What we have learnt from Drosophila model organism: the coordination between insulin signaling pathway and tumor cells.

Cancer development is related to a variety of signaling pathways which mediate various cellular processes including growth, survival, division and competition of cells, as well as cell-cell interaction. The insulin signaling pathway interacts with different pathways and plays a core role in the regulations of all these processes. In this study, we reviewed recent studies on the relationship between the insulin signaling pathway and tumors using the Drosophila melanogaster model. We found that on one hand, the insulin pathway is normally hyperactive in tumor cells, which promotes tumor growth, and on the other hand, tumor cells can suppress the growth of healthy tissues via inhibition of their insulin pathway. Moreover, systematic disruption in glucose homeostasis also facilitates cancer development by different mechanisms. The studies on how the insulin network regulates the behaviors of cancer cells may help to discover new therapeutic treatments for cancer.

1-Hydroxypyrene mediates renal fibrosis through aryl hydrocarbon receptor signalling pathway.

BACKGROUND AND PURPOSE: In chronic kidney disease (CKD), patients inevitably reach end-stage renal disease and require renal transplant. Evidence suggests that CKD is associated with metabolite disorders. However, the molecular pathways targeted by metabolites remain enigmatic. Here, we describe roles of 1-hydroxypyrene in mediating renal fibrosis. EXPERIMENTAL APPROACH: We analysed 5406 urine and serum samples from patients with Stage 1-5 CKD using metabolomics, and 1-hydroxypyrene was identified and validated using longitudinal and drug intervention cohorts as well as 5/6 nephrectomised and adenine-induced rats. KEY RESULTS: We identified correlations between the urine and serum levels of 1-hydroxypyrene and the estimated GFR in patients with CKD onset and progression. Moreover, increased 1-hydroxypyrene levels in serum and kidney tissues correlated with decreased renal function in two rat models. Up-regulated mRNA expression of aryl hydrocarbon receptor and its target genes, including CYP1A1, CYP1A2 and CYP1B1, were observed in patients and rats with progressive CKD. Further we showed up-regulated mRNA expression of aryl hydrocarbon receptor and its three target genes, plus up-regulated nuclear aryl hydrocarbon receptor protein levels in mice and HK-2 cells treated with 1-hydroxypyrene, which caused accumulation of extracellular matrix components. Treatment with aryl hydrocarbon receptor short hairpin RNA or flavonoids inhibited mRNA expression of aryl hydrocarbon receptor and its target genes in 1-hydroxypyrene-induced HK-2 cells and mice. CONCLUSION AND IMPLICATIONS: Metabolite 1-hydroxypyrene was demonstrated to mediate renal fibrosis through activation of the aryl hydrocarbon receptor signalling pathway. Targeting aryl hydrocarbon receptor may be an alternative therapeutic strategy for CKD progression.

Visualization Analysis of the Trends and Hot Spots of BiochemistryExperiment Teaching Based on CiteSpace / 中国生物化学与分子生物学报

Biochemistry is a very important basic course for biology and medical disciplines, and it is one of the most rapidly developing and dynamic disciplines since the 21st century. Since theoretical teaching of biochemistry is very abstract, experiment teaching is an important part of understanding relevant theories and mastering practical skills. In the process of experiment teaching, it is always a key concern for teachers to keep abreast of new teaching concepts, new teaching methods, new teaching hotspots, and keep up with teaching trends. To this end, in this paper, the annual number of published papers, periodical distribution, research keywords, current status of research, hotspots and development trends of biochemical experiment teaching and research in China from 2011. 1. 1 to 2020. 12. 31 were visualized and analyzed by using CiteSpace with China National Knowledge Infrastructure (CNKI) as the data source. It was found that the number of articles published in each year remained basically stable, and the high frequency words were " biochemistry", " experimental teaching", " teaching reform", " biochemistry experiment", " reform", " teaching method", " innovation ability" and " teaching mode". The words with higher intensity are " flipped classroom" and " microlearning". Through timeline analysis, we found that the identities of " teaching" and " learning" are being exchanged, and improving students' independent learning ability has become the mainstream. The teaching mode combining advanced technology such as " virtual simulation" and " online teaching" has become the development trend and frontier of biochemistry experiment teaching. This paper aims to provide reference for the sustainable development of biochemistry experiment teaching in China through the above analysis.

microRNAs in chronic kidney disease.

Chronic kidney disease (CKD) results in high morbidity and mortality worldwide causing a huge socioeconomic burden. MicroRNA (miRNA) exert critical regulatory functions by targeting downstream genes and have been associated with many pathophysiologic processes including CKD. In fact, many studies have shown that the expression of various miRNAs was significantly changed in CKD. Current investigations have focused on revealing the relationship between miRNAs and CKD states including diabetic nephropathy, lupus nephritis, focal segmental glomerulosclerosis and IgA nephropathy. In this review, we summarize the latest advances elucidating miRNA involvement in the progression of CKD and demonstrate that miRNAs have the potential to be effective biomarkers and therapeutic targets for subsequent treatment.

Three-dimensional finite element analysis on stress distribution after greater trochanter bone flap for treating osteonecrosis of the femoral head / 中国组织工程研究

BACKGROUND: Three-dimensional finite element analysis has been used by many scholars from department of orthopedics, but the results of postoperative evaluation of hip preserving treatment for osteonecrosis of femoral head are different. OBJECTIVE: To study the biomechanical changes of the femoral head and the biomechanical changes of the proximal femur after greater trochanter bone flap for the treatment of femoral head necrosis using three-dimensional finite element method, and to verify the mechanical safety and effectiveness. METHODS: One case of unilateral femoral head necrosis in ARCOIII stage undergoing parallel vascularized greater trochanter bone flap transplantation was selected. Computed Tomography data of proximal femur were collected before and 6 months after the operation, and preserved in DICOM format. With the aid of computer technology, professional medical modeling software, MIMICS and HYPERMESH, were used to establish the three-dimensional geometric models of the proximal femur. These models were divided into normal group, necrosis group and repair group. Finite element analysis software ANSYS was utilized to simulate human body standing and movement in different situations. The model was divided by free mesh, and given material parameters to establish normal proximal femur, femoral head necrosis and bone defect. Greater trochanter bone flap was applied in repairing three-dimensional finite element model of bone defect. Loads were loaded on different finite element models. The maximum displacement of the femoral head and the stress distribution in the proximal femur of the three groups were observed under different loading models. RESULTS AND CONCLUSION: (1) Under the same load, the maximum displacement of the three sets of models was 0.61 mm in the normal group, 0.66 mm in the necrosis group, and 0.61 mm in the repair group, respectively. Maximum Von Mises stress was greater in necrosis model than in the normal molding. The maximum Von Mises stress gradually decreased in the repair model, and was close to normal value. (2) Three groups of models showed stress concentration above the rotor in femoral neck region. The maximum stress in the trochanteric position was higher in necrosis models than in normal models. The maximum stress in this region gradually increased after repair, but was still lower than the failure stress of bone. (3) The results confirm that the maximum stress and the maximum displacement are closer to the normal value after greater trochanter bone flap for treatment of osteonecrosis of the femoral head. The greater trochanter is safe and reliable for repairing bone defect of femoral head.

The Transgenic RNAi Project at Harvard Medical School: Resources and Validation.

To facilitate large-scale functional studies in Drosophila, the Drosophila Transgenic RNAi Project (TRiP) at Harvard Medical School (HMS) was established along with several goals: developing efficient vectors for RNAi that work in all tissues, generating a genome-scale collection of RNAi stocks with input from the community, distributing the lines as they are generated through existing stock centers, validating as many lines as possible using RT-qPCR and phenotypic analyses, and developing tools and web resources for identifying RNAi lines and retrieving existing information on their quality. With these goals in mind, here we describe in detail the various tools we developed and the status of the collection, which is currently composed of 11,491 lines and covering 71% of Drosophila genes. Data on the characterization of the lines either by RT-qPCR or phenotype is available on a dedicated website, the RNAi Stock Validation and Phenotypes Project (RSVP, http://www.flyrnai.org/RSVP.html), and stocks are available from three stock centers, the Bloomington Drosophila Stock Center (United States), National Institute of Genetics (Japan), and TsingHua Fly Center (China).

Behaviors of uis ng foreign medical and health information resources on Intre net:A review / 中华医学图书情报杂志

Thirty investigation items coveredin 30 foreign papers published by 17 countries were analyzed with medical and healthinformation resourceson Internet as its starting point , followed by an elaboration on the informa-tion needs, information access, information retrieval, information assessmentand information using behaviors in different user groups.

Correlation of DPPIV expression with clinicopathological features and prognosis in epithelial ovarian carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of dipeptidyl peptidase IV (DPPIV) in patients with epithelial ovarian carcinoma (EOC) and its clinical significance.</p><p><b>METHODS</b>Immunohistochemistry (IHC) was used to detect the expression of DPPIV protein in 378 formalin-fixed paraffin-embedded EOC tissue samples. The expression of DPPIV mRNA in 86 EOC tissue samples were examined by in situ hybridization (ISH) using specific FITC-labelled RNA probes. Forty-two samples of normal ovarian tissues were used as control. Statistical analyses were carried out by Chi-square test, Spearman rank correlation and Kaplan-Meier method.</p><p><b>RESULTS</b>Among the 378 epithelial ovarian carcinomas, 351 (92.9%) showed a positive expression of DPPIV protein, while only 25/42 (59.5%) of normal ovaries had a positive expression by semi-quantitative IHC analysis. The expression level of DPPIV protein was significantly lower in the normal ovaries than that in ovarian carcinomas (chi(2) = 18.4, P = 0.001). There was no significant correlation between the expression of DPPIV protein and age, FIGO stage and histological grade (P > 0.05). However, the expression of DPPIV protein was significantly associated with histological type (chi(2) = 28.5, P = 0.005). The patients with high level expression of DPPIV protein likely had a poor prognosis in terms of overall survival (P = 0.02). Of the 86 patients, 84 (97.7%)showed positive expression of DPPIV mRNA, also higher than that in normal ovarian tissues (P < 0.05). A statistically significant correlation between DPPIV mRNA and protein expression was observed (r(s) = 0.66, P = 0.001).</p><p><b>CONCLUSION</b>DPPIV may be involved in the carcinogenesis of ovarian cancer, and may become a potential prognostic marker for epithelial ovarian carcinoma.</p>

Expression of seprase in effusions from patients with epithelial ovarian carcinoma / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Seprase plays an important role in malignant cell invasion and metastasis by degrading the extracellular matrix. However, its clinical significance remains largely unknown. The objective of the current study was to evaluate the expression of seprase in effusions from patients with epithelial ovarian carcinoma and its clinical values.</p><p><b>METHODS</b>Immunohistochemistry was used to examine the expression of seprase protein in a series of 74 malignant peritoneal (n = 64) and pleural (n = 10) effusions from Norwegian patients with epithelial ovarian carcinoma. Additionally, 34 effusions were evaluated using the Western blotting. Nine reactive effusions, obtained from patients with benign lesions, served as a control group. Statistical analyses were carried out by Chi-square test and Kaplan-Meier method.</p><p><b>RESULTS</b>In the 74 malignant effusion specimens, 57 (77.02%) were positive for seprase, while only 2 (22.22%) of the control group were positively stained (P = 0.001). In the malignant effusions, 17 (22.97%), 22 (29.73%), 22 (29.73%), 13 (17.57%) had negative, weak, moderate and strong seprase protein expression, respectively. The expression of seprase protein was predominant in cytoplasm of carcinoma cells. Increased seprase protein was negatively associated with the overall survival rate of the patients (P = 0.03). However, there was no significant correlation between protein expression and FIGO stage, age, histology, and histological grade. By Western blotting, 27 of the 34 effusions showed the presence of both 170-kD dimeric form and 97-KD monomeric form of seprase while only 1 of the 34 had 170-KD dimeric form, which was consistent with the results of immunohistochemistry (P = 0.05).</p><p><b>CONCLUSIONS</b>Seprase may be involved in the development of ovarian cancer, and is a potential predictive marker for the disease.</p>

Expression and significance of Edg4 and Edg7 in the placentas of patients with hypertensive disorder complicating pregnancy / 中华妇产科杂志

Objective To study Edg4 and Edg7 expression in placenta of women with hypertensive disorder complicating pregnancy,and to investigate the relation between the expression of lysophosphatidic acid(LPA)and hypertensive disorder complicating pregnancy.Methods Immunohistochemical SP method was used to measure the expressions of Edg4 and Edg7 in placenta of women with normal pregnancy,20 women with gestational hypertension,20 with mild preeclampsia,and with severe preeclampsia.Results (1)Location:immunohistoehemical staining for Edg4 and Edg7 protein were located at the membrane and endoehylema of cytotrophoblast as well as decidua cells.(2)The positive expression of Edg4 protein and Edg7 protein on membrane and endochylema of cytotrophoblast was 25% and 20%(normal women),60% and 40%(gestational hypertension),80% and 65%(mild preeclampsia),and 83.3% and 86.7%(severe preeclampsia).The expression of Edg4 and Edg7 protein in mild preeclampsia and severe preeclampsia was significantly correlated with the degree of differentiation(P0.05). (3)The positive expression of Edg4 protein and Edg7 protein on membrane and endochylema of decidua was 20% and 25%(normal pregnancy),55% and 50%(gestational hypertension),70% and 55%(mild preeclampsia),and 83.3% and 73.3%(severe preeclampsia)respectively.The expression of Edg4 and Edg7 protein in mild preeclampsia and severe preeclampsia showed a significant correlation with the degree of differentiation(P0.05).Conclusions The high expression of Edg4 and Edg7 protein in the placentas of patients with hypertensive disorder complicating pregnancy indicates that LPA combines with Edg4 and Edg7,inducing the occurrence of hypertensive disorder complicating pregnancy.

Expression of phosphorylated protein kinase B and PTEN protein in ovarian epithelial cancer / 中华妇产科杂志

Objective To analyze the expression of phosphorylated protein kinase B(pAKT)and PTEN protein in ovarian epithelial cancer and to investigate the correlations between their expression and prognosis of ovarian epithelial cancers.Methods Expression of pAKT and PTEN in 12 normal ovarian tissues,20 benign tumors,12 borderline tumors and 80 cases of ovarian epithelial cancers were detected by immunohistochemical method,and their correlations were analyzed.Results The positive expression of pAKT in normal ovarian and benign tumor tissues were significantly lower than that in ovarian epithelial cancers(8%,10% vs 55%;P

Vector construction and silencing effect of Edg4 gene targeted small interfering RNA in ovarian cancer cell line / 中华妇产科杂志

Objective To construct the recombinant eukaryotic expression vector pRNAT-U6,1- siEdg4 which curries small interfering RNA(siRNA)of Edg4 and observe the silencing effect of Edg4 gene targeted siRNA in ovarian cancer cell line SKOV3.Methods The Edg4 gene-targeted hairpin siRNA sequence was designed according to the Edg4 sequence in Genbank,and the two complementary oligo nucleotide strands were synthesized and annealed and inserted into the pRNAT-U6.1 plasmid to build a recombinant Edg4 siRNA eukaryotic expression vector,which was sequenced and identified to contain the correct Edg4 siRNA sequence.The human ovarian carcinoma cell lines SKOV3 were transfeeted with the vector using lipofeetamine method.The efficiency of transfecting cells was observed with fluorescent microscope and the mRNA expression level of Edg4 gene was detected by real time quantitative PCR.The LPA levels in cell supernatants were detected using a biochemical method.And the apoptosis of SKOV3 cells induced by the vector was evaluated by flow cytometry.Results The recombinant eukaryotic expression vector was confirmed to contain correct Edg4 siRNA sequence by PCR and sequencing.After transfection large amounts of green fluorescence were seen in plasma and nuclei of SKOV3 cells and the positive cell rates were 64%.The expression level of Edg4 mRNA in transfeeted SKOV3 cell line was significantly decreased (0.05?0.01 vs 0.29?0.04,P