Differential Expression of miRNAs in Amyotrophic Lateral Sclerosis Patients.

Amyotrophic lateral sclerosis (ALS) is a progressive motor neuron disease that affects nerve cells in the brain and spinal cord, causing loss of muscle control, muscle atrophy and in later stages, death. Diagnosis has an average delay of 1 year after symptoms onset, which impairs early management. The identification of a specific disease biomarker could help decrease the diagnostic delay.

VUS: A functional analysis to differentiate pathogenic from benign variants identified in clinical diagnostic panels for breast cancer.

Genetic testing for susceptibility genes through next‑generation sequencing (NGS) has become a widely used technique. Using this, a number of genetic variants have been identified, several of which are variants of unknown significance (VUS). These VUS can either be pathogenic or benign.

Tomato Processing By-Products Valorisation through Ohmic Heating Approach.

Tomato by-products from processing industries have a higher potential to be reused as a source of bioactive compounds. Reliable national data on tomato by-products and physicochemical characterisation that will inform and find effective planning on tomato waste management in Portugal is absent. To help obtain this knowledge, selected Portugal companies were recruited to obtain representative samples of by-products generation, and physicochemical composition was evaluated.

The Complex Dynamic of Phase I Drug Metabolism in the Early Stages of Doxorubicin Resistance in Breast Cancer Cells.

The altered activity of drug metabolism enzymes (DMEs) is a hallmark of chemotherapy resistance. Cytochrome P450s (CYPs), mainly CYP3A4, and several oxidoreductases are responsible for Phase I metabolism of doxorubicin (DOX), an anthracycline widely used in breast cancer (BC) treatment. This study aimed to investigate the role of Phase I DMEs involved in the first stages of acquisition of DOX-resistance in BC cells.

Motor dysfunction in as a biomarker for developmental neurotoxicity.

Adequate alternatives to conventional animal testing are needed to study developmental neurotoxicity (DNT). Here, we used kinematic analysis to assess DNT of known (toluene (TOL) and chlorpyrifos (CPS)) and putative (β-N-methylamino-L-alanine (BMAA)) neurotoxic compounds. was exposed to these compounds during development and evaluated for survival and adult kinematic parameters using the FlyWalker system, a kinematics evaluation method.

New "Omics" Approaches as Tools to Explore Mechanistic Nanotoxicology.

In the last years, "omics" approaches have been applied to study the toxicity of nanomaterials (NM) with the aim of obtaining insightful information on their biological effects. One of the most developed "omics" field, transcriptomics, expects to find unique profiles of differentially-expressed genes after exposure to NM that, besides providing evidence of their mechanistic mode of action, may also be used as biomarkers for biomonitoring purposes. Moreover, several NM have been associated with epigenetic alterations, i.

Bioactivity and Bioaccessibility of Bioactive Compounds in Gastrointestinal Digestion of Tomato Bagasse Extracts.

A nutrient-rich diet is a key to improving the chemical signals, such as antioxidants, which modulate pathogens' resistance in the gut and prevent diseases. A current industrial problem is the generation of undervalued by-products, such as tomato bagasse, which are rich in bioactive compounds and of commercial interest (carotenoids and phenolic compounds). This work analyzed the effect of gastrointestinal digestion on the bioactivity and bioaccessibility of carotenoids and phenolic compounds from tomato bagasse extracts.

Anthocyanin Recovery from Grape by-Products by Combining Ohmic Heating with Food-Grade Solvents: Phenolic Composition, Antioxidant, and Antimicrobial Properties.

Usually, wine-making by-products are discarded, presenting a significant environmental impact. However, they can be used as a source of bioactive compounds. Moreover, consumers' increasing demand for naturally nutritious and healthy products requires new formulations and food product improvement, together with sustainable, environmentally friendly extraction methods.

Male and female breast cancer: the two faces of the same genetic susceptibility coin.

Background: Breast cancer (BC) is the most common cancer in women. In contrast, male BC is about 100 times less common than in women, being considered a rare disease. Male BC may be a distinctive subtype of BC and available data seems to indicate that male BC has a higher dependence on genetic variants than female BC.

In Vitro Gastrointestinal Digestion Impact on the Bioaccessibility and Antioxidant Capacity of Bioactive Compounds from Tomato Flours Obtained after Conventional and Ohmic Heating Extraction.

In times of pandemic and when sustainability is in vogue, the use of byproducts, such as fiber-rich tomato byproducts, can be an asset. There are still no studies on the impact of extraction methodologies and the gastrointestinal tract action on bioactive properties. Thus, this study used a solid fraction obtained after the conventional method (SFCONV) and a solid fraction after the ohmic method (SFOH) to analyze the effect of the gastrointestinal tract on bioactive compounds (BC) and bioactivities.

Copy number variations and constitutional chromothripsis (Review).

Both copy number variations (CNVs) and chromothripsis are phenomena that involve complex genomic rearrangements. Chromothripsis results in CNVs and other structural changes. CNVs are frequently observed in the human genome.

ABC Efflux Transporters and the Circuitry of miRNAs: Kinetics of Expression in Cancer Drug Resistance.

Cancer drug resistance (CDR) is a major problem in therapeutic failure. Over 90% of patients with metastatic cancer present CDR. Several mechanisms underlie CDR, including the increased expression of efflux ABC transporters and epigenetic phenomena.

MicroRNAs and cancer drug resistance: over two thousand characters in search of a role.

MicroRNAs (miRNAs), a group of small regulatory noncoding RNAs, transformed our thinking on gene regulation. More than two thousand human miRNAs have been identified thus far. These bind imperfectly to the 3'-untranslated region of target mRNA and have been involved in several pathological conditions including cancer.

Regulation of ABCB1 activity by microRNA-200c and microRNA-203a in breast cancer cells: the quest for microRNAs' involvement in cancer drug resistance.

ABCB1 is a major player in cancer drug resistance. The purpose of this study was to functionally assess the regulation of ABCB1 activity in a doxorubicin-resistant breast cancer cell line by miR-200c and miR-203. Human breast carcinoma cell lines MCF-7 (Doxorubicin-sensitive and not expressing ABCB1) and KCR (Doxorubicin-resistant and expressing ABCB1) were used to evaluate the expression levels of miR-200c and miR-203 by Real-time quantitative PCR (RT-qPCR).

Genotoxic alkenylbenzene flavourings, a contribution to risk assessment.

Alkenylbenzenes, such as estragole, myristicin and eugenol, are present is several flavourings, functional foods, plant food supplements (PFS) and in complementary and alternative medicines (CAM) including herbal medicines. The increase in consumption in functional foods observed worldwide requires a strict analysis of the scientific validity of their benefits and risk-benefit ratio associated with their intake. Some instances of acute toxicity have been reported associated with the use of herbal medicines and PFS, in particular because quality control is poor, and this poses a risk especially in internet marketed products.

New endoperoxides highly active in vivo and in vitro against artemisinin-resistant Plasmodium falciparum.

Background: The emergence and spread of Plasmodium falciparum resistance to artemisinin-based combination therapy in Southeast Asia prompted the need to develop new endoperoxide-type drugs.

Methods: A chemically diverse library of endoperoxides was designed and synthesized. The compounds were screened for in vitro and in vivo anti-malarial activity using, respectively, the SYBR Green I assay and a mouse model.

Down syndrome and microRNAs.

In recent years numerous studies have indicated the importance of microRNAs (miRNA/miRs) in human pathology. Down syndrome (DS) is the most prevalent survivable chromosomal disorder and is attributed to trisomy 21 and the subsequent alteration of the dosage of genes located on this chromosome. A number of miRNAs are overexpressed in down syndrome, including miR-155, miR-802, miR- 125b-2, let-7c and miR-99a.

The drug transporter ABCB1 c.3435C>T SNP influences artemether-lumefantrine treatment outcome.

Malaria treatment performance is potentially influenced by pharmacogenetic factors. This study reports an association study between the ABCB1 c.3435C>T, CYP3A4*1B (g.

Genetic Susceptibility in Acute Pancreatitis: Genotyping of GSTM1, GSTT1, GSTP1, CASP7, CASP8, CASP9, CASP10, LTA, TNFRSF1B, and TP53 Gene Variants.

Objectives: Genetic testing could play a critical role in diagnosis and prognosis of acute pancreatitis (AP) and guide effective therapeutic interventions. We hypothesized that genetic polymorphisms in apoptosis and oxidative stress genes could determine incidence or severity in AP.

Methods: We conducted a hospital-based case-control study in a white Portuguese population (133 AP patients and 232 age- and sex-matched healthy controls) to evaluate the role of 15 gene polymorphisms (2 deletions and 13 single nucleotide polymorphisms [SNPs]) in oxidative stress (GSTM1, GSTT1, GSTP1) and apoptosis genes (CASP7, CASP8, CASP9, CASP10, LTA, TNFRSF1B, TP53) in AP.

Prognostic value of microRNA-203a expression in breast cancer.

Tumor heterogeneity and the poor outcome of breast cancer (BC) patients have led researchers to define new markers of this disease. In recent years, microRNA expression patterns have proven to be valuable disease indicators. The level of miR-203a, in particular, was shown to be altered in different types of cancer.

Integration of HIV in the Human Genome: Which Sites Are Preferential? A Genetic and Statistical Assessment.

Chromosomal fragile sites (FSs) are loci where gaps and breaks may occur and are preferential integration targets for some viruses, for example, Hepatitis B, Epstein-Barr virus, HPV16, HPV18, and MLV vectors. However, the integration of the human immunodeficiency virus (HIV) in Giemsa bands and in FSs is not yet completely clear. This study aimed to assess the integration preferences of HIV in FSs and in Giemsa bands using an in silico study.

Methods for Studying MicroRNA Expression and Their Targets in Formalin-Fixed, Paraffin-Embedded (FFPE) Breast Cancer Tissues.

Drug resistance remains a burden in cancer treatment. In the past few years molecular genetics brought a new hope with personalized therapy. This individual approach allows the identification of genetic profiles that will respond better to a given treatment and consequently get a better outcome.

MicroRNAs and Cancer Drug Resistance.

The discovery of small regulatory noncoding RNAs revolutionized our thinking on gene regulation. The class of microRNAs (miRs), a group of small noncoding RNAs (20-22 nt in length) that bind imperfectly to the 3'-untranslated region of target mRNA, has been insistently implicated in several pathological conditions including cancer. Indeed, major hallmarks of cancer, such as cell differentiation, cell proliferation, cell cycle, cell survival, and cell invasion, has been described as being regulated by miRs.