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Checkpoint Inhibitor Pneumonitis Induced by Programmed Death-1 Antibody: A Case Report and Literature Review 程序性死亡-1抗体诱导的检查点抑制剂肺炎1例报告及文献复习
Pub Date : 2021-06-23 DOI: 10.26420/jstemcellrestransplant.2021.1039
Y. Zheng, J. Li, D. Chen, Y. Li, L. Dai, L. Huang, M. Wang
Immune Checkpoint Inhibitors (ICIs) are effective treatment therapies for majority advanced tumours. However, the immune-related Adverse Events (irAEs) triggered by ICIs may affect human organs, including skin, lungs, pituitary, thyroid, blood and digestive system, leading to immunotoxicity in these organs. Checkpoint Inhibitor Pneumonitis (CIP) is one of the irAEs that could cause mortality, thereby needs special attention from the clinical physicians. In the present manuscript, the CIP occurred in a unilateral lung in one patient case with advanced oesophageal cancer treated with anti-PD-1 was analysed. Furthermore, a literature review was conducted to investigate its pathogenesis, clinical features, associated risk factors, prevention and the correlation with ICI efficacy, providing valuable information for clinical physicians.
免疫检查点抑制剂(ICIs)是大多数晚期肿瘤的有效治疗方法。然而,ICIs引发的免疫相关不良事件(irAEs)可能影响人体器官,包括皮肤、肺、垂体、甲状腺、血液和消化系统,导致这些器官的免疫毒性。检查点抑制剂肺炎(Checkpoint Inhibitor Pneumonitis, CIP)是引起死亡的irAEs之一,需要引起临床医生的特别重视。本文对1例晚期食管癌经抗pd -1治疗后单侧肺发生的CIP进行了分析。并对其发病机制、临床特点、相关危险因素、预防及与ICI疗效的相关性进行文献综述,为临床医师提供有价值的信息。
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引用次数: 0
NPS2143 Modulates the Phenotypic Switching of PASMCs by Inhibiting Autophagy in Hypoxia-Induced Pulmonary Hypertension NPS2143通过抑制缺氧诱导的肺动脉高压自噬调节PASMCs的表型转换
Pub Date : 2021-06-16 DOI: 10.26420/jstemcellrestransplant.2021.1038
L. Wang, H. Shao, B. Che, N. Wang, X. Peng, C. Wei
Background and Objectives: Pulmonary Artery Hypertension (PAH) is considered as a malignant tumor in cardiovascular disease. Our previous study found that Calcium-Sensing Receptor (CaSR) is involved in pulmonary vascular remodeling in hypoxic pulmonary hypertension (HPH). However, the relationship of Pulmonary Artery Smooth Muscle Cell (PASMC) phenotypic switching, proliferation, and autophagy in CaSR-related HPH remain unclear. The purpose of this study was to detect the role of a CaSR antagonist, NPS2143, on the vascular remodeling by autophagy modulation under hypoxia. Methods: Hypoxic rat PAH model were simulated in vivo. Meanwhile, mean Pulmonary Artery Pressure (mPAP) was measured while RVI, WT%, and WA% indices were calculated. Immunohistochemistry and Western blot were used to detect phenotypic switching and cell proliferation in pulmonary arteriole. Cell viability was determined in vitro by CCK8 and cell cycle. Cell proliferation, phenotypic switching, autophagy level and PI3K/Akt/mTOR pathways were investigated in human PASMCs through mRNA or Western blot methods. Results: Rats with hypoxic-induced PAH had an increased mPAP, RVI, WT% and WA%. Moreover, expression of CaSR was significantly increased, followed by activation of autophagy (increased LC3b and decreased p62), phenotypic switching of PASMCs (reduced calponin, SMA-a and increased OPN) and pulmonary vascular remodeling. However, NPS2143 weakened these hypoxic effects. The results using hypoxic-induced human PASMCs confirmed that NPS2143 suppressed autophagy and reversed phenotypic switching in vitro by inhibiting PI3K/Akt/mTOR pathways. Conclusions: Our study demonstrates that NPS2143 was conducive to inhibit the proliferation and reverse phenotypic switching of PASMCs by regulating autophagy levels in HPH and vascular remodeling.
背景与目的:肺动脉高压(PAH)被认为是心血管疾病中的恶性肿瘤。我们前期研究发现,钙敏感受体(CaSR)参与了缺氧性肺动脉高压(HPH)的肺血管重构。然而,肺动脉平滑肌细胞(PASMC)表型转换、增殖和自噬在casr相关HPH中的关系尚不清楚。本研究的目的是检测CaSR拮抗剂NPS2143在缺氧条件下通过自噬调节血管重构中的作用。方法:建立大鼠体内缺氧PAH模型。同时测量平均肺动脉压(mPAP),计算RVI、WT%、WA%等指标。免疫组织化学和Western blot检测肺小动脉的表型转换和细胞增殖。体外用CCK8和细胞周期测定细胞活力。通过mRNA或Western blot方法研究人PASMCs细胞增殖、表型转换、自噬水平和PI3K/Akt/mTOR通路。结果:缺氧诱导的PAH大鼠mPAP、RVI、WT%、WA%升高。此外,CaSR的表达显著升高,随之而来的是自噬的激活(LC3b升高,p62降低),PASMCs的表型转换(calponin、SMA-a降低,OPN升高)和肺血管重构。然而,NPS2143削弱了这些缺氧作用。使用缺氧诱导的人PASMCs的结果证实,NPS2143通过抑制PI3K/Akt/mTOR通路抑制自噬并逆转表型转换。结论:我们的研究表明,NPS2143通过调节HPH和血管重构中的自噬水平,有助于抑制PASMCs的增殖和逆转表型转换。
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引用次数: 0
The Bulky Dermoid Cyst of the Floor of the Mouth 口腔底部巨大的皮样囊肿
Pub Date : 2021-06-11 DOI: 10.26420/jstemcellrestransplant.2021.1037
S. Z, Y. H, G. L., G. H., G. H., Qiu C, C. H
Bulky dermoid cysts of the floor of the mouth are very rare and may induce functional disorder. We present a 68-year-old Chinese woman who presented a painless swelling in right mandibular. Physical examination revealed a painless, soft, poor mobility, doughlike mass swelling which was reached to the floor of the mouth, and MRI showed a circumscribed mass of about 20.0×10.0×12.0 cm size. After complete excision of the cyst through an extraoral approach, histology diagnosed dermoid cyst. Dermoid cyst is uncommon found in the floor of the mouth, where there is a soft, painless, associated dyspnea, dysphagia and dysarthria. Imaging may assist diagnosis. Definitive diagnosis is founded on the histology specimen. According to the location and size of the cyst on each occasion, enucleation via intraoral or extraoral approach will be chosen treatment for cyst in the floor of the mouth. Although malignant degeneration of dermoid cyst of the floor of mouth is extremely rare, there are also such a situation reports. Thus, it is important to remove a cyst before the opportunity for malignancy.
庞大的口腔底皮样囊肿是非常罕见的,可引起功能障碍。我们提出一个68岁的中国妇女谁提出了一个无痛的肿胀在右下颌骨。体格检查示无痛、柔软、活动能力差、面团状肿物,肿物延伸至口腔底部,MRI示有边界肿物,大小约20.0×10.0×12.0 cm。经口外入路完全切除囊肿后,组织学诊断为皮样囊肿。皮样囊肿不常见于口腔底部,有柔软,无痛,相关的呼吸困难,吞咽困难和构音障碍。影像可辅助诊断。最终诊断建立在组织学标本上。对于口腔底部的囊肿,可根据每次囊肿的位置和大小,选择经口内或口外入路进行除核。虽然口腔底皮样囊肿的恶性变性极为罕见,但也有这样的情况报道。因此,在出现恶性肿瘤之前切除囊肿是很重要的。
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引用次数: 0
Driver Gene Mutations and Risk of Lymph Node Metastasis in Non-Small Cell Lung Cancer 非小细胞肺癌的驱动基因突变与淋巴结转移风险
Pub Date : 2021-05-20 DOI: 10.26420/jstemcellrestransplant.2021.1035
Z Feiyue, Z. Li, Zhang Bing, Chen Benchao, Wan Shuting, Du-Juan Yu, L Gaofeng
Non-Small Cell Lung Cancer (NSCLC) lymph node status is closely related to its diagnosis, treatment, and prognosis. The lymph node status is an important basis for formulating clinical treatment strategies of NSCLC, therefore comprehensive and profound understanding of risk factors for lymph node metastasis is essential. There are many known factors for lymph node metastasis in NSCLC, such as pathological subtypes, tumor size, tumor location. Meanwhile, whether the mutation of the driver gene affects the lymph node metastasis is still lacking enough research. This article aims to elaborate the relationship between NSCLC driver gene mutation and lymph node metastasis, from NSCLC lymph node metastasis-related risk factors, driver genes and lymph node metastasis, metastatic lymph node mutation status analysis and detection these several aspects to summarize the latest research progress in NSCLC driver gene mutation and lymph node metastasis risk. It also fully explained the correlation between driver gene mutations and NSCLC tumor biological behaviors such as lymph node metastasis.
非小细胞肺癌(NSCLC)的淋巴结状态与其诊断、治疗和预后密切相关。淋巴结状况是制定NSCLC临床治疗策略的重要依据,因此全面深入了解淋巴结转移的危险因素至关重要。NSCLC的淋巴结转移有很多已知的因素,如病理亚型、肿瘤大小、肿瘤位置等。同时,驱动基因的突变是否影响淋巴结转移还缺乏足够的研究。本文旨在阐述NSCLC驱动基因突变与淋巴结转移的关系,从NSCLC淋巴结转移相关危险因素、驱动基因与淋巴结转移、转移淋巴结突变状态分析及检测这几个方面综述NSCLC驱动基因突变与淋巴结转移风险的最新研究进展。这也充分解释了驱动基因突变与NSCLC肿瘤生物学行为如淋巴结转移的相关性。
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引用次数: 0
Stem Cells Applications in Therapeutics and Site-Specific Genome Editing Through CRISPR Cas9 System 干细胞在治疗学中的应用以及通过CRISPR Cas9系统进行位点特异性基因组编辑
Pub Date : 2021-04-25 DOI: 10.26420/JSTEMCELLRESTRANSPLANT.2021.1036
Muhammad Javed Iqbal, Muhammad Mukheed, A. Khan, S. Irfan, Usama Hayat, Muhammad Umair Khalid, M. Raza, Kainat Amjad, Marriyam Tallat
Stem cells are immature cells that have ability to differentiate into all specific and mature cells in body. The two main characteristics of stem cells are selfrenewable and ability to differentiate into all mature, functional and adult cells types. There are the two major classes a) pluripotent stem cells which have potential to differentiate in all adult cell and b) multipotent stem cells which have capacity to differentiate into many adult cells but not in all cell types. Due to the self-renewable ability stem cells are used in therapeutics, tissue regeneration, disease modeling, regenerative medicines and to treat cardiovascular diseases, neural disorders such as Parkinson’s disease and most importantly to treat carcinomas. The human induced pluripotent stem cells provide a great platform to study and treatment of human diseases because these are able to differentiate into many functional and specialized adult cells of body. The genome editing tools such as CRISPR Cas9 system and TALENs are used to generate multiple DNA variants in hPSCs by inducing site specific mutations, frame shift mutation and deletion. In present days CRISPR Cas9 is more efficient and frequent method for genome editing which is derived from bacterial cell.
干细胞是一种未成熟的细胞,具有分化为体内所有特定的成熟细胞的能力。干细胞的两个主要特征是可自我再生和能够分化为所有成熟的、功能性的和成体的细胞类型。有两大类:a)多能干细胞,有可能分化成所有的成人细胞;b)多能干细胞,有能力分化成许多成人细胞,但不是所有的细胞类型。由于干细胞的自我再生能力,它被用于治疗、组织再生、疾病建模、再生药物和治疗心血管疾病、神经系统疾病如帕金森病,最重要的是用于治疗癌症。人类诱导多能干细胞能够分化成多种功能特异的成体细胞,为人类疾病的研究和治疗提供了良好的平台。利用CRISPR Cas9系统和TALENs等基因组编辑工具,通过诱导位点特异性突变、移框突变和缺失,在hPSCs中产生多种DNA变异。目前,CRISPR Cas9是一种更有效、更常用的基因组编辑方法,它来源于细菌细胞。
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引用次数: 2
Stem Cells Applications in Therapeutics and Site-Specific Genome Editing Through CRISPR Cas9 System 干细胞在治疗学中的应用以及通过CRISPR Cas9系统进行位点特异性基因组编辑
Pub Date : 2021-02-06 DOI: 10.26420/jstemcellrestransplant.2021.1033
Javed M, K. A, Mukheed M
Stem cells ae immature cells that have ability to differentiate into all specific and mature cells in body. The two main characteristics of stem cells are selfrenewable and ability to differentiate into all mature, functional and adult cells types. There are the two major classes a) pluripotent stem cells which have potential to differentiate in all adult cell and b) multipotent stem cells which have capacity to differentiate into many adult cells but not in all cell types. Due to the self-renewable ability stem cells are use in therapeutics, tissue regeneration, disease modeling and regenerative medicines and to treat cardiovascular diseases, neural disorders such as Parkinson’s disease and most importantly to treat carcinomas. The human induced pluripotent stem cells provide a great platform to study and treatment of human diseases because these are able to differentiate into many functional and specialized adult cells of body. The genome editing tools such as CRISPR Cas9 system and TALENs are used to generate multiple DNA variants in hPSCs by inducing site specific mutations, frame shift mutation and deletion. In present days CRISPR Cas9 is more efficient and frequent method for genome editing which is derived from bacterial cell.
干细胞是一种未成熟的细胞,具有分化为体内所有特定的成熟细胞的能力。干细胞的两个主要特征是可自我再生和能够分化为所有成熟的、功能性的和成体的细胞类型。有两大类:a)多能干细胞,有可能分化成所有的成人细胞;b)多能干细胞,有能力分化成许多成人细胞,但不是所有的细胞类型。由于具有自我再生的能力,干细胞被用于治疗、组织再生、疾病建模和再生药物,以及治疗心血管疾病、帕金森病等神经疾病,最重要的是治疗癌症。人类诱导多能干细胞能够分化成多种功能特异的成体细胞,为人类疾病的研究和治疗提供了良好的平台。利用CRISPR Cas9系统和TALENs等基因组编辑工具,通过诱导位点特异性突变、移框突变和缺失,在hPSCs中产生多种DNA变异。目前,CRISPR Cas9是一种更有效、更常用的基因组编辑方法,它来源于细菌细胞。
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引用次数: 0
Pediatric Stroke and Cell-Based Treatment – Pivotal Role of Brain Plasticity 儿童中风和细胞治疗-脑可塑性的关键作用
Pub Date : 2019-05-04 DOI: 10.26420/JSTEMCELLRESTRANSPLANT.2019.1029
A. Jensen
Pediatric cerebrovascular disorders like stroke are among the top 10 causes of death in children, with rates highest in the first year of life, while survivors may face lifelong sequelae, disability, and/or cerebral palsy for which there is no cure at present. Individual treatments using human autologous cord blood Mononuclear Cells (hucbMNC) containing stem cells have yielded promising results. However, stroke is an entity with heterogenic etiologies including arterial ischemic stroke, hemorrhagic stroke, hemorrhagic infarction, and sinus venous thrombosis in newborns, infants, children, and adults. Hence, any attempt to examine care, non-cellular or cell-based therapies has to merit the specific characteristics of this heterogeneity as far as age, symptoms, diagnostics, pathophysiology, histopathology, clinical course and prevalence are concerned. This review describes the various etiologies of stroke for the Neonatal/Perinatal and childhood subsets of the pediatric population as a basis for established non-cellular and novel cell-based therapeutic approaches using cord blood mononuclear cells in the preclinical and clinical setting. In addition, due to its fundamental importance for cell-based therapeutic strategies for stroke, an account of brain plasticity along with blood-brain barrier function and the distinctions between the developing brain and the adult brain is provided. It is concluded that on the present balance of evidence the pathophysiological characteristics associated with plasticity of the developing brain are closely linked to the pharmacological action of hucbMNC in such a way that cell-based treatment might be more efficacious in pediatric stroke than in adult stroke.
中风等儿童脑血管疾病是儿童死亡的十大原因之一,在生命的第一年发病率最高,而幸存者可能面临终身后遗症、残疾和/或目前无法治愈的脑瘫。使用含有干细胞的人自体脐带血单个核细胞(hucbMNC)进行个体化治疗已经取得了令人鼓舞的结果。然而,卒中是一个具有异质性病因的实体,包括动脉缺血性卒中、出血性卒中、出血性梗死和窦静脉血栓形成,发生于新生儿、婴儿、儿童和成人。因此,就年龄、症状、诊断、病理生理学、组织病理学、临床病程和患病率而言,任何检查护理、非细胞或细胞基础疗法的尝试都必须考虑到这种异质性的具体特征。这篇综述描述了新生儿/围产期和儿童亚群中风的各种病因,作为在临床前和临床环境中使用脐带血单个核细胞建立非细胞和新型细胞治疗方法的基础。此外,由于其对基于细胞的中风治疗策略的基本重要性,脑可塑性与血脑屏障功能以及发育中的大脑与成人大脑之间的区别的解释也被提供。结论是,根据目前的证据平衡,与发育中的大脑可塑性相关的病理生理特征与hucbMNC的药理作用密切相关,因此基于细胞的治疗可能对儿童中风比成人中风更有效。
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引用次数: 4
Adult Stem Cells and Diabetes Therapy. 成体干细胞与糖尿病治疗。
Pub Date : 2015-01-01 Epub Date: 2015-12-31
Handenur Ilgun, Joseph William Kim, LuGuang Luo

The World Health Organization estimates that diabetes will be the fourth most prevalent disease by 2050. Developing a new therapy for diabetes is a challenge for researchers and clinicians in field. Many medications are being used for treatment of diabetes however with no conclusive and effective results therefore alternative therapies are required. Stem cell therapy is a promising tool for diabetes therapy, and it has involved embryonic stem cells, adult stem cells, and pluripotent stem cells. In this review, we focus on adult stem cells, especial human bone marrow stem cells (BM) for diabetes therapy, its history, and current development. We discuss prospects for future diabetes therapy such as induced pluripotent stem cells which have popularity in stem cell research area.

世界卫生组织估计,到2050年,糖尿病将成为第四大流行疾病。开发一种新的治疗糖尿病的方法对该领域的研究人员和临床医生来说是一个挑战。许多药物被用于治疗糖尿病,但没有决定性和有效的结果,因此需要替代疗法。干细胞治疗是一种很有前途的糖尿病治疗工具,它涉及胚胎干细胞、成体干细胞和多能干细胞。本文就成体干细胞,特别是人骨髓干细胞在糖尿病治疗中的应用及其历史和发展现状作一综述。讨论了近年来干细胞研究领域中备受关注的诱导多能干细胞等治疗糖尿病的前景。
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引用次数: 0
期刊
Journal of stem cell research and transplantation
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