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High RRM2 Correlates with Mitochondrial and Immune Responses in the Eosinophilic Subtype of Clear Cell Renal Cell Carcinoma. 高 RRM2 与透明细胞肾细胞癌嗜酸性亚型的线粒体和免疫反应有关
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-11-02 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S478993
Xinqing Zhu, Abdullah Al-Danakh, Yuli Jian, Mohammed Safi, Sijie Luo, Qiwei Chen, Shujing Wang, Deyong Yang

Background: Clear cell renal cell carcinoma (ccRCC), the predominant subtype of RCC, is distinguished by unique biological characteristics and heterogeneity, including eosinophilic and clear subtypes. Notwithstanding progress in therapy, immune checkpoint inhibitors (ICIs), and tyrosine kinase inhibitors (TKIs), the prognosis for individuals with metastatic ccRCC remains poor, presumably owing to metabolic alterations leading to mitochondrial dysfunction, which affects treatment response variability.

Methods: We analyzed histological and immunohistochemical data from a cohort at Dalian Medical University's First Affiliated Hospital alongside RNA-sequencing transcriptome data from the TCGA database. Histologically, eosinophilic and clear ccRCC subtypes were evaluated using Kaplan-Meier and Cox proportional hazards models for survival analysis and prognosis. Differential gene expression (DEG) analysis and Gene Set Enrichment Analysis were performed to explore transcriptomic differences and relevant pathways.

Results: The study discovered substantial histological and molecular differences between the eosinophilic and clear cell subtypes of ccRCC. The eosinophilic subtype linked with frequent high-grade tumors (69.05% eosinophil vs 35.35% clear) and a poorer prognosis (HR=2.659, 95% CI:1.437-4.919, P=0.002). DEG analysis revealed distinct expression patterns among subtypes and identified a risk score signature that remained significant even after adjusting for clinical variables (HR=3.967, 95% CI: 1.665-9.449, P=0.002), showing less favorable survival in the high-risk group (P < 0.0001). RRM2 emerged as the most prognostic gene from this risk score, particularly in the eosinophilic subtype, alongside other clinical variables. By IHC, RRM2 shows high IHC score in eosinophilic compared to clear subtype (P=0.019). In addition, highly expressed RRM2 correlates with poor outcomes and is linked to mitochondrial genes, immunological pathways, and ICIs treatment.

Conclusion: These findings show significant differences in prognosis between subtypes. RRM2 was the most prognostic gene from the discovered novel risk score signature associated with subtypes. Future research is essential to validate these insights and their therapeutic implications for ccRCC management.

背景:透明细胞肾细胞癌(ccRCC)是RCC的主要亚型,具有独特的生物学特征和异质性,包括嗜酸性亚型和透明亚型。尽管在治疗、免疫检查点抑制剂(ICIs)和酪氨酸激酶抑制剂(TKIs)方面取得了进展,但转移性ccRCC患者的预后仍然很差,这可能是由于代谢改变导致线粒体功能障碍,从而影响了治疗反应的可变性:我们分析了大连医科大学附属第一医院队列中的组织学和免疫组化数据,以及TCGA数据库中的RNA测序转录组数据。采用Kaplan-Meier和Cox比例危险度模型对嗜酸性和透明性ccRCC亚型进行了生存分析和预后评估。进行了差异基因表达(DEG)分析和基因组富集分析,以探索转录组差异和相关通路:研究发现,嗜酸性亚型和透明细胞亚型的ccRCC在组织学和分子学上存在很大差异。嗜酸性细胞亚型与高分化肿瘤(嗜酸性细胞占69.05%,透明细胞占35.35%)和较差的预后有关(HR=2.659,95% CI:1.437-4.919,P=0.002)。DEG分析揭示了亚型之间不同的表达模式,并确定了一个风险评分特征,该特征即使在调整临床变量后仍有意义(HR=3.967,95% CI:1.665-9.449,P=0.002),显示高风险组的生存率较低(P <0.0001)。RRM2与其他临床变量一起成为该风险评分中最具预后性的基因,尤其是在嗜酸性粒细胞亚型中。通过 IHC,RRM2 在嗜酸性亚型中的 IHC 得分高于透明亚型(P=0.019)。此外,高表达的RRM2与不良预后相关,并与线粒体基因、免疫途径和ICIs治疗有关:结论:这些研究结果表明,不同亚型的预后存在明显差异。RRM2是已发现的与亚型相关的新型风险评分特征中最具预后性的基因。未来的研究对于验证这些见解及其对ccRCC管理的治疗意义至关重要。
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引用次数: 0
Guanxinning for Residual Inflammation of Stable Coronary Artery Disease: A Pilot Randomized Controlled Trial. 冠心宁治疗稳定型冠状动脉疾病的残余炎症:一项试点随机对照试验
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-11-02 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S490896
Tielong Chen, Jianwu Zheng, Cheng Bao, Yu Wang, Shiwang Wang, Lu Liang, Li Zhang, Hui Zhang, Chaoxia Ji, Jian Wang, Xudong Zhang, Guangli Zhu, Houyong Zhu

Background: Despite statins and other medications central to atherosclerotic cardiovascular disease (ASCVD) secondary prevention, stable coronary artery disease (SCAD) patients remain at significant cardiovascular risk, partly due to residual inflammation risk (RIR). This study aims to assess if adding Guanxinning to standard ASCVD therapy further mitigates RIR in SCAD patients.

Methods: In a prospective, randomized, single-blind endpoint design, 50 patients with SCAD who received ASCVD standardized treatment strategy were randomly assigned to either take Guanxinning tablets (4 tablets, thrice daily) or no Guanxinning tablets and were followed up for an average of 12 weeks. The primary outcomes were changes in inflammation-related indicators, including interleukin-2 (IL-2), IL-4, IL-6, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP).

Results: Compared with the control group, the intervention group showed significantly greater decreases in the levels of IL-2, IL-6, TNF-α, and hs-CRP (all P < 0.05). However, there was no significant difference in the IL-4 level between the two groups (P > 0.05). Compared with the control group, there were also significant improvements in endothelial function-related indicators (vascular endothelial growth factor (VEGF), nitric oxide (NO), and peroxisome proliferator-activated receptor-γ (PPAR-γ)), blood lipid profile (total cholesterol (Tch), low-density lipoprotein cholesterol (LDL-C)), and chest pain related scores (angina and Traditional Chinese medicine syndrome scores) in the intervention group (all P<0.05). There was no significant difference in the triglyceride (TG) and carotid intima-media thickness between the two groups (P<0.05). Compared to the control group, there was no significant difference in the white blood cell line, liver and kidney function, anemia, and bleeding in the intervention group (all P<0.05).

Conclusion: The addition of Guanxinning tablets (4 tablets, thrice daily) to the standard treatment strategy for ASCVD was associated with a reduction in the RIR in patients with SCAD and demonstrated good safety.

背景:尽管他汀类药物和其他药物是动脉粥样硬化性心血管疾病(ASCVD)二级预防的核心药物,但稳定型冠状动脉疾病(SCAD)患者仍有很大的心血管风险,部分原因是残余炎症风险(RIR)。本研究旨在评估在标准 ASCVD 治疗中加入冠心宁是否能进一步减轻 SCAD 患者的 RIR:在一项前瞻性、随机、单盲终点设计中,50名接受ASCVD标准化治疗策略的SCAD患者被随机分配到服用关欣宁片(4片,每天三次)或不服用关欣宁片,并接受平均12周的随访。主要结果是炎症相关指标的变化,包括白细胞介素-2(IL-2)、IL-4、IL-6、肿瘤坏死因子-α(TNF-α)和高敏C反应蛋白(hs-CRP):与对照组相比,干预组的 IL-2、IL-6、TNF-α 和 hs-CRP 水平明显降低(均 P < 0.05)。然而,两组之间的 IL-4 水平没有明显差异(P > 0.05)。与对照组相比,干预组的血管内皮功能相关指标(血管内皮生长因子(VEGF)、一氧化氮(NO)和过氧化物酶体增殖激活受体-γ(PPAR-γ))、血脂情况(总胆固醇(Tch)、低密度脂蛋白胆固醇(LDL-C))和胸痛相关评分(心绞痛和中医综合征评分)也有明显改善(均为 PC结论:在急性心血管疾病的标准治疗策略中加入冠心宁片(每天三次,每次4片)可降低SCAD患者的RIR,并显示出良好的安全性。
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引用次数: 0
Enhancement of Antioxidative and Anti-Inflammatory Activities of Corn Silk Polysaccharides After Selenium Modification. 硒改性后玉米丝多糖抗氧化和抗炎活性的增强
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S467665
Yu-Yun Zheng, Xin-Yi Tong, Da-Ying Zhang, Jian-Ming Ouyang

Objective: This study aimed to study the effect of selenium modification on the bioactivity of corn silk polysaccharides, particularly its antioxidant and anti-inflammatory functions.

Methods: HNO3-NaSeO3 was used to selenize degraded corn silk polysaccharides (DCSP). The structure and physicochemical properties of DCSP and selenized corn silk polysaccharides (Se-DCSP) were characterized by inductively coupled plasma emission spectroscopy, Fourier-transform infrared, ultraviolet-visible spectroscopy, nuclear magnetic resonance, nanometer, scanning electron microscopy, and thermogravimetric analysis. The protective effects of DCSP and Se-DCSP on HK-2 cells damaged by nano-calcium oxalate and the changes of inflammatory factors were detected by laser confocal microscopy, flow cytometry, and fluorescence microscopy.

Results: The selenium content of DCSP and Se-DCSP were 19.5 and 1226.7 μg/g, respectively. Compared with DCSP, Se-DCSP showed significantly improved biological activity, including the scavenging ability of various free radicals (increased by about 2-3 times), the intracellular reactive oxygen content (decreased by about 1.5 times), and the mitochondrial membrane potential (decreased by about 2.5 times). Moreover, cell viability and morphological recovery ability were improved. Compared with DCSP, Se-DCSP significantly down-regulated HK-2 cell inflammatory factors MCP-1 (about 1.7 times), NLRP3, and NO (about 1.5 times).

Conclusion: The antioxidant activity and the ability to down-regulate the expression of inflammatory factors of Se-DCSP were significantly enhanced compared with DCSP, and Se-DCSP can better protect HK-2 cells from oxidative damage, indicating that Se-DCSP has a stronger potential ability to inhibit kidney stone formation.

研究目的方法:采用 HNO3-NaSeO3 对降解玉米丝多糖(DCSP)进行硒化。采用电感耦合等离子体发射光谱、傅立叶变换红外光谱、紫外-可见光谱、核磁共振、纳米、扫描电子显微镜和热重分析等方法对降解玉米丝多糖(DCSP)和硒化玉米丝多糖(Se-DCSP)的结构和理化性质进行了表征。激光共聚焦显微镜、流式细胞仪和荧光显微镜检测了 DCSP 和 Se-DCSP 对受纳米草酸钙损伤的 HK-2 细胞的保护作用以及炎症因子的变化:结果:DCSP 和 Se-DCSP 的硒含量分别为 19.5 和 1226.7 μg/g。与 DCSP 相比,Se-DCSP 的生物活性明显提高,包括清除各种自由基的能力(提高约 2-3 倍)、细胞内活性氧含量(降低约 1.5 倍)和线粒体膜电位(降低约 2.5 倍)。此外,细胞活力和形态恢复能力也得到了提高。与 DCSP 相比,Se-DCSP 能显著下调 HK-2 细胞的炎症因子 MCP-1(约 1.7 倍)、NLRP3 和 NO(约 1.5 倍):结论:与DCSP相比,Se-DCSP的抗氧化活性和下调炎症因子表达的能力明显增强,能更好地保护HK-2细胞免受氧化损伤,表明Se-DCSP具有更强的抑制肾结石形成的潜在能力。
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引用次数: 0
Cross-Sectional and Longitudinal Associations of Serum LRG1 with Severity and Prognosis Among Adult Community-Acquired Pneumonia Patients. 成人社区获得性肺炎患者血清 LRG1 与病情严重程度和预后的横向和纵向关系
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S485932
Yingli Wang, Yalin Jiang, Meiling Xie, Bin Qi, Kunpeng Pu, Wenjie Du, Qingqing Zhang, Mengmeng Ma, Ziyong Chen, Yongxia Guo, Hui Qian, Kaiqin Wang, Tulei Tian, Lin Fu, Xiaofei Zhang

Background: Leucine-rich α-2 glycoprotein 1 (LRG1) is associated with various inflammatory lung diseases. Nevertheless, the connection between LRG1 and adult community-acquired pneumonia (CAP) individuals was still not well understood. Through a prospective cohort study, the correlations of serum LRG1 with severity and prognosis were evaluated in CAP patients.

Methods: The study encompassed 327 patients who received the diagnosis of CAP. We collected fasting venous blood and clinical features. Serum LRG1 was detected by ELISA. CAP severity was assessed using various scoring systems. The prognostic outcomes were observed through follow-up visits.

Results: The level of serum LRG1 at admission was gradually increased with CAP severity scores. Serum LRG1 level shown positive associations with inflammatory indices, including C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Linear and logistic regression analyses suggested that serum LRG1 at admission was positively associated with severity scores and the risk of death in CAP patients. Serum LRG1 in combination with CAP severity scores significantly increased the predictive powers for severity and death compared with single serum LRG1 or severity scores.

Conclusion: The study revealed positive connections of serum LRG1 levels with severity and poor prognosis in CAP patients, suggesting LRG1 partakes into the physiological processes of CAP. Serum LRG1 may be regarded as a potential biomarker in predicting the severity and death among CAP patients.

背景:富亮氨酸 α-2 糖蛋白 1(LRG1)与多种肺部炎症性疾病有关。然而,人们对 LRG1 与成人社区获得性肺炎(CAP)之间的关系仍不甚了解。通过一项前瞻性队列研究,对 CAP 患者血清 LRG1 与病情严重程度和预后的相关性进行了评估:研究涵盖了 327 名确诊为 CAP 的患者。我们收集了空腹静脉血和临床特征。通过 ELISA 检测血清 LRG1。使用各种评分系统评估 CAP 的严重程度。通过随访观察预后结果:结果:入院时血清 LRG1 水平随 CAP 严重程度评分逐渐升高。血清 LRG1 水平与炎症指数(包括 C 反应蛋白(CRP)、降钙素原(PCT)和白细胞介素-6(IL-6))呈正相关。线性和逻辑回归分析表明,入院时的血清 LRG1 与 CAP 患者的严重程度评分和死亡风险呈正相关。与单一血清 LRG1 或严重程度评分相比,血清 LRG1 与 CAP 严重程度评分相结合可显著提高对严重程度和死亡的预测能力:研究显示,血清 LRG1 水平与 CAP 患者的严重程度和不良预后呈正相关,表明 LRG1 参与了 CAP 的生理过程。血清 LRG1 可被视为预测 CAP 患者病情严重程度和死亡的潜在生物标志物。
{"title":"Cross-Sectional and Longitudinal Associations of Serum LRG1 with Severity and Prognosis Among Adult Community-Acquired Pneumonia Patients.","authors":"Yingli Wang, Yalin Jiang, Meiling Xie, Bin Qi, Kunpeng Pu, Wenjie Du, Qingqing Zhang, Mengmeng Ma, Ziyong Chen, Yongxia Guo, Hui Qian, Kaiqin Wang, Tulei Tian, Lin Fu, Xiaofei Zhang","doi":"10.2147/JIR.S485932","DOIUrl":"10.2147/JIR.S485932","url":null,"abstract":"<p><strong>Background: </strong>Leucine-rich α-2 glycoprotein 1 (LRG1) is associated with various inflammatory lung diseases. Nevertheless, the connection between LRG1 and adult community-acquired pneumonia (CAP) individuals was still not well understood. Through a prospective cohort study, the correlations of serum LRG1 with severity and prognosis were evaluated in CAP patients.</p><p><strong>Methods: </strong>The study encompassed 327 patients who received the diagnosis of CAP. We collected fasting venous blood and clinical features. Serum LRG1 was detected by ELISA. CAP severity was assessed using various scoring systems. The prognostic outcomes were observed through follow-up visits.</p><p><strong>Results: </strong>The level of serum LRG1 at admission was gradually increased with CAP severity scores. Serum LRG1 level shown positive associations with inflammatory indices, including C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). Linear and logistic regression analyses suggested that serum LRG1 at admission was positively associated with severity scores and the risk of death in CAP patients. Serum LRG1 in combination with CAP severity scores significantly increased the predictive powers for severity and death compared with single serum LRG1 or severity scores.</p><p><strong>Conclusion: </strong>The study revealed positive connections of serum LRG1 levels with severity and poor prognosis in CAP patients, suggesting LRG1 partakes into the physiological processes of CAP. Serum LRG1 may be regarded as a potential biomarker in predicting the severity and death among CAP patients.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"7951-7962"},"PeriodicalIF":4.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Interplay of TLR4 and SARS-CoV-2: Possible Involvement of microRNAs [Letter]. TLR4 与 SARS-CoV-2 的相互作用:微 RNA 的可能参与 [信函]。
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-11-01 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S501862
Roberto Gambari, Alessia Finotti
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引用次数: 0
Association of Stress Hyperglycemia Ratio and in-Hospital Mortality in Patients with Sepsis: A Two Center Retrospective Cohort Study. 应激性高血糖比率与败血症患者院内死亡率的关系:双中心回顾性队列研究。
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-30 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S476898
Chaoping Ma, Weisong Jiang, Juan Li, Wenwu Sun, Jiyuan Zhang, Peixian Xu, Yiran Guo, Ning Ning, Jiaoyan Li, Bing Zhao, Enqiang Mao, Chengjin Gao

Introduction: In critically ill patients, the stress hyperglycemia ratio (SHR) was significantly associated with mortality. However, the relationship between SHR and mortality in septic patients is still unclear.In this study, patients with sepsis from two Chinese academic centers were identified and divided into quartiles based on SHR levels.

Methods: Multivariable regression analysis will be used to determine associations between SHR and clinical outcomes in sepsis patients.The Kaplan-Meier curve was used to predict mortality in various groups of septic patients.

Results: A total of 1835 septic patients were included in the study.The in-hospital, 30-day, and 60-day mortality rates for all septic patients were 22.8%, 18.7%, and 21.7%, respectively. Increased SHR was significantly associated with hospital mortality in multivariate regression analysis.These results were further confirmed in the adjusted analysis, where the hospital mortality and the 60-day mortality of the highest SHR quartile were significantly increased compared to the lowest SHR quartile. However, the highest SHR quartile was not associated with 30-day mortality.In addition, the risk of in-hospital mortality, 30-day mortality and 60-day mortality showed a consistent upward trend with increasing SHR quartile. The survival curve showed that the worst prognosis was in the fourth SHR quartile.

Discussion: In conclusion, SHR was significantly associated with hospital mortality in patients with sepsis. This finding indicates that the SHR may be useful in identifying septic patients at higher risk of hospital mortality.

简介在危重病人中,应激性高血糖比值(SHR)与死亡率显著相关。本研究对来自中国两家学术中心的败血症患者进行了鉴定,并根据 SHR 水平将其分为四分位:方法:采用多变量回归分析确定SHR与脓毒症患者临床结局之间的关系,并采用Kaplan-Meier曲线预测各组脓毒症患者的死亡率:所有败血症患者的院内死亡率、30天死亡率和60天死亡率分别为22.8%、18.7%和21.7%。在多变量回归分析中,SHR的增加与住院死亡率明显相关。这些结果在调整分析中得到了进一步证实,与SHR最低的四分位数相比,SHR最高的四分位数的住院死亡率和60天死亡率明显增加。此外,随着 SHR 四分位数的增加,住院死亡率、30 天死亡率和 60 天死亡率的风险呈持续上升趋势。存活率曲线显示,SHR四分位数的预后最差:讨论:总之,SHR 与败血症患者的住院死亡率密切相关。这一发现表明,SHR 可能有助于识别住院死亡率风险较高的败血症患者。
{"title":"Association of Stress Hyperglycemia Ratio and in-Hospital Mortality in Patients with Sepsis: A Two Center Retrospective Cohort Study.","authors":"Chaoping Ma, Weisong Jiang, Juan Li, Wenwu Sun, Jiyuan Zhang, Peixian Xu, Yiran Guo, Ning Ning, Jiaoyan Li, Bing Zhao, Enqiang Mao, Chengjin Gao","doi":"10.2147/JIR.S476898","DOIUrl":"10.2147/JIR.S476898","url":null,"abstract":"<p><strong>Introduction: </strong>In critically ill patients, the stress hyperglycemia ratio (SHR) was significantly associated with mortality. However, the relationship between SHR and mortality in septic patients is still unclear.In this study, patients with sepsis from two Chinese academic centers were identified and divided into quartiles based on SHR levels.</p><p><strong>Methods: </strong>Multivariable regression analysis will be used to determine associations between SHR and clinical outcomes in sepsis patients.The Kaplan-Meier curve was used to predict mortality in various groups of septic patients.</p><p><strong>Results: </strong>A total of 1835 septic patients were included in the study.The in-hospital, 30-day, and 60-day mortality rates for all septic patients were 22.8%, 18.7%, and 21.7%, respectively. Increased SHR was significantly associated with hospital mortality in multivariate regression analysis.These results were further confirmed in the adjusted analysis, where the hospital mortality and the 60-day mortality of the highest SHR quartile were significantly increased compared to the lowest SHR quartile. However, the highest SHR quartile was not associated with 30-day mortality.In addition, the risk of in-hospital mortality, 30-day mortality and 60-day mortality showed a consistent upward trend with increasing SHR quartile. The survival curve showed that the worst prognosis was in the fourth SHR quartile.</p><p><strong>Discussion: </strong>In conclusion, SHR was significantly associated with hospital mortality in patients with sepsis. This finding indicates that the SHR may be useful in identifying septic patients at higher risk of hospital mortality.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"7939-7950"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Integrated Small Intestine Microbiota and Serum Metabolomics Reveal the Potential Mechanisms of Wine Steaming in Alleviating Rhubarb-Induced Diarrhea. 综合小肠微生物群和血清代谢组学揭示蒸酒缓解大黄所致腹泻的潜在机制
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-30 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S479654
Ya-Ya Bai, Rui Tian, Yan Qian, Qiao Zhang, Chong-Bo Zhao, Yong-Gang Yan, Li Zhang, Shi-Jun Yue, Yu-Ping Tang

Background: Long-term use of rhubarb (RH) commonly leads to diarrhea, which can be alleviated by steaming with wine. However, the specific mechanism by which wine steaming alleviates RH-induced diarrhea remains unknown.

Objective: This study aims to reveal the underlying mechanisms of wine steaming in alleviating RH-induced diarrhea by examining small intestinal flora and serum metabolomics.

Methods: Major anthraquinone and anthrone components were detected using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Eighty-four ICR mice were randomly divided into control, RH, and RH steamed with wine (PRH) groups and were administered RH and PRH (1, 4, and 8 g/kg, i.g). for 14 consecutive days. Histopathological analysis was performed using hematoxylin-eosin staining. Levels of inflammatory factors and tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in the small intestine were measured. The small intestine content was analyzed using 16S rRNA sequencing, and UPLC-MS was used to analyze endogenous metabolites.

Results: Levels of major anthraquinone and anthrone components decreased in PRH. Both RH and PRH groups showed varying degrees of loose stools and increased fecal water rates; the RH group exhibited more severe effects. Compared with the control group, RH caused small intestine injuries, increased levels of inflammatory cytokines, downregulated the expression of ZO-1 and occludin, and induced gut microbiota (GM) imbalance. The relative abundance of Lactobacillus decreased, while the relative abundance of Shigella and Streptococcus increased. However, PRH had a milder impact than RH. The glycerophospholipid metabolic pathway was involved in this effect. The levels of inflammatory cytokines and potential metabolites (sn-glycero-3-phosphoethanolamine) were positively correlated with Streptococcus infection, while the levels of ZO-1 and occludin were negatively correlated with Streptococcus infection. GM imbalance and abnormal glycerophospholipid metabolism contributed to impaired intestinal barrier function and inflammatory factor release, which may underlie RH-induced diarrhea, though PRH had a weaker effect.

Conclusion: PRH alleviated RH-induced diarrhea by recovering GM balance, reducing ZO-1 and occludin expression, and decreasing the release of inflammatory factors. This mechanism may be linked to the reduced anthraquinone content. This study is the first to explore the mechanism of wine steaming in alleviating RH-induced diarrhea through small intestinal flora and serum metabolomics. It provides data to support the broader clinical use of RH and its safer application.

背景:长期服用大黄(RH)通常会导致腹泻,用葡萄酒蒸煮可以缓解腹泻。然而,葡萄酒蒸煮缓解大黄引起的腹泻的具体机制仍不清楚:本研究旨在通过检测小肠菌群和血清代谢组学,揭示葡萄酒蒸煮缓解 RH 引起的腹泻的内在机制:采用超高效液相色谱-质谱法(UPLC-MS)检测主要的蒽醌和蒽酮成分。将 84 只 ICR 小鼠随机分为对照组、RH 组和红酒蒸 RH 组(PRH),连续 14 天分别给予 RH 和 PRH(1、4 和 8 克/千克,i.g)。使用苏木精-伊红染色进行组织病理学分析。测量了小肠中的炎症因子和紧密连接蛋白(Zonula occludens-1 (ZO-1)和occludin)的水平。使用 16S rRNA 测序分析小肠内容物,并使用 UPLC-MS 分析内源性代谢物:结果:PRH组主要蒽醌和蒽酮成分的含量下降。RH组和PRH组均出现不同程度的稀便和粪便含水量增加;RH组的影响更为严重。与对照组相比,RH 组造成小肠损伤、炎症细胞因子水平升高、ZO-1 和闭塞素表达下调,并诱导肠道微生物群(GM)失衡。乳酸杆菌的相对丰度下降,而志贺氏菌和链球菌的相对丰度上升。不过,PRH 的影响比 RH 轻微。甘油磷脂代谢途径参与了这种影响。炎症细胞因子和潜在代谢物(sn-甘油-3-磷乙醇胺)的水平与链球菌感染呈正相关,而 ZO-1 和闭塞素的水平与链球菌感染呈负相关。GM失衡和甘油磷脂代谢异常导致肠屏障功能受损和炎症因子释放,这可能是RH诱导腹泻的原因,但PRH的作用较弱:结论:PRH通过恢复GM平衡、减少ZO-1和闭塞素的表达以及减少炎症因子的释放,缓解了RH诱导的腹泻。这一机制可能与蒽醌含量减少有关。本研究首次通过小肠菌群和血清代谢组学探讨了蒸酒缓解 RH 引起的腹泻的机制。它为更广泛地临床使用 RH 及其更安全的应用提供了数据支持。
{"title":"Integrated Small Intestine Microbiota and Serum Metabolomics Reveal the Potential Mechanisms of Wine Steaming in Alleviating Rhubarb-Induced Diarrhea.","authors":"Ya-Ya Bai, Rui Tian, Yan Qian, Qiao Zhang, Chong-Bo Zhao, Yong-Gang Yan, Li Zhang, Shi-Jun Yue, Yu-Ping Tang","doi":"10.2147/JIR.S479654","DOIUrl":"10.2147/JIR.S479654","url":null,"abstract":"<p><strong>Background: </strong>Long-term use of rhubarb (RH) commonly leads to diarrhea, which can be alleviated by steaming with wine. However, the specific mechanism by which wine steaming alleviates RH-induced diarrhea remains unknown.</p><p><strong>Objective: </strong>This study aims to reveal the underlying mechanisms of wine steaming in alleviating RH-induced diarrhea by examining small intestinal flora and serum metabolomics.</p><p><strong>Methods: </strong>Major anthraquinone and anthrone components were detected using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Eighty-four ICR mice were randomly divided into control, RH, and RH steamed with wine (PRH) groups and were administered RH and PRH (1, 4, and 8 g/kg, i.g). for 14 consecutive days. Histopathological analysis was performed using hematoxylin-eosin staining. Levels of inflammatory factors and tight junction proteins, zonula occludens-1 (ZO-1) and occludin, in the small intestine were measured. The small intestine content was analyzed using 16S rRNA sequencing, and UPLC-MS was used to analyze endogenous metabolites.</p><p><strong>Results: </strong>Levels of major anthraquinone and anthrone components decreased in PRH. Both RH and PRH groups showed varying degrees of loose stools and increased fecal water rates; the RH group exhibited more severe effects. Compared with the control group, RH caused small intestine injuries, increased levels of inflammatory cytokines, downregulated the expression of ZO-1 and occludin, and induced gut microbiota (GM) imbalance. The relative abundance of <i>Lactobacillus</i> decreased, while the relative abundance of <i>Shigella</i> and <i>Streptococcus</i> increased. However, PRH had a milder impact than RH. The glycerophospholipid metabolic pathway was involved in this effect. The levels of inflammatory cytokines and potential metabolites (sn-glycero-3-phosphoethanolamine) were positively correlated with <i>Streptococcus</i> infection, while the levels of ZO-1 and occludin were negatively correlated with <i>Streptococcus</i> infection. GM imbalance and abnormal glycerophospholipid metabolism contributed to impaired intestinal barrier function and inflammatory factor release, which may underlie RH-induced diarrhea, though PRH had a weaker effect.</p><p><strong>Conclusion: </strong>PRH alleviated RH-induced diarrhea by recovering GM balance, reducing ZO-1 and occludin expression, and decreasing the release of inflammatory factors. This mechanism may be linked to the reduced anthraquinone content. This study is the first to explore the mechanism of wine steaming in alleviating RH-induced diarrhea through small intestinal flora and serum metabolomics. It provides data to support the broader clinical use of RH and its safer application.</p>","PeriodicalId":16107,"journal":{"name":"Journal of Inflammation Research","volume":"17 ","pages":"7851-7868"},"PeriodicalIF":4.2,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Mitophagy and Ferroptosis in Sepsis-Induced ALI/ARDS: Molecular Mechanisms, Interactions and Therapeutic Prospects of Medicinal Plants. 脓毒症诱发的 ALI/ARDS 中的有丝分裂和铁蛋白沉积:药用植物的分子机制、相互作用和治疗前景。
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S488655
Huixin Cheng, Xuehan Wang, Juyi Yao, Chunbo Yang, Jian Liu

Sepsis is a common critical illness characterized by high mortality rates and a significant disease burden. In the context of sepsis-induced organ dysfunction, the lungs are among the initial organs affected, which may progress to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Recent studies have highlighted the crucial roles of mitophagy and ferroptosis in the development and progression of sepsis-induced ALI/ARDS. Identifying key convergence points in these processes may provide valuable insights for the treatment of this condition. In recent years, certain herbs and their bioactive compounds have demonstrated unique benefits in managing sepsis-induced ALI/ARDS by modulating mitophagy or ferroptosis. This review summary the mechanisms of mitophagy and ferroptosis, explores their interactions, and emphasizes their regulatory roles in the progression of sepsis-induced ALI/ARDS. Additionally, it offers a novel perspective on treatment strategies by summarizing various herbs and their bioactive compounds relevant to this condition.

败血症是一种常见的危重病,其特点是死亡率高、疾病负担重。在脓毒症诱发的器官功能障碍中,肺是最初受影响的器官之一,可能发展为急性肺损伤(ALI)和急性呼吸窘迫综合征(ARDS)。最近的研究强调了有丝分裂和铁蛋白沉积在脓毒症诱发的 ALI/ARDS 的发生和发展过程中的关键作用。确定这些过程中的关键汇合点可为治疗这种疾病提供有价值的见解。近年来,某些草药及其生物活性化合物通过调节有丝分裂或铁凋亡,在治疗脓毒症诱发的 ALI/ARDS 方面显示出独特的疗效。本综述总结了有丝分裂和铁突变的机制,探讨了它们之间的相互作用,并强调了它们在败血症诱发的 ALI/ARDS 进展过程中的调节作用。此外,它还总结了与该病症相关的各种草药及其生物活性化合物,为治疗策略提供了新的视角。
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引用次数: 0
Effect of Laparoscopic Inguinal Hernia Repairs on Inflammatory Factors, Oxidative Stress Levels and Postoperative Recovery. 腹腔镜腹股沟疝修补术对炎症因子、氧化应激水平和术后恢复的影响
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S480105
Bo Yang, Changhu Xie, Yuxing Lv, Yinquan Wang

Objective: To unravel the effects of different laparoscopic inguinal hernia repairs (IHRs) on inflammatory factors, oxidative stress, and postoperative recovery of inguinal hernia (IH) patients.

Methods: A total of 88 patients for laparoscopic treatment of IH were studied in a retrospective cohort, and were randomized into the transabdominal preperitoneal (TAPP) repair group (n = 44) and the total extraperitoneal (TEP) repair group (n = 44) according to the method of treatment. Patients in the TAPP group underwent laparoscopic TAPP IHR, while patients in the TEP group underwent laparoscopic TEP IHR. Visual analogue scores (VAS) were measured at 1, 3, and 7 d after repair. Gastrin (GAS), motilin (MTL), matrix metalloproteinase (MMP)-2, MMP-9, and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assessed by enzyme-linked immunosorbent assay. Superoxide dismutase (SOD) was tested by spectrophotometry and malondialdehyde (MDA) and β-endorphin (β-EP) were examined by radioimmunoprecipitation. Total antioxidant capacity (T-AOC) was evaluated by chemical colorimetry, quality of life was evaluated by SF-36, and fibrinogen (FIB), C-reactive protein (CRP), antitrypsin (al-AT), and interleukin-6 (IL-6) levels were determined by immunoturbidimetry. Complications and postoperative recurrence were recorded.

Results: VAS scores in the TEP group were lower than those in the TAPP group. Operative time, hospital stay, time for postoperative activity out of bed, and time taken to exhaust were shorter in the TEP group than in the TAPP group. Intraoperative blood loss was less in the TEP group than in the TAPP group. GAS, MTL, SOD, and T-AOC were higher, and MDA, β-EP, CRP, FIB, alAT, IL-6, MMP-2, MMP-9, and TIMP-1 were lower in the TEP group than the TAPP group. Quality of life was improved in the TEP group compared with the TAPP group. There was no significant difference in the rate of postoperative complications and recurrence rates between both groups of patients.

Conclusion: For IHs, laparoscopic TEP repair can effectively relieve pain, reduce inflammatory factors and oxidative stress indices, and facilitate postoperative recovery.

目的揭示不同腹腔镜腹股沟疝修补术(IHR)对腹股沟疝(IH)患者炎症因子、氧化应激和术后恢复的影响:回顾性队列共研究了88例腹腔镜治疗IH的患者,并根据治疗方法随机分为经腹腔腹膜前(TAPP)修补术组(44例)和全腹膜外(TEP)修补术组(44例)。TAPP 组患者接受腹腔镜 TAPP IHR,TEP 组患者接受腹腔镜 TEP IHR。在修复后 1、3 和 7 d 测量视觉模拟评分(VAS)。胃泌素(GAS)、动情素(MTL)、基质金属蛋白酶(MMP)-2、MMP-9 和金属蛋白酶组织抑制剂-1(TIMP-1)通过酶联免疫吸附试验进行评估。超氧化物歧化酶(SOD)采用分光光度法检测,丙二醛(MDA)和β-内啡肽(β-EP)采用放射免疫沉淀法检测。化学比色法评估了总抗氧化能力(T-AOC),SF-36评估了生活质量,免疫比浊法测定了纤维蛋白原(FIB)、C反应蛋白(CRP)、抗胰蛋白酶(al-AT)和白细胞介素-6(IL-6)水平。记录并发症和术后复发情况:结果:TEP 组的 VAS 评分低于 TAPP 组。TEP 组的手术时间、住院时间、术后下床活动时间和排气时间均短于 TAPP 组。TEP 组的术中失血量少于 TAPP 组。与 TAPP 组相比,TEP 组的 GAS、MTL、SOD 和 T-AOC 较高,MDA、β-EP、CRP、FIB、alAT、IL-6、MMP-2、MMP-9 和 TIMP-1 较低。与 TAPP 组相比,TEP 组的生活质量有所改善。两组患者的术后并发症发生率和复发率无明显差异:结论:对于 IHs,腹腔镜 TEP 修复术可有效缓解疼痛,减少炎症因子和氧化应激指数,促进术后恢复。
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引用次数: 0
Clinical Features and Electroencephalogram Analysis of Brain Network Functional Connectivity in Anti-Leucine-Rich Glioma-Inactivated 1 Antibody Encephalitis. 抗富含亮氨酸胶质瘤激活的 1 型抗体脑炎脑网络功能连接的临床特征和脑电图分析
IF 4.2 2区 医学 Q2 IMMUNOLOGY Pub Date : 2024-10-29 eCollection Date: 2024-01-01 DOI: 10.2147/JIR.S485190
Xiaosu Guo, Huimin Shi, Yuteng Sun, Yuan Xing, Xin Guo, Zhiyuan Shen, Mengyi Zheng, Yaxin Zhang, Yicun Jia, Ye Li, Junqiang Bao, Shujuan Tian

Purpose: To summarize the clinical manifestations, laboratory findings, and magnetic resonance imaging (MRI) characteristics of anti-leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis (anti-LGI1 antibody encephalitis) and explore the electroencephalogram (EEG) features.

Patients and methods: We retrospectively analyzed the medical history of 16 patients diagnosed with anti-LGI1 antibody encephalitis at the First Hospital of Hebei Medical University from 2021 to 2023. EEGs of patients with anti-LGI1 antibody encephalitis and healthy individuals were analyzed. Based on Video-EEG signal analysis of EEG δ, θ, α, β frequency bands, weighted phase lag index values were calculated to form brain network matrices, studying differences in coherence between brain regions of patients with anti-LGI1 antibody encephalitis and healthy individuals.

Results: Patients with anti-LGI1 antibody encephalitis often presented with subacute onset seizures and cognitive decline. Routine test of cerebrospinal fluid was mostly normal. Serum testing revealed hyponatremia in 62.50% of patients, along with positive serum antinuclear antibodies, decreased vitamin B12, and abnormal cytokines such as interleukin-6. Head MRI revealed abnormal lesions related to the disease in seven cases (43.75%), mainly located in the unilateral or bilateral frontal and temporal lobes of the hippocampus. The EEG mainly showed generalized and focal slow waves, sometimes with focal discharges. Brain network functional connectivity analysis found a significant weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands. Intravenous pulse corticosteroids and intravenous immunoglobulin are first-line immunotherapies for anti-LGI1 antibody-related encephalitis. The disease recovery and cognitive decline improved in most patients.

Conclusion: Anti-LGI1 antibody encephalitis is characterized by seizures and cognitive dysfunction. Serum may show abnormalities in immune indicators such as cytokines. Head MRI mainly reveals abnormal signals in the frontal-temporal lobes and the hippocampus. EEG brain network connectivity analysis reveals characteristic weakening of functional connections in the frontal-temporal lobe in the δ and β frequency bands.

目的:总结富亮氨酸胶质瘤灭活1(LGI1)抗体脑炎(抗LGI1抗体脑炎)的临床表现、实验室检查结果和磁共振成像(MRI)特征,并探讨脑电图(EEG)特征:我们回顾性分析了2021年至2023年在河北医科大学第一医院确诊的16例抗LGI1抗体脑炎患者的病史。分析了抗 LGI1 抗体脑炎患者和健康人的脑电图。根据对脑电图δ、θ、α、β频段的视频脑电信号分析,计算加权相位滞后指数值,形成脑网络矩阵,研究抗LGI1抗体脑炎患者与健康人脑区相干性的差异:结果:抗LGI1抗体脑炎患者通常表现为亚急性发作和认知能力下降。脑脊液常规检查大多正常。血清检测显示,62.50%的患者出现低钠血症,血清抗核抗体阳性,维生素 B12 减少,白细胞介素-6 等细胞因子异常。头部核磁共振成像(MRI)显示,7 例患者(43.75%)出现与疾病相关的异常病变,主要位于海马的单侧或双侧额叶和颞叶。脑电图主要显示泛发性和局灶性慢波,有时伴有局灶性放电。脑网络功能连接分析发现,额颞叶δ和β频段的功能连接明显减弱。静脉注射脉冲皮质类固醇和静脉注射免疫球蛋白是抗LGI1抗体相关脑炎的一线免疫疗法。结论:抗-LGI1 抗体相关性脑炎是一种常见的慢性疾病,大多数患者的病情恢复和认知能力下降都有所改善:结论:抗 LGI1 抗体脑炎的特点是癫痫发作和认知功能障碍。血清可显示细胞因子等免疫指标异常。头部磁共振成像主要显示额颞叶和海马的异常信号。脑电图脑网络连接分析显示,额颞叶δ和β频段的功能连接特征性减弱。
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引用次数: 0
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Journal of Inflammation Research
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