Cardiovascular diseases (CVDs) constitute the prime cause of global mortality, with an immense impact on patient quality of life and disability. Clinical evidence has revealed a strong connection ...between cellular senescence and worse cardiac outcomes in the majority of CVDs concerning both ischemic and nonischemic cardiomyopathies. Cellular senescence is characterized by cell cycle arrest accompanied by alterations in several metabolic pathways, resulting in morphological and functional changes. Metabolic rewiring of senescent cells results in marked paracrine activity, through a unique secretome, often exerting deleterious effects on neighboring cells. Here, we recapitulate the hallmarks and key molecular pathways involved in cellular senescence in the cardiac context and summarize the different roles of senescence in the majority of CVDs. In the last few years, the possibility of eliminating senescent cells in various pathological conditions has been increasingly explored, giving rise to the field of senotherapeutics. Therefore, we additionally attempt to clarify the current state of this field with a focus on cardiac senescence and discuss the potential of implementing senolytics as a treatment option in heart disease.
Cellular senescence refers to a stress response aiming to preserve cellular and, therefore, organismal homeostasis. Importantly, deregulation of mitochondrial homeostatic mechanisms, manifested as ...impaired mitochondrial biogenesis, metabolism and dynamics, has emerged as a hallmark of cellular senescence. On the other hand, impaired mitostasis has been suggested to induce cellular senescence. This review aims to provide an overview of homeostatic mechanisms operating within mitochondria and a comprehensive insight into the interplay between cellular senescence and mitochondrial dysfunction.
Emotional eating (EE) is a disordered eating behaviour which may lead to overeating. It is not clear whether EE presents to an equal degree among adults, regardless of their body mass index (BMI) ...status. The aim of this study was to assess whether there is a difference in degree of EE between adults with healthy weight, overweight and obesity.
MEDLINE and APA PsycINFO databases were searched from inception up to January 2022 for studies that reported EE scores from validated questionnaires. The quality of all included studies was assessed using the AXIS tool. Meta-analysis used random effects and standardised mean difference (SMD). Heterogeneity was investigated using I
statistics and sensitivity analyses.
A total of 11 studies with 7207 participants were included in the meta-analysis. Degree of EE was greater in adults with a BMI above the healthy range, compared to adults with a healthy BMI (SMD 0.31, 95% CI 0.17 to 0.45; I
= 85%). However, subgroup analysis found that degree of EE was greater only in adults with obesity (SMD 0.61, 95% CI 0.41 to 0.81; I
= 62%), and there was no difference in degree of EE between adults with overweight and those with a healthy BMI.
Degree of EE is greater among adults living with obesity, compared to adults with a healthy BMI, indicating a need for behavioural support to support EE among people living with obesity seeking weight management. Future research should examine the long-term effectiveness of interventions for EE.
Pneumocystis jirovecii pneumonia (PCP) can affect various types of immunocompromised patients. We sought to evaluate the diagnostic accuracy of (1 → 3)-β-D-glucan (BDG) for the diagnosis of PCP. We ...carried out a meta-analysis of relevant studies, identified through PubMed and Scopus. Eligible studies were those that reported BDG diagnostic data in cases with documented PCP and controls with other conditions. Cases of invasive fungal infections and healthy controls were excluded. We performed a bivariate meta-analysis of sensitivity and specificity and constructed a hierarchical summary receiver operating characteristics (HSROC) curve. Fourteen studies were included in the meta-analysis. BDG data were analysed for 357 PCP cases and 1723 controls. The average (95% confidence interval) sensitivity and specificity of BDG were 94.8% (90.8–97.1%) and 86.3% (81.7–89.9%), respectively. The positive and negative likelihood ratios were 6.9 (5.1–9.3) and 0.06 (0.03–0.11), respectively. The area under the HSROC curve was 0.965 (0.945–0.978). Serum BDG shows excellent sensitivity and very good specificity in the diagnosis of PCP. Still, in clinical practice the test results should be interpreted in the context of the underlying clinical characteristics of the individual patient.
Mitochondria have emerged as key players regarding cellular homeostasis not only due to their contribution regarding energy production through oxidative phosphorylation, but also due to their ...involvement in signaling, ion regulation, and programmed cell death. Indeed, current knowledge supports the notion that mitochondrial dysfunction is a hallmark in the pathogenesis of various diseases. Mitochondrial biogenesis and function require the coordinated action of two genomes: nuclear and mitochondrial. Unfortunately, both intrinsic and environmental genotoxic insults constantly threaten the integrity of nuclear as well as mitochondrial DNA. Despite the extensive research that has been made regarding nuclear genome instability, the importance of mitochondrial genome integrity has only recently begun to be elucidated. The specific architecture and repair mechanisms of mitochondrial DNA, as well as the dynamic behavior that mitochondria exert regarding fusion, fission, and autophagy participate in mitochondrial genome stability, and therefore, cell homeostasis.
(1) Background: SARS-CoV-2 T cell immunity is rapidly activated following SARS-CoV-2 infection and vaccination and is crucial for controlling infection progression and severity. The aim of the ...present study was to compare the levels of T cell responses to SARS-CoV-2 between cohorts of subjects with hybrid immunity (convalescent and vaccinated), vaccinated naïve (non-exposed) and convalescent unvaccinated subjects. (2) Methods: We performed a retrospective descriptive analysis of data collected from the medical records of adult individuals who were consecutively examined at a large, private Medical Center of Attica from September 2021 to September 2022 in order to be examined on their own initiative for SARS-CoV-2 T cell immunity response. They were divided into three groups: Group A: SARS-CoV-2 convalescent and vaccinated subjects; Group B: SARS-CoV-2 naïve vaccinated subjects; Group C: SARS-CoV-2 convalescent unvaccinated subjects. The SARS-CoV-2 T cell response was estimated against spike (S) and nucleocapsid (N) structural proteins by performing the methodology T-SPOT.COVID test. (3) Results: A total of 530 subjects were retrospectively included in the study, 252 females (47.5%) and 278 (52.5%) males ranging from 13 to 92 years old (mean 55.68 ± 17.0 years). Among them, 66 (12.5%) were included in Group A, 284 (53.6%) in Group B and 180 (34.0%) in Group C. Among the three groups, a reaction against S antigen was reported in 58/66 (87.8%) of Group A, 175/284 (61.6%) of Group B and 146/180 (81.1%) of Group C (chi-square,
< 0.001). Reaction against N antigen was present in 49/66 (74.2%) of Group A and in 140/180 (77.7%) of Group C (chi-square,
= 0.841). The median SFC count for S antigen was 24 (range from 0-218) in Group A, 12 (range from 0-275) in Group B and 18 (range from 0-160) in Group C (Kruskal-Wallis test,
< 0.001; pairwise comparisons: groups A-B,
< 0.001; groups A-C,
= 0.147; groups B-C,
< 0.001). The median SFCs count for N antigen was 13 (range 0-82) for Group A and 18 (range 0-168) for Group C (Kruskal-Wallis test,
= 0.27 for A-C groups). (4) Conclusions: Our findings suggest that natural cellular immunity, either alone or combined with vaccination, confers stronger and more durable protection compared to vaccine-induced cellular immunity.
The genome is exposed daily to many deleterious factors. Ubiquitination is a mechanism that regulates several crucial cellular functions, allowing cells to react upon various stimuli in order to ...preserve their homeostasis. Ubiquitin ligases act as specific regulators and actively participate among others in the DNA damage response (DDR) network. UBE4B is a newly identified member of E3 ubiquitin ligases that appears to be overexpressed in several human neoplasms. The aim of this review is to provide insights into the role of UBE4B ubiquitin ligase in DDR and its association with p53 expression, shedding light particularly on the molecular mechanisms of carcinogenesis.
(ProQuest: ... denotes formulae and/or non-USASCII text omitted) The Cygnus region is a very bright and complex portion of the TeV sky, host to unidentified sources and a diffuse excess with respect ...to conventional cosmic-ray propagation models. Two of the brightest TeV sources, MGRO J2019+37 and MGRO J2031+41, are analyzed using Milagro data with a new technique, and their emission is tested under two different spectral assumptions: a power law and a power law with an exponential cutoff. The new analysis technique is based on an energy estimator that uses the fraction of photomultiplier tubes in the observatory that detect the extensive air shower. The photon spectrum is measured in the range 1-100 TeV using the last three years of Milagro data (2005-2008), with the detector in its final configuration. An F-test indicates that MGRO J2019+37 is better fit by a power law with an exponential cutoff than by a simple power law. The best-fitting parameters for the power law with exponential cutoff model are a normalization at 10 TeV of ... x 10 super(-10) s super(-1) m super(-2) TeV super(-1), a spectral index of ... and a cutoff energy of ... TeV. MGRO J2031+41 shows no evidence of a cutoff. The best-fitting parameters for a power law are a normalization of ... x 10 super(-10) s super(-1) m super(-2) TeV super(-1) and a spectral index of ... The overall flux is subject to a ~30% systematic uncertainty. The systematic uncertainty on the power-law indices is ~0.1. Both uncertainties have been verified with cosmic-ray data. A comparison with previous results from TeV J2032+4130, MGRO J2031+41, and MGRO J2019+37 is also presented.
Simultaneous Swift and Fermi observations of gamma-ray bursts (GRBs) offer a unique broadband view of their afterglow emission, spanning more than 10 decades in energy. We present the sample of X-ray ...flares observed by both Swift and Fermi during the first three years of Fermi operations. While bright in the X-ray band, X-ray flares are often undetected at lower (optical), and higher (MeV to GeV) energies. We show that this disfavors synchrotron self-Compton processes as the origin of the observed X-ray emission. We compare the broadband properties of X-ray flares with the standard late internal shock model, and find that in this scenario, X-ray flares can be produced by a late-time relativistic (Gamma > 50) outflow at radii R ~ 10 super(13)-10 super(14) cm. This conclusion holds only if the variability timescale is significantly shorter than the observed flare duration, and implies that X-ray flares can directly probe the activity of the GRB central engine.
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