Phytochemical Profiling and Biological Activities of Pericarps and Seeds Reveal the Controversy on "Enucleation" or "Nucleus-Retaining" of Cornus officinalis Fruits.

The fruits of Cornus officinalis are used not only as a popular health food to tonify the liver and kidney, but also as staple materials to treat dementia and other age-related diseases. The pharmacological function of C. officinalis fruits with or without seeds is controversial for treating some symptoms in a few herbal prescriptions. However, the related metabolite and pharmacological information between its pericarps and seeds are largely deficient. Here, comparative metabolomics analysis between C. officinalis pericarps and seeds were conducted using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry, and therapeutic effects were also evaluated using several in vitro bioactivity arrays (antioxidant activity, α-glucosidase and cholinesterase inhibitory activities, and cell inhibitory properties). A total of 499 secondary metabolites were identified. Thereinto, 77 metabolites were determined as key differential metabolites between C. officinalis pericarps and seeds, and the flavonoid biosynthesis pathway was identified as the most significantly different pathway. Further, 47 metabolites were determined as potential bioactive constituents. In summary, C. officinalis seeds, which demonstrated higher contents in total phenolics, stronger in vitro antioxidant activities, better α-glucosidase and butyrylcholinesterase inhibitory activities, and stronger anticancer activities, exhibited considerable potential for food and health fields. This work provided insight into the metabolites and bioactivities of C. officinalis pericarps and seeds, contributing to their precise development and utilization.

Regorafenib combined with programmed cell death-1 inhibitor against refractory colorectal cancer and the platelet-to-lymphocyte ratio's prediction on effectiveness.

BACKGROUND: The effectiveness of regorafenib plus programmed cell death-1 (PD-1) inhibitor in treating microsatellite stable (MSS) metastatic colorectal cancer (mCRC) remains controversial. AIM: To investigate the benefits of regorafenib combined with PD-1 inhibitor in treating MSS mCRC and explore indicators predicting response. METHODS: This retrospective study included a total of 30 patients with microsatellite stable metastatic colorectal cancer treated with regorafenib combined with programmed cell death-1 inhibitor at Henan Provincial People's Hospital between December 2018 and December 2020. During a 4-wk treatment cycle, regorafenib was performed for 3 continuous weeks. PD-1 inhibitor was intravenously injected starting on the first day of the oral intake of regorafenib. We reviewed tumor response, progression-free survival (PFS), overall survival, and treatment-related adverse events (TRAEs) and evaluated association between platelet-to-lymphocyte ratio (PLR) and outcomes in this retrospective study. RESULTS: Stable disease and progressive disease were found in 18 (60.0%) and 12 (40.0%) patients, respectively. The disease control rate was 60.0%. The median follow-up time was 12.0 mo, and median PFS was 3.4 mo [95% confidence interval (CI): 2.2-4.6 mo]. Of the 12 patients with progressive disease, 10 (83.3%) had liver metastasis before starting the combined treatment. Among the 18 patients with SD, 10 (55.6%) did not have liver metastases. One patient without liver metastases at baseline was found with a substantially prolonged PFS of 11.2 mo. The liver metastasis, the choice of programmed cell death-1 inhibitor other than nivolumab or pembrolizumab and previous exposure to regorafenib was't associated with treatment outcome. The median PFS in the low-PLR group was 4.2 mo (95%CI: 3.5-4.9 mo), compared with 2.8 mo (95%CI: 1.4-4.2 mo) in the high-PLR group (P = 0.005). The major TRAEs included hand-foot syndrome (33.3%), hypertension (23.3%), malaise (20.0%), and gastrointestinal reaction (16.7%). The incidence of grade 3 TRAEs was 13.3% (4/30), which comprised abnormal capillary proliferation (n = 1), transaminase elevation (n = 1), and hand-foot syndrome (n = 2). No grade 4 or higher toxicity was observed. CONCLUSION: Regorafenib combined with PD-1 inhibitor could lead to a longer PFS in some patients with MSS mCRC. The PLR might be a prediction of the patient response to this therapy.

Long noncoding RNA PXN-AS1-L promotes the malignancy of nasopharyngeal carcinoma cells via upregulation of SAPCD2.

Accumulating evidences highlight the critical roles of long noncoding RNAs (lncRNAs) in a variety of cancers. LncRNA PXN-AS1-L was previously shown to exert oncogenic roles in hepatocellular carcinoma. However, the expression, role, and molecular mechanism of PXN-AS1-L in nasopharyngeal carcinoma (NPC) malignancy remain unknown. Here, we determined that PXN-AS1-L is upregulated in NPC tissues and cell lines. Increased expression of PXN-AS1-L predicts worse prognosis of NPC patients. PXN-AS1-L overexpression promotes NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. PXN-AS1-L silencing suppresses NPC cell proliferation, migration, and invasion in vitro. Mechanistically, PXN-AS1-L directly interacts with SAPCD2 mRNA 3'-untranslated region, prevents the binding of microRNAs-AGO silencing complex to SAPCD2 mRNA, and upregulates the mRNA and protein level of SAPCD2. SAPCD2 is also increased in NPC tissues. The expression of SAPCD2 is significantly positively associated with that of PXN-AS1-L in NPC tissues. Gain-of-function and loss-of-function experiments demonstrated that SAPCD2 also promotes NPC cell proliferation, migration, and invasion. Furthermore, depletion of SAPCD2 significantly reverses the roles of PXN-AS1-L in promoting NPC cell proliferation, migration, and invasion in vitro, and NPC tumor growth in vivo. In conclusion, lncRNA PXN-AS1-L is upregulated in NPC and promoted NPC malignancy by upregulating SAPCD2 via direct RNA-RNA interaction.

[Influence of Ginkgo biloba extract on proliferation of ACC-2 cell, Survivin and TIP30 gene expression in adenoid cystic carcinoma of lacrimal gland].

Exploring the influence of extract of Ginkgo biloba (EGB) on the proliferation, apoptosis of ACC-2 cell in lacrimal adenoid cystic carcinoma and analyzing the influence of EGB on the gene expression of Survivin and TIP30 based on the levels of the gene and protein. ACC-2 cell in human with ACC of lacrimal gland disposed by EGB of different concentration was in vitro cultured. MTT method was used for cell proliferation detection. Annexin V/PI double-staining flow cytometer was used to detect cell apoptosis and cell cycle. Survivin and TIP30 gene expression together with protein expression were analyzed by RT-PCR and Western blotting. And it is indicated that EGB has inhibitory effect on the proliferation of ACC-2 cell in vitro. Furthermore, the dose-effect relationship was significant. Compared with the control group, it had statistical difference (P <0.01). The inhibitory concentration 50% (ICso) is 88 mg . L-1. By flow cytometer examination, it was indicated that EGB can gradually increase ACC-2 cell in G0-G1 stage and decrease it in G2-M and S stage. With the increase of dose, the apoptosis rate of ACC-2 cell obviously increased (P <0.05 or P <0.01). Both of the expression results of RT-PCR and Western hybrid proteins have showed that the concentration of EGB increased, it could be seen a significant decrease in Survivin gene expression (P <0.01). Meanwhile, the TIP30 gene expression got a significant increase. Therefore, EGB can effectively inhibit ACC-2 cell Survivin gene expression in human with adenoid cysistic carcinoma of larcrimal gland as well as promoting TIP30 gene expression, inducing the ACC-2 cell apoptosis and inhibiting tumor cell proliferation, which provided a certain theoretical and experimental basis for the application of Chinese herbal medicinal ingredient in the treatment of tumors.