Gossypol Inhibits Metastasis of Lung Cell Carcinoma by Reversing Epithelial to Mesenchymal Transition and Suppressing Proteases Activity.

Gossypol, a natural polyphenolic compound, possesses antivirus activity and induces cell death of different types of tumors. However, the efficacy of gossypol on lung carcinoma metastases and epithelial to mesenchymal transition remains unknown. The aim of the present work was to determine the cellular and molecular mechanism of the anti-cancer and anti-metastatic efficacies of gossypol on human lung carcinoma cells. Gossypol showed a marked suppression of the viability, motility, and invasion in H1299 and A549 cells. Zymography assay showed that gossypol was sufficient to suppress the activities of urokinase-type plasminogen activator and matrix metalloproteinase-2. Gossypol reversed TGF-ß-induced epithelial to mesenchymal transition. Gossypol reduced vimentin, p-FAK, p-Src and p-paxillin. In vivo studies of gossypol were performed using subcutaneous inoculation and tail vein injection of A549 into immunodeficient BALB/c nude mice and severe combined immunodeficient mice.

An IoT Real-Time Potable Water Quality Monitoring and Prediction Model Based on Cloud Computing Architecture.

In order to achieve the Sustainable Development Goals (SDG), it is imperative to ensure the safety of drinking water. The characteristics of each drinkable water, encompassing taste, aroma, and appearance, are unique. Inadequate water infrastructure and treatment can affect these features and may also threaten public health. This study utilizes the Internet of Things (IoT) in developing a monitoring system, particularly for water quality, to reduce the risk of contracting diseases. Water quality components data, such as water temperature, alkalinity or acidity, and contaminants, were obtained through a series of linked sensors. An Arduino microcontroller board acquired all the data and the Narrow Band-IoT (NB-IoT) transmitted them to the web server. Due to limited human resources to observe the water quality physically, the monitoring was complemented by real-time notifications alerts via a telephone text messaging application. The water quality data were monitored using Grafana in web mode, and the binary classifiers of machine learning techniques were applied to predict whether the water was drinkable or not based on the data collected, which were stored in a database. The non-decision tree, as well as the decision tree, were evaluated based on the improvements of the artificial intelligence framework. With a ratio of 60% for data training: at 20% for data validation, and 10% for data testing, the performance of the decision tree (DT) model was more prominent in comparison with the Gradient Boosting (GB), Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM) modeling approaches. Through the monitoring and prediction of results, the authorities can sample the water sources every two weeks.

The Force-Frequency Characteristics of Quartz Wafers under a Cantilever Beam Structure.

This study investigated the force-frequency characteristics of quartz wafers inside a cantilever beam frame. Firstly, the force-frequency coefficient formula of quartz wafers with fixed ends under axial force was analyzed. Firstly, the formula for the force-frequency coefficient of quartz wafers with fixed ends under axial force was analyzed. A force-frequency coefficient formula suitable for cantilever beam structures was derived by considering the changes in surface stress and stiffness of quartz wafers with fixed ends and one end under force on the other. Subsequently, the formula's accuracy was verified by experiments, and the accuracy was more than 92%. In addition, strain simulation analysis was performed on three different shapes of quartz wafers, and experimental verification was carried out on two of them. The results revealed that trapezoidal quartz wafers and cantilever beam structures exhibited superior stress distribution to rectangular chips. Furthermore, by positioning electrodes at various locations on the surface of the quartz chip, it was observed that, as the electrodes moved closer to the fixed end, the force-frequency coefficient of the rectangular quartz chip increased, along with an increase in chip strain under the cantilever structure. In summary, this study provides a new approach for designing cantilever quartz resonator sensors in the future.

Scleroderma-like Lesions in a Patient Undergoing Combined Pembrolizumab and Routine Chemotherapy: A Case Report and Literature Review.

Triple-negative breast cancer (TNBC) represents a challenging malignancy with limited treatment options and a poor prognosis. Adjuvant therapies, including chemotherapy and immune checkpoint inhibitors (ICI), are commonly employed following breast conservation surgery. However, these treatments can lead to various adverse effects, including cutaneous complications and connective tissue disorders. Here, we present the case of a 54-year-old woman with TNBC who developed morphea, a form of localized scleroderma, following adjuvant chemotherapy and pembrolizumab administration. This case highlights the rarity of drug-induced morphea and emphasizes the importance of recognizing and managing such adverse events in breast cancer patients. We discuss the clinical characteristics, diagnostic challenges, and treatment considerations associated with drug-induced scleroderma-like lesions, as well as the potential mechanisms underlying their development. Furthermore, we review the literature on the incidence, clinical features, and outcomes of scleroderma-like lesions induced by chemotherapy and ICIs. This case underscores the need for increased awareness of immune-related adverse events in patients receiving immunotherapy, as well as the importance of individualized treatment approaches to optimize patient care and outcomes.

Adaptive Autonomous Protocol for Secured Remote Healthcare Using Fully Homomorphic Encryption (AutoPro-RHC).

The outreach of healthcare services is a challenge to remote areas with affected populations. Fortunately, remote health monitoring (RHM) has improved the hospital service quality and has proved its sustainable growth. However, the absence of security may breach the health insurance portability and accountability act (HIPAA), which has an exclusive set of rules for the privacy of medical data. Therefore, the goal of this work is to design and implement the adaptive Autonomous Protocol (AutoPro) on the patient's remote healthcare (RHC) monitoring data for the hospital using fully homomorphic encryption (FHE). The aim is to perform adaptive autonomous FHE computations on recent RHM data for providing health status reporting and maintaining the confidentiality of every patient. The autonomous protocol works independently within the group of prime hospital servers without the dependency on the third-party system. The adaptiveness of the protocol modes is based on the patient's affected level of slight, medium, and severe cases. Related applications are given as glucose monitoring for diabetes, digital blood pressure for stroke, pulse oximeter for COVID-19, electrocardiogram (ECG) for cardiac arrest, etc. The design for this work consists of an autonomous protocol, hospital servers combining multiple prime/local hospitals, and an algorithm based on fast fully homomorphic encryption over the torus (TFHE) library with a ring-variant by the Gentry, Sahai, and Waters (GSW) scheme. The concrete-ML model used within this work is trained using an open heart disease dataset from the UCI machine learning repository. Preprocessing is performed to recover the lost and incomplete data in the dataset. The concrete-ML model is evaluated both on the workstation and cloud server. Also, the FHE protocol is implemented on the AWS cloud network with performance details. The advantages entail providing confidentiality to the patient's data/report while saving the travel and waiting time for the hospital services. The patient's data will be completely confidential and can receive emergency services immediately. The FHE results show that the highest accuracy is achieved by support vector classification (SVC) of 88% and linear regression (LR) of 86% with the area under curve (AUC) of 91% and 90%, respectively. Ultimately, the FHE-based protocol presents a novel system that is successfully demonstrated on the cloud network.

Reduction of invasion and cell stemness and induction of apoptotic cell death by Cinnamomum cassia extracts on human osteosarcoma cells.

Cinnamomum cassia possesses antioxidative activity and induces the apoptotic properties of various cancer types. However, its effect on osteosarcoma invasion and cancer stemness remains ambiguous. Here, we examined the molecular evidence of the anti-invasive effects of ethanoic C. cassia extracts (CCE). Invasion and migration were obviously suppressed after the expression of urokinase-type plasminogen activator and matrix metalloprotein 2 in human osteosarcoma 143B cells were downregulated. CCE reversed epithelial-to-mesenchymal transition (EMT) induced by transforming growth factor ß1 and downregulated mesenchymal markers, such as snail-1 and RhoA. CCE suppressed self-renewal property and the expression of stemness genes (aldehyde dehydrogenase, Nanog, and CD44) in the 143B cells. CCE suppressed cell viability, reduced the colony formation of osteosarcoma cancer cells, and induced apoptotic cell death in the 143B cells, as indicated by caspase-9 activation. The xenograft tumor model of immunodeficient BALB/c nude mice showed that CCE administered in vivo through oral gavage inhibited the growth of implanted 143B cells. These findings indicated that CCE inhibited the invasion, migration, and cancer stemness of the 143B cells. CCE reduced proliferation of 143B cell possibly because of the activation of caspase-9 and the consequent apoptosis, suggesting that CCE is a potential anticancer supplement for osteosarcoma.

The effect of weather, air pollution and seasonality on the number of patient visits for epileptic seizures: A population-based time-series study.

OBJECTIVE: The objective of the study was to explore the influences of seasonality, meteorological conditions, and air pollution exposure on the number of patients who visit the hospital due to seizures. METHODS: Outpatient and inpatient data from the National Health Insurance Database of Taiwan from 2009 to 2013, meteorological data from the Meteorological Bureau, and air pollution exposure data from the Taiwan Air Quality Monitoring Stations were collected and integrated into daily time series data. The following data processing and analysis results are based on the mean of the 7 days' lag data of the 18 meteorological condition/air pollution exploratory factors to identify the critical meteorological conditions and air pollution exposure factors by executing univariate analysis. The average hospital visits for seizure per day by month were used as an index of observation. The effect of seasonality has also been examined. RESULTS: The average visits per day by month had a significant association with 10 variables. Overall, the number of visits due to these factors has been estimated to be 71.529 (13.7%). The most obvious factors affecting the estimated number of visits include ambient temperature, CH4, and NO. Six air pollutants, namely CH4, NO, CO, NO2, PM2.5, and NMHC had a significantly positive correlation with hospital visits due to seizures. Moreover, the average daily number of hospital visits was significantly high in January and February (winter season in Taiwan) than in other months (R2 = 0.422). CONCLUSION: The prediction model obtained in this study indicates the necessity of rigorous monitoring and early warning of these air pollutants and climate changes by governments. Additionally, the study provided a firm basis for establishing prediction models to be used by other countries or for other diseases.

Association of urate-lowering drugs with the risk of future urolithiasis in patients with gout: A population-based nested case-control study.

BACKGROUND: Patients with gout have an increased risk of urolithiasis and usually need urate-lowering therapy (ULT) for the prevention of disease progression. However, there is a paucity of clinical data regarding the risk of future urolithiasis in ULT users. METHODS: This nested case-control study was performed using the Taiwan National Health Insurance Research Database. The aim of this study was to examine whether ULT (xanthine oxidase inhibitors [XOIs] or uricosuric agents) is associated with risk of future urolithiasis in patients with gout. Data were collected from January 2000 to December 2012. RESULTS: This study included 2307 case patients and 2307 matched controls. Case patients had gout that developed into urolithiasis, and control patients had gout but were not diagnosed with urolithiasis during the study period. Patients had a mean age of 56.3 years at diagnosis of gout, and 83.2% were male patients. No association was detected between use of XOIs or uricosuric agents and risk of future urolithiasis. Furthermore, there was no significant difference in the risk of future urolithiasis in patients exposed to various cumulative days of XOI or uricosuric prescriptions. CONCLUSION: The present study provides evidence that neither XOIs nor uricosuric agents are associated with risk of future urolithiasis in patients with gout. Before the availability of more clinical evidence, ensuring high fluid intake and prospective monitoring of urolithiasis development are still important for uricosuric agent users.

IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1.

T helper (Th)2 cytokines such as interleukin (IL)-4 and IL-13 control immune function by acting on leukocytes. They also regulate multiple responses in non-hematopoietic cells. During pregnancy, IL-4 and IL-13 facilitate alveologenesis of mammary glands. This particular morphogenesis generates alveoli from existing ducts and requires substantial cell proliferation. Using 3D cultures of primary mouse mammary epithelial cells, we demonstrate that IL-4 and IL-13 promote cell proliferation, leading to enlargement of mammary acini with partially filled lumens. The mitogenic effects of IL-4 and IL-13 are mediated by STAT6 as inhibition of STAT6 suppresses cell proliferation and improves lumen formation. In addition, IL-4 and IL-13 stimulate tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Prolonged treatment with these cytokines leads to increased IRS-1 abundance, which, in turn, amplifies IL-4- and IL-13-stimulated IRS-1 tyrosine phosphorylation. Through signaling crosstalk between IL-4/IL-13 and insulin, a hormone routinely included in mammary cultures, IRS-1 tyrosine phosphorylation is further enhanced. Lowering IRS-1 expression reduces cell proliferation, suggesting that IRS-1 is involved in IL-4- and IL-13-stimulated cell proliferation. Thus, a Th2-dominant cytokine milieu during pregnancy confers mammary gland development by promoting cell proliferation.

A propositional AI system for supporting epilepsy diagnosis based on the 2017 epilepsy classification: Illustrated by Dravet syndrome.

PURPOSE: The 2017 epilepsy and seizure diagnosis framework emphasizes epilepsy syndromes and the etiology-based approach. We developed a propositional artificial intelligence (AI) system based on the above concepts to support physicians in the diagnosis of epilepsy. METHODS: We analyzed and built ontology knowledge for the classification of seizure patterns, epilepsy, epilepsy syndrome, and etiologies. Protégé ontology tool was applied in this study. In order to enable the system to be close to the inferential thinking of clinical experts, we classified and constructed knowledge of other epilepsy-related knowledge, including comorbidities, epilepsy imitators, epilepsy descriptors, characteristic electroencephalography (EEG) findings, treatments, etc. We used the Ontology Web Language with Description Logic (OWL-DL) and Semantic Web Rule Language (SWRL) to design rules for expressing the relationship between these ontologies. RESULTS: Dravet syndrome was taken as an illustration for epilepsy syndromes implementation. We designed an interface for the physician to enter the various characteristics of the patients. Clinical data of an 18-year-old boy with epilepsy was applied to the AI system. Through SWRL and reasoning engine Drool's execution, we successfully demonstrate the process of differential diagnosis. CONCLUSION: We developed a propositional AI system by using the OWL-DL/SWRL approach to deal with the complexity of current epilepsy diagnosis. The experience of this system, centered on the clinical epilepsy syndromes, paves a path to construct an AI system for further complicated epilepsy diagnosis.

PPARα plays an important role in the migration activity, and the expression of CYP2S1 and CYP1B1 in chrysin-treated HCT116 cells.

OBJECTIVE: This study aimed to examine the metabolising effect of chrysin by investigating the mRNA expression levels of PPARα and its related cellular mechanisms in HCT116 cells. RESULTS: The mRNA expression of PPARα was significantly induced in HCT116 cells following treatment with chrysin for 36 h, but the mRNA expression of PPARα was inhibited, when the cells were treated with a combination of chrysin and MK886 (PPARα inhibitor). This phenomenon proved that the incorporation of MK886 lowers the expression levels of PPARα, thus enabling us to study the function of PPARα. The cell population of the G0/G1 phase significantly increased in chrysin-treated cells, which was accompanied by a decrease in the percentage of S phase cell population after 12 h of treatment. However, treatments of HCT116 cells with chrysin only or a combination of chrysin and MK886 did not show the opposite situation in the G0/G1 and S phase cell populations, indicating that the expression of PPARα may not be associated with the cell cycle in the treated cells. The migration rate in chrysin-treated HCT116 cells was reduced significantly after 24 and 36 h of treatments. However, the activity was revived, when the expression of PPARα was inhibited, indicating that the migration activity of chrysin-treated cells is likely correlated with the expression of PPARα. Comparison of the CYP2S1 and CYP1B1 mRNA expression in chrysin only treated, and a combination of chrysin and MK886-treated HCT116 cells for 24 and 36 h showed a significant difference in the expression levels, indicating that PPARα inhibitor could also modify the expression of CYP2S1 and CYP1B1. CONCLUSION: The study indicates that PPARα may play an essential role in regulating the migration activity, and the expression of CYP2S1 and CYP1B1 in chrysin-treated colorectal cancer cells.

Predictors of five-year relapse rates of youths with substance abuse who underwent a family-oriented therapy program.

BACKGROUND: Substance abuse among young people has become a serious public health problem for years. The risk of relapse among illicit drug use is essential for developing adequate substance reuse prevention policies. The purpose of the current study is to investigate the potential predictor in long-term relapse rates among young patients that underwent a family-based treatment program. METHODS: To perform this study, 103 young patients with substance use (mean age: 16.2 years, 78.6% male) were referred to participate in a 10-week family-based treatment program. At the beginning and at the end of the treatment, the patients were required to fill out the Chinese Craving Beliefs Questionnaire (CCBQ), the Adolescents' Behavior-problem Scale (ABS), and the Family APGAR. Furthermore, the patients' caregivers had to fill out the Family APGAR, the 12-item version of the Chinese Health Questionnaire (CHQ), and the Parenting Stress Index (PSI). All patients were followed up for 5 years in order to observe their long-term outcomes regarding substance use relapse. RESULTS: During the 10-week family-oriented programs, the CCBQ scores, the CHQ scores and the Child-domain of PSI significantly decreased. Better changes in patients' behavioral problems during the treatment program predicted a lesser likelihood of substance use relapse in the subsequent 5 years. Furthermore, methamphetamine or 3,4-methylenedioxy-methamphetamine use and living in single-parent families were two factors associated with higher relapse rates. CONCLUSIONS: The changes in patients' behavioral problems during the treatment program may serve as a predictor of substance use relapse over the subsequent 5 years. This study's findings provide insight about substance use prevention and serve as a reference for policy-making.

Characterization of 18F-PM-PBB3 (18F-APN-1607) Uptake in the rTg4510 Mouse Model of Tauopathy.

Misfolding, aggregation, and cerebral accumulation of tau deposits are hallmark features of Alzheimer's disease. Positron emission tomography study of tau can facilitate the development of anti-tau treatment. Here, we investigated a novel tau tracer 18F-PM-PBB3 (18F-APN-1607) in a mouse model of tauopathy. Dynamic PET scans were collected in groups of rTg4510 transgenic mice at 2-11 months of age. Associations between distribution volume ratios (DVR) and standardized uptake value ratios (SUVR) with cerebellum reference were used to determine the optimal scanning time and uptake pattern for each age. Immunohistochemistry staining of neurofibrillary tangles and autoradiography study was performed for ex vivo validation. An SUVR 40-70 min was most consistently correlated with DVR and was used in further analyses. Significant increased 18F-PM-PBB3 uptake in the brain cortex was found in six-month-old mice (+28.9%, p < 0.05), and increased further in the nine-month-old group (+38.8%, p < 0.01). The trend of increased SUVR value remained evident in the hippocampus and striatum regions except for cortex where uptake becomes slightly reduced in 11-month-old animals (+37.3%, p < 0.05). Radioactivity distributions from autoradiography correlate well to the presence of human tau (HT7 antibody) and hyperphosphorylated tau (antibody AT8) from the immunohistochemistry study of the adjacent brain sections. These findings supported that the 40-70 min 18F-PM-PBB3 PET scan with SUVR measurement can detect significantly increased tau deposits in a living rTg4510 transgenic mouse models as early as six-months-old. The result exhibited promising dynamic imaging capability of this novel tau tracer, and the above image characteristics should be considered in the design of longitudinal preclinical tau image studies.

µ2-Dependent endocytosis of N-cadherin is regulated by ß-catenin to facilitate neurite outgrowth.

Circuit formation in the brain requires neurite outgrowth throughout development to establish synaptic contacts with target cells. Active endocytosis of several adhesion molecules facilitates the dynamic exchange of these molecules at the surface and promotes neurite outgrowth in developing neurons. The endocytosis of N-cadherin, a calcium-dependent adhesion molecule, has been implicated in the regulation of neurite outgrowth, but the mechanism remains unclear. Here, we identified that a fraction of N-cadherin internalizes through clathrin-mediated endocytosis (CME). Two tyrosine-based motifs in the cytoplasmic domain of N-cadherin recognized by the µ2 subunit of the AP-2 adaptor complex are responsible for CME of N-cadherin. Moreover, ß-catenin, a core component of the N-cadherin adhesion complex, inhibits N-cadherin endocytosis by masking the 2 tyrosine-based motifs. Removal of ß-catenin facilitates µ2 binding to N-cadherin, thereby increasing clathrin-mediated N-cadherin endocytosis and neurite outgrowth without affecting the steady-state level of surface N-cadherin. These results identify and characterize the mechanism controlling N-cadherin endocytosis through ß-catenin-regulated µ2 binding to modulate neurite outgrowth.

N-Cadherin Regulates Cell Migration Through a Rab5-Dependent Temporal Control of Macropinocytosis.

Macropinocytosis is a clathrin-independent endocytic pathway implicated in fluid uptake, pathogen invasion and cell migration. During collective cell migration, macropinocytosis occurs primarily at membrane ruffles arising from the leading edges of migrating cells. We report here that N-cadherin (Ncad) regulates the tempo of macropinocytosis and thereby influences wound-induced collective cell migration. Using live-cell and super-resolution imaging techniques, we observed that Ncad formed clusters at the membrane ruffles and macropinosomes. De-clustering of Ncad by an interfering antibody impaired the recruitment of Rab5-an early endosomal marker-to the macropinosomes. Moreover, we demonstrated that Ncad interacts with Rab5, and laser ablation of Ncad caused Rab5 to dissociate from the macropinosomes. Although Rab5 detached from macropinosomes upon the de-clustering of Ncad, the recruitment of late endosomal marker Rab7 occurred earlier. Consequently, both centripetal trafficking of macropinosomes and collective migration were accelerated due to de-clustering of Ncad. Thus, our results suggest that Ncad is involved in the maturation of macropinocytosis through Rab5 recruitment, linking macropinocytosis and cell migration through a novel function of Ncad.

Cinnamomum Cassia Extracts Suppress Human Lung Cancer Cells Invasion by Reducing u-PA/MMP Expression through the FAK to ERK Pathways.

Cinnamomum cassia exhibits antioxidative, apoptotic, and cytostatic properties. These activities have been attributed to the modulation of several biological processes and are beneficial for possible pharmaceutical applications. However, the potential of C. cassia in retarding lung adenocarcinoma cells metastasis remains ambiguous. We determined whether C. cassia extract (CCE) reduces metastasis of human lung adenocarcinoma cells. The results showed that CCE treatment (up to 60 µg/mL) for 24 h exhibited no cytotoxicity on the A549 and H1299 cell lines but inhibited the motility, invasiveness, and migration of these cells by repressing matrix metalloproteinase (MMP)-2 and urokinase-type plasminogen activator (u-PA). CCE also impaired cell adhesion to collagen. CCE significantly reduced p-focal adhesion kinase (FAK) Tyr397, p-FAK Tyr925, p-extracellular signal-regulated kinases (ERK)1/2, and Ras homolog gene family (Rho)A expression. CCE showed anti-metastatic activity of A549 and H1299 cells by repressing u-PA/MMP-2 via FAK to ERK1/2 pathways. These findings may facilitate future clinical trials of lung adenocarcinoma chemotherapy to confirm the promising results.

Everolimus suppresses invasion and migration of renal cell carcinoma by inhibiting FAK activity and reversing epithelial to mesenchymal transition in vitro and in vivo.

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and the major cause of mortality in urological cancer. Most patients with RCC are asymptomatic until the disease is advanced and unresectable. In this situation, systemic therapy with immunotherapy or molecularly targeted therapy agents play an important role in therapeutic strategy. Everolimus (EVE), an m-TOR inhibitor, has the potential to inhibit tumor progression at multiple levels and is indicated for the treatment of advanced RCC in patients whose disease has metastasis. In this study, we provide molecular evidence associated with the antimetastatic effect of everolimus by demonstrating the suppression of lung metastasis of 786-O cells in mouse model. This effect was associated with reduced protein expressions of p-FAK (Tyr 925), p-Src (Tyr416), Vimentin, and RhoA and also with increased the E-cadherin protein expression. In summary, these findings provide new insights into the molecular mechanisms involved in the antimetastatic effect of everolimus and are thus valuable in the treatment of metastatic RCC.

Cinnamomum cassia extracts reverses TGF-ß1-induced epithelial-mesenchymal transition in human lung adenocarcinoma cells and suppresses tumor growth in vivo.

Metastasis is the most common cause of cancer-related mortality in patients, and epithelial-mesenchymal transition (EMT) is essential for cancer metastasis and antidrug resistance. Cinnamomum cassia has several antioxidative, anti-inflammatory, and anticancer biological effects. However, the anti-EMT effect of C. cassia in human lung carcinoma is rarely reported. In this study, we determined whether C. cassia extracts (CCE) reduces the EMT and tumor growth of human lung adenocarcinoma cells. CCE inhibited the transforming growth factor (TGF)-ß1-induced cell motility and invasiveness of A549 and H1299 cells by repressing matrix metalloproteinase-2 and urokinase-type plasminogen activator as well as impaired cell adhesion to collagen. CCE also affected the TGF-ß1-induced EMT by downregulating the expression of vimentin and fibronectin and upregulating E-cadherin. The nude mice xenograft model showed that CCE reduced A549 tumor growth. Thus, CCE possesses antimetastatic activity of A549 and H1299 cells by affecting EMT and suppressing A549 tumor growth in vivo. This result suggested that CCE could be used as an antimetastatic agent or as an adjuvant for anticancer therapy.

Duchesnea indica extract suppresses the migration of human lung adenocarcinoma cells by inhibiting epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a process through which epithelial cells are transformed into mesenchymal cells; EMT diminishes cell polarity and cell-cell adhesion in cancer cells, leading to enhanced migratory and invasive properties. In this experiment, zymography, cell invasion, and migration assays were performed. Results indicated that Duchesnea indica extracts (DIE) inhibited highly metastatic A549 and H1299 cells by reducing the secretions of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Cell adhesion assay also demonstrated that DIE reduced the cell adhesion properties. Western blot analysis showed that DIE down-regulated the expression of N-cadherin, fibronectin, and vimentin, which are mesenchymal markers, and enhanced that of E-cadherin, which is an epithelial marker. In vivo study showed that tumor growth was significantly reduced in BALB/c nude mouse xenograft model administered with oral gavage of DIE. Therefore, DIE could be exhibits potential as a phytochemical-based platform for prevention and treatment of lung cancer. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2053-2063, 2017.

Randomized study of danoprevir/ritonavir-based therapy for HCV genotype 1 patients with prior partial or null responses to peginterferon/ribavirin.

BACKGROUND & AIMS: Chronic hepatitis C treatment for prior non-responders to peginterferon (PegIFN)/ribavirin remains suboptimal. The MATTERHORN study evaluated regimens containing ritonavir-boosted danoprevir (danoprevir/r) in prior PegIFN alfa/ribavirin non-responders. METHODS: Prior partial responders (N=152) were randomized to 24 weeks of twice-daily danoprevir/r 100/100mg, mericitabine 1000 mg and ribavirin 1000/1200 mg (IFN-free); danoprevir/r plus PegIFN alfa-2a/ribavirin (triple); or danoprevir/r, mericitabine and PegIFN alfa-2a/ribavirin (Quad). Prior null responders (N=229) were randomized to 24 weeks of IFN-free therapy, or quad alone (Quad 24) or quad plus 24-weeks of PegIFN alfa-2a/ribavirin (Quad 48). The primary endpoint was sustained virological response (HCV RNA <25 IU/ml) 24 weeks after end-of-treatment (SVR24). Due to high relapse rates, genotype (G) 1a patients in IFN-free arms were offered additional PegIFN alfa-2a/ribavirin. RESULTS: Among prior partial responders, SVR24 rates were 46.2%, 51.0%, and 86.0%, in the IFN-free, Triple and Quad arms, respectively; among prior null responders, SVR24 rates were 45.5%, 80.5%, and 83.8% respectively. Relapse rates were lower and SVR24 rates higher in G1b-infected than G1a-infected patients. SVR24 rates in G1a and G1b patients randomized to Quad were 75.0% and 96.2%, respectively, in the partial Quad arm, and 68.1% and 100%, respectively, in the null Quad 24 arm. Treatment failure was associated with resistance to danoprevir, but not to mericitabine, and was more common in G1a infected patients. Treatment was well-tolerated. CONCLUSIONS: Danoprevir/r, mericitabine plus PegIFN alfa-2a/ribavirin was well-tolerated and produced high overall SVR24 rates in prior partial and null responders to PegIFN alfa/ribavirin. In contrast, IFN-free regimens were associated with unacceptably high relapse rates.