Therapeutic effect and psychological impact of aspirin plus edaravone on patients with cerebral infarction.

BACKGROUND: Cerebral infarction (CI) is characterized by a high prevalence, disability, and mortality. Timely or improper treatment greatly affects patient prognosis. AIM: To explore the drug efficacy of aspirin plus edaravone and to explore their effect on quality of life (QOL), anxiety and depression in CI patients. METHODS: We retrospectively analyzed the records of 124 CI patients treated between June 2019 and February 2021 who were assigned to an observation group (OG) (combination therapy of aspirin and edaravone, 65 patients) or a control group (CG) (aspirin monotherapy, 59 patients). The therapeutic effects, pre- and posttreatment National Institutes of Health Stroke Scale (NIHSS) scores, activities of daily living, degree of cognitive impairment, protein levels of glial fibrillary acidic protein (GFAP), neuron-specific enolase (NSE) and S-100B, occurrence of adverse reactions, and serum high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-α were evaluated, detected and compared between the two groups. Finally, posttreatment QOL, anxiety, and depression were assessed by the Medical Outcomes Study 36- Item Short Form Health Survey Scale, Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS), respectively. RESULTS: Compared with the CG, the OG had markedly better therapeutic effects, greater improvements in activities of daily living, and better alleviation in cognitive dysfunction after treatment, as well as lower posttreatment NIHSS scores and serum NSE, GFAP, S-100B, hs-CRP, IL-6, and TNF-α levels; the OG was similar to the CG in terms of adverse reactions but was better than the CG in terms of posttreatment QOL; and the OG also had lower SDS and SAS scores than the CG after treatment. CONCLUSION: Aspirin plus edaravone had a good curative effect on CI. It can reverse cranial nerve damage in patients, improve neurological function and prognosis, and alleviate inflammation, anxiety, and depression; thus, it is considered safe and worthy of clinical application.

Macular edema after siponimod treatment for multiple sclerosis: a case report and literature review.

BACKGROUND: As a modulator of the sphingosine 1-phosphate receptor, siponimod is administered as a therapeutic intervention for multiple sclerosis. A previous phase 3 study first reported siponimod-associated macular edema. Since that report, there were only few relevant reports in clinical settings. Here, we report a case of secondary progressive multiple sclerosis developed macular edema after siponimod treatment. We also review the progress of sphingosine 1-phosphate receptor modulators, elaborate on accepted mechanisms in treating multiple sclerosis, and discuss the causation of siponimod-associated macular edema. CASE PRESENTATION: A 38-year-old Chinese female patient with secondary progressive multiple sclerosis, who had recurrent numbness of the limbs and right leg fatigue, developed mild macular edema following 4 months of siponimod treatment. The macular edema resolved after discontinuing the medication, and did not recur after resuming siponimod. CONCLUSION: Although siponimod-associated macular edema may be rare, mild, transitory, and manageable, it cannot be ignored and requires ongoing vigilance.

Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 µL exosomes via the tail vein (200 µg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1ß release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

[Effect of p65 gene inhibited by siRNA on differention of rat marrow mesenchymal stem cells into neurons].

OBJECTIVE: To investigate the effect of p65 gene inhibited by siRNA on neuronic differentiation in the marrow mesenchymal stem cells (MSCs). METHODS: The MSCs were transfected with Rn-p65-siRNA. Fasudil hydrochloride induced MSCs differentiating into neurons. The non-transfected group and negative control group (transfected with negative control siRNA marked by Cy3) were used as controls. The fluorescence expressed by transfected MSCs were observed under inverted fluorescence microscope at 24 h,48 h and 72 h after transfected with negative control siRNA. The viability of MSCs was detected by MTT at 24 h, 48 h and 72 h after transfected with Rn-p65-siRNA. The expressions of p65 mRNA and protein in MSCs were detected by RT-PCR and Western blot respectively. The expressions of p65 protein, NSE, MAP-2 and glial fibrillary acidic protein (GFAP) were detected by immunocytochemical method after transfection for 6 h. RESULTS: The fluorescence of MSCs was mostly displayed after transfection of 72 hours and the efficiency of transfection was up to 83.3% ± 3.8%. Meanwhile, the p65 mRNA and p65 protein expressed by MSCs of transfected group were significantly decreased (P < 0.05); MTT displayed that the viability of MSCs was also significantly reduced (P < 0.05). The best efficiency of induction was observed in the transfected group. There were higher expressions of NSE and MAP-2 than the other group (P < 0.05). CONCLUSION: The p65 gene inhibited by siRNA can promote the marrow mesenchymal stem cells to differentiate into neurons.

[Effect of notch signaling on differentiation of rat marrow mesenchymal stem cells into neurons induced by fasudil hydrochloride].

OBJECTIVE: To investigate the effect of notch signaling on differentiation of rat bone marrow mesenchymal stem cells (MSCs) into neurons induced by fasudil hydrochloride. METHODS: The experiments were divided into non-transfected group, transfected group (transfected with Rn-Notch1-siRNA), positive control group (transfected with Rn-MAPK-1 Control siRNA) and negative control group (transfected with negative control siRNA). Fasudil hydrochloride induced MSCs differentiating into neurons. The fluorescence expressed by transfected MSCs were observed under inverted fluorescence microscope. The expression of notch1 mRNA, Hes1 mRNA and MAPK1 mRNA in MSCs was detected by RT-PCR. The expression of Notch1 protein, NSE, neurofilament M (NF-M) and glial fibrillary acidic protein(GFAP)was detected by immunocytochemical method. The viability of MSCs was detected by MTT. RESULTS: (1) The fluorescence of MSCs was mostly displayed after transfection for 72 h and the efficiency of transfection was up to 91.3% +/- 4.2%. Meanwhile, the notch1 mRNA and Hes1 mRNA expressed by MSCs of transfected group were significantly decreased (P < 0.05) and MTT displayed that the viability of MSCs was also significantly reduced (P < 0.05). (2) Fasudil hydrochloride could induce MSCs differentiate into neurons and the best efficiency of induction was observed in the transfected group. There was higher expression of NSE and neurofilament-M (NF-M) than the other groups (P < 0.05). CONCLUSION: There may be notch1 signaling and Rho/Rho GTPase signaling synergy on differentiation of rat bone marrow stromal cell into neurons induced by fasudil hydrochloride and they jointly promote the differentiation of MSCs into neurons.