TRIB3 promotes pulmonary fibrosis through inhibiting SLUG degradation by physically interacting with MDM2

Pulmonary fibrosis (PF) is the pathological structure of incurable fibroproliferative lung diseases that are attributed to the repeated lung injury-caused failure of lung alveolar regeneration (LAR). Here, we report that repetitive lung damage results in a progressive accumulation of the transcriptional repressor SLUG in alveolar epithelial type II cells (AEC2s). The abnormal increased SLUG inhibits AEC2s from self-renewal and differentiation into alveolar epithelial type I cells (AEC1s). We found that the elevated SLUG represses the expression of the phosphate transporter SLC34A2 in AEC2s, which reduces intracellular phosphate and represses the phosphorylation of JNK and P38 MAPK, two critical kinases supporting LAR, leading to LAR failure. TRIB3, a stress sensor, interacts with the E3 ligase MDM2 to suppress SLUG degradation in AEC2s by impeding MDM2-catalyzed SLUG ubiquitination. Targeting SLUG degradation by disturbing the TRIB3/MDM2 interaction using a new synthetic staple peptide restores LAR capacity and exhibits potent therapeutic efficacy against experimental PF. Our study reveals a mechanism of the TRIB3-MDM2-SLUG-SLC34A2 axis causing the LAR failure in PF, which confers a potential strategy for treating patients with fibroproliferative lung diseases.

Research Progress on Application of Ultrasonic Microbubbles in Treatment of Liver Cancer / 肿瘤防治研究

Ultrasound therapy and considerable progress in molecular imaging technologies have allowed the use of ultrasonic microbubbles not only in image enhancement but also in targeted drug or gene delivery as drug or gene carriers, respectively. Hence, ultrasound microbubbles carrying drugs or genes have become a novel type of tumor-targeting therapy technology. They do not emit radiation and are thus safe. Additionally, they are efficient and easy to reuse and facilitate drug or gene release. All these features offer attractive prospects for the treatment of liver cancer and provide novel treatment ideas for the disease. This article reviews the mechanism, applications, and existing problems of ultrasonic microbubbles in the treatment of liver cancer.

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury. Pulmonary fibrosis (PF) is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells. In this study, we report that P21 expression was increased in alveolar epithelial type 2 cells (AEC2s) in a time-dependent manner following multiple bleomycin-induced PF. Repeated injury of AEC2s resulted in telomere shortening and triggered P21-dependent cell senescence. AEC2s with elevated expression of P21 lost their self-renewal and differentiation abilities. In particular, elevated P21 not only induced cell cycle arrest in AEC2s but also bound to P300 and β-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction. Meanwhile, senescent AEC2s triggered myofibroblast activation by releasing profibrotic cytokines. Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF. The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development, which suggests a potential strategy for the treatment of fibrotic lung diseases.

Advances in the amplification of HER2 in metastatic colorectal cancer / 国际肿瘤学杂志

Several studies have shown that human epidermal growth factor receptor 2 (HER2) amplification could be a predictive biomarker of resistance to anti-epidermal growth factor receptor monoclonal antibodies in patients with RAS wild-type metastatic colorectal cancer (mCRC). Dual HER2 inhibition with trastuzumab plus lapatinib or pertuzumab has shown promising preliminary anti-tumoral efficacy in RAS wild-type mCRC. HER2-targeted therapeutic strategies have the potential to change the treatment paradigm for a clinically relevant subgroup of patients with mCRC.

Applying emerging technologies to improve diabetes treatment.

Insulin, as the most important drug for the treatment of diabetes, can effectively control the blood glucose concentration in humans. Due to its instability, short half-life, easy denaturation and side effects, the administration way of insulin are limited to subcutaneous injection accompany with poor glucose control and low patient compliance. In recent years, emerging insulin delivery systems have been developed in diabetes research. In this review, a variety of stimuli-responsive insulin delivery systems with their response mechanism and regulation principle are described. Further, the introduction of stem cell transplantation and mobile application based delivery technologies are prudent for the diabetes treatment. This article also discusses the advantages and limitations of current strategies, along with the opportunities and challenges for future insulin therapy.

Screening different HPV genotypes infection and type-specific in cervical exfoliated cells of women in Yili area of Xinjiang Uygur Autonomous Region, China / 中华预防医学杂志

Objective@#To investigate the infection status and genotype distribution of cervical human papillomavirus (HPV) in women of different ethnic groups and different ages in Yili, Xinjiang Uygur Autonomous Region (Xinjiang).@*Methods@#By using the convenient sampling method, 54 760 women from November 2015 to May 2017 seeking for service in gynecological clinics in a general hospital in Yili, Xinjiang, were selected as the research subjects, and 3 445 samples of cervical mucous exfoliative cells were collected, and the social information of their ethnic and age was collected at the same time. The inclusion criteria were those with sexual life, cervical integrity, and ethnic groups for Han or Uygur or Kazak. PCR-reverse dot blot hybridization was used to detect HPV genotyping in exfoliated cells, and chi-square test was used to compare the difference of HPV positive rate among different ethnic groups. Then, according to ethnicity and age, the differences in positive rates of different ages and ethnic groups were compared in each layer.@*Results@#The positive rate of HPV was 25.6% (882 cases), of which the Han, Uygur and Kazakh were 27.9% (564 cases), 22.9% (196 cases) and 21.6% (122 cases), and the difference was statistically significant (χ2=13.80, P=0.001). The most prevalent high-risk genotypes of Han women were HPV16/52/58, accounting for 24.8% (140 cases), 17.7% (100 cases) and 9.8% (55 cases), respectively. The most prevalent high-risk genotypes of Uygur women were HPV16/52/53, accounting for 34.2% (67 cases), 12.8% (25 cases), 9.2% (18 cases), respectively. The most prevalent high-risk genotypes of Kazak were HPV16/52/53, accounting for 37.7% (46 cases), 17.2% (21 cases), 12.3% (15 cases), respectively. The highest rate of HPV in Uygur patients aged ≥61 years was 41.5% (22 cases), and the lowest in group 36-40 years old, 15.9% (21 cases), the difference between different age groups was statistically significant (χ2=35.01, P<0.001).@*Conclusion@#The positive rate of HPV infection among Han, Uygur and Kazak in Yili Prefecture of Xinjiang was different, and the HPV positive genotype differs among different ethnic groups.

Autophagy in ageing and ageing-related diseases / 药学学报

Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.

Establishment and application of TLR2 receptor-based cell screening model / 药学学报

TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.

Analysis on current situation of ordinary medical college undergraduates' contact with scientific research at early stage / 中华医学教育探索杂志

Objective To analyze the current situation and influence factors of ordinary medical college undergraduates' contact with scientific research at early stage in order to provide references for scientific research.Methods Totally 1940 students majoring in clinical medicine,imaging,traditional Chinese medicine and nursing (2008 -2010 grade) in China Three Gorges University were enrolled to do questionnaine and SPSS 17.0 was used to do statistical analysis.Results Totally 1653copies of questionnaires were collected from 1940 students,the recovery rate was 85.21％.Two hundred and nineteen students ( 13.25％ ) participated in scientific research,65.28％ students thought college propaganda to be ordinary,95.43％ students got benefits from scientific research.The main influence factors of scientific research were lack of time (23.73％),insufficient knowledge reserves (22.03％) and researchers' own problems (39.73％).Conclusions Medical school should expand the range of scientific research and strengthen propaganda.Medical students should arrange research time and constantly improve their comprehensive ability so as to achieve good results.