JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Xiaoli Cui,Di Yang,Zhihong Zhang,Chunmei Wang,He Li,Jinghui Sun,Tianyu Zhang,Mengyang Wang
Ethnopharmacological relevance Forsythiae Fructus, a classic heat-clearing and detoxifying herb in traditional Chinese medicine (TCM), is widely used for inflammatory conditions. Its primary bioactive component, Forsythoside A (FTA), exhibits potent anti-inflammatory and antioxidant activities. Given that hypertensive nephropathy is characterized by chronic inflammation, oxidative stress, and fibrosis-hallmarks that correspond to “heat” and “toxin” pathologies in TCM theory-Forsythiae Fructus represents a rational candidate for HN therapy. However, the precise mechanisms by which FTA inhibits HN progression remain incompletely elucidated. Aim of the study This study aims to investigate the protective effects of FTA against Ang II-induced HN and to elucidate the underlying signaling mechanisms. Materials and methods We established HN models in C57BL/6 mice and NRK-52E cells using Ang II. The effects of FTA on renal injury were investigated through renal dysfunction indicators and tissue staining. RNA sequencing, molecular docking, CETSA and SPR technologies were employed to explore potential target sites and mechanisms of FTA in renal injury. Results FTA mitigated Ang II-induced renal injury by reducing renal dysfunction markers (Cr, BUN and Alb/Cr), restoring renal tissue architecture, and decreasing inflammatory markers ( Ilb, Il6, Tnf ), without exerting antihypertensive effects. RNA sequencing revealed associations with mTOR and ASCL1.Taken together, our in vivo and in vitro data reveal that FTA binds to ASCL1 and inhibits its activity, subsequently blocking the downstream CCNB1/mTOR pathway to confer renal protection. This inhibition promotes mitophagy and inhibits ferroptosis, ultimately alleviating renal injury. Conclusions This study confirmed that FTA can bind to ASCL1, targeting the ASCL1-CCNB1/mTOR pathway to protect the kidney from Ang II-induced injury, offering broad therapeutic prospects for the treatment of HN.
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产品关联
DOI
PubMed
高影响因子
CANCER RESEARCH
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2025
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IF 16.6
Ding Wen,Zhu Jianzheng,Mo Jianshan,Ouyang Shumin,Liu Guopin,Su Yingxue,Sun Danyuan,Ye Jiangling,Wu Yanle,Yan Jiayu,Xue Menghan,Yue Peibin,Lu Jin-jian,Wang Libin,Wang Yandong,Zhang Xiaolei
Small cell lung cancer (SCLC) is a highly aggressive malignancy with limited therapeutic options. Neuroendocrine differentiation is a prominent feature of SCLC. This study identified VGF, a secreted neuropeptide precursor, as a critical regulator of neuroendocrine differentiation in SCLC, particularly the ASCL1+ subtype. VGF orchestrated upregulation of the transcription factor ASCL1 through a CREB-dependent mechanism, thereby promoting neuroendocrine differentiation. Furthermore, VGF mediated the transformation of fibroblasts into cancer-associated fibroblasts (CAFs), establishing metabolic coupling between SCLC cells and CAFs via lactate exchange. A therapeutic strategy targeting VGF and monocarboxylate transporter 1 (MCT-1) disrupted neuroendocrine differentiation and SCLC-CAF metabolic coupling, demonstrating significant efficacy in both in vitro and in vivo models. Together, this study provides insights into the mechanisms underlying SCLC neuroendocrine differentiation and reveals targets and therapeutic strategies for advanced SCLC.
研究领域:
癌症生物学
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分子生物学
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神经生物学
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细胞信号传导
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肿瘤微环境
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代谢调控
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PubMed
高影响因子
CELL PROLIFERATION
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2023
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IF 8.5
Zihui Xu,Yanan Guo,Kangjian Xiang,Dongchang Xiao,Mengqing Xiang
Glaucoma and other optic neuropathies lead to progressive and irreversible vision loss by damaging retinal ganglion cells (RGCs) and their axons. Cell replacement therapy is a potential promising treatment. However, current methods to obtain RGCs have inherent limitations, including time-consuming procedures, inefficient yields and complex protocols, which hinder their practical application. Here, we have developed a straightforward, rapid and efficient approach for directly inducing RGCs from mouse embryonic fibroblasts (MEFs) using a combination of triple transcription factors (TFs): ASCL1, BRN3B and PAX6 (ABP). We showed that on the 6th day following ABP induction, neurons with molecular characteristics of RGCs were observed, and more than 60% of induced neurons became iRGCs (induced retinal ganglion cells) in the end. Transplanted iRGCs had the ability to survive and appropriately integrate into the RGC layer of mouse retinal explants and N-methyl- D -aspartic acid (NMDA)-damaged retinas. Moreover, they exhibited electrophysiological properties typical of RGCs, and were able to regrow dendrites and axons and form synaptic connections with host retinal cells. Together, we have established a rapid and efficient approach to acquire functional RGCs for potential cell replacement therapy to treat glaucoma and other optic neuropathies.
研究领域:
神经科学
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细胞生物学
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再生医学
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DOI
PubMed
高影响因子
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