Design, synthesis, bio-evaluation, and in silico studies of some N-substituted 6-(chloro/nitro)-1H-benzimidazole derivatives as antimicrobial and anticancer agents.

A new series of 6-substituted 1H-benzimidazole derivatives were synthesized by reacting various substituted aromatic aldehydes with 4-nitro-o-phenylenediamine and 4-chloro-o-phenylenediamine through condensation using sodium metabisulfite as the oxidative reagent. The N-substituted 6-(chloro/nitro)-1H-benzimidazole derivatives were prepared from the 6-substituted 1H-benzimidazole derivatives and substituted halides using potassium carbonate by conventional methods as well as by exposure to microwave irradiation. Seventy-six 1H-benzimidazole derivatives have been synthesized in moderate to excellent yields with the microwave-assisted method (40 to 99%). Compounds 1d, 2d, 3s, 4b, and 4k showed potent antibacterial activity against Escherichia coli, Streptococcus faecalis, MSSA (methicillin-susceptible strains of Staphylococcus aureus), and MRSA (methicillin-resistant strains of Staphylococcus aureus) with MIC (the minimum inhibitory concentration) ranging between 2 and 16 µg mL-1 as compared to ciprofloxacin (MIC = 8-16 µg mL-1), in particular compound 4k exhibits potent fungal activity against Candida albicans and Aspergillus niger with MIC ranging between 8 and 16 µg mL-1 compared with the standard drug fluconazole (MIC = 4-128 µg mL-1). In addition, compounds 1d, 2d, 3s, 4b, and 4k also showed the strongest anticancer activity among the synthesized compounds against five tested cell lines with IC50 (half-maximal inhibitory concentration) ranging between 1.84 and 10.28 µg mL-1, comparable to paclitaxel (IC50 = 1.38-6.13 µM). Furthermore, the five most active compounds showed a good ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile in comparison to ciprofloxacin, fluconazole, and paclitaxel as reference drugs. Molecular docking predicted that dihydrofolate reductase protein from Staphylococcus aureus is the most suitable target for both antimicrobial and anticancer activities, and vascular endothelial growth factor receptor 2 and histone deacetylase 6 are the most suitable targets for anticancer activity of these potent compounds.

Nano-Lipids Based on Ginger Oil and Lecithin as a Potential Drug Delivery System.

Lipid nanoparticles based on lecithin are an interesting part of drug delivery systems. However, the stability of lecithin nano-lipids is problematic due to the degradation of lecithin, causing a decrease in pH. In this study, the modification of the conventional nano-lipid-based soybean lecithin was demonstrated. Ginger-oil-derived Zingiber officinale was used along with lecithin, cholesterol and span 80 to fabricate nano-lipids (GL nano-lipids) using a thin-film method. TEM and a confocal microscope were used to elucidate GL nano-lipids' liposome-like morphology. The average size of the resultant nano-lipid was 249.1 nm with monodistribution (PDI = 0.021). The ζ potential of GL nano-lipids was negative, similarly to as-prepared nano-lipid-based lecithin. GL nano-lipid were highly stable over 60 days of storage at room temperature in terms of size and ζ potential. A shift in pH value from alkaline to acid was detected in lecithin nano-lipids, while with the incorporation of ginger oil, the pH value of nano-lipid dispersion was around 7.0. Furthermore, due to the richness of shogaol-6 and other active compounds in ginger oil, the GL nano-lipid was endowed with intrinsic antibacterial activity. In addition, the sulforhodamine B (SRB) assay and live/dead imaging revealed the excellent biocompatibility of GL nano-lipids. Notably, GL nano-lipids were capable of carrying hydrophobic compounds such as curcumin and performed a pH-dependent release profile. A subsequent characterization showed their suitable potential for drug delivery systems.

Identification and Capture of Phenolic Compounds from a Rapeseed Meal Protein Isolate Production Process By-Product by Macroporous Resin and Valorization Their Antioxidant Properties.

In this study, phenolic compounds from an aqueous protein by-product from rapeseed meal (RSM) were identified by HPLC-DAD and HPLC-ESI-MS, including sinapine, sinapic acid, sinapoyl glucose, and 1,2-di-sinapoyl gentibiose. The main phenolic compound in this by-product was sinapine. We also performed acid hydrolysis to convert sinapine, and sinapic acid derivatives present in the permeate, to sinapic acid. The adsorption of phenolic compounds was investigated using five macroporous resins, including XAD4, XAD7, XAD16, XAD1180, and HP20. Among them, XAD16 showed the highest total phenolic contents adsorption capacities. The adsorption behavior of phenolic compounds was described by pseudo-second-order and Langmuir models. Moreover, thermodynamics tests demonstrated that the adsorption process of phenolic compounds was exothermic and spontaneous. The highest desorption ratio was obtained with 30% (v/v) and 70% (v/v) ethanol for sinapine and sinapic acid, respectively, with a desorption ratio of 63.19 ± 0.03% and 94.68 ± 0.013%. DPPH and ABTS tests revealed that the antioxidant activity of the hydrolyzed fraction was higher than the non-hydrolyzed fraction and higher than the one of vitamin C. Antioxidant tests demonstrated that these phenolic compounds could be used as natural antioxidants, which can be applied in the food industry.

Multicriteria Optimization of Phenolic Compounds Capture from a Sunflower Protein Isolate Production Process by-Product by Adsorption Column and Assessment of Their Antioxidant and Anti-Inflammatory Effects.

The aim of this study was to valorize liquid effluent from the sunflower protein isolate process by extracting phenolic compounds it contains. To do so, XAD7 resin was used. A multicriteria optimization methodology based on design of experiments showed the optimal conditions were adsorption flow rate of 15 BV/h at pH 2.7, a desorption flow rate at 120 BV/h with ethanol/water 50% (v/v). The best trade-off between purity and recovery yields resulted in the production of a fraction containing 76.05% of chlorogenic acid (CGA) whose biological properties were evaluated. DPPH and ABTS tests showed that this fraction had a higher radical scavenging capacity than vitamin C. In vitro assays have shown that this fraction, when used at a concentration corresponding to 50 or 100 µM of CGA, does not present any cytotoxicity on human THP-1 cells differentiated into macrophages. In addition, this fraction when added prior to the inflammatory stimulus (LPS) can reduce tumor necrosis factor-alpha (TNF-α) production by 22%, thereby highlighting its protective properties against future inflammation.

Multiple Electric Energy Consumption Forecasting Using a Cluster-Based Strategy for Transfer Learning in Smart Building.

Electric energy consumption forecasting is an interesting, challenging, and important issue in energy management and equipment efficiency improvement. Existing approaches are predictive models that have the ability to predict for a specific profile, i.e., a time series of a whole building or an individual household in a smart building. In practice, there are many profiles in each smart building, which leads to time-consuming and expensive system resources. Therefore, this study develops a robust framework for the Multiple Electric Energy Consumption forecasting (MEC) of a smart building using Transfer Learning and Long Short-Term Memory (TLL), the so-called MEC-TLL framework. In this framework, we first employ a k-means clustering algorithm to cluster the daily load demand of many profiles in the training set. In this phase, we also perform Silhouette analysis to specify the optimal number of clusters for the experimental datasets. Next, this study develops the MEC training algorithm, which utilizes a cluster-based strategy for transfer learning the Long Short-Term Memory models to reduce the computational time. Finally, extensive experiments are conducted to compare the computational time and different performance metrics for multiple electric energy consumption forecasting on two smart buildings in South Korea. The experimental results indicate that our proposed approach is capable of economical overheads while achieving superior performances. Therefore, the proposed approach can be applied effectively for intelligent energy management in smart buildings.

A New Approach for Construction of Geodemographic Segmentation Model and Prediction Analysis.

Customer retention is invariably the top priority of all consumer businesses, and certainly it is one of the most critical challenges as well. Identifying and gaining insights into the most probable cause of churn can save from five to ten times in terms of cost for the company compared with finding new customers. Therefore, this study introduces a full-fledged geodemographic segmentation model, assessing it, testing it, and deriving insights from it. A bank dataset consisting 11,000 instances, which consists of 10,000 instances for training and 10,000 instances for testing, with 14 attributes, has been used, and the likelihood of a person staying with the bank or leaving the bank is computed with the help of logistic regression. Base on the proposed model, insights are drawn and recommendations are provided. Stepwise logistic regression methods, namely, backward elimination method, forward selection method, and bidirectional model are constructed and contrasted to choose the best among them. Future forecasting of the models has been done by using cumulative accuracy profile (CAP) curve analysis.

Folate-PEG/Hyd-curcumin/C18-g-PSI micelles for site specific delivery of curcumin to colon cancer cells via Wnt/ß-catenin signaling pathway.

Curcumin shows a potential anticancer activity, as it is involved in signaling pathway suppressing ß-catenin response transcription. In this study, the effects of curcumin released from the biocompatible and biodegradable polyaspartamide based micelles on colon cancer treatment via the Wnt/ß-catenin signaling pathway are investigated. Hydrophobic octadecylamine (C18) and hydrophilic O-(2-aminoethyl) polyethylene glycol (PEG) were grafted on a polysuccinimide (PSI) backbone for micelle formation. Folic acid (FA) was employed to facilitate the targeting activity to colon cancer cells and curcumin was conjugated via acid cleavable linkage, hydrazone (Hyd) to provide the pH sensitive drug release. Two types of micellar structures, Folate-PEG/Hyd-Curcumin/C18-g-PSI (FA-Cur) and PEG/Hyd-Curcumin/C18-g-PSI (NFA-Cur), were synthesized and their chemical structure was identified by 1H NMR spectroscopy. The cytotoxicity carried out by MTT assay informed that the cell viability of FA-Cur treated SW480 was much lower than that of NFA-Cur treated one at the concentration > 0.25 µg mL-1. Western blot assay showed that FA-Cur inhibited the target genes, cyclin D1 and c-myc, more strongly than NFA-Cur at the concentration > 0.5 µg mL-1. From these results, FA-Cur micelles are expected to be a promising candidate for colon anti-cancer via inhibiting Wnt/ß-catenin pathway.

Chrysoviruses in Magnaporthe oryzae.

Magnaporthe oryzae, the fungus that causes rice blast, is the most destructive pathogen of rice worldwide. A number of M. oryzae mycoviruses have been identified. These include Magnaporthe oryzae. viruses 1, 2, and 3 (MoV1, MoV2, and MoV3) belonging to the genus, Victorivirus, in the family, Totiviridae; Magnaporthe oryzae. partitivirus 1 (MoPV1) in the family, Partitiviridae; Magnaporthe oryzae. chrysovirus 1 strains A and B (MoCV1-A and MoCV1-B) belonging to cluster II of the family, Chrysoviridae; a mycovirus related to plant viruses of the family, Tombusviridae (Magnaporthe oryzae. virus A); and a (+)ssRNA mycovirus closely related to the ourmia-like viruses (Magnaporthe oryzae. ourmia-like virus 1). Among these, MoCV1-A and MoCV1-B were the first reported mycoviruses that cause hypovirulence traits in their host fungus, such as impaired growth, altered colony morphology, and reduced pigmentation. Recently we reported that, although MoCV1-A infection generally confers hypovirulence to fungi, it is also a driving force behind the development of physiological diversity, including pathogenic races. Another example of modulated pathogenicity caused by mycovirus infection is that of Alternaria alternata chrysovirus 1 (AaCV1), which is closely related to MoCV1-A. AaCV1 exhibits two contrasting effects: Impaired growth of the host fungus while rendering the host hypervirulent to the plant, through increased production of the host-specific AK-toxin. It is inferred that these mycoviruses might be epigenetic factors that cause changes in the pathogenicity of phytopathogenic fungi.

Vietnamese American Women's Beliefs and Perceptions About Breast Cancer and Breast Cancer Screening: A Community-Based Participatory Study.

INTRODUCTION: Although breast cancer (BC) rates are declining in White non-Hispanic American women, they are increasing among Vietnamese American women (VAW) at 1.2% (95% confidence interval [0.1, 2.2]) per year. BC screening rates (64%) are below the national rates (81.1%). This article explores VAW's beliefs about BC and screening. METHOD: Using community-based participatory qualitative descriptive methods, 40 VAW were recruited from Oregon, and four focus groups were conducted. A directed content analysis was used. RESULTS: Main themes were as follows: deferred to a health care provider or relying on self-detection and symptoms; fear of BC versus fear of procedural pain; limited knowledge; motivation by observing others' journey in BC death or survivorship; body image concern; "living carefree," "good fortune-having good health"; and coverage for a mammogram expense means health care access. DISCUSSION: Tailored interventions should address mammogram knowledge, fear, erroneous information, body image, fate and luck, and promoting access.

Health Care Providers' Perspectives on Barriers and Facilitators to Cervical Cancer Screening in Vietnamese American Women.

INTRODUCTION: Vietnamese American women (VAW) are diagnosed and die at twice the rate than White non-Hispanic American women (16.8/100,000 vs. 8.1/100,000 and 4.4/100,000 vs. 2.4/100,000, respectively). Despite efforts to increase cervical cancer (CC) screening among VAW, the participation rates are persistently low (69% to 81%). The purpose of this study was to explore health care providers' (HCPs) perspectives on barriers and facilitators to CC screening in VAW. METHOD: This qualitative descriptive pilot study, used open-ended semistructured interviews with 10 HCPs. RESULTS: The HCPs had two to 23 years treating VAW. Major barriers and facilitators identified by the HCPs were as follows: VAW's decision making about CC screening; sexual health divide; language discordance, relying on interpreters; breaking suspicion; VAW's exposure to health sources of CC screening; sustainable trust; and motivated health care practices. DISCUSSION: HCPs perceived the reasons for VAW not being screened or delaying CC screening were due to their lack of knowledge, cultural barriers, language, and issues related to trust.

Interactive CO-learning for Research Engagement and Education (I-COREE) Curriculum to Build Capacity Between Community Partners and Academic Researchers.

The voice of diverse communities continues to be minimal in academic research. Few models exist for education and training of new research topics and terminology and building partnership capacity in community-engaged research. Little is known about integrative education and training when building participatory research partnerships for sustainability and developing trust and rapport. Community partners at an Asian community-based health and social services center in a large metropolitan area wanted to explore the cultural context of a health-assistive smart home that monitors and auto-alerts with changes in health. With historical and recent rising trends in culturally insensitive research in several diverse communities, the concept of technology-enabled monitoring in the privacy of one's home brings uncertainty. Academic nurse researchers and community partners co-created a culturally safe integrative education and training curriculum, the Interactive CO-learning for Research Engagement and Education (I-COREE). The purpose was to design, implement, and evaluate the curriculum to respond to the community partners' needs to create a culturally safe space through an integrative education and training to facilitate building partnership capacity for research engagement including developing trust and rapport and addressing uncertainties in health-assistive technologies. Popular education tenets informed the curriculum. Twelve academic and community partners participated, four were team teachers who co-led the session. Implementation of the experiential, multimodal co-learning activities were conducted within ahalf-day. The curriculum evaluation indicated that it helped bridge critical conversations about partners' fears of the unknown, approach culturally sensitive topics safely, and trust and rapport. Key elements may be translatable to other partnerships.

Feasibility of a Multicomponent Breast Health Education Intervention for Vietnamese American Immigrant Women.

PURPOSE/OBJECTIVES: To determine the feasibility and acceptability of an intervention with targeted cultural and health belief messages to increase rates of mammography among Vietnamese American (VA) immigrant women. 
. DESIGN: One-group, pre-/post-test, pilot, quasiexperimental design.
. SETTING: Portland, Oregon, metropolitan area. 
. SAMPLE: 40 VA immigrant women aged 50 years or older.
. METHODS: Participants who had not had a mammogram within the past 12 months were recruited. The intervention consisted of one interactive group teaching session, followed by individual counseling delivered about 10 days later to overcome barriers to screening. Participants completed a baseline survey prior to the group teaching and again at 12 weeks after the session.
. MAIN RESEARCH VARIABLES: The intervention, guided by the Transtheoretical Model of Change and the Health Belief Model, involved movement in stage of change based on women's readiness, as well as perceived susceptibility, perceived benefits, perceived common barriers, and perceived cultural barriers. Mammogram completion and knowledge of breast cancer and mammography were examined.
. FINDINGS: The recruitment response rate was 58%. Knowledge about breast cancer, breast cancer susceptibility, and the benefits of mammography as related to breast cancer significantly increased following the intervention.
. CONCLUSIONS: Acceptability of the targeted program, good feasibility, and very low attrition was achieved. 
. IMPLICATIONS FOR NURSING: This intervention can be adapted for other populations, including other Asian groups, and other cancer screenings.

Adaptation and testing of instruments to measure cervical cancer screening factors among Vietnamese immigrant women.

PURPOSE: Vietnamese American women diagnosed with cervical cancer are more likely to have advanced cancer than non-Hispanic White women. We sought to (a) develop a culturally sensitive Vietnamese translation of the Revised Susceptibility, Benefits, and Barriers Scale; Cultural Barriers to Screening Inventory; Confidentiality Issues Scale; and Quality of Care from the Health Care System Scale and (b) examine the psychometric properties. DESIGN: Cross-sectional study with 201 Vietnamese immigrant women from the Portland, Oregon, metropolitan area. METHOD: We used a community-based participatory research approach and the U.S. Census Bureau's team approach to translation. RESULTS: Cronbach's alpha ranged from .57 to .91. The incremental fit index ranged from .83 to .88. DISCUSSION AND CONCLUSIONS: The instruments demonstrated moderate to strong subscale internal consistency. Further research to assess structural validity is needed. IMPLICATIONS FOR PRACTICE: Our approaches to translation and psychometric examination support use of the instruments in Vietnamese immigrant women.

Novel interaction of the Z-DNA binding domain of human ADAR1 with the oncogenic c-Myc promoter G-quadruplex.

Both G-quadruplex and Z-DNA can be formed in G-rich and repetitive sequences on genome, and their formation and biological functions are controlled by specific proteins. Z-DNA binding proteins, such as human ADAR1, have a highly conserved Z-DNA binding domain having selective affinity to Z-DNA. Here, our study identifies the Z-DNA binding domain of human ADAR1 (hZαADAR1) as a novel G-quadruplex binding protein that recognizes c-myc promoter G-quadruplex formed in NHEIII1 region and represses the gene expression. An electrophoretic migration shift assay shows the binding of hZαADAR1 to the intramolecular c-myc promoter G-quadruplex-forming DNA oligomer. To corroborate the binding of hZαADAR1 to the G-quadruplex, we conducted CD and NMR chemical shift perturbation analyses. CD results indicate that hZαADAR1 stabilizes the parallel-stranded conformation of the c-myc G-quadruplex. The NMR chemical shift perturbation data reveal that the G-quadruplex binding region in hZαADAR1 was almost identical with the Z-DNA binding region. Finally, promoter assay and Western blot analysis show that hZαADAR1 suppresses the c-myc expression promoted by NHEIII1 region containing the G-quadruplex-forming sequence. This finding suggests a novel function of Z-DNA binding protein as a regulator of G-quadruplex-mediated gene expression.

A dsRNA mycovirus, Magnaporthe oryzae chrysovirus 1-B, suppresses vegetative growth and development of the rice blast fungus.

A double-stranded RNA (dsRNA) mycovirus was found in isolate S-0412-II 2a of the rice blast fungus Magnaporthe oryzae. Sequence analysis of the five dsRNA segments (dsRNA1 through dsRNA5) revealed that this mycovirus is closely related to Magnaporthe oryzae chrysovirus 1-A (MoCV1-A), tentatively classified as a member of the Chrysoviridae; therefore, it was named Magnaporthe oryzae chrysovirus 1-B (MoCV1-B). Virus particles were spherical and composed of the ORF1, ORF3 and ORF4 proteins. MoCV1-B-infected isolate S-0412-II 2a showed a more severe impaired phenotype than the MoCV1-A-infected isolate. In a virus-cured isolate, normal growth was restored, implied that MoCV1-B could be involved in this observed phenotype. An unanticipated result was the occurrence of a fungal isolate lacking dsRNA5. The nonessential dsRNA5 had higher sequence identity (96%) with dsRNA5 of MoCV1-A than with the other dsRNA segments (71-79%), indicating that dsRNA5 could be a portable genomic element between MoCV1-A and MoCV1-B.

In silico identification of poly(ADP-ribose)polymerase-1 inhibitors and their chemosensitizing effects against cisplatin-resistant human gastric cancer cells.

Poly(ADP-ribose)polymerase-1 (PARP-1) enzyme is involved in the repair of DNA damages made by certain anticancer agents. It is suggested that PARP-1 inhibitors potentiate the cytotoxic effects and circumvent the resistance of DNA-modifying anticancer agents such as cisplatin. In this study, we conducted virtual screening of Korea Chemical Bank database targeting PARP-1 and identified several potent PARP-1 inhibitors with submicromolar IC50 values (77-79 nM). We then examined the chemosensitization of cisplatin by pre-treatment of PARP-1 inhibitors in cisplatin-resistant human gastric cancer cells. Our results show that PARP-1 inhibitors suppress the formation of poly(ADP-ribose) and enhance the cytotoxicity of cisplatin.

G-quadruplex binding ligands: from naturally occurring to rationally designed molecules.

Guanine-rich nucleic acid sequences are known to form G-quadruplex - four-stranded DNA or RNA structures stabilized by an array of Hoogsteen hydrogen bonds. G-quadruplex structures are involved in the modulation of gene expression at the transcription and translation levels. Accordingly, G-quadruplexes are considered as novel therapeutic targets for anticancer drug development. In this review, the authors provide a brief, up-to-date summary of G-quadruplex binding ligands, including naturally occurring molecules, synthetic compounds, and molecules identified by computational database screening. The key structural motifs of G-quadruplex binding ligands, that is, an aromatic core and basic side chains, are addressed in the context of how these molecules interact with G-quadruplex. A better understanding of these interactions would facilitate the rational design of ligands selective for DNA or RNA G-quadruplex.

Increased expression of p27 is associated with the cisplatin resistance in gastric cancer cell line YCC-3.

The major obstacle of treating cancer patients is acquisition of chemoresistance, in which treated tumor cells become insensitive after chronic drug exposure. To study the mechanism of acquired cisplatin resistance, we established a cisplatin-resistant human gastric cancer cell line. The cisplatin-resistant cell line (YCC-3/R) was isolated after exposing the gastric cancer cell line, YCC-3, to a constant concentration (0.5 microg/mL) of cisplatin for 12 months. The expression of cell cycle regulatory proteins (p53, Bax, p21, p27) in the YCC-3/R were investigated by western blot analysis. The cisplatin treatment significantly down-regulated the p53 and p21 expression level, while up-regulated the p27 expression in the YCC-3/R cells compared to the parental cells. The Bax expression level was similar in both cells. These results suggest that the p27 dependent-cell cycle arrest may prevent cisplatin-induced apoptosis and give enough time to repair the DNA damage in the YCC-3/R cells.

Neuroimaging of traumatic brain injury.

In this article, the neuroradiological evaluation of traumatic brain injury is reviewed. Different imaging strategies in the assessment of traumatic brain injury are initially discussed, and this is followed by a review of the imaging characteristics of both primary and secondary brain injuries. Computed tomography remains the modality of choice for the initial assessment of acute head injury because it is fast, widely available, and highly accurate in the detection of skull fractures and acute intracranial hemorrhage. Magnetic resonance imaging is recommended for patients with acute traumatic brain injury when the neurological findings are unexplained by computed tomography. Magnetic resonance imaging is also the modality of choice for the evaluation of subacute or chronic traumatic brain injury. Mild traumatic brain injury continues to be difficult to diagnose with current imaging technology. Advanced magnetic resonance techniques, such as diffusion-weighted imaging, magnetic resonance spectroscopy, and magnetization transfer imaging, can improve the identification of traumatic brain injury, especially in the case of mild traumatic brain injury. Further research is needed for other advanced imaging methods such as magnetic source imaging, single photon emission tomography, and positron emission tomography.

Design, synthesis, and biological evaluation of novel constrained meta-substituted phenyl propanoic acids as peroxisome proliferator-activated receptor alpha and gamma dual agonists.

In an effort to develop dual PPARalpha/gamma activators with improved therapeutic efficacy, a series of diaryl alpha-ethoxy propanoic acid compounds comprising two aryl groups linked by rigid oxime ether or isoxazoline ring were designed and synthesized and their biological activities were examined. Most of the compounds possessing an oxime ether linker were more potent PPARgamma activators than the lead PPARalpha/gamma dual agonist, tesaglitazar in vitro. Compound 18, one of the derivatives with an oxime ether linker, was found to selectively transactivate PPARgamma (EC 50 = 0.028 microM) over PPARalpha (EC 50 = 7.22 microM) in vitro and lower blood glucose in db/ db mice more than muraglitazar after oral treatment for 11 days.