Two new alkaloids produced by Dothideomycetes sp. BMC-101 isolated from the Magnolia grandiflora.

AbstactA total of 16 fungal strains were isolated from fresh leaves and flowers of Magnolia grandiflora and the EtOAc extracts of them were assayed for antitumor activities. Among these, the fungus Dothideomycetes sp. BMC-101 with broad spectrum inhibition was selected for further study. Four alkaloids (1-4) including two new compounds (2-(hydroxyimino)-3-phenylpropanoyl)-L-phenylalanine (1) and 8-Acetyl-bisdethiobis(methylsulfanyl)apoaranotin (4)) were isolated from Dothideomycetes sp. BMC-101. The structure of 1 was characterized with an oxime moiety formed by the condensation of two phenylalanines. To our knowledge, this is the first report on a fungal phenylalanine derivative with an oxime moiety.

Semi-Synthesis and In Vitro Anti-Cancer Evaluation of Magnolol Derivatives.

Magnolol (MAG), a biphenolic neolignan, has various biological activities including antitumor effects. In this study, 15 MAG derivatives were semi-synthesized and evaluated for their in vitro anticancer activities. From these derivatives, compound 6a exhibited the best cytotoxic activity against four human cancer cell lines, with IC50 values ranging from 20.43 to 28.27 µM. Wound-healing and transwell assays showed that compound 6a significantly inhibited the migration and invasion of MDA-MB-231 cells. In addition, Western blotting experiments, performed using various concentrations of 6a, demonstrated that it downregulates the expression of HIF-1α, MMP-2, and MMP-9 in a concentration-dependent manner. Overall, these results suggest that substituting a benzyl group having F atoms substituted at the C2 position on MAG is a viable strategy for the structural optimization of MAG derivatives as anticancer agents.

N-Me-trichodermamide B isolated from Penicillium janthinellum, with antioxidant properties through Nrf2-mediated signaling pathway.

A new trichodermamide-like alkaloid, N-Me-trichodermamide B (compound 1), was isolated from a marine fungus Penicillium janthinellum HDN13-309. The structure and absolute configuration of compound 1 were determined by extensive NMR analysis and the modified Mosher's method. This new alkaloid exhibited cellular protection from the H2O2-induced oxidative damage, and the mechanism study revealed that this antioxidant activity was regulated through Nrf2-mediated signaling pathway in HaCaT human keratinocytes. In addition, the inhibitor of p38 abrogated compound 1-induced phosphorylation of p38, up-expression of HO-1, and the nuclear localization of Nrf2. As a result, it suggested that this new alkaloid-induced antioxidant signaling pathway might be initiated through activation of p38.

Tanshinone IIA affects the HDL subfractions distribution not serum lipid levels: Involving in intake and efflux of cholesterol.

AIM OF STUDY: Tanshinone IIA is an active component of the traditional Chinese medicine. This study aimed at investigating the mechanism of tanshinone IIA on anti-atherosclerosis, which may be because of that Tanshinone IIA can affect the HDL subfractions distribution and then regulate reverse cholesterol transport. MATERIALS AND METHODS: A model of hyperlipidaemia in rats was used. Tanshinone IIA was given daily after hyperlipidaemia. In vivo, lipid deposition and morphological changes in liver were analyzed; HDL subfractions and lipid level in serum as well as in liver were measured; the expression of genes related to cholesterol intake in liver and peritoneal macrophage cholesterol efflux were evaluated. In vitro, HepG2 cells and THP-1 cells were pretreated with tanshinone IIA and subsequently with ox-LDL to evaluate the total cholesterol and the expression of related genes. RESULTS: Tanshinone IIA reduced the lipid deposition in liver. Moreover, it did not affect the serum lipid levels but reduced the levels of HDL middle subfractions and increased the levels of HDL large subfractions. Furthermore, tanshinone IIA could regulate the expressions of CYP7A1, LDL-R, SREBP2 and LCAT in the liver as well as the ABCA1 and CD36 in macrophage cells which is involving in the cholesterol intake and efflux respectively. It could reduce lipid accumulation caused by ox-LDL induction, and that also regulate the expressions of LDL-R, HMGCR and SREBP2 in HepG2 and ABCA1, CD36 in THP-1 cells. CONCLUSION: A novel finding that tanshinone IIA was not reduce the serum lipid level but affects the HDL subfractions distribution and thereby regulating the intake and efflux of cholesterol.

Exopisiod B and farylhydrazone C, two new alkaloids from the Antarctic-derived fungus Penicillium sp. HDN14-431.

Two new compounds, exopisiod B (1) and farylhydrazone C (2), together with two known compounds (3-4), were isolated from the Antarctic-derived fungus Penicillium sp. HDN14-431. Their structures including absolute configurations were elucidated by spectroscopic methods and TDDFT ECD calculations. The cytotoxicity and antimicrobial activities of all compounds were tested.

[Intervention of Huayu Qutan Recipe on liver SREBP-2 signal pathway of hyperlipidemia rats of pi deficiency syndrome].

OBJECTIVE: To explore the intervention of Huayu Qutan Recipe (HQR) on liver SREBP-2 signal pathway of hyperlipidemia rats of Pi deficiency syndrome (PDS). METHODS: Totally 100 SPF grade SD rats were randomly divided into the blank control group, the hyperlipidemia group, the hyperlipidemia treatment group, the PDS hyperlipidemia group, and the PDS hyperlipidemia treatment group, 20 in each group. Common granular forage was fed to rats in the blank control group. High fat forage was fed to rats in the hyperlipidemia group and the hyperlipidemia treatment group. Rats in the PDS hyperlipidemia group and the PDS hyperlipidemia treatment group were treated with excessive labor and improper diet for modeling. They were administered refined lard by gastrogavage (3 mL each time, twice per day) and fed with high fat forage on the odd days, and fed with wild cabbage freely on even days. The modeling lasted for 30 days. Rats in the hyperlipidemia treatment group and PDS hyperlipidemia treatment group were administered with Huayu Qutan Recipe (20 mL/kg) by gastrogavage, once a day, for 30 successive days. Levels of serum cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and serum amylase (AMY) were detected by automatic biochemical analyzer. D-xylose excretion rate was determined using phloroglucinol method. Morphological changes of liver and the lipid deposition in liver were observed using HE stain and oil red O stain respectively, mRNA and protein expression levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), cholesterol 7α-hydroxylase 1 (CYP7A1), LDL-R, and sterol regulatory element binding protein-2 (SREBP-2) were detected using real time RT-PCR and Western blotting. RESULTS: Compared with the blank control group, serum levels of TC (1.84 ± 0.19 mmol/L, 2.23 ± 0.43 mmol/L) and LDL-C (0.99 ± 0.24 mmol/L, 1.13 ± 0.56 mmol/L) were higher in the hyperlipidemia group and the PDS hyperlipidemia group, serum levels of HDL-C (0.41 ± 0.66 mmol/L, 0.41 ± 0.11 mmol/L) and AMY activities (351 ± 45 mmol/L, 153 ± 30 mmol/L) were lower, and urinary D-xylose excretion rates were lower (26.9 ± 2.1 ng/mL, 15.0 ± 1.7 ng/mL) (all P < 0.05). Lipid deposition occurred in liver cells. Much fat vacuoles occurred in the cytoplasm. Expression levels of HMGCR, CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver significantly decreased (P < 0.01). Compared with the hyperlipidemia group, serum levels of TC and LDL-C significantly increased (P < 0. 05), AMY activities and urinary D-xylose excre- tion rates significantly decreased in the PDS hyperlipidemia group (P < 0.01). A large amount of lipid deposition occurred in liver. The atrophy of liver cells was obviously seen. Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly lower (P < 0.01, P < 0.05). Serum levels of TC and LDL-C significantly decreased (P < 0.05), AMY activities and urinary D-xylose excretion rates significantly increased in the hyperlipidemia treatment group (P < 0.01). Expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01, P < 0.05). Compared with the PDS hyperlipidemia group, serum level of TC significantly decreased (P < 0.05), HDL-C levels, AMY activities and urinary D-xylose excretion rates significantly increased in the PDS hyperlipidemia treatment group (P < 0.01),expression levels of CYP7A1, LDL-R, and SREBP-2 mRNA and proteins in liver were significantly increased (P < 0.01). Similar changes occurred in the two treatment groups. CONCLUSIONS: Pi deficiency exacerbates abnormal serum TC level and the lipid deposition in liver. These might be related to regulating expression levels of LDL-R, HMGCR, and CYP7A1 genes in the SREBP-2 signal pathway. HQR could regulate this pathway to intervene abnormal metabolism of TC.

Primary malignant melanoma of the esophagus combined with squamous cell carcinoma: A case report.

BACKGROUND: Primary malignant melanoma of the esophagus is a rare malignant tumor of the esophagus, and its combination with squamous cell carcinoma is also rare. Here, we report the diagnosis and treatment of a case of primary esophageal malignant melanoma combined with squamous cell carcinoma. CASE SUMMARY: A middle-aged man underwent gastroscopy for dysphagia. Gastroscopy revealed multiple bulging esophageal lesions, and after pathologic and immunohistochemical analyses, the patient was finally diagnosed with "malignant melanoma with squamous cell carcinoma". This patient received comprehensive treatment. After one year of follow-up, the patient was in good condition, and the esophageal lesions seen on gastroscopy were controlled, but unfortunately, liver metastasis occurred. CONCLUSION: When multiple esophageal lesions are present, the possibility of multiple pathological sources should be considered. This patient was diagnosed with primary esophageal malignant melanoma combined with squamous cell carcinoma.

Is endoscopic mucosal ablation a valid option for treating colon polyps?

The present letter to editor is related to endoscopic mucosal ablation (EMA). EMA is safe and effective in the treatment of colonic polyps when endoscopic resection is not possible or available, but the indication of EMA should be determined for a further large number of studies. EMA should be used with caution for larger lesions.

Anti-metastatic effect of 131I-labeled Buthus martensii Karsch chlorotoxin in gliomas.

The present study investigated the underlying molecular mechanism by which Buthus martensii Karsch chlorotoxin (BmK CT) inhibits the invasion and metastasis of glioma cells and the possibility of 131I­labeled BmK CT (131I­BmK CT) as a novel targeted agent for the treatment of glioma. The impact of BmK CT with and without 131I radiolabeling on the invasion and metastasis of glioma cells in vitro was studied. Cell viability was assessed using Cell Counting Kit­8 and plate colony formation assays in order to confirm the cytotoxicity of BmK CT and 131I­BmK CT at different concentrations. Transwell invasion and wound­healing assays were conducted in order to investigate the inhibitory effects BmK CT and 131I­BmK CT on cell migration and invasion. Furthermore, western blotting, ELISA immunofluorescence and a gelatin zymography assay were performed to evaluate changes in the protein expression levels of glioma cells following treatment with BmK CT or 131I­BmK CT. The results indicated that BmK CT inhibits the invasion and metastasis of glioma cells via regulation of tissue inhibitor of metalloproteinase­2 expression and that 131I­BmK CT has the potential to be a novel targeted therapeutic drug for glioma.

Evaluation and clinical significance of cyclin-dependent kinase5 expression in cervical lesions: a clinical research study in Guangxi, China.

BACKGROUND: Studies have been reported that cyclin-dependent kinase5 (CDK5) was associated with the development of several cancers. However, the relationship between CDK5 level and clinicopathological factors is still poorly understood in cervical diseases. The aim of the current study was to investigate the expression of CDK5 and its clinical significance in variant cervical lesions. METHODS: Immunohistochemistry (IHC) was used to detect CDK5 expression in 54 cases of chronic cervicitis, 42 cases of condyloma acuminate (CA), 38 cases of carcinoma in situ, and 360 cases of cervical cancers [adenocarcinoma, n = 63; squamous cell carcinoma (SCC), n = 263; adenosquamous carcinoma, n = 34]. The clinicopathological characteristics in relation to CDK5 were examined by Pearson's Chi-square test. RESULTS: The positive rates of CDK5 were 27.8, 31.0, 50, 54.0, 58.8, and 62.7 % in chronic cervicitis, CA, carcinoma in situ, adenocarcinoma, adenosquamous carcinoma and SCC, respectively. Statistically analysis showed that CDK5 expression in cervical cancer tissues was higher than non-cervical cancer tissues (inflammation and CA) (P < 0.001). The overexpression of CDK5 was significantly correlated with lymph node metastasis (r = 0.317; P < 0.001), histological type (r = 0.198; P < 0.001), FIGO stage (r = 0.358; P < 0.001), TNM stage (r = 0.329; P < 0.001) and pathological grade (r = 0.259; P < 0.001) in cervical lesions evaluated by Pearson's Chi-square test. Furthermore, the positive relationships were found between CDK5 and lymph node metastasis (P < 0.001), FIGO stage (P < 0.001), TNM stage (P < 0.001) and pathological grade (P < 0.001) in SCC. CDK5 was positively interrelated to TNM stage (P = 0.017) in adenosquamous carcinoma. CONCLUSIONS: CDK5 may play a vital role in the development of cervical cancer, which may be a marker for the diagnosis, therapy and prognosis of cervical cancer.