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PD-L1 expression in breast invasive ductal carcinoma with incomplete pathological response to neoadjuvant chemotherapy PD-L1在新辅助化疗不完全病理反应的乳腺浸润性导管癌中的表达
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221078433
Ahmad Alhesa, Heyam A. Awad, Sarah Bloukh, Mahmoud Al-Balas, Mohammed El-Sadoni, Duaa Qattan, Bilal Azab, T. Saleh
Objectives: To investigate the expression of programmed death-ligand 1 (PD-L1) in breast cancer in association with incomplete pathological response (PR) to neoadjuvant chemotherapy (NAC). Methods PD-L1 expression was evaluated using immunohistochemistry in post-operative, post-NAC samples of 60 patients (n = 60) diagnosed with breast invasive ductal carcinoma with incomplete PR to NAC, including 31 matched pre-NAC and post-NAC samples (n = 31). PD-L1 protein expression was assessed using three scoring approaches, including the tumor proportion score (TPS), the immune cell score (ICS), and the combined tumor and immune cell score (combined positive score, CPS) with a 1% cut-off. Results In the post-operative, post-NAC samples (n = 60), positive expression rate of PD-L1 was observed in 18.3% (11/60) of cases by TPS, 31.7% (19/60) by ICS, and 25% (15/60) by CPS. In matched samples, positive expression rate of PD-L1 was observed in 19.3% (6/31) of patients by TPS, 51.6% (16/31) by ICS, and 19.3% (6/31) by CPS in pre-NAC specimens, while it was observed in 22.6% (7/31) of matched post-NAC samples by TPS, 22.6% (7/31) by ICS, and 19.3% (6/31) by CPS. In the matched samples, there was a significant decrease in PD-L1 immunoexpression using ICS in post-NAC specimens (McNemar’s, p = 0.020), while no significant differences were found using TPS and CPS between pre- and post-NAC samples (p = 1.000, p = 0.617; respectively). PD-L1 immunoexpression determined by TPS or CPS was only significantly associated with ER status (p = 0.022, p = 0.021; respectively), but not with other clinicopathological variables. We could not establish a correlation between PD-L1 expression and the overall survival rate (p > 0.05). There were no significant differences in the tumor infiltrating lymphocytes count between the paired pre- and post-NAC samples (t = 0.581, p = 0.563 or Wilcoxon’s Signed Rank test; z = -0.625, p = 0.529). Conclusion Our findings indicate that PD-L1 protein expression in infiltrating immune cells was significantly reduced in breast tumors that developed incomplete PR following the exposure to NAC.
目的:探讨程序性死亡配体1(PD-L1)在癌症中的表达与新辅助化疗不完全病理反应(PR)的关系。方法应用免疫组织化学方法对60例(n=60)诊断为乳腺浸润性导管癌伴不完全PR至NAC的患者术后、NAC后样本中PD-L1的表达进行评估,包括31例匹配的NAC前后样本(n=31)。使用三种评分方法评估PD-L1蛋白表达,包括肿瘤比例评分(TPS)、免疫细胞评分(ICS)和肿瘤和免疫细胞综合评分(阳性综合评分,CPS),截止值为1%。结果在术后NAC后样本(n=60)中,TPS、ICS和CPS的PD-L1阳性表达率分别为18.3%(11/60)、31.7%(19/60)和25%(15/60)。在匹配样本中,在NAC前样本中,通过TPS、ICS和CPS分别在19.3%(6/31)、51.6%(16/31)和19.3%(6/11)的患者中观察到PD-L1的阳性表达率,而通过TPS、ICS22.6%(7/31)和CPS在22.6%(6/31。在匹配的样本中,使用ICS的PD-L1免疫表达在NAC后样本中显著降低(McNemar’s,p=0.020),而使用TPS和CPS的PD-L1在NAC前和NAC后样品之间没有发现显著差异(分别为p=1.000,p=0.617)。TPS或CPS测定的PD-L1免疫表达仅与ER状态显著相关(分别为p=0.022,p=0.021),而与其他临床病理变量无关。我们不能确定PD-L1表达与总生存率之间的相关性(p>0.05)。NAC前后配对的肿瘤浸润淋巴细胞计数没有显著差异(t=0.581,p=0.563或Wilcoxon符号秩检验;z=-0.625,p=0.529)在暴露于NAC后出现不完全PR的乳腺肿瘤中,细胞显著减少。
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引用次数: 5
Elevated number of IL-21+ TFH and CD86+CD38+ B cells in blood of renal transplant recipients with AMR under conventional immuno-suppression. 在常规免疫抑制下,患有 AMR 的肾移植受者血液中 IL-21+ TFH 和 CD86+CD38+ B 细胞数量升高。
IF 3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211048027
Jing Liu, Tongyu Tang, Zhihui Qu, Li Wang, Rui Si, Haifeng Wang, Yanfang Jiang

The objective of this study is to detect the number of different subsets of TFH and B cells in renal transplant recipients (RTR) with antibody-mediated acute rejection (AMR), acute rejection (AR), chronic rejection (CR), or transplant stable (TS). The present study was a prospective study. The numbers of ICOS +, PD-1+ and IL-21+ TFH, CD86+, CD38+, CD27+, and IgD- B cells in 21 patients with end-stage renal disease (ESRD) and post-transplant times were measured by flow cytometry. The level of serum IL-21 was detected by ELISA. The numbers of circulating CD4+CXCR5+, CD4+CXCR5+ICOS+, CD4+CXCR5+PD-1+, CD4+CXCR5+IL-21+ TFH, CD19+CD86+, and CD19 +CD86+CD38+ B cells as well as the level of serum IL-21 in the AMR, AR, and CR groups at post-transplantation were significantly higher than those at pre-transplantation. In contrast, the number of circulating CD19+CD27+IgD B cells was significantly increased in the TS groups in respect to the other groups. Moreover, the numbers of circulating CD4+CXCR5+IL-21+ TFH cells, CD19+CD86+CD38+ B cells as well as the level of serum IL-21 were positive related to the level of serum Cr while showing negative correlated with the values of eGFR in the AMR groups at post-transplantation for 4 and 12 weeks. Circulating TFH cells may be a biomarker in RTR with AMR, which can promote the differentiation of B cells into plasma cells by activating B cells, thereby promoting disease progression.

本研究的目的是检测存在抗体介导的急性排斥反应(AMR)、急性排斥反应(AR)、慢性排斥反应(CR)或移植稳定(TS)的肾移植受者(RTR)中 TFH 和 B 细胞不同亚群的数量。本研究是一项前瞻性研究。通过流式细胞术测量了21例终末期肾病(ESRD)患者的ICOS+、PD-1+和IL-21+ TFH、CD86+、CD38+、CD27+和IgD- B细胞的数量以及移植后的时间。血清中 IL-21 的水平通过 ELISA 检测。AMR组、AR组和CR组移植后循环CD4+CXCR5+、CD4+CXCR5+ICOS+、CD4+CXCR5+PD-1+、CD4+CXCR5+IL-21+ TFH、CD19+CD86+和CD19+CD86+CD38+ B细胞的数量以及血清IL-21的水平均显著高于移植前。相比之下,TS 组循环 CD19+CD27+IgD B 细胞的数量明显高于其他组。此外,在移植后4周和12周,AMR组的循环CD4+CXCR5+IL-21+ TFH细胞、CD19+CD86+CD38+ B细胞数量以及血清IL-21水平与血清Cr水平呈正相关,而与eGFR值呈负相关。循环中的TFH细胞可能是RTR合并AMR的生物标志物,可通过激活B细胞促进B细胞分化为浆细胞,从而促进疾病进展。
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引用次数: 0
Abnormal sperm morphology is associated with sensitization to inhaled allergens. 精子形态异常与吸入过敏原致敏有关。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211066718
Rafał Adamczak, Natalia Ukleja-Sokołowska, Magdalena Pasińska, Joanna Zielińska, Mateusz Leśny, Mariusz Dubiel

Background: Allergy is associated with the loss of tolerance of environmental antigens, combined with a pathological immune response. There were no studies up to date that would show whether the quality of semen decreases in people with allergic diseases.

Material and methods: The research included men who reported to the Gynecological Outpatient Clinic due to reproductive difficulties, defined as the lack of pregnancy after one year of regular intercourse. Semen quality was assessed according to the World Health Organization (WHO) standard. All patients underwent skin prick tests with the most important inhalation allergens (such as hazel, silver birch, mugwort, rye, dog, cat, Dermatophagoides farinae, Dermatophagoides pteronyssinus, alder, Alternaria alternata, Cladosporium herbarum, and grass mix). The data was statistically analyzed.

Results: Results of 52 patients aged 25-52 years (34.62 ± 4.96) were analyzed. The mean BMI (Body mass index) was 28.25 (+ -3.77). It was found that 38 men (73%) had increased body weight, and 14 men (26.9%) were obese (BMI > = 30). 13 patients were smokers (25%), and 24 patients (46%) had skin tests positive for at least one inhaled allergen. Sperm tail defects were statistically more significant in patients allergic to birch, rye, cat, alder, and grass. In patients allergic to Alternaria alternata, head defects were statistically more significant (p < .05). No association was found between allergy to house dust mites, mugwort, hazel, and dogs and the deterioration of semen.

Conclusion: Allergy due to inhalation allergens had an influence on the quality of male semen. Further research is necessary to establish the immunological bases of this phenomenon.

背景:过敏与环境抗原耐受性的丧失有关,并伴有病理性免疫反应。目前还没有研究表明患有过敏性疾病的人精液质量是否会下降。材料和方法:该研究包括因生殖困难(定义为在一年的正常性交后没有怀孕)而到妇科门诊就诊的男性。精液质量按世界卫生组织(WHO)标准评定。所有患者均行皮肤点刺试验,其中包括最重要的吸入性过敏原(如榛子、白桦、艾草、黑麦、狗、猫、粉棘棘球蚴、翼状棘球蚴、桤木、交替棘球蚴、草本棘球蚴和草混合物)。对数据进行统计学分析。结果:分析25 ~ 52岁患者52例(34.62±4.96)。平均BMI(身体质量指数)为28.25(±3.77)。结果发现体重增加38例(73%),肥胖14例(26.9%)(BMI > = 30)。13名患者是吸烟者(25%),24名患者(46%)的皮肤试验至少对一种吸入过敏原呈阳性。在对桦树、黑麦、猫、桤木和草过敏的患者中,精子尾部缺陷在统计上更为显著。在对互花草过敏的患者中,头部缺陷的发生率有统计学意义(p < 0.05)。没有发现对室内尘螨、艾草、榛子和狗过敏与精液恶化之间的联系。结论:吸入性变应原对男性精液质量有影响。需要进一步的研究来确定这一现象的免疫学基础。
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引用次数: 1
Single nucleotide polymorphism rs 2070874 at Interleukin-4 is associated with increased risk of type 1 diabetes mellitus independently of human leukocyte antigens 白细胞介素-4的单核苷酸多态性rs 2070874与1型糖尿病风险增加相关,与人类白细胞抗原无关
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221090330
A. Osman, I. Brema, Alaa AlQurashi, A. Al-jurayyan, Benjamin Bradley, Muaawia Hamza
Introduction Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of insulin-producing pancreatic beta (β-) cells. Previous studies suggested an imbalance between and pro- and anti-inflammatory cytokines exacerbates T1DM development. Objectives We aimed to test the hypothesis that patients with T1DM carry a higher frequency of regulatory genes associated with low levels of the anti-inflammatory cytokines interleukin-4 (IL-4), its receptor (IL-4R), and interleukin-10 (IL-10). Methods Accordingly, we compared frequencies of five different single nucleotide polymorphisms (SNPs) in T1DM patients and healthy controls who had been typed for HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Results The frequencies of rs2070874 (IL-4) alleles C and T differed between T1DM patients and controls (cp = 0.0065), as did their codominant (cp = 0.026) and recessive (cp = 0.015) models. Increased frequencies were observed in T1DM patients for HLA alleles: DRB1*03 (pc < 0.0013), DRB1*04 (cp = 0.0169), DQA1*03 (cp = 0.0222), DQA1*05 (cp < 0.0006), DQB1*02 (cp = 0.0005), and DQB1*06 (cp < 0.0005). And lower frequencies were observed for: DRB1*07 (cp = 0.0078), DRB1*11 (cp = 0.0013), DRB1*13 (cp < 0.0364), DRB1*15 (cp < 0.0013), DQA1*01 (cp < 0.0006), and DQA1*02 (cp = 0.0348). Certain DRB1: DQA1: DQB1 haplotypes showed greater frequencies, including, 03:05:02 (p < 0.0001) and 04:03:03 (p = 0.0017), whereas others showed lower frequencies, including, 07:02:02 (p = 0.0032), 11:05:03 (p = 0.0007), and 15:01:06 (p = 0.0002). Stratification for the above HLA haplotypes with rs2070874 C/C exhibited no significant differences between T1DM patients overall and controls. However, when stratified for the vulnerable HLA haplotype (03:05:02/04:03:03), young patients in whom T1DM began at ≤13 years had a higher frequency of the SNP (rs2070874 C/C); a gene associated with low IL-4 production (p < 0.024). Conclusion This study suggests that possession of the rs2070874 C/C genotype, which is associated with low production of IL-4, increases the risk of T1DM in young individuals carrying vulnerable HLA alleles/haplotypes.
1型糖尿病(T1DM)的特点是自身免疫破坏产生胰岛素的胰腺β (β-)细胞。先前的研究表明,促炎性和抗炎性细胞因子之间的失衡会加剧T1DM的发展。我们的目的是验证T1DM患者携带与低水平抗炎细胞因子白介素-4 (IL-4)、其受体(IL-4R)和白介素-10 (IL-10)相关的调控基因频率较高的假设。方法比较了HLA-DRB1、HLA-DQA1和HLA-DQB1基因分型的T1DM患者和健康对照者5种不同单核苷酸多态性(snp)的频率。结果rs2070874 (IL-4)等位基因C和T的频率在T1DM患者和对照组中存在差异(cp = 0.0065),共显性(cp = 0.026)和隐性(cp = 0.015)模式也存在差异。T1DM患者HLA等位基因DRB1*03 (pc < 0.0013)、DRB1*04 (cp = 0.0169)、DQA1*03 (cp = 0.0222)、DQA1*05 (cp < 0.0006)、DQB1*02 (cp = 0.0005)、DQB1*06 (cp < 0.0005)的频率增高。DRB1*07 (cp = 0.0078)、DRB1*11 (cp = 0.0013)、DRB1*13 (cp < 0.0364)、DRB1*15 (cp < 0.0013)、DQA1*01 (cp < 0.0006)、DQA1*02 (cp = 0.0348)的频率较低。DRB1: DQA1: DQB1单倍型的频率较高,包括03:05:02 (p < 0.0001)和04:03:03 (p = 0.0017),而其他单倍型的频率较低,包括07:02:02 (p = 0.0032)、11:05:03 (p = 0.0007)和15:01:06 (p = 0.0002)。以上HLA单倍型rs2070874 C/C的分层在T1DM患者和对照组之间没有显著差异。然而,当对HLA易感单倍型(03:05:02/04:03:03)进行分层时,T1DM开始于≤13岁的年轻患者具有更高的SNP频率(rs2070874 C/C);与低IL-4产生相关的基因(p < 0.024)。结论在携带HLA易感等位基因/单倍型的年轻人中,携带rs2070874 C/C基因型(与IL-4的低产生相关)会增加T1DM的风险。
{"title":"Single nucleotide polymorphism rs 2070874 at Interleukin-4 is associated with increased risk of type 1 diabetes mellitus independently of human leukocyte antigens","authors":"A. Osman, I. Brema, Alaa AlQurashi, A. Al-jurayyan, Benjamin Bradley, Muaawia Hamza","doi":"10.1177/03946320221090330","DOIUrl":"https://doi.org/10.1177/03946320221090330","url":null,"abstract":"Introduction Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of insulin-producing pancreatic beta (β-) cells. Previous studies suggested an imbalance between and pro- and anti-inflammatory cytokines exacerbates T1DM development. Objectives We aimed to test the hypothesis that patients with T1DM carry a higher frequency of regulatory genes associated with low levels of the anti-inflammatory cytokines interleukin-4 (IL-4), its receptor (IL-4R), and interleukin-10 (IL-10). Methods Accordingly, we compared frequencies of five different single nucleotide polymorphisms (SNPs) in T1DM patients and healthy controls who had been typed for HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Results The frequencies of rs2070874 (IL-4) alleles C and T differed between T1DM patients and controls (cp = 0.0065), as did their codominant (cp = 0.026) and recessive (cp = 0.015) models. Increased frequencies were observed in T1DM patients for HLA alleles: DRB1*03 (pc < 0.0013), DRB1*04 (cp = 0.0169), DQA1*03 (cp = 0.0222), DQA1*05 (cp < 0.0006), DQB1*02 (cp = 0.0005), and DQB1*06 (cp < 0.0005). And lower frequencies were observed for: DRB1*07 (cp = 0.0078), DRB1*11 (cp = 0.0013), DRB1*13 (cp < 0.0364), DRB1*15 (cp < 0.0013), DQA1*01 (cp < 0.0006), and DQA1*02 (cp = 0.0348). Certain DRB1: DQA1: DQB1 haplotypes showed greater frequencies, including, 03:05:02 (p < 0.0001) and 04:03:03 (p = 0.0017), whereas others showed lower frequencies, including, 07:02:02 (p = 0.0032), 11:05:03 (p = 0.0007), and 15:01:06 (p = 0.0002). Stratification for the above HLA haplotypes with rs2070874 C/C exhibited no significant differences between T1DM patients overall and controls. However, when stratified for the vulnerable HLA haplotype (03:05:02/04:03:03), young patients in whom T1DM began at ≤13 years had a higher frequency of the SNP (rs2070874 C/C); a gene associated with low IL-4 production (p < 0.024). Conclusion This study suggests that possession of the rs2070874 C/C genotype, which is associated with low production of IL-4, increases the risk of T1DM in young individuals carrying vulnerable HLA alleles/haplotypes.","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":"41917862","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
A new indicator: The diagnostic value of CD8+T/B lymphocyte ratio in sepsis progression. CD8+T/B淋巴细胞比值在脓毒症进展中的诊断价值。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221123164
Yizhi Peng, Xiaofan Wang, Sheng Yin, Min Wang

Objective: To reveal the value of single lymphocyte subpopulation and their ratios in the progression of sepsis.

Methods: From January 2019 to March 2021, 39 sepsis patients, 16 septic shock patients, and 50 healthy volunteers were recruited in the Second Xiangya Hospital for this cross-sectional study. The absolute quantitation of CD4+T, CD8+T, B lymphocytes, and NK cells in peripheral blood were determined by flow cytometry. SPSS Software was used to analyze the results.

Results: On the whole, the numbers of lymphocytes in the sepsis group and in the septic shock group were lower than that in the healthy control group. Surprisingly, the percentage of CD8+T lymphocytes in the septic shock group was slightly higher than that in the sepsis group. The percentage of B lymphocytes in the sepsis group was higher than that in the healthy control group. The AUC of CD8+T/B was 0.724, with the sensitivity and specificity being 75.00% and 71.79%, respectively.

Conclusion: The immune expression pattern of patients with sepsis was not a simple decrease in the number of lymphocytes. The change in the ratios of lymphocyte subpopulation might be more meaningful along the development and progression of sepsis. The ratio of CD8+T/B could be used to diagnose the progression of sepsis and reduce the misdiagnosis rate to a certain extent.

目的:探讨单淋巴细胞亚群及其比值在脓毒症进展中的价值。方法:选取湘雅第二医院2019年1月至2021年3月39例败血症患者、16例感染性休克患者和50名健康志愿者进行横断面研究。采用流式细胞术测定外周血CD4+T、CD8+T、B淋巴细胞和NK细胞的绝对定量。采用SPSS软件对结果进行分析。结果:脓毒症组和脓毒性休克组的淋巴细胞数量总体上低于健康对照组。令人惊讶的是,感染性休克组的CD8+T淋巴细胞百分比略高于败血症组。脓毒症组B淋巴细胞百分比高于健康对照组。CD8+T/B的AUC为0.724,敏感性75.00%,特异性71.79%。结论:脓毒症患者的免疫表达模式不是简单的淋巴细胞数量减少。淋巴细胞亚群比例的变化可能在脓毒症的发生和发展过程中更有意义。CD8+T/B比值可用于诊断脓毒症的进展,在一定程度上降低误诊率。
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引用次数: 1
Evodiamine suppresses the progression of non-small cell lung carcinoma via endoplasmic reticulum stress-mediated apoptosis pathway in vivo and in vitro 吴茱萸碱通过内质网应激介导的细胞凋亡途径抑制非小细胞肺癌的体内外进展
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221086079
Yu-ting Li, Yuming Wang, Xiaoqun Wang, Lulu Jin, Lu Yang, Jinli Zhu, Hongwu Wang, Fang Zheng, H. Cui, Xiaojiang Li, Yingjie Jia
Background Evodiamine (EVO) is one of the major components isolated from Evodia rutaecarpa (Juss.). Recent studies have shown that EVO has an anti-cancer effect. However, the pharmacological mechanism by which EVO impacts cancer is still poorly understood. Objectives This study focused on asking the anti-cancer effect of EVO in human non-small cell lung carcinoma (NSCLC), and in particular to investigate whether EVO acts via modulating the endoplasmic reticulum stress (ERS)-mediated apoptosis pathway. Materials and Methods A Lewis lung carcinoma (LLC) tumor-bearing mouse model was treated with low-dose EVO (5 mg/kg) and high-dose EVO (10 mg/kg) intraperitoneally for 14 d. The effects of EVO on tumor growth, apoptosis, and ERS were assessed. In addition, NSCLC A549 and LLC cells were treated with EVO in vitro. The effects of EVO on cell proliferation, apoptosis, and ERS were investigated. Finally, 4-phenylbutyric acid (4-PBA), an ERS inhibitor, was used to validate whether EVO induced apoptosis of NSCLC cells by modulating ERS. Results EVO treatment significantly inhibited tumor growth in LLC tumor-bearing mice. H&E staining indicated that EVO treatment reduced the number of tumor cells and the nucleo-plasmic ratio. Immunostaining showed that EVO treatment significantly decreased the expression of Ki-67. TUNEL staining revealed that EVO induced apoptosis in the tumor. Likewise, EVO treatment up-regulated the expression of apoptosis-related genes and proteins and increased activation of the ERS pathway in the tumor. Additionally, EVO inhibited cell proliferation and increased cell apoptotic rates in A549 and LLC cells. EVO also increased the expression levels of genes and proteins associated with ERS-mediated apoptosis pathway in vitro. The effects of EVO on apoptosis were abolished by 4-PBA treatment. Conclusions Our study demonstrated that EVO suppresses the progression of NSCLC by modulating the ERS-mediated apoptosis pathway.
背景:evolodiamine (EVO)是从吴茱萸(jurs .)中分离得到的主要成分之一。最近的研究表明EVO有抗癌作用。然而,EVO影响癌症的药理学机制仍然知之甚少。目的探讨EVO对人非小细胞肺癌(NSCLC)的抗癌作用,特别是EVO是否通过调节内质网应激(ERS)介导的细胞凋亡途径起作用。材料与方法采用低剂量EVO (5 mg/kg)和高剂量EVO (10 mg/kg)腹腔注射Lewis肺癌(LLC)荷瘤小鼠模型14 d,观察EVO对肿瘤生长、凋亡和ERS的影响。此外,体外用EVO处理NSCLC A549和LLC细胞。观察EVO对细胞增殖、凋亡和ERS的影响。最后,利用ERS抑制剂4-苯基丁酸(4-PBA)验证EVO是否通过调节ERS诱导NSCLC细胞凋亡。结果EVO能明显抑制LLC荷瘤小鼠的肿瘤生长。H&E染色显示EVO处理后肿瘤细胞数量减少,核质比降低。免疫染色显示EVO处理显著降低Ki-67的表达。TUNEL染色显示EVO诱导肿瘤细胞凋亡。同样,EVO处理上调了肿瘤中凋亡相关基因和蛋白的表达,增加了ERS通路的激活。此外,EVO还能抑制A549和LLC细胞的增殖,增加细胞凋亡率。EVO还增加了体外ers介导的凋亡通路相关基因和蛋白的表达水平。4-PBA可消除EVO对细胞凋亡的影响。结论EVO通过调节ers介导的凋亡通路抑制NSCLC的进展。
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引用次数: 2
IP-10 and complement activation as friend or foe in COVID-19 IP-10和补体激活在COVID-19中的作用
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221096202
Saowalak Bunprakob, Pasin Hemachudha, Chanida Ruchisrisarod, Thirawat Supharatpariyakorn, T. Hemachudha
Introduction The Innate immune system senses danger signals of COVID-19 infection and produce an orchestration of cellular, complement and cytokines cascades. These led to the approach using immunosuppressive agents. It is intriguing whether certain biomarkers can aid the proper administration of such drugs. Methods Plasma specimens of 58 COVID-19 patients with differing severity, from very mild illness (group A), mild (group B), moderate (group C), and severe/critical illness (group D) were assayed for cyto-chemokines and terminal complement complex (SC5b-9) during the course of diseases. None received anti-IL-6 therapy, there was no mortality in this cohort. Results IP-10 and RANTES levels were dominant cytokines. IP-10 levels increased significantly in all groups when compared between pre-nadir and nadir phases (group A, p =0.428; group B =0.034; group C =0.159; group D <0.001) and in groups B and D when compared between nadir and recovery phases (p <0.001). RANTES levels were elevated in all groups across all phases with no significant differences. SC5b-9 levels increased significantly as compared to healthy controls [pre-nadir- group A versus healthy, p =0.122; group B-D versus healthy, p =0.021); nadir-group A versus healthy, p =0.003; group B-D versus healthy, p <0.001; recovery phase (p <0.001)] but not between groups A and B-D at pre-nadir (p=0.606). Conclusion The absence of significant pro-inflammatory responses and early elevation of IP-10 levels and complement activation may be favorable and necessary for viral elimination in COVID-19 patients. Expression of distinct cyto-chemokines during each clinical phase may be useful for guiding proper therapeutic interventions on alleviating thrombo-inflammation responses to COVID-19 infection.
简介先天免疫系统感知新冠肺炎感染的危险信号,并产生细胞、补体和细胞因子级联的协调。这导致了使用免疫抑制剂的方法。某些生物标志物是否有助于此类药物的正确给药,这一点很有趣。方法对58例新冠肺炎轻、轻、中、重、危重患者(A组)的血浆标本进行细胞趋化因子和终末补体复合体(SC5b-9)检测。没有人接受抗IL-6治疗,该队列中没有死亡。结果IP-10和RANTES水平是主要的细胞因子。IP-10水平在所有组中在最低点前和最低点之间比较时均显著升高(A组,p=0.428;B组=0.034;C组=0.159;D组<0.001),在B组和D组中,在最低点和恢复期之间比较时(p<0.001)。RANTES水平在所有阶段的所有组中均升高,无显著差异。与健康对照组相比,SC5b-9水平显著升高[最低点前-A组与健康组,p=0.122;B-D组与健康,p=0.021);最低点组A与健康组相比,p=0.003;B-D与健康组比较,p<0.001;恢复期(p<0.001)],但在最低点前(p=0.606),A组和B-D组之间没有显著的促炎反应和早期升高IP-10水平和补体激活对于新冠肺炎患者的病毒消除可能是有利和必要的。在每个临床阶段表达不同的细胞趋化因子可能有助于指导适当的治疗干预措施,以减轻新冠肺炎感染的血栓炎症反应。
{"title":"IP-10 and complement activation as friend or foe in COVID-19","authors":"Saowalak Bunprakob, Pasin Hemachudha, Chanida Ruchisrisarod, Thirawat Supharatpariyakorn, T. Hemachudha","doi":"10.1177/03946320221096202","DOIUrl":"https://doi.org/10.1177/03946320221096202","url":null,"abstract":"Introduction The Innate immune system senses danger signals of COVID-19 infection and produce an orchestration of cellular, complement and cytokines cascades. These led to the approach using immunosuppressive agents. It is intriguing whether certain biomarkers can aid the proper administration of such drugs. Methods Plasma specimens of 58 COVID-19 patients with differing severity, from very mild illness (group A), mild (group B), moderate (group C), and severe/critical illness (group D) were assayed for cyto-chemokines and terminal complement complex (SC5b-9) during the course of diseases. None received anti-IL-6 therapy, there was no mortality in this cohort. Results IP-10 and RANTES levels were dominant cytokines. IP-10 levels increased significantly in all groups when compared between pre-nadir and nadir phases (group A, p =0.428; group B =0.034; group C =0.159; group D <0.001) and in groups B and D when compared between nadir and recovery phases (p <0.001). RANTES levels were elevated in all groups across all phases with no significant differences. SC5b-9 levels increased significantly as compared to healthy controls [pre-nadir- group A versus healthy, p =0.122; group B-D versus healthy, p =0.021); nadir-group A versus healthy, p =0.003; group B-D versus healthy, p <0.001; recovery phase (p <0.001)] but not between groups A and B-D at pre-nadir (p=0.606). Conclusion The absence of significant pro-inflammatory responses and early elevation of IP-10 levels and complement activation may be favorable and necessary for viral elimination in COVID-19 patients. Expression of distinct cyto-chemokines during each clinical phase may be useful for guiding proper therapeutic interventions on alleviating thrombo-inflammation responses to COVID-19 infection.","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":"45538333","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: 4
C1q/TNF-related protein-1: Potential biomarker for early diagnosis of autism spectrum disorder. C1q/TNF相关蛋白-1:早期诊断自闭症谱系障碍的潜在生物标记物。
IF 3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221079471
Hamed Raeisy, Paria Bayati, Farshid Noorbakhsh, Mitra Hakim Shooshtari, Mehrdad Eftekhar Ardebili, Mehdi Shekarabi, Nazanin Mojtabavi

Introduction: Autism spectrum disorders (ASDs) are neurodevelopmental diseases characterized by communication inabilities, social interaction impairment, repetitive behavior, as well as learning problems. Although the exact mechanism underlying this disease is still obscure, researchers believe that several factors play a significant role in its development and pathogenesis. Some authors have reported an association between adipokines family and autism. C1q/TNF-related protein-1 (CTRP1) is a member of the adipokines family, and we hypothesized that this adipokine might have an influential role in the pathogenesis of ASDs. Since there is no specific marker for screening the disease, we evaluated CTRP1 as a potential marker for achieving this purpose.

Methods: Blood samples were collected from 82 (41 ASDs boys, 41 healthy boys as controls) children aged 5-7 years old. CTRP1 gene expression and CTRP1 serum level were measured by quantitative realtime-PCR and enzyme-linked immunosorbent assay methods, respectively.

Results: It was found that CTRP1 is significantly elevated in autistic children in comparison to healthy controls, both at the gene expression level, as well as at the serum level; demonstrating a good diagnostic value with a good range of sensitivity and specificity for detecting ASDs.

Conclusion: CTRP1 expression is elevated in ASDs boys aged 5-7 years old, suggesting a role for this adipokine in ASDs pathophysiology. Also, receiver operating characteristic curve analyses revealed that this adipokine could be utilized as a diagnostic biomarker for differentiating ASDs patients from healthy individuals along with other recently proposed biomarkers.

简介自闭症谱系障碍(ASDs)是一种神经发育疾病,以沟通障碍、社会交往障碍、重复行为和学习问题为特征。尽管这种疾病的确切机制尚不清楚,但研究人员认为,有几个因素在其发展和发病机制中起着重要作用。一些学者报告了脂肪因子家族与自闭症之间的联系。C1q/TNF相关蛋白-1(CTRP1)是脂肪因子家族的成员之一,我们推测这种脂肪因子可能在自闭症的发病机制中起着重要作用。由于目前还没有筛查该疾病的特异性标志物,我们将 CTRP1 作为一种潜在的标志物进行了评估:方法:我们采集了 82 名 5-7 岁儿童(41 名 ASD 男孩,41 名健康男孩作为对照)的血样。方法:采集 82 名 5-7 岁儿童(41 名 ASD 男孩,41 名健康男孩作为对照)的血液样本,分别采用实时定量 PCR 法和酶联免疫吸附法测定 CTRP1 基因表达和 CTRP1 血清水平:结果:研究发现,与健康对照组相比,自闭症儿童的 CTRP1 在基因表达水平和血清水平上都明显升高;这表明 CTRP1 在检测 ASD 方面具有良好的诊断价值,并具有较高的灵敏度和特异性:结论:CTRP1 在 5-7 岁的 ASD 男孩中表达升高,表明这种脂肪因子在 ASD 的病理生理学中发挥作用。此外,接收器操作特征曲线分析表明,该脂肪因子可与其他最新提出的生物标记物一起用作诊断生物标记物,以区分 ASD 患者和健康个体。
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引用次数: 0
Laboratory biomarker predictors for disease progression and outcome among Egyptian COVID-19 patients 埃及COVID-19患者疾病进展和结局的实验室生物标志物预测指标
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221096207
L. Fathalla, Lamyaa Kamal, Omina Salaheldin, Mahmoud Khalil, Mahmoud M. Kamel, Hagar H. Fahim, Youssef A. S. Abdel-Moneim, Jawaher A. Abdulhakim, A. S. Abdel-Moneim, Yomna M El-Meligui
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic resulted in more than five hundred million infected cases worldwide. The current study aimed to screen the correlation of different laboratory findings with disease severity and clinical outcomes of coronavirus disease (COVID-19) among Egyptian patients to obtain prognostic indicators of disease severity and outcome. A total of 112 laboratory-confirmed COVID-19 patients were examined. According to the severity of the disease, these patients were divided into three main groups: mild, moderate and severe cases. In addition, clinical characteristics and laboratory findings, including Hb, platelet count, white blood cell count, lymphocyte percentage, neutrophil percentage, neutrophil lymphocyte ratio (NLR), D-dimer, highly sensitive C-reactive protein (HS-CRP), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and creatinine, were measured. The presence of hypertension and/or diabetes was found to be a significant risk factor for disease severity and poor outcome. Increased respiratory rate, levels of SpO2, HS-CRP, D-dimer, NLR, ALT, LDH, lymphopenia and neutrophilia, as well as changes in chest computed tomography (CT), were associated with increased disease severity and fatal consequences. Highly sensitive C-reactive protein, D-dimer, NLR and LDH constituted excellent predictors for both disease severity and death. Laboratory biomarkers, such as HS-CRP, D-dimer, NLR and LDH, are excellent predictors for both disease severity and death. They can predict mortality in patients at the time of admission secondary to SARS-CoV-2 infection and can help physicians identify high-risk patients before clinical deterioration.
严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)大流行导致全球感染病例超过5亿例。本研究旨在筛选埃及冠状病毒病(COVID-19)患者不同实验室检查结果与疾病严重程度和临床转归的相关性,获得疾病严重程度和转归的预后指标。共检测实验室确诊病例112例。根据病情的严重程度,将这些患者分为轻、中、重度三组。此外,还测量了临床特征和实验室结果,包括Hb、血小板计数、白细胞计数、淋巴细胞百分比、中性粒细胞百分比、中性粒细胞淋巴细胞比率(NLR)、d -二聚体、高敏c反应蛋白(HS-CRP)、丙氨酸转氨酶(ALT)、乳酸脱氢酶(LDH)和肌酐。发现高血压和/或糖尿病的存在是疾病严重程度和不良预后的重要危险因素。呼吸频率增加、SpO2、HS-CRP、d -二聚体、NLR、ALT、LDH、淋巴细胞减少症和中性粒细胞增多以及胸部计算机断层扫描(CT)的变化与疾病严重程度增加和致命后果相关。高度敏感的c反应蛋白、d -二聚体、NLR和LDH是疾病严重程度和死亡的优秀预测因子。实验室生物标志物,如HS-CRP、d -二聚体、NLR和LDH,是疾病严重程度和死亡的极好预测指标。它们可以预测患者在入院时继发于SARS-CoV-2感染的死亡率,并可以帮助医生在临床恶化之前识别高危患者。
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引用次数: 3
Is there any predictor for relapse after treatment withdrawal in autoimmune hepatitis patients in the real life? 现实生活中自身免疫性肝炎患者停药后是否有复发的预测因子?
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221077860
Bilger Çavuş, Filiz Akyuz, Raim İliaz, Alp Atasoy, Umit Akyuz, Kadir Demir, Fatih Besisik, Sabahattin Kaymakoglu

Backgrounds and aims: In autoimmune hepatitis, there are uncertainties about whether to discontinue the treatment, when the treatment should be discontinued, and the risks of relapse in the cases where remission is achieved with immunosuppressive therapy. In this study, patients with AIH, whose immunosuppressive treatments were discontinued, were evaluated for the rates of remission and the risk of relapse.

Materials and methods: A total of 119 patients, who were diagnosed with AIH based on the AIHG scoring systems between 1990 and 2015, were evaluated. Patients were receiving standard azathioprine and steroid therapy. The treatment was discontinued in patients, who had been receiving treatment for at least 2 years, who had no clinical complaints, and whose aminotransferases were normal and when an increase occurred in AST values more than two times the normal after the treatment was interrupted, the case was considered as a relapse.

Results: Among the patients, 83%(n = 99) were women. When the patients were diagnosed with AIH, their mean age was 36 ± 16(8-79) years; 70.6%(n = 84) were type 1, 3.4%(n = 4) type 2, and 26%(n = 31) were autoantibody-negative AIH. At the time of discontinuation, liver biopsy was performed in 8 of the patients and minimal-mild abnormalities were detected. Patients whose treatment was discontinued received treatment for an average of 101 ± 75(range: 24-280, median: 68.5) months; and, they were followed up for an average of 19 (1-110) months during the period without medication. Relapse occurred in 67%(n = 12) of the patients with drug withdrawal. Relapse occurred within the first 12 months in 67% of these patients (n = 8) and developed with an acute hepatitis attack in 42%. None of the clinical, laboratory, and histological data were found to be effective on relapse.

Conclusion: In patients with AIH, relapse occurs in two-thirds of patients within an average of 19 month after the discontinuation of the medication. Most relapses occur at the early period and they are accompanied by an acute hepatitis attack.

背景和目的:在自身免疫性肝炎中,是否应该停止治疗,何时应该停止治疗,以及在免疫抑制治疗获得缓解的情况下复发的风险存在不确定性。在这项研究中,对停止免疫抑制治疗的AIH患者的缓解率和复发风险进行了评估。材料与方法:对1990 - 2015年间根据AIHG评分系统诊断为AIH的119例患者进行评估。患者接受标准硫唑嘌呤和类固醇治疗。治疗至少2年,无临床主诉,转氨酶正常,停药后AST升高超过正常2倍者,视为复发。结果:患者中女性占83%(n = 99)。确诊为AIH时,患者平均年龄36±16(8-79)岁;70.6%(n = 84)为1型,3.4%(n = 4)为2型,26%(n = 31)为自身抗体阴性AIH。在停药时,8例患者进行了肝活检,发现了轻微的异常。停止治疗的患者接受治疗的平均时间为101±75个月(范围:24-280,中位数:68.5);在不给药期间,平均随访19个月(1 ~ 110个月)。停药后复发的患者占67%(n = 12)。67%的患者(n = 8)在前12个月内复发,42%的患者出现急性肝炎发作。临床、实验室和组织学资料均未发现对复发有效。结论:在AIH患者中,三分之二的患者在停药后平均19个月内复发。大多数复发发生在早期,并伴有急性肝炎发作。
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引用次数: 1
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International Journal of Immunopathology and Pharmacology
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