• 文章类型: Journal Article
    银屑病是一种常见的炎症性皮肤病,严重影响患者的生活质量。银屑病的诊断主要依据临床和病理特征,评估取决于银屑病面积和严重程度指数(PASI)。然而,很少有可靠和准确的评估方法来评估病变的严重程度和治疗效果。这项工作从GEO数据集中鉴定了17个模型基因,并通过LASSO回归建立了6个银屑病评估模型,线性回归,和随机森林分开。在不同的GEO数据集中对模型进行了训练和评估。所有6个模型在训练和测试数据中准确地分类了银屑病皮损和非皮损,并显示良好的AUC。在生物制品处理的样品中,模型评分与病变严重程度呈正相关,与治疗时间呈负相关。因此,模型具有评估治疗效果的潜力。此外,在角质形成细胞中检测模型基因的表达,IMQ诱导的银屑病小鼠的皮肤,和牛皮癣患者的病变。在细胞因子刺激的角质形成细胞和银屑病病变中,模型基因的RNA和蛋白质水平如预期的那样增加。这项工作提供了评估银屑病皮损严重程度和生物制剂治疗效果的新方法。
    Psoriasis is a common inflammatory skin disease that seriously affects the patient\'s quality of life. The diagnosis of psoriasis is mainly based on clinical and pathological features, and the assessment depends on the psoriasis area and severity index (PASI). However, there are few reliable and accurate evaluation methods to assess lesion severity and therapeutic effects. This work identified 17 model genes from GEO datasets and established 6 psoriasis evaluation models by LASSO regression, linear regression, and random forest separately. Models were trained and evaluated in different GEO datasets. All 6 models accurately classified psoriatic lesions and non-lesional skin in training and testing data, and showed good AUC. In biologics-treated samples, the model scores were positively correlated with the severity of lesions and negatively correlated with treatment length. Thus, models have the potential to assess the therapeutic effects. In addition, the expression of model genes was examined in keratinocytes, skin of IMQ-induced psoriatic mice, and lesions of psoriasis patients. The RNA and protein levels of model genes increased in cytokine-stimulated keratinocytes and psoriatic lesions as expected. This work provides new methods to assess the lesion severity and therapeutic effects of biologics in psoriasis.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    特应性皮炎(AD)是一种以瘙痒为特征的慢性炎症性皮肤病,表皮屏障功能障碍,和不平衡的炎症反应。AD病理生理学涉及由T辅助细胞-2驱动的失调的免疫应答。许多因素,包括活性氧(ROS),通过引起细胞损伤和导致皮肤屏障功能障碍的炎症参与AD的发病机理。这篇叙述性综述旨在全面概述天然分子和抗氧化剂化合物的作用,强调其在AD预防和管理中的潜在治疗价值。它们包括维生素D,维生素E,吡哆醇,维生素C,类胡萝卜素,还有褪黑激素.一些研究报告了抗氧化剂水平与AD改善之间的统计学显着关联,然而,抗氧化剂补充剂的结果相互矛盾,尤其是维生素D,没有导致AD的改善。因此,这些膳食营养因子治疗AD的临床疗效需要在临床试验中进一步评估.同时,抗氧化剂可以以个性化的方式纳入AD患者的管理,根据疾病的严重程度量身定制,合并症,和个人需求。
    Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, epidermal barrier dysfunction, and an unbalanced inflammatory reaction. AD pathophysiology involves a dysregulated immune response driven by T helper-2 cells. Many factors, including reactive oxygen species (ROS), are involved in AD pathogenesis by causing cellular damage and inflammation resulting in skin barrier dysfunction. This narrative review aims to provide a comprehensive overview of the role of natural molecules and antioxidant compounds, highlighting their potential therapeutic value in AD prevention and management. They include vitamin D, vitamin E, pyridoxine, Vitamin C, carotenoids, and melatonin. Some studies report a statistically significant association between antioxidant levels and improvement in AD, however, there are conflicting results in which antioxidant supplementation, especially Vitamin D, did not result in improvement in AD. Therefore, the clinical efficacy of these dietary nutritional factors in the treatment of AD needs to be further evaluated in clinical trials. Meanwhile, antioxidants can be incorporated into the management of AD patients in a personalized manner, tailored to the severity of the disease, comorbidities, and individual needs.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    先前的研究表明,雄激素性脱发(AGA)患者的LncRNARP11-818O24.3水平显着降低。本研究探讨了LncRNARP11-818O24.3是否促进毛囊恢复及其可能的机制。通过H&E和溴脱氧尿苷(BrdU)染色观察丙酸睾酮诱导的毛发改变和皮肤组织病理学变化,以评估LncRNARP11-818O24.3在C57BL/6J小鼠中的治疗效果。在体外LncRNARP11-818O24.3转染的人毛囊干细胞(HFSC)中分析细胞活力。通过转录组基因测序和qRT-PCR研究了信号通路和促增殖因子。LncRNARP11-818O24.3转染成功恢复了AGA小鼠的毛发生长和毛囊细胞。在一系列的HFSC体外研究中,LncRNARP11-818O24.3转染大大促进了细胞增殖,减少了细胞凋亡。转录组基因测序提示LncRNARP11-818O24.3上调磷脂酰肌醇3-激酶(PI3K)-Akt途径。qRT-PCR结果显示,LncRNARP11-818O24.3转染后,成纤维细胞生长因子(FGF)-2上调14倍。LncRNARP11-818O24.3的毛囊恢复活性可能涉及FGF2和PI3K-Akt的上调以促进毛囊干细胞存活。这些数据不仅为AGA的发展提供了理论依据,而且为AGA患者提供了一种新的治疗方法。
    在线版本包含补充材料,可在10.1007/s10616-024-00624-3获得。
    A previous study indicated that patients with androgenic alopecia (AGA) have significantly reduced levels of LncRNA RP11-818O24.3. This study investigates whether LncRNA RP11-818O24.3 promotes hair-follicle recovery and its possible mechanism. Hair alteration and cutaneous histopathological changes induced by testosterone propionate were observed by H&E and bromodeoxyuridinc (BrdU) stain to evaluate the therapeutic effect of LncRNA RP11-818O24.3 in C57BL/6 J mice. The cellular viability was analyzed in LncRNA RP11-818O24.3-transfected human hair-follicle stem cells (HFSCs) in vitro. The signaling pathways and pro-proliferative factors were investigated by transcriptomic gene sequencing and qRT-PCR. LncRNA RP11-818O24.3 transfection successfully recovered hair growth and hair-follicle cells in AGA mice. In a series of HFSC studies in vitro, LncRNA RP11-818O24.3 transfection greatly promoted cellular proliferation and decreased cellular apoptosis. Transcriptome gene sequencing suggested that the phosphatidylinositol 3-kinase (PI3K)-Akt pathway was upregulated by LncRNA RP11-818O24.3. The qRT-PCR results showed that fibroblast growth factor (FGF)-2 was 14-times upregulated after LncRNA RP11-818O24.3 transfection. Hair-follicle recovery activity of LncRNA RP11-818O24.3 may involve the upregulation of FGF2 and PI3K-Akt to promote follicle stem cell survival. These data not only provide a theoretical basis for AGA development but also reveal a novel therapeutic method for AGA patients.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s10616-024-00624-3.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    合并结肠黑色素瘤的膀胱异常罕见。对临床医生构成诊断挑战。虽然罕见,它值得考虑作为潜在的鉴别诊断,特别是在没有黑色素瘤病史的患者中,由于其侵袭性而存在持续性血尿。我们介绍了一例55岁的女性恶性黑色素瘤,累及结肠和膀胱,并伴有血尿。鉴于病例的稀缺性和临床管理方法的可变性,迫切需要研究工作,以建立标准化方案并进行试验,以指导这一罕见实体的临床实践。
    Urinary bladder with concurrent colonic melanoma is an exceptionally uncommon occurrence, posing a diagnostic challenge for clinicians. While rare, it warrants consideration as a potential differential diagnosis, particularly in patients without a history of melanoma who present with persistent hematuria due to its aggressive nature. We present a case of a 55-year-old female with malignant melanoma involving the colon and urinary bladder presenting with hematuria. Given the scarcity of cases and variability in clinical management approaches, there is a pressing need for research efforts to establish standardized protocols and conduct trials to guide clinical practice in this rare entity.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    目标:本研究旨在评估新的2022年美国风湿病学会(ACR)/欧洲风湿病学协会联盟(EULAR)标准在先前诊断为抗中性粒细胞胞浆抗体相关血管炎(AAV)的土耳其成年患者中的适用性。患者和方法:164名患者(96名男性,68名女性;平均年龄:49.6±14.4岁;范围,在2016年7月至2022年5月之间由经验丰富的风湿病学家诊断为AAV的18至87年)被纳入这项回顾性横断面研究,并根据1990年ACR标准重新分类,欧洲药品管理局(EMEA)算法,和2022年ACR/EULAR标准。对于外部验证,83名患者(48名男性,35名女性;平均年龄:47.3±17.5岁;范围,包括19至81岁)诊断为免疫球蛋白(Ig)A血管炎。结果:一百二十六(76.8%)患者患有肉芽肿合并多血管炎(GPA),13例(7.9%)患者有嗜酸性肉芽肿伴多血管炎(EGPA),25例(15.2%)患者患有显微镜下多血管炎(MPA)。根据标准,2022年ACR/EULARAAV分类标准和EMEA算法的未分类患者数为9例(5.5%).新标准与临床医生的诊断几乎完全一致(Cohen的kappa系数[κ]=0.858,对于EGPA,κ=0.820,对于MPA,κ=0.847)。2022年ACR/EULAR分类标准与EMEA算法的一致性的kappa统计数据为GPA的0.794,EGPA为0.820,MPA为0.700。确诊为IgA血管炎的83例患者中,没有一个可以归类为GPA,EGPA,或使用新的ACR/EULARAAV分类标准的MPA。结论:2022年AAV的ACR/EULAR分类标准与临床诊断和EMEA算法基本或完全一致。
    Objectives: This study aimed to evaluate the applicability of the new 2022 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) criteria in Turkish adult patients previously diagnosed with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Patients and methods: One hundred sixty-four patients (96 males, 68 females; mean age: 49.6±14.4 years; range, 18 to 87 years) diagnosed with AAV by experienced rheumatologists between July 2016 and May 2022 were included in this retrospective cross-sectional study and reclassified based on the 1990 ACR criteria, the European Medicines Agency (EMEA) algorithm, and the 2022 ACR/EULAR criteria. For external validation, 83 patients (48 males, 35 females; mean age: 47.3±17.5 years; range, 19 to 81 years) diagnosed with immunoglobulin (Ig)A vasculitis were included. Results: One hundred twenty-six (76.8%) patients had granulomatosis with polyangiitis (GPA), 13 (7.9%) patients had eosinophilic granulomatosis with polyangiitis (EGPA), and 25 (15.2%) patients had microscopic polyangiitis (MPA). According to the criteria, the number of unclassified patients was nine (5.5%) for both the 2022 ACR/EULAR AAV classification criteria and the EMEA algorithm. The new criteria had an almost perfect agreement with the clinician\'s diagnosis (Cohen\'s kappa coefficient [κ]=0.858 for GPA, κ=0.820 for EGPA, and κ=0.847 for MPA). The kappa statistics for agreement of 2022 ACR/EULAR classification criteria with the EMEA algorithm were found 0.794 for GPA, 0.820 for EGPA, and 0.700 for MPA. None of the 83 patients diagnosed with IgA vasculitis could be classified as GPA, EGPA, or MPA using the new ACR/EULAR AAV classification criteria. Conclusion: The 2022 ACR/EULAR classification criteria for AAV showed substantial or perfect agreement with the clinical diagnosis and the EMEA algorithm.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    Takayasu动脉炎(TA)是一种病因不明的自身免疫实体,可引起大中型动脉肉芽肿性增厚。常见症状包括跛行,头痛,头晕,晕厥,视觉变化,还有心悸.不同的心脏表现,比如缺血性心脏病,显著的主动脉瓣反流,肺动脉高压,与TA相关联,尽管它们很少表现为充血性心力衰竭。无线电成像,包括CT血管造影和MR血管造影,随着更具侵入性的程序,如传统的血管造影,通常用于诊断。用皮质类固醇治疗,类固醇保护剂,生物制剂,和血运重建程序。这里,有一例17岁的印度女性主诉腹痛.几年前她被诊断出患有桥本甲状腺炎,还有充血性心力衰竭的病史.在一般检查中,由于双侧颈动脉杂音的存在,上肢的血压不对称。所有四肢的伸肌表面也存在广泛的鳞片状病变,提示牛皮癣。放射成像证实了TA的诊断。CT血管造影还显示腹腔干和胃左动脉近端完全闭塞,这可能是她症状的原因.患者接受皮质类固醇联合甲氨蝶呤治疗,以及其他支持性药物。TA伴充血性心力衰竭在文献中偶尔有描述,而TA与牛皮癣的关联更为罕见。各种自身免疫性疾病的同时发生是常见的,但是桥本甲状腺炎的三合会,牛皮癣,与心脏衰竭的初始表现是独特的。由于自身免疫性疾病的共同发生,为了获得最佳的健康结果,必须进行早期和全面的患者评估和全面的研究。
    Takayasu arteritis (TA) is an autoimmune entity of unknown aetiology causing granulomatous thickening of large and medium-sized arteries. Common symptoms include claudication, headaches, dizziness, syncope, visual changes, and palpitations. Diverse cardiac manifestations, such as ischemic heart disease, significant aortic regurgitation, and pulmonary hypertension, are associated with TA, although they rarely manifest as congestive heart failure. Radio-imaging, including CT angiography and MR angiography, along with more invasive procedures such as conventional angiography, are often used for diagnosis. Treatment is done with corticosteroids, steroid-sparing agents, biologics, and revascularization procedures. Here, we have a case of a 17-year-old Indian female who presented to us with a complaint of abdominal pain. She was diagnosed with Hashimoto\'s thyroiditis a few years ago, along with a history of congestive heart failure. On general examination, blood pressure was asymmetrical in the upper limbs with the presence of bilateral carotid bruit. There was also the presence of extensive scaly lesions on the extensor surface of all four limbs, suggestive of psoriasis. Radio-imaging confirmed the diagnosis of TA. CT angiography also showed total occlusion of the celiac trunk and proximal left gastric artery, which was likely the cause of her symptoms. The patient received treatment with corticosteroids in conjunction with methotrexate, along with other supportive drugs. TA with congestive heart failure has been occasionally described in the literature, while the association of TA with psoriasis is much rarer. The simultaneous occurrence of various autoimmune diseases is common, but the triad of Hashimoto thyroiditis, psoriasis, and TA with an initial presentation of heart failure is unique. Due to the common co-occurrence of autoimmune conditions, early and thorough patient evaluation with comprehensive studies is imperative for optimal health outcomes.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    白癜风是一种自身免疫性疾病,其特征是皮肤色素沉着丧失,目前尚无有效的治疗方法。本研究旨在探讨SIRT7作为介导多种疾病进展的重要脱琥珀酶,及其在白癜风进展中的作用机制。
    在本研究中利用正常人黑素细胞(NHM)PIG1和白癜风人黑素细胞(VHM)PIG3V。通过检测酪氨酸酶活性研究了沉默蛋白7(SIRT7)和Ezrin(EZR)对黑色素合成的作用,黑色素含量,α-MSH电平,和黑色素相关标志物的蛋白质水平。EZR的功能是通过救援实验确定的,虽然通过生物信息学分析研究了潜在的机制,免疫共沉淀(co-IP),免疫沉淀(IP),和蛋白质印迹技术。
    结果表明,只有SIRT7在白癜风人黑素细胞中高表达,其中敲低SIRT7转化为黑素细胞中黑色素合成增加。机械上,SIRT7敲低促进了EZR在Lys(K)60位点的琥珀酰化。此外,过表达EZR诱导黑素细胞中更高的黑色素合成,而其敲除通过抑制SIRT7敲除诱导的黑色素合成而发挥相反的作用。
    SIRT7通过抑制EZR的琥珀酰化而抑制黑素细胞中的黑色素合成。这些发现旨在为白癜风的治疗提供新的理论基础。
    UNASSIGNED: Vitiligo is an autoimmune disease characterized by loss of skin pigmentation and currently has no effective treatment. This study aimed to investigate the function of SIRT7, being an important desuccinylase mediating multiple disease progression, and its mechanism in vitiligo progression.
    UNASSIGNED: Normal human melanocytes (NHM) PIG1 and vitiligo human melanocytes (VHM) PIG3V were utilized in this research. The role of sirtuin 7 (SIRT7) and Ezrin (EZR) on melanin synthesis was investigated by detecting tyrosinase activity, melanin content, α-MSH levels, and the protein levels of melanin-related markers. The function of EZR was identified via rescue experiments, while the underlying mechanism was investigated via bioinformatic analysis, co-immunoprecipitation (co-IP), immunoprecipitation (IP), and Western blot techniques.
    UNASSIGNED: Results showed that only SIRT7 was highly expressed in vitiligo human melanocytes, where knockingdown SIRT7 translated into increased melanin synthesis in melanocytes. Mechanistically, SIRT7 knockdown promoted the succinylation of EZR at the Lys (K)60 site. Moreover, overexpressing EZR induced higher melanin synthesis in melanocytes, while its knocking down exerted the opposite effect by inhibiting SIRT7 knockdown-induced melanin synthesis.
    UNASSIGNED: SIRT7 inhibited melanin synthesis in melanocytes by suppressing the succinylation of EZR. These findings are envisaged to provide a novel theoretical basis for vitiligo treatment.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    皮肤是身体的重要屏障组织。必须精确控制皮肤中的免疫反应,否则会导致严重的疾病,如牛皮癣,特应性皮炎,或致病性感染。研究证据越来越多地证明了神经支配的重要作用,即,感觉和交感信号,调节皮肤免疫力。值得注意的是,在皮肤病中已经观察到这种神经结构的神经病变,暗示他们直接参与各种病理过程。深入了解皮肤神经病及其免疫调节作用的机制可能有助于揭示治疗干预的新切入点。这里,我们总结了神经性事件和皮肤免疫之间的神经免疫相互作用,强调这一新兴研究前沿的当前知识和未来观点。
    Skin is a vital barrier tissue of the body. Immune responses in the skin must be precisely controlled, which would otherwise cause severe disease conditions such as psoriasis, atopic dermatitis, or pathogenic infection. Research evidence has increasingly demonstrated the essential roles of neural innervations, i.e., sensory and sympathetic signals, in modulating skin immunity. Notably, neuropathic changes of such neural structures have been observed in skin disease conditions, implicating their direct involvement in various pathological processes. An in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic interventions. Here, we summarize the neuroimmune interactions between neuropathic events and skin immunity, highlighting the current knowledge and future perspectives of this emerging research frontier.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Journal Article
    二维(2D)细胞培养是发现皮肤活性剂的重要工具。成纤维细胞和角质形成细胞,更罕见的成纤维细胞-角质形成细胞共培养,通常用于此目的,其中通过与覆盖的生长培养基混合来添加测试化合物。然而,这种方法是次优的,因为它缺乏角质层成分。角质层充当选择性看门人,并且对抗许多化合物的皮内渗透,所述化合物在与细胞直接接触时具有生物活性。一种解决方案是使用重组表皮,但是这种方法既昂贵又耗时。这里,提出了一个模型,其中2D细胞培养的简单和方便与让人联想到皮肤角质层的疏水屏障的优点相结合。这个模型是用皮肤相关溶剂测试的,以及“裸露的”亲水和包封的化合物。使用细胞活力和胶原刺激作为读数。结果表明,在2D细胞培养物顶部掺入角质层替代物屏障降低了常见化妆品溶剂的细胞毒性,二甲基异山梨醇(dmi),在细胞培养中,并修改了添加的活性物质(抗坏血酸磷酸镁[MAP]和低聚原花青素[OPCs]/果聚糖生物聚合物)的生物活性,这取决于它们穿透脂质层的能力。一起来看,这些结果表明,与传统的2D系统相比,该细胞培养模型在旨在发现和分析皮肤活性化合物的工作流程中具有更好的生理相关性。
    Two-dimensional (2D) cell culture is an important tool in the discovery of skin-active agents. Fibroblasts and keratinocytes, more rarely fibroblast-keratinocyte cocultures, are usually used for that purpose, where test compounds are added by mixing with the overlaying growth medium. However, such an approach is suboptimal because it lacks the stratum corneum component. The stratum corneum acts as a selective gatekeeper and opposes the intradermal permeation of many compounds that are bioactive when placed in direct contact with cells. One solution is to use reconstituted epidermis, but this approach is costly and time consuming. Here, a model is proposed, where the simplicity and convenience of the 2D cell culture is combined with the advantage of a hydrophobic barrier reminiscent of the skin horny layer. This model was tested with skin-relevant solvents, as well as with \"naked\" hydrophilic and encapsulated compounds. Cell viability and collagen stimulation were used as readouts. The results showed that the incorporation of a stratum corneum-substitute barrier on top of a 2D cell culture reduced the cytotoxicity of a common cosmetic solvent, dimethyl isosorbide (DMI), in cell culture and modified the bioactivity of the added actives (magnesium ascorbyl phosphate [MAP] and oligomeric proanthocyanidins [OPCs]/levan biopolymer), which became dependent on their ability to penetrate through a lipidic layer. Taken together, these results indicate a better physiological relevance of this cell culture model in workflows aimed at the discovery and analysis of skin-active compounds than conventional 2D systems.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

  • 文章类型: Case Reports
    布劳综合征(BS),是一种自身炎症性肉芽肿病,其特征是皮肤有明显的三联征,接头,和结节病类似的眼部疾病,但在结节病中经常观察到的肺部受累很少。BS患者的肉芽肿表现出明显的形态,表明慢性炎症反应旺盛。BS患者可能有肉芽肿性肺病变,这需要早期诊断。为了确定是否需要对肺部病变进行治疗干预,检查经支气管镜肺冷冻活检标本并积累肺部受累的BS病例可能有助于将来改善BS管理。
    Blau syndrome (BS), is an autoinflammatory granulomatosis disease characterized by a distinct triad of skin, joint, and eye disorders similar to those of sarcoidosis, but the lung involvement frequently observed in sarcoidosis are rare. Granulomas from patients with BS displayed a distinct morphology indicating an exuberant chronic inflammatory response. Patients with BS may have granulomatous lung lesions, which require early diagnosis. To determine whether therapeutic intervention is needed for lung lesions, examining transbronchial lung cryobiopsy specimens and accumulating cases of BS with lung involvement could be contributed to improving BS management in the future.
    导出

    更多引用

    收藏

    翻译标题摘要

    我要上传

       PDF(Pubmed)

公众号