scholarly journals Role of Sex in the Therapeutic Targeting of p53 Circuitry

2021 ◽  
Vol 11 ◽  
Author(s):  
Francesca Mancini ◽  
Ludovica Giorgini ◽  
Emanuela Teveroni ◽  
Alfredo Pontecorvi ◽  
Fabiola Moretti
Keyword(s):  
Age Of Onset ◽  
Preclinical Studies ◽  
Therapeutic Approaches ◽  
Related Factors ◽  
Therapeutic Targeting ◽  
Estrogenic Hormones ◽  
Preclinical And Clinical Studies ◽  
P53 Network ◽  
The Relationship

Sex profoundly affects cancer incidence and susceptibility to therapy, with sex hormones highly contributing to this disparity. Various studies and omics data suggest a relationship between sex and the oncosuppressor p53 circuitry, including its regulators MDM2 and MDM4. Association of this network with genetic variation underlies sex-related altered cancer risk, age of onset, and cancer sensitivity to therapy. Moreover, sex-related factors, mainly estrogenic hormones, can affect the levels and/or function of the p53 network both in hormone-dependent and independent cancer. Despite this evidence, preclinical and clinical studies aimed to evaluate p53 targeted therapy rarely consider sex and related factors. This review summarizes the studies reporting the relationship between sex and the p53 circuitry, including its associated regulators, MDM2 and MDM4, with particular emphasis on estrogenic hormones. Moreover, we reviewed the evaluation of sex/hormone in preclinical studies and clinical trials employing p53-target therapies, and discuss how patients’ sex and hormonal status could impact these therapeutic approaches.

scholarly journals Systems Biology and Bile Acid Signalling in Microbiome-Host Interactions in the Cystic Fibrosis Lung

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 766
Author(s):  
David F. Woods ◽  
Stephanie Flynn ◽  
Jose A. Caparrós-Martín ◽  
Stephen M. Stick ◽  
F. Jerry Reen ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Bile Acids ◽  
Host Response ◽  
Signal Molecules ◽  
Therapeutic Approaches ◽  
Related Factors ◽  
Host Interactions ◽  
Important Host ◽  
Respiratory Microbiota

The study of the respiratory microbiota has revealed that the lungs of healthy and diseased individuals harbour distinct microbial communities. Imbalances in these communities can contribute to the pathogenesis of lung disease. How these imbalances occur and establish is largely unknown. This review is focused on the genetically inherited condition of Cystic Fibrosis (CF). Understanding the microbial and host-related factors that govern the establishment of chronic CF lung inflammation and pathogen colonisation is essential. Specifically, dissecting the interplay in the inflammation–pathogen–host axis. Bile acids are important host derived and microbially modified signal molecules that have been detected in CF lungs. These bile acids are associated with inflammation and restructuring of the lung microbiota linked to chronicity. This community remodelling involves a switch in the lung microbiota from a high biodiversity/low pathogen state to a low biodiversity/pathogen-dominated state. Bile acids are particularly associated with the dominance of Proteobacterial pathogens. The ability of bile acids to impact directly on both the lung microbiota and the host response offers a unifying principle underpinning the pathogenesis of CF. The modulating role of bile acids in lung microbiota dysbiosis and inflammation could offer new potential targets for designing innovative therapeutic approaches for respiratory disease.

scholarly journals Adolescents’ Intuitive Appraisal, Attributions and Emotions for their Relationships with their Parents

2012 ◽  
Vol 2 (6) ◽  
pp. 22
Author(s):  
Georgia Stephanou ◽  
Georgios Gkavras
Keyword(s):  
Relative Strength ◽  
Related Factors ◽  
Parent Relationships ◽  
General Outcome ◽  
Controllable Factors ◽  
Adolescent Parent ◽  
Parent Relationship ◽  
The Impact ◽  
The Relationship

This study study aimed to examine (a) adolescents’ attributions and emotions for their subjectively perceived good and bad relationships with their parents, (b) the association of the intuitive and attributional appraisals of the adolescent-parent relationship with the subsequent emotions, and (c) the role of the perceived importance of the good adolescent-parent relationship in the generation of attributions and emotions, and in the impact of attributions on emotions. The sample comprised 670 adolescents, both genders, aged 14-17 years old, representing various parental socioeconomic levels. The results showed that: (a) It was extremely important for the adolescents to have good relationships with their parents, (b) the perceived good adolescent-parent relationships were attributed to internal, stable and personal controllable factors, along with parent- and self-parent interactive- related factors, while the estimated as bad relationships were attributed to external, stable, personal uncontrollable and external controllable factors (parents’ negative properties), (c) the adolescents experienced intense positive and negative emotions (mainly, general / outcome- dependent) for the perceived good and bad relationships with their parents, respectively, (d) both intuitive and attributional appraisals of the relationship were associated with the emotions, particularly in the perceived bad adolescent-parent relationship, and (e) the relative strength of the association of the attributional dimensions with the emotions varied between the perceived good and bad adolescent-parent relationship and across the various emotions. Keywords: Adolescent-Parent Relationship, Attributions, Emotions, Intuitive Appraisal.

scholarly journals Mesenchymal Stem Cell Therapies for Paraplegia: Preclinical and Clinical Studies

Paraplegia ◽  
2021 ◽  
Author(s):  
Fereshteh Azedi ◽  
Kazem Mousavizadeh ◽  
Mohammad Taghi Joghataei
Keyword(s):  
Spinal Cord ◽  
Blood Clot ◽  
Spinal Column ◽  
Preclinical Studies ◽  
Loss Of Function ◽  
Stem Cell Therapies ◽  
Cell Therapies ◽  
Cord Injury ◽  
Preclinical And Clinical Studies

Paraplegia is the damage or loss of function in motor and/or sensory abilities. This insult can be observed in the thoracic, lumbar, or sacral parts of spinal column. Besides, paraplegia may be occurring because of any injuries or diseases of the lower segments or peripheral nerves or by cerebral palsy (CP). This damage can be seen as a result of a tumor or blood clot on the spinal cord. By now, there is not any curative treatment for paraplegia. Using mesenchymal stem cells (MSCs) in the treatment of spinal cord injury is a promising tested strategy because of their simplicity of isolation/preservation and their properties. Several preclinical studies in this field can be found; however, MSCs showed weak and conflicting outcomes in trials. In this chapter book, we will discuss about the therapeutic role of these cells in the treatment of paraplegia, with emphasis on their characterization, relevance, boundaries, and prospect views.

scholarly journals Iron metabolismin conditions of infection. Review

2020 ◽  
pp. 90-99
Author(s):  
Yuriy P. Orlov ◽  
N. V Govorova ◽  
V. N Lukach ◽  
G. A Baitugaeva ◽  
A. V Klementyev ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Medical Literature ◽  
Bacterial Flora ◽  
Medical Community ◽  
Therapeutic Approaches ◽  
Iron Supply ◽  
Review Analysis ◽  
The Relationship ◽  
Iron Exchange

The purpose of writing the review. Analysis of publications on the role of iron metabolism in the manifestation of the septic process and the dependence of bacterial flora activity on the conditions of their access to iron. Methods. More than 200 publications in pubmed, Medline, EMBASE medical literature databases were analyzed between 2000 and 2018 using the search words: iron and infection, iron and sepsis, iron exchange, iron and bacteria - including and available works in domestic (e-library) literature. Results. The review uses materials from 61 publications that meet the challenges of the search and reflect both the relationship between iron exchange and the development of the septic process and the importance for the medical community of understanding the identified relationships in the search for future therapeutic approaches. Conclusion. The review provides evidence of direct iron involvement in the manifestation of the septic process caused by various bacterial (q/-) and fungal flora. Introduction of iron-hesing agents and ciderophon - conjugate drugs to infected patients today seems to be a biologically acceptable approach as an auxiliary therapy in the treatment of septic process caused by pathogens dependent on iron supply (many bacterial and fungal pathogens), but the problem that is being raised certainly requires further experimental and clinical research.

scholarly journals The Mediating Role of Alexithymia in the Relationship Between Defense Mechanisms and Tendency to High-risk Behaviors Among Adolescents

2021 ◽  
Vol 11 (1) ◽  
pp. 29-36
Author(s):  
Zahra Nikmanesh ◽  
◽  
Mehdi Darvish Molla ◽  
Mehrnosh Mehranfard ◽  
◽  
...  
Keyword(s):  
High School Students ◽  
High Risk ◽  
Path Analysis ◽  
Risk Behaviors ◽  
Defense Mechanisms ◽  
Related Factors ◽  
High Risk Behaviors ◽  
Mediating Role ◽  
The Relationship

Background: Although high-risk behaviors lead to adverse physical, psychological, and sociological consequences, less attention has been paid to identifying their related factors. The aim of this study was to investigate the mediating role of alexithymia in the relationship between defense mechanisms and high-risk behaviors among adolescents in Zahedan. Methods: In this descriptive-correlative study, junior and senior high school students of Zahedan, Iran were studied in the academic year 2015-2016. A sample of 250 (125 males and 125 females) students were chosen by multi-stage cluster sampling and asked to complete the Defense Style Questionnaire (DSQ), Toronto Alexithymia Scale (TAS), and the Risk-Taking Scale (IARS) for Iranian Adolescents. Data analysis was conducted by measuring coefficients of correlation and performing a path analysis. Results: Path analysis showed a significant correlation between defense mechanisms and alexithymia (P<0.01) and a significant correlation was found between immature defense mechanisms and high-risk behaviors (P<0.01). Conclusion: In the relationship between dysfunctional defense mechanisms and high-risk activities, alexithymia played a mediating role. It can be inferred that dysfunctional defense mechanisms play a key role in high-risk activities by influencing alexithymia.

Multifaceted link between cancer and inflammation

2011 ◽  
Vol 32 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Gautam Sethi ◽  
Muthu K. Shanmugam ◽  
Lalitha Ramachandran ◽  
Alan Prem Kumar ◽  
Vinay Tergaonkar
Keyword(s):  
Hypoxia Inducible Factor ◽  
Nuclear Factor Κb ◽  
Activator Protein 1 ◽  
Oxygen Intermediates ◽  
Related Factors ◽  
Preclinical And Clinical Studies ◽  
Tumour Initiation ◽  
Cancer And Inflammation ◽  
Transcription 3

Increasing evidence from epidemiological, preclinical and clinical studies suggests that dysregulated inflammatory response plays a pivotal role in a multitude of chronic ailments including cancer. The molecular mechanism(s) by which chronic inflammation drives cancer initiation and promotion include increased production of pro-inflammatory mediators, such as cytokines, chemokines, reactive oxygen intermediates, increased expression of oncogenes, COX-2 (cyclo-oxygenase-2), 5-LOX (5-lipoxygenase) and MMPs (matrix metalloproteinases), and pro-inflammatory transcription factors such as NF-κB (nuclear factor κB), STAT3 (signal transducer and activator of transcription 3), AP-1 (activator protein 1) and HIF-1α (hypoxia-inducible factor 1α) that mediate tumour cell proliferation, transformation, metastasis, survival, invasion, angiogenesis, chemoresistance and radioresistance. These inflammation-associated molecules are activated by a number of environmental and lifestyle-related factors including infectious agents, tobacco, stress, diet, obesity and alcohol, which together are thought to drive as much as 90% of all cancers. The present review will focus primarily on the role of various inflammatory intermediates responsible for tumour initiation and progression, and discuss in detail the critical link between inflammation and cancer.

Marketing and family-related factors affecting food label use: the mediating role of consumer knowledge

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Daleen Van der Merwe ◽  
Hanli de Beer ◽  
Marli Nel ◽  
Susanna M. Ellis
Keyword(s):  
Food Choices ◽  
Healthy Food ◽  
Objective Knowledge ◽  
Food Label ◽  
Healthy Foods ◽  
Related Factors ◽  
Content Type ◽  
Mediating Role ◽  
The Relationship

PurposeThis study investigated the influence of marketing- and family-related factors on consumers' in-store usage of different types of food label information. Furthermore, the authors determined the mediating role of consumers' knowledge about healthy foods between these factors and their label consultation.Design/methodology/approachThe authors conducted a survey among 223 purposively selected South African working female consumers via social media. Subjective and objective knowledge about healthy foods, the importance of marketing- and family-related factors and the extent of food label usage were determined. Structural equation modelling served to test the mediating effect of knowledge in the relationship of the marketing and family-related factors with food label usage.FindingsMarketing-related factors demonstrated a strong direct effect on food label usage. Subjective knowledge about healthy foods mediated the relationship between family members' dietary needs and food label usage. However, objective knowledge was not a mediator.Practical implicationsRespondents' firm reliance on marketing-related factors (instead of knowledge) during food label usage is not in the best interest of consumers' healthy food choices. Healthy food choices based on factual knowledge rather than marketing efforts are necessary to establish long-term healthy food habits, hence the need for retailers' response in supplying healthier food options. Role players in consumer education should focus on increasing consumers' healthy food knowledge.Originality/valueIn the context of rising awareness of public health concerns, healthy food choice among consumers is essential. This study contributes to the complexity of consumers' need to make healthy food choices within an economic-driven marketing environment.

scholarly journals Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation

2019 ◽  
Vol 59 (1) ◽  
pp. 237-261 ◽  
Author(s):  
Miguel Moutinho ◽  
Juan F. Codocedo ◽  
Shweta S. Puntambekar ◽  
Gary E. Landreth
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Nuclear Receptors ◽  
Motor Impairment ◽  
Therapeutic Approaches ◽  
New Findings ◽  
Wide Range ◽  
Preclinical And Clinical Studies ◽  
Lost In Translation

Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases.

scholarly journals Investigating the moderating role of intercultural factors on consumer cross-shopping behavior

2020 ◽  
Vol 9 (2) ◽  
pp. 139-151
Author(s):  
Hayiel Hino
Keyword(s):  
Ethnic Minority ◽  
Shopping Behavior ◽  
Future Research ◽  
Related Factors ◽  
Study Results ◽  
Majority Population ◽  
Israeli Arabs ◽  
The Relationship ◽  
Moderating Role

The concept of prejudice has become increasingly important to scientific thinking about relations between groups. Yet, despite extensive research, little is known about how prejudice affects consumer buying behavior, especially regarding activities that involve purchasing products and services thereby crossing to suppliers from the dominant community.  The purpose of this study is twofold: to examine the influence of both positive and negative prejudices on cross-shopping intention in the context of an ethnic minority-majority group relationship; and, to investigate the moderating influence of intercultural-related factors (i.e. online contact, social interaction, and acculturation) on the relationship between negative prejudice and cross-shopping intention. A sample consisting of 202 respondents was obtained from across ethnic-minority consumers (the Israeli Arabs) who routinely interact online and offline with individuals from the majority population (Israeli Jews). The conceptual framework and hypothesis are tested using the partial least squares analyses (PLS). The study results provide a better understanding of the conflicting effects of positive and negative prejudice on cross-shopping intention. Additionally, results shed light on the moderating role of intercultural factors on the relationship between negative prejudice and cross-shopping intention. Implications are identified together with consideration of the study limitations and avenues for future research.

The Therapeutic Impact of New Migraine Discoveries

2019 ◽  
Vol 26 (34) ◽  
pp. 6261-6281 ◽  
Author(s):  
László Vécsei ◽  
Melinda Lukács ◽  
János Tajti ◽  
Ferenc Fülöp ◽  
József Toldi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Preventive Treatment ◽  
Therapeutic Strategies ◽  
Migraine Treatment ◽  
Preclinical Studies ◽  
Therapeutic Approaches ◽  
Trigeminovascular System ◽  
Glutamate Receptor Antagonists

Background: Migraine is one of the most disabling neurological conditions and associated with high socio-economic costs. Though certain aspects of the pathomechanism of migraine are still incompletely understood, the leading hypothesis implicates the role of the activation of the trigeminovascular system. Triptans are considered to be the current gold standard therapy for migraine attacks; however, their use in clinical practice is limited. Prophylactic treatment includes non-specific approaches for migraine prevention. All these support the need for future studies in order to develop innovative anti-migraine drugs. Objective: The present study is a review of the current literature regarding new therapeutic lines in migraine research. Methods: A systematic literature search in the database of PUBMED was conducted concerning therapeutic strategies in a migraine published until July 2017. Results: Ongoing clinical trials with 5-HT1F receptor agonists and glutamate receptor antagonists offer promising new aspects for acute migraine treatment. Monoclonal antibodies against CGRP and the CGRP receptor are revolutionary in preventive treatment; however, further long-term studies are needed to test their tolerability. Preclinical studies show positive results with PACAP- and kynurenic acid-related treatments. Other promising therapeutic strategies (such as those targeting TRPV1, substance P, NOS, or orexin) have failed to show efficacy in clinical trials. Conclusion: Due to their side-effects, current therapeutic approaches are not suitable for all migraine patients. Especially frequent episodic and chronic migraine represents a therapeutic challenge for researchers. Clinical and preclinical studies are needed to untangle the pathophysiology of migraine in order to develop new and migraine-specific therapies.

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