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Linear IGA bullous dermatosis potentially triggered by vaccination. 可能由疫苗接种引发的线性 IGA 大疱性皮肤病。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211021218
Alberto Corrà, Veronica Bonciolini, Lavinia Quintarelli, Alice Verdelli, Marzia Caproni

Linear IgA bullous dermatosis (LABD) is a mucocutaneous autoimmune blistering disease affecting both adults and children. It is caused by IgA antibodies targeting multiple antigens along the basement membrane zone, leading to disruption of dermoepidermal junction and development of bullous lesions which often presents in characteristic arrangement. Although most LABD cases have been reported to be idiopathic, different triggers have been described, including several drugs and infection. However, the occurrence of vaccine-induced cases of LABD is not widely known and accepted due to the few reports available. We present two cases of LABD occurred following different triggers, rising the suspicion for a possible pathogenetic role of vaccines.

线性 IgA 大疱性皮肤病(LABD)是一种粘膜自身免疫性水疱病,成人和儿童均可患病。它是由针对基底膜区多种抗原的 IgA 抗体引起的,导致真皮表皮交界处的破坏和大疱性皮损的发展,通常呈特征性排列。虽然大多数 LABD 病例被报告为特发性,但也有不同诱因的描述,包括几种药物和感染。然而,由于现有报道较少,疫苗诱发的 LABD 病例尚未被广泛知晓和接受。我们介绍了两例在不同诱因下发生的 LABD 病例,使人们更加怀疑疫苗可能具有致病作用。
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引用次数: 0
MicroRNA-30 inhibits the growth of human ovarian cancer cells by suppressing RAB32 expression. MicroRNA-30通过抑制RAB32的表达抑制人卵巢癌细胞的生长。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211058642
Yan Zhang, Min Zhou, Kun Li

Introduction: MicroRNAs (miRs) exhibit the potential to act as therapeutic targets for the management of human cancers including ovarian cancer. The role of microRNA-30 (miR-30) via modulation of RAB32 expression has not been studied in ovarian cancer. Consistently, the present study was designed to characterize the molecular role of miR-30/RAB32 axis in human ovarian cancer.

Methods: Cell viability was determined by MTT assay. Expression analysis was carried out by qRT-PCR. Dual luciferase assay was used to confirm the interaction between miR-30 and RAB32. Scratch-heal and transwell chamber assays were used to monitor the cell migration and invasion. Western blotting and immunofluorescence assays were used to determine the protein expression.

Results: The results revealed significant (p < 0.05) downregulation of miR-30 in human ovarian cancer cell lines. Overexpression of miR-30 in ovarian SK-OV-3 and A2780 cancer cells significantly (p < 0.05) inhibited their proliferation. Besides, ovarian cancer cells overexpressing miR-30 showed significantly (p < 0.05) lower migration and invasion. The miR-30 upregulation also altered the expression pattern of marker proteins of epithelial-mesenchymal transition in ovarian cancer cells. In silico analysis predicted RAB32 as the molecular target of miR-30 at post-transcriptional level. The silencing of RAB32 mimicked the tumor-suppressive effects of miR-30 overexpression in ovarian cancer cells. Nonetheless, overexpression of RAB32 could prevent the tumor-suppressive effects of miR-30 on SK-OV-3 and A2780 cancer cells.

Conclusion: Taken together, the results suggest the tumor-suppressive role of miR-30 and point towards the therapeutic utility of miR-30/RAB32 molecular axis in the management of ovarian cancer.

MicroRNAs (miRs)显示出作为包括卵巢癌在内的人类癌症治疗靶点的潜力。microRNA-30 (miR-30)通过调节RAB32表达在卵巢癌中的作用尚未被研究。同样,本研究旨在表征miR-30/RAB32轴在人卵巢癌中的分子作用。方法:采用MTT法测定细胞活力。采用qRT-PCR进行表达分析。双荧光素酶测定证实miR-30与RAB32之间的相互作用。采用刮刮法和通孔室法监测细胞迁移和侵袭。Western blotting和免疫荧光法检测蛋白表达。结果:miR-30在人卵巢癌细胞系中表达显著下调(p < 0.05)。miR-30在卵巢SK-OV-3和A2780癌细胞中过表达,可显著抑制其增殖(p < 0.05)。此外,过表达miR-30的卵巢癌细胞迁移和侵袭能力明显降低(p < 0.05)。miR-30上调也改变了卵巢癌细胞上皮-间质转化标记蛋白的表达模式。在硅分析预测RAB32是miR-30转录后水平的分子靶标。RAB32的沉默模拟了卵巢癌细胞中miR-30过表达的肿瘤抑制作用。然而,RAB32的过表达可以阻止miR-30对SK-OV-3和A2780癌细胞的肿瘤抑制作用。结论:综上所述,这些结果提示了miR-30的肿瘤抑制作用,并指出miR-30/RAB32分子轴在卵巢癌治疗中的治疗作用。
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引用次数: 5
Autoimmune hepatitis in Egyptian children: A single center experience 埃及儿童自身免疫性肝炎:单中心经验
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/20587384211073265
E. Mogahed, H. El-Karaksy, Heba Zaki, H. Abdullatif
Background and aim Autoimmune hepatitis (AIH) has variable clinical manifestations and should be considered in the diagnostic work-up of any patient with cryptogenic liver disease. The aim of the study was to determine the clinical, biochemical, histopathological characteristics and treatment outcome of AIH in Egyptian children. Patients and methods This observational study was conducted at the Pediatric Hepatology Unit at Cairo University Pediatric Hospital, Egypt. All children (<18 years of age) presenting from 2009 to 2016 with established diagnosis of AIH were included. Medical history, clinical examination, and results of investigations were retrieved from patients’ files. The main outcome measures included the rate of remission, relapses, and mortality. Results The study included 34 children with AIH. Twenty patients (58%) presented with chronic liver disease. There was a history of concomitant autoimmune diseases in 5 patients. Transaminases were elevated in all patients. There was synthetic dysfunction in 58%. Twenty-four patients (70.5%) had AIH-1, while nine patients (26.4%) had AIH-2 and one patient (2.9%) had autoantibody negative AIH. Piecemeal necrosis was observed in the liver biopsy of 79% of our cohort. Approximately 80% achieved biochemical remission (88% received combined therapy of prednisolone and azathioprine). About half of the patients developed relapses. One patient died of liver cell failure. Conclusion In children with liver disease, a diagnosis of AIH should be considered. In those patients, AIH-1 is more common than AIH-2. Prednisolone monotherapy or combined with azathioprine could achieve remission, but relapse is still common. Treatment non-adherence is the main risk factor for relapse.
背景和目的自身免疫性肝炎(AIH)具有多种临床表现,在任何隐源性肝病患者的诊断检查中都应予以考虑。本研究的目的是确定埃及儿童AIH的临床、生化、组织病理学特征和治疗结果。患者和方法本观察性研究在埃及开罗大学儿科医院儿科肝病科进行。所有2009年至2016年确诊为AIH的儿童(<18岁)被纳入研究。从患者档案中检索病史、临床检查和调查结果。主要结局指标包括缓解率、复发率和死亡率。结果纳入34例AIH患儿。20例(58%)患者表现为慢性肝病。5例患者有自身免疫性疾病合并史。所有患者转氨酶均升高。58%存在合成功能障碍。AIH-1 24例(70.5%),AIH-2 9例(26.4%),自身抗体阴性AIH 1例(2.9%)。在我们的队列中,79%的肝脏活检观察到碎片性坏死。大约80%达到生化缓解(88%接受强的松龙和硫唑嘌呤联合治疗)。大约一半的患者出现了复发。一名患者死于肝细胞衰竭。结论肝病患儿应考虑AIH的诊断。在这些患者中,AIH-1比AIH-2更常见。强的松龙单药或联合硫唑嘌呤可达到缓解,但复发仍然常见。治疗不依从是复发的主要危险因素。
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引用次数: 1
Association of baseline parameters with year 0 and year 1 acute exacerbations in male patients with chronic obstructive pulmonary disease 男性慢性阻塞性肺病患者基线参数与0年和1年急性加重的关系
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221099073
Yu-Ping Chang, Yu-Mu Chen, Ya-Chun Chang, Shih-Feng Liu, Wen-Feng Fang, T. Chao, Chao-Chien Wu, Huang-Chih Chang, Meng-Chih Lin, Yung-Che Chen
Objectives Acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) can affect health status, hospitalization and readmission rates, and disease progression. This study aimed to identify independent markers associated with COPD AEs. Methods This study included male patients with COPD and collected data regarding their AEs and baseline clinical parameters. Results We included 149 male patients. Among them, 58 were included in the year 0 high-AE group and 91 in the low-AE group. Multivariate analysis revealed that the high-AE group had higher white blood cell count, lower serum albumin level, and post-bronchodilator (BD) forced expiratory volume in one second (FEV1) (%) with a combined receiver operating characteristic curve (ROC) of 0.721 (p < 0.001). Additionally, 34 patients were included in the year 1 high-AE group and 70 in the low-AE group (p < 0.001). Multivariate analysis revealed that the high-AE group had higher platelet count, positive asthma history, and lower pre-BD FEV1 (%) with a combined ROC of 0.782 (p < 0.001). Conclusion In male patients with COPD, baseline white blood cell count, albumin level, and post-BD FEV1 (%) were correlated with year 0 AE; on the other hand, baseline platelet count, positive asthma history, and pre-BD FEV1 (%) were associated with year 1 AE.
目的慢性阻塞性肺病(COPD)的急性加重(AE)会影响健康状况、住院率和再入院率以及疾病进展。本研究旨在确定与COPD AE相关的独立标志物。方法本研究纳入男性COPD患者,收集他们的AE和基线临床参数数据。结果纳入149例男性患者。其中0年高AE组58例,低AE组91例。多因素分析显示,高AE组的白细胞计数较高,血清白蛋白水平较低,支气管扩张剂(BD)后1秒用力呼气量(FEV1)(%),联合受试者工作特征曲线(ROC)为0.721(p<0.001)。此外,1年高AE组有34名患者,低AE组有70名患者(p<0.001)。多因素分析显示,高AE组血小板计数较高,有哮喘阳性史,BD前FEV1(%)较低,合并ROC为0.782(p<001),BD后FEV1(%)与0年AE相关;另一方面,基线血小板计数、阳性哮喘史和BD前FEV1(%)与1年AE相关。
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引用次数: 0
COVID-19 diversity: A case of multisystem inflammatory syndrome in children masquerading as juvenile systemic lupus erythematosus. COVID-19 多样性:一例伪装成幼年系统性红斑狼疮的儿童多系统炎症综合征。
IF 3 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221131981
Ali Sobh, Madiha Abdalla, Ashraf M Abdelrahman, Doaa Mosad Mosa

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection may present with some systemic lupus erythematosus (SLE) manifestations intermingled with Kawasaki disease features. These emerging presentations were dubbed under the umbrella term 'multisystem inflammatory syndrome in children (MIS-C)'. A one and half-year-old girl, admitted to Mansoura University Children's Hospital (MUCH) with fever, bad general condition, vomiting, widespread maculopapular, vasculitic rash, hands and feet oedema, oral ulceration, arthralgia and lymphadenopathy. Moreover, bicytopenia, positive antinuclear, anti-double-stranded DNA antibodies and low C3 qualified her as a case of juvenile SLE. Despite the child received the initial therapy of immunosuppressive medication, her general condition deteriorated with fever persistence and rash exacerbation. At that time, the skin of her hands and feet started to peel. Thus, an expanded study for other alternatives was obligatory; SARS-CoV-2 infection testing revealed positive IgG serology, and retesting for lupus autoantibodies turned negative. HRCT chest showed bilateral basal consolidation with ground-glass appearance. Furthermore, Echo exhibited coronary artery dilation with thrombus inside. This evolution raised the concern for COVID-related MIS-C syndrome. This report provides a model of COVID-19 heterogeneity with protean immune-related manifestations. This case has a unique presentation that necessities its description, in order to provide a nidus for future studies in this new entity.

严重急性呼吸系统综合征冠状病毒-2(SARS-CoV-2)感染可能会出现一些系统性红斑狼疮(SLE)表现,并与川崎病的特征混杂在一起。这些新出现的表现被称为 "儿童多系统炎症综合征(MIS-C)"。一名一岁半的女孩因发热、全身状况不佳、呕吐、广泛的斑丘疹、血管炎皮疹、手足水肿、口腔溃疡、关节痛和淋巴结病入住曼苏尔大学儿童医院(MUCH)。此外,双血细胞减少、抗核抗体阳性、抗双链 DNA 抗体和低 C3 使她成为一名幼年系统性红斑狼疮患者。尽管患儿接受了免疫抑制药物的初步治疗,但她的全身状况还是恶化了,发烧持续不退,皮疹加重。当时,她的手脚皮肤开始脱皮。SARS-CoV-2感染检测显示IgG血清学阳性,狼疮自身抗体复查结果为阴性。胸部 HRCT 显示双侧基底合并症,呈磨玻璃样。此外,回波显示冠状动脉扩张,内有血栓。这一演变引发了对 COVID 相关 MIS-C 综合征的担忧。本报告提供了一个具有蛋白免疫相关表现的 COVID-19 异质性模型。该病例表现独特,有必要对其进行描述,以便为今后研究这一新实体提供基础。
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引用次数: 0
Syk promotes phagocytosis by inducing reactive oxygen species generation and suppressing SOCS1 in macrophage-mediated inflammatory responses. 在巨噬细胞介导的炎症反应中,Syk通过诱导活性氧生成和抑制SOCS1来促进吞噬。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221133018
Young-Su Yi, Han Gyung Kim, Ji Hye Kim, Woo Seok Yang, Eunji Kim, Jae Gwang Park, Nur Aziz, Narayanan Parameswaran, Jae Youl Cho

Objective: Inflammation, a vital innate immune response against infection and injury, is mediated by macrophages. Spleen tyrosine kinase (Syk) regulates inflammatory responses in macrophages; however, its role and underlying mechanisms are uncertain.

Materials and methods: In this study, overexpression and knockout (KO) cell preparations, phagocytosis analysis, confocal microscopy, reactive oxygen species (ROS) determination, mRNA analysis, and immunoprecipitation/western blotting analyses were used to investigate the role of Syk in phagocytosis and its underlying mechanisms in macrophages during inflammatory responses.

Results: Syk inhibition by Syk KO, Syk-specific small interfering RNA (siSyk), and a selective Syk inhibitor (piceatannol) significantly reduced the phagocytic activity of RAW264.7 cells. Syk inhibition also decreased cytochrome c generation by inhibiting ROS-generating enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and ROS scavenging suppressed the phagocytic activity of RAW264.7 cells. LPS induced the tyrosine nitration (N-Tyr) of suppressor of cytokine signaling 1 (SOCS1) through Syk-induced ROS generation in RAW264.7 cells. On the other hand, ROS scavenging suppressed the N-Tyr of SOCS1 and phagocytosis. Moreover, SOCS1 overexpression decreased phagocytic activity, and SOCS1 inhibition increased the phagocytic activity of RAW264.7 cells.

Conclusion: These results suggest that Syk plays a critical role in the phagocytic activity of macrophages by inducing ROS generation and suppressing SOCS1 through SOCS1 nitration during inflammatory responses.

目的:炎症是一种重要的先天免疫反应,是由巨噬细胞介导的。脾酪氨酸激酶(Syk)调节巨噬细胞的炎症反应;然而,其作用和潜在机制尚不确定。材料和方法:本研究采用过表达和敲除(KO)细胞制备、吞噬分析、共聚焦显微镜、活性氧(ROS)测定、mRNA分析和免疫沉淀/western blotting分析等方法,研究Syk在炎症反应中巨噬细胞吞噬中的作用及其潜在机制。结果:Syk KO、Syk特异性小干扰RNA (siSyk)和选择性Syk抑制剂(piceatanol)抑制Syk可显著降低RAW264.7细胞的吞噬活性。Syk抑制还通过抑制脂多糖(LPS)刺激的RAW264.7细胞中ROS生成酶来减少细胞色素c的生成,清除ROS抑制RAW264.7细胞的吞噬活性。LPS通过syk诱导的ROS生成诱导RAW264.7细胞中细胞因子信号1抑制因子(SOCS1)的酪氨酸硝化(N-Tyr)。另一方面,ROS清除抑制了SOCS1的N-Tyr和吞噬作用。此外,SOCS1过表达降低了RAW264.7细胞的吞噬活性,SOCS1抑制提高了RAW264.7细胞的吞噬活性。结论:这些结果表明,Syk在炎症反应中诱导ROS生成,并通过SOCS1硝化抑制SOCS1,在巨噬细胞的吞噬活性中起关键作用。
{"title":"Syk promotes phagocytosis by inducing reactive oxygen species generation and suppressing SOCS1 in macrophage-mediated inflammatory responses.","authors":"Young-Su Yi,&nbsp;Han Gyung Kim,&nbsp;Ji Hye Kim,&nbsp;Woo Seok Yang,&nbsp;Eunji Kim,&nbsp;Jae Gwang Park,&nbsp;Nur Aziz,&nbsp;Narayanan Parameswaran,&nbsp;Jae Youl Cho","doi":"10.1177/03946320221133018","DOIUrl":"https://doi.org/10.1177/03946320221133018","url":null,"abstract":"<p><strong>Objective: </strong>Inflammation, a vital innate immune response against infection and injury, is mediated by macrophages. Spleen tyrosine kinase (Syk) regulates inflammatory responses in macrophages; however, its role and underlying mechanisms are uncertain.</p><p><strong>Materials and methods: </strong>In this study, overexpression and knockout (KO) cell preparations, phagocytosis analysis, confocal microscopy, reactive oxygen species (ROS) determination, mRNA analysis, and immunoprecipitation/western blotting analyses were used to investigate the role of Syk in phagocytosis and its underlying mechanisms in macrophages during inflammatory responses.</p><p><strong>Results: </strong>Syk inhibition by Syk KO, Syk-specific small interfering RNA (siSyk), and a selective Syk inhibitor (piceatannol) significantly reduced the phagocytic activity of RAW264.7 cells. Syk inhibition also decreased cytochrome c generation by inhibiting ROS-generating enzymes in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and ROS scavenging suppressed the phagocytic activity of RAW264.7 cells. LPS induced the tyrosine nitration (N-Tyr) of suppressor of cytokine signaling 1 (SOCS1) through Syk-induced ROS generation in RAW264.7 cells. On the other hand, ROS scavenging suppressed the N-Tyr of SOCS1 and phagocytosis. Moreover, SOCS1 overexpression decreased phagocytic activity, and SOCS1 inhibition increased the phagocytic activity of RAW264.7 cells.</p><p><strong>Conclusion: </strong>These results suggest that Syk plays a critical role in the phagocytic activity of macrophages by inducing ROS generation and suppressing SOCS1 through SOCS1 nitration during inflammatory responses.</p>","PeriodicalId":14046,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":"36 ","pages":"3946320221133018"},"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/94/05/10.1177_03946320221133018.PMC9548688.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33497894","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: 1
Time-serial expression of toll-like receptor 4 signaling during polymicrobial sepsis in rats 多微生物脓毒症大鼠中toll样受体4信号的时序表达
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221090021
En-Pei Lee, Mao-Jen Lin, Han-Ping Wu
Sepsis caused by aggressive infection is a severe clinical problem with an increasing incidence worldwide. Toll-like receptors and their common adapter myeloid differentiation factor 88 (MyD88) can activate immune responses by recognizing a foreign microbe’s product. This study aimed to identify the different time expression of TLR four signaling pathway in an experimental rodent model of polymicrobial sepsis. A randomized animal study was investigated in rats with septic peritonitis induced by cecal ligation and puncture (CLP). The expressions of MyD88-dependent pathway biomarkers, including MyD88, nuclear factor-κB (NF-κB), and serum tumor necrosis factor-α (TNF-α), were analyzed and compared to the sham controls at the different time points after CLP surgery. CLP-induced sepsis increased liver MyD88 mRNA expression and protein expression compared to the control groups at 2 h after surgery. The MyD88 mRNA and protein expressions in rats with CLP-induced sepsis marked increased at 4 and 6 h, and their NF-κB activities and serum TNF-α levels also increased at 4 h after CLP surgery (both p < .05). The different serial expression of MyD88-ependent pathway during sepsis may be used as biomarkers during sepsis. These results may provide further helpful information for using pro-inflammatory biomarkers of innate immunity such as MyD88 and TNF-α in clinical sepsis or related abdominal surgical emergency in the future.
侵袭性感染引起的败血症是一个严重的临床问题,在全球范围内发病率不断上升。Toll样受体及其常见的衔接粒细胞分化因子88(MyD88)可以通过识别外来微生物的产物来激活免疫反应。本研究旨在确定TLR-four信号通路在多微生物败血症实验啮齿动物模型中的不同时间表达。一项随机动物研究在大鼠盲肠结扎穿孔(CLP)引起的败血症性腹膜炎中进行了研究。在CLP手术后的不同时间点,分析MyD88依赖性通路生物标志物的表达,包括MyD88、核因子-κB(NF-κB)和血清肿瘤坏死因子-α(TNF-α),并与假对照进行比较。CLP诱导的败血症与对照组相比,在2 手术后h。CLP诱导的脓毒症大鼠的MyD88mRNA和蛋白表达在4和6时显著增加 h、 κB活性和血清TNF-α水平也在4 CLP手术后h(均p<0.05)。脓毒症期间MyD88依赖性通路的不同序列表达可作为脓毒症的生物标志物。这些结果可能为将来在临床败血症或相关腹部外科急诊中使用MyD88和TNF-α等先天免疫的促炎生物标志物提供进一步的有用信息。
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引用次数: 1
Exploring the antihyperglycemic potential of tetrapeptides devised from AdMc1 via different receptor proteins inhibition using in silico approaches 利用计算机方法通过不同受体蛋白抑制AdMc1设计的四肽的抗高血糖潜力
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221103120
Ghulam Mustafa, H. S. Mahrosh, M. Zafar, S. A. Attique, Rawaba Arif
Introduction: Diabetes mellitus is a heterogenous group of chronic metabolic disorders that results due to deficiency in insulin secretion and signalling. Multiple factors held responsible for onset of diabetes due to defects in glucose metabolism and cellular signalling mechanism. Over the past few years, many plant derived bioactive compounds have been recorded with increased efficacy and fewer side-effects against variety of diseases. Methods: In the current study, molecular docking and molecular dynamics simulation approaches were employed to evaluate the tetrapeptides devised from AdMc1 protein of Momordica charantia. Due to unavailability of appropriate template for modelling of 3D structure of AdMc1 protein, I-TASSER server was employed for prediction of good quality tertiary structure. Predicted model was refined by GalaxyRefine Web and evaluated by Verify 3D, ERRAT and Ramachandran plot analysis. Next, a ready-to-dock library of fifty tetrapeptides as potent inhibitors was prepared and docked against aldose reductase (AR), protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, α-amylase and glycogen synthase kinase 3-beta as receptor proteins. Molecular dynamics (MD) simulation was performed on Schrodinger’s Desmond Module to check stability of the best docking complex. Results: Top five ligands were selected against each receptor protein based on their binding pattern and docking scores. Among selected ligands (i.e. VEID, TVEV, AYAY, EEIA, ITTV, TTIT, LPSM, RGIE, TTVE and EIAR) followed all parameters in drug scanning and ADMET screening tests. The MD simulations confirmed that the best selected peptide (i.e. VEID) docked with AR and PTP1B was structurally stable. Conclusion: In the light of overall results of all analyses employed in this study, the selected ligands could be further processed as potential hypoglycaemic drug candidates.
引言:糖尿病是一组异质性的慢性代谢紊乱,由胰岛素分泌和信号传导不足引起。由于葡萄糖代谢和细胞信号机制的缺陷,多种因素导致糖尿病的发病。在过去的几年里,许多植物衍生的生物活性化合物被记录在案,对各种疾病具有更高的疗效和更少的副作用。方法:采用分子对接和分子动力学模拟方法对苦瓜AdMc1蛋白中的四肽进行鉴定。由于没有合适的模板来模拟AdMc1蛋白的3D结构,I-TASSER服务器被用于预测高质量的三级结构。预测模型通过GalaxyRefineWeb进行细化,并通过Verify 3D、ERRAT和Ramachandran图分析进行评估。接下来,制备了50种四肽作为有效抑制剂的现成对接文库,并对接醛糖还原酶(AR)、蛋白酪氨酸磷酸酶1B(PTP1B)、α-葡萄糖苷酶、α-淀粉酶和糖原合成酶激酶3-β作为受体蛋白。在薛定谔的德斯蒙德模块上进行了分子动力学(MD)模拟,以检查最佳对接复合体的稳定性。结果:根据它们的结合模式和对接得分,针对每种受体蛋白选择了前五个配体。在选定的配体(即VEID、TVEV、AYAY、EEIA、ITTV、TTIT、LPSM、RGIE、TTVE和EIAR)中,遵循药物扫描和ADMET筛选测试中的所有参数。MD模拟证实,与AR和PTP1B对接的最佳选择肽(即VEID)在结构上是稳定的。结论:根据本研究中所有分析的总体结果,所选配体可以作为潜在的降血糖药物候选进行进一步处理。
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引用次数: 5
Omicron variant of SARS-CoV-2 infection elicits cross-protective immunity in people who received boosters or infected with variant strains. SARS-CoV-2的组粒变异感染在接受增强剂或感染变异菌株的人群中引起交叉保护性免疫。
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221133001
Selia Chowdhury, Md Shahraj Chowdhury, Nurjahan Shipa Chowdhury, Samia Chowdhury, Shajeda Chowdhury
Introduction The B.1.1.529 (Omicron) variant of SARS-CoV-2 is the most antigenically unique SARS-CoV-2 variant of concern to date, which is currently widespread across the world. Omicron variant and its sublineages contain a plethora of mutations than other variants of concern, which increases their transmissibility and virulence. Concerns regarding potential immunological evasion have been reignited by emerging subvariants of the Omicron variant. Determining the effectiveness of Omicron-induced immunity and whether it is cross-protective against other variants is a crucial aspect of the research. Method A systematic search of relevant articles until September 25, 2022, from databases such as PubMed, Scopus, Google Scholar, and ScienceDirect was done independently by two authors. A total of 11 articles discussing about immunological evasion of different Omicron subvariants were included in the study. Results Numerous studies have demonstrated that Omicron variant causes a restricted immune response after infection. Omicron infection boosts preexisting vaccine-induced immunity, but it may not be enough to establish widespread, cross-neutralizing humoral immunity in unvaccinated people. Conclusion Due to co-circulation and the emergence of novel SARS-CoV-2 variants, findings highlight the importance of booster vaccinations for immune protection. More studies should focus on the efficacy of Omicron-induced immunity, its cross-protective properties against other variants, and development of a universal vaccine.
简介:SARS-CoV-2的B.1.1.529 (Omicron)变体是迄今为止最受关注的抗原性最独特的SARS-CoV-2变体,目前在全球范围内广泛传播。与其他变异相比,组粒变异及其亚谱系含有过多的突变,这增加了它们的传播性和毒性。对潜在的免疫逃避的担忧已经被新出现的Omicron变体亚变体重新点燃。确定欧米克隆诱导免疫的有效性以及它是否对其他变异具有交叉保护作用是该研究的一个关键方面。方法:由两位作者独立系统检索PubMed、Scopus、Google Scholar、ScienceDirect等数据库中截至2022年9月25日的相关文章。本研究共收录了11篇讨论不同Omicron亚变免疫逃避的文章。结果:大量研究表明,Omicron变异在感染后引起有限的免疫反应。组粒感染增强了先前存在的疫苗诱导免疫,但它可能不足以在未接种疫苗的人群中建立广泛的、交叉中和的体液免疫。结论:由于共循环和新型SARS-CoV-2变体的出现,研究结果强调了加强疫苗接种对免疫保护的重要性。更多的研究应该集中在欧米克隆诱导免疫的功效,它对其他变异的交叉保护特性,以及通用疫苗的开发上。
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引用次数: 2
Blood phenotype O and indirect bilirubin are associated with lower, early COVID-19-related mortality: A retrospective study. 血液O型和间接胆红素与较低的早期covid -19相关死亡率相关:一项回顾性研究
IF 3.5 3区 医学 Q3 IMMUNOLOGY Pub Date : 2022-01-01 DOI: 10.1177/03946320221133952
Alaa Efat, Sabry Shoeib, Ali ElKholy, Osama Saied Hussein Aboelela, Doaa Elshamy

Objectives: To evaluate the ABO blood type and indirect bilirubin to predict early mortality in adults with severe COVID-19.

Methods: This retrospective observational study was conducted on 268 adult patients with laboratory-confirmed COVID-19 who had attended the intensive care unit (ICU), Quena general hospital and Luxor International Hospital, and other hospitals or centers for the treatment of COVID-19, during the period from January 2021 till December 2021.

Results: Relation between mortality and ABO group were highly significant, as we found non-O blood group with more risk of early mortality and intensive care unit admission ICU. There were significant differences between dead and alive cases as regards platelets, white blood cells WBCs (neutrophil, lymphocyte), albumin, liver enzymes aspartate transeferase (AST), alanine transferase (ALT), total direct and indirect bilirubin, creatinine, and urea.

Conclusion: There was a highly significant relation between dead cases and ABO blood group as between the O and non-O groups; also, group O was associated with less severe manifestations and or ventilation and less mortality in patients with severe COVID-19 infection. Direct bilirubin >0.5 was found to be the best predictor for mortality in cases with COVID-19 so indirect bilirubin may be considered a good protector against complications of the infection.

目的:评价ABO血型和间接胆红素对成人重症COVID-19早期死亡的预测价值。方法:对2021年1月至2021年12月期间在重症监护病房(ICU)、奎纳综合医院和卢克索国际医院等医院或中心接受COVID-19治疗的268例实验室确诊的成年COVID-19患者进行回顾性观察研究。结果:死亡率与ABO血型之间的关系非常显著,非o型血患者早期死亡和入住ICU的风险更高。在血小板、白细胞(中性粒细胞、淋巴细胞)、白蛋白、肝酶(天冬氨酸转移酶(AST)、丙氨酸转移酶(ALT)、总直接胆红素、总间接胆红素、总肌酐、总尿素等指标上,死亡组与活组有显著差异。结论:死亡病例与ABO血型、O型血与非O型血有极显著相关;此外,O组与严重COVID-19感染患者的严重症状和/或通气程度较低以及死亡率较低相关。直接胆红素>0.5被发现是COVID-19病例死亡率的最佳预测因子,因此间接胆红素可能被认为是预防感染并发症的良好保护因子。
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引用次数: 1
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International Journal of Immunopathology and Pharmacology
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