Potential role of the microbiome in liver injury during COVID-19: Further research is needed

Although different studies have associated coronavirus disease 2019(COVID-19)with the occurrence of liver injury,the hepatic injury route during the COVID-19 course is not yet fully understood.In order to better understand the mechanisms of the disease,the human gut microbiota has been the subject of extensive discussion in the context of COVID-19 pathophysiology.However,many questions remain,including the risks of liver injury due to COVID-19 specific populations.Further research in this field could allow the discovery of new personalized treatment strategies aimed at improving the microbiota composition,thereby reducing COVID-19 severity and its complications in different populations.In this article,we discussed basic mechanisms of severe acute respiratory syndrome coronavirus 2 infection and recent evidence on the relationship between COVID-19,the gut microbiome and liver injury as well as proposed recommendations for further research.

Inequity in the global distribution of monkeypox vaccines

Monkeypox(mpox)has been a public health emergency of international concern that emerged in mid-2022 and has spread to 110 countries.The clinical findings of the disease vary according to the seriousness of the cases.Although its case fatality risk has not been high,a significant percentage of patients require hospitalization.In this context,local initiatives were taken to extend the limited supply of vaccines against the disease;however,such measures have not been sufficient to contain the spread of cases and ensure an equitable distribution of health resources.As a result,endemic regions of low-income countries continue to have insufficient access to mpox vaccination.Despite this and considering the global scope of the disease,there is still little discussion in the literature about the difficulties in achieving adequate vaccination coverage rates for the target population of interest.In this article,we briefly discussed general aspects of the disease,including its surveillance,the current global context of challenges for mpox vaccination,and issues on global allocation of health resources as well as proposed related recommendations.

Resveratrol corrects aberrant splicing of RYR1 pre-mRNA and Ca2+ signal in myotonic dystrophy type 1 myotubes

Myotonic dystrophy type 1(DM1) is a spliceopathy related to the mis-splicing of several genes caused by sequestration of nuclear transcriptional RNA-binding factors from non-coding CUG repeats of DMPK pre-mRNAs. Dysregulation of ryanodine receptor 1(RYR1), sarcoplasmatic/endoplasmatic Ca^2+-ATPase(SERCA) and α1 S subunit of voltage-gated Ca^2+ channels(Cav1.1) is related to Ca^2+ homeostasis and excitation-contraction coupling impairment. Though no pharmacological treatment for DM1 exists, aberrant splicing correction represents one major therapeutic target for this disease. Resveratrol(RES, 3,5,4′-trihydroxy-trans-stilbene) is a promising pharmacological tools for DM1 treatment for its ability to directly bind the DNA and RNA influencing gene expression and alternative splicing. Herein, we analyzed the therapeutic effects of RES in DM1 myotubes in a pilot study including cultured myotubes from two DM1 patients and two healthy controls. Our results indicated that RES treatment corrected the aberrant splicing of RYR1, and this event appeared associated with restoring of depolarization-induced Ca^2+ release from RYR1 dependent on the electro-mechanical coupling between RYR1 and Cav1.1. Interestingly, immunoblotting studies showed that RES treatment was associated with a reduction in the levels of CUGBP Elav-like family member 1, while RYR1, Cav1.1 and SERCA1 protein levels were unchanged. Finally, RES treatment did not induce any major changes either in the amount of ribonuclear foci or sequestration of muscleblind-like splicing regulator 1. Overall, the results of this pilot study would support RES as an attractive compound for future clinical trials in DM1. Ethical approval was obtained from the Ethical Committee of IRCCS Fondazione Policlinico Universitario A. Gemelli, Rome, Italy(rs9879/14) on May 20, 2014.

Relationship between MRI pertusion and clinical severity in multiple sclerosis

Perfusion alterations within several brain regions have been shown in multiple sclerosis patients using different magnetic resonance imaging(MRI)techniques.Furthermore,MRI-derived brain perfusion metrics have been investigated in association with multiple sclerosis phenotypes,physical disability,and cognitive impairment.However,a review focused on these aspects is still missing.Our aim was to review all the studies investigating the relationship between perfusion MRI and clinical severity during the last fifteen years to understand the clinical relevance of these findings.Perfusion differences among phenotypes were observed both with 1.5T and 3T scanners,with progressive multiple sclerosis presenting with lower perfusion values than relapsing-remitting multiple sclerosis patients.However,only 3T scanners showed a statistically significant distinction.Controversial results about the association between MRI-derived perfusion metrics and physical disability scores were found.However,the majority of the studies showed that lower brain perfusion and longer transit time are associated with more severe physical disability and worse cognitive performances.

Microglia-oligodendrocyte intercellular communication: role of extracellular vesicle lipids in functional signalling

The term microglia refers to the group of resident brain immune-cells that are responsible,mainly,for the immune response and the homeostasis of the brain.Unlike monocyte-derived macrophages that infiltrate the brain,microglia are longlived cells which arise exclusively from the embryonic yolk sac(Stratoulias et al.,2019).Impairment in microglia functions is at the basis for the development of multiple brain diseases,including multiple sclerosis and neurodegenerative diseases.In the last decade,the number of research articles and reviews dealing with the role of microglia in the pathogenesis of brain disorders has exponentially increased.

Alpha-synuclein as a biomarker in Parkinson's disease: focus on neural derived extracelluar vesicles

The prevalence of Parkinson’s disease(PD)is rapidly increasing,and more than 12 million people are expected to suffer from PD by 2040.PD is a highly invalidating neurodegenerative condition that arises from the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta.The main cause for such degeneration is the formation of cytoplasmic inclusions known as Lewy bodies.

Blood extracellular vesicles (EVs) of central nervous system origin: a window into the brain

Extracellular vesicles(EVs)are heterogeneous nano-sized vesicles of endocytic origin shed into blood and other body fluids such as urine,saliva,seminal fluid,ascites,amniotic liquid,synovial fluid,breast milk and cerebrospinal fluid(CSF)by quite all cell types.EVs actively contribute to intercellular communication as they carry bioactive molecules that are selectively incorporated by the originating cell and are delivered to recipient cells over long and short distances(Simons and Raposo,2009).EVs can be divided into three main groups according to their size and cellular origin:1)exosomes(40–120 nm),that have an endocytic origin and are formed by inward budding of the limiting membrane of multivescicular bodies,which fuse with the plasma membrane and release exosomes into the extracellular space;2)microvesicles(50–1000 nm),budding directly off the plasma membrane;3)apoptotic bodies(>1000 nm),which are released during apoptosis.Besides originating via distinct processes,different subtypes of EVs carry different proteins within their membrane and luminal compartments that reflect the phenotype of the tissue of origin.

What do we know about the role of lncRNAs in multiple sclerosis?

Multiple sclerosis is a chronic, inflammatory and degenerative disease of the central nervous system of unknown aetiology although well-defined evidence supports an autoimmune pathogenesis. So far, the exact mechanisms leading to autoimmune diseases are still only partially understood. We know that genetic, epigenetic, molecular, and cellular factors resulting in pathogenic inflammatory responses are certainly involved. Long non-coding RNAs(lncRNAs) are non-protein coding transcripts longer than 200 nucleotides that play an important role in both innate and acquired immunity, so there is great interest in lncRNAs involved in autoimmune diseases. The research on multiple sclerosis has been enriched with many studies on the molecular role of lncRNAs in the pathogenesis of the disease and their potential application as diagnostic and prognostic biomarkers. In particular, many multiple sclerosis fields of research are based on the identification of lncRNAs as possible biomarkers able to predict the onset of the disease, its activity degree, its progression phase and the response to disease-modifying drugs. Last but not least, studies on lncRNAs can provide a new molecular target for new therapies, missing, so far, a cure for multiple sclerosis. While our knowledge on the role of lncRNA in multiple sclerosis has recently improved, further studies are required to better understand the specific role of lncRNAs in this neurological disease. In this review, we present the most recent studies on molecular characterization of lncRNAs in multiple sclerosis disorder discussing their clinical relevance as biomarkers for diagnosis and treatments.