scholarly journals The Role of Dysfunctional Adipose Tissue in Pancreatic Cancer: A Molecular Perspective

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1849 ◽  
Author(s):  
Davide Brocco ◽  
Rosalba Florio ◽  
Laura De Lellis ◽  
Serena Veschi ◽  
Antonino Grassadonia ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Normal Weight ◽  
Therapeutic Options ◽  
Therapeutic Interventions ◽  
Fat Accumulation ◽  
Adipose Organ ◽  
The Impact

Pancreatic cancer (PC) is a lethal malignancy with rising incidence and limited therapeutic options. Obesity is a well-established risk factor for PC development. Moreover, it negatively affects outcome in PC patients. Excessive fat accumulation in obese, over- and normal-weight individuals induces metabolic and inflammatory changes of adipose tissue microenvironment leading to a dysfunctional adipose “organ”. This may drive the association between abnormal fat accumulation and pancreatic cancer. In this review, we describe several molecular mechanisms that underpin this association at both local and systemic levels. We focus on the role of adipose tissue-derived circulating factors including adipokines, hormones and pro-inflammatory cytokines, as well as on the impact of the local adipose tissue in promoting PC. A discussion on potential therapeutic interventions, interfering with pro-tumorigenic effects of dysfunctional adipose tissue in PC, is included. Considering the raise of global obesity, research efforts to uncover the molecular basis of the relationship between pancreatic cancer and adipose tissue dysfunction may provide novel insights for the prevention of this deadly disease. In addition, these efforts may uncover novel targets for personalized interventional strategies aimed at improving the currently unsatisfactory PC therapeutic options.

scholarly journals Neonatal Immune System Ontogeny: The Role of Maternal Microbiota and Associated Factors. How Might the Non-Human Primate Model Enlighten the Path?

Vaccines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 584
Author(s):  
Natalia Nunez ◽  
Louis Réot ◽  
Elisabeth Menu
Keyword(s):  
Immune System ◽  
Mode Of Delivery ◽  
Microbial Colonization ◽  
Therapeutic Interventions ◽  
Primate Model ◽  
Neonatal Immune System ◽  
Gastrointestinal Colonization ◽  
The Impact ◽  
Human Primate

Interactions between the immune system and the microbiome play a crucial role on the human health. These interactions start in the prenatal period and are critical for the maturation of the immune system in newborns and infants. Several factors influence the composition of the infant’s microbiota and subsequently the development of the immune system. They include maternal infection, antibiotic treatment, environmental exposure, mode of delivery, breastfeeding, and food introduction. In this review, we focus on the ontogeny of the immune system and its association to microbial colonization from conception to food diversification. In this context, we give an overview of the mother–fetus interactions during pregnancy, the impact of the time of birth and the mode of delivery, the neonate gastrointestinal colonization and the role of breastfeeding, weaning, and food diversification. We further review the impact of the vaccination on the infant’s microbiota and the reciprocal case. Finally, we discuss several potential therapeutic interventions that might help to improve the newborn and infant’s health and their responses to vaccination. Throughout the review, we underline the main scientific questions that are left to be answered and how the non-human primate model could help enlighten the path.

scholarly journals Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

2021 ◽  
Vol 10 (4) ◽  
pp. 835
Author(s):  
Manoja P. Herath ◽  
Jeffrey M. Beckett ◽  
Andrew P. Hills ◽  
Nuala M. Byrne ◽  
Kiran D. K. Ahuja
Keyword(s):  
Diabetes Mellitus ◽  
Adipose Tissue ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Fat Mass ◽  
Metabolic Disorders ◽  
Later Life ◽  
Therapeutic Interventions ◽  
Increased Risk ◽  
The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

The impact of Traditional Chinese Medicine on mitophagy in disease models

2021 ◽  
Vol 27 ◽  
Author(s):  
Li-Ping Yu ◽  
Ting-Ting Shi ◽  
Yan-Qin Li ◽  
Jian-Kang Mu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Disease Models ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

scholarly journals Gormony zhirovoy tkani i funktsional'nayaaktivnost' shchitovidnoy zhelezy

2010 ◽  
Vol 7 (4) ◽  
pp. 8-11 ◽  
Author(s):  
N A Petunina ◽  
N E Al'tshuler ◽  
N G Rakova ◽  
L V Trukhina
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
The Impact ◽  
The Relationship ◽  
Tissue Hormones

The review presents a recent data from the literature on the physiologic and pathophysiologic role of adipose tissue hormones (adiponectin, resistin, leptin). The article details the role of adipocytokines in atherogenesis. It also presents the results of studies depicting the relationship between subclinical hypothyroidism, lipid metabolism and insulin resistance as well as the impact of thyroid dysfunction upon the secretion of adipocytokines.

scholarly journals Circulating Leukocytes and Oxidative Stress in Cardiovascular Diseases: A State of the Art

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Speranza Rubattu ◽  
Maurizio Forte ◽  
Salvatore Raffa
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Stress Level ◽  
Mononuclear Cells ◽  
Pathological Condition ◽  
Clinical Manifestations ◽  
Therapeutic Interventions ◽  
Oxidative Stress Level ◽  
The Impact

Increased oxidative stress from both mitochondrial and cytosolic sources contributes to the development and the progression of cardiovascular diseases (CVDs), and it is a target of therapeutic interventions. The numerous efforts made over the last decades in order to develop tools able to monitor the oxidative stress level in patients affected by CVDs rely on the need to gain information on the disease state. However, this goal has not been satisfactorily accomplished until now. Among others, the isolation of circulating leukocytes to measure their oxidant level offers a valid, noninvasive challenge that has been tested in few pathological contexts, including hypertension, atherosclerosis and its clinical manifestations, and heart failure. Since leukocytes circulate in the blood stream, it is expected that they might reflect quite closely both systemic and cardiovascular oxidative stress and provide useful information on the pathological condition. The results of the studies discussed in the present review article are promising. They highlight the importance of measuring oxidative stress level in circulating mononuclear cells in different CVDs with a consistent correlation between degree of oxidative stress and severity of CVD and of its complications. Importantly, they also point to a double role of leukocytes, both as a marker of disease condition and as a direct contributor to disease progression. Finally, they show that the oxidative stress level of leukocytes reflects the impact of therapeutic interventions. It is likely that the isolation of leukocytes and the measurement of oxidative stress, once adequately developed, may represent an eligible tool for both research and clinical purposes to monitor the role of oxidative stress on the promotion and progression of CVDs, as well as the impact of therapies.

scholarly journals Oxidative Stress and Adipocyte Biology: Focus on the Role of AGEs

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Florence Boyer ◽  
Jennifer Baraka Vidot ◽  
Alexis Guerin Dubourg ◽  
Philippe Rondeau ◽  
M. Faadiel Essop ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
Advanced Glycation Endproducts ◽  
Glycated Albumin ◽  
Major Health Problem ◽  
Glycation Endproducts ◽  
Diabetes Progression ◽  
The Impact ◽  
Pathologic Processes

Diabetes is a major health problem that is usually associated with obesity, together with hyperglycemia and increased advanced glycation endproducts (AGEs) formation. Elevated AGEs elicit severe downstream consequences via their binding to receptors of AGEs (RAGE). This includes oxidative stress and oxidative modifications of biological compounds together with heightened inflammation. For example, albumin (major circulating protein) undergoes increased glycoxidation with diabetes and may represent an important biomarker for monitoring diabetic pathophysiology. Despite the central role of adipose tissue in many physiologic/pathologic processes, recognition of the effects of greater AGEs formation in this tissue is quite recent within the obesity/diabetes context. This review provides a brief background of AGEs formation and adipose tissue biology and thereafter discusses the impact of AGEs-adipocyte interactions in pathology progression. Novel data are included showing how AGEs (especially glycated albumin) may be involved in hyperglycemia-induced oxidative damage in adipocytes and its potential links to diabetes progression.

Sex differences on adipose tissue remodeling: from molecular mechanisms to therapeutic interventions

2020 ◽  
Vol 98 (4) ◽  
pp. 483-493 ◽  
Author(s):  
Alexandra Moreira-Pais ◽  
Rita Ferreira ◽  
João Sérgio Neves ◽  
Rui Vitorino ◽  
Daniel Moreira-Gonçalves ◽  
...  
Keyword(s):  
Sex Differences ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Tissue Remodeling ◽  
Therapeutic Interventions ◽  
Adipose Tissue Remodeling

scholarly journals Deficiency of Growth Differentiation Factor 3 Protects against Diet-Induced Obesity by Selectively Acting on White Adipose

2009 ◽  
Vol 23 (1) ◽  
pp. 113-123 ◽  
Author(s):  
Joseph J. Shen ◽  
Lihua Huang ◽  
Liunan Li ◽  
Carolina Jorgez ◽  
Martin M. Matzuk ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Normal Weight ◽  
Metabolic Rates ◽  
Wild Type ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Differentiation Factor ◽  
Tgfβ Superfamily

Growth differentiation factor 3 (GDF3) is a member of the TGFβ superfamily. White adipose is one of the tissues in which Gdf3 is expressed, and it is the only tissue in which expression increases in response to high-fat diet. We generated Gdf3−/− mice, which were indistinguishable from wild-type mice and had normal weight curves on regular diet. However, on high-fat diet Gdf3−/− mice were resistant to the obesity that normally develops in wild-type mice. Herein we investigate the physiological and molecular mechanisms that underlie this protection from diet-induced obesity and demonstrate that GDF3 deficiency selectively affects white adipose through its influence on basal metabolic rates. Our results are consistent with a role for GDF3 in adipose tissue, with consequential effects on energy expenditure that ultimately impact adiposity.

scholarly journals Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells

2017 ◽  
Vol 8 (7) ◽  
pp. e2924-e2924 ◽  
Author(s):  
Yuran Gao ◽  
Zhicheng Zhang ◽  
Kai Li ◽  
Liying Gong ◽  
Qingzhu Yang ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Cells ◽  
Ectopic Expression ◽  
Pancreatic Cancer Cell Line ◽  
Mesenchymal Transition ◽  
Gemcitabine Resistance ◽  
Pancreatic Cancer Cells ◽  
Sense Strand ◽  
The Impact

AbstractThe acquisition of epithelial–mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance. Knockdown of linc-DYNC2H1-4 decreased the invasive behavior of BxPC-3-Gem cells while ectopic expression of linc-DYNC2H1-4 promoted the acquisition of EMT and stemness of the parental sensitive cells. Linc-DYNC2H1-4 upregulated ZEB1, the EMT key player, which led to upregulation and downregulation of its targets vimentin and E-cadherin respectively, as well as enhanced the expressions of CSC makers Lin28, Nanog, Sox2 and Oct4. Linc-DYNC2H1-4 is mainly located in the cytosol. Mechanically, it could sponge miR-145 that targetsZEB1,Lin28,Nanog,Sox2,Oct4to restore these EMT and CSC-associated genes expressions. We proved thatMMP3, the nearby gene of linc-DYNC2H1-4 in the sense strand, was also a target of miR-145. Downregulation ofMMP3by miR-145 was reverted by linc-DYNC2H1-4, indicating that competing with miR-145 is one of the mechanisms for linc-DYNC2H1-4 to regulateMMP3. In summary, our results explore the important role of linc-DYNC2H1-4 in the acquisition of EMT and CSC, and the impact it has on gemcitabine resistance in pancreatic cancer cells.

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