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Seasonal variation in the associations between self-reported long-COVID symptoms and IL-6 signalling-related factors (particularly the rs2228145 variant of the IL-6R gene): A clinical study.
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-22 DOI: 10.1016/j.cyto.2025.156884
Katie Rees , Rebecca Aicheler , Lee Butcher , Alan Dodd , John Geen , Ceri Lynch , Isabel Massey , Keith Morris , Brian Tennant , Richard Webb
This observational study focused on the impact of Interleukin-6 (IL-6)-related factors (notably the IL-6 receptor (IL-6R) gene's rs2228145 polymorphism) on long-COVID risk in individuals who had previously experienced COVID-19 infection(s). The purpose of the study was to better understand such factors' contribution to long-COVID risk, and thus possibly initiate future strategies for using IL-6-related factors as biomarkers predictive of risk (while also obtaining data that may influence long-COVID management and treatment more generally).
DNA and blood samples, plus questionnaire responses regarding long-COVID symptoms (including chronic fatigue and cognitive impairment), were collected from 175 participants who had previously experienced COVID-19 infection(s). Potential associations between self-reported long-COVID symptoms and participants' rs2228145 genotypes (determined using TaqMan-based genotyping assays) and/or their circulating IL-6, sIL-6R and sgp130 levels (determined using ELISA) were evaluated.
Univariate-regression analyses demonstrated that odds of exhibiting long-COVID symptoms increased with severity/number of previous COVID-19 infection(s) and with hypertension as a co-morbidity, while vaccination decreased the likelihood of developing long-COVID. While long-COVID sufferers exhibited higher IL-6 signalling activity than healthy control individuals, rs2228145 genotype was not associated with long-COVID odds-ratios in- the entire-study cohort. Following identification of significant seasonal variations within our dataset, the entire-study cohort was stratified depending on when samples/questionnaire responses were obtained. In the resulting ‘summer’ sub-cohort (but not the ‘winter’ sub-cohort), the rs2228145 AA genotype was significantly over-represented amongst those exhibiting long-COVID symptoms, and long-COVID odds-ratios were significantly reduced for the CC and AC genotypes.
While interpretation is complicated by seasonal variations, these findings may be of medical/biomedical value. Importantly, as IL-6 was higher in long-COVID sufferers than healthy controls, and rs2228145 AA genotype-bearing individuals within our ‘summer’ sub-cohort were at elevated risk of developing long-COVID, these findings point towards possible future use of IL-6 and/or rs2228145 genotype as biomarkers predictive of long-COVID risk, which may bring advantages regarding management and treatment of long-COVID.
{"title":"Seasonal variation in the associations between self-reported long-COVID symptoms and IL-6 signalling-related factors (particularly the rs2228145 variant of the IL-6R gene): A clinical study.","authors":"Katie Rees ,&nbsp;Rebecca Aicheler ,&nbsp;Lee Butcher ,&nbsp;Alan Dodd ,&nbsp;John Geen ,&nbsp;Ceri Lynch ,&nbsp;Isabel Massey ,&nbsp;Keith Morris ,&nbsp;Brian Tennant ,&nbsp;Richard Webb","doi":"10.1016/j.cyto.2025.156884","DOIUrl":"10.1016/j.cyto.2025.156884","url":null,"abstract":"<div><div>This observational study focused on the impact of Interleukin-6 (IL-6)-related factors (notably the IL-6 receptor (IL-6R) gene's rs2228145 polymorphism) on long-COVID risk in individuals who had previously experienced COVID-19 infection(s). The purpose of the study was to better understand such factors' contribution to long-COVID risk, and thus possibly initiate future strategies for using IL-6-related factors as biomarkers predictive of risk (while also obtaining data that may influence long-COVID management and treatment more generally).</div><div>DNA and blood samples, plus questionnaire responses regarding long-COVID symptoms (including chronic fatigue and cognitive impairment), were collected from 175 participants who had previously experienced COVID-19 infection(s). Potential associations between self-reported long-COVID symptoms and participants' rs2228145 genotypes (determined using TaqMan-based genotyping assays) and/or their circulating IL-6, sIL-6R and sgp130 levels (determined using ELISA) were evaluated.</div><div>Univariate-regression analyses demonstrated that odds of exhibiting long-COVID symptoms increased with severity/number of previous COVID-19 infection(s) and with hypertension as a co-morbidity, while vaccination decreased the likelihood of developing long-COVID. While long-COVID sufferers exhibited higher IL-6 signalling activity than healthy control individuals, rs2228145 genotype was not associated with long-COVID odds-ratios in- the entire-study cohort. Following identification of significant seasonal variations within our dataset, the entire-study cohort was stratified depending on when samples/questionnaire responses were obtained. In the resulting ‘summer’ sub-cohort (but not the ‘winter’ sub-cohort), the rs2228145 AA genotype was significantly over-represented amongst those exhibiting long-COVID symptoms, and long-COVID odds-ratios were significantly reduced for the CC and AC genotypes.</div><div>While interpretation is complicated by seasonal variations, these findings may be of medical/biomedical value. Importantly, as IL-6 was higher in long-COVID sufferers than healthy controls, and rs2228145 AA genotype-bearing individuals within our ‘summer’ sub-cohort were at elevated risk of developing long-COVID, these findings point towards possible future use of IL-6 and/or rs2228145 genotype as biomarkers predictive of long-COVID risk, which may bring advantages regarding management and treatment of long-COVID.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156884"},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471280","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
Circulating inflammatory cytokines and risk of aortic stenosis: A Mendelian randomization analysis
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-21 DOI: 10.1016/j.cyto.2025.156887
Xiaohan Qiu , Jijun Wu , Zehao Chen , Yu Zhang , Luying Cao , Ning Wang , Junlin Teng , Cong Su , Congyi Cheng , Fen Wang , Wenqiang Chen

Background

Observational studies have consistently reported positive associations between inflammatory biomarkers and the risk of developing aortic stenosis (AS). However, it is crucial to acknowledge that conventional observational studies are prone to various forms of bias, including reverse causation and residual confounding. To delve deeper into unraveling the potential causal relationship between inflammatory biomarkers and aortic stenosis, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis.

Methods

In order to explore the causal effect of exposure to various circulating cytokines on the risk of developing AS, we carefully selected AS datasets as the exposures from the summary statistics of the genome-wide association study (GWAS) conducted by FinnGen. The dataset consisted of a sample size of 3283 for AS cases and 210,463 for controls. To estimate the MR analysis, we primarily adopted the inverse variance weighted (IVW) method. Additionally, we employed complementary methods, including Weighted Median, MR Egger, Weighted Mode, and Simple Mode, to analyze the causal associations comprehensively. In order to assess the presence of heterogeneity, we utilized Cochran's Q statistic and MR-Egger regression. To ensure the robustness and consistency of our findings, we conducted a leave-one-out analysis.

Result

We observed a positive association between interleukin-18 (IL-18) levels and AS (odds ratio [OR] per standard deviation [SD] = 1.080; 95 % confidence interval [CI] 1.024 to 1.139), as well as between interferon-gamma levels (IFN-γ) and AS (OR per SD = 1.157; 95 % CI 1.028 to 1.302). Conversely, we found an inverse association between interleukin-13 (IL-13) levels and AS (OR per SD = 0.942; 95 % CI 0.890 to 0.997), as well as between interleukin-5 (IL-5) levels and AS (OR per SD = 0.892; 95 % CI 0.804 to 0.990).

Conclusion

Our research enhances the current understanding of the role of specific inflammatory biomarker pathways in aortic stenosis. Nevertheless, further validation is required to assess the viability of targeting these cytokines through pharmacological or lifestyle interventions as potential treatments for aortic stenosis.
{"title":"Circulating inflammatory cytokines and risk of aortic stenosis: A Mendelian randomization analysis","authors":"Xiaohan Qiu ,&nbsp;Jijun Wu ,&nbsp;Zehao Chen ,&nbsp;Yu Zhang ,&nbsp;Luying Cao ,&nbsp;Ning Wang ,&nbsp;Junlin Teng ,&nbsp;Cong Su ,&nbsp;Congyi Cheng ,&nbsp;Fen Wang ,&nbsp;Wenqiang Chen","doi":"10.1016/j.cyto.2025.156887","DOIUrl":"10.1016/j.cyto.2025.156887","url":null,"abstract":"<div><h3>Background</h3><div>Observational studies have consistently reported positive associations between inflammatory biomarkers and the risk of developing aortic stenosis (AS). However, it is crucial to acknowledge that conventional observational studies are prone to various forms of bias, including reverse causation and residual confounding. To delve deeper into unraveling the potential causal relationship between inflammatory biomarkers and aortic stenosis, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>In order to explore the causal effect of exposure to various circulating cytokines on the risk of developing AS, we carefully selected AS datasets as the exposures from the summary statistics of the genome-wide association study (GWAS) conducted by FinnGen. The dataset consisted of a sample size of 3283 for AS cases and 210,463 for controls. To estimate the MR analysis, we primarily adopted the inverse variance weighted (IVW) method. Additionally, we employed complementary methods, including Weighted Median, MR Egger, Weighted Mode, and Simple Mode, to analyze the causal associations comprehensively. In order to assess the presence of heterogeneity, we utilized Cochran's Q statistic and MR-Egger regression. To ensure the robustness and consistency of our findings, we conducted a leave-one-out analysis.</div></div><div><h3>Result</h3><div>We observed a positive association between interleukin-18 (IL-18) levels and AS (odds ratio [OR] per standard deviation [SD] = 1.080; 95 % confidence interval [CI] 1.024 to 1.139), as well as between interferon-gamma levels (IFN-γ) and AS (OR per SD = 1.157; 95 % CI 1.028 to 1.302). Conversely, we found an inverse association between interleukin-13 (IL-13) levels and AS (OR per SD = 0.942; 95 % CI 0.890 to 0.997), as well as between interleukin-5 (IL-5) levels and AS (OR per SD = 0.892; 95 % CI 0.804 to 0.990).</div></div><div><h3>Conclusion</h3><div>Our research enhances the current understanding of the role of specific inflammatory biomarker pathways in aortic stenosis. Nevertheless, further validation is required to assess the viability of targeting these cytokines through pharmacological or lifestyle interventions as potential treatments for aortic stenosis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156887"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463816","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
LINC-PINT suppresses the progression of acute myeloid leukemia via miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-19 DOI: 10.1016/j.cyto.2025.156883
Lei Xiang , Xue Lin , Yong Wu

Background

Long noncoding RNA (lncRNA) long intergenic non-protein-coding RNA, p53-induced transcript (LINC-PINT) has shown a crucial role in cancer cells. However, its function in acute myeloid leukemia (AML) is unclear.

Methods

The expression levels of LINC-PINT and miR-767-5p in AML patients were measured through quantitative real-time PCR. The interaction between miR-767-5p and LINC-PINT or suppressor of zeste 12 (SUZ12) was verified by RNA immunoprecipitation (RIP) assay and luciferase reporter assay. SUZ12-mediated JAK/STAT signaling pathway was further confirmed using western blotting and immunoprecipitation. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by CCK-8 and flow cytometry. Tumor formation was examined by a nude mice model in vivo.

Results

The low expression of LINC-PINT was significantly related to ELN risk stratification (p = 0.028). Ectopic expression of LINC-PINT restrained the proliferation and cell cycle G1/S transition and promoted apoptosis in AML cell lines (THP-1 and HL-60). LINC-PINT overexpression curbed tumor growth. LINC-PINT positively regulated SUZ12 by functioning as a sponge of miR-767-5p. There was a negative correlation between miR-767-5p and LINC-PINT in AML (r = −0.3316, p = 0.0336). Co-expression of miR-767-5p reversed the impacts of LINC-PINT on AML cells. MiR-767-5p enhanced the aggressiveness of AML, which was counteracted by overexpression of SUZ12. Additionally, SUZ12 downregulated HDAC1 to reduce STAT3 phosphorylation and acetylation in AML cells.

Conclusions

Overall, LINC-PINT serves as a tumor suppressor in AML through the miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway, presenting a potential therapeutic target for AML.
{"title":"LINC-PINT suppresses the progression of acute myeloid leukemia via miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway","authors":"Lei Xiang ,&nbsp;Xue Lin ,&nbsp;Yong Wu","doi":"10.1016/j.cyto.2025.156883","DOIUrl":"10.1016/j.cyto.2025.156883","url":null,"abstract":"<div><h3>Background</h3><div>Long noncoding RNA (lncRNA) long intergenic non-protein-coding RNA, p53-induced transcript (LINC-PINT) has shown a crucial role in cancer cells. However, its function in acute myeloid leukemia (AML) is unclear.</div></div><div><h3>Methods</h3><div>The expression levels of LINC-PINT and miR-767-5p in AML patients were measured through quantitative real-time PCR. The interaction between miR-767-5p and LINC-PINT or suppressor of zeste 12 (SUZ12) was verified by RNA immunoprecipitation (RIP) assay and luciferase reporter assay. SUZ12-mediated JAK/STAT signaling pathway was further confirmed using western blotting and immunoprecipitation. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by CCK-8 and flow cytometry. Tumor formation was examined by a nude mice model in vivo.</div></div><div><h3>Results</h3><div>The low expression of LINC-PINT was significantly related to ELN risk stratification (<em>p</em> = 0.028). Ectopic expression of LINC-PINT restrained the proliferation and cell cycle G1/S transition and promoted apoptosis in AML cell lines (THP-1 and HL-60). LINC-PINT overexpression curbed tumor growth. LINC-PINT positively regulated SUZ12 by functioning as a sponge of miR-767-5p. There was a negative correlation between miR-767-5p and LINC-PINT in AML (<em>r</em> = −0.3316, <em>p</em> = 0.0336). Co-expression of miR-767-5p reversed the impacts of LINC-PINT on AML cells. MiR-767-5p enhanced the aggressiveness of AML, which was counteracted by overexpression of SUZ12. Additionally, SUZ12 downregulated HDAC1 to reduce STAT3 phosphorylation and acetylation in AML cells.</div></div><div><h3>Conclusions</h3><div>Overall, LINC-PINT serves as a tumor suppressor in AML through the miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway, presenting a potential therapeutic target for AML.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156883"},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445419","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
Investigation of TNF and related lncRNAs in diabetic nephropathy
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-18 DOI: 10.1016/j.cyto.2025.156892
Seyed Mohsen Aghaei-Zarch , Leila Mahmoudieh , Mohammad Miryounesi , Maryam Aghazadeh , Mehran Reihani-Ardabili , Marzieh Zamani , Marzieh Motallebi , Abolfazl Movafagh

Background

Diabetic nephropathy (DN) is a significant driver of end-stage renal disease, requiring kidney replacement therapies such as transplantation and dialysis. Given the critical importance of understanding the onset and progression of DN, we sought to explore the expression levels of tumor necrosis factor (TNF) and related long noncoding RNAs (lncRNAs) in diabetic patients with and without DN, as well as in pre-diabetic individuals, compared to healthy controls. We further explored the involvement of TNF and TNF-related lncRNAs in high glucose (HG)-induced apoptosis of human embryonic kidney (HEK)-293 cells.

Material and method

In the current cross-sectional investigation, we compare the expression levels of lncRNA myocardial infarction-associated transcript (MIAT), lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and TNF in 50 healthy individuals, 50 people with prediabetes, 50 patients with type 2 diabetes mellitus (T2DM), and 50 patients with T2DM- DN. We cultured HEK293 cells in a HG condition (100 mM glucose) to establish a cellular model of DN, while HEK293 cells cultured in a normal-glucose environment (5 mM glucose) served as controls. We further assess apoptosis in HEK293 cells via flow cytometry analysis. Moreover, we evaluated the expression levels of lncRNA MIAT, lncRNA NEAT1, and TNF in HG and normal-glucose (NG) groups to investigate their potential involvement in HEK293 cell apoptosis and the pathogenesis of DN.

Result

Our findings reveal a significant upregulation of lncRNA MIAT, lncRNA NEAT1, and TNF in T2DM and T2DM-associated DN groups compared to prediabetic individuals and healthy controls (p < 0.05). Furthermore, HG conditions significantly increased the apoptotic rate of HEK293 cells. Additionally, the expression levels of TNF, lncRNA MIAT, and lncRNA NEAT1 were increased in HEK-293 cells cultured in a HG.

Conclusion

In conclusion, our findings indicate a significant role for the TNF gene and associated lncRNAs, such as lncRNA MIAT and lncRNA NEAT1, in podocyte apoptosis and the development of DN.
{"title":"Investigation of TNF and related lncRNAs in diabetic nephropathy","authors":"Seyed Mohsen Aghaei-Zarch ,&nbsp;Leila Mahmoudieh ,&nbsp;Mohammad Miryounesi ,&nbsp;Maryam Aghazadeh ,&nbsp;Mehran Reihani-Ardabili ,&nbsp;Marzieh Zamani ,&nbsp;Marzieh Motallebi ,&nbsp;Abolfazl Movafagh","doi":"10.1016/j.cyto.2025.156892","DOIUrl":"10.1016/j.cyto.2025.156892","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) is a significant driver of end-stage renal disease, requiring kidney replacement therapies such as transplantation and dialysis. Given the critical importance of understanding the onset and progression of DN, we sought to explore the expression levels of tumor necrosis factor (TNF) and related long noncoding RNAs (lncRNAs) in diabetic patients with and without DN, as well as in pre-diabetic individuals, compared to healthy controls. We further explored the involvement of TNF and TNF-related lncRNAs in high glucose (HG)-induced apoptosis of human embryonic kidney (HEK)-293 cells.</div></div><div><h3>Material and method</h3><div>In the current cross-sectional investigation, we compare the expression levels of lncRNA myocardial infarction-associated transcript (MIAT), lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and TNF in 50 healthy individuals, 50 people with prediabetes, 50 patients with type 2 diabetes mellitus (T2DM), and 50 patients with T2DM- DN. We cultured HEK293 cells in a HG condition (100 mM glucose) to establish a cellular model of DN, while HEK293 cells cultured in a normal-glucose environment (5 mM glucose) served as controls. We further assess apoptosis in HEK293 cells via flow cytometry analysis. Moreover, we evaluated the expression levels of lncRNA MIAT, lncRNA NEAT1, and TNF in HG and normal-glucose (NG) groups to investigate their potential involvement in HEK293 cell apoptosis and the pathogenesis of DN.</div></div><div><h3>Result</h3><div>Our findings reveal a significant upregulation of lncRNA MIAT, lncRNA NEAT1, and TNF in T2DM and T2DM-associated DN groups compared to prediabetic individuals and healthy controls (<em>p</em> &lt; 0.05). Furthermore, HG conditions significantly increased the apoptotic rate of HEK293 cells. Additionally, the expression levels of TNF, lncRNA MIAT, and lncRNA NEAT1 were increased in HEK-293 cells cultured in a HG.</div></div><div><h3>Conclusion</h3><div>In conclusion, our findings indicate a significant role for the TNF gene and associated lncRNAs, such as lncRNA MIAT and lncRNA NEAT1, in podocyte apoptosis and the development of DN.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156892"},"PeriodicalIF":3.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429617","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 intricate ballet of inflammation and autophagy: Insights from Mycoplasma gallisepticum-infected HD11 cells
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-18 DOI: 10.1016/j.cyto.2025.156895
Yuquan Guo , Wanying Hu , Jiaqi Hu, Shun Wang, Rui Li, Jichang Li, Jiaxin Bao, Chunli Chen

Objectives

Mycoplasma gallisepticum (M. gallisepticum) infection often leads to inflammatory damage and immunosuppression. Macrophages play a crucial role as the primary immune defense in chickens, with their inflammatory response and autophagy levels critical. This study aimed to explore the relationship between NLRP3 inflammasome and autophagy in HD11 cells within 12 h after M. gallisepticum infection.

Methods

To investigate this, the HD11 cell model of M. gallisepticum infection was established using the CCK8 (Cell Counting Kit-8) method in this study. The study observed changes in M. gallisepticum-induced inflammation, oxidative stress, and autophagy levels through various methods including transmission electron microscopy (TEM), RT-qPCR, ELISA (enzyme linked immunosorbent assay), 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), JC-1 and Western blot.

Results

TEM revealed that the nuclear membrane was damaged, the number of damaged mitochondria increased, and autophagosomes were detected at 4 and 8 h after M. gallisepticum infection. ELISA and RT-qPCR results indicated that M. gallisepticum induced oxidative stress and inflammation damage. Fluorescence analysis demonstrated an increase in intracellular reactive oxygen species (ROS) content and a continuous decrease in mitochondrial membrane potential (MMP) post-M. gallisepticum infection. Additionally, the NF-κB/NLRP3 signaling pathway remained consistently activated during M. gallisepticum infection. After M. gallisepticum infection, autophagy levels decreased significantly at 1 and 12 h, but increased significantly at 4 and 8 h.

Conclusions

M. gallisepticum infection triggers the activation of the NLRP3 inflammasome in HD11 cells, leading to inflammatory damage. Additionally, it causes fluctuations in autophagy levels, characterized by a wavy pattern of decrease, increase, and subsequent decrease.
{"title":"The intricate ballet of inflammation and autophagy: Insights from Mycoplasma gallisepticum-infected HD11 cells","authors":"Yuquan Guo ,&nbsp;Wanying Hu ,&nbsp;Jiaqi Hu,&nbsp;Shun Wang,&nbsp;Rui Li,&nbsp;Jichang Li,&nbsp;Jiaxin Bao,&nbsp;Chunli Chen","doi":"10.1016/j.cyto.2025.156895","DOIUrl":"10.1016/j.cyto.2025.156895","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Mycoplasma gallisepticum</em> (<em>M. gallisepticum</em>) infection often leads to inflammatory damage and immunosuppression. Macrophages play a crucial role as the primary immune defense in chickens, with their inflammatory response and autophagy levels critical. This study aimed to explore the relationship between NLRP3 inflammasome and autophagy in HD11 cells within 12 h after <em>M. gallisepticum</em> infection.</div></div><div><h3>Methods</h3><div>To investigate this, the HD11 cell model of <em>M. gallisepticum</em> infection was established using the CCK8 (Cell Counting Kit-8) method in this study. The study observed changes in <em>M. gallisepticum</em>-induced inflammation, oxidative stress, and autophagy levels through various methods including transmission electron microscopy (TEM), RT-qPCR, ELISA (enzyme linked immunosorbent assay), 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), JC-1 and Western blot.</div></div><div><h3>Results</h3><div>TEM revealed that the nuclear membrane was damaged, the number of damaged mitochondria increased, and autophagosomes were detected at 4 and 8 h after <em>M. gallisepticum</em> infection. ELISA and RT-qPCR results indicated that <em>M. gallisepticum</em> induced oxidative stress and inflammation damage. Fluorescence analysis demonstrated an increase in intracellular reactive oxygen species (ROS) content and a continuous decrease in mitochondrial membrane potential (MMP) post-<em>M. gallisepticum</em> infection. Additionally, the NF-κB/NLRP3 signaling pathway remained consistently activated during <em>M. gallisepticum</em> infection. After <em>M. gallisepticum</em> infection, autophagy levels decreased significantly at 1 and 12 h, but increased significantly at 4 and 8 h.</div></div><div><h3>Conclusions</h3><div><em>M. gallisepticum</em> infection triggers the activation of the NLRP3 inflammasome in HD11 cells, leading to inflammatory damage. Additionally, it causes fluctuations in autophagy levels, characterized by a wavy pattern of decrease, increase, and subsequent decrease.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156895"},"PeriodicalIF":3.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436898","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
Molecular study and determining the levels of some interleukins in children with Entamoeba histolytica
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-17 DOI: 10.1016/j.cyto.2025.156890
Ayser I. Abdul-Aziz
The processes by which amebiasis causes host mucosal inflammation are not entirely understood. In order to identify Entamoeba histolytica molecularly and measure the amounts of certain interleukins in children who were infected, this study was conducted. It was conducted between April and Stamper 2024. In Medical City, Baghdad, Iraq, 290 children suffering from diarrhea who were between the ages of 1 and 13 had their stool and blood samples taken. The microscopic examination showed that 128(44.1 %) children out of 290 were infected with Entamoeba spp. while when the samples were examined using the RT-PCR technique, it was found that the number of positive samples was 53(36.6 %) for E. histolytica The percentage of infected male children was 41.5 % while, the percentage of female children was 58.5 %. For interleukins, IL-2 was significantly increased in infected children (265.02 ± 11.78) compared with control (89.36 ± 5.19 pg/ml). IL-4 was significantly increased in infected children (249.11 ± 12.47 pg/ml) compared with control (54.84 ± 1.93 pg/ml). IL-6 was significantly increased in infected children (7.28 ± 1.57 pg/ml) compared with control (2.11 ± 0.42 pg/ml). IL-17 was significantly increased (P < 0.05) in infected children (15.46 ± 1.93 pg/ml) compared with control (7.06 ± 0.67 pg/ml). According to this research, PCR technology is a more sensitive and accurate way to diagnose E. histolytica than the direct method with an optical microscope. Inconclusion, this study found that children with E. histolytica had considerably increased serum levels of several interleukins, including IL-2, IL-4, IL-6, and IL-17.
{"title":"Molecular study and determining the levels of some interleukins in children with Entamoeba histolytica","authors":"Ayser I. Abdul-Aziz","doi":"10.1016/j.cyto.2025.156890","DOIUrl":"10.1016/j.cyto.2025.156890","url":null,"abstract":"<div><div>The processes by which amebiasis causes host mucosal inflammation are not entirely understood. In order to identify <em>Entamoeba histolytica</em> molecularly and measure the amounts of certain interleukins in children who were infected, this study was conducted. It was conducted between April and Stamper 2024. In Medical City, Baghdad, Iraq, 290 children suffering from diarrhea who were between the ages of 1 and 13 had their stool and blood samples taken. The microscopic examination showed that 128(44.1 %) children out of 290 were infected with Entamoeba spp. while when the samples were examined using the RT-PCR technique, it was found that the number of positive samples was 53(36.6 %) for <em>E. histolytica</em> The percentage of infected male children was 41.5 % while, the percentage of female children was 58.5 %. For interleukins, IL-2 was significantly increased in infected children (265.02 ± 11.78) compared with control (89.36 ± 5.19 pg/ml). IL-4 was significantly increased in infected children (249.11 ± 12.47 pg/ml) compared with control (54.84 ± 1.93 pg/ml). IL-6 was significantly increased in infected children (7.28 ± 1.57 pg/ml) compared with control (2.11 ± 0.42 pg/ml). IL-17 was significantly increased (<em>P</em> &lt; 0.05) in infected children (15.46 ± 1.93 pg/ml) compared with control (7.06 ± 0.67 pg/ml). According to this research, PCR technology is a more sensitive and accurate way to diagnose <em>E. histolytica</em> than the direct method with an optical microscope. Inconclusion, this study found that children with <em>E. histolytica</em> had considerably increased serum levels of several interleukins, including IL-2, IL-4, IL-6, and IL-17<em>.</em></div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156890"},"PeriodicalIF":3.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429615","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
Interleukin-4 ameliorates macrophage lipid stress through promoting cholesterol efflux and lipid homeostasis
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-14 DOI: 10.1016/j.cyto.2025.156869
Kuo-Ting Ho , Fang-Yeh Chu , Yi-Kai Lin , Ho-Hsun Chin , Shun-Chun Yang , Ching-Ping Yang , Yih-Hsin Chang
Over-nutrition and lipid metabolic abnormalities are correlated with obesity and type 2 diabetes mellitus (T2DM). Individuals with long-term hyperglycemia and dyslipidemia are susceptible to life-threatening complications such as atherosclerosis. Excess amounts of modified low density lipoprotein (mLDL) attract circulating monocytes to resident at arterial wall and differentiate into pro-inflammatory M1 macrophages. M1 cells uptake mLDL through scavenger receptors-mediated endocytosis, leading to increased lipids influx, cholesterol accumulation and foam cell formation. Besides, macrophages are attracted and infiltrated into the hypertrophic adipose tissue to mediate microenvironmental lipid metabolism. Our previous studies demonstrate that anti-inflammatory interleukin-4 (IL-4) regulates lipid metabolism by inhibiting lipid accumulation and promoting lipolysis of mature adipocytes. The effects of IL-4-polarized M2 macrophages on 3T3-L1 adipogenesis and macrophage-adipocyte interaction were explored in the present study. Our results showed lipid deposits and lipid droplets (LDs)-anchored perilipin of adipocytes cultured in IL-4-polarized M2-conditioned medium (M2-CM) were decreased, while adipogenesis-driving transcription factors and critical lipid metabolic enzymes remained unaffected. It indicates that M2-secreted mediators down-regulate lipid deposits and LDs formation in late adipogenic phase rather than interfering early programming phase and lipid synthesis machinery. In addition, IL-4 reduced intracellular lipid loads by up-regulating cholesterol efflux ATP-binding cassette transporter A1 (ABCA1) and ABCG1 despite cholesterol influx CD36 was also elevated. Accordingly, IL-4 shows beneficial effects to prevent atherosclerosis via promoting catabolism of the internalized lipids and cholesterol efflux, thus efficiently reduces lipid overload and foam cell formation. These findings illustrate novel roles and protective function of IL-4 to reduce the risk of atherosclerosis incidence by efficiently promoting macrophage cholesterol efflux and lipid homeostasis.
{"title":"Interleukin-4 ameliorates macrophage lipid stress through promoting cholesterol efflux and lipid homeostasis","authors":"Kuo-Ting Ho ,&nbsp;Fang-Yeh Chu ,&nbsp;Yi-Kai Lin ,&nbsp;Ho-Hsun Chin ,&nbsp;Shun-Chun Yang ,&nbsp;Ching-Ping Yang ,&nbsp;Yih-Hsin Chang","doi":"10.1016/j.cyto.2025.156869","DOIUrl":"10.1016/j.cyto.2025.156869","url":null,"abstract":"<div><div>Over-nutrition and lipid metabolic abnormalities are correlated with obesity and type 2 diabetes mellitus (T2DM). Individuals with long-term hyperglycemia and dyslipidemia are susceptible to life-threatening complications such as atherosclerosis. Excess amounts of modified low density lipoprotein (mLDL) attract circulating monocytes to resident at arterial wall and differentiate into pro-inflammatory M1 macrophages. M1 cells uptake mLDL through scavenger receptors-mediated endocytosis, leading to increased lipids influx, cholesterol accumulation and foam cell formation. Besides, macrophages are attracted and infiltrated into the hypertrophic adipose tissue to mediate microenvironmental lipid metabolism. Our previous studies demonstrate that anti-inflammatory interleukin-4 (IL-4) regulates lipid metabolism by inhibiting lipid accumulation and promoting lipolysis of mature adipocytes. The effects of IL-4-polarized M2 macrophages on 3T3-L1 adipogenesis and macrophage-adipocyte interaction were explored in the present study. Our results showed lipid deposits and lipid droplets (LDs)-anchored perilipin of adipocytes cultured in IL-4-polarized M2-conditioned medium (M2-CM) were decreased, while adipogenesis-driving transcription factors and critical lipid metabolic enzymes remained unaffected. It indicates that M2-secreted mediators down-regulate lipid deposits and LDs formation in late adipogenic phase rather than interfering early programming phase and lipid synthesis machinery. In addition, IL-4 reduced intracellular lipid loads by up-regulating cholesterol efflux ATP-binding cassette transporter A1 (ABCA1) and ABCG1 despite cholesterol influx CD36 was also elevated. Accordingly, IL-4 shows beneficial effects to prevent atherosclerosis via promoting catabolism of the internalized lipids and cholesterol efflux, thus efficiently reduces lipid overload and foam cell formation. These findings illustrate novel roles and protective function of IL-4 to reduce the risk of atherosclerosis incidence by efficiently promoting macrophage cholesterol efflux and lipid homeostasis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156869"},"PeriodicalIF":3.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419772","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
A pilot investigation on inflammatory markers and theta burst stimulation protocol interaction along a three-month recovery course following an isolated upper limb fracture
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-12 DOI: 10.1016/j.cyto.2025.156885
Bénédicte Robitaille , Alberto Herrero Babiloni , Marianne Jodoin , Marie-Michèle Briand , Dominique M. Rouleau , Louis De Beaumont
This study investigates the effects of theta burst stimulation (TBS) on inflammatory markers in patients with isolated upper limb fractures (IULF). Participants underwent a 10-day TBS intervention following a randomized matched pair design. Blood samples collected at three time points were analyzed for inflammatory biomarkers, mainly including interleukin-1 receptor antagonist (IL-1Ra), IL-1β, and IL-6. Results revealed a significant interaction between TBS and time for IL-1Ra, indicating a more pronounced decrease in IL-1Ra expression over time in the active TBS group. However, IL-6 levels decreased over time regardless of TBS intervention, suggesting a natural decline in response to injury. No significant interaction was found for IL-1β. While IL-1Ra levels were associated with higher functional disability prior to treatment initiation, active TBS intervention led to a decrease of IL-1Ra levels at both follow-up time points. These changes were not associated with alterations in pain or disability, suggesting that TBS may primarily influence recovery processes independent of pain modulation. Notably, IL-1β levels were negatively correlated with disability in the active TBS group at the 3-month follow-up. This study sheds light on the potential of TBS to modulate inflammatory responses in orthopedic trauma, emphasizing the need for further research to elucidate its therapeutic implications. Clinical Significance: TBS may offer a promising adjunctive therapy for promoting functional recovery in patients with upper limb fractures.
{"title":"A pilot investigation on inflammatory markers and theta burst stimulation protocol interaction along a three-month recovery course following an isolated upper limb fracture","authors":"Bénédicte Robitaille ,&nbsp;Alberto Herrero Babiloni ,&nbsp;Marianne Jodoin ,&nbsp;Marie-Michèle Briand ,&nbsp;Dominique M. Rouleau ,&nbsp;Louis De Beaumont","doi":"10.1016/j.cyto.2025.156885","DOIUrl":"10.1016/j.cyto.2025.156885","url":null,"abstract":"<div><div>This study investigates the effects of theta burst stimulation (TBS) on inflammatory markers in patients with isolated upper limb fractures (IULF). Participants underwent a 10-day TBS intervention following a randomized matched pair design. Blood samples collected at three time points were analyzed for inflammatory biomarkers, mainly including interleukin-1 receptor antagonist (IL-1Ra), IL-1β, and IL-6. Results revealed a significant interaction between TBS and time for IL-1Ra, indicating a more pronounced decrease in IL-1Ra expression over time in the active TBS group. However, IL-6 levels decreased over time regardless of TBS intervention, suggesting a natural decline in response to injury. No significant interaction was found for IL-1β. While IL-1Ra levels were associated with higher functional disability prior to treatment initiation, active TBS intervention led to a decrease of IL-1Ra levels at both follow-up time points. These changes were not associated with alterations in pain or disability, suggesting that TBS may primarily influence recovery processes independent of pain modulation. Notably, IL-1β levels were negatively correlated with disability in the active TBS group at the 3-month follow-up. This study sheds light on the potential of TBS to modulate inflammatory responses in orthopedic trauma, emphasizing the need for further research to elucidate its therapeutic implications. Clinical Significance: TBS may offer a promising adjunctive therapy for promoting functional recovery in patients with upper limb fractures.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156885"},"PeriodicalIF":3.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143388360","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
Prognostic valule of vasoactive drug score, NT-proBNP, and blood lactate level at 6 h post-admission in adult sepsis patients:A single-center, retrospective study
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-10 DOI: 10.1016/j.cyto.2025.156891
Xiaokang Peng , Fang Ye , Jiao Wang , Linnan Li , Chenghua Wang , Hongfeng Yang
<div><h3>Background</h3><div>Sepsis is a prevalent and critical condition triggered by an exaggerated immune response to specific infectious agents. The classification of the severity of sepsis plays a fundamental role in early identification and structured management, aiding in the prediction of increased risk of mortality. Despite the utilization of numerous biomarkers in sepsis diagnosis and treatment guidance, the early identification and prediction of sepsis still pose significant challenges.</div></div><div><h3>Objective</h3><div>To assess the prognostic value of vasoactive-inotropic score (VIS), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and 6 h blood lactate after admission in adult sepsis patients.</div></div><div><h3>Methods</h3><div>177 adult sepsis patients were enrolled in a cross-sectional study. Based on their 28-day outcome upon admission, patients were divided into a death group (<em>n</em> = 52) and a survival group (<em>n</em> = 125). Clinical data from both groups were collected. Univariate analysis and binary logistic regression were employed to identify independent risk factors for poor prognosis in adult sepsis patients. Receiver operating characteristic curve (ROC) analysis was performed to determine the predictive value of VIS, NT-proBNP, and blood lactate level at 6 h after admission for adult sepsis patients. Kaplan-Meier method was utilized to analyze the relationship between VIS, NT-proBNP, blood lactate level at 6 h after admission, and survival prognosis among adult sepsis patients.</div></div><div><h3>Results</h3><div>1. VIS (OR: 7.117; 95 % CI: 1.648–30.738; <em>P</em> = 0.009), NT-proBNP (OR: 1.296; 95 % CI: 1.026–1.637; <em>P</em> = 0.030), SOFA score (OR:1.232; 95 % CI: 1.031–1.473; P = 0. 02) and blood lactate at 6 h after admission (OR: 3.484; 95 % CI: l.416–8.573; <em>p</em> = 0.007) were independent risk factors for poor prognosis of adult sepsis. 2. VIS, NT-proBNP, and blood lactate at 6 h after admission were positively correlated with SOFA scores (<em>r</em> = 0 0.255, 0.388, and 0.l89 respectively, <em>P</em> < 0.05). 3. ROC curve analysis showed that the area under the curve (AUC) of VIS, NT-proBNP, and blood lactate at 6 h after admission for predicting poor prognosis in adult sepsis patients was 0.673, 0.790, and 0.702 respectively. When the cut-off values were 3.86, l.69,and 3.35, the sensitivity was 40.5 %, 71.8 %, and 59.3 %, the specificity was88.2 %, 65.8 %, and 72.9 %, and the Youden index was 0.288, 0.501, and 0.324, respectively. 3. Kaplan-Meier analysis revealed statistically significant differences in survival prognosis between patients with VIS >1.69 and VIS ≤1.69 (Log-rank χ<sup>2</sup> = 18.404, <em>P</em> < 0.001), NT-proBNP >3.86 and NT-proBNP ≤3.86 (Log-rank χ<sup>2</sup> = 38.282, P < 0.001), as well as blood lactate >3.35 and blood lactic acid ≤3.35 after a duration of 6 h from admission (Log-rank χ<sup>2</sup> = 11.776, P < 0.001).</div></div><div><
{"title":"Prognostic valule of vasoactive drug score, NT-proBNP, and blood lactate level at 6 h post-admission in adult sepsis patients:A single-center, retrospective study","authors":"Xiaokang Peng ,&nbsp;Fang Ye ,&nbsp;Jiao Wang ,&nbsp;Linnan Li ,&nbsp;Chenghua Wang ,&nbsp;Hongfeng Yang","doi":"10.1016/j.cyto.2025.156891","DOIUrl":"10.1016/j.cyto.2025.156891","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Sepsis is a prevalent and critical condition triggered by an exaggerated immune response to specific infectious agents. The classification of the severity of sepsis plays a fundamental role in early identification and structured management, aiding in the prediction of increased risk of mortality. Despite the utilization of numerous biomarkers in sepsis diagnosis and treatment guidance, the early identification and prediction of sepsis still pose significant challenges.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Objective&lt;/h3&gt;&lt;div&gt;To assess the prognostic value of vasoactive-inotropic score (VIS), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and 6 h blood lactate after admission in adult sepsis patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;177 adult sepsis patients were enrolled in a cross-sectional study. Based on their 28-day outcome upon admission, patients were divided into a death group (&lt;em&gt;n&lt;/em&gt; = 52) and a survival group (&lt;em&gt;n&lt;/em&gt; = 125). Clinical data from both groups were collected. Univariate analysis and binary logistic regression were employed to identify independent risk factors for poor prognosis in adult sepsis patients. Receiver operating characteristic curve (ROC) analysis was performed to determine the predictive value of VIS, NT-proBNP, and blood lactate level at 6 h after admission for adult sepsis patients. Kaplan-Meier method was utilized to analyze the relationship between VIS, NT-proBNP, blood lactate level at 6 h after admission, and survival prognosis among adult sepsis patients.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;1. VIS (OR: 7.117; 95 % CI: 1.648–30.738; &lt;em&gt;P&lt;/em&gt; = 0.009), NT-proBNP (OR: 1.296; 95 % CI: 1.026–1.637; &lt;em&gt;P&lt;/em&gt; = 0.030), SOFA score (OR:1.232; 95 % CI: 1.031–1.473; P = 0. 02) and blood lactate at 6 h after admission (OR: 3.484; 95 % CI: l.416–8.573; &lt;em&gt;p&lt;/em&gt; = 0.007) were independent risk factors for poor prognosis of adult sepsis. 2. VIS, NT-proBNP, and blood lactate at 6 h after admission were positively correlated with SOFA scores (&lt;em&gt;r&lt;/em&gt; = 0 0.255, 0.388, and 0.l89 respectively, &lt;em&gt;P&lt;/em&gt; &lt; 0.05). 3. ROC curve analysis showed that the area under the curve (AUC) of VIS, NT-proBNP, and blood lactate at 6 h after admission for predicting poor prognosis in adult sepsis patients was 0.673, 0.790, and 0.702 respectively. When the cut-off values were 3.86, l.69,and 3.35, the sensitivity was 40.5 %, 71.8 %, and 59.3 %, the specificity was88.2 %, 65.8 %, and 72.9 %, and the Youden index was 0.288, 0.501, and 0.324, respectively. 3. Kaplan-Meier analysis revealed statistically significant differences in survival prognosis between patients with VIS &gt;1.69 and VIS ≤1.69 (Log-rank χ&lt;sup&gt;2&lt;/sup&gt; = 18.404, &lt;em&gt;P&lt;/em&gt; &lt; 0.001), NT-proBNP &gt;3.86 and NT-proBNP ≤3.86 (Log-rank χ&lt;sup&gt;2&lt;/sup&gt; = 38.282, P &lt; 0.001), as well as blood lactate &gt;3.35 and blood lactic acid ≤3.35 after a duration of 6 h from admission (Log-rank χ&lt;sup&gt;2&lt;/sup&gt; = 11.776, P &lt; 0.001).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156891"},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377480","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
Maternal cytokine and cellular adhesion molecules profile in pregnant women with and without congenital heart disease.
IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-10 DOI: 10.1016/j.cyto.2025.156886
Francois Dos Santos, Philip J. Steer, Mark R. Johnson

Introduction

Despite corrective surgery, patients with congenital heart disease (CHD) have residual regions of disturbed oscillatory blood flow which can induce upregulation of proinflammatory cytokines and adhesion molecules. Data on cytokine and cellular adhesion molecule (CAM) profiles in low risk pregnancy and pregnancy complicated by CHD are limited. The objective of this work was to study the profile of IL-6, IL-10, TNFα, ghrelin, GROα, and ICAM/VCAM in pregnancy in women with and without CHD and test the hypothesis that the circulating levels of these are correlated with obstetric outcomes.

Methods

Prospective study of women ≥18 years carrying a singleton low risk pregnancy low-risk (LR-group) and pregnant women with CHD (CHD-group). Study visits were conducted between 10 and 14, 18–22 and 30–34 weeks' gestation with blood sampling for immune profiling using the Bio-Plex® Multiplex Immunoassay. The immune profile was investigated in both groups and correlated with obstetric outcomes. This study was approved by the Health Research Authority and the London South East Research Ethics Committee (REC reference: 17/LO/0970).

Results

Forty-five samples in 30 participants with CHD and 45 gestational age-matched samples from 34 low-risk pregnant women were analysed. Women in the CHD-group delivered earlier (38 + 6 weeks vs 39 + 4 weeks, p = 0.005) and had smaller babies (2940 g, 30.0 centile vs 3415 g, 63.5 centile, p < 0.001). There were no significant differences in the levels of IL-6, IL-10 or TNFαin both groups across trimesters. Levels of GROα increased in both groups but less so in the CHD group. Levels of ghrelin decreased in both groups but less so in the CHD group. Levels of ICAM decreased as pregnancy progressed in the CHD group. Levels of VCAM increased in both groups but more significantly in the CHD-group (second trimester, p < 0.001; third trimester, p = 0.045). Women in the CHD-group had higher levels if IL-6 (p = 0.005) and ICAM (p < 0.001) lower levels of IL-10 in the third trimester (p = 0.018). There was a significant positive association between levels of IL-6 in the first trimester and birthweight centiles (rs = 1.00, p < 0.001) in the CHD group.

Conclusion

There was minimal fluctuation in the levels of the studies cytokines during pregnancy with exception of GROα and ghrelin, both implicated in fetal growth. Women with CHD had higher levels of proinflammatory cytokines and ICAM in the first trimester, and lower levels of IL-10 in the third trimester, suggesting a more proinflammatory state. High levels of VCAM in the CHD group could be secondary to endothelial activation.
{"title":"Maternal cytokine and cellular adhesion molecules profile in pregnant women with and without congenital heart disease.","authors":"Francois Dos Santos,&nbsp;Philip J. Steer,&nbsp;Mark R. Johnson","doi":"10.1016/j.cyto.2025.156886","DOIUrl":"10.1016/j.cyto.2025.156886","url":null,"abstract":"<div><h3>Introduction</h3><div>Despite corrective surgery, patients with congenital heart disease (CHD) have residual regions of disturbed oscillatory blood flow which can induce upregulation of proinflammatory cytokines and adhesion molecules. Data on cytokine and cellular adhesion molecule (CAM) profiles in low risk pregnancy and pregnancy complicated by CHD are limited. The objective of this work was to study the profile of IL-6, IL-10, TNFα, ghrelin, GRO<em>α</em>, and ICAM/VCAM in pregnancy in women with and without CHD and test the hypothesis that the circulating levels of these are correlated with obstetric outcomes.</div></div><div><h3>Methods</h3><div>Prospective study of women ≥18 years carrying a singleton low risk pregnancy low-risk (LR-group) and pregnant women with CHD (CHD-group). Study visits were conducted between 10 and 14, 18–22 and 30–34 weeks' gestation with blood sampling for immune profiling using the <em>Bio-Plex® Multiplex Immunoassay</em>. The immune profile was investigated in both groups and correlated with obstetric outcomes. This study was approved by the Health Research Authority and the London South East Research Ethics Committee (REC reference: 17/LO/0970).</div></div><div><h3>Results</h3><div>Forty-five samples in 30 participants with CHD and 45 gestational age-matched samples from 34 low-risk pregnant women were analysed. Women in the CHD-group delivered earlier (38 + 6 weeks <em>vs</em> 39 + 4 weeks, <em>p</em> = 0.005) and had smaller babies (2940 g, 30.0 centile <em>vs</em> 3415 g, 63.5 centile, <em>p</em> &lt; 0.001). There were no significant differences in the levels of IL-6, IL-10 or TNFαin both groups across trimesters. Levels of GRO<em>α</em> increased in both groups but less so in the CHD group. Levels of ghrelin decreased in both groups but less so in the CHD group. Levels of ICAM decreased as pregnancy progressed in the CHD group. Levels of VCAM increased in both groups but more significantly in the CHD-group (second trimester, <em>p</em> &lt; 0.001; third trimester, <em>p</em> = 0.045). Women in the CHD-group had higher levels if IL-6 (<em>p</em> = 0.005) and ICAM (p &lt; 0.001) lower levels of IL-10 in the third trimester (<em>p</em> = 0.018). There was a significant positive association between levels of IL-6 in the first trimester and birthweight centiles (r<sub>s</sub> = 1.00, <em>p</em> &lt; 0.001) in the CHD group.</div></div><div><h3>Conclusion</h3><div>There was minimal fluctuation in the levels of the studies cytokines during pregnancy with exception of GRO<em>α</em> and ghrelin, both implicated in fetal growth. Women with CHD had higher levels of proinflammatory cytokines and ICAM in the first trimester, and lower levels of IL-10 in the third trimester, suggesting a more proinflammatory state. High levels of VCAM in the CHD group could be secondary to endothelial activation.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156886"},"PeriodicalIF":3.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378619","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
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Cytokine
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