EUROPEAN JOURNAL OF HISTOCHEMISTRY
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2022
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IF 1.966
Haixia Li,Ning Su,Yaqiao Zhu,Wei Wang,Meihong Cai,Xiaohuan Luo,Wei Xia,Song Quan
Recurrent implantation failure (RIF) is defined as failure to achieve clinical pregnancy after at least 3 transfers of good-quality embryos by natural or artificial means. RIF is often a complex problem with a wide variety of etiologies and mechanisms as well as treatment options. In this study, using immunohistochemistry and Western blot, we demonstrated that the expression of leukemia inhibitory factor (LIF), Janus kinase 1 (JAK1), and signal transducer and activator of transcription 3 (STAT3) was increased, while that of suppressor of cytokine signaling 1 (SOCS1) was decreased in RIF patients. Growth hormone (GH) administration proved to have positive effects on embryo implantation in RIF patients, but the action mechanism of GH has not been elucidated yet. To this aim, we studied the effects of GH on the proliferation in vitro of endometrial adenocarcinoma Ishikawa cells. GH stimulated the expression of LIF and SOCS1, and through SOCS1 inhibits the expression of phosphorylated STAT3, and finally inhibits the occurrence of RIF. Excessive phosphorylation of STAT can lead to decreased endometrial receptivity and abnormal embryo implantation. We also examined the effects of LIF overexpression and an LIF inhibitor (EC330) on the JAK/STAT pathway. LIF promoted cell proliferation, and the up-regulation of LIF increased the expression of SOCS1 and JAK1/STAT3 pathway-related genes in Ishikawa cells. As GH can inhibit the JAK1/STAT3 pathway through LIF, we hypothesize that upregulating SOCS1 may be a potential approach to treat RIF at the molecular level. GH can inhibit the JAK1/STAT3 pathway through LIF, up-regulating SOCS1 to treat RIF at the molecular level.
研究领域:
生殖生物学
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分子生物学
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内分泌学
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PubMed
高影响因子
Biomaterials Science
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2022
·Vol. 11
·期 1
·263-277
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IF 7.59
Zexuan Yu,Mengtong Wu,Yingshuang Huang,Yishu Wang,Yijun Chen,Qiulin Long,Ziming Lin,Lingjing Xue,Caoyun Ju,Can Zhang
Dendritic cells (DCs) that can prime antitumor responses show great potential in tumor immunotherapy, whereas the unsatisfactory effect which can be ascribed in part to the high expression of inhibitory cytokines, such as the suppressor of cytokine signaling 1 (SOCS1), restricts their application. Thus, silencing these genes in DCs is essential for DC-based therapy. However, safe and effective delivery of siRNA to DCs still faces challenges. Herein, we designed single-component lipid nanoparticles comprising a solely cationic lipid (OA2) for introducing siRNA into mouse DCs in order to inhibit the immunosuppressive gene and boost the effector responses of DC-based therapy. Compared to other multi-component lipid nanoparticles, single-component lipid nanoparticles are theoretically easy-to-control and detective, which is beneficial for future translation. We showed that the application of OA2 lipid nanoparticles significantly downregulated the expression of SOCS1 in DCs over 50%, compared with the commercial lipofectine2000. Besides, the treatment of OA2 lipid nanoparticles had no influence on the antigen capture of DCs. Thus, we fabricated a SOCS1-downregulated DC vaccine pulsed with Ova antigen and demonstrated that the antigen presentation and pro-inflammatory factor secretion ability of DCs were improved due to the SOCS1 downregulation, leading to an ameliorated immunosuppressive tumor microenvironment and finally exhibiting potent tumor prevention and suppression in B16-Ova tumor-bearing mice. Single-component lipid nanoparticles, which provide an available vector platform for siRNA delivery to primary DCs, appear to be a potent tool to engineer DCs and in turn boost DC-based tumor immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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分子生物学
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免疫治疗
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PubMed
高影响因子
EXPERIMENTAL DERMATOLOGY
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2019
·Vol. 28
·期 11
·1227-1236
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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
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分子生物学
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光动力疗法
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Si-yu Liu,Chang-qing Wang,Tong-tong Luo,Gui-juan Cui,Yuan Zhang,Xing-ju Zou,Zi-jian Zhang,Wen-xiu Liu,Chen Sun,Cheng Peng
Ethnopharmacological relevance Scutellaria baicalensis , a traditional Chinese medicine herb, has been classically used to treat diarrhea and dysentery caused by damp heat in Traditional Chinese Medicine. And it has been demonstrated to alleviate colonic mucosal inflammation in ulcerative colitis. However, the mechanism through which its main active ingredient, baicalin, alleviates ulcerative colitis remains unclear. Aim of the study This study investigated whether baicalin regulates macrophages to ameliorate ulcerative colitis through the JAK1/STAT1/SOCS1 pathway. Materials and methods LPS-induced RAW264.7 cells were used to investigate the anti-inflammatory and regulatory effects of baicalin on macrophage polarization. The NO content was assessed by a Griess assay, and label-free optical diffraction tomography for live-cell imaging and confocal imaging were conducted to observe macrophage polarization and analyze the expression of CD86 and CD206. The protective effect of baicalin on DSS-induced colitis mice was evaluated through the Disease Activity Index (DAI) system, endoscopy, enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) staining, Alcian Blue periodic acid Schiff (AB-PAS) staining, and immunofluorescence. Macrophages in the lamina propria of the colon were analyzed by tiling light sheet microscopy imaging and flow cytometry. Western blotting (WB) was used to evaluate the expression of JAK1/STAT1/SOCS1 pathway members, and the expression of the downstream transcription factors were quantified through qPCR. Key results Baicalin markedly inhibited NO levels induced by LPS and delayed the timing and quantity of macrophage polarization toward the M1 phenotype. Furthermore, baicalin ameliorated the symptoms of colitis in mice, such as diarrhea, hematochezia, weight loss, colon shortening, decreased spleen weight, pathological changes, intestinal mucosal barrier dysfunction, and decreased DAI and inflammatory factor levels. Moreover, baicalin promoted macrophage polarization toward the M2 phenotype and inhibited the polarization of M1 macrophages in the intestinal lamina propria. Mechanistically, baicalin inhibited the phosphorylation of JAK1 and STAT1 and restored the negative feedback inhibition of JAK1/STAT1 by upregulating SOCS1. In addition, baicalin reduced the mRNA levels of downstream genes. Conclusions and implications Baicalin can alleviate intestinal inflammation, ameliorate intestinal barrier damage, and regulate macrophage polarization by inhibiting M1 macrophage polarization in an ulcerative colitis model. This protective effect was achieved through the JAK1/STAT1/SOCS1 pathway.
研究领域:
药理学
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免疫学
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民族药理学
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分子生物学
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胃肠病学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
·
IF 5.6
Siyu Liu,Guijuan Cui,Tongtong Luo,Yang Zhang,Yihan Yuan,Fu Peng,Chen Sun,Cheng Peng
Ulcerative colitis (UC) is a chronic idiopathic intestinal inflammatory disease, and its onset is closely related to immune disorders and intestinal barrier defects. Paeoniflorin (PF) is a natural component with anti-inflammatory and immunomodulatory activities. This study aims to explore whether PF can alleviate UC by regulating macrophage polarization and protecting intestinal barrier homeostasis. The results demonstrated that PF significantly improved colitis in mice induced by DSS, manifested as a reduction in disease activity index score, alleviation of colonic edema, restoration of colonic length, inhibition of spleen enlargement, maintenance of intestinal tissue structure integrity, and protection of intestinal barrier function. In vitro, PF not only inhibited apoptosis following DSS-induced injury, but also upregulated the expression of tight junction protein ZO-1, mucin MUC2, and epithelial adhesion molecule E-cadherin. Moreover, PF could inhibit the polarization of RAW264.7 macrophages to the M1 phenotype and promote their transformation to the M2. Mechanism studies further revealed that PF could inhibit JAK1/STAT1 phosphorylation and upregulate SOCS1 protein expression. In conclusion, this study suggests that PF may exert therapeutic effects on UC by regulating macrophage polarization and enhancing intestinal barrier function through modulation of the JAK1/STAT1/SOCS1 pathway.
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PubMed
高影响因子
APOPTOSIS
·
2025
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IF 8.1
Huang Xiangyang,Liu Yi,Fu Hangling,Rong Xia,Zhao Yiheng
Systemic sclerosis (SSc) is a life-threatening autoimmune disease characterized by progressive skin and organ fibrosis. Although interferon signaling is dysregulated in SSc, the role of interferon-induced proteins like IFIT3 in the skin fibrosis of SSC remains unclear. Here, we demonstrate that IFIT3 expression is significantly elevated ( p < 0.01) in SSc fibroblasts and promotes fibrosis via SOCS1-dependent activation of the EGFR/VEGF axis. Silencing IFIT3 upregulated SOCS1 ( p < 0.05), suppressed EGFR/VEGF ( p < 0.01), and inhibited fibroblast proliferation/migration ( p < 0.01). In a bleomycin-induced SSc model, IFIT3 knockdown ameliorated skin/lung collagen deposition and fibrosis ( p < 0.05). Our findings reveal a novel mechanism whereby IFIT3 regulates EGFR and VEGF through down-regulating SOCS1 in SSc fibrosis, identifying IFIT3 as a novel therapeutic target for SSc.
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PubMed
高影响因子
PHARMACOLOGY
·
2024
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IF 2.9
Zhong Wenyan,Chen Jingjing,Xu Guangfu,Xiao Li
Introduction: To investigate the effect and mechanism of Kaempferol on alcoholic steatohepatitis. Methods: C57BL/6 N mice were utilized to establish Binge-on-Chronic alcohol exposure mice model. Kaempferol was given as the interventional drug to chronic alcohol-fed mice for six weeks to assess its effects. In vitro, intestinal epithelial Caco-2 cells were stimulated by alcohol, and miRNA-155 mimics were used to further study the effect of kaempferol to miRNA-155 signaling in intestinal epithelial cells. HE staining and oil red O staining were used to observe the liver and intestinal tissue damage in each group of mice, and ALT, AST, IL-1B and TNF-a were detected by kits; LPS expression was detected by ELISA kit, and the expression of IL-1B and TNF-a was assessed by qRT-PCR; activated inflammatory response of liver and colon tissue and the related signalling pathway activation. Results: Kaempferol treatment significantly improved pathological changes such as steatosis and vacuolated lesions in liver tissue of the alcohol diet model group, and reduced serum ALT and AST enzyme activities and liver tissue interleukin-1β and tumour necrosis factor-α mRNA expression levels. Kaempferol significantly reduced the expression of miRNA-155 in the intestinal tissue of alcohol-fed mice, significantly increased their SOCS1 protein expression, inhibited the activation of nuclear factor kappa-B and significantly increased the production of the intestinal tight junction proteins occludin and ZO-1. What's more, kaempferol significantly reduced serum LPS levels in ASH mice. In vitro experiments showed that compared with the control group, kaempferol significantly inhibited the expression level of miRNA-155 in Caco-2 cells under ethanol exposure, decreased the activation of nuclear factor kappa-B, led to an increase in the expression of SOCS1 protein, and increased the production level of occludin protein in Caco-2 cells under the effect of alcohol. In contrast, overexpression of miRNA-155 significantly decreased occludin and SOCS1 protein production and increased nuclear factor kappa-B activation levels in Caco-2 cells, and the administration of kaempferol significantly inhibited this effect. Conclusion: Kaempferol improved the stability of gut barrier function to ameliorate hepatic injury induced by alcohol intake through enhancing occludin protein expression, by targeting miR-155 to inhibit the excessive inflammatory response in the intestine
研究领域:
药理学
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肝病学
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胃肠病学
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分子生物学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 12.5
Siyuan Meng,Fangnan Lv,Jieqing Chen,Linlin Tao,Hao Guo,Danhui Wang,Jie Sun,Jian Li,Ning Liu,Wei Xu,Meirong Huo
A biomimetic antigen outpost is engineered to sustainably co-deliver tumor antigens, siSOCS1, and Mn 2+ adjuvant. • Plasma gel recruits DCs to the injection site, while CRT on nanovaccines acts as an "eat-me" signal to enhance antigen uptake. • SOCS1 silencing and PD-L1 blockade synergistically empower DCs to more effectively prime and activate cytotoxic T lymphocytes (CTLs). • PD-L1 blockade further protects activated CTLs from tumor cell-mediated exhaustion, enabling sustained tumor killing and potent antitumor immunity in TNBC models. Tumor vaccines represent a promising immunotherapy approach but are challenged by rapid systemic clearance, low immunogenicity, and various immunosuppressive mechanisms. To overcome these issues, we created a biomimetic antigen outpost system to enhance vaccine delivery and immune activation. This system uses cationic 1,2-dihydroxybenzene-modified poly- l -lysine to co-load small interfering RNA targeting cytokine-suppressing factor 1 (siSOCS1) and immunoadjuvant (Mn 2+ ) as the core. This core is further coated with calreticulin (CRT)-enriched tumor cell membranes to form a nanovaccine (CRTM/PBM siSOCS1 ), which is ultimately encapsulated in a plasma gel (PG@CRTM/PBM siSOCS1 ). This design prolongs the vaccine's in vivo retention, recruits dendritic cells (DCs) by simulating subcutaneous hemorrhage signals, and enhances effective antigen uptake through CRT-mediated “eat me” signals. Upon DC internalization, the nanovaccine undergoes non-lysosomal trafficking, avoiding siSOCS1 degradation. The efficient SOCS1 silencing alleviates intracellular immunosuppressive feedback and, together with synergistic DC activation by antigens and Mn 2+ , further promotes DC maturation and antigen cross-presentation. In a triple-negative breast cancer model, the combination with anti-PD-L1 antibody simultaneously blocked PD-L1 on both mature DCs and tumor cells, significantly enhancing cytotoxic T lymphocyte function at both the immune priming and effector stages, and demonstrating potent antitumor efficacy. This multi-level intervention strategy provides a promising platform for enhancing cancer immunotherapy. Download: Download high-res image (112KB) Download: Download full-size image
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