NSMAF

Last update 08 May 2025

Basic Info

Synonyms

Factor associated with N-SMase activation, Factor associated with neutral sphingomyelinase activation, FAN

+ [5]

Introduction

Couples the p55 TNF-receptor (TNF-R55 / TNFR1) to neutral sphingomyelinase (N-SMASE). Specifically binds to the N-smase activation domain of TNF-R55. May regulate ceramide production by N-SMASE.

100 Clinical Results associated with NSMAF

100 Translational Medicine associated with NSMAF

0 Patents (Medical) associated with NSMAF

107

Literatures (Medical) associated with NSMAF

01 Aug 2025·Journal of Hazardous Materials

Polyethylene microplastics impair chicken growth through gut microbiota-induced hepatic fatty acid metabolism dysfunction

Article

Author: Hua, Liting ; Zhang, Qiuyue ; Wang, Lei ; Wang, Yu ; Xu, Jiaping ; Cheng, Zhipeng ; Qiao, Biting ; Zhao, Hongzhi ; Zhao, Leicheng ; Sun, Hongwen ; Yao, Yiming ; Zhu, Hongkai ; Li, Yongcheng

Microplastics (MPs) negatively impact various terrestrial animals, but their comprehensive effects on Gallus gallus domesticus, key agricultural and ecological species connecting people and the environment, are not well-documented. This study investigates the effects of polyethylene (PE) MPs and phthalate esters (PAEs) on chicken growth, liver metabolism, and gut microbiota using multi-omics and 16S rRNA sequencing technology. Results show that PE MPs, particularly those containing PAEs, significantly reduced body weight gain and hepatic triglyceride levels by up to 71.2 % and 50.1 %, respectively (p < 0.05). The clean MPs affected energy metabolism, while PAE-spiked MPs disrupted fatty acid metabolism and triggered immune and inflammatory responses in the liver. Key genes related to fatty acid metabolism such as FAN, SCD and ELOVL5 were significantly downregulated, leading to imbalances in lipid metabolism. These disruptions in PAE-spiked MPs exposure were associated with the altered gut microbiota balance, including increased Firmicutes/Bacteroidetes ratios and changes in Actinobacteriota and Proteobacteria abundance. Totally, the study highlights a "Trojan Horse" effect, where MPs act as carriers for PAEs, intensifying toxicity through gut-liver axis interactions. The findings emphasize the role of gut microbiota in mediating liver dysfunction and impaired growth.

01 Jan 2025·Journal of Advanced Research

Fangchinoline eliminates intracellular Salmonella by enhancing lysosomal function via the AMPK-mTORC1-TFEB axis

Article

Author: Liu, Yuan ; Wang, Zhiqiang ; Xu, Tianqi ; He, Mengping ; Wu, Huihui ; Zhao, Yurong

INTRODUCTIONSalmonella, a foodborne zoonotic pathogen, is a significant cause of morbidity and mortality in animals and humans globally. With the prevalence of multidrug-resistant strains, Salmonellosis has become a formidable challenge. Host-directed therapy (HDT) has recently emerged as a promising anti-infective approach for treating intracellular bacterial infections.OBJECTIVESPlant-derived natural products, owing to their structural and functional diversity, are increasingly being explored and utilized as encouraging candidates for HDT compounds. This study aims to identify and screen natural compounds with potential as HDT for the treatment of intracellular Salmonella infections.METHODSA cell-based screening approach was deployed to identify natural compounds capable of mitigating the intracellular replication of S. enterica. Safety and efficacy of the candidate compounds were evaluated using multiple animal models. RNA sequencing, ELISA, and immunoblotting analyses were conducted to elucidate the underlying mechanisms of action.RESULTSOur results reveal that fangchinoline (FAN) effectively reduces S. enterica survival both in vitro and in vivo. Meanwhile, FAN also displays anti-infective activity against other intracellular pathogens, including multidrug-resistant isolates. A 14-day safety evaluation in mice showed no significant toxic or adverse effects from FAN administration. RNA sequencing analysis reveals an upregulation of lysosome pathways in S. enterica-infected cells treated with FAN. Mechanistic studies indicate that FAN increases acid lysosomal quantities and fosters autophagic response in Salmonella-infected cells via the AMPK-mTORC1-TFEB axis. In addition, FAN alleviates the inflammatory response in Salmonella-infected cells by inactivating the NF-κB pathway.CONCLUSIONOur findings suggest that FAN represents a lead HDT compound for tackling recalcitrant infections caused by intracellular bacterial pathogens.

01 Dec 2024·Cellular Signalling

Fangchinoline inhibits metastasis and reduces inflammation-induced epithelial-mesenchymal transition by targeting the FOXM1-ADAM17 axis in hepatocellular carcinoma

Article

Author: Abd El-Aty, A M ; Wang, Mengyuan ; Fang, Shiji ; Ji, Jiansong ; Zhang, Xinbin ; Chen, Minjiang ; Wang, Jianbo ; Zhang, Yeyu ; Zhang, Huajun ; Rajamanickam, Vinothkumar ; Zhao, Zhongwei ; Linnebacher, Michael ; Zheng, Liyun

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Efforts have been focused on developing new anti-HCC agents and understanding their pharmacology. However, few agents have been able to effectively combat tumor growth and invasiveness due to the rapid progression of HCC. In this study, we discovered that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid derived from Stephania tetrandra S. Moore, effectively inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells. FAN treatment also led to the suppression of IL6 and IL1β release, as well as the expression of inflammation-related proteins such as COX-2 and iNOS, and the activation of the NF-κB pathway, thereby reducing inflammation-related EMT. Additionally, FAN directly bound to forkhead box protein M1 (FOXM1), resulting in decreased levels of FOXM1 proteins and disruption of the FOXM1-ADAM17 axis. Our in vivo findings confirmed that FAN effectively hindered the growth and lung metastasis of HCCLM3-xenograft tumors. Importantly, the upregulation of FOXM1 in HCC tissue suggested that targeting FOXM1 inhibition with FAN or its inhibitors could be a promising therapeutic approach for HCC. Overall, this study elucidated the anti-tumor effects and potential pharmacological mechanisms of FAN, and proposed that targeting FOXM1 inhibition may be an effective therapeutic strategy for HCC with potential clinical applications.

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NSMAF

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