Nonalcoholic steatohepatitis (NASH) is a common clinical condition that can lead to advanced liver diseases. Lack of effective pharmacotherapies for NASH is largely attributable to an incomplete understanding of its pathogenesis. The deubiquitinase cylindromatosis (CYLD) plays key roles in inflammation and cancer. Here we identified CYLD as a suppressor of NASH in mice and in monkeys. CYLD is progressively degraded upon interaction with the E3 ligase TRIM47 in proportion to NASH severity. We observed that overexpression of Cyld in hepatocytes concomitantly inhibits lipid accumulation, insulin resistance, inflammation and fibrosis in mice with NASH induced in an experimental setting. Mechanistically, CYLD interacts directly with the kinase TAK1 and removes its K63-linked polyubiquitin chain, which blocks downstream activation of the JNK-p38 cascades. Notably, reconstitution of hepatic CYLD expression effectively reverses disease progression in mice with dietary or genetically induced NASH and in high-fat diet-fed monkeys predisposed to metabolic syndrome. Collectively, our findings demonstrate that CYLD mitigates NASH severity and identify the CYLD-TAK1 axis as a promising therapeutic target for management of the disease.

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Reactive oxygen species (ROS), in moderate amounts, play an essential role in regulating different physiological functions in organisms. However, increased amounts of ROS may cause oxidative stress and damage to biomolecules, leading to a variety of diseases including inflammation and even cancer. Therefore, ROS scavenging reagents are needed to maintain healthy levels of ROS. With considerable advances in nanotechnology, nanozymes possess SOD or CAT-like activities with outstanding free radical scavenging activity, facile synthesis conditions, and excellent biocompatibility. Based on these extraordinary properties, nanozymes has been used to modulate the redox homeostasis and relieve the ROS-related injury. This has led to the emergence of nanozyme-based therapies. In the current review, we presented recently developed applications of nanozymes to treat ROS-dependent disorders with an emphasis on inflammatory and brain diseases.

Radix Polygalae is a traditional Chinese medicine that has been used as a sedative and to improve memory for a number of years. The impact of Radix Polygalae in patients with Alzheimer's disease has been investigated. However the mechanisms underlying its effects remain unclear. In the current study, the toxicity of various doses (100, 40, 20, 10, 5 and 0 µg/ml) of Radix Polygalae was measured in the human neuroblastoma cell line (SH-SY5Y) using an MTT assay. Changes in amyloid β (Aβ) levels in the supernatant of Chinese hamster ovary (CHO) cells overexpressing β-amyloid pro-protein (APP) and BACE1 (CHO-APP/BACE1), were detected using an ELISA assay. In order to confirm that the Aβ reduction was associated with autophagy, the autophagy marker protein, light chain 3 (LC3), was measured by western blot analysis and autophagosomes were assessed using MDC staining. In addition, the mechanism underlying the autophagy induced by Radix Polygalae was analyzed using western blotting to measure the protein expression of mammalian target of rapamycin (mTOR), p70s6k, Raptor, protein kinase B and adenosine monophosphate-activated protein kinase (AMPK), in addition to the phosphorylated forms of these proteins. The results demonstrated no significant toxicity of Radix Polygalae in SH-SY5Y cells, at a dose of 100 µg/ml. The secretion of Aβ was markedly reduced following treatment with Radix Polygalae, and this reduction occurred in a dose-dependent manner. The autophagy levels were shown to be enhanced in the drug treatment group, using fluorescence microscopy. In addition, levels of LC3Ⅱ/LC3Ⅰ, the marker protein of autophagy, were also increased. The results of the current study suggest that Radix Polygalae may aid in the elimination of the Aβ peptide, via the induction of autophagy, by the AMPK/mTOR signaling pathway. These results may provide a basis for further kin vivo investigation.

Background Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in China. The role of the bacteria present in ESCC tissue in neoplastic progression has not been fully elucidated. This study aimed to uncover different bacterial communities in ESCC tissues and examine the correlation between the abundance of the esophageal flora and clinicopathologic characteristics of ESCC. Results Microorganisms in tumors and normal tissues showed obvious clustering characteristics. The abundance of Fusobacterium (P = 0.0052) was increased in tumor tissues. The high level of Fusobacterium nucleatum was significantly associated with pT stage (P = 0.039) and clinical stage (P = 0.0039). The WES data showed that COL22A1, TRBV10–1, CSMD3, SCN7A and PSG11 were present in only the F. nucleatum-positive ESCC samples. GO and protein domain enrichment results suggested that epidermal growth factor might be involved in the regulation of cell apoptosis in F. nucleatum-positive ESCC. Both a higher mutational burden and F. nucleatum-positive was observed in tumors with metastasis than in tumors without metastasis. Conclusion F. nucleatum is closely related to the pT stage and clinical stage of ESCC. The abundance of F. nucleatum and tumor mutation burden may be used in combination as a potential method to predict metastasis in ESCC.