Radix Scrophulariae Extracts Exert Effect on Hyperthyroidism via MST1/Hippo Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of Radix Scrophulariae (RS) extracts in the treatment of hyperthyroidism rats by regulating proliferation, apoptosis, and autophagy of thyroid cell through the mammalian sterile 20-like kinase 1 (MST1)/Hippo pathway.@*METHODS@#Twenty-four rats were randomly divided into 4 groups according to a random number table: control, model group, RS, and RS+Hippo inhibitor (XMU-MP-1) groups (n=6 per group). Rats were gavaged with levothyroxine sodium tablet suspension (LST, 8 μ g/kg) for 21 days except for the control group. Afterwards, rats in the RS group were gavaged with RS extracts at the dose of 1,350 mg/kg, and rats in the RS+XMU-MP-1 group were gavaged with 1,350 mg/kg RS extracts and 1 mg/kg XMU-MP-1. After 15 days of administration, thyroid gland was taken for gross observation, and histopathological changes were observed by hematoxylin-eosin staining. The structure of Golgi secretory vesicles in thyroid tissues was observed by transmission electron microscopy. The expression of thyrotropin receptor (TSH-R) was observed by immunohistochemistry. Terminal-deoxynucleoitidyl transferase mediated nick end labeling assay was used to detect cell apoptosis in thyroid tissues. Real-time quantity primer chain reaction and Western blot were used to detect the expressions of MST1, p-large tumor suppressor gene 1 (LATS1), p-Yes1 associated transcriptional regulator (YAP), proliferating cell nuclear antigen (PCNA), G1/S-specific cyclin-D1 (Cyclin D1), B-cell lymphoma-2 (Bcl-2), Caspase-3, microtubule-associated proeins light chain 3 II/I (LC3-II/I), and recombinant human autophagy related 5 (ATG5). Thyroxine (T4) level was detected by enzyme-linked immunosorbent assay.@*RESULTS@#The thyroid volume of rats in the model group was significantly increased compared to the normal control group (P<0.01), and pathological changes such as uneven size of follicular epithelial cells, disorderly arrangement, and irregular morphology occurred. The secretion of small vesicles by Golgi apparatus was reduced, and the expressions of receptor protein TSH-R and T4 were significantly increased (P<0.01), while the expressions of MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 were significantly decreased (P<0.01). The expressions of Bcl-2, PCNA, and cyclin D1 were significantly increased (P<0.01). Compared with the model group, RS extracts reduced the volume of thyroid gland, improved pathological condition of the thyroid gland, promoted secretion of the secretory vesicles with double-layer membrane structure in thyroid Golgi, significantly inhibited the expression of TSH-R and T4 levels (P<0.01), upregulated MST1, p-LATS1, p-YAP, Caspase-3, LC3-II/I, and ATG5 expressions (P<0.01), and downregulated Bcl-2, PCNA, and Cyclin D1 expressions (P<0.01). XMU-MP-1 inhibited the intervention effects of RS extracts (P<0.01).@*CONCLUSION@#RS extracts could inhibit proliferation and promote apoptosis and autophagy in thyroid tissues through MST1/Hippo pathway for treating hyperthyroidism.

Resveratrol inhibits pancreatic stellate cell activation through modulating the Hippo signal pathway / 西安交通大学学报(医学版)

Objective: To investigate the inhibitory effect of resveratrol on the activation of pancreatic stellate cells and to explore the role of the Hippo signaling pathway in it. Methods: Pancreatic stellate cells (PSCs) were isolated by trypsin digestion and then treated with resveratrol. Western blot and immunofluorescence staining were used to detect the activation of the cells. Transwell invasion assay and Western blot were used to detect the invasive ability of Panc-1 and the expressions of E-cadherin and Vimentin in pancreatic cancer cells (PCs)-PSCs indirect co-culture conditions. Results: Resveratrol could inhibit the activation of PSCs and inhibit YAP, CTGF and CYR61 expressions. After co-culture with PSCs condition medium pre-treated with resveratrol, the invasive ability of Panc-1 cells was significant reduced (P<0.05). E-cadherin expression was increased while Vimentin expression was decreased (P<0.05). Conclusion: Resveratrol can inhibit the activation of pancreatic stellate cells via inhibiting YAP expression and can also inhibit the invasion and EMT transformation of Panc-1 cells under co-culture conditions.

Progress in genetics of NPHP related signaling pathway / 国际儿科学杂志

Nephronophthisis(NPHP),an autosomal recessive cystic kidney disease,is the most frequent genetic cause for end stage renal failure in the first thirty years of life.NPHP can be caused by Mutations in 22 genes(NPHP1-20,NPHPL1,NPHPL2),with abnormal structure or function of primary cilia,involved in Hh,Wnt,Hippo,DDR signaling pathways.Elucidating the pathogenic genes and possible pathogenesis would make a difference in prevention,diagnosis,treatment,prognosis,and genetic counseling of NPHP.This article reviews the pathogenic genetics and related signaling pathways.

Yes-associated protein modulation of human glioma cell growth invitro / 中国肿瘤临床

Objective:This study aimed to explore the effect of Yes-associated protein (YAP) on the growth of the human glioma cell line LN229. Methods:YAPsiRNA was transfected into LN229 cells to knock down the YAP expression. The downregulation of the YAP expression was identified through Western Blot analysis. Colorimetric assay using methyl-thiazolyl-tetrazolium was applied to evaluate cell proliferation ability. Cell invasive activity was examined using Transwell assay. Flow cytometry and AnnexinV were used to detect cell cycle and apoptosis, respectively. The relevant molecules regulating proliferation, invasion, cell cycle progression, and apoptosis were examined through Western Blot analysis. Results:The YAP expression was downregulated after YAPsiRNA was trans-fected into LN229 glioma cells. Reduced YAP expression could arrest the cell cycle at G0/G1 phase, inhibit cell proliferation and inva-sion, and promote apoptosis. The expression of the proliferating cell nuclear antigen (Ki-67), matrix metallopeptidase-9 (MMP-9), cy-clin D1, and Bcl-2 were downregulated. Conclusion:The downregulation of YAP in LN229 cells suppresses cell proliferation and inva-sion, as well as promotes cell apoptosis. This study provides a novel evidence for further study on Hippo-YAP signal pathway in molec-ular pathology of glioma.