Ochratoxin A (OTA), mainly produced by Aspergillus and Penicillum species, is one of the most important mycotoxin contaminants in agricultural products. It is detrimental to human health because of its nephrotoxicity, hepatotoxicity, carcinogenicity, teratogenicity, and immunosuppression. OTA structurally consists of adihydrocoumarin moiety linked with l-phenylalanine via an amide bond. OTA biosynthesis has been putatively hypothesized, although several contradictions exist on some processes of the biosynthetic pathway. We discuss recent information on molecular studies of OTA biosynthesis despite insufficient genetic background in detail. Accordingly, genetic regulation has also been explored with regard to the interaction between the regulators and the environmental factors. In this review, we focus on three aspects of OTA: OTA-producing strains, OTA biosynthetic pathway and the regulation mechanisms of OTA production. This can pave the way to assist in protecting food and feed from OTA contamination by understanding OTA biosynthetic pathway and regulatory mechanisms.

Neural stem cells (NSCs) show therapeutic potential for ischemia in young-adult animals. However, the effect of aging on NSC therapy is largely unknown. In this work, NSCs were transplanted into aged (24-month-old) and young-adult (3-month-old) rats at 1 day after stroke. Infarct volume and neurobehavioral outcomes were examined. The number of differentiated NSCs was compared in aged and young-adult ischemic rats and angiogenesis and neurogenesis were also determined. We found that aged rats developed larger infarcts than young-adult rats after ischemia (Po0.05). The neurobehavioral outcome was also worse for aged rats comparing with young-adult rats. Brain infarction and neurologic deficits were attenuated after NSC transplantation in both aged and young-adult rats. The number of survived NSCs in aged rats was similar to that of the young-adult rats (P40.05) and most of them were differentiated into glial fibrillary acidic protein þ (GFAP þ ) cells. More importantly, angiogenesis and neurogenesis were greatly enhanced in both aged and young-adult rats after transplantation compared with phosphate-buffered saline (PBS) control (Po0.05), accompanied by increased expression of vascular endothelial growth factor (VEGF). Our results showed that NSC therapy reduced ischemic brain injury, along with increased angiogenesis and neurogenesis in aged rats, suggesting that aging-related microenvironment does not preclude a beneficial response to NSCs transplantation during cerebral ischemia.

Ochratoxin A (OTA) is a toxic secondary metabolite produced by and species that widely contaminate food and feed. We sequenced and assembled the complete ∼37 Mb genome of fc-1, a well-known producer of OTA. Key genes of the OTA biosynthetic pathway were identified by comparative genomic analyses with five other sequenced OTA-producing fungi,, ,, , and OTA production was completely inhibited in the deletion mutants (- and ), and OTA biosynthesis was restored by feeding a post-block substrate to the corresponding mutant. The OTA biosynthetic pathway was unblocked with the addition of heterologously expressed halogenase in the mutant. OTA biosynthesis begins with PKS (), utilizing acetyl-CoA and malonyl-CoA to synthesize 7-methylmellein, which is oxidized to OTβ by cytochrome P450 monooxygenase (). OTβ and L-β-phenylalanine are combined by NRPS () to form an amide bond to synthesize OTB. Finally, OTB is chlorinated by halogenase () to OTA. The - genes were expressed at low levels in the mutant. A second regulator, otaR2, which is adjacent to the biosynthetic gene, could modulate only the expression of, and Thus, we have identified a consensus OTA biosynthetic pathway that can be used to prevent and control OTA synthesis, and to understand variation and production of the intermediate components in the biosynthetic pathway. Ochratoxin A (OTA) is a significant mycotoxin that contaminates cereal products, coffee, grapes, wine, cheese and meat. OTA is nephrotoxic, carcinogenic, teratogenic and immunotoxic. OTA contamination is a serious threat to food safety, endangers human health and can cause huge economic losses. At present, more than 20 species of the genera and are known to produce OTA. Here, we demonstrate that a consensus OTA biosynthetic pathway exists in all OTA-producing fungi and that is encoded by a gene cluster containing four highly conserved biosynthetic genes and a bZIP transcription factor.

Our data suggest that timing and cell dose of transplantation determine the therapeutic effects after focal ischemia by modulating poststroke neuroinflammation.

It is well known that tea has a variety of beneficial impacts on human health, including anti-obesity effects. It is well documented that green tea and its constituent catechins suppress obesity, but the effects of other types of tea on obesity and the potential mechanisms involved are not yet fully understood. In this study, we investigated the suppression of adiposity by oolong, black and pu-erh tea and characterized the underlying molecular mechanism in vivo. We found that the consumption of oolong, black or pu-erh tea for a period of one week significantly decreased visceral fat without affecting body weight in male ICR mice. On a mechanistic level, the consumption of tea enhanced the phosphorylation of AMP-activated protein kinase (AMPK) in white adipose tissue (WAT). This was accompanied by the induction of WAT protein levels of uncoupling protein 1 and insulin-like growth factor binding protein 1. Our results indicate that oolong, black and pu-erh tea, and in particular, black tea, suppresses adiposity via phosphorylation of the key metabolic regulator AMPK and increases browning of WAT.

Procyanidins are the oligomeric or polymeric forms of epicatechin and catechin. In this study, we isolated and purified dimer to tetramer procyanidins from black soybean seed coat and investigated the anti-hyperglycemic effects by focusing on glucose transporter 4 (GLUT4) translocation and the underlying molecular mechanism in skeletal muscle of mice. The anti-hyperglycemic effects of procyanidins were also compared with those of monomer (−)-epicatechin (EC) and major anthocyanin, cyanidin-3-O-β-glucoside (C3G). To investigate GLUT4 translocation and its related signaling pathways, ICR mice were orally given procyanidins, EC and C3G in water at 10 μg/kg body weight. The mice were sacrificed 60 min after the dose of polyphenols, and soleus muscle was extracted from the hind legs. The results showed that trimeric and tetrameric procyanidins activated both insulin- and AMPK-signaling pathways to induce GLUT4 translocation in muscle of ICR mice. We confirmed that procyanidins suppressed acute hyperglycemia with an oral glucose tolerance test in a dose-dependent manner. Of these beneficial effects, cinnamtannin A2, one of the tetramers, was the most effective. In conclusion, procyanidins, especially cinnamtannin A2, significantly ameliorate postprandial hyperglycemia at least in part by promoting GLUT4 translocation to the plasma membrane by activating both insulin- and AMPK-signaling pathways.

Rice sheath blight, caused by Rhizoctonia solani is one of the major diseases of rice. The pathogen infects rice plants directly through stomata or using lobate appressoria and hyphal masses called infection cushions. The infection structures were normally found at 36 h post-inoculation. During infection, the pathogenesis-related genes, PR1b and PBZ1 were induced in rice plants. To identify rice genes induced early in the defense response, suppression subtractive hybridization (SSH) was used to generate a cDNA library enriched for transcripts differentially expressed during infection by R. solani. After differential screening by membrane-based hybridization and subsequent confirmation by reverse Northern blot analysis, selected clones were sequenced. Fifty unique cDNA clones were found and assigned to five different functional categories. Most of the genes were not previously identified as being induced in response to pathogens. We examined expression of 100 rice genes induced by infection with Magnaporthe grisea, Xanthomonas oryzae pv. oryze (Xoo) and X. oryzae pv. oryzicola (Xooc). Twenty-five of them were found to be differentially expressed after the sheath blight infection, suggesting overlap of defense responses to different fungal and bacterial pathogens infection.

In Aspergillus and Penicillium species, an essential pH-response transcription factor pacC is involved in growth, pathogenicity, and toxigenicity. To investigate the connection between ochratoxin A (OTA) biosynthesis and ambient pH, the AopacC in Aspergillus ochraceus was functionally characterized using a loss-of-function mutant. The mycelium growth was inhibited under pH 4.5 and 10.0, while the sporulation increased under alkaline condition. A reduction of mycelium growth and an elevation of sporulation was observed in Δ AopacC mutant. Compared to neutral condition, OTA contents were respectively reduced by 71.6 and 79.8% under acidic and alkaline conditions. The expression of AopacC increased with the elevated pH, and deleting AopacC dramatically decreased OTA production and biosynthetic genes Aopks expression. Additionally, the Δ AopacC mutant exhibited attenuated infection ability toward pear fruits. These results suggest that AopacC is an alkaline-induced regulator responsible for growth and OTA biosynthesis in A. ochraceus and this regulatory mechanism might be pH-dependent.