EXPERIMENTAL DERMATOLOGY
·
2019
·Vol. 28
·期 11
·1227-1236
·
IF 2.868
Fei Yi,Xiaoli Zheng,Fang Fang,Jiaan Zhang,Bingrong Zhou,Xiangsheng Chen
Background Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is a well-known treatment for non-hypertrophic actinic keratoses and superficial basal-cell carcinomas. Objectives In this study, we first revealed that ALA-PDT treatment effectively ameliorated the psoriasis-like lesion in imiquimod (IMQ)-induced mouse model and further explored the potential molecular mechanism and related signalling pathways during the treatment. Besides, we also confirmed a significant alleviation of ALA-PDT therapy on IFN-γ-induced over-proliferation of keratinocytes. Methods H&E staining was conducted to reveal the histological changes of mice in different groups. The different expression levels of RNA were illustrated by using QRT-PCR. Western blot was performed to confirm the various expression levels of protein in mice. In vitro, cell proliferation and cell cycle were evaluated by cell counting kit-8 and flow cytometry assay, respectively. Results The result showed that ALA-PDT’s anti-proliferation effect and regulation on Socs1 /3, JAK1 /2 and K17 in IFN-γ-induced keratinocytes were largely weakened by NAC, indicating that ALA-PDT attenuated the proliferation of IFN-γ-induced keratinocytes by enhancing ROS level. Conclusions These results demonstrated that ALA-PDT largely activated the productivity of Socs1 /3 in a ROS-dependent manner. Socs1 /3 is a potential blocker in JAK signalling pathway and inhibits the proliferation and keratinization of keratinocytes in psoriasis.
研究领域:
皮肤科
·
分子生物学
·
光动力疗法
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2025
·Vol. 29
·期 6
·e70470
·
IF 4.2
Chuchu Xu,Renjun Zhu,Qingfeng Dai,Yaoqing Li,Gengyuan Hu,Kelong Tao,Yuhong Xu,Guangen Xu,Guolin Zhang
The main reason for the failure of chemotherapy therapies based on 5-Fluorouracil (5-Fu) is the development of resistance to 5-Fu in cancer patients, particularly those with colorectal cancer. Tissue inhibitor of metalloproteinases 2 (TIMP-2) has been shown to be associated with colorectal cancer (CRC), but its correlation with 5-Fu resistance in colorectal cancer has not been thoroughly studied. We screen the expression of different cytokines through Cytokine array. CCK-8 assay was conducted to evaluate the IC 50 of 5-Fu and cell proliferation. ELISA and RT-qPCR were performed to detect TIMP-2 expression levels in cells and patient serum. Western blotting was utilised to analyse the differences in the expression of proteins related to signalling pathways in cells. Through cytokine array screening, we found that the expression of TIMP-2 was significantly increased in CRC drug-resistant cell lines. In addition, the expression of TIMP-2 in the serum of patients with CRC resistance to 5-Fu was significantly increased. Subsequent mechanistic experiments showed that TIMP-2 regulated the resistance of CRC cells to 5-Futhrough the JAK–STAT signalling pathway. Moreover, anti-TIMP-2 antibody or small molecule drug LY2784544 targeting the JAK–STAT signalling pathway can effectively reverse the resistance of CRC cells to 5-Fu. It is exactly TIMP-2 that mediates the resistance of CRC to 5-Fu through the JAK–STAT signalling pathway. Targeting drugs for TIMP-2 or the JAK–STAT signalling pathway are expected to be opportunities to reverse 5-Fu resistance in CRC.
研究领域:
肿瘤学
·
分子生物学
·
药物研发
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Hui-Ying Xu,Meng-Ting Jiang,Yu-Feng Yang,Yisha Huang,Wei-Dong Yang,Hong-Ye Li,Xiang Wang
Fucoxanthin, an abundant carotenoid in marine algae, has garnered attention for its diverse health benefits, including anti-inflammatory and anticancer properties. Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation and damage. This study investigated the therapeutic potential of fucoxanthin extracted from Phaeodactylum tricornutum in collagen-induced RA. Our results demonstrated that fucoxanthin significantly alleviated RA symptoms, including weight loss, joint swelling, and decreased appetite. Histological analysis revealed that fucoxanthin mitigated synovial inflammation, cartilage damage, and bone erosion. Mechanistically, transcriptomic analysis and cell experiments indicated that fucoxanthin suppressed the JAK-STAT signaling pathway by downregulating the expression of inflammatory cytokines, such as IL-6 and IL-1β. Furthermore, metagenomic analysis suggested that fucoxanthin restored the altered gut microbiota composition associated with RA. These findings highlight the therapeutic potential of fucoxanthin from P. tricornutum in the management of RA by targeting multiple pathways, including inflammation and gut microbiota.
研究领域:
药理学
·
免疫学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Environmental Research and Public Health
·
2016
·Vol. 13
·期 11
·1085
·
IF 2.035
Yiyang Jia,Te Liu,Liting Zhou,Jian Zhu,Juan Wu,Di Sun,Jin Xu,Qi Wang,Huaiji Chen,Feng Xu,Yuezhu Zhang,Tianrong Zhang,Hongbo Liu,Lin Ye
The most widely used plasticizer, di-(2-ethylhexyl) phthalate (DEHP), is known to affect lipid metabolism and adipogenesis. We studied the effects of dietary DEHP exposure on metabolism in rats as well as the role of the JAK/STAT pathway in this process. Eighty rats were exposed to DEHP (0, 5, 50 and 500 mg/kg/d) through dietary intake for 4 weeks. We then collected blood samples, liver, and adipose tissues to detect modifications in the levels of serum lipids, leptin, adiponectin and insulin. JAK3, STAT5a and PPARγ expression were detected at both the gene and protein levels. The activation of JAK3 and STAT5a was also detected. The DEHP-exposed rats had increased body weight, serum lipid, insulin, and leptin levels. Moreover, the JAK3/STAT5a pathway was activated in the adipose tissue; however, this pathway was not activated in the liver. The mRNA of SREBP-1c in the liver was increased significantly among each of the groups, in contrast to the levels found in the mature SREBP-1c protein form. Furthermore, the expression ofFABP4,AcoxandFASnwas decreased in the liver, but increased in adipose tissue. Thus, we conclude that exposure to DEHP reduces the hydrolysis of lipid and promotes triglyceride accumulation by oppositely regulating the activation state of JAK/STAT pathway in the liver and adipose tissue, resulting in the disorder of body lipid metabolism and obesity.Keywords:di-(2-ethylhexyl) phthalate;JAK/STAT;lipid metabolism;adipose tissue
研究领域:
毒理学
·
代谢研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2022
·Vol. 11
·期 12
·2360
·
IF 7.675
Jian Jin,Yiyi Shan,Liangliang Zhang,Zhengchang Wu,Shenglong Wu,Mingan Sun,Wenbin Bao
Fumonisin B1 (FB1) is a mycotoxin that poses a great threat to agricultural production and the health of humans and animals. Pterostilbene (PTE) is a natural plant polyphenolic compound with good anti-inflammatory, antioxidant and cell regeneration effects, yet its effectiveness in treating FB1-induced cytotoxicity remains to be explored. In this study, we used porcine alveolar macrophages (3D4/21) as a model to characterize the cytotoxicity induced by FB1, and to investigate the potential alleviating effect of PTE on FB1-induced cytotoxicity. We demonstrate that FB1 induces cytotoxicity, apoptosis, pro-inflammatory cytokine production and mitochondrial damage, which can be largely recovered by PTE treatment, suggesting the promising application of PTE to treat FB1-induced damage. Mechanistically, FB1 activates the JAK/STAT signaling pathway, while PTE attenuates FB1-induced cytotoxicity through the inhibition of key JAK/STAT genes such asJAK2andSTAT3. Overall, our study characterized the molecular mechanism for FB1-induced cytotoxicity and found PTE to be a promising component which can alleviate FB1-induced cytotoxicity by interfering in the activation of JAK/STAT pathway.Keywords:fumonisin B1;pterostilbene;alveolar macrophage;cytotoxicity;JAK/STAT signaling pathway;pig
研究领域:
毒理学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2025
·
IF 2.8
Yaqi Li,Zhanbing Sun,Yuqi Tong,Chenxi Yan,Lian Huang,Zhaohui Zhang
Beryllium and its compounds are classified as carcinogens, and prolonged exposure can trigger chronic beryllium disease. The Janus kinase–signal transducer and activator of transcription (JAK-STAT) signaling is known to play a critical role in the development and progression of numerous diseases. Leukemia inhibitory factor (LIF), a key upstream cytokine of the JAK-STAT pathway, has been implicated in regulating inflammatory responses and epithelial-mesenchymal transition (EMT) in various diseases. However, the specific involvement of the JAK-STAT pathway and LIF in beryllium sulfate (BeSO₄)–induced EMT in human bronchial epithelial (16HBE) cells remains unclear. To investigate the regulatory mechanisms, we examined the effects of BeSO₄ on 16HBE cells and targeted the JAK-STAT pathway using both pharmacological inhibition (niclosamide) and genetic silencing of LIF. Subsequently, we assessed cell morphology, proliferative capacity, inflammatory protein levels, and EMT marker expression. Our findings demonstrated that BeSO₄ exposure inhibited 16HBE cell proliferation and activated the JAK-STAT pathway. Pretreatment with niclosamide significantly mitigated cellular inflammation and the EMT process induced by BeSO₄. Additionally, silencing LIF markedly reduced JAK-STAT pathway activation and decreased the expression of EMT markers. This study uncovers a novel mechanism underlying BeSO₄-induced EMT in 16HBE cells, providing valuable insights into the molecular mechanisms of toxicity induced by beryllium and its compounds.
研究领域:
毒理学
·
细胞生物学
·
呼吸系统疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2024
·
IF 3.7
Yao Zuo,Hongwen Li,Xiaochao Wang,Yejin Liang,Caihong Huang,Guanye Nai,Jingrong Ruan,Wenzheng Dong,Xiang Lu
Acute myeloid leukemia (AML) is a relatively common malignant hematological disease whose development is mostly associated with abnormal activation of the JAK/STAT3 signaling pathway. Our previous study revealed that SAR317461, a novel JAK2/STAT3 inhibitor, can effectively inhibit the activation of the JAK2/STAT3 signaling pathway and has significant damaging and pro-apoptotic effects on AML cell lines. This project aims to build upon our prior research to enhance the application of SAR317461 in AML. The surface modification of liposomes with the CD34 antibody, along with the inclusion of the SAR317461 and cytarabine (a common AML chemotherapeutic agent), is observed. Due to the high expression of CD34 on the surface of AML cells, the nanoliposome could target AML cells specifically, further achieving an effective treatment for AML through the synergistic effect of JAK2/STAT3 inhibitors and chemotherapeutic agents. The implementation of this project will provide more theoretical support and ideas for the clinical application of JAK/STAT3 inhibitors in malignant tumors and for overcoming chemotherapy resistance.
研究领域:
肿瘤学
·
血液学
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Wenjing Pu,Xuesheng Chu,Shiwen Xu,Xueyan Dai,Li Xiao,Ting Cui,Bingyan Huang,Guoliang Hu,Caiying Zhang
Molybdenum (Mo) is an essential nutrient in living organisms. Although numerous researchers have noticed the health damage caused by excessive Mo, the underlying mechanism of excessive Mo-induced nephrotoxicity remains poorly understood. A gene crosstalk called competitive endogenous RNAs (ceRNAs) can interpret many regulatory mechanisms molecularly. But there are few researches have tried to explain the damage mechanism of excess Mo to organisms through ceRNAs network. To clarify this, the study explored the changes in lncRNAs and miRNAs expression profiles in the kidney of ducks exposed to excess Mo for 16 weeks. The sequencing results showed that Mo exposure caused differential expression of 144 lncRNAs and 14 miRNAs. The occurrence of inflammation through the JAK/STAT axis was observed and the lncRNA-00072124/miR-308/OSMR axis was verified by a double luciferase reporter assay. Overexpression of miR-308 and RNA interference of OSMR reduced Mo-induced inflammatory factors, while miR-308 knockdown showed the opposite effect. Simultaneously, lncRNA-00072124 affected OSMR function as a ceRNA. Taken together, these results concluded that Mo exposure activated the JAK/STAT axis and induced inflammation mediated by the lncRNA-00072124/miR-308/OSMR crosstalk. The results might provide new views for revealing the toxic effects of excess Mo in duck kidneys.
研究领域:
毒理学
·
分子生物学
·
动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2025
·
IF 6.2
Yi Wu,Yilin Ling,Yuqi Yang,Haoxing Long,Linghao Kong,Peiyang Song,Yujie Lu,Wanqiu Zhao,Wei Wang,Jingrong Zhu,Nan Wang
Obesity is a growing global health concern associated with severe metabolic disorders, necessitating the development of safer and more effective therapeutic strategies. Soybean sprout peptides (SSPs), derived from germinated soybeans, are bioactive compounds with potential antiobesity effects. This study aimed to investigate the molecular mechanisms of SSPs through an integrated approach combining network pharmacology, molecular docking, and in vivo experiments. SSP sequences were identified using UPLC-Orbitrap-MS/MS, and their bioactivity was predicted using PeptideRanker. Network pharmacology identified key SSP targets, including AKT1, SRC, STAT3, ESR1, FOS, and NFKB1, which are implicated in the PI3K-Akt and JAK-STAT pathways. Molecular docking validated strong interactions between SSPs and these targets. In vivo, SSP administration significantly reduced body weight gain, abdominal fat accumulation, and serum lipid abnormalities in high-fat-diet-induced obese mice while modulating gut microbiota composition by restoring the Firmicutes-to-Bacteroidetes ratio and reducing pathogenic taxa. Fecal metabolomics revealed that SSP alleviated oxidative stress and improved amino acid metabolism, contributing to its antiobesity effects. These findings suggest that SSP holds promise as a functional food ingredient or nutraceutical for obesity prevention and management.
研究领域:
营养学
·
分子生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Lei Zhao,Siyuan Han,Chengzhi Chai
Ethnopharmacological relevance Huangkui capsule (HKC), a Chinese patent medicine, has been widely used in China as adjuvant therapy for chronic kidney disease (CKD). It displays superior anti-proteinuria efficacy than losartan in patients with CKD at stages 1–2, however, the mechanism of HKC alleviating proteinuria has not been well elucidated. Aim of the study This study aims to confirm the therapeutic effect and investigate associated underlying mechanism of HKC against proteinuria by in vivo and in vitro experiments. Materials and methods We established a doxorubicin (DOX) induced proteinuria mouse model to evaluate kidney function by biochemical markers measurement and to observe histopathological alterations by hematoxylin and eosin (H&E), Masson's trichrome and Periodic Acid-Schiff (PAS)-stained sections of renal, respectively. Moreover, the expressions of Nephrin and Podocin were measured by immunohistochemistry (IHC) and western blotting analysis to investigate podocyte damage. Furthermore, we established Mouse Podocyte Clone-5 (MPC-5) injury model to identify the active components of HKC against podocyte damage by detecting the expressions of Nephrin, Podocin, and ZO-1 proteins. At last, the key protein levels of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway were assessed by western blotting analysis to explore the underlying mechanism of HKC against proteinuria. Results Our results showed that HKC administration for three consecutive weeks dose-dependently ameliorated both renal function and histopathological damages, elevated the expressions of Nephrin and Podocin, the pivotal molecules maintaining filtration function of the podocyte, indicating the promising protective effect against podocyte injury under DOX exposure. Consistently, in vitro experiments showed HKC administration effectively reversed the abnormal expressions of Nephrin and Podocin in MPC-5 cells treated with DOX, suggesting its protective effect against podocyte injury to maintain filtration barrier integrity. In addition, Hibifolin was identified as the most active ingredients in HKC, which suppressed upstream JAK2/STAT3 and PI3K/Akt pathway phosphorylation to maintain the structural and functional integrity of podocyte filtration barrier. Of note, AG490 , a selective JAK2 inhibitor , was used to further affirm the role of Hibifolin involving in regulation JAK2/STAT3. Conclusions Our study suggested that HKC may protect podocytes via JAK2/STAT3 and PI3K/Akt pathway to display its effects of ameliorating proteinuria.
研究领域:
药理学
·
肾病学
·
民族药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
npj Precision Oncology
·
2025
·Vol. 9
·期 1
·1-15
·
IF 8
Huo Ran,Xu Quan-guo,You Yi-qing,Chen Yan-lin,Su Guang-jian,Yang Kun-rong,Xiao Yan-ping,Xue Zhong,Li Yang-jin,Sun Pei,Cui Zhao-lei,Lin Ying-ying,Guo Jun-ying,Xu Hai-yan,Chen Zhao-shuo,Xie Wen-ting,Xu Shao-hua,Chen Min-yong,Wu Jing,He Shi-jie,Xiao Zhen-zhou,Chen Yan
Hepatocellular carcinoma (HCC) is a prevalent and deadly cancer. Gut microbiota affect tumor immunity and immunotherapy efficacy, but the exact mechanisms are unclear. A study compared gut microbiota in HCC patients and healthy controls (HC) using 16S rDNA analysis and metabolomics. It found higher levels of Bifidobacterium and a positive correlation between Bifidobacterium and isobutyric acid in HC group. Animal models showed that the combination of HC fecal matter and αPD-1 treatment reduced tumor volume more effectively than the combination of HCC fecal matter and αPD-1. The combination of Bifidobacterium or isobutyrate with αPD-1 also decreased tumor size. In vitro, isobutyrate-stimulated CD8 + T cells increased IFN-γ secretion, suppressed liver cancer cells, and downregulated the JAK/STAT3 pathway. Combined treatments increased CD8 + T cells and IFN-γ levels and reduced JAK/STAT3 signaling in the tumor microenvironment. This suggests that Bifidobacterium and isobutyrate can inhibit tumor growth, offering insights into gut microbiota-host interactions and potential strategies to overcome HCC immunotherapy resistance.
研究领域:
癌症研究
·
免疫学
·
微生物学
·
分子生物学
·
胃肠病学
·
生物信息学
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Shi Liu,Xinlin Jia,Jina Hao,Dapeng Zhang,Shengchao Yang,Bin Dai,Yuanqing Mao,Yongsheng Li
Cell senescence or apoptosis contributes to self-failure and functional loss in specialized cells, leading to incapacity of the body to repair specific damages. Senescent bone marrow mesenchymal stem cells (BMSCs) lose their proliferative abilities and secrete senescence-associated secretory phenotype (SASP), hindering their participation in bone defect repair. Hence, the effective suppression of cell senescence is crucial to restore the self-repair capacity of body to treat bone defects. Since the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway is associated with SASP secretion, herein, we propose a new strategy to inhibit this pathway to suppress SASP secretion and enhance osteoblast activity based on a novel hierarchically biomimetic nanostructural electrospun scaffold with JAK inhibitors (JAKi, Ruxolitinib) loaded. As validated by in vitro and in vivo experiments, the JAKi loaded scaffold reduces SASP expression effectively and alleviates senescent cell burden, creating a pro-regeneration microenvironment that enhances osteoblast function and mineralization activity as well as rejuvenating the bone repair capacity. These findings offer insights into the regulatory role of cellular senescence in bone aging and provide a new and effective strategy to treat age-related bone defects by delivery of JAKi to locally aging bone defect sites. This article is protected by copyright. All rights reserved
研究领域:
生物材料学
·
组织工程学
·
再生医学
✓ 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）