Apmis最新文献

{"title":"Examining the Role of Virulence Proteins From Pathogenic Anaerobes in the Initiation of Colorectal Cancer","authors":"Vinoj Gopalakrishnan,&nbsp;Vaijayanthi Saravanan,&nbsp;Maria Infant Majula Shifani Mahendran,&nbsp;Vinoth Boopathy,&nbsp;Rajan Vaithianathan,&nbsp;Sowmya Srinivasan,&nbsp;Srikrishna Krishnamurthy","doi":"10.1111/apm.70041","DOIUrl":"https://doi.org/10.1111/apm.70041","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is a rising threat in modern populations, driven by reduced dietary fiber intake, pollution, poor hygiene, and especially the overuse of antibiotics. Anaerobe-induced CRC has emerged as a focal area in current research, with particular attention to anaerobic pathogenic bacteria such as <i>Helicobacter pylori</i>, <i>Fusobacterium nucleatum</i>, <i>Solobacterium moorei</i>, <i>Bacteroides fragilis</i> toxin (BFT), <i>Peptostreptococcus anaerobius</i>, and <i>Parvimonas micra</i>. Pathogens inhabit concerning niche within the gut, releasing virulence factors that disrupt gut microbiota homeostasis, leading to significant dysbiosis and chronic inflammation. Persistent inflammatory state activates various inflammatory markers, triggering cancer-associated signaling pathways. Moreover, bacterial toxins and biofilm formation exacerbate these effects by activating multiple malignant signaling pathways. Review explores recent advances in therapeutic strategies, emphasizing the importance of a deeper understanding of anaerobes and their pivotal roles in CRC progression. We highlight the major anaerobes likely to be classified as grade I carcinogens in the future and underscore the critical need for effective interventions to mitigate their impact on CRC development.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 7","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Therapeutic Response to Molecular Hydrogen in Autoimmune Diseases via Immunophenotyping","authors":"Shan-Wen Lui,&nbsp;Ting-Yu Hsieh,&nbsp;Jeng-Wei Lu,&nbsp;Yi-Jung Ho,&nbsp;Feng-Cheng Liu","doi":"10.1111/apm.70040","DOIUrl":"https://doi.org/10.1111/apm.70040","url":null,"abstract":"<div>\u0000 \u0000 <p>Autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), are characterized by immune dysregulation that leads to chronic inflammation and organ damage. Current therapeutic strategies—including corticosteroids, immunosuppressants, and biologics—often exhibit variable efficacy and are associated with potential adverse effects. Molecular hydrogen, recognized for its ability to scavenge mitochondrial reactive oxygen species and inhibit the NLRP3 inflammasome, has emerged as a promising adjunctive treatment. However, its immunomodulatory effects remain insufficiently defined. This study aimed to evaluate the immunological effects of molecular hydrogen-assisted therapy (MHAT) on immune cell subsets and to identify potential predictive biomarkers of treatment efficacy. A total of 25 patients with autoimmune diseases who received MHAT were included (RA: <i>n</i> = 14; SLE: <i>n</i> = 7; others: <i>n</i> = 4, including one each with psoriatic arthritis, primary Sjögren's syndrome, immune-related interstitial lung disease, and diffuse idiopathic skeletal hyperostosis). An additional 15 untreated RA patients served as controls for the assessment of MHAT-induced changes in lymphocyte profiles and type 1 regulatory T (Tr1) cells. MHAT was administered orally at a daily dose of 170 mg hydrogen-enriched coral calcium for three months. Immune phenotyping of T cells, B cells, and regulatory T cells was performed using flow cytometry before and after treatment. Among the 108 immune subsets analyzed, 15 exhibited significant changes, including 11 T cell and 4 B cell subsets. Disease-specific immune modulation was observed in RA patients, particularly characterized by increased proportions of programmed cell death protein 1 (PD-1⁺) T cells and Fas⁺ B cells, and a marked reduction in Tr1 cells compared to patients with SLE or other autoimmune diseases. Based on baseline immune profiles and the percent change in fatigue scores (assessed by the Brief Fatigue Inventory, BFI-T), a Hydrogen-assisted Treatment Response Prediction Index (HRPI) was developed, demonstrating strong predictive performance (ROC = 0.9375, <i>p</i> = 0.0118). HRPI values below −0.3 predicted favorable clinical responses, whereas values near zero were associated with poor outcomes. HRPI shows potential as a predictive biomarker for MHAT efficacy and guides personalized autoimmune treatment.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 7","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144519912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Account of a Research Expedition to Greenland in 1908 by Marie and August Krogh—Early 20th Century Experimental Physiology in the Field","authors":"Adam Bencard","doi":"10.1111/apm.70032","DOIUrl":"https://doi.org/10.1111/apm.70032","url":null,"abstract":"","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum miR-181a-5p Serves as a Diagnostic Biomarker for Sepsis and Predicts Clinical Outcomes","authors":"Huibo Li,&nbsp;Geng Yuan,&nbsp;Gang Luo,&nbsp;Xiangzhe Ni,&nbsp;Shuang Wu,&nbsp;Haiyun Chu,&nbsp;Ying Xiong","doi":"10.1111/apm.70037","DOIUrl":"https://doi.org/10.1111/apm.70037","url":null,"abstract":"<div>\u0000 \u0000 <p>MicroRNA (miRNA) shows promise as a biomarker for sepsis diagnosis and prognosis. In the present investigation, we examined the potential of miR-181a-5p as a clinical diagnostic and prognostic indicator for sepsis. This study enrolled 119 sepsis patients and 125 controls. Serum miR-181a-5p levels were assessed via RT-qPCR, revealing a significant upregulation in sepsis patients. The receiver operating characteristic (ROC) curve indicated miR-181a-5p could distinguish sepsis patients with 73.11% sensitivity and 89.60% specificity (AUC = 0.879). Pearson's analysis showed serum miR-181a-5p positively correlated with disease severity scores (APACHE II and SOFA), procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA), and negative with glutathione peroxidase (GSH-Px). Kaplan–Meier survival analysis revealed that elevated serum miR-181a-5p levels were associated with a worse 28-day prognosis in sepsis patients (log-rank <i>p</i> = 0.022). In summary, this study identifies serum miR-181a-5p as a diagnostic and prognostic biomarker for sepsis, significantly linked to disease severity, inflammation, and oxidative stress, providing new avenues for sepsis management.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144367414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Significance of Immunohistochemical Surrogate Molecular Sub-Typing of Small Cell Lung Carcinoma","authors":"Sananda Kumar,&nbsp;Navneet Singh,&nbsp;Parul Gupta,&nbsp;Rajender Kumar,&nbsp;Suvradeep Mitra,&nbsp;Amanjit Bal","doi":"10.1111/apm.70035","DOIUrl":"https://doi.org/10.1111/apm.70035","url":null,"abstract":"<div>\u0000 \u0000 <p>Small cell lung carcinoma (SCLC) was considered a homogenous tumor both morphologically and genetically. Gene expression profiling of SCLC has revealed existence of four distinct subtypes within the SCLC which may impact the prognosis and therapeutic outcome. In the present study, surrogate molecular subtyping of SCLC was done using immunohistochemistry. Histologically confirmed cases of SCLC were included in the study. For molecular sub-typing, primary antibodies specific for ASCL1, POU2F3, NEUROD1, and YAP1 were used. The results were also correlated with baseline demographic and clinical parameters as well as treatment outcome. ASCL1, NEUROD1, and POU2F3 were expressed in 68 (67.3%), 15 (14.9%) and 3 (3.0%) cases, respectively. YAP1 showed cytoplasmic expression in 3 cases (3.0%). ASCL1 and NEUROD1 were co-expressed in 6.9% of cases. The remaining 25.7% of cases were negative for or had low expression of all four transcription factors. SCLC cases were thus classified as ASCL1-dominant, NEUROD1-dominant, ASCL1/NEUROD1 co-expressing, POU2F3-dominant, and Quadruple-negative subtypes. We did not recognize the YAP1 subtype. The overall survival was significantly reduced in the ASCL1 subtype compared to other subtypes. Sub-classification of SCLC patients may help in predicting the prognosis in such patients and may also help in guiding the therapy in the future.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunohistochemical Profiling of Interferon-Stimulated Genes in Histopathological Specimens: A Potential Screening Approach for Viral Infections","authors":"Christian Thomsen,&nbsp;Svend Birkelund,&nbsp;Rasmus Røge","doi":"10.1111/apm.70034","DOIUrl":"https://doi.org/10.1111/apm.70034","url":null,"abstract":"<p>Thomsen C, Birkelund S, Røge R. Immunohistochemical profiling of interferon-stimulated genes in histopathological specimens: A potential screening approach for viral infections. Identifying viral infections in histopathological specimens can pose a diagnostic challenge. Increased expression of interferon-stimulated genes (ISGs) may serve as a potential screening marker for such infections. This study undertakes a comparative analysis of ISG immunohistochemical expression in various tissue types, encompassing both normal and inflamed tissues, including both viral and nonviral etiologies. Archival formalin-fixed paraffin-embedded (FFPE) tissues with confirmed viral infection (<i>n</i> = 27) and nonviral inflammation (<i>n</i> = 15) were analyzed. Tissue microarrays (TMAs) were constructed and stained with antibodies against ISGs: Human myxovirus resistance protein 1 (MxA), RIG-I, MDA5, PKR, and PD-L1. Qualitative assessment compared their upregulation to five normal controls of each tissue type. MxA exhibited significantly increased upregulation in viral infections compared to nonviral inflammation (OR 6.53 [CI 1.59, 26.79]), with sensitivity and specificity of 0.70 (0.50, 0.86) and 0.73 (0.45, 0.92), respectively. The remaining ISGs showed no significant differences and had moderate sensitivity and low specificity. In conclusion, while MxA, PD-L1, PKR, MDA5, and RIG-I generally showed upregulation in most viral infections, variability was observed. MxA holds promise as a viral infection screening marker in FFPE samples, but its utility may be limited by an inadequate interferon response to certain viruses.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the Potential Role of SIGNR1(CD209b) in Shaping Gut Microbiota During the Early Postnatal Life","authors":"Nihal Hasan,&nbsp;Sizhe Zhu,&nbsp;Tie Chen","doi":"10.1111/apm.70033","DOIUrl":"https://doi.org/10.1111/apm.70033","url":null,"abstract":"<div>\u0000 \u0000 <p>Increasing evidence suggests a significant interconnection between developing several chronic diseases later in adult life and early-life gut microbiota composition. Postnatal is crucial in shaping gut microbiota, maintaining immune balance, and establishing microbe-host interactions. However, the molecular mechanisms that contribute to shaping gut microbiota in early life remain poorly understood. During this crucial phase, various innate immune receptors play an active role in influencing the gut microbiota. The DC-SIGN receptor and its mouse homolog, SIGNR1, act as a sensor, facilitating communication between microorganisms, particularly Gram-negative bacteria, and the host's immune system. This study aimed to investigate the role of the SIGNR1 receptor in shaping the gut microbiota composition during early life in a murine model. The results showed that Firmicutes was the most abundant phylum in SIGNR1 KO mice, while WT mice displayed a higher abundance of Proteobacteria. Functional composition analysis demonstrated that the proportion of Gram-negative bacteria was notably lower in KO mice compared to WT mice. In addition, the absence of SIGNR1 is associated with alterations in immune response and metabolic pathways, highlighting its potential indirect role in modulating the microbiota. Finally, these results suggest that SIGNR1 may influence early-life gut microbiota composition through direct and indirect mechanisms.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed Bacterial Neutrophil Recruitment and Bacterial Bone Dispersion: New Identified Factors in Peri-Prosthetic Joint Infection Development. Insights From an Adult Minipig Model","authors":"Katrine Top Hartmann,&nbsp;Anton Alexander Nolte Peterlin,&nbsp;Marie Høy Hansen,&nbsp;Julie Knippel Melsted Birch,&nbsp;Anders Odgaard,&nbsp;Bent Aalbæk,&nbsp;Mads Holm Christensen,&nbsp;Ida Thaarup,&nbsp;Thomas Bjarnsholt,&nbsp;Karen L. de Mesy Bentley,&nbsp;Andreas Petersen,&nbsp;Henrik Elvang Jensen,&nbsp;Louise Kruse Jensen","doi":"10.1111/apm.70031","DOIUrl":"https://doi.org/10.1111/apm.70031","url":null,"abstract":"<p>Clinically relevant animal models of peri-prosthetic joint infection (PJI) are essential for studying infection initiation and progression. This study developed a PJI model in adult Göttingen minipigs, explicitly focusing on the early stages of infection to gain new perceptions of PJI initiation. The model was established by drilling a hole into the femoral head, followed by inoculation with either <i>Staphylococcus aureus</i> (<i>n</i> = 6) or saline (<i>n</i> = 4) and inserting a stainless-steel screw. The animals were euthanized within 2 or 3 days post-inoculation. Comprehensive bone and joint pathology analyses were performed. All <i>S. aureus</i> inoculated animals had bacteria reisolated from bone, screw, synovial fluid, and synovial membrane. Histology revealed numerous bacterial colonies in the peri-implant bone tissue, many of which were unaccompanied by neutrophils, indicating delayed neutrophil recruitment to bacteria. In contrast, all synovial membrane-located bacteria were recognized by the immune system. Digital pathology measures showed deep bacterial dispersion within the bone, at a far distance from the point of inoculation. This study presents a new PJI model, which facilitates the investigation of infection initiation and supports studies aimed at preventing PJI. The study uncovered two previously unknown insights into the development of PJI: delayed bacterial neutrophil recruitment and widespread osseous bacterial dissemination within 48 h.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 6","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/apm.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144213983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing PMMA Cements With Manually Added Antimicrobial Agents","authors":"Martina Humez,&nbsp;Mustafa Citak,&nbsp;Stefan Luck,&nbsp;Philip Linke,&nbsp;Thorsten Gehrke,&nbsp;Christian Paul,&nbsp;Klaus-Dieter Kühn","doi":"10.1111/apm.70029","DOIUrl":"https://doi.org/10.1111/apm.70029","url":null,"abstract":"<div>\u0000 \u0000 <p>Periprosthetic joint infection (PJI) is an infrequent yet severe complication. A fundamental aspect of PJI treatment involves the use of polymethylmethacrylate (PMMA) cement augmented with antibiotics. For therapeutic application, it is often necessary to manually mix antibiotics with commercially produced PMMA cements. However, the potential issues arising from this manual admixing have not been thoroughly documented. This study aims to elucidate the impact of additional homogenization through dry mixing of a polymer-active substance blend on the quality of manually mixed PMMA cement. In this laboratory-based investigation, four cement samples were prepared using various methods for the manual incorporation and homogenization of the antibiotic vancomycin. The reference controls were Copal G + V and Copal G + C pro (Heraeus Medical GmbH, Wehrheim, Germany), representing commercially available PMMA cements and a closed mixing system. The samples were analyzed for mechanical, microbiological, and microscopic properties. The mechanical and microbiological analyses revealed no statistically significant differences between the manually mixed samples and the references. However, microscopic examination of the mixing cartridges' inner surfaces indicated scratching and signs of abrasion during the mixing process. The manual incorporation of antibiotics into PMMA cement should be limited to specific indications, with a preference for using commercially available mixtures whenever possible.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Natural Killer Cell-Related Genes as Potential Diagnostic Biomarkers for Pediatric Sepsis","authors":"Zhihong Liu,&nbsp;Minghua Su,&nbsp;Peiqi Wan,&nbsp;Xiumei Zhen,&nbsp;Lixia He,&nbsp;Huan Liang","doi":"10.1111/apm.70030","DOIUrl":"https://doi.org/10.1111/apm.70030","url":null,"abstract":"<div>\u0000 \u0000 <p>Pediatric sepsis is a prevalent severe condition with a high disability rate and mortality. The purpose of this study was to investigate how NK cell-related genes (NKGs) function in the diagnosis of pediatric sepsis. Differential analysis and Venn analysis were utilized to screen differentially expressed NKGs (DE-NKGs) in pediatric sepsis. The PPI network of DE-NKGs was generated using STRING. Candidate drugs are predicted using the CMAP database. miRNA and transcription factor (TF) targeting hub genes were screened using the Networkanalyst website. A total of 22 DE-NKGs were identified, which were mainly enriched in immune-related biological processes. Ten hub genes that were filtered out from DE-NKGs exhibited good diagnostic performance. Immune infiltration analysis revealed that macrophages and neutrophils had higher infiltration abundance in the pediatric sepsis group, whereas NK cells had higher infiltration abundance in the normal group. NKGs (LCK, FCER1G, PRF1, CD247, GZMB, CD2, CCL4, KLRD1, CCL5, and ITGB2) with diagnostic performance were successfully predicted, and some potential miRNAs, TFs, and candidate drugs were also predicted. In conclusion, this study threw light on a comprehensive understanding of the role of NK cells in pediatric sepsis.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}