Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

[Change of Hepcidin in Patients with Iron Overload at the Tibet Plateau].

OBJECTIVE: To explore the possible etiological factors of iron overload through detecting plasma hepcidin level of adult males at Tibet plateau. METHODS: 81 Tibetan male adult patients hospitalized in our department during January 2017 - December 2018 were selected, and divided into iron overload group and non-iron overload group. The difference in serum ferritin, serum iron, total iron binding capacity, hemoglobin, HBSAg, ALT, AST, albumin, creatinine and hepcidin of patients in each group were tested. To analyze the differences between groups. The regression analysis was applied to analyze the relationship between laboratory index and hepcidin. RESULTS: The plasma hepcidin of iron overload group was significantly higher than that of the non-iron overload group [93.69 (65.57-133.92) ng/ml vs 63.93 (40.01-90.65) ng/ml] (P=0.005). And there was a positive correlation between plasma hepcidin and ferritin (ß=0.03 ng/ml，95%CI 0.01-0.05) (P<0.01) and BMI (ß=5.71 ng/ml，95%CI 0.54-10.88) (P<0.05）. CONCLUSION: Iron overload at Tibet plateau can not be attributed to hepcidin deficiency in Tibetan adult male patients. Iron metabolism disorders in Tibetan population may be associated with metabolic syndrome.

Serum Ferritin Independently Predicts the Incidence of Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus.

AIM: This study aimed to determine whether serum ferritin (SF) is an independent risk factor of the incidence of chronic kidney disease (CKD) and rapid renal function decline (RFD) in male Tibetan patients with type 2 diabetes mellitus (T2DM). METHODS: We performed a retrospective cohort study that included 191 male Tibetan patients with T2DM without CKD. Patients were divided into three groups according to the level of SF. The following outcomes were measured: cumulative incidence of chronic kidney disease [i.e. estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 and/or urinary albumin/creatine ratio (ACR) ≥30 mg/g] and RFD (i.e. decrease in eGFR of ≥25% from baseline or a decline rate of ≥3 mL/min per 1.73 m2 annually). RESULTS: In total, over a median follow-up period of 23 months, 30 (15.7%) and 89 patients (46.6%) developed CKD and RFD. In multivariable Cox models, a 100 ng/mL increment in SF was associated with a 1.12-fold (95% CI: 1.02-1.24) higher adjusted risk for incidence of CKD. The adjusted-HR of CKD was 1.31 (95% CI: 0.38-4.53) and 2.92 (95% CI: 0.87-9.77) for those in tertile 2 and tertile 3, respectively, compared with the patients in tertile 1. However, SF was not significantly associated with RFD (adjusted-HR: 1.06, 95% CI: 0.99-1.14). CONCLUSION: Serum ferritin independently predicts the incidence of CKD in male Tibetan patients with T2DM. High levels of serum ferritin may play a role in the pathogenesis leading to the development of CKD in T2DM.

[Isolation and Study on the Aflatoxin Genes of Aflatoxin-producing Fungi in Paprika Samples in Chengdu].

OBJECTIVE: To isolate aflatoxin-producing strains from paprika samples and to do a preliminarily study on the relationship between aflatoxin-producing ability and the genes aflR, omt-1 and ver-1. METHODS: Fungi were isolated by traditional culture method. Potential aflatoxin-producing strains were screened by phenotypic traits and multiplex PCR. After these potential aflatoxin-producing strains cultured in the toxigenic culture medium, the levels of aflatoxin B, (AFB1) of the cultures were tested with ELISA method. The phylogenetic tree of aflR, omt-1 and ver-1 was constructed to explore the relationship between these genes and the AFB1-producing capacity. RESULTS: 17 potential aflatoxin-producing fungi were isolated. The ratio of positive toxigenic strains is 64. 71%. 11 isolates were positive in AFB1 detection while existing high sequence homology with AS 3. 4408, 6 isolates were negative in AFB1 detection while existing high sequence homology with Aspergillus oryzae. CONCLUSION: Aspergillus flavus are potential candidates for aflatoxin control. Not all Aspergillus flavus have AFB1-producing capacity, aflR gene had a direct relation to AFB1-producing capacity, while ver-1 and omt-1 were related to the level of AFB1 producing.

[Non-modified magnetic beads coupled with multiple real-time PCR for detection and quantification of mycotoxigenic fungi in paprika samples].

OBJECTIVE: To establish a method for detecting 3 common toxigenic molds (Aspergillus, Penicillium, and Fusarium) based on non-modified magnetic beads coupled with multiple real-time PCR (NMB-multiple qPCR). METHODS: The primers and genus-specific probes were designed based on the rDNA sequences to develop a multiple real-time PCR using non-modified magnetic bead to enrichment of fungal spores. The sensitivity, specificity and repeatability of this assay were evaluated. RESULTS: The detection limit of this assay for spiked samples was 10(4) CFU/g, demonstrating a 10-fold greater detection sensitivity of this assay than that of real-time PCR. The NMB-multiple qPCR assay also showed good specificity and reproducibility and yielded comparable results with those by traditional colony counting method for spiked samples (P>0.05). CONCLUSION: NMB-multiple qPCR assay we established allows rapid and sensitive detection of common mycotoxigenic fungi in paprika.

Versatile synthesis of thiol- and amine-bifunctionalized silica nanoparticles based on the ouzo effect.

In this article, we report a novel, nanoprecipitation-based method for preparing silica nanoparticles with thiol and amine cofunctionalization. (3-Mercaptopropyl)trimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) were used as the organosilane precursors, which were subjected to acid-catalyzed polycondensation in an organic phase containing a water-miscible solvent (e.g., dimethyl sulfoxide). A pale colloidal solution could be immediately formed when the preincubated organic phase was directly injected into water. The initial composition ratio between MPTMS and APTMS is an important factor governing the formation of nanoparticles. Specifically, large, unstable micrometer-sized particles were formed for preparation using MPTMS as the sole silane source. In contrast, when APTMS was used alone, no particles could be formed. By reducing the fraction of APTMS (or increasing that of MPTMS) in the initial mixture of organosilanes, the formation of nanometer-sized particles occurred at a critical fraction of APTMS (i.e., 25%). Remarkably, a tiny fraction (e.g., 1%) of APTMS was sufficient to produce stable nanoparticles with a hydrodynamic diameter of about 200 nm. Other factors that would also affect particle formation were determined. Moreover, an interesting temperature effect on particle formation was observed. The TEM micrographs show spherical nanospheres with mean sizes of 130-150 nm in diameter. The solid-state (29)Si NMR spectra demonstrate that the hybrid silica materials contain fully and partially condensed silicon structures. The bifunctionalized silica nanoparticles have positive zeta potentials whose magnitudes are positively correlated with the amount of APTMS. The total thiol content, however, is negatively correlated with the amount of APTMS. The cationic nanoparticles can bind an antisense oligonucleotide in a composition-dependent manner.