scholarly journals Impact of Circadian Desynchrony on Spermatogenesis: A Mini Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Ferdinando Fusco ◽  
Nicola Longo ◽  
Marco De Sio ◽  
Davide Arcaniolo ◽  
Giuseppe Celentano ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Clinical Evidence ◽  
Clock Genes ◽  
Semen Parameters ◽  
Current Evidence ◽  
Sexual Hormones ◽  
Knock Out ◽  
Study Heterogeneity ◽  
The Impact ◽  
Circulating Levels

The purpose of this mini review is to provide data about pre-clinical and clinical evidence exploring the impact of circadian desynchrony on spermatogenesis. Several lines of evidence exist demonstrating that disruption of circadian rhythms may interfere with male fertility. Experimental knock-out or knock-down of clock genes, physiologically involved in the regulation of circadian rhythms, are associated with impairments of fertility pathways in both animal and human models. Moreover, disruption of circadian rhythms, due to reduction of sleep duration and/or alteration of its architecture can negatively interfere in humans with circulating levels of male sexual hormones as well as with semen parameters. Unfortunately, current evidence remains low due to study heterogeneity.

scholarly journals Cancer clocks in tumourigenesis: the p53 pathway and beyond

2021 ◽  
Vol 28 (4) ◽  
pp. R95-R110
Author(s):  
Ewan M Stephenson ◽  
Laura E J Usselmann ◽  
Vinay Tergaonkar ◽  
David M Virshup ◽  
Robert Dallmann
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Cancer Biology ◽  
Cell Cycle Progression ◽  
Clock Genes ◽  
Human Cancer ◽  
Epidemiologic Studies ◽  
Current Evidence

Circadian rhythms regulate a vast array of physiological and cellular processes, as well as the hormonal milieu, to keep our cells synchronised to the light–darkness cycle. Epidemiologic studies have implicated circadian disruption in the development of breast and other cancers, and numerous clock genes are dysregulated in human tumours. Here we review the evidence that circadian rhythms, when altered at the molecular level, influence cancer growth. We also note some common pitfalls in circadian-cancer research and how they might be avoided to maximise comparable results and minimise misleading data. Studies of circadian gene mutant mice, and human cancer models in vitro and in vivo, demonstrate that clock genes can impact tumourigenesis. Clock genes influence important cancer-related pathways, ranging from p53-mediated apoptosis to cell cycle progression. Confusingly, clock dysfunction can be both pro- or anti-tumourigenic in a model and cell type-specific manner. Due to this duality, there is no canonical mechanism for clock interaction with tumourigenic pathways. To understand the role of the circadian clock in patients’ tumours requires analysis of the molecular clock status compared to healthy tissue. Novel mathematical approaches are under development, but this remains largely aspirational, and is hampered by a lack of temporal information in publicly available datasets. Current evidence broadly supports the notion that the circadian clock is important for cancer biology. More work is necessary to develop an overarching model of this connection. Future studies would do well to analyse the clock network in addition to alterations in single clock genes.

scholarly journals The vascular clock: a new insight into endothelial cells and pericytes crosstalk

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
V Mastrullo ◽  
R S Matos ◽  
J H McVey ◽  
P Gupta ◽  
P Madeddu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Blood Vessels ◽  
Molecular Clock ◽  
Clock Genes ◽  
Public Institution ◽  
Perivascular Cells ◽  
Rhythmic Expression ◽  
The Impact

Abstract Background/Introduction Circadian rhythms, defined as biological oscillations with a period of circa 24h, regulate many physiological processes in the cardiovascular system, such as vascular function, vascular tone, blood pressure, heart rate and thrombus formation [1]. The vasculature responds to the main pacemaker located in the brain, but it also possesses its own clock. Indeed, a molecular clock has been identified in endothelial cells (EC) and smooth muscle cells (SMC). The disruption of the circadian clock profoundly affects cardiovascular functionality with adverse cardiovascular events such as myocardial infarction or stroke showing a 24h rhythmicity with a peak incidence in the early morning. Among several mechanisms affected by circadian dysregulation, angiogenesis plays a fundamental role in homeostasis and development of new blood vessels. EC and pericytes (PC) are the two main cell populations in the capillaries, and their physical and paracrine interaction drives and regulates the sprouting. However, the presence and the role of circadian rhythms in pericytes and whether the molecular clock affects the endothelial/pericyte interactions remain unexplored. Purpose The aim of this study is to identify a molecular clock in human vascular pericytes and elucidate the impact of the circadian clock on the formation of new blood vessels. Methods Human primary PC were synchronised and the rhythmicity of clock genes measured by luminescence, immunofluorescence, and qPCR. Synchronised PC were co-cultured with Bmal1::LUC human primary EC. The effect of PC synchronisation and circadian clock disruption by shRNA on EC clock genes and angiogenic potential were measured by luminescence and Matrigel assay, respectively. A macroporous polyurethane scaffold was developed for 3D co-cultures. Results PC presented rhythmic expression of the principal circadian genes with a circa 24h period but in our experimental setting, EC did not show circadian rhythmicity. Synchronised PC supported the rhythmic expression of the clock gene Bmal1 in EC in a contact co-culture system, suggesting a secondary form of EC molecular clock regulation. Non-contact co-cultures failed to synchronise EC. Furthermore, when the clock was disrupted in PC, their capacity to support EC's tube-forming capacity on Matrigel was impaired; clock disruption in EC did not affect angiogenesis, supporting the hypothesis that a disrupted clock in perivascular cells affects angiogenesis. In a 3D tissue engineering scaffold seeded with both EC and PC, the synchronisation of the clock led to the development of organised vascular-like structures around the scaffold's pores, as compared to the non-synchronised condition where cells appeared disorganised. Conclusion This study defines for the first time the existence of an endogenous molecular circadian clock in perivascular cells and suggests implications for circadian clock synchronisation in physiological and therapeutic angiogenesis. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): University of Surrey Doctoral CollegeUniversity of Surrey Bioprocess and Biochemical Engineering (BioProChem) Group.

scholarly journals Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility

2020 ◽  
Vol 21 (11) ◽  
pp. 3943
Author(s):  
Francesca Sciarra ◽  
Edoardo Franceschini ◽  
Federica Campolo ◽  
Daniele Gianfrilli ◽  
Francesco Pallotti ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Circadian Clock ◽  
Clock Genes ◽  
Hormone Secretion ◽  
The Body ◽  
Molecular Networks ◽  
Industrialized Countries ◽  
Suprachiasmatic Nuclei ◽  
Sexual Hormones ◽  
Fine Tune

Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called “clock genes” that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic–pituitary–gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders.

scholarly journals The Relationship between Circulating ANGPTL8/Betatrophin Concentrations and Adult Obesity: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Jingjing Ye ◽  
Yu Qin ◽  
Dong Wang ◽  
Ling Yang ◽  
Guoyue Yuan
Keyword(s):  
Meta Analysis ◽  
Relevant Literature ◽  
Public Health Problem ◽  
Current Evidence ◽  
Adult Obesity ◽  
Study Heterogeneity ◽  
Obese Subjects ◽  
The Impact ◽  
The Relationship ◽  
Synthesis And Degradation

In this study, we evaluated the relationship between circulating betatrophin levels and obesity. Obesity is a common public health problem that is increasing globally. Betatrophin, a newly identified protein, is predominantly expressed in white and brown fat tissues and in the liver. Growing evidence suggests that betatrophin plays a pivotal role in metabolism, including the synthesis and degradation of lipids in cells, and adipocyte differentiation. Previous studies have assessed the association between circulating betatrophin levels and obesity; however, this relationship remains unclear. Therefore, our study is aimed at examining the impact of betatrophin on obesity using a meta-analysis of the current evidence. We performed a meta-analysis to quantify the relationship between betatrophin levels and obesity. A literature search was conducted through the EMBASE, Web of Science, and MEDLINE databases. Retrieved studies were screened, without any language restrictions to identify relevant literature published up to December 2018. Observational studies, in which the association between circulating concentrations of betatrophin and obesity was evaluated, were considered suitable for the systematic review. Of the 65 manuscripts retrieved, 9 datasets from 6 studies, involving 681 participants, detected an association between circulating betatrophin and obesity. Circulating betatrophin levels of obese subjects were higher than those of nonobese subjects (random−effects weighted mean difference WMD=0.250 μg/mL, 95% CI: 0.048–0.451, I2=94.8%, p=0.015), yet with significant between-study heterogeneity. This heterogeneity appeared to be modified by glycemic status but not by age, the ELISA kits used, sample source, or body mass index. The high circulating betatrophin concentration may directly increase the risk of obesity in adults. Betatrophin may serve as a therapeutic target for obesity in adults.

scholarly journals Mathematical modeling informs the impact of changes in circadian rhythms and meal patterns on insulin secretion

2019 ◽  
Vol 317 (1) ◽  
pp. R98-R107 ◽  
Author(s):  
Seul-A Bae ◽  
Ioannis P. Androulakis
Keyword(s):  
Insulin Secretion ◽  
Circadian Rhythms ◽  
Metabolic Diseases ◽  
Clock Genes ◽  
Daily Variation ◽  
Environmental Signals ◽  
Global Clock ◽  
Obesity And Diabetes ◽  
Increased Risk ◽  
The Impact

Disruption of circadian rhythms has been associated with metabolic syndromes, including obesity and diabetes. A variety of metabolic activities are under circadian modulation, as local and global clock gene knockouts result in glucose imbalance and increased risk of metabolic diseases. Insulin release from the pancreatic β cells exhibits daily variation, and recent studies have found that insulin secretion, not production, is under circadian modulation. As consideration of daily variation in insulin secretion is necessary to accurately describe glucose-stimulated insulin secretion, we describe a mathematical model that incorporates the circadian modulation via insulin granule trafficking. We use this model to understand the effect of oscillatory characteristics on insulin secretion at different times of the day. Furthermore, we integrate the dynamics of clock genes under the influence of competing environmental signals (light/dark cycle and feeding/fasting cycle) and demonstrate how circadian disruption and meal size distribution change the insulin secretion pattern over a 24-h day.

scholarly journals Association of Genetic Polymorphisms and Serum Levels of IL-6 and IL-8 with the Prognosis in Children with Neuroblastoma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 529
Author(s):  
Silvia Selene Moreno-Guerrero ◽  
Arturo Ramírez-Pacheco ◽  
Luz María Rocha-Ramírez ◽  
Gabriela Hernández-Pliego ◽  
Pilar Eguía-Aguilar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Genetic Polymorphisms ◽  
Poor Prognosis ◽  
Serum Levels ◽  
Control Group ◽  
Mexican Children ◽  
Genotype Frequencies ◽  
Pcr Rflp ◽  
The Impact ◽  
Circulating Levels

There is evidence that high circulating levels of IL-6 and IL-8 are markers of a poor prognosis in various types of cancer, including NB. The participation of these cytokines in the tumor microenvironment has been described to promote progression and metastasis. Our objective was to evaluate the prognostic role of genetic polymorphisms and serum levels of IL-6 and IL-8 in a cohort of Mexican pediatric patients with NB. The detection of the SNPs rs1800795 IL-6 and rs4073 and rs2227306 IL-8 was carried out by PCR-RFLP and the levels of cytokines were determined by the ELISA method. We found elevated circulating levels of IL-8 and IL-6 in NB patients compared to the control group. The genotype frequencies of the rs1800795 IL-6 and rs4073 IL-8 variants were different between the patients with NB and the control group. Likewise, the survival analysis showed that the GG genotypes of rs1800795 IL-6 (p = 0.014) and AA genotypes of rs4073 IL-8 (p = 0.002), as well as high levels of IL-6 (p = 0.009) and IL-8 (p = 0.046), were associated with lower overall survival. We confirmed the impact on an adverse prognosis in a multivariate model. This study suggests that the SNPs rs1800795 IL-6 and rs4073 IL-8 and their serum levels could be promising biomarkers of a poor prognosis, associated with overall survival, metastasis, and a high risk in Mexican children with NB.

Type A aortic dissection: involvement of carotid artery and impact on cerebral malperfusion

2020 ◽  
pp. 021849232098432
Author(s):  
Wahaj Munir ◽  
Jun Heng Chong ◽  
Amer Harky ◽  
Mohamad Bashir ◽  
Benjamin Adams
Keyword(s):  
Carotid Artery ◽  
Aortic Dissection ◽  
Type A ◽  
Current Evidence ◽  
Management Approach ◽  
Complex Nature ◽  
Acute Type ◽  
Type A Aortic Dissection ◽  
Cerebral Malperfusion ◽  
The Impact

Acute type A aortic dissection is a surgical emergency and management of such pathology can be complex with poor outcomes when there is organ malperfusion. Carotid artery involvement is present in 30% of patients diagnosed with acute type A aortic dissection, and given its emergency and complex nature, there is much controversy regarding the approach, extent of treatment, and timing of the intervention. It is clear that the occurrence of cerebral malperfusion adds an extra layer of complexity to the decision-making framework for treatment. Standardization and validation of the optimal management approach is required, and this should ideally be addressed with large-scale studies. Nonetheless, current literature supports the need for rapid recognition and diagnosis of acute type A aortic dissection with cerebral malperfusion, immediate and extensive surgical repair, and the appropriate use of cerebral perfusion techniques. This paper aims to discuss the current evidence regarding the impact of carotid artery involvement in both the management and outcomes of acute type A aortic dissection.

scholarly journals Antimicrobial Use in COVID-19 Patients in the First Phase of the SARS-CoV-2 Pandemic: A Scoping Review

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 745
Author(s):  
Wenjuan Cong ◽  
Ak Narayan Poudel ◽  
Nour Alhusein ◽  
Hexing Wang ◽  
Guiqing Yao ◽  
...  
Keyword(s):  
Critical Illness ◽  
Scoping Review ◽  
Clinical Evidence ◽  
Length Of Hospital Stay ◽  
Severity Of Illness ◽  
Antibiotic Prescribing ◽  
Antimicrobial Use ◽  
Clinical Scenarios ◽  
Scoping Reviews ◽  
The Impact

This scoping review provides new evidence on the prevalence and patterns of global antimicrobial use in the treatment of COVID-19 patients; identifies the most commonly used antibiotics and clinical scenarios associated with antibiotic prescribing in the first phase of the pandemic; and explores the impact of documented antibiotic prescribing on treatment outcomes in COVID-19 patients. The review complies with PRISMA guidelines for Scoping Reviews and the protocol is registered with the Open Science Framework. In the first six months of the pandemic, there was a similar mean antibiotic prescribing rate between patients with severe or critical illness (75.4%) and patients with mild or moderate illness (75.1%). The proportion of patients prescribed antibiotics without clinical justification was 51.5% vs. 41.9% for patients with mild or moderate illness and those with severe or critical illness. Comparison of patients who were provided antibiotics with a clinical justification with those who were given antibiotics without clinical justification showed lower mortality rates (9.5% vs. 13.1%), higher discharge rates (80.9% vs. 69.3%), and shorter length of hospital stay (9.3 days vs. 12.2 days). In the first 6 months of the pandemic, antibiotics were prescribed for COVID-19 patients regardless of severity of illness. A large proportion of antibiotic prescribing for mild and moderate COVID-19 patients did not have clinical evidence of a bacterial co-infection. Antibiotics may not be beneficial to COVID-19 patients without clinical evidence of a bacterial co-infection.

Reducing Broad Spectrum Antimicrobial Use in Extracorporeal Membrane Oxygenation (ECMO): Reduce AMMO Study

2021 ◽  
Author(s):  
Aditya Shah ◽  
Priya Sampathkumar ◽  
Ryan W Stevens ◽  
John K Bohman ◽  
Brian D Lahr ◽  
...  
Keyword(s):  
Time Series ◽  
Extracorporeal Membrane Oxygenation ◽  
Broad Spectrum ◽  
Antimicrobial Prophylaxis ◽  
Current Evidence ◽  
Antimicrobial Use ◽  
Infection Rates ◽  
Interrupted Time Series Analysis ◽  
Membrane Oxygenation ◽  
The Impact

Abstract Background The use of extracorporeal membrane oxygenation (ECMO) in critically ill adults is increasing. There are currently no guidelines for antimicrobial prophylaxis. We analyzed 7 years of prophylactic antimicrobial use across three time series for patients on ECMO at our institution in the development, improvement, and streamlining of our ECMO antimicrobial prophylaxis protocol. Study design and Methods In this quasi-experimental interrupted time series analysis, we evaluated the impact of an initial ECMO antimicrobial prophylaxis protocol, implemented in 2014, on antimicrobial use and NHSN reportable infection rates. Then, following a revision and streamlining of the protocol in November 2018, we re-evaluated the same metrics. Results Our study population included 338 ICU patients who received ECMO between July 2011 and November 2019. After implementation of the first version of the protocol we did not observe significant changes in antimicrobial use or infection rates in these patients; however, following revision and streamlining of the protocol, we demonstrated a significant reduction in broad spectrum antimicrobial use for prophylaxis in patients on ECMO without any evidence of a compensatory increase in infection rates. Conclusion Our final protocol significantly reduces broad spectrum antimicrobial use for prophylaxis in patients on ECMO. We propose a standard antimicrobial prophylaxis regimen for patients on ECMO based on current evidence and our experience.

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