Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88's effects on the gut microbiota.

Although radiation therapy is a cornerstone of modern management of malignancies, various side effects are inevitably linked to abdominal and pelvic cancer after radiotherapy. Radiation-mediated gastrointestinal (GI) toxicity impairs the life quality of cancer survivors and even shortens their lifespan. Hydrogen has been shown to protect against tissue injuries caused by oxidative stress and excessive inflammation, but its effect on radiation-induced intestinal injury was previously unknown. In the present study, we found that oral gavage with hydrogen-water increased the survival rate and body weight of mice exposed to total abdominal irradiation (TAI); oral gavage with hydrogen-water was also associated with an improvement in GI tract function and the epithelial integrity of the small intestine. Mechanistically, microarray analysis revealed that hydrogen-water administration upregulated miR-1968-5p levels, thus resulting in parallel downregulation of MyD88 expression in the small intestine after TAI exposure. Additionally, high-throughput sequencing showed that hydrogen-water oral gavage resulted in retention of the TAI-shifted intestinal bacterial composition in mice. Collectively, our findings suggested that hydrogen-water might be used as a potential therapeutic to alleviate intestinal injury induced by radiotherapy for abdominal and pelvic cancer in preclinical settings.

[Analysis of Therapy and Efficacy after Remission of Acute Myeloid Leukemia].

OBJECTIVE: To investigate the therapy and efficacy after remission of patients with acute myeloid leukemia (AML). METHODS: The clinical data of 110 patients diagnosed as AML treated from 2008 to 2013 were analyzed retrospectively. According to different consolidation therapy regimens, the patients were divided into 4 groups:1 ID-Ara-C group, 2 ID-Ara-C group, 3-4 ID-Ara-C group, allogeneic hematopoietic stem cell transplantation (allo-HSCT) group. The disease-free survival (DFS) and overall survival (OS) were analyzed retrospectovely. RESULTS: 110 patients were completely remittend by 1-2 couses. The median follow-up time was 26.8 months, 35 cases relapsed and 58 cases died, the median DFS and OS were 20.5 and 26.8 months. The 3-year DFS of 1, 2, 3-4 ID-Ara-C and allo-HSCT groups were 0%, 36.1%, 37.5% and 67.9% respectively. The 5-year DFS of 1, 2, 3-4 ID-Ara-C and allo-HSCT groups were 0%, 30.1%, 37.5% and 63.0%. The 3-year OS rates of 1, 2 ID-Ara-C groups, 3-4 ID-Ara-C group and allo-HSCT group were 24.0%, 36.0%, 58.3% and 67.8%. The 5-year OS of 1, 2 ID-Ara-C grous, 3-4 ID-Ara-C and allo-HSCT group were 24.0%, 36.0%, 58.3% and 67.8% respectively. The 5-year OS rates of 1 ID-Ara-C group, 2 ID-Ara-C group, 3-4 ID-Ara-C group were 0%,30.0%,35.0% and 62.9% respectively. The multifactor analysis indicated that the courses of ID-Ara-C and allo-HSCT were independent risk factors for DFS and OS. CONCLUSION: ≥2 ID-Ara-C regimen may be used as one regimen of consolidation therapy for patients with AML after remission.

Hmgn5 functions downstream of Hoxa10 to regulate uterine decidualization in mice.

Although Hmgn5 is involved in the regulation of cellular proliferation and differentiation, its physiological function during decidualization is still unknown. Here we showed that Hmgn5 was highly expressed in the decidual cells. Silencing of Hmgn5 expression by specific siRNA reduced the proliferation of uterine stromal cells and expression of Ccnd3 and Cdk4 in the absence or presence of estrogen and progesterone, whereas overexpression of Hmgn5 exhibited the opposite effects. Simultaneously, Hmgn5 might induce the expression of Prl8a2 and Prl3c1 which were 2 well-known differentiation markers for decidualization. In the uterine stromal cells, cAMP analog 8-Br-cAMP and progesterone could up-regulate the expression of Hmgn5, but the up-regulation was impeded by H89 and RU486, respectively. Attenuation of Hmgn5 expression could block the differentiation of uterine stromal cells in response to cAMP and progesterone. Further studies found that regulation of cAMP and progesterone on Hmgn5 expression was mediated by Hoxa10. During in vitro decidualization, knockdown of Hmgn5 could abrogate Hoxa10-induced upregulation of Prl8a2 and Prl3c1, while overexpression of Hmgn5 reversed the inhibitory effects of Hoxa10 siRNA on the expression of Prl8a2 and Prl3c1. In the stromal cells undergoing decidualization, Hmgn5 might act downstream of Hoxa10 to regulate the expression of Cox-2, Vegf and Mmp2. Collectively, Hmgn5 may play an important role during mouse decidualization.

[Protective Effect of S-isopentenyl-L-cysteine against DNA Damage in Irradiated Mice].

OBJECTIVE: To evaluate the protective effect of S-isopentenyl-L-cysteine,a new cysteine derivative,on DNA damage induced by radiation by using acute radiation injury animal models. METHODS: Forty ICR mice were randomly divided into five groups:the control group,1.0Gy gamma irradiation group,1.0Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,7.2Gy gamma irradiation group,and 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group,with 8 mice in each group.The comet assay and bone marrow polychromatic micronucleus experiments were performed to evaluate the double-strand DNA breaks in ICR mice exposed to 1.0 and 7.2Gy gamma-ray, respectively. RESULTS: The tail DNA percentage,tail length,tail moment,and olive tail moment of peripheral blood lymphocytes in 7.2Gy gamma irradiation group were significantly higher than that of the control group (P<0.01).And it was also observed that above experimental indexes of 7.2Gy gamma irradiation combined with S-isopentenyl-L-cysteine group was significantly less than that of 7.2Gy gamma irradiation group (P<0.05). In addition,the micronucleus rate of 1.0Gy gamma irradiation group and 7.2Gy gamma irradiation group were both significantly higher than in the control group (P<0.01). In addition,in mice given S-isopentenyl-L-cysteine before irradiation,the micronucleus rate of ICR mice exposed to 1.0 and 7.2Gy gamma-ray decreased from (39.5000 ± 3.3141)‰ to (28.1667±4.1345)‰ (P=0.033) and from (76.5000 ± 4.6242)‰ to (22.8333 ± 3.6553)‰(P=0.000),respectively. The bone marrow polychromatic micronucleus experiment indicated that the value of polychromatic erythrocyte (PCE)/normochromatic erythrocyte(NCE) of ICR mice exposed to 1.0 and 7.2Gy gamma-ray was less than the control group(P<0.05). Meanwhile,after irradiating by certain dose,the value of PCE/NCE in mice given S-isopentenyl-L-cysteine before irradiation was significantly higher than the corresponding groups (P<0.05). CONCLUSION: S-isopentenyl-L-cysteine has a good protective effect against DNA damage induced by radiation.