Rationale: Chemoresistance is a major challenge in the clinical management of patients with breast cancer. Mutant p53 proteins tend to form aggregates that promote tumorigenesis in cancers. We here aimed to explore the mechanism for the generation of mutant p53 aggregates in breast cancer and assess its role in inducing chemoresistance. Methods: Expression of BCL2-associated athanogene 2 (BAG2) was evaluated by qRT-PCR, western blotting, and immunohistochemistry in breast cancer patient specimens. The significance of BAG2 expression in prognosis was assessed by Kaplan-Meier survival analysis and the Cox regression model. The roles of BAG2 in facilitating the formation of mutant p53 aggregates were analyzed by co-immunoprecipitation, immunofluorescence, and semi-denaturing detergent-agarose gel electrophoresis assays. The effects of BAG2 on the chemoresistance of breast cancer were demonstrated by cell function assays and mice tumor models. Results: In the present study, we found that BAG2 was significantly upregulated in relapse breast cancer patient tissues and high BAG2 was associated with a worse prognosis. BAG2 localized in mutant p53 aggregates and interacted with misfolded p53 mutants. BAG2 exacerbated the formation of the aggregates and recruited HSP90 to promote the propagation and maintenance of the aggregates. Consequently, BAG2-mediated mutant p53 aggregation inhibited the mitochondrial apoptosis pathway, leading to chemoresistance in breast cancer. Importantly, silencing of BAG2 or pharmacological targeting of HSP90 substantially reduced the aggregates and increased the sensitivity of chemotherapy in breast cancer. Conclusion: These findings reveal a significant role of BAG2 in the chemoresistance of breast cancer via exacerbating mutant p53 aggregates and suggest that BAG2 may serve as a potential therapeutic target for breast cancer patients with drug resistance.
The structural characteristics of rare-earth permanent magnet synchronous generator with radial excitation was analyzed.The way to determine the sizes of permanent magnet and the new ways of capacitance compensation and calculation were presented.The simply operating principle of voltage-stabilizing circuit was also presented and the experimental results were given and analyzed.
Background:Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age worldwide. Traditional Chinese Medicine (TCM) effectively alleviates the clinical symptoms of PCOS. Methods: Relevant literature on TCM for treating PCOS was collected from the China National Knowledge Infrastructure (CNKI), and data mining tools identified the core drug group. The TCMSP database retrieved the active ingredients and targets of the core drug group and through screening data from GeneCard, OMIM, PharmGkb, DrugBank, and Uniprot disease databases to obtain common targets for drugs and diseases. The Cytoscape software constructed the "ingredients-targets" network. Meanwhile, the protein interaction database (STRING) constructed the potential target protein interaction network. The CytoNCA plug-in of Cytoscape screened the core targets. GO functional, and KEGG enrichment analyses of intersection targets were performed using the R statistical software. The molecular docking technology verified the relationship between the core ingredients and targets. Results: A total of 175 prescriptions were extracted from the CNKI literature, including 212 Chinese medicinals. Angelica sinensis, Cuscuta chinensis, and Rehmannia root were selected as the core drug group. Preliminary screening obtained 13 active ingredients and 446 potential targets. The mechanism of action is related to the 175 significantly enriched pathways, including lipid and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, MAPK, TNF, and PI3K-Akt signaling pathways. The absolute value of binding energies of quercetin, kaempferol, and isorhamnetin with NCOA2, PGR, and PTGS2 were over 5.0 Kcal / mol, indicating good docking results. Conclusions: The main active ingredients, action targets, and related pathways for treating PCOS using Angelica sinensis, Cuscuta chinensis, and Rehmannia root is discussed. The study confirmed the effects of Angelica sinensis, Cuscuta chinensis, and Rehmannia root for treating PCOS, providing a reference for clinical practice.
To examine the association of dietary patterns with chronic diseases and their indicators.Using the data from 2002 National Nutrition and Health Survey, we divided the subjects into clusters according to their dietary patterns classified by different percentage of energy intake from cereal foods, carbohydrate and fat, respectively. The analysis of variance was used to identify the difference in chronic disease prevalence across clusters of subjects while controlling for age, gender and geographic regions. Logistic regression analysis was applied to calculate the odd ratios (OR) for association of chronic disease and each dietary pattern, after adjusted for age, gender, region, energy intake, leisure time.The higher percentage of energy intake from cereals was significantly associated with lower body mass index (BMI), lower total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C). While it was significantly associated with lower risk for overweight/obesity, hypertension, high total cholesterol, high triglyceride (TG) and high LDL-C, but the prevalence of underweight was significantly higher in the cluster of subjects with cereal energy share more than 75%. The higher percentage of energy intake from fat was significantly associated with higher BMI, higher total cholesterol and higher LDL-C, which accordingly, was significantly associated with higher risk for overweight/obesity, hypertension, high total cholesterol, triglyceride and high LDL-C.Our study confirmed the important role of dietary pattern in chronic disease control; in particular, appropriate percentage of energy intake from fat and cereals/carbohydrates are beneficial to control and prevention of chronic diseases.
[Purpose] To investigate the characteristics of cancer incidence from 35 cancer registries in China. [Methods] The population-based cancer registration data of all new cases were collected from 35 local cancer registries in China. The data were sorted, checked and analyzed according to “China Cancer Registration Guideline”and“Cancer Registration: Principles and Methods, IARC”. [Results] Thirty-five cancer registries covered 56 032 310 population(male,28 433 441; female, 27 598 869), accounted for 4.34% of total population in China. The new incidence cases were 120 942, 68 623 for male and 52 319 for female in 2003. The crude incidence for all cancer registries ranked from 73.8/105 to 372.7/105. The highest crude incidence was 372.7/105 in Yangzhong city, secondly, 337.7/105 in Shanghai; the lowest crude incidence was 73.8/105 in Shenzhen city. [Conclusion] Lung, stomach, esophagus,liver cancer and female breast cancer are the leading cancer incidence which harm health seriously. It should be the major issue in cancer prevention and control.
A dynamic energy dispatch strategy based on frequency bias is presented for the photovoltaic-diesel-energy storage microgrid, which aims at frequency fluctuation caused by the sudden change of load and the characteristic of photovoltaic microsource. According to the frequency bias forming principle of diesel generator and the demand for steady operation and power quality of microgrid, a three-stage dynamic energy dispatch strategy based on proportional-derivative (PD) preceding is achieved, which overcomes the shortcoming of PD strategy. This modified strategy is implemented in the established microgrid system, and two pairs of contrast experiments are made to verify the suppression effect of system frequency fluctuation. The experiments have proved that this strategy for dynamic energy dispatching can mitigate the frequency fluctuation caused by photovoltaic microsource and load sudden change to some extent, thus it is a feasible solution to improving power quality and stability of microgrid.
Chronic diseases which claim 85% of deaths,have become the major threat to human health in China.However,despite the central government's emphasis and years of experience,the work of prevention and control of chronic diseases in China is still faced with great challenges,for instance lack of multi-department cooperation,maro policy breakthrough and funding especially preventative investment.It's required to establish multi-discipline and multi-department system for chronic disease prevention and control,increase investment and adjust expenditure structure,advance health system ability and improve public policy,so as to promote public policy in terms of chronic disease prevention and control.
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