American Journal of Pathology最新文献_第10页

Chronic Coinfection with Pseudomonas aeruginosa and Normal Colony Staphylococcus aureus Causes Lung Structural Damage in the Cystic Fibrosis Rat 铜绿假单胞菌和正常菌落金黄色葡萄球菌的慢性联合感染会导致囊性纤维化大鼠肺部结构损伤。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-02-01 DOI: 10.1016/j.ajpath.2024.09.008

Gretchen E. Bollar , Johnathan D. Keith , Denise D. Stanford , Ashley M. Oden , S. Vamsee Raju , T. Spencer Poore , Susan E. Birket

{"title":"Chronic Coinfection with Pseudomonas aeruginosa and Normal Colony Staphylococcus aureus Causes Lung Structural Damage in the Cystic Fibrosis Rat","authors":"Gretchen E. Bollar , Johnathan D. Keith , Denise D. Stanford , Ashley M. Oden , S. Vamsee Raju , T. Spencer Poore , Susan E. Birket","doi":"10.1016/j.ajpath.2024.09.008","DOIUrl":"10.1016/j.ajpath.2024.09.008","url":null,"abstract":"<div><div>Cystic fibrosis (CF) respiratory outcomes are heavily influenced by complications of infection. <em>Pseudomonas aeruginosa</em> and <em>Staphylococcus aureus</em> are the most common colonizers of the cystic fibrosis lung, and frequently overlap to cause chronic and persistent coinfections associated with severe disease. However, the dynamics of <em>P. aeruginosa</em> and <em>S. aureus</em> coinfection and its impacts on the development of CF lung structural damage are poorly understood. Additionally, small colony variants (SCVs) of <em>S. aureus</em> have been associated with <em>P. aeruginosa</em> infections in people with CF, but their role in disease progression is largely unknown. In this work, the CF rat was used to model chronic lung coinfection with <em>P. aeruginosa</em> and <em>S. aureus</em>, using clinically and laboratory-derived normal colony and SCV strains of <em>S. aureus</em> to evaluate the impact of phenotype on clinical outcomes. Rats coinfected with clinically derived <em>S. aureus</em> of both phenotypes experienced increased inflammation in the lung. However, only the combination of <em>P. aeruginosa</em> and clinically normal colony <em>S. aureus</em> led to lung structural decline, including mucus obstruction and bronchiectasis. Regression analyses showed that the damage was associated with a higher burden of <em>P. aeruginosa</em>. These data indicate that chronic coinfection with normal colony <em>S. aureus</em> and <em>P. aeruginosa</em> may support the progression CF lung decline driven by <em>P. aeruginosa</em>, which might be avoided when coinfecting <em>S. aureus</em> exhibits the SCV phenotype.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 2","pages":"Pages 174-187"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CDR1as Deficiency Prevents Photoreceptor Degeneration by Regulating miR-7a-5p/α-syn/Parthanatos Pathway in Retinal Detachment CDR1as 缺陷通过调节视网膜脱离中的 miR-7a-5p/α-syn/Parthanatos 通路防止感光细胞退化

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-02-01 DOI: 10.1016/j.ajpath.2024.10.015

Feiyu Jin, Yuanye Yan, Ziyang Ye, Lisong Wang, Can Deng, Jiazhen Jiang, Kai Dong

{"title":"CDR1as Deficiency Prevents Photoreceptor Degeneration by Regulating miR-7a-5p/α-syn/Parthanatos Pathway in Retinal Detachment","authors":"Feiyu Jin, Yuanye Yan, Ziyang Ye, Lisong Wang, Can Deng, Jiazhen Jiang, Kai Dong","doi":"10.1016/j.ajpath.2024.10.015","DOIUrl":"10.1016/j.ajpath.2024.10.015","url":null,"abstract":"<div><div>Retinal detachment (RD) is the separation of the neural retina from the retinal pigment epithelium, with photoreceptor degeneration being a major cause of irreversible vision loss. Herein, ischemia and hypoxia after RD decreased the level of miR-7a-5p (miR-7) and promoted the expression of its main target, α-synuclein (α-syn), which activated the parthanatos pathway and led to photoreceptor damage. Circular RNA CDR1as is an antisense transcript of cerebellar degeneration–associated protein 1, which functions as a “sponge” for miR-7, thereby regulating the abundance and activity of miR-7. In this study, CDR1as expression was elevated after RD. Adeno-associated virus serotype 9 vector containing the shRNA-CDR1as sequence was used to inhibit CDR1as expression via subretinal injection. Hematoxylin and eosin staining and transmission electron microscopy revealed that the morphology and outer nuclear layer thickness of the retina were preserved and photoreceptor cell death was decreased after experimental RD in mice. Mechanistically, CDR1as deficiency significantly increased the expression of miR-7, then decreased the expression of α-syn, poly (ADP-ribose) polymerase 1, apoptosis-inducing factor, and migration inhibitory factor. Furthermore, visual function was improved as shown by Morris water maze experiments in the mouse model of RD. These findings suggest a surprisingly neuroprotective role for CDR1as deficiency, which is probably mediated by enhancing miR-7 activity and inhibiting α-syn/poly (ADP-ribose) polymerase 1/apoptosis-inducing factor pathway, thereby preventing photoreceptor degeneration.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 2","pages":"Pages 293-305"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The mRNA Stability of PIEZO1, Regulated by Methyltransferase-Like 3 via N6-Methylation of Adenosine Modification in a YT521-B Homology Domain Family 2–Dependent Manner, Facilitates the Progression of Diabetic Retinopathy PIEZO1 的 mRNA 稳定性由 METTL3 通过 m6A 修饰以 YTHDF2 依赖性方式调控，促进了糖尿病视网膜病变的进展。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-02-01 DOI: 10.1016/j.ajpath.2024.10.007

Ning Han , Na Yu , Li Yu

{"title":"The mRNA Stability of PIEZO1, Regulated by Methyltransferase-Like 3 via N6-Methylation of Adenosine Modification in a YT521-B Homology Domain Family 2–Dependent Manner, Facilitates the Progression of Diabetic Retinopathy","authors":"Ning Han , Na Yu , Li Yu","doi":"10.1016/j.ajpath.2024.10.007","DOIUrl":"10.1016/j.ajpath.2024.10.007","url":null,"abstract":"<div><div>Diabetic retinopathy (DR) is the major ocular complication of diabetes caused by chronic hyperglycemia, which leads to incurable blindness. Currently, the effectiveness of therapeutic interventions is limited. This study aimed to investigate the function of piezo-type mechanosensitive ion channel component 1 (PIEZO1) and its potential regulatory mechanism in DR progression. PIEZO1 expression was up-regulated in the retinal tissues of streptozotocin-induced diabetic mice and high-glucose (HG)–triggered Müller cells. Functionally, the knockdown of <em>PIEZO1</em> improved the abnormal retinal function of diabetic mice and impeded inflammatory cytokine secretion and gliosis of Müller cells under HG conditions. Mechanistic investigations using RNA immunoprecipitation—real-time quantitative PCR, methylation RNA immunoprecipitation–real-time quantitative PCR, and luciferase reporter assays demonstrated that PIEZO1 was a downstream target of methyltransferase-like 3 (METTL3). METTL3-mediated N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) modification within the coding sequence of <em>PIEZO1</em> mRNA significantly shortened its half-life. In HG-stimulated cells, there was a negative regulatory relationship between PIEZO1 and YTH (YT521-B homology) domain family 2 (YTHDF2), a recognized m<sup>6</sup>A reader. The loss of YTHDF2 resulted in an extended half-life of PIEZO1 in cells with overexpression of METTL3, indicating that the effect of METTL3 on the mRNA stability of <em>PIEZO1</em> was dependent on YTHDF2. Taken together, this study demonstrated the protective role of the <em>PIEZO1</em> silencing in DR development, and that the degradation of <em>PIEZO1</em> mRNA is accelerated by METTL3/YTHDF2-mediated m<sup>6</sup>A modification.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 2","pages":"Pages 265-280"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peroxisome Proliferator-Activated Receptor α/γ and Cannabinoid Receptor 2 Agonist Attenuated Nonalcoholic Steatohepatitis Exosome-Related Abnormalities in Mice 慢性 PPARα/γ 和 CB2R 激动剂治疗可减轻 NASH 小鼠内脏脂肪组织（VAT）衍生的细胞外囊泡相关的 VAT 和肠道异常。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-02-01 DOI: 10.1016/j.ajpath.2024.10.006

Chia-Chang Huang , Ching-Hsiang Wang , Hsiao-Yun Yeh , Hung-Cheng Tsai , Ching-Wen Yang , Tzu-Hao Li , Chien-Wei Su , Ying-Ying Yang , Han-Chieh Lin , Ming-Chih Hou

{"title":"Peroxisome Proliferator-Activated Receptor α/γ and Cannabinoid Receptor 2 Agonist Attenuated Nonalcoholic Steatohepatitis Exosome-Related Abnormalities in Mice","authors":"Chia-Chang Huang , Ching-Hsiang Wang , Hsiao-Yun Yeh , Hung-Cheng Tsai , Ching-Wen Yang , Tzu-Hao Li , Chien-Wei Su , Ying-Ying Yang , Han-Chieh Lin , Ming-Chih Hou","doi":"10.1016/j.ajpath.2024.10.006","DOIUrl":"10.1016/j.ajpath.2024.10.006","url":null,"abstract":"<div><div>This study explored the mechanisms and effects of 1 month of peroxisome proliferator-activated receptor (PPAR)α/γ agonist aleglitazar (10 mg/kg per day) or cannabinoid receptor 2 (CB<sub>2</sub>R) agonist JWH015 (3 mg/kg per day), alone or combined, on visceral adipose tissue (VAT)–derived extracellular vesicle (EV) release and associated systemic/VAT inflammation, decreased VAT capillary density/fibrosis, and intestinal inflammation/hyperpermeability in nonalcoholic steatohepatitis (NASH) mice. High EV release from VAT of NASH mice was associated with severe systemic/VAT/intestinal inflammation, reduced capillary network of VAT, and intestinal hyperpermeability. Combined JWH015 with aleglitazar treatment suppressed high-fat diet–induced obesity/adiposity, inhibited VAT expansion, reduced VAT inflammation/fibrosis, normalized VAT capillary network, and attenuated intestinal mucosal injury, inflammation, and hyperpermeability in NASH + aleglitazar + JWH015 mice. The inhibition of adipose tissue (AT)–derived EV release and hypoxia-inducible factor (HIF)1α levels in AT-derived EV, normalization of CB<sub>2</sub>R, PPARα, PPARγ, PPARγ1, PPARγ2, tight junction proteins, vascular endothelial growth factor/CD31 expression, and down-regulation of HIF1α, monocyte chemoattractant protein-1, and transforming growth factor-β1 were observed in the VAT and intestine of the NASH + aleglitazar + jwh015 group. <em>In vitro</em> experiments revealed that PPARα/γ and CB<sub>2</sub>R activation attenuated NASH AT-derived EV–induced pathogenic changes in the J774/SVEC4-10/Caco2/3T3-L1 cell system. This study suggested that VAT-derived EVs contribute to the pathogenesis of NASH and that combined PPARα/γ and CB<sub>2</sub>R agonist treatment ameliorated the abovementioned abnormalities of NASH mice.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 2","pages":"Pages 188-203"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Core of Keratocan-Negative Cells Survives in Old Corneal Scars 陈旧角膜疤痕中存活着角膜阴性细胞的核心。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-02-01 DOI: 10.1016/j.ajpath.2024.10.017

Hadi Joud , Meisam Asgari , Victoria Emerick , Mei Sun , Marcel Y. Avila , Curtis E. Margo , Edgar M. Espana

{"title":"A Core of Keratocan-Negative Cells Survives in Old Corneal Scars","authors":"Hadi Joud , Meisam Asgari , Victoria Emerick , Mei Sun , Marcel Y. Avila , Curtis E. Margo , Edgar M. Espana","doi":"10.1016/j.ajpath.2024.10.017","DOIUrl":"10.1016/j.ajpath.2024.10.017","url":null,"abstract":"<div><div>Corneal scars originate from keratocyte-derived fibroblasts and myofibroblasts that are ultimately cleared through apoptosis or revert to keratocytes. A mouse model expressing the keratocyte lineage–specific reporter <em>KeraRT/tetO-Cre/mTmG</em> (I-<em>KeramTmG</em>) was used to elucidate cell phenotype dynamics during scar maturation. In this model, tdTomato (red) is expressed in all keratocan-negative cells, while enhanced green fluorescent protein (green) is expressed only by keratocytes. A 1-mm full-thickness keratotomy was generated in adult I-<em>KeramTmG</em> mice. The presence of keratocytes was determined at 3, 6, and 10 months after injury. At 3 and 6 months, few green cells were visualized at the scar borders, while few or no green cells were seen in the central (core) scar. At 10 months, a few green cells and a majority of red cells were observed throughout the scar. Proliferation of stromal cells after injury was studied by 5-ethynyl-2′-deoxyuridine labeling and Ki-67 staining. Both assays showed proliferation only during the first 2 weeks after injury. Second harmonic generation microscopy showed thickened and irregularly arranged collagen fibers in scars, suggesting that neither extracellular matrix organization nor cell phenotype had changed significantly at 10 months after injury. Findings from <em>in vivo</em> experiments suggest that in old corneal scars, a nonkeratocyte phenotype persists in an abnormal matrix with unique characteristics that probably prevent the regression of fibroblasts and myofibroblasts to keratocytes or invasion of surrounding keratocytes.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 2","pages":"Pages 281-292"},"PeriodicalIF":4.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

This Month in AJP 本月在AJP

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-02-01 DOI: 10.1016/j.ajpath.2024.12.001

引用次数: 0

EMILIN-1 Suppresses Cell Proliferation through Altered Cell Cycle Regulation in Head and Neck Squamous Cell Carcinoma EMILIN-1通过改变头颈部鳞状细胞癌的细胞周期调节来抑制细胞增殖。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-01-30 DOI: 10.1016/j.ajpath.2025.01.010

Pichaya Chanpanitkitchote , Jiratchaya Nuanpirom , Warut Pongsapich , Nithi Asavapanumas , Simone Mendler , Nadine Wiesmann , Juergen Brieger , Natini Jinawath

{"title":"EMILIN-1 Suppresses Cell Proliferation through Altered Cell Cycle Regulation in Head and Neck Squamous Cell Carcinoma","authors":"Pichaya Chanpanitkitchote , Jiratchaya Nuanpirom , Warut Pongsapich , Nithi Asavapanumas , Simone Mendler , Nadine Wiesmann , Juergen Brieger , Natini Jinawath","doi":"10.1016/j.ajpath.2025.01.010","DOIUrl":"10.1016/j.ajpath.2025.01.010","url":null,"abstract":"<div><div>Extracellular matrix (ECM) proteins play an important role in the pathological processes of tumor development and progression. Elastic microfibril interface located protein-1 (EMILIN-1), an ECM glycoprotein, is linked to cell adhesion and migration. It was identified from head and neck squamous cell carcinoma (HNSCC) tissues that down-regulated EMILIN-1. It is associated with an increased risk of secondary primary malignancy development in HNSCC and hypothesized to function as a tumor suppressor in HNSCC. This study showed that EMILIN-1 expression in HNSCC tissues was specific to the stromal area, and secreted-EMILIN-1 level was higher in fibroblasts isolated from HNSCC tissues than in HNSCC cells. EMILIN-1 overexpression decreased cell proliferation, migration, and invasion in FaDu and CAL27 cells. Knockdown of EMILIN-1 in HNSCC cancer-associated fibroblasts induced cell proliferation and migration. The conditioned medium from EMILIN-1 knockdown cancer-associated fibroblasts increased HNSCC cell proliferation, and the co-culture system enhanced cancer cell migration and invasion. RNA-sequencing analysis revealed that the cell cycle and aurora kinase signaling were the most significant enrichment pathways, confirmed at the protein level. Furthermore, in an <em>in ovo</em> chick chorioallantoic membrane model, overexpression of EMILIN-1 in FaDu cells reduced tumor size and Ki-67–positivity and increased cleaved caspase-3–positive cells. These findings suggest that EMILIN-1 suppresses HNSCC growth partly through the down-regulation of cell cycle and aurora kinase signaling pathways.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 5","pages":"Pages 995-1012"},"PeriodicalIF":4.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Liver X Receptor–Growth Differentiation Factor 15 Activation Drives Profibrotic Changes in the Aqueous Outflow Tract of Uveitic Glaucoma LXR-GDF15激活驱动青光眼水流出道纤维化改变

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-01-30 DOI: 10.1016/j.ajpath.2025.01.007

Hyun Hee Ju , Jiyoung Lee , Seon-Kyu Kim , Seon-Young Kim , Jin-Hyun Ahn , Nikolai Skiba , Vasantha Rao , Jin A. Choi

{"title":"Liver X Receptor–Growth Differentiation Factor 15 Activation Drives Profibrotic Changes in the Aqueous Outflow Tract of Uveitic Glaucoma","authors":"Hyun Hee Ju , Jiyoung Lee , Seon-Kyu Kim , Seon-Young Kim , Jin-Hyun Ahn , Nikolai Skiba , Vasantha Rao , Jin A. Choi","doi":"10.1016/j.ajpath.2025.01.007","DOIUrl":"10.1016/j.ajpath.2025.01.007","url":null,"abstract":"<div><div>Cytomegalovirus (CMV)–induced anterior uveitis is linked to increased intraocular pressure, suggesting profibrotic changes in the eye's drainage system. Previous studies on the aqueous humor (AH) of patients with CMV uveitic glaucoma (UG) highlighted the activation of the liver X receptor (LXR) pathway, yet a potential that it has a role in increased intraocular pressure remained unelucidated. Herein, the LXR pathway's role in AH outflow in UG was explored. Global transcriptional analysis revealed that LXR activation primarily induces transforming growth factor-β signaling, with growth differentiation factor 15 (GDF-15), a growth factor in the transforming growth factor-β superfamily, being one of the most up-regulated genes in LXR-agonist–treated trabecular meshwork cells. GDF-15 levels showed a twofold expression in the AH of patients with UG (<em>n</em> = 44) compared with controls (<em>n</em> = 24; <em>P</em> = 0.024) and increased with more anti-glaucoma eyedrops and glaucoma surgeries (<em>P</em> < 0.05). LXRα/β and GDF-15 were found in human outflow tissue and were up-regulated by lipopolysaccharide and CMV infection. In an experimental endotoxin uveitis model, GDF-15 levels were up-regulated by the treatment with LXR agonists and lipopolysaccharide. In human trabecular meshwork cells, LXR agonists triggered actin stress fiber formation and α-smooth muscle actin expression, both reduced by GDF-15 neutralization. These results suggest that the LXR–GDF-15 pathway contributes to profibrotic changes in UG and plays a role in disease pathogenesis.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 5","pages":"Pages 941-959"},"PeriodicalIF":4.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ascending Vaginal Infection in Mice Induces Preterm Birth and Neonatal Morbidity 小鼠阴道上行感染可诱发早产和新生儿发病。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-01-30 DOI: 10.1016/j.ajpath.2025.01.008

Ashley K. Boyle , Konstantina Tetorou , Natalie Suff , Laura Beecroft , Margherita Mazzaschi , Rajvinder Karda , Mariya Hristova , Simon N. Waddington , Donald Peebles

{"title":"Ascending Vaginal Infection in Mice Induces Preterm Birth and Neonatal Morbidity","authors":"Ashley K. Boyle , Konstantina Tetorou , Natalie Suff , Laura Beecroft , Margherita Mazzaschi , Rajvinder Karda , Mariya Hristova , Simon N. Waddington , Donald Peebles","doi":"10.1016/j.ajpath.2025.01.008","DOIUrl":"10.1016/j.ajpath.2025.01.008","url":null,"abstract":"<div><div>Preterm birth (PTB; delivery before 37 weeks), the main cause of neonatal death worldwide, can lead to adverse neurodevelopmental outcomes, as well as lung and gut pathology. PTB can be associated with ascending vaginal infection. Ascending <em>Escherichia coli</em> infection in pregnant mice induces PTB and reduces pup survival. The current study demonstrated that this model recapitulates the pathology observed in human preterm neonates (namely, neuroinflammation, lung injury, and gut inflammation). In neonatal brains, there is widespread cell death, microglial activation, astrogliosis, and reduced neuronal density. The utility of this model was validated by assessing the efficacy of maternal cervical gene therapy with an adeno-associated viral vector containing human β defensin 3. This improved pup survival and reduced tumor necrosis factor alpha mRNA expression in perinatal pup brains exposed to <em>E. coli</em>. This model provides a unique opportunity to evaluate the therapeutic benefit of preterm labor interventions on perinatal pathology.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 5","pages":"Pages 891-906"},"PeriodicalIF":4.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tumor Cellularity Assessment Using Artificial Intelligence Trained on Immunohistochemistry-Restained Slides Improves Selection of Lung Adenocarcinoma Samples for Molecular Testing 利用人工智能对ihc抑制的载玻片进行肿瘤细胞性评估，提高了肺腺癌分子检测样本的选择。

IF 4.7 2区医学

American Journal of Pathology Pub Date : 2025-01-30 DOI: 10.1016/j.ajpath.2025.01.009

Arkadiusz Gertych , Natalia Zurek , Natalia Piaseczna , Kamil Szkaradnik , Yujie Cui , Yi Zhang , Karolina Nurzynska , Bartłomiej Pyciński , Piotr Paul , Artur Bartczak , Ewa Chmielik , Ann E. Walts

{"title":"Tumor Cellularity Assessment Using Artificial Intelligence Trained on Immunohistochemistry-Restained Slides Improves Selection of Lung Adenocarcinoma Samples for Molecular Testing","authors":"Arkadiusz Gertych , Natalia Zurek , Natalia Piaseczna , Kamil Szkaradnik , Yujie Cui , Yi Zhang , Karolina Nurzynska , Bartłomiej Pyciński , Piotr Paul , Artur Bartczak , Ewa Chmielik , Ann E. Walts","doi":"10.1016/j.ajpath.2025.01.009","DOIUrl":"10.1016/j.ajpath.2025.01.009","url":null,"abstract":"<div><div>Tumor cellularity (TC) in lung adenocarcinoma slides submitted for molecular testing is important in identifying actionable mutations, but lack of best practice guidelines results in high interobserver variability in TC assessments. An artificial intelligence (AI)–based pipeline developed to assess TC in hematoxylin and eosin (H&E) whole slide images (WSIs) and in tumor areas (TAs) within WSIs includes a new model (CaBeSt-Net) trained to mask cancer cells, benign epithelial cells, stroma in H&E WSIs using immunohistochemistry-restained slides, and a model to detect all cell nuclei. High masking accuracy (>91%) by CaBeSt-Net computed using 1024 H&E regions of interest and intraclass correlation coefficient >0.97 assessing TC assessments reliability by one pathologist and AI in 20 test regions of interest supported the pipeline's applicability to TC assessment in 50 study H&E WSIs. Using the pipeline, TCs assessed in TAs and WSIs were compared with those by three pathologists. Reliabilities of these ratings by the pathologists supported by the pipeline were good (intraclass correlation coefficient >0.82, <em>P</em> < 0.0001). The consistency of sample categorizations as inadequate or adequate (TC ≤ 20% cut point) for molecular testing among the pathologists assessing TCs without AI support was moderate in TAs (κ = 0.410, <em>P</em> < 0.0001) and slight in WSIs (κ = 0.132, nonsignificant). With AI support, the consistency was substantial in both WSIs (κ = 0.602, <em>P</em> < 0.0001) and TAs (κ = 0.704, <em>P</em> < 0.0001). By visualizing cancer and measuring TC in the sample, this novel AI-based pipeline assists pathologists in selecting samples for molecular testing.</div></div>","PeriodicalId":7623,"journal":{"name":"American Journal of Pathology","volume":"195 5","pages":"Pages 907-922"},"PeriodicalIF":4.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0