FOOD CHEMISTRY
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2025
·
IF 9.8
Wenze Li,Weichen You,Xiaofan Yang,Yi Wang,Rimao Hua,Saraschandra Naraginti,Meiqing Zhu
As a typical chiral organophosphate insecticide, the enantiomer of profenofos exhibits significant bioselective toxicity in the environment. This study investigates the enantioselective effects of chiral profenofos and 2-Bromo-4-chlorophenol on BSA. Multispectral analysis confirmed that S/R -profenofos and 2-Bromo-4-chlorophenol alterd the microenvironment of BSA, decreasing the α-helices content from 53.6 % to 52.9 %, 53.0 %, and 52.8 %. The binding constants K a for the interaction of S/R -profenofos and 2-Bromo-4-chlorophenol with BSA were 4.70, 4.66 and 4.23 × 10 4 M −1 , respectively. The LC 50 of S/R -profenofos and 2-Bromo-4-chlorophenol for zebrafish were about 0.670, 0.739 and 0.954 mg/L, while the acetylcholinesterase inhibition rate were 86.64 %, 81.21 % and 73.64 %, respectively. The toxicity levels follows the pattern of S -profenofos> R -profenofos>2-Bromo-4-chlorophenol, which was also confirmed by the molecular docking and cell experiments. This study evaluated the interaction mechanism between chiral pesticides and model proteins at the molecular level, providing a new perspective on the food safety risk of chiral pesticides.
研究领域:
环境科学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
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2012
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IF 2.532
Haichen Niu,Yingwei Zheng,Tanzeel Huma,Joshua D. Rizak,Ling Li,Guimei Wang,He Ren,Liqi Xu,Jianzhen Yang,Yuanye Ma,Hao Lei
Previous studies have shown that olfactory impairment by disrupting the olfactory epithelium prior to morphine administration attenuated the development addiction-related behaviors . However, it is unclear whether olfactory impairment will affect the expression of already established addiction-related behaviors. To address this issue, mice were conditioned with morphine to induce behavioral sensitization and condition placed preference (CPP). After an abstinence period, the animals were subjected to either an intranasal ZnSO 4 effusion (ZnE) or sham treatment with saline. Behavioral sensitization and CPP reinstatement were evaluated 24 h later, as well as the expression of c-Fos protein, a marker of activated neural sites, in brain regions of interest. It was found that ZnE treatment attenuated morphine-induced behavioral sensitization and reinstatement of CPP. Compared to the saline-treated ones, the ZnE-treated animals showed reduced c-Fos expression in the nucleus accumbens (NAc) associated with behavioral sensitization, and in the NAc, cingulate cortex , dentate gyrus , amygdala , lateral hypothalamus and ventral tegmental area associated with CPP reinstatement. Together, these results demonstrated that acute olfactory impairment could attenuate already established addiction-related behaviors and expression of c-Fos in drug addiction related brain regions, perhaps by affecting the coordination between reward and motivational systems in the brain.
研究领域:
神经科学
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药理学
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DOI
高影响因子
Frontiers in Cell and Developmental Biology
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2026
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IF 5.3
Yuanjie Sun,Haosheng Lin,Wenqian Zhu,Liuchang Niu,Yilin Li,Yuan Huang,Qingxian Chang
Background/Objective Early-onset fetal growth restriction (FGR) is a severe pregnancy complication caused by placental dysfunction. Although superficial trophoblast invasion and sterile inflammation are recognized as characteristics, the specific cellular driving factors and molecular mechanisms that lead to the dysregulation of the immune-trophoblast microenvironment remain unclear. Methods We constructed a high-resolution single-nucleus transcriptomic (snRNA-seq) atlas of placental tissues from patients with early-onset FGR and their matched normal controls. By integrating bioinformatics methods, such as pseudotime trajectory inference, gene regulatory network analysis (SCENIC), and intercellular communication modeling (CellChat), along with in vitro validation approaches, such as hypoxia-induced macrophage models, recombinant protein stimulation, and RT-qPCR, we identified specific changes associated with this disease. Results Our research revealed impaired differentiation trajectories of trophoblast cells, characterized by the absence of a critical intermediate state essential for acquiring invasiveness. At the same time, we identified a pathogenic Hofbauer cell subset (HBC5), which increases in number in FGR and exhibits high regulon activity of FOS and NFKB1. In vitro experiments have confirmed that hypoxia triggers the polarization of HBC5-like macrophages, leading to the upregulation of pro-inflammatory factors such as CCL4. Furthermore, the CellChat analysis combined with functional validation indicates that the CCL4 produced by HBC5 significantly induces mitochondrial stress markers GDF15 and APP in trophoblast cells, resulting in dysregulation of the placental microenvironment. Mechanistically, unlike physiological HBC that provide trophic support, HBC5 shows impaired secretion of IGF1, and implements dual blockade of inflammation and metabolism on Extravillous Trophoblasts (EVT) and the vascular system through CCL chemokines and NAMPT signaling pathways. Moreover, we have elucidated a vicious cycle: trophoblast cells under stress conditions release danger signals such as GDF15 and APP, which may continuously maintain the pathogenic immune polarization state of HBC5, and polarized HBC5 in turn stimulates trophoblast cells. Conclusion Our study reveals that the HBC5 subset with high FOS/NFKB1 regulon activity acts as a key mediator of placental niche dysregulation. The identified HBC5-CCL4-Trophoblast stress axis provides a potential therapeutic target for early-onset FGR.
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DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 22
·7509
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IF 4.6
Xin Wu,Zili Yang,Mengwei Bu,Jiang Duan,Aidong Zhang
Fosmidomycin (FOS) is a naturally occurring compound active against the 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) enzyme in the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway, and using it as a template for lead structure design is an effective strategy to develop new active compounds. In this work, by replacing the hydroxamate unit of FOS with pyrazole, isoxazole and the related heterocycles that also have metal ion binding affinity, while retaining the monophosphonic acid in FOS or replacing it with a bisphosphonic acid group, heterocycle-containing mono- and bisphosphonic acid compounds as FOS analogs were designed. The key steps involved in the facile synthesis of these FOS analogs included the Michael addition of diethyl vinylphosphonate or tetraethyl vinylidenebisphosphonate to β-dicarbonyl compounds and the subsequent cyclic condensation with hydrazine or hydroxylamine. Two additional isoxazolinone-bearing FOS analogs were synthesized via the Michaelis–Becker reaction with diethyl phosphite as a key step. The bioactivity evaluation on model plants demonstrated that several compounds have better herbicidal activities compared to FOS, with the most active compound showing a 3.7-fold inhibitory activity onArabidopsis thaliana, while on the roots and stalks ofBrassica napusL. andEchinochloa crus-galliin a pre-emergence inhibitory activity test, the activities of this compound were found to be 3.2- and 14.3-fold and 5.4- and 9.4-fold, respectively, and in a post-emergency activity test onAmaranthus retroflexusandEchinochloa crus-galli, 2.2- and 2.0-fold inhibition activities were displayed. Despite the significant herbicidal activity, this compound exhibited a DXR inhibitory activity lower than that of FOS but comparable to that of other non-hydroxamate DXR inhibitors, and the dimethylallyl pyrophosphate rescue assay gave no statistical significance, suggesting that a different target might be involved in the inhibiting process. This work demonstrates that using bioisosteric replacement can be considered as a valuable strategy to discover new FOS analogs that may have high herbicidal activities.
研究领域:
植物学
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药物化学
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Xin-Yao Li,Bang-Yin Tan,Yue Zhang,Yan-Lin Lv,Yun-Li Zhao,Xiao-Dong Luo
Ethnopharmacological relevance Stemona sessilifolia (Miq.) Miq. has been employed in traditional medicine for its potential renal benefits, including anti-edema, diuretic, and anti-jaundice properties. However, the renoprotective effects related to these traditional uses remain to be fully elucidated. Aim of the study : To investigate the therapeutic efficacy of S . sessilifolia against hyperuricemic nephropathy and elucidate its underlying signaling pathway. Materials and methods A hyperuricemic nephropathy mouse model, induced by potassium oxonate and hypoxanthine, was employed to evaluate the renal protection of the extract of S. sessilifolia through biochemical tests and histopathological observation. Transcriptomic analysis was applied to explore potential signaling pathways. Subsequently, bioassay-guided isolation was conducted during phytochemical investigation. Uric acid-induced HK-2 cells were then employed to validate the renal cytoprotective effects of the isolated compounds. Results Treatment with S. sessilifolia extract significantly reduced serum uric acid, creatinine, and urea nitrogen levels by 65.15%, 47.95%, and 49.1%, respectively. Additionally, it decreased urinary protein excretion, and ameliorated renal injury and fibrosis in mice. The protective effects might be exerted by inhibiting the c-Myc/c-Fos/MAPK signaling pathway to maintain the homeostasis of renal tissue. Moreover, the bioactive compound stemoninine protected HK-2 cells against uric acid-induced oxidative stress, inflammatory response, proliferation, migration, and apoptosis. Conclusion The S. sessilifolia extract and its major bioactive compound, stemoninine, protected against hyperuricemic nephropathy by suppressing the c-Myc/c-Fos/MAPK signaling pathway.
研究领域:
民族药理学
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肾病学
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植物化学
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分子生物学
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信号转导
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2020
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IF 3.37
Zuotian Wu,Gaohua Wang,Huiling Wang,Ling Xiao,Yanyan Wei,Can Yang
Background Recent studies indicate that antidepressants treatment restores neuronal plasticity. In contrast, some researchers claim that serotonergic antidepressants, including fluoxetine (FLU), may exacerbate neuronal plasticity, which is contradictory and rarely studied. Since almost those studies exposed cells with drugs for 1–2 days as treatment models of antidepressants, it is possible that FLU exposure for longer periods would have opposite effects on neuronal plasticity. Results In the present study, we examined the effects of FLU exposure (up to 3 days) on the neuronal plasticity in differentiated PC12 cells. The cell viability shown a slight decrease at day 2 (93.5 ± 3.5 %), followed by a highly significant decrease at day 3(71.4 ± 4.4 %). As previously reported, neuronal plasticity was significantly upregulated by FLU exposure at day 1. However, the neurite length, activity-regulated cytoskeleton-associated protein (Arc) and c-Fos mRNA were inhibited with FLU exposure at day 3. Similarly, the expression of tubulin, which play important roles in the neuronal plasticity, was the same result. Furthermore, we found α-tubulin interacted with collapsing response mediator protein 2(CRMP2), which is related to neuronal plasticity, and the regulation of CRMP2 activity influenced the neurite length, Arc, c-Fos and tubulin expression. Conclusions The results demonstrated that neuronal plasticity was increased by FLU exposure at day 1, but exposure with FLU for more than 2 days had opposite effect on it. The reduction in neuronal plasticity with FLU exposure for more than 2 days might be involved in some aspects of the therapeutic effect of antidepressant on depression.
研究领域:
神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
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IF 4.4
Du Ailin,Chen Yingying,Qiao Siyu,Dong Jiaxing,Li Yulin,Cao Bokai,Zhao Rongyu,Zhang Ruiling
Introduction: Chronic alcoholism is one of the most common neurological diseases in modern society. However, the key mechanisms underlying learning and memory impairments caused by chronic alcohol exposure remain unclear. In this study, a microRNA-messenger RNA (miRNA-mRNA) network was constructed to explore the potential function of key genes in chronic alcohol exposure, their effects on the hippocampus, and their mechanisms which facilitate brain injury in mice.Methods: The Morris water maze test was used to assess the learning ability of mice in each group. Mitochondrial ATPase activity and H2S levels in the hippocampi of mice were determined. Differentially expressed miRNAs and mRNAs in the mouse hippocampus were identified using second-generation sequencing. Using the TargetScan, miRTarBase, and miRDB databases, we predicted miRNA target genes and constructed a miRNA-mRNA regulatory network. Furthermore, using the Gene Ontology and KEGG databases we performed functional enrichment and protein-protein interaction analyses. Real-time quantitative polymerase chain reaction (qPCR) and other methods were employed to verify the mRNA expression of related genes.Results: The Morris water maze test revealed that mice exposed to chronic alcohol exhibited a significantly reduced learning ability compared to the control group (p < 0.05). Compared with the control group, the activity of mitochondrial ATPase in the hippocampal tissue of alcohol-treated mice was significantly decreased (p < 0.01), suggesting brain injury. In the model group, H2S significantly increased in the mice hippocampi (p < 0.01), indicating that chronic alcohol exposure could activate cystathionineβ-synthase (CBS) and catalyze the mass formation of H2S, suggesting brain injury. A total of 208 differentially expressed miRNAs and 377 differentially expressed mRNAs were screened through bioinformatic analysis. Enrichment analysis indicated that the main pathways were involved in neurodegeneration and regulation of the Wnt signaling pathway. The PCR detected a significant downregulation in the expressions of FOS and EGR1 genes.Discussion: Consequently, chronic alcohol exposure may regulate the expression of FOS and EGR1 in the hippocampus through miR-222-3p, miR-132-3p, miR-212-3p, and miR-191-5p, reduce the activity of hippocampal mitochondrial ATPase, activate CBS, catalyze the large amount of H2S formation, and destroy the mitochondrial structure, resulting in decreased learning ability. Our findings revealed valuable genes and miRNAs for the study of chronic alcohol exposure.
研究领域:
神经生物学
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分子生物学
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生物信息学
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产品关联
DOI
PubMed
高影响因子
Immunity & Ageing
·
2026
·Vol. 23
·期 1
·12
·
IF 8.3
Sun Ruiqing,Luo Lan,Chen Yang,Sun Liangjie,Huo Yuhao,Ding Chong,Wang Yixiang
Background Senile osteoporosis (SOP) is becoming a critical public health burden particularly in aging societies due to escalating fracture susceptibility among elderly populations. Despite advances in SOP research, the mechanistic role of immune cell alterations in senile osteoporosis remains unclear. Methods As a validated SOP model, senescence-accelerated mouse prone 6 (SAMP6) mice were used for mechanistic studies, comparing with age- and gender-matched controls-senescence-accelerated mouse resistant 1 (SAMR1) mice. We combined micro-CT, molecular biology and histological techniques to assess the bone mineral density in femurs. To investigate dynamic interactions and differential pathways of immune cells within the bone marrow microenvironment, we employed a multi-omics integration strategy including single-cell RNA sequencing, transcriptome sequencing and flow cytometry. Furthermore, we conducted multicolor immunofluorescence and multiplex cytokine analysis to verify the above results. Moreover, we utilized BaF3 and RAW 264.7 cell lines to study the cell interactions during osteoclastogenesis and BX471(a CCR1 antagonist) was used to block this process. Results SAMP6 mice showed a marked decline in bone mass accompanied by elevated reactive oxygen species (ROS) level in 3-month-old. The single-cell RNA sequencing of bone marrow revealed that a prominent depletion of B lymphocytes, with pro-B cells exhibiting the most pronounced reduction. Multi-omics integration analysis of pro-B cells suggested a significant activation of the Fos/Jun (AP-1) transcription complex accompanied by upregulation of chemokine CCL3 in the SAMP6 group. In vitro assays showed that H 2 O 2 -induced oxidative stress in BaF3 cells triggers Fos/Ccl3 axis activation and promoted osteoclastogenesis in RAW 264.7 cells. Moreover, blocking CCR1 with BX471 could suppress this effect. Conclusions Our findings suggest that the elevation of ROS levels within bone marrow microenvironment accelerates immune-senescence of B lymphocytes, characterized by a significant reduction in progenitor B-cell populations, which subsequently activates the Fos/Jun-mediated stress signaling pathway. The cascade ultimately results in the overexpression of CCL3, further promoting osteoclastogenesis of macrophage through CCL3-CCR1 axis. CCR1 antagonist could alleviate pro-inflammatory osteoclast formation, revealing a potential therapeutic target for senile osteoporosis.
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2019
·Vol. 458
·期 1
·71-78
·
IF 2.884
Ba Fang,Zhou Yuxin,Zhou Jie,Chen Xueyun
Repetitive transcranial magnetic stimulation (rTMS) is a technique protecting neurons against diverse neurodegenerative disorders by delivering magnetic stimuli into the brain through the intact scalp. In the current study, the protection effect of rTMS on Parkinson’s disease (PD) and the associated mechanism driving the treatment were explored. The PD symptoms were induced using 6-OHDA in mice, and the effect of rTMS of two frequencies (1 Hz and 10 Hz) on the cognitive behaviors and neuron viability was detected. Afterwards, the level of Aβ 1–42 and activity of MKK7-ERK-Fos-APP axis under the administration of rTMS were recorded as well. The intracranial injection of 6-OHDA impaired the cognitive behaviors of the mice in the test of Morris water maze as well as reducing the viability and number of neurons in PD mice. After the treatment of rTMS of both frequencies, the cognitive function of mice was improved and the neuron viability and number were restored in mice brain tissues. The administration of rTMS also increased the cerebrospinal fluid (CSF) level of Aβ 1–42 in PD mice, which was accompanied by the suppressed levels of p-MKK7, p-ERK1/2, p–c-Fos, and APP. Moreover, the effect of rTMS on mice nerve system was all exerted in a frequency-dependent manner. In conclusion, the findings outlined in the current study affirmed the protection effect of rTMS against PD. The anti-PD function of rTMS was associated with the suppression of MKK7-ERK-Fos-APP axis, which subsequently resulted in the increased CSF Aβ 1–42 level and decreased brain Aβ 1–42 level.
研究领域:
神经科学
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药理学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
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2025
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IF 2
Xiao Li,Hui Yang,Ming Qian,Hang Liu,Shuang Zuo,Jin-Chun Liu,Wei-Hong Ge,Lin Zhou
Vincristine (VCR) is a commonly used clinical anti-cancer drug, but it can also induce neurotoxicity and cause vincristine-induced neuropathic pain (VINP). The metabotropic glutamate receptor 5 (mGluR5) within spinal dorsal horn neurons regulates the transmission of pain mediated by glutamate. In this study, we investigated for the first time the role of mGluR5 in the transmission of noxious information in VINP. Expression of mGluR5 protein was significantly increased in the spinal cord from days 6 to 14 after VCR injection. Immunofluorescence double staining showed that mGluR5 colocalized with the neuron-specific marker NeuN. The intrathecal administration of MPEP (a specific antagonist of mGluR5) or DHPG (an agonist of mGluR5) influenced the pain threshold and mGluR5 protein expression in VINP mice. The expression of c-Fos protein was also affected by MPEP. Furthermore, simulated blockade of intracellular mGluR5 site by intrathecal injection of small interfering RNA (siRNA) of the excitatory amino acid transporter 3 (EAAT3) reduced mechanical allodynia and thermal hyperalgesia and suppressed the expression of mGluR5 and c-Fos proteins. The results collectively indicate that mGluR5 site in spinal dorsal horn neurons may be involved in the regulation of intracellular nociceptive signal transmission in VINP, and the expression of c-Fos largely depends on the intracellular mGluR5.
研究领域:
神经科学
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药理学
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疼痛研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Medicine
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2024
·
IF 3.1
Zhongzhu Ai,Dongfeng Yuan,Jingyi Cai,Ruotong Dong,Wei Liu,Daonian Zhou
Background: Pruritus ani (PA), a neurofunctional dermatosis, is one of the most common complications of hemorrhoids, which seriously affects the quality of life of patients. Medical hemorrhoid gel (MHG), a product mainly composed of herbal medicine, is widely used for treatment of PA clinically. This study aim to assess the alleviating effect and mechanism of MHG on PA based on rectal epidermis-spinal cord-brain axis using animal models.Methods: A chloroquine-induced mouse itching model and a croton oil preparation-induced rat hemorrhoid model were established to evaluate anti-PA effect of MHG. Scratching behaviors of mice were recorded, and histopathology of mice skin and rat ano-rectal tissues was observed through H&E staining. Network pharmacology and western blotting were employed to explore potential mechanism of MHG.Results: The study indicated that MHG significantly alleviated chloroquine-induced skin itching and improved pathological injuries in mice skin and rat ano-rectal tissues. Network pharmacology suggested that MHG might regulate the JAK/STAT signaling pathway. Experimental findings showed that MHG significantly downregulated TRPV1 and TRPA1 in rectal tissue, c-Fos and GRPR in spinal cord tissue, and 5-HT1a protein in brain tissue, while upregulating TRPM8 protein in rectal tissue. Furthermore, MHG inhibited the activation of the JAK2/STAT3 signaling pathway in the rectal epidermis-spinal cord-brain axis.Conclusion: MHG improves PA by inhibiting the transmission of itching signals in rectal epidermis-spinal cord-brain axis via the JAK2/STAT3 signaling pathway, providing experimental evidence for its clinical application.
研究领域:
药理学
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神经科学
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皮肤病学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
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2025
·
IF 2.8
Ayiheng Yelinaer,Mahan Wuluhan,Xie Zengru
Background Effective therapies remain elusive for devastating osteolysis in osseous echinococcosis, thus necessitating mechanistic exploration. To elucidate the molecular mechanism by which echinococcal infection promotes osteoclast differentiation and activation via the IL-1β/c-Fos/NFATc1 signaling axis in pathological osteolysis of osseous echinococcosis. Methods Retrospective RT-qPCR analysis quantified mRNA expression of osteoclastogenesis-associated inflammatory factors (TNF-α, IL-1β, IL-6, IL-8) in bone cyst tissues from 21 osseous echinococcosis patients versus histologically normal bone adjacent to tumors in 21 matched bone tumor controls. Murine RAW 264.7 monocytes/macrophages were divided into: (i) Untreated control; (ii) Osteoclast induction (100 ng/mL RANKL + 25 ng/mL M-CSF); (iii-v) Induction + hydatid antigen B (25/50/75 ng/mL); (vi) Induction + antigen B (75 ng/mL) + IL-1β antagonist (canakinumab, 10 ng/mL). TRAP staining identified osteoclasts (≥ 3 nuclei), with positive cell percentage calculated across ≥ 5 random fields. ELISA measured cytokine levels in supernatants; Western blot quantified c-Fos, NFATc1, Cathepsin K, and MMP9 expression. Results Bone cyst tissues exhibited elevated TNF-α, IL-1β, IL-6, and IL-8 mRNA versus controls ( P < 0.05). Antigen B (25–75 ng/mL) dose-dependently increased TRAP⁺ cells and inflammatory cytokines versus induction group ( P < 0.05). c-Fos, NFATc1, Cathepsin K, and MMP9 were upregulated in induction and antigen B (75 ng/mL) groups versus control ( P < 0.05), with further elevation in antigen B (75 ng/mL) group versus induction ( P < 0.05). Canakinumab reversed these protein increases versus antigen B (75 ng/mL) group ( P < 0.05). Conclusion Echinococcal infection promotes pathological osteoclastogenesis and osteolysis through IL-1β/c-Fos/NFATc1 signaling activation.
研究领域:
免疫学
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分子生物学
·
传染病学
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骨代谢
·
信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）