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BACKGROUD: Multiple Sclerosis (MS) is a complex and chronic autoimmune disease that affects the central nervous system. Inflammation and demyelination characterize it, which results in a range of neurological impairments. The increasing worldwide occurrence of MS, affecting an estimated 2.8 million individuals in 2020, highlights the urgent requirement for further research to tackle the significant impact it has on individuals and healthcare systems globally. OBJECTIVE: In this study, we wanted to explore the complex function of the endoplasmic reticulum (ER) in the origin, development, and resolution of MS, emphasizing its importance in neuroinflammatory illnesses. The ER has become a central focus in comprehending the pathogenesis of MS. Upon reviewing the literature, we observed a lack of thorough analysis that explores the involvement of endoplasmic reticulum stress in multiple sclerosis. Thus, we aimed through this research to examine the correlations between ER stress and its influence on immunological dysregulation, demyelination, and neurodegeneration in MS. FINDINGS: Based on the latest clinical trials, we suggested theories that explore possible biomarkers linked to ER stress and the unfolded protein response. Identifying molecules that are suggestive of early stages of illness and can serve as prognostic tools for improving our understanding of the heterogeneity of MS and offering novel approaches for managing the disease. Finally, through our comprehensive search, we wanted to offer a plan for future research, suggesting new and creative methods for managing MS and encouraging the creation of specific treatments that aim to reduce the impact of MS on individuals worldwide.

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BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by inflammatory assaults on the central nervous system (CNS), particularly on the optic nerves and spinal cord. In recent years, a wider range of clinical manifestations of this complex disease have been observed, emphasizing the importance of gaining a more profound understanding beyond optic neuritis (ON) and transverse myelitis (TM). CURRENT KNOWLEDGE: This study explores the many clinical symptoms of NMOSD, including common and uncommon presentations. Distinctive aspects of ON, TM, and diencephalic/brainstem syndromes are examined, highlighting their unique characteristics in contrast to conditions such as multiple sclerosis. We also discuss extra-CNS involvement, such as unusual signs, including muscle involvement, retinal injury, auditory impairment, and rhinological symptoms. AIMS AND OBJECTIVES: Our study intends to highlight the wide range and complexity of NMOSD presentations, emphasizing the significance of identifying unusual symptoms for precise diagnosis and prompt management. The specific processes that contribute to the varied clinical presentation of NMOSD are not well understood despite existing information. This emphasizes the necessity for more study to clarify the mechanisms that cause different symptoms and discover new treatment targets for this complex autoimmune disorder. CONCLUSION: It is essential to acknowledge the complex and varied clinical manifestations of NMOSD to enhance diagnosis, treatment, and patient results. By enhancing our comprehension of the fundamental processes and investigating innovative therapeutic approaches, we may aim to enhance the quality of life for persons impacted by this illness.

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Sleep paralysis (SP) is a mixed state of consciousness and sleep, combining features of rapid eye movement (REM) sleep with those of wakefulness. The exact cause of SP is unknown, and its prevalence varies among the studies. We aim to identify SP's global prevalence, the affected population's characteristics, and the SP's clinical picture. We searched three databases (PubMed, Scopus, and Web of Science (WoS)) using a unique search strategy to identify eligible studies. All observational studies identifying the prevalence or frequency of sleeping paralysis were included. No exclusions are made based on country, race, or questionnaire. The analysis was performed using the latest version of R software (R Core Team, Vienna, Austria). The analysis included 76 studies from 25 countries with 167,133 participants. The global prevalence of SP was 30% (95% CI (22%, 39%)). There were similar frequencies of isolated SP and SP (33%, 95% CI (26%, 42%), I2 = 97%, P <0.01; 31%, 95% CI (21%, 43%), I2 = 100%, P = 0, respectively). A subgroup analysis showed that the majority of those who experienced SP were psychiatric patients (35%, 95% CI (20%, 55%), I2 = 96%, P <0.01). The prevalence among non-psychiatric patients was among students (34%, 95% CI (23%, 47%), I2 = 100%, P = 0). Auditory and visual hallucinations were reported in 24.25% of patients. Around 4% had only visual hallucinations. Meta-regression showed no association between the frequency of SP and sex. Publication bias was detected among the included studies through visual inspection of funnel plot asymmetry. Our findings revealed that 30% of the population suffered from SP, especially psychiatric patients and students. The majority of SP cases lacked associated hallucinations, while a noteworthy proportion experienced combined visual and auditory hallucinations.

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Cell cycle regulatory proteins plays a pivotal role in the development and progression of many human malignancies. Identification of their biological functions as well as their prognostic utility presents an active field of research. As a continuation of the ongoing efforts to elucidate the molecular characteristics of clear cell renal cell carcinoma (ccRCC); we present a comprehensive bioinformatics study targeting the prognostic and mechanistic role of cyclin-dependent kinase inhibitor 3 (CDKN3) in ccRCC. The ccRCC cohort from the Cancer Genome Atlas Program was accessed through the UCSC Xena browser to obtain CDKN3 mRNA expression data and their corresponding clinicopathological variables. The independent prognostic signature of CDKN3 was evaluated using univariate and multivariate Cox logistic regression analysis. Gene set enrichment analysis and co-expression gene functional annotations were used to discern CDKN3-related altered molecular pathways. The tumor immune microenvironment was evaluated using TIMER 2.0 and gene expression profiling interactive analysis. CDKN3 upregulation is associated with shortened overall survival (hazard ratio [HR] = 2.325, 95% confident interval [CI]: 1.703-3.173, P < .0001) in the Cancer Genome Atlas Program ccRCC cohort. Univariate (HR: 0.426, 95% CI: 0.316-0.576, P < .001) and multivariate (HR: 0.560, 95% CI: 0.409-0.766, P < .001) Cox logistic regression analyses indicate that CDKN3 is an independent prognostic variable of the overall survival. High CDKN3 expression is associated with enrichment within the following pathways including allograph rejection, epithelial-mesenchymal transition, mitotic spindle, inflammatory response, IL-6/JAK/STAT3 signaling, spermatogenesis, TNF-α signaling via NF-kB pathway, complement activation, KRAS signaling, and INF-γ signaling. CDKN3 is also associated with significant infiltration of a wide spectrum of immune cells and correlates remarkably with immune-related genes. CDKN3 is a poor prognostic biomarker in ccRCC that alters many molecular pathways and impacts the tumor immune microenvironment.

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