Advanced Science
·
2025
·
IF 14.1
Xueying Cheng,Shuangyu Liu,Yu Zhang,Kang Peng,Muge Qile,Chao Wu,Mengyun Dou,Liu Liu,Na Yang,Rui Liu,Guiyang Zhang,Liangping Ni,Gaolin Liang,Fang Yang,Ye Zhang,Shufang He
The heat-sensitive transient receptor potential vanilloid 1 (TRPV1), which is highly expressed on cardiac sensory neurons, reportedly plays a crucial role in transmitting nociceptive signals from the heart to the spinal cord during myocardial ischemia and reperfusion. Here, iron oxide nanocubes (FeNCs) are developed that are conjugated with an antibody against the extracellular portion of TRPV1, and they are named FeNCs-TRPV1. In F11 cell line and primary dorsal root ganglion neurons, FeNCs-TRPV1 specifically activate TRPV1 channels and trigger Ca 2+ influx through magnetothermal effect under an alternating current magnetic field (ACMF). Intraspinally injected FeNCs-TRPV1 induced TRPV1 desensitization in rats exposed to repetitive and transient ACMF before ischemia, resulting in the inhibition of TRPV1-mediated Ca 2+ signaling and neuropeptide release in the spinal cord during myocardial ischemia and reperfusion. Consequently, FeNCs-TRPV1 reduce cardiac injury and ventricular arrhythmia, enhance the activity of prosurvival kinases, and inhibit myocardial cell apoptosis. These findings suggest that magnetic nanomaterials-mediated remote regulation of spinal TRPV1 can be a novel non-invasive neuromodulation therapy for the treatment of myocardial ischemia-reperfusion (IR) injury.
研究领域:
纳米医学
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心血管研究
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神经心脏病学
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生物医学工程
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分子神经科学
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PubMed
高影响因子
Pharmaceuticals
·
2026
·
IF 5.7
Xiaoyi Qiu,Lisha Chen,Ting Han,Hongji Wang,Juping Xing,Jiayi Zheng,Changshui Xu
Background/Objectives:Diabetic neuropathic pain (DNP) is a common complication of diabetes characterized by sensory abnormalities, including mechanical allodynia and thermal hyperalgesia. This study aimed to investigate the effects of naringin on experimental DNP and evaluate its association with dorsal root ganglion (DRG) neuronal injury, TRPV1-related calcium imbalance, and inflammatory signaling.Methods:Primary rat DRG neurons were exposed to high-glucose/high-free-fatty-acid (HGHF) conditions (50 mM glucose and 0.60 mM free fatty acids) and treated with naringin (40 or 80 μM). Cell viability, apoptosis, intracellular Ca2+levels, gene/protein expression, and signaling changes were assessed using CCK-8 assay, Annexin V-FITC/PI flow cytometry, Fluo-4 AM imaging, qRT-PCR, and Western blotting. Male Sprague–Dawley rats were fed a high-fat/high-sucrose diet for 4 weeks, injected with streptozotocin (35 mg kg−1), and treated with naringin (50 mg kg−1day−1) by gavage for 2 weeks.Results:HGHF exposure increased neuronal injury, TRPV1 expression, intracellular Ca2+accumulation, and p38 MAPK/NF-κB signaling activation. Naringin attenuated these changes in vitro, with stronger effects observed at 80 μM. In DNP rats, naringin improved pain-related behaviors, partially alleviated metabolic abnormalities, reduced TRPV1 expression and serum IL-1β/TNF-α levels, and decreased phosphorylation of p38 MAPK, NF-κB p65, and ERK in DRGs.Conclusions:Naringin alleviated experimental DNP-associated behavioral and molecular abnormalities, suggesting potential protective effects involving neuronal injury, calcium regulation, and inflammatory responses.
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BIOSENSORS & BIOELECTRONICS
·
2026
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IF 11.8
Jiehua Zhang,Xinxin Chen,Ni Zhao,Haihua Xu
Thermal nociceptive sensors capable of distinguishing innocuous and noxious thermal stimuli are crucial for self-protective humanoid robotics, adaptive prosthetics and intelligent human-machine interactions. However, most artificial thermal nociceptors lack the threshold-like, nonlinear and ion-mediated required to emulate biological thermal nociception mediated by transient receptor potential vanilloid 1(TRPV1), a key heat-activated ion channel protein in humans. Here, we report a neuromorphic thermal nociceptive sensing system consisting of an ion-regulated thermal sensor (iRTS) and an ion-gated synaptic transistor (iGST) based on layered semiconductors. Through ionic modulation of nonlinear thermally activated charge transport in the layered WSe 2 /MoS 2 heterojunction, the iRTS exhibits a clear turning point at ∼320 K, close to the human noxious-heat perception threshold, beyond which the thermally evoked current increases nonlinearly with a high sensitivity of up to ∼35% K −1 , while maintaining an ultrahigh resolution of 0.005 K and an mA-level thermally evoked output current. By integrating the iRTS with the iGST, these thermal nociceptive signals are further converted into post-synaptic outputs that exhibit adaptive threshold modulation and sensitization behaviors, including hyperalgesia and allodynia—key features of biological thermal nociception. In addition, the iGST output is quantitatively mapped to a projected robotic finger-angle response, extending the artificial nociceptive pathway from thermal sensing and synaptic processing to behavior-level output. These results establish a high-performance neuromorphic thermal nociceptive sensor platform and offer a device-level strategy for intelligent robotics and adaptive human–machine interfaces.
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2026
·Vol. 27
·期 16
·7475
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IF 5.6
Galong Li,Dongyan Li,Bin Lan,Yuanyuan Cheng,Hongxia Liang,Wenli Zhang,Xiaopan Xu,Hongbing Lu
Drug-mediated intravesical therapy is a widely used treatment approach for bladder cancer (BCa), which is limited by poor tumor accumulation and the toxicity of drugs. Herein, a facile approach utilizing magnetic hyperthermia therapy (MHT) for BCa treatment is reported through intravesical instillation of tumor-targeting iron oxide nanoparticles (IONPs), which are coated with anti-FGFR3 antibodies for specific binding to FGFR3 overexpressed on BCa cells. The antibody coating significantly enhanced targeting ability and increased cancer cell uptake. Under an alternating magnetic field (AMF), the IONPs magnetothermally activated TRPV1 on the endoplasmic reticulum (ER) of BCa and induced Ca2+overload in RT4 BCa cells. The magnetothermal treatment significantly upregulated the pro-apoptotic gene expression of Bax, Pro-caspase-3, and Cytc in RT4 cells, and downregulated the anti-apoptotic effector gene Bcl-2, ultimately causing augmented apoptosis in cancer cells. The application of intravesical FGFR3-targeting MHT successfully resulted in greater suppression of tumor growth and improved survival rate of mice, compared to the control, IONP, and AMF-treated groups. These results hold significant potential as a transformative modality toward BCa therapeutic application.
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PHYTOMEDICINE
·
2023
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IF 7.9
Meihao Peng,Jintao Li,Jie Zhou,Bowen Zhang,Jiaqing Liao,Di Yang,Yu Wang,Yixi Yang,Rui Li,Xue Tang,Qiuxia Lu,Qi Zhao
Background Asthma is a chronic inflammatory disease that is challenging to treat. Fritillaria unibracteata var. wabuensis (FUW) is the plant origin for the famous Chinese antitussive medicine Fritillaria Cirrhosae Bulbus. The total alkaloids of Fritillaria unibracteata var. wabuensis bulbus (TAs-FUW) have anti-inflammatory properties and may be used to treat asthma. Purpose To explore whether TAs-FUW have bioactivity against airway inflammation and a therapeutic effect on chronic asthma. Methods The alkaloids were extracted via ultrasonication in a cryogenic chloroform-methanol solution after ammonium-hydroxide percolation of the bulbus. UPLC-Q-TOF/MS was used to characterize the composition of TAs-FUW. An ovalbumin (OVA)-induced asthmatic mouse model was established. We used whole-body plethysmography, ELISA , western blotting , RT-qPCR, and histological analyses to assess the pulmonary pathological changes in these mice after TAs-FUW treatment . Additionally, TNF-α/IL-4–induced inflammation in BEAS-2B cells was used as an in vitro model, whereby the effects of various doses of TAs-FUW on the TRPV1/Ca 2+ -dependent NFAT-induced expression of TSLP were assessed. Stimulation and inhibition of TRPV1 receptors by capsaicin (CAP) and capsazepine (CPZ), respectively, were used to validate the effect of TAs-FUW. Results The UPLC-Q-TOF/MS analysis revealed that TAs-FUW mainly contain six compounds (peiminine, peimine, edpetiline, khasianine, peimisine, and sipeimine). TAs-FUW improved airway inflammation and obstruction, mucus secretion , collagen deposition, and leukocyte and macrophage infiltration, and downregulated TSLP by inhibiting the TRPV1/NFAT pathway in asthmatic mice. In vitro , the application of CPZ demonstrated that the TRPV1 channel is involved in TNF-α/IL-4–mediated regulation of TSLP. TAs-FUW suppressed TNF-α/IL-4–induced TSLP generation expression by regulating the TRPV1/Ca 2+ /NFAT pathway. Furthermore, TAs-FUW reduced CAP-induced TSLP release by inhibiting TRPV1 activation. Notably, sipeimine and edpetiline each were sufficient to block the TRPV1-mediated Ca 2+ influx. Conclusion Our study is the first to demonstrate that TNF-α/IL-4 can activate the TRPV1 channel. TAs-FUW can alleviate asthmatic inflammation by suppressing the TRPV1 pathway and thereby preventing the increase in cellular Ca 2+ influx and the subsequent NFAT activation. The alkaloids in FUW may be used for complementary or alternative therapies in asthma.
研究领域:
药理学
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免疫学
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呼吸医学
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植物科学
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DOI
PubMed
高影响因子
Chinese Medicine
·
2026
·
IF 7.4
Qing Zhang,Ziyun Chen,Qingyong Yu,Hanwen Wang,Yucui Jiang,Lan Zhou,Guang Yu,Zongxiang Tang,Changming Wang
Background Cancer-induced bone pain (CIBP) remains a debilitating clinical challenge due to its complex pathogenesis and limited therapeutic options. Tetrahydropalmatine (THP), an active alkaloid from Corydalis tuber , has shown analgesic potential, but its specific mechanisms in mitigating CIBP- especially its interactions with neural factors and immune cells-remain incompletely understood. This study aimed to investigate the efficacy of THP in alleviating CIBP and clarify its underlying mechanisms, with a focus on the roles of transient receptor potential vanilloid 1 (TRPV1), substance P (SP), and macrophage dynamics in a mouse model of CIBP. Methods Using a multidisciplinary approach, we established a CIBP model in male C57BL/6 mice (and TRPV1-knockout mice) via intramedullary injection of lung cancer cells. Behavioral assessments were performed to evaluate mechanical, thermal, and cold allodynia, as well as spontaneous pain, following daily oral administration of THP (80 mg/kg) from day 7 post-modeling. Molecular and cellular analyses included immunofluorescence staining, real-time PCR, ELISA (to quantify SP, cytokines, and Tac1 expression), calcium imaging (to measure TRPV1-mediated calcium influx in DRG neurons), scratch assays (to assess macrophage migration), and flow cytometry (to analyze macrophage polarization in RAW 264.7 cells). Results THP significantly alleviated CIBP-related allodynia and spontaneous pain in mice. Mechanistically, THP directly inhibited TRPV1 function in the primary phase (≤ 14 days post-modeling) (with an IC 50 of 77.9 µM), reducing SP release from DRG neurons and suppressing macrophage recruitment to DRG and sciatic nerve via the TRPV1-SP pathway. Importantly, THP directly promoted the polarization of recruited macrophages toward the anti-inflammatory M2 phenotype, as evidenced by downregulated iNOS, TNF-α, IL-1β and upregulated CD206, IL-4, IL-10 in vitro (RAW264.7 cells) and in vivo. These effects were abrogated in TRPV1-knockout mice, confirming TRPV1 as a critical mediator in the primary phase. Conclusion In conclusion, THP mitigates CIBP through a dual mechanism: regulating macrophage recruitment via the TRPV1-SP pathway in the early stage to inhibit CIBP initiation and directly modulating the migrated macrophage polarization. This study provides novel insights into THP’s analgesic mechanisms and supports its potential as a preclinical candidate for CIBP treatment. Graphical Supplementary Information The online version contains supplementary material available at 10.1186/s13020-026-01359-3.
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Hanbin Chen,Guanghong Li,Lin Deng,Nan Xu,Simon Ming-Yuen Lee,Xiaowei Nie,Jin-Song Bian
Introduction: Pain is a complex phenomenon involving physiological and psychological responses to noxious stimuli. Long-term opioid or NSAID use leads to reduced efficacy and tolerance. Initially a thermosensitive receptor, TRPV1 is increasingly recognized as a target for analgesic intervention.Methods: Our investigation is focused on the exploration of novel TRPV1 antagonists derived from natural sources through computational screening methodologies, aiming to assess their efficacy as analgesic agents.Results: Among the compounds screened, a promising TRPV1 antagonist named pinocembrin-7-o-3-o-galloyl-4-6-hexahydroxydiphenoyl-beta-d-glucoside (PINO) has exhibited superior stability in its interaction with TRPV1 through virtual screening and molecular dynamics simulation. A dosage of 20 mg/kg of PINO had been shown to reduce the writhing response in acetic acid-induced mice, elevate the thermal pain threshold in the hot water tail-flick and hot plate assays, and concurrently increase the mechanical pain threshold in CFA-induced inflammatory pain models in mice. Moreover, in a murine Lewis lung carcinoma cell line LL-induced bone cancer pain model, PINO also effectively raised the thermal and mechanical pain thresholds in mice. Furthermore, PINO had been found to attenuate the production and gene expression of pro-inflammatory cytokines. The underlying mechanism was attributed to the suppression of NF-κB and MAPK signaling cascades.Discussion: This innovative compound represents a prospective avenue for the management of acute, chronic, and bone cancer pain, providing a viable alternative analgesic option for individuals suffering from such conditions.
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Molecular Pain
·
2025
·
IF 2.8
Yu-Na Cheng,Ming-Zhu Zhang,Cui-Qing Xie,Zhi-Qi Li,You-Feng Ge,Zhao-Hui Jin,Zhi-Hua Luo,Chen-Yang Zheng,Liang Chen,dong fang,Chen-Guang Niu,Jin-Jin He
Bone cancer pain (BCP), one of the most intractable symptoms in patients with cancer, remains poorly understood and lacks effective therapeutic interventions. In this study, we employed an established rat model of BCP induced by intratibial injection of MRMT-1 mammary carcinoma cells. Transcriptomic profiling of the L4-L6 dorsal root ganglia (DRGs) revealed an upregulation of the amino acid transporter SLC38A3. This finding was further confirmed by time-dependent increases in both its mRNA and protein levels. Immunofluorescence co-localization indicated that SLC38A3 was expressed in NF200-, CGRP-, and IB4-positive neurons within the L4-L6 DRGs, and its expression was upregulated in the BCP model. Concomitantly, the transient receptor potential vanilloid 1 (TRPV1) expression in BCP rat DRGs was dynamically upregulated at both the mRNA and protein levels, aligning temporally with pain hypersensitivity. Lentivirus-mediated overexpression or knockdown of SLC38A3 in the DRGs led to a corresponding upregulation or downregulation of TRPV1-expression. Activation of the PI3K/AKT signaling pathway corresponds with BCP-related pain behaviors and expression patterns of SLC38A3 and TRPV1. Bexarotene alleviates BCP in rats by suppressing the aberrant overexpression of SLC38A3, thereby blocking the PI3K/AKT signaling pathway-mediated upregulation of TRPV1. These findings indicate that SLC38A3, through its downstream PI3K/AKT-TRPV1 axis, may serve as a potential molecular mechanism for analgesia in BCP.
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PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Qin Yeyu,Xie Jing,Zheng Ruihe,Li Yuhang,Wang Haixia
Doxorubicin (DOX) is one of the most common chemotherapeutic anti-cancer drugs. However, its clinical use is restricted by serious cardiotoxicity. Oleoylethanolamide (OEA), a structural congener of endocannabinoid anandamide, is the endogenous agonist of peroxisome proliferator activated-receptor α (PPARα) and transient receptor potential cation channel vanilloid-1 (TRPV1), and involved in many physiological processes. The present study aimed to determine whether OEA treatment protects against DOX-induced cytotoxicity (DIC) and gain insights into the underlying mechanism that mediate these effects. Our data revealed that Oleoylethanolamide treatment improved the myocardial structure in DOX-challenged mice by attenuating cardiac oxidative stress and cell apoptosis. OEA also alleviated DOX-induced oxidative stress and apoptosis dysregulation in HL-1 cardiomyocyte. These effects were mediated by activation of TRPV1 and upregulation of PI3K/ Akt signaling pathway. Inhibition of TRPV1 and PI3K reversed the protective effects of OEA. Taken together, our data suggested that OEA protects against DIC through a TRPV1- mediated PI3K/ Akt pathway.
研究领域:
药理学
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心脏病学
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分子生物学
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PubMed
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Nanomedicine-Nanotechnology Biology and Medicine
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2024
·
IF 4.2
Yuan Gao,Jun Wang,Weiwei Zhang,Fei Ge,Wanzhen Li,Feiyang Xu,Ting Cui,Xing Li,Kai Yang,Yugui Tao
Calcium overload therapy refers to the condition of intracellular Ca 2+ overload, which causes mitochondrial damage and leads to the uncontrolled release of apoptotic factors into the cytoplasm through the open mitochondrial permeability pore. Based on this, it is playing an increasingly important role in the field of oncology due to its good efficacy and small side effects. However, the regulation of calcium homeostasis by cancer cells themselves, insufficient calcium ions (Ca 2+ ) in tumor sites and low efficiency of calcium entering tumor have limited its efficacy, resulting in unsatisfactory therapeutic effect. Therefore, a novel CAP/BSA@TCP-ZIF-8 nanoparticle drug carrier system was constructed that can provide Ca 2+ from exogenous sources for pH-controlled degradation and drug release at the same time. Both in vivo and in vitro experiments have proved that the nanomaterial can activate TRPV1 channels and provide exogenous Ca 2+ to cause Ca 2+ overload and apoptosis, thus achieving anti-tumor effects.
研究领域:
肿瘤学
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纳米技术
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药学
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生物医学工程
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PubMed
高影响因子
ACS Applied Bio Materials
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2022
·
IF 0
Mei Zhou,Boying Li,Ning Li,Mengying Li,Chengfen Xing
Ca2+ overload is caused by the abnormal accumulation of Ca2+, which is a potential therapeutic strategy for inhibiting tumor growth. However, due to the limited intracellular Ca2+ concentration, its anticancer effect is non-significant. Herein, near-infrared (NIR)-responsive nanoparticles NPs-PCa (DPPC-DSPE-PEG2000-NH2@PDPP@CaO2@DOX) were designed and prepared to achieve photothermal trigger of Ca2+ release, thereby increasing intracellular Ca2+ content. Furthermore, the nanoparticles convert light to heat to activate the transient receptor potential cation channel subfamily V member 1 (TRPV1) ion channels, allowing external Ca2+ to flow into the cells, further increasing the Ca2+ concentration. NPs-PCa nanoparticles overcome the limitation of insufficient concentration by increasing Ca2+ in both internal and external approaches. Meanwhile, an imbalance of intracellular Ca2+ induces mitochondrial dysfunction and ultimately results in cancer cell death. This study provides an effective strategy for inhibiting breast cancer tumor growth by regulating Ca2+ concentration.
研究领域:
癌症研究
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纳米技术
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治疗学
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分子生物学
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PubMed
Food & Function
·
2024
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IF 5.1
Meitong Liu,Jiakang Guo,Jing Lu,Yuelin Chen,Xuming Deng,Shengzhuo Zhang,Shuang Guan
Capsaicin (CAP), the active ingredient in hot chilli peppers, has anti-inflammatory and hepatoprotection effects. Acute alcoholic liver injury (AALI) is liver damage caused by acute alcohol abuse, which can lead to severe liver lesions and even be life-threatening. Pyroptosis is inflammation-related programmed cell death characterized by membrane rupture and plays a key role in AALI. The endosomal sorting complexes required for transport (ESCRT) proteins can gather at damaged areas of the membrane to facilitate the process of sealing the membrane. In this study, we found that CAP could relieve acute alcohol-induced pyroptosis of hepatocytes in vitro and in vivo. Mechanically, we found that CAP could alleviate acute alcohol-induced pyroptosis by activating the ESCRT-III-dependent membrane repair machinery. Furthermore, the data showed that CAP induced ESCRT-III protein expression by activating transient receptor potential vanilloid member 1 (TRPV1) on the cell membrane and Ca2+ influx. TRPV1 inhibitor capsazepine (CPZ) inhibited the relief effect of CAP on acute alcohol-induced pyroptosis. Overall, these results showed that CAP might activate ESCRT-III-dependent membrane repair machinery through Ca2+ influx, which is regulated by TRPV1 calcium channels, therefore mitigating acute alcohol-induced pyroptosis. Our research provides a new perspective on a naturally active food product to promote cell repair and relieve AALI.
研究领域:
药理学
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细胞生物学
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肝病学
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PubMed
高影响因子
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