Production of the antifungal biopesticide physcion through the combination of microbial fermentation and chemical post-treatment.

Physcion is an anthraquinone compound observed dominantly in medicinal herbs. This anthraquinone possesses a variety of pharmaceutically important activities and has been developed to be a widely used antifungal biopesticide. Herein, we report on the effective preparation of 3R-torosachrysone (4), a tetrahydroanthracene precursor of physcion, in Aspergillus oryzae NSAR1 by heterologous expression of related genes mined from the phlegmacins-producing ascomycete Talaromyces sp. F08Z-0631. Conditions for converting 4 into physcion were studied and optimized, leading to the development of a concise approach for extracting high-purity physcion from the alkali-treated fermentation broth of the 4-producing A. oryzae strain.

Successful management of life-threatening aortoesophageal fistula: A case report and review of the literature.

BACKGROUND: Aortoesophageal fistula (AEF) is a rare but life-threatening cause of upper gastrointestinal bleeding. Only a handful of cases of successful management of AEF caused by esophageal cancer have been reported. The purpose of this study is to report a case of AEF managed by endovascular aortic repair and review the relevant literature. CASE SUMMARY: A 66-year-old man with upper gastroenterology bleeding presented at the Emergency Department of our hospital complaining of chest pain, fever and hematemesis for 6 h. He had vomited 400 mL of bright-red blood and experienced severe chest pain 6 h prior. He had a past medical history of advanced esophageal cancer. He received chemoradiotherapy but stopped 8 mo prior because of intolerance. A chest contrast computed tomographic scan revealed communication between the esophagus and the descending aorta as well as a descending aortic pseudoaneurysm. According to the symptoms and imaging findings, AEF was our primary consideration. The patient underwent aortic angiography, which indicated AEF and descending aortic pseudoaneurysm. Emergency percutaneous thoracic endovascular aortic repair (TEVAR) of the descending aorta was performed, and bleeding was controlled after TEVAR. He received antibiotics and was discharged after treatment. However, he died 2 mo after the TEVAR due to cancer progression. CONCLUSION: Although AEF is a lethal condition, timely diagnosis and TEVAR may successfully control bleeding.

Melatonin Induces AGS Gastric Cancer Cell Apoptosis via Regulating PERK/eIF2α and HSF1/NF-κB Signaling Pathway.

OBJECTIVE: Melatonin exhibits numerous anti-cancer activities in the treatment of human cancers. Nevertheless, the mechanisms of anti-gastric cancer effect of melatonin is still unclear. The aim of the study is to investigate the interaction between melatonin, endoplasmic reticulum (ER) stress, NF-κB signaling and HSF1 protein in gastric cancer cells. METHODS: In the current study, we used CCK-8, flow cytometry and Western blot to research anticancer mechanism of melatonin in AGS cells. RESULTS: The data demonstrated that melatonin could suppress cell proliferation and increase cell apoptosis. We explore that the ER stress and NF-kB signaling pathways play crucial roles in the cell apoptosis process. Of note, melatonin increased the expression of p-PERK and p-eIF2α, and decreased the expression of p-P65 and p-IκBα. A combination of melatonin and PERK inhibitor (GSK2606414) or NF-κB inhibitor (Bay11-7082) suppressed the activation PERK/eIF2α and NF-κB signaling pathway. Subsequently, the expression of HSF1 protein was upregulated by melatonin and kept its expression by Bay 11-7082. CONCLUSION: These results suggest that melatonin induces AGS cell apoptosis by up-regulating PERK/eIF2α and downregulating NF-κB signaling pathway.

Exploring kinetics, removal mechanism and possible transformation products of tigecycline by Chlorella pyrenoidosa.

The accumulation of antibiotics in wastewater leads to broad antibiotic resistance, threating human health. Microalgae have been receiving attention due to their ability to remove antibiotics from wastewater. Tigecycline (TGC) is a broad-spectrum glycylcycline antibiotic. It has not been investigated for removal by microalgae. The removal kinetics of TGC by Chlorella pyrenoidosa were evaluated under different initial dry cell densities, TGC concentrations, temperatures and light intensity conditions. Approximately 90% of TGC could be removed when the TGC concentration was 10 mg∙L-1 and the initial dry cell density was more than 0.2 g∙L-1. A low value of TGC per g dry cell weight ratio led to a high removal efficiency of TGC. The initial dry cell density of microalgae was also critical for the removal of TGC. A high initial dry cell density is better than a low initial dry cell density to remove TGC when the ratio of the TGC concentration to dry cell weight are the same at the beginning of the cultivation. The removal mechanisms were investigated. Photolysis was a slow process that did not lead to removal at the beginning. Adsorption, hydrolysis, photolysis and biodegradation by microalgae were the main contributors to the removal of TGC. TGC was easily hydrolyzed under high -temperature conditions. Three transformation products of TGC by microalgae were identified. The stability of TGC was evaluated in water and salt solutions of citric acid, K2HPO4·3H2O and ferric ammonium citrate. TGC was stable in ultrapure water and citric acid solution. TGC was hydrolyzed in K2HPO4·3H2O and ferric ammonium citrate solutions.

Growth Performance and Antioxidative Response of Chlorella pyrenoidesa, Dunaliella salina, and Anabaena cylindrica to Four Kinds of Ionic Liquids.

Ionic liquids are widely used for lipid and pigment extractions from microalgae. It is possible that ionic liquids are discharged into environments. The evaluation of growth performance and antioxidative response of ionic liquids to microalgae is helpful to explore the stress regulation mechanism and investigate possible environmental risk. Ionic liquids induce production of reactive oxygen species (ROS) to microalgae. These oxidative stresses are possible from cations, anions, and salinity. In this study, the growth inhibitions of [BMIM]Br, [BMIM]Cl, [EMIM]Cl, and [EMIM]EtOSO3 to Anabaena cylindrica, Chlorella pyrenoidesa, and Dunaliella salina were evaluated. It was interesting that Br- and two kinds of cations, [BMIM] and [EMIM], had significant effects on growth inhibitions of these microalgae. IC50 values of these ionic liquids for A. cylindrica, C. pyrenoidesa, and D. salina were also estimated based on the results of growth inhibitions. It was proved that [EMIM]Cl is relatively harmless to C. pyrenoidesa and D. salina, and [EMIM]EtOSO3 is relatively or practically harmless to C. pyrenoidesa. [BMIM]Br and [BMIM]Cl are practically harmless to A. cylindrica and C. pyrenoidesa, and relatively harmless to D. salina. More than 0.8 g/L [EMIM]EtOSO3 led to bleaching of both A. cylindrica and D. salina at 48 h which was shown that the anion, EtOSO3-, had higher inhibition to A. cylindrica and D. salina than Cl-. In addition, high concentration of ionic liquids led to reductions of chlorophyll content in these three kinds of microalgae, increase of ROS levels and malondialdehyde contents for most of the cases. High concentration of ionic liquids also increased the activities of superoxide dismutase in three kinds of microalgae. There were positive correlations between ROS levels or MDA content, and inhibitions ratios of these ionic liquids to microalgae except [EMIM]Cl to A. cylindrica. These antioxidant enzymes were beneficial for reducing the ROS induced by ionic liquids.

Effects of three antibiotics on growth and antioxidant response of Chlorella pyrenoidosa and Anabaena cylindrica.

Antibiotics are essential for treatments of bacterial infection and play important roles in the fields of aquaculture and animal husbandry. Antibiotics are accumulated in water and soil due to the excessive consumption and incomplete treatment of antibiotic wastewater. The accumulation of antibiotics in ecological systems leads to global environmental risks. The toxic effects of spiramycin (SPI), tigecycline (TGC), and amoxicillin (AMX) on Chlorella pyrenoidesa and Anabaena cylindrica were evaluated based on growth inhibition experiments, and determinations of ROS production and antioxidant enzyme activities (catalase, superoxide dismutase, and malondialdehyde). Half maximal effective concentrations (EC50) of TGC, SPI, and AMX for A. cylindrica were 62.52 µg/L, 38.40 µg/L, and 7.66 mg/L, respectively. Those were 6.20 mg/L, 4.58 mg/L, and > 2 g/L for C. pyrenoidesa, respectively. It was shown that A. cylindrica was much more sensitive to these antibiotics than C. pyrenoidesa. In addition, EC50 values of SPI and TGC were lower than that of AMX. It was indicated that SPI and TGC had higher toxic than AMX to C. pyrenoidesa and A. cylindrica. The current study is helpful to evaluating possible ecological risks of TGC, SPI, and AMX by green microalgae and cyanobacteria.

Association between gene methylation and HBV infection in hepatocellular carcinoma: A meta-analysis.

Gene methylation is an epigenetic alteration in hepatocellular carcinoma (HCC), and hepatitis B virus (HBV) plays a crucial role in carcinogenesis of HCC. However, the association between gene methylation and HBV infection in HCC remains unclear. In our study, we conducted a comprehensive meta-analysis to evaluate the association. A total of 1,148 studies were initially retrieved from some literature database. After a four-step filtration, we obtained 69 case-control studies in this meta-analysis. Our results showed six genes (p16, RASSF1A, GSTP1, APC, p15 and SFRP1) in HBV-positive carcinoma tissues, one gene (GSTP1) in HBV-positive adjacent tissues and two gene (p16 and APC) in HBV-positive carcinoma serums, which were significantly hypermethylated. Subgroup meta-analysis by geographical populations revealed that GSTP1 methylation was significantly higher in HBV-positive carcinoma tissues in China and Japan. In addition, p16 and RASSF1A methylation was significantly higher in China but not in Japan. Our study indicated that HBV infection could induce DNA methylation in HCC and DNA methylation could lead to the development of HBV-related HCC.

Baicalin attenuates diet induced nonalcoholic steatohepatitis by inhibiting inflammation and oxidative stress via suppressing JNK signaling pathways.

Nonalcoholic steatohepatitis may develop into hepatic cirrhosis. The therapeutic drugs for NASH are absent. Baicalin (BC) has hepatoprotective effect, while whether BC could prevent the development of NASH is unknown. This study aimed to investigate the effect of BC on the development of diet induced NASH and the possible mechanisms involved. Mice were fed with high fat and high cholesterol (HFC) diet to establish a NASH model, BC (0.5% w/w) was added into the diet to evaluate its effect on NASH. Mice fed an HFC diet developed NASH in 12 weeks. BC administration attenuated hepatic steatosis, inflammation and fibrosis induced by HFC diet. The NALFD activity score (NAS) was sharply decreased by BC. Mice serum ALT and AST were decreased in the BC group. BC decreased hepatic inflammatory cell infiltration, inflammatory genes (MCP-1, TNFα) and fibrosis genes (COL1, α-SMA, TGFß) mRNA expression. BC has antioxidant function evidenced by upregulated hepatic GSH and SOD levels and downregulated MDA levels. BC restored some oxidative stress markers including 4-HNE, 8-OHdG in liver. Western blot analysis stated that BC suppressed pro-inflammatory COX-2 levels, pro-oxidative CYP2E1 levels and phosphorylation of JNK in mice liver. Collectively, BC can attenuate diet induced NASH and the mechanism in which possibly due to its anti-inflammatory and anti-oxidant effects via blockade of the activation of JNK.

Honokiol attenuates diet-induced non-alcoholic steatohepatitis by regulating macrophage polarization through activating peroxisome proliferator-activated receptor γ.

BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) may develop into hepatic cirrhosis. This study aimed to investigate whether honokiol could prevent NASH induced by high-cholesterol and high-fat (CL) diet in mice and the possible mechanism involved. METHODS: Mice were fed with CL diet for 12 weeks to establish a NASH model; honokiol (0.02% w/w in diet) was added to evaluate its effect on NASH. Murine peritoneal macrophages, RAW264.7 and ANA-1 cells, were used to explore the possible mechanisms of honokiol on macrophage polarization. RESULTS: Mice developed NASH after fed with CL diet for 12 weeks. Honokiol supplementation alleviated insulin resistance, hepatic steatosis, inflammation, and fibrosis induced by CL diet. Immunohistochemistry showed that honokiol induced more M2 macrophages in livers compared with CL diet alone. Honokiol decreased M1 marker genes (TNFα and MCP-1) and increased M2 marker gene (YM-1, IL-10, IL-4R and IL-13) expression in mice liver compared with CL diet. Moreover, treatment with honokiol lowered alanine aminotransferase and aspartate aminotransferase in serum and preserved liver from lipid peroxidation, evidenced by lowered hepatic malondialdehyde level. Honokiol has antioxidant function, as honokiol upregulated hepatic glutathione and superoxide dismutase level and downregulated hepatic CYP2E1 protein level. Hepatic peroxisome proliferator-activated receptor γ (PPARγ) and its target genes were upregulated by honokiol. Furthermore, honokiol (10 µM) treatment in mouse peritoneal cells, RAW264.7 cells and ANA-1 cells, led to M2 macrophage polarization, whereas a PPARγ antagonist, GW9662, abolished this effect of honokiol. CONCLUSIONS: Honokiol can attenuate CL diet-induced NASH and the mechanism in which possibly is polarizing macrophages to M2 phenotype via PPARγ activation.

Multiple tumor-associated microRNAs modulate the survival and longevity of dendritic cells by targeting YWHAZ and Bcl2 signaling pathways.

Tumors use a wide array of immunosuppressive strategies, such as reducing the longevity and survival of dendritic cells (DCs), to diminish immune responses and limit the effect of immunotherapy. In this study, we found that tumors upregulate the expression of multiple microRNAs (miRNAs), such as miR-16-1, miR-22, miR-155, and miR-503. These tumor-associated miRNAs influenced the survival and longevity of DCs by affecting the expression of multiple molecules that are associated with apoptotic signaling pathways. Specifically, miR-22 targeted YWHAZ to interrupt the PI3K/Akt and MAPK signaling pathways, and miR-503 downregulated Bcl2 expression. The result of the increased expression of miR-22 and miR-503 in the tumor-associated DCs was their reduced survival and longevity. Thus, tumor-associated miRNAs can target multiple intracellular signaling molecules to cause the apoptosis of DCs in the tumor environment. Use of miR-22 and miR-503 as inhibitors may therefore represent a new strategy to improve DC-based immunotherapies against tumors.