New perspectives in the search for reliable biomarkers in alzheimer disease

Background and Objectives: The search for accurate biomarkers in Alzheimer Disease (AD), on of the most devastating neurodegenerative diseases, remains essential to enable an early prognosis and diagnosis of the disease and to provide more efficient ther- apeutic strategies. A wide variety of potential biomarkers are has been identified by neuroimaging tech- niques and by the analysis of fluid samples, such as cerebrospinal fluid (CSF) or blood. Recently, a growing number of studies are focused on the discovery of reliable blood- based biomarkers in blood, especially in the prodromal stage of AD, which can predict the conversion of asymptomatic cases to AD demented cases. In this review, the latest challenges in the search for accurate biomarkers of AD is re- vised, in particular, an update in blood-based biomarkers is described in depth. Conclusions: Finally, the close link among AD and other neurodegenerative diseases is discussed, mainly based on the last discovered mutation, the chromosome 9 open reading frame 72, C9ORF72

Sex differences in constitutive autophagy

Sex bias has been described nowadays in biomedical research on animal models, although sexual dimorphism has been confirmed widely under pathological and physiological conditions. The main objective of our work was to study the sex differences in constitutive autophagy in spinal cord and skeletalmuscle tissue fromwild type mice. To examine the influence of sex on autophagy, mRNA and proteins were extracted from male and female mice tissues.The expressions of microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (p62), markers to monitor autophagy, were analyzed at 40, 60, 90, and 120 days of age.We found significant sex differences in the expression of LC3 and p62 in both tissues at these ages. The results indicated that sex and tissue specific differences exist in constitutive autophagy.These data underlined the need to include both sexes in the experimental groups to minimize any sex bias

Metastasis of spindle cell malignant melanoma in gallbladder

Malignant melanoma is an aggressive neoplasm with a high tendency to metastasize. Gastrointestinal metastases, although described in the literature, are infrequent. We present the case of a 51-year-old male patient with a surfcial spreading melanoma stage IIIc with BRAF mutation who presented a gallbladder outgrowth lesion, compatible with a polyp. A signifcant growth of the lesion was observed in subsequent TC studies and a laparoscopic cholecystectomy was performed. The anatomopathological study of the specimen confrmed the diagnosis of gallbladder metastasis due to epithelioid and spindle cell malignant melanoma. The presence of a gallbladder lesion in the context of a patient diagnosed with melanoma should establish the diagnostic suspicion of metastasis, and an early extension study and laparoscopic cholecystectomy should be considered. The palliative surgical approach to avoid hepatobiliary symptomatology can be considered

Inflammasome in als skeletal muscle: Nlrp3 as a potential biomarker

Since NLRP3 inflammasome plays a pivotal role in several neurodegenerative disorders, we hypothesized that levels of inflammasome components could help in diagnosis or prognosis of amyotrophic lateral sclerosis (ALS). Gene and protein expression was assayed by RT-PCR and Western blot. Spearman’s correlation coefficient was used to determine the linear correlation of transcriptional expression levels with longevity throughout disease progression in mice models. Kaplan-Meier analysis was performed to evaluate MCC950 effects (NLRP3 inhibitor) on lifespan of SOD1G93A mice. The results showed significant alterations in NLRP3 inflammasome gene and protein levels in the skeletal muscle of SOD1G93A mice. Spearman’s correlation coefficient revealed a positive association between Nlrp3 transcriptional levels in skeletal muscle and longevity of SOD1G93A mice (r = 0.506; p = 0.027). Accordingly, NLRP3 inactivation with MCC950 decreased the lifespan of mice. Furthermore, NLRP3 mRNA levels were significantly elevated in the blood of ALS patients compared to healthy controls (p = 0.03). In conclusion, NLRP3 could be involved in skeletal muscle pathogenesis of ALS, either through inflammasome or independently, and may play a dual role during disease progression. NLRP3 gene expression levels could be used as a biomarker to improve diagnosis and prognosis in skeletal muscle from animal models and also to support diagnosis in clinical practice with the blood of ALS patients

Competing endogenous rna networks as biomarkers in neurodegenerative diseases

Protein aggregation is classically considered the main cause of neuronal death in neurodegenerative diseases (NDDs). However, increasing evidence suggests that alteration of RNA metabolism is a key factor in the etiopathogenesis of these complex disorders. Non-coding RNAs are the major contributor to the human transcriptome and are particularly abundant in the central nervous system, where they have been proposed to be involved in the onset and development of NDDs. Interestingly, some ncRNAs (such as lncRNAs, circRNAs and pseudogenes) share a common functionality in their ability to regulate gene expression by modulating miRNAs in a phenomenon known as the competing endogenous RNA mechanism. Moreover, ncRNAs are found in body fluids where their presence and concentration could serve as potential non-invasive biomarkers of NDDs. In this review, we summarize the ceRNA networks described in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, amyotrophic lateral sclerosis and spinocerebellar ataxia type 7, and discuss their potential as biomarkers of these NDDs. Although numerous studies have been carried out, further research is needed to validate these complex interactions between RNAs and the alterations in RNA editing that could provide specific ceRNET profiles for neurodegenerative disorders, paving the way to a better understanding of these diseases

A statistical correlation of sunquakes based on their seismic and white-light emission

Several mechanisms have been proposed to explain the transient seismic emission, i.e. “sunquakes,” from some solar flares. Some theories associate high-energy electrons and/or white-light emission with sunquakes. High-energy charged particles and their subsequent heating of the photosphere and/or chromosphere could induce acoustic waves in the solar interior. We carried out a correlative study of solar flares with emission in hard X-rays, enhanced continuum emission at 6173 Å, and transient seismic emission. We selected those flares observed by the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) with a considerable flux above 50 keV between 1 January 2010 and 26 June 2014. We then used data from the Helioseismic and Magnetic Imager onboard the Solar Dynamic Observatory to search for excess visible-continuum emission and new sunquakes not previously reported. We found a total of 18 sunquakes out of 75 flares investigated. All of the sunquakes were associated with an enhancement of the visible continuum during the flare. Finally, we calculated a coefficient of correlation for a set of dichotomic variables related to these observations. We found a strong correlation between two of the standard helioseismic detection techniques, and between sunquakes and visible-continuum enhancements. We discuss the phenomenological connectivity between these physical quantities and the observational difficulties of detecting seismic signals and excess continuum radiation