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Short-chain dehydrogenase/reductases (SDRs) belong to the NAD(P)(H)-dependent oxidoreductase superfamily, which have various functions of catalyzing oxidation/reduction reactions and have been generally used as powerful biocatalysts in the production of pharmaceuticals. In this study, ScSDR1 and ScSDR2, two new SDRs have been identified and characterized from Stachybotrys chartarum 3.5365. Substrate scope investigation revealed that both of the enzymes possessed the ability to oxidize β-OH to ketone specifically, and exhibited substrate promiscuity and high stereo-selectivity for efficiently catalyzing the structurally different prochiral ketones to chiral alcohols. These findings not only suggest that ScSDR1 and ScSDR2 might be potent synthetic tools in drug research and development, but also provide good examples for further engineered enzymes with higher efficiency and stereo-selectivity. [ABSTRACT FROM AUTHOR]

Aim. A meta-analysis was conducted to estimate the impact of connective tissue growth factor (CTGF) on outcomes in patients with digestive system cancers. Methods. A systemic literature survey was performed by searching the Cochrane Library and PubMed databases for articles that evaluated the impact of CTGF on outcomes in patients with digestive system cancers. Hazard ratios and 95% confidence intervals were calculated for prognostic factors, overall and recurrence-free survival using RevMan 5.3 software. Results. This meta-analysis was conducted to evaluate a total of 11 studies that included 1730 patients. The results showed that elevated CTGF expression was significantly correlated with advanced age, larger tumor size, multiple tumors, and vascular invasion. Subgroup analysis by cancer type revealed increased risk for lymph node metastasis and advanced tumor node metastasis (TNM) stage in gastric cancer, compared with colorectal cancer. An unfavorable effect of elevated CTGF levels on overall survival was found in patients with hepatocellular carcinoma and patients with gastric cancer, while survival was improved in colorectal cancer patients with high CTGF expression, compared to those with normal levels of CTGF. Conclusions. Elevated CTGF expression may be a novel biomarker for disease status and predicted survival outcomes in patients with specific digestive system cancers. [ABSTRACT FROM AUTHOR]

Huanglian Jiedu plaster (HJP) is a kind of Chinese patent medicine that contains four medicinal plants. It has been clinically proven to be beneficial for the treatment of tumor-associated radiation dermatitis. However, the underlying mechanism of HJP on radiation dermatitis remains unclear. This study aims to investigate the therapeutic effect of HJP on X-ray-induced radiation dermatitis, and how HJP improves the inflammatory response and skin damage of radiation dermatitis. In this study, We selected a case of esophageal cancer as a clinical demonstration of the efficacy of radiation dermatitis. The patient received a total radiation dose of 7000cGY, and treatment by HJP for 14 days.RD mouse models were established through continuous irradiation with X-ray (800cGY) on the right hind limb of mice for 5 days, and the treatment group mice was applied HJP to the irradiated skin for 15 days from modeling. An inflammatory cellular model was induced through irradiation with X-ray (100cGY) in JB6 cells and a co-culture system of JB6 cell and macrophage was established to examine the effect and mechanism of HJP on the inflammatory interaction of these two cells. The activation of HMGB1-TLR4-NF-κB signaling pathway, and the levels of epidermal injury related factors and inflammatory cytokins were subsequently detected. The results showed that HJP can significantly alleviate X-ray-induced skin injury, inhibiting skin inflammation and reducing the expression of inflammatory cytokins (IL-1β, IL-6, TNF-α) and epidermal damage related factors (Integrin β1, CXCL9 and Cytokeratin17), as well as significantly down-regulated the protein level of HMGB1 (a key DAMPs factor) in vivo and in vitro. Cell co-culture experiments demonstrated that HMGB1 released from X-ray-induced JB6 cells can promote inflammatory response of macrophage, which then feedback aggravate epithelial cell damage, notably, HJP can significantly improve radiation skin lesion by inhibiting HMGB1-mediated inflammatory interaction between epithelial cells and macrophages. In summary, these findings indicated the role of HJP in the treatment of RD by inhibiting the inflammatory interaction between macrophage and JB6 cells mediated by HMGB1, which may provide a reliable therapeutic method for RD. Furthermore, HMGB1 may be an effective target for HJP to inhibit inflammation and ameliorate skin damage in RD. [Display omitted] • HJP can alleviate X-ray-induced skin injury, inhibit skin inflammatory reaction. • HMGB1 can promote JB6's damages by mediating the inflammatory interaction with BMDM. • HJP can inhibit HMGB1-mediated inflammatory interaction. [ABSTRACT FROM AUTHOR]

Flowering time and plant height are important agronomic traits for crop production. In this study, we characterized a semi-dwarf and late flowering (dlf1) mutation of rice that has pleiotropic effects on these traits. The dlf1 mutation was caused by a T-DNA insertion and the cloned Dlf1 gene was found to encode a WRKY transcription factor (OsWRKY11). The dlf1 mutant contains a T-DNA insertion at the promoter region, leading to enhanced accumulation of Dlf1 transcripts, resulting in a semidominant mutation. The dlf1 mutation suppressed the transcription of Ehd2/RID1/OsId1 and its downstream flowering-time genes including Hd1, Ehd1 and Hd3a under both long-day (LD) and short-day (SD) conditions. Knock-down of Dlf1 expression exhibited early flowering at LD condition related to the wild-type plants. Accumulation of Dlf1 mRNA was observed in most tissues, and two splicing forms of Dlf1 cDNAs were obtained (OsWRKY11.1 and OsWRKY11.2). These two proteins showed transactivation activity in yeast cells. Dlf1 protein was found to be localized in the nucleus. Enhanced expression of OsWRKY11.2 or its 5′ truncated gene showed similar phenotypes to the dlf1 mutant, suggesting that it might function as a negative regulator. We conclude that Dlf1 acts as a transactivator to downregulate Ehd2/RID1/OsId1 in the signal transduction pathway of flowering and plays an important role in the regulation of plant height in rice. [ABSTRACT FROM AUTHOR]

Background and Purpose: Paeoniflorin (PF) has ameliorative effects on learning and memory impairment and cerebral ischaemia in rats and has protective effects against the degeneration of dopaminergic neurons in substantia nigra. The neuroprotective effects of PF are most probably derived from its anti-inflammatory property. Abnormally high levels of intercellular adhesion molecule-1 (ICAM-1) have been found to be associated with a wide range of inflammatory and immune responses. Here we studied whether PF regulates the levels of ICAM-1 elevated in LPS-activated differentiated human monocytic U937 cells and TNF-α-stimulated human umbilical vein endothelial cells (HUVECs).Experimental Approach: mRNA levels were evaluated by RT-PCR. Protein levels were evaluated by Western blot analysis. An immunofluorescence technique was used to estimate NF-κB translocation, and NF-κB binding to nuclear DNA was determined by EMSA.Key Results: PF inhibited ICAM-1 expression elevated in LPS-induced U937 cells and TNF-α-stimulated HUVECs. Although previous reports showed that PF's action is mediated by activating adenosine A₁ receptors, application of a selective adenosine A₁ receptor antagonist did not change the inhibitory effect of PF in our experiments. To elucidate the underlying mechanisms of the effect of PF, we studied its effect on signalling pathways upstream of ICAM-1 expression. PF suppressed the activation of the NF-κB pathway, which regulates the expression of ICAM-1. The TLR4 and MAPK pathways were shown not to be involved in the effects of PF in these cells.Conclusions and Implications: PF inhibits ICAM-1 expression in LPS-treated U937 cells and TNF-α-stimulated HUVECs by suppressing the activation of the NF-κB pathway. [ABSTRACT FROM AUTHOR]

Abstract: Western blot has been used to study the time-course effect of the two most popular parkinsonian neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, i.p.) and 6-hydroxydopamine (6-OHDA, intra-substantia nigra), on the expression of several regulators of G-protein signaling (RGS2, 4 and 9) in striatum in rodents. During the few days after MPTP challenge, there was a decline (as expected) in tyrosine hydroxylase expression in the mouse striatum that was accompanied by a decline in RGS9 protein; the latter was specific and did not extend to RGS2 or RGS4 which were resistant to the MPTP challenge. Much the same pattern was observed in rats after 6-OHDA challenge, again, specific to RGS9, although the effect takes a few weeks, rather than a few days, to develop. These results may be helpful for the understanding of molecular mechanism underlying Parkinson''s disease (PD) and RGS9 might involve in the striatal function associated with PD. [Copyright &y& Elsevier]

Abstract: Garlic oil (GO) has been shown to partially attenuate ethanol-induced fatty liver, but the underlying mechanisms remain unclear. The current study was designed to evaluate the protective effects of GO against ethanol-induced steatosis in vitro and in vivo, and to explore potential mechanisms by investigating the sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferators-activated receptor-α (PPAR-α), cytochrome P4502E1 (CYP2E1), and etc. In the in vitro study, human normal cell LO2 was exposed to 100mM ethanol in the presence or absence of GO for 24h. We found that ethanol increased the protein levels of n-SREBP-1c and CYP2E1, but decreased the protein levels of PPAR-α, which was significantly attenuated by GO co-treatment. In the in vivo study, male Kun-Ming mice were pretreated with single dose of GO (50–200mg/kg body weight) at 2h before ethanol (4.8g/kg body weight) exposure. The changes of n-SREBP-1c, PPAR-α and CYP2E1 were paralleled well to those of in vitro study. Furthermore, GO significantly reduced the protein levels of fatty acid synthase (FAS), and suppressed ethanol-induced hepatic mitochondrial dysfunction. These results suggested that GO had the potential to ameliorate alcoholic steatosis which might be related to its modulation on SREBP-1c, PPAR-α, and CYP2E1. [Copyright &y& Elsevier]