NSUN5-FTH1 Axis Inhibits Ferroptosis to Promote the Growth of Gastric Cancer Cells.

Recent studies revealed that NOP2/Sun RNA methyltransferase 5 (NSUN5) - ferritin heavy chain (FTH1) pathway is associated with ferroptosis in stem cells, whereas its roles in gastric cancer are still unclear. Our study aims to investigate the roles of the NSUN5-FTH1 axis in gastric cancer (GC) and its molecular mechanisms. Stable cell lines were constructed on SGC7901 cells by using shRNAs and pcDNA3.1 expression vectors, respectively. CCK-8 kits were used to determine cell viability. Biochemicals assays were used to detect lipid reactive oxygen species (ROS) and intracellular Fe2+ levels. RNA immunoprecipitation assay, qPCR, and Western blotting were used to determine the changes in biomarkers. GC xenograft mouse model was established to confirm the observation in vivo. An elevation of NSUN5 was observed in GC tumor tissues. NSUN5 inhibited ferroptosis including decreasing cell viability and increasing levels of lipid ROS and Fe2+ in GC cells. Besides, a positive correlation was also observed between NSUN5 and FTH1. Interestingly, NSUN5 regulated the levels of FTH1, instead of FTH1 regulating NSUN5 in GC cells. NSUN5-FTH1 axis regulated erastin-induced ferroptosis in SGC7901 cells. Consistently, silencing NSUN5 or FTH1 inhibited the growth of the SGC7901 tumor in vivo. NSUN5-FTH1 axis promoted the growth of GC cells in part by the regulation of ferroptosis.

Homocysteine promotes atherosclerosis through macrophage pyroptosis via endoplasmic reticulum stress and calcium disorder.

BACKGROUND: Elevated plasma homocysteine levels, known as hyperhomocysteinemia, have been identified as an independent risk factor for atherosclerosis and related cardiovascular diseases. Macrophage pyroptosis-mediated inflammation is crucial in the development of atherosclerosis, but the underlying mechanisms remain unclear. METHODS: A hyperhomocysteinemia atherosclerotic model with ApoE-/- mice fed with a high-methionine diet was constructed to investigate the role of plasma homocysteine in atherosclerosis. THP-1-derived macrophages were used to investigate the mechanisms by which Hcy regulates pyroptosis. RESULTS: We found that hyperhomocysteinemia resulted in larger atherosclerotic plaques and more secretion of inflammatory cytokines, while these effects were attenuated in Caspase-1 knockdown mice. Likewise, in vitro experiments demonstrated that treatment of macrophages with homocysteine resulted in NLRP3 inflammasome activation and pyroptosis, as evidenced by cleavage of Caspase-1, production of downstream IL-1ß, elevation of lactate dehydrogenase activity, and extensive propidium iodide-positive staining of cells. These were all inhibited by Caspase-1 inhibitor. In addition, excessive generation of reactive oxygen species was associated with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential and ATP synthesis. Moreover, further experiments revealed that homocysteine induced endoplasmic reticulum stress, enhanced communication between the endoplasmic reticulum and mitochondria, and consequently contributed to calcium disorder. Furthermore, the endoplasmic reticulum stress inhibitor, 4PBA, the calcium chelator, BAPTA, and calcium channel inhibitor, 2-APB significantly improved macrophage pyroptosis. CONCLUSION: Homocysteine accelerates atherosclerosis progression by enhancing macrophages pyroptosis via promoting endoplasmic reticulum stress, endoplasmic reticulum-mitochondria coupling, and disturbing of calcium disorder.

Biocontrol potential of Trichoderma harzianum CGMCC20739 (Tha739) against postharvest bitter rot of apples.

This study investigated the biocontrol ability of Trichoderma harzianum CGMCC20739 (Tha739) against apple bitter rot caused by Colletotrichum gloeosporioides. In vitro tests, Tha739 inhibited the mycelial growth of C. gloeosporioides. Microscopic observation showed that Tha739 grew in parallel with, coiled around, and deformed the hyphae of C. gloeosporioides. Tha739-derived metabolites decreased the conidia production of C. gloeosporioides. In vivo tests, the lesion diameters of wounded apples treated with Tha739 1 h before C. gloeosporioides were lower than those of wounded apples treated with Tha739 after pathogen inoculation. In addition, compared with the apples inoculated with C. gloeosporioides only, the disease index of unwounded apples inoculated with Tha739 and C. gloeosporioides decreased by 2.17-fold. Furthermore, compared with the control, the total soluble solid contents of apples treated with Tha739 were 9.02 % and 1.54 % higher at 1 and 3 d, respectively. The titratable acidity contents of apples treated with Tha739 were 10.02 % and 14.58 % higher than those in the control at 1 and 3 d after treatment, respectively. The soluble sugar content and weight loss in Tha739 treatment group and control were not significantly different. The results showed that Tha739 could control apple bitter rot and maintain the nutritional quality of the fruit. Thus, T. harzianum Tha739 is a potentially biocontrol agent for harvested apples.

miR-146b-5p promotes colorectal cancer progression by targeting TRAF6.

Increasing evidence highlights the multiple roles of microRNAs (miRs) in the tumorigenesis of colorectal cancer (CRC); however, the molecular mechanism, particularly the target of miR-146b-5p in CRC has not been fully elucidated. The present study aimed to elucidate the influence of miR-146b-5p via regulating tumor necrosis factor receptor-associated factor 6 (TRAF6) in CRC. The expression levels of miR-146b-5p and TRAF6 in CRC tissue and cells were determined by reverse transcription quantitative PCR and western blotting. Binding between miR-146b-5p and TRAF6 was examined using a dual luciferase reporter gene assay. The impact of miR-146b-5p and TRAF6 on proliferation and migration of CRC cells was determined using Cell Counting Kit-8 and Transwell assays, respectively. An animal model of CRC was established to determine the carcinogenic effect of the miR-146b-5p-TRAF6 axis. The results demonstrated that miR-146b-5p was highly expressed in CRC tissue samples compared with in normal adjacent tissue samples and in CRC cells compared with in the normal NCM460 cell line, whereas TRAF6 was expressed at low levels. Overexpression of miR-146b-5p decreased TRAF6 expression in CRC HT29 and SW620 cells. miR-146b-5p targeted and inhibited TRAF6 expression in CRC cells. Furthermore, transfection with a miR-146b-5p mimic promoted the proliferation, migration and invasion of CRC cells and tumor growth; however, these effects were abolished by TRAF6 overexpression. Transfection with a miR-146b-5p inhibitor suppressed the proliferation of CRC cells. Taken together, the results from the present study demonstrated that miR-146b-5p could enhance the initiation and tumorigenesis of CRC by targeting TRAF6. These results will help elucidate the mechanisms underlying CRC development and will facilitate the development of targeted therapy for CRC.

Plaque Erosion: A Distinctive Pathological Mechanism of Acute Coronary Syndrome.

Plaque erosion (PE) is one of the most important pathological mechanisms underlying acute coronary syndrome (ACS). The incidence of PE is being increasingly recognized owing to the development and popularization of intracavitary imaging. Unlike traditional vulnerable plaques, eroded plaques have unique pathological characteristics. Moreover, recent studies have revealed that there are differences in the physiopathological mechanisms, biomarkers, and clinical outcomes between PE and plaque rupture (PR). Accurate diagnosis and treatment of eroded plaques require an understanding of the pathogenesis of PE. In this review, we summarize recent scientific discoveries of the pathological characteristics, mechanisms, biomarkers, clinical strategies, and prognosis in patients with PE.

[Effect of ectomycorrhizal fungi on the seedlings growth of Korea spruce].

To enhance the effects of ectomycorrhizal fungi to promote the growth of Korea spruce seedlings, based on previous research, the combinations of different ectomycorrhizal fungi strains were screened by dual culture method. 3 years transplanting seedlings of Korea spruce were inoculated by different combinations of ectomycorrhizal fungi strains using lister inoculating method in the field, and those were inoculated by different single strains were designed as control respectively. Thus the effects of different combinations and different single fungus strains to promote the growth of Korea spruces were studied. The results showed that all single strains and combinations in this experiment can promote the growth of Korea spruce seedlings. The growth characteristics of seedlings were observed 100 days after inoculation. The growth promoting effect of strain L15 was the best in all combinations and single strains. Comparing with control, the average height of seedlings inoculated by strain L15 was increased 30.88%, the average collar diameter of these was increased 15.29%. The growth promoting effect of combinations L15/025 or L15/009 were better than strain 009 or 025. Comparing with control, the leaf chlorophyll contents of seedling inoculated by strain 010 and combination L15/025 were increased significantly, the contents of chlorophyll a were increased 59.15% and 54.61% respectively, and the contents of chlorophyll b were increased 76.34% and 67.78% respectively. Except seedling inoculated by strain 010, the activities of hydrogen peroxidase of other treated seedlings were lower than one of control. The root activities of all treated seedlings were lower than one of control. In conclusion, inoculation by the mixture of high-effect strain and other single strain weakens the effect of high-effect strain to promote the growth of Korea spruce seedlings, the activity of hydrogen peroxidase and the root activity of seedling are not correlated with its biomass.