Fe3+-binding transferrin nanovesicles encapsulating sorafenib induce ferroptosis in hepatocellular carcinoma

Youmei Xiao,Zhanxue Xu,Yuan Cheng,Rufan Huang,Yuan Xie,Hsiang‑i Tsai,Hualian Zha,Lifang Xi,Kai Wang,Xiaoli Cheng,Yanfeng Gao,Changhua Zhang,Fang Cheng,Hongbo Chen 한국생체재료학회 2023 생체재료학회지 Vol.27 No.00

Background Ferroptosis, iron-dependent cell death, is an established mechanism for cancer suppression, particularly in hepatocellular carcinoma (HCC). Sorafenib (SOR), a frontline drug for the treatment of HCC, induces ferroptosis by inhibiting the Solute Carrier family 7 member 11 (SLC7A11), with inadequate ferroptosis notably contributing to SOR resistance in tumor cells. Methods To further verify the biological targets associated with ferroptosis in HCC, an analysis of the Cancer Genome Atlas (TCGA) database was performed to find a significant co-upregulation of SLC7A11 and transferrin receptor (TFRC), Herein, cell membrane-derived transferrin nanovesicles (TF NVs) coupled with Fe3+ and encapsulated SOR (SOR@TF-Fe3+ NVs) were established to synergistically promote ferroptosis, which promoted the iron transport metabolism by TFRC/TF-Fe3+ and enhanced SOR efficacy by inhibiting the SLC7A11. Results In vivo and in vitro experiments revealed that SOR@TF-Fe3+ NVs predominantly accumulate in the liver, and specifically targeted HCC cells overexpressing TFRC. Various tests demonstrated SOR@TF-Fe3+ NVs accelerated Fe3+ absorption and transformation in HCC cells. Importantly, SOR@TF-Fe3+ NVs were more effective in promoting the accumulation of lipid peroxides (LPO), inhibiting tumor proliferation, and prolonging survival rates in HCC mouse model than SOR and TF- Fe3+ NVs alone. Conclusions The present work provides a promising therapeutic strategy for the targeted treatment of HCC.

Interference of periostin attenuates pathological changes, proinflammatory markers and renal fibrosis in diabetic kidney injury

Duan Xiaoting,Chen Cheng,Liu Xiaoli,Wang Taoxia,Feng Shuning,Li Jianwei,Li Guiying 한국유전학회 2023 Genes & Genomics Vol.45 No.11

Background Diabetic nephropathy (DN) is a prevalent complication of diabetes, in which inflammation and fibrosis are the significant pathogenesis. Periostin is a matricellular protein that functions on stabilizing the extracellular matrix by binding to integrins during development. This study aimed to explored the role of periostin in DN. Methods The animal and cell models of DN were constructed in streptozocin (STZ)-induced mice and high glucose-challenged human mesangial cells (HMCs). The role of periostin in pathological changes, inflammation and fibrosis in DN was investigated through biochemical detection, HE and Masson staining and scores, western blot, enzyme‑linked immunosorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) assays. Results Knockdown of periostin counteracted the STZ-induced the ratio of kidney weight and body weight, and the concentrations of urine albumin excretion (UAE), serum creatinine (Scr), urine albumin/creatinine ratio (UACR) and blood urea nitrogen (BUN) in mice. Moreover, silencing of periostin alleviated the pathological manifestations and reduced the concentrations of IL-6, TNF-α and IL-1β in mice kidney tissues and sera. Also, downregulation of periostin decreased the relative protein expression of fibronectin, collagen IV and α-SMA in kidney tissues. Meanwhile, interference of periostin attenuated the levels of pro-inflammation factors and the expressions of fibrosis markers in HG-induced HMCs. Conclusion Interference of periostin resisted DN via attenuating the pro-inflammatory cytokines release and renal fibrosis in diabetic kidney injury. Our study establishes a basis for its further study and underlying application in clinical practice in diagnosing and treating diabetic kidney injury or other relevant diseases.

Fabrication of platinum nano-crystallites decorated TiO2 nano-tube array photoelectrode and its enhanced photoelectrocatlytic performance for degradation of aspirin and mechanism

Yuqi Cui,Qi Meng,Xiaoyong Deng,Qiuling Ma,Huixuan Zhang,Xiaoli Li,Mingzheng Xie,Qingfeng Cheng,Xiuwen Cheng 한국공업화학회 2016 Journal of Industrial and Engineering Chemistry Vol.43 No.-

In this study, Pt NCs/TiO2 NTAs photoelectrode was fabricated through anodization process, followed byrecycle pulse electrodeposition strategy. Subsequently, physicochemical properties of the resultingsamples were studied systematically. Results indicated that Pt NCs/TiO2 NTAs photoelectrode exhibitedintense light absorbance both in the UV and visible region, high transient photocurrent density of0.089 mA cm 2 and open circuit potential of 0.275 V cm 2. In addition, 98.3% of aspirin could beeliminated within 4 h Xenon illumination with the help of +0.4 V potential. Furthermore, it can beconcluded that two tentative pathways for PEC degradation of aspirin were proposed and confirmed.

Visible light photocatalytic removal performance and mechanism of diclofenac degradation by Ag3PO4 sub-microcrystals through response surface methodology

Jianfeng Gou,Qiuling Ma,Yuqi Cui,Xiaoyong Deng,Huixuan Zhang,Xiuwen Cheng,Xiaoli Li,Mingzheng Xie,Qingfeng Cheng,Huiling Liu 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.49 No.-

In this study, high visible light response and charge separation efficiency of body-centered cubic Ag3PO4sub-microcrystals were fabricated through ultrasound-precipitation process. Additionally, the parameterswere optimized by photocatalytic (PC) removal degradation of diclofenac based on response surfacemethodology. Results indicated that the PC removal efficiency of diclofenac was significantly affected byAg3PO4 content and pH value. Under the optimized conditions, 99.9% of diclofenac could be degradedwithin 16 min Xenon illumination. Furthermore, three PC removal degradation pathways of diclofenacwere proposed, including OH-adduct to aromatic ring, direct oxidation by photoinduced holes anddecarboxylation of side chain from the parent compound.

IRE1α protects against osteoarthritis by regulating progranulin-dependent XBP1 splicing and collagen homeostasis

Liang Li,Zhang Fengmei,Feng Naibo,Kuang Biao,Fan Mengtian,Chen Cheng,Pan Yiming,Zhou Pengfei,Geng Nana,Li Xingyue,Xian Menglin,Deng Lin,Li Xiaoli,Kuang Liang,Luo Fengtao,Tan Qiaoyan,Xie Yangli,Guo Fen 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Osteoarthritis (OA) is a full-joint, multifactorial, degenerative and inflammatory disease that seriously affects the quality of life of patients due to its disabling and pain-causing properties. ER stress has been reported to be closely related to the progression of OA. The inositol-requiring enzyme 1α/X-box-binding protein-1 spliced (IRE1α/XBP1s) pathway, which is highly expressed in the chondrocytes of OA patients, promotes the degradation and refolding of abnormal proteins during ER stress and maintains the stability of the ER environment of chondrocytes, but its function and the underlying mechanisms of how it contributes to the progression of OA remain unclear. This study investigates the role of IRE1α/ERN1 in OA. Specific deficiency of ERN1 in chondrocytes spontaneously resulted in OA-like cartilage destruction and accelerated OA progression in a surgically induced arthritis model. Local delivery of AdERN1 relieved degradation of the cartilage matrix and prevented OA development in an ACLT-mediated model. Mechanistically, progranulin (PGRN), an intracellular chaperone, binds to IRE1α, promoting its phosphorylation and splicing of XBP1u to generate XBP1s. XBP1s protects articular cartilage through TNF-α/ERK1/2 signaling and further maintains collagen homeostasis by regulating type II collagen expression. The chondroprotective effect of IRE1α/ERN1 is dependent on PGRN and XBP1s splicing. ERN1 deficiency accelerated cartilage degeneration in OA by reducing PGRN expression and XBP1s splicing, subsequently decreasing collagen II expression and triggering collagen structural abnormalities and an imbalance in collagen homeostasis. This study provides new insights into OA pathogenesis and the UPR and suggests that IRE1α/ERN1 may serve as a potential target for the treatment of joint degenerative diseases, including OA.

Proteomic analyses on the browning of shade-dried Thompson seedless grape

Liu Fengjuan,Huang Wenshu,Feng Zuoshan,Tao Yongxia,Fan Yingying,He Weizhong,Li XiaoLi,Fang Xiaotong,Wang Cheng,Bai Yujia 한국응용생명화학회 2021 Applied Biological Chemistry (Appl Biol Chem) Vol.64 No.3

China is one of the main producers in the worldwide raisin market. Most China’s raisins are produced in Xinjiang where the Thompson seedless grape ( Vitis vinifera L.cv.Thompson seedless) is the main variety of green raisin. However, the browning of Thompson seedless grape during drying has been well-acknowledged as the primary factor affecting the development of the raisin industry. Data independent acquisition (DIA)-based protein profiling was performed on fresh and shade-dried Thompson seedless grapes. As a result, 5431 proteins were identified, among which the amounts of 739 proteins in fresh grape were found to be significantly different with those in dried grape. The functional annotation based on the Blast2GO showed that the ‘organic substance metabolic process’, ‘regulation of molecular function’, ‘enzyme regulator activity’, and ‘isomerase activity’ related proteins became very active during browning. Further analyses revealed that the browning-related proteins, which with significant different amounts in fresh and in dried grapes, are primarily involved in the phenylpropanoid biosynthesis, tyrosine metabolism, phenylalanine metabolism, oxidative phosphorylation metabolism, plutathione metabolism, peroxisome pathway, and fatty acid degradation. And five random differential proteins were verified with parallel reaction monitoring (PRM). The PRM results were in agreement with the DIA data. The main browning-related proteins of Thompson seedless grape were identified in this study. Their properties were tested, and their roles in the browning mechanism were indicated. This will lay base to a better understanding on the enzymatic browning of Thompson seedless grape, and it will also provide guidance for controlling the quality of Thompson seedless grapes in industry.

The management of hydatidiform mole with lung nodule: a retrospective analysis in 53 patients

Xiao Li,Yaping Xu,Yuanyuan Liu,Xiaodong Cheng,Xinyu Wang,Weiguo Lu,Xing Xie 대한부인종양학회 2019 Journal of Gynecologic Oncology Vol.30 No.2

Objective: To investigate the significance of lung nodule in hydatidiform mole, we retrospectively compared the clinical outcomes of those patients treated with different strategies. Methods: The patients were divided into three groups: chemotherapy immediately once lung nodule was detected (group 1, n=17), delayed chemotherapy until human chorionic gonadotrophin (hCG) level met the diagnostic criteria for gestational trophoblastic neoplasia (GTN) (group 2, n=18), and hCG surveillance alone until hCG level was normalized spontaneously (group 3, n=18). The clinical parameters of these patients were collected and analyzed. Results: Totally 53 (4.0%) patients were included from 1,323 cases with molar pregnancy during past 16 years. Among them, the diameters of lung nodules were 0.3–2.5 cm. Chemotherapy cycles for achieving hCG normalization and the failure rate of first-line chemotherapy in group 1 were significantly increased than that in group 2 (5 vs. 3 cycles, p=0.000, 58.8% vs. 11.1%, p=0.005). The hCG level of all 18 cases in group 3 was normalized spontaneously within 6 months. Of those, lung nodules of 9 patients disappeared spontaneously, accounting for 25% (9/36) of patients who initially selected observation. The proportion of single nodule in group 3 was significantly higher than that in group 2 (10/18 vs. 2/18, p=0.012). Conclusion: Our results suggest that lung nodule alone is not an adequate indication of chemotherapy in molar pregnancy. hCG surveillance is safe for patients with lung nodule, especially with single nodule, as long as their hCG levels do not meet International Federation of Gynecology and Obstetrics diagnostic criteria for GTN.