Biomarkers associated with functional improvement after stroke rehabilitation: a systematic review and meta-analysis of randomized controlled trials.

Objective: This study aims to identify blood and cerebrospinal fluid biomarkers that are correlated to the functional improvement of stroke patients after rehabilitation therapy, and provide ideas for the treatment and evaluation of stroke patients. Methods: The PubMed, Web of Science, and Embase databases were searched for articles published in the English language, from inception to December 8, 2022. Results: A total of 9,810 independent records generated 50 high-quality randomized controlled trials on 119 biomarkers. Among these records, 37 articles were included for the meta-analysis (with a total of 2,567 stroke patients), and 101 peripheral blood and cerebrospinal fluid biomarkers were included for the qualitative analysis. The quantitative analysis results revealed a moderate quality evidence that stroke rehabilitation significantly increased the level of brain-derived neurotrophic factor (BDNF) in serum. Furthermore, the low-quality evidence revealed that stroke rehabilitation significantly increased the concentration of serum noradrenaline (NE), peripheral blood superoxide dismutase (SOD), peripheral blood albumin (ALB), peripheral blood hemoglobin (HB), and peripheral blood catalase (CAT), but significantly decreased the concentration of serum endothelin (ET) and glutamate. In addition, the changes in concentration of these biomarkers were associated with significant improvements in post-stroke function. The serum BNDF suggests that this can be used as a biomarker for non-invasive brain stimulation (NIBS) therapy, and to predict the improvement of stroke patients. Conclusion: The concentration of serum BNDF, NE, ET and glutamate, and peripheral blood SOD, ALB, HB and CAT may suggest the function improvement of stroke patients.

Non-invasive brain stimulation effectively improves post-stroke sensory impairment: a systematic review and meta-analysis.

More than half of stroke patients experience sensory dysfunction that affects their quality of life. Previous training modalities are ineffective in improving sensory function. In contrast, non-invasive brain stimulation (NIBS) is a new promising intervention for stroke rehabilitation. The aim of this meta-analysis was to summarize the current effectiveness of NIBS in the treatment of post-stroke sensory dysfunction. Articles published in PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), Chinese scientific journals full-text database (VIP), and Wanfang database from the inception to March 8, 2023 were searched. There were no restrictions on language. A total of 14 RCTs were included (combined n = 804). Moderate-quality evidence suggested that NIBS significantly improved sensory function after stroke, and significant effects were observed up to 1 year after the intervention. In subgroup analysis, treatment with transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS) was significantly more effective than controls for recovery of sensory function in stroke patients. Stimulation of the primary motor cortex (M1), primary somatosensory cortex (S1) or M1 + S1 stimulation sites significantly improved sensory function. NIBS for sensory dysfunction showed significant therapeutic potential in patients with different stages of stroke. No significant effects were observed in subjects with less than 10 NIBS stimulations. Significant therapeutic effects were observed with either high-frequency or low-frequency rTMS.

esiRNA to eri-1 and adar-1 genes improving high doses of c-myc-directed esiRNA effect on mouse melanoma growth inhibition.

Knockdown of c-myc expression via RNAi is expected to be an efficient approach to suppress tumor growth. In our preliminary study, we intraperitoneally injected different doses of c-myc-directed esiRNA (esic-MYC, c-myc-directed Escherichia coli expressed and enzyme digested siRNA) into C57BL6/6J mice with bearing B16 melanoma to investigate the inhibitory effect of esic-MYC on tumor growth. However, in high dose esic-MYC treatment groups, the tumor growth inhibition was less efficient than that of low dose treatment groups. Considering the negative regulation roles of eri-1 and adar-1 genes in RNA interference, we downregulated either/both of the two genes with c-myc gene by RNAi. Our results showed esiMERI-1 (esiRNA of mouse eri-1 gene) and esiMADAR-1 (esiRNA of mouse adar-1 gene) could rescue the tumor growth suppression in the high dose esic-MYC treatment groups obviously. The data strongly suggest that silencing of eri-1 and adar-1 homologs of human being should be concerned for cancer therapy by RNAi approach.