Prescribed fires, smoke exposure, and hospital utilization among heart failure patients.

BACKGROUND: Prescribed fires often have ecological benefits, but their environmental health risks have been infrequently studied. We investigated associations between residing near a prescribed fire, wildfire smoke exposure, and heart failure (HF) patients' hospital utilization. METHODS: We used electronic health records from January 2014 to December 2016 in a North Carolina hospital-based cohort to determine HF diagnoses, primary residence, and hospital utilization. Using a cross-sectional study design, we associated the prescribed fire occurrences within 1, 2, and 5 km of the patients' primary residence with the number of hospital visits and 7- and 30-day readmissions. To compare prescribed fire associations with those observed for wildfire smoke, we also associated zip code-level smoke density data designed to capture wildfire smoke emissions with hospital utilization amongst HF patients. Quasi-Poisson regression models were used for the number of hospital visits, while zero-inflated Poisson regression models were used for readmissions. All models were adjusted for age, sex, race, and neighborhood socioeconomic status and included an offset for follow-up time. The results are the percent change and the 95% confidence interval (CI). RESULTS: Associations between prescribed fire occurrences and hospital visits were generally null, with the few associations observed being with prescribed fires within 5 and 2 km of the primary residence in the negative direction but not the more restrictive 1 km radius. However, exposure to medium or heavy smoke (primarily from wildfires) at the zip code level was associated with both 7-day (8.5% increase; 95% CI = 1.5%, 16.0%) and 30-day readmissions (5.4%; 95% CI = 2.3%, 8.5%), and to a lesser degree, hospital visits (1.5%; 95% CI: 0.0%, 3.0%) matching previous studies. CONCLUSIONS: Area-level smoke exposure driven by wildfires is positively associated with hospital utilization but not proximity to prescribed fires.

Knowledge and acceptance of malaria vaccine among parents of under-five children of malaria endemic areas in Bangladesh: A cross-sectional study.

BACKGROUND: Malaria exists as an endemic in many countries including Bangladesh and the malaria vaccine is not yet available here. The study aimed to assess the level of knowledge and acceptance of the malaria vaccination among the parents of children under the age of five in Bangladesh's malaria-endemic areas and the sociodemographic, behavioural, and household factors associated with the acceptance and knowledge of the malaria vaccine. METHODS: From January to March 2022, a cross-sectional study was conducted in all five malaria-endemic districts of Bangladesh, involving 405 parents of children under the age of 5 who met the inclusion criteria. Multiple logistic regression was used to analyze the factor affecting parents' acceptance and knowledge of malaria vaccination in children under five and other variables. RESULTS: Majority (54%) of the respondents were mothers. Almost half (49%) of the respondents were aged between 26 and 35 years old and around 90% were from rural areas. A small portion (20%) of the participants were housewives and 46% of them completed primary education. Overall, 70% of the study participants reported that they would accept malaria vaccination independently. About one-fourth (25%) heard about the malaria vaccine and 48% of them mentioned health professionals as the source of information. Knowledge of malaria vaccination was found associated with residence, income, and family size. Acceptance and knowledge were both associated with residence, education, occupation, income, and family size. In a multivariable analysis, housing structure, house wall, house window, knowledge of malaria, testing for malaria, and being diagnosed with malaria were all associated with knowledge of and acceptance of getting vaccinated against malaria. CONCLUSIONS: The present study highlights the necessity of creating awareness of malaria vaccines in epidemic areas of Bangladesh. This study offers crucial data to develop a policy for a novel malaria vaccine, supporting its adoption in Bangladesh. PUBLIC CONTRIBUTION: This study was based on interviews. The interviewees were recruited as public representatives from the malaria-endemic area to assist us in building an understanding of knowledge and acceptance of the malaria vaccine among parents of under-five children in Bangladesh.

Effectiveness of Skill-Building Interventions for Informal Caregivers of Adults with Cancer: a Systematic Review.

Over 19 million people worldwide were diagnosed with cancer in 2020. Informal caregivers of adults with cancer play an important role in helping their loved ones with cancer yet often receive little support in developing the necessary skills for caregiving. A systematic review of skill-building interventions for informal caregivers of adults with cancer was conducted across three electronic databases for academic articles published through February 2022. PRISMA reporting guidelines were followed throughout this review, the Mixed Methods Appraisal Tool was used to assess study quality, and results were summarized in a narrative synthesis. The main components of skill-building interventions examined include caregiving preparedness, communication, and self-care. Nine of the 11 included articles showed that interventions effectively built skills for informal caregivers. The articles reviewed had a wide variety of intervention strategies, outcome measures, and study designs. Two of the 11 articles mentioned vulnerable and key groups, and no studies were performed in low- and middle-income countries. Findings generally support implementing skill-building interventions for informal caregivers of adults with cancer; however, further research is necessary to determine the most effective approaches for improving caregiver skills and reaching vulnerable and key populations.

Simvastatin inhibits stem cell proliferation in human leiomyoma via TGF-ß3 and Wnt/ß-Catenin pathways.

Uterine leiomyoma (UL) is the most common gynaecologic tumour, affecting an estimated 70 to 80% of women. Leiomyomas develop from the transformation of myometrial stem cells into leiomyoma stem (or tumour-initiating) cells. These cells undergo self-renewal and differentiation to mature cells, both are necessary for the maintenance of tumour stem cell niche and tumour growth, respectively. Wnt/ß-catenin and TGF-ß/SMAD pathways, both overactive in UL, promote stem cell self-renewal, crosstalk between stem and mature cells, cellular proliferation, extracellular matrix (ECM) accumulation and drive overall UL growth. Recent evidence suggests that simvastatin, an antihyperlipidemic drug, may have anti-leiomyoma properties. Herein, we investigated the effects of simvastatin on UL stem cells. We isolated leiomyoma stem cells by flow cytometry using DyeCycle Violet staining and Stro-1/CD44 surface markers. We found that simvastatin inhibits proliferation and induces apoptosis in UL stem cells. In addition, it also suppressed the expression of the stemness markers Nanog, Oct4 and Sox2. Simvastatin significantly decreased the production of the key ECM proteins, collagen 1 and fibronectin. Finally, it inhibited genes and/or proteins expression of TGF-ß1, 2 and 3, SMAD2, SMAD4, Wnt4, ß-Catenin, LRP6, AXIN2 and Cyclin D1 in UL stem cells, all are key drivers of the TGF-ß3/SMAD2 and Wnt4/ß-Catenin pathways. Thus, we have identified a novel stem cell-targeting anti-leiomyoma simvastatin effect. Further studies are needed to replicate these findings in vivo.

Nudix hydrolase 15 (NUDT15) loss-of-function variants in an Australian inflammatory bowel disease population.

BACKGROUND: Thiopurine-related adverse events such as leukopenia, liver dysfunction and pancreatitis are associated with variants in the NUDT15 gene. Loss-of-function (low or no enzyme activity) alleles are more common in Asian and Hispanic populations. The prevalence of these variants in the Australian inflammatory bowel disease (IBD) population has not yet been reported. AIM: To evaluate the presence of NUDT15 loss-of-function alleles *2,*3,*9 in the Australian IBD population. METHODS: The NUDT15 screening cohort included 423 IBD patients from Brisbane, Australia. Study patients were recruited by: (i) retrospective review of clinical charts for thiopurine-related severe adverse events; (ii) pathology data (white blood cell (WBC) and neutrophil counts). NUDT15 genotyping was performed using polymerase chain reaction (PCR)-high-resolution melt (HRM), TaqMan genotyping and Sanger sequencing. RESULTS: NUDT15 mutation R139C (allele *3) was identified in 8 of 423 (1.9%) IBD patients. Seven of eight patients were R139C heterozygous (C/T) and one patient was R139C homozygous (T/T). One of the C/T group and the T/T patient developed thiopurine-induced myelosuppression (TIM) within 60 days of dosing. One patient in the C/T group developed TIM after 60 days of thiopurine dosing. The remaining five patients in the C/T group did not show TIM; however, other thiopurine-related events could not be ruled out and therefore careful monitoring over a long period is recommended. CONCLUSIONS: This is the first study to report the frequency of NUDT15 haplotypes *2,*3,*9 in an Australian IBD population. The most common variant detected was the R139C mutation. PCR and Sanger sequencing are efficient and cost-effective approaches for NUDT15 genotyping.

Simvastatin-loaded liposome nanoparticles treatment for uterine leiomyoma in a patient-derived xenograft mouse model: a pilot study.

Uterine leiomyomas are complex tumours with limited medical treatment options. Simvastatin is used to treat hypercholesterolaemia and has shown promising effects as a treatment option for leiomyomas. Previously, our group demonstrated a promising effect of simvastatin treatment in a patient-derived xenograft mouse model. Here, we tested the efficacy of simvastatin liposomal nanoparticles (NPs). After bilateral leiomyoma xenograft implantation, mice (N = 12) were divided into three treatment arms: control, simvastatin and simvastatin-loaded liposome NPs (simvastatin-NPs). Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP; however, the results were not significant. Due to low bioavailability and short half-life of simvastatin, liposomal NPs have the potential to enhance drug delivery, however, in this study NP did not provide improvement over simvastatin, but did demonstrate their potential for the delivery of simvastatin.Impact statementWhat is already known on this subject? Simvastatin treatment in a patient-derived xenograft mouse model reduced tumour growth and decreased proliferation.What do the results of this study add? Treatment with simvastatin significantly reduced tumour volume and inhibited the Ki67 expression when compared to the control group. There was a trend of reduced tumour volume and Ki67 expression after treatment with simvastatin-NP, however, it did not improve the efficacy of simvastatin at reducing tumour growth and proliferation.What are the implications of these findings for clinical practice and/or further research? More studies are needed to optimise the formulation of NPs to further enhance the sustainable delivery of simvastatin.

Wnt/ß-catenin signaling pathway in uterine leiomyoma: role in tumor biology and targeting opportunities.

Uterine leiomyoma is the most common tumor of the female reproductive system and originates from a single transformed myometrial smooth muscle cell. Despite the immense medical, psychosocial, and financial impact, the exact underlying mechanisms of leiomyoma pathobiology are poorly understood. Alterations of signaling pathways are thought to be instrumental in leiomyoma biology. Wnt/ß-catenin pathway appears to be involved in several aspects of the genesis of leiomyomas. For example, Wnt5b is overexpressed in leiomyoma, and the Wnt/ß-catenin pathway appears to mediate the role of MED12 mutations, the most common mutations in leiomyoma, in tumorigenesis. Moreover, Wnt/ß-catenin pathway plays a paracrine role where estrogen/progesterone treatment of mature myometrial or leiomyoma cells leads to increased expression of Wnt11 and Wnt16, which induces proliferation of leiomyoma stem cells and tumor growth. Constitutive activation of ß-catenin leads to myometrial hyperplasia and leiomyoma-like lesions in animal models. Wnt/ß-catenin signaling is also closely involved in mechanotransduction and extracellular matrix regulation and relevant alterations in leiomyoma, and crosstalk is noted between Wnt/ß-catenin signaling and other pathways known to regulate leiomyoma development and growth such as estrogen, progesterone, TGFß, PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, IGF, Hippo, and Notch signaling. Finally, evidence suggests that inhibition of the canonical Wnt pathway using ß-catenin inhibitors inhibits leiomyoma cell proliferation. Understanding the molecular mechanisms of leiomyoma development is essential for effective treatment. The specific Wnt/ß-catenin pathway molecules discussed in this review constitute compelling candidates for therapeutic targeting.

Simvastatin modulates estrogen signaling in uterine leiomyoma via regulating receptor palmitoylation, trafficking and degradation.

Uterine leiomyomas or fibroids are the most common tumors of the female reproductive tract. Estrogen (E2), a steroid-derived hormone, and its receptors (ERs), particularly ER-α, are important drivers for the development and growth of leiomyomas. We previously demonstrated that simvastatin, a drug used for hyperlipidemia, also possesses anti-leiomyoma properties. The aim of this work is to investigate the impact of simvastatin on ER-α signaling in leiomyoma cells, including its expression, downstream signaling, transcriptional activity, post-translational modification, trafficking and degradation. Primary and immortalized human uterine leiomyoma (HuLM) cells were used for in vitro experiments. Immunodeficient mice xenografted with human leiomyoma tissue explants were used for in vivo studies. Leiomyoma samples were obtained from patients enrolled in an ongoing double-blinded, phase II, randomized controlled trial. Here, we found that simvastatin significantly reduced E2-induced proliferation and PCNA expression. In addition, simvastatin reduced total ER-α expression in leiomyoma cells and altered its subcellular localization by inhibiting its trafficking to the plasma membrane and nucleus. Simvastatin also inhibited E2 downstream signaling, including ERK and AKT pathways, E2/ER transcriptional activity and E2-responsive genes. To explain simvastatin effects on ER-α level and trafficking, we examined its effects on ER-α post-translational processing. We noticed that simvastatin reduced ER-α palmitoylation; a required modification for its stability, trafficking to plasma membrane, and signaling. We also observed an increase in ubiquitin-mediated ER-α degradation. Importantly, we found that the effects of simvastatin on ER-α expression were recapitulated in the xenograft leiomyoma mouse model and human tissues. Thus, our data suggest that simvastatin modulates several E2/ER signaling targets with potential implications in leiomyoma therapy and beyond.

Reliability and financial feasibility assessment of a community rainwater harvesting system considering precipitation variability due to climate change.

This study proposes a community rainwater harvesting (RWH) system as an alternative water supply solution for Paikgacha, a water-scarce coastal urban area in Bangladesh. Although individual household-based RWH systems have been implemented in many areas in Bangladesh, to date, no study has been conducted designing a community RWH system and assessing its reliability and financial feasibility. This study employs historical observed and available climate model predicted future rainfall data into stormwater management model (SWMM) for rainfall-runoff simulation of the community RWH, and compares SWMM's performance with rational formula based estimation. We then calculate volumetric and time reliability of the proposed system and assess its financial viability. We observe good agreement in reliability curves generated by SWMM and rational formula-based model. Under the historical rainfall scenario, our proposed community RWH shows up to 99% reliability for 100 L per day household demand, given that proper community size and storage tank size are chosen. Predicted rainfall pattern of 2041-2070 period shows similar reliability-tank size relation to that of historical observed rainfall; however, predicted high precipitation intensity during 2021-2040 and 2071-2100 seem to assist the system in attaining higher reliability. Cost-benefit analysis indicates the financial viability of the proposed system. Finally, we develop a nomograph incorporating interactive factors of RWH, which would ease decision making by the policymakers regarding the implementation of community RWH.

Simvastatin ameliorates altered mechanotransduction in uterine leiomyoma cells.

BACKGROUND: Uterine leiomyomas, the most common tumors of the female reproductive system, are characterized by excessive deposition of disordered stiff extracellular matrix and fundamental alteration in the mechanical signaling pathways. Specifically, these alterations affect the normal dynamic state of responsiveness to mechanical cues in the extracellular environment. These mechanical cues are converted through integrins, cell membrane receptors, to biochemical signals including cytoskeletal signaling pathways to maintain mechanical homeostasis. Leiomyoma cells overexpress ß1 integrin and other downstream mechanical signaling proteins. We previously reported that simvastatin, an antihyperlipidemic drug, has antileiomyoma effects through cellular, animal model, and epidemiologic studies. OBJECTIVE: This study aimed to examine the hypothesis that simvastatin might influence altered mechanotransduction in leiomyoma cells. STUDY DESIGN: This is a laboratory-based experimental study. Primary leiomyoma cells were isolated from 5 patients who underwent hysterectomy at the Department of Gynecology and Obstetrics of the Johns Hopkins University Hospital. Primary and immortalized human uterine leiomyoma cells were treated with simvastatin at increasing concentrations (0.001, 0.01, 0.1, and 1 µM, or control) for 48 hours. Protein and mRNA levels of ß1 integrin and extracellular matrix components involved in mechanical signaling were quantified by quantitative real-time polymerase chain reaction, western blotting, and immunofluorescence. In addition, we examined the effect of simvastatin on the activity of Ras homolog family member A using pull-down assay and gel contraction. RESULTS: We found that simvastatin significantly reduced the protein expression of ß1 integrin by 44% and type I collagen by 60% compared with untreated leiomyoma cells. Simvastatin-treated cells reduced phosphorylation of focal adhesion kinase down to 26%-60% of control, whereas it increased total focal adhesion kinase protein expression. Using a Ras homolog family member A pull-down activation assay, we observed reduced levels of active Ras homolog family member A in simvastatin-treated cells by 45%-85% compared with control. Consistent with impaired Ras homolog family member A activation, simvastatin treatment reduced tumor gel contraction where gel area was 122%-153% larger than control. Furthermore, simvastatin treatment led to reduced levels of mechanical signaling proteins involved in ß1 integrin downstream signaling, such as A-kinase anchor protein 13, Rho-associated protein kinase 1, myosin light-chain kinase, and cyclin D1. CONCLUSION: The results of this study suggest a possible therapeutic role of simvastatin in restoring the altered state of mechanotransduction signaling in leiomyoma. Collectively, these findings are aligned with previous epidemiologic studies and other reports and support the need for clinical trials.

Therapeutic and preventive properties of honey and its bioactive compounds in cancer: an evidence-based review.

Despite the much improved therapeutic approaches for cancer treatment that have been developed over the past 50 years, cancer remains a major cause of mortality globally. Considerable epidemiological and experimental evidence has demonstrated an association between ingestion of food and nutrients with either an increased risk for cancer or its prevention. There is rising interest in exploring agents derived from natural products for chemoprevention or for therapeutic purposes. Honey is rich in nutritional and non-nutritional bioactive compounds, as well as in natural antioxidants, and its potential beneficial function in human health is becoming more evident. A large number of studies have addressed the anti-cancer effects of different types of honey and their phenolic compounds using in vitro and in vivo cancer models. The reported findings affirm that honey is an agent able to modulate oxidative stress and has anti-proliferative, pro-apoptotic, anti-inflammatory, immune-modulatory and anti-metastatic properties. However, despite its reported anti-cancer activities, very few clinical studies have been undertaken. In the present review, we summarise the findings from different experimental approaches, including in vitro cell cultures, preclinical animal models and clinical studies, and provide an overview of the bioactive profile and bioavailability of the most commonly studied honey types, with special emphasis on the chemopreventive and therapeutic properties of honey and its major phenolic compounds in cancer. The implications of these findings as well as the future prospects of utilising honey to fight cancer will be discussed.

Radiolabeled 6-(2, 3-Dichlorophenyl)-N4-methylpyrimidine-2, 4-diamine (TH287): A Potential Radiotracer for Measuring and Imaging MTH1.

MTH1 (MutT homolog 1) or NUDT1 (Nudix Hydrolase 1), also known as oxidized purine nucleoside triphosphatase, has potential as a biomarker for monitoring cancer progression and quantifying target engagement for relevant therapies. In this study, we validate one MTH1 inhibitor TH287 as a PET MTH1 radiotracer. TH287 was radiolabeled with tritium and the binding of [3H]TH287 to MTH1 was evaluated in live glioblastoma cells (U251MG) through saturation and competitive binding assays, together with in vitro enzymatic assays. Furthermore, TH287 was radiolabeled with carbon-11 for in vivo microPET studies. Saturation binding assays show that [3H]TH287 has a dissociation constant (Kd) of 1.97 ± 0.18 nM, Bmax of 2676 ± 122 fmol/mg protein for U251MG cells, and nH of 0.98 ± 0.02. Competitive binding assays show that TH287 (Ki: 3.04 ± 0.14 nM) has a higher affinity for MTH1 in U251MG cells compared to another well studied MTH1 inhibitor: (S)-crizotinib (Ki: 153.90 ± 20.48 nM). In vitro enzymatic assays show that TH287 has an IC50 of 2.2 nM in inhibiting MTH1 hydrolase activity and a Ki of 1.3 nM from kinetics assays, these results are consistent with our radioligand binding assays. Furthermore, MicroPET imaging shows that [11C]TH287 gets into the brain with rapid clearance from the brain, kidney, and heart. The results presented here indicate that radiolabeled TH287 has favorable properties to be a useful tool for measuring MTH1 in vitro and for further evaluation for in vivo PET imaging MTH1 of brain tumors and other central nervous system disorders.

Relevance of functional foods in the Mediterranean diet: the role of olive oil, berries and honey in the prevention of cancer and cardiovascular diseases.

The traditional Mediterranean diet (MedDiet) is a well-known dietary pattern associated with longevity and improvement of life quality as it reduces the risk of the most common chronic pathologies, such as cancer and cardiovascular diseases (CVDs), that represent the principal cause of death worldwide. One of the most characteristic foods of MedDiet is olive oil, a very complex matrix, which constitutes the main source of fats and is used in the preparation of foods, both raw as an ingredient in recipes, and in cooking. Similarly, strawberries and raspberries are tasty and powerful foods which are commonly consumed in the Mediterranean area in fresh and processed forms and have attracted the scientific and consumer attention worldwide for their beneficial properties for human health. Besides olive oil and berries, honey has lately been introduced in the MedDiet thanks to its relevant nutritional, phytochemical and antioxidant profile. It is a sweet substance that has recently been classified as a functional food. The aim of this review is to present and discuss the recent evidence, obtained from in vitro, in vivo and epidemiological studies, on the potential roles exerted by these foods in the prevention and progression of different types of cancer and CVDs.

Development of Land-Use/Land-Cover Maps Using Landsat-8 and MODIS Data, and Their Integration for Hydro-Ecological Applications.

The Athabasca River watershed plays a dominant role in both the economy and the environment in Alberta, Canada. Natural and anthropogenic factors rapidly changed the landscape of the watershed in recent decades. The dynamic of such changes in the landscape characteristics of the watershed calls for a comprehensive and up-to-date land-use and land-cover (LULC) map, which could serve different user-groups and purposes. The aim of the study herein was to delineate a 2016 LULC map of the Athabasca River watershed using Landsat-8 Operational Land Imager (OLI) images, Moderate Resolution Imaging Spectroradiometer (MODIS)-derived enhanced vegetation index (EVI) images, and other ancillary data. In order to achieve this, firstly, a preliminary LULC map was developed through applying the iterative self-organizing data analysis (ISODATA) clustering technique on 24 scenes of Landsat-8 OLI. Secondly, a Terra MODIS-derived 250-m 16-day composite of 30 EVI images over the growing season was employed to enhance the vegetation classes. Thirdly, several geospatial ancillary datasets were used in the post-classification improvement processes to generate a final 2016 LULC map of the study area, exhibiting 14 LULC classes. Fourthly, an accuracy assessment was carried out to ensure the reliability of the generated final LULC classes. The results, with an overall accuracy and Cohen's kappa of 74.95% and 68.34%, respectively, showed that coniferous forest (47.30%), deciduous forest (16.76%), mixed forest (6.65%), agriculture (6.37%), water (6.10%), and developed land (3.78%) were the major LULC classes of the watershed. Fifthly, to support the data needs of scientists across various disciplines, data fusion techniques into the LULC map were performed using the Alberta merged wetland inventory 2017 data. The results generated two useful maps applicable for hydro-ecological applications. Such maps depicted two specific categories including different types of burned (approximately 6%) and wetland (approximately 30%) classes. In fact, these maps could serve as important decision support tools for policy-makers and local regulatory authorities in the sustainable management of the Athabasca River watershed.

Structure-stability relationship of anthocyanins under cell culture condition.

This work aims to evaluate the structure-stability relationship of anthocyanins in cell culture. An early degradation time (CT10) and half-degradation time (CT50) were used to characterise the stability of 10 of the most common anthocyanins, incubated with DMEM at 37 °C, pH = 7.4, 5% CO2 for different time periods. According to the glycosylation, the glycosylated forms were more stable than the not glycosylated forms. The methylation at 3'' or 5' position at ring B enhanced their stability; contrarily, the hydroxylation at 3' or 5' position at ring B weakened their stability. Glycosylated forms were much more stable in water than in the culture medium. Although not glycosylated forms were also instable in water, their stability was improved compared with culture medium. Together with the cell culture experiments and, in order to avoid artefacts, stability tests of polyphenols should be performed in parallel experiments with DMEM.

PgMYB2, a MeJA-Responsive Transcription Factor, Positively Regulates the Dammarenediol Synthase Gene Expression in Panax Ginseng.

The MYB transcription factor family members have been reported to play different roles in plant growth regulation, defense response, and secondary metabolism. However, MYB gene expression has not been reported in Panax ginseng. In this study, we isolated a gene from ginseng adventitious root, PgMYB2, which encodes an R2R3-MYB protein. Subcellular localization revealed that PgMYB2 protein was exclusively detected in the nucleus of Allium cepa epidermis. The highest expression level of PgMYB2 was found in ginseng root and it was significantly induced by plant hormones methyl jasmonate (MeJA). Furthermore, the binding interaction between PgMYB2 protein and the promoter of dammarenediol synthase (DDS) was found in the yeast strain Y1H Gold. Moreover, the electrophoretic mobility shift assay (EMSA) identified the binding site of the interaction and the results of transiently overexpressing PgMYB2 in plants also illustrated that it may positively regulate the expression of PgDDS. Based on the key role of PgDDS gene in ginsenoside synthesis, it is reasonable to believe that this report will be helpful for the future studies on the MYB family in P. ginseng and ultimately improving the ginsenoside production through genetic and metabolic engineering.

Targeting molecular pathways in cancer stem cells by natural bioactive compounds.

Cancer Stem Cells (CSCs) or Tumor-Initiating Cells (TICs) are a small sub-population of cells within the tumor, able to give chemio- and radio-resistance and cause the onset of metastasis and the presence of relapses; for these reasons, they are recently becoming a potential target for anticancer therapy. One of the main characteristics of these cells is the self-renewal through the capability of modulating different molecular signalling pathways, including Wnt/ß-Catenin, Sonic Hedgehog and Notch pathways. Natural bioactive compounds such as resveratrol, epigallocatechin, curcumin, quercetin, ellagic acid, anthocyanins and other compounds and extracts can have a direct or indirect effect on these molecular pathways, decreasing the pathological activities of CSCs. This review aims to report and summarize the in vitro and in vivo studies about the preventive, therapeutic and chemosensitizing effects of these natural bioactive compounds on CSCs deriving from different types of tumors.

Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells.

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2'-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

Beeswax by-Products Efficiently Counteract the Oxidative Damage Induced by an Oxidant Agent in Human Dermal Fibroblasts.

The antioxidant capacity and the phytochemical composition of two by-products from beeswax recycling processes were recently investigated. The aim of the present work was to evaluate the efficacy of one of these by-products, MUD1, against the oxidative stress induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) in human dermal fibroblast (HDF) cells. After a preliminary viability assay, the protective effect of MUD1 was investigated through the measurement of apoptosis level, the reactive oxygen species (ROS) and nitrite (NO2-) production, the level of protein and lipid biomarkers (carbonyl groups, total glutathione and thiobarbituric acid-reactive substance) of oxidative damage, and the measurement of antioxidant enzymes activities (glutatione peroxidase, glutathione reductase, glutathione transferase, superoxide dismutase and catalase). The obtained results showed that MUD1 exerted protective effects on HDF, increasing cell viability and counteracted the oxidative stress promoted by AAPH-treatment, and improved mitochondria functionality and wound healing capacities. This work shows the antioxidant effects exerted by beeswax by-products, demonstrating for the first time their potential against oxidative stress in human dermal fibroblast cells; however, further research will be necessary to evaluate their potentiality for human health by more deeply in vitro and in vivo studies.

Phenolic Compounds Isolated from Olive Oil as Nutraceutical Tools for the Prevention and Management of Cancer and Cardiovascular Diseases.

Non-communicable diseases (NCDs) have become the largest contributor to worldwide morbidity and mortality. Among them, cancer and cardiovascular diseases (CVDs) are responsible for a 47% of worldwide mortality. In general, preventive approaches modifying lifestyle are more cost-effective than treatments after disease onset. In this sense, a healthy diet could help a range of NCDs, such as cancer and CVDs. Traditional Mediterranean Diet (MD) is associated by the low-prevalence of certain types of cancers and CVDs, where olive oil plays an important role. In fact, different epidemiological studies suggest that olive oil consumption prevents some cancers, as well as coronary heart diseases and stroke incidence and mortality. Historically, the beneficial health effects of virgin olive oil (VOO) intake were first attributed to the high concentration of monounsaturated fatty acids. Nowadays, many studies indicate that phenolic compounds contained in olive oil have positive effects on different biomarkers related to health. Among them, phenolic compounds would be partially responsible for health benefits. The present work aims to explore, in studies published during the last five years, the effects of the main phenolic compounds isolated from olive oil on different cancer or CVD aspects, in order to clarify which compounds have more potential to be used as nutraceuticals with preventive or even therapeutic properties.