Mechanism of Innate Immune Response Induced by Albizia julibrissin Saponin Active Fraction Using C2C12 Myoblasts.

Albizia julibrissin saponin active fraction (AJSAF), is a prospective adjuvant with dual Th1/Th2 and Tc1/Tc2 potentiating activity. Its adjuvant activity has previously been proven to be strictly dependent on its spatial co-localization with antigens, highlighting the role of local innate immunity in its mechanisms. However, its potential targets and pathways remain unclear. Here, its intracellular molecular mechanisms of innate immune response were explored using mouse C2C12 myoblast by integrative analysis of the in vivo and in vitro transcriptome in combination with experimental validations. AJSAF elicited a temporary cytotoxicity and inflammation towards C2C12 cells. Gene set enrichment analysis demonstrated that AJSAF regulated similar cell death- and inflammatory response-related genes in vitro and in vivo through activating second messenger-MAPK-CREB pathways. AJSAF markedly enhanced the Ca2+, cAMP, and reactive oxygen species levels and accelerated MAPK and CREB phosphorylation in C2C12 cells. Furthermore, Ca2+ chelator, CREB inhibitor, and MAPK inhibitors dramatically blocked the up-regulation of IL-6, CXCL1, and COX2 in AJSAF-treated C2C12 cells. Collectively, these results demonstrated that AJSAF induced innate immunity via Ca2+-MAPK-CREB pathways. This study is beneficial for insights into the molecular mechanisms of saponin adjuvants.

Treatment effect of apatinib combined chemotherapy as second-line or above therapy in patients with advanced gastric cancer or adenocarcinoma of the gastroesophageal junction.

This study aimed to compare the therapeutic effects between apatinib combined chemotherapy and chemotherapy alone as second-line or above therapy in advanced gastric cancer (GC) or adenocarcinoma of the gastroesophageal junction (AGEJ). The clinical data of advanced GC or AGEJ patients, including sex, age, Eastern Cooperative Oncology Group (ECOG) grading, chemotherapy regimen, pathological grading, location of primary lesion, previous gastrectomy, metastases, previous chemotherapy or radiotherapy were retrospectively collected, and the progression-free survival (PFS) was recorded. 127 patients underwent apatinib combined chemotherapy and 60 patients underwent chemotherapy regimen alone. Disease control rate (DCR) of patients with apatinib combined chemotherapy was higher than that of chemotherapy alone (P=0.033). A Kaplan-Meier (KM) plot showed that PFS was significantly longer in patients receiving apatinib combined chemotherapy than those treated by chemotherapy alone (P = 0.002). The PFS of patients with a number of metastatic lesions ≤ 2 was obviously longer than that of patients with a number of metastatic lesions > 2 (P < 0.001). Cox regression analysis revealed that PFS was independently associated with the number of metastatic lesions >2 (HR=2.129, 95% CI: 1.256-3.608, P=0.005) and treatment methods (chemotherapy alone or apatinib combined chemotherapy) (HR=1.427, 95% CI: 1.055-1.930, P=0.021). Compared with chemotherapy alone, apatinib combined chemotherapy could significantly improve DCR and prolong the PFS in advanced GC or AGEJ cases who had failed in at least first-line chemotherapy with acceptable tolerance.

Rapid annotation and structural characterization of saponins in the active fraction of Albizia julibrissin by high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry based on accurate mass database.

The purified active fraction of Albizia julibrissin saponin was proved to be a promising adjuvant candidate for vaccine. In this study, a simple, convenient, and practical strategy was established for characterizing the saponins in this purified active fraction. The personal accurate mass database including chemical structure, molecular formula, and theoretical mass was first constructed by collecting 110 reported known saponins from genus Albizia species. The raw data was obtained by high-performance liquid chromatography coupled with quadrupole time of flight mass spectrometry. The potential compounds were extracted from raw data, and matched with the accurate mass databases. A series of saponin compounds were predicted and their chemical structures were characterized by interpreting the tandem mass spectrometry data. A total of 29 saponins including 10 new compounds and 5 first found saponins from A. julibrissin were successfully characterized in this purified active fraction using this new strategy.