Association Between Serum Neurofilament Light Chain and Neurochemistry Deficits in Patients with Spinocerebellar Ataxia Type 3.

Extensive evidence supports the claim that the serum neurofilament light chain (sNfL) can be used as a biomarker to monitor disease severity in patients with spinocerebellar ataxia type 3 (SCA3). However, little is known about the associations between sNfL levels and neurochemical alterations in SCA3 patients. In this study, we performed a cross-sectional study to analyze the association between sNfL and brain metabolic changes in SCA3 patients. The severity of ataxia was assessed by using the Scale for the Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS). The sNfL levels and brain metabolic changes, represented by N-acetyl aspartate (NAA)/creatine (Cr) and choline complex (Cho)/Cr ratios, were measured by a single-molecule array and proton magnetic resonance spectroscopy, respectively. In this cohort, we observed consistently elevated sNfL levels and reduced brain metabolites in the cerebellar hemispheres, dentate nucleus, and cerebellar vermis. However, this correlation was further validated in the cerebellar cortex after analysis using pairwise comparisons and a Bonferroni correction. Taken together, our results further confirmed that sNfL levels were increased in SCA3 patients and were negatively correlated with metabolic changes in the cerebellar cortex. Our data also support the idea that sNfL levels are a promising potential complementary biomarker for patients with SCA3.

Effectiveness of High-Frequency Repetitive Transcranial Magnetic Stimulation in Patients With Spinocerebellar Ataxia Type 3.

OBJECTIVE: To investigate the effectiveness of high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) on improvement of clinical symptoms in patients with spinocerebellar ataxia type 3 (SCA3). METHODS: Sixteen SCA3 participants diagnosed by genetic testing were enrolled in this sham-controlled and double-blind trial. They received either a 2-week 10-Hz rTMS intervention or sham stimulation targeting the vermis and cerebellum. The Scale for Assessment and Rating of Ataxia and the International Cooperative Ataxia Rating Scale were completed at baseline and poststimulation. RESULTS: Compared with baseline, the HF-rTMS group demonstrated a significant improvement in the total Scale for Assessment and Rating of Ataxia ( P < 0.0001) and the International Cooperative Ataxia Rating Scale scores ( P = 0.002). After 2-week treatment, the real group exhibited decreasing pattern in 3 subgroups, especially for limb kinetic function ( P < 0.0001). CONCLUSIONS: Short-term HF-rTMS treatment is a potentially promising and feasible tool for rehabilitation in patients with SCA3. Studies with long-term follow-up need to be carried out in the future and further need to assess gait, limb kinetic function, speech and oculomotor disorders.

A Novel SACS Variant Identified in a Chinese Patient: Case Report and Review of the Literature.

Mutations in the SACS gene have been linked to autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS). It is a clinically and genetically heterogeneous disease characterized by slow progressive ataxia, spasticity, sensorimotor neuropathy, and a combination of other manifestations, such as lack of spasticity, hearing loss, and epileptic seizures. Currently, there have been very few case reports regarding the SACS gene mutation in Chinese patients. Here, we describe a 35-year-old Chinese patient carrying a novel variant in SACS (c.11486C>T) presenting with progressive ataxia and demyelinating peripheral neuropathy. We then reviewed 22 Chinese cases carrying SACS gene mutations, including our patient. All of them had a cerebellar ataxia gait and showed cerebellar atrophy on brain magnetic resonance imaging (MRI). A total of 28 SACS mutations were identified in these patients. Our study further expands the mutation spectrum of the SACS gene and contributes to the evaluation of genotype-phenotype correlations.

MicroRNA-625 inhibits cell invasion and epithelial-mesenchymal transition by targeting SOX4 in laryngeal squamous cell carcinoma.

INTRODUCTION: Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignant cancer, but the molecular mechanisms underlying its development and progression remain largely elusive. The purpose of the present study is to investigate the expression profile and functional role of microRNA-625 (miR-625) in LSCC. MATERIALS AND METHODS: LSCC tissues and adjacent normal tissues were collected from 86 LSCC patients. The expression levels of miR-625 and SOX4 mRNA in tissues and cells were detected by RT-qPCR analysis. The expression levels of SOX4 and EMT-related proteins were detected by western blot analysis. In vitro cell proliferation, migration, and invasion were detected by MTT assay, colony formation assay, wound healing assay, and transwell invasion assay, respectively. Dual-luciferase reporter assay was performed to verify the binding relationship between miR-625 and the 3'-UTR of SOX4. RESULTS: The results demonstrated that miR-625 is significantly down-regulated in clinical LSCC tissues, and its low expression may be closely associated with unfavorable clinicopathological characteristics of LSCC patients. Overexpression of miR-625 significantly suppressed the proliferation, migration, invasion, and EMT of LSCC cells. Furthermore, SOX4 was validated as a direct target of miR-625 in LSCC cells, and rescue experiments suggested that restoration of SOX4 blocked the tumor suppressive role of miR-625 in LSCC cells. CONCLUSIONS: Taken together, these findings highlighted a critical role of miR-625 in the pathogenesis of LSCC, and restoration of miR-625 could be considered as a potential therapeutic strategy against this fatal disease.

The impact of lncRNA MG3 on laryngeal cancer cell growth, cycle, and apoptosis related factors.

Laryngeal cancer is a common head and neck malignant tumor. Long non-coding RNA (lncRNA) is a kind of RNA at the length more than 200 nucleotides that cannot code protein. They widely exist in the human genome. Maternally expressed gene 3 (MG3) is a kind of lncRNA that is associated with various malignant tumors development. This study explores the influence of MG3 on laryngeal cancer Hep-2 cell growth, cycle, and apoptosis related factors. Hep2 cells transfected by MG3 were treated as experimental group, while untransfected Hep2 cells were treated as control. MG3 expression was tested by real time PCR. Cell proliferation was evaluated by MTT assay. Cell cycle was determined by flow cytometry. Bcl-2, Bax, and survivin protein levels were detected by Western blot. MG3 expression significantly increased in Hep2 cells compared with control (P < 0.05). Hep2 cell OD value and cell percentage in S phase were obviously declined, while cell apoptosis were markedly enhanced (P < 0.05). OD value and cell percentage in S phase apparently reduced in 12 h, 24 h, and 48 h from experimental group (P < 0.05). Bcl-2 and survivin protein downregulated, while Bax protein elevated in experimental group following time extension (P < 0.05). MG3 overexpression inhibited laryngeal cancer Hep2 cell proliferation and arrested cell cycle with time dependence, which may achieve by suppressing Bcl-2 and survivin protein, and facilitating Bax protein expression.

Effect of antidepressants on spatial memory deficit induced by dizocilpine.

Cognitive deficits are a core symptom of schizophrenia. It is controversial whether antidepressants could improve cognitive symptoms in schizophrenia patients. The present study was designed to identify the therapeutic effect of antidepressants on cognitive deficits in schizophrenia. In the present study, adolescent rats were repeatedly exposed to dizocilpine, which can induce cognitive deficits associated with schizophrenia. Then these rats were treated by six antidepressants (fluvoxamine, sertraline, paroxetine, escitalopram, venlafaxine, mirtazapine) or vehicle. The rats in the control group were exposed to vehicle during the study. Lastly, all rats' spatial memory (a major part of cognition) was assessed using the Morris water maze (MWM) test, and the density of hippocampal parvalbumin (PV) interneurons was evaluated to explore possible mechanisms underlying spatial memory change in schizophrenia. The results of the present study supported the hypothesis of a therapeutic effect of fluvoxamine and escitalopram on spatial memory deficit induced by dizocilpine. Additionally, the data of the present study suggested that fluvoxamine and escitalopram remitted hippocampal PV interneuron reduction induced by dizocilpine. The neuroprotective effect of fluvoxamine and escitalopram may partly explain the therapeutic effect of antidepressants on spatial memory deficit in schizophrenia patients.