Soluble HLA-G (sHLA-G) measurement might be useful as an early diagnostic biomarker and screening test for gastric cancer.

Gastric cancer (GC) is the fifth most frequent malignancy worldwide and has a high mortality rate related to late diagnosis. Although the gold standard for the GC diagnosis is endoscopy with biopsy, nonetheless, it is not cost-effective and is invasive for the patient. The Human leukocyte antigen G (HLA-G) molecule is a checkpoint of the immune response. Its overexpression in cancer is associated with immune evasion, metastasis, poor prognosis, and lower overall survival. We evaluate the plasma levels of soluble HLA-G, (sHLA-G) in patients with GC and benign gastric pathologies using an ELISA test. A higher concentration of sHLA-G in patients with GC than in those with benign pathologies, higher levels of plasma sHLA-G in women with GC compared with men and significant differences in the sHLA-G levels between the benign gastric pathologies evaluated, was our main findings. As no significant differences were found between the GC assessed stages in our study population, we suggest that sHLA-G is not an adequate marker for staging GC, but it does have diagnostic potential. In addition to providing information on the potential of sHLA-G as a diagnostic marker for GC, our study demonstrate that HLA-G molecules can be found in the membrane of exosomes, which highlights the need to perform studies with a larger number of samples to explore the functional implications of HLA-G positive exosomes in the context of gastric cancer, and to determine the clinical significance and possible applications of these findings in the development of non-invasive diagnostic methods.

Diet-induced changes in fecal microbiota composition and diversity in dogs (Canis lupus familiaris): A comparative study of BARF-type and commercial diets.

BACKGROUND: Diet is known to strongly modulate the composition of the gut microbiota, thereby affecting health conditions and disease. Natural BARF-type and commercial diets have been used for feeding pets (e.g. dogs and cats) promoting changes in the canine microbiota in terms of abundance, richness, and diversity that may favor certain metabolic processes and resistance to certain infectious agents. Therefore, the present study sought to identify microbiota changes in dogs fed with a BARF-type diet versus dogs fed with a commercial diet by sequencing the V4 region of the 16S rRNA gene. METHODS: The microbiota of dogs fed with the BARF-diet (n = 20) and commercial-diet (n = 26) was studied using fecal samples. A metabarcoding strategy was employed by sequencing the V4 hypervariable region of the 16S rRNA gene using the Illumina HiSeq platform. DADA2 was used to assess the quality profile of the reads and to determine the core sample inference algorithm of the reads to infer amplicon sequence variants (ASVs). The taxonomic assignment was performed using sequences from the Silva v138 formatted reference database. The microbial diversity analysis was performed using the R package Phyloseq, which was used to calculate diversity and abundance indices and construct the respective graphs. Linear discriminant analysis (LDA) effect size analysis (LEfSe) was used to identify the differentially abundant taxa in the BARF group versus the commercial-diet group. RESULTS: The diet causes changes in fecal microbiota composition and diversity, with richness and diversity being higher in BARF-fed dogs. Beta diversity analyses confirmed that diet is directly related to microbiota composition regardless of breed or sex. Differentially enriched taxa were identified in each of the diets as Fusobacterium, Bacteroides, and Clostridium perfringens in BARF-fed dogs and Prevotella, Turicibacter, Faecalibacterium, and Peptacetobacter (Clostridium) hiranonis, mostly relevant in carbohydrate metabolism, in commercial-fed dogs. CONCLUSIONS: This study is the first one carried out in dogs from Colombia that seeks to identify changes in the intestinal microbiota concerning natural BARF type diet and commercial diet using a metabarcoding approach. Important differences were identified in terms of richness, diversity, and differentially enriched bacteria in each of the diets. The microbiota of dogs fed the BARF diet was characterized by higher richness and diversity compared to the commercial diet. However, it was identified that BARF-fed dogs can potentially acquire more opportunistic infections by pathogens of importance such as C. perfringens. Most of the taxa enriched in commercial diet-fed dogs are linked to carbohydrate metabolism, which may be directly related to diet composition.

Primary Breast Angiosarcoma: Comparative Transcriptome Analysis.

Primary breast angiosarcoma, with de novo appearance and not associated with exposure to radiation or lymphedema, is a rare pathology representing less than 0.05% of the neoplasms related to this organ. The pathology is characterized by its aggressiveness, poor prognosis, and difficulties in its differential diagnosis. This article reports the case of a 55-year-old white woman with no family history of cancer, with a rapidly growing mass in the left mammary gland that ulcerates and bleeds. It is confirmed as primary breast angiosarcoma by immunostaining in the tumor tissue for CD31, CD34, and FLI-1. In addition, a sample of neoplastic and healthy tissues is collected from the patient for RNA sequencing; the results are contrasted with a tissue sample from a patient with Luminal A subtype of breast cancer, as well as data from other cases of angiosarcoma available in public databases. These findings revealed a genetic profile associated with the immune and inflammatory response in the patient's sample when compared to available angiosarcoma data; these molecular patterns are consistent with other recent studies. Due to the rarity of the disease, the studies carried out on each patient contribute to the expanding knowledge of the etiology and molecular pathways that are still partially known and continue to be the subject of research. Aside from a comparative transcriptome study, this article aims to provide an update on the state of knowledge about this disease.

Identification of Two Exosomal miRNAs in Circulating Blood of Cancer Patients by Using Integrative Transcriptome and Network Analysis.

Exosomes carry molecules of great biological and clinical interest, such as miRNAs. The contents of exosomes vary between healthy controls and cancer patients. Therefore, miRNAs and other molecules transported in exosomes are considered a potential source of diagnostic and prognostic biomarkers in cancer. Many miRNAs have been detected in recent years. Consequently, a substantial amount of miRNA-related data comparing patients and healthy individuals is available, which contributes to a better understanding of the initiation, development, malignancy, and metastasis of cancer using non-invasive sampling procedures. However, a re-analysis of available ncRNA data is rare. This study used available data about miRNAs in exosomes comparing healthy individuals and cancer patients to identify possible global changes related to the presence of cancer. A robust transcriptomic analysis identified two common miRNAs (miR-495-3p and miR-543) deregulated in five cancer datasets. They had already been implicated in different cancers but not reported in exosomes circulating in blood. The study also examined their target genes and the implications of these genes for functional processes.

Bioinformatic Tools for the Analysis and Prediction of ncRNA Interactions.

Noncoding RNAs (ncRNAs) play prominent roles in the regulation of gene expression via their interactions with other biological molecules such as proteins and nucleic acids. Although much of our knowledge about how these ncRNAs operate in different biological processes has been obtained from experimental findings, computational biology can also clearly substantially boost this knowledge by suggesting possible novel interactions of these ncRNAs with other molecules. Computational predictions are thus used as an alternative source of new insights through a process of mutual enrichment because the information obtained through experiments continuously feeds through into computational methods. The results of these predictions in turn shed light on possible interactions that are subsequently validated experimentally. This review describes the latest advances in databases, bioinformatic tools, and new in silico strategies that allow the establishment or prediction of biological interactions of ncRNAs, particularly miRNAs and lncRNAs. The ncRNA species described in this work have a special emphasis on those found in humans, but information on ncRNA of other species is also included.

Regulation of Antitumor Immune Responses by Exosomes Derived from Tumor and Immune Cells.

Exosomes are lipid membrane-enclosed vesicles released by all cell types that act at the paracrine or endocrine level to favor cell differentiation, tissue homeostasis, organ remodeling and immune regulation. Their biosynthesis begins with a cell membrane invagination which generates an early endosome that matures to a late endosome. By inward budding of the late endosome membrane, a multivesicular body (MVB) with intraluminal vesicles (ILVs) is generated. The fusion of MVBs with the plasma membrane releases ILVs into the extracellular space as exosomes, ranging in size from 30 to 100 nm in diameter. The bilipid exosome membrane is rich in cholesterol, ceramides and phosphatidylserine and can be loaded with DNA, RNA, microRNAs, proteins and lipids. It has been demonstrated that exosome secretion is a common mechanism used by the tumor to generate an immunosuppressive microenvironment that favors cancer development and progression, allowing tumor escape from immune control. Due to their ability to transport proteins, lipids and nucleic acids from the cell that gave rise to them, exosomes can be used as a source of biomarkers with great potential for clinical applications in diagnostic, prognostic or therapeutic areas. This article will review the latest research findings on exosomes and their contribution to cancer development.