Downregulation of lncRNA AFAP1-AS1 by oridonin inhibits the epithelial-to-mesenchymal transition and proliferation of pancreatic cancer cells.

Recent studies have demonstrated that the expression of the long non-coding RNA (lncRNA) AFAP1-AS1 in pancreatic cancer is negatively correlated with survival and prognosis. However, the effects of oridonin and lncRNA AFAP1-AS1 on the epithelial-to-mesenchymal transition (EMT) and migration of pancreatic cancer cells have not been fully elucidated. Surgery is the only potentially curative method for pancreatic cancer, but postoperative recurrence and metastasis are common. The aim of the present study was to assess the effect of oridonin and lncRNA AFAP1-AS1 silencing on pancreatic cancer cells. The pancreatic cancer cell lines BxPC-3 and PANC-1 cells were transfected with siAFAP1-AS1 and its negative control (siNC). After that, oridonin was used to treat the siAFAP1-AS1-transfected cells. The expression of lncRNA AFAP1-AS1 was downregulated in the pancreatic cancer cell lines BxPC-3 and PANC-1. The apoptosis and cell cycle progression of pancreatic cancer cells were evaluated by flow cytometry and Hoechst 33258 staining. Metastasis and invasion of BxPC-3 and PANC-1 cells were detected by transwell migration assay, real-time cell analysis, and western blot analysis. Cells were transfected with the lentiviral siAFAP1-AS1 and siNC, and tumorigenesis was evaluated in BALB/C nude mice. Immunohistochemical examination was used to verify the effects of oridonin and siAFAP1-AS1 on pancreatic cancer. The results demonstrated that the combination of oridonin and siAFAP1-AS1 inhibited pancreatic cancer cell proliferation, induced apoptosis, arrested cell cycle progression, prevented the migration, regulated EMT-related protein expression in BxPC-3 and PANC-1 cells, and inhibited pancreatic cancer cell tumorigenicity and EMT in nude mice.

Risk of dermatologic and mucosal adverse events associated with PD-1/PD-L1 inhibitors in cancer patients: A meta-analysis of randomized controlled trials.

BACKGROUND: Programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are promising cancer immunotherapy. Their dermatologic safety profiles are still poorly understood. The purpose of this article is to evaluate the incidence of selected dermatologic and mucosal adverse effects (AEs) and determine the risk of developing these adverse events associated with PD-1/PD-L1 inhibitors, compared with chemotherapy or ipilimumab. METHODS: PubMed was searched for eligible studies (up to February 21, 2019). Only phase II and phase III randomized controlled trials (RCTs) compared with chemotherapy or ipilimumab monotherapy were included in this meta-analysis. RESULTS: A total 11,465 patients from 18 clinical trials were included in this meta-analysis. Rash and pruritus were the most frequently reported dermatologic AE, with incidence 11.8% and 12.2% respectively. Compared with patients receiving chemotherapy, PD-1/PD-L1 inhibitor treated patients had higher risk of developing rash (RR = 1.84), pruritus (RR = 3.74) and vitiligo (RR = 9.54), and also lower risk in developing mucosal inflammation (RR = 0.26), stomatitis (RR = 0.26), and alopecia (RR = 0.03). Additionally, anti-PD1/PD-L1 drugs had similar risk of developing rash and lower risk of inducing pruritus compared to ipilimumab. In the subgroup analysis, PD-L1 inhibitor demonstrated better safety than PD-1 inhibitor in developing rash, with RR = 1.38 and RR = 2.11, respectively. CONCLUSION: Our meta-analysis concluded that anti PD-1/PD-L1 drugs have different dermatological and mucosal safety profile compared to conventional therapy, and differences of dermatological toxicity between PD-1 and PD-L1 inhibitor warrant further investigation.

Benzopyran derivatives from endophytic Daldinia eschscholzii JC-15 in Dendrobium chrysotoxum and their bioactivities.

Five new benzopyran derivatives (2-6) and a new natural product (1) were isolated from endophytic Daldinia eschscholzii in Dendrobium chrysotoxum and determined as (R)-2,3-dihydro-2,5-dihydroxy-2-methylchromen-4-one (1), (2R, 4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol (2), (R)-3-methoxyl-1-(2,6-dihydroxy phenyl)-butan-1-one (3), 7-O-α-d-ribosyl-5-hydroxy-2-methyl-4H-chromen-4-one (4), 7-O-α-d-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one (5), daldinium A (6). These compounds were evaluated for their antimicrobial activity, anti-acetylcholinesterase, nitric oxide inhibition, anticoagulant, photodynamic antimicrobial activities and glucose uptake of adipocytes. Some compounds showed photoactive antimicrobial activities and glucose uptake stimulating activities.

New Bisabosquals from Stachybotrys sp. PH30583 Elicited on Solid Media.

Stachybotrys sp. PH30583 cultured in liquid medium only led to one structure type of novel isochroman dimers. Using the one strain-many compounds strategy, the reinvestigation of the metabolites from Stachybotrys sp. PH30583 cultured in rice solid medium led to the isolation of four triprenyl phenols, including two new bisabosquals and two known phenylspirodrimanes. Nitrobisabosquals A and B (1 and 2) are the first case of pyrrolidone-bisabosquals reported in literature. Totally different compounds were isolated using rice solid medium, compared with those isolated using liquid medium, so that rice solid medium presents a key factor in the production of triprenyl phenols. Compound 1 exhibited cytotoxicity against tumor cells, A-549, HL-60, MCF-7 SMMC-7721, and SW480, as well as weak anticoagulant activity with activated partial thromboplastin time (APTT) of 32.1 ± 0.17 s (p < 0.05 vs. Con.) at a concentration of 5 mM. Triprenyl phenol metabolites could be used as chemotaxonomic markers for Stachybotrys.

Oridonin inhibition and miR­200b­3p/ZEB1 axis in human pancreatic cancer.

The relationship among oridonin, miR-200b-3p and pancreatic cancer on epithelial-to-mesenchymal transition (EMT) was investigated for the molecular mechanism or signaling pathways on the migration in pancreatic cancer. BxPC-3 and PANC-1 cells were cultivated and the IC50 of oridonin in BxPC-3 and PANC-1 cells were obtained by the CCK-8 array. The expression of miR­200b-3p was verified by using real-time PCR and its target gene was predicted. BxPC-3 and PANC-1 cells were treated with oridonin or transfected by miR-200b-3p, those cells were used for western blot assay, Transwell assay, ELISA, immunofluorescence staining, tumorigenesis assay in nude mice and immunohistochemical assay to verify the effects of oridonin or miR-200b-3p on pancreatic cancer. We found that oridonin inhibited the proliferation of BxPC-3 and PANC-1 cells in a dose-dependent manner. miR-200b-3p was downregulated by oridonin in BxPC-3 and PANC-1 cells. ZEB1 was a target gene for miR-200b-3p. Oridonin or overexpression of miR­200b-3p can inhibit the cell migration in BxPC-3 and PANC-1 cells. miR-200b-3p can inhibit the EMT and oridonin can inhibit the expression of ZEB1, N-cadherin and fibronectin but not increase the expression of E-cadherin, while the cell adhesion molecules ICAM-1 and VCAM-1 were decreased by oridonin in BxPC-3 and PANC-1 cells and the cytoskeleton was altered by oridonin in PANC-1 cells compared with the control. In summary, the results demonstrate that miR­200b-3p was able to inhibit the EMT of human pancreatic cancer in vivo and in vitro by targeted ZEB1. In vitro, oridonin had a certain effect on the migration in BxPC-3 and PANC-1 cells, but not though type III EMT by miR-200-3p/ZEB1 axis, and may be related to type â…¡ EMT, tumor microenvironment or altering the cytoskeleton. In vivo, oridonin inhibited the cancer migration in the nude mouse model though inhibiting EMT.

Oridonin alters the expression profiles of microRNAs in BxPC-3 human pancreatic cancer cells.

BACKGROUND: Oridonin, an ingredient used in traditional Chinese medicine, has been demonstrated to play an important role in antitumour effects, but the mechanism underlying its antitumour properties is still not clear. METHODS: To verify the anti-cancer effects of oridonin via a miRNA-dependent mechanism, comprehensive miRNA expression profiling of oridonin-treated BxPC-3 human pancreatic cancer cells was performed using a miRNA microarray assay based on Sanger miR-Base Release 20, followed by a validation using real-time PCR. MicroRNA target prediction and Gene Ontology and KEGG pathway analysis were performed to investigate possible pathways involved. RESULTS: The results showed that 105 miRNAs were significantly differentially expressed (signal reading >500, p ≤ 0.01, |Log2-value| ≥1) in oridonin-treated BxPC-3 human pancreatic cancer cells. CONCLUSIONS: Our data indicates that oridonin inhibits BxPC-3 cells probably through regulating the expression of miRNAs. Interruption of miRNA profiling may provide new therapeutic methods for the clinical treatment of pancreatic cancer.

[Eosinophils apoptosis in asthmatic children].

UNLABELLED: Prominent eosinophil airway inflammation is important in the pathogenesis of asthma. There is increasing evidence that the disorder of eosinophil apoptosis contributes to the mechanism. But most of the studies have been done in vitro or on animal models, very few were done among the adult asthmatics in vivo. OBJECTIVE: The aim of this study was to elucidate the relationship between the apoptotic eosinophils and Bcl-2 in asthmatic children in vivo. METHODS: Eleven mild to moderate asthmatic patients were recruited and the range of age was 7 - 14 years (9 males, 2 females), meanwhile 7 patients with lower respiratory infection were recruited as control and the range of age was 9 - 14 years (5 males, 2 females). Before and after inhaled glucocorticoid (GC) induced sputum, bronchoalveolar lavage (BAL), bronchial mucosa specimens and peripheral blood were obtained for measuring and comparing the changes of apoptotic EG(2)(+) cell by combining the techniques of TUNEL and immunohistochemistry, meanwhile the expression of Bcl-2 in bronchial mucosa specimens was measured by using the immunohistochemical assay. RESULTS: Before the inhalation of GC, the apoptotic EG(2)(+) cells in asthmatics were significantly lower than that in control group (P < 0.01), and the numbers of EG(2)(+) cell in asthmatics group were significantly higher than that in control group (P < 0.001). After the treatment apoptotic EG(2)(+) cells in asthmatics were increased (P < 0.01), and the numbers of EG(2)(+)cell were decreased (P < 0.01, P < 0.05 and P < 0.05, respectively), FEV(1)% was increased (P < 0.05). Before the inhalation of GC, the numbers of Bcl-2(+) cell in asthmatic airway submucosa were higher than that in control group (P < 0.05) but after the treatment the number of Bcl-2(+) cell did not change significantly. (4) Before and after GC treatment the percentages of apoptotic eosinophils of peripheral blood in vivo had no significant changes compared with those of control subjects (P > 0.05). There was a positive correlation between apoptosis of EG(2)(+) cell in sputum, BAL, airway submucosa and FEV(1)% (P < 0.05). CONCLUSION: Apoptosis of EG(2)(+) cell decreased in the airway of asthmatic children and inducing EOS apoptosis is one of the important mechanism of inhaled GC therapy for asthma.