Cytokine最新文献_第4页

CCL19/MIP-3β as a key mediator in the production of anti-GPIIb/IIIa antibody-producing B cells in patients with chronic hepatitis C

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-19 DOI: 10.1016/j.cyto.2025.156915

Junki Iida , Haruki Uojima , Takashi Satoh , Masaya Sugiyama , Akira Take , Yoshihiko Sakaguchi , Kazuyoshi Gotoh , Hisashi Hidaka , Shunji Hayashi , Yasuhito Tanaka , Makoto Otsu , Chika Kusano

The roles of specific cytokines and chemokines in modulating the production of anti-GPIIb/IIIa antibody-producing B cells remain poorly understood. We aimed to assess key mediators that influence the number of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells in patients with hepatitis C virus (HCV). This study used a subset of a previously reported cohort in Japan. We first evaluated the number of anti-GPIIb/IIIa antibody-producing B cells using an enzyme-linked immunospot assay in samples from 22 patients who received direct-acting antivirals (DAA)-based therapy and achieved a sustained virological response (SVR). To identify the key mediators, we then analyzed levels of cytokines, chemokines, and inflammation markers in serum samples obtained from the same cohort using Bio-Plex Multiplex Immunoassays. The analysis revealed a significant correlation between the frequency of anti-GPIIb/IIIa antibody-producing B cells and CCL19/macrophage inflammatory protein-3 beta (MIP-3β) (r = 0.590, p = 0.006). After DAA treatment for HCV, both the frequency of these B cells and the levels of CCL19/MIP-3β significantly decreased. Furthermore, the frequency of anti-GPIIb/IIIa antibody-producing B cells and levels of CCL19/MIP-3β were significantly higher in the thrombocytopenia group compared to the non-thrombocytopenia group (p = 0.001 and p = 0.029, respectively). These results suggest that CCL19/MIP-3β may be a key mediator in the production of anti-GPIIb/IIIa antibody-producing B cells in patients with HCV.

{"title":"CCL19/MIP-3β as a key mediator in the production of anti-GPIIb/IIIa antibody-producing B cells in patients with chronic hepatitis C","authors":"Junki Iida , Haruki Uojima , Takashi Satoh , Masaya Sugiyama , Akira Take , Yoshihiko Sakaguchi , Kazuyoshi Gotoh , Hisashi Hidaka , Shunji Hayashi , Yasuhito Tanaka , Makoto Otsu , Chika Kusano","doi":"10.1016/j.cyto.2025.156915","DOIUrl":"10.1016/j.cyto.2025.156915","url":null,"abstract":"<div><div>The roles of specific cytokines and chemokines in modulating the production of anti-GPIIb/IIIa antibody-producing B cells remain poorly understood. We aimed to assess key mediators that influence the number of anti-glycoprotein (GP) IIb/IIIa antibody-producing B cells in patients with hepatitis C virus (HCV). This study used a subset of a previously reported cohort in Japan. We first evaluated the number of anti-GPIIb/IIIa antibody-producing B cells using an enzyme-linked immunospot assay in samples from 22 patients who received direct-acting antivirals (DAA)-based therapy and achieved a sustained virological response (SVR). To identify the key mediators, we then analyzed levels of cytokines, chemokines, and inflammation markers in serum samples obtained from the same cohort using Bio-Plex Multiplex Immunoassays. The analysis revealed a significant correlation between the frequency of anti-GPIIb/IIIa antibody-producing B cells and CCL19/macrophage inflammatory protein-3 beta (MIP-3β) (<em>r</em> = 0.590, <em>p</em> = 0.006). After DAA treatment for HCV, both the frequency of these B cells and the levels of CCL19/MIP-3β significantly decreased. Furthermore, the frequency of anti-GPIIb/IIIa antibody-producing B cells and levels of CCL19/MIP-3β were significantly higher in the thrombocytopenia group compared to the non-thrombocytopenia group (<em>p</em> = 0.001 and <em>p</em> = 0.029, respectively). These results suggest that CCL19/MIP-3β may be a key mediator in the production of anti-GPIIb/IIIa antibody-producing B cells in patients with HCV.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156915"},"PeriodicalIF":3.7,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143644628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Gastric mucosal CD8+TRM cells are recruited through CXCR5-CXCL13 axis in Helicobacter pylori infected subjects

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-14 DOI: 10.1016/j.cyto.2025.156904

Tingting Xia , Zelin Zhang , Jia Xie, Hanmei Yuan, Yayi Ren, Yue Xu, Jie Ning, Bin Li, Chao Wu

Gastric mucosal CD8⁺ tissue-resident memory T (CD8⁺T_RM) cells are increased in Helicobacter pylori (H. pylori) infected subjects, but the characteristics and chemotactic mechanism of CD8⁺T_RM cells remain unknown. We demonstrated that C-X-C chemokine receptor 5 (CXCR5) was upregulated on gastric mucosal CD8⁺T_RM cells, and gastric CXCL13 was dominantly secreted by dendritic cells and macrophages in H. pylori infected subjects. Gastric mucosal CD8⁺T_RM cells from CagA+ H. pylori infected subjects was increased and could secrete more IFN-γ and TNF-α to engage in local immune response. The number of gastric mucosal CD8⁺T_RM cells and the expression of CXCL13 was elevated in H. pylori infected individuals with the development of gastric diseases. In conclusion, gastric mucosal CD8⁺T_RM cells are increased from CagA+ H. pylori infected subjects and could be recruited through CXCL13-CXCR5 axis, which mainly release IFN-γ and TNF-α in H. pylori related immune response.

{"title":"Gastric mucosal CD8+TRM cells are recruited through CXCR5-CXCL13 axis in Helicobacter pylori infected subjects","authors":"Tingting Xia , Zelin Zhang , Jia Xie, Hanmei Yuan, Yayi Ren, Yue Xu, Jie Ning, Bin Li, Chao Wu","doi":"10.1016/j.cyto.2025.156904","DOIUrl":"10.1016/j.cyto.2025.156904","url":null,"abstract":"<div><div>Gastric mucosal CD8<sup>+</sup> tissue-resident memory T (CD8<sup>+</sup>T<sub>RM</sub>) cells are increased in <em>Helicobacter pylori</em> (<em>H. pylori</em>) infected subjects, but the characteristics and chemotactic mechanism of CD8<sup>+</sup>T<sub>RM</sub> cells remain unknown. We demonstrated that C-X-C chemokine receptor 5 (CXCR5) was upregulated on gastric mucosal CD8<sup>+</sup>T<sub>RM</sub> cells, and gastric CXCL13 was dominantly secreted by dendritic cells and macrophages in <em>H. pylori</em> infected subjects. Gastric mucosal CD8<sup>+</sup>T<sub>RM</sub> cells from CagA+ <em>H. pylori</em> infected subjects was increased and could secrete more IFN-γ and TNF-α to engage in local immune response. The number of gastric mucosal CD8<sup>+</sup>T<sub>RM</sub> cells and the expression of CXCL13 was elevated in <em>H. pylori</em> infected individuals with the development of gastric diseases. In conclusion, gastric mucosal CD8<sup>+</sup>T<sub>RM</sub> cells are increased from CagA+ <em>H. pylori</em> infected subjects and could be recruited through CXCL13-CXCR5 axis, which mainly release IFN-γ and TNF-α in <em>H. pylori</em> related immune response.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156904"},"PeriodicalIF":3.7,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143620152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Soluble tumour necrosis factor receptor 1 predicts hospitalization in children and young adults with dengue virus infection in the Philippines

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-12 DOI: 10.1016/j.cyto.2025.156911

Vanesse Li , Hridesh Mishra , Michelle Ngai , Valerie M. Crowley , Vanessa Tran , Maria Salome Siose Painaga , James Yared Gaite , Patrick Hamilton , Andrea L. Conroy , Kevin C. Kain , Michael T. Hawkes

Background

Dengue fever is a common cause of acute febrile illness in the tropics and requires hospitalization for intravenous (IV) fluid therapy in a minority of patients. Predicting which patients will progress to severe disease is challenging. Soluble tumour necrosis factor receptor 1 (sTNFR1) is associated with severe dengue and may have prognostic value.

Methods

Prospective cohort study of outpatients in the Philippines with dengue fever, confirmed by NS1 antigenemia or IgM seropositivity. sTNFR1 was measured at presentation and patients were followed for 14–21 days for hospitalization (primary outcome), duration of stay, IV fluid resuscitation, hemoconcentration, and thrombocytopenia (secondary outcomes).

Results

244 patients (median age 9 years, 40 % female, 26 % uncomplicated dengue, 73 % dengue with warning signs, 0.82 % severe dengue) were included. The median sTNFR1 plasma concentration was 3000pg/mL (IQR 2400–3700) at clinic presentation, decreasing to 1800 (IQR 1600–2100) after recovery. 181 patients (74 %) required hospitalization. Plasma sTNFR1 concentration > 2800 pg/mL, measured at clinic presentation, was associated with subsequent hospitalization (relative risk 1.5, 95 %CI 1.2–1.7, p < 0.0001). Elevated sTNFR1 was also associated with longer duration of stay, IV fluid requirement, hemoconcentration, and thrombocytopenia. sTNFR1 was also associated with a marker of systemic inflammation (procalcitonin), and circulating markers of endothelial activation (Ang2, sTie-2, sVCAM-1, and endoglin).

Conclusion

Elevated sTNFR1 is predictive of subsequent hospitalization among outpatients with DENV infection. It shows promise as a marker that could guide triage to reduce the large healthcare burden of dengue in resource-constrained settings.

{"title":"Soluble tumour necrosis factor receptor 1 predicts hospitalization in children and young adults with dengue virus infection in the Philippines","authors":"Vanesse Li , Hridesh Mishra , Michelle Ngai , Valerie M. Crowley , Vanessa Tran , Maria Salome Siose Painaga , James Yared Gaite , Patrick Hamilton , Andrea L. Conroy , Kevin C. Kain , Michael T. Hawkes","doi":"10.1016/j.cyto.2025.156911","DOIUrl":"10.1016/j.cyto.2025.156911","url":null,"abstract":"<div><h3>Background</h3><div>Dengue fever is a common cause of acute febrile illness in the tropics and requires hospitalization for intravenous (IV) fluid therapy in a minority of patients. Predicting which patients will progress to severe disease is challenging. Soluble tumour necrosis factor receptor 1 (sTNFR1) is associated with severe dengue and may have prognostic value.</div></div><div><h3>Methods</h3><div>Prospective cohort study of outpatients in the Philippines with dengue fever, confirmed by NS1 antigenemia or IgM seropositivity. sTNFR1 was measured at presentation and patients were followed for 14–21 days for hospitalization (primary outcome), duration of stay, IV fluid resuscitation, hemoconcentration, and thrombocytopenia (secondary outcomes).</div></div><div><h3>Results</h3><div>244 patients (median age 9 years, 40 % female, 26 % uncomplicated dengue, 73 % dengue with warning signs, 0.82 % severe dengue) were included. The median sTNFR1 plasma concentration was 3000pg/mL (IQR 2400–3700) at clinic presentation, decreasing to 1800 (IQR 1600–2100) after recovery. 181 patients (74 %) required hospitalization. Plasma sTNFR1 concentration > 2800 pg/mL, measured at clinic presentation, was associated with subsequent hospitalization (relative risk 1.5, 95 %CI 1.2–1.7, <em>p</em> < 0.0001). Elevated sTNFR1 was also associated with longer duration of stay, IV fluid requirement, hemoconcentration, and thrombocytopenia. sTNFR1 was also associated with a marker of systemic inflammation (procalcitonin), and circulating markers of endothelial activation (Ang2, sTie-2, sVCAM-1, and endoglin).</div></div><div><h3>Conclusion</h3><div>Elevated sTNFR1 is predictive of subsequent hospitalization among outpatients with DENV infection. It shows promise as a marker that could guide triage to reduce the large healthcare burden of dengue in resource-constrained settings.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156911"},"PeriodicalIF":3.7,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143600769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exosome-mediated communication between T cells and dendritic cells: Implications for therapeutic strategies

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-11 DOI: 10.1016/j.cyto.2025.156914

Tahereh Kashkoulinejad Kouhi

Cell communication is crucial for coordinating physiological functions in multicellular organisms, with exosomes playing a significant role. Exosomes mediate intercellular communication by transporting proteins, lipids, and nucleic acids between cells. These small, membrane-bound vesicles, derived from the endosomal pathway, are integral to various biological processes, including signal transmission and cellular behavior modulation. Recent advances highlight the potential of exosomes, especially dendritic cell-derived exosomes (DEXs), for diagnostic and therapeutic applications, particularly in cancer immunotherapy. DEXs are distinguished by their ability to present antigens and stimulate immune responses more effectively than exosomes from other cell types. They carry a cargo rich in immunostimulatory molecules and MHC-peptide complexes, which facilitate robust T-cell activation and enhance tumor-specific immune responses. The unique properties of DEXs, such as their ability to cross biological barriers and resist tumor-induced immunosuppression, position them as promising candidates for therapeutic applications. Here, I review the reports on the bidirectional interaction between dendritic cells and T cells through exosomes and their role in medicine.

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引用次数: 0

Fluoxetine mitigates hypothermia and inflammatory responses in lipopolysaccharide-induced systemic inflammation: Insights into serotonergic and hypothalamic thermoregulatory mechanisms

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-08 DOI: 10.1016/j.cyto.2025.156909

Isis P. Trajano , Luis Henrique Angenendt Costa , Patrícia Passaglia , Wanderson S. Santos , Jonathas Rodrigo dos Santos , Luciane Carla Alberici , Luiz G.S. Branco

An abnormally elevated mortality rate is evident in cases of sepsis. To study specific mechanisms of sepsis experimentally, lipopolysaccharide (LPS) systemically administered has been used as a model, in which an exaggerated immune response, neurochemistry settings, and fever following hypothermia take place. Notably, systemic inflammation (SI) can modulate the central serotonergic pathways and being influenced by it. This influence extends to the hypothalamus, which holds a hierarchical significance in the control of body temperature (Tb). This study investigates the potential impact of orally administered fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) given orally for 7 days before on LPS-induced SI (1.5 mg/kg, i.v.) in rats. The assessment involved monitoring Tb, heat loss index (HLI), along non-shivering thermogenesis assessed by oxygen consumption. Cytokine levels in the spleen and blood, along with nitric oxide (NO), and prostaglandins (PGs) E₂ and D_2, levels were also measured. The findings reveal increased plasma NO, cytokines in plasma and spleen, and hypothalamus PGE₂ levels during SI. Interestingly, FLX mitigated LPS-induced hypothermia, accompanied by a reduction in plasma and splenic NO, interleukins (IL) 6, and 10. Additionally, the results align with the hypothesis that hypothermia, blunted by FLX, develops in fact in a regulated form, as an adaptive strategy.

{"title":"Fluoxetine mitigates hypothermia and inflammatory responses in lipopolysaccharide-induced systemic inflammation: Insights into serotonergic and hypothalamic thermoregulatory mechanisms","authors":"Isis P. Trajano , Luis Henrique Angenendt Costa , Patrícia Passaglia , Wanderson S. Santos , Jonathas Rodrigo dos Santos , Luciane Carla Alberici , Luiz G.S. Branco","doi":"10.1016/j.cyto.2025.156909","DOIUrl":"10.1016/j.cyto.2025.156909","url":null,"abstract":"<div><div>An abnormally elevated mortality rate is evident in cases of sepsis. To study specific mechanisms of sepsis experimentally, lipopolysaccharide (LPS) systemically administered has been used as a model, in which an exaggerated immune response, neurochemistry settings, and fever following hypothermia take place. Notably, systemic inflammation (SI) can modulate the central serotonergic pathways and being influenced by it. This influence extends to the hypothalamus, which holds a hierarchical significance in the control of body temperature (Tb). This study investigates the potential impact of orally administered fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) given orally for 7 days before on LPS-induced SI (1.5 mg/kg, i.v.) in rats. The assessment involved monitoring Tb, heat loss index (HLI), along non-shivering thermogenesis assessed by oxygen consumption. Cytokine levels in the spleen and blood, along with nitric oxide (NO), and prostaglandins (PGs) E<sub>2</sub> and D<sub>2,</sub> levels were also measured. The findings reveal increased plasma NO, cytokines in plasma and spleen, and hypothalamus PGE<sub>2</sub> levels during SI. Interestingly, FLX mitigated LPS-induced hypothermia, accompanied by a reduction in plasma and splenic NO, interleukins (IL) 6, and 10. Additionally, the results align with the hypothesis that hypothermia, blunted by FLX, develops in fact in a regulated form, as an adaptive strategy.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156909"},"PeriodicalIF":3.7,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Association between serum levels of inflammatory mediators and periodontitis severity in people with down syndrome

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-06 DOI: 10.1016/j.cyto.2025.156910

Katia M.M. Veloso , Monique M.M. Mouchrek , Joana A.B. de Sousa , Cecília C.C. Ribeiro , Vandilson P. Rodrigues , Bruno B. Benatti

Evidence suggests that individuals with Down syndrome (DS) have a high prevalence of periodontal disease (PD). Factors such as muscular hypotonia, macroglossia, intellectual deficits, and reduced motor coordination, often combined with inadequate dietary habits, contribute to the development of PD. Additionally, a compromised immune response may explain the altered inflammatory profile that affects the systemic and oral health of this population. This study aimed to analyze the relationship between serum levels of inflammatory cytokines (IFN-γ, IL-10, IL-17, IL-1β, IL-4, and TNF-α) and the severity of periodontitis in individuals with DS. We conducted a case-control study involving individuals with DS (n = 43) and non-syndromic individuals (n = 20). All participants underwent a clinical periodontal examination that included measurements of probing pocket depth (PPD), clinical attachment level (CAL), gingival bleeding index (GBI), and visible plaque index (VPI). Participants were classified into stages of periodontitis: stage 1 and stages 2–4, forming two subgroups within both the case and control groups. Serum levels of IFN-γ, IL-10, IL-17, IL-1β, IL-4, and TNF-α were compared between subgroups and analyzed as continuous variables for independent samples. We compared the four subgroups while considering the stage of periodontitis and the presence of DS. The relationship between DS and the stages 2–4 periodontitis with inflammatory marker levels was analyzed using linear regression models, adjusted for age and sex. The results showed no association between periodontitis severity and serum cytokine levels in any of the subgroups (P > 0.05). However, DS was associated with reduced serum levels of IFN-γ and increased serum levels of IL-10, IL-1β, IL-4, and TNF-α (P < 0.05). These findings suggest that individuals with DS have increased serum levels of inflammatory cytokines compared to non-syndromic individuals, regardless of the severity of periodontitis.

{"title":"Association between serum levels of inflammatory mediators and periodontitis severity in people with down syndrome","authors":"Katia M.M. Veloso , Monique M.M. Mouchrek , Joana A.B. de Sousa , Cecília C.C. Ribeiro , Vandilson P. Rodrigues , Bruno B. Benatti","doi":"10.1016/j.cyto.2025.156910","DOIUrl":"10.1016/j.cyto.2025.156910","url":null,"abstract":"<div><div>Evidence suggests that individuals with Down syndrome (DS) have a high prevalence of periodontal disease (PD). Factors such as muscular hypotonia, macroglossia, intellectual deficits, and reduced motor coordination, often combined with inadequate dietary habits, contribute to the development of PD. Additionally, a compromised immune response may explain the altered inflammatory profile that affects the systemic and oral health of this population. This study aimed to analyze the relationship between serum levels of inflammatory cytokines (IFN-γ, IL-10, IL-17, IL-1β, IL-4, and TNF-α) and the severity of periodontitis in individuals with DS. We conducted a case-control study involving individuals with DS (<em>n</em> = 43) and non-syndromic individuals (<em>n</em> = 20). All participants underwent a clinical periodontal examination that included measurements of probing pocket depth (PPD), clinical attachment level (CAL), gingival bleeding index (GBI), and visible plaque index (VPI). Participants were classified into stages of periodontitis: stage 1 and stages 2–4, forming two subgroups within both the case and control groups. Serum levels of IFN-γ, IL-10, IL-17, IL-1β, IL-4, and TNF-α were compared between subgroups and analyzed as continuous variables for independent samples. We compared the four subgroups while considering the stage of periodontitis and the presence of DS. The relationship between DS and the stages 2–4 periodontitis with inflammatory marker levels was analyzed using linear regression models, adjusted for age and sex. The results showed no association between periodontitis severity and serum cytokine levels in any of the subgroups (<em>P</em> > 0.05). However, DS was associated with reduced serum levels of IFN-γ and increased serum levels of IL-10, IL-1β, IL-4, and TNF-α (<em>P</em> < 0.05). These findings suggest that individuals with DS have increased serum levels of inflammatory cytokines compared to non-syndromic individuals, regardless of the severity of periodontitis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156910"},"PeriodicalIF":3.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of VEGF in Cancer angiogenesis and tumorigenesis: Insights for anti-VEGF therapy

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-05 DOI: 10.1016/j.cyto.2025.156908

Zijun Shi , Mengmeng Kuai , Baohua Li , Carlos Frimpong Akowuah , Zhenyu Wang , Ye Pan , Min Tang , Xiaoyue Yang , Peng Lü

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis, playing a pivotal role in both physiological and pathological processes. It promotes the formation of new blood vessels and activates downstream signaling pathways that regulate endothelial cell function. This review highlights recent advancements in the understanding of VEGF's molecular structure and its isoforms, as well as their implications in disease progression. It also explores the mechanisms of VEGF inhibitors. While VEGF inhibitors show promise in the treatment of cancer and other diseases, their clinical use faces significant challenges, including drug resistance, side effects, and complex interactions with other signaling pathways. To address these challenges, future research should focus on: (i) enhancing the understanding of VEGF subtypes and their distinct roles in various diseases, supporting the development of personalized treatment strategies; (ii) developing combination therapies that integrate VEGF inhibitors with other targeted treatments to overcome resistance and improve efficacy; (iii) optimizing drug delivery systems to reduce off-target effects and enhance therapeutic outcomes. These approaches aim to improve the effectiveness and safety of VEGF-targeted therapies, offering new possibilities for the treatment of VEGF-related diseases.

{"title":"The role of VEGF in Cancer angiogenesis and tumorigenesis: Insights for anti-VEGF therapy","authors":"Zijun Shi , Mengmeng Kuai , Baohua Li , Carlos Frimpong Akowuah , Zhenyu Wang , Ye Pan , Min Tang , Xiaoyue Yang , Peng Lü","doi":"10.1016/j.cyto.2025.156908","DOIUrl":"10.1016/j.cyto.2025.156908","url":null,"abstract":"<div><div>Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis, playing a pivotal role in both physiological and pathological processes. It promotes the formation of new blood vessels and activates downstream signaling pathways that regulate endothelial cell function. This review highlights recent advancements in the understanding of VEGF's molecular structure and its isoforms, as well as their implications in disease progression. It also explores the mechanisms of VEGF inhibitors. While VEGF inhibitors show promise in the treatment of cancer and other diseases, their clinical use faces significant challenges, including drug resistance, side effects, and complex interactions with other signaling pathways. To address these challenges, future research should focus on: (i) enhancing the understanding of VEGF subtypes and their distinct roles in various diseases, supporting the development of personalized treatment strategies; (ii) developing combination therapies that integrate VEGF inhibitors with other targeted treatments to overcome resistance and improve efficacy; (iii) optimizing drug delivery systems to reduce off-target effects and enhance therapeutic outcomes. These approaches aim to improve the effectiveness and safety of VEGF-targeted therapies, offering new possibilities for the treatment of VEGF-related diseases.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156908"},"PeriodicalIF":3.7,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The restoration of immunity characterized by the recovery of myeloid dendritic cells represent a favorable response to methylprednisolone therapy for HBV-ACLF patients: A prospective cohort study

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-03-04 DOI: 10.1016/j.cyto.2025.156894

Lin Jia , Wei-Ping He , Hui-Chun Xing , Juan Li , Hong-Wei Yu , Wei Hou , Ran Xue , Juan Zhao , Qing-Hua Meng

Background

The use of methylprednisolone (MP) is still controversial for hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). We aimed to explore the change in dendritic cells (DCs) during MP treatment in HBV-ACLF to guide the use of MP to improve patient's prognosis.

Methods

Patients with HBV-ACLF were prospectively allocated to groups given methylprednisolone intravenously (1.5 mg/kg/day for the first 3 days, 1 mg/kg/day for the second 2 days, and 0.5 mg/kg/day for the last 2 days, MP group, n = 36) plus standard treatment or standard treatment only (CM group, n = 34). The phenotype [myeloid and plasmacytoid DCs (mDCs, pDCs)] and function of DCs (IL-12 and IFN-α production) were measured at baseline (0d), 3d, 7d, 10d, 14d, 28d, and then monthly until 3 months. Patients' survival was assessed until day 90.

Results

The 3-month survival rate was significantly higher in the MP group than the control (72.0 % vs. 35.5 %，P < 0.01). The phenotype and function of DCs were suppressed in the MP group. The mDCs counts was lower in non-survivors compared to survivors at baseline. Patients with a decline in mDCs counts at the 7th day and a continuous increase in mDCs counts from the 10th day presented a better outcome for patients with MP treatment. Bilirubin was the only relative factor for the restoration of mDCs in the MP group (odds ratio, 0.991; 95 % confidence interval, 0.984–0.999; P = 0.023).

Conclusions

Methylprednisolone could improve the outcome of HBV-ACLF by inhibiting the circulating mDCs counts. And the recovery of mDCs counts after methylprednisolone treatment could represent a favorable response. We can consider monitoring the circulating DCs counts to guide the use of MP in HBV-ACLF in order to improve patient outcomes.

{"title":"The restoration of immunity characterized by the recovery of myeloid dendritic cells represent a favorable response to methylprednisolone therapy for HBV-ACLF patients: A prospective cohort study","authors":"Lin Jia , Wei-Ping He , Hui-Chun Xing , Juan Li , Hong-Wei Yu , Wei Hou , Ran Xue , Juan Zhao , Qing-Hua Meng","doi":"10.1016/j.cyto.2025.156894","DOIUrl":"10.1016/j.cyto.2025.156894","url":null,"abstract":"<div><h3>Background</h3><div>The use of methylprednisolone (MP) is still controversial for hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF). We aimed to explore the change in dendritic cells (DCs) during MP treatment in HBV-ACLF to guide the use of MP to improve patient's prognosis.</div></div><div><h3>Methods</h3><div>Patients with HBV-ACLF were prospectively allocated to groups given methylprednisolone intravenously (1.5 mg/kg/day for the first 3 days, 1 mg/kg/day for the second 2 days, and 0.5 mg/kg/day for the last 2 days, MP group, <em>n</em> = 36) plus standard treatment or standard treatment only (CM group, <em>n</em> = 34). The phenotype [myeloid and plasmacytoid DCs (mDCs, pDCs)] and function of DCs (IL-12 and IFN-α production) were measured at baseline (0d), 3d, 7d, 10d, 14d, 28d, and then monthly until 3 months. Patients' survival was assessed until day 90.</div></div><div><h3>Results</h3><div>The 3-month survival rate was significantly higher in the MP group than the control (72.0 % vs. 35.5 %，<em>P</em> < 0.01). The phenotype and function of DCs were suppressed in the MP group. The mDCs counts was lower in non-survivors compared to survivors at baseline. Patients with a decline in mDCs counts at the 7th day and a continuous increase in mDCs counts from the 10th day presented a better outcome for patients with MP treatment. Bilirubin was the only relative factor for the restoration of mDCs in the MP group (odds ratio, 0.991; 95 % confidence interval, 0.984–0.999; <em>P</em> = 0.023).</div></div><div><h3>Conclusions</h3><div>Methylprednisolone could improve the outcome of HBV-ACLF by inhibiting the circulating mDCs counts. And the recovery of mDCs counts after methylprednisolone treatment could represent a favorable response. We can consider monitoring the circulating DCs counts to guide the use of MP in HBV-ACLF in order to improve patient outcomes.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156894"},"PeriodicalIF":3.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cationic liposomes encapsulating IL-2 selectively induce apoptosis and significantly reduce the secretion of cytokines on M1-murine polarized macrophages

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-02-28 DOI: 10.1016/j.cyto.2025.156903

C.A. Vargas-Ángeles , L. Trujillo-Cirilo , E. Sierra-Mondragón , R. Rangel-Corona , B. Weiss-Steider

Inflammatory diseases pose a global challenge due to the critical role of macrophages in their pathogenesis. This study evaluated the effects of cationic liposomes encapsulating IL-2 (LIP-IL-2) on murine peritoneal macrophages (MP) polarized towards M1 and M2 phenotypes. M1 MP (CD86⁺), which overexpressed IL-2Rα and CD14 receptors, underwent apoptosis following LIP-IL-2 treatment, whereas M2 MP (CD206⁺) were unaffected. Furthermore, LIP-IL-2 significantly reduced the secretion of pro-inflammatory cytokines, including IL-6, TNF-α, IFN-γ, and IL-12, exclusively in M1 macrophages. These findings suggest that LIP-IL-2 could serve as a promising therapeutic tool for chronic inflammatory diseases by selectively inducing apoptosis in pro-inflammatory M1 macrophages without affecting M2 ones, opening avenues for targeted therapies in diseases where chronic macrophage-mediated inflammation is a key factor.

炎症性疾病是一项全球性挑战，因为巨噬细胞在这些疾病的发病机制中起着至关重要的作用。本研究评估了包裹IL-2的阳离子脂质体（LIP-IL-2）对极化为M1和M2表型的小鼠腹腔巨噬细胞（MP）的影响。经 LIP-IL-2 处理后，过度表达 IL-2Rα 和 CD14 受体的 M1 MP（CD86+）会发生凋亡，而 M2 MP（CD206+）则不受影响。此外，LIP-IL-2 还能显著减少促炎细胞因子的分泌，包括 IL-6、TNF-α、IFN-γ 和 IL-12，且仅在 M1 巨噬细胞中存在。这些研究结果表明，LIP-IL-2 可选择性地诱导促炎性 M1 巨噬细胞凋亡，而不影响 M2 巨噬细胞，从而为慢性巨噬细胞介导的炎症是一个关键因素的疾病的靶向治疗开辟了道路，可作为慢性炎症性疾病的一种有前途的治疗工具。

引用次数: 0

SAA1 as a key mediator of immune inflammatory pathways in fungal keratitis through FOXO3a phosphorylation regulation

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2025-02-27 DOI: 10.1016/j.cyto.2025.156898

Yihe Liu , Jing Hong , Rongmei Peng

Objective

Fungal keratitis (FK) is a severe ocular infection, with its underlying molecular mechanisms remaining incompletely understood. This study aimed to identify and investigate key genes involved in immune-inflammatory responses associated with FK pathogenesis using bioinformatics and in vitro assays.

Methods

Transcriptomic data from the Gene Expression Omnibus (GEO) database (GSE58291) were analyzed using the limma package to identify differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to evaluate significant biological processes and pathways related to DEGs. Weighted gene co-expression network analysis (WGCNA) identified gene modules linked with FK-associated DEGs, and Venn diagram analysis highlighted core genes. Receiver operating characteristic (ROC) analysis assessed diagnostic potential. Immune cell composition was analyzed using CIBERSORT, and correlations between key genes and immune cells were evaluated. In vitro, human corneal epithelial cells (HCEC) were stimulated with Aspergillus fumigatus (A.F.), and pro-inflammatory cytokine expression (IL-1β, TNF-α, IL-6) was assessed using enzyme-linked immunosorbent assay (ELISA). Western blot and quantitative real-time polymerase chain reaction (RT-qPCR) analyzed FOXO3a phosphorylation and gene expression changes post-SAA1 siRNA transfection.

Results

A total of 101 DEGs were identified, with WGCNA revealing 6 co-expression network modules, with significant associations noted in yellow and black modules. Nine shared genes were identified in DEGs and modules, with SAA1 strongly linked to FK pathogenesis. SAA1 expression was positively correlated with neutrophils, T cells CD4 memory activated, T cells gamma delta, and activated mast cells. Upon stimulation with A.F., cytokine expression increased, peaking at 24 h. Inhibition of SAA1 reduced FOXO3a phosphorylation and pro-inflammatory cytokine levels, underscoring SAA1's role in FK inflammation via FOXO3a regulation.

Conclusion

SAA1 is a key gene in FK, promoting inflammation by modulating FOXO3a phosphorylation. This highlights its potential as a therapeutic target in managing FK-related inflammation.

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引用次数: 0