[Effect of bone marrow mononuclear cell transplantation on miRNA-21 and miRNA-155 expression in mice with ulcerative colitis].

Objective: To investigate the effect of bone marrow mononuclear cell transplantation on the expression of miRNA-21 and miRNA-155 in mice with ulcerative colitis(UC). Methods: Healthy and clean KM mice aged 6-8 weeks were randomly divided into transplantation group, model group and normal control group with 15 mice in each group. In the transplantation group and model group, dextran sodium sulfate (DSS) was used to establish the model for 24 h. The mice in the transplantation group were injected with 0.4 ml of 4 ', 6-diaminol-2-phenylindole (DAPI) -labeled P3-BM-MNCs cell suspension (3.2×10(6) cells/ml), and the mice in the model group and the normal control group were injected with 0.4 ml phosphate buffer (PBS).UC disease activity index (DAI) was used to test the general condition of mice; HE staining was used to observe the pathological changes of colon tissue; Real-time quantitative PCR was used to detect the expression of miRNA-21 and miRNA-155 mRNA. Results: DAI scores of normal control group, model group and transplantation group were 0 (0,1), 3.1 (2.8,3.3) and 2.7 (2.4,3.1),respectively. Compared with normal control group, the DAI score of model group and transplantation group was higher (P<0.05), and the DAI score of transplantation group was lower than that of model group (P<0.05). The gross scores of tissue injury in normal control group, model group and transplantation group were 0 (0, 1), 3 (3, 4) and 1 (1, 2), respectively,and the pathological scores of tissue injury were 0 (0, 1), 16 (12, 16) and 6 (6, 8), respectively,compared with the normal control group. The tissue injury score of the model group and the transplantation group was higher (P<0.05), and the tissue injury score of the transplantation group was lower than that of the model group (P<0.05). The expression levels of miRNA-21 mRNA in normal control group, model group and transplantation group were 0.87±0.15, 2.38±0.29 and 1.59±0.32, respectively, and the expression levels of miRNA-155 mRNA were 1.87±0.46, 7.38±1.97 and 3.92±0.84, respectively, compared with the normal control group, the expression of miRNA-21 and miRNA-155 mRNA in the model group and transplantation group was higher (P<0.01), the expression of miRNA-21 and miRNA-155 mRNA in the transplantation group was lower than that of the model group (P<0.05). Conclusion: Bone marrow mononuclear cell transplantation can improve the histopathological and DAI scores of mice with UC, which may be related to the down-regulation of miRNA-21 and miRNA-155 mRNA expression.

A study on regulatory mechanism of miR-223 in ulcerative colitis through PI3K/Akt-mTOR signaling pathway.

OBJECTIVE: The aim of this study was to explore the regulatory mechanism of micro ribonucleic acid (miR)-223 in ulcerative colitis (UC) through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)-mammalian target of rapamycin (mTOR) signaling pathway. MATERIALS AND METHODS: A total of 36 Sprague-Dawley (SD) rats were randomly divided into three groups, including normal group (n=12), model group (n=12) and inhibitor group (n=12). Rats in the normal group received no treatment. Rats in the model group were used to establish a UC model. Meanwhile, rats in the inhibitor group underwent intraperitoneal injection of inhibitor and establishment of the UC model. Subsequently, specimens were obtained for detection. Immunohistochemistry was applied to measure the expression of mTOR. Western blotting was adopted to determine the relative protein expressions of P85, P110 and phosphorylated Akt (p-Akt). Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression of miR-223. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) was utilized to determine cell apoptosis. Furthermore, an enzyme-linked immunosorbent assay (ELISA) was conducted to measure the content of interleukin-1 beta (IL-1ß) and IL-6. RESULTS: Immunohistochemistry showed that the positive expression of mTOR increased remarkably in the model group and inhibitor group when compared with that of the normal group (p<0.05). However, it decreased notably in the inhibitor group when compared with the model group (p<0.05). Western blotting indicated that the protein expressions of P85, P110 and p-Akt in model group and inhibitor group were significantly higher than the ones of the normal group (p<0.05). However, the inhibitor group showed markedly lower relative protein expressions of P85, P110 and p-Akt than the ones of the model group (p<0.05). Compared with the normal group, the expression level of miR-223 was significantly elevated in model group and inhibitor group (p<0.05). However, there was no significant difference in the mRNA expression of miR-233 between the model group and the inhibitor group (p>0.05). The apoptosis rate of the cells increased prominently in the model group and in the inhibitor group when compared with the normal group (p<0.05). However, it was remarkably reduced in the inhibitor group than the model group (p<0.05). In comparison with the normal group, the content of IL-1ß and IL-6 was significantly up-regulated in the model group and in the inhibitor group (p<0.05). However, it declined notably in the inhibitor group compared with the model group (p<0.05). CONCLUSIONS: MiR-223 can trigger cell apoptosis and inflammation in UC by up-regulating the PI3K/Akt-mTOR signaling pathway.

[Spectrum and case fatality of inpatients with malignant tumors from 1995 to 2014 in Shenzhen city].

Objective: To analyze the epidemiological features, spectrum and case fatality of malignant tumor patients in Shenzhen city, to provide evidence for the development of prevention and treatment strategies on malignant tumor in Shenzhen. Methods: All the hospitalized malignant tumor patients including deaths, were monitored from 1995 to 2014 in Shenzhen, and data was analyzed by SPSS 20.0 software. Results: There were 160 988 inpatients of malignant tumors between 1995 and 2014 in Shenzhen. The top three hospitalized tumors were lung (13.64%), liver (11.13%) and breast (7.86%) cancers. Numbers of the malignant tumor inpatients had been rapidly increasing during the past 20 years, 12.3 times in 2014 higher than in 1995. The total number of deaths due to malignant tumors was 19 460. Deaths of the top three malignant tumors were lung (24.40%), liver (19.84%) and colorectal (8.63%) cancers and the number of deaths was increasing, 12.5 times higher in 2014 than in 1995. The overall case fatality rate was 12.09%. The annual percent change (APC) of malignant tumors case fatality rate was 9.7%(95%CI: 2.0%-18.0%), during 1995-2003, with an increasing trend (t=2.72, P<0.05). The APC of case fatality rate during 2003-2014 was -3.4%(95%CI: -7.6%-1.1%), but the decreasing trend (t=-1.63, P>0.05) was not statistically significant. The top three major malignant tumors related to case fatality rate were lung cancer (21.62%), liver cancer (21.39%), and esophageal cancer (16.50%). The case fatality rates of leukemia and liver cancer had decreased during the past 20 years. The case fatality rates of cancers in lung, esophagus, stomach, breast, colorectal and nasopharyngeal, had all increased. The number of male patients was significantly exceeding the females (χ(2)=41.691, P<0.01), with sex ratio as 1.65∶1. From age 35 and on, the number of deaths due to malignant tumors increased significantly, with the peak after 60 years of age. Conclusions: The number of malignant tumor inpatients had an annual increase as well as the case fatality rate. Cancers in lung, liver appeared the leading causes of death among the malignant tumor patients, with elderly in particular. Strategies related to the prevention and treatment of cancers in lung, liver should be strengthened.

FLZ protects dopaminergic neuron through activating protein kinase B/mammalian target of rapamycin pathway and inhibiting RTP801 expression in Parkinson's disease models.

The pathogenesis of Parkinson's disease is characterized by progressive degeneration of dopaminergic neurons in substantia nigra (SNpc). FLZ, a novel synthetic squamosamide derivative from a Chinese herb, has been shown to have neuroprotective effects in experimental Parkinson's disease (PD) models. However, it is still unclear whether FLZ protects against PD through regulating the function of dopaminergic system. In this study, we carried out a set of in vitro and in vivo experiments to address these questions. Oral administration of FLZ significantly improved motor dysfunction of mice challenged by MPTP. The beneficial effects of FLZ on motor behavior attributed to the elevation of dopamine level in striatum, tyrosine hydroxylase (TH)-positive cells, and TH activity in the middle brain of mouse. Mechanism study showed that treatment of FLZ increased the phosphorylation of activating protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Using LY294002 to block phosphoinositide 3-kinases (PI3K)/Akt signaling pathway prevented the phosphorylation of mTOR and attenuated the neuroprotection of FLZ in MN9D cells challenged by MPP(+). In addition, FLZ reduced the expression of RTP801, an important protein in PD, in mice and cells intoxicated by MPTP/MPP(+). Taken together, these results revealed a novel role that FLZ elevated TH expression and activity in dopaminergic neuron through activation of Akt/mTOR survival pathway and inhibition of RTP801 in MPTP/MPP(+)-induced PD models. The data also provided evidence that FLZ had potent neuroprotecive effects and might become a new promising anti-PD drug.