Essential Oils: Chemistry and Pharmacological Activities-Part II.

The importance of essential oils and their components in the industrial sector is attributed to their chemical characteristics and their application in the development of products in the areas of cosmetology, food, and pharmaceuticals. However, the pharmacological properties of this class of natural products have been extensively investigated and indicate their applicability for obtaining new drugs. Therefore, this review discusses the use of these oils as starting materials to synthesize more complex molecules and products with greater commercial value and clinic potential. Furthermore, the antiulcer, cardiovascular, and antidiabetic mechanisms of action are discussed. The main mechanistic aspects of the chemopreventive properties of oils against cancer are also presented. The data highlight essential oils and their derivatives as a strategic chemical group in the search for effective therapeutic agents against various diseases.

Assessing nutrition-related knowledge, attitudes, and practices towards breast cancer prevention among female students at the Federal University of Oye-Ekiti, Nigeria.

BACKGROUND: Breast cancer remains a complex disease and leading cause of cancer-related death in Nigerian women. Recently, the role of nutrition has been highlighted in the etiology of breast cancer. METHODS: The aim of this research was to evaluate the nutrition-related knowledge, attitude, and practices of female university students. We also investigated the correlation between their demographic characteristics and their knowledge and attitudes of the survey participants. A descriptive cross-sectional study was carried out among female students at the Federal University of Oye (FUOYE), Nigeria. Participants completed self-administered questionnaires designed to assess their knowledge, attitude, and practices concerning cancer prevention. Statistical analysis was performed using SPSS 20, and significance was set at p < 0.05. RESULTS: Out of the 402 students who received the questionnaire, 300 completed it. The average age of the participants was 21.26 years with a standard deviation of 2.68. There was generally limited knowledge regarding breast cancer risk factors, with 45% of participants citing family history as the most recognized risk factor. Overall, knowledge level was influenced by the participants' permanent place of residence and course of study. Attitudes towards the impact of maternal and paternal nutrition on breast cancer prevention were notably low. Additionally, less than half of the participants demonstrated good dietary practices. CONCLUSION: This study revealed low levels of nutrition-related knowledge concerning cancer prevention, accompanied by poor dietary habits among the participants. These results suggest a possible link between inadequate knowledge about breast cancer prevention and the observed poor dietary practices among the participants. The frequent consumption of unhealthy foods among the participants may be a pointer to higher risk of breast cancer in the future, emphasizing a need for health education targeted at this group.

Anthocyanins Reduce Cell Invasion and Migration through Akt/mTOR Downregulation and Apoptosis Activation in Triple-Negative Breast Cancer Cells: A Systematic Review and Meta-Analysis.

BACKGROUND: Studies have suggested the chemopreventive effects of anthocyanins on breast cancer carcinogenesis. This systematic review and meta-analysis aimed to evaluate the effect of anthocyanins on triple-negative breast cancer cells (TNBC) cultured in vitro. METHODS: We searched for all relevant studies that evaluated the mechanisms of migration, invasion, Akt/mTOR and MAPK pathways, and apoptosis, using PubMed and Scopus. Means and standard deviation were used, and a randomized effects model was applied, with a confidence interval of 95%. Statistical heterogeneity between studies was assessed using the Chi2 test and I2 statistics. All analyses were performed using RevMan software (version 5.4). RESULTS: Eleven studies were included in the systematic review and ten in the meta-analysis, where the roles of anthocyanin-enriched extract or cyanidin-3-O-glucoside (C-3-O-G) on MDA-MB-231 and MDA-MB-453 cells were investigated. DISCUSSION: There was a significant reduction in invasion (mean difference: -98.64; 95% CI: -153.98, -43.3; p ˂ 0.00001) and migration (mean difference: -90.13; 95% CI: -130.57, -49.68; p ˂ 0.00001) in TNBC cells after anthocyanins treatment. Anthocyanins also downregulated Akt (mean difference: -0.63; 95% CI: -0.70, -0.57; p ˂ 0.00001) and mTOR (mean difference: -0.93; 95% CI: -1.58, -0.29; p = 0.005), while JNK (mean difference: -0.06; 95% CI: -1.21, 1.09; p = 0.92) and p38 (mean difference: 0.05; 95% CI: -1.32, 1.41; p = 0.95) were not modulated. There was also an increase in cleaved caspase-3 (mean difference: 1.13; 95% CI: 0.11, 2.16; p = 0.03), cleaved caspase-8 (mean difference: 1.64; 95% CI: 0.05, 3.22; p = 0.04), and cleaved PARP (mean difference: 0.93; 95% CI: 0.54, 1.32). Although the difference between control and anthocyanin groups was not significant regarding apoptosis rate (mean difference: 3.63; 95% CI: -2.88, 10.14; p = 0.27), the analysis between subgroups showed that anthocyanins are more favorable in inducing overall apoptosis (p ˂ 0.00001). CONCLUSION: The results show that anthocyanins hold promise in fighting against TNBC, but their effects should not be generalized. In addition, further primary studies should be conducted so that more accurate conclusions can be drawn.

Effect of Paternal Diet on Spermatogenesis and Offspring Health: Focus on Epigenetics and Interventions with Food Bioactive Compounds.

Infertility is a growing public health problem. Consumption of antioxidant bioactive food compounds (BFCs) that include micronutrients and non-nutrients has been highlighted as a potential strategy to protect against oxidative and inflammatory damage in the male reproductive system induced by obesity, alcohol, and toxicants and, thus, improve spermatogenesis and the fertility parameters. Paternal consumption of such dietary compounds could not only benefit the fathers but their offspring as well. Studies in the new field of paternal origins of health and disease show that paternal malnutrition can alter sperm epigenome, and this can alter fetal development and program an increased risk of metabolic diseases and breast cancer in adulthood. BFCs, such as ascorbic acid, α-tocopherol, polyunsaturated fatty acids, trace elements, carnitines, N-acetylcysteine, and coenzyme Q10, have been shown to improve male gametogenesis, modulate epigenetics of germ cells, and the epigenetic signature of the offspring, restoring offspring metabolic health induced by stressors during early life. This indicates that, from a father's perspective, preconception is a valuable window of opportunity to start potential nutritional interventions with these BFCs to maximize sperm epigenetic integrity and promote adequate fetal growth and development, thus preventing chronic disease in adulthood.

Selenium Supplementation during Puberty and Young Adulthood Mitigates Obesity-Induced Metabolic, Cellular and Epigenetic Alterations in Male Rat Physiology.

Selenium (Se) role in obesity is not clear. In addition, information on Se's role in male physiology, specifically in obesity, is scarce. We conducted this study to evaluate the efficacy of Se supplementation, specifically during puberty until young adulthood, against obesity-induced deregulation of metabolic, cellular, and epigenetic parameters in epididymal fat and/or sperm cells in a rat model. High-fat-diet consumption by male rats during puberty and young adulthood significantly increased body weight, adipocyte size, oxidative stress, deregulated expression of genes associated with inflammation (Adiponectin, IL-6, TNF-α), adipogenesis (CEBPα), estrogen biosynthesis (CYP19) and epigenetic processes in epididymal adipose tissue (Dnmt3a), as well as altered microRNA expression vital for spermatogenesis in sperm cells (miR-15b and miR-497). On the other hand, Se supplementation significantly decreased oxidative stress and mitigated these molecular/epigenetic alterations in epididymal adipose tissue or sperm cells. Our results indicate that selenium supplementation during puberty/young adulthood could improve male physiology in the context of obesity. In addition, it suggests that Se could potentially positively affect offspring health.

Multidisciplinary management of chronic atopic dermatitis in children and adolescents: a prospective pilot study.

BACKGROUND: Atopic dermatitis (AD) is a chronic, pruritic disorder affecting 10-20% of children and is associated with psychological issues and impaired quality of life (QoL). The role of psychosocial support in the treatment of AD is increasingly important. We studied the impact of a multidisciplinary clinic (MDC) in the management of AD in a tertiary children's hospital in Singapore. METHODS: We performed a prospective pilot interventional study on 34 pediatric patients with AD and concomitant psychosocial impairment. Patients were recruited into an MDC, comprising a dermatologist, clinical psychologist and medical social worker. AD severity was scored using Scoring Atopic Dermatitis (SCORAD), while QoL was assessed using the Children's Dermatology Life Quality Index Questionnaire (CDLQI) and Family Dermatology Life Quality Index Questionnaire (FDLQI). Biopsychosocial assessments and interventions were also performed. Eighty-three percent of patients received cognitive behavioral therapy, while 40% received social work intervention. RESULTS: There was an overall improvement in mean SCORAD, CDLQI, and FDLQI scores across MDC visits. A correlation between AD severity and QoL was established. A patient satisfaction survey showed improvement in severity, understanding, and control of the disease. CONCLUSION: Our study suggests the effectiveness of a multidisciplinary approach in managing pediatric AD patients with psychosocial co-morbidities.

Maternal obesity during pregnancy leads to adipose tissue ER stress in mice via miR-126-mediated reduction in Lunapark.

AIMS/HYPOTHESIS: Levels of the microRNA (miRNA) miR-126-3p are programmed cell-autonomously in visceral adipose tissue of adult offspring born to obese female C57BL/6J mice. The spectrum of miR-126-3p targets and thus the consequences of its dysregulation for adipocyte metabolism are unknown. Therefore, the aim of the current study was to identify novel targets of miR-126-3p in vitro and then establish the outcomes of their dysregulation on adipocyte metabolism in vivo using a well-established maternal obesity mouse model. METHODS: miR-126-3p overexpression in 3T3-L1 pre-adipocytes followed by pulsed stable isotope labelling by amino acids in culture (pSILAC) was performed to identify novel targets of the miRNA. Well-established bioinformatics algorithms and luciferase assays were then employed to confirm those that were direct targets of miR-126-3p. Selected knockdown experiments were performed in vitro to define the consequences of target dysregulation. Quantitative real-time PCR, immunoblotting, histology, euglycaemic-hyperinsulinaemic clamps and glucose tolerance tests were performed to determine the phenotypic and functional outcomes of maternal programmed miR-126-3p levels in offspring adipose tissue. RESULTS: The proteomic approach confirmed the identity of known targets of miR-126-3p (including IRS-1) and identified Lunapark, an endoplasmic reticulum (ER) protein, as a novel one. We confirmed by luciferase assay that Lunapark was a direct target of miR-126-3p. Overexpression of miR-126-3p in vitro led to a reduction in Lunapark protein levels and increased Perk (also known as Eif2ak3) mRNA levels and small interference-RNA mediated knockdown of Lunapark led to increased Xbp1, spliced Xbp1, Chop (also known as Ddit3) and Perk mRNA levels and an ER stress transcriptional response in 3T3-L1 pre-adipocytes. Consistent with the results found in vitro, increased miR-126-3p expression in adipose tissue from adult mouse offspring born to obese dams was accompanied by decreased Lunapark and IRS-1 protein levels and increased markers of ER stress. At the whole-body level the animals displayed glucose intolerance. CONCLUSIONS/INTERPRETATION: Concurrently targeting IRS-1 and Lunapark, a nutritionally programmed increase in miR-126-3p causes adipose tissue insulin resistance and an ER stress response, both of which may contribute to impaired glucose tolerance. These findings provide a novel mechanism by which obesity during pregnancy leads to increased risk of type 2 diabetes in the offspring and therefore identify miR-126-3p as a potential therapeutic target.

MRI predictors for brain invasion in meningiomas.

BACKGROUND AND PURPOSE: In the 2016 revision of the World Health Organization classification of central nervous system tumours, brain invasion was added as an independent histological criterion for the diagnosis of a World Health Organization grade II atypical meningioma. The aim of this study was to assess whether magnetic resonance imaging characteristics can predict brain invasion for meningiomas. MATERIALS AND METHODS: We conducted a retrospective review of all meningiomas resected at our institution between 2005 and 2016 which had preoperative magnetic resonance imaging and included brain tissue within the pathology specimen. One hundred meningiomas were included in the study, 60 of which had histopathological brain invasion, 40 of which did not. Magnetic resonance imaging characteristics of tumours were evaluated for potential predictors of brain invasion. Tumour location, size, perilesional oedema, contour, cerebrospinal fluid cleft, peritumoral cyst, dural venous sinus invasion, bone invasion, hyperostosis and the presence of enlarged pial arteries and veins were evaluated. Data were analysed using conventional chi-square, Fisher's exact test and logistic regression. RESULTS: The volume of peritumoral oedema was significantly higher in the brain-invasive meningioma group compared to the non-brain-invasive group. The presence of a complete cleft was a rare finding that was only found in non-brain-invasive meningiomas. The presence of enlarged pial feeding arteries was a rare finding that was only found in brain-invasive meningiomas. CONCLUSIONS: An increased volume of perilesional oedema is associated with the likelihood of brain invasion for meningiomas.

Guide RNA Engineering Enables Dual Purpose CRISPR-Cpf1 for Simultaneous Gene Editing and Gene Regulation in Yarrowia lipolytica.

Yarrowia lipolytica has fast become a biotechnologically significant yeast for its ability to accumulate lipids to high levels. While there exists a suite of synthetic biology tools for genetic engineering in this yeast, there is a need for multipurposed tools for rapid strain generation. Here, we describe a dual purpose CRISPR-Cpf1 system that is capable of simultaneous gene disruption and gene regulation. Truncating guide RNA spacer length to 16 nt inhibited nuclease activity but not binding to the target loci, enabling gene activation and repression with Cpf1-fused transcriptional regulators. Gene repression was demonstrated using a Cpf1-Mxi1 fusion achieving a 7-fold reduction in mRNA, while CRISPR-activation with Cpf1-VPR increased hrGFP expression by 10-fold. High efficiency disruptions were achieved with gRNAs 23-25 bp in length, and efficiency and repression levels were maintained with multiplexed expression of truncated and full-length gRNAs. The developed CRISPR-Cpf1 system should prove useful in metabolic engineering, genome wide screening, and functional genomics studies.

A Standardized Protocol for Efficient and Reliable Quality Control of Brain Registration in Functional MRI Studies.

Automatic alignment of brain anatomy in a standard space is a key step when processing magnetic resonance imaging for group analyses. Such brain registration is prone to failure, and the results are therefore typically reviewed visually to ensure quality. There is however no standard, validated protocol available to perform this visual quality control (QC). We propose here a standardized QC protocol for brain registration, with minimal training overhead and no required knowledge of brain anatomy. We validated the reliability of three-level QC ratings (OK, Maybe, Fail) across different raters. Nine experts each rated N = 100 validation images, and reached moderate to good agreement (kappa from 0.4 to 0.68, average of 0.54 ± 0.08), with the highest agreement for "Fail" images (Dice from 0.67 to 0.93, average of 0.8 ± 0.06). We then recruited volunteers through the Zooniverse crowdsourcing platform, and extracted a consensus panel rating for both the Zooniverse raters (N = 41) and the expert raters. The agreement between expert and Zooniverse panels was high (kappa = 0.76). Overall, our protocol achieved a good reliability when performing a two level assessment (Fail vs. OK/Maybe) by an individual rater, or aggregating multiple three-level ratings (OK, Maybe, Fail) from a panel of experts (3 minimum) or non-experts (15 minimum). Our brain registration QC protocol will help standardize QC practices across laboratories, improve the consistency of reporting of QC in publications, and will open the way for QC assessment of large datasets which could be used to train automated QC systems.

Bioactive food compounds, epigenetics and chronic disease prevention: Focus on early-life interventions with polyphenols.

Consumption of bioactive compounds such as polyphenols, isothiocyanates, sulfur-containing compounds and terpenoids, found in fruits and vegetables, is associated with prevention of chronic disease. These bioactive food compounds elicit their protective effects through complex mechanisms at the cellular and molecular, including epigenetic levels. According to the Developmental Origins of Health and Disease (DOHaD) paradigm, in utero exposure to stressors such as malnutrition through maternal diet would impair fetal development and epigenetically program increased risk of metabolic diseases and some cancers in adult life. In addition, a role for fathers´ diet during preconception on their offspring health and chronic disease susceptibility has also emerged. This highlights early life as a promising window of opportunity for starting dietary interventions focusing on preventing chronic diseases. However, knowledge on the potential beneficial impact of early life exposure to bioactive food compounds is limited. Among the studies that have investigated bioactive food compounds in the context of DOHaD, most have focused on the impact of dietary polyphenols. Thus, in this review we discuss experimental evidence supporting a role for the dietary polyphenols resveratrol, genistein, epigallocatechin-3-gallate and anthocyanins in chronic disease prevention considering a perspective from early-life interventions through maternal and paternal diets and focusing on epigenetics as a potential underlying mechanism.

Dietary zinc deficiency or supplementation during gestation increases breast cancer susceptibility in adult female mice offspring following a J-shaped pattern and through distinct mechanisms.

Zinc is required for fetal development and is involved in key processes associated with breast carcinogenesis. We evaluated whether maternal zinc deficiency or supplementation during gestation influences female offspring susceptibility to breast cancer in adulthood. C57BL/6 mice consumed during gestation control (30 p.p.m. zinc), zinc-deficient (8 p.p.m) or zinc-supplemented (45 p.p.m.) diets. Maternal zinc supplementation increased in female mice offspring the incidence of chemically-induced mammary adenocarcinomas that were heavier, compared to control group. This was accompanied by a decreased number of terminal end buds, increased cell proliferation and apoptosis, and increased tumor suppressors p21, p53 and Rassf1, Zfp382 and Stat3 expression in mammary glands, as well as increased zinc status. Although maternal zinc deficiency did not alter the incidence of these lesions, it also induced heavier mammary adenocarcinomas, compared to control group. These effects were accompanied by a decreased number of terminal end buds, increased proto-oncogenes c-Myc and Lmo4 expression and H3K9Me3 and H4K20Me3 epigenetic marks in mammary glands of offspring, and decreased zinc status and increased levels of oxidative marker malondialdehyde. The data suggest that both maternal zinc deficiency and supplementation during gestation programmed increased breast cancer susceptibility in adult mice offspring following a J-shaped pattern through distinct mechanisms.

Hypercaloric Diet-Induced Obesity and Obesity-Related Metabolic Disorders in Experimental Models.

Overnutrition and obesity have developed into a major public health problem across different parts of the world. Epidemiological studies have shown that excessive intake of dietary components, such as fatty acids and/or sugars, can promote obesity. In this context, the use of dietary intervention in animal models that respond to a diet similar to humans is useful to understand this preventable, multifactorial disease. The aim of this chapter is to aid researchers in choosing specific nutritional interventions and animal strains to induce obesity and obesity-related morbidities in experimental models.

Nutritional Programming Effects on Development of Metabolic Disorders in Later Life.

Developmental programming resulting from maternal malnutrition can lead to an increased risk of metabolic disorders such as obesity, insulin resistance, type 2 diabetes and cardiovascular disorders in the offspring in later life. Furthermore, many conditions linked with developmental programming are also known to be associated with the aging process. This review summarizes the available evidence about the molecular mechanisms underlying these effects, with the potential to identify novel areas of therapeutic intervention. This could also lead to the discovery of new treatment options for improved patient outcomes.

Developmental Origins of Breast Cancer: A Paternal Perspective.

The developmental origins of breast cancer have been considered predominantly from a maternal perspective. Although accumulating evidence suggests a paternal programming effect on metabolic diseases, the potential impact of fathers' experiences on their daughters' breast cancer risk has received less attention. In this chapter, we focus on the developmental origins of breast cancer and examine the emerging evidence for a role of fathers' experiences.

Investigation of Paternal Programming of Breast Cancer Risk in Female Offspring in Rodent Models.

Emerging experimental evidence show that fathers' experiences during preconception can influence their daughters' risk of developing breast cancer. Here we describe detailed protocols for investigation in rats and mice of paternally mediated breast cancer risk programming effects.

Selenium and Breast Cancer Risk: Focus on Cellular and Molecular Mechanisms.

Selenium (Se) is a micronutrient with promising breast cancer prevention and treatment potential. There is extensive preclinical evidence of Se mammary carcinogenesis inhibition. Evidence from epidemiological studies is, however, unclear and intervention studies are rare. Here, we examine Se chemoprotection, chemoprevention, and chemotherapy effects in breast cancer, focusing on associated cellular and molecular mechanisms. Se exerts its protective actions through multiple mechanisms that involve antioxidant activities, induction of apoptosis, and inhibition of DNA damage, cell proliferation, angiogenesis, and invasion. New aspects of Se actions in breast cancer have emerged such as the impact of genetic polymorphisms on Se metabolism and response, new functions of selenoproteins, epigenetic modulation of gene expression, and long-term influence of early-life exposure on disease risk. Opportunity exists to design interventional studies with Se for breast cancer prevention and treatment taking into consideration these key aspects.

Low-Energy Virtual Monochromatic Dual-Energy Computed Tomography Images for the Evaluation of Head and Neck Squamous Cell Carcinoma: A Study of Tumor Visibility Compared With Single-Energy Computed Tomography and User Acceptance.

OBJECTIVE: Dual-energy computed tomography (CT) 40-keV virtual monochromatic images (VMIs) have been reported to improve visualization of head and neck squamous cell carcinoma, but a direct comparison to single-energy CT (SECT) is lacking, and there is debate regarding subjective user preference. We compared 40-keV VMIs with SECT and performed a subjective evaluation of their utility and acceptability for clinical use. METHODS: A total of 60 dual-energy CT and 60 SECT scans from 2 different institutions were evaluated. Tumor conspicuity was evaluated objectively using absolute and relative attenuation and subjectively by 3 head and neck specialists and 3 general radiologists. RESULTS: Tumors had significantly higher absolute and relative attenuation on 40-keV VMIs (P < 0.0001). Subjectively, the 40-keV VMIs improved visualization, with substantial (κ, 0.61-0.80) to almost perfect (κ, 0.81-1) interrater agreements. CONCLUSIONS: The 40-keV VMIs improve tumor visibility objectively and subjectively both by head and neck specialists and general radiologists.