Liquidhope: methylome and genomic profiling from very limited quantities of plasma-derived DNA.

Analysis of the methylome of tumor cell-free deoxyribonucleic acid (DNA; cfDNA) has emerged as a powerful non-invasive technique for cancer subtyping and prognosis. However, its application is frequently hampered by the quality and total cfDNA yield. Here, we demonstrate the feasibility of very low-input cfDNA for whole-methylome and copy-number profiling studies using enzymatic conversion of unmethylated cysteines [enzymatic methyl-seq (EM-seq)] to better preserve DNA integrity. We created a model for predicting genomic subtyping and prognosis with high accuracy. We validated our tool by comparing whole-genome CpG sequencing with in situ cohorts generated with bisulfite conversion and array hybridization, demonstrating that, despite the different techniques and sample origins, information on cfDNA methylation is comparable with in situ cohorts. Our findings support use of liquid biopsy followed by EM-seq to assess methylome of cancer patients, enabling validation in external cohorts. This advance is particularly relevant for rare cancers like neuroblastomas where liquid-biopsy volume is restricted by ethical regulations in pediatric patients.

Use of Functional Foods and Oral Supplements as Adjuvants in Cancer Treatment.

In cancer patients treated with radiotherapy to the abdominopelvic region, dietary modifications and the use of functional foods (fortified food with added ingredients to provide specific health improving benefits, such as antioxidants, omega-3 fatty acids, and glutamine), may contribute to the improvement of the toxic effects of treatment, including nausea, diarrhea, and constipation, among others. With the aim of analyzing which coadjuvant foods benefit these patients, scientific evidence was gathered by a group of experts. For these patients, the authors recommend a diet that includes sufficient foods rich in antioxidants and polyphenols instead of supplements. Docosahexaenoic and eicosapentaenoic acids have proven useful for the management of anorexia/cachexia in pancreatic cancer patients. Probiotics composed of Lactobacillus spp. and Bifidobacterium spp. are regarded as safe even in patients with neutropenia and have been proven to decrease gastrointestinal symptoms. Several factors should be considered before probiotic supplementation, these include the stage of the disease, radiation dose, and symptomatology of each patient. There is no demonstrated clear benefit to the use of glutamine, so it is not recommended due to its high cost.

Evaluation of circulating tumor DNA by electropherogram analysis and methylome profiling in high-risk neuroblastomas.

Background: Liquid biopsy has emerged as a promising, non-invasive diagnostic approach in oncology because the analysis of circulating tumor DNA (ctDNA) reflects the precise status of the disease at diagnosis, progression, and response to treatment. DNA methylation profiling is also a potential solution for sensitive and specific detection of many cancers. The combination of both approaches, DNA methylation analysis from ctDNA, provides an extremely useful and minimally invasive tool with high relevance in patients with childhood cancer. Neuroblastoma is an extracranial solid tumor most common in children and responsible for up to 15% of cancer-related deaths. This high death rate has prompted the scientific community to search for new therapeutic targets. DNA methylation also offers a new source for identifying these molecules. However, the limited blood sample size which can be obtained from children with cancer and the fact that ctDNA content may occasionally be diluted by non-tumor cell-free DNA (cfDNA) complicate optimal quantities of material for high-throughput sequencing studies. Methods: In this article, we present an improved method for ctDNA methylome studies of blood-derived plasma from high-risk neuroblastoma patients. We assessed the electropherogram profiles of ctDNA-containing samples suitable for methylome studies, using 10 ng of plasma-derived ctDNA from 126 samples of 86 high-risk neuroblastoma patients, and evaluated several bioinformatic approaches to analyze DNA methylation sequencing data. Results: We demonstrated that enzymatic methyl-sequencing (EM-seq) outperformed bisulfite conversion-based method, based on the lower proportion of PCR duplicates and the higher percentage of unique mapping reads, mean coverage, and genome coverage. The analysis of the electropherogram profiles revealed the presence of nucleosomal multimers, and occasionally high molecular weight DNA. We established that 10% content of the mono-nucleosomal peak is sufficient ctDNA for successful detection of copy number variations and methylation profiles. Quantification of mono-nucleosomal peak also showed that samples at diagnosis contained a higher amount of ctDNA than relapse samples. Conclusions: Our results refine the use of electropherogram profiles to optimize sample selection for subsequent high-throughput analysis and support the use of liquid biopsy followed by enzymatic conversion of unmethylated cysteines to assess the methylomes of neuroblastoma patients.

Novel Nanotechnological Strategies for Skin Anti-aging.

BACKGROUND: Nanoparticle formulations development for anti-aging treatment is increasing due to their multifunctional properties. These nanotechnological strategies can target cellular/ molecular pathways of the skin affected by the aging process. However, a review of these strategies is required to discuss their efficacy/safety and establish the needs for further research. OBJECTIVE: Innovative nanotechnological advances for skin anti-aging/rejuvenation are summarized and discussed in this work. METHODS: The information in this review was extracted from recent and relevant studies using nanotechnology for anti-aging treatment from scientific databases. RESULTS AND DISCUSSION: Results show an enhanced skin anti-aging effect of actives-loaded nanoparticles of next generation (nanostructured lipid carriers, fullerenes, transfersomes, protransfersomes, niosomes, ethosomes, transethosomes, glycerosomes, phytosomes) compared with nanocarriers of first generation or conventional formulations. Anti-aging active ingredients such as, flavonoids (rutin, hesperidin, quercetagetine, quercetin, epigallocatechin-3-gallate, myricetin, silibinin, curcuminoids, isoflavones); vitamins (E, D₃, CoQ10); acids (hyaluronic, ascorbic, rosmarinic, gallic); extracts (Citrus sinensis, Tagetes erecta L., Achillea millefolium L., Citrus aurantium L., Glycyrrhiza glabra L., Aloe vera, propolis earned by Apis mellifera); and other compounds (adenosine, beta-glucan, heptapetide DEETGEF, resveratrol, cycloastragenol, melatonin, botulinum toxin, grapeseed oil), have been successfully entrapped into nanoparticles for skin rejuvenation. This encapsulation has improved their solubility, bioavailability, stability, permeability, and effectivity for skin anti-aging, providing a controlled drug release with minimized side effects. CONCLUSION: Recent studies show a trend of anti-aging herbal active ingredients-loaded nanoparticles, enhancing the moisturizing, antioxidant, regenerating and photoprotective activity of the skin. Suitable safety/shelf-life stability of these novel formulations is key to a successful translation to the clinic/industry.

Antitumor Effect of Epigallocatechin Gallate and Vincristine in Mice with L5178Y Lymphoma.

The main objective of research into new therapies is the search for more efficacy and fewer toxic effects in cancer treatments. On one hand, vincristine (VCR) is a chemotherapeutic used in different kinds of tumors. On the other hand, epigallocatechin gallate (EGCG) is a green tea metabolite that has shown an antineoplastic effect in diverse investigations, so the objective of this work is to evaluate the antitumor effects of the EGCG/VCR combination on tumor volume and survival. To achieve this objective, the solid model of lymphoma L5178Y was used in BALB/c mice with different doses of VCR, EGCG, and their combination allowed tumor growth and survival time recording. After tumor collection, measurements, and immunohistochemistry for p53, Bcl2, and Cyclin D1 were performed. The results showed that the EGCG/vincristine combination had a greater antitumor effect than those effects of vincristine and EGCG. It can be attributed to the fact that the greatest inhibition of Bcl2 was present in gathering of EGCG harvest with vincristine. Therefore, the combination of EGCG with vincristine has a better antineoplastic effect by inhibiting tumor development and increasing survival on both substances independently.

Bizarreness and Emotion Identification in Grete Stern Photomontages: Gender and Age Disparities.

Although the International Affective Picture System (IAPS) is used to evaluate emotions (valence, arousal, and dominance evoked by a large set of photographs), bizarre images in works of art have not been assessed with the IAPS procedures. Understood here as strange, non-sense, and absurd mental contents or expressions accompanied by surprise and confusion emotions, bizarreness was assessed after healthy adult volunteers assigned this specified variable to 140 Grete Stern's photomontages overtly intended to illustrate strange, absurd, and non-sensical contents in dream reports. The images were presented to 21 Young Males (YM) and 30 Young Females (YF) who were instructed to use the IAPS Self-Assessment Manikin, along with an additional bizarre-to-normal scale, to evaluate their response to them. The valence and the bizarre-to-normal ratings showed a dissimilar pattern of distribution between genders. Ratings of scales were different, and a greater variation in scales occurred according to gender. When bizarreness was appraised, gender differences became more evident especially for YF, who rated half of the images as bizarre, and with a diminished feeling of control, while the neutral and normal images were deemed more pleased and controlled. Valence, bizarreness, and dominance formed a different component than arousal in both groups. Negative correlations between valence and dominance, and between valence and bizarreness were also found in both groups, plus a positive one for dominance and bizarreness in YF, along with curvilinear relationships among all scales. On a second experiment, 10 photomontages evaluated by YF as bizarre or as normal were administered to 18 Old Males (OM) and 28 Old Females (OF). OF's arousal showed less neutral evaluations than OM's. In OF the bizarre images evoked either more excitation or calmness than in OM. The distribution of the bizarre-to-normal scale was significantly different across the evaluations in YM, YF, OM, and OF. The use of this extended IAPS instrument to explore bizarreness and emotional variables in response to art images seems suitable and potentially valuable to characterize bizarre, absurd, or non-sensical mental states and their brain correlates.