6-Methoxydihydrosanguinarine exhibits cytotoxicity and sensitizes TRAIL-induced apoptosis of hepatocellular carcinoma cells through ROS-mediated upregulation of DR5.

6-methoxydihydrosanguinarine (6-MS), a natural benzophenanthridine alkaloid extracted from Macleaya cordata (Willd.) R. Br, has shown to trigger apoptotic cell death in cancer cells. However, the exact mechanisms involved have not yet been clarified. The current study reveals the underlying mechanisms of 6-MS-induced cytotoxicity in hepatocellular carcinoma (HCC) cells and investigates whether 6-MS sensitizes TNF-related apoptosis inducing ligand (TRAIL)-induced apoptosis. 6-MS was shown to suppress cell proliferation and trigger cell cycle arrest, DNA damage, and apoptosis in HCC cells. Mechanisms analysis indicated that 6-MS promoted reactive oxygen species (ROS) generation, JNK activation, and inhibits EGFR/Akt signaling pathway. DNA damage and apoptosis induced by 6-MS were reversed following N-acetyl-l-cysteine (NAC) treatment. The enhancement of PARP cleavage caused by 6-MS was abrogated by pretreatment with JNK inhibitor SP600125. Furthermore, 6-MS enhanced TRAIL-mediated HCC cells apoptosis by upregulating the cell surface receptor DR5 expression. Pretreatment with NAC attenuated 6-MS-upregulated DR5 protein expression and alleviated cotreatment-induced viability reduction, cleavage of caspase-8, caspase-9, and PARP. Overall, our results suggest that 6-MS exerts cytotoxicity by modulating ROS generation, EGFR/Akt signaling, and JNK activation in HCC cells. 6-MS potentiates TRAIL-induced apoptosis through upregulation of DR5 via ROS generation. The combination of 6-MS with TRAIL may be a promising strategy and warrants further investigation.

Natural Product Citronellal can Significantly Disturb Chitin Synthesis and Cell Wall Integrity in Magnaporthe oryzae.

BACKGROUND: Natural products are often favored in the study of crop pests and diseases. Previous studies have shown that citronellal has a strong inhibition effect on Magnaporthe oryzae. The objective of this study was to clarify its mechanism of action against M. oryzae. RESULTS: Firstly, the biological activity of citronellal against M. oryzae was determined by direct and indirect methods, and the results show that citronellal had a strong inhibition effect on M. oryzae with EC50 values of 134.00 mg/L and 70.48 µL/L air, respectively. Additionally, a preliminary study on its mechanism of action was studied. After citronellal treatment, electron microscopy revealed that the mycelium became thin and broken; scanning electron microscopy revealed that the mycelium was wrinkled and distorted; and transmission electron microscopy revealed that the mycelium cell wall was invaginated, the mass wall of mycelium was separated, and the organelles were blurred. The mycelium was further stained with CFW, and the nodes were blurred, while the mycelium was almost non-fluorescent after PI staining, and there was no significant difference in the relative conductivity of mycelium. In addition, chitinase was significantly enhanced, and the expression of chitin synthesis-related genes was 17.47-fold upregulated. Finally, we found that the efficacy of citronellal against the rice blast was as high as 82.14% according to indoor efficacy tests. CONCLUSION: These results indicate that citronellal can affect the synthesis of chitin in M. oryzae and damage its cell wall, thereby inhibiting the growth of mycelium and effectively protecting rice from rice blasts.

Left-turning vehicle-pedestrian conflicts at signalized intersections with traffic lights: Benefit or harm? A two-stage study.

PURPOSE: Vehicle-pedestrian conflicts are common at road intersections when traffic lights change. However, the impact of traffic light on transportation safety and efficiency remains poorly understood. METHODS: A two-stage study was used to survey the proportion of intersections with conflicting traffic lights and the related transportation efficiency and safety were evaluated as well. First, a cross-sectional study estimated the proportion of signalized intersections with conflicting left-turning vehicle-pedestrian traffic lights in Changsha city, China. Second, a natural experiment compared transportation efficiency and safety between intersections with and without conflicting left-turning vehicle-pedestrian traffic lights. Risky conflicts, where motor vehicles violated laws and failed to yield to pedestrians in crosswalk were used as a surrogate for transportation safety. The number of motor vehicles and pedestrians passing through the intersections per second and per meter were used to estimate transportation efficiency. Data were collected and analyzed in 2015 (from March to December). A search of online news from domestic media sources was also conducted to collect pedestrian injury data occurring at the intersections. RESULTS: About one-fourth (57/216) intersections had conflicting left-turning traffic lights (95% CI: 20.5%, 32.3%). Risky vehicle-pedestrian conflicts were more frequently observed at intersections with conflicting lights compared to those without (incidence rate ratio (IRR) = 3.13; pedestrians: IRR = 4.02), after adjusting for type of day (weekday vs. weekend), the time period of observation, and motor vehicles traffic flow. Intersections without conflicting vehicle-pedestrian traffic lights had similar transportation efficiency to those with conflicting lights after controlling for covariates (p > 0.05). The systematic review of news media reports yielded 10 left-turning vehicle-pedestrian crash events between 2011 and 2017, involving 11 moderate or severe pedestrian injuries and 3 fatal pedestrian injuries. CONCLUSION: Over one-fourth of road intersections in Changsha city, China have conflicting left-turning traffic lights. Conflicting traffic lights cannot improve transportation efficiency, but increase risky conflicts between vehicles and pedestrians.

Solitary fibrous tumor of small bowel mesentery with postoperative bowel obstruction: a case report and review of literature.

Solitary fibrous tumor (SFT) which is an extremely rare clinical entity has been reported infrequently. Most commonly it is distinguished into pleural and extrapleural forms, with same morphological resemblance. There has been many literatures reported regarding extrapleural form of SFT but few cases of SFT originating from small bowel mesentery have been reported till now. We here report one case of SFT of small bowel mesentery with some eventful postoperative bowel obstruction and literature review.