Evolution of enhanced innate immune evasion by SARS-CoV-2.

The emergence of SARS-CoV-2 variants of concern suggests viral adaptation to enhance human-to-human transmission1,2. Although much effort has focused on the characterization of changes in the spike protein in variants of concern, mutations outside of spike are likely to contribute to adaptation. Here, using unbiased abundance proteomics, phosphoproteomics, RNA sequencing and viral replication assays, we show that isolates of the Alpha (B.1.1.7) variant3 suppress innate immune responses in airway epithelial cells more effectively than first-wave isolates. We found that the Alpha variant has markedly increased subgenomic RNA and protein levels of the nucleocapsid protein (N), Orf9b and Orf6-all known innate immune antagonists. Expression of Orf9b alone suppressed the innate immune response through interaction with TOM70, a mitochondrial protein that is required for activation of the RNA-sensing adaptor MAVS. Moreover, the activity of Orf9b and its association with TOM70 was regulated by phosphorylation. We propose that more effective innate immune suppression, through enhanced expression of specific viral antagonist proteins, increases the likelihood of successful transmission of the Alpha variant, and may increase in vivo replication and duration of infection4. The importance of mutations outside the spike coding region in the adaptation of SARS-CoV-2 to humans is underscored by the observation that similar mutations exist in the N and Orf9b regulatory regions of the Delta and Omicron variants.

SARS-CoV-2 sensing by RIG-I and MDA5 links epithelial infection to macrophage inflammation.

SARS-CoV-2 infection causes broad-spectrum immunopathological disease, exacerbated by inflammatory co-morbidities. A better understanding of mechanisms underpinning virus-associated inflammation is required to develop effective therapeutics. Here, we discover that SARS-CoV-2 replicates rapidly in lung epithelial cells despite triggering a robust innate immune response through the activation of cytoplasmic RNA sensors RIG-I and MDA5. The inflammatory mediators produced during epithelial cell infection can stimulate primary human macrophages to enhance cytokine production and drive cellular activation. Critically, this can be limited by abrogating RNA sensing or by inhibiting downstream signalling pathways. SARS-CoV-2 further exacerbates the local inflammatory environment when macrophages or epithelial cells are primed with exogenous inflammatory stimuli. We propose that RNA sensing of SARS-CoV-2 in lung epithelium is a key driver of inflammation, the extent of which is influenced by the inflammatory state of the local environment, and that specific inhibition of innate immune pathways may beneficially mitigate inflammation-associated COVID-19.

Disrupting HIV-1 capsid formation causes cGAS sensing of viral DNA.

Detection of viral DNA by cyclic GMP-AMP synthase (cGAS) is a first line of defence leading to the production of type I interferon (IFN). As HIV-1 replication is not a strong inducer of IFN, we hypothesised that an intact capsid physically cloaks viral DNA from cGAS. To test this, we generated defective viral particles by treatment with HIV-1 protease inhibitors or by genetic manipulation of gag. These viruses had defective Gag cleavage, reduced infectivity and diminished capacity to saturate TRIM5α. Importantly, unlike wild-type HIV-1, infection with cleavage defective HIV-1 triggered an IFN response in THP-1 cells that was dependent on viral DNA and cGAS. An IFN response was also observed in primary human macrophages infected with cleavage defective viruses. Infection in the presence of the capsid destabilising small molecule PF-74 also induced a cGAS-dependent IFN response. These data demonstrate a protective role for capsid and suggest that antiviral activity of capsid- and protease-targeting antivirals may benefit from enhanced innate and adaptive immunity in vivo.

A virological view of tenascin-C in infection.

Tenascin-C is a large extracellular matrix glycoprotein with complex, not yet fully unveiled roles. Its context- and structure-dependent modus operandi renders tenascin-C a puzzling protein. Since its discovery ∼40 years ago, research into tenascin-C biology continues to reveal novel functions, the most recent of all being its immunomodulatory activity, especially its role in infection, which is just now beginning to emerge. Here, we explore the role of tenascin-C in the immune response to viruses, including SARS-CoV-2 and HIV-1. Recently, tenascin-C has emerged as a biomarker of disease severity during COVID-19 and other viral infections, and we highlight relevant RNA sequencing and proteomic analyses that suggest a correlation between tenascin-C levels and disease severity. Finally, we ask what the function of this protein during viral replication is and propose tenascin-C as an intercellular signal of inflammation shuttled to distal sites via exosomes, a player in the repair and remodeling of infected and damaged tissues during severe infectious disease, as well as a ligand for specific pathogens with distinct implications for the host.

Image reconstruction algorithm for laser-induced ultrasonic imaging: The single sensor scanning synthetic aperture focusing technique.

This paper aims to implement a laser-induced ultrasound imaging reconstruction method based on the delay-and-sum beamforming through the synthetic aperture focusing technique (SAFT) for a circular scanning, performed with a tomograph that had one acoustic sensor and a system that rotates the sample around a fixed axis. The proposed method, called the Single-sensor Scanning Synthetic Aperture Focusing Technique, considers the size of the sensor and the detection procedure inside the SAFT's algebra. This image reconstruction method was evaluated numerically, using the Green function for the laser-induced ultrasound wave equation to generate a forward problem, and experimentally, using a solid object of polylactic acid, and a Sprague-Dawley rat heart located in a tissue-mimicking phantom. The resulting images were compared to those obtained from the time reversal and the conventional delay-and-sum reconstruction algorithms. The presented method removes the sidelobe artifacts and the comet tail sign, which produces a more distinguishable target on the image. In addition, the proposed method has a faster performance and lower computational load. The implementation of this method in photoacoustic microscopy techniques for image reconstruction is discussed.

SARS-CoV-2 vaccination patterns in a private hematology and internal medicine outpatient clinic.

OBJECTIVE: Determine the proportion of vaccinated patients in a private hematology and internal medicine outpatient clinic and potential factors in adherence in at-risk patients (due to onco-hematological diseases). MATERIALS AND METHODS: This is a cross-sectional study of outpatients from a private clinic. We applied a non-validated instrument to all patients attending the outpatient clinic from May to October 2021. According to the primary diagnosis, we classified patients into onco-hematological and non-onco-hematological patients. Since national authorities exclusively executed and planned the rollout of vaccines, the order and eligibility defined by authorities of vaccination was considered when conducting the analysis and patients were classified according to the their corresponding group. RESULTS: 397 participants were accrued, 269 (68%) had an onco-hematological condition. In the whole group, 73 (18.3%) had a history of infection. Vaccination history was present in 286 persons (72%); 82% had two doses. In the subset of 269 persons with an onco-hematological condition, 191 (71%) were vaccinated, whereas 95 participants with non-hematological conditions (73%) had received the vaccine. Vaccination status was associated with age (OR 1.07, 95%CI: 1.03,1.10, p<0.0001) and body mass index (OR 1.11, 95%CI: 1.04,1.17, p<0.0001). CONCLUSIONS: According to our study, vaccination adherence at our center is significantly different from the nationwide proportion of vaccines.

Families of doctors at Academia Nacional de Medicina de México.

INTRODUCTION: The decision to get involved in the study and practice of medicine is not easy. Within the scientific environment, achieving both professional and personal success requires a strict discipline, where effort becomes an essential part of daily life; in addition, having family support becomes crucial in order for not to lose hope when confronting the different adversities that arise during medical training. OBJECTIVE: To identify families where at least two members belong to the Academia Nacional de Medicina de México (ANMM). METHODS: A cross-sectional study was carried out to identify families of Mexican doctors where at least two members, consanguineous or in-laws, have been or are ANMM members through a review of 2017 ANMM Directory and personal contact with the different academics. RESULTS: Information on 45 families belonging to the ANMM was collected. CONCLUSIONS: From this study, it is possible to show the great influence that some doctors have in their family environment, which makes the study of medicine attractive as a life project.

INTRODUCCIÓN: La decisión de involucrarse en el estudio y la práctica de la medicina no es fácil. Dentro del ambiente científico, alcanzar el éxito tanto profesional como personal requiere de una disciplina estricta en donde el esfuerzo se vuelve parte esencial de la vida diaria, además, el tener el apoyo familiar se vuelve un pilar para no perder la ilusión ante las distintas adversidades que se presentan en la formación médica. OBJETIVO: Identificar a las familias donde mínimo dos miembros pertenecen a la Academia Nacional de Medicina. MÉTODOS: Se llevó a cabo un estudio transversal para analizar las familias de médicos mexicanos en las que por lo menos dos miembros, consanguíneos o políticos, han sido o son miembros de la Academia Nacional de Medicina de México por medio de la consulta del Directorio de la Academia Nacional de Medicina del año 2017 y el contacto de manera personal con los distintos académicos. RESULTADOS: Se recolectó información de 45 familias pertenecientes a la Academia Nacional de Medicina de México. CONCLUSIONES: A partir de este estudio es posible evidenciar la gran influencia que emiten algunos médicos en su entorno familiar, que hace que el estudio de la medicina sea atractivo como proyecto de vida.

Width/Length Ratio in Maxillary Anterior Teeth. Comparative Study of Esthetic Preferences among Professionals and Laypersons.

PURPOSE: Many studies have examined the esthetic preferences of professionals in the maxillary anterior region; however, only a few have taken into account the ratios that are more frequent within the population or other ratios suggested in the literature as ideal. Previous studies also failed to compare them with the esthetic preferences of the lay population with regards to the smile. The purpose of this study is to highlight the differences when perceiving the esthetics of smiles between general dentists and laypersons, and linking them with the width/length of the maxillary anterior teeth. MATERIALS AND METHODS: Photographs of the full face of a female subject were modified with Photoshop CS regarding the length/width relationships of the 6 maxillary anterior teeth. The three modifications made were: (a) 80% length/width, (b) 85%, length/width, and (c) 85% length/width in central incisors, 80% length/width in lateral incisors and canines. Three sequences of photograph pairs were created with different ratios and presented in PowerPoint to a sample of 100 general dentists and 100 laypersons. RESULTS: The ratio considered as the most esthetic by the majority of the judges was 85% for central incisors and 80% for lateral incisors and canines, with a statistically significant difference (p < 0.01). There was no statistically significant difference in the esthetic preferences of the studied populations either due to gender or professional experience of the dentists (p > 0.01). CONCLUSIONS: According to the results obtained in this study, professionals and laypersons considered a width/length ratio of 85% for maxillary central incisors and 80% for lateral incisors and canines as the most esthetic for maxillary anterior teeth. These results do not support findings from other studies previously published with similar ratios in central incisors, lateral incisors, and canines. CLINICAL IMPLICATION: Today clinicians practice in a treatment environment where not only function and utility but also esthetics is demanded in almost every procedure. Restoring/maintaining function is considered essential in any restorative dentistry treatment, but the esthetic aspects of any treatment should never be forgotten. This study was motivated by the increasing importance of obtaining a better appreciation of the perception of smile beauty, and of the role of maxillary teeth width/length ratio on the perception of dental esthetics.

Increased Expression Profile and Functionality of TLR6 in Peripheral Blood Mononuclear Cells and Hepatocytes of Morbidly Obese Patients with Non-Alcoholic Fatty Liver Disease.

Current evidence suggests that gut dysbiosis drives obesity and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Toll-like receptor 2 (TLR2) and TLR6 specifically recognize components of Gram-positive bacteria. Despite the potential implications of TLR2 in NAFLD pathogenesis, the role of TLR6 has not been addressed. Our aim is to study a potential role of TLR6 in obesity-related NAFLD. Forty morbidly obese patients undergoing bariatric surgery were prospectively studied. Cell surface expression of TLR2 and TLR6 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated monocytes were cultured with specific TLR2/TLR6 agonists and intracellular production of cytokines was determined by flow-cytometry. In liver biopsies, the expression of TLR2 and TLR6 was analyzed by immunohistochemistry and cytokine gene expression using RT-qPCR. TLR6 expression in PBMCs from non-alcoholic steatohepatitis (NASH) patients was significantly higher when compared to those from simple steatosis. The production of pro-inflammatory cytokines in response to TLR2/TLR6 stimulation was also significantly higher in patients with lobular inflammation. Hepatocyte expression of TLR6 but not that of TLR2 was increased in NAFLD patients compared to normal liver histology. Deregulated expression and activity of peripheral TLR6 in morbidly obese patients can mirror the liver inflammatory events that are well known drivers of obesity-related NASH pathogenesis. Moreover, TLR6 is also significantly overexpressed in the hepatocytes of NAFLD patients compared to their normal counterparts. Thus, deregulated TLR6 expression may potentiate TLR2-mediated liver inflammation in NAFLD pathogenesis, and also serve as a potential peripheral biomarker of obesity-related NASH.

Wearable biomedical measurement systems for assessment of mental stress of combatants in real time.

The Spanish Ministry of Defense, through its Future Combatant program, has sought to develop technology aids with the aim of extending combatants' operational capabilities. Within this framework the ATREC project funded by the "Coincidente" program aims at analyzing diverse biometrics to assess by real time monitoring the stress levels of combatants. This project combines multidisciplinary disciplines and fields, including wearable instrumentation, textile technology, signal processing, pattern recognition and psychological analysis of the obtained information. In this work the ATREC project is described, including the different execution phases, the wearable biomedical measurement systems, the experimental setup, the biomedical signal analysis and speech processing performed. The preliminary results obtained from the data analysis collected during the first phase of the project are presented, indicating the good classification performance exhibited when using features obtained from electrocardiographic recordings and electrical bioimpedance measurements from the thorax. These results suggest that cardiac and respiration activity offer better biomarkers for assessment of stress than speech, galvanic skin response or skin temperature when recorded with wearable biomedical measurement systems.

Parkinsonism-hyperpyrexia, a rare consequence of deep brain stimulator malfunction in advanced Parkinson's disease.

Parkinsonism-hyperpyrexia syndrome (PHS) is a rare neurological emergency that shares clinical features with neuroleptic malignant syndrome. It is usually due to sudden deprivation of dopaminergic treatment, although there are cases related to failure of the deep brain stimulation system.

Mapping Differential Protein-Protein Interaction Networks using Affinity Purification Mass Spectrometry.

Proteins congregate into complexes to perform fundamental cellular functions. Phenotypic outcomes, in health and disease, are often mechanistically driven by the remodeling of protein complexes by protein-coding mutations or cellular signaling changes in response to molecular cues. Here, we present an affinity purification-mass spectrometry (APMS) proteomics protocol to quantify and visualize global changes in protein-protein interaction (PPI) networks between pairwise conditions. We describe steps for expressing affinity-tagged "bait" proteins in mammalian cells, identifying purified protein complexes, quantifying differential PPIs, and visualizing differential PPI networks. Specifically, this protocol details steps for designing affinity-tagged "bait" gene constructs, transfection, affinity purification, mass spectrometry sample preparation, data acquisition, database search, data quality control, PPI confidence scoring, cross-run normalization, statistical data analysis, and differential PPI visualization. Our protocol discusses caveats and limitations with applicability across cell types and biological areas. For complete details on the use and execution of this protocol, please refer to Bouhaddou et al. 20231.

CRISPR-Cas9 screen of E3 ubiquitin ligases identifies TRAF2 and UHRF1 as regulators of HIV latency in primary human T cells.

During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1. We found 10 E3s significantly positively or negatively affected HIV infection in activated primary CD4+ T cells, including UHRF1 (pro-viral) and TRAF2 (anti-viral). Furthermore, deletion of either TRAF2 or UHRF1 in three JLat models of latency spontaneously increased HIV transcription. To verify this effect, we developed a CRISPR-compatible resting primary human CD4+ T cell model of latency. Using this system, we found that deletion of TRAF2 or UHRF1 initiated latency reactivation and increased virus production from primary human resting CD4+ T cells, suggesting these two E3s represent promising targets for future HIV latency reversal strategies. IMPORTANCE: HIV, the virus that causes AIDS, heavily relies on the machinery of human cells to infect and replicate. Our study focuses on the host cell's ubiquitination system which is crucial for numerous cellular processes. Many pathogens, including HIV, exploit this system to enhance their own replication and survival. E3 proteins are part of the ubiquitination pathway that are useful drug targets for host-directed therapies. We interrogated the 116 E3s found in human immune cells known as CD4+ T cells, since these are the target cells infected by HIV. Using CRISPR, a gene-editing tool, we individually removed each of these enzymes and observed the impact on HIV infection in human CD4+ T cells isolated from healthy donors. We discovered that 10 of the E3 enzymes had a significant effect on HIV infection. Two of them, TRAF2 and UHRF1, modulated HIV activity within the cells and triggered an increased release of HIV from previously dormant or "latent" cells in a new primary T cell assay. This finding could guide strategies to perturb hidden HIV reservoirs, a major hurdle to curing HIV. Our study offers insights into HIV-host interactions, identifies new factors that influence HIV infection in immune cells, and introduces a novel methodology for studying HIV infection and latency in human immune cells.

Sensorized garments and textrode-enabled measurement instrumentation for ambulatory assessment of the autonomic nervous system response in the ATREC project.

Advances in textile materials, technology and miniaturization of electronics for measurement instrumentation has boosted the development of wearable measurement systems. In several projects sensorized garments and non-invasive instrumentation have been integrated to assess on emotional, cognitive responses as well as physical arousal and status of mental stress through the study of the autonomous nervous system. Assessing the mental state of workers under stressful conditions is critical to identify which workers are in the proper state of mind and which are not ready to undertake a mission, which might consequently risk their own life and the lives of others. The project Assessment in Real Time of the Stress in Combatants (ATREC) aims to enable real time assessment of mental stress of the Spanish Armed Forces during military activities using a wearable measurement system containing sensorized garments and textile-enabled non-invasive instrumentation. This work describes the multiparametric sensorized garments and measurement instrumentation implemented in the first phase of the project required to evaluate physiological indicators and recording candidates that can be useful for detection of mental stress. For such purpose different sensorized garments have been constructed: a textrode chest-strap system with six repositionable textrodes, a sensorized glove and an upper-arm strap. The implemented textile-enabled instrumentation contains one skin galvanometer, two temperature sensors for skin and environmental temperature and an impedance pneumographer containing a 1-channel ECG amplifier to record cardiogenic biopotentials. With such combinations of garments and non-invasive measurement devices, a multiparametric wearable measurement system has been implemented able to record the following physiological parameters: heart and respiration rate, skin galvanic response, environmental and peripheral temperature. To ensure the proper functioning of the implemented garments and devices the full series of 12 sets have been functionally tested recording cardiogenic biopotential, thoracic impedance, galvanic skin response and temperature values. The experimental results indicate that the implemented wearable measurement systems operate according to the specifications and are ready to be used for mental stress experiments, which will be executed in the coming phases of the project with dozens of healthy volunteers.

Network modeling suggests HIV infection phenocopies PI3K-AKT pathway mutations to enhance HPV-associated cervical cancer.

Women coinfected with human immunodeficiency virus type 1 (HIV-1) and human papillomavirus (HPV) are six times as likely to develop invasive cervical carcinoma compared to those without HIV. Unlike other HIV-associated cancers, the risk of cervical cancer development does not change when HPV/HIV coinfected women begin antiretroviral therapy, suggesting HIV-associated immune suppression is not a key driver of cervical cancer development in coinfected women. Here, we investigated whether the persistent secretion of inflammatory factors in HIV-positive patients on antiretroviral therapy could enhance cancer signaling in HPV-infected cervical cells via endocrine mechanisms. We integrated previously reported HIV-induced secreted inflammatory factors (Hi-SIFs), HIV and HPV virus-human protein interactions, and cervical cancer patient genomic data using network propagation to understand the pathways underlying disease development in HPV/HIV coinfection. Our results pinpointed the PI3K-AKT signaling pathway to be enriched at the interface between Hi-SIFs and HPV-host molecular networks, in alignment with PI3K pathway mutations being prominent drivers of HPV-associated, but HIV independent, cervical cancer development. Furthermore, we experimentally stimulated cervical cells with 14 Hi-SIFs to assess their ability to activate PI3K-AKT signaling. Strikingly, we found 8 factors (CD14, CXCL11, CXCL9, CXCL13, CXCL17, AHSG, CCL18, and MMP-1) to significantly upregulate AKT phosphorylation (pAKT-S473) relative to a phosphate buffered saline control. Our findings suggest that Hi-SIFs cooperate with HPV infection in cervical cells to over-activate PI3K-AKT signaling, effectively phenocopying PI3K-AKT pathway mutations, resulting in enhanced cervical cancer development in coinfected women. Our insights could support the design of therapeutic interventions targeting the PI3K-AKT pathway or neutralizing Hi-SIFs in HPV/HIV coinfected cervical cancer patients.

Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets.

Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT.

Impact of SARS-CoV-2 ORF6 and its variant polymorphisms on host responses and viral pathogenesis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. ORF6 plays key roles in interferon antagonism and viral pathogenesis by interfering with nuclear import and specifically the translocation of IRF and STAT transcription factors. Additionally, ORF6 inhibits cellular mRNA export, resulting in the remodeling of the host cell proteome, and regulates viral protein expression. Interestingly, the ORF6:D61L mutation that emerged in the Omicron BA.2 and BA.4 variants exhibits reduced interactions with Nup98-Rae1 and consequently impairs immune evasion. Our findings highlight the role of ORF6 in antagonizing innate immunity and emphasize the importance of studying the immune evasion strategies of SARS-CoV-2.

Preclinical evidence for mitochondrial DNA as a potential blood biomarker for chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious dose-limiting side effect of several first-line chemotherapeutic agents including paclitaxel, oxaliplatin and bortezomib, for which no predictive marker is currently available. We have previously shown that mitochondrial dysfunction is associated with the development and maintenance of CIPN. The aim of this study was to evaluate the potential use of mitochondrial DNA (mtDNA) levels and complex I enzyme activity as blood biomarkers for CIPN. Real-time qPCR was used to measure mtDNA levels in whole blood collected from chemotherapy- and vehicle-treated rats at three key time-points of pain-like behaviour: prior to pain development, at the peak of mechanical hypersensitivity and at resolution of pain-like behaviour. Systemic oxaliplatin significantly increased mtDNA levels in whole blood prior to pain development. Furthermore, paclitaxel- and bortezomib-treated animals displayed significantly higher levels of mtDNA at the peak of mechanical hypersensitivity. Mitochondrial complex I activity in whole blood was assessed with an ELISA-based Complex I Enzyme Activity Dipstick Assay. Complex I activity was not altered by any of the three chemotherapeutic agents, either prior to or during pain-like behaviour. These data demonstrate that blood levels of mtDNA are altered after systemic administration of chemotherapy. Oxaliplatin, in particular, is associated with higher mtDNA levels before animals show any pain-like behaviour, thus suggesting a potential role for circulating mtDNA levels as non-invasive predictive biomarker for CIPN.

miRNAs in multiple sclerosis: A clinical approach.

Micro-RNAs (miRNAs) are noncoding, single stranded segments of RNA measuring 19 to 25 nucleotides in length. They play an active role in autoimmune diseases, including multiple sclerosis (MS). These structures have been studied given their implication in the process of diagnosis, disease development, treatment and prognosis of MS. Given the progressive and neurodegenerative nature of MS, miRNAs have been identified as critical mediators and molecular pinpoints of the disease, which poses them as excellent candidates for the obtention of suitable biomarkers and treatment targets. This review condenses recent findings on the role of miRNAs in multiple sclerosis, including their role in MS etiology and molecular mechanisms of the disease, exploitation of miRNAs as diagnostic tools and biomarkers, miRNAs as treatment option or target for MS, and their significance as predictors of disease prognosis.