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Mechanistic Insights into Tanshinone IIA in the Amelioration of Post-Thyroidectomy Hypoparathyroidism 丹参酮 IIA 在改善甲状腺切除术后甲状旁腺功能减退症方面的机理研究
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024052462
Xiaoyu Qian, Lin Li, Liang Chen, Chao Shen, Jian Tang
Background: Thyroidectomy causes impaired blood supply to the parathyroid glands, which leads to hypoparathyroidism. Tanshinone IIA (Tan IIA) is helpful in blood activation and cardiovascular protection. Therefore, the efficacy of Tan IIA in improving hypoparathyroidism was explored in this study.
Methods: New Zealand white rabbits were utilized to establish a unilateral parathyroid gland ischemia injury model. The model was created by selectively ligating the main blood supply vessel of one parathyroid gland, and the rabbits were then divided into three groups receiving 1, 5, and 10 mg/kg of Tan IIA. Serum calcium and parathyroid hormone (PTH) levels were measured using specialized assay kits. Immunohistochemistry was used to assess the microvessel density (MVD) in parathyroid glands. Western blotting (WB) was used to analyze protein expression related to the PI3K/AKT signaling pathway and the pathway-associated HIF-1α and VEGF. Moreover, MMP-2 and MMP-9 involved in angiogenesis were detected by WB.
Results: Tan IIA treatment effectively restored serum calcium and PTH levels in a dose-dependent manner. Notably, MVD in the parathyroid glands increased significantly, especially at higher doses. The Tan IIA treatment also elevated the p-PI3K/PI3K and p-AKT/AKT ratios, indicating that the PI3K/AKT pathway was reactivated. Moreover, Tan IIA significantly restored the decreased expression levels of VEGF and HIF-1α caused by parathyroid surgery. Additionally, Tan IIA increased MMP-2 and MMP-9 levels.
Conclusion: Tan IIA activates the PI3K/AKT pathway, promotes angiogenesis by modulating VEGF, HIF-1α, MMP-2, and MMP-9, thereby further enhancing MVD within the parathyroid glands. This study demonstrates that Tan IIA improved post-thyroidectomy hypoparathyroidism.
背景:甲状腺切除术会导致甲状旁腺供血障碍,从而导致甲状旁腺功能减退。丹参酮 IIA(Tan IIA)有助于活血和保护心血管。因此,本研究探讨了丹参酮 IIA 对改善甲状旁腺功能减退症的疗效:方法:利用新西兰白兔建立单侧甲状旁腺缺血损伤模型。方法:利用新西兰白兔建立单侧甲状旁腺缺血损伤模型,选择性地结扎一侧甲状旁腺的主要供血血管,然后将兔子分为三组,分别服用1、5和10毫克/千克的Tan IIA。血清钙和甲状旁腺激素(PTH)水平是用专门的检测试剂盒测定的。免疫组化法用于评估甲状旁腺的微血管密度(MVD)。Western blotting(WB)用于分析与PI3K/AKT信号通路以及与该通路相关的HIF-1α和VEGF相关的蛋白质表达。此外,还通过 WB 检测了参与血管生成的 MMP-2 和 MMP-9:结果:坦 IIA 治疗可有效恢复血钙和 PTH 水平,且呈剂量依赖性。值得注意的是,甲状旁腺的 MVD 显著增加,尤其是在高剂量时。Tan IIA治疗还升高了p-PI3K/PI3K和p-AKT/AKT比率,表明PI3K/AKT通路被重新激活。此外,Tan IIA还能明显恢复甲状旁腺手术导致的血管内皮生长因子和HIF-1α表达水平的下降。此外,Tan IIA还能提高MMP-2和MMP-9的水平:Tan IIA可激活PI3K/AKT通路,通过调节VEGF、HIF-1α、MMP-2和MMP-9促进血管生成,从而进一步增强甲状旁腺内的MVD。本研究表明,丹参二酮能改善甲状腺切除术后的甲状旁腺功能减退症。
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引用次数: 0
Diagnostic and Prognostic Value of Peripheral Neutrophil CD64 Index in Elderly Patients with Community-Acquired Pneumonia 社区获得性肺炎老年患者外周中性粒细胞 CD64 指数的诊断和预后价值
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024050769
Yan Li, Jing Zhang, Suhang Wang, Jie Cao
Community-acquired pneumonia (CAP) is a leading cause of hospitalization and mortality in the elderly. The peripheral blood neutrophil CD64 (nCD64) index is increasingly recognized for its association with poor pneumonia prognosis. A comprehensive investigation involving 128 elderly patients diagnosed with CAP, including 96 with non-severe CAP and 32 with severe CAP, from January 2020 to January 2021 was performed. The nCD64 index, CD4+, CD8+, C-reactive protein (CRP), white blood cell (WBC) count, procalcitonin (PCT), neutrophil (NEUT), and B lymphocyte count were determined using flow cytometry. Our findings reveal that patients with severe CAP exhibited significantly higher levels of nCD64 index, NEUT, WBC, CRP, and PCT. Intriguingly, lower CRP, nCD64 index, CURB-65 score, and PCT were associated with a higher survival rate. Notably, the nCD64 index demonstrated remarkable predictive efficiency for 28-d survival in CAP patients [area under the curve (AUC) = 0.907], surpassing other markers and even showing enhanced predictive power when combined with the CURB-65 score (AUC = 0.905). Furthermore, a negative association was observed between the nCD64 index and both CD4+, CD4+/CD8+ ratios, and B lymphocytes, highlighting its potential role in immune dysregulation. These findings underscore the critical importance of the nCD64 index in the early diagnosis, risk stratification, and prognostic evaluation of infections and immune responses in elderly CAP patients.
社区获得性肺炎(CAP)是老年人住院和死亡的主要原因。外周血中性粒细胞 CD64(nCD64)指数与肺炎预后不良的关系日益得到认可。2020 年 1 月至 2021 年 1 月期间,对 128 名确诊为 CAP 的老年患者进行了全面调查,其中包括 96 名非重症 CAP 患者和 32 名重症 CAP 患者。采用流式细胞术测定了 nCD64 指数、CD4+、CD8+、C 反应蛋白(CRP)、白细胞(WBC)计数、降钙素原(PCT)、中性粒细胞(NEUT)和 B 淋巴细胞计数。我们的研究结果表明,重症 CAP 患者的 nCD64 指数、NEUT、WBC、CRP 和 PCT 水平明显较高。耐人寻味的是,较低的 CRP、nCD64 指数、CURB-65 评分和 PCT 与较高的存活率相关。值得注意的是,nCD64 指数对 CAP 患者 28 天生存率的预测效果显著[曲线下面积(AUC)= 0.907],超过了其他标志物,甚至在与 CURB-65 评分(AUC = 0.905)相结合时显示出更强的预测能力。此外,还观察到 nCD64 指数与 CD4+、CD4+/CD8+ 比率和 B 淋巴细胞之间存在负相关,这突出表明了它在免疫失调中的潜在作用。这些发现强调了 nCD64 指数在老年 CAP 患者感染和免疫反应的早期诊断、风险分层和预后评估中的重要性。
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引用次数: 0
Serum interleukin 6 and ferritin levels are the independent risk factors for pneumonia in elderly patients 血清白细胞介素 6 和铁蛋白水平是老年患者肺炎的独立风险因素
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024051340
Hao Yuan, Jing Tian, Lu Wen
Pneumonia is a common infection in elderly patients. We explored the correlations of serum interleukin-6 (IL-6) and ferritin (SF) levels with immune function/disease severity in elderly pneumonia patients. Study subjects included 151 pneumonia/58 healthy geriatrics, with their age/sex/body mass index (BMI)/disease course and severity/blood pressure/C-reactive protein (CRP)/procalcitonin (PCT)/smoking status documented. The disease severity was evaluated by pneumonia severity index (PSI). T helper 17 (Th17)/regulatory T (Treg) cell ratios and IL-6/SF/immunoglobulin G (IgG)/Th17 cytokine (IL-21)/Treg cytokine (IL-10) levels were assessed using flow cytometry/ELISA. The correlations between these indexes/independent risk factors in elderly patients with severe pneumonia were evaluated by Spearman/multivariate logistic regression analyses. Patients showed obvious differences in smoking and CRP/PCT levels. Pneumonia patients exhibited up-regulated Th17 cell ratio and serum IL-6/SF/IL-21/IL-10/IgG levels, down-regulated Treg cell ratio, and more evident differences were noted in severe cases. Serum IL-6/SF levels were positively correlated with disease severity, immune function, and IL-21/IL-10/IgG levels. Smoking history and IL-6/SF levels were identified as independent risk factors in severe pneumonia geriatrics. Collectively, serum IL-6 and SF levels in elderly pneumonia patients were conspicuously positively correlated with disease severity and IL-21/IL-10/IgG levels. CRP, PCT, IL-6, and SF levels were independent risk factors for severe pneumonia in elderly patients.
肺炎是老年患者的一种常见感染。我们探讨了老年肺炎患者血清白细胞介素-6(IL-6)和铁蛋白(SF)水平与免疫功能/疾病严重程度的相关性。研究对象包括151名肺炎患者/58名健康老年患者,记录了他们的年龄/性别/体重指数(BMI)/病程和严重程度/血压/反应蛋白(CRP)/降钙素原(PCT)/吸烟状况。疾病严重程度通过肺炎严重程度指数(PSI)进行评估。使用流式细胞术/ELISA 评估了 T 辅助细胞 17(Th17)/调节性 T(Treg)细胞比率和 IL-6/SF/ 免疫球蛋白 G(IgG)/Th17 细胞因子(IL-21)/Treg 细胞因子(IL-10)水平。通过斯皮尔曼/多元逻辑回归分析评估了老年重症肺炎患者这些指标/独立危险因素之间的相关性。患者在吸烟和 CRP/PCT 水平方面存在明显差异。肺炎患者的Th17细胞比例和血清IL-6/SF/IL-21/IL-10/IgG水平上调,Treg细胞比例下调,重症患者的差异更为明显。血清IL-6/SF水平与疾病严重程度、免疫功能和IL-21/IL-10/IgG水平呈正相关。吸烟史和 IL-6/SF 水平被认为是老年重症肺炎的独立危险因素。总之,老年肺炎患者的血清IL-6和SF水平与疾病严重程度和IL-21/IL-10/IgG水平呈显著正相关。CRP、PCT、IL-6和SF水平是老年重症肺炎患者的独立危险因素。
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引用次数: 0
Effects of different doses of dexmedetomidine on the prevention of postoperative sleep disturbance and serum neurotransmitter level in patients under general anesthesia 不同剂量右美托咪定对预防全身麻醉患者术后睡眠障碍和血清神经递质水平的影响
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024051294
Huifei Lu, Fei He, Ying Huang, Zhongliang Wei
Postoperative sleep disturbance is a common issue that affects recovery in patients undergoing general anesthesia. Dexmedetomidine (Dex) has a potential role in improving postoperative sleep quality. Thus, we evaluated the effects of different doses of Dex on postoperative sleep disturbance and serum neurotransmitters in patients undergoing radical gastrectomy under general anesthesia. Patients were assigned to the control, NS, and Dex (Dex-L/M/H) groups based on different treatment doses [0.2, 0.4, 0.6 μg/(kg·h)]. The Athens Insomnia Scale (AIS) and ELISA kits were used to assess sleep disturbance and serum neurotransmitter (GABA, 5-HT, NE) levels before surgery and on postoperative days 1/4/7. The effects of different doses of Dex on postoperative sleep disturbance incidence and serum neurotransmitter levels were analyzed by Fisher exact test, one-way and repeated measures ANOVA. Patients had no differences in gender, age, body mass index, operation time, and bleeding volume. Different doses of Dex reduced the postoperative AIS score of patients under general anesthesia, improved their sleep, and increased serum levels of 5-HT, NE, and GABA. Furthermore, the effects were dose-dependent within the range of safe clinical use doses. Specifically, Dex at doses of 0.2, 0.4, 0.6 μg/(kg·h) reduced postoperative AIS score, elevated serum neurotransmitter levels, and reduced postoperative sleep disturbance incidence. Collectively, Dex has a potential preventive effect on postoperative sleep disturbance in patients undergoing general anesthesia for radical gastrectomy. The optimal dose of Dex is between 0.2 and 0.6 μg/(kg·h), which significantly reduces the incidence of pos
术后睡眠障碍是影响全身麻醉患者康复的常见问题。右美托咪定(Dex)具有改善术后睡眠质量的潜在作用。因此,我们评估了不同剂量的右美托咪定对全身麻醉下接受根治性胃切除术的患者术后睡眠障碍和血清神经递质的影响。根据不同的治疗剂量[0.2、0.4、0.6 μg/(kg-h)],患者被分配到对照组、NS 组和 Dex(Dex-L/M/H)组。采用雅典失眠量表(AIS)和酶联免疫吸附试剂盒评估术前和术后第1/4/7天的睡眠障碍和血清神经递质(GABA、5-羟色胺、NE)水平。不同剂量的Dex对术后睡眠障碍发生率和血清神经递质水平的影响通过费舍尔精确检验、单因素和重复测量方差分析进行了分析。患者的性别、年龄、体重指数、手术时间和出血量均无差异。不同剂量的 Dex 可降低全身麻醉患者的术后 AIS 评分,改善其睡眠,提高血清中 5-羟色胺、NE 和 GABA 的水平。此外,在临床安全使用剂量范围内,这些效果与剂量有关。具体来说,0.2、0.4、0.6 μg/(kg-h)剂量的 Dex 可降低术后 AIS 评分、升高血清神经递质水平并减少术后睡眠障碍的发生率。总之,Dex 对接受根治性胃切除术全身麻醉的患者术后睡眠障碍具有潜在的预防作用。地塞米松的最佳剂量为 0.2 至 0.6 μg/(kg-h),可显著降低术后睡眠障碍的发生率。
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引用次数: 0
Identification of Metabolism-Related Prognostic Biomarkers and Immune Features of Head and Neck Squamous Cell Carcinoma 头颈部鳞状细胞癌代谢相关预后生物标志物和免疫特征的鉴定
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024050754
Rongjin Zhou, Junguo Wang
We aimed to identify an effective metabolic subtype and risk score to predict survival and immunotherapy response in head and neck squamous cell carcinoma (HNSCC). Data were obtained from an online database. We screened significant prognostic metabolism-related genes between the normal and tumor groups using a series of bioinformatics methods. Based on the selected prognostic genes, we conducted a subtype analysis to identify significantly different subtypes in HNSCC. We then investigated survival, immune features, and hallmark differences among different subtypes. LASSO was utilized to identify optimal genes for the risk score model construction. Finally, distribution of the risk score samples was analyzed for different subtypes. A total of 32 significantly prognostic metabolism-related genes were screened, and all samples were grouped into two subtypes: cluster 1 and cluster 2. Cluster 1 had worse survival. Different immune cell infiltration (CD8 T cells, macrophages, and regulatory T cells) and immune checkpoint gene expression (PD-1 and CLAT-4) were observed between the two clusters. Twelve optimal genes were involved in risk score model, and high-risk group had poorer survival. Cluster 1 contained more high-risk samples (60%). Finally, four genes CAV1, GGT6, PYGL, and HS3ST1 were identified as significantly related to immune cells, and these genes were differentially expressed in the normal oral epithelial cells and HNSCC cells. The subtypes and risk score model in the study provide a promising biomarker for prognosis and immunotherapy response.
我们旨在确定一种有效的代谢亚型和风险评分,以预测头颈部鳞状细胞癌(HNSCC)的生存率和免疫疗法反应。数据来自在线数据库。我们使用一系列生物信息学方法筛选了正常组和肿瘤组之间重要的预后代谢相关基因。根据筛选出的预后基因,我们进行了亚型分析,以确定HNSCC中明显不同的亚型。然后,我们研究了不同亚型的生存率、免疫特征和标志性差异。我们利用 LASSO 来确定构建风险评分模型的最佳基因。最后,我们分析了不同亚型的风险评分样本分布情况。共筛选出32个对预后有明显影响的代谢相关基因,并将所有样本分为两个亚型:群组1和群组2。第 1 组的生存率较低。在两个群组之间观察到了不同的免疫细胞浸润(CD8 T细胞、巨噬细胞和调节性T细胞)和免疫检查点基因表达(PD-1和CLAT-4)。风险评分模型涉及12个最佳基因,高风险组的生存率较低。群组1包含更多的高风险样本(60%)。最后,四个基因CAV1、GGT6、PYGL和HS3ST1被认定与免疫细胞显著相关,这些基因在正常口腔上皮细胞和HNSCC细胞中的表达存在差异。该研究中的亚型和风险评分模型为预后和免疫治疗反应提供了一种有前景的生物标志物。
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引用次数: 0
Clinical significance of serum CTRP3 level in the prediction of cardiac dysfunction and intestinal mucosal barrier dysfunction in patients with severe acute pancreatitis 血清 CTRP3 水平在预测重症急性胰腺炎患者心脏功能障碍和肠黏膜屏障功能障碍方面的临床意义
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024051292
Qiang Shao, Lin Sun
C1q/tumor necrosis factor-related protein 3 (CTRP3) has been demonstrated to play a protective role in mice with severe acute pancreatitis (SAP). However, its clinical significance in SAP remains unknown. This study was conducted to explore the clinical values of serum C1q/tumor necrosis factor-related protein 3 (CTRP3) level in the diagnosis of cardiac dysfunction (CD) and intestinal mucosal barrier dysfunction (IMBD) in SAP. Through RT-qPCR, we observed decreased CTRP3 level in the serum of SAP patients. Serum CTRP3 level was correlated with C-reactive protein, procalcitonin, creatine, modified computed tomography severity index score, and Acute Physiology and Chronic Health Evaluation II score. The receiver-operating characteristic curve revealed that CTRP3 serum level < 1.005 was conducive to SAP diagnosis with 72.55% sensitivity and 60.00% specificity, CTRP3 < 0.8400 was conducive to CD diagnosis with 80.49% sensitivity and specificity 65.57%, CTRP3 < 0.8900 was conducive to IMBD diagnosis with 94.87% sensitivity and 63.49% specificity, and CTRP3 < 0.6250 was conducive to the diagnosis of CD and IMBD co-existence with 65.22% sensitivity and 89.87% specificity. Generally, CTRP3 was downregulated in the serum of SAP patients and served as a candidate biomarker for the diagnosis of SAP and SAP-induced CD and IMBD.
C1q/ 肿瘤坏死因子相关蛋白 3(CTRP3)已被证实在重症急性胰腺炎(SAP)小鼠体内发挥保护作用。然而,其在 SAP 中的临床意义仍然未知。本研究旨在探讨血清 C1q/肿瘤坏死因子相关蛋白 3(CTRP3)水平在诊断 SAP 中心脏功能障碍(CD)和肠粘膜屏障功能障碍(IMBD)中的临床价值。通过 RT-qPCR,我们观察到 SAP 患者血清中 CTRP3 水平下降。血清 CTRP3 水平与 C 反应蛋白、降钙素原、肌酸、改良计算机断层扫描严重程度指数评分以及急性生理学和慢性健康评估 II 评分相关。接受者工作特征曲线显示,CTRP3 血清水平 < 1.005 有利于 SAP 诊断,灵敏度为 72.55%,特异度为 60.00%;CTRP3 < 0.8400 有利于 CD 诊断,灵敏度为 80.49%,特异度为 65.57%,CTRP3 <0.8900有利于IMBD诊断,灵敏度为94.87%,特异度为63.49%,CTRP3 <0.6250有利于CD和IMBD并存的诊断,灵敏度为65.22%,特异度为89.87%。总体而言,CTRP3在SAP患者血清中下调,可作为诊断SAP和SAP诱发的CD和IMBD的候选生物标志物。
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引用次数: 0
The protective effect and mechanism of mild hypothermia on pig lung injury after cardiopulmonary resuscitation 轻度低温对心肺复苏后猪肺损伤的保护作用及机制
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024052420
Jinlin Ren, Fangfang Zhu, Dongdong Sang, Mulin Cong, Shujuan Jiang
Objective: To explore the protective effect and mechanism of mild hypothermia on lung tissue damage after cardiopulmonary resuscitation in pigs. Methods: In this experiment, we electrically stimulated 16 pigs (30±2kg) for 10 minutes to cause ventricular fibrillation. The successfully resuscitated animals were randomly divided into two groups, a mild hypothermia group and a control group. We took arterial blood 0.5h, 1h, 3h and 6h after ROSC recovery in the two groups of animals for blood gas analysis. We observed the structural changes of lung tissue under an electron microscope and calculate the wet weight/dry weight (W/D) ratio. We quantitatively analyzed the expression differences of representative inflammatory factors (IL-6 and TNF-α) through the Elisa test. We detected the expression levels of Bax, Bcl-2 and Caspase-3 proteins in lung tissues by Western blot. Results: The 3 h and 6 h after spontaneous circulation was restored, compared with the control group, PaO2/FiO2 decreased significantly (P <0.05). In addition, the pathological changes, lung W/D and lung MDA of the mild hypothermia group were better than those of the control group. The levels of IL-6 and TNF-α in the lung tissue of the mild hypothermia group were significantly lower than those of the control group (P <0.05). The content of Caspase-3 and Bax in the mild hypothermia group was significantly lower than that of the control group. Conclusion: Our experiments have shown that mild hypothermia can reduce lung tissue damage after cardiopulmonary resuscitation.
目的探讨轻度低温对猪心肺复苏后肺组织损伤的保护作用和机制。方法实验中,我们对 16 头猪(30±2 千克)进行了 10 分钟的电刺激,以引起心室颤动。成功复苏的动物被随机分为两组,即轻度低体温组和对照组。我们分别在两组动物ROSC恢复后0.5小时、1小时、3小时和6小时抽取动脉血进行血气分析。在电子显微镜下观察肺组织的结构变化,并计算湿重/干重比(W/D)。通过Elisa试验定量分析代表性炎症因子(IL-6和TNF-α)的表达差异。通过 Western 印迹检测肺组织中 Bax、Bcl-2 和 Caspase-3 蛋白的表达水平。结果自发循环恢复后3 h和6 h,与对照组相比,PaO2/FiO2明显下降(P <0.05)。此外,轻度低体温组的病理变化、肺W/D和肺MDA均优于对照组。轻度低体温组肺组织中IL-6和TNF-α的水平明显低于对照组(P <0.05)。轻度低体温组 Caspase-3 和 Bax 的含量明显低于对照组。结论我们的实验表明,轻度低体温可以减轻心肺复苏后的肺组织损伤。
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引用次数: 0
Exploring mechanism of Zilongjin in treating lung adenocarcinoma based on network pharmacology combined with experimental verification 基于网络药理学结合实验验证探索紫龙胆治疗肺腺癌的机制
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2024-01-01 DOI: 10.1615/critrevimmunol.2024051316
Kang Zhang, Xiaoqun Chen
Objective: Zilongjin (ZLJ) is a common Traditional Chinese medicine for lung adenocarcinoma (LUAD) treatment. However, its mechanisms of action remain to be elucidated. Network pharmacology was used to explore underlying mechanisms of ZLJ on LUAD.Methods: The disease-related targets were found out from the GeneCards and DisGeNET databases. Active compounds and targets of ZLJ were obtained from the HIT, TCMSP, and TCMID databases. Then, the protein-protein interaction (PPI) network was built by STRING database to identify core-hub targets of ZLJ in LUAD. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enriched regulatory pathways of targets. Molecular docking analysis were used to evaluate interactions between potential targets and active compounds. Finally, qRT-PCR method was further to verify the results of network pharmacology.Results: A total of 124 LUAD-related targets of ZLJ and 5 active compounds of ZLJ from the relevant databases were screened out. Among these target proteins, JUN, CDH1, PPARG, and FOS were core-hub genes in PPI network. GO and KEGG pathway enrichment analysis indicated that these targets might regulate the PPAR signaling pathway in LUAD. JUN, PPARG, and FOS levels were upregulated, while CDH1 level was downregulated in LUAD cells.Conclusion: This study discerned that ZLJ may target genes such as JUN, FOS, PPARG, and CDH1 via the PPAR signaling pathway in LUAD, offering foundational insights for further exploration of ZLJ in clinical applications.
目的:紫龙胆(ZLJ)是治疗肺腺癌(LUAD)的常用中药。然而,其作用机制仍有待阐明。本研究采用网络药理学方法来探讨 ZLJ 对肺腺癌的潜在作用机制:方法:从GeneCards和DisGeNET数据库中找到与疾病相关的靶点。从 HIT、TCMSP 和 TCMID 数据库中获取 ZLJ 的活性化合物和靶点。然后,利用 STRING 数据库构建了蛋白-蛋白相互作用(PPI)网络,以确定 ZLJ 在 LUAD 中的核心-枢纽靶点。接着,利用基因本体论(GO)和京都基因组百科全书(KEGG)分析了靶点的富集调控通路。分子对接分析用于评估潜在靶点与活性化合物之间的相互作用。最后,进一步采用qRT-PCR方法验证了网络药理学的结果:结果:从相关数据库中筛选出了124个ZLJ的LUAD相关靶点和5个ZLJ的活性化合物。在这些靶蛋白中,JUN、CDH1、PPARG和FOS是PPI网络中的核心枢纽基因。GO和KEGG通路富集分析表明,这些靶标可能调控LUAD中的PPAR信号通路。在LUAD细胞中,JUN、PPARG和FOS水平上调,而CDH1水平下调:本研究发现,ZLJ可通过PPAR信号通路靶向LUAD中的JUN、FOS、PPARG和CDH1等基因,为进一步探索ZLJ的临床应用提供了基础性见解。
{"title":"Exploring mechanism of Zilongjin in treating lung adenocarcinoma based on network pharmacology combined with experimental verification","authors":"Kang Zhang, Xiaoqun Chen","doi":"10.1615/critrevimmunol.2024051316","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051316","url":null,"abstract":"Objective: Zilongjin (ZLJ) is a common Traditional Chinese medicine for lung adenocarcinoma (LUAD) treatment. However, its mechanisms of action remain to be elucidated. Network pharmacology was used to explore underlying mechanisms of ZLJ on LUAD.\u0000Methods: The disease-related targets were found out from the GeneCards and DisGeNET databases. Active compounds and targets of ZLJ were obtained from the HIT, TCMSP, and TCMID databases. Then, the protein-protein interaction (PPI) network was built by STRING database to identify core-hub targets of ZLJ in LUAD. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enriched regulatory pathways of targets. Molecular docking analysis were used to evaluate interactions between potential targets and active compounds. Finally, qRT-PCR method was further to verify the results of network pharmacology.\u0000Results: A total of 124 LUAD-related targets of ZLJ and 5 active compounds of ZLJ from the relevant databases were screened out. Among these target proteins, JUN, CDH1, PPARG, and FOS were core-hub genes in PPI network. GO and KEGG pathway enrichment analysis indicated that these targets might regulate the PPAR signaling pathway in LUAD. JUN, PPARG, and FOS levels were upregulated, while CDH1 level was downregulated in LUAD cells.\u0000Conclusion: This study discerned that ZLJ may target genes such as JUN, FOS, PPARG, and CDH1 via the PPAR signaling pathway in LUAD, offering foundational insights for further exploration of ZLJ in clinical applications.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"59 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139551724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Enhancing Human Treg Cell Induction through Engineered Dendritic Cells and Zinc Supplementation 通过工程树突状细胞和锌补充剂增强人类 Treg 细胞诱导能力
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 10.1615/critrevimmunol.2023050325
Nisar Shaikh, Xiao-Bing Zhang, Maisa Abdalla, David Baylink, Xiaolei Tang
Regulatory T (Treg) cells hold promise for the ultimate cure of immune-mediated diseases. However, how to effectively restore Treg function in patients remains unknown. Previous reports suggest that activated dendritic cells (DCs) de novo synthesize locally high concentrations of 1,25-dihydroxy vitamin D, i.e., the active vitamin D or 1,25(OH)2D by upregulating the expression of 25-hydroxy vitamin D 1α-hydroxylase. Although 1,25(OH)2D has been shown to induce Treg cells, DC-derived 1,25(OH)2D only serves as a checkpoint to ensure well-balanced immune responses. Our animal studies have shown that 1,25(OH)2D requires high concentrations to generate Treg cells, which can cause severe side effects. In addition, our animal studies have also demonstrated that dendritic cells (DCs) overexpressing the 1α-hydroxylase de novo synthesize the effective Treg-inducing 1,25(OH)2D concentrations without causing the primary side effect of hypercalcemia (i.e., high blood calcium levels). This study furthers our previous animal studies and explores the efficacy of the 1α-hydroxylase-overexpressing DCs in inducing human CD4+FOXP3+ regulatory T (Treg) cells. We discovered that the Treg-inducing doses of 1,25(OH)2D were within a range, not the higher, the better. Additionally, our data corroborated that the 1α-hydroxylase-overexpressing DCs synthesized 1,25(OH)2D within this concentration range in vivo, thus facilitating effective Treg cell induction. Moreover, this study demonstrated that α-hydroxylase expression levels were pivotal for DCs to induce Treg cells because physiological 25(OH)D levels were sufficient for the engineered but not parental DCs to enhance Treg cell induction. Int
调节性 T(Treg)细胞有望最终治愈免疫介导疾病。然而,如何有效恢复患者的 Treg 功能仍是未知数。以前的报告表明,活化的树突状细胞(DC)通过上调 25- 羟基维生素 D 1α- 羟化酶的表达,在局部从头合成高浓度的 1,25-二羟基维生素 D,即活性维生素 D 或 1,25(OH)2D。虽然 1,25(OH)2D 已被证明能诱导 Treg 细胞,但 DC 衍生的 1,25(OH)2D 只是确保免疫反应平衡的一个检查点。我们的动物实验表明,1,25(OH)2D 需要高浓度才能生成 Treg 细胞,而高浓度会导致严重的副作用。此外,我们的动物实验还证明,过表达 1α- 羟化酶的树突状细胞(DCs)能从头合成有效的 Treg 诱导浓度的 1,25(OH)2D,而不会引起高钙血症(即高血钙)这一主要副作用。这项研究进一步推进了我们之前的动物实验,并探索了1α-羟化酶外表达的DC在诱导人类CD4+FOXP3+调节性T(Treg)细胞方面的功效。我们发现,1,25(OH)2D的Treg诱导剂量在一定范围内,并非越高越好。此外,我们的数据还证实,1α-羟化酶脱表达的DC在体内合成的1,25(OH)2D也在这个浓度范围内,从而促进了Treg细胞的有效诱导。此外,这项研究还证明了α-羟化酶的表达水平是DC诱导Treg细胞的关键,因为生理25(OH)D水平足以使工程DC而非亲代DC增强Treg细胞诱导。中
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引用次数: 0
Platelet exosome-derived miR-223-3p regulates pyroptosis in the cell model of sepsis-induced acute renal injury by targeting mediates NLRP3 血小板外泌体来源的miR-223-3p通过靶向介导的NLRP3调节脓毒症诱导的急性肾损伤细胞模型中的焦亡
IF 1.3 4区 医学 Q4 IMMUNOLOGY Pub Date : 2023-12-01 DOI: 10.1615/critrevimmunol.2023051651
Peng Wan, Xiang Tan, Mengting Sheng, Yan Xiang, Peng Wang, Min Yu
Background The present study investigated that the roles and mechanisms of platelet-derived exosomes in sepsis-induced acute renal injury.Methods The blood samples of septic patients and healthy controls were collected for clinical examination. The plasma level of miR-223-3p and NLRP3 mRNA were analyzed by qRT-PCR and the serum IL-1β and creatinine levels were quantified by ELISA(Enzyme-linked immunosorbent assay). C57BL/6 mice injected with LPS(lipopolysaccharide) were employed as the animal model for sepsis-induced acute renal injury. Human coronary artery endothelial cells(HCAECs) were treated with TNF-α as a cellular model for sepsis-induced endothelial damages.Results The number of PMP(platelet-derived microparticles) in patients with sepsis was increased. The level of miR-223-3p in the platelet exosomes isolated from the serum sample in patients with sepsis was significantly lower than that of the healthy controls. The level of miR-223-3p was also decreased in the platelet exosomes of mouse model with sepsis-induced acute renal injury. Downregulating miR-223-3p promoted sepsis-induced acute renal injury in mice model, while the administration of miR-223-3p reduced the inflammation in endothelial cells of sepsis-induced acute renal injury. NLRP3 (NLR Family Pyrin Domain Containing 3) was identified as one target of miR-223-3p in the platelet exosomes of sepsis-induced acute kidney injury. MiR-223-3p attenuated NLRP3-induced pyroptosis in endothelial cell model of sepsis-induced acute kidney injury.Conclusion In summary, platelet exosome-derived miR-223-3p regulates NLRP3 inflammasome and pyroptosis of endothelial cells in model of sepsis-induced acute renal
本研究旨在探讨血小板源性外泌体在脓毒症急性肾损伤中的作用和机制。方法采集脓毒症患者及健康对照者的血液进行临床检查。采用qRT-PCR分析血浆miR-223-3p和NLRP3 mRNA水平,ELISA(酶联免疫吸附法)测定血清IL-1β和肌酐水平。以C57BL/6小鼠为研究对象,注射LPS(脂多糖)作为脓毒症致急性肾损伤动物模型。用TNF-α处理人冠状动脉内皮细胞(HCAECs)作为脓毒症诱导的内皮损伤的细胞模型。结果脓毒症患者血小板源性微粒(PMP)数量增加。脓毒症患者血清样本中分离的血小板外泌体中miR-223-3p水平明显低于健康对照组。脓毒症急性肾损伤小鼠模型血小板外泌体中miR-223-3p水平也降低。下调miR-223-3p可促进小鼠脓毒症急性肾损伤,而给予miR-223-3p可减轻脓毒症急性肾损伤内皮细胞的炎症反应。NLRP3 (NLR家族Pyrin Domain Containing 3)在脓毒症诱导的急性肾损伤的血小板外泌体中被鉴定为miR-223-3p的一个靶点。MiR-223-3p减轻nlrp3诱导的脓毒症急性肾损伤内皮细胞模型中的焦亡。综上所述,血小板外泌体来源的miR-223-3p调节脓毒症急性肾模型中NLRP3炎性体和内皮细胞焦亡
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Critical Reviews in Immunology
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