Cytotoxic and molecular evaluation of spilanthol obtained from Acmella oleracea (L.) R. K. Jansen (jambu) in human gastric cancer cells.

Acmella oleracea (L.) is a plant popularly known as jambu in the Brazilian Amazon. This species has several biological properties, such as anaesthetic, antioxidant and anti-inflammatory activities, among others. However, there is limited information on its anticancer activity. In this context, this study aims to evaluate the effects of the hydroethanolic extract of jambu and its active compound (spilanthol) on gastric cancer cells. Hydroethanolic jambu inflorescence extract was obtained, and spilanthol was isolated by HPLC. Biological cytotoxicity assays were determined using MTT tests. In addition, an in silico study using molecular docking evaluated the inhibitory properties of spilanthol against JAK1 and JAK2 proteins. The results showed that the hydroethanolic extract and the isolated compound spilanthol exhibited cytotoxicity against cancer cells. Molecular docking revealed that spilanthol has inhibitory potential for JAK1 and JAK2 proteins. Thus, extract of jambu and spilanthol can be a possible candidate for the treatment of gastric carcinoma.

Antimicrobial Activity and Molecular Docking Studies of the Biotransformation of Diterpene Acanthoic Acid Using the Fungus Xylaria sp.

Biotransformations are reactions mediated by microorganisms, such as fungi. These bioreactions have high chemo- and stereoselectivity on organic substrates and can be applied in the search for new bioactive compounds. In this study, acanthoic acid (AA) was biotransformed using the fungus Xylaria sp., giving the novel compound 3ß,7ß-dihydroxyacanthoic acid (S1). Both the AA and the product S1 were tested against Gram-positive and Gram-negative bacteria. To identify and validate possible biological targets as enzymes or proteins involved in the activity observed in vitro, we used the molecular docking method. Hydroxylation at the C-3 and C-7 positions of the biotransformation product enhanced its activity against Escherichia coli as well as its binding affinity and interactions with superoxide dismutase 1 (SOD1; PDB ID 4A7G). Based on our results, the SOD1 enzyme was suggested to be a possible target for the antioxidant activity of product S1.

Extracellular vesicle microRNAs in celiac disease patients under a gluten-free diet, and in lactose intolerant individuals.

BACKGROUND: Celiac disease (CD) is an autoimmune disorder triggered by an abnormal immunological response to gluten ingestion and is associated with deregulated expression of cellular microRNAs (miRNAs) of the gut mucosa. It is frequently misdiagnosed as lactose intolerance (LI) due to symptom resemblance. Microvilli loss may be counteracted by a rigorous gluten-free diet (GFD). AIMS: To identify altered extracellular vesicle miRNAs from plasma among CD patients on GFD (n=34), lactose intolerant individuals on restrictive diet (n=14) and controls (n=23), and to predict biological pathways in which these altered miRNAs may play a part. METHODS: Five different small RNA samples of each group were pooled twice and then screened by new-generation sequencing. Four miRNAs were selected to be quantified by RT-qPCR in the entire sample. RESULTS: The levels of four miRNAs - miR-99b-3p, miR-197-3p, miR-223-3p, and miR-374b-5p - differed between CD patients and controls (P<0.05). Apart from miR-223-3p, all these miRNAs tended to have altered levels also between LI and controls (P<0.10). The results for miR-99b-3p and miR-197-3p between CD and controls were confirmed by RT-qPCR, which also indicated different levels of miR-99b-3p and miR-374b-5p between CD-associated LI and LI (P<0.05). CONCLUSIONS: These miRNAs may have targets that affect cell death, cell communication, adhesion, and inflammation modulation pathways. Hence, altered miRNA levels could be associated with CD-related aspects and gut mucosa recovery.

Long Non-Coding RNAs in Multifactorial Diseases: Another Layer of Complexity.

Multifactorial diseases such as cancer, cardiovascular conditions and neurological, immunological and metabolic disorders are a group of diseases caused by the combination of genetic and environmental factors. High-throughput RNA sequencing (RNA-seq) technologies have revealed that less than 2% of the genome corresponds to protein-coding genes, although most of the human genome is transcribed. The other transcripts include a large variety of non-coding RNAs (ncRNAs), and the continuous generation of RNA-seq data shows that ncRNAs are strongly deregulated and may be important players in pathological processes. A specific class of ncRNAs, the long non-coding RNAs (lncRNAs), has been intensively studied in human diseases. For clinical purposes, lncRNAs may have advantages mainly because of their specificity and differential expression patterns, as well as their ideal qualities for diagnosis and therapeutics. Multifactorial diseases are the major cause of death worldwide and many aspects of their development are not fully understood. Recent data about lncRNAs has improved our knowledge and helped risk assessment and prognosis of these pathologies. This review summarizes the involvement of some lncRNAs in the most common multifactorial diseases, with a focus on those with published functional data.

Effect of low-elastic modulus liner and base as stress-absorbing layer in composite resin restorations.

OBJECTIVES: The aim of this study was to evaluate the effectiveness of liner and base materials to reduce the stress resulting from polymerization shrinkage. The null hypothesis tested was that the presence of low-viscosity liner and base materials under the composite resin restoration reduces the polymerization shrinkage stress. METHODS: A quasi-three-dimensional photoelastic model of a second premolar with a class I preparation was restored using four experimental groups (n=7): RC, resin composite (Filtek Z250); FLRC, flowable liner (Filtek Flow)+resin composite restoration; VLRC, resin-modified glass-ionomer liner+resin composite restoration; and VBRC, resin-modified glass-ionomer base+resin composite restoration. The maximum shear stresses (tau(max)) were calculated along the adhesive interface in 13 predefined and standardized point locations. Data were submitted to one-way ANOVA, followed by a Tukey's post hoc test (p<0.05). RESULTS: A significant difference was found among the experimental groups (p=0.001); therefore, the null hypothesis was rejected. The mean maximum shear stress was: 38.0kPa for RC, 52.1kPa for FLRC, 72.8kPa for VLRC, and 90.2kPa for VBRC. The polymerization shrinkage stress level from least to greatest was: RC