Umbilical Cord Blood and UC-MSCs Combined with Low-Dose Immunosuppressant in the Treatment of Elderly Patients with Pure Red Cell Aplastic: A Case Series.

INTRODUCTION: At present, cyclosporine (CsA) is the first-line treatment for Pure Red Cell Aplasia (PRCA), but CsA administration can be associated with a number of side effects due to its high toxicity. Therefore, it is urgent to explore a safe and effective treatment for elderly patients who cannot be treated with conventional doses of CsA, especially those with multiple complications. Allogeneic Stem Cell Transplantation (ASCT) for PRCA is a promising treatment, but reports of using umbilical cord blood (UCB) are very rare. CASE PRESENTATION: In this report, UCB and umbilical cord mesenchymal stem cells (UC-MSCs) combined with low-dose CsA (1-3mg/kg/d) were used to treat 3 elderly patients who were diagnosed with PRCA combined with multiple complications in heart, lung, and renal. The treatments were successful without complications, and 12 months after stem cell infusion, the blood tests of the patients came normal. Moreover, the function of the liver, heart, and kidney continued to be stable. CONCLUSION: This report provides an effective regimen of using UCB and UC-MSCs combined with low-dose CsA (1-3 mg/kg/d) to treat PRCA, especially for elderly patients with multiple complications who cannot use the conventional dosage.

Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress.

BACKGROUND: Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. METHODS: Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. RESULTS: GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. CONCLUSIONS: GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

Effects of intravenous thrombolysis with alteplase combined with edaravone on cerebral hemodynamics and T lymphocyte level in patients with acute cerebral infarction.

Our study aimed to investigate the effect of intravenous thrombolysis with alteplase and edaravone on cerebral hemodynamics and T lymphocyte level in patients harboring acute cerebral infarction.There involved a total of 118 patients with acute cerebral infarction from November 2017 to May 2019 in our hospital were randomly divided into 2 groups: the observation group (59 patients were treated with intravenous thrombolysis with alteplase combined with edaravone) and the control group (59 patients were treated with intravenous thrombolysis of alteplase). The clinical effect, neurological function, cerebral hemodynamic index, T lymphocyte level, oxygen free radical scavenging level and oxidative stress index of the 2 groups were observed and compared.Before the treatment, there were no significant differences in neurological function, cerebral hemodynamic indexes, T-lymphocyte level, oxygen free radical scavenging level and oxidative stress indexes between the 2 groups (P > .05). After the treatment, the neurological function, cerebral hemodynamic indexes, T-lymphocyte level, oxygen free radical scavenging level and oxidative stress indexes of the 2 groups were significantly improved. In addition, the observation group exerted greater beneficial effect in terms of the clinical effect, neurologic function, cerebral hemodynamic index, T lymphocyte level, oxygen free radical scavenging level and oxidative stress index than those of the control group (P < .05).The intravenous thrombolysis with alteplase and edaravone is effective in the treatment of acute cerebral infarction, which also provides better results in terms of improving the clinical efficacy and prognosis of patients and might be an alternative option for clinical practice.

Effects of oxiracetam combined with ginkgo biloba extract in the treatment of acute intracerebral hemorrhage: A clinical study.

PURPOSE: The present clinical study was conducted to investigate the effect of oxiracetam combined with ginkgo biloba extract in treating patients with acute intracerebral hemorrhage. METHODS: Ninety-eight patients with acute cerebral hemorrhage admitted to our hospital were divided into three groups. The differences of brain edema and cerebral hemorrhage were compared between the three groups after 1 and 2 weeks of treatment, and the recovery of neurological function, serum inflammatory factors, AQP-4, MMP-9, cognitive function, activities of daily living, and adverse reactions were compared between the three groups after 2 weeks of treatment. RESULTS: There was no significant difference among the three groups before treatment (p > .05). After treatment, the recovery of neurological function, serum inflammatory factors, AQP-4, MMP-9 levels, cognitive function, and activities of daily living were improved. Among them, the neurological function recovery, serum inflammatory factors, AQP-4, MMP-9 levels, cognitive function, and activities of daily living in the combined treatment group and the control group elicited greater results than those in the routine group. The results of the combined treatment group showed the most significant difference (p < .05). The concentration of IL-6 decreased from 135.98 ± 12.54 to 91.83 ± 7.69 pg/ml, AQP-4 from 227.55 µg/L ± 21.06 to 114.31 ± 9.22 µg/L, and MMP-9 from 172.39 ± 9.81 to 94.98 ± 5.01 ng/ml. In addition, the neurological function recovery, the levels of serum inflammatory factors, cognitive function, and activities of daily living in the combined treatment group were better than those in the control group (p < .05). The mean score of MRS in the combined treatment group decreased from 3.36 ± 0.98 at admission to 1.91 ± 0.38. CONCLUSION: Oxiracetam combined with Ginkgo biloba extract in the treatment of acute cerebral hemorrhage has a significant improvement effect.

RRM2 elicits the metastatic potential of breast cancer cells by regulating cell invasion, migration and VEGF expression via the PI3K/AKT signaling.

Breast cancer is the second leading primary cause for cancer-related mortality among women and metastasis to the brain is a disastrous event for patients with increasing incidence. A previous study confirmed the critical function of RRM2 in breast cancer cell growth. Unfortunately, the role and fundamental molecular mechanism of RRM2 in breast cancer metastasis remains elusive. In the current study, higher RRM2 expression was validated in breast cancer tissues, especially in the brain metastasis group. Simultaneously, the expression of RRM2 was increased in breast cancer cells relative to the normal breast epithelial cell line MCF-10A, concomitant with higher levels of RRM2 in the highly metastatic MDA-MB-231 cell line relative to the weakly metastatic MCF-7 cell line. Knockdown of RRM2 by small interfering-RRM2 transfection notably suppressed the malignant metastatic behavior of breast cancer cells, including invasion and migration. Simultaneously, RRM2 downregulation also restrained the transcription and release of vascular endothelial growth factor (VEGF) in breast cancer cells. Moreover, inhibition of RRM2 dampened the activation of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signaling by decreasing phosphorylated-AKT and downstream matrix metalloproteinases-2 expression. Intriguingly, reactivation of the PI3K/AKT pathway with its agonist insulin-like growth factor-1 reversed the adverse effects of RRM2 suppression on cancer cell invasion, migration and VEGF expression. Together, these findings suggest that RRM2 may act as a pro-metastatic factor to facilitate breast cancer metastasis by evoking cell invasion, migration and VEGF expression through the PI3K/AKT signaling pathway. This study may provide an attractive target for metastatic intervention in breast cancer.

miR-30c Impedes Glioblastoma Cell Proliferation and Migration by Targeting SOX9.

miR-30c has been acknowledged as a tumor suppressor in various human cancers, such as ovarian cancer, gastric cancer, and prostate cancer. However, the role of miR-30c in glioblastoma (GBM) needs to be investigated. In our study, we found that the expression of miR-30c was significantly downregulated in GBM tissues and cell lines. We found that overexpression of miR-30c inhibited cellular proliferation of GBM cells in vitro and in vivo. More GBM cells were arrested in the G0 phase after miR-30c overexpression. Moreover, we showed that miR-30c overexpression suppressed the migration and invasion of GBM cells. Mechanistically, we found that SOX9 was a direct target of miR-30c in GBM cells. Overexpression of miR-30c inhibited the mRNA and protein levels of SOX9 in GBM cells. Moreover, there was a negative correlation between the expression of miR-30c and SOX9 in GBM tissues. Finally, we showed that restoration of SOX9 in GBM cells reversed the proliferation, migration, and invasion of GBM cells transfected with miR-30c mimic. Collectively, our results demonstrated that miR-30c suppressed the proliferation, migration, and invasion of GBM cells via targeting SOX9.

Significant association of BDNF rs6265 G>A polymorphism with susceptibility to epilepsy: a meta-analysis.

INTRODUCTION: Previously published articles have suggested that BDNF rs6265 G>A polymorphism is a potential risk factor for epilepsy. However, the results were not consistent. METHODS: We conducted a meta-analysis to explore the association between BDNF rs6265 G>A polymorphism and epilepsy risk. Four online databases were searched, and related studies were reviewed from their inception up to June 20, 2017. ORs and corresponding 95% CIs were used to calculate the associations of each genetic model. Overall, 10 case-control publications involving 9,512 subjects were included in this meta-analysis. RESULTS: Significant associations were found between BDNF rs6265 G>A polymorphism and epilepsy (A vs G: OR=0.88, 95% CI=0.83-0.94, P<0.01, I2=0%; GA vs GG: OR=0.88, 95% CI=0.79-0.97, P=0.01, I2=0%; AA vs GG: OR=0.79, 95% CI=0.70-0.90, P<0.01, I2=0%; GA+AA vs GG: OR=0.85, 95% CI=0.77-0.94, P<0.01, I2=0%; AA vs GG+GA: OR=0.85, 95% CI=0.76-0.95, P=0.01, I2=0%). Subgroup analysis also showed similar results in an Asian population. CONCLUSION: Our meta-analysis indicated that BDNF rs6265 G>A polymorphism might be involved in epilepsy susceptibility, especially in the Asian population.

Hsa_circ_0007534/miR-761/ZIC5 regulatory loop modulates the proliferation and migration of glioma cells.

Increasing evidences demonstrate the essential roles of circular RNAs (circRNAs) in human cancers. However, the study about the functions of circRNAs in glioma remains very limited. In the present study, we found that circRNA hsa_circ_0007534 was highly expressed in glioma tissues compared to normal brain tissues. Furthermore, we found that knockdown of hsa_circ_0007534 significantly inhibited the proliferation and migration of glioma cells. In mechanism, we showed that hsa_circ_0007534 could sponge miR-761 to repress its availability in glioma cells. We found that inhibition of miR-761 could rescue the suppressed proliferation and migration of glioma cells by hsa_circ_0007534 knockdown. Moreover, we explored the downstream mechanism and found that ZIC5 was a target of miR-761. We showed that hsa_circ_0007534 promoted the expression of ZIC5 by inhibiting miR-761 in glioma cells. And restoration of ZIC5 expression significantly reversed the effects of hsa_circ_0007534 knockdown on glioma cell proliferation and migration. In summary, our results demonstrated that hsa_circ_0007534 serves as an oncogene in glioma via promoting ZIC5 expression by repressing miR-761 availability. Our results suggested that hsa_circ_0007534/miR-761/ZIC5 regulatory loop might be a promising therapeutic target for glioma treatment.

miR-34a deficiency in APP/PS1 mice promotes cognitive function by increasing synaptic plasticity via AMPA and NMDA receptors.

MicroRNA (miR)-34a was recently determined to contribute to the pathological development of Alzheimer's disease (AD). miR-34a deficiency significantly attenuates cognitive deficits in amyloid precursor protein (APP)/presenilin 1 (PS1) mice; however, its role in early AD pathology and the underlying mechanisms remain elusive. Here, we confirmed that the increase of miR-34a expression in APP/PS1 mice was earlier than the relevant AD pathological characteristics, such as amyloid-ß production, amyloid plaque deposition, and cognitive deficits. Furthermore, because predicted miR-34a target genes were broadly linked to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-d-aspartate (NMDA) receptors, we evaluated synaptic plasticity by investigating high-frequency conditioning tetanus-induced excitatory postsynaptic potential, which revealed that synaptic plasticity was promoted in miR-34a knockout/APP/PS1 mice. Therefore, we assessed the expression of the presynaptic components synaptophysin and postsynaptic density protein 95 (PSD95) and found that synaptophysin and PSD95 were not altered by miR-34a deficiency. Additionally, the synaptic strength (vesicular fusion, vesicular docking, and transporting) was either not significantly changed. We also evaluated the levels of AMPA and NMDA receptors, which showed that the expression of AMPA and NMDA receptors was markedly upregulated in APP/PS1 mice with miR-34a deficiency. We conclude that miR-34a is involved in synaptic deficits in AD pathological development, which was, at least in part, due to the inhibition of NMDA (by miR-34a-5p) and AMPA (by miR-34a-3p) receptor expression.