Pivotal Role of GSTO2 in Ferroptotic Neuronal Injury After Intracerebral Hemorrhage.

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.

[Antitumor effect of baicalin on rat brain glioma].

OBJECTIVE: To investigate the therapeutic mechanism of baicalin on rat brain glioma. METHODS: Deep brain glioma models were established by injection of glioma cell line C6 cells into the brain of Wistar rats. The rats at 7 days after modeling were randomly divided into tumor control group (0.9% NaCl solution 30 mg×kg(-1)×d(-1) gavage)and experimental groups. The experimental rats was divided into 3 groups: low dose group (50 mg×kg(-1)×d(-1)), middle dose group (100 mg×kg(-1)×d(-1)) and high dose group (200 mg×kg(-1)×d(-1)), given the baicalin by gavage. Pathological and electron microscopic changes were observed. The expressions of p53 and Bcl-2 were determined by immunohistochemistry, and the changes of MRI, the average survival time and body weight of the rats in each group after treatments were analyzed. RESULTS: Compared with the control group, the tumor diameter and volume of high dose group rats before sacrifice were significantly reduced (P < 0.01), and the survival time was significantly prolonged (P < 0.01). Immunohistochemistry revealed strong positive expression rate of mutant p53 (84.47 ± 3.74)% and moderately positive rate (47.28 ± 2.38)% in the control group, significantly higher than that in the negative group (12.91 ± 1.07)% (P < 0.01). The positive rate of mutant p53 of the high dose group was (46.42 ± 2.19)%, significantly lower than that of the control group (84.47 ± 3.74)% (P < 0.01). The expression rate of Bcl-2 in the control group was strongly positive (86.51 ± 4.17)% and moderate positive (48.19 ± 2.11)%, significantly higher than that of the negative group (10.36 ± 1.43)% (P < 0.01). Electron microscopy revealed that baicalin caused damages of the cell nuclei and organelles in the gliomas. CONCLUSIONS: Baicalin has significant inhibitory effect on glioma in vivo, and its mechanism may be related to cell apoptosis induced by down-regulated expression of mutant p53, but not related with Bcl-2 expression.

[Treatment of hematopathy by tiaohe ganpi recipe in assisting the hematopoietic stem cell transplantation].

OBJECTIVE: To observe the clinical efficacy and the survival of hematopathy patients by Tiaohe Ganpi Recipe (TGR) in assisting the hematopoietic stem cell transplantation (HSCT), thus finding out new thinking ways and methods for Chinese medicine in intervening HSCT. METHODS: Twenty-seven hematopathy patients scheduled to receive HSCT were randomly assigned to two groups, thirteen in the control group and fourteen in the treatment group. They were treated with the conventional treatment of HSCT, but TGR was additionally given to patients in the treatment group during the whole course. All patients were followed up till December 31, 2009 (with the median follow-up time of twenty-five months). The hemopoietic rebuilding time, the implantation state, the therapy correlated mortality, the recurrence rate, preconditioning correlated complications, and graft-versus-host disease (GVHD), the survival time, the survival probability, and so on in the two groups were observed and compared. RESULTS: Better results were obtained in the treatment group in the survival time (41.6 +/- 6.5 months vs. 21.0 +/- 5.9 months), the survival probability (78.6% vs. 30.8%), the 1-3-year cumulative interval survival rate (80.8% vs. 46.2%, 69.3% vs. 34.6%, and 69.3% vs. 34.6%, respectively), the therapy correlated mortality (0 vs. 30.8%), and the death risk (all P < 0.05). As time went by, the cumulative survival rate decreased and the death risk increased gradually in both groups. There was insignificant difference in the hemopoietic rebuilding time (17.9 +/- 7. 9 days vs. 18.1 +/- 6.8 days), the implantation state, the occurrence rate of preconditioning correlated complications (14.3% vs. 23.1%), GVHD occurrence, and the recurrence rate (21.4% vs. 23.1%, P > 0.05). CONCLUSION: TGR could lower the therapy correlated mortality, prolong the survival time, and improve the cumulative survival rate in the HSCT treatment of hematopathy patients, playing efficacy enhancing and toxicity reducing effect.