Bone marrow mesenchymal stem cell-derived exosomal MiR-338-3p represses progression of hepatocellular carcinoma by targeting ETS1.

The present study aims to explore the function of human bone marrow mesenchymal stem cell (BMSC)-derived exosomal micro ribonucleic acid (miR)-338-3p in hepatocellular carcinoma (HCC) and further investigate its effect on HCC cell functions. Firstly, BMSCs were co-cultured with HCC cells, and BMSC-derived exosomes were identified. Next, Transwell assay and methyl thiazolyl tetrazolium (MTT) experiments were carried out to detect the effects of miR-338-3p and E26 transformation specific-1 (ETS1) on the viability, invasion, migration, and apoptosis of HCC cells through the exosomes derived from BMSCs. Furthermore, the targeting relationship between miR-338-3p and EST1 was verified via bioinformatics study and dual-luciferase reporter gene analysis. Additionally, Western blotting (WB) was carried out to measure the expression levels of EST1 and other proteins in HCC cells. It was found that BMSCs inhibited HCC cell proliferation, invasion and migration, and induced cell apoptosis, while the inhibitors of exosomes played the opposite roles. In addition, the up-regulation of exosomal miR-338-3p or the silencing of EST1 restrained HCC cell proliferation, invasion and migration, and induced cell apoptosis. In conclusion, BMSC-derived exosomal miR-338-3p delays the development of HCC by down-regulating EST1, providing a new promising treatment target for HCC.

Genomic and phylogenetic evidence that Maize rough dwarf and Rice black-streaked dwarf fijiviruses should be classified as different geographic strains of a single species.

Maize rough dwarf disease (MRDD) has long been known as one of the most devastating viral diseases of maize worldwide and is caused by single or complex infection by four fijiviruses: Maize rough dwarf virus (MRDV) in Europe and the Middle East, Mal de Rio Cuarto virus (MRCV) in South America, rice black-streaked dwarf virus (RBSDV), and Southern rice black-streaked dwarf virus (SRBSDV or Rice black-streaked dwarf virus 2, RBSDV-2) in East Asia. These are currently classified as four distinct species in the genus Fijivirus, family Reoviridae, but their taxonomic status has been questioned. To help resolve this, the nucleotide sequences of the ten genomic segments of an Italian isolate of MRDV have been determined, providing the first complete genomic sequence of this virus. Its genome has 29144 nucleotides and is similar in organization to those of RBSDV, SRBSDV, and MRCV. The 13 ORFs always share highest identities (81.3-97.2%) with the corresponding ORFs of RBSDV and phylogenetic analyses of the different genome segments and ORFs all confirm that MRDV clusters most closely with RBSDV and that MRCV and SRBSDV are slightly more distantly related. The results suggest that MRDV and RBSDV should be classified as different geographic strains of the same virus species and we suggest the name cereal black-streaked dwarf fijivirus (CBSDV) for consideration.

The expression of the BRM and MMP2 genes in thoracic aortic aneurysm and aortic dissection.

OBJECTIVE: To study the expression, roles, and clinical significance of Brahma (BRM) and matrix metalloproteinase 2 (MMP2) in the thoracic aortic aneurysm and aortic dissection. PATIENTS ND METHODS: Arterial specimens from 20 cases of thoracic aortic dissection and 38 cases of thoracic aortic aneurysm, as well as normal tissue were collected, paraffin-embedded, sectioned, and stained with anti-BRM and MMP2 monoclonal antibodies. Sections were analyzed by immunofluorescence, and the distribution and expression of BRM and MMP2 in the aortic wall were determined. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to measure the expression of BRM and MMP2 mRNA in the thoracic aortic aneurysm, thoracic aortic dissection, and normal tissues. The expression of MMP2 and BRM protein in these tissues was analyzed by Western blot. SPSS 17.0 statistical software was used for data analysis. RESULTS: MMP2 and BRM (mRNA and protein) were expressed in arterial tissue from thoracic aortic aneurysms and aortic dissections. Immunofluorescence also showed that BRM and MMP2 were expressed in the thoracic aortic aneurysm and aortic dissection tissue. The expression was very high in thoracic aortic aneurysm tissue. The differences in expression of BRM and MMP2 in the different arterial tissues were statistically significant (p<0.01). CONCLUSIONS: Expression of BRM and MMP2 in the thoracic aortic aneurysm and aortic dissection is very high, indicating that BRM and MMP2 may play important roles in the occurrence and development of thoracic aortic aneurysm and aortic dissection. They may represent potential targets for the treatment of thoracic aortic aneurysm and aortic dissection and provide a new basis for clinical diagnosis.

Direct oxidative coupling of thiols and benzylic ethers via C(sp(3))-H activation and C-O cleavage to lead thioesters.

An unprecedented C-S formation method via direct oxidative C(sp(3))-H bond functionalization and C-O cleavage of benzylic ethers was developed. Various thioesters including thioester structure containing drug intermediates could be achieved by this convenient, metal and base free method in satisfactory yields.

First Report of Powdery Mildew of Hexinia polydichotoma Caused by Leveillula lactucae-serriolae in China.

Hexinia polydichotoma (Ostenf) H.L. Yang (synonym Chondrilla polydichotoma Ostenf.) is an indigenous sand-binding plant that is widely distributed only in the desert regions of Northwest China. During the summer of 2007, severe outbreaks of a previously unknown powdery mildew were observed in the Taklimakan Desert in Xinjiang, China. Almost 95% of the plants surveyed were affected in this area. The upper surfaces of the stem were covered with white mycelia and the corresponding abaxial surfaces of infected leaves were chlorotic. Affected young, green stems also showed extended chlorosis. As the disease progressed, the infected stems turned yellow and necrotic. Heavy infection resulted in death of the plants. The primary conidia of the fungus were lanceolate with apical pointed, rarely cylindrical or subcylindrical with attenuated apex. They measured 53 to 73 × 15 to 21 µm and had a surface with a net of irregular rides and warts. Subcylindrical or subclavate secondary conidia with rounded ends measuring 50 to 77 × 13 to 20 µm were observed. The ascomata are subgregarious to scattered, globose, and 165 to 200 µm in diameter that are immersed in the dense mycelial tomentum. Numerous and well-developed appendages on the lower half of the ascomata are irregularly branched and can be as long as up to the ascomata diameter. The appendages measure 79 to 106 × 5 to 10 µm and are aseptate, thin walled, and smooth. Asci are numerous (usually more than 20 per ascoma), stalked, clavate-ovoid to nearly cylindrical, and contain two spores (rarely one or three). Ascospores are ellipsoid, hyaline, and measure 25 to 35 × 14 to 20 µm. On the basis of these characteristics, the fungus was identified as Leveillula lactucae-serriolae (2). A voucher specimen was deposited in the Herbarium of Martin Luther University, Halle, Germany (Accession No. HAL 2439F). To confirm the identification, the internal transcribed spacer (ITS) rDNA was amplified and sequenced, and deposited in GenBank (Accession No. HQ821500). Comparison with sequences available in the GenBank database revealed that the ITS sequence shares 99% similarity with that of L. lactucaeserriolae on Lactuca serriola from Iran (Accession No. AB044375.1) (1). Thus, the pathogen was identified as L. lactucae-serriolae based on the host plant species, anamorph morphology, and ITS sequence. Pathogenicity was confirmed through inoculation by gently pressing a diseased stem onto the stem of healthy H. polydichotoma plants. Five inoculated plants were kept under a plastic humid chamber, whereas the same number of noninoculated plants served as the control. The plants were placed under natural conditions (25 to 28°C) with 80 to 90% humidity. At 15 days after inoculation, typical symptoms of powdery mildew developed on the inoculated plants. No symptoms were seen on the control plants. To our knowledge, this is the first report of L. lactucaeserriolae in China and the first record of L. lactucae-serriolae on H. polydichotoma in the world ( http://nt.ars-grin.gov/fungaldatabases/index.cfm ). Because the plant is becoming widely cultivated in the Taklimakan Desert for use in sand-binding, the powdery mildew poses a serious threat to desertification control. References: (1) S. A. Khodaparast et al. Mycol Res. 105:909. 2001. (2) S. A. Khodaparast et al. Mycoscience 43:459, 2002.