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Mimicry of Tumour-Associated Carbohydrates: Is It a Promising Option for Cancer Treatment? 肿瘤相关碳水化合物的模拟:它是癌症治疗的一个有希望的选择吗?
Pub Date : 2023-03-23 DOI: 10.3390/immuno3020009
V. Segatori, Gretel M. Ferreira, S. Rojo, Aylen Camila Nogueira, Jeremías Omar Castillo, Cynthia Antonella Gulino, M. Gabri
Modulation of the immune system has been demonstrated as a powerful approach to treating cancer. Immunotherapies are generally classified as active or passive according to their ability to trigger the immune system. During the last decades, information regarding the relevance of aberrant glycosylation as a major player in tumour biology encouraged expectations for the development of new therapeutic strategies directed at glycans. Several tumour-associated carbohydrate antigens (TACAs) have been identified and validated as suitable immunotherapeutic targets, leading to promising therapeutic developments. It is known that TACAs are poorly immunogenic since they are unable to trigger a proper immune response. Given that they are not presented by major histocompatibility complex (MHC) molecules and that they induce immune tolerance, the development of active immunotherapeutic strategies against TACAs is a real challenge. However, antitumor strategies based on mimetics of TACAs have been developed and show promising results. Active immunotherapies based on TACAs mimicry can currently be grouped into strategies based on the use of mimetic peptides and anti-idiotype (Id) antibodies. In this review, we discussed the scientific basis on which these strategies are based and the available therapeutic options that have shown the best results in preclinical studies and in clinical practice.
免疫系统的调节已被证明是治疗癌症的一种有效方法。根据其触发免疫系统的能力,免疫疗法通常分为主动或被动。在过去的几十年里,关于异常糖基化作为肿瘤生物学主要参与者的相关性的信息鼓励了针对聚糖开发新的治疗策略的期望。几种肿瘤相关碳水化合物抗原(TACAs)已被确定并验证为合适的免疫治疗靶点,导致有希望的治疗发展。众所周知,TACAs的免疫原性很差,因为它们不能引发适当的免疫反应。鉴于它们不是由主要组织相容性复合体(MHC)分子呈现,并且它们诱导免疫耐受,开发针对TACAs的主动免疫治疗策略是一个真正的挑战。然而,基于TACAs模拟物的抗肿瘤策略已经开发出来并显示出良好的效果。基于TACAs模拟的主动免疫疗法目前可分为基于模拟肽和抗独特型(Id)抗体的策略。在这篇综述中,我们讨论了这些策略所依据的科学依据,以及在临床前研究和临床实践中显示出最佳结果的可用治疗方案。
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引用次数: 0
MicroRNA Let-7 Plays an Important Role in the Immunopathology of COVID-19: A Systematic Review MicroRNA Let-7在COVID-19免疫病理中发挥重要作用:系统综述
Pub Date : 2023-03-22 DOI: 10.3390/immuno3010008
Renato Luís Pessôa, Gustavo da Rosa Abreu, R. B. de Oliveira
COVID-19 has presented itself as a challenging task to medical teams and researchers throughout the world, since the outbreak of SARS-CoV-2 started in the Chinese city of Wuhan. To this day, there are still new variants emerging, and the knowledge about the mechanisms used by the virus to infect cells and perpetuate itself are still not well understood. The scientific community is still trying to catch up with the velocity of new variants and, consequently, the new physiological pathways that appear along with it. It is known that the new coronavirus plays a role in changing many molecular pathways to take control of the infected cells. Many of these pathways are related to control genomic expression of certain genes by epigenetic ways, allowing the virus to modulate immune responses and cytokines production. The let-7 family of microRNAs, for instance, are known to promote increased viral fusion in the target cell through a mechanism involving the transmembrane serine protease 2 (TMPRSS2). It was also demonstrated they are able to increase the inflammatory activity through the NF-κB/IL-6/let-7/LIN-28 axis. In addition, let-7 overexpression led to a reduction in inflammatory cytokines and chemokines expression (IL-6, IL-8 and TNF-α). Interestingly, the cytokines modulated by the let-7 family are related to COVID-19-induced cytokine storm observed in patients undergoing clinical phase three. Thus, let-7 can be considered a novel and attractive biomarker for therapeutic purpose. Based on that, the present study aims to critically analyze the immunopathological mechanisms of the microRNA let-7 in the infection caused by SARS-CoV-2.
自SARS-CoV-2在中国武汉爆发以来,COVID-19对全世界的医疗团队和研究人员来说都是一项具有挑战性的任务。直到今天,仍然有新的变种出现,关于病毒感染细胞和使自身永存的机制的知识仍然没有得到很好的理解。科学界仍在努力追赶新变异的速度,因此,新的生理途径也随之出现。众所周知,新型冠状病毒在改变许多分子途径以控制感染细胞方面发挥作用。这些途径中有许多与通过表观遗传方式控制某些基因的基因组表达有关,从而使病毒能够调节免疫反应和细胞因子的产生。例如,已知let-7 microrna家族通过涉及跨膜丝氨酸蛋白酶2 (TMPRSS2)的机制促进靶细胞中病毒融合的增加。研究还表明,它们能够通过NF-κB/IL-6/let-7/LIN-28轴增加炎症活性。此外,let-7过表达导致炎症细胞因子和趋化因子(IL-6、IL-8和TNF-α)表达降低。有趣的是,let-7家族调节的细胞因子与临床三期患者中观察到的covid -19诱导的细胞因子风暴有关。因此,let-7可以被认为是一种新颖而有吸引力的用于治疗目的的生物标志物。基于此,本研究旨在批判性地分析microRNA let-7在SARS-CoV-2感染中的免疫病理机制。
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引用次数: 2
Immune Dynamics Involved in Acute and Convalescent COVID-19 Patients COVID-19急性和恢复期患者的免疫动力学研究
Pub Date : 2023-03-17 DOI: 10.3390/immuno3010007
A. Silva-Junior, Lucas da Silva Oliveira, Nara Caroline Toledo Belezia, A. Tarragô, A. G. Costa, Adriana Malheiro
COVID-19 is a viral disease that has caused millions of deaths around the world since 2020. Many strategies have been developed to manage patients in critical conditions; however, comprehension of the immune system is a key factor in viral clearance, tissue repairment, and adaptive immunity stimulus. Participation of immunity has been identified as a major factor, along with biomarkers, prediction of clinical outcomes, and antibody production after infection. Immune cells have been proposed not only as a hallmark of severity, but also as a predictor of clinical outcomes, while dynamics of inflammatory molecules can also induce worse consequences for acute patients. For convalescent patients, mild disease was related to higher antibody production, although the factors related to the specific antibodies based on a diversity of antigens were not clear. COVID-19 was explored over time; however, the study of immunological predictors of outcomes is still lacking discussion, especially in convalescent patients. Here, we propose a review using previously published studies to identify immunological markers of COVID-19 outcomes and their relation to antibody production to further contribute to the clinical and laboratorial management of patients.
2019冠状病毒病是一种病毒性疾病,自2020年以来已在全球造成数百万人死亡。已经制定了许多策略来管理危重病人;然而,对免疫系统的理解是病毒清除、组织修复和适应性免疫刺激的关键因素。免疫的参与已被确定为一个主要因素,与生物标志物、临床结果预测和感染后的抗体产生一起。免疫细胞不仅被认为是严重程度的标志,而且还被认为是临床结果的预测指标,而炎症分子的动态也可能对急性患者造成更严重的后果。对于恢复期患者,轻度疾病与较高的抗体产生有关,尽管与基于抗原多样性的特异性抗体相关的因素尚不清楚。随着时间的推移,人们对COVID-19进行了探索;然而,免疫预测预后的研究仍然缺乏讨论,特别是在恢复期患者中。在此,我们建议对先前发表的研究进行回顾,以确定COVID-19结局的免疫学标记物及其与抗体产生的关系,以进一步为患者的临床和实验室管理做出贡献。
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引用次数: 1
The RadScopal Technique as an Immune Adjuvant to Treat Cancer 雷达内镜技术作为一种免疫佐剂治疗癌症
Pub Date : 2023-02-18 DOI: 10.3390/immuno3010006
H. Barsoumian, Jerry Hsu, Selene Nanez, Yun Hu, Ethan Y. Hsu, T. S. Riad, N. Puebla-Osorio, M. Angelica Cortez, J. W. Welsh
Since the momentous discovery of X-rays, high-dose radiotherapy (H-XRT) has been a cornerstone for combating cancer. The high-energy electromagnetic waves induce direct damage to tumor-cells’ DNA, thereby halting cell growth and proliferation, and eventually leading to tumor eradication. Furthermore, recent evidence suggests that H-XRT may have immunomodulatory properties which arise from its ability to induce the release of neoantigens, which in turn prime T-cells and contribute to T-cell repertoire diversity. Throughout the years, there have been different treatment modalities introduced as complements to H-XRT that have yielded greater results than monotherapy alone. In this review, we will discuss preclinical and clinical data related to the recently introduced low-dose radiotherapy (L-XRT) modality. We will also explore the justification for combining L-XRT and H-XRT, which became known as the “RadScopal Technique”, as a novel immune adjuvant to treat cancer. In this analysis, we detail and dissect the physiological mechanisms of action of each modality and describe the synergistic amalgamation effect observed on primary and metastatic tumors. Finally, we will explore the impetus for further studies to investigate combinations of the “RadScopal Technique” with various immune-oncology drug candidates.
自从x射线的重大发现以来,高剂量放疗(H-XRT)一直是对抗癌症的基石。高能电磁波会直接破坏肿瘤细胞的DNA,从而阻止细胞生长和增殖,最终导致肿瘤根除。此外,最近的证据表明,H-XRT可能具有免疫调节特性,这源于其诱导新抗原释放的能力,而新抗原的释放反过来又激活t细胞并促进t细胞库的多样性。多年来,已经引入了不同的治疗方式作为H-XRT的补充,这些治疗方式比单独的单一治疗产生了更大的效果。在这篇综述中,我们将讨论与最近引入的低剂量放疗(L-XRT)模式相关的临床前和临床数据。我们还将探讨L-XRT和H-XRT联合使用的理由,这被称为“RadScopal技术”,作为一种新的免疫佐剂治疗癌症。在本分析中,我们详细剖析了每种模式的生理作用机制,并描述了在原发性和转移性肿瘤中观察到的协同合并效应。最后,我们将探索进一步研究的动力,以研究“RadScopal技术”与各种免疫肿瘤候选药物的组合。
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引用次数: 0
Evaluation of the Anti-Inflammatory Properties of Mastic Oil Extracted from Pistacia lentiscus var. chia 黄连木乳香油抗炎性能的评价
Pub Date : 2023-02-13 DOI: 10.3390/immuno3010005
K. Spyridopoulou, Georgios Aindelis, Georgia Kolezaki, A. Tiptiri-Kourpeti, K. Chlichlia
Mastic oil (MO) is extracted from the resin of the bark of Pistacia lentiscus var. chia, a tree abundantly grown in the Greek island of Chios. Various biological activities, such as antimicrobial, anticancer and antioxidant, have been associated with the dietary intake of MO. However, little is known about MO’s potential anti-inflammatory effects, while some of its main chemical constituents were reported to exert significant anti-inflammatory activity. This study aims to assay the bioactivity of MO on in vitro and in vivo experimental inflammation models, in particular on LPS-stimulated RAW264.7 macrophages, murine primary peritoneal macrophages and a model of zymosan-induced peritonitis in BALB/c mice. The per os administration of MO inhibited the recruitment of macrophages into the peritoneal cavity of zymosan-treated mice, but did not affect neutrophil mobilisation or the levels of IL-6 or TNF-α in the peritoneal fluid. Similarly, IL-6 and TNF-α secretion in primary LPS-stimulated macrophages was not affected by MO, but the levels of phosphoproteins that activate inflammation in macrophages were differentially regulated. Finally, MO and some of its individual constituents reduced nitric oxide (NO), prostaglandin E2 and TNF-α levels in supernatants of LPS-stimulated RAW264.7 cells and inhibited their phagocytosis rate. Our data imply that MO may promote an anti-inflammatory transition in macrophages due to the combined bioactivities of its individual constituents. Thus, as a mixture of various compounds, MO seems to affect multiple molecular mechanisms that are involved in the development of inflammation. Therefore, more research, focusing on MO’s individual constituents and employing various pre-clinical inflammation models that activate different mechanisms, is required for a detailed investigation of the oil’s potential anti-inflammatory activity.
乳胶油(MO)是从黄松木(Pistacia lentiscus vara . chia)树皮的树脂中提取出来的,黄松木生长在希腊的希俄斯岛(Chios)。各种生物活性,如抗菌、抗癌和抗氧化,都与膳食摄入相关联。然而,对MO的潜在抗炎作用知之甚少,而其一些主要化学成分被报道具有显著的抗炎活性。本研究旨在检测MO对体外和体内实验炎症模型的生物活性,特别是对lps刺激的RAW264.7巨噬细胞、小鼠原代腹膜巨噬细胞和酶生蛋白诱导的BALB/c小鼠腹膜炎模型的生物活性。注射MO可抑制巨噬细胞向腹腔募集,但不影响中性粒细胞动员,也不影响腹膜液中IL-6或TNF-α的水平。同样,原代lps刺激的巨噬细胞中IL-6和TNF-α的分泌不受MO的影响,但巨噬细胞中激活炎症的磷酸化蛋白水平受到差异调节。最后,MO及其部分成分可降低lps刺激RAW264.7细胞上清液中一氧化氮(NO)、前列腺素E2和TNF-α水平,抑制其吞噬率。我们的数据表明,由于其单个成分的联合生物活性,MO可能促进巨噬细胞的抗炎转变。因此,作为多种化合物的混合物,MO似乎影响了参与炎症发展的多种分子机制。因此,需要更多的研究,关注油的单个成分,并采用各种临床前炎症模型来激活不同的机制,以详细研究油的潜在抗炎活性。
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引用次数: 0
Combining CAR T Cell Therapy and Oncolytic Virotherapy for Pediatric Solid Tumors: A Promising Option 联合CAR - T细胞疗法和溶瘤病毒疗法治疗儿童实体瘤:一个有希望的选择
Pub Date : 2023-01-20 DOI: 10.3390/immuno3010004
Jianming He, Faryal Munir, D. Ragoonanan, W. Zaky, S. Khazal, P. Tewari, J. Fueyo, C. Gomez-Manzano, Hong Jiang
Despite advances in treatment options, the clinical outcomes of pediatric patients with advanced solid tumors have hardly improved in decades, and alternative treatment options are urgently needed. Innovative therapies, such as chimeric antigen receptor (CAR) T cells and oncolytic viruses (OVs), are currently being evaluated in both adults and children with refractory solid tumors. Because pediatric solid tumors are remarkably diverse and biologically different from their adult counterparts, more research is required to develop effective treatment regimens for these patients. Here, we first summarize recent efforts and advances in treatments for pediatric solid tumors. Next, we briefly introduce the principles for CAR T cell therapy and oncolytic virotherapy and clinical trials thereof in pediatric patients. Finally, we discuss the basis for the potential benefits of combining the two approaches in pediatric patients with advanced solid tumors.
尽管治疗方案有所进步,但数十年来,儿童晚期实体瘤患者的临床结果几乎没有改善,迫切需要替代治疗方案。嵌合抗原受体(CAR) T细胞和溶瘤病毒(OVs)等创新疗法目前正在对成人和儿童难治性实体瘤进行评估。由于儿童实体瘤具有显著的多样性,并且在生物学上与成人实体瘤不同,因此需要更多的研究来为这些患者制定有效的治疗方案。在这里,我们首先总结了近年来儿童实体瘤治疗的努力和进展。接下来,我们简要介绍CAR - T细胞疗法和溶瘤病毒疗法的原理及其在儿科患者中的临床试验。最后,我们讨论了结合两种方法治疗晚期实体瘤儿童患者的潜在益处的基础。
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引用次数: 2
Acknowledgment to the Reviewers of Immuno in 2022 对《免疫》杂志2022年审稿人的感谢
Pub Date : 2023-01-16 DOI: 10.3390/immuno3010003
High-quality academic publishing is built on rigorous peer review [...]
高质量的学术出版建立在严格的同行评审的基础上[…]
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引用次数: 0
Plasma Cytokine Levels and Cytokine Genetic Polymorphisms in Patients with Metastatic Breast Cancer Receiving High-Dose Chemotherapy 接受大剂量化疗的转移性乳腺癌患者血浆细胞因子水平和细胞因子遗传多态性
Pub Date : 2023-01-14 DOI: 10.3390/immuno3010002
R. Lafrenie, M. Bewick, Carly A. Buckner, M. Conlon
Differences in the baseline levels of serum cytokines or in single-nucleotide polymorphisms (SNPs) in cytokine genes may be useful to predict outcomes for patients being treated for metastatic breast cancer. We have measured the plasma levels and characterized individual SNPs for IL-1RA, IL-1b, IL-2, IL-6 and TNFa in 130 patients with metastatic breast cancer treated with high-dose chemotherapy. Patients were treated with high-dose cyclophosphamide (Group 1, 74 patients) or high-dose paclitaxel-containing regimens (Group 2, 56 patients). A high plasma level of IL-1RA and a SNP in the IL-1RA gene indicated a better prognosis for patients in Group 1 (but not Group 2). However, the level of plasma IL-1RA did not correlate with the SNP genotype. A high plasma level of IL-6 or TNFa indicated a poorer outcome for patients in Group 1 although the SNP genotypes for the IL-6 and TNFa SNPs were not associated with differences in outcome. The plasma levels of IL-1b and IL-2 and the genotype of the IL-1b SNPs did not indicate differences in outcome. Although, individually, plasma levels of cytokine or “risk” SNP genotypes may not indicate outcome, in combination there was an increased trend to predict outcome for patients treated with high-dose cyclophosphamide but not high-dose paclitaxel. These results suggest that the immune cytokines may be useful as prognostic biomarkers in the treatment of patients with metastatic breast cancer treated with different types of chemotherapy.
血清细胞因子基线水平或细胞因子基因单核苷酸多态性(snp)的差异可能有助于预测转移性乳腺癌患者的治疗结果。我们测量了130例接受大剂量化疗的转移性乳腺癌患者的血浆水平,并表征了IL-1RA、IL-1b、IL-2、IL-6和TNFa的个体snp。患者接受高剂量环磷酰胺(第1组,74例)或高剂量含紫杉醇方案(第2组,56例)治疗。高血浆IL-1RA水平和IL-1RA基因SNP表明1组患者预后较好(而不是2组)。然而,血浆IL-1RA水平与SNP基因型无关。血浆中IL-6或TNFa的高水平表明第一组患者的预后较差,尽管IL-6和TNFa SNP的SNP基因型与预后差异无关。血浆中IL-1b和IL-2的水平以及IL-1b snp的基因型没有显示结果的差异。虽然单独来看,血浆细胞因子水平或“风险”SNP基因型可能不能预示预后,但综合来看,高剂量环磷酰胺治疗而非高剂量紫杉醇治疗的患者预测预后的趋势有所增加。这些结果表明,免疫细胞因子可能是治疗转移性乳腺癌患者的预后生物标志物,并接受不同类型的化疗。
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引用次数: 0
Immune Modulatory Effects of Ketogenic Diet in Different Disease Conditions 生酮饮食在不同疾病条件下的免疫调节作用
Pub Date : 2022-12-25 DOI: 10.3390/immuno3010001
Shivani Srivastava, V. Pawar, Anuradha Tyagi, K. Sharma, Vinay Kumar, S. Shukla
Interceding nutrients have been acquiring increased attention and prominence in the field of healing and deterrence of various disorders. In this light, the present article encompasses several facets of ketogenic diet as an immunomodulator with respect to its expansive clinical applications. Accordingly, several scientific records, models, and case histories, including viral infections, cancer, chronic diseases, e.g., cardiovascular diseases, epilepsy, as well as numerous other neuro-disorders, are assembled, revealing a profound influence of KD in favor of improvement in the patient’s condition. We accentuate possible manifold mechanisms of KD that require further exploration.
在各种疾病的治疗和威慑领域,调解营养素已获得越来越多的关注和突出。鉴于此,本文涵盖了生酮饮食作为免疫调节剂的几个方面,以及其广泛的临床应用。因此,一些科学记录、模型和病例史,包括病毒感染、癌症、慢性疾病,如心血管疾病、癫痫,以及许多其他神经疾病,都被收集起来,揭示了KD对改善患者状况的深远影响。我们强调了需要进一步探索的KD可能的多种机制。
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引用次数: 6
Uptake and Advanced Therapy of Butyrate in Inflammatory Bowel Disease 丁酸盐在炎症性肠病中的吸收和高级治疗
Pub Date : 2022-11-25 DOI: 10.3390/immuno2040042
Shinji Ota, H. Sakuraba
The pathogenesis and refractory nature of inflammatory bowel disease (IBD) are related to multiple factors, including genetic factors, environmental factors, and abnormalities in gut microbial diversity, which lead to decreased levels of short-chain fatty acids (SCFAs). Among SCFAs, butyrate plays an important role in mucosal barrier maintenance, serves as an energy source in intestinal epithelial cells (IECs), and exhibits anti-inflammatory effects; therefore, it is a particularly important factor in gut homeostasis. Changes in gut microbiota and butyrate levels affect the outcomes of drug therapy for IBD. Butyrate is mainly absorbed in the large intestine and is transported by monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1). During gut inflammation, butyrate utilization and uptake are impaired in IECs. Dysbiosis and low abundance of butyrate affect fecal microbiota transplantation and anticancer immunotherapy. Although butyrate administration has been reported as a treatment for IBD, its effects remain controversial. In this review, we discuss butyrate absorption and metabolism in patients with IBD and their relationship with drug therapy.
炎症性肠病(IBD)的发病机制和难治性与多种因素有关,包括遗传因素、环境因素和肠道微生物多样性异常,导致短链脂肪酸(SCFAs)水平下降。在scfa中,丁酸盐在粘膜屏障维持中起重要作用,是肠上皮细胞(IECs)的能量来源,并具有抗炎作用;因此,它在肠道内稳态中是一个特别重要的因素。肠道菌群和丁酸盐水平的变化影响IBD药物治疗的结果。丁酸盐主要在大肠内吸收,通过单羧酸转运体1 (MCT1)和钠偶联单羧酸转运体1 (SMCT1)进行转运。在肠道炎症期间,IECs对丁酸盐的利用和摄取受到损害。生态失调和低丁酸盐丰度影响粪便微生物群移植和抗癌免疫治疗。虽然丁酸盐治疗IBD有报道,但其效果仍存在争议。在这篇综述中,我们讨论了丁酸盐在IBD患者中的吸收和代谢及其与药物治疗的关系。
{"title":"Uptake and Advanced Therapy of Butyrate in Inflammatory Bowel Disease","authors":"Shinji Ota, H. Sakuraba","doi":"10.3390/immuno2040042","DOIUrl":"https://doi.org/10.3390/immuno2040042","url":null,"abstract":"The pathogenesis and refractory nature of inflammatory bowel disease (IBD) are related to multiple factors, including genetic factors, environmental factors, and abnormalities in gut microbial diversity, which lead to decreased levels of short-chain fatty acids (SCFAs). Among SCFAs, butyrate plays an important role in mucosal barrier maintenance, serves as an energy source in intestinal epithelial cells (IECs), and exhibits anti-inflammatory effects; therefore, it is a particularly important factor in gut homeostasis. Changes in gut microbiota and butyrate levels affect the outcomes of drug therapy for IBD. Butyrate is mainly absorbed in the large intestine and is transported by monocarboxylate transporter 1 (MCT1) and sodium-coupled monocarboxylate transporter 1 (SMCT1). During gut inflammation, butyrate utilization and uptake are impaired in IECs. Dysbiosis and low abundance of butyrate affect fecal microbiota transplantation and anticancer immunotherapy. Although butyrate administration has been reported as a treatment for IBD, its effects remain controversial. In this review, we discuss butyrate absorption and metabolism in patients with IBD and their relationship with drug therapy.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81123782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
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