An increasing number of women with cardiac disease come up with the idea of becoming pregnant. Immigrants are frequently affected by valvular heart disease. Recently, arrhythmias, high blood pressure ...and ischemic heart disease affect many less-young pregnant women. Finally, grown-up patients with congenital heart disease have now entered their fertility period (particularly following the Fontan operation). Pregnancy is legitimate and frequently cannot be restrained; it calls for a careful evaluation of all its treatment aspects by a multidisciplinary team and the cardiologist role is of the utmost importance. A few conditions make pregnancy a hazard to both mother and fetus: pulmonary hypertension, left ventricular failure, left-heart obstruction, Marfan syndrome with aortic dilatation, and cyanosis. Most remaining cases are compatible with an (almost) normal course whereby mothers can be reassured. However, all items covered by guidelines should be met, according to the quality imperative.
In order to better understand the pathogenesis of Parkinson's Disease (PD) it is important to consider possible contributory factors inherent to the aging process, as age-related changes in a number ...of physiological systems (perhaps incurred within particular environments) appear to influence the onset and progression of neurodegenerative disorders. Accordingly, we posit that a principal mechanism underlying PD is inflammaging, i.e. the chronic inflammatory process characterized by an imbalance of pro- and anti-inflammatory mechanisms which has been recognized as operative in several age-related, and notably neurodegenerative diseases. Recent conceptualization suggests that inflammaging is part of the complex adaptive mechanisms (“re-modeling”) that are ongoing through the lifespan, and which function to prevent or mitigate endogenous processes of tissue disruption and degenerative change(s). The absence of an adequate anti-inflammatory response can fuel inflammaging, which propagates on both local (i.e.- from cell to cell) and systemic levels (e.g.- via exosomes and other molecules present in the blood). In general, this scenario is compatible with the hypothesis that inflammaging represents a hormetic or hormetic-like effect, in which low levels of inflammatory stress may prompt induction of anti-inflammatory mediators and mechanisms, while sustained pro-inflammatory stress incurs higher and more durable levels of inflammatory substances, which, in turn prompt a local-to-systemic effect and more diverse inflammatory response(s). Given this perspective, new treatments of PD may be envisioned that strategically are aimed at exerting hormetic effects to sustain anti-inflammatory responses, inclusive perhaps, of modulating the inflammatory influence of the gut microbiota.
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•Aging is the major risk factor for Parkinson's Disease.•Inflammaging is a basic mechanism in neurodegeneration.•Inflammaging could be considered as a hormetic adaptation with opposite effects during the life.•Senescent and inflammatory cells (astrocytes, microglia) are present in the brain of PD patients.•Gut microbiota dysbiosis is associated with PD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Age‐related changes in the brain reflect a dynamic interaction of genetic, epigenetic, phenotypic, and environmental factors that can be temporally restricted or more longitudinally present ...throughout the lifespan. Fundamental to these mechanisms is the capacity for physiological adaptation through modulation of diverse molecular and biochemical signaling occurring from the intracellular to the network‐systemic level throughout the brain. A number of agents that affect the onset and progression of Parkinson's disease (PD)‐like effects in experimental models exhibit temporal features, and mechanisms of hormetic dose responses. These findings have particular significance since the hormetic dose response describes the amplitude and range of potential therapeutic effects, thereby affecting the design and conduct of studies of interventions against PD (and other neurodegenerative diseases), and may also be important to a broader consideration of hormetic processes in resilient adaptive responses that might afford protection against the onset and/or progression of PD and related disorders.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Lichen Planopilaris (LPP) is a lymphatic disease affecting the scalp that is characterized by a chronic and destructive inflammation process, named as 'cicatricial alopecia' in which the hair ...follicles are targeted and may involve predominantly lymphocytes or neutrophils. Scalp and biopsy layers have never been used to investigate microbial community composition and its relative taxa abundances in LPP. We sought to examine the significant taxa of this chronic relapsing inflammatory skin disease, together with inspect the existing connections with metabolic pathways featuring this microbial community. We used a multilevel analysis based on 16S rRNA marker sequencing in order to detect OTU abundances in pathologic/healthy samples, real time PCR for measuring the levels of IL-23 interleukin expression and urinary metabolomics to find out volatile organic metabolites (VOMs). By using a linear regression model, we described peculiar taxa that significantly differentiated LPP and healthy samples. We inspected taxa abundances and interleukin mRNA levels and the Microbacteriaceae family resulted negatively correlated with the IL-23 expression. Moreover, starting from 16S taxa abundances, we predicted the metabolic pathways featuring this microbial community. By inspecting microbial composition, sample richness, metabolomics profiles and the relative metabolic pathways in a cohort of LPP and healthy samples we deepened the contribution of significant taxa that are connected to inflammation maintenance and microbiota plasticity in LPP pathology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In Alzheimer's disease (AD) basic research and drug discovery, mouse models are essential resources for uncovering biological mechanisms, validating molecular targets and screening potential ...compounds. Both transgenic and non-genetically modified mouse models enable access to different types of AD-like pathology in vivo. Although there is a wealth of genetic and biochemical studies on proposed AD pathogenic pathways, as a disease that centrally features cognitive failure, the ultimate readout for any interventions should be measures of learning and memory. This is particularly important given the lack of knowledge on disease etiology – assessment by cognitive assays offers the advantage of targeting relevant memory systems without requiring assumptions about pathogenesis. A multitude of behavioral assays are available for assessing cognitive functioning in mouse models, including ones specific for hippocampal-dependent learning and memory. Here we review the basics of available transgenic and non-transgenic AD mouse models and detail three well-established behavioral tasks commonly used for testing hippocampal-dependent cognition in mice – contextual fear conditioning, radial arm water maze and Morris water maze. In particular, we discuss the practical considerations, requirements and caveats of these behavioral testing paradigms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A large portion of the human genome transcribes RNA sequences that do not code for any proteins. The first of these sequences was identified in 1993, and the best known noncoding RNAs are microRNA ...(miRNAs). It is now fully established that miRNAs regulate approximately 30% of the known genes that codify proteins. miRNAs are involved in several biological processes, like cell proliferation, differentiation, apoptosis and metastatization. These RNA products regulate gene expression at the post-transcriptional level, modulating or inhibiting protein expression by interacting with specific sequences of mRNAs. Mature miRNAs can be detected in blood plasma, serum and also in a wide variety of biological fluids. They can be found associated with proteins, lipids as well as enclosed in exosome vesicles. We know that circulating miRNAs (C-miRNAs) can regulate several key cellular processes in tissues different from the production site. C-miRNAs behave as endogenous mediators of RNA translation, and an extraordinary knowledge on their function has been obtained in the last years. They can be secreted in different tissue cells and associated with specific pathological conditions. Significant evidence indicates that the initiation and progression of several pathologies are “highlighted” by the presence of specific C-miRNAs, underlining their potential diagnostic relevance as clinical biomarkers. Here we review the current literature on the possible use of this new class of molecules as clinical biomarkers of diseases.
Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors characterized by aggressive behavior, high risk of distant recurrence, and poor survival. Chemotherapy is still the main ...therapeutic approach for this subgroup of patients, therefore, progress in the treatment of TNBC remains an important challenge. Data derived from molecular technologies have identified TNBCs with different gene expression and mutation profiles that may help developing targeted therapies. So far, however, only a few of these have shown to improve the prognosis and outcomes of TNBC patients. Robust predictive biomarkers to accelerate clinical progress are needed. Herein, we review prognostic and predictive biomarkers in TNBC, discuss the current evidence supporting their use, and look at the future of this research field.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Hormesis defines the limits of lifespan Calabrese, Edward J.; Osakabe, Naomi; Di Paola, Rosanna ...
Ageing research reviews,
11/2023, Volume:
91
Journal Article
Peer reviewed
Open access
This commentary provides a novel synthesis of how biological systems adapt to a broad spectrum of environmental and age-related stresses that are underlying causes of numerous degenerative diseases ...and debilitating effects of aging. It proposes that the most fundamental, evolutionary-based integrative strategy to sustain and protect health is based on the concept of hormesis. This concept integrates anti-oxidant, anti-inflammatory and cellular repair responses at all levels of biological organization (i.e., cell, organ and organism) within the framework of biphasic dose responses that describe the quantitative limits of biological plasticity in all cells and organisms from bacteria and plants to humans. A major feature of the hormetic concept is that low levels of biological, chemical, physical and psychological stress upregulate adaptive responses that not only precondition, repair and restore normal functions to damaged tissues/organs but modestly overcompensate, reducing ongoing background damage, thereby enhancing health beyond that in control groups, lacking the low level "beneficial" stress. Higher doses of such stress often become counterproductive and eventually harmful. Hormesis is active throughout the life-cycle and can be diminished by aging processes affecting the onset and severity of debilitating conditions/diseases, especially in elderly subjects. The most significant feature of the hormetic dose response is that the limits of biological plasticity for adaptive processes are less than twice that of control group responses, with most, at maximum, being 30-60 % greater than control group values. Yet, these modest increases can make the difference between health or disease and living or dying. The quantitative features of these adaptive hormetic dose responses are also independent of mechanism. These features of the hormetic dose response determine the capacity to which systems can adapt/be protected, the extent to which biological performance (e.g., memory, resistance to injury/disease, wound healing, hair growth or lifespan) can be enhanced/extended and the extent to which synergistic interactions may occur. Hormesis defines the quantitative rules within which adaptive processes operate and is central to evolution and biology and should become transformational for experimental concepts and study design strategies, public health practices and a vast range of therapeutic strategies and interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The stria vascularis, located in the inner ear, consists of three layers, one of which is the blood-labyrinth barrier (BLB). It is formed by endothelial cells, sealed together to prevent the passage ...of toxic substances from the blood to the inner ear, by pericytes and perivascular-resident macrophage-like melanocyte.
There are various causes that lead to hearing loss, and among these are noise-induced and autoimmune hearing loss, ear disorders related to ototoxic medication, Ménière's disease, and age-related hearing loss. For all of these, major therapeutic interventions include drug-loaded nanoparticles,
intratympanic or intracochlear delivery.
Since many pathologies associated with hearing loss are characterized by a weakening of the BLB, in this review, the molecular mechanisms underlying the response to damage of BLB cellular components have been discussed. In addition, insight into the role of hormetic nutrients against hearing loss pathology is proposed.
BLB cellular components of neurovascular cochlear unit play important physiological roles, owing to their impermeable function against all ototoxic substances that can induce damage. Studies are needed to investigate the cross talk occurring between these cellular components to exploit their possible role as novel targets for therapeutic interventions that may unravel future path based on the use of hormetic nutrients.
40, 542-563.
Autism spectrum disorder (ASD) includes a heterogeneous group of complex neurodevelopmental disorders characterized by atypical behaviors with two core pathological manifestations: deficits in social ...interaction/communication and repetitive behaviors, which are associated with disturbed redox homeostasis. Modulation of cellular resilience mechanisms induced by low levels of stressors represents a novel approach for the development of therapeutic strategies, and in this context, neuroprotective effects of a wide range of polyphenol compounds have been demonstrated in several in vitro and in vivo studies and thoroughly reviewed. Mushrooms have been used in traditional medicine for many years and have been associated with a long list of therapeutic properties, including antitumor, immunomodulatory, antioxidant, antiviral, antibacterial, and hepatoprotective effects. Our recent studies have strikingly indicated the presence of polyphenols in nutritional mushrooms and demonstrated their protective effects in different models of neurodegenerative disorders in humans and rats. Although their therapeutic effects are exerted through multiple mechanisms, increasing attention is focusing on their capacity to induce endogenous defense systems by modulating cellular signaling processes such as nuclear factor erythroid 2 related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) pathways. Here we discuss the protective role of hormesis and its modulation by hormetic nutrients in ASD.
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