MiR-133a Is Functionally Involved in Doxorubicin-Resistance in Breast Cancer Cells MCF-7 via Its Regulation of the Expression of Uncoupling Protein 2

The development of novel targeted therapies holds promise for conquering chemotherapy resistance, which is one of the major hurdles in current breast cancer treatment. Previous studies indicate that mitochondria uncoupling protein 2 (UCP-2) is involved in the development of chemotherapy resistance in colon cancer and lung cancer cells. In the present study we found that lower level of miR133a is accompanied by increased expression of UCP-2 in Doxorubicin-resistant breast cancer cell cline MCF-7/Dox as compared with its parental cell line MCF-7. We postulated that miR133a might play a functional role in the development of Doxorubicin-resistant in breast cancer cells. In this study we showed that: 1) exogenous expression of miR133a in MCF-7/Dox cells can sensitize their reaction to the treatment of Doxorubicin, which is coincided with reduced expression of UCP-2; 2) knockdown of UCP-2 in MCF-7/Dox cells can also sensitize their reaction to the treatment of Doxorubicin; 3) intratumoral delivering of miR133a can restore Doxorubicin treatment response in Doxorubicin-resistant xenografts in vivo, which is concomitant with the decreased expression of UCP-2. These findings provided direct evidences that the miR133a/UCP-2 axis might play an essential role in the development of Doxorubicin-resistance in breast cancer cells, suggesting that the miR133a/UCP-2 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in breast cancer.     

Depression,Social Support,and Coping Styles among Pregnant Women after the Lushan Earthquake in Ya’an,China

Aim

The aim of this study is to assess the depression of pregnant women in the aftermath of an earthquake, and to identify the social support that they obtained, their coping styles and socio-demographic factors associated with depression.

Methods

A total of 128 pregnant women from three hospitals in the epicenter area were recruited immediately after the Ya’an earthquake. Their depression was investigated using the Edinburgh Postnatal Depression Scale (EPDS) with a cutoff score of 14; the social support that they obtained was measured using the Social Support Questionnaire; and their coping styles were assessed using the Coping Styles Questionnaire.

Results

Immediately after the earthquake, the incidence rate of depression in pregnant women was 35.2%, higher than that of the general pregnant population (7%-14%). The EPDS scores were significantly correlated with gestation age at the time of the earthquake, objective support, subjective support, use of support, negative coping style, and positive coping style. The regression analysis indicated that risk factors of prenatal depression include the number of children, relatives wounded, subjective support, and coping styles. A further analysis of the interaction between social support and two types of coping styles with depression showed that there was interaction effect between subjective social support and positive coping styles in relation to EPDS scores. There was an inverse relationship between low EPDS scores and positive coping styles and high social support, and vice versa.

Conclusion

The timing of the occurrence of the earthquake may not necessarily affect the progress of the illness and recovery from depression, and psychological intervention could be conducted in the immediate aftermath after the earthquake. The impact of coping styles on prenatal depression appeared to be linked with social support. Helping pregnant women to adopt positive coping styles with good social support after a recent major earthquake, which is a stressor, may reduce their chances of developing prenatal depression.     

Hexanucleotide Repeat Expansion in C9ORF72 Is Not Detected in the Treatment-Resistant Schizophrenia Patients of Chinese Han

Hexanucleotide (GGGGCC) repeat expansion in C9ORF72 (HRE) causes frontotemporal lobar degeneration, frontotemporal dementia–amyotrophic lateral sclerosis, and amyotrophic lateral sclerosis. HRE was also seen in the genomes of patients suffering from several other degenerative diseases. However, whether it is present in the treatment-resistant schizophrenia patients remains unknown. Genotyping 386 patients suffering from treatment-resistant schizophrenia using the method of Repeat-Primed PCR, we reported here that no HRE was detected in the patients of Chinese Han.     

Impaired Frontal-Basal Ganglia Connectivity in Male Adolescents with Conduct Disorder

Alack of inhibition control has been found in subjects with conduct disorder (CD), but the underlying neuropathophysiology remains poorly understood. The current study investigated the different mechanism of inhibition control in adolescent-onset CD males (n = 29) and well-matched healthy controls (HCs) (n = 40) when performing a GoStop task by functional magnetic resonance images. Effective connectivity (EC) within the inhibition control network was analyzed using a stochastic dynamic causality model. We found that EC within the inhibition control network was significantly different in the CD group when compared to the HCs. Exploratory relationship analysis revealed significant negative associations between EC between the IFG and striatum and behavioral scale scores in the CD group. These results suggest for the first time that the failure of inhibition control in subjects with CD might be associated with aberrant connectivity of the frontal–basal ganglia pathways, especially between the IFG and striatum.     

树鼩脐带间充质干细胞与抗小鼠、人CD抗体的交叉反应性

目的观察树鼩的细胞是否与抗鼠或抗人的CD抗体反应。方法采树鼩外周血与小鼠的CD3、CD4、CD8抗体反应。再分离培养树鼩的脐带间充质干细胞,分别与抗小鼠的CD29-FITC、Sca-1-PE、CD90-PE反应,与抗人的CD44-FITC、CD29-FITC、CD13-FITC、CD34-FITC反应。结果树鼩外周血与小鼠的CD3、CD4、CD8抗体不发生反应,但树鼩的脐带间充质干细胞与抗小鼠的CD29-FITC抗体发生反应,阳性率为99.8﹪。树鼩的脐带间充质干细胞与抗人的CD44-FITC抗体发生反应,阳性率为99.7﹪。结论树鼩的外周血与小鼠的CD抗体不反应,但树鼩的脐带间充质干细胞与小鼠的CD29-FITC抗体和人的CD44-FITC抗体反应效果较好。     

Transforming Growth Factor TGFβ Increases Levels of Microtubule-Associated Protein MAP1S and Autophagy Flux in Pancreatic Ductal Adenocarcinomas

Background and Aim

Autophagy is a cellular process to regulate the turnover of misfolded/aggregated proteins or dysfunctional organelles such as damaged mitochondria. Microtubule-associated protein MAP1S (originally named C19ORF5) is a widely-distributed homologue of neuronal-specific MAP1A and MAP1B with which autophagy marker light chain 3 (LC3) was originally co-purified. MAP1S bridges autophagic components with microtubules and mitochondria through LC3 and positively regulates autophagy flux from autophagosomal biogenesis to degradation. The MAP1S-mediated autophagy suppresses tumorigenesis as suggested in a mouse liver cancer model and in prostate cancer patients. The TGFβ signaling pathway plays a central role in pancreatic tumorigenesis, and high levels of TGFβ suggest a tumor suppressive function and predict a better survival for some patients with resectable pancreatic ductal adenocarcinoma. In this study, we try to understand the relationship between TGFβ and MAP1S-mediated autophagy in pancreatic ductal adenocarcinoma.

Methods

We collected the tumor and its adjacent normal tissues from 33 randomly selected patients of pancreatic ductal adenocarcinomas to test the association between TGFβ and autophagy markers MAP1S and LC3. Then we tested the cause and effect relation between TGFβ and autophagy markers in cultured pancreatic cancer cell lines.

Results

Here we show that levels of TGFβ and autophagy markers MAP1S and LC3 are dramatically elevated in tumor tissues from patients with pancreatic ductal adenocarcinomas. TGFβ increases levels of MAP1S protein and enhances autophagy flux.

Conclusion

TGFβ may suppress the development of pancreatic ductal adenocarcinomas by enhancing MAP1S-mediated autophagy.