Phomopsis (Diaporthe) Species as the Cause of Soybean Seed Decay in Korea

Soybeans are an important crop known to harbour a complex of Diaporthe and Phomopsis species. This complex has been reported to be involved in several soybean diseases, including Phomopsis seed decay. In this study, two species of Diaporthe/Phomopsis fungi from soybean plants were identified by morphological and molecular characterizations. Koch's postulates were confirmed by pathogenicity tests on hypocotyls of soybean seedlings. Phomopsis longicolla was found to be the most common and virulent pathogen to soybeans in Korea. Phomopsis sp., which was considered as a new soybean pathogen, might have been introduced from other plants given that similar strains of Phomopsis sp. have infected fruit trees in China, Japan and Portugal and vegetable plants in the United States.     

TGFA and IRF6 Contribute to the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate in Northeast China

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) are common birth defects with a complex etiology. Multiple interacting loci and possible environmental factors influence the risk of NSCL/P. 12 single nucleotide polymorphisms (SNPs) in 7 candidate genes were tested using an allele-specific primer extension for case-control and case-parent analyses in northeast China in 236 unrelated patients, 185 mothers and 154 fathers, including 128 complete trios, and 400 control individuals. TGFA and IRF6 genes showed a significant association with NSCL/P. In IRF6, statistical evidence of an association between rs2235371 (p = 0.003), rs2013162 (p<0.0001) and NSCL/P was observed in case-control analyses. Family based association tests (FBATs) showed over-transmission of the C allele at the rs2235371 polymorphism (p = 0.007). In TGFA, associations between rs3771494, rs3771523 (G3822A), rs11466285 (T3851C) and NSCL/P were observed in case-control and FBAT analyses. Associations between other genes (BCL3, TGFB3, MTHFR, PVRL1 and SUMO1) and NSCL/P were not detected.     

Novel 2-aminooctahydrocyclopentalene-3a-carboxamides as potent CCR2 antagonists

Novel CCR2 antagonists with a novel 2-aminooctahydrocyclopentalene-3a-carboxamide scaffold were designed. SAR studies led to a series of potent compounds. For example, compound 51 had a good PK profile in both dog and monkey, and exhibited excellent efficacy when dosed orally in an inflammation model in hCCR2 KI mice. In addition, an asymmetric synthesis to the core structures was developed.     

Juglone,isolated from Juglans mandshurica Maxim,induces apoptosis via down-regulation of AR expression in human prostate cancer LNCaP cells

Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim. Recent studies have shown that juglone had various pharmacological effects such as anti-viral, anti-bacterial and anti-cancer. However, its anti-cancer activity on human prostate cancer LNCaP cell has not been examined. Thus, the current study was designed to elucidate the molecular mechanism of apoptosis induced by juglone in androgen-sensitive prostate cancer LNCaP cells. MTT assay was performed to examine the anti-proliferative effect of juglone. Occurrence of apoptosis was detected by Hoechst 33342 staining and flow cytometry in LNCaP cells treated with juglone for 24 h. The result shown that juglone inhibited the growth of LNCaP cells in a dose-dependent manner. Morphological changes of apoptotic body formation after juglone treatment were observed by Hoechst 33342 staining. This apoptotic induction was associated with loss of mitochondrial membrane potential, and caspase-3, -9 activation. Moreover, we found that juglone significantly inhibited the expression levels of androgen receptor (AR) and prostate-specific antigen (PSA) in a dose-dependent manner, as well as abrogated up-regulation of AR and PSA genes with and/or without dihydrotestosterone (DHT). Take together, our results demonstrated that juglone might induce the apoptosis in LNCaP cell via down-regulation of AR expression. Therefore, our results indicated that juglone may be a potential candidate of drug for androgen-sensitive prostate cancer.     

Tumour epithelial expression levels of endocannabinoid markers modulate the value of endoglin-positive vascular density as a prognostic marker in prostate cancer

Fatty acid amide hydrolase (FAAH) is responsible for the hydrolysis of the endogenous cannabinoid (CB) receptor ligand anandamide. Here we have investigated whether the expression levels of FAAH and CB₁ receptors influence the prognostic value of markers of angiogenesis in prostate cancer. Data from a cohort of 419 patients who were diagnosed with prostate cancer at transurethral resection for lower urinary tract symptoms, of whom approximately 2/3 had been followed by expectancy, were used. Scores for the angiogenesis markers endoglin and von Willebrand factor (vWf), the endocannabinoid markers fatty acid amide hydrolase (FAAH) and cannabinoid CB₁ receptors and the cell proliferation marker Ki-67 were available in the database. For the cases followed by expectancy, the prognostic value of endoglin was dependent upon the tumour epithelial FAAH immunoreactivity (FAAH-IR) and CB₁IR scores, and the non-malignant epithelial FAAH-IR scores, but not the non-malignant CB₁IR scores or the tumour blood vessel FAAH-IR scores. This dependency upon the tumour epithelial FAAH-IR or CB₁IR scores was less apparent for vWf, and was not seen for Ki-67. Using an endoglin cut-off value of 10 positively stained vessels per core and a median split of tumour FAAH-IR, four groups could be generated, with 15 year of disease-specific survival (%) of 68 ± 7 (low endoglin, low FAAH), 45 ± 11 (high endoglin, low FAAH), 77 ± 6 (low endoglin, high FAAH) and 21 ± 10 (high endoglin, high FAAH). Thus, the cases with high endoglin and high FAAH scores have the poorest rate of disease-specific survival. At diagnosis, the number of cases with tumour stages 1a–1b relative to stages 2–4 was sensitive to the endoglin score in a manner dependent upon the tumour FAAH-IR. It is concluded that the prognostic value of endoglin as a marker of neovascularisation in prostate cancer can be influenced by the expression level of markers of the endocannabinoid system. This article is part of a Special Issue entitled Lipid Metabolism in Cancer.     

Expression pattern of vasa in gonads of sea cucumber Apostichopus japonicus during gametogenesis and reproductive cycle

The vasa gene is a reliable germline marker to study the origin and development of germ cells and gonads, although the gene product (mRNA or protein) varies between different species. However, there has been little study on vasa genes in holothuroids to date. Here we determined the expression characteristics of the Apostichopus japonicus vasa gene (Aj-vasa) during gametogenesis in the ovary and testis using in situ hybridization and immunohistochemistry. During oogenesis, the expression pattern of Aj-vasa coincided at the mRNA and protein levels. Intensive signals in oogonia decreased gradually with the development of oocytes. Interestingly, the pattern was different during spermatogenesis. The Aj-vasa mRNA level was the highest in spermatogonia, reduced in spermatocytes, low in spermatids and absent in spermatozoa, but the Aj-VASA protein was restricted to spermatogonia and early spermatocytes. These expression characteristics of Aj-vasa persisted in both male and female gonads throughout the reproductive cycle. Our findings show that Aj-vasa mRNA is a good marker for studying the origin and migration of germline cells; moreover, Aj-VASA is a useful tool to identify spermatogonia in A. japonicus. Our findings indicate that Aj-vasa is vital in the development and differentiation of germ cells.     

A let-7/Fas double-negative feedback loop regulates human colon carcinoma cells sensitivity to Fas-related apoptosis

α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38 kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.