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Salvianolic acid B attenuates the inflammatory response in atherosclerosis by regulating MAPKs/ NF-κB signaling pathways in LDLR-/- mice and RAW264.7 cells 丹酚酸B通过调节LDLR-/-小鼠和RAW264.7细胞的MAPKs/ NF-κB信号通路,减轻动脉粥样硬化中的炎症反应
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221079468
Yifan Zhang, Xiaoteng Feng, Min Du, Jie Ding, Ping Liu
Objectives: Salvianolic acid B (Sal B) is the main effective water-soluble component of Salvia miltiorrhiza. In this study, the anti-inflammatory effect of Sal B was explored in high-fat-diet (HFD)-induced LDLR-/- mice and oxidized low-density-lipoprotein (ox-LDL)-induced or lipopolysaccharide (LPS)-induced RAW264.7 cells. Methods: The LDLR-/- mice were randomly divided into four groups after 12 weeks of high-fat diet. Then, the mice were administrated with 0.9% saline or Sal B (25 mg/kg) or Atorvastatin (1.3 mg/kg) for 12 weeks. RAW 264.7 cells were induced with ox-LDL/LPS, or ox-LDL/LPS plus different concentrations of Sal B (1.25 μg/mL, 2.5 μg/mL, 5 μg/mL), or ox-LDL plus Sal B plus MAPKs activators. ELISA was used for detecting serum lipid profiles and inflammatory cytokines, RT-qPCR used for gene expression, Oil Red O used for plaque sizes, and immunofluorescence staining used for NF-κB p65 and TNF-α production. Inflammation-related proteins and MAPKs pathways were detected by Western Blot. Results: The results showed that Sal B decreased the levels of serum lipids (TC, TG, and LDL-C), attenuated inflammatory cytokines, and improved lipid accumulation in the aorta. Sal B also attenuated the elevation of inflammatory cytokines induced by ox-LDL or LPS in RAW264.7 cells, and the phosphorylation of MAPKs/NF-κB pathways in the aorta and RAW264.7 cells, resulting in a significant decrease in the contents of p-JNK, p-ERK 1/2, p-P38, p-IκB, and p-NF-κB p65. Conclusions: Sal B could exert anti-inflammatory effects on atherosclerosis via MAPKs/NF-κB signaling pathways in vivo and in vitro.
目的:丹参酚酸B (Salvianolic acid B, Sal B)是丹参的主要有效水溶性成分。本研究探讨了Sal B在高脂饮食(HFD)诱导的LDLR-/-小鼠和氧化低密度脂蛋白(ox-LDL)诱导或脂多糖(LPS)诱导的RAW264.7细胞中的抗炎作用。方法:高脂饮食12周后,将LDLR-/-小鼠随机分为4组。然后给予0.9%生理盐水或Sal B (25 mg/kg)或阿托伐他汀(1.3 mg/kg)连续12周。用ox-LDL/LPS、ox-LDL/LPS加不同浓度的Sal B (1.25 μg/mL、2.5 μg/mL、5 μg/mL)或ox-LDL加Sal B加MAPKs激活剂诱导RAW 264.7细胞。ELISA检测血脂和炎症因子,RT-qPCR检测基因表达,Oil Red O检测斑块大小,免疫荧光染色检测NF-κB p65和TNF-α的产生。Western Blot检测炎症相关蛋白和MAPKs通路。结果:结果显示,Sal B降低了血脂(TC、TG和LDL-C)水平,减轻了炎症细胞因子,改善了主动脉脂质积累。Sal B还能降低ox-LDL或LPS诱导的RAW264.7细胞中炎症因子的升高,以及主动脉和RAW264.7细胞中MAPKs/NF-κB通路的磷酸化,导致p-JNK、p-ERK 1/2、p-P38、p- i -κB、p-NF-κB p65含量显著降低。结论:Sal B在体内和体外均可通过MAPKs/NF-κB信号通路对动脉粥样硬化发挥抗炎作用。
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引用次数: 9
A monoclonal antibody against basic fibroblast growth factor attenuates cisplatin resistance in lung cancer by suppressing the epithelial-mesenchymal transition. 抗碱性成纤维细胞生长因子单克隆抗体通过抑制上皮-间质转移减轻癌症顺铂耐药性
IF 3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221105134
Penghui Hu, Kaman So, Hongjie Chen, Qimou Lin, Meng Xu, Yiguang Lin

Objectives: To investigate the underlying mechanisms of how the basic fibroblast growth factor monoclonal antibody (bFGFmAb) attenuates cisplatin (DDP) resistance in lung cancer using A549 cells and cisplatin-resistant A549 cells (A549/DDP). Methods: Cancer cell proliferation, cell viability, and 50% inhibitory concentration (IC50) of cisplatin were assessed. Transwell assays were utilized to evaluate the invasion activity of tumor cells in response to treatment. Epithelial-to-mesenchymal transition markers and drug resistance proteins were analysed using Western blots. Results: We demonstrate that the bFGFmAb inhibits the proliferation and invasion of both A549 and A549/DDP cells. The bFGFmAb increases cisplatin sensitivity of both A549 and A549/DDP cells as evidenced by an increase in the IC50 of cisplatin in A549 and A549/DDP cells. Furthermore, bFGFmAb significantly increases the expression of E-cadherin, whilst decreasing the expression of N-cadherin and bFGF in both cell lines, thereby showing inhibition of epithelial-to-mesenchymal transition. In addition, we demonstrate that bFGFmAb significantly reduces the expression of the lung resistance protein. Conclusions: Our data suggests that the humanized bFGFmAb is a promising agent to attenuate cisplatin resistance in NSCLC. The underlying mechanism for this effect of bFGFmAb may be associated with the inhibition of epithelial-to-mesenchymal transition and reduced expression of lung resistance protein.

目的:探讨碱性成纤维细胞生长因子单克隆抗体(bFGFmAb)在A549细胞和顺铂耐药A549细胞(A549/DDP)中减轻肺癌顺铂(DDP)耐药的潜在机制。方法:观察肿瘤细胞增殖、细胞活力及顺铂50%抑制浓度(IC50)。采用Transwell法评价肿瘤细胞对治疗的侵袭活性。采用Western blots分析上皮-间质转化标志物和耐药蛋白。结果:我们发现bFGFmAb对A549和A549/DDP细胞的增殖和侵袭均有抑制作用。bFGFmAb增加A549和A549/DDP细胞的顺铂敏感性,A549和A549/DDP细胞中顺铂的IC50增加证明了这一点。此外,bFGFmAb显著提高了E-cadherin的表达,同时降低了两种细胞系中N-cadherin和bFGF的表达,从而抑制了上皮细胞向间质细胞的转化。此外,我们证明bFGFmAb显著降低肺抵抗蛋白的表达。结论:我们的数据表明,人源化bFGFmAb是一种有希望减轻NSCLC顺铂耐药的药物。bFGFmAb这种作用的潜在机制可能与抑制上皮-间质转化和降低肺抵抗蛋白的表达有关。
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引用次数: 0
Bisphenol-A/Radiation mediated inflammatory response activates EGFR/KRAS/ERK1/2 signaling pathway leads to lung carcinogenesis incidence 双酚A/辐射介导的炎症反应激活EGFR/KRAS/ERK1/2信号通路导致肺癌发生
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221092918
O. A. Abo-Zaid, F. Moawed, H. Hassan, E. Moustafa
Background Bisphenol (BPA) and ionizing radiation exposure (IR) are potent oxidants that cause free radical induction, leading to signaling pathway activation that alters cell growth. Due to the insufficient knowledge of the impact of BPA and IR on the lungs, the current study determined the impact of BPA and IR on the lung tissue of adult female Wistar rats. Methods Forty Wister female rats were used in this study and were randomly divided into four groups. The rats received BPA (150 mg/kg body weight/day for 6 weeks) and were exposed to IR at 2 Gy/week up to 12 Gy for 6 weeks. Results It was found that BPA and IR possess a harmful effect on the lungs via induction of oxidative stress, confirmed by increasing levels of malondialdehyde (MDA), nitric oxide, myeloperoxidase (MPO), and lactate dehydrogenase (LDH). Exposure to BPA and IR activates inflammatory cytokines TNF-α, IL-6, IL-1β, growth factors such as TGF-β, and gastrin-releasing peptides. BPA/IR exposures induced phosphorylated expression p-ERK1/2 and p-MEK1/2 associated with triggering of the GPER/EGFR/KRAS signaling factors, resulting in matrix metalloproteinase-2 and 9 overexpression and the development of lung tumors. Our findings support the causal role of two deleterious environmental pollutants BPA and IR, via the cytotoxicity in the respiratory system in the form of severe lung damage resulting in cancerous cells.
背景双酚(BPA)和电离辐射暴露(IR)是引起自由基诱导的强效氧化剂,导致信号通路激活,从而改变细胞生长。由于对BPA和IR对肺部的影响知之甚少,目前的研究确定了BPA和IR对于成年雌性Wistar大鼠肺组织的影响。方法选用Wister雌性大鼠40只,随机分为4组。大鼠接受BPA(150mg/kg体重/天,持续6周),并暴露于2Gy/周至12Gy的IR,持续6个星期。结果BPA和IR通过诱导氧化应激对肺部产生有害影响,丙二醛(MDA)、一氧化氮、髓过氧化物酶(MPO)和乳酸脱氢酶(LDH)水平升高证实了这一点。暴露于BPA和IR会激活炎性细胞因子TNF-α、IL-6、IL-1β、生长因子如TGF-β和胃泌素释放肽。BPA/IR暴露诱导磷酸化表达p-ERK1/2和p-MEK1/2,与GPER/EGFR/KRAS信号因子的触发相关,导致基质金属蛋白酶-2和9过表达和肺肿瘤的发展。我们的研究结果支持了两种有害环境污染物BPA和IR的因果作用,它们通过呼吸系统中的细胞毒性,以严重的肺损伤的形式导致癌细胞。
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引用次数: 3
Detection of exosomal miR-18a and miR-222 levels in Egyptian patients with hepatic cirrhosis and hepatocellular carcinoma 埃及肝硬化和肝细胞癌患者外泌体miR-18a和miR-222水平的检测
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221097832
E. Elghoroury, E. Abdelghaffar, Eman Awadallah, S. Kamel, D. Kandil, E. M. Hassan, M. Hassan, Mahmoud M. Kamel, M. Gomaa, L. Fathalla
Background Hepatocellular carcinoma (HCC) is known to be the second leading cause of cancer-related mortality worldwide. For improving the prognosis as well as reducing the rate of mortality, early diagnosis of HCC is a must. Aims This study was conducted to assess the ability of the serum expression of exosomal miR-18a and miR-222 to differentiate and diagnose patients with HCC, patients with liver cirrhosis, and healthy controls. Methods This study included 51 patients with liver cirrhosis, 51 patients with HCC on top of hepatitis C virus (HCV) infection, and 50 healthy controls. Results miR-18a and miR-222 were assessed using reverse transcription-polymerase chain reaction. MiR-18a and miR-222 levels were significantly higher in the liver cirrhosis and HCC groups than the control group (p ˂ 0.001). However, no statistically significant difference was found between patients with HCC and liver cirrhosis (p = 0.4 for miR-18a and p = 0.1 for miR-222). ROC curve analyses to evaluate the diagnostic performances of the two miRNAs as important noninvasive diagnostic markers revealed a best cutoff value of 2 for miR-18a to differentiate between liver cirrhosis, HCC, and healthy controls. And for mir-222, a cutoff value of 1.7 and 1.9 showed the highest specificity for discrimination between liver cirrhosis, HCC, and healthy controls, respectively. Moreover, logistic regression model revealed that miR-18a expression was independent predictive factor in HCC patients (p = 0.004), while miR-222 expression was independent predictive factor in liver cirrhosis patients (p < 0.001). Conclusion miR-18a and miR-222 were significantly discriminative markers between patients with liver cirrhosis and HCC and healthy individuals. Therefore, they have a prognostic rather than a diagnostic value. Moreover, miR-18a and miR-222 could be useful in identifying liver injuries, including fibrosis and cirrhosis.
背景众所周知,肝细胞癌(HCC)是全球癌症相关死亡率的第二大原因。为了改善预后并降低死亡率,HCC的早期诊断是必须的。本研究旨在评估血清外泌体miR-18a和miR-222的表达对HCC患者、肝硬化患者和健康对照的鉴别诊断能力。方法本研究包括51例肝硬化患者、51例丙型肝炎病毒(HCV)感染的HCC患者和50名健康对照。结果应用逆转录聚合酶链反应检测miR-18a和miR-222。肝硬化和HCC组的MiR-18a和MiR-222水平显著高于对照组(p 0.001)。然而,HCC患者和肝硬化患者之间没有发现统计学上的显著差异(MiR-18a的p=0.4,MiR-222的p=0.1)。评估两种miRNA作为重要的非侵入性诊断标志物的诊断性能的ROC曲线分析显示,miR-18a区分肝硬化、HCC和健康对照的最佳截止值为2。对于mir-222,1.7和1.9的临界值分别显示出区分肝硬化、HCC和健康对照组的最高特异性。此外,logistic回归模型显示,miR-18a在HCC患者中的表达是独立的预测因素(p=0.004),而miR-222在肝硬化患者中是独立的预示因素(p<0.001)。结论miR-18a和miR-222是肝硬化和HCC患者与健康人之间的显著鉴别标志物。因此,它们具有预后而非诊断价值。此外,miR-18a和miR-222可用于识别肝损伤,包括纤维化和肝硬化。
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引用次数: 5
Clinical and hematological characteristics of 300 COVID-19 patients in Erbil, Kurdistan Region, Iraq 伊拉克库尔德斯坦地区埃尔比勒300例新冠肺炎患者临床及血液学特征分析
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221085465
Rundk Ahmad Hwaiz, Sahar Mohammed Zaki Abdullah, S. J. Jalal Balaky, K. Ali, M. Merza, Shakhawan Assad Khailani, N. Shabila
Background COVID-19 primarily presents as a respiratory tract infection, but studies indicate that it could be considered a systemic disease that can spread to affect multiple organ systems, including respiratory, cardiovascular, gastrointestinal, hematopoietic, neurological, and immune systems. Objective To describe and analyze the clinical and hematological characteristics of 300 hospitalized COVID-19 patients in Erbil, Kurdistan. Methods This retrospective study included 300 patients of any age admitted to hospital due to confirmed COVID-19 between September 2020 and February 2021. Cases were diagnosed by reverse transcriptase polymerase chain reaction assays of nasopharyngeal swab specimens. Results The highest proportion of patients were aged 21–40 years. The most common symptoms among the patients were myalgia (66.7%), fatigue (62.3%), headache (50.7%), and chest pain (52.7%). Differences in hematological and biochemical parameters were observed between deceased and recovered patients. Only the mid-range absolute count percentage (MID%) was significantly higher in the recovered patients than in the deceased ones (6.41% vs. 4.48, p = 0.019). Death was significantly higher among older patients (>40 years) than younger ones (≤40 years) (6.8% vs. 1.3%, p = 0.015), diabetic than non-diabetic (10.8% vs. 3%, p = 0.047), and those having chronic diseases than those without chronic diseases (10.6% vs. 2.1%, p = 0.006). Conclusions Different hematological and biochemical parameter findings were observed among the COVID-19 patients. Low MID%, older age, and presence of diabetes mellitus and chronic disease were significantly associated with death among COVID-19 patients.
背景COVID-19主要表现为呼吸道感染,但研究表明,它可以被认为是一种全身性疾病,可传播到影响多器官系统,包括呼吸系统、心血管系统、胃肠道、造血系统、神经系统和免疫系统。目的描述和分析库尔德斯坦埃尔比勒地区300例新冠肺炎住院患者的临床和血液学特征。方法回顾性研究纳入2020年9月至2021年2月期间因COVID-19确诊入院的300例任意年龄患者。病例通过鼻咽拭子标本逆转录酶聚合酶链反应诊断。结果21 ~ 40岁患者占比最高。患者最常见的症状为肌痛(66.7%)、疲劳(62.3%)、头痛(50.7%)和胸痛(52.7%)。死亡患者与康复患者血液学和生化指标存在差异。只有康复患者的中期绝对计数百分比(MID%)显著高于死亡患者(6.41% vs. 4.48, p = 0.019)。老年患者(40岁以下)的死亡率明显高于年轻患者(≤40岁)(6.8%比1.3%,p = 0.015),糖尿病患者比非糖尿病患者(10.8%比3%,p = 0.047),有慢性疾病的患者比无慢性疾病的患者(10.6%比2.1%,p = 0.006)。结论新冠肺炎患者血液学和生化指标存在差异。低MID%、年龄较大、存在糖尿病和慢性疾病与COVID-19患者的死亡显著相关。
{"title":"Clinical and hematological characteristics of 300 COVID-19 patients in Erbil, Kurdistan Region, Iraq","authors":"Rundk Ahmad Hwaiz, Sahar Mohammed Zaki Abdullah, S. J. Jalal Balaky, K. Ali, M. Merza, Shakhawan Assad Khailani, N. Shabila","doi":"10.1177/03946320221085465","DOIUrl":"https://doi.org/10.1177/03946320221085465","url":null,"abstract":"Background COVID-19 primarily presents as a respiratory tract infection, but studies indicate that it could be considered a systemic disease that can spread to affect multiple organ systems, including respiratory, cardiovascular, gastrointestinal, hematopoietic, neurological, and immune systems. Objective To describe and analyze the clinical and hematological characteristics of 300 hospitalized COVID-19 patients in Erbil, Kurdistan. Methods This retrospective study included 300 patients of any age admitted to hospital due to confirmed COVID-19 between September 2020 and February 2021. Cases were diagnosed by reverse transcriptase polymerase chain reaction assays of nasopharyngeal swab specimens. Results The highest proportion of patients were aged 21–40 years. The most common symptoms among the patients were myalgia (66.7%), fatigue (62.3%), headache (50.7%), and chest pain (52.7%). Differences in hematological and biochemical parameters were observed between deceased and recovered patients. Only the mid-range absolute count percentage (MID%) was significantly higher in the recovered patients than in the deceased ones (6.41% vs. 4.48, p = 0.019). Death was significantly higher among older patients (>40 years) than younger ones (≤40 years) (6.8% vs. 1.3%, p = 0.015), diabetic than non-diabetic (10.8% vs. 3%, p = 0.047), and those having chronic diseases than those without chronic diseases (10.6% vs. 2.1%, p = 0.006). Conclusions Different hematological and biochemical parameter findings were observed among the COVID-19 patients. Low MID%, older age, and presence of diabetes mellitus and chronic disease were significantly associated with death among COVID-19 patients.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47007397","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: 2
Changes in immune profile affect disease progression in hepatocellular carcinoma 免疫谱的改变影响肝细胞癌的疾病进展
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221078476
F. Fathi, R. Saidi, H. Banafshe, M. Arbabi, M. Lotfinia, H. Motedayyen
Objective: Hepatocellular carcinoma (HCC) as a chronic liver condition is largely associated with immune responses. Previous studies have revealed that different subsets of lymphocytes play fundamental roles in controlling or improving the development and outcome of solid tumors like HCC. Hence, this study aimed to investigate whether immune system changes were related to disease development in HCC patients. Methods: Peripheral blood mononuclear cells were isolated from 30 HCC patients and 30 healthy volunteers using Ficoll density centrifugation. The isolated cells were stained with different primary antibodies and percentages of different immune cells were determined by flow cytometry. Results: HCC patients indicated significant reductions in the numbers of CD4+ cells, Tbet+IFNγ+cells, and GATA+IL-4+cells in peripheral blood in comparison with healthy individuals (p < 0.05). There was no significant change in IL-17+RORγt+cells between patient and healthy groups. In contrast, Foxp3+CD127lowcell frequency was significantly higher in patients than healthy subjects (p < 0.0001). The numbers of Th1, Th2, and Th17 cells were significantly lower in HCC patients than healthy control (p < 0.0001), although the reduction in Th2 cell numbers was not statistically significant. On the contrary, Treg percentage showed a significant increase in patients compared to healthy subjects (p < 0.0001). Other data revealed that Th1, Th2, and Th17 cell frequencies were significantly higher in healthy individuals than patients with different TNM stages of HCC, with the exception of Th2 in patients with stage II HCC (p < 0.01–0.05). Treg percentage was significantly increased in patients with different TNM stages (p < 0.0001). Among all CD4+ T cells, the frequency of Th2 cell was significantly associated with TNM stages of HCC (p < 0.05). Conclusion: Our data provide further evidence to show that immune changes may participate in determining HCC progression and disease outcome. However, it should be mentioned that more investigations are needed to clarify our results and explain possible impacts of other immune cells on the pathogenesis of HCC.
目的:肝细胞癌(HCC)作为一种慢性肝病,在很大程度上与免疫反应有关。先前的研究表明,不同的淋巴细胞亚群在控制或改善HCC等实体瘤的发展和预后方面发挥着重要作用。因此,本研究旨在调查HCC患者的免疫系统变化是否与疾病发展有关。方法:采用Ficoll密度离心法从30例HCC患者和30例健康志愿者中分离出外周血单个核细胞。用不同的第一抗体对分离的细胞进行染色,并通过流式细胞术测定不同免疫细胞的百分比。结果:与健康人相比,HCC患者外周血CD4+细胞、Tbet+IFNγ+细胞和GATA+IL-4+细胞数量显著减少(p<0.05)。患者组和健康组之间IL-17+RORγt+细胞没有显著变化。相反,Foxp3+CD127低细胞频率在患者中显著高于健康受试者(p<0.0001)。尽管Th2细胞数量的减少没有统计学意义,但HCC患者的Th1、Th2和Th17细胞数量显著低于健康对照组(p<0.001)。相反,与健康受试者相比,患者的Treg百分比显著增加(p<0.0001)。其他数据显示,健康个体的Th1、Th2和Th17细胞频率显著高于不同TNM HCC分期的患者,II期HCC患者的Th2除外(p<0.01–0.05)。不同TNM分期的患者Treg百分比显著增加(p<0.0001)。在所有CD4+T细胞中,Th2细胞的频率与HCC的TNM分期显著相关(p<0.05)。结论:我们的数据提供了进一步的证据,表明免疫变化可能参与决定HCC的进展和疾病结果。然而,值得一提的是,还需要更多的研究来澄清我们的结果,并解释其他免疫细胞对HCC发病机制的可能影响。
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引用次数: 3
The effect of valproic acid on SLC5A8 expression in gonad-intact and gonadectomized rat thymocytes. 丙戊酸对无性腺和性腺切除大鼠胸腺细胞中 SLC5A8 表达的影响
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211051954
Milda Juknevičienė, Ingrida Balnytė, Angelija Valančiūtė, Jūratė Stanevičiūtė, Kęstutis Sužiedėlis, Donatas Stakišaitis

Background: Valproic acid (VPA) pharmacological mechanisms are related to the anti-inflammatory and anti-viral effects. VPA is a histone deacetylases inhibitor and serves a role in its immunomodulatory impacts. VPA has complex effects on immune cell's mitochondrial metabolism. The SLC5A8 transporter of short fatty acids has an active role in regulating mitochondrial metabolism. The study aimed to investigate whether SLC5A8 expresses the sex-related difference and how SLC5A8 expression depends on gonadal hormones, VPA treatment, and NKCC1 expression in rat thymocytes.

Methods: Control groups and VPA-treated gonad-intact and gonadectomized Wistar male and female rats were investigated (n = 6 in a group). The VPA 300 mg/kg/day in drinking water was given for 4 weeks. The SLC5A8 (Slc5a8 gene) and NKCC1 (Slc12a2 gene) RNA expressions were determined by the RT-PCR method.

Results: The higher Slc5a8 expression was found in the gonad-intact males than respective females (p = 0.004). VPA treatment decreased the Slc5a8 expression in gonad-intact and castrated males (p = 0.02 and p = 0.03, respectively), and increased in gonad-intact female rats compared to their control (p = 0.03). No significant difference in the Slc5a8 expression between the ovariectomized female control and VPA-treated females was determined (p > 0.05). VPA treatment alters the correlation between Slc5a8 and Slc12a2 gene expression in thymocytes of gonad-intact rats.

Conclusion: VPA effect on the Slc5a8 expression in rat thymocytes is gender- and gonadal hormone-dependent.

背景:丙戊酸(VPA)的药理机制与抗炎和抗病毒作用有关。VPA 是一种组蛋白去乙酰化酶抑制剂,具有免疫调节作用。VPA 对免疫细胞的线粒体代谢有复杂的影响。短脂肪酸的 SLC5A8 转运体在调节线粒体代谢方面发挥着积极作用。本研究旨在探讨大鼠胸腺细胞中 SLC5A8 的表达是否存在性别差异,以及 SLC5A8 的表达如何依赖于性腺激素、VPA 处理和 NKCC1 的表达:方法:研究对象为对照组和经 VPA 处理的性腺未受损和性腺切除的 Wistar 雄性和雌性大鼠(每组 6 只)。VPA 300 毫克/千克/天,连续 4 周。采用 RT-PCR 方法检测 SLC5A8(Slc5a8 基因)和 NKCC1(Slc12a2 基因)的 RNA 表达:结果:未触及性腺的雄性动物的 Slc5a8 表达量高于雌性动物(p = 0.004)。与对照组相比,VPA 处理降低了性腺未受影响的雄性大鼠和阉割雄性大鼠的 Slc5a8 表达(p = 0.02 和 p = 0.03),增加了性腺未受影响的雌性大鼠的 Slc5a8 表达(p = 0.03)。卵巢切除的雌性对照组与经 VPA 处理的雌性对照组之间的 Slc5a8 表达无明显差异(p > 0.05)。VPA改变了性腺未受损大鼠胸腺细胞中Slc5a8和Slc12a2基因表达的相关性:结论:VPA 对大鼠胸腺细胞中 Slc5a8 表达的影响与性别和性腺激素有关。
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引用次数: 0
Protective effect of baicalin against arsenic trioxide-induced acute hepatic injury in mice through JAK2/STAT3 signaling pathway. 黄芩苷通过JAK2/STAT3信号通路对三氧化二砷诱导的小鼠急性肝损伤的保护作用
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211073397
Qianqian He, Xiaoqi Sun, Muqing Zhang, Li Chu, Yang Zhao, Yongchao Wu, Jianping Zhang, Xue Han, Shengjiang Guan, Chao Ding

Baicalin (BA) is a kind of flavonoid that is isolated from Scutellaria baicalensis Georgi, which has been verified to have hepatoprotective effects in some diseases. However, the role of BA in acute hepatic injury induced by arsenic trioxide (ATO) remains unclear. The aim of this study was to investigate the protective action of BA on acute hepatic injury induced by ATO and to probe its possible mechanism. Mice were pretreated with BA (50, 100 mg/kg) by gavage. After 7 h, ATO (7.5 mg/kg) was injected intraperitoneally to induce liver injury. After 7 days of treatment, serum and hepatic specimens were collected and assayed to evaluate the hepatoprotective effect of BA. Pathological sections and the liver function index indicated that ATO caused significant liver injury. The fluorescence of reactive oxygen species and oxidative stress indicators showed that ATO also increased oxidative stress. The inflammatory markers in ATO-induced mice also increased significantly. Staining of the terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic factor assay showed that apoptosis increased. However, with BA pretreatment, these changes were significantly weakened. In addition, BA treatment promoted the expression of proteins related to the JAK2/STAT3 signaling pathway. The results suggest that BA can ameliorate acute ATO-induced hepatic injury in mice, which is related to the inhibition of oxidative stress, thereby reducing inflammation and apoptosis. The mechanism of this protection is potentially related to the JAK2/STAT3 signaling pathway.

黄芩苷(Baicalin, BA)是从黄芩中分离得到的一类黄酮类化合物,已被证实对某些疾病有保护肝脏的作用。然而,BA在三氧化二砷(ATO)致急性肝损伤中的作用尚不清楚。本研究旨在探讨BA对ATO致急性肝损伤的保护作用,并探讨其可能的机制。小鼠分别灌胃BA(50、100 mg/kg)预处理。7 h后,腹腔注射ATO (7.5 mg/kg)诱导肝损伤。治疗7 d后,采集血清和肝脏标本,评价BA对肝脏的保护作用。病理切片及肝功能指标显示ATO对大鼠肝损伤明显。活性氧荧光和氧化应激指标显示,ATO也增加了氧化应激。ato诱导小鼠的炎症指标也显著升高。末端脱氧核苷酸转移酶dUTP缺口末端标记和凋亡因子检测显示细胞凋亡增加。然而,经过BA预处理,这些变化明显减弱。此外,BA处理促进了JAK2/STAT3信号通路相关蛋白的表达。结果提示,BA可改善ato诱导的小鼠急性肝损伤,其机制可能与抑制氧化应激有关,从而减少炎症和细胞凋亡。这种保护的机制可能与JAK2/STAT3信号通路有关。
{"title":"Protective effect of baicalin against arsenic trioxide-induced acute hepatic injury in mice through JAK2/STAT3 signaling pathway.","authors":"Qianqian He,&nbsp;Xiaoqi Sun,&nbsp;Muqing Zhang,&nbsp;Li Chu,&nbsp;Yang Zhao,&nbsp;Yongchao Wu,&nbsp;Jianping Zhang,&nbsp;Xue Han,&nbsp;Shengjiang Guan,&nbsp;Chao Ding","doi":"10.1177/20587384211073397","DOIUrl":"https://doi.org/10.1177/20587384211073397","url":null,"abstract":"<p><p>Baicalin (BA) is a kind of flavonoid that is isolated from <i>Scutellaria baicalensis</i> Georgi, which has been verified to have hepatoprotective effects in some diseases. However, the role of BA in acute hepatic injury induced by arsenic trioxide (ATO) remains unclear. The aim of this study was to investigate the protective action of BA on acute hepatic injury induced by ATO and to probe its possible mechanism. Mice were pretreated with BA (50, 100 mg/kg) by gavage. After 7 h, ATO (7.5 mg/kg) was injected intraperitoneally to induce liver injury. After 7 days of treatment, serum and hepatic specimens were collected and assayed to evaluate the hepatoprotective effect of BA. Pathological sections and the liver function index indicated that ATO caused significant liver injury. The fluorescence of reactive oxygen species and oxidative stress indicators showed that ATO also increased oxidative stress. The inflammatory markers in ATO-induced mice also increased significantly. Staining of the terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic factor assay showed that apoptosis increased. However, with BA pretreatment, these changes were significantly weakened. In addition, BA treatment promoted the expression of proteins related to the JAK2/STAT3 signaling pathway. The results suggest that BA can ameliorate acute ATO-induced hepatic injury in mice, which is related to the inhibition of oxidative stress, thereby reducing inflammation and apoptosis. The mechanism of this protection is potentially related to the JAK2/STAT3 signaling pathway.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"36 ","pages":"20587384211073397"},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/ce/10.1177_20587384211073397.PMC8801635.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39866131","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: 6
Patients with treated autoimmune hepatitis and persistent suppression of plasmacytoid dendritic cells: A different point of view 接受治疗的自身免疫性肝炎患者和浆细胞样树突状细胞的持续抑制:不同的观点
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211068667
I. P. dos Santos, Mayra T de Assunção, R. Mauch, N. Sandy, M. T. Nolasco da Silva, M. A. Bellomo-Brandão, A. G. Riccetto
Objectives: Plasmacytoid dendritic cells (pDCs) have been shown to have a role in autoimmune diseases, but their role in Autoimmune Hepatitis (AIH) is not completely clear. In the present study, we assessed the frequency of pDCs in peripheral blood of AIH patients under long-term standard immunosuppressive therapy. Methods: This cross-sectional analysis enrolled 27 AIH patients and 27 healthy controls. We analyzed and compared their proportion of pDCs, CD4+, CD8+, γδ T cells, CD25+ regulatory T (Treg) cells, FoxP3+, Foxp3+CD39+ Treg cells, total B (CD19+) cells, and plasma cells (CD38+) in peripheral blood using flow cytometry immunophenotyping. Results: AIH patients had a lower percentage of pDCs (median frequencies of 0.2% vs. 0.4%; p = .002) and higher expression of CD8 T cells (32.5% vs 28.6%; p = 0.008) in peripheral blood, when compared to healthy controls. We did not find statistically significant differences between the groups regarding the other cell subtypes.Conclusion: Our data suggest a persistent suppression of pDCs in AIH patients, along with increased CD8 T cell activity, years after AIH diagnosis and despite of good clinical response to treatment, thus pointing to a role of pDCs in the AIH pathogenesis.
目的:浆细胞样树突状细胞(pDC)已被证明在自身免疫性疾病中发挥作用,但其在自身免疫型肝炎(AIH)中的作用尚不完全清楚。在本研究中,我们评估了在长期标准免疫抑制治疗下AIH患者外周血中pDC的频率。方法:该横断面分析纳入了27名AIH患者和27名健康对照。我们使用流式细胞术免疫表型分析和比较了外周血中pDCs、CD4+、CD8+、γδT细胞、CD25+调节性T(Treg)细胞、FoxP3+、FoxP3+CD39+Treg细胞、总B(CD19+)细胞和浆细胞(CD38+)的比例。结果:与健康对照组相比,AIH患者外周血中pDC的百分比较低(中位频率为0.2%对0.4%;p=0.002),CD8 T细胞的表达较高(32.5%对28.6%;p=0.008)。在其他细胞亚型方面,我们没有发现两组之间存在统计学上的显著差异。结论:我们的数据表明,在AIH诊断数年后,尽管对治疗有良好的临床反应,但AIH患者的pDC持续受到抑制,同时CD8 T细胞活性增加,从而表明pDC在AIH发病机制中的作用。
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引用次数: 1
Clinical and quality of life assessment in patients with latex allergy during COVID-19 pandemic: Possible protective role of continuous latex immunotherapy 新冠肺炎大流行期间乳胶过敏患者的临床和生活质量评估:持续乳胶免疫疗法可能的保护作用
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221100367
A. Di Rienzo, S. Urbani, D. Longhino, Caterina Sarnari, A. Buonomo, A. Rizzi, A. Aruanno, E. Nucera
Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 ± 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.
简介:在新冠肺炎大流行期间,大量使用个人防护装备可能会引发乳胶过敏患者的严重不良反应,并可能对他们的生活质量产生负面影响。方法:通过调查,本研究旨在:(a)评估严重急性呼吸系统综合征冠状病毒2型大流行期间乳胶过敏患者的过敏反应发生率;(b) 评估持续乳胶舌下免疫疗法(SLIT)在此期间的保护作用;以及(c)评估大流行期间天然橡胶胶乳过敏(NRLA)患者的生活质量。结果:67例乳胶过敏患者(9男58女,平均年龄45.9±11.4岁)被纳入本研究。我们记录了13例(34.2%)荨麻疹/血管性水肿(U/A),9例(23.6%)呼吸系统症状(呼吸困难、呼吸急促和喘息)和7例(18.4%)过敏反应。在接受连续SLIT的患者中,我们观察到U/A(p<0.001)、呼吸道症状(p<001)、过敏反应(p=0.003)、住院(p=0.014)和较低的治疗剂量的病例较少。我们比较了SF-36问卷在接受连续和非连续SLIT的患者中的结果,这两组之间的得分存在显著性差异。结论:我们的研究首次调查了新冠肺炎大流行对NRLA患者的临床和生活质量的影响。
{"title":"Clinical and quality of life assessment in patients with latex allergy during COVID-19 pandemic: Possible protective role of continuous latex immunotherapy","authors":"A. Di Rienzo, S. Urbani, D. Longhino, Caterina Sarnari, A. Buonomo, A. Rizzi, A. Aruanno, E. Nucera","doi":"10.1177/03946320221100367","DOIUrl":"https://doi.org/10.1177/03946320221100367","url":null,"abstract":"Introduction: During COVID-19 pandemic, the massive use of Personal Protective Equipment could provoke severe adverse reactions in latex allergy patients and could negatively affect their quality of life. Methods: Trough a survey the study aimed: (a) to evaluate the incidence of allergic reactions in patients with latex allergy during the SARS-CoV-2 pandemic; (b) to evaluate the protective role of continuous latex sublingual immunotherapy (SLIT) during this period; and (c) to evaluate quality of life of natural rubber latex allergy (NRLA) patients during the pandemic. Results: 67 patients (9 males and 58 females, mean age of 45.9 ± 11.4 years) suffering from latex allergy were included in the present study. We recorded among our patients 13 cases (34.2%) of urticarial/angioedema (U/A), 9 cases (23.6%) of respiratory symptoms (dyspnoea, shortness of breath and wheezing) and 7 cases (18.4%) of anaphylaxis. In patients who underwent continuous SLIT, we observed less cases of U/A (p < 0.001), respiratory symptoms (p < 0.001), anaphylaxis (p = 0.003), hospitalizations (p = 0.014) and a lower therapy administration. We compared the results of SF-36 questionnaire in patients who underwent continuous and not-continuous SLIT with a significance differences score between these two groups. Conclusions: Our study is the first that investigated the clinical and quality of life effects of COVID-19 pandemic in NRLA patients.","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42816535","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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International Journal of Immunopathology and Pharmacology
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