Francisco J. Enguita

University of Lisbon | UL · Faculty of Medicine

Background: MicroRNAs (miRNAs) are key players in cardiovascular development and disease. However, not only miRNAs of a cardiac origin have a critical role in heart function. Recent studies have demonstrated that miR-122-5p, a hepatic miRNA, increases in the bloodstream during ischemic cardiogenic shock and it is upregulated in the infarcted myoca...

Background: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia in western countries. The factors governing the progression of AF to a permanent chronic condition are still not well characterized. Among epigenetic factors, non-coding RNAs (ncRNAs) such as miRNAs and lncRNAs have been recently described as important players involved in...

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we determined a circulating miRNA, miR-2392, is directly involved with SARS-CoV-2 machinery during host infection. S...

Micro-RNAs (miRNAs) are a class of non-coding RNAs (ncRNAs) that act as post-transcriptional regulators of gene expression. Since their discovery in 1993, they have been the subject of deep study due to their involvement in many important biological processes. Compared with other ncRNAs, miRNAs are generated from devoted transcriptional units which...

Rationale: Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on th...

Acute myeloid leukemia (AML) is one of the most prevalent hematological malignancies. miRNAs play roles in cancer initiation and progression in various cancer types by post-transcriptional regulation of gene expression. The aim of this study is to investigate the mechanisms in the development and progression of acute myeloid leukemia and to identif...

MicroRNAs (miRNAs) have been implicated in human disorders, from cancers to infectious diseases. Targeting miRNAs or their target genes with small molecules offers opportunities to modulate dysregulated cellular processes linked to diseases. Yet, predicting small molecules associated with miRNAs remains challenging due to the small size of small mo...

In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female he...

Zika virus (ZIKV), a mosquito‐borne Flavivirus of international concern, causes congenital microcephaly in newborns and Guillain–Barré syndrome in adults. ZIKV capsid (C) protein, one of three key structural proteins, is essential for viral assembly and encapsidation. In dengue virus, a closely related flavivirus, the homologous C protein interacts...

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during...

Aims We hypothesize that miRs are key players in the dynamics of the hypertrophy phenotype in aortic stenosis (AS) patients. In our study, we aimed to identify the transcriptional patterns (protein-coding transcripts and miRs) from myocardial sample biopsies that could be associated with the absence of left ventricular (LV) mass regression after ao...

PINK1, a mitochondria targeted Serine/Threonine kinase, regulates ATP production by phosphorylating the Complex I subunit NdufA10. However, when in the presence of depolarized mitochondria, PINK1 phosphorylates ubiquitin and Parkin triggering mitochondria clearance. Mutations in PINK1 have been linked to early-onset recessive familial forms of Park...

Our previous research revealed a key microRNA signature that is associated with spaceflight that can be used as a biomarker and to develop countermeasure treatments to mitigate the damage caused by space radiation. Here, we expand on this work to determine the biological factors rescued by the countermeasure treatment. We performed RNA-sequencing a...

In the era of renewed space exploration, comprehending the effects of the space environment on human health, particularly for deep space missions, is crucial. While extensive research exists on the impacts of spaceflight, there is a gap regarding female reproductive risks. We hypothesize that space stressors could have enduring effects on female he...

A hallmark of autoimmune diseases like multiple sclerosis (MS) is an imbalance between CD4 ⁺ T cell subsets, namely pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3 ⁺ regulatory cells (Treg). Here we investigated which and how microRNAs (miRNAs) regulate these CD4 ⁺ T cell subsets in a pre-clinical model of MS. We estab...

Human gene research studies that describe wrongly identified nucleotide sequence reagents have been mostly identified in journals of low to moderate impact factor, where unreliable findings could be considered to have limited influence on future research. This study examined whether papers describing wrongly identified nucleotide sequences are also...

We are delighted to share with you our thirteenth Journal Club and highlight some of the most interesting papers published recently [...]

The orphan gene of SARS-CoV-2, ORF10, is the least stud- ied gene in the virus responsible for the COVID-19 pandemic. Recent experimentation indicated ORF10 expression moder- ates innate immunity in vitro. However, whether ORF10 af- fects COVID-19 in humans remained unknown. We determine that the ORF10 sequence is identical to the Wuhan-Hu-1 ances-...

COVID-19, the disease caused by SARS-CoV-2, has caused significant morbidity and mortality worldwide. The betacoronavirus continues to evolve with global health implications as we race to learn more to curb its transmission, evolution, and sequelae. The focus of this review, the second of a three-part series, is on the biological effects of the SAR...

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral proteins bind to host mitochondrial proteins, likely inhibiting oxidative phosphorylation (OXPHOS) and stimulating glycolysis. We analyzed mitochondrial gene expression in nasopharyngeal and autopsy tissues from patients with coronavirus disease 2019 (COVID-19). In nasopharyngeal sa...

The central role of RNA molecules in cell biology has been an expanding subject of study since the proposal of the “RNA world” hypothesis 60 years ago [...]

Dengue virus (DENV) is a single-stranded (+)-sense RNA virus that infects humans and mosquitoes, posing a significant health risk in tropical and subtropical regions. Mature virions are composed of an icosahedral shell of envelope (E) and membrane (M) proteins circumscribing a lipid bilayer, which in turn contains a complex of the approximately 11...

Hypoxia-inducible factors (HIFs) are the main regulatory factors implicated in the adaptation of cancer cells to hypoxic stress, which has provoked much interest as an attractive target for the design of promising chemotherapeutic agents. Since indirect HIF inhibitors (HIFIs) lead to the occurrence of various side effects, the need of the hour is t...

(1) Background: Acetaminophen (APAP), an active component of many analgesic and antipyretic drugs, is one of the most concerning trace contaminants in the environment and is considered as an emergent pollutant of marine and aquatic ecosystems. Despite its biodegradability, APAP has become a recalcitrant compound due to the growth of the global popu...

197 words) Human gene research studies that describe wrongly identified nucleotide sequence reagents have been mostly identified in journals of low to moderate impact factor, where unreliable findings could be considered to have limited influence on future research. This study examined whether papers describing wrongly identified nucleotide sequenc...

N‐methyl‐D‐aspartate receptors (NMDARs) are critical for the maturation and plasticity of glutamatergic synapses. In the hippocampus, NMDARs mainly contain GluN2A and/or GluN2B regulatory subunits. The amyloid precursor protein (APP) has emerged as a putative regulator of NMDARs, but the impact of this interaction to their function is largely unkno...

From our previous work we have shown a key miRNA signature that is associated with spaceflight can be used as a biomarker and countermeasure to mitigate the damage caused by space radiation. Here, we have further expanded on this work to determine key biological factors that are being rescued by the countermeasure treatment. We performed RNA-sequen...

Treatable targets that hinder heart failure development following myocardial infarction remain limited. Through an unbiased transcriptional regulation study for ischemic heart disease, we identified the protein disrupted in schizophrenia 1 (DISC1), which has been almost solely characterized in the brain. Here, we show that loss of DISC1 is a major...

The interplay between lncRNAs, RNA-binding proteins and viral genome during SARS-CoV-2 infection reveals strong connections with regulatory events involved in RNA metabolism and immune response

Through the exchange of lipids, proteins, and nucleic acids, extra-cellular vesicles (EV) allow for cell-cell communication across distant cells and tissues to regulate a wide range of physiological and pathological processes. Although some molecular mediators have been discovered, the mechanisms underlying the selective sorting of miRNAs into EV r...

Viral infections are complex processes based on an intricate network of molecular interactions. The infectious agent hijacks components of the cellular machinery for its profit, circumventing the natural defense mechanisms triggered by the infected cell. The successful completion of the replicative viral cycle within a cell depends on the function...

MicroRNAs (miRNAs) are a class of small noncoding RNAs of about 19–25 nucleotides acting as negative posttranscriptional regulators of gene expression. The miRNA regulatory action is exerted through their association with an RNA-induced silencing complex (RISC), which will be guided by the sequence complementarity between the miRNA and its cognate...

Bioinformatic methods are essential tools to narrow down and select the number of potential targets of a given miRNA, and a complementary approach to facilitate the wet-lab biological validation. However, the prediction of miRNA targets is a challenging enterprise due to the small size of miRNAs and their limited complementarity to the target, whic...

The main regulatory factors during the adaptation of cancer cells to hypoxic stress are the hypoxia-inducible factors (HIFs), which are being increasingly recognized as an interesting and challenging target for the design of new chemotherapeutic molecules. HIF2A was found to have an large internal hydrophilic cavity within its PAS-B domain, unique...

ncRNA journal cover showning the core structure of Dicer enzyme in complex with a synthetic pre-miRNA and determined by cryoEM.

We are delighted to share with you our seventh Journal Club and highlight some of the most interesting papers published recently [...]

Nature is composed of an extremely diverse population of organisms with different metabolic abilities that can be mined for tailored applications in the biotechnology and synthetic biology disciplines. Biological information stored within genomes is encoded by a combination of four nucleotides and organized into structural and regulatory units. Thi...

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing — involving genetics, imaging, or cardiovascular techniques — makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNA...

53 MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene 54 regulation that have a major impact on many diseases and provides an exciting avenue towards 55 antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, 56 miR-2392, that is directly involved with SARS-CoV-2 machinery du...

Dilated cardiomyopathy (DCM) is the third most common cause of heart failure. The multidisciplinary nature of testing - involving genetics, imaging, or cardiovascular techniques - makes its diagnosis challenging. Novel and reliable biomarkers are needed for early identification and tailored personalized management. Peripheral circular RNAs (circRNA...

(1) Background: ochratoxins are mycotoxins produced by filamentous fungi with important implications in the food manufacturing industry due to their toxicity. Decontamination by specific ochratoxin-degrading enzymes has become an interesting alternative for the treatment of contaminated food commodities. (2) Methods: using a structure-based approac...

Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers a...

Neo-Darwinism presumes that biological variation is a product of random genetic replication errors and natural selection. Cognition-Based Evolution (CBE) asserts a comprehensive alternative approach to phenotypic variation and the generation of biological novelty. In CBE, evolutionary variation is the product of natural cellular engineering that pe...

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation that have a major impact on many diseases and provides an exciting avenue towards antiviral therapeutics. From patient transcriptomic data, we have discovered a circulating miRNA, miR-2392, that is directly involved with SARS-CoV-2 machinery during host in...

This study investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities, on luteal function in pigs. Piglets were injected subcutaneously with MXC (20 μg/kg body weight) or corn oil (control) between postnatal Days 1 and 10 (N =...

Breast cancer is a heterogeneous disease, which is the most common malignancy in women. The incidence and mortality rates of breast cancer indicate that it is the leading cause of cancer-related with deaths. circRNAs operate as part of competing endogenous RNAs (ceRNAs) mechanisms, which play critical roles in the different biological processes of...

Esters are organic compounds widely represented in cellular structures and metabolism, originated by the condensation of organic acids and alcohols. Esterification reactions are also used by chemical industries for the production of synthetic plastic polymers. Polyester plastics are an increasing source of environmental pollution due to their intri...

Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. Ninety-four participants were recruited, i...

Modern biology is founded on integrative and systemic approaches that can be applied to the study of cells and their components. On its origins, molecular biology grew using a reductionist approach that studied very specific biological processes and mechanisms with a lot of detail. However, the accumulation of isolated units of information required...

The mechanisms that regulate the systemic extent of atherosclerosis are not fully understood. We investigated whether the expression of circulating miRNAs is associated with the extent of stable atherosclerosis to a single territory or multiple territories (polyvascular) and with the severity of atherosclerosis in each territory. Ninety-four partic...

Histoplasma capsulatum affects healthy and immunocompromised individuals, sometimes causing a severe disease. This fungus has two morphotypes, the mycelial (infective) and the yeast (parasitic) phases. MicroRNAs (miRNAs) are small RNAs involved in the regulation of several cellular processes, and their differential expression has been associated wi...

Background: Circular RNAs (circRNAs) are known to participate in lung cancer. However, their role in spinal metastasis (SM) of lung adenocarcinoma remains elusive. In this study, we determined that hsa_circ_0006571 serves as a sponge for miR-138, which targets sirtuin 1 (Sirt1) in the development of SM. Methods: A human circRNA microarray was perfo...

The malaria parasite Plasmodium obligatorily infects and replicates inside hepatocytes surrounded by a parasitophorous vacuole membrane (PVM), which is decorated by the host-cell derived autophagy protein LC3. We have previously shown that the parasite-derived, PVM-resident protein UIS3 sequesters LC3 to avoid parasite elimination by autophagy from...

Plasmodium parasites possess a translocon that exports parasite proteins into the infected erythrocyte. Although the translocon components are also expressed during the mosquito and liver stage of infection, their function remains unexplored. Here, using a combination of genetic and chemical assays, we show that the translocon component Exported Pr...

Introduction The mechanisms underlying the different phenotypic presentations of atherosclerosis are still poorly understood. MicroRNAs regulate genetic expression at the post-transcriptional level and each has specific biological functions. MicroRNAs could therefore be useful for understanding the epigenetic drivers for development of isolated cor...

BACKGROUND Paracoccidioides spp. causes paracoccidioidomycosis (PCM), an important and frequent systemic mycosis that occurs in Latin America. The infectious process begins with contact between the fungus and lung cells, and the molecular pattern of this interaction is currently poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that r...

Circular RNAs are a large group of non-coding RNAs with a closed-loop structure. circRNAs play significant roles in many biological processes as miRNA sponges, regulators for gene transcription, combining with RNA-binding proteins and translation of protein. Nowadays, circRNAs have become a research hotspot in the field of cancer and molecular biol...

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death in the world, and about 80% of the cases are associated with hepatitis B or C. Genetic and epigenetic alterations are accumulated over decades of chronic injury and may affect the functioning of tumor suppressor genes and protooncogenes. Studies have evidenced the rol...