Three-Carbon Linked Dihydroartemisinin-Isatin Hybrids: Design, Synthesis and Their Antiproliferative Anticancer Activity.

Fifteen dihydroartemisinin-isatin hybrids (5a-e and 6a-j) linked with three-carbon were designed, synthesized. The antiproliferative activity against lung cancer cell lines including drug-sensitive A549, doxorubicin-resistant A549 (A549/DOX) and cisplatin-resistant A549 (A549/DDP) lung cancer cell lines was tested. The cytotocivity towards normal lung epithelial BEAS-2B cell line was also investigated. From the structure-activity relationship (SAR), it was found that hydrogen bond donors (especially hydroxime and thiosemicarbazide) at C-3 position and electron-withdrawing groups (fluoro and chloro) at C-5 position of isatin moiety were beneficial for the activity. A significant part of them (half maximal inhibitory concentration/IC50: 5.72-55.52 µM) demonstrated considerable antiproliferative activity, and the activity was superior to that of dihydroartemisinin (IC50: 69.42-88.03 µM) and artemisinin (IC50: >100 µM). In particular, two hybrids 6a, e (IC50: 5.72-9.84 µM) were not inferior to doxorubicin (IC50: 4.06 µM) and cisplatin (IC50: 9.38 µM) against drug-sensitive A549 cells and were more potent than doxorubicin (IC50: 54.32 and 15.10 µM) and cisplatin (IC50: 19.74 and 66.89 µM) against multidrug-resistant A549/DOX and A549/DDP lung cancer cell lines. In addition, hybrids 6a, e (IC50: >100 µM) showed no toxicity towards BEAS-2B cells, proving their excellent selectivity profile. Furthermore, hybrid 6a also possessed good stability in mouse and human microsomes, as well as excellent pharmacokinetic properties. Accordingly, hybrid 6a could serve as a promising anti-lung cancer chemotherapeutic candidate for further preclinical evaluations.

Elevated LOXL2 expression by LINC01347/miR-328-5p axis contributes to 5-FU chemotherapy resistance of colorectal cancer.

Chemotherapy resistance after curative surgery is a major contributor to the mortality of colorectal cancer (CRC). Detailed mechanism studies of specific molecular alterations are critical to improving the available therapies for long-term disease administration. We explored the functional role of LINC01347 in chemotherapy resistance of CRC. Elevated LINC01347 expression was correlated with CRC disease progression during chemotherapy treatment. However, the functional role of LINC01347 and mechanism remained undefined. In this study, we demonstrated that elevated LINC01347 expression was correlated with late clinical stage and poor prognosis in CRC tumor tissues with TCGA data. Exogenous LINC01347 expression promoted cell proliferation and 5-FU resistance of CRC cells, while LINC01347 knockdown attenuated cell growth and 5-FU resistance in vitro and in vivo. Molecular analysis indicated that LINC01347 participated in the transcriptional regulation of LOXL2 by sponging miR-328-5p. LOXL2 knockdown impaired the LINC01347 overexpression induced 5-FU resistance in CRC cells. The clinical analysis supported miR-328-5p/LOXL2 as a candidate biomarker for chemotherapy resistance of CRC patients. Our study provided a molecular basis for the development of 5-FU based chemotherapy resistance in CRC by LINC01347/miR-328/LOXL2 axis. We identified LINC01347 as a prognostic biomarker and potential therapeutic target against 5-FU based chemotherapy resistance of CRC.

Flexoelectric and dielectric effects in uniform lying helix cholesteric liquid crystals under cell boundary conditions.

 Flexoelectric effect and dielectric effect in uniform lying helix (ULH) cholesteric liquid crystals under cell boundary conditions of periodic anchoring at the bottom and vertical anchoring at the top are studied. They can be quantitatively analyzed by theoretically simulation of the polar angle and the tilt angle. It is found that a good ULH texture can be formed inside under periodic boundary conditions and the bulk director is not affected by the surface anchoring strength. The induced rotation angle of the helical axis by the flexoelectric effect is slightly non-uniform with the position, and the coupling of the flexoelectric effect and dielectric effect increases the inhomogeneous change. Our results will provide an accurate theory basis for the formation of a good ULH texture and the influence of dielectric effect on the optical axis.

Identification of potential prognostic biomarkers for breast cancer using WGCNA and PPI integrated techniques.

In this study, we aimed to detect promising prognostic factors of breast cancer and interpreted the relevant mechanisms using an integrated bioinformatics analysis. RNA sequencing profile of breast cancer was downloaded from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, which were combined as a group (TCGA_GTEx). GSE70947 dataset was from Gene Expression Omnibus. Blue and turquoise modules, respectively identified in TCGA_GTEx database and GSE70947 dataset using weighted co-expression network analysis (WGCNA), were both notably associated with breast cancer. By comparing genes in the two significant modules with differentially expressed genes (DEGs), we obtained a set of 40 shared genes, which were mainly enriched in chromosome segregation and mismatch repair pathway. After protein-protein interaction (PPI) network and overall survival analysis, two hub genes EXO1 and KIF4A were extracted from the set of 40 shared genes, which were up-regulated and associated with the dismal outcome of breast cancer patients. There was a notable negative correlation between EXO1 and KIF4A expression and age of breast cancer patients, whereas a positive relationship with two another clinical traits stage and tumor category was detected. Univariate and multivariate Cox regression analysis revealed that the two hub genes could be independent prognostic factors of breast cancer. Mechanistically, gene correlation analysis suggested that EXO1 and KIF4A exerted their oncogenic role via promoting breast cancer cell proliferation. Overall, our findings identify two promising individual prognostic predictors of breast cancer and pave the new way for diagnosis and therapy strategy of breast cancer.

Annexin A13 predicts poor prognosis for lung adenocarcinoma patients and accelerates the proliferation and migration of lung adenocarcinoma cells by modulating epithelial-mesenchymal transition.

This study aimed to investigate the role of ANXA13 in lung adenocarcinoma (LUAD) growth, migration, and the underlying mechanisms. Firstly, in the TCGA dataset for LUAD, ANXA13 is found to be highly expressed in patients with LUAD and high expression of ANXA13 predicted poor outcomes in LUAD patients. Consistently, the data of qRT-PCR showed that the expression of ANXA13 was higher in LUAD cell lines (Calu-3, LTEP-a-2, and NCI-H1395) than that in normal lung cell line BEAS2B. Then, we performed gain- and loss of function of ANXA13 in NCI-H1395 and Calu-3 cells, respectively. The results displayed that deficiency of ANXA13 suppresses cell proliferation, invasion, and migration in Calu-3 cells and overexpression of ANXA13 augments cell proliferation, invasion, and migration in NCI-H1395 cells. Finally, it was found that silencing of ANXA13 obviously raised the protein expression levels of E-cadherin and reduced the protein levels of N-cadherin, Vimentin, and Snail in Calu-3 cells whereas overexpression of ANXA13 obviously receded the protein expression levels of E-cadherin and enhanced the protein levels of N-cadherin, Vimentin, and Snail in NCI-H1395 cells. This study analyzed the biological effects of ANXA13 in LUAD cells, indicating that ANXA13 could regard as a therapeutic target for LUAD.

Prediabetes, diabetes, and other CVD-related conditions among Asian populations in Los Angeles County, 2014.

Objective: To assess the prevalence of four common health conditions related to cardiovascular disease risk among Asians in Los Angeles County. Methods: A survey of Asians in Los Angeles County was conducted utilizing purposive sampling to recruit from the region's Service Planning Areas 3 and 4; these underserved areas contain high density of Asian populations. Descriptive and multivariable regression analyses were performed to explore and describe potential associations between self-reported diagnoses of prediabetes, diabetes, hypertension, and high cholesterol and body mass index (measured with non-Asian versus Asian cut points) by race/ethnicity (Chinese/Filipino/Korean/Taiwanese/Thai/Vietnamese). Results: The survey response rate was nearly 60%. The analysis included 1,377 Asians, self-identified as either Chinese (n = 700), Filipino (n = 69), Korean (n = 339), Taiwanese (n = 48), Thai (n = 115), or Vietnamese (n = 106). Results showed that, in comparison to other Asians, Filipinos had the highest risks for two of the four conditions described. Other results by subgroup affirmed a similar heterogeneous pattern of Asian health locally. Conclusions: These and other results from the survey point to potential gaps in healthcare needs of Asians, and to opportunities where local public health efforts could help increase these populations' access to cardiovascular disease-related health and social services.

Reasons why low-income people in urban areas do not drink tap water.

BACKGROUND: Despite its higher cost and potential environmental effect compared with those of tap water, bottled water consumption has been increasing over the past decade, especially in low-income communities in which children are at a higher risk of developing caries. METHODS: The authors used a systematic sequential sampling design for the Water Consumption Survey to collect information about water consumption beliefs and practices from clients attending 4 public health centers in Los Angeles County (LAC). The authors used health belief model constructs to examine why some low-income residents in LAC do not drink tap water. RESULTS: From October through December 2013, 1,230 participants completed the Water Consumption Survey (86% response rate); the authors included 1,171 participants in the final analysis. Hispanic and African-American participants accounted for the largest proportions (38% and 37%, respectively). Overall, 48% of participants reported drinking tap water daily compared with 58% who reported drinking bottled water daily. The health belief model construct of perceived health risks (that is, perceived threats) significantly predicted why survey participants did not drink tap water. Other results revealed several misconceptions about tap water fluoridation and differences in beliefs about tap water safety according to income level. CONCLUSIONS: Fluoridated tap water is a low-cost, ecologically friendly resource that provides health benefits seldom found in bottled water. However, mistrust about the quality and safety of tap water may make those in low-income communities more vulnerable to the effects of not receiving adequate fluoride and thus at higher risk of developing caries. PRACTICAL IMPLICATIONS: Future interventions should encourage tap water use by dispelling misconceptions and educating low-income people in urban areas of LAC about the health benefits of fluoridated tap water and the safety of its sources. In addition, patient encounters could be an opportunity for pediatric dentists, general dentists, and other health care providers to reinforce the health benefits of tap water fluoridation and its use.

Self-Reported Interest to Participate in a Health Survey if Different Amounts of Cash or Non-Monetary Incentive Types Were Offered.

The objective of this study was to assess monetary and non-monetary factors that can influence the decision to participate in a future health survey. A questionnaire was administered to eligible, low-income participants (n = 1502) of the 2012 Los Angeles County Health and Nutrition Examination Survey (LAHANES-II). Multivariable regression analyses were performed to describe factors potentially associated with future intent to participate in similar survey designs. The results of the survey suggest that, overall, female participants had a greater interest in participating under a variety of incentive scenarios. Compared to the 25-34 age group, older participants (35-44, 45-84) reported more interest to participate if $10 cash [prepaid gift/debit card], a coupon for product/travel, or a small item [e.g., granola bar, t-shirt, pen] was offered, whereas younger participants (18-24) reported greater interest for $25 cash or a coupon for product/travel. Non-Whites, when compared to Whites/Non-Hispanics, reported greater interest to participate if any of the incentives was offered. High school graduates, when compared to those with some college education, reported greater interest to participate if $10 cash, a small item, or a lottery ticket was offered. Presence of two or more chronic conditions increased interest while concerns about participation in LAHANES-II was associated with reduced interest to participate in future health-related surveys. The results suggest that both incentives and non-monetary considerations (e.g., personal concerns about participating and individual level characteristics) can influence the decision to participate in health-related surveys and offer insights into strategies that can improve response rates for these assessments that are often used to inform community planning.

Niche partition of Bacteriovorax operational taxonomic units along salinity and temporal gradients in the Chesapeake Bay reveals distinct estuarine strains.

The predatory Bacteriovorax are Gram-negative bacteria ubiquitous in saltwater systems that prey upon other Gram-negative bacteria in a similar manner to the related genus Bdellovibrio. Among the phylogenetically defined clusters of Bacteriovorax, cluster V has only been isolated from estuaries suggesting that it may be a distinct estuarine phylotype. To assess this hypothesis, the spatial and temporal distribution of cluster V and other Bacteriovorax phylogenetic assemblages along the salinity gradient of Chesapeake Bay were determined. Cluster V was expected to be found in significantly greater numbers in low to moderate salinity waters compared to high salinity areas. The analyses of water and sediment samples from sites in the bay revealed cluster V to be present at the lower salinity and not high salinity sites, consistent with it being an estuarine phylotype. Cluster IV had a similar distribution pattern and may also be specifically adapted to estuaries. While the distribution of clusters V and IV were similar for salinity, they were distinct on temperature gradients, being found in cooler and in warmer temperatures, respectively. The differentiation of phylotype populations along the salinity and temporal gradients in Chesapeake Bay revealed distinct niches inhabited by different phylotypes of Bacteriovorax and unique estuarine phylotypes.

Prey bacteria shape the community structure of their predators.

Although predator-prey interactions among higher organisms have been studied extensively, only few examples are known for microbes other than protists and viruses. Among the bacteria, the most studied obligate predators are the Bdellovibrio and like organisms (BALOs) that prey on many other bacteria. In the macroscopical world, both predator and prey influence the population size of the other's community, and may have a role in selection. However, selective pressures among prey and predatory bacteria have been rarely investigated. In this study, Bacteriovorax, a predator within the group of BALOs, in environmental waters were fed two prey bacteria, Vibrio vulnificus and Vibrio parahaemolyticus. The two prey species yielded distinct Bacteriovorax populations, evidence that selective pressures shaped the predator community and diversity. The results of laboratory experiments confirmed the differential predation of Bacteriovorax phylotypes on the two bacteria species. Not only did Bacteriovorax Cluster IX exhibit the versatility to be the exclusive efficient predator on Vibrio vulnificus, thereby, behaving as a specialist, but was also able to prey with similar efficiency on Vibrio parahaemolyticus, indicative of a generalist. Therefore, we proposed a designation of versatilist for this predator. This initiative should provide a basis for further efforts to characterize the predatory patterns of bacterial predators. The results of this study have revealed impacts of the prey on Bacteriovorax predation and in structuring the predator community, and advanced understanding of predation behavior in the microbial world.

Phenotypic and molecular characterization of Solobacterium moorei isolates from patients with wound infection.

Though seldom reported, Solobacterium moorei, which was first described in 2000, has been identified in specimens from patients with root canals, periradicular lesions, periodontal disease, dentoalveolar abscesses, bacteremia, septic thrombophlebitis, and halitosis. In the present study, we describe 9 cases of mixed wound infection, from a pool of 400 surgical wound infections that we have studied, in which S. moorei was isolated or found in a clone library. All isolates of S. moorei were identified by 16S rRNA gene sequence analysis, and then six were examined for their physiological and biochemical characteristics and for antimicrobial susceptibility. The results of the present study indicate that Solobacterium moorei may be a significant component in some mixed surgical wound infections and that surgical management and antimicrobial therapy may be indicated when these bacteria are identified in significant situations.

Development and evaluation of a quantitative real-time PCR assay for the detection of saltwater Bacteriovorax.

Bdellovibrio-and-like-organisms (BALOs) are small, Gram-negative predatory bacteria with the ability to prey on a wide variety of Gram-negative bacteria, and which may have a significant ecological role. Detection and quantification of BALOs by culture-dependent methods are complicated, as their reproduction is dependent upon the use of appropriate prey. For this reason, a sensitive and specific molecular detection method was developed. This paper describes a SYBR Green-based real-time PCR (quantitative PCR) assay that combines the use of a specific 16S rDNA primer with a universal primer for quantitative detection of halophilic Bacteriovorax. 16S rDNA sequences from 174 BALO strains, including both halophilic and freshwater, were aligned and a consensus region was identified that is unique to the halophilic Bacteriovorax strains. A specific primer was designed and analysed for specificity. The PCR conditions were optimized to obtain high specificity and sensitivity. The specificity was evaluated by testing a series of halophilic Bacteriovorax samples and prey specimens, including both pure cultures and environmental saltwater samples. A linear and reproducible standard curve was obtained over a range of 10(1)-10(6) gene copies and the detection limit was determined to be 10 copies of 16S rRNA gene per reaction. The results presented in this study validate the procedure as a rapid, sensitive and accurate method for the detection and quantification of halophilic Bacteriovorax in environmental saltwater samples. It is anticipated that this culture-independent method will facilitate future investigations of the distribution and population dynamics of these interesting predatory bacteria, leading to a better understanding of their ecological role.