Alatains A and B, unique hetero-dimeric polyphenols from Cassia alata and their anti-tobacco mosaic virus activity.

Two structurally unique polyphenols, alatains A (1) and B (2), were isolated from the bark of Cassia alata. Their structures were elucidated on the basis of spectroscopic analysis. Compounds 1 and 2 represent a new type of hetero-dimeric polyphenols with a C-14-C-5' linkage, biogenetically formed by an unusual intermolecular oxidative phenol-coupling reaction between a chromone unit and an isocoumarin moiety. Moreover, compounds 1 and 2 showed significant anti-tobacco mosaic virus (anti-TMV) inhibition IC50 values of 18.8 and 11.4 µM, respectively. Alatains A and B also exhibited promising protective effects on TMV infection of the host plants (Nicotiana tabacum) with the inhibition rates of 54.6% and 69.7% at the concentration of 20 µM, respectively. The results provided a new structural template for potential anti-TMV agent discovery.

Mutation analysis of Chinese sporadic congenital sideroblastic anemia by targeted capture sequencing.

BACKGROUND: Congenital sideroblastic anemias (CSAs) comprise a group of heterogenous genetic diseases that are caused by the mutation of various genes involved in heme biosynthesis, iron-sulfur cluster biogenesis, or mitochondrial solute transport or metabolism. However, approximately 40% of patients with CSA have not been found to have pathogenic gene mutations. In this study, we systematically analyzed the mutation profile in 10 Chinese patients with sporadic CSA. FINDINGS: We performed targeted deep sequencing analysis in ten patients with CSA using a panel of 417 genes that included known CSA-related genes. Mitochondrial genomes were analyzed using next-generation sequencing with a mitochondria enrichment kit and the HiSeq2000 sequencing platform. The results were confirmed by Sanger sequencing. The ALAS2 mutation was detected in one patient. SLC25A38 mutations were detected in three patients, including three novel mutations. Mitochondrial DNA deletions were detected in two patients. No disease-causing mutations were detected in four patients. CONCLUSION: To our knowledge, the pyridoxine-effective mutation C471Y of ALAS2, the compound heterozygous mutation W87X, I143Pfs146X, and the homozygous mutation R134C of SLC25A38 were found for the first time. Our findings add to the number of reported cases of this rare disease and to the CSA pathogenic mutation database. Our findings expand the phenotypic profile of mitochondrial DNA deletion mutations. This work also demonstrates the application of a congenital blood disease assay and targeted capture sequencing for the genetic screening analysis and diagnosis of heterogenous genetic CSA.

Dihydroxanthenones from the fermentation product of an endophytic fungus Gliomastix murorum.

Three new dihydroxanthones, muroxanthenones A-C (1-3), together with three known dihydroxanthones (4-6) were isolated from the fermentation products of an endophytic fungus Gliomastix murorum. Their structures were elucidated by spectroscopic methods, including extensive 1D and 2D NMR techniques. Compound 3 showed high cytotoxicities against NB4 and PC3 cell with IC(50) values of 2.2 and 2.8 µM. The other compounds also showed moderate cytotoxicities for some tested cell lines with IC(50) values between 4.1 and 9.5 µM.

Xanthone derivatives from the fermentation products of an endophytic fungus Phomopsis sp.

Three new xanthones, 1,5-dihydroxy-3-hydroxyethyl-6-methoxycarbonylxanthone (1), 1-hydroxy-5- methoxy-3-hydroxyethyl-6-methoxycarbonylxanthone (2), and 1-hydroxy-3-hydroxyethyl- 8-ethoxycarbonylxanthone (3), along with seven known xanthones (4-10) were isolated from the fermentation products of an endophytic fungus Phomopsis sp.. Their structures were elucidated by spectroscopic methods including extensive 1D- and 2D-NMR techniques. Compounds 1-10 were also tested for their cytotoxicity against five human tumor cell lines (NB4, A549, SHSY5Y, PC3, and MCF7) by MTT method using paclitaxel as positive control. Compounds 1 and 3 showed cytotoxicity against A549 cell lines with IC50 values of 3.6 and 2.5 µM, respectively. In addition, 1 was cytotoxic to MCF7 cells with IC50 value of 2.7 µM.

Bioactive dibenzocyclooctadiene lignans from the stems of Schisandra neglecta.

Seven new unusual dibenzocyclooctadiene lignans, neglignans A-G (1-7), together with 16 known dibenzocyclooctadiene lignans, were isolated from the stems of Schisandra neglecta. Compounds 1 and 2 are the first dibenzocyclooctadiene lignans bearing a carboxyl group at C-4, and compounds 3 and 4 are the first 7,8-seco-dibenzocyclooctadiene lignans found from Nature. The new compounds (1-7) and several of the known compounds were evaluated for their anti-HIV activity and cytotoxicity. Compounds 2 and 6 showed anti-HIV-1 activities with therapeutic index values greater than 50, and compound 4 showed cytotoxicity against the NB4 and SHSY5Y cancer cell lines with IC50 values of 2.9 and 3.3 µM, respectively.

Discovery and validation of prognostic markers in gastric cancer by genome-wide expression profiling.

AIM: To develop a prognostic gene set that can predict patient overall survival status based on the whole genome expression analysis. METHODS: Using Illumina HumanWG-6 BeadChip followed by semi-supervised analysis, we analyzed the expression of 47,296 transcripts in two batches of gastric cancer patients who underwent surgical resection. Thirty-nine samples in the first batch were used as the training set to discover candidate markers correlated to overall survival, and thirty-three samples in the second batch were used for validation. RESULTS: A panel of ten genes were identified as prognostic marker in the first batch samples and classified patients into a low- and a high-risk group with significantly different survival times (P = 0.000047). This prognostic marker was then verified in an independent validation sample batch (P = 0.0009). By comparing with the traditional Tumor-node-metastasis (TNM) staging system, this ten-gene prognostic marker showed consistent prognosis results. It was the only independent prognostic value by multivariate Cox regression analysis (P = 0.007). Interestingly, six of these ten genes are ribosomal proteins, suggesting a possible association between the deregulation of ribosome related gene expression and the poor prognosis. CONCLUSION: A ten-gene marker correlated with overall prognosis, including 6 ribosomal proteins, was identified and verified, which may complement the predictive value of TNM staging system.