Just before 2020 began, a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), brought for humans a potentially fatal disease known as coronavirus disease 2019 (COVID-19). The world has thoroughly been affected by COVID-19, while there has been little progress towards understanding the pathogenesis of COVID-19. Patients with a severe phenotype of disease and those who died from the disease have shown hyperinflammation and were more likely to develop neurological manifestations, linking the clinical disease with neuroimmunological features. Anosmia frequently occurs early in the course of COVID-19. The prevalence of anosmia would be influenced by self-diagnosis as well as self-misdiagnosis in patients with COVID-19. Despite this, the association between anosmia and COVID-19 has been a hope for research, aiming to understand the pathogenesis of COVID-19. Studies have suggested differently probable mechanisms for the development of anosmia in COVID-19, including olfactory cleft syndrome, postviral anosmia syndrome, cytokine storm, direct damage of olfactory sensory neurons, and impairment of the olfactory perception center in the brain. Thus, the observation of anosmia would direct us to find the pathogenesis of COVID-19 in the central nervous system, and this is consistent with numerous neurological manifestations related to COVID-19. Like other neurotropic viruses, SARS-CoV-2 might be able to enter the central nervous system via the olfactory epithelium and induce innate immune responses at the site of entry. Viral replication in the nonneural olfactory cells indirectly causes damage to the olfactory receptor nerves, and as a consequence, anosmia occurs. Further studies are required to investigate the neuroimmunology of COVID-19 in relation to anosmia.
MicroRNAs (miRNAs) refer to a class of small endogenous non-coding RNAs that regulate gene expression at the post-transcriptional level. Emerging studies have shown that miRNAs play critical roles in tumorigenesis and cancer progression. However, roles and mechanisms of miRNA dysregulation in the pathogenesis of meningioma are not fully understood. Here, we first reviewed existing research of aberrantly expressed miRNAs identified by high throughput microarray profiling in meningioma. We also explored the potential of miRNA as biomarkers and therapeutic targets for novel treatment paradigms of meningiomas. In addition, we summarized recent researches that focused on the possible mechanisms involved in miRNA-mediate meningioma occurrence and progression. This review provides an overview of miRNA deregulation in meningioma and indicates the potential of miRNAs to be used as biomarkers or novel therapeutic targets.
While the “physiological” aging process is associated with declines in motor and cognitive features, these changes do not significantly impair functions and activities of daily living. Differently, motor and cognitive impairment constitute the most common phenotypic expressions of neurodegeneration. Both manifestations frequently coexist in the same disease, thus making difficult to detect “pure” motor or cognitive conditions. Movement disorders are often characterized by cognitive disturbances, and neurodegenerative dementias often exhibit the occurrence of movement disorders. Such a phenotypic overlap suggests approaching these conditions by highlighting the commonalities of entities traditionally considered distinct. In the present review, we critically reappraised the common clinical and pathophysiological aspects of neurodegeneration in both animal models and patients, looking at motricity as a trait d’union over the spectrum of neurodegeneration and focusing on synaptopathy and oscillopathy as the common pathogenic background. Finally, we discussed the possible role of movement as neuroprotective intervention in neurodegenerative conditions, regardless of the etiology. The identification of commonalities is critical to drive future research and develop novel possible disease-modifying interventions.
Major depressive disorder (MDD) symptoms commonly occur after trauma-exposure, both alone and in combination with post-traumatic stress disorder (PTSD). This article reviews recent research on comorbidity between these disorders, including its implications for symptom severity and response to treatment. Despite considerable symptom overlap, the two disorders represent distinct constructs and depend, at least in part, on separate biological mechanisms. Both, however, are also clearly related to stress psychopathology. We recommend that more research focus specifically on the study of individual differences in symptom expression in order to identify distinct subgroups of individuals and develop targeted treatments. However, a barrier to this line of inquiry is the trend of excluding particular patients from clinical trials of new interventions based on symptom severity or comorbidity. Another obstacle is the overreliance on self-report measures in human research. We argue that developing computer-based behavioral measures in order to supplement self-report can help address this challenge. Furthermore, we propose that these measures can help tie findings from human and non-human animal research. A number of paradigms have been used to model MDD-and PTSD-like behavior in animals. These models remain valuable for understanding the biological basis of these disorders in humans and for identifying potential interventions, but they have been underused for the study of comorbidity. Although the interpretation of animal behavior remains a concern, we propose that this can also be overcome through the development of close human analogs to animal paradigms.
Autism spectrum disorders (ASD) diagnostic procedure still lacks a uniform biological marker. This review gathers the information on microRNAs (miRNAs) specifically as a possible source of biomarkers of ASD. Extracellular vesicles, and their subset of exosomes, are believed to be a tool of cell-to-cell communication, and they are increasingly considered to be carriers of such a marker. The interest in studying miRNAs in extracellular vesicles grows in all fields of study and therefore should not be omitted in the field of neurodevelopmental disorders. The summary of miRNAs associated with brain cells and ASD either studied directly in the tissue or biofluids are gathered in this review. The heterogeneity in findings from different studies points out the fact that unified methods should be established, beginning with the determination of the accurate patient and control groups, through to sample collection, processing, and storage conditions. This review, based on the available literature, proposes the standardized approach to obtain the results that would not be affected by technical factors. Nowadays, the method of high-throughput sequencing seems to be the most optimal to analyze miRNAs. This should be followed by the uniformed bioinformatics procedure to avoid misvalidation. At the end, the proper validation of the obtained results is needed. With such an approach as is described in this review, it would be possible to obtain a reliable biomarker that would characterize the presence of ASD.
Histone deacetylases (HDACs) can regulate the progression of various cancers, while their roles in oral cancer cells are not well known. Our present study found that the HDAC1 was over expressed in oral squamous cell carcinoma (OSCC) cells and tissues. Targeted inhibition of HDAC1 via its specific inhibitor PCI24781 or siRNA can inhibit the proliferation of OSCC cells and increase their sensitivity to the chemo-sensitivity such as doxorubicin treatment. HDAC1 can regulate the expression of proliferating cell nuclear antigen (PCNA) via decreasing its mRNA stability. While over expression of PCNA can attenuate HDAC1 inhibition induced suppression of cell proliferation. We checked the expression of various miRNAs which can target the 3′UTR of PCNA. Results showed that HDAC1 can negative regulate the expression of miR-154-5p, inhibitor of miR-154-5p can attenuate PCI24781 treatment decreased PCNA expression and cell proliferation. Collectively, our present study suggested that HDAC1 can promote the growth and progression of OSCC via regulation of miR-154-5p/PCNA signals.
Chaperones of the 70 kDa heat shock protein (Hsp70) superfamily are key components of the cellular proteostasis system. Together with its co-chaperones, Hsp70 forms proteostasis subsystems that antagonize protein damage during physiological and stress conditions. This function stems from highly regulated binding and release cycles of protein substrates, which results in a flow of unfolded, partially folded and misfolded species through the Hsp70 subsystem. Specific factors control how Hsp70 makes decisions regarding folding and degradation fates of the substrate proteins. In this review, we summarize how the flow of Hsp70 substrates is controlled in the cell with special emphasis on recent advances regarding substrate release mechanisms.
We aimed to investigate the impact of oxytocin on serum thiol/disulphide and malonylyldialdehyde (MDA)/glutathione balance under acute stress (AS) and chronic stress (CS) exposure in rats. Animals were allocated into control (C), AS and CS groups, then the groups subdivided as intranasal oxytocin or saline applied groups, randomly. Animals in the AS or CS groups were exposed to combined cold-immobilisation stress. Salivary corticosterone levels and elevated plus maze (EPM) scores were used to assess stress response. MDA, glutathione, thiol-disulphide levels were measured in the serum samples. Oxytocin treatment attenuated stress response regardless of the stress duration verified by lower corticosterone level and favorable profile in EPM parameters measured. Furthermore, oxytocin modulated oxidant profile suggesting lowered oxidant stress with decreased serum MDA/glutathione and disulfide/native thiol ratios. Oxytocin improves the response of organism to stress via both its anxiolytic and antioxidant effects. That’s why it can be considered as a protective measure to employ methods to increase endogenous oxytocin and/or to apply exogenous oxytocin to prevent stress-induced increase in oxidant stress, which plays a pivotal role in the pathogenesis of various stress-related diseases.