Building an artificial cardiac microenvironment. A focus on the extracellular matrix

The increased knowledge in cell signals and stem cell differentiation, together with the development of new technologies, such as 3D bioprinting, has made the generation of artificial tissues more feasible for in vitro studies and in vivo applications. In the human body, cell fate, function, and survival are determined by the microenvironment, a rich and complex network composed of extracellular matrix (ECM), different cell types, and soluble factors. They all interconnect and communicate, receiving and sending signals, modulating and responding to cues. In the cardiovascular field, the culture of stem cells in vitro and their differentiation into cardiac phenotypes is well established, although differentiated cardiomyocytes often lack the functional maturation and structural organization typical of the adult myocardium. The recreation of an artificial microenvironment as similar as possible to the native tissue, though, has been shown to partly overcome these limitations, and can be obtained through the proper combination of ECM molecules, different cell types, bioavailability of growth factors (GFs), as well as appropriate mechanical and geometrical stimuli. This review will focus on the role of the ECM in the regulation of cardiac differentiation, will provide new insights on the role of supporting cells in the generation of 3D artificial tissues, and will also present a selection of the latest approaches to recreate a cardiac microenvironment in vitro through 3D bioprinting approaches

Editorial: Fibrosis and inflammation in tissue pathophysiology

In adult mammals, tissue damage activates a wound healing response with acute inflammation followed by either complete repair (for low-grade damage or in highly regenerative tissues, such as the liver) or replacement fibrosis (for extensive damage or in poorly regenerative tissues, such as the myocardium). Persistent damage and repeated insults sustain continuous activation of repair pathways leading to chronic inflammation, progressive tissue fibrosis and sclerosis. Despite the evolutionary advantage conferred by scarring as a rapid repair mechanism, chronic fibrosis leads to tissue adverse remodeling and impaired function. Persistent low-level inflammation and fibrosis are observed in many pathological conditions (e.g. hypertension, obesity, diabetes, genetic diseases), and lead to further complications including atherosclerosis and ischemic events, organ failure, autoimmune diseases, cancer, aging, and reduced resilience to infectious diseases. Pathological fibrosis plays a major role in a wide range of diseases, accounting for an increasingly large fraction of mortality cases worldwide. While recent advances have unveiled many environmental and genetic causes of fibrotic disorders, a better understanding of both ubiquitous and tissue-specific regulatory pathways and cellular dynamics could help to design new targeted therapies, and to identify the etiology of idiopathic diseases. Within this Research Topic, we invite submission of articles (reviews, original research, or methodology articles) on the pathophysiological role of fibrosis and inflammation in different tissues. Areas to be covered include, but are not limited to: - genetic and environmental causes of persistent low-level inflammation and fibrosis (e.g. autoimmunity, hypertension, obesity, diabetes, genetic diseases, latent infections); - comorbidities including systemic sclerosis, neurological disorders, organ failure (heart, skeletal muscle, kidney, liver, lungs), cancer, and reduced resilience to infectious diseases; - in vivo (animal models) and in vitro (organoids, tissue culture) modelling of fibrotic diseases for the discovery of novel therapeutic targets and potential tissue-specific treatments; - vascular responses to inflammation and inflammation of vascular tissues; - system biology approaches to identify molecular and cellular networks leading to chronic inflammation and fibrosis

Air-coupled, focused ultrasonic dispersion spectrum reconstruction in plates

This paper presents and demonstrates a noncontact method for measuring the Lamb wave dispersion spectrum of a plate. Noncontact air-coupled source and receive transducers are used with line-focus mirrors and 50–700 kHz broadband apparatus for simultaneous measurement over a broad spectrum of refractive angles and multiple guided modes. Broadband, wide-angle wave forms are measured as a function of position. The Fourier transform of these wave forms from the t – x domain to the v – k domain gives an approximate spectrum of the dispersion relation. We measure the dispersion spectra of Lucite™, aluminum, balsa wood, and a carbon fiber epoxy laminate, and show that the measured spectra agree well with the dispersion relation calculated from Lamb wave theory

Functional impairment of human resident cardiac stem cells by the cardiotoxic antineoplastic agent trastuzumab

Trastuzumab (TZM), a monoclonal antibody against the ERBB2 protein, increases survival in ERBB2-positive breast cancer patients. Its clinical use, however, is limited by cardiotoxicity. We sought to evaluate whether TZM cardiotoxicity involves inhibition of human adult cardiac-derived stem cells, in addition to previously reported direct adverse effects on cardiomyocytes. To test this idea, we exposed human cardiosphere-derived cells (hCDCs), a natural mixture of cardiac stem cells and supporting cells that has been shown to exert potent regenerative effects, to TZM and tested the effects in vitro and in vivo. We found that ERBB2 mRNA and protein are expressed in hCDCs at levels comparable to those in human myocardium. Although clinically relevant concentrations of TZM had no effect on proliferation, apoptosis, or size of the c-kit-positive hCDC subpopulation, in vitro assays demonstrated diminished potential for cardiogenic differentiation and impaired ability to form microvascular networks in TZM-treated cells. The functional benefit of hCDCs injected into the border zone of acutely infarcted mouse hearts was abrogated by TZM: infarcted animals treated with TZM + hCDCs had a lower ejection fraction, thinner infarct scar, and reduced capillary density in the infarct border zone compared with animals that received hCDCs alone (n = 12 per group). Collectively, these results indicate that TZM inhibits the cardiomyogenic and angiogenic capacities of hCDCs in vitro and abrogates the morphological and functional benefits of hCDC transplantation in vivo. Thus, TZM impairs the function of human resident cardiac stem cells, potentially contributing to TZM cardiotoxicity

Chronically Sun-damaged Melanomas Express Low Levels of Nuclear Glutathione-S-transferase-π: An Epidemiological and Clinicopathological Study in Italy

The detoxifying enzyme glutathione–s–transferase pi (GST–π) is present in keratinocytes and melanocytes and exerts a protective role against tumour progression. Melanomas close to melanocytic naevus remnants occur less frequently on sun-exposed areas, whereas solar dermal elastosis, hallmark of chronic sun-damage, characterise melanomas on sun-exposed skin. We evaluated the expression of GST-π in 113 melanomas associated to melanocytic naevus remnants or to solar dermal elastosis, classified according to clinical characteristics, history of sun exposure, histological subtypes and AJCC staging. Chronically sun-damaged melanomas, identified by moderate–severe solar dermal elastosis, showed a lower nuclear GST-π expression and a higher thickness than those related to melanocytic naevus remnants (p < 0.03). Multivariate logistic regression analysis demonstrated that male gender and chronic sun-exposure are independent risk factors significantly associated to melanomas localised on the trunk (OR = 3.36, 95% CI: 1.31–8.65; OR = 5.97, 95% CI: 1.71–20.87). If confirmed on a larger series, lower expression of nuclear GST-π in melanom

The prevalence of cubital tunnel syndrome: A cross-sectional study in a U.S. metropolitan cohort

BACKGROUND: Although cubital tunnel syndrome is the second most common peripheral mononeuropathy (after carpal tunnel syndrome) encountered in clinical practice, its prevalence in the population is unknown. The objective of this study was to evaluate the prevalence of cubital tunnel syndrome in the general population. METHODS: We surveyed a cohort of adult residents of the St. Louis metropolitan area to assess for the severity and localization of hand symptoms using the Boston Carpal Tunnel Questionnaire Symptom Severity Scale (BCTQ-SSS) and the Katz hand diagram. We identified subjects who met our case definitions for cubital tunnel syndrome and carpal tunnel syndrome: self-reported hand symptoms associated with a BCTQ-SSS score of >2 and localization of symptoms to the ulnar nerve or median nerve distributions. RESULTS: Of 1,001 individuals who participated in the cross-sectional survey, 75% were women and 79% of the cohort was white; the mean age (and standard deviation) was 46 ± 15.7 years. Using a more sensitive case definition (lax criteria), we identified 59 subjects (5.9%) with cubital tunnel syndrome and 68 subjects (6.8%) with carpal tunnel syndrome. Using a more specific case definition (strict criteria), we identified 18 subjects (1.8%) with cubital tunnel syndrome and 27 subjects (2.7%) with carpal tunnel syndrome. CONCLUSIONS: The prevalence of cubital tunnel syndrome in the general population may be higher than that reported previously. When compared with previous estimates of disease burden, the active surveillance technique used in this study may account for the higher reported prevalence. This finding suggests that a proportion of symptomatic subjects may not self-identify and may not seek medical treatment. CLINICAL RELEVANCE: This baseline estimate of prevalence for cubital tunnel syndrome provides a valuable reference for future diagnostic and prognostic study research and for the development of clinical practice guidelines

Free Wave Propagation in Plates of General Anisotropic Media

The propagation of Lamb waves in plates has been the subject of numerous investigations since their postulation by Lamb in 1916 [1,2]. Most of the work in existence deals with various aspects of these guided waves in plates of isotropic materials. Comparatively speaking a limited number of results has appeared in which Lamb or horizontaly polarized SH wave propagation in anisotropic plates has been considered in any detail. For Lamb waves, theoretical analyses have been reported in plates of cubic [3,4], transversely isotropic [5,6], and orthotropic [7,9] media

Ischemic heart disease pathophysiology paradigms overview. from plaque activation to microvascular dysfunction

Ischemic heart disease still represents a large burden on individuals and health care resources worldwide. By conventions, it is equated with atherosclerotic plaque due to flow-limiting obstruction in large–medium sized coronary arteries. However, clinical, angiographic and autoptic findings suggest a multifaceted pathophysiology for ischemic heart disease and just some cases are caused by severe or complicated atherosclerotic plaques. Currently there is no well-defined assessment of ischemic heart disease pathophysiology that satisfies all the observations and sometimes the underlying mechanism to everyday ischemic heart disease ward cases is misleading. In order to better examine this complicated disease and to provide future perspectives, it is important to know and analyze the pathophysiological mechanisms that underline it, because ischemic heart disease is not always determined by atherosclerotic plaque complication. Therefore, in order to have a more complete comprehension of ischemic heart disease we propose an overview of the available pathophysiological paradigms, from plaque activation to microvascular dysfunction

Airborne non-contact and contact broadband ultrasounds for frequency attenuation profile estimation of cementitious materials

[EN] In this paper, the study of frequency-dependent ultrasonic attenuation in strongly heterogeneous cementitious materials is addressed. To accurately determine the attenuation over a wide frequency range, it is necessary to have suitable excitation techniques. We have analysed two kinds of ultrasound techniques: contact ultrasound and airborne non-contact ultrasound. The mathematical formulation for frequency-dependent attenuation has been established and it has been revealed that each technique may achieve similar results but requires specific different calibration processes. In particular, the airborne non-contact technique suffers high attenuation due to energy losses at the air-material interfaces. Thus, its bandwidth is limited to low frequencies but it does not require physical contact between transducer and specimen. In contrast, the classical contact technique can manage higher frequencies but the measurement depends on the pressure between the transducer and the specimen. Cement specimens have been tested with both techniques and frequency attenuation dependence has been estimated. Similar results were achieved at overlapping bandwidth and it has been demonstrated that the airborne non-contact ultrasound technique could be a viable alternative to the classical contact technique.The authors acknowledge the support from University College Cork (Ireland), Universidad Politecnica de Valencia and the Spanish Administration under grant BIA2014-55311-C2-2-P and Salvador Madariaga's Programme (PR2016-00344/PR2017-00658).Gosálbez Castillo, J.; Wright, W.; Jiang, W.; Carrión García, A.; Genovés, V.; Bosch Roig, I. (2018). Airborne non-contact and contact broadband ultrasounds for frequency attenuation profile estimation of cementitious materials. Ultrasonics. 88:148-156. https://doi.org/10.1016/j.ultras.2018.03.011S1481568