Reverse effect of Semaphorin-3F on rituximab resistance in diffuse large B-cell lymphoma via the Hippo pathway / 中华医学杂志(英文版)

BACKGROUND@#Exploring the underlying mechanism of rituximab resistance is critical to improve the outcomes of patients with diffuse large B-cell lymphoma (DLBCL). Here, we tried to identify the effects of the axon guidance factor semaphorin-3F (SEMA3F) on rituximab resistance as well as its therapeutic value in DLBCL.@*METHODS@#The effects of SEMA3F on the treatment response to rituximab were investigated by gain- or loss-of-function experiments. The role of the Hippo pathway in SEMA3F-mediated activity was explored. A xenograft mouse model generated by SEMA3F knockdown in cells was used to evaluate rituximab sensitivity and combined therapeutic effects. The prognostic value of SEMA3F and TAZ (WW domain-containing transcription regulator protein 1) was examined in the Gene Expression Omnibus (GEO) database and human DLBCL specimens.@*RESULTS@#We found that loss of SEMA3F was related to a poor prognosis in patients who received rituximab-based immunochemotherapy instead of chemotherapy regimen. Knockdown of SEMA3F significantly repressed the expression of CD20 and reduced the proapoptotic activity and complement-dependent cytotoxicity (CDC) activity induced by rituximab. We further demonstrated that the Hippo pathway was involved in the SEMA3F-mediated regulation of CD20. Knockdown of SEMA3F expression induced the nuclear accumulation of TAZ and inhibited CD20 transcriptional levels via direct binding of the transcription factor TEAD2 and the CD20 promoter. Moreover, in patients with DLBCL, SEMA3F expression was negatively correlated with TAZ, and patients with SEMA3F low TAZ high had a limited benefit from a rituximab-based strategy. Specifically, treatment of DLBCL cells with rituximab and a YAP/TAZ inhibitor showed promising therapeutic effects in vitro and in vivo .@*CONCLUSION@#Our study thus defined a previously unknown mechanism of SEMA3F-mediated rituximab resistance through TAZ activation in DLBCL and identified potential therapeutic targets in patients.

Historical Evolution and Textual Research on Classic Prescription Danggui Buxuetang / 中国实验方剂学杂志

Danggui Buxuetang， derived from Clarifying Doubts about Damage from Internal and External Causes （Volume 2）： Treatise on Heat Injury to Stomach Qi（《内外伤辨惑论卷中·暑伤胃气论》） by LI Dongyuan in the Jin and Yuan dynasties， is a classic and famous formula for tonifying qi and generating blood that has been inherited and promoted by successive generations of medical practitioners and has been included in the "Catalogue of Ancient Classical Prescriptions （First Batch）" published by the National Administration of Traditional Chinese Medicine in 2018. The paper analyzed the historical origin， composition， dosage， processing， preparation， decocting， and taking methods， efficacy， and application of the classic formula Danggui Buxuetang by consulting ancient and modern literature and combining the key information examination principles of ancient classic prescriptions. A total of 604 pieces of information on relevant ancient literature were collected， including 186 ancient Chinese medical books， of which 40 （five in the Jin and Yuan dynasties， 19 in the Ming Dynasty， and 16 in the Qing Dynasty） had detailed records of composition， processing， and dosage. Danggui Buxuetang is mainly comprised of Astragali Radix and Angelicae Sinensis Radix. According to the ancient and modern dose conversion， there are 37.3-38.1 g of Astragali Radix and 7.5-7.6 g of Angelicae Sinensis Radix in the formula. Astragali Radix is preferably fried with honey and Angelicae Sinensis Radix with wine. Astragali Radix and Angelicae Sinensis Radix are decocted with 600 mL of water to 300 mL， and taken warm before meals. The main effect of this formula are described in ancient books as blood deficiency and fever， with symptoms of muscle fever， dryness and heat， irritability and thirst， red eyes and face， sleeplessness in daytime and night， and surging and feeble pulse which is weak under hard pressing， and it is a famous formula for replenishing qi and generating blood. Modern research shows that Danggui Buxuetang is commonly used in the treatment of various kinds of anemia， diabetic nephropathy， tumors， and cardiovascular and cerebrovascular diseases. The above research results can provide a reference for the subsequent development and research on the classic formula Danggui Buxuetang.