Background: Cachexia is a multifactorial syndrome highly associated with specific tumour types, but the causes of variation in cachexia prevalence and severity are unknown. While circulating plasma mediators (soluble cachectic factors) derived from tumours have been implicated with the pathogenesis of the syndrome, these associations were generally based on plasma concentration rather than tissue‐specific gene expression levels. Here, we hypothesized that tumour gene expression profiling of cachexia‐inducing factors (CIFs) in human cancers with different prevalence of cachexia could reveal potential cancer‐specific cachexia mediators and biomarkers of clinical outcome.Methods: First, we combined uniformly processed RNA sequencing data from The Cancer Genome Atlas and Genotype‐Tissue Expression databases to characterize the expression profile of secretome genes in 12 cancer types (4651 samples) compared with their matched normal tissues (2737 samples). We systematically investigated the transcriptomic data to assess the tumour expression profile of 25 known CIFs and their predictive values for patient survival. We used the Xena Functional Genomics tool to analyse the gene expression of CIFs according to neoplastic cellularity in pancreatic adenocarcinoma, which is known to present the highest prevalence of cachexia.Results: A comprehensive characterization of the expression profiling of secreted genes in different human cancers revealed pathways and mediators with a potential role in cachexia within the tumour microenvironment. Cytokine‐related and chemokine‐related pathways were enriched in tumour types frequently associated with the syndrome. CIFs presented a tumour‐specific expression profile, in which the number of upregulated genes was correlated with the cachexia prevalence (r²: 0.80; P value: 0.002) and weight loss (r²: 0.81; P value: 0.002). The distinct gene expression profile, according to tumour type, was significantly associated with prognosis (P value ≤ 1.96 E‐06). In pancreatic adenocarcinoma, the upregulated CIF genes were associated with tumours presenting low neoplastic cellularity and high leucocyte fraction and not with tumour grade.Conclusions: Our results present a biological dimension of tumour‐secreted elements that are potentially useful to explain why specific cancer types are more likely to develop cachexia. The tumour‐specific profile of CIFs may help the future development of better targeted therapies to treat cancer types highly associated with the syndrome.

Due to the high burden of dengue disease worldwide, a better understanding of the interactions between dengue virus (DENV) and its human host cells is of the outmost importance. Although microRNAs modulate the outcome of several viral infections, their contribution to DENV replication is poorly understood. We investigated the microRNA expression profile of primary human macrophages challenged with DENV and deciphered the contribution of microRNAs to infection. To this end, human primary macrophages were challenged with GFP-expressing DENV and sorted to differentiate between truly infected cells (DENV-positive) and DENV-exposed but non-infected cells (DENV-negative cells). The miRNAome was determined by small RNA-Seq analysis and the effect of differentially expressed microRNAs on DENV yield was examined. Five microRNAs were differentially expressed in human macrophages challenged with DENV. Of these, miR-3614-5p was found upregulated in DENV-negative cells and its overexpression reduced DENV infectivity. The cellular targets of miR-3614-5p were identified by liquid chromatography/mass spectrometry and western blot. Adenosine deaminase acting on RNA 1 (ADAR1) was identified as one of the targets of miR-3614-5p and was shown to promote DENV infectivity at early time points post-infection. Overall, miRNAs appear to play a limited role in DENV replication in primary human macrophages. The miRNAs that were found upregulated in DENV-infected cells did not control the production of infectious virus particles. On the other hand, miR-3614-5p, which was upregulated in DENV-negative macrophages, reduced DENV infectivity and regulated ADAR1 expression, a protein that facilitates viral replication. Dengue is the most common mosquito-borne disease worldwide and it is an increasing global concern for public health as its etiological agent, dengue virus (DENV), keeps spreading around the globe. Currently there are no specific antiviral therapies available to treat disease. Macrophages are important target cells during natural DENV infection of humans. Here, we unraveled the importance of miRNAs in DENV replication in human primary macrophages. The expression profile of miRNAs was determined in truly DENV-infected cells and cells that were exposed but not productively infected by the virus by RNA sequencing. We revealed that only five miRNAs are regulated in primary macrophages challenged with DENV. These results show that miRNAs do not play a major role in DENV replication. Unexpectedly, we did identify a miRNA with moderate yet significant antiviral properties to DENV. Moreover, miRNA-3614-5p was found to not only decrease DENV but also West Nile virus infectivity. Mass spectrometry and bioinformatics analysis identified adenosine deaminase acting on RNA 1 (ADAR1) as one of the targets. Moreover, ADAR1 was observed to promote the early stages of DENV replication. Collectively, our study broadens the knowledge of the contribution of human miRNAs in shaping the network of interactions between DENV and its human host cells.

Methods to determine blood-meal sources of hematophagous Triatominae bugs (Chagas disease vectors) are serological or based on PCR employing species-specific primers or heteroduplex analysis, but these are expensive, inaccurate, or problematic when the insect has fed on more than one species. To solve those problems, we developed a technique based on HRM analysis of the mitochondrial gene cytochrome B (Cyt b). This technique recognized 14 species involved in several ecoepidemiological cycles of the transmission of Trypanosoma cruzi and it was suitable with DNA extracted from intestinal content and feces 30 days after feeding, revealing a resolution power that can display mixed feedings. Field samples were analyzed showing blood meal sources corresponding to domestic, peridomiciliary and sylvatic cycles. The technique only requires a single pair of primers that amplify the Cyt b gene in vertebrates and no other standardization, making it quick, easy, relatively inexpensive, and highly accurate. Chagas disease is one of the most important tropical diseases in America. This disease is caused by the parasite Trypanosoma cruzi and transmitted through the feces of blood-sucking insects known as triatomines. Different species of insects have different habits and food sources that confer variable degrees of epidemiological importance. In this paper, we propose the use of High Resolution Melting (HRM) analysis of cytochrome b (cyt b) gene PCR products to identify blood-food sources in triatomines. This tool can effectively differentiate blood-meal sources of insects collected from the field. Such data allows for targeted investigations of insect species that are likely to be involved in the transmission of the parasite to humans in different regions. This knowledge is very important because it allows establishing and designing vector control and surveillance strategies according to each geographical area and to stop the transmission of the parasite to human populations by insects.

Cardiac cachexia (CC) is a common complication of heart failure (HF) associated with muscle wasting and poor patient prognosis. Although different mechanisms have been proposed to explain muscle wasting during CC, its pathogenesis is still not understood. Here, we described an integrative analysis between miRNA and mRNA expression profiles of muscle wasting during CC. Global gene expression profiling identified 1,281 genes and 19 miRNAs differentially expressed in muscle wasting during CC. Several of these deregulated genes are known or putative targets of the altered miRNAs, including miR-29a-3p, miR-29b-3p, miR-210-5p, miR-214, and miR-489. Gene ontology analysis on integrative mRNA/miRNA expression profiling data revealed miRNA interactions affecting genes that regulate extra-cellular matrix (ECM) organization, proteasome protein degradation, citric acid cycle and respiratory electron transport. We further identified 11 miRNAs, including miR-29a-3p and miR-29b-3p, which target 21 transcripts encoding the collagen proteins related to ECM organization. Integrative miRNA and mRNA global expression data allowed us to identify miRNA target genes involved in skeletal muscle wasting in CC. Our functional experiments in C2C12 cells confirmed that miR-29b down-regulates collagen genes and contributes to muscle cell atrophy. Collectively, our results suggest that key ECM-associated miRNAs and their target genes may contribute to CC in HF.