Combined transplantation of neural stem cells and bone marrow mesenchymal stem cells promotes neuronal cell survival to alleviate brain damage after cardiac arrest via microRNA-133b incorporated in extracellular vesicles.

Neural stem cell (NSC) transplantation has prevailed as a promising protective strategy for cardiac arrest (CA)-induced brain damage. Surprisingly, the poor survival of neuronal cells in severe hypoxic condition restricts the utilization of this cell-based therapy. Extracellular vesicles (EVs) transfer microRNAs (miRNAs) between cells are validated as the mode for the release of several therapeutic molecules. The current study reports that the bone marrow mesenchymal stem cells (BMSCs) interact with NSCs via EVs thereby affecting the survival of neuronal cells. Hypoxic injury models of neuronal cells were established using cobalt chloride, followed by co-culture with BMSCs and NSCs alone or in combination. BMSCs combined with NSCs elicited as a superior protocol to stimulate neuronal cell survival. BMSCs-derived EVs could protect neuronal cells against hypoxic injury. Silencing of miR-133b incorporated in BMSCs-derived EVs could decrease the cell viability and the number of NeuN-positive cells and increase the apoptosis in the CA rat model. BMSCs-derived EVs could transfer miR-133b to neuronal cells to activate the AKT-GSK-3ß-WNT-3 signaling pathway by targeting JAK1. Our study demonstrates that NSCs promotes the release of miR-133b from BMSCs-derived EVs to promote neuronal cell survival, representing a potential therapeutic strategy for the treatment of CA-induced brain damage.

Mesenchymal stem cell­derived extracellular vesicles prevent neural stem cell hypoxia injury via promoting miR­210­3p expression.

Neural stem cells (NSCs) have the potential to give rise to offspring cells and hypoxic injury can impair the function of NSCs. The present study investigated the effects of mesenchymal stem cell (MSC)­derived extracellular vesicles (EVs) on NSC injury, as well as the underlying mechanisms. MSC­EVs were isolated and identified via morphological and particle size analysis. Cobalt chloride was used to establish a hypoxic injury model in NSCs. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was conducted to detect apoptosis. Reverse transcription­quantitative PCR was performed to detect the expression levels of miR­210­3p, and western blotting was used to detect the expression levels of apoptosis­inducing factor (AIF) and Bcl­2 19 kDa interacting protein (BNIP3). Compared with the control group, NSC apoptosis, and the expression of miR­210­3p, AIF and BNIP3 were significantly higher in the cobalt chloride­induced hypoxia group. By contrast, treatment with MSC­EVs further increased miR­210­3p expression levels, but reduced NSC apoptosis and the expression levels of AIF and BNIP3 compared with the model group (P<0.05). In addition, miR­210­3p inhibitor reduced miR­210­3p expression, but promoted hypoxia­induced apoptosis and the expression levels of AIF and BNIP3 compared with the model group (P<0.05). Collectively, the results suggested that MSC­EVs prevented NSC hypoxia injury by promoting miR­210­3p expression, which might reduce AIF and BNIP3 expression levels and NSC apoptosis.

Influence of strengthened hemoperfusion combined with continuous venovenous hemofiltration on prognosis of patients with acute paraquat poisoning: SHP + CVVH improve prognosis of acute PQ patients.

BACKGROUND: The success rate of rescue is extremely low in acute paraquat poisoning. This study aimed to assess whether strengthened hemoperfusion (SHP) combined with continuous venovenous hemofiltration (CVVH) improves prognosis in patients with acute paraquat poisoning. METHODS: Patients from January 2005 to December 2018 were enrolled retrospectively. All selected patients were administered conventional therapy. They were divided according to the received treatments in the conventional therapy, hemoperfusion (HP), CVVH, SHP and SHP + CVVH groups. Follow-up was implemented until the 90th day after poisoning. Other outcomes included all-cause mortality on the 15th day after poisoning, and the percentages of respiratory failure and mechanical ventilation use. RESULTS: The study included 487 patients,and 211 died in all. Mortality rate in the SHP + CVVH group on the 90th day after poisoning was significantly decreased compared with those of other groups (p<0.001). Survival curves of all groups showed significant differences (p<0.001). SHP combined with CVVH was an independent factor reducing mortality risk (p<0.001). Mortality rate in the SHP + CVVH group on the 15th day after poisoning was also significantly decreased (p < 0.05). The proportions of patients in the SHP + CVVH group with acute respiratory failure and mechanical ventilation were significantly lower than those of other groups (p < 0.05). CONCLUSIONS: SHP with CVVH may decrease the mortality rate of patients with acute paraquat poisoning on the 90th day after poisoning and improve the prognosis.

Multiple organ dysfunction and rhabdomyolysis associated with moonwort poisoning: Report of four cases.

BACKGROUND: Moonwort is a widely used Chinese herbal medicine. It has various pharmacological effects, such as relieving cough and preventing asthma. To date, multiple organ dysfunction and rhabdomyolysis caused by moonwort poisoning have not been reported. CASE SUMMARY: Here we report four cases of moonwort poisoning that presented with multiple organ dysfunction and rhabdomyolysis accompanied by vomiting, fatigue, and muscle aches. One patient was an adult male, two were adult females, and one was a boy, with an age range of 7-64 years. The adults were treated with hemoperfusion and symptomatic therapies, while the child was treated with plasma exchange and symptomatic therapies. All four patients recovered. CONCLUSION: Blood purification combined with symptomatic treatment may be an effective method for managing multiple organ dysfunction and rhabdomyolysis caused by acute moonwort poisoning.

miR-9 stimulation enhances the differentiation of neural stem cells with zoanthamine by regulating Notch signaling.

The protective effect of zoanthamine on Alzheimer's disease by enhancing differentiation of neural stem cells (NSCs) was evaluated. NSCs were isolated from C57BL/6 mice and assessed by cell viability and apoptosis assays. The cells were separated into five different groups: green fluorescent protein (GFP; transfected with GFP), amyloid precursor protein (APP; transfected with APP), APP + zoanthamine, APP + miR-9 inhibitor, and APP + miR-9 inhibitor + zoanthamine. The effects of zoanthamine on the differentiation of NSCs was determined. Moreover, the effects of zoanthamine on the expression of miR-9 and Notch signalling pathway members was assessed by western blot analysis and reverse-transcription polymerase chain reaction. There was a significant increase in cell viability and a decrease in apoptosis of NSCs in the APP + zoanthamine group compared with the APP group. Treatment with zoanthamine attenuated miR-9 expression and neuronal cell differentiation in APP-treated NSCs. Moreover, in the APP + miR-9 inhibitor group, neuronal cell differentiation and miR-9 expression were significantly reduced, and treatment with zoanthamine reduced the number of differentiated cells and miR-9 expression compared with the APP + miR-9 inhibitor group. There was a significant reduction in the expression of Hes1 and NICD proteins in the APP + zoanthamine group relative to the APP group. In addition, the levels of Hes1 and NICD were enhanced by inhibition of miR-9 but zoanthamine prevented these increases. In conclusion, these results suggest that treatment with zoanthamine enhances the differentiation of NSCs by regulating Notch signalling via elevated miR-9 expression.

Effects of recombinant human growth hormone on growth of human gastric carcinoma xenograft model in nude mice.

AIM: To study effects of recombinant human growth hormone (rhGH) on growth of a human gastric carcinoma cell in vivo. METHODS: Experimental mice were divided into control group, rhGH group, oxaliplatin (L-OHP) group and rhGH+L-OHP group. Cultured human gastric carcinoma cells BGC823 were inoculated into right axilla of nude mice and carcinoma xenograft model was established successfully. Inhibitory rate of xenograft tumor growth was estimated by measuring tumor volume; expression of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 proteins of xenograft tumor was detected using immunohistochemical S-P method. RESULTS: Tumor growth inhibitory rate, the positive expression rate of PCNA, Bax and Bcl-2 were 49.3%, 58.2%, 65.2% and 59.2% in rhGH+L-OHP group respectively; 46.6%, 62.5%, 59.7% and 64.7% in L-OHP group; 5.0%, 82.7%, 23.2% and 82.2% in rhGH group and 0, 77.8%, 23.5% and 80.3% in control group. There was significant difference between rhGH+L-OHP group (or L-OHP group ) and control group or rhGH group (P < 0.05), whereas there were no significant differences (P > 0.05) between L-OHP group and rhGH+L-OHP group and between rhGH group and control group. CONCLUSION: rhGH does not accelerate the proli-feration of human gastric cancer cell in vivo.