Effective Multi-Object Tracking via Global Object Models and Object Constraint Learning.

Effective multi-object tracking is still challenging due to the trade-off between tracking accuracy and speed. Because the recent multi-object tracking (MOT) methods leverage object appearance and motion models so as to associate detections between consecutive frames, the key for effective multi-object tracking is to reduce the computational complexity of learning both models. To this end, this work proposes global appearance and motion models to discriminate multiple objects instead of learning local object-specific models. In concrete detail, it learns a global appearance model using contrastive learning between object appearances. In addition, we learn a global relation motion model using relative motion learning between objects. Moreover, this paper proposes object constraint learning for improving tracking efficiency. This study considers the discriminability of the models as a constraint, and learns both models when inconsistency with the constraint occurs. Therefore, object constraint learning differs from the conventional online learning for multi-object tracking which updates learnable parameters per frame. This work incorporates global models and object constraint learning into the confidence-based association method, and compare our tracker with the state-of-the-art methods on public available MOT Challenge datasets. As a result, we achieve 64.5% MOTA (multi-object tracking accuracy) and 6.54 Hz tracking speed on the MOT16 test dataset. The comparison results show that our methods can contribute to improve tracking accuracy and tracking speed together.

Permethrin inhibits tube formation and viability of endothelial cells.

BACKGROUND: Exposure to environmental chemicals has been linked with endothelial dysfunction, which is a leading cause of human diseases, including atherosclerosis. Permethrin is a frequently used synthetic pyrethroid insecticide for which longer exposure may cause toxicity in several types of tissues and the development of metabolic diseases, including atherosclerosis, obesity and diabetes. The present study was designed to evaluate the potential adverse effect of permethrin on the function and activity of human endothelial cells. RESULTS: Permethrin was found to repress migration and tube formation by human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, as well as to significantly repress their viability after 24 and 48 h of treatment. Furthermore, increased reactive oxygen species (ROS) production was observed in cells treated with permethrin, and the permethrin-induced repression of cell viability was ROS-dependent. Permethrin did not influence apoptosis, necrosis or mitochondrial membrane potential in HUVECs. CONCLUSION: The results of the present study suggest that permethrin represses angiogenesis and viability through ROS-dependent and cell growth-, apoptosis- and necrosis-independent means. © 2022 Society of Chemical Industry.

Mirabegron for treatment of overactive bladder symptoms in patients with Parkinson's disease: A double-blind, randomized placebo-controlled trial (Parkinson's Disease Overactive bladder Mirabegron, PaDoMi Study).

AIMS: This study aimed to investigate the efficacy and safety of mirabegron for Parkinsonism patients with overactive bladder (OAB) symptoms in a randomized, placebo-controlled, multicenter study. MATERIALS AND METHODS: Inclusion criteria are Parkinsonism with OAB symptoms for 4 weeks or more, OAB symptom score (OABSS) questionnaire scores greater than 2, and OABSS urgency question scores greater than 1. After a 2-week wash-out period, the patients were randomized into placebo and mirabegron groups at visit 2. Visit 3 was performed after 4 weeks of medication. Mirabegron was prescribed to the two groups for the rest of the study period at visit 4. RESULT: The mean age was 68.1 ± 8.1 years and 72 males and 64 females were included. A total of 136 patients were screened, 117 patients were randomized, and 25 patients dropped out. The OABSS scores were significantly different between the two groups at Weeks 4 and 8. The OABSS scores became the same in the two groups at Week 12 (visit 5). The postvoid residual urine volume showed a mild increase to 64 ml in the mirabegron group compared to the placebo group at visit 4. Adverse events occurred in 27 patients (23.1%). The degree was mild in 26 cases (78.8%), moderate in five (15.2%), and severe in two (6.1%). Only 13 cases (39.4%) showed medication-related adverse events. Acute urinary retention occurred in a single case. The treatment satisfaction questionnaires showed no significant differences between the two groups. CONCLUSION: Mirabegron was effective in treating OAB symptoms in patients with Parkinsonism with acceptable adverse events.

Polyphenol Containing Sorghum Brans Exhibit an Anti-Cancer Effect in Apc Min/+ Mice Treated with Dextran Sodium Sulfate.

Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.

A mechanistic review: potential chronic disease-preventive properties of sorghum.

Sorghum is one of the most widely cultivated crops, and is used in foods, domestic animal feedstuffs, alcohol production, and biofuels. Recently, many research groups have demonstrated that sorghum contains various components that are strongly associated with the prevention of major human chronic diseases such as obesity, diabetes, atherosclerosis, cancer, and inflammation. However, to use sorghum more widely as a food for the potential prevention and treatment of human chronic diseases, more studies will be required to elucidate the biological mechanisms. In this review paper, we highlight multiple findings to propose a mechanistic link between sorghum consumption and reduced risk of chronic diseases. © 2020 Society of Chemical Industry.

Effect of udenafil administration on postmicturition dribbling in men: a prospective, multicenter, double-blind, placebo-controlled, randomized clinical study.

PURPOSE: Postmicturition dribbling (PMD) is a stressful symptom in middle-aged men characterized by urinary leakage after the completion of normal voiding. Appropriate treatments have not yet been introduced. This study assessed the efficacy of treatment of PMD with 75 mg udenafil daily. MATERIALS AND METHODS: The study included 138 men with regular sexual lifestyles. The Hallym PMD questionnaire (HPMDQ) was used to assess PMD symptoms. After all basic examinations, patients were randomly assigned to either udenafil or placebo. Patients completed the surveys, uroflowmetry (UFM), a bladder scan, and the paper test during the follow-up visit. RESULTS: The mean age of the patients was 57.6 years. PMD with one of every three urinations was experienced by 59 patients (42.8%), whereas 45 patients (32.6%) experienced PMD with two of every three urinations. PMD with every urination was experienced by 34 patients (24.6%). More than half of the patients (89 patients, 65.4%) indicated that persistent PMD symptoms would likely result in moderate to severe discomfort in their daily activities. As time passed, the udenafil group showed significant improvement in PMD symptoms (p = 0.001). CONCLUSION: Udenafil 75 mg once daily can be an effective treatment for patients with PMD symptoms.

Recent Trends in Transurethral Surgeries and Urological Outpatient Procedures: a Nationwide Population-based Cohort Study.

BACKGROUND: Demographic change and advances in technology affect transurethral surgery and outpatient procedures in the urologic field. There are few population-based studies that accurately assess the trend of transurethral surgery and outpatient procedures including diagnostic tests. We investigated the recent epidemiologic trends in transurethral surgeries and urological outpatient procedures from 2009 to 2016 in Korea using the entire population-based cohort. METHODS: We analyzed medical service claim data of transurethral surgery, urological outpatient procedures submitted by medical service providers from the Health Insurance Review and Assessment Service from 2009 to 2016. RESULTS: Transurethral ureter surgery increased by 134.9% from 14,635 in 2009 to 34,382 in 2016 (B = 2,698; R² = 0.98; P < 0.001). The transurethral bladder surgery increased by 65.5% from 12,482 in 2009 to 20,658 in 2016 (B = 1,149; R² = 0.97; P < 0.001). Over the 8-years period, there were not significant changes in transurethral prostate (B = 43; R² = 0.04; P = 0.617) and urethral surgery (B =-12; R² = 0.18; P = 0.289). The significantly increasing trends in cystoscopy (B = 5,260; R² = 0.95; P < 0.001) and uroflowmetry (B = 53,942; R² = 0.99; P < 0.001) were observed during the 8-year period. There was no difference in bladder catheterization during the 8-year period. Urodynamic study (UDS: B =-2,156; R² = 0.77; P = 0.003) and electrical stimulation treatment (EST: B =-1,034; R² = 0.87; P < 0.001) significantly decreased. CONCLUSION: In Korea, transurethral ureter surgery and transurethral bladder surgery have been continuously increasing. Transurethral prostate surgery and transurethral urethral surgery remained constant with no increase or decrease. Cystoscopy and uroflowmetry continue to increase, while UDS and EST continue to decrease.

Identification of epithelial-specific ETS-1 (ESE-1) as a tumor suppressor and molecular target of green tea compound, EGCG.

Epithelial specific ETS-1 (ESE-1) belongs to the E26 transformation-specific transcription factor superfamily and is of great interest as a potential target for managing several types of cancer. Despite its clinical significance, the documented effects of ESE-1 on cancer development and progression are contradictory and its underlying biological mechanism of action remains elusive. The objectives of this study are to investigate whether ESE-1 is a tumor suppressor and to identify dietary anti-cancer compound to activate ESE-1 expression in human colon cancer model. ESE-1 knockout and xenograft mouse models were used to examine the effect of ESE-1 in colon tumorigenesis. Stable human colon cancer cell lines were used for in vitro mechanistic studies. ESE-1 knockout in mice increased azoxymethane (AOM)-induced and dextran sulfate sodium (DSS)-promoted formation of aberrant crypt foci (ACF). Conversely, overexpression of ESE-1 suppressed tumorigenicity in a xenograft mouse study, and repressed anchorage-independent growth and migration/invasion in human colon cancer cells. Full length ESE-1 localized abundantly in the nucleus, and internal deletion of nuclear localization sequence 2 (NLS2) reduced nuclear ESE-1. Three lysine residues (318 KKK320 ) in the NLS2 determine its nuclear localization. We identified epigallocatechin-3-gallate (EGCG) that acts as a transcriptional activator of ESE-1 in human colon cancer cells. These findings propose a novel and promising molecular target of dietary anti-cancer compounds for prevention of colon cancer.

Effect of tadalafil 5 mg on post-micturition dribble in men with lower urinary tract symptoms: a multicentre, double-blind, randomized, placebo-controlled trial.

OBJECTIVES: To compare the effects of taking tadalafil 5 mg and placebo once daily on post-micturition dribble (PMD) in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: Our prospective, randomized, double-blind, placebo-controlled, multicentre trial enrolled 102 men with PMD and other LUTS. PMD was assessed using the Hallym Post-Micturition Dribble Questionnaire (HPMDQ) and according to PMD volume. Over a 12-week period, patients took either tadalafil 5 mg (n = 51) or placebo (n = 51) once daily and their HPMDQ and PMD volume results were evaluated. Adverse events (AEs) were also reported. RESULTS: Over the course of 12 weeks, total HPMDQscores and PMD volumes improved significantly more in the tadalafil group than in the placebo group (reduction of total HPMDQ score of ≥2 points in the tadalafil and placebo group in 68.8% and 31.9% of patients (P < 0.001) and decreased mean PMD volume in the tadalafil and placebo group at 0.48 mL and 0.22  mL, respectively (P = 0.046). Specifically, PMD frequency decreased and quality of life increased significantly more in the tadalafil group than in the placebo group (P = 0.029 and P < 0.001, respectively). Furthermore, 66.7% of the tadalafil group reported moderate and significant PMD improvement, whereas only 4.2% reported that tadalafil was ineffective. Treatment-emergent AEs did not significantly differ between the groups (all P > 0.05), and no serious AEs were observed. CONCLUSION: Taking tadalafil 5 mg once daily reduced PMD symptom severity and PMD volume in men with PMD, without inducing serious AEs, more effectively than placebo, suggesting that taking tadalafil 5 mg once daily may be an effective and well-tolerated PMD treatment.

A Comparison of the Efficacy and Safety Between Hyaluronic Acid and Polylactic Acid Filler Injection in Penile Augmentation: A Multicenter, Patient/Evaluator-Blinded, Randomized Trial.

BACKGROUND: Studies about the clinical utility of fillers on penile augmentation (PA) are lacking. Furthermore, no randomized study has compared the utilities of fillers. AIM: To compare the efficacy and safety between hyaluronic acid (HA) and polylactic acid (PLA) filler injection for PA. METHODS: This prospective, randomized patient/evaluator-blind, comparative multicenter study consisted of an initial 2-week baseline period and 48-week patient/evaluator-blind post-injection period. 72 patients with small penis syndrome were enrolled from 3 institutions between March-July 2016. Patients were divided into 2 groups: the HA group, comprising 36 patients injected with HA, and the PLA group, comprising 36 patients injected with PLA. MAIN OUTCOME MEASURES: Penile girth and satisfaction were assessed at baseline and at 4, 12, 24, and 48 weeks after injection. RESULTS: Penile girth increases adequately lasted ≤48 weeks in both groups (16.95 ± 10.53 and 13.49 ± 9.98 mm of mean increase in the HA and PLA groups, respectively; P < .001). The mean penile girth increase in the HA group was significantly greater than that in the PLA group at 4 weeks (P < .001). Subsequently, it gradually decreased and was no longer significantly different at 48 weeks (P = .075). Satisfaction levels increased after injection and were maintained ≤48 weeks. No significant differences were observed in the overall satisfaction level between the groups (P > .05). Filler injection-related adverse events were mild and transient and occurred in 1 and 3 patients in the HA and PLA groups, respectively. CLINICAL IMPLICATIONS: This study provides an overview of the efficacy and safety of HA and PLA fillers, which are the most commonly used soft tissue fillers for PA. STRENGTH AND LIMITATIONS: This study, to our knowledge, is the first to compare the efficacy and safety between different filler injections for human PA. However, it was impossible to perform a researcher-blinded trial because of the unique properties of fillers, and 31 patients (43.1%) were dropped during the study period. CONCLUSIONS: Both HA and PLA filler injections for PA led to a significant augmentative effect without serious adverse events and had clinically comparable efficacy and safety. Yang DY, Ko K, Lee SH, et al. A Comparison of the Efficacy and Safety Between Hyaluronic Acid and Polylactic Acid Filler Injection in Penile Augmentation: A Multicenter, Patient/Evaluator-Blinded, Randomized Trial. J Sex Med 2019;16:577-585.

A Prediction Model Using Machine Learning Algorithm for Assessing Stone-Free Status after Single Session Shock Wave Lithotripsy to Treat Ureteral Stones.

PURPOSE: The aim of this study was to develop and validate a decision support model using a machine learning algorithm to predict treatment success after single session shock wave lithotripsy in ureteral stone cases. MATERIALS AND METHODS: Of the 1,803 patients treated with shock wave lithotripsy we selected those with ureteral stones who had preoperative computerized tomography available. Treatment success after single session shock wave lithotripsy was defined as freedom from stones or residual stone fragments less than 2 mm long on computerized tomography or plain x-ray of the kidneys, ureters and bladder 2 weeks later. Decision tree analysis was done using a machine learning algorithm to identify relevant parameters. A decision support model was developed to calculate the probability of treatment success. RESULTS: A total of 791 patients were enrolled in study. Mean ± SD stone length was 5.9 ± 2.3 mm and mean stone volume was 89.3 ± 140.0 mm3. The overall treatment success rate after SWL was 64.4% (509 cases). The rate for upper, middle and lower ureter stones was 59.8%, 65.5% and 69.6%, respectively. On decision tree analysis the top 3 performance criteria factors were volume, length and HU. Decision models were constructed with all possible combinations of factors. The model with 15 factors had greater than 92% accuracy and an average ROC AUC of 0.951. CONCLUSIONS: We applied a machine learning algorithm, a subfield of artificial intelligence, to predict the outcome after single session shock wave lithotripsy for ureteral stones. A 92.29% accurate decision model was developed with 15 factors and an average ROC AUC of 0.951.

The transgluteal approach to shockwave lithotripsy to treat distal ureter stones: a prospective, randomized, and multicenter study.

PURPOSE: We compared the outcomes of SWL to treat distal ureter stones with regard to the conventional prone and supine positions using the transgluteal approach through the greater sciatic foramen. METHODS: A prospective, randomized, single-blind, and multicenter study was conducted between October 2014 and July 2015. The inclusion criteria were radio-opaque distal ureter stones with a maximum diameter of 0.5-2 cm as measured on a CT scan. The included 160 patients were randomly assigned to two groups: the prone group (n = 80; treated in the conventional prone position) and the transgluteal group (n = 80; treated in the supine position using a transgluteal approach). In the latter group, the focused shock wave was transmitted through the greater sciatic foramen with the head positioned at a 40° angle to the vertical. "Stone-free" was defined as the complete clearance of stone fragments, assessed using a CT scan at 2 weeks after treatment. Overall satisfaction was self-reported using a 0-5 Likert scale. RESULTS: The overall efficacy was 66.9%. The stone-free rate was significantly higher in the transgluteal group (72.6%) than in the prone group (54.7%; odds ratio 2.413, 95% CI 1.010-5.761, P = 0.023). No serious adverse events due to treatment were observed in either group. The satisfaction score of the transgluteal group was 4.21 ± 0.81, and 83.6% were willing to repeat the same procedure if necessary. CONCLUSIONS: SWL using the transgluteal approach via a supine position through the greater sciatic foramen was more effective than via the conventional prone position. Furthermore, this approach provided a comparably safe and satisfactory procedure.

Author Correction to: The transgluteal approach to shockwave lithotripsy to treat distal ureter stones: a prospective, randomized, and multicenter study.

The funding number was incorrect in the original published article. The correct funding number should read as follows.

Development of an Mg-Based Alloy with High Hydriding and Dehydriding Rates and Large Hydrogen Storage Capacity by Adding TaF5.

A sample with a composition of 95 wt% Mg + 5 wt% TaF5 (named Mg-5TaF5) was prepared by reactive mechanical grinding. The activation of Mg-5TaF5 was not necessary, and Mg-5TaF5 had an effective hydrogen storage capacity (the quantity of hydrogen absorbed for 60 min) larger than 5 wt%. At the first cycle (n = 1), the sample absorbed 4.50 wt% H for 10 min and 5.06 wt% H for 60 min at 593 K under 12 bar H2. At n = 1, the sample desorbed 1.58 wt% H for 10 min and 4.93 wt% H for 60 min at 593 K under 1.0 bar H2. The Mg-5TaF5 sample dehydrided at n = 3 contained MgF2 and Ta2H. The hydriding-dehydriding cycling of the sample, which forms MgF2 and Ta2H by reaction with hydrogen, is considered to produce defects on the surface of and inside the Mg particles, to create clean surfaces, and to reduce the particle size of Mg, due to the repetition of expansion with hydrogen absorption and contraction with hydrogen release. Mg-5TaF5 had a higher hydriding rate and a higher dehydriding rate after an incubation period and greater quantities of hydrogen absorbed and desorbed for 60 min than Mg-10TaF5, Mg-10MnO, or Mg-10Fe2O3.

Improvement in the Hydrogen-Storage Characteristics of Magnesium Hydride by Grinding with Sodium Alanate and Transition Metals in a Hydrogen Atmosphere.

In this work, MgH2 was used as a starting material instead of Mg. The sample was prepared by grinding MgH2 with sodium alanate and transition metals in a hydrogen atmosphere. Its hydriding and dehydriding properties were measured followed by X-ray diffraction (XRD) analyses and observations of its microstructure. Activation was not required for the 86MgH2 + 10Ni + 2NaAlH4 + 2Ti sample. At the first cycle (n = 1), the sample absorbed 4.96, 5.28 and 5.36 wt% H for 10, 15 and 60 min, respectively, at 593 K in 12 bar H2, showing that the sample absorbed quite a large amount of hydrogen for 60 min (nearly 5.5 wt% H). The initial hydriding rate increased as the temperature increased from 423 K to 553 K and decreased from 553 K to 593 K. The sample showed quite high hydriding rates at relatively low temperatures 423 K (at n = 1) and 473 K (at n = 2) in 12 bar H2, compared with those of other metallic element(s) or compound(s)-added Mg or MgH2 alloys, absorbing 2.89 wt% H for 5 min, 2.97 wt% H for 10 min, and 3.31 wt% H for 60 min at 473 K.

Arctigenin represses TGF-ß-induced epithelial mesenchymal transition in human lung cancer cells.

Arctigenin (ARC) is a lignan that is abundant in Asteraceae plants, which show anti-inflammatory and anti-cancer activities. The current study investigated whether ARC affects cancer progression and metastasis, focusing on EMT using invasive human non-small cell lung cancer (NSCLC) cells. No toxicity was observed in the cells treated with different doses of ARC (12-100 µM). The treatment of ARC repressed TGF-ß-stimulated changes of metastatic morphology and cell invasion and migration. ARC inhibited TGF-ß-induced phosphorylation and transcriptional activity of smad2/3, and expression of snail. ARC also decreased expression of N-cadherin and increased expression of E-cadherin in dose-dependent and time-dependent manners. These changes were accompanied by decreased amount of phospho-smad2/3 in nucleus and nuclear translocation of smad2/3. Moreover, ARC repressed TGF-ß-induced phosphorylation of ERK and transcriptional activity of ß-catenin. Our data demonstrate anti-metastatic activity of ARC in lung cancer model.

Natural variation in CIRCADIAN CLOCK ASSOCIATED 1 is associated with flowering time in Brassica rapa.

Flowering time is a very important agronomic trait and the development of molecular markers associated with this trait can facilitate crop breeding. CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), a core oscillator component of circadian rhythms that affect metabolic pathways in plants, has been implicated in flowering time control in species of Brassica. CCA1 gene sequences from three Brassica rapa inbred lines, showing either early flowering or late flowering phenotypes, were analyzed and a high level of sequence variation was identified, especially within the fourth intron. Using this information, three PCR primer sets were designed and tested using various inbred lines of B. rapa. The usage of InDel markers was further validated by evaluation of flowering time and high resolution melting (HRM) analysis. Both methods, PCR and HRM, validated the use of newly developed markers. Additional sequence analyses of Brassica plants with diploid (AA, BB, or CC) and allotetraploid genomes further confirmed a large number of sequence polymorphisms in the CCA1 gene, including insertions/deletions in the fourth intron. Our results demonstrated that sequence variations in CCA1 can be used to develop valuable trait-related molecular markers for Brassica crop breeding.

Correlation between overactive bladder symptom score and neuropsychological parameters in Alzheimer's disease patients with lower urinary tract symptom.

PURPOSE: To examine an association between the overactive bladder symptom score (OABSS) and neuropsychological parameters. Moreover, we investigate the factors that affect each item in the questionnaire. MATERIALS AND METHODS: A total of 376 patients (males: 184; females: 192) with probable Alzheimer's disease (AD) were recruited. Cognitive testing was conducted using the Mini Mental Status Examination (MMSE), Clinical Dementia Rating (CDR) scale, Global Deterioration Scale (GDS), and Barthel Activities of Daily Living (ADL). Lower urinary tract symptom (LUTS) was assessed using OABSS and voiding diary. RESULTS: The prevalence of overactive bladder (OAB) (defined as OABSS ≥3 with na urgency score of ≥2) in patients with AD was 72.6%. Among the OAB subjects, the most common severity of symptom was moderate (72.6%), followed by mild (21.2%), and severe (5.8%). It was found that OABSS had a very high correlation with aging (r=0.75; p<0.001). When compared with neuropsychological parameters, it was found that OABSS was highly correlated with the CDR scores (r=0.446; p<0.001). However, no significant correlation was found between the changes in OABSS scores and those in other neuropsychological parameters. Based on the individual symptom scores, urgency incontinence was highly correlated with the CDR scores (r=0.43; p<0.001). CONCLUSIONS: OABSS is a useful tool in assessing AD patients with LUTS. There was a consistent positive association between OABSS severity, including urgency incontinence, and CDR scores.

Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and p53.

Osteosarcoma is the most common bone cancer. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Currently, much anticancer therapy uses drugs that affect oncogenes/tumor suppressor genes, such as p53 (up-regulation) and Sp1 (down-regulation). Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Building on this knowledge, we evaluated the ability of trans-chalcone to reduce viability, to induce apoptosis, and to alter gene expression of p53 and Sp1 in human osteosarcoma cell lines. We found that treatment of trans-chalcone inhibited growth of osteosarcoma cells in a dose- and time-dependent manner, with significant inhibition at 10 µM after 48 h; apoptosis was also induced in a dose-dependent manner, with 1.9- and 3.6-fold induction at 10 µM and 50 µM, respectively, compared to non-treated cells. Further experiments suggest that trans-chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. trans-chalcone and its derivatives could be important in the development of future clinical trials in osteosarcoma. © 2015 Wiley Periodicals, Inc.

TCF4 Is a Molecular Target of Resveratrol in the Prevention of Colorectal Cancer.

The Wnt/ß-catenin pathway plays an essential role in the tumorigenesis of colorectal cancer. T-cell factor-4 (TCF4) is a member of the TCF/LEF (lymphoid enhancer factor) family of transcription factors, and dysregulation of ß-catenin is decisive for the initiation and progression of colorectal cancer. However, the role of TCF4 in the transcriptional regulation of its target gene remained poorly understood. Resveratrol is a dietary phytoalexin and present in many plants, including grape skin, nuts and fruits. Although resveratrol has been widely implicated in anti-tumorigenic and pro-apoptotic properties in several cancer models, the underlying cellular mechanisms are only partially understood. The current study was performed to elucidate the molecular mechanism of the anti-cancer activity of resveratrol in human colorectal cancer cells. The treatment of resveratrol and other phytochemicals decreased the expression of TCF4. Resveratrol decreases cellular accumulation of exogenously-introduced TCF4 protein, but did not change the TCF4 transcription. The inhibition of proteasomal degradation using MG132 (carbobenzoxy-Leu-Leu-leucinal) and lactacystin ameliorates resveratrol-stimulated down-regulation of TCF4. The half-life of TCF4 was decreased in the cells exposed to resveratrol. Resveratrol increased phosphorylation of TCF4 at serine/threonine residues through ERK (extracellular signal-regulated kinases) and p38-dependent pathways. The TCF4 knockdown decreased TCF/ß-catenin-mediated transcriptional activity and sensitized resveratrol-induced apoptosis. The current study provides a new mechanistic link between resveratrol and TCF4 down-regulation and significant benefits for further preclinical and clinical practice.