Can dietary flavonoids be useful in the personalized treatment of colorectal cancer?

Activating mutations in the oncogenes KRAS, BRAF and PI3K define molecular colorectal cancer (CRC) subtypes because they play key roles in promoting CRC development and in determining the efficacy of chemotherapeutic agents such as 5-fluorouracil and anti-epidermal growth factor receptor monoclonal antibodies. Survival of patients with cancers displaying these molecular profiles is low. Given the limited efficacy of therapeutic strategies for CRC presenting mutational activations in mitogen-activated protein kinase and/or PI3K pathways, developing combination therapies with natural flavonoids or other phytochemicals with demonstrated effects on these pathways (and little or no toxic effects) may constitute a valuable path forward. Much has been published on the anticancer effects of dietary phytochemicals. However, even an exhaustive characterization of potential beneficial effects produced by in vitro studies cannot be extrapolated to effects in humans. So far, the available data constitute a good starting point. Published results show quercetin and curcumin as possibly the best candidates to be further explored in the context of adjuvant CRC therapy either as part of dietary prescriptions or as purified compounds in combination regimens with the drugs currently used in CRC treatment. Clinical trial data is still largely missing and is urgently needed to verify relevant effects and for the development of more personalized treatment approaches.Portuguese Foundation for Science and Technology (FCT), No. UIDB/04469/2020; I&D&I AgriFood XXI, No. NORTE-01-0145-FEDER-000041; and Fundo Europeu de Desenvolvimento Regional (FEDER) through the NORTE 2020 program (Programa Operacional Regional do Norte 2014/2020).info:eu-repo/semantics/publishedVersio

A Study to Assess Users’ Preferences for Intelligent Personal Assistance and Improve their Mass Adoption

Despite the dissemination and wide availability of Intelligent Personal Assistants (IPA), such systems have not reached the popularity expected. One reason for this is the users\u27 lack of trust in IPA and their providers. Another reason is the IPA\u27s limited performance and skill set, which in turn is due to the intentional segregation of IPAs in proprietary ecosystems. Enabling IPAs to communicate and exchange data with each other could help IPAs improve performance and thus their acceptance among users. Further, certifications and suitable marketing strategies can also contribute towards their mass adop-tion, by fostering user\u27s trust in IPA and their providers. To better understand the incentives necessary to instigate mass adoption of interoperable IPAs, this paper presents a survey which captures the po-tential users\u27 attitude towards interoperable IPAs and their attitude towards different marketing strate-gies which could increase users’ trust in IPAs. The ultimate purpose of this ongoing research is to develop design recommendations and an efficient incentive system that can foster the mass adoption of IPAs

Quercetin synergistically induces sensitivity to 5-fluorouracil through p53 modulation in colorectal cancer cells

Colorectal tumors (CRC) with microsatellite instability (MSI) show resistance to chemotherapy with 5-fluorouracil (5-FU), the most widely used pharmacological drug for CRC treatment. The aims of this study were to identify compounds that increase sensitivity of MSI CRC cells to 5-FU and characterize their dependence on the p53 status of the cells. Two MSI human CRC derived cell lines were used: CO115 wildtype for p53 and HCT15 that harbors a p53 mutation. The sensitivity of these cells to 5-FU was evaluated by TUNEL assay and the effects on apoptosis induction of co-incubation of the flavonoids, quercetin (Q) or luteolin (L), with 5-FU were characterized. The mechanisms of apoptosis induction were assessed by western blot and p53 mediated effects confirmed by small interference RNA (siRNA) in CO115 and in HCT116 wt and p53 knockout cells. Our results demonstrate that CO115 is more sensitive to 5-FU than the p53 mutated HCT15. Additive effects on apoptosis were shown for L (in both cell lines) and Q (in HCT15). In CO115 Q synergistically induced apoptosis with 5-FU. Apoptosis induction was caspase dependent in CO115 cells but not in HCT15 cells. Both flavonoids increased p53 expression in both cell lines, an effect particularly remarkable for Q. The synergistic effect of Q and 5-FU in CO115 involved the activation of the mitochondrial pathway with an increase in the expression of cleaved caspase 9 and 3 and PARP, as well as a decrease in Bcl-2 expression. Importantly, knockdown of p53 by siRNA in CO115 cells and p53 knockout in HCT116 cells totally abrogated apoptosis induction, demonstrating the dependence on p53 modulation of apoptosis induction by Q. This study suggests the potential applicability of these phytochemicals for enhancement 5-FU efficiency in CRC therapy, especially Q in p53 wild-type tumors.Fundação para a Ciência e a Tecnologia (FCT

Student and Faculty Awareness and Attitudes about Students with Disabilities

Every year an increasing number of students with disabilities are graduating from high school and entering into postsecondary education. In an effort to assess the university climate for students with disabilities a survey was conducted on a large Northeastern campus. The survey focused on the attitudes, beliefs, and knowledge of university students and faculty on disability-related issues. Results are presented from undergraduate, graduate, and faculty perspectives. Most students and faculty report positive attitudes and interactions with students with disabilities, however these interactions are often limited and awkward. Disability issues are not often presented in the classroom content and the majority of faculty do not announce the availably of accommodations in the classroom. Implications for postsecondary institutions are explored

“The Bright and the Dark Side of Smart Lights” The Protective Effect of Smart City Infrastructures

In this paper, we investigate the protective effect of smart street lighting on public safety. Smart lights have a variety of features, such as video surveillance or gun-shot detection. Some of these features can have a deterrent effect on crime. Other features, however, such as adaptive brightness control, may also encourage crime. Using a comprehensive dataset on the crimes committed in downtown San Diego (CA) during 1st May 2017 and 30th April 2018, we investigate the crime rates a priori and posterior to the installation of smart lights in this area. The results of the empirical analysis suggest that smart lights have a statistically significant negative impact on crime and that their installation increases the safety of citizens

Hypericum androsaemum water extract inhibits proliferation in human colorectal cancer cells through effects on MAP kinases and PI3K/Akt pathway

MAP kinase and PI3K/Akt signalling pathways are commonly altered in colorectal carcinoma (CRC) leading to tumor growth due to increased cell proliferation and inhibition of apoptosis. Several species of the genus Hypericum are used in Portugal to prepare herbal teas to which digestive tract effects are attributed. In the present study, the antiproliferative and proapoptotic effects of the water extracts of H. androsaemum (HA) and H. perforatum (HP) were investigated in two human colon carcinoma-derived cell lines, HCT15 and CO115, which harbour activating mutations of KRAS and BRAF, respectively. Contrarily to HP, HA significantly inhibited cell proliferation and induced apoptosis in both cell lines. HA decreased BRAF and phospho-ERK expressions in CO115, but not in HCT15. HA also decreased Akt phosphorylation in CO115 and induced p38 and JNK in both cell lines. HA induced cell cycle arrest at S and G2/M phases as well as caspase-dependent apoptosis in both cell lines. Chlorogenic acid (CA), the main phenolic compound present in the HA extract and less represented in the HP water extract, did, however, not show any of those effects when used individually. In conclusion, water extract of HA, but not of HP, controlled CRC proliferation and specifically acted on mutant and not wild-type BRAF. The effect of HA was, however, not due to CA alone.CPRX was supported by the Foundation for Science and Technology (FCT), Portugal, through the grant SFRH/BD/27524/2006 and the work was supported by the FCT research grants PTDC/AGR-AAM/70418/2006 (HypericumBiotech) and PEst-C/BIA/UI4050/2011. All projects are co-funded by the program COMPETE from QREN with co-participation from the European Community fund FEDER

Drivers of Adoption of Contact Tracing Mobile Applications

Contact Tracing Mobile Apps emerged as a new IT-enabled tool with the potential to slow down infection COVID-19 transfers and thus save lives. However, despite their inherent capability to make a substantial technical contribution to fighting the pandemic, the adoption of CTMAs lags behind expectations. Against this background, our work seeks to produce a systematic and nuanced understanding of hitherto unconsidered yet significant determinants of CTMA adoption. On a more general note, we seek to derive valuable insights that can support decision-makers to accelerate CTMAs\u27 adoption. Based on a large-scale study with 1,027 participants, we present new contextualized determinants that explain individuals’ decision to adopt CTMAs. We also find that early in the process of adopting CTMAs, decision-makers have several levers at their disposal to influence the adoption of CTMAs. In contrast, decision makers\u27 ability to influence individuals\u27 adoption of CTMAs is more limited at later stages of the process

Ursolic acid induces cell death and modulates autophagy through JNK pathway in apoptosis-resistant colorectal cancer cells

Colorectal carcinomas (CRCs) with P53 mutations have been shown to be resistant to chemotherapy with 5-fluorouracil (5-FU), the most widely used chemotherapeutic drug for CRC treatment. Autophagy is emerging as a promising therapeutic target for drug-resistant tumors. In the present study, we tested the effects of ursolic acid (UA), a natural triterpenoid, on cell death mechanisms and its effects in combination with 5-FU in the HCT15 p53 mutant apoptosis-resistant CRC cell line. The involvement of UA in autophagy and its in vivo efficacy were evaluated. Our data show that UA induces apoptosis independent of caspases in HCT15 cells and enhances 5-FU effects associated with an activation of c-jun N-terminal kinase (JNK). In this cell line, where this compound has a more pronounced effect on the induction of cell death compared to 5-FU, apoptosis corresponds only to a small percentage of the total cell death induced by UA. UA also modulated autophagy by inducing the accumulation of LC3 and p62 levels with involvement of JNK pathway, which indicates a contribution of autophagy on JNK-dependent induction of cell death by UA. By using nude mice xenografted with HCT15 cells, we verified that UA was also active in vivo decreasing tumor growth rate. In conclusion, this study shows UA's anticancer potential both in vitro and in vivo. Induction of cell death and modulation of autophagy in CRC-resistant cells were shown to involve JNK signaling.C.P.R.X. and D.F.N.P. were supported by the Foundation for Science and Technology (FCT), Portugal, through grants SFRH/BD/27524/2006 and SFRH/BD/64817/2009, respectively. C.P.W. was guest professor at University of Copenhagen through the grant SFRH/BSAB/918/2009. The work was supported by FCT research grants PTDC/QUI-BIQ/101392/2008 (NaturAge) and PEst-C/BIA/UI4050/2011. All projects are co-funded by the program COMPETE from QREN with co-participation from the European Community fund FEDER