more severe ED (P = .037 and P < .001, respectively), while Apo B was significantly increased in patients with more severe ED (P = .002). According to the ROC curve, Apo A/Apo B had a medium diagnostic value for risk of ED with an AUC of 0.743 (95% CI: 0.68-0.80). For moderate-to-severe ED, 3 apolipoprotein indexes, including Apo B, Apo A, and Apo A/Apo B had medium diagnostic performance with AUCs of 0.759 (95% CI: 0.66-0.84), 0.703 (95% CI: 0.60-0.79), and 0.808 (95% CI: 0.72-0.88), respectively. CLINICAL IMPLICATIONS: Our results can inform cardiologists in the assessment of ED in patients with CHD. STRENGTHS AND LIMITATIONS: This study is the first to investigate the association between apolipoprotein and ED in China. The major limitations are that our sample size was too small to have matched controls without ED for different Apo levels. CONCLUSION: Our results showed that Apo B, Apo A, and Apo A/Apo B can be used as markers to evaluate the risk of ED and that these proteins play an important role in the etiology of ED. Li X, Li D. The Suggestive Effect of Apo A, Apo B, and Apo A/Apo B on Erectile Dysfunction. J Sex Med 2021;18:448-456.

Is mild erectile dysfunction associated with severe psychological symptoms in Chinese patients with moderate-to-severe chronic prostatitis/chronic pelvic pain syndrome?

This study aimed to assess the association between psychological disorders and erectile dysfunction (ED) in patients with different degrees of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). This was a retrospective study conducted from June 2017 to October 2019 and included 182 outpatients. Patients were interviewed using the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. The National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) and the International Index of Erectile Function-5 (IIEF-5) were used for the evaluation of CP/CPPS and ED. The Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used to assess anxiety symptoms and depressive symptoms. The number of patients with mild CP/CPPS and mild ED, mild CP/CPPS and moderate-to-severe ED, moderate-to-severe CP/CPPS and mild ED, and moderate-to-severe CP/CPPS and moderate-to-severe ED was 69 (37.9%), 36 (19.8%), 35 (19.2%), and 42 (23.1%), respectively. The corresponding PHQ-9 scores of the four groups were 6.22, 7.19, 10.69, and 7.71, respectively. The corresponding GAD-7 scores of the four groups were 5.26, 6.31, 8.77, and 6.36, respectively. Among patients with moderate-to-severe CP/CPPS, the PHQ-9 and GAD-7 scores of the moderate-to-severe ED group were significantly lower than those of the mild ED group (P = 0.007 and P = 0.010, respectively). The prevalence of ED and premature ejaculation (PE) in patients with moderate-to-severe CP/CPPS was significantly higher than that in patients with mild CP/CPPS (P = 0.001 and P = 0.024, respectively). Our findings proved that the severity of ED was negatively associated with psychological symptoms in outpatients with moderate-to-severe CP/CPPS.

The Significance of Coherent Transformation on Grain Refinement and Consequent Enhancement in Toughness.

Coherent transformation is considered to be an effective approach to refine the microstructure and enhance toughness of structural steels. However, there are gaps in the knowledge on the key aspects of microstructure that govern toughness. In this regard, a low alloyed experimental steel with lean chemistry was subjected to a simple heat treatment involving austenitization at different temperatures, followed by quenching and tempering to obtain bainitic microstructures with different boundary composition. The microstructure of the four experimental steels was characterized by electron backscattered diffraction and mechanical properties were determined. The study indicated that the density of high angle grain boundaries does not adequately reflect the change of ductile-to-brittle transition temperatures (DBTT) of the experimental steels. Thus, we propose here a new mechanism on reducing DBTT from the perspective of misorientation of boundary, which takes into consideration these aspects in defining DBTT. One is inhibition effect on cleavage fracture by boundaries with high {100}-plane misorientation angles, and the other is ductility improvement by boundaries with high {110}-plane misorientation angles. Furthermore, the contribution of prior austenite grain boundary, packet boundary, block boundary, and sub-block boundary on toughness is also analyzed.

A rare case report of laryngopharyngeal polyp formation following anterior cervical discectomy and fusion (ACDF).

BACKGROUND: Anterior Cervical Discectomy and Fusion (ACDF) has been regarded as the "gold standard" treatment of cervical spondylosis. Though it has good outcomes, many complications still exist, such as loss of fixation, degeneration of adjacent segments, dysphagia and pharyngeal perforation. In view of current literature, this study is the first to report a case of laryngopharyngeal polyp following ACDF. CASE PRESENTATION: A 63 year old male patient suffered from cervical spine hyperextension after trauma accompanied by numbness of the hands and decreased muscle strength in both upper limbs. Anterior cervical fusion surgery was performed in our hospital, after which the patient's upper limb numbness disappeared and muscle strength returned to normal. In the fifth month after surgery, the patient developed a sore throat and dysphagia. Symptoms gradually worsened, and the patient was hospitalized four times, subsequently undergoing tracheotomy, internal fixation removal, and polypectomy. The patient's pronunciation, breathing, and swallowing functions returned to normal, and the incision healed. After a one-year follow-up, the polyp did not recur. CONCLUSIONS: Laryngopharyngeal polyp formation following ACDF has yet to be reported in literature. By excluding esophageal fistula as soon as possible, removing internal fixation and polypectomy serves as the best treatment in relieving patient symptoms.

Is milder psychological stress responsible for more severe erectile dysfunction?

China is a sexually conservative country compared with Western countries. To evaluate the psychological characteristics of Chinese erectile dysfunction (ED) patients, we conducted a cross-sectional study of 153 ED outpatients. Patients were interviewed with the Structured Interview on Erectile Dysfunction (SIEDY) for pathogenic quantification. ED was measured by International Index of Erectile Function (IIEF). Depression and anxiety were evaluated with 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalised Anxiety Disorder Scale (GAD-7) respectively. Most patients (74.5%) were <40 years old. IIEF-5 were significantly correlated with SIEDY scale 3 (r = .16, p = .040) and GAD-7 (p = .15, p = .033). The SIEDY scale 1 increased with age, but the IIEF-5, SIEDY scale 3, PHQ-9 and GAD-7 decreased with age. A negative correlation was observed between ED and psychological stress, which conflicts with many Western-country studies. Younger patients were characterised by milder ED but more psychological stress, while older patients were characterised by worse ED but less psychological stress. Which may be responsible for the conflicting result. Meanwhile, the much younger age distribution among Chinese ED outpatients may indicate that quite a few older ED patients (≥40 years) in China do not seek outpatient service which should merit more attention.

Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease?

INTRODUCTION: Erectile dysfunction (ED) and cardiovascular diseases (CVDs) share many common risk factors. ED could be a strong independent predictive factor of CVDs. Furthermore, the treatment of ED had been shown to be beneficial for cardiovascular diseases. However, the association between ED and CVDs has been reported scarcely in the literature. AIM: To investigate urologists' perception, diagnosis, and treatment of CVDs in patients with ED. METHODS: The study was conducted as a prospective study from November 2018 through February 2019, including urologists aged 18-64 years. All participants completed a survey of the knowledge of ED via an online questionnaire platform in 7 WeChat groups of urologists. WeChat is the most popular multipurpose messaging and social media in China. MAIN OUTCOME MEASURE: The main outcomes were the answers that urologists chose or filled. RESULTS: 449 urologists were included. Most of participants (375, 83.5%) agreed that CVDs are associated with ED. Only 231 participants (51.4%) thought ED was an independent disorder. The awareness of the association between ED and CVDs is significantly higher among male urologists than their female counterparts. Although 378 (83.6%) participants believed that the progression of these 2 diseases was consistent, only 181 (44.9%) would do conjoined assessment of both CVDs and ED. In addition, most urologists only considered conventional treatment, such as psychological intervention (341, 75.4%) and phosphodiesterase type 5 inhibitor (PDE5i) therapy (318, 70.4%) for their patients, whereas 339 urologists (88.3%) claimed that they would treat CVDs in patients with both ED and CVDs. 344 (76.6%) urologists showed some concerns over PDE5is. CONCLUSION: Urologists' assessment of CVDs in patients with ED was disappointing especially among young and female urologists or those working in underserved areas. Besides, the urologists' treatments of ED were not updated, and their attitudes toward the safety and effectiveness of PDE5is for CVDs were not optimistic. Li D, Li X, Peng A, et al. Do Urologists Really Recognize the Association Between Erectile Dysfunction and Cardiovascular Disease? Sex Med 2020;8:195-204.

Deguelin inhibits RANKL-induced osteoclastogenesis in vitro and prevents inflammation-mediated bone loss in vivo.

Excessive bone resorption by osteoclasts (OCs) plays an important role in lytic bone diseases, such as osteoporosis. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent; however, its effect on OCs remains unclear. To the best of our knowledge, this is the first study to report that deguelin inhibits the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis, messenger RNA expression of osteoclastic-specific genes, and osteoclastic bone resorption, in primary bone marrow-derived macrophages. At the molecular level, deguelin markedly blocked RANKL-induced osteoclastogenesis by attenuating the phosphorylation of NF-κB p65 and inhibiting p65 nuclear translocation. In addition, deguelin suppressed the downstream expression of nuclear factor of activated T-cell cytoplasmic 1, which is a crucial transcription factor in OC differentiation. Consistent with the in vitro results, deguelin inhibited lipopolysaccharide-induced bone resorption by suppressing osteoclastogenesis. Taken together, our findings reveal that deguelin has antiosteoclastic effects in vitro and in vivo and possesses potential as a new therapeutic option for osteolytic bone diseases.

X-linked inhibitor of apoptosis protein inhibitor Embelin induces apoptosis via PI3K/Akt pathway and inhibits invasion in osteosarcoma cells.

BACKGROUND: Embelin is an active compound identified as a novel X-linked inhibitor of apoptosis protein (XIAP) inhibitor from the Embelia ribes that exhibits various medicinal effects including anti-inflammatory and anticancer activities. However, the therapeutic effect of Embelin to human osteosarcoma is not yet determined. OBJECTIVES: In this study, we evaluated the sensitizing potential of Embelin on promoting apoptosis to cause osteosarcoma cell death and inhibiting its invasion. METHODS: We uesd 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide to detect the survival rates of osteosarcoma cells, Western blot to detect the expression of proteins in U-2 OS and MG63 cells, and fluorescence microscope to observe the morphology of apoptotic cells. RESULTS: The survival of osteosarcoma cells decreased, When Embelin was used. Obvious condensed and flared fluorescence was observed, when used high-dose Embelin. There was an increase of caspase-3, cleaved caspase-3, caspase-8, and caspase-9 in Embelin group, while PI3K, AKt, p-AKt, X-linked inhibitor of apoptosis protein, and MMP-9 were downregulated. The invasion of Embelin application was significantly lower than that of the control application. CONCLUSION: Embelin promoted apoptosis via XIAP and PI3K/Akt signaling pathway. XIAP inhibitor Embelin inducing apoptosis could cause osteosarcoma cell death and inhibit its invasion.

Combined application of Embelin and tumor necrosis factor-related apoptosis-inducing ligand inhibits proliferation and invasion in osteosarcoma cells via caspase-induced apoptosis.

Embelin, as an inhibitor of the X-linked inhibitor of apoptosis protein (XIAP), may induce apoptosis in various types of cancer cells. The present study aimed to determine the effect of Embelin on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of osteosarcoma cells. Embelin and TRAIL were applied to U2OS and MG63 cells, respectively or in combination. MTT was initially used to detect the difference in survival rates between the group receiving combined application of 100 ng/ml TRAIL and 20 µmol/l Embelin and the individual application groups. Light microscopic quantification was used to detect the morphology of the osteosarcoma cells in each group. Determination of cell apoptosis was subsequently performed using flow cytometry. The invasive ability of the cells was detected by a Transwell assay, prior to relative protein expression being determined by western blot analysis. Based on all the test data, it was revealed that the survival rates and the invasive ability were significantly lower following the combined application of 100 ng/ml TRAIL and 20 µmol/l Embelin than following the individual application of either (P<0.01). Additionally, upregulating expression of caspases, as well as death receptor 5, and downregulating expression of XIAP and matrix metalloproteinase 9 (MMP-9), had more significant effects in the combined group compared with the individual group and the control group. All these results suggested that Embelin may enhance TRAIL-induced apoptosis and inhibit the invasion of human osteosarcoma cells.

Irregular Implant Design Decreases Periimplant Stress and Strain Under Oblique Loading.

OBJECTIVES: To investigate whether a different implant geometry with the same potential contact surface area (PCSA) affects the principal stress and strains in bone. MATERIAL AND METHODS: Three-dimensional finite-element models were created with a single endosseous implant embedded in bone. The irregular (IR) dental root-analog implant and regular (R) cylindrical implant with the same PCSA 350 mm were modeled, keeping the size of the thinnest implant wall 0.8 mm, and the thinnest bone wall 1 mm. The regular or irregular abutments were either 4.5 mm lower than the platform of the implants or 5 mm higher than the platform of the implants, both with the taper 1.44°. A 100 N vertical or 100 N vertical/50 N horizontal occlusal loading was applied. The biomechanical behaviors of periimplant bone were recorded. RESULTS: The IR implant design experienced lower periimplant stress and strain under oblique loading than that of R implant design. In the IR implant design, comparable stress in bone, implant, and abutment were found under 100 N vertical loading or 100 N vertical/50 N horizontal loading. In the R implant design, much higher stress in bone, implant, and abutment were found under 100 N vertical/50 N horizontal loading than that under 100 N vertical loading. CONCLUSION: Irregular dental root-analog implant is a biomechanically favorable design principle for decreasing periimplant stress and strain under oblique loading.

Fangchinoline suppresses the proliferation, invasion and tumorigenesis of human osteosarcoma cells through the inhibition of PI3K and downstream signaling pathways.

Osteosarcoma is the most common malignant bone tumor. Most patients diagnosed with osteosarcoma are less than 20 years of age. Osteosarcoma cells proliferate rapidly and invade other tissues. At present, neoadjuvant chemotherapy is the primary pharmacodynamic strategy to prevent the progression of osteosarcoma. However, adverse effects of this strategy limit its long­term application. Previous research has shown that fangchinoline exerts antitumor effects on several types of tumor cells; however, its effect on osteosarcoma cells remains unknown. The present study evaluated the effects of fangchinoline on the proliferation, apoptosis, migration and invasion of osteosarcoma cells in vitro and on their tumorigenesis in vivo and determined the possible underlying mechanism of action. Fangchinoline­treated MG63 and U20S cells showed significantly decreased proliferation and significantly increased apoptosis. Fangchinoline markedly suppressed the migration and invasion of the MG63 cells. Fangchinoline­treated MG63 cells showed significantly decreased expression of phosphoinositide 3­kinase (PI3K) and Aktp­Thr308. Moreover, fangchinoline­treated MG63 cells showed downregulated expression of cyclin D1 and matrix metalloproteinase 2 and 9, which act downstream of PI3K, and upregulated expression of caspase­3 and caspase­8. Furthermore, fangchinoline suppressed the growth of subcutaneous osteosarcoma tumors in Balb/c mice subcutaneously injected with osteosarcoma cells. These findings suggest that fangchinoline inhibits the progression of osteosarcoma by suppressing the proliferation, migration and invasion and by accelerating the apoptosis of osteosarcoma cells. In addition, our results suggest that the mechanism underlying the antitumor effects of fangchinoline involve the inhibition of PI3K and its downstream signaling pathways.

Galangin suppresses human osteosarcoma cells: An exploration of its underlying mechanism.

Osteosarcoma is the most common malignant bone tumor that frequently affects adolescents. Osteosarcoma cells tend to proliferate and invade other tissues such as those of the lungs. Currently, neoadjuvant chemotherapy is the primary strategy to prevent tumor progression. However, its adverse effects result in poor long-term outcomes. Previous research has shown that galangin exhibits antitumor properties on several types of cancer cells; however its effect on osteosarcoma cells is yet unknown. The aims of this study were to evaluate the effects of galangin on the proliferation, apoptosis, migration, and invasion of osteosarcoma cells and to explore the underlying mechanisms. We found that the proliferation of MG63 and U20S osteosarcoma cells decreased significantly, while the apoptosis of MG63 cells accelerated significantly after exposure to galangin. In addition, the migration and invasion of MG63 cells were significantly inhibited by galangin. Moreover, phosphoinositide 3-kinase (PI3K) and Aktp-Thr308 expression levels were found to be significantly lower in galangin-treated MG63 cells than in the control cells, and the protein expression levels of their downstream regulators cyclin D1 and matrix metalloproteinase 2/9 were also downregulated in galangin-treated groups, while those of p27Kip1, caspase-3, and caspase-8 were upregulated. These findings suggest that galangin suppresses osteosarcoma cells by inhibiting their proliferation and invasion and accelerating their apoptosis, and the mechanism may be associated with the inhibition of PI3K and its downstream signaling pathway.