Objective : To investigate the effect and mechanism of puerarin on the proliferation , invasion and apop- tosis of breast cancer cell HCC1806 via network pharmacology , molecular docking and in vitro experiments . Methods: The data of breast cancer and mitochondrial diseases were collected from GEO database , and the differentially expressed genes were analyzed by GEO2R . Overlapping genes between breast cancer and mitochondrial database were analyzed by Venn diagram . GO and KEGG enrichment analyzed the overlapping genes . STRING and Cyto- scape analyzed overlapping gene interaction networks and screen core genes . Interaction between puerarin and core genes was docked with autodock . Cell proliferation , apoptosis and invasion capacity were measured by CCK-8 , EdU , TUNEL and Transwell experiments , mitochondrial membrane potential was measured by Mito-Tracker experi- ments and protein expression levels were measured by Western blot. Anti-tumor efficacy of puerarin was analyzed by subcutaneous xenograft of breast cancer and immunohistochemical assay in vivo . Results : Among 132 overlap- ping genes in breast cancer and mitochondrial disease , 10 core differentially expressed genes were selected . Among these core genes , dual serine/threonine and tyrosine protein kinase (DST) was low expressed in breast cancer tis- sues . Puerarin bound to DST , up-regulated its expression , inhibited the proliferation and invasion of HCC1806 breast cancer cells , promoted breast cell apoptosis , increased the expression levels of apoptosis-related proteins Cleaved-Caspase 3 and Bax , down-regulated the expression of anti-apoptosis protein Bcl-2 , and decreased mito- chondrial membrane potential . In vivo , puerarin inhibited the growth of breast cancer and up-regulated the expres- sion of DST in tumor tissues . Conclusion Puerarin inhibits the proliferation and invasion of breast cancer cells , promotes the apoptosis of cancer cells and inhibits breast cancer growth .

This study aimed to investigate the effects of geniposide(GP) on the expression of prokineticin(PK2) and prokineticin receptor 1(PKR1) in db/db mice with diabetic nephropathy(DN), so as to explore how the PK2 signaling pathway participated in the pathological changes of DN and whether GP exerted the therapeutic effect through this signaling pathway. Male mice were randomly divided into four groups, namely db/m, db/db, db/db+GP, and db/m+GP groups, with five in each group. The mice in the db/db+GP and db/m+GP groups were gavaged with 150 mg·kg~(-1) GP for eight successive weeks. Afterwards, all the mice were sacrificed and the renal tissues were embedded. The morphological changes in glomerulus and renal tubules were observed by Masson and PAS staining. The expression levels of PK2, PKR1, and Wilm's Tumor Protein 1(WT_1) in podocytes were detected by immunohistochemistry, and the protein expression levels of PK2 and PKR1 in mouse kidney by Western blot. The morphological results showed serious glomerular and tubular fibrosis(Masson), high glomerular and tubular injury score(PAS), increased glomerular mesangial matrix, thickened basement membrane, exfoliated brush border of renal tubules, decreased WT_1 in glomerular podocytes, and massive loss of podocytes in the db/db group. After administration with GP, the glomerular and tubular fibrosis was alleviated, accompanied by improved glomerular basement membrane and renal tubule brush edge, and up-regulated WT_1. As revealed by further protein detection, in the db/db group, the expression levels of PK2 and PKR1 and p-Akt/Akt ratio declined, whereas the ratio of Bax/Bcl-2 rose. Ho-wever, PKR2 and p-ERK/ERK ratio did not change significantly. After administration with GP, the PK2 and PKR1 expression was elevated, and p-Akt/Akt ratio was increased. There was no obvious change in PKR2, Bax/Bcl-2 ratio, or p-ERK/ERK ratio. All these have demonstrated that GP improves the renal damage in DN mice, and PK2/PKR1 signaling pathway may be involved in such protection, which has provided reference for clinical treatment of DN with GP.
Animals ; Diabetes Mellitus ; Diabetic Nephropathies/genetics* ; Iridoids ; Kidney ; Male ; Mice ; Signal Transduction

OBJECTIVETo investigate the effect of tetrandrine (Tet) on the expression of bax, bcl-2, and transforming growth factor-β2 (TGF-β2) mRNA in cultured human fibroblasts of Tenon's capsules (TCFS) and explore its possible mechanism.

METHODSThe third passage of TCFS cultured in vitro were exposed to 1×10(-5) mol/L Tet for 24 h, and real-time fluorescence quantitative PCR was used to detect the changes in the expressions of bax, bcl-2, and TGF-β2 mRNA.

RESULTSThe expression level of bax mRNA was obviously higher, while bcl-2 and TGF-β2 mRNA levels were significantly lower in Tet-treated TCFS than those in the control cells (P<0.05).

CONCLUSIONTet can inhibit the proliferation of TCFS possibly by reducing the expressions of bcl-2 and TGF-β2 mRNA, enhancing the expression of bax mRNA and inducing cell apoptosis, suggesting its potential in preventing fibrous scar formation after glaucoma filtration surgery.

Apoptosis ; Benzylisoquinolines ; pharmacology ; Cell Proliferation ; drug effects ; Cells, Cultured ; Cicatrix ; metabolism ; prevention & control ; Fibroblasts ; cytology ; drug effects ; metabolism ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Tenon Capsule ; cytology ; Transforming Growth Factor beta2 ; genetics ; metabolism ; bcl-2-Associated X Protein ; genetics ; metabolism

Objective To study the mutation rate of hereditary deafness genes found in the newborn babies and to explore the feasibility of routine screening of congenital deafness for the newborns.Method The cord blood were taken to tcst four common deafness genes using gene chip technology in newborn infants born in our Hospital from May 2015 to May 2017 and screening of hearing was performed 48 hours after birth.x2 test was used to analyze the results of gene screening and the hearing screening data obtained after 42 days.Result A total of 2 615 newborns were enrolled in the study and 2 455 cases passed the hearing screening test 48 hours after birth (the passing rate was 93.9％).143 cases passed the hearing screening after 42 days with the passing rate of 99.3％.The mutation of deafness gene from the newborn's cord blood was detected in 107 cases with the rate of 4.1％.96 of 107 infants with deafness gene mutations passed the hearing screening (89.7％).While in infants without this mutation,2 502 cases passed the hearing screening (99.8％,2 502/2 508).The rate of hearing defects in children with deafness gene mutation was significantly higher than those without this gene mutation,and the difference was statistically significant (x2 =160.199,P ＜0.001).Of the 107 cases,the most common mutation was GJB2 (49 cases,45.8％),followed by SLC26A4 (37 cases,34.6％) and mtDNA 12SrRNA (13 cases,12.1％),while the GJB3 was the least (8 cases,7.5％).6 cases were diagnosed the neonate hearing loss at 3 months in 17 newborns who failed to pass repeat screening test 42 days after birth.Among them,hearing loss was caused by the mutation in 5 cases.Conclusion The main mutated genes in children with deafness were GJB2 and SLC26A4 in this study.The combination of hearing screening of newborns and gene test is clinically feasible.The deafness genes in the normal hearing carriers can be detected in time.It is of great advantage for early intervention and treament of the infants early.