Flavonoid glycosides from the fruits of Embelia ribes and their anti-oxidant and α-glucosidase inhibitory activities.

Three new flavonoid glycosides, embeliaflavosides A-C (1-3), together with eight known flavonoid glycosides (4-11), were isolated from the fruits of Embelia ribes. Their structures were established based on the analyses of spectroscopic data. Compounds 1-11 were evaluated for antioxidant and α-glucosidase inhibitory activities. The results revealed that compounds 1-11 owned significant ABTS radical scavenging activity with IC50 values of 2.52-9.78 µM, and DPPH scavenging activity with IC50 values of 7.56-26.47 µM, respectively. However, α-glucosidase inhibition assay indicated that all the isolates were inactive.[Formula: see text].

Resolvin D2 prevents inflammation and oxidative stress in the retina of streptozocin-induced diabetic mice.

Diabetic retinopathy is the main ocular complication of diabetes mellitus. The aim of this study was to investigate the protective effect and mechanism of resolvin D2 (RvD2) on diabetic retinopathy. Streptozocin-induced C57/BJ diabetic mice were divided into three groups: normal control, diabetes mellitus, and diabetes plus RvD2 treatment. After three months of diabetic model induction, exogenous RvD2 was injected, monthly for three months, into the vitreous cavity of mice in the diabetic treatment group. Retinal vascular leakage, ganglion cell apoptosis, inflammatory factor expression, and oxidative stress factors were detected one month after the last injection. The levels of retinal vascular leakage and ganglion cell apoptosis in diabetic mice treated with RvD2 were significantly lower than those in untreated diabetic mice, as were the retinal levels of inflammatory factors and oxidative stress. In conclusion, RvD2 might be used as a retinal protective factor for diabetes mellitus by reducing inflammation and oxidative stress.

A potential prognostic marker and therapeutic target: SPOCK1 promotes the proliferation, metastasis, and apoptosis of pancreatic ductal adenocarcinoma cells.

Pancreatic ductal adenocarcinoma (PDAC), a common malignancy originated from the digestive system worldwide, has a poor clinical outcome. SPOCK1 is a widely investigated member of the Ca2+ -binding proteoglycan family and functions as an essential driver in several cancers. However, the complex regulatory role of SPOCK1 in PDAC is unclear. Bioinformatics analysis predicted an interrelationship between increased SPOCK1 expression and the clinical characteristics of patients with PDAC. The SPOCK1 expression levels in fresh tissue samples were confirmed, and SPOCK1 expression was then knocked down by lentivirus-mediated short hairpin RNA. Cell proliferation, metastasis, and apoptosis were detected through Cell Counting Kit-8, colony formation assays, invasion and migration assays, flow cytometric analysis, quantitative real-time polymerase chain reaction, and Western blot experiment. On the basis of the Cancer Genome Atlas database, we found a significantly higher level of SPOCK1 in PDAC than in adjacent nontumor tissues. Patients with PDAC with high SPOCK1 expression exhibited shorter overall survival time, as well as disease-free survival time. The knockdown of SPOCK1 significantly decreased the proliferation and metastasis of PCNA-1 and MIA PaCa-2 cells. Moreover, the knockdown of SPOCK1 led to cell cycle arrest in G0/G1 phase and increased the proportion of apoptotic PDAC cells by regulating members of the caspase and Bcl-2 families. Our data proved that SPOCK1 is a critical regulator of tumor proliferation and metastasis in PDAC cells. Therefore, SPOCK1 might be a potential prognostic and therapeutic target molecule in PDAC.

A novel MKK gene (EcMKK6) in Epinephelus coioides: Identification, characterization and its response to Vibrio alginolyticus and SGIV infection.

Mitogen-activated protein kinase 6 (MKK6) is one of the major important central regulatory proteins response to environmental and physiological stimuli. In this study, a novel MKK6, EcMKK6, was isolated from Epinephelus coioides, an economically important cultured fish in China and Southeast Asian counties. The open reading frame (ORF) of EcMKK6 is 1077 bp encoding 358 amino acids. EcMKK6 contains a serine/threonine protein kinase (S_TKc) domain, a tyrosine kinase catalytic domain, a conserved dual phosphorylation site in the SVAKT motif and a conserved DVD domain. By in situ hybridization (ISH) with Digoxigenin-labeled probe, EcMKK6 mainly located at the cytoplasm of cells, and a little appears in the nucleus. EcMKK6 mRNA can be detected in all eleven tissues examined, but the expression level is different in these tissues. After challenge with Vibrio alginolyticus and Singapore grouper iridovirus (SGIV), the transcription level of EcMKK6 was apparently up-regulated in the tissues examined. The data demonstrated that the sequence and the characters of EcMKK6 were conserved, EcMKK6 showed tissue-specific expression profiles in healthy grouper, and the expression was significantly varied after pathogen infection, indicating that EcMKK6 may play important roles in E. coioides during pathogen-caused inflammation.

C-Methylated flavanones from the rhizomes of Matteuccia intermedia and their α-glucosidase inhibitory activity.

One new flavanonol, demethylmatteucinol (1), and nine new flavanone glucoside derivatives, matteflavosides H-J (2-4) and matteuinterates A-F (5-10), were isolated from the rhizomes of Matteuccia intermedia C.Chr., along with 21 known flavanones (11-31). Notably, all of them contain C-methylation in the A-ring. The structures of the compounds were elucidated by spectroscopic methods and chemical derivatization. The α-glycosidase inhibition assay indicated that compounds 12-17 showed potent inhibitory activity with IC50 values of 12.4-69.7 µM, which suggested their hypoglycemic effect.

New alkylresorcinols from the fruits of Embelia ribes.

Nine new alkylresorcinols, designated as embelialkylresorcinols A-I (1-9), along with five known compounds (10-14) were isolated from the fruits of Embelia ribes. Their structures were elucidated by extensive spectroscopic analysis (1D, 2D NMR and HRESIMS), optical rotation data and modified Mosher method. Notably, embelialkylresorcinols A-H (1-8), possessing double aromatic rings linked with an aliphatic chain, are reported from the genus of Embelia (Myrsinaceae) for the first time. Most of the isolated compounds were evaluated for cytotoxic activity, and the results indicated that compounds 3, 5, 6 and 8 displayed moderate cytotoxicity against three human cancer cell lines (Hep3B, A549 and HCC1806) with IC50 values ranging from 23.06 to 41.49 µM.

Clinical application of bupivacaine in non-catheter infiltration anesthesia during vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To evaluate the effect of bupivacaine in non-catheter infiltration anesthesia during vitretomy operation.·METHODS:Fifty-eight patients (58 eyes) with vitreous retinal surgery were selected. Patients were randomly divided into observation group ( 28 eyes ) and control group ( 30 eyes ) . The observation group were received non-catheter infiltration anesthesia. The control group were received traditional Sub- Tenon's block ( STB ) . Degree of pain, basic vital signs, the duration of anesthesia and analgesia grade were recorded and compared between two groups.·RESULTS: No significant difference was found in the 11-point numeric rating scale ( NRS - 11 scoring ) of anesthesia process, sclera incision, intraocular operation and the end of operation between two groups (P>0. 05). The difference were not significant in heart rate and blood pressure between two groups(P>0. 05). There was statistically significant difference in the duration of anesthesia between two groups (P<0. 05).·CONCLUSION: Both groups can provide the same anesthetic effect. Compared to STB, non - catheter infiltration anesthesia takes short time, and it is a safe and effective anesthesia methods. In addition, compare to the mixture of bupivacaine and lidocaine injection, bupivacaine injection can provide the same anesthetic effect.

Decreased expression and prognostic role of cytoplasmic BRSK1 in human breast carcinoma: correlation with Jab1 stability and PI3K/Akt pathway.

OBJECTIVE: Jun activation domain-binding protein 1 (Jab1) was overexpressed in breast cancer, which was involved in degradation of the cyclin-dependent kinase inhibitor p27(Kip1). The objective of this study was to examine the effect of brain specific kinase 1 (BRSK1) expression on Jab1 over-expression and related signaling pathway in breast cancer. METHODS: Immunohistochemical analysis was performed in 95 human breast carcinoma samples and the data were correlated with clinicopathologic features. Furthermore, Western blot analysis was performed for BRSK1 and Jab1 in breast carcinoma samples and cell lines to evaluate their protein levels and molecular interaction. RESULTS: We found that the cytoplasmic BRSK1 expression was inversely associated with Jab1 expression (P<0.01) and correlated significantly with histologic grade (P=0.006), however nuclear BRSK1 expression couldn't obtain similar results. Kaplan-Meier analysis revealed that survival curves of low versus high expressers of cytoplasmic BRSK1 and Jab1 showed a highly significant separation in breast cancer (P<0.01). While in vitro, following release of breast cancer cell lines from serum starvation, the expression of Jab1, phosphor-Akt (p-Akt) was up-regulated, whereas BRSK1 and p27(Kip1) were decreased. Treatment of phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 could diminish Jab1 expression but increase BRSK1 expression. In addition, we employed siRNA technique to knock down Jab1 and/or BRSK1 expression and observed their effects on MDA-MB-231 cell growth. CONCLUSIONS: BRSK1 is a novel tumor suppressor in breast cancer which inversely correlated with Jab1 expression, may involve in the restoring Jab1-induced suppression of p27(Kip1) and may regulate cell cycle through the PI3K/Akt pathway.

Knocking down the expression of adenylate cyclase-associated protein 1 inhibits the proliferation and migration of breast cancer cells.

Adenylate cyclase-associated protein 1 (CAP1) is a conserved protein that was found to be up-regulated in breast cancer and related to the migration of breast cancer. We verified its roles in breast cancer specimens and cell lines. In our results, 71 of 100 specimens of breast cancer showed high levels of CAP1 by immunohistochemistry. Associated with statistical analysis, we saw that CAP1 was related to the grade of breast cancer. In MDA-MB-231, the expression of CAP1 was the highest and by knocking down the expression of CAP1 in MDA-MB-231, its ability for proliferating and migrating apparently decreased and induced changes in morphology, which were related to the arrangement of F-actin. Therefore, CAP1 might be a potential molecular targeted therapy for surgery and immune treatment.