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Deep-Tissue In Vivo Imaging Using Bioluminescence in a Mouse Infection Model and the Path to High Sensitivity With Near-Infrared Luminescence 利用生物发光技术在小鼠感染模型中进行体内深部组织成像及高灵敏度近红外发光途径。
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-05-06 DOI: 10.1111/1348-0421.13225
Daiki Yamaguchi, Keita Oki, Yuki Kaya, Yoshiaki Sakairi, Yuji Morita, Go Kamoshida

The analysis of bacterial infections using animal models has primarily relied on the average evaluation of many individuals at specific time points. Consequently, tracking temporal changes in an infection within the same individual is challenging. InVivo imaging techniques enable the longitudinal assessment of infection in the same individual while reducing the number of animals required. Understanding the dynamics of bacterial infections over time is crucial for elucidating disease mechanisms and developing effective treatment strategies. In this review, we summarize the In Vivo imaging techniques used to detect bacterial colonization in deep tissues in animal models of bacterial infection, along with efforts to enhance their sensitivity. In particular, we introduce a recently developed In Vivo imaging system that employs near-infrared luminescence to achieve high sensitivity and versatility. Furthermore, we discuss strategies for further improving its sensitivity.

使用动物模型分析细菌感染主要依赖于许多个体在特定时间点的平均评估。因此,追踪同一个体感染的时间变化是具有挑战性的。体内成像技术能够对同一个体的感染进行纵向评估,同时减少所需的动物数量。了解细菌感染随时间的动态变化对于阐明疾病机制和制定有效的治疗策略至关重要。在这篇综述中,我们总结了用于检测细菌在细菌感染动物模型中深层组织定植的体内成像技术,以及提高其敏感性的努力。特别是,我们介绍了最近开发的一种采用近红外发光的体内成像系统,以实现高灵敏度和多功能性。此外,我们还讨论了进一步提高其灵敏度的策略。
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引用次数: 0
Issue Information – Cover 发行资料-封面
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-05-04 DOI: 10.1111/1348-0421.13139

Cover photograph: Functions of soluble and membrane-bound C-type lectins against pathogens. A) Soluble C-type lectins are multimerized and inactivate pathogens by agglutinating or coating their surfaces. They also activate complement to kill pathogens and promote phagocytosis by opsonization. B) Membrane-bound C-type lectins are called C-type lectin receptors (CLRs). CLRs take up pathogens via endocytosis and degrade and inactivate them in lysosomes. The degraded antigens are presented on MHC-II, inducing an acquired immune response. C) CLRs associated with ITAM adapter molecules such as FcRg and DAP12 induce various inflammatory responses necessary for host defense. D) CLRs with hemITAM in the cytoplasmic region directly transmit activation signals. E) CLRs with the inhibitory motif ITIM suppress host immune responses. This can either suppress excessive inflammation caused by pathogens or allow pathogens to evade host immunity. F) ITAM has two sides. Many pathogen ligands are multivalent and transmit activation signals through ITAM, but monovalent ligands transmit inhibitory signals. G) Some CLRs capture pathogens on the cell surface and pass them to other pathogen recognition receptors. Microbiol Immunol: 69:257-269. Article link here

封面图片:可溶性和膜结合c型凝集素对病原体的作用。A)可溶性c型凝集素多聚并通过凝集或包覆其表面灭活病原体。它们也激活补体杀死病原体并通过调理促进吞噬作用。B)膜结合的c型凝集素称为c型凝集素受体(CLRs)。clr通过内吞作用吸收病原体,并在溶酶体中降解和灭活病原体。降解抗原呈现在MHC-II上,诱导获得性免疫反应。C)与ITAM适配器分子(如FcRg和DAP12)相关的clr诱导宿主防御所需的各种炎症反应。D)细胞质区含有半itam的clr直接传递激活信号。E)含有抑制基序ITIM的clr抑制宿主免疫反应。这既可以抑制病原体引起的过度炎症,也可以使病原体逃避宿主免疫。F) ITAM有两面性。许多病原体配体是多价的,通过ITAM传递激活信号,而单价配体传递抑制信号。G)一些clr捕获细胞表面的病原体并将其传递给其他病原体识别受体。中国生物医学工程学报(英文版);文章链接
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引用次数: 0
Coculture of Bifidobacterium bifidum G9-1 With Butyrate-Producing Bacteria Promotes Butyrate Production 两歧双歧杆菌G9-1与产丁酸菌共培养促进丁酸生产。
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-23 DOI: 10.1111/1348-0421.13224
Haruka Yokota, Yoshiki Tanaka, Hiroshi Ohno

Supplementation with Bifidobacterium bifidum G9-1 (BBG9-1) has been established to enhance the production of butyrate, a short-chain fatty acid (SCFA) known for its beneficial effects in alleviating constipation. We hypothesized that BBG9-1 alters gut microbiota such that bacteria that produce butyric acid from lactate and acetate become more abundant. In this study, we sought to determine whether BBG9-1 promotes the growth of butyrate-producing bacteria and thereby enhances butyrate production. BBG9-1 was cocultured with different butyrate-producing bacteria to compare differences in the SCFA production of cocultures and monocultures. We indeed detected significant increases in the production of SCFAs in cocultures compared to monocultures. Moreover, lactate and butyrate production increased in a time-dependent manner in the BBG9-1 and Faecalibacterium prausnitzii ID 6052 coculture. In addition, acetate production in cocultures initially increased until 16 h, followed by a decline between 20 and 24 h, and a subsequent significant increase at 48 h. Comparatively, lactate and acetate production in the BBG9-1 and Anaerostipes caccae JCM 13470T coculture peaked at 16 h and declined thereafter, and butyrate production increased in a time-dependent manner. In contrast, lactate, acetate, and butyrate production in the BBG9-1 and Roseburia hominis JCM 17582T coculture increased in a time-dependent manner. These findings indicate that butyrate-producing bacteria increase butyrate production by utilizing BBG9-1-produced lactate and acetate. Thus, the butyrate-mediated physiological activity of BBG9-1 could be attributed to an indirect enhancement of butyrate production.

补充两歧双歧杆菌G9-1 (BBG9-1)已被证实可以促进丁酸盐的产生,丁酸盐是一种短链脂肪酸(SCFA),具有缓解便秘的有益作用。我们假设BBG9-1改变了肠道微生物群,使从乳酸和醋酸盐中产生丁酸的细菌变得更加丰富。在这项研究中,我们试图确定BBG9-1是否促进丁酸产菌的生长,从而提高丁酸产量。BBG9-1与不同的丁酸产菌共培养,比较共培养和单培养的SCFA产量的差异。与单一培养相比,我们确实检测到共培养中scfa的产量显著增加。此外,在BBG9-1和prausnitzii Faecalibacterium ID 6052共培养中,乳酸和丁酸盐产量呈时间依赖性增加。此外,共培养中乙酸的产量最初增加到16 h,随后在20 ~ 24 h之间下降,随后在48 h显著增加。相比之下,BBG9-1与厌氧菌卡氏球菌JCM 13470T共培养的乳酸和乙酸产量在16 h达到峰值,随后下降,丁酸产量呈时间依赖性增加。相比之下,BBG9-1和Roseburia hominis JCM 17582T共培养的乳酸、乙酸和丁酸产量呈时间依赖性增加。这些结果表明,产丁酸菌通过利用bbg9 -1产生的乳酸和乙酸来提高丁酸产量。因此,丁酸盐介导的BBG9-1的生理活性可归因于间接增强丁酸盐的产生。
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引用次数: 0
GAS-J, a User-Friendly Browser Application for Genome Assembly, emm-Typing, MLST Typing, and Virulence Factor Gene Detection of Streptococcus pyogenes GAS-J,一个用于化脓性链球菌基因组组装、emm分型、MLST分型和毒力因子基因检测的用户友好浏览器应用程序。
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-20 DOI: 10.1111/1348-0421.13223
Norihiko Takemoto, Kohei Ogura, Yuan Gao, Rumi Okuno, Masaya Yamaguchi, Yujiro Hirose, Masayuki Ono, Shigetada Kawabata, Tadayoshi Ikebe, Takashi Hamabata, Tohru Miyoshi-Akiyama

Clinical isolates of Streptococcus pyogenes are usually classified using emm and multilocus sequence typing (MLST). Recently, whole genome sequencing (WGS) has been employed for emm typing and MLST analysis. WGS data provides additional information on the presence of virulence factor genes. To enable researchers unfamiliar with bioinformatics to analyze WGS data of S. pyogenes, we opened an online tool named GAS-J, which automatically outputs emm types, sequence types (STs), carriage of virulence factor genes, and phylogenetic trees. The tool accepts raw short-read data as inputs, since it includes the velvet assembler. In all isolates, the emm typing results from this tool were identical to those obtained by conventional PCR and Sanger sequencing, even in cases where isolates had pseudo-emm (emm-like) genes. STs are determined by performing a BLAST search using seven alleles as references. To detect S. pyogenes virulence factor genes, we prepared a new data set containing 620 related proteins. Users may choose which isolates to include in SNP-based phylogenetic tree from a pool of 406 isolates with epidemiological data. The data set includes isolates whose symptoms (STSS or non-STSS) were diagnosed based on the STSS criteria of the Japan Communicable Disease Prevention Law. GAS-J application is available at http://gasj.ncgm.go.jp. The data of isolates are going to be updated in the future.

临床分离的化脓性链球菌通常采用emm和多位点序列分型(MLST)进行分类。近年来,全基因组测序(WGS)已被用于emm分型和MLST分析。WGS数据提供了关于毒力因子基因存在的额外信息。为了使不熟悉生物信息学的研究人员能够分析化脓链球菌的WGS数据,我们开放了一个名为GAS-J的在线工具,该工具可以自动输出emm类型、序列类型(STs)、毒力因子基因携带和系统发育树。该工具接受原始的短读数据作为输入,因为它包含了天鹅绒汇编程序。在所有分离株中,该工具的emm分型结果与传统PCR和Sanger测序获得的结果相同,即使在分离株具有伪emm (emm样)基因的情况下也是如此。STs是通过使用7个等位基因作为参考执行BLAST搜索来确定的。为了检测化脓链球菌毒力因子基因,我们准备了一个包含620个相关蛋白的新数据集。用户可以从406株具有流行病学数据的分离株中选择将哪些分离株纳入基于snp的系统发育树。该数据集包括根据《日本传染病防治法》的STSS标准诊断出症状(STSS或非STSS)的分离株。GAS-J应用程序可从http://gasj.ncgm.go.jp获得。分离株的数据将在未来进行更新。
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引用次数: 0
Transcriptome Profiling and Viral−Human Interactome Insights Into HBV-Driven Oncogenic Alterations in Hepatocellular Carcinoma 转录组分析和病毒-人相互作用组洞察hbv驱动的肝细胞癌的致癌改变。
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-17 DOI: 10.1111/1348-0421.13219
Anilkumar I. Ananthakrishnan, Althaf Mahin, Thottethodi Subrahmanya Keshava Prasad, Chandran S. Abhinand

Hepatocellular carcinoma (HCC) is the primary form of liver cancer that poses a significant global health concern due to its increasing incidence rates and diverse etiology. Chronic infection induced by hepatitis B virus (HBV) is a prominent etiological factor influencing the development of HCC. Although recent advances in multi-omics approaches have facilitated extensive exploration of HCC molecular characteristics, translating the characteristics of subtypes into clinical applications has been challenging due to parameters like limited sample size and complex classifiers for early detection. In the present study, we performed transcriptomics profiling of HBV-infected HCC patient tissue data to gather comprehensive insights into the intricate molecular mechanisms underlying HBV-associated HCC, specifically, viral protein interactions that influence the expression of oncogenes. The 1059 differentially expressed genes (DEGs) identified across two GEO data sets revealed upregulation of cell cycle and mitosis-related genes, alongside downregulation of genes involved in fatty acid degradation and cytochrome P450 activity. CDK1 and CDC20 which are part of the top cluster and hub gene from interactome analysis were identified as potential markers for HBV-positive HCC through gene expression pattern and overall survival analysis. Additionally, 19 DEGs showing significance in HCC development were identified as interacting partners with HBV proteins. Among them, the interaction of HBsAg with ALB and SHBG and their downregulation correlates to the lower testosterone levels identified in HBV and HCC patients. Together, the study enhances the understanding of the heterogeneity and molecular pathogenesis of HBV-positive HCC.

肝细胞癌(HCC)是肝癌的主要形式,由于其发病率不断上升和病因多样,引起了重大的全球健康问题。乙型肝炎病毒(HBV)引起的慢性感染是影响HCC发展的重要病因。尽管多组学方法的最新进展促进了对HCC分子特征的广泛探索,但由于样本量有限和早期检测的分类器复杂等参数,将亚型特征转化为临床应用一直具有挑战性。在本研究中,我们对hbv感染的HCC患者组织数据进行转录组学分析,以全面了解hbv相关HCC的复杂分子机制,特别是影响癌基因表达的病毒蛋白相互作用。在两个GEO数据集中鉴定的1059个差异表达基因(DEGs)显示细胞周期和有丝分裂相关基因上调,同时参与脂肪酸降解和细胞色素P450活性的基因下调。CDK1和CDC20是相互作用组分析中top cluster和hub基因的一部分,通过基因表达模式和总生存分析确定为hbv阳性HCC的潜在标志物。此外,在HCC发展中具有重要意义的19个deg被确定为HBV蛋白的相互作用伙伴。其中,HBsAg与ALB和SHBG的相互作用及其下调与HBV和HCC患者睾酮水平较低相关。总之,该研究增强了对hbv阳性HCC的异质性和分子发病机制的理解。
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引用次数: 0
Cytotoxic T Lymphocyte Density and PD-L1 Expression Predict the Response to Anti-PD1 Therapy in Recurrent Oral Squamous Cell Carcinoma 细胞毒性T淋巴细胞密度和PD-L1表达预测复发性口腔鳞状细胞癌抗pd1治疗的反应。
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-13 DOI: 10.1111/1348-0421.13220
Mayuko Yamashita, Hiromu Yano, Yoshihiro Komohara, Rin Yamada, Yukio Fujiwara, Masatoshi Hirayama, Yuki Seki, Ryoji Yoshida, Hideki Nakayama

Oral squamous cell carcinoma (OSCC) is one of the most common head and neck cancers, and immunotherapy targeting programmed cell death 1 (PD-1) has become a treatment option for recurrent OSCC after surgery and radiation therapy. However, few studies have identified definitive biomarkers for predicting patient response to anti-PD1 therapy in OSCC. In the present study, biopsy specimens were obtained from 23 patients with recurrent OSCC who were subsequently treated with anti-PD1 therapy. Immunohistochemical examinations of CD3, CD8, FOXP3, CD103, CD163, programmed cell death ligand 1 (PD-L1), HLA-A/B/C, HLA-DR, and β2 microglobulin were performed, and their correlation with clinical response was statistically analyzed. We found that an increased density of CD8-positive lymphocytes and increased PD-L1 expression predicted a favorable response to anti-PD1 therapy in recurrent OSCC. In contrast, clinical factors such as age and sex, and immune-related factors such as HLA-Classes I and II, were not associated with the response to anti-PD1 therapy. Taken together, our results suggest that immunohistochemical analysis of CD8 and PD-L1 may be useful for predicting the efficacy of anti-PD1 therapy in recurrent OSCC.

口腔鳞状细胞癌(Oral squamous cell carcinoma, OSCC)是最常见的头颈部癌症之一,针对程序性细胞死亡1 (programmed cell death 1, PD-1)的免疫治疗已成为手术和放疗后复发性OSCC的治疗选择。然而,很少有研究确定了预测OSCC患者对抗pd1治疗反应的明确生物标志物。在本研究中,从23例复发性OSCC患者中获得活检标本,这些患者随后接受抗pd1治疗。进行CD3、CD8、FOXP3、CD103、CD163、程序性细胞死亡配体1 (PD-L1)、HLA-A/B/C、HLA-DR、β2微球蛋白的免疫组化检测,并统计分析其与临床疗效的相关性。我们发现cd8阳性淋巴细胞密度的增加和PD-L1表达的增加预示着复发性OSCC对抗pd1治疗的有利反应。相反,临床因素,如年龄和性别,以及免疫相关因素,如hla - I类和II类,与抗pd1治疗的反应无关。综上所述,我们的研究结果表明,CD8和PD-L1的免疫组织化学分析可能有助于预测复发性OSCC抗pd1治疗的疗效。
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引用次数: 0
Crohn's Disease‒Associated Escherichia coli BasRS Is Involved in Fimbriae Expression, Contributing to Epithelial Cell Invasion 克罗恩病相关大肠杆菌BasRS参与菌毛表达,促进上皮细胞侵袭
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-13 DOI: 10.1111/1348-0421.13221
Tsuyoshi Miki, Masahiro Ito, Takeshi Haneda, Yun-Gi Kim

Crohn's disease‒associated adherent-invasive Escherichia coli (AIEC) colonizes the gut lumen through Type 1 fimbriae. We demonstrated that the two-component signal transduction system BasRS is involved in the expression of fimbriae in the AIEC strain LF82, as evidenced by the reduced transcriptional activity of fimA in an LF82 mutant lacking BasRS. Consequently, the basRS mutant showed decreased invasiveness to HeLa cells, which was restored by introducing a plasmid expressing fimbriae in a BasRS-independent manner. These findings may provide new prospects for developing therapeutic interventions for AIEC-related Crohn's disease.

克罗恩病相关的粘附-侵袭性大肠杆菌(AIEC)通过1型菌毛在肠道内定植。我们证明了双组分信号转导系统BasRS参与了AIEC菌株LF82中纤毛的表达,在缺乏BasRS的LF82突变体中,fimA的转录活性降低。因此,basRS突变体对HeLa细胞的侵袭性降低,通过引入以不依赖basRS的方式表达菌毛的质粒使其恢复。这些发现可能为开发aiec相关克罗恩病的治疗干预措施提供新的前景。
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引用次数: 0
Expression Purification and Immunogenicity Detection of HtsA + FtsB Fusion Protein From Streptococcus pyogenes 化脓性链球菌HtsA + FtsB融合蛋白的表达、纯化及免疫原性检测
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-11 DOI: 10.1111/1348-0421.13217
Jing Li, Yan Ju, Min Jiang, Jing-Xi Wang, Sha Li, Xiao-Yan Yang

Lipoproteins are a class of potential vaccine candidates for Streptococcus pyogenes. The present study was conducted to purify and detect the immunogenicity of the fusion protein HtsA + FtsB of the iron transport lipoproteins HtsA and FtsB of S. pyogenes. The recombinant expression vector pBAD-htsA + ftsB was successfully constructed, and the fusion protein HtsA + FtsB with a purity above 95% was successfully obtained. Western blot analysis confirmed that the HtsA + FtsB fusion protein had good antigenicity and could be specifically recognized by both HtsA antiserum and FtsB antisera, and the antibody specificity of the HtsA + FtsB fusion protein was good. ELISA results showed that IgG antibody levels were significantly increased in the HtsA + FtsB fusion protein immunization group compared to the PBS control group. Additionally, cytokine levels, including IL-2, IFN-γ, IL-4, IL-6, and IL-17A, were significantly elevated. Furthermore, the antiserum from HtsA + FtsB-immunized mice enhanced the opsonophagocytic activity against S. pyogenes. The HtsA + FtsB fusion protein has strong immunogenicity and potential as a candidate vaccine for S. pyogenes.

脂蛋白是一类潜在的化脓性链球菌候选疫苗。本研究纯化并检测化脓性链球菌铁转运脂蛋白HtsA和FtsB融合蛋白HtsA + FtsB的免疫原性。成功构建了重组表达载体pBAD-htsA + ftsB,成功获得了纯度在95%以上的HtsA + ftsB融合蛋白。Western blot分析证实HtsA + FtsB融合蛋白具有良好的抗原性,可被HtsA抗血清和FtsB抗血清特异性识别,且HtsA + FtsB融合蛋白的抗体特异性较好。ELISA结果显示,与PBS对照组相比,HtsA + FtsB融合蛋白免疫组IgG抗体水平显著升高。此外,细胞因子水平,包括IL-2、IFN-γ、IL-4、IL-6和IL-17A显著升高。此外,HtsA + ftsb免疫小鼠的抗血清增强了对化脓性葡萄球菌的调理吞噬活性。HtsA + FtsB融合蛋白具有很强的免疫原性和作为化脓性葡萄球菌候选疫苗的潜力。
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引用次数: 0
RETRACTION: Chlamydia Pneumoniae Induces Interleukin-6 and Interleukin-10 in Human Gingival Fibroblastsle 撤回:肺炎衣原体诱导人牙龈成纤维细胞中白细胞介素-6和白细胞介素-10。
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-08 DOI: 10.1111/1348-0421.13218

RETRACTION: A. Rizzo, R. Paolillo, A.G. Lanza, L. Guida, M. Annunziata, and C.R. Carratelli, “Chlamydia Pneumoniae Induces Interleukin-6 and Interleukin-10 in Human Gingival Fibroblasts,” Microbiology and Immunology 52, no. 9 (2008): 447–454, https://doi.org/10.1111/j.1348-0421.2008.00059.x.

The above article, published online on 1 September 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Chikara Kaito; the Japanese Society for Bacteriology, the Japanese Society for Virology, and the Japanese Society for Host Defense Research; and John Wiley & Sons Australia, Ltd. The retraction has been agreed due to duplication of images and data in Figures 1, 3, and 4 that overlap with an earlier article by the authors. Additionally, there is high similarity in the text of the two articles, without attribution to the earlier work. The authors did not respond to our requests for comment.

引用本文:A. Rizzo, R. Paolillo, A.G. Lanza, L. Guida, M. Annunziata, C.R. Carratelli,“肺炎衣原体诱导牙龈成纤维细胞中白细胞介素-6和白细胞介素-10的研究”,微生物学与免疫学,第52期。9 (2008): 447-454, https://doi.org/10.1111/j.1348-0421.2008.00059.x.The上述文章于2008年9月1日在线发表在Wiley在线图书馆(wileyonlinelibrary.com)上,经期刊主编Chikara Kaito同意撤回;日本细菌学学会、日本病毒学学会和日本宿主防御研究学会;约翰·威利&;澳大利亚之子有限公司由于图1、3和4中的图像和数据与作者之前的文章重叠,已同意撤回。此外,这两篇文章的文本有很高的相似性,没有归因于早期的工作。作者没有回应我们的置评请求。
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引用次数: 0
Issue Information – Cover 发行资料-封面
IF 1.9 4区 医学 Q4 IMMUNOLOGY Pub Date : 2025-04-07 DOI: 10.1111/1348-0421.13137

Cover photograph: Supersulfides play various roles in biological systems. Microbiol Immunol: 69:191-202. Article link here

封面图片:超硫化物在生物系统中扮演着各种各样的角色。中华微生物学杂志(英文版);69:191-202。文章链接
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引用次数: 0
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