JOURNAL OF MEDICINAL CHEMISTRY
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2026
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IF 7.3
Yao Tan,Tao Ma,Siyuan Li,Chenxing Xu,Yu Han,Dongting Zhangsun,Xiaopeng Zhu,Sulan Luo
The α7 nicotinic acetylcholine receptor (α7 nAChR) modulates neuroimmune signaling but remains poorly characterized in peripheral disease due to a lack of visualization tools. We developed the fluorescent probe LvID-BDP by conjugating a BODIPY fluorophore to the high-affinity α7 nAChR-targeting peptide LvID. LvID-BDP showed high quantum yield, robust photostability, and sufficient physiological stability for biological imaging. Electrophysiology characterized LvID-BDP as a potent α7 nAChR antagonist, exhibiting a half-maximal inhibitory concentration (IC50) of 119.2 nM while retaining high affinity and specificity for the receptor. In murine colon sections, LvID-BDP specifically labeled α7 nAChR, showing strong antibody colocalization (Pearson’s R = 0.87) while revealing macrophage-selective enrichment (Pearson’s R = 0.85). This probe detected α7 nAChR alterations in engineered and inflamed macrophages and quantified its expression in inflammatory bowel disease (IBD) tissues. LvID-BDP provides a valuable pharmacological tool for specific α7 nAChR visualization in peripheral disease contexts, advancing pathological mechanism research.
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高影响因子
ONCOLOGY REPORTS
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2018
·Vol. 39
·期 3
·1475-1484
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IF 2.976
Lei Yu,Bo Jiang,Zhifeng Chen,Xin Wang,Dongxue Shang,Xiaopo Zhang,Yongxue Sun,Jinghui Yang,Yubin Ji
Cytisine, a quinolizidine alkaloid, is one of the major bioactive components found in the small tree Sophora Alopecuraides L., and is a traditional Chinese medicine that is used for treating hepatitis and liver cancer. In the 1960s, quinolizidine alkaloids were reported to exhibit inhibitory effects on tumour cell proliferation in several types of cancer cells. However, few studies have investigated the effect of cytisine on liver cancer. Our team confirmed that cytisine induced apoptosis in HepG2 cells via a mitochondrial pathway. The primary aim of the present study was to evaluate the endoplasmic reticulum (ER) stress caused by calcium overload in cytisine‑induced apoptosis in HepG2 cells and the molecular mechanisms of this phenomenon. In addition, the present study was undertaken to evaluate the expression of α7‑nAChR when apoptosis was induced by cytisine in HepG2 cells. In the present study, transmission electron microscopy was used to observe the morphological appearance of HepG2 cells. The apoptosis of the cells with cytoplasmic vacuolization was significant under electron microscopy. Apoptotic bodies, the expansion of the ER, and swelling of mitochondria were observed in the HepG2 cells after cytisine treatment. Flow cytometric analysis demonstrated that the apoptosis rate of HepG2 cells was upregulated. In addition, the intracellular calcium concentration was detected by laser confocal fluorescence microscopy. The laser confocal fluorescence microscopy showed that the calcium concentration was increased in a dose‑dependent manner. The activity of caspase‑4 was evaluated by an enzyme‑linked analyser, and the expression levels of CHOP, JNK, p‑JNK and α7‑nAChR were assessed via western blot analysis. In the present study, we observed that cytisine induced ER stress‑inducing factors and CHOP and p‑JNK1/2 protein expression, and it increased the JNK protein expression in the HepG2 cells. Furthermore, α7‑nAChR protein expression was promoted in a dose‑dependent manner after cytisine treatment. These findings suggest that cytisine induced the ER stress‑mediated apoptotic pathway via activation of CHOP, JNK and caspase‑4 in HepG2 cells, and cytisine is a potential new target compound for nAchRs (nicotinic acetylcholine receptors) to treat liver cancer.
研究领域:
药理学
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细胞生物学
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肿瘤学
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BRAIN BEHAVIOR AND IMMUNITY
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2026
·
IF 7.5
Anxin Cao,Yiran Liu,Dexin Qi,Ziyu Li,Yahan Du,Qian Xu,Jianmei Yue,Long Zheng,Yu Wang,Jiaxue Cui,Chenyu Chen,Tongfei Ren,Jianhan Lin,Xiao Liu,Haishui Shi,Ninging Cai,Xiaohui Yu
Prenatal adversities disrupt the development of the gut microbiota and thereby increase the risk of neuropsychiatric disorders in later life. However, the effects of prenatal antibiotic exposure on aggressive behavior in adulthood and the underlying gut–brain mechanisms remain poorly defined. Here, we showed that low-dose exposure to the fluoroquinolone ciprofloxacin during late gestation increased defensive aggressive behavior in adult male offspring. Prenatal ciprofloxacin exposure thinned the colonic mucus layer, reduced MUC2 secretion, and depleted mucosa-associated Lactobacillus species, thereby reshaping the microbial ecosystem and disturbing systemic phosphatidylcholine (PC) homeostasis. This microbiota–lipid dysregulation is accompanied by reduced hippocampal α7 nicotinic acetylcholine receptor (α7 nAChR) expression, increased microglial activation and a pro-inflammatory cytokine profile, as well as increased neuronal activity in the hippocampus. Correlation analyses further linked altered PC species to bacterial taxa, supporting a microbiota-associated PC–α7 nAChR axis in the regulation of defensive aggression. Importantly, post-weaning supplementation with either phosphatidylcholine or Lactobacillus reuteri ( L. reuteri) attenuated defensive aggression in adult offspring prenatally exposed to ciprofloxacin. Altogether, these findings provide new insights into the gut–lipid–brain mechanisms by which prenatal antibiotics program aggressive behavior in adulthood and highlight phosphatidylcholine or L. reuteri supplementation as promising interventions for alleviating aggression abnormalities induced by prenatal antibiotic exposure.
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高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2026
·
IF 4.1
Zihan Li,Boxuan Xie,Xilei Liu,Zihan He,Zhongwei Zhang,Jianming Zhou,Tong Zhou,Huai Wang
As the most frequently occurring cancer worldwide, lung cancer is notoriously diagnosed at advanced stages, resulting in high mortality rates. The primary factor underlying this persistent global health burden remains tobacco consumption. Nicotine, a key component of cigarette smoke, is one of the major contributing factors to the development of lung cancer, but the molecular mechanisms remain incompletely elucidated. α7-nAChR, β2-AR, and HGF/c-Met are known to contribute to lung cancer development, respectively. However, the specific signaling cascade through which they interact in nicotine-induced malignancy is unclear. In this study, using CCK-8 assays across a range of concentrations (0–5 μM), we determined that 1 μM nicotine treatment for 48 h optimally enhances A549 cell proliferation, establishing this condition for subsequent experiments. This study uncovers nicotine’s role in driving malignant behaviors including proliferation, migration, and invasion in nonsmall cell lung cancer A549 cells. Notably, nicotine potently stimulated migration and invasion, accompanied by upregulation of Cyclin D1 and MMP-2, and downregulation of BAX, BAD, and Caspase-3. Mechanistically, nicotine induced synergistic engagement of α7-nAChR and β2-AR, leading to activation of the HGF/c-Met/PI3K/AKT axis and enhancing the secretion of both HGF and MMP-2. Importantly, we reveal a previously unrecognized bidirectional regulatory loop between α7-nAChR and β2-AR that functionally converges on the HGF/c-Met axis, which acts as a critical signaling hub to drive the downstream PI3K/AKT pathway and facilitate tumor progression. Our findings provide the first evidence of a coordinated α7-nAChR/β2-AR interface regulating HGF/c-Met signaling that orchestrates both intracellular signaling and extracellular secretory programs in nicotine-promoted lung cancer progression. This offers innovative insights for identifying potential antitumor therapeutic targets and presents novel perspectives for the prevention and clinical management of lung cancer, particularly in smokers with nonsmall cell lung cancer.
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高影响因子
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