Uterine Scarring Leads to Adverse Pregnant Consequences by Impairing the Endometrium Response to Steroids

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Zhilang Li ◽  
Xiaotao Bian ◽  
Yeling Ma ◽  
Qian Yang ◽  
Wentong Jia ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Cell Hyperplasia ◽  
Uterine Incision ◽  
Molecular Features ◽  
Pathologic Features ◽  
Myometrial Smooth Muscle Cell ◽  
Increasing Risk ◽  
Fiber Deposition ◽  
Adverse Pregnancy ◽  
Uterine Scar

Abstract Uterine surgical scarring is an increasing risk factor for adverse pregnant consequences that threaten fetal-maternal health. The detailed molecular features of scar implantation remain largely unknown. We aim to study the pathologic features of uterine surgical scarring and the mechanisms of compromised pregnancy outcomes of scar implantation. We generated a mouse model of uterine surgical scarring with a uterine incision penetrating the myometrium to endometrium to examine the pathologic changes and transcriptome profiles of uterine scarring at various postsurgery (PS) time points, as well as features of the feto-maternal interface during scar implantation. We found that uterine surgical scar recovery was consistently poor at PS3 until PS90, as shown by a reduced number of endometrial glands, inhibition of myometrial smooth muscle cell growth but excessive collagen fiber deposition, and massive leukocyte infiltration. Transcriptome annotation indicated significant chronic inflammation at the scarring site. At the peri-implantation and postimplantation stages, abnormal expression of various steroid-responsive genes at the scarring site was in parallel with lumen epithelial cell hyperplasia, inappropriate luminal closure, and disorientation of the implanted embryo, restricted stromal cell proliferation, and defective decidualization. High embryonic lethality (around 70%) before E10.5 was observed, and the small amount of survival embryos at E10.5 exhibited restricted growth and aberrant placenta defects including overinvasion of trophoblast cells into the decidua and insufficient fetal blood vessel branching in the labyrinth. The findings indicate that chronic inflammation and compromised responses to steroids in uterine scar tissues are the pivotal molecular basis for adverse pregnancy consequences of scar implantation.

scholarly journals Regulatory Effects of Nur77 on Airway Remodeling and ASMC Proliferation in House Dust Mite-Induced Asthma

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Kun Wang ◽  
Muyun Wang ◽  
Yan Shang ◽  
Yanan He ◽  
Qiang Li ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Lung Diseases ◽  
Airway Remodeling ◽  
Vital Role ◽  
Cell Hyperplasia ◽  
Asthma Model ◽  
Dust Mite ◽  
Asthma Patients ◽  
Antioxidant Gene Expression ◽  
Regulatory Effects

Airway remodeling played a vital role in the development of asthma, and airway smooth muscle (ASM) mass was its hallmark. However, few strategies targeting ASM remodeling were developed in treating asthma. Nur77 was the transcription factor nuclear receptor involved in the pathogenesis of several lung diseases. Nur77 distribution and expression were determined in an HDM-mediated allergic asthma model. Its effect on airway hyperresponsiveness (AHR), chronic inflammation, and ASM remodeling in asthmatic mice was evaluated using a lentivirus-mediated shRNA. Possible mechanisms were explored by examining Nur77 actions and its underlying pathways in primary human AMC cells (ASMCs). In this study, we reported that Nur77 expression was mainly distributed along ASM and increased in lungs of HDM-challenged mice. Nur77 depletion by lentivirus-mediated shRNA ameliorated AHR, chronic inflammation, goblet cell hyperplasia, and airway remodeling in the asthmatic mouse model. By means of primary human ASMC, we discovered that Nur77 upregulation by HDM stimulation promoted cell proliferation and ROS production, as well as reduced antioxidant gene expression. These alterations might associate with MFN2/MAPK/AKT pathways. These findings broadened our understanding of airway remodeling and ASMC proliferation, which might provide a novel therapeutic target for asthma patients.

Lung Tumors With Neuroendocrine Morphology: Essential Radiologic and Pathologic Features

2008 ◽  
Vol 132 (7) ◽  
pp. 1055-1061 ◽  
Author(s):  
Teri J. Franks ◽  
Jeffrey R. Galvin
Keyword(s):  
Neuroendocrine Tumors ◽  
Classification Systems ◽  
World Health ◽  
National Library ◽  
Molecular Features ◽  
Distinct Subset ◽  
Pathologic Features ◽  
The World ◽  
Health Organization

Abstract Context.—Tumors with neuroendocrine morphology are a distinct subset of lung neoplasms sharing characteristic histologic, immunohistochemical, ultrastructural, and molecular features. Objective.—To review the current histologic classification and the diagnostic criteria for the major categories of neuroendocrine tumors of the lung. Data Sources.—Published classification systems from the World Health Organization and pertinent peer-reviewed articles indexed in PubMed (National Library of Medicine) form the basis of this review. Conclusions.—Accurate classification of the neuroendocrine tumors of the lung requires knowledge of specific criteria separating the major categories, which is essential for determining prognosis and treatment.

scholarly journals Morphological and Genetic Heterogeneity of Synchronous Multifocal Lung Adenocarcinoma in a Chinese Cohort

2020 ◽  
Author(s):  
Donglin Zhu ◽  
Dan Cao ◽  
Minghong Shen ◽  
Jinghuan Lv
Keyword(s):  
Lung Cancer ◽  
Primary Lung Cancer ◽  
Gene Mutations ◽  
Tumor Location ◽  
Chinese Patients ◽  
Molecular Testing ◽  
Additional Tool ◽  
Molecular Features ◽  
Pathologic Features ◽  
Genotypic Analysis

Abstract Background: Synchronous multifocal lung cancer (SMLC) is seen with increasing frequency in clinical practice globally. Because of innate variation in clinical management and outcome, it is vital to distinguish properly between synchronous multifocal primary lung cancer (SMPLC) and intrapulmonary metastasis (IM). The pathologic features and principal classification criteria of multifocal lung cancer remain unclear. Methods: We have collected a unique cohort of Chinese patients with SMLC, and fully explored the morphologic, immunohistochemical, and molecular features of the disease. Twenty-one SMLC patients with a total of 50 tumors were included in our study. The pathological features presented by these cases were analyzed, including tumor location, tumor size, pathological types, predominant pattern of adenocarcinoma, and immunohistochemical staining. We undertook molecular testing of nine driver oncogenes associated with lung cancer, including EGER, KRAS, BRAF, NRAS, ALK, ROS1, RET, HER2, and PIK3CA. Results: According to Martini-Melamed classification and refined standard, 8 and 17 cases were considered as SMPLC respectively. Gene mutations were identified in 18 tumors (36%). There were 12 patients had different gene mutations. Conclusions: We demonstrate that conventional morphological assessment is not sufficient to establish clearly the clonal relationship of SMPLC. Instead the evaluation of histological subtypes, including non-mucinous adherent components, is required. Multiplex genotypic analysis may also prove a useful additional tool.

scholarly journals Single-cell transcriptional analyses of spasmolytic polypeptide-expressing metaplasia arising from acute drug injury and chronic inflammation in the stomach

Gut ◽  
2019 ◽  
Vol 69 (6) ◽  
pp. 1027-1038 ◽  
Author(s):  
Kevin A Bockerstett ◽  
Scott A Lewis ◽  
Kyle J Wolf ◽  
Christine N Noto ◽  
Nicholas M Jackson ◽  
...  
Keyword(s):  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Single Cell ◽  
Chronic Inflammation ◽  
Intrinsic Factor ◽  
Drug Induced ◽  
Cell Hyperplasia ◽  
Tissue Samples ◽  
Spasmolytic Polypeptide ◽  
The Individual

ObjectiveSpasmolytic polypeptide-expressing metaplasia (SPEM) is a regenerative lesion in the gastric mucosa and is a potential precursor to intestinal metaplasia/gastric adenocarcinoma in a chronic inflammatory setting. The goal of these studies was to define the transcriptional changes associated with SPEM at the individual cell level in response to acute drug injury and chronic inflammatory damage in the gastric mucosa.DesignEpithelial cells were isolated from the gastric corpus of healthy stomachs and stomachs with drug-induced and inflammation-induced SPEM lesions. Single cell RNA sequencing (scRNA-seq) was performed on tissue samples from each of these settings. The transcriptomes of individual epithelial cells from healthy, acutely damaged and chronically inflamed stomachs were analysed and compared.ResultsscRNA-seq revealed a population Mucin 6 (Muc6)+gastric intrinsic factor (Gif)+ cells in healthy tissue, but these cells did not express transcripts associated with SPEM. Furthermore, analyses of SPEM cells from drug injured and chronically inflamed corpus yielded two major findings: (1) SPEM and neck cell hyperplasia/hypertrophy are nearly identical in the expression of SPEM-associated transcripts and (2) SPEM programmes induced by drug-mediated parietal cell ablation and chronic inflammation are nearly identical, although the induction of transcripts involved in immunomodulation was unique to SPEM cells in the chronic inflammatory setting.ConclusionsThese data necessitate an expansion of the definition of SPEM to include Tff2+Muc6+ cells that do not express mature chief cell transcripts such as Gif. Our data demonstrate that SPEM arises by a highly conserved cellular programme independent of aetiology and develops immunoregulatory capabilities in a setting of chronic inflammation.

scholarly journals Renal Cell Carcinoma in the Era of Precision Medicine: From Molecular Pathology to Tissue-Based Biomarkers

2018 ◽  
Vol 36 (36) ◽  
pp. 3553-3559 ◽  
Author(s):  
Sabina Signoretti ◽  
Abdallah Flaifel ◽  
Ying-Bei Chen ◽  
Victor E. Reuter
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Checkpoint Inhibitors ◽  
Predictive Biomarkers ◽  
Molecular Features ◽  
Pathologic Features ◽  
Clear Cell Rcc ◽  
Metastatic Rcc

Renal cell carcinoma (RCC) is not a single entity but includes various tumor subtypes that have been identified on the basis of either characteristic pathologic features or distinctive molecular changes. Clear cell RCC is the most common type of RCC and is characterized by dysregulation of the von Hippel Lindau/hypoxia-inducible factor pathway. Non–clear cell RCC represents a more heterogeneous group of tumors with diverse histopathologic and molecular features. In the past two decades, the improved understanding of the molecular landscape of RCC has led to the development of more effective therapies for metastatic RCC, which include both targeted agents and immune checkpoint inhibitors. Because only subsets of patients with metastatic RCC respond to a given treatment, predictive biomarkers are needed to guide treatment selection and sequence. In this review, we describe the key histologic features and molecular alterations of RCC subtypes and discuss emerging tissue-based biomarkers of response to currently available therapies for metastatic disease.

Inequity Embodied

2019 ◽  
pp. 24-41
Author(s):  
Tyan Parker Dominguez
Keyword(s):  
African American ◽  
Allostatic Load ◽  
The Body ◽  
Medical Risk ◽  
Lower Socioeconomic ◽  
Wear And Tear ◽  
Increasing Risk ◽  
Adverse Pregnancy ◽  
Traditional Risk Factors ◽  
Stress Burden

This chapter examines African American women’s disproportionate risk of low birth weight, preterm delivery, and infant and maternal mortality, and the ways in which race, gender, and class oppression create a unique matrix of stress burden that increases allostatic load (i.e., weathering or wear and tear on the body), thereby increasing risk for these adverse pregnancy-related outcomes. The chapter describes how traditional risk factors, such as health behavior, medical risk, and lower socioeconomic status, do not account for racial disparities in childbearing health, and it utilizes a stress paradigm for explaining how the intersectional burden of race, gender, and class inequity can affect African American pregnancy women. The chapter concludes by noting several mobilization efforts that are underway to eliminate health disparities in adverse birth outcomes by promoting health equity that is fair and just opportunities to be healthy.

Prevention and Management of Respiratory Diseases Including Lung Cancer Through Exercise Interventions

2018 ◽  
Vol 3 (6) ◽  
Keyword(s):  
Chronic Inflammation ◽  
Respiratory Diseases ◽  
Disease Process ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Pathological Feature ◽  
Cell Hyperplasia ◽  
Exercise Interventions ◽  
Asthma Patients ◽  
Potential Risk Factors

The objective of the paper is to create awareness among people about alternative and complimentary methods to protect themselves from respiratory diseases like asthma, bronchitis, chronic obstructive lung disease, cancer etc. The following changes take place in airways as a result of Lung diseases 1) Inflammation: Is a physiological process and plays the role of immunological defense against infection, injury or allergy 2) Hyper secretion of mucus: is a major pathological feature of Airway diseases. It is the result of goblet cell hyperplasia in respiratory mucosa and is a prominent feature of inflammation. Acute inflammation is a defense process and where as Chronic inflammation is a disease process. Chronic Inflammation and mucus hyper secretion are a potential risk factors for an accelerated loss of lung function. It is a common feature in elderly.. The thick viscous mucus in the Lungs will be conducive to pathogens. Continued inflammation and mucus hyper Secretion may significantly contribute to transformation of normal cells into cancer cells ( often as a result of chemical , viral or radioactive damage to genes) 3) Broncospasm: is an additional factor in asthma patients. The three factors together cause breathlessness.

Ependymoma and Chordoma

Neurosurgery ◽  
2020 ◽  
Vol 87 (5) ◽  
pp. 860-870
Author(s):  
Adrian B Levine ◽  
Derek Wong ◽  
Mostafa Fatehi ◽  
Stephen Yip
Keyword(s):  
Clinical Implications ◽  
Prognostic Role ◽  
The Past ◽  
Molecular Tests ◽  
Molecular Features ◽  
Pathologic Features ◽  
Active Research ◽  
Craniospinal Axis ◽  
Comprehensive Study

Abstract Ependymoma and chordoma are 2 tumors that occur throughout the craniospinal axis, and for which the extent of neurosurgical resection has a key prognostic role. Both tumors have distinctive pathologic features, yet can present significant diagnostic challenges to pathologists in cases without classical histology. The molecular understanding of ependymoma has had significant advances in the past decade, with the identification of 9 molecular groups with significant prognostic and clinical implications, while a comprehensive study of chordoma further emphasized the key role of brachyury overexpression in its pathogenesis. In this review, we discuss the pathogenesis, radiology and gross pathology, histology, and molecular features of these 2 tumors, as well as active research into targeted therapies, with an emphasis on practical diagnostic challenges, and the use of immunohistochemical and molecular tests in routine diagnostic practice.

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