Melatonin reduces inflammation in intestinal cells, organoids and intestinal explants.

Inflammatory bowel diseases (IBDs) are chronic and recurrent diseases that often occur in young people and place a heavy burden on public health in both developed and developing countries. Melatonin has been confirmed to be useful in various diseases, including Alzheimer's disease, liver injuries and diseases, and cancers, while its role in IBDs remains unclear. To uncover the function of melatonin in IBDs, three intestinal models, including Caco-2 cells, 3D intestinal organoids and intestinal explants, were used. It was found that different concentrations of melatonin could significantly inhibit the expression levels of NFκB and its downstream cytokines, including IL6 and IL8 in Caco-2 cells (*P < 0.05, **P < 0.01), 3D intestinal organoids (*P < 0.05, **P < 0.01) and intestinal explants (*P < 0.05, **P < 0.01). Melatonin abolished the activation of LPS on the expression levels of NFκB, IL6, and IL8 in three intestinal models (*P < 0.05, **P < 0.01, ***P < 0.001). Importantly, the roles of melatonin in the regulation of inflammation was dependent on its receptor (i.e., MTNR1), since it was found that silencing of the melatonin receptor (MTNR1A) abolished the reduction in inflammation induced by melatonin in Caco-2 cells (***P < 0.001) and 3D intestinal organoids (***P < 0.01, ****P < 0.0001). Herein, the findings in this study might provide useful information for understanding the pathogenesis of IBDs and developing novel drugs to treat the diseases.

Pathway and rate-limiting step of glyphosate degradation by Aspergillus oryzae A-F02.

Aspergillus oryzae A-F02, a glyphosate-degrading fungus, was isolated from an aeration tank in a pesticide factory. The pathway and rate-limiting step of glyphosate (GP) degradation were investigated through metabolite analysis. GP, aminomethylphosphonic acid (AMPA), and methylamine were detected in the fermentation liquid of A. oryzae A-F02, whereas sarcosine and glycine were not. The pathway of GP degradation in A. oryzae A-F02 was revealed: GP was first degraded into AMPA, which was then degraded into methylamine. Finally, methylamine was further degraded into other products. Investigating the effects of the exogenous addition of substrates and metabolites showed that the degradation of GP to AMPA is the rate-limiting step of GP degradation by A. oryzae A-F02. In addition, the accumulation of AMPA and methylamine did not cause feedback inhibition in GP degradation. Results showed that degrading GP to AMPA was a crucial step in the degradation of GP, which determines the degradation rate of GP by A. oryzae A-F02.

Optimization of liquid-state fermentation conditions for the glyphosate degradation enzyme production of strain Aspergillus oryzae by ultraviolet mutagenesis.

This study aimed to obtain strains with high glyphosate-degrading ability and improve the ability of glyphosate degradation enzyme by the optimization of fermentation conditions. Spore from Aspergillus oryzae A-F02 was subjected to ultraviolet mutagenesis. Single-factor experiment and response surface methodology were used to optimize glyphosate degradation enzyme production from mutant strain by liquid-state fermentation. Four mutant strains were obtained and named as FUJX 001, FUJX 002, FUJX 003, and FUJX 004, in which FUJX 001 gave the highest total enzyme activity. Starch concentration at 0.56%, GP concentration at 1,370 mg/l, initial pH at 6.8, and temperature at 30°C were the optimum conditions for the improved glyphosate degradation endoenzyme production of A. oryzae FUJX 001. Under these conditions, the experimental endoenzyme activity was 784.15 U/100 ml fermentation liquor. The result (784.15 U/100 ml fermentation liquor) was approximately 14-fold higher than that of the original strain. The result highlights the potential of glyphosate degradation enzyme to degrade glyphosate.

Endoscopic inguinal lymphadenectomy for penile carcinoma and genital malignancy: a preliminary report.

BACKGROUND AND PURPOSE: Open radical inguinal lymphadenectomy is reported to have morbidity as high as 50%. We describe our endoscopic inguinal lymphadenectomy that aims at decreasing the morbidity of the procedure without compromising the oncologic outcomes. PATIENTS AND METHODS: Eleven groin dissections were undertaken in seven male patients. The procedure was performed via three ports. The first one was a 10-mm incision 3 mm distal to the apex of the femoral triangle. Two additional trocars (10 mm and 5 mm) were positioned 6 cm medially and laterally to the apex of the triangle, respectively. Taking the great saphenous vein as a landmark, the superficial and deep components were dissected. The boundaries of dissection were the same as those of radical inguinal lymphadenectomy. The numbers of lymph nodes harvested were recorded. The morbidity was retrospectively analyzed. RESULTS: The mean operative time was 126 minutes. The mean number of lymph nodes was 12.3. The averaged output of drainage per leg was 50.8 mL each day. There were only three minor complications: One patient had hypercarbia and pneumoderm, and another had 50 mL of seroma; the third had 180 mL of lymphocele. Follow-up ranged from 4 to 27 months (mean 16.3); there was no evidence of recurrence and other sequelae. CONCLUSIONS: Endoscopic inguinal lymphadenectomy is feasible for patients with penile cancer and genital malignancy. The technique reduces the risk of complication rate, and the oncologic outcome is highly promising. Larger studies, longer term follow-up are needed to assess the oncologic control and possible morbidity.