scholarly journals White-Matter Repair as a Novel Therapeutic Target for Early Adversity

2021 ◽  
Vol 15 ◽  
Author(s):  
Rafiad Islam ◽  
Arie Kaffman
Keyword(s):  
Molecular Mechanisms ◽  
Mammalian Species ◽  
Network Connectivity ◽  
Clinical Work ◽  
Therapeutic Interventions ◽  
Early Adversity ◽  
And Behavior ◽  
White Matter Repair ◽  
The Impact ◽  
Novel Therapeutic

Early adversity (EA) impairs myelin development in a manner that persists later in life across diverse mammalian species including humans, non-human primates, and rodents. These observations, coupled with the highly conserved nature of myelin development suggest that animal models can provide important insights into the molecular mechanisms by which EA impairs myelin development later in life and the impact of these changes on network connectivity, cognition, and behavior. However, this area of translational research has received relatively little attention and no comprehensive review is currently available to address these issues. This is particularly important given some recent mechanistic studies in rodents and the availability of new agents to increase myelination. The goals of this review are to highlight the need for additional pre-clinical work in this area and to provide specific examples that demonstrate the potential of this work to generate novel therapeutic interventions that are highly needed.

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 Extracellular HSP90 Machineries Build Tumor Microenvironment and Boost Cancer Progression

2021 ◽  
Vol 9 ◽  
Author(s):  
Pietro Poggio ◽  
Matteo Sorge ◽  
Laura Seclì ◽  
Mara Brancaccio
Keyword(s):  
Tumor Microenvironment ◽  
Cell Surface ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Diagnostic Tools ◽  
Surface Receptors ◽  
And Behavior ◽  
Cancer Cell Signaling ◽  
The Impact ◽  
Stimulation Of

HSP90 is released by cancer cells in the tumor microenvironment where it associates with different co-chaperones generating complexes with specific functions, ranging from folding and activation of extracellular clients to the stimulation of cell surface receptors. Emerging data indicate that these functions are essential for tumor growth and progression. The understanding of the exact composition of extracellular HSP90 complexes and the molecular mechanisms at the basis of their functions in the tumor microenvironment may represent the first step to design innovative diagnostic tools and new effective therapies. Here we review the impact of extracellular HSP90 complexes on cancer cell signaling and behavior.

scholarly journals The Contribution of Endothelial Dysfunction in Systemic Injury Subsequent to SARS-Cov-2 Infection

2020 ◽  
Vol 21 (23) ◽  
pp. 9309
Author(s):  
Jessica Maiuolo ◽  
Rocco Mollace ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Blood Vessels ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Vascular Complications ◽  
Therapeutic Interventions ◽  
The Impact

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells, which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of a SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to a detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with the ACE2 receptor located in the endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function, which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease, leading to irreversible tissue damage and death of people with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated with the interaction of SARS CoV-2 with the ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

scholarly journals Minireview: Translational Animal Models of Human Menopause: Challenges and Emerging Opportunities

Endocrinology ◽  
2012 ◽  
Vol 153 (8) ◽  
pp. 3571-3578 ◽  
Author(s):  
Roberta Diaz Brinton
Keyword(s):  
Animal Models ◽  
Hormone Therapy ◽  
Predictive Validity ◽  
Clinical Care ◽  
Mammalian Species ◽  
Progesterone Receptors ◽  
Therapeutic Interventions ◽  
Clinical Issues ◽  
Discovery Research ◽  
The Impact

Increasing importance is placed on the translational validity of animal models of human menopause to discern risk vs. benefit for prediction of outcomes after therapeutic interventions and to develop new therapeutic strategies to promote health. Basic discovery research conducted over many decades has built an extensive body of knowledge regarding reproductive senescence across mammalian species upon which to advance animal models of human menopause. Modifications to existing animal models could rapidly address translational gaps relevant to clinical issues in human menopausal health, which include the impact of 1) chronic ovarian hormone deprivation and hormone therapy, 2) clinically relevant hormone therapy regimens (cyclic vs. continuous combined), 3) clinically relevant hormone therapy formulations, and 4) windows of opportunity and optimal duration of interventions. Modifications in existing animal models to more accurately represent human menopause and clinical interventions could rapidly provide preclinical translational data to predict outcomes regarding unresolved clinical issues relevant to women's menopausal health. Development of the next generation of animal models of human menopause could leverage advances in identifying genotypic variations in estrogen and progesterone receptors to develop personalized menopausal care and to predict outcomes of interventions for protection against or vulnerability to disease. Key to the success of these models is the close coupling between the translational target and the range of predictive validity. Preclinical translational animal models of human menopause need to keep pace with changes in clinical practice. With focus on predictive validity and strategic use of advances in genetic and epigenetic science, new animal models of human menopause have the opportunity to set new directions for menopausal clinical care for women worldwide.

scholarly journals The Impact of Spirituality and Spiritually-Oriented Therapeutic Interventions on Schizophrenia Patients

2019 ◽  
Vol 4 (3) ◽  
pp. 309-320
Author(s):  
Özge Erduran-Tekin
Keyword(s):  
Short Term Memory ◽  
Well Being ◽  
Therapeutic Interventions ◽  
General Definition ◽  
Schizophrenic Patients ◽  
Spiritual Counseling ◽  
Definition Of ◽  
And Behavior ◽  
The Impact ◽  
Counseling Practices

Schizophrenia, with its various aspects that are as yet as unexplainable and which causes those suffering from it to move away from relationships and reality, is a severe psychiatric disorder that usually deteriorates thinking and behavior from an early age. A general definition of schizophrenia has been mentioned for the purpose of this study without describing the types of schizophrenia in detail. The main axis of the study is what role spirituality may have in increasing schizophrenic patients’ well-being, which is the last step in the model for their medical treatment. A lack of deterioration in patients’ consciousness and short-term memory is very important in order for them to be able to understand the therapeutic practices; the study discusses spiritual counseling practices that can be studied with schizophrenic patients who have no problems in these areas. The study evaluates the concept of insight in schizophrenia patients from different perspectives and includes spiritual counseling practices that can be done with schizophrenia patients possessing high levels of insight. The study continues by examining which individual spiritual counseling practices are possible for patients with schizophrenia and presents the example of group counseling over spiritual counseling practices for patients with schizophrenia as well as which counseling practices can be done for schizophrenic patients and their families. The main aim of this study is to present to clinicians, psychologists, and psychological counselors working in the field a general review of the literature on studies that have examined the relationship between schizophrenia and spirituality and to give them ideas into how to integrate spiritual counseling practices into the process while working with schizophrenia patients and their relatives.

scholarly journals The Contribution of Endothelial Dysfunction in Systemic Injury Subsequent to SARS-Cov-2 Infection

2020 ◽  
Author(s):  
Jessica Maiuolo ◽  
Rocco Mollace ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Blood Vessels ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Vascular Inflammation ◽  
Vascular Complications ◽  
Therapeutic Interventions ◽  
The Impact

Abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection is associated, alongside with lung infection and respiratory disease, to cardiovascular dysfunction that occurs at any stage of the disease. This includes ischemic heart disease, arrhythmias, and cardiomyopathies. The common pathophysiological link between SARS-CoV-2 infection and the cardiovascular events is represented by coagulation abnormalities and disruption of factors released by endothelial cells which contribute in maintaining the blood vessels into an anti-thrombotic state. Thus, early alteration of the functionality of endothelial cells, which may be found soon after SARS-CoV-2 infection, seems to represent the major target of SARS CoV-2 disease state and accounts for the systemic vascular dysfunction that leads to detrimental effect in terms of hospitalization and death accompanying the disease. In particular, the molecular interaction of SARS-CoV-2 with ACE2 receptor located in endothelial cell surface, either at the pulmonary and systemic level, leads to early impairment of endothelial function which, in turn, is followed by vascular inflammation and thrombosis of peripheral blood vessels. This highlights systemic hypoxia and further aggravates the vicious circle that compromises the development of the disease leading to irreversible tissue damage and death of patients with SARS CoV-2 infection. The review aims to assess some recent advances to define the crucial role of endothelial dysfunction in the pathogenesis of vascular complications accompanying SARS-CoV-2 infection. In particular, the molecular mechanisms associated to the interaction of SARS CoV-2 with ACE2 receptor located on the endothelial cells are highlighted to support its role in compromising endothelial cell functionality. Finally, the consequences of endothelial dysfunction in enhancing pro-inflammatory and pro-thrombotic effects of SARS-CoV-2 infection are assessed in order to identify early therapeutic interventions able to reduce the impact of the disease in high-risk patients.

scholarly journals Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder

2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Hadar Shalev ◽  
Yonatan Serlin ◽  
Alon Friedman
Keyword(s):  
Blood Brain Barrier ◽  
Clinical Data ◽  
Molecular Mechanisms ◽  
Neurovascular Unit ◽  
Animal Experiments ◽  
Network Connectivity ◽  
Brain Barrier ◽  
Local Inflammatory Response ◽  
Blood Brain ◽  
And Behavior

The mechanisms underlying the development and progression of psychiatric illnesses are only partially known. Clinical data suggest blood-brain barrier (BBB) breakdown and inflammation are involved in some patients groups. Here we put forward the “BBB hypothesis” and abnormal blood-brain communication as key mechanisms leading to neuronal dysfunction underlying disturbed cognition, mood, and behavior. Based on accumulating clinical data and animal experiments, we propose that events within the “neurovascular unit” are initiated by a focal BBB breakdown, and are associated with dysfunction of brain astrocytes, a local inflammatory response, pathological synaptic plasticity, and increased network connectivity. Our hypothesis should be validated in animal models of psychiatric diseases and BBB breakdown. Recently developed imaging approaches open the opportunity to challenge our hypothesis in patients. We propose that molecular mechanisms controlling BBB permeability, astrocytic functions, and inflammation may become novel targets for the prevention and treatment of psychiatric disorders.

Bone Metastases: Molecular Mechanisms and Novel Therapeutic Interventions

2010 ◽  
Vol 32 (3) ◽  
pp. 611-636 ◽  
Author(s):  
Dionysios J. Papachristou ◽  
Efthimia K. Basdra ◽  
Athanasios G. Papavassiliou
Keyword(s):  
Bone Metastases ◽  
Molecular Mechanisms ◽  
Therapeutic Interventions ◽  
Novel Therapeutic

scholarly journals The Role of Dietary Polyphenols on Adult Hippocampal Neurogenesis: Molecular Mechanisms and Behavioural Effects on Depression and Anxiety

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Gisele Pereira Dias ◽  
Nicole Cavegn ◽  
Alina Nix ◽  
Mário Cesar do Nascimento Bevilaqua ◽  
Doris Stangl ◽  
...  
Keyword(s):  
Environmental Enrichment ◽  
Molecular Mechanisms ◽  
Mammalian Species ◽  
Hippocampal Neurogenesis ◽  
Adult Hippocampal Neurogenesis ◽  
Voluntary Exercise ◽  
Therapeutic Interventions ◽  
Anxiety And Depression ◽  
Dietary Polyphenols ◽  
Positive Effects

Although it has been long believed that new neurons were only generated during development, there is now growing evidence indicating that at least two regions in the brain are capable of continuously generating functional neurons: the subventricular zone and the dentate gyrus of the hippocampus. Adult hippocampal neurogenesis (AHN) is a widely observed phenomenon verified in different adult mammalian species including humans. Factors such as environmental enrichment, voluntary exercise, and diet have been linked to increased levels of AHN. Conversely, aging, stress, anxiety and depression have been suggested to hinder it. However, the mechanisms underlying these effects are still unclear and yet to be determined. In this paper, we discuss some recent findings addressing the effects of different dietary polyphenols on hippocampal cell proliferation and differentiation, models of anxiety, and depression as well as some proposed molecular mechanisms underlying those effects with particular focus on those related to AHN. As a whole, dietary polyphenols seem to exert positive effects on anxiety and depression, possibly in part via regulation of AHN. Studies on the effects of dietary polyphenols on behaviour and AHN may play an important role in the approach to use diet as part of the therapeutic interventions for mental-health-related conditions.

The parent-offspring microbiome and neurobehavioral development

2019 ◽  
Vol 42 ◽  
Author(s):  
Jeffrey R. Alberts ◽  
Christopher Harshaw ◽  
Gregory E. Demas ◽  
Cara L. Wellman ◽  
Ardythe L. Morrow
Keyword(s):  
Mammalian Species ◽  
Social Emotional ◽  
Behavioral Measures ◽  
Neurobehavioral Development ◽  
Emotional Function ◽  
Neurobehavioral Outcomes ◽  
Methodological Approaches ◽  
And Behavior

Abstract We identify the significance and typical requirements of developmental analyses of the microbiome-gut-brain (MGB) in parents, offspring, and parent-offspring relations, which have particular importance for neurobehavioral outcomes in mammalian species, including humans. We call for a focus on behavioral measures of social-emotional function. Methodological approaches to interpreting relations between the microbiota and behavior are discussed.

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