Grub polypeptide extracts protect against oxidative stress through the NRF2-ARE signaling pathway

Jingyang Chen,Yingjian Sun,Shan Huang,Hong Shen,Yongjie Chen 한국통합생물학회 2021 Animal cells and systems Vol.25 No.6

Grub polypeptide extracts (GPEs) have antioxidant effects; however, their underlying molecular mechanisms are unknown. This study explored the antioxidant molecular mechanism of GPE via the nuclear factor-erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) signaling pathway in C2C12 muscle satellite cells exposed to oxidative stress. The effects of GPE/or H2O2 on C2C12 were investigated by the MTT (3- (4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide) viability assay and immunofluorescence and small interfering RNA (siRNA) analyses. The cell viability, cell damage, intracellular reactive oxygen species (ROS) levels, and NRF2 signaling pathways related to proteins were measured. GPE significantly increased the antioxidant capacity of cells, evident by increased cell viability and decreased lactate dehydrogenase leakage, DNA damage, malondialdehyde content, and ROS level. GPE also markedly increased mRNA expression levels and activities of antioxidant enzymes including superoxidase 1 and 2, catalase, and glutathione peroxidase. In addition, GPE increased the gene and protein expression of NRF2 and heme oxygenase 1 by promoting NRF2 translocation from the cytoplasm to the nucleus and activating NRF2-ARE signaling pathways. The antioxidant effects of GPE through these signaling pathways were further confirmed by NRF2-specific siRNA silencing. Thus, GPE enhances antioxidant capacity and alleviates oxidative damage of C2C12 cells via the NRF2-ARE signaling pathway.

Chrysin Attenuates Oxidative Stress to Alleviate Sevoflurane-Induced Cognitive Impairments in Aged Rats

Chen Caiping,Zeng Jingyang,Luo Bo,Li Shunyuan 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.5

Objective Anesthesia-induced cognitive impairments are common for elder patients after surgery. Oxidative stress is the predominant factor contributing to the impairments. This study was to assess the therapeutic potential of an anti-oxidative naturally occurring flavonoid, chrysin, in attenuating sevoflurane-induced cognitive impairments in rat models.Methods Rat models of cognitive impairments were constructed by exposing aged rats (18 months old) to sevoflurane for 2 h. Chrysin was administered via oral gavage at the dose of 25, 50, and 100 mg/kg/day for seven days. The elevated plus maze test was used to assess anxiety and explorative behaviors. Spatial memory tests were performed using novel object recognition test, object location memory task, and water maze experiments. Oxidative stress was evaluated by measuring levels of malondialdehyde, nicotinamide adenine dinucleotide phosphate, 4-hydroxynonenal, and glutathione using colorimetric assays. Quantitative real-time polymerase chain reaction and Western blot were used to analyze how chrysin affects nuclear factor E2-related factor (Nrf) signaling.Results While sevoflurane anesthesia led to significant decline in cognitive performance in object recognition test, object location memory task, and water maze test, chrysin exerted significant effects in alleviating the impairments. Oxidative stress was also reduced in the hippocampus tissue of rats after chrysin intake. Nrf signaling was activated by chrysin treatment in sevoflurane-induced cognitive impairment models.Conclusion Chrysin was effective in alleviating cognitive impairments induced by sevoflurane anesthesia, which was at least in part facilitated by its effects in reducing oxidative stress via activating Nrf signaling.

Prognostic Value of the Evolution of HER2-Low Expression after Neoadjuvant Chemotherapy

Youzhao Ma,Mingda Zhu,Jingyang Zhang,Minhao Lv,Xiuchun Chen,Zhenzhen Liu 대한암학회 2023 Cancer Research and Treatment Vol.55 No.4

Purpose Patients with human epidermal growth factor receptor 2 (HER2)–low advanced breast cancer can benefit from trastuzumab deruxtecan. Given the unclear prognostic characteristics of HER2-low breast cancer, we investigated the prognostic characteristics of HER2-low expression from primary tumor to residual disease after neoadjuvant chemotherapy (NACT). Materials and Methods The data of HER2-negative patients receiving NACT at our center were collected. Pathological complete response (pCR) rate were compared between HER2-0 and HER2-low patients. The evolution of HER2 expression from primary tumor to residual disease and its impact on disease-free survival (DFS) were examined. Results Of the 690 patients, 494 patients had HER2-low status, of which 72.3% were hormone receptor (HR)–positive (p < 0.001). The pCR rates of HER2-low and HER2-0 patients (14.2% vs. 23.0%) showed no difference in multivariate analysis regardless of HR status. No association was observed between DFS and HER2 status. Of the 564 non-pCR patients, 57 (10.1%) changed to HER2-positive, and 64 of the 150 patients (42.7%) with HER2-0 tumors changed to HER2-low. HER2-low (p=0.004) and HR-positive (p=0.010) tumors before NACT were prone to HER2 gain. HER2 gain patients had a better DFS compared with HER2-negative maintained patients (87.9% vs. 79.5%, p=0.048), and the DFS of targeted therapy group was better than that of no targeted therapy group (92.4% vs. 66.7%, p=0.016). Conclusion Although HER2-low did not affect the pCR rate and DFS, significant evolution of HER2-low expression after NACT creates opportunities for targeted therapy including trastuzumab.

AKA-PLA: Enhanced AKA Based on Physical Layer Authentication

( Jing Yang ),( Xinsheng Ji ),( Kaizhi Huang ),( Ming Yi ),( Yajun Chen ) 한국인터넷정보학회 2017 KSII Transactions on Internet and Information Syst Vol.11 No.7

Existing authentication mechanisms in cellular mobile communication networks are realized in the upper layer by employing cryptographic techniques. Authentication data are broadcasted over the air in plaintext, enabling attackers to completely eavesdrop on the authentication and get some information about the shared secret key between legitimate nodes. Therefore, reusing the same secret key to authenticate several times results in the secret key`s information leakage and high attacking rate. In this paper, we consider the most representative authentication mechanism, Authentication and Key Agreement (AKA), in cellular communication networks and propose an enhanced AKA scheme based on Physical Layer Authentication (AKA-PLA). Authentication responses generated by AKA are no longer transmitted in plaintext but masked by wireless channel characteristics, which are not available to adversaries, to generate physical layer authentication responses by a fault-tolerant hash method. The authenticator sets the threshold according to the authentication requirement and channel condition, further verifies the identity of the requester based on the matching result of the physical layer authentication responses. The performance analyses show that the proposed scheme can achieve lower false alarm rate and missing rate, which are a pair of contradictions, than traditional AKA. Besides, it is well compatible with AKA.

Taurocholic acid promotes hepatic stellate cell activation via S1PR2/p38 MAPK/YAP signaling under cholestatic conditions

Jing Yang,Xujiao Tang,Zhu Liang,Mingzhu Chen,Lixin Sun 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.2

Background/Aims: Disrupted bile acid regulation and accumulation in the liver can contribute to progressive liver damage and fibrosis. However, the effects of bile acids on the activation of hepatic stellate cells (HSCs) remain unclear. This study investigated the effects of bile acids on HSC activation during liver fibrosis, and examined the underlying mechanisms. Methods: The immortalized HSCs, LX-2 and JS-1cells were used for the in vitro study. in vitro, the adeno-associated viruses adeno-associated virus-sh-S1PR2 and JTE-013 were used to pharmacologically inhibit the activity of S1PR2 in a murine model of fibrosis induced by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet. Histological and biochemical analyses were performed to study the involvement of S1PR2 in the regulation of fibrogenic factors as well as the activation properties of HSCs. Results: S1PR2 was the predominant S1PR expressed in HSCs and was upregulated during taurocholic acid (TCA) stimulation and in cholestatic liver fibrosis mice. TCA-induced HSC proliferation, migration and contraction and extracellular matrix protein secretion were inhibited by JTE-013 and a specific shRNA targeting S1PR2 in LX-2 and JS-1 cells. Meanwhile, treatment with JTE-013 or S1PR2 deficiency significantly attenuated liver histopathological injury, collagen accumulation, and the expression of fibrogenesis-associated genes in mice fed a DDC diet. Furthermore, TCAmediated activation of HSCs through S1PR2 was closely related to the yes-associated protein (YAP) signaling pathway via p38 mitogen-activated protein kinase (p38 MAPK). Conclusions: TCA-induced activation of the S1PR2/p38 MAPK/YAP signaling pathways plays a vital role in regulating HSC activation, which might be therapeutically relevant for targeting cholestatic liver fibrosis.