scholarly journals Intrauterine Hypoxia and Epigenetic Programming in Lung Development and Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 944
Author(s):  
Yajie Tong ◽  
Shuqing Zhang ◽  
Suzette Riddle ◽  
Lubo Zhang ◽  
Rui Song ◽  
...  
Keyword(s):  
Lung Development ◽  
Preterm Labor ◽  
Developmental Disorders ◽  
Developmental Plasticity ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Expression Control ◽  
Epigenetic Programming ◽  
Intrauterine Hypoxia ◽  
Oxygen Conditions

Clinically, intrauterine hypoxia is the foremost cause of perinatal morbidity and developmental plasticity in the fetus and newborn infant. Under hypoxia, deviations occur in the lung cell epigenome. Epigenetic mechanisms (e.g., DNA methylation, histone modification, and miRNA expression) control phenotypic programming and are associated with physiological responses and the risk of developmental disorders, such as bronchopulmonary dysplasia. This developmental disorder is the most frequent chronic pulmonary complication in preterm labor. The pathogenesis of this disease involves many factors, including aberrant oxygen conditions and mechanical ventilation-mediated lung injury, infection/inflammation, and epigenetic/genetic risk factors. This review is focused on various aspects related to intrauterine hypoxia and epigenetic programming in lung development and disease, summarizes our current knowledge of hypoxia-induced epigenetic programming and discusses potential therapeutic interventions for lung disease.

Effects of Maternal Obesity and Gestational Diabetes Mellitus on the Placenta: Current Knowledge and Targets for Therapeutic Interventions

2020 ◽  
Vol 19 (2) ◽  
pp. 176-192
Author(s):  
Samantha Bedell ◽  
Janine Hutson ◽  
Barbra de Vrijer ◽  
Genevieve Eastabrook
Keyword(s):  
Diabetes Mellitus ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Maternal Obesity ◽  
Environmental Changes ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Placental Development ◽  
Exchange Site ◽  
And Function

: Obesity and gestational diabetes mellitus (GDM) are becoming more common among pregnant women worldwide and are individually associated with a number of placenta-mediated obstetric complications, including preeclampsia, macrosomia, intrauterine growth restriction and stillbirth. The placenta serves several functions throughout pregnancy and is the main exchange site for the transfer of nutrients and gas from mother to fetus. In pregnancies complicated by maternal obesity or GDM, the placenta is exposed to environmental changes, such as increased inflammation and oxidative stress, dyslipidemia, and altered hormone levels. These changes can affect placental development and function and lead to abnormal fetal growth and development as well as metabolic and cardiovascular abnormalities in the offspring. This review aims to summarize current knowledge on the effects of obesity and GDM on placental development and function. Understanding these processes is key in developing therapeutic interventions with the goal of mitigating these effects and preventing future cardiovascular and metabolic pathology in subsequent generations.

scholarly journals Unique Aspects of the Developing Lung Circulation: Structural Development and Regulation of Vasomotor Tone

2016 ◽  
Vol 6 (4) ◽  
pp. 407-425 ◽  
Author(s):  
Yuangsheng Gao ◽  
David N. Cornfield ◽  
Kurt R. Stenmark ◽  
Bernard Thébaud ◽  
Steven H. Abman ◽  
...  
Keyword(s):  
Lung Development ◽  
Lung Diseases ◽  
Vascular Tone ◽  
Current Knowledge ◽  
Normal Lung ◽  
Pulmonary Vasculature ◽  
Structural Development ◽  
Vasomotor Tone ◽  
Disease States ◽  
Vasculogenesis And Angiogenesis

This review summarizes our current knowledge on lung vasculogenesis and angiogenesis during normal lung development and the regulation of fetal and postnatal pulmonary vascular tone. In comparison to that of the adult, the pulmonary circulation of the fetus and newborn displays many unique characteristics. Moreover, altered development of pulmonary vasculature plays a more prominent role in compromised pulmonary vasoreactivity than in the adult. Clinically, a better understanding of the developmental changes in pulmonary vasculature and vasomotor tone and the mechanisms that are disrupted in disease states can lead to the development of new therapies for lung diseases characterized by impaired alveolar structure and pulmonary hypertension.

scholarly journals Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1100
Author(s):  
Sofia Koustoulidou ◽  
Mark W. H. Hoorens ◽  
Simone U. Dalm ◽  
Shweta Mahajan ◽  
Reno Debets ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Tumour Microenvironment ◽  
Therapeutic Interventions ◽  
Great Promise ◽  
Cancer Associated Fibroblasts ◽  
Functional Heterogeneity ◽  
Radioligand Therapy ◽  
Targeted Interventions ◽  
Theranostic Applications ◽  
Complex Origin

Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand therapy and staging in cancers with a distinct CAF population.

scholarly journals Cellular and Molecular Players in the Interplay between Adipose Tissue and Breast Cancer

2021 ◽  
Vol 22 (3) ◽  
pp. 1359
Author(s):  
Francesca Reggiani ◽  
Paolo Falvo ◽  
Francesco Bertolini
Keyword(s):  
Breast Cancer ◽  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Preclinical Research ◽  
The World ◽  
Adipose Cells

The incidence and severity of obesity are rising in most of the world. In addition to metabolic disorders, obesity is associated with an increase in the incidence and severity of a variety of types of cancer, including breast cancer (BC). The bidirectional interaction between BC and adipose cells has been deeply investigated, although the molecular and cellular players involved in these mechanisms are far from being fully elucidated. Here, we review the current knowledge on these interactions and describe how preclinical research might be used to clarify the effects of obesity over BC progression and morbidity, with particular attention paid to promising therapeutic interventions.

scholarly journals Animal models of bronchopulmonary dysplasia. The term mouse models

2014 ◽  
Vol 307 (12) ◽  
pp. L936-L947 ◽  
Author(s):  
Jessica Berger ◽  
Vineet Bhandari
Keyword(s):  
Animal Models ◽  
Lung Injury ◽  
Mouse Models ◽  
Bronchopulmonary Dysplasia ◽  
Lung Development ◽  
Invasive Mechanical Ventilation ◽  
Therapeutic Interventions ◽  
Contributing Factors ◽  
Short Term ◽  
Injury Models

The etiology of bronchopulmonary dysplasia (BPD) is multifactorial, with genetics, ante- and postnatal sepsis, invasive mechanical ventilation, and exposure to hyperoxia being well described as contributing factors. Much of what is known about the pathogenesis of BPD is derived from animal models being exposed to the environmental factors noted above. This review will briefly cover the various mouse models of BPD, focusing mainly on the hyperoxia-induced lung injury models. We will also include hypoxia, hypoxia/hyperoxia, inflammation-induced, and transgenic models in room air. Attention to the stage of lung development at the timing of the initiation of the environmental insult and the duration of lung injury is critical to attempt to mimic the human disease pulmonary phenotype, both in the short term and in outcomes extending into childhood, adolescence, and adulthood. The various indexes of alveolar and vascular development as well as pulmonary function including pulmonary hypertension will be highlighted. The advantages (and limitations) of using such approaches will be discussed in the context of understanding the pathogenesis of and targeting therapeutic interventions to ameliorate human BPD.

scholarly journals Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

2014 ◽  
Vol 94 (4) ◽  
pp. 1027-1076 ◽  
Author(s):  
M. A. Hanson ◽  
P. D. Gluckman
Keyword(s):  
Animal Studies ◽  
Developmental Plasticity ◽  
Current Knowledge ◽  
Evolutionary Developmental Biology ◽  
Noncommunicable Disease ◽  
Normal Range ◽  
Physiological Processes ◽  
New Concepts ◽  
Health And Disease ◽  
Underlying Mechanisms

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.

Nuclear receptor Nur77: its role in chronic inflammatory diseases

2021 ◽  
Author(s):  
Sanne C. Lith ◽  
Carlie J.M. de Vries
Keyword(s):  
Nuclear Receptor ◽  
Inflammatory Disease ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Experimental Models ◽  
Therapeutic Interventions ◽  
Alternative Mechanism ◽  
Signaling Complex

Abstract Nur77 is a nuclear receptor that has been implicated as a regulator of inflammatory disease. The expression of Nur77 increases upon stimulation of immune cells and is differentially expressed in chronically inflamed organs in human and experimental models. Furthermore, in a variety of animal models dedicated to study inflammatory diseases, changes in Nur77 expression alter disease outcome. The available studies comprise a wealth of information on the function of Nur77 in diverse cell types and tissues. Negative cross-talk of Nur77 with the NFκB signaling complex is an example of Nur77 effector function. An alternative mechanism of action has been established, involving Nur77-mediated modulation of metabolism in macrophages as well as in T cells. In this review, we summarize our current knowledge on the role of Nur77 in atherosclerosis, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, and sepsis. Detailed insight in the control of inflammatory responses will be essential in order to advance Nur77-targeted therapeutic interventions in inflammatory disease.

HYPOTHYROID PREVALENCE DURING PREGNANCY IN LAST ONE DECADE IN INDIA

2021 ◽  
pp. 48-54
Author(s):  
Avani Pradhan ◽  
Kamlesh Choure ◽  
Amrit Gupta
Keyword(s):  
Birth Weight ◽  
Preterm Labor ◽  
Universal Screening ◽  
Developmental Disorders ◽  
Obstetric Outcome ◽  
Low Birth Weight Infants ◽  
Endocrine Disorder ◽  
Mother And Child ◽  
The Status ◽  
Current Scenario

Hypothyroidism during pregnancy is the most commonly found endocrine disorder. Its effect during pregnancy has widely been studied among women to understand the pathophysiology, outcomes, and prevalence. We collected data from several studies of last One Decade from separately studied population among all across the country regarding hypothyroid abundance. We compared more than 61 online available studies for the validation of data prevalence and to understand the status of associated risks to the mother and child in current scenario. Various risks like preeclampsia, preterm labor, anemia, IUGR, spontaneous birth, still birth, low birth weight infants, have been claimed associated in more than thirty ve studies from the nation, few of them also lighted shed on developmental disorders in neonates born under such conditions. This study conserves biggest data of 43,282 women studied for such condition. Here we found 6,952 women effected by hypothyroid, which makes an average prevalence of 14.2% and it ranges from 2.5% (lowest) - 33.82% (highest) in different places in pregnant women. This gure is higher than the reported global prevalence. These studies also found increased number of bad obstetric outcome for antenatal and postnatal risks in mothers. To prevent consequences universal screening should be acquired.

Missing links — epigenetic regulators of the pancreatic cancer–associated inflammation

2021 ◽  
Vol 135 (10) ◽  
pp. 1289-1293
Author(s):  
Gregor Werba ◽  
Tamas A. Gonda
Keyword(s):  
Pancreatic Cancer ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Cancers ◽  
Novel Treatment ◽  
Epigenetic Regulator ◽  
Novel Treatment Strategies

Abstract Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.

scholarly journals MIlitary Combat Mental Health Framework

2020 ◽  
pp. bmjmilitary-2020-001439
Author(s):  
Martin Bricknell
Keyword(s):  
Mental Health ◽  
Military Service ◽  
Current Knowledge ◽  
Armed Forces ◽  
Well Being ◽  
Therapeutic Interventions ◽  
Future Research ◽  
The Subject ◽  
Mental Well Being ◽  
Military Combat

This paper describes a framework for understanding military combat mental health based on the possible mental ill-health consequences of exposure to ‘potential trauma events’ for members of the armed forces and after their military service as veterans. It uses a life course approach that maps an individual’s mental well-being against four ‘states’: fit, reacting, injured and ill. It then considers five categories of factors that influence the risk of mental illness from this exposure based on research evidence; prejoining vulnerability, resilience, precipitating, treatment and recovery. This framework offers a structure to debate current knowledge, inform policy and therapeutic interventions, provide education and to guide future research into the subject.

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