BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2025
·
IF 2.2
Xiaoyun Yang,Yi Wang,Yujin Feng,Feng Wang,Lijuan Gao,Yueheng Wang
Myocardial infarction is often accompanied by symptoms of myocardial fibrosis, causing myocardial systolic and diastolic dysfunction. High levels of TMAO are considered to be strongly connected to cardiovascular diseases occurrence. The objective of this investigation was to determine whether formal TMAO affects the development of cardiac muscle fibers. The left anterior descending (LAD) coronary artery was ligated to construct myocardial infarction mouse model, while the control group mouse was only operated vessel separation. According to whether or not TMAO intervention is given, mice were divided into control, TMAO, myocardial infarction model(model), and myocardial infarction model + TMAO(model + TMAO). TMAO and model + TMAO group received 0.24 % TMAO in drinking water for one month. After modeling, echocardiography assessed cardiac function, and cardiac tissues were collected for analysis. Masson staining observed collagen deposition, while immunohistochemistry was conducted to identify fibronectin, collagen III, collagen I, and JAK/STAT pathway related proteins levels. In vitro, mouse cardiac fibroblasts were cultured and treated with varying TMAO concentrations (0, 300, 600, 900 μM), and Western blot was carried out to analyse changes in fibronectin, collagen III, and collagen I. Subsequently, the JAK2/STAT3 pathway inhibitor AG490 was utilized to treat cells and further examine the changes of fibronectin and collagen. The in vivo data showed TMAO significantly increases fibrosis and upregulates fibronectin, collagen III, and collagen I. In vitro experiments indicated that TMAO promotes fibronectin, collagen III, and collagen I levels through regulating the JAK2/STAT3 pathway, ultimately accelerating fibrosis.
研究领域:
心血管疾病研究
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xiangrui Meng,Xue Zhan,Hang Xiao,Songtao Li,Xuelian Zhang,Li Ma,Yiyao Liu,Jianyuan Tang
Natural killer (NK) cell-based immunotherapy is a promising approach for treating solid tumors and hematological malignancies. However, its therapeutic efficacy is limited by poor tumor infiltration and suppressive tumor microenvironment. Here, we introduce a rapid, simple, and efficient solution: bovine serum albumin-stabilized ultra-small (4 nm) NK cell nano-engagers, termed Bi 2 Se 3 @BSA nanodots (Nds). These Nds, responsive to high H 2 O 2 levels in tumor cell environments, enhance near-infrared (NIR)-II photothermic immunotherapy. In vitro and in vivo experiments demonstrate their effectiveness in activating photothermal therapy (PTT)-induced immunogenic cell death (ICD), initiating immune cascade reactions, and stimulating immune response activation. By upregulating NKG2D, RAE-1, and secreting cytokines such as IFN-γ and TNF-α, targeted NK cell infiltration is achieved, reversing the immunosuppressive tumor microenvironment and optimizing NK cell cytotoxicity. Transcriptomic analysis confirms the association of immune response activation with the IL-6/JAK2/STAT3 signaling pathway. Notably, combining these nano-engagers with immune checkpoint inhibitors (aPD-1) significantly enhances therapeutic efficacy, facilitating tumor eradication and reducing recurrence risk. Taken together, NK cell nano-engagers inhibit the IL-6/JAK2/STAT3 signaling pathway, target NK cell activation, stimulate immune functions, and improve the immunosuppressive microenvironment. This study presents an alternative strategy for NK cell-based immunotherapy and highlights this promising tool for cancer immunotherapy.
研究领域:
肿瘤免疫学
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纳米医学
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2024
·
IF 4.3
Ruijie Wang,Ning Zhou,Jinfang Xue,Yan Li,Yang Wang,Huadong Zhu,Chuanzhu Lv
Background: In sepsis, the lung is one of the worst affected organs, often leading to acute lung injury (ALI). More and more evidence suggests that macrophages are also involved in the pathogenesis of ALI. In our previous study, we successfully synthesized Iron-capsaicin-based nanoparticles (Fe-CAP NPs) and found that it could inhibit the secretion of inflammatory cytokines to alleviate ALI. Here, we further explore the anti-inflammatory mechanism of Fe-CAP NPs.Methods: Bone marrow-derived macrophages (BMDM) and C57 mice were divided into four groups: control group, lipopolysaccharide (LPS) group, CAP + LPS group and Fe-CAP + LPS group. Western blot and Immunofluorescence were used to detect the expression of macrophage phenotypic markers CD86 and CD206 in BMDM and lung tissue. Fluorescence microbeads, Transwell and ROS kit were used to detect the phagocytosis, migration and ROS clearing capability of BMDM. Western blot was used to detect the expression of JAK2/STAT3 pathway and apoptosis proteins in BMDM. TUNEL kit and H&E staining were used to evaluate apoptosis and pathological changes in lung tissue.Results: In vitro, CD86 expression was increased in LPS, but decreased after Fe-CAP pretreatment. CD206 expression was the opposite. Fe-CAP reduced phagocytosis, migration and scavenged ROS in LPS-treated BMDM. Fe-CAP inhibited P-JAK2 and P-STAT3 expression and reduced apoptosis. In vivo, Fe-CAP improved lung histopathology and reduced apoptosis in lung tissue of LPS group. CD86 expression was increased in lung tissue of LPS group, but decreased in Fe-CAP preconditioning, and CD206 expression was reversed.Conclusion: Fe-CAP NPs could alleviate sepsis-induced ALI by regulating the polarization and function of macrophages, reducing ROS level and apoptosis.
研究领域:
免疫学
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药理学
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肺病学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Xun He,Jingsong Liu,Yugang Gong,Wei Lu,Xiaowei Sha,Chang Cao,Yanqun Li,Jiawei Wang
Background Evidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. Purpose Therefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. Study design The C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). Methods The optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4 + CD25 + FOXP3 + , CD4 + and CD8 + of skin tissue. And the levels of CD4 + and CD8 + , p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. Results Compared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4 + CD25 + FOXP3 + and CD4 + cells, while inhibited the number of CD8 + positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. Conclusion Amygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.
研究领域:
药理学
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免疫学
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皮肤科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2024
·
IF 3.8
Ting Liu,Zhentao Cheng,Derong Song,Erpeng Zhu,Hui Li,Rutao Lin,Zhiling Wan,Shunxing Liu,Zeguang Gong,Chunlan Shan
Mycoplasma gallinarum ( MG ) can cause infectious respiratory diseases in poultry that are chronic. Arbutin (AR) possesses anti-inflammatory, bacteriostatic, antitussive, and expectorant pharmacological effects, but whether it exerts regulatory effects on MG -induced pneumonia and fibrosis remains unclear. The study results unveiled that pulmonary connective tissue hyperplasia, pulmonary capillary congestion, and inflammatory cell infiltration, as well as serum levels of cytokines (i.e., TNF-α, IL-1β, IL-6, and IL-10), were elevated after MG infection. Collagen fibers were significantly deposited in the lung tissue from MG -infected chicks. Furthermore, the expression levels of key factors in the JAK2/STAT3 and TGF-β/Smad pathways markedly increased. AR intervention significantly alleviated MG -induced pneumonic injury, and reduced collagen deposition and the expression of fibrosis markers in the lung tissue. AR reduced the degree of pulmonary fibrosis by regulating key factors of the JAK2/STAT3 signaling pathway in the MG -infected HD11 cells. Thus, AR effectively reduced the expression of inflammatory factors by regulating the JAK2/STAT3 signaling pathway, thereby improving lung inflammation and fibrosis.
研究领域:
兽医学
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药理学
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呼吸系统疾病
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分子生物学
✓ 已验证
产品关联
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
✓ 已验证
DOI
PubMed
高影响因子
Anti-Cancer Agents in Medicinal Chemistry
·
2024
·Vol. 24
·期 18
·1360-1370
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IF 2.6
Linjin Li,Chengpeng Li,Feilong Miao,Wu Chen,Xianghui Kong,Ruxian Ye,Feng Wang
Background Cisplatin is a key therapeutic agent for bladder cancer, yet the emergence of cisplatin resistance presents a significant clinical challenge. Objective This study aims to investigate the potential and mechanisms of cyclanoline (Cyc) in overcoming cisplatin resistance. Methods Cisplatin-resistant T24 and BIU-87 cell models (T24/DR and BIU-87/DR) were established by increasing gradual concentration. Western Blot (WB) assessed the phosphorylation of STAT3, JAK2, and JAK3. T24/DR and BIU-87/DR cell lines were treated with selective STAT3 phosphorylation modulators, and cell viability was evaluated by CCK-8. Cells were subjected to cisplatin, Cyc, or their combination. Immunofluorescence (IHC) examined p-STAT3 expression. Protein and mRNA levels of apoptosis-related and cell cycle-related factors were measured. Changes in proliferation, invasion, migration, apoptosis, and cell cycle were monitored. In vivo, subcutaneous tumor transplantation models in nude mice were established, assessing tumor volume and weight. Changes in bladder cancer tissues were observed through HE staining, and the p-STAT3 was assessed via WB and IHC. Results Cisplatin-resistant cell lines were successfully established, demonstrating increased phosphorylation of STAT3, JAK2, and JAK3. Cisplatin or Cyc treatment decreased p-STAT3, inhibited invasion and migration, and induced apoptosis and cell cycle arrest in the G0/G1 phase in vitro. In vivo, tumor growth was significantly suppressed, with extensive tumor cell death. IHC and WB consistently showed a substantial downregulation of STAT3 phosphorylation. These changes were more pronounced when cisplatin and Cyc were administered in combination. Conclusion Cyc reverses cisplatin resistance via JAK/STAT3 inhibition in bladder cancer, offering a potential clinical strategy to enhance cisplatin efficacy in treating bladder cancer.
研究领域:
肿瘤学
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药理学
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分子生物学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-13
·
IF 3.8
Yao Fei,Yuan Qin,Yan Yichao,Liang Guoqiang,Zhou Liang,Xu Heng,Gao Shaomei,Zou Ting,Zhang Lurong
Yu-Ping-Feng-San (YPF) is a famous classical Chinese medicine formula known for its ability to boost immunity. YPF has been applied to enhance the immune status of tumor patients in clinical practice. However, there is still a lack of research on its immune regulatory effects and mechanisms in the tumor microenvironment. This study was designed to investigate the effects and mechanism of YPF on improving the immune suppression state of hepatocellular carcinoma (HCC) microenvironment. In an orthotopic mouse model of HCC, YPF improved the immune microenvironment of HCC immunosuppression, enhanced the maturation of dendritic cells (DCs), promoted the release of IL-12, and decreased the presence of JAK2, p-JAK2, STAT3, and p-STAT3 proteins in both tumor tissue and paracancerous tissues. YPF also could promote the maturation and reduce the activation of JAK2, p-JAK2, STAT3, and p-STAT3 proteins of mouse bone marrow-derived DCs induced by culture medium or tumor supernatant in vitro . Transient transfection of siRNA-STAT3 with DCs resulted in an increase in its maturation and its secretion of IL-12. On the whole, these combined effects of YPF served to ameliorate the HCC immune suppression microenvironment, which conducive to immune cells play the role of immune surveillance and killing liver cancer cells. The mechanisms of these combined effects were, at least in part, related to its inhibition of the activated JAK2-STAT3 signaling pathway in DCs within the HCC microenvironment.
研究领域:
肿瘤学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2021
·Vol. 9
·期 7
·3722-3731
·
IF 2.863
Lin Zhu,Yingjuan Liu,Xiaolin Wu,Yuqian Ren,Qinghua Zhang,Leiming Ren,Yunliang Guo
Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo , CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.
研究领域:
神经科学
·
衰老研究
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
·
2019
·
IF 2.086
Rui-Li Zhu,Ying-Kun Zhi,Lang Yi,Jin-Fang Luo,Jing Li,Sha-Sha Bai,Liang Liu,Pei-Xun Wang,Hua Zhou,Yan Dong
Objective: To investigate the cellular mechanism that sinomenine (SIN) inhibits inflammation in macrophages induced by LPS through α7 nicotinic acetylcholine receptor (α7nAChR).Materials and methods: RAW264.7 cells were stimulated with LPS and treated by SIN or nicotine (Nic). A selective antagonist of α7nAChR, α-bungarotoxin (BTX) was used to block α7nAChR. AG490 was used to inhibit JAK2 activation. ELISA was performed to detect the levels of TNF-α and MCP-1. Western blotting was used to analyze the expression of MIF, MMP-9, CD14, TLR4, STAT3 and p-STAT3. Intracellular-free calcium level was measured by Fluorescent probe fluo-3/AMResults: SIN inhibited the production of TNF-α, MCP-1, MIF, and MMP-9, decreased the expression of CD14 and TLR4, and inhibited the release of intracellular-free calcium from intracellular stores in RAW 264.7 cells stimulated by LPS. JAK-specific inhibitor AG490 attenuated the inhibitory effect of SIN on TNF-α. SIN increased the phosphorylation of STAT3. And the above effects of SIN were attenuated by antagonist of α7nAChR.Conclusions: SIN can decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages.
研究领域:
免疫学
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药理学
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细胞生物学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yu Wang,Meihao Peng,Xin Yang,Liming Tu,Jiamin Liu,Yixi Yang,Rui Li,Xue Tang,Yuqing Hu,Guowu Zhang,Qi Zhao,Qiuxia Lu
ABSTRACT Ethnopharmacological relevance Fritillaria cirrhosa D. Don (FCD) is a traditional Chinese medicine used to treat respiratory disorders, known for its effects in clearing heat, moistening the lungs, resolving phlegm, and relieving cough. Additionally, the total alkaloids extracted from FCD can alleviate asthma symptoms and reduce airway inflammation. However, no studies have investigated the effects of total alkaloids on lung macrophages. Aim of the study This study explored whether the total alkaloids of FCD (TAs-FCD) reduce M2 macrophage polarization and, consequently, attenuate airway remodeling in asthmatic mice. This study further elucidated its mechanism of action in treating allergic asthma. Materials and methods The extracted TAs-FCD was analyzed for its composition using UPLC-Q-TOF/MS. Network pharmacology was employed to identify the active ingredients and potential mechanisms of TAs-FCD in the treatment of allergic asthma. A mouse model of ovalbumin-induced allergic asthma was established, adopted, and validated through in vivo experiments. Hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time fluorescence quantitative polymerase chain reaction (q-PCR) were used to investigate the role of TAs-FCD in inhibiting M2 macrophage polarization in the context of allergic asthma. Results A total of 66 active ingredients were screened from 116 compounds using SWISSADME. The targets of these 66 compounds were predicted by SwissTargetPrediction, resulting in 808 unique drug targets after excluding duplicates. Additionally, 1,756 targets related to allergic asthma were identified from the DisGeNET, Genecard, and OMIM databases. This led to 267 cross-targets between the active ingredient targets and allergic asthma targets, including interleukin (IL)-1β, tumor necrosis factor (TNF), and STAT3. Animal experiments demonstrated that TAs-FCD improved histopathological injury in mouse lungs, reduced peri-airway collagen fiber accumulation, airway mucus secretion, and airway smooth muscle proliferation. TAs-FCD also lowered IL-1β, TNF-α and IL-4 levels in lung tissues and alleviated airway inflammation. Furthermore, TAs-FCD significantly reduced levels of Arg1 and CD206, which are closely associated with M2 macrophages, and downregulated the expression of p-STAT3 and p-JAK2. Conclusion TAs-FCD may inhibit M2 macrophage polarization by regulating the JAK2/STAT3 pathway, thereby alleviating airway remodeling and inflammation in allergic asthmatic mice.
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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中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2016
·
IF 2.551
Zhilin Qi,Shimei Qi,Liefeng Ling,Jun Lv,Zunyong Feng
Salidroside (SAL) is an active ingredient isolated from the Rhodiola rosea , has potent anti-inflammatory effect, but the mechanism is still elusive. The purpose of this study is to verify the effects of SAL on LPS-induced inflammatory response and investigate the possible underlying molecular mechanism. RAW264.7 cells were pre-incubated with SAL for 2 h, then stimulated with or without LPS for another 16 h. The levels of TNF-α, MCP-1, IL-6, and PGE2 were detected by ELISA , and the production of NO was determined by nitrite analysis. The expression levels of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were detected by Western blotting . In RAW264.7 cells and murine peritoneal macrophages, the activation of signal molecules was also measured by Western blot. The nuclear translocation of STAT3 was determined by Laser confocal and nucleocytoplasmic separation experiments. Our results showed that SAL attenuated the productions of TNF-α, IL-6, MCP-1, PGE2 and NO dose dependently. SAL also suppressed LPS-induced expressions of iNOS and COX-2 significantly. Further studies revealed that SAL down-regulated the phosphorylation of JAK2-STAT3 signaling pathway and reduced the nuclear translocation of STAT3 induced by LPS in RAW264.7 cells and primary peritoneal macrophages. In addition, consistent with the results in vitro, in the model of mice acute lung injury (ALI) induced by LPS, SAL reduced the infiltration of inflammatory cells and decreased the levels of serum TNF-α and IL-6 obviously. Taken together, these data indicated that SAL exerted anti-inflammatory action via down-regulating LPS-induced activation of JAK2-STAT3 pathway and suppressing STAT3 transfer into the nucleus at least in part.
研究领域:
药理学
·
免疫学
·
细胞生物学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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