Merging total synthesis and NMR technology for deciphering the realistic structure of natural 2,6-dideoxyglycosides.

The structural identification and efficient synthesis of bioactive 2,6-dideoxyglycosides are daunting challenges. Here, we report the total synthesis and structural revision of a series of 2,6-dideoxyglycosides from folk medicinal plants Ecdysanthera rosea and Chonemorpha megacalyx, which feature pregnane steroidal aglycones bearing an 18,20-lactone and glycans consisting of 2,6-dideoxy-3-O-methyl-ß-pyranose residues, including ecdysosides A, B, and F and ecdysantheroside A. All the eight possible 2,6-dideoxy-3-O-methyl-ß-pyranoside stereoisomers (of the proposed ecdysantheroside A) have been synthesized that testify the effective gold(I)-catalyzed glycosylation methods for the synthesis of various 2-deoxy-ß-pyranosidic linkages and lays a foundation via nuclear magnetic resonance data mapping to identify these sugar units which occur promiscuously in the present and other natural glycosides. Moreover, some synthetic natural compounds and their isomers have shown promising anticancer, immunosuppressive, anti-inflammatory, and anti-Zika virus activities.

Galangin inhibits programmed cell death-ligand 1 expression by suppressing STAT3 and MYC and enhances T cell tumor-killing activity.

BACKGROUND: The flavonoid galangin (3,5,7-trihydroxyflavone) is derived from the root of Alpinia officinarum Hance, an edible and medicinal herb. Galangin has many biological activities, such as anti-inflammatory, anti-microbial, anti-viral, anti-obesogenic, and anti-oxidant effects. However, the anti-tumor mechanism of galangin remains unclear. PURPOSE: To elucidate the anti-tumor mechanisms of galangin in vitro and in vivo. METHODS: MTT, western blotting, immunoprecipitation, RT-PCR, and immunofluorescence assays were used to assess the mechanism of galangin inhibiting PD-L1 expression. The effect of galangin on T cell activity was analyzed in Hep3B/T cell co-cultures. Colony formation, EdU, migration, and invasion assays were performed to explore the effect of galangin on cancer progression and metastasis. Anti-tumor effects of galangin were investigated in a xenograft model. RESULTS: Galangin inhibited PD-L1 expression dose-dependently, which plays a major role in tumor progression. Moreover, galangin blocked STAT3 activation through the JAK1/JAK2/Src signaling pathway and Myc activation through the Ras/RAF/MEK/ERK signaling pathway. Galangin reduced PD-L1 expression by suppressing STAT3 and Myc cooperatively. Galangin increased the killing effect of T cells on tumor cells in Hep3B/T cell co-cultures. Moreover, galangin inhibited tumor cell proliferation, migration, and invasion through PD-L1. In vivo experiments showed that galangin suppressed tumor growth. CONCLUSION: Galangin enhances T-cell activity and inhibits tumor cell proliferation, migration, and invasion through PD-L1. The current study emphasizes the anti-tumor properties of galangin, offering new insights into the development of tumor therapeutics targeting PD-L1.

Significance of interstitial fibrosis and p16 in papillary thyroid carcinoma.

We enrolled 264 patients with papillary thyroid carcinoma (PTC). We performed immunohistochemical detection of p16 and determined the degree of interstitial fibrosis (IF). The expression of p16 was associated with pathological tumor-node-metastasis (pTNM) stage and age (p < 0.05). The cancer-specific survival (CSS) was longer in p16-negative patients (195.73 vs. 181.78 months, p = 0.007). p16 was significantly related to the degree of IF (r = 0.130, p = 0.035). PTC patients with no or mild fibrosis tended to have a larger tumor (p = 0.045). The degree of fibrosis was related to the proportion of papillary structure components (p = 0.025). Univariate and multivariate survival analyses showed that relapse-free survival (RFS) was longer in patients with moderate/severe IF (p < 0.05). In summary, p16 was correlated with prognosis and IF of PTC. Patients with moderate/severe IF tend to have better prognosis in RFS.

SNHG1/miR-556-5p/TCF12 feedback loop enhances the tumorigenesis of meningioma through Wnt signaling pathway.

Meningioma, as a sort of the malignantly intracranial tumors, has captured public attention for its second-highest morbidity all over the world. Long noncoding RNAs (lncRNAs), including lncRNA SNHG1, have been well known as essential players in the development of diverse cancers. However, the biological effect and regulatory mechanism of SNHG1 have not been mentioned in meningioma. In this work, it was discovered that SNHG1 was overexpressed in meningioma cell lines. SNHG1 deficiency restrained cell growth as well as accelerated apoptosis. Then mechanism experiments demonstrated that SNHG1 functioned as the role of sponging miR-556-5p and negatively regulated miR-556-5p expression. Moreover, it was verified that TCF12 is the direct downstream target of miR-556-5p. Furthermore, SNHG1/miR-556-5p/TCF12 axis promoted cell proliferation and suppressed cell apoptosis in meningioma via activating the Wnt signaling pathway. In the end, it was confirmed that TCF12 expression was positively regulated by SNHG1, and TCF12 could promote transcription of SNHG1 through binding with the promoter region of SNHG1. In conclusion, the SNHG1/miR-556-5p/TCF12 feedback loop promotes the tumorigenesis of meningioma through the Wnt signaling pathway.

Safflower yellow promotes angiogenesis through p-VHL/ HIF-1α/VEGF signaling pathway in the process of osteogenic differentiation.

OBJECTIVE: Safflower yellow (SY) is an active component ofCarthamus tinctorius L. that is widely used in orthopedics. This study aimed to evaluate the role of SY in angiogenesis and osteogenic differentiation. METHODS: The migration and in vitro angiogenesis of SY (4.5, 9.0, 18 µg/ml)-treated human umbilical vein endothelial cells (HUVEC-12) were assessed by transwell and tube formation assay, respectively. Osteogenic differentiation ability was detected by alkaline phosphatase (ALP) and Alizarin Red S staining. The mRNA and protein expressions of related markers were determined by RT-qPCR and Western blot. RESULTS: The migration and tube formation ability of HUVEC-12 were promoted by SY. Furthermore, SY facilitated the angiogenesis and osteogenic differentiation in the co-culture of HUVEC-12 and BMSCs by increasing hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), Angiopoietin-2 (Ang-2), ALP, runt-related transcription factor 2 (Runx2) and osteopontin-1 (OPN-1) levels. Inhibition of HIF-1α expression by 3-(5-hydroxymethl-2-furyl)-1-benzylindazole (YC-1), restrained SY-induced proliferation, migration and angiogenesis of HUVEC-12 and the increased protein levels of VEGF, Ang-2, ALP, Runx2 and OPN-1. Finally, WD repeat and SOCS box-containing protein-1 (WSB-1)/Von Hippel-Lindau protein (p-VHL) pathway was involved in the beneficial effect of SY. CONCLUSION: SY promotes osteogenic differentiation via enhancing angiogenesis by regulating pVHL/HIF-1α/VEGF signaling pathway.

[Tracing Investigation of a Quartan Malaria Case in Shanghai].

Objective: To find out the infection source of a quartan malaria case. Methods: Methods The clinical, laboratory and epidemiological information of the patient was collected. The epidemiological investigation and rapid diagnostic test （RDT） were conducted in the surrounding population. Vectors were investigated. Results: Blood film test showed the presense of Plasmodium malariae. Bone marrow aspiration revealed active proliferation of bone marrow as well as granulocytes, red blood cells and giant cells. RDT test showed positive result for Plasmodium. Nested PCR resulted in a specific band of 144 bp, consistent with the positive control. The patient was treated with dihydroartemisinin piperaquine phosphate tablet（2 tab×bid×2 d, po）. Tracing investigation showed that the patient had no history of surgery or blood transfusion within 3 years before the disease onset, and had travelling history in Hainan Province and Haimen City in 2005 and 2013 respectively. There was no case of local infection within 5 years in the patient's area of residence. Twenty-five families including 35 individuals in the area where the patient lived were investigated and all had negative results for the RDT test. In addition, none showed symptom of fever within the past 2 weeks. No Anopheles sinensis was found in the vector investigation. Conclusion: This is a case of quartan malaria with a long latency, and the patient has been infected in other provinces.