Aflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological solutions for aflatoxin detoxification are environmentally friendly and a cheaper alternative than chemical methods. The aims of the current study were to investigate: (1) the ability of MSMEG_5998, an aflatoxin-degrading F420H2-dependent reductase from Mycobacterium smegmatis, to degrade aflatoxin B1 (AFB1) and reduce AFB1-caused damage in HepG2 cell culture model; and (2) whether a thioredoxin (Trx) linkage of MSMEG_5998 enhanced the enzyme activity. We show that Trx-linked MSMEG_5998 degraded 63% AFB1 and native MSMEG_5998 degraded 31% after 4 h at 22 °C, indicating that the Trx-linked enzyme had a better AFB1-degrading ability. In a HepG2 cell culture model, Trx-linked MSMEG_5998 reduced DNA damage and p53-mediated apoptosis caused by AFB1 to a greater extent than the native enzyme. These findings suggest that Trx-linked MSMEG_5998 could potentially be developed to protect the liver from AFB1 damage, or as a candidate protein to reduce AFB1-related toxicity in animals.
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5-Fluorouracil (5-FU) is used in the treatment of head and neck cancer patients. However, adverse effects experienced such as mucositis and poor appetite may lead to interruption in chemotherapy. The aim of this study is to evaluate the efficacy of GMI, one fungal immunomodulatory protein found in Ganoderma microsporum, for mucositis induced by 5-FU in a mouse model. Mice were administered 5-FU intraperitoneally for 4 days per cycle for a total of 2 chemotherapy cycles. In addition, mice were pretreated with GMI or phosphate-buffered saline 3 days before 5-FU intraperitoneal injection and daily until day 14. On histological analysis, GMI prevented 5-FU-induced damage to the intestinal mucosa and tongue epithelium. We also demonstrated that GMI enhanced the cytotoxicity of 5-FU in 2 oral cancer cell lines, while GMI could not promote this effect in an oral normal cell. In conclusion, GMI alleviates 5-FU-induced damage and decelerates cell death in normal alimentary tract tissue.
While catecholamines like epinephrine (E) and norepinephrine (NE) are commonly used in emergency medicine, limited studies have discussed the harm of exogenously induced catecholamine overdose. We investigated the possible toxic effects of excessive catecholamine administration on cardiopulmonary function and structure via continuous 6 h intravenous injection of E and/or NE in rats. Heart rate, echocardiography, and ventricular pressure were measured throughout administration. Cardiopulmonary structure was also assessed by examining heart and lung tissue. Consecutive catecholamine injections induced severe tachycardia. Echocardiography results showed NE caused worse dysfunction than E. Simultaneously, both E and NE led to higher expression of Troponin T and connexin43 in the whole ventricles, which increased further with E+NE administration. The NE and E+NE groups showed severe pulmonary edema while all catecholamine-administering groups demonstrated reduced expression of receptor for advanced glycation end products and increased connexin43 levels in lung tissue. The right ventricle was more vulnerable to catecholamine overdose than the left. Rats injected with NE had a lower survival rate than those injected with E within 6 h. Catecholamine overdose induces acute lung injuries and ventricular cardiomyopathy, and E+NE is associated with a more severe outcome. The similarities of the results between the NE and E+NE groups may indicate a predominant role of NE in determining the overall cardiopulmonary damage. The results provide important clinical insights into the pathogenesis of catecholamine storm.
Background:Cancer patients usually suffer from intensive chemotherapy-related oral mucositis (OM), yet limited effective treatment can rapidly alleviate OM severity.Methods:This prospective study examined the efficacy of Reishimmune-S containing one fungal immunomodulatory protein, GMI on OM in patients with head and neck cancer. Patients with head and neck cancer and the diagnosis of chemotherapy-related OM were enrolled randomizedly to receive standard supportive care with/without Reishimmune-S 500 mg/day orally for consecutive 14 days. Due to intolerance to standard supportive care alone in the control arm, only the experimental arm with Reishimmune-S supplementation was analyzed in our trial. OM grading was evaluated as the primary outcome on day 1, 8, and 15. Secondary outcomes were absolute neutrophil counts and quality of life assessed by the EORTC-QLQ-H&N 35 questionnaire on day 1, 8, and 15.Results:Reishimmune-S supplement significantly reduced OM grading both at day 8 and 15. Trouble with social contact and weight loss conditions were also improved by Reishimmune-S. Reishimmune-S did not significantly affect absolute neutrophil counts during the 15-day follow-up.Conclusion:Reishimmune-S supplement potentially alleviates the severity of chemotherapy-mediated OM.
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