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The Role of Anti-DFS70 in the Diagnosis of Systemic Autoimmune Rheumatic Diseases 抗dfs70在系统性自身免疫性风湿病诊断中的作用
Pub Date : 2023-11-14 DOI: 10.3390/biologics3040019
Liudmila Zotova, Victoria Kotova, Zakhar Kuznetsov
The diagnosis of systemic autoimmune rheumatic disease (SARD) or its exclusion is carried out taking into account the results of immunological studies, primarily antinuclear antibodies (ANA) and specific autoantibodies. Often, during ANA analysis via indirect immunofluorescence reaction on cellular and tissue substrates, a dense fine speckled 70 (DFS70) fluorescence pattern is observed. Studies on the diagnostic significance of antibodies to anti-DFS70 allow for optimizing the stepwise diagnosis of SARD. Currently, a two-step strategy for laboratory diagnostic investigation is recommended: in the first step, ANA screening is performed, and in the second step, patients with positive results undergo confirmatory tests to detect specific antibodies against individual nuclear antigens. The detection of anti-DFS70 in ANA-seropositive patients without clinical and/or other specific serological markers characteristic of a particular disease within the SARD group may be considered a negative prognostic marker. Also, in the process of decision making in clinical practice, we should remember that anti-DFS70 can be found in the blood of patients with a different, non-SARD pathology and that most people showing anti-DFS70 are healthy individuals.
系统性自身免疫性风湿病(SARD)的诊断或排除要考虑免疫学研究的结果,主要是抗核抗体(ANA)和特异性自身抗体。通常,在细胞和组织底物上通过间接免疫荧光反应进行ANA分析时,可以观察到密集的细斑点70 (DFS70)荧光模式。研究抗dfs70抗体的诊断意义,可以优化SARD的逐步诊断。目前,实验室诊断调查建议采取两步策略:第一步,进行ANA筛查,第二步,结果阳性的患者进行确认试验,以检测针对单个核抗原的特异性抗体。在无临床和/或SARD组中特定疾病特征的其他特异性血清学标志物的ana血清阳性患者中检测到抗dfs70可被视为阴性预后标志物。此外,在临床实践决策过程中,我们应该记住,抗dfs70可以在不同的非sard病理患者的血液中发现,并且大多数显示抗dfs70的人是健康个体。
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引用次数: 0
Is Metagenomics the Future Routine Diagnosis Tool for Brain Abscesses? About a Case 宏基因组学是脑脓肿未来的常规诊断工具吗?关于一个案例
Pub Date : 2023-10-27 DOI: 10.3390/biologics3040018
William Lars, Claudie Lamoureux, Jérémy Picard, Christophe Rodriguez, Clémence Beauruelle, Luc Quaesaet, Geneviève Héry-Arnaud, Séverine Ansart, Anne Coste
Shotgun metagenomics (SMg) usefulness for brain abscess diagnosis is not known. We describe a case of brain abscess diagnosed with SMg and provide a review of the literature. A 70-year-old woman was diagnosed with multiple brain abscesses. Standard culture techniques and 16S rRNA gene sequencing of abscess samples remained negative. SMg finally revealed the presence of sequences from Streptococcus anginosus and Fusobacterium nucleatum, leading to antimicrobial treatment adaptation and corticosteroids initiation. The patient finally recovered. A literature review retrieved fifteen other cases of brain abscesses diagnosed with SMg. SMg results led to changes in patient management in most cases. The existing literature about the performances of SMg, its advantages, future evolutions, and limitations is then discussed. SMg place in routine should be evaluated and defined through prospective studies.
散弹枪宏基因组学(SMg)在脑脓肿诊断中的作用尚不清楚。我们描述一个病例的脑脓肿诊断为SMg和提供文献回顾。一名70岁的妇女被诊断患有多发性脑脓肿。标准培养技术及16S rRNA基因测序结果均为阴性。SMg最终揭示了来自血管链球菌和核梭杆菌的序列,导致抗菌素治疗的适应和皮质类固醇的启动。病人终于康复了。文献回顾了另外15例被诊断为SMg的脑脓肿。在大多数情况下,SMg结果导致患者管理的改变。然后讨论了关于SMg的性能、优点、未来发展和局限性的现有文献。SMg在日常生活中的地位应通过前瞻性研究进行评估和界定。
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引用次数: 0
Neoantigens: The Novel Precision Cancer Immunotherapy 新抗原:新型精准癌症免疫疗法
Pub Date : 2023-10-18 DOI: 10.3390/biologics3040017
Tiantian Zhang, Esaw Kurban, Zhe Wang
The past few decades have witnessed the remarkable progress of cancer immunotherapy. Neoantigens, also known as tumor-specific antigens, are novel antigens originating from tumor-specific alterations such as genomic mutations, dysregulated RNA splicing, and post-translational modifications. Neoantigens, recognized as non-self entities, trigger immune responses that evade central and peripheral tolerance mechanisms. With the notable strides in cancer genomics facilitated by next-generation sequencing technologies, neoantigens have emerged as a promising avenue for tumor-specific immunotherapy grounded in genomic profiling-based precision medicine. Furthermore, a growing number of preclinical and clinical investigations are harnessing the potential synergies between neoantigens and other immunotherapies such as adoptive cell therapy and immune checkpoint inhibitors. In this review, we will provide a comprehensive perspective encompassing the trajectory of neoantigens, neoantigen design strategies, and the diverse array of clinical applications inherent in immunotherapy strategies centered around neoantigens. Moreover, we delve into the inherent prospects and challenges that accompany the clinical adoption of neoantigen-based immunotherapies while also putting forth potential solutions to address these challenges.
在过去的几十年里,癌症免疫治疗取得了显著的进展。新抗原,也被称为肿瘤特异性抗原,是源于肿瘤特异性改变的新抗原,如基因组突变、RNA剪接失调和翻译后修饰。新抗原,被认为是非自我实体,引发免疫反应,逃避中枢和外周耐受机制。随着下一代测序技术在癌症基因组学方面的显著进步,新抗原已经成为基于基因组谱的精准医学的肿瘤特异性免疫治疗的有前途的途径。此外,越来越多的临床前和临床研究正在利用新抗原与其他免疫疗法(如过继细胞疗法和免疫检查点抑制剂)之间的潜在协同作用。在这篇综述中,我们将提供一个全面的视角,包括新抗原的发展轨迹,新抗原设计策略,以及以新抗原为中心的免疫治疗策略中固有的各种临床应用。此外,我们深入研究了伴随临床采用基于新抗原的免疫疗法的固有前景和挑战,同时也提出了解决这些挑战的潜在解决方案。
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引用次数: 0
Dose-Dependency of the Glycemic Response to Polyphenol-Rich Sugarcane Extract (PRSE) 富含多酚的甘蔗提取物(PRSE)对血糖反应的剂量依赖性
Pub Date : 2023-10-10 DOI: 10.3390/biologics3040016
Matthew Flavel, Julian Neoh, Kosta Fremielle Lim
Foods high in available carbohydrates, such as plain white sugar or sucrose, increase the postprandial blood glucose levels that may aggravate the risk of developing Type 2 Diabetes. One class of compounds that is gaining popularity due to its potential application in reducing the release of sugars for absorption into the body is polyphenols. The study aimed to investigate the effect of adding different doses of polyphenol-rich sugarcane extract (PRSE) to sucrose to lower the postprandial glycemia of the participants in a non-randomized study. The four test samples’ Glycemic Index (GI) values were calculated based on the standardized recommended methodology by comparing the area under the curve (AUC) of the test samples against the glucose standard. The glucose concentration curves were similar for the four test foods. The glucose response curves, and GI values were decreased in a dose-dependent manner. The results of this study indicate that PRSE-coated sugar can lower postprandial glycemia in normal individuals. Additionally, decreasing GI values with an increasing concentration of polyphenols suggests a dose-dependent effect between polyphenol levels and GI.
富含碳水化合物的食物,如白糖或蔗糖,会增加餐后血糖水平,可能会增加患2型糖尿病的风险。有一类化合物越来越受欢迎,因为它在减少糖的释放以吸收到体内的潜在应用是多酚。在一项非随机研究中,研究了在蔗糖中加入不同剂量的富含多酚的甘蔗提取物(PRSE)对降低参与者餐后血糖的影响。四种测试样品的血糖指数(GI)值根据标准化推荐方法,通过比较测试样品的曲线下面积(AUC)与葡萄糖标准计算。四种试验食品的葡萄糖浓度曲线相似。葡萄糖反应曲线和GI值呈剂量依赖性降低。本研究结果表明,prse包被糖可以降低正常人的餐后血糖。此外,GI值随着多酚浓度的增加而降低,表明多酚水平与GI之间存在剂量依赖效应。
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引用次数: 0
Robust Porcine GFR Measurement with Radiotracers and Only Late Blood Samples 用放射性示踪剂和仅晚期血液样本测定猪GFR
Pub Date : 2023-09-29 DOI: 10.3390/biologics3040015
Lars Jødal, Juan Ignacio Brignone, Pui-Ki Chan Ladefoged, Lars Lund, Trine Borup Andersen
(1) Pigs are physiologically very relevant as animal models of human physiology. Radiotracer methods for porcine GFR (glomerular filtration rate) determination exist but require full-curve blood sampling or the application of correction formulas, which vary among studies. (2) We used porcine GFR data (40 datapoints from 20 juvenile pigs) for which the GFR was measured as the plasma clearance of [99mTc]Tc-DTPA. The reference clearance (Cl, GFR; range 41–85 mL/min) was measured from the full curve under the data. For simpler determination, an approximate clearance, Cl1, was based on the last five blood samples (acquired 120–240 min post injection). (3) The following formula for the GFR was developed: Cl = 1.27 · (Cl1)0.92. The spread (SD) was within 4% of the reference GFR. A comparison with the literature data showed that our correction formula was robust in pigs of various breeds, sizes up to approximately 200 kg, and GFRs up to approximately 400 mL/min, with a spread of up to 8%. The formula was also applicable for iohexol as the tracer. (4) A formula was developed that allows porcine GFR to be measured using only 4–5 late blood samples. This new formula can be applied across a wide range of swine breeds, animal sizes, and GFR ranges, allowing for robust determination of the GFR in pigs without full-curve blood sampling and without urine collection.
(1)猪作为人类生理的动物模型在生理学上是非常相关的。目前存在测定猪肾小球滤过率的放射性示踪剂方法,但需要全曲线采血或应用校正公式,这在不同的研究中有所不同。(2)我们使用猪GFR数据(来自20头仔猪的40个数据点),GFR作为血浆中[99mTc]Tc-DTPA的清除率。参考间隙(Cl, GFR;范围41-85 mL/min)从数据下的全曲线测量。为了更简单的测定,根据注射后120-240分钟采集的最后5份血液样本,获得近似的清除率Cl1。(3)得到GFR的计算公式:Cl = 1.27·(Cl1)0.92。差值(SD)在参考GFR的4%以内。与文献数据的比较表明,我们的修正公式适用于各种品种的猪,体型约为200公斤,gfr约为400 mL/min,传播率可达8%。该公式同样适用于碘己醇作为示踪剂。(4)开发了一种公式,可以仅使用4 - 5份晚期血液样本来测量猪GFR。该新公式可广泛应用于猪品种、动物大小和GFR范围,无需全曲线血液采样和尿液收集即可可靠地测定猪的GFR。
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引用次数: 0
The Dawn of In Vivo Gene Editing Era: A Revolution in the Making 体内基因编辑时代的黎明:一场酝酿中的革命
Pub Date : 2023-09-25 DOI: 10.3390/biologics3040014
Sarfaraz K. Niazi
Gene or genome editing (GE) revises, removes, or replaces a mutated gene at the DNA level; it is a tool. Gene therapy (GT) offsets mutations by introducing a “normal” version of the gene into the body while the diseased gene remains in the genome; it is a medicine. So far, no in vivo GE product has been approved, as opposed to 22 GT products approved by the FDA, and many more are under development. No GE product has been approved globally; however, critical regulatory agencies are encouraging their entry, as evidenced by the FDA issuing a guideline specific to GE products. The potential of GE in treating diseases far supersedes any other modality conceived in history. Still, it also presents unparalleled risks—from off-target impact, delivery consistency and long-term effects of gene-fixing leading to designer babies and species transformation that will keep the bar high for the approval of these products. These challenges will come to the light of resolution only after the FDA begins approving them and opening the door to a revolution in treating hundreds of untreatable diseases that will be tantamount to a revolution in the making. This article brings a perspective and a future analysis of GE to educate and motivate developers to expand GE products to fulfill the needs of patients.
基因或基因组编辑(GE)在DNA水平上修改、删除或替换突变基因;它是一个工具。基因疗法(GT)通过将“正常”版本的基因引入体内,而患病基因仍留在基因组中,从而抵消突变;它是一种药。到目前为止,还没有一种体内转基因产品获得批准,而FDA已经批准了22种转基因产品,还有更多的产品正在开发中。全球还没有转基因产品获得批准;然而,关键的监管机构正在鼓励他们进入,正如FDA发布的针对GE产品的指导方针所证明的那样。基因工程在治疗疾病方面的潜力远远超过历史上设想的任何其他模式。尽管如此,它也带来了无与伦比的风险——从脱靶影响、输送一致性和基因修复的长期影响,导致设计婴儿和物种转化,这将使这些产品的批准门槛很高。只有在FDA开始批准这些挑战,并为治疗数百种无法治愈的疾病的革命打开大门之后,这些挑战才会得到解决,这将相当于一场正在酝酿中的革命。本文对GE进行了展望和未来分析,以教育和激励开发人员扩展GE产品以满足患者的需求。
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引用次数: 1
Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells 揭示多发性硬化症的免疫发病机制:质母细胞和致病T细胞的动态舞蹈
Pub Date : 2023-09-14 DOI: 10.3390/biologics3030013
Yasunari Matsuzaka, Ryu Yashiro
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by multiple lesions occurring temporally and spatially. Additionally, MS is a disease that predominates in the white population. In recent years, there has been a rapid increase in the number of patients, and it often occurs in young people, with an average age of onset of around 30 years old, but it can also occur in children and the elderly. It is more common in women than men, with a male-to-female ratio of approximately 1:3. As the immunopathogenesis of MS, a group of B cells called plasmablasts controls encephalomyelitis via IL-10 production. These IL-10-producing B cells, called regulatory B cells, suppress inflammatory responses in experimental mouse models of autoimmune diseases including MS. Since it has been clarified that these regulatory B cells are plasmablasts, it is expected that the artificial control of plasmablast differentiation will lead to the development of new treatments for MS. Among CD8-positive T cells in the peripheral blood, the proportion of PD-1-positive cells is decreased in MS patients compared with healthy controls. The dysfunction of inhibitory receptors expressed on T cells is known to be the core of MS immunopathology and may be the cause of chronic persistent inflammation. The PD-1+ CD8+ T cells may also serve as indicators that reflect the condition of each patient in other immunological neurological diseases such as MS. Th17 cells also regulate the development of various autoimmune diseases, including MS. Thus, the restoration of weakened immune regulatory functions may be a true disease-modifying treatment. So far, steroids and immunosuppressants have been the mainstream for autoimmune diseases, but the problem is that this kills not only pathogenic T cells, but also lymphocytes, which are necessary for the body. From this understanding of the immune regulation of MS, we can expect the development of therapeutic strategies that target only pathogenic immune cells.
多发性硬化症(MS)是一种慢性中枢神经系统炎症性脱髓鞘疾病,其特征是在时间和空间上发生多发性病变。此外,多发性硬化症是一种在白人人群中占主导地位的疾病。近年来,患者数量迅速增加,多见于年轻人,平均发病年龄在30岁左右,但也可发生在儿童和老年人身上。女性比男性更常见,男女比例约为1:3。作为MS的免疫发病机制,一组被称为浆母细胞的B细胞通过产生IL-10来控制脑脊髓炎。这些产生il -10的B细胞,被称为调节性B细胞,在包括ms在内的自身免疫性疾病的实验小鼠模型中抑制炎症反应。由于已经明确这些调节性B细胞是质母细胞,预计在外周血中cd8阳性T细胞中,人工控制质母细胞分化将导致ms的新治疗方法的发展。与健康对照相比,MS患者的pd -1阳性细胞比例降低。抑制受体在T细胞上表达的功能障碍是MS免疫病理的核心,可能是慢性持续性炎症的原因。PD-1+ CD8+ T细胞在ms等其他免疫性神经疾病中也可以作为反映每个患者病情的指标,Th17细胞还调节包括ms在内的各种自身免疫性疾病的发展,因此,恢复减弱的免疫调节功能可能是一种真正的疾病修饰治疗。到目前为止,类固醇和免疫抑制剂一直是治疗自身免疫性疾病的主流药物,但问题是,这不仅会杀死致病性T细胞,还会杀死人体所必需的淋巴细胞。从对MS免疫调节的理解出发,我们可以期待只针对致病免疫细胞的治疗策略的发展。
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引用次数: 0
A Current Review on the Role of Prebiotics in Colorectal Cancer 益生元在结直肠癌中的作用研究进展
Pub Date : 2023-08-22 DOI: 10.3390/biologics3030012
Anna Shrifteylik, Morgan Maiolini, Matthew E. Dufault, Daniel L Austin, B. Subhadra, Purushottam Lamichhane, Rahul Renukadas Deshmukh
Colorectal cancer (CRC) is one of the leading causes of death in the United States and worldwide. Recent evidence has corroborated a strong correlation between poor diet and the development of CRC, and further research is being conducted to investigate the association between intestinal microbiome and the development of cancer. New studies have established links with certain foods and synthetic food compounds that may be effective in reducing the risk for carcinogenesis by providing protection against cancer cell proliferation and antagonizing oncogenic pathways. Prebiotics are gaining popularity as studies have demonstrated chemo-preventive as well as anticancer potential of prebiotics. This paper aims to discuss the wide definition and scope of prebiotics by reviewing the studies that provide insights into their effects on human health in the context of colorectal cancer.
结直肠癌(CRC)是美国和世界范围内死亡的主要原因之一。最近的证据证实了不良饮食与结直肠癌的发展之间存在很强的相关性,并且正在进行进一步的研究来调查肠道微生物组与癌症发展之间的关系。新的研究已经确定了某些食物和合成食物化合物之间的联系,这些食物和合成食物化合物可能通过提供防止癌细胞增殖和拮抗致癌途径来有效降低致癌风险。由于研究证明了益生元的化学预防和抗癌潜力,益生元越来越受欢迎。本文旨在通过综述益生元在结直肠癌背景下对人类健康影响的研究,讨论益生元的广泛定义和范围。
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引用次数: 0
Precision Medicine in a Community Cancer Center: Pan-Cancer DNA/RNA Sequencing of Tumors Reveals Clinically Relevant Gene Fusions 社区癌症中心的精准医学:肿瘤泛癌DNA/RNA测序揭示临床相关基因融合
Pub Date : 2023-08-04 DOI: 10.3390/biologics3030011
S. Darabi, Carlos E. Zuazo, David Braxton, B. Eisenberg, M. Demeure
Background: Gene fusions occur when two independent genes form a hybrid gene through genomic rearrangements, which often leads to abnormal expression and function of an encoded protein. In hematological and solid cancers, oncogenic fusions may be prognostic, diagnostic, or therapeutic biomarkers. Improved detection and understanding of the functional implications of such fusions may be beneficial for patient care. Methods: We performed a retrospective analysis of our internal genomic database to identify known and novel gene fusions in different solid tumors seen in our community cancer center. We then investigated the clinical implications of the fusions we identified. Results: We identified 420 known oncogenic fusions and 25 unclassified gene fusions across twenty-six different cancer types. Of 420 fusion-positive tumors with known fusions, there were 366 unique gene fusions. Conclusions: About 10% of tumors investigated had oncogenic fusions, which supports the notion that comprehensive molecular profiling, including RNA sequencing, should be provided for patients with advanced cancers.
背景:当两个独立的基因通过基因组重排形成一个杂交基因时,就会发生基因融合,这通常会导致编码蛋白的异常表达和功能。在血液学和实体癌中,致瘤融合可能是预后、诊断或治疗性生物标志物。对这种融合的功能影响的更好的检测和理解可能有利于病人的护理。方法:我们对我们的内部基因组数据库进行回顾性分析,以确定在我们社区癌症中心看到的不同实体瘤中已知的和新的基因融合。然后我们研究了我们确定的融合的临床意义。结果:我们在26种不同的癌症类型中鉴定了420个已知的致癌融合和25个未分类的基因融合。在420例已知融合阳性肿瘤中,有366例独特的基因融合。结论:约10%的肿瘤存在致癌融合,这支持了对晚期癌症患者应提供包括RNA测序在内的全面分子谱分析的观点。
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引用次数: 0
Administration of Collagen Peptide Prevents the Progression of Pulmonary Fibrosis in Bleomycin-Treated Mice 给予胶原肽可防止博莱霉素治疗小鼠肺纤维化的进展
Pub Date : 2023-07-28 DOI: 10.3390/biologics3030010
Minami Yoshihara, Chisaki Asatsuma, Ayuna Masuko, Keiya Iwaasa, Yuki Saito-Matsuzawa, H. Sone, S. Kamiyama
Collagen peptides (CPs) are food-derived peptides that possess a variety of bioactive properties. Our study investigates the effects of CP on pulmonary fibrosis in bleomycin (BLM)-treated mice. C57BL/6J mice were subcutaneously injected with BLM for two weeks followed by a three-week experimental diet containing 25 mg/g of CP derived from chicken feet. Supplementation with CP suppressed the increase in lung weight and disruption of lung architecture observed in mice treated with BLM. BLM-treated mice also exhibited higher hydroxyproline content and increased expression levels of type I and III collagen subunit genes in the lungs. CP supplementation exerted no effect on these collagen-related factors; however, it significantly suppressed the gene expression of fibronectin and inflammation-related molecules in the lungs of BLM-treated mice. These findings suggest that CP administration prevents the development of pulmonary fibrosis by acting as an anti-inflammatory agent.
胶原蛋白肽(CPs)是一种食物来源的肽,具有多种生物活性。本研究探讨了CP对博来霉素(BLM)治疗小鼠肺纤维化的影响。C57BL/6J小鼠皮下注射BLM 2周,随后给予含25 mg/g鸡爪CP的实验饮食3周。补充CP抑制了BLM小鼠肺重量的增加和肺结构的破坏。blm处理的小鼠也表现出更高的羟脯氨酸含量和肺中I型和III型胶原亚基基因表达水平的增加。补充粗蛋白质对这些胶原蛋白相关因子没有影响;然而,它显著抑制了blm处理小鼠肺中纤维连接蛋白和炎症相关分子的基因表达。这些发现表明,CP可作为抗炎剂预防肺纤维化的发生。
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引用次数: 0
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Biologics (Basel, Switzerland)
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