Association of serum Spp1 levels with disease progression in ALS and SBMA.

OBJECTIVE: In comparison with amyotrophic lateral sclerosis (ALS), the contribution of neuroinflammation in spinobulbar muscular atrophy (SBMA) has been less explored. We investigated the role of neuroinflammation in the pathogenesis of ALS and SBMA by analyzing systemic inflammatory markers and osteopontin (Spp1). METHODS: This study involved 105 ALS, 77 SBMA, and 55 healthy controls. We measured their systemic inflammatory markers, serum Spp1, and cytokine levels (interferon-γ, interleukin [IL]-1ß, IL-6, IL-8, IL-10, tumor necrosis factor-α, and IL-17A), investigated correlations between Spp1 levels and clinical features, and evaluated ALS survival rates according to Spp1 levels. RESULTS: In the ALS group, systemic inflammatory markers were significantly higher than in the control and SBMA groups. Spp1 levels were observed to be higher in ALS patients, but the difference was not statistically significant among the study groups. Cytokine profiles were comparable. In ALS, higher Spp1 levels were correlated with lower ALS Functional Rating Scale-Revised (ALSFRS-R) scores (r = -0.25, p = 0.02) and faster disease progression rate (r = 0.37, p < 0.001). After adjusting for other prognostic indicators, high Spp1 levels were independently associated with shorter survival in ALS patients (hazard ratio 13.65, 95% confidence interval 2.57-72.53, p < 0.01). INTERPRETATION: Neuroinflammation does not appear to be a primary contributor to the pathogenesis of SBMA. Serum Spp1 levels may serve as a reliable biomarker for disease progression and prognosis in ALS. These findings expand our understanding of these two distinct motor neuron disorders and offer a potential biomarker for future studies.

Serum C3 complement levels predict prognosis and monitor disease activity in Guillain-Barré syndrome.

OBJECTIVE: Biomarkers are needed to predict prognosis and disease activity in patients with Guillain-Barré syndrome (GBS). The complement system is a key player in the pathogenesis of GBS. This study aimed to assess the potential utility of serum complement proteins as novel biomarkers in GBS. METHODS: We reviewed the medical records of 76 GBS patients with C3 and C4 measurements during hospitalization between 2010 and 2021. Clinical outcomes were correlated with baseline serum C3, C4, and seven additional predictors: four existing biomarkers (GM1, albumin, immunoglobulin G, neutrophil-lymphocyte ratio) and three clinical factors from the modified Erasmus GBS outcome score model. Five complement activation products (C3a, C4a, C5a, soluble C5b-9, factor Bb) were measured in 35 patients and were compared with C3 and C4 levels. Longitudinal changes in C3 and C4 levels were compared with the disease course in 12 patients. RESULTS: Higher C3, but not C4, was associated with poorer outcomes: lower Medical Research Council sum scores (MRCSS), higher GBS disability score (GBSDS), longer hospitalization, and more frequent treatment-related fluctuations. Age, MRCSS at admission, and baseline serum C3 were significant independent indicators of 1- and 3-month GBSDS. We found that C3 was positively correlated with C3a (r = 0.32) and C5a (r = 0.37), which indicates an activated complement cascade with high C3. Longitudinal change of C3 coincided with clinical severity of the disease course. INTERPRETATION: This study highlights the use of serum C3 as a novel mechanistic biomarker in GBS. Larger prospective studies are needed to validate our findings.

CRISPR-Cas9 mediated genome editing of Huntington's disease neurospheres.

BACKGROUND: Huntington's disease (HD) is a fatal genetic disease caused by polyglutamine aggregation encoded by an expanded CAG repeat in the huntingtin gene (HTT). In this study, we cultured neurospheres derived from R6/2 mice, a representative animal model of HD, as an in vitro model. GuideRNAs were designed to induce large deletion or frameshift indel mutation of CAG expansion. These gRNAs and Cas9 were delivered to the R6/2 neurospheres and disease-related phenotypes were observed. METHODS AND RESULTS: Deletion or indel mutation of the CAG repeat was confirmed by PCR, T7E1 assay and sequencing of the edited neurospheres. Edited neurospheres showed decreased polyglutamine aggregation compared with control HD neurospheres. In the edited neurosphere, we confirmed the upregulation of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and brain-derived neurotrophic factor (BDNF), whose reduced expressions are closely involved in the disease progression. In addition, flow cytometry result showed an increase in cell viability with an overall decrease in necrotic and apoptotic populations among edited R6/2 neurospheres. Additional siRNA experiments confirmed that the increased viability was decreased through inhibition of PGC-1α or BDNF. CONCLUSION: Our study confirmed that CAG repeat of R6/2 mouse-derived neurospheres can be edited through CRISPR-Cas9. Editing of CAG repeat sequence decreases polyglutamine aggregation and cellular apoptosis of HD neurospheres, which may be related to the increased expressions of PGC-1α and BDNF. Our data provide the evidence that CRISPR-Cas9 mediated genome editing has therapeutic potential on HD neuronal cells.

Nanomaterials for IoT Sensing Platforms and Point-of-Care Applications in South Korea.

Herein, state-of-the-art research advances in South Korea regarding the development of chemical sensing materials and fully integrated Internet of Things (IoT) sensing platforms were comprehensively reviewed for verifying the applicability of such sensing systems in point-of-care testing (POCT). Various organic/inorganic nanomaterials were synthesized and characterized to understand their fundamental chemical sensing mechanisms upon exposure to target analytes. Moreover, the applicability of nanomaterials integrated with IoT-based signal transducers for the real-time and on-site analysis of chemical species was verified. In this review, we focused on the development of noble nanostructures and signal transduction techniques for use in IoT sensing platforms, and based on their applications, such systems were classified into gas sensors, ion sensors, and biosensors. A future perspective for the development of chemical sensors was discussed for application to next-generation POCT systems that facilitate rapid and multiplexed screening of various analytes.