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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DOI
PubMed
高影响因子
ARCHIVES OF GYNECOLOGY AND OBSTETRICS
·
2022
·Vol. 306
·期 1
·115-125
·
IF 2.493
Zhu Bo,Chen Yumei,Guo Min,zhang Chenhui,Huang Lingxiao,Pan Qiangwei,Lin Tao,Lu Yiyi,Shen Xiaolu,Zhang Hongping
Purpose Adenomyosis is a common gynecological disease, but its pathogenesis and treatment options are not yet completely clear. This study aimed to investigate the analgesic effect of berberine on tamoxifen-induced neonatal mouse adenomyosis and its curative effects on the disease. Methods The mouse adenomyosis model was established in neonatal female mice via oral administration of tamoxifen suspended solution. Adenomyosis mice were given berberine by intraperitoneal injection with the dosage of 5, 10, and 20 mg/kg body weight, respectively, at 17 weeks after birth. The pain sensation of the mice was evaluated by hotplate and tail-flick tests. The mRNA levels of gene expression were detected by RT-qPCR. The protein expression was analyzed by ELISA and Western blot. Results Berberine reduced the uterine weight, suppressed the myometrial infiltration of ectopic endometrium, improved the hotplate and tail-flick latency of the adenomyosis mice. Mechanistically, berberine downregulated the expression of genes related to pain and inflammation, such as TRPV1, COX-2, VEGF and OTR, impaired the inflammatory response at the DRG site, and inhibited the expression of TLR4 in DRG and uterine tissues. Conclusions Berberine attenuates hyperalgesia and exhibits analgesic and therapeutic effects on adenomyosis mice.
研究领域:
药理学
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妇科学
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疼痛研究
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炎症
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DOI
PubMed
高影响因子
Theranostics
·
2023
·
IF 12.4
Jiqian Zhang,Shasha Zhu,Mingxu Zhao,Mengni Zhou,Xiaoling Zhu,Xin Qing,Zhilai Yang,Pengfei Wei,Guoying Zhang,Weiling He,Yongqiang Yu,Xuesheng Liu
Rationale: Tumor ablation can cause severe pain to patients, but there is no satisfactory means of analgesia available. In addition, recurrence of residual tumors due to incomplete ablation threatens patient safety. Photothermal therapy (PTT), a promising approach for tumor ablation, also faces the aforementioned problems. Therefore, developing novel photothermal agents that can efficiently relieve PTT-associated pain and potentiate the PTT efficacy are urgently needed. Methods: The Pluronic F127 hydrogel doped with indocyanine green (ICG) was served as photothermal agent for PTT. Mouse model that inoculation of tumor near the sciatic nerve was constructed to assess the PTT-evoked pain. Subcutaneous and sciatic nerve vicinal tumor-bearing mice were used to test the efficacy of PTT. Results: PTT-evoked pain depends on an increase in tumor temperature and is accompanied by the activation of TRPV1. A simple introduction of local anesthetic (LA) ropivacaine into ICG-loaded hydrogels relieves PTT-induced pain and exerts long-lasting analgesia compared with opioid analgesia. More interestingly, ropivacaine upregulates major histocompatibility complex class I (MHC-I) in tumor cells by impairing autophagy. Therefore, a hydrogel co-doped with ropivacaine, TLR7 agonist imiquimod and ICG was rationally designed. In the hydrogel system, imiquimod primes tumor-specific CD8 + T cells through promoting DCs maturation, and ropivacaine facilitates tumor cells recognition by primed CD8 + T cells through upregulating MHC-I. Consequently, the hydrogel maximumly increases CD8 + T cells infiltration into tumor and potentiates PTT efficacy. Conclusion: This study for the first time provides an LA-dopped photothermal agents for painless PTT and innovatively proposes that a LA can be used as an immunomodulator to potentiate the PTT efficacy.
研究领域:
癌症治疗
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生物医学工程
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药学
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免疫学
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DOI
PubMed
高影响因子
Frontiers in Medicine
·
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
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2022
·
IF 6.656
Di Zhang,Bei Jing,Zhenni Chen,Xin Li,Huimei Shi,Yachun Zheng,Shiquan Chang,Guoping Zhao
Background Nonsteroidal anti-inflammatory drugs are used to relieve sciatica, but their effects are not satisfactory. Purpose This study aimed to explore the therapeutic effects of ferulic acid on sciatica. Methods Thirty-two SD rats were randomly divided into 4 groups, i.e., sham operation group, chronic constriction injury (CCI) group, mecobalamin group, and ferulic acid group. We conducted behavioural tests, ELISA, PCR, Western blots, and immunofluorescence analysis. Specific inhibitors were used in cell experiments to explore the related mechanisms. Results Thermal hyperalgesia was induced after CCI operation, and ferulic acid relieved thermal hyperalgesia. In addition, ferulic acid decreased the IL1β, IL6, TNF-α, and CRP mRNA levels; the IBA-1, iNOS, IL1β, RhoA, RhoA-GTP, COX2, Rock1, TRPV1, TRPA1, and p-p38MAPK levels in dorsal root ganglion (DRG) neurons; and the LPS, CRP, substance P (SP), and prostaglandin E2 (PGE2) levels in serum, and these levels were higher in the CCI group. In the cell experiments, LPS induced M1 polarization of GMI-R1 cells via the RhoA/Rock pathway. Ferulic acid attenuated LPS-induced M1 polarization by decreasing the levels of M1 polarization markers, including IL1β, IL6, TNF-α, iNOS, and CD32, and increased M2 polarization by increasing the levels of M2 polarization markers, including CD206 and Arg-1. LPS treatment clearly increased the iNOS, IL1β, RhoA, Rock1, Rock2 and p-p38 MAPK levels and reduced Arg-1 expression, and ferulic acid reversed these changes. Conclusion Ferulic acid can inhibit peripheral sensitization by reducing the levels of inflammatory factors, TRPA1 and TRPV1 through the RhoA/p38 MAPK pathway to alleviate sciatica.
研究领域:
药理学
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神经科学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Exploration
·
2025
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IF 22.5
Galong Li,Xin Qiao,Yu Zhao,Dongyan Li,Guigen Zhang,Xiaoli Liu,Fulin Chen,Huaning Wang,Hongbing Lu,Jin Zhou,Changyong Wang,Haiming Fan
Magnetothermal neuromodulation is a minimally invasive, deep-brain accessible, and tether-free technique. The precisely timed activation of thermosensitive ion channels, such as TRPV1, with local heat generated using magnetic nanoparticles is crucial for efficient neuromodulation. Nevertheless, this technique is greatly hindered by its long stimulus-response time and high safety risks due to the poor heat-generating performance of the nanomediators. Herein, we report the establishment of a ferrimagnetic vortex iron oxide nanoring (FVIO)-mediated magnetothermal neurostimulation technique that is efficient and safe. Compared with widely used superparamagnetic iron oxide nanomediators (SPIOs), the FVIOs triggered Ca 2+ influx into HEK293T cells and cortical neurons at an Fe concentration of 51 µg mL −1 , which is 20.27-fold lower than that needed for SPIOs. In vivo magnetothermal stimulation in the central nucleus of the amygdala of mice further demonstrated that FVIOs with the optimal dose of 0.05 µg evoked fear behaviors with an average latency of 2.51 s, which was 2.3-fold faster than that in the SPIO (0.80 µg)-treated group. More importantly, FVIOs-mediated stimulation not only exhibited negligible histopathological alterations and proinflammatory cytokine expression but also successfully elicited fear behaviors in transgene-free mice. The FVIO-mediated efficient and safe neuromodulation has the potential for future neuroscience exploitation and neurological disease treatment.
研究领域:
神经科学
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纳米医学
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生物医学工程
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磁热疗
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神经调控
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DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-14
·
IF 14.7
Wang Chenlu,Zhou Liping,Liu Chengzhe,Qiao Jiaming,Han Xinrui,Wang Luyang,Liu Yaxi,Xu Bi,Qiu Qinfang,Zhang Zizhuo,Wang Jiale,Zhou Xiaoya,Zeng Mengqi,Yu Lilei,Fu Lei
Autonomic nervous system disorders play a pivotal role in the pathophysiology of cardiovascular diseases. Regulating it is essential for preventing and treating acute ventricular arrhythmias (VAs). Photothermal neuromodulation is a nonimplanted technique, but the response temperature ranges of transient receptor potential vanilloid 1 (TRPV1) and TWIK-related K + Channel 1 (TREK1) exhibit differences while being closely aligned, and the acute nature of VAs require that it must be rapid and precise. However, the low photothermal conversion efficiency (PCE) still poses limitations in achieving rapid and precise treatment. Here, we achieve a nearly perfect blackbody absorption and a high PCE in the second near infrared (NIR-II) window (73.7% at 1064 nm) via a Pt nanoparticle shell (PtNP-shell). By precisely manipulating the photothermal effect, we successfully achieve rapid and precise multimodal neuromodulation encompassing neural activation (41.0–42.9 °C) and inhibition (45.0–46.9 °C) in a male canine model. The NIR-II photothermal modulation additionally achieves multimodal reversible autonomic modulation and confers protection against acute VAs associated with myocardial ischemia and reperfusion injury in interventional therapy.
研究领域:
生物医学工程
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心脏病学
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神经科学
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光热治疗
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DOI
PubMed
高影响因子
Nano Convergence
·
2022
·Vol. 9
·期 1
·1-13
·
IF 10.038
Liu Jiansheng,Li Jiajia,Zhang Shu,Ding Mengbin,Yu Ningyue,Li Jingchao,Wang Xiuhui,Li Zhaohui
Infrared neural stimulation with the assistance of photothermal transducers holds great promise as a mini-invasive neural modulation modality. Optical nanoparticles with the absorption in the near-infrared (NIR) window have emerged as excellent photothermal transducers due to their good biocompatibility, surface modifiability, and tunable optical absorption. However, poor activation efficiency and limited stimulation depth are main predicaments encountered in the neural stimulation mediated by these nanoparticles. In this study, we prepared a targeted polydopamine (PDA)-coated gold (Au) nanoparticles with specific binding to thermo-sensitive ion channel as nanotransducers for second near-infrared (NIR-II) photo-stimulation of neurons in rats. The targeted Au nanoparticles were constructed via conjugation of anti-TRPV1 antibody with PEGylated PDA-coated Au nanoparticles and thus exhibited potent photothermal performance property in the second NIR (NIR-II) window and converted NIR-II light to heat to rapidly activate Ca2+ influx of neurons in vitro. Furthermore, wireless photothermal stimulation of neurons in living rat successfully evoke excitation in neurons in the targeted brain region as deep as 5 mm beneath cortex. This study thus demonstrates a remote-controlled strategy for neuromodulation using photothermal nanotransducers.
研究领域:
神经科学
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纳米技术
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Jie Sheng,Ziyue Zu,Jianchen Qi,Yugang Zhang,Haoguang Wu,Zhicheng Wang,Yu Miao,Tao Zheng,Sheng Wang,Linlin Zhang,Guangming Lu,Longjiang Zhang
Atherosclerosis (AS), characterized by endothelial injury, progressive inflammation, and lipid deposition, can cause adverse cardiovascular events. However, effectively addressing all these pathological conditions simultaneously is challenging. To devise a comprehensive treatment strategy for AS, we developed a nanoparticle-based mild photothermal therapy (PTT) approach, which controlled the temperature within the range of 42–45 ℃, creating a unique 'hot spring' effect. The nanoparticles used in this therapy consist of a core made of zeolitic imidazolate framework-8 (ZIF-8) nanoparticles loaded with indocyanine green (IR820), and an outer shell made of L-arginine (LA)-modified polydopamine (PDA), which is further modified with hyaluronic acid (HA) to target plaques. In vitro studies have demonstrated that mild PTT can open the TRPV1 channel in foam cells and regulate lipid metabolic diseases by maintaining a controlled temperature range of 42–45 ℃. Furthermore, the LA-PDA shell has anti-inflammatory properties, decreasing NLRP3 expression. Moreover, the eNOS/NO pathway was activated by LA, promoting the healing of injured endothelial cells (ECs). Additionally, the increased temperature enhances HSP90 expression, thereby helping to maintain eNOS. In vivo studies further confirmed that the HLPIZ-guided ‘hot spring’ effect has impressive anti-atherosclerotic capability by scavenging lipids, reducing inflammation, and repairing injured ECs simultaneously. In conclusion, our study confirmed that HLPIZ-guided mild PTT can exhibit a ‘hot spring’ effect, effectively regulating three key pathophysiological processes of AS, being a novel, potentially effective strategy for anti-AS therapy.
研究领域:
心血管疾病
·
纳米技术
·
治疗策略
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炎症
·
脂质代谢
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产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2022
·Vol. 10
·期 5
·748-756
·
IF 7.571
Shuangling Wang,Jie Lv,Yu Pang,Shuyang Hu,Yulong Lin,Meng Li
Despite significant achievement in chemotherapy, the off-target actions and low pharmaceutical selectivity of the therapeutic agents still limit their clinical efficacy. Herein, a multifunctional nanoplatform which integrates chemotherapy, chemodynamic therapy (CDT) and photoactivation of TRPV1 channels has been successfully established for specific cancer therapy. Polydopamine (PDA) coated hollow prussian blue nanocages (hPBNCs) are used as the photothermal switches and drug carriers for loading chemotherapeutic drug, doxorubicin (Dox). Conjugating with the TRPV1 antibodies enables the nanoplatform to bind specifically to TRPV1 channels on the plasma membrane of the TRPV1-positive cancer cells and then activate them by local heating upon NIR irradiation, leading to the over-influx of Ca2+. Critically, the laser irradiation can be carefully controlled to not only open the TRPV1 channels but also avoid burning of tumors by hyperthermia. Moreover, the exposed hPBNCs in the acidic tumor cells can decompose endogenous H2O2 into ˙OH by Fenton reaction to realize CDT, which further aggravates cancer cell apoptosis. Together with the chemotherapy caused by Dox, our nanoplatform displays an enhanced anticancer effect both in vitro and in vivo. Our work provides a powerful means for site-specific cancer synergetic therapy with high spatial and temporal resolution.
研究领域:
癌症研究
·
纳米技术
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光热治疗
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药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
iScience
·
2024
·
IF 4.6
Juan Li,Zhen Li,Yanbo Liu,Yijing Li,Yanqiong Wu,Anne Manyande,Zhixiao Li,Hongbing Xiang
Summary The pathogenesis of hyperalgesia is complex and can lead to poor clinical treatment. Our study revealed that epididymal white adipose tissue (eWAT) from spared nerve injury (SNI) mice is involved in the occurrence of hyperalgesia after adipose tissue transplantation. We also showed that lysophosphatidylcholine (LPC) is enriched in the eWAT of SNI mice using non-targeted metabolomic analysis and verified that the levels of LPC in plasma and the anterior cingulate cortex (ACC) region increased following eWAT transplantation. Based on the immunohistochemistry results, we observed that LPC in the ACC region activated microglia via the TRPV1/CamkⅡ pathway. Meanwhile, the disruption of perineuronal nets (PNNs) around PV + neurons in ACC promoted hyperalgesia, and the loss of PNNs and PV + interneurons might be due to microglial phagocytosis. These findings elucidate the mechanism underlying hyperalgesia from the perspective of lipid metabolite LPC and PNNs and provide potential strategies for the treatment of hyperalgesia.
研究领域:
神经科学
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疼痛研究
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代谢组学
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免疫组化
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产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2025
·
IF 9.8
Yanyan Cao,Meng Tao,Anan Xu,Zheng Tu,Shanshan Wang,Qinyan Yu,Sixu Li,Zhengquan Liu
Black tea contains sweet aroma compounds (SACs) with sweetening potential. However, a systematic understanding of their composition, enhancing effects, and underlying mechanisms is lacking. This study identified 14 key SACs in global sweet-aroma black teas using headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry. Electronic tongue and sensory validation confirmed their sweetness-enhancing effects in a sugar-free black tea beverage and revealed their inherent taste properties (sweetness, astringency, pungency, and cooling). Molecular docking and dynamics simulation elucidated the stable bindings of T1R2/T1R3-benzeneacetaldehyde/ β -damascenone, α -amylase-benzeneacetaldehyde, TRPV1-geraniol, and TRPM8-methyl salicylate, mediated by hydrogen bonding and hydrophobic interactions. These protein-ligand complexes were proposed to modulate sweetness, sweet aftertaste, heat-evoked sweetness, and cooling-enhanced sweetness, respectively. Consequently, this study demonstrates that SACs enhance sweetness through cross-modal interactions and inherent taste properties, providing novel mechanistic insights and actionable strategies for flavor optimization in tea beverages and other food products.
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PubMed
高影响因子
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