Colistin (COL) belongs to the polymyxin group of drugs, which possesses a positive charge and interacts with lipopolysaccharide (LPS) of Gram-negative bacterial outer membranes. Acinetobacter baumannii, a bacterium in the “ESKAPE” group of “priority pathogens,” has acquired resistance against the majority of available antibiotics, including the last resort antibiotic COL. Though plasmid-encoded acquisition of mcr-genes has been associated with clinical resistance, efflux, loss of LPS by inactivation of the biosynthetic pathway (lpxACD), and modifications of target LPS by products of chromosomal pmrCAB genes has been ascribed to resistance evolution. Systemic characterization of trade-offs and traits accompanying the evolution of COL resistance in the bacteria remains unaccomplished. Here we report adaptive evolution of extreme COL resistance of the reference strain A. baumannii ATCC19606. Systemic phenotypic characterization of the mutants revealed hyperbiofilm formation and a striking decrease in fitness as the major evolution-associated attributes. Comprehensive antibiotic susceptibility profiling indicated collateral sensitivity against vancomycin and fosfomycin. Whole genome sequencing of the resistant strains led to the identification of mutations associated with COL resistance. Phenotypic characterization of three COL-resistant clinical isolates of A. baumannii revealed similarity with experimentally evolved resistant mutants in one of the isolates, in which none of the mcr-genes could be detected.
{"title":"Identification of Evolutionary Trade-Offs Associated With High-Level Colistin Resistance in Acinetobacter baumannii","authors":"Kusumita Acharya, Upasana Bhattacharya, Shatarupa Biswas, Nilanjan Pradhan, Sunandini Bhattacharya, Mallika Ghosh, Arijit Bhattacharya","doi":"10.1111/apm.70121","DOIUrl":"10.1111/apm.70121","url":null,"abstract":"<div>\u0000 \u0000 <p>Colistin (COL) belongs to the polymyxin group of drugs, which possesses a positive charge and interacts with lipopolysaccharide (LPS) of Gram-negative bacterial outer membranes. <i>Acinetobacter baumannii</i>, a bacterium in the “ESKAPE” group of “priority pathogens,” has acquired resistance against the majority of available antibiotics, including the last resort antibiotic COL. Though plasmid-encoded acquisition of <i>mcr</i>-genes has been associated with clinical resistance, efflux, loss of LPS by inactivation of the biosynthetic pathway (<i>lpx</i>ACD), and modifications of target LPS by products of chromosomal <i>pmr</i>CAB genes has been ascribed to resistance evolution. Systemic characterization of trade-offs and traits accompanying the evolution of COL resistance in the bacteria remains unaccomplished. Here we report adaptive evolution of extreme COL resistance of the reference strain <i>A. baumannii ATCC</i>19606. Systemic phenotypic characterization of the mutants revealed hyperbiofilm formation and a striking decrease in fitness as the major evolution-associated attributes. Comprehensive antibiotic susceptibility profiling indicated collateral sensitivity against vancomycin and fosfomycin. Whole genome sequencing of the resistant strains led to the identification of mutations associated with COL resistance. Phenotypic characterization of three COL-resistant clinical isolates of <i>A. baumannii</i> revealed similarity with experimentally evolved resistant mutants in one of the isolates, in which none of the <i>mcr</i>-genes could be detected.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145755009","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}
Atrial fibrillation (AF) ranks among the most prevalent cardiovascular diseases, and its prevalence is increasing over the years. Atrial fibrosis is one of the key causes of AF. This study aimed to investigate miR-490-3p levels in AF and the regulatory effect of the miR-490-3p/TGFBR1 axis on atrial fibrosis. In this study, RT-qPCR was utilized to detect miR-490-3p and TGFBR1 levels in AF patients. ROC was utilized to assess the diagnostic value of miR-490-3p in AF. Logistic regression was utilized to analyze left atrial fibrosis risk factors in AF patients. The AF cell model was established using human cardiac fibroblasts (HCFs). In vitro experiments included CCK-8 viability assay and luciferase reporter assay. The levels of fibrotic factors were detected using western blot. miR-490-3p expression in AF patients was clearly lower. miR-490-3p had good diagnostic ability for AF and was a risk factor. Luciferase assays confirmed TGFBR1 as a target of miR-490-3p. In vitro cell experiments confirmed that TGFBR1 overexpression can rescue the inhibitory effect of miR-490-3p on HCFs proliferation and fibrotic factor expression. In conclusion, miR-490-3p may act as a potential AF marker and inhibit the occurrence of atrial fibrosis through the miR-490-3p/TGFBR1 axis.
{"title":"MiR-490-3p/TGFBR1 Axis Prevents Atrial Fibrillation by Inhibiting Cellular Fibrosis","authors":"Xueshan Zhang, Zongliang Yu","doi":"10.1111/apm.70098","DOIUrl":"10.1111/apm.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>Atrial fibrillation (AF) ranks among the most prevalent cardiovascular diseases, and its prevalence is increasing over the years. Atrial fibrosis is one of the key causes of AF. This study aimed to investigate miR-490-3p levels in AF and the regulatory effect of the miR-490-3p/TGFBR1 axis on atrial fibrosis. In this study, RT-qPCR was utilized to detect miR-490-3p and TGFBR1 levels in AF patients. ROC was utilized to assess the diagnostic value of miR-490-3p in AF. Logistic regression was utilized to analyze left atrial fibrosis risk factors in AF patients. The AF cell model was established using human cardiac fibroblasts (HCFs). In vitro experiments included CCK-8 viability assay and luciferase reporter assay. The levels of fibrotic factors were detected using western blot. miR-490-3p expression in AF patients was clearly lower. miR-490-3p had good diagnostic ability for AF and was a risk factor. Luciferase assays confirmed TGFBR1 as a target of miR-490-3p. In vitro cell experiments confirmed that TGFBR1 overexpression can rescue the inhibitory effect of miR-490-3p on HCFs proliferation and fibrotic factor expression. In conclusion, miR-490-3p may act as a potential AF marker and inhibit the occurrence of atrial fibrosis through the miR-490-3p/TGFBR1 axis.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145740701","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}
Wei Li, Yijian Zhang, Hongwei Yang, Junyu Guo, Boqian Wang
End-stage renal disease (ESRD) threatens human lives due to the high incidence rate of complications. Vascular calcification is a severe complication of ESRD inducing major adverse cardiovascular events (MACEs). This study enrolled 205 patients diagnosed with chronic kidney disease (CKD), including 95 patients diagnosed at end stages. The clinical significance of miR-378a-3p was assessed from the perspectives of early screening, risk prediction, and MACE prediction. The regulation of vascular calcification by miR-378a-3p was estimated through inflammation, osteogenic differentiation, Ca2+ concentration, and cell proliferation in human vascular smooth muscle cells (hVSMCs). Significant downregulation of miR-378a-3p was observed in ESRD patients, which discriminated ESRD patients from early-stage CKD patients and predicted the risk of ESRD. Lower serum miR-378a-3p levels were observed in ESRD patients developing vascular calcification and were identified as a risk factor for the occurrence of MACEs. Overexpression of miR-378a-3p could alleviate calcified culture medium-induced inflammation, osteogenic differentiation, increasing Ca2+, and decreasing cell proliferation of hVSMCs. SULF1 was negatively regulated by miR-378a-3p. The overexpression of SULF1 reversed the protective effect of miR-378a-3p on vascular calcification. miR-378a-3p acted as a biomarker for screening ESRD and predicting adverse outcomes of patients. miR-378a-3p regulated vascular calcification through targeting SULF1.
{"title":"Circulating miR-378a-3p Screens End-Stage Renal Disease Patients, Predicts the Occurrence of MACEs, and Regulates Vascular Calcification via Targeting SULF1","authors":"Wei Li, Yijian Zhang, Hongwei Yang, Junyu Guo, Boqian Wang","doi":"10.1111/apm.70097","DOIUrl":"10.1111/apm.70097","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>End-stage renal disease (ESRD) threatens human lives due to the high incidence rate of complications. Vascular calcification is a severe complication of ESRD inducing major adverse cardiovascular events (MACEs). This study enrolled 205 patients diagnosed with chronic kidney disease (CKD), including 95 patients diagnosed at end stages. The clinical significance of miR-378a-3p was assessed from the perspectives of early screening, risk prediction, and MACE prediction. The regulation of vascular calcification by miR-378a-3p was estimated through inflammation, osteogenic differentiation, Ca<sup>2+</sup> concentration, and cell proliferation in human vascular smooth muscle cells (hVSMCs). Significant downregulation of miR-378a-3p was observed in ESRD patients, which discriminated ESRD patients from early-stage CKD patients and predicted the risk of ESRD. Lower serum miR-378a-3p levels were observed in ESRD patients developing vascular calcification and were identified as a risk factor for the occurrence of MACEs. Overexpression of miR-378a-3p could alleviate calcified culture medium-induced inflammation, osteogenic differentiation, increasing Ca<sup>2+</sup>, and decreasing cell proliferation of hVSMCs. SULF1 was negatively regulated by miR-378a-3p. The overexpression of SULF1 reversed the protective effect of miR-378a-3p on vascular calcification. miR-378a-3p acted as a biomarker for screening ESRD and predicting adverse outcomes of patients. miR-378a-3p regulated vascular calcification through targeting SULF1.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720744","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}
Gro Tunheim, Marta Baranowska-Hustad, Fridtjof Lund-Johansen, Even Fossum, Sabin Bhandari, Liva Kukule, Thea Kristine Rogne Møller, Elisabeth L. Vikse, Terese Bekkevold, Fredrik Oftung, Anna Hayman Robertson, Lisbeth M. Næss
Antibody levels induced by SARS-CoV-2 infection have been reported to be associated with specific symptoms, disease severity, and viral load. In this study we investigated whether antibody responses were associated with virus type (Alpha B.1.1.7 or non-variants of concern (non-VOC)), viral load and clinical outcome in unvaccinated non-hospitalized adults with PCR-confirmed SARS-CoV-2 infection. Serum samples, questionnaires and symptom diaries were collected longitudinally (Day 0–180) between May 2020 and June 2021. IgG levels against ancestral Wuhan antigens and antibodies inhibiting RBD-ACE2 interaction were measured by multiplex immunoassay and flowcytometry, respectively. Antibody neutralization assays were performed with B.1 and B.1.1.7 viruses. Viral load was measured by digital-droplet PCR, and virus isolates were sequenced. Factors influencing IgG levels were investigated using Bayesian multilevel models. Alpha-cases had 2.6–3.2-fold higher IgG levels against RBD, nucleocapsid, and spike on Day 14, and higher antibody-mediated inhibition of ACE2-RBD interaction compared to non-VOC cases. Alpha-cases displayed 1.8- and 5.4-fold higher neutralizing antibody titers than non-VOC cases against B.1 and B1.1.7, respectively, but both non-VOC and Alpha cases displayed the lowest ratio of binding to neutralizing antibodies against their infecting virus type. Alpha cases reported more symptoms than non-VOC cases, but the severity of disease was similar. Nausea was significantly associated with higher IgG levels, while no association was found for viral load, despite Alpha cases having higher viral loads than non-VOC cases. This study shows higher antibody responses induced by the more transmissible Alpha virus compared to earlier non-VOC variants after mild SARS-CoV-2 infection. Reporting of nausea was positively associated with IgG levels.
{"title":"SARS-CoV-2 Infection With Alpha B.1.1.7 Virus Induced Higher Antibody Responses Than Earlier Non-VOC Variants During the First Waves of the COVID-19 Pandemic in Norway","authors":"Gro Tunheim, Marta Baranowska-Hustad, Fridtjof Lund-Johansen, Even Fossum, Sabin Bhandari, Liva Kukule, Thea Kristine Rogne Møller, Elisabeth L. Vikse, Terese Bekkevold, Fredrik Oftung, Anna Hayman Robertson, Lisbeth M. Næss","doi":"10.1111/apm.70102","DOIUrl":"10.1111/apm.70102","url":null,"abstract":"<p>Antibody levels induced by SARS-CoV-2 infection have been reported to be associated with specific symptoms, disease severity, and viral load. In this study we investigated whether antibody responses were associated with virus type (Alpha B.1.1.7 or non-variants of concern (non-VOC)), viral load and clinical outcome in unvaccinated non-hospitalized adults with PCR-confirmed SARS-CoV-2 infection. Serum samples, questionnaires and symptom diaries were collected longitudinally (Day 0–180) between May 2020 and June 2021. IgG levels against ancestral Wuhan antigens and antibodies inhibiting RBD-ACE2 interaction were measured by multiplex immunoassay and flowcytometry, respectively. Antibody neutralization assays were performed with B.1 and B.1.1.7 viruses. Viral load was measured by digital-droplet PCR, and virus isolates were sequenced. Factors influencing IgG levels were investigated using Bayesian multilevel models. Alpha-cases had 2.6–3.2-fold higher IgG levels against RBD, nucleocapsid, and spike on Day 14, and higher antibody-mediated inhibition of ACE2-RBD interaction compared to non-VOC cases. Alpha-cases displayed 1.8- and 5.4-fold higher neutralizing antibody titers than non-VOC cases against B.1 and B1.1.7, respectively, but both non-VOC and Alpha cases displayed the lowest ratio of binding to neutralizing antibodies against their infecting virus type. Alpha cases reported more symptoms than non-VOC cases, but the severity of disease was similar. Nausea was significantly associated with higher IgG levels, while no association was found for viral load, despite Alpha cases having higher viral loads than non-VOC cases. This study shows higher antibody responses induced by the more transmissible Alpha virus compared to earlier non-VOC variants after mild SARS-CoV-2 infection. Reporting of nausea was positively associated with IgG levels.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12696439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145720887","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}
This study was conducted to determine the frequency of high-grade pancreatic intraepithelial lesions (HG-PanIN) and the cancerization of ducts (COD), a phenomenon in which invasive cancer spreads within the pancreatic duct, and the differences between mucous profiles in pancreatic ductal adenocarcinoma. Immunohistochemistry for p53, SMAD4 and mucin was performed on 103 lesions in 97 cases. Carcinoma in situ (CIS) with p53 and SMAD4 staining that were different from invasive carcinoma were classified as HG-PanIN, while CIS with staining consistent with invasive carcinoma were classified as COD. CIS lesions were classified as 63 COD (61.2%) and 29 HG-PanIN (28.2%). The CODs consisted of 30 lesions (47.6%) with aberrant p53 and SMAD4, 26 lesions (41.3%) with aberrant p53, and 7 lesions (11.1%) with aberrant SMAD4. Fourteen HG-PanIN lesions (48.3%) had aberrant p53. MUC1 positivity was lower in COD (27 lesions; 42.9%) and HG-PanIN (16 lesions; 55.2%) than in invasive carcinoma (81 lesions; 83.5%) (p < 0.01). MUC6 was positive in 17 HG-PanIN lesions (58.6%)—higher than in invasive carcinoma (18 lesions; 18.6%) and COD (8 lesions; 12.7%) (p < 0.001). This study classified CIS as COD and HG-PanIN and found that the MUC6 expression of COD and HG-PanIN differed.
{"title":"Immunohistochemical Classification of High-Grade Pancreatic Intraepithelial Neoplasia and Ductal Cancerization in Pancreatic Ductal Adenocarcinoma Using p53, SMAD4, and Mucin Expression","authors":"Yumi Nozawa-Yoshimura, Kazuyuki Ishida, Masato Onozaki, Akihiro Kawabe, Taku Aoki","doi":"10.1111/apm.70106","DOIUrl":"10.1111/apm.70106","url":null,"abstract":"<p>This study was conducted to determine the frequency of high-grade pancreatic intraepithelial lesions (HG-PanIN) and the cancerization of ducts (COD), a phenomenon in which invasive cancer spreads within the pancreatic duct, and the differences between mucous profiles in pancreatic ductal adenocarcinoma. Immunohistochemistry for p53, SMAD4 and mucin was performed on 103 lesions in 97 cases. Carcinoma in situ (CIS) with p53 and SMAD4 staining that were different from invasive carcinoma were classified as HG-PanIN, while CIS with staining consistent with invasive carcinoma were classified as COD. CIS lesions were classified as 63 COD (61.2%) and 29 HG-PanIN (28.2%). The CODs consisted of 30 lesions (47.6%) with aberrant p53 and SMAD4, 26 lesions (41.3%) with aberrant p53, and 7 lesions (11.1%) with aberrant SMAD4. Fourteen HG-PanIN lesions (48.3%) had aberrant p53. MUC1 positivity was lower in COD (27 lesions; 42.9%) and HG-PanIN (16 lesions; 55.2%) than in invasive carcinoma (81 lesions; 83.5%) (<i>p</i> < 0.01). MUC6 was positive in 17 HG-PanIN lesions (58.6%)—higher than in invasive carcinoma (18 lesions; 18.6%) and COD (8 lesions; 12.7%) (<i>p</i> < 0.001). This study classified CIS as COD and HG-PanIN and found that the MUC6 expression of COD and HG-PanIN differed.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12686848/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707044","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}
Long non-coding RNAs (lncRNAs) are crucial regulators of hepatocellular carcinoma (HCC) development. The objective of the present investigation was to examine the lncRNA HOXC-AS1 levels in HCC and to explore the function of the HOXC-AS1/miR-876-3p/NR3C1 axis in HCC. Relative HOXC-AS1, miR-876-3p, and NR3C1 levels in tumor and paracancerous specimens were assessed by quantitative RT-PCR. sh-HOXC-AS1 was transfected into HCC cells to analyze its effects on HCC. The detection of cell growth, migration, and invasiveness was conducted by the CCK-8 assay along with Transwell analysis. Flow cytometry was employed to assess cell apoptosis. To evaluate the prognostic significance of HOXC-AS1, a Kaplan–Meier survival analysis was carried out. HOXC-AS1 was increased in HCC specimens in comparison with paracancerous tissues. Patients with high HOXC-AS1 levels had lower disease-free survival and overall survival rates than cases with low HOXC-AS1 levels (p < 0.001). Silencing HOXC-AS1 reduced the growth, migration, and invasiveness of HCC cells while promoting their apoptosis. As the direct target gene, miR-876-3p is negatively related to HOXC-AS1 levels. miR-876-3p could reverse the functions of HOXC-AS1 for HCC cells by targeting NR3C1. Upregulation of HOXC-AS1 promotes HCC progression through the miR-876-3p/NR3C1 axis.
{"title":"LncRNA HOXC-AS1 Promotes Tumor Progression via miR-876-3p/NR3C1 in Hepatocellular Carcinoma","authors":"Di Wu, Yan Qu, Yichuan Zhang, Ruiting Li","doi":"10.1111/apm.70108","DOIUrl":"10.1111/apm.70108","url":null,"abstract":"<div>\u0000 \u0000 <p>Long non-coding RNAs (lncRNAs) are crucial regulators of hepatocellular carcinoma (HCC) development. The objective of the present investigation was to examine the lncRNA HOXC-AS1 levels in HCC and to explore the function of the HOXC-AS1/miR-876-3p/NR3C1 axis in HCC. Relative HOXC-AS1, miR-876-3p, and NR3C1 levels in tumor and paracancerous specimens were assessed by quantitative RT-PCR. sh-HOXC-AS1 was transfected into HCC cells to analyze its effects on HCC. The detection of cell growth, migration, and invasiveness was conducted by the CCK-8 assay along with Transwell analysis. Flow cytometry was employed to assess cell apoptosis. To evaluate the prognostic significance of HOXC-AS1, a Kaplan–Meier survival analysis was carried out. HOXC-AS1 was increased in HCC specimens in comparison with paracancerous tissues. Patients with high HOXC-AS1 levels had lower disease-free survival and overall survival rates than cases with low HOXC-AS1 levels (<i>p</i> < 0.001). Silencing HOXC-AS1 reduced the growth, migration, and invasiveness of HCC cells while promoting their apoptosis. As the direct target gene, miR-876-3p is negatively related to HOXC-AS1 levels. miR-876-3p could reverse the functions of HOXC-AS1 for HCC cells by targeting NR3C1. Upregulation of HOXC-AS1 promotes HCC progression through the miR-876-3p/NR3C1 axis.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713177","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}
This study aimed to investigate the distribution, maturity, and prognostic significance of tertiary lymphoid structures (TLS) in primary breast cancer (BC), and to analyze the relationship between TLS clinicopathological features and the tumor immune microenvironment. Sixty postoperative tumor samples from patients with primary BC were retrospectively analyzed. The presence and maturity of TLS in tumor tissues were evaluated by immunohistochemical staining. The association of status and clinicopathological characteristics of TLS with immune cell infiltration was analyzed. Recurrence-free survival (RFS) and predictive factors were assessed using Kaplan–Meier survival analysis and univariate/multivariate logistic regression. TLS was detected in 35 (58.33%) patients, including 23 cases of secondary follicle-like TLS, 8 cases of early TLS, and 4 cases of primary follicle-like TLS. Compared with the non-TLS group, the TLS group showed significantly higher expression of estrogen receptor and progesterone receptor (p < 0.05). The presence of TLS was significantly associated with improved RFS (HR = 0.163, p = 0.035), with secondary follicle-like TLS showing the most favorable survival trend. TLS-positive tumors had significantly increased infiltration of CD4+ T cells (p = 0.004), while CD8+ T cell infiltration was slightly higher but not statistically significant. The presence of TLS, especially mature TLS, is associated with favorable clinicopathological features and improved prognosis in patients with primary BC, along with increased CD4+ T cell infiltration, suggesting an important role of TLS in regulating the tumor immune microenvironment. TLS may serve as a potential biomarker for prognosis evaluation and a target for immunomodulatory strategies in BC.
{"title":"Prognostic Value of Tertiary Lymphoid Structures in Primary Breast Cancer and Their Association With Immune Microenvironment","authors":"YunXia Xu, ShuiLong Liu, XiaoKai Ling, FenHua Wang, Jian Qian","doi":"10.1111/apm.70114","DOIUrl":"10.1111/apm.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>This study aimed to investigate the distribution, maturity, and prognostic significance of tertiary lymphoid structures (TLS) in primary breast cancer (BC), and to analyze the relationship between TLS clinicopathological features and the tumor immune microenvironment. Sixty postoperative tumor samples from patients with primary BC were retrospectively analyzed. The presence and maturity of TLS in tumor tissues were evaluated by immunohistochemical staining. The association of status and clinicopathological characteristics of TLS with immune cell infiltration was analyzed. Recurrence-free survival (RFS) and predictive factors were assessed using Kaplan–Meier survival analysis and univariate/multivariate logistic regression. TLS was detected in 35 (58.33%) patients, including 23 cases of secondary follicle-like TLS, 8 cases of early TLS, and 4 cases of primary follicle-like TLS. Compared with the non-TLS group, the TLS group showed significantly higher expression of estrogen receptor and progesterone receptor (<i>p</i> < 0.05). The presence of TLS was significantly associated with improved RFS (HR = 0.163, <i>p</i> = 0.035), with secondary follicle-like TLS showing the most favorable survival trend. TLS-positive tumors had significantly increased infiltration of CD4<sup>+</sup> T cells (<i>p</i> = 0.004), while CD8<sup>+</sup> T cell infiltration was slightly higher but not statistically significant. The presence of TLS, especially mature TLS, is associated with favorable clinicopathological features and improved prognosis in patients with primary BC, along with increased CD4<sup>+</sup> T cell infiltration, suggesting an important role of TLS in regulating the tumor immune microenvironment. TLS may serve as a potential biomarker for prognosis evaluation and a target for immunomodulatory strategies in BC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145713180","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}
Type 2 diabetes mellitus is linked to liver dysfunction and gut dysbiosis, and probiotics, especially Lactobacillus strains, are considered potential biotherapeutics for improving metabolic health. In this study, 15 lactic acid bacteria were isolated from traditional dairy products in Northwestern Iran and assessed for probiotic properties, including acid and bile tolerance, aggregation, hydrophobicity, antibacterial activity, and safety. Strain ad1 exhibited high acid (71.13% ± 0.62% at pH 2.5, 3 h) and bile tolerance (74.31% ± 0.65% at 0.3% oxgall, 4 h), strong autoaggregation (69.61%), and broad antibacterial activity, notably against Staphylococcus aureus (21.4 mm inhibition zone). Additionally, it was non-hemolytic and sensitive to all eight tested antibiotics. To evaluate its antidiabetic potential, ad1 was administered to streptozotocin-induced diabetic rats for 4 weeks. Results showed significant reductions in ALT (60.6 ± 1.3 to 45.5 ± 0.8 U/L), AST (93.5 ± 1.0 to 60.1 ± 1.2 U/L), ALP (264.1 ± 34.2 to 191.3 ± 28.2 U/L), and blood glucose (311.9 ± 37.2 to 153.1 ± 36.9 mg/dL, p < 0.05). Histopathological analysis confirmed reduced hepatic damage and steatosis. In conclusion, Lacticaseibacillus casei strain ad1 shows strong probiotic potential, along with hepatoprotective and antihyperglycemic effects, making it a promising candidate for T2DM management.
{"title":"Probiotic Potential of Lacticaseibacillus casei Isolated From Traditional Dairy Products and Its Hepatoprotective Effects in STZ-Induced Diabetic Rats","authors":"Yousef Nami, Parsa Johari, Alireza Dehnad","doi":"10.1111/apm.70112","DOIUrl":"10.1111/apm.70112","url":null,"abstract":"<div>\u0000 \u0000 <p>Type 2 diabetes mellitus is linked to liver dysfunction and gut dysbiosis, and probiotics, especially <i>Lactobacillus</i> strains, are considered potential biotherapeutics for improving metabolic health. In this study, 15 lactic acid bacteria were isolated from traditional dairy products in Northwestern Iran and assessed for probiotic properties, including acid and bile tolerance, aggregation, hydrophobicity, antibacterial activity, and safety. Strain <span>ad</span>1 exhibited high acid (71.13% ± 0.62% at pH 2.5, 3 h) and bile tolerance (74.31% ± 0.65% at 0.3% oxgall, 4 h), strong autoaggregation (69.61%), and broad antibacterial activity, notably against <i>Staphylococcus aureus</i> (21.4 mm inhibition zone). Additionally, it was non-hemolytic and sensitive to all eight tested antibiotics. To evaluate its antidiabetic potential, <span>ad</span>1 was administered to streptozotocin-induced diabetic rats for 4 weeks. Results showed significant reductions in ALT (60.6 ± 1.3 to 45.5 ± 0.8 U/L), AST (93.5 ± 1.0 to 60.1 ± 1.2 U/L), ALP (264.1 ± 34.2 to 191.3 ± 28.2 U/L), and blood glucose (311.9 ± 37.2 to 153.1 ± 36.9 mg/dL, <i>p</i> < 0.05). Histopathological analysis confirmed reduced hepatic damage and steatosis. In conclusion, <i>Lacticaseibacillus casei</i> strain <span>ad</span>1 shows strong probiotic potential, along with hepatoprotective and antihyperglycemic effects, making it a promising candidate for T2DM management.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666842","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}
Alexander Arum, Emilie Korsgaard Andreasen, Helle Pedersen, Trine Dahl Nielsen, Peter Frandsen, Birgitte Tønnes Pedersen, Estrid Hogdall, Jesper Bonde
Elimination of cervical cancer requires broad access to and participation in cervical screening. Self-sampling has emerged as a robust technology that simplifies access; however, few self-sampling devices are independently validated regarding sample quality. This study compares the quality of three self-sampling devices: Evalyn (Rovers), currently used in Denmark, the FLOQSwab (Copan) and the modified FLOQSwab: SensiGrip. Women residing in the Capital Region of Denmark, accepting screening by self-sampling, were offered a kit containing the following combinations of devices: (1) Evalyn, FLOQSwab, (2) Evalyn, SensiGrip or (3) FLOQSwab, SensiGrip. Returned kits were analyzed using the validated BD Onclarity HPV assay on the COR instrument (BD). A total of 1677 women participated. Sample quality was similar across devices, also when stratifying into age groups. Two hundred thirty-two women (13.9%) tested positive for one or more oncogenic HPV types. Pairwise concordance analysis for each group showed an overall agreement between 93.5% and 95%. Analytical and diagnostic performance of samples collected by the three self-sampling devices resulted in similar quality and HPV detection. Hence the sample quality is not a determinant in the choice of sampling device and focus on other factors such as cost, women's preference or size and weight can take precedence.
{"title":"Large-Scale Study Comparing Analytical and Diagnostic Quality of Three HPV Self-Sampling Devices for At-Home Cervical Cancer Screening","authors":"Alexander Arum, Emilie Korsgaard Andreasen, Helle Pedersen, Trine Dahl Nielsen, Peter Frandsen, Birgitte Tønnes Pedersen, Estrid Hogdall, Jesper Bonde","doi":"10.1111/apm.70109","DOIUrl":"10.1111/apm.70109","url":null,"abstract":"<p>Elimination of cervical cancer requires broad access to and participation in cervical screening. Self-sampling has emerged as a robust technology that simplifies access; however, few self-sampling devices are independently validated regarding sample quality. This study compares the quality of three self-sampling devices: Evalyn (Rovers), currently used in Denmark, the FLOQSwab (Copan) and the modified FLOQSwab: SensiGrip. Women residing in the Capital Region of Denmark, accepting screening by self-sampling, were offered a kit containing the following combinations of devices: (1) Evalyn, FLOQSwab, (2) Evalyn, SensiGrip or (3) FLOQSwab, SensiGrip. Returned kits were analyzed using the validated BD Onclarity HPV assay on the COR instrument (BD). A total of 1677 women participated. Sample quality was similar across devices, also when stratifying into age groups. Two hundred thirty-two women (13.9%) tested positive for one or more oncogenic HPV types. Pairwise concordance analysis for each group showed an overall agreement between 93.5% and 95%. Analytical and diagnostic performance of samples collected by the three self-sampling devices resulted in similar quality and HPV detection. Hence the sample quality is not a determinant in the choice of sampling device and focus on other factors such as cost, women's preference or size and weight can take precedence.</p>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12673633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666810","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}
Fly ash concrete (FAC) biodeterioration caused by fungal biofilm is a major problem for the building sector. Both biodeterioration of FACs and the effectiveness of nanosilica coating for its prevention were assessed in laboratory conditions. According to preliminary tests, Aspergillus tamarii caused higher biodeterioration on FAC than Aspergillus niger. In subsequent tests, FAC cubes (10 cm × 10 cm × 10 cm) were utilised to create three setups: control (Set-C), biodeterioration infected with A. tamarii (Set-B), and preventive set (Set-P), which contained the growth of both A. tamarii on nanocoated cubes. After 6 months, the Set-B cubes had obvious fungal colonisation and surface damage, while the Set-P cubes exhibited less degradation. The Set-P cubes showed less calcium ion leaching and improved compressive strength than the Set-B. The concrete in Set-B lost 17.42% of its compressive strength, compared to 7.34% in Set-P. The biodeterioration caused by A. tamarii is successfully prevented by the silicon oxide nanocoating. The calcium leaching from the FAC as a result of carboxylic acids generated by the studied fungus was confirmed by the FTIR and EDXRF observation. This work reveals the mechanisms and potentiality of nano-silica coatings on concrete to control fungal biofilm growth.
由真菌生物膜引起的粉煤灰混凝土（FAC）生物劣化是困扰建筑行业的一个主要问题。在实验室条件下评估了活性炭的生物劣化和纳米二氧化硅涂层对其预防的有效性。初步试验表明，柽鹿曲霉比黑曲霉对FAC的生物降解作用更大。在随后的试验中，使用FAC立方体（10 cm × 10 cm × 10 cm）创建了三种设置：对照组（set - c）、感染了柽柽鱼的生物变质组（set - b）和预防组（set - p），其中两种柽柽鱼都在纳米涂层立方体上生长。6个月后，Set-B立方体有明显的真菌定植和表面损伤，而Set-P立方体降解较少。与Set-B相比，Set-P的钙离子浸出较少，抗压强度提高。b组混凝土抗压强度损失17.42%，p组混凝土抗压强度损失7.34%。氧化硅纳米涂层成功地防止了柽柽鱼的生物变质。通过FTIR和EDXRF观察，证实了真菌产生的羧酸对FAC中钙的浸出作用。这项工作揭示了纳米二氧化硅涂层在混凝土上控制真菌生物膜生长的机制和潜力。
{"title":"Application of a Nano-Silica Coating on Fly Ash Concrete Controlling Fungal Biofilm Based Biodeterioration","authors":"Jyoti Saha, Anirban Chaudhuri, Sangsaptak Dutta, Subarna Bhattacharyya, Punarbasu Chaudhuri","doi":"10.1111/apm.70101","DOIUrl":"10.1111/apm.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>Fly ash concrete (FAC) biodeterioration caused by fungal biofilm is a major problem for the building sector. Both biodeterioration of FACs and the effectiveness of nanosilica coating for its prevention were assessed in laboratory conditions. According to preliminary tests, <i>Aspergillus tamarii</i> caused higher biodeterioration on FAC than <i>Aspergillus niger</i>. In subsequent tests, FAC cubes (10 cm × 10 cm × 10 cm) were utilised to create three setups: control (Set-C), biodeterioration infected with <i>A. tamarii</i> (Set-B), and preventive set (Set-P), which contained the growth of both <i>A. tamarii</i> on nanocoated cubes. After 6 months, the Set-B cubes had obvious fungal colonisation and surface damage, while the Set-P cubes exhibited less degradation. The Set-P cubes showed less calcium ion leaching and improved compressive strength than the Set-B. The concrete in Set-B lost 17.42% of its compressive strength, compared to 7.34% in Set-P. The biodeterioration caused by <i>A. tamarii</i> is successfully prevented by the silicon oxide nanocoating. The calcium leaching from the FAC as a result of carboxylic acids generated by the studied fungus was confirmed by the FTIR and EDXRF observation. This work reveals the mechanisms and potentiality of nano-silica coatings on concrete to control fungal biofilm growth.</p>\u0000 </div>","PeriodicalId":8167,"journal":{"name":"Apmis","volume":"133 12","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145659938","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}
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