siRNA Therapeutics: From Bench Lab. to Clinics.

The discovery of the RNA interference (RNAi) mechanism in 1998 by Andrew Fire and Craig C [...

Recruitment of the 40S ribosomal subunit by the West Nile virus 3' UTR promotes the cross-talk between the viral genomic ends for translation regulation.

Flaviviral RNA genomes are composed of discrete RNA structural units arranged in an ordered fashion and grouped into complex folded domains that regulate essential viral functions, e.g. replication and translation.

Aptamers' Potential to Fill Therapeutic and Diagnostic Gaps.

More than 30 years ago, in 1990, three independent research groups published several papers demonstrating that genetics could be performed in vitro in the absence of living organisms or cells [...

Endoscopy-Assisted Craniosynostosis Surgery without Postoperative Helmet Molding Therapy.

Objective: Endoscopy-assisted craniosynostosis surgery (EACS) yields excellent surgical outcomes by minimizing blood loss, operative time, and hospital stays. Postoperative helmet therapy (PHT), commonly employed for head shape correction, involves frequent adjustments, potential complications, and high costs. Given the rising cost of helmet therapy, reduced insurance coverage, and limited availability in low- and middle-income countries, understanding success rates without helmet use is crucial.

Inter- and Intramolecular RNA-RNA Interactions Modulate the Regulation of Translation Mediated by the 3' UTR in West Nile Virus.

RNA viruses rely on genomic structural elements to accomplish the functions necessary to complete the viral cycle. These elements participate in a dynamic network of RNA-RNA interactions that determine the overall folding of the RNA genome and may be responsible for the fine regulation of viral replication and translation as well as the transition between them. The genomes of members of the genus are characterized by a complexly folded 3' UTR with a number of RNA structural elements that are conserved across isolates of each species.

Presigmoid approach preserving the superior petrosal sinus in a pontine cavernous malformation associated to abnormal venous drainage of the brainstem: how I do it.

Background: The presigmoid approach classically includes the ligature and section of the superior petrosal sinus to get a wider visibility window to the antero-lateral brainstem surface. In some cases, the separation of this venous structure should not be performed.

Method: We present our experience getting safely to a pontine cavernous malformation through a conventional mastoidectomy presigmoid approach preserving an ingurgitated superior petrosal sinus because the association with an abnormal venous drainage of the brainstem.

The Genomic 3' UTR of Flaviviruses Is a Translation Initiation Enhancer.

Viruses rely on the cellular machinery of host cells to synthesize their proteins, and have developed different mechanisms enabling them to compete with cellular mRNAs for access to it. The genus is a large group of positive, single-stranded RNA viruses that includes several important human pathogens, such as West Nile, Dengue and Zika virus. The genome of flaviviruses bears a type 1 cap structure at its 5' end, needed for the main translation initiation mechanism.

In Vitro Methods to Decipher the Structure of Viral RNA Genomes.

RNA viruses encode essential information in their genomes as conserved structural elements that are involved in efficient viral protein synthesis, replication, and encapsidation. These elements can also establish complex networks of RNA-RNA interactions, the so-called RNA interactome, to shape the viral genome and control different events during intracellular infection. In recent years, targeting these conserved structural elements has become a promising strategy for the development of new antiviral tools due to their sequence and structural conservation.

Abo Blood Group, Atherothrombotic Comorbidities, and COVID-19: A Case-Control Study of their Association in the Mexican Population.

Background: COVID-19 has been associated with negative results in patients with A blood group and with a better evolution in O blood group individuals.

Aim: Because the evidence regarding ABO blood groups and COVID was empirically not that clear in our country, we tested the association regarding COVID-19 and blood groups.

Material And Methods: Adult patients were enrolled in this prospective, case-control, observational multicenter study.

CriTER-A: A Novel Temperature-Dependent Noncoding RNA Switch in the Telomeric Transcriptome of .

The telomeric transcriptome of has been involved in thermal stress response. One of the telomeric transcripts, the so-called CriTER-A variant, is highly overexpressed upon heat shock. On the other hand, its homologous variant CriTER-B, which is the most frequently encoded noncoding RNA in the telomeres of , is only slightly affected by thermal stress.

Information Encoded by the Flavivirus Genomes beyond the Nucleotide Sequence.

The genus comprises numerous, small, single positive-stranded RNA viruses, many of which are important human pathogens. To store all the information required for their successful propagation, flaviviruses use discrete structural genomic RNA elements to code for functional information by the establishment of dynamic networks of long-range RNA-RNA interactions that promote specific folding. These structural elements behave as true cis-acting, non-coding RNAs (ncRNAs) and have essential regulatory roles in the viral cycle.

Two Examples of RNA Aptamers with Antiviral Activity. Are Aptamers the Wished Antiviral Drugs?

The current Covid-19 pandemic has pointed out some major deficiencies of the even most advanced societies to fight against viral RNA infections. Once more, it has been demonstrated that there is a lack of efficient drugs to control RNA viruses. Aptamers are efficient ligands of a great variety of molecules including proteins and nucleic acids.

The Role of the RNA-RNA Interactome in the Hepatitis C Virus Life Cycle.

RNA virus genomes are multifunctional entities endowed with conserved structural elements that control translation, replication and encapsidation, among other processes. The preservation of these structural RNA elements constraints the genomic sequence variability. The hepatitis C virus (HCV) genome is a positive, single-stranded RNA molecule with numerous conserved structural elements that manage different steps during the infection cycle.

Structure and function analysis of the essential 3'X domain of hepatitis C virus.

The 3'X domain of hepatitis C virus has been reported to control viral replication and translation by modulating the exposure of a nucleotide segment involved in a distal base-pairing interaction with an upstream 5BSL3.2 domain. To study the mechanism of this molecular switch, we have analyzed the structure of 3'X mutants that favor one of the two previously proposed conformations comprising either two or three stem-loops.

Potential of the Other Genetic Information Coded by the Viral RNA Genomes as Antiviral Target.

In addition to the protein coding information, viral RNA genomes code functional information in structurally conserved units termed functional RNA domains. These RNA domains play essential roles in the viral cycle (e.g.

The HCV genome domains 5BSL3.1 and 5BSL3.3 act as managers of translation.

The RNA genome of the hepatitis C virus (HCV) encodes a single open reading frame (ORF) containing numerous functional elements. Among these, the cis-acting replication element (CRE) at the 3' end of the viral ORF, has become of increasing interest given its dual role as a viral translation repressor and replication enhancer. Long-range RNA-RNA contacts mediated by the CRE build the structural scaffold required for its proper functioning.

A Dual Interaction Between the 5'- and 3'-Ends of the Melon Necrotic Spot Virus (MNSV) RNA Genome Is Required for Efficient Cap-Independent Translation.

In eukaryotes, the formation of a 5'-cap and 3'-poly(A) dependent protein-protein bridge is required for translation of its mRNAs. In contrast, several plant virus RNA genomes lack both of these mRNA features, but instead have a 3'-CITE (for cap-independent translation enhancer), a RNA element present in their 3'-untranslated region that recruits translation initiation factors and is able to control its cap-independent translation. For several 3'-CITEs, direct RNA-RNA long-distance interactions based on sequence complementarity between the 5'- and 3'-ends are required for efficient translation, as they bring the translation initiation factors bound to the 3'-CITE to the 5'-end.

Hepatocellular carcinoma-associated depletion of the netrin-1 receptor Uncoordinated Phenotype-5A (UNC5A) skews the hepatic unfolded protein response towards prosurvival outcomes.

In the liver, HBV and HCV infections, exposure to toxics, genetic and metabolic disorders may induce endoplasmic reticulum (ER) stress and the unfolding protein response (UPR). The UPR allows cells to reach ER homeostasis after lumen overload, but also fosters survival of damaged cells and therefore HCC onset. Dependence receptors such as UNC5A trigger apoptosis when unbound to their ligands.

The 5BSL3.2 Functional RNA Domain Connects Distant Regions in the Hepatitis C Virus Genome.

Viral genomes are complexly folded entities that carry all the information required for the infective cycle. The nucleotide sequence of the RNA virus genome encodes proteins and functional information contained in discrete, highly conserved structural units. These so-called functional RNA domains play essential roles in the progression of infection, which requires their preservation from one generation to the next.

Reciprocal antagonism between the netrin-1 receptor uncoordinated-phenotype-5A (UNC5A) and the hepatitis C virus.

Hepatitis C virus (HCV) infection is a leading cause of hepatocellular carcinoma (HCC), mainly through cirrhosis induction, spurring research for a deeper understanding of HCV versus host interactions in cirrhosis. The present study investigated crosstalks between HCV infection and UNC5A, a netrin-1 dependence receptor that is inactivated in cancer. UNC5A and HCV parameters were monitored in patients samples (n=550) as well as in in vitro.

Development of Optimized Inhibitor RNAs Allowing Multisite-Targeting of the HCV Genome.

Engineered multivalent drugs are promising candidates for fighting infection by highly variable viruses, such as HCV. The combination into a single molecule of more than one inhibitory domain, each with its own target specificity and even a different mechanism of action, results in drugs with potentially enhanced therapeutic properties. In the present work, the anti-HCV chimeric inhibitor RNA HH363-10, which has a hammerhead catalytic domain and an aptamer RNA domain, was subjected to an in vitro selection strategy to isolate ten different optimised chimeric inhibitor RNAs.

Functional Information Stored in the Conserved Structural RNA Domains of Flavivirus Genomes.

The genus comprises a large number of small, positive-sense single-stranded, RNA viruses able to replicate in the cytoplasm of certain arthropod and/or vertebrate host cells. The genus, which has some 70 member species, includes a number of emerging and re-emerging pathogens responsible for outbreaks of human disease around the world, such as the West Nile, dengue, Zika, yellow fever, Japanese encephalitis, St. Louis encephalitis, and tick-borne encephalitis viruses.