B7-H3 confers stemness characteristics to gastric cancer cells by promoting glutathione metabolism through AKT/pAKT/Nrf2 pathway / 中华医学杂志(英文版)

BACKGROUND@#Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism.@*METHODS@#GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis.@*RESULTS@#B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02).@*CONCLUSIONS@#B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.

Partial correlation analysis between blood pressure and anthropometric parameters among children / 中国组织工程研究

BACKGROUND: Blood pressure of children increases with ages, and is related to anthropometric parameters, diet, sports, and other factors. To analyze relative factor of a little high blood pressure of children provides a scientific evidence for prevention and cure of primary hypertension. OBJECTIVE: To investigate correlation between blood pressure and anthropometric parameters among children. DESIGN: Cross-sectional study. SETTING: Department of Hygiene of Weifang Medical College. PARTICIPANTS: According to cluster sampling, 1 546 pupils in grade three or four were selected from a primary school for physical examination and questionnaires. Totally 1 508 pupils with complete data were regarded as the subjects.METHODS: Partial correlation analysis was used to analyze correlation between blood pressure and anthropometric parameters among children.MAIN OUTCOME MEASURES: Correlation among anthropometric parameters, systolic pressure and diastolic pressure.RESULTS: ① Correlation coefficients of systolic pressure with sex, age, height, body mass, chest circumference of Peason were 0.078, 0.166, 0.337, 0.313 and 0.304 (P ＜ 0.01). ② Correlation coefficients of diastolic pressure with sex, age, height, body mass, chest circumference of Peason were 0.047, 0.120, 0.268, 0.271 and 0.251 (P ＜ 0.01). ③ After controlling two effect of anthropometric parameters on each other, systolic pressure and diastolic pressure were only correlated with height and chest circumference (P ＜ 0.01), but was not correlated with age, sex and body mass (P ＞ 0.05). CONCLUSION: After controlling the effect of anthropometric parameters on each other, systolic pressure and diastolic pressure of children were positively correlated with height and chest circumference.