Treadmill exercise exerts a synergistic effect with bone marrow mesenchymal stem cell-derived exosomes on neuronal apoptosis and synaptic-axonal remodeling

Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

Correlating interleukin-10 promoter gene polymorphisms with human cerebral infarction onset

Evidence suggests that interleukin-10（IL-10） deficiency exacerbates inflammation and worsens the outcome of brain ischemia. In view of the critical role of the single nucleotide polymorphic sites-1082（A/G） and-819（C/T） in the promoter region of the IL-10 gene, we hypothesized that they are associated with cerebral infarction morbidity in the Chinese Han population. We genotyped these allelic gene polymorphisms by amplification refractory mutation system-polymerase chain reaction methods in 181 patients with cerebral infarction（cerebral infarction group） and 115 healthy subjects（control group）. We identified significant differences in genotype distribution and allele frequency of the IL-10-1082 A/G allele between cerebral infarction and control groups（χ2 = 6.643, P = 0.010）. The IL-10-1082 A allele frequency was significantly higher in the cerebral infarction group（92.3%） than in the control group（86.1%）（P = 0.015）. Moreover, cerebral infarction risk of the AA genotype was 2-fold higher than with the AG genotype（OR = 2.031, 95%CI： 1.134-3.637）. In addition, AA genotype together with hypertension was the independent risk factor of cerebral infarction（OR = 2.073, 95%CI： 1.278-3.364）. No statistical difference in genotype distribution or allele frequency of IL-10-819 C/T was found between cerebral infarction and control groups（P 〉 0.05）. These findings suggest that the IL-10-1082 A/G gene polymorphism is involved in cerebral infarction, and increased A allele frequency is closely associated with occurrence of cerebral infarction.

An Arabidopsis mutant atcsr-2 exhibits high cadmium stress sensitivity involved in the restriction of H_2S emission

The gene AtCSR encodes peptidyl-prolyl cis/trans isomerases (PPIases) that accelerate energetically unfavorable cis/trans isomerization of the peptide bond preceding proline production.In our studies,we found that AtCSR was associated with cadmium (Cd)-sensitive response in Arabidopsis.Our results show that AtCSR expression was triggered by Cd-stress in wild type Arabidopsis.The expression of some genes responsible for Cd2+ transportation into vacuoles was induced,and the expression of the iron-regulated transporter 1 (IRT1) related to Cd2+ absorption from the environment was not induced in wild type with Cd2+ treatment.The expression of Cd-transportation related genes was not in response to Cd-stress,whereas IRT expression increased dramatically in atcsr-2 with Cd2+ treatment.The expression of glutathione 1 (GSH1) was consistent with GSH being much lower in atcsr-2 in comparison with the wild type with Cd2+ treatment.Additionally,malondialdehyde (MDA),hydrogen peroxide,and Cd2+ contents,and activities of some antioxidative enzymes,differed between the wild type and atcsr-2.Hydrogen sulfide (H2S) has been confirmed as the third gas-transmitter over recent years.The findings revealed that the expression pattern of H2 S-releasing related genes and that of Cd-induced chelation and transportation genes matched well in the wild type and atcsr-2,and H2S could regulate the expression of the Cd-induced genes and alleviate Cd-triggered toxicity.Finally,one possible suggestion was given:down-regulation of atcsr-2,depending on H2S gas-transmitter not only weakened Cd2+ chelation,but also reduced Cd2+ transportation into vacuoles,as well as enhancing the Cd2+ assimilation,thus rendering atcsr-2 mutant sensitive to Cd-stress.