Mariano Bizzarri

Mariano Bizzarri
Sapienza University of Rome | la sapienza · Department of Experimental Medicine

Associate Professor

About

195
Publications
57,193
Reads
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4,219
Citations
Introduction
Main research fields • Tumor microenvironment • Systems Biology approach in the integrative understanding of cell and tumour biology • Proteomic and metabolomic analysis of cells in microgravity • Cytoskeleton and fractal shape analysis in Biology and in Space Biology • Biophysical study of complex systems in Biology • Fractal and mathematical integrative analysis of biological and clinical images and dynamics data • Development of micro-electronic sensor devices in biochemistry
Additional affiliations
March 1996 - present
Sapienza University of Rome
Position
  • Professor (Associate)
Description
  • My research is mainly involved in investigating the biophysical factors that shape cell form (fractal analysis), tissue-3D organization and cell functions.
Education
October 1975 - December 1980
Sapienza University of Rome
Field of study
  • Medicine

Publications

Publications (195)
Article
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The increased concern regarding the reduction in female fertility and the impressive numbers of women undergoing fertility treatment support the existence of environmental factors beyond inappropriate programming of developing ovaries. Among these factors are pyrethroids, which are currently some of the most commonly used pesticides worldwide. The...
Article
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The currently accepted theory on the influence of DNA mutations on carcinogenesis (the Somatic Mutation Theory, SMT) is facing an increasing number of controversial results that undermine the explanatory power of mutated genes considered as “causative” factors. Intriguing results have demonstrated that several critical genes may act differently, as...
Article
Introduction: Myo-inositol (MI) and d-chiro-inositol (DCI) play a key role in ovarian physiology, as they are second messengers of insulin and gonadotropins. Ex-vivo and in-vitro experiments demonstrate that both isomers are deeply involved in steroid biosynthesis, and that reduced MI-to-DCI ratios are associated with pathological imbalance of sex...
Article
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Alpha-lipoic acid (ALA) plays a key role in many physiological processes, exerting anti-inflammatory, immunomodulatory, antioxidant, detoxifying, and insulin sensitizing activities. Since ALA improves insulin resistance (IR), it has been suggested that ALA could be beneficial it in the treatment of PCOS. The natural polyol myo-Inositol (myo-Ins) an...
Chapter
Current studies on “personalized medicine” focus prevalently on network-based models of genome function. Since the eighties, the agenda of pharmacology discovery was dictated by aiming at discovering key, causative targets. In this perspective, genes assume a fundamental “causal” role while cells simply act as causal proxies, dispensable because th...
Article
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We investigated menstrual irregularities after the first and second doses of the COVID-19 vaccine. Women answered a customised online questionnaire (ClinicalTrial.gov ID: NCT05083065) aimed to assess the vaccine type, the phase of the menstrual cycle during which the vaccine was administered, the occurrence of menstrual irregularities after the fir...
Article
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Microgravity impairs tissue organization and critical pathways involved in the cell-microenvironment interplay, where fibroblasts have a critical role. We exposed dermal fibroblasts to simulated microgravity by means of a Random Positioning Machine (RPM), a device that reproduces conditions of weightlessness. Molecular and structural changes were a...
Chapter
The multilevel organization of nature is self-evident: proteins do interact among them to give rise to an organized metabolism and the same hierarchical organization is in action for gene expression, tissue and organ architectures, and ecological systems.The still more common approach to such state of affairs is to think that causally relevant even...
Article
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The agenda of pharmacology discovery in the field of personalized oncology was dictated by the search of molecular targets assumed to deterministically drive tumor development. In this perspective, genes play a fundamental “causal” role while cells simply act as causal proxies, i.e., an intermediate between the molecular input and the organismal ou...
Article
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Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently bo...
Article
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OBJECTIVE: The quality of the embryo is crucial for the outcome of in vitro fertilization; however, the ability to accurately distinguish embryos with the highest reproductive potential from others is not entirely reliable. Most of the methods of classification of embryos in Assisted Reproductive Technologies (ART) are subjective and in clinical pr...
Article
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Background. Health and social management of the SARS-CoV-2 epidemic, responsible for the COVID-19 disease, requires both screening tools and diagnostic procedures. Reliable screening tests aim at identifying (truely) infectious individuals that can spread the viral infection and therefore are essential for tracing and harnessing the epidemic diffus...
Article
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This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage...
Article
The deregulation of PI3K/Akt signaling is among the most causes in inducing the acquisition of a metastatic phenotype in breast cancer cells, leading to Epithelial-Mesenchymal Transition (EMT). Inhibition of the PI3K/Akt pathway is known to be beneficial in the clinical setting. However, the activation of secondary pathways and toxicity profiles of...
Article
Myo-inositol and D-chiro-inositol are insulin sensitising agents. In the ovary, myo-inositol acts as second messenger of Follicle Stimulating Hormone (FSH). Both molecules were administered to Polycystic Ovary Syndrome (PCOS) women. The gynaecologist Vittorio Unfer was the first to give specific value to myo-inositol for the treatment of PCOS: this...
Article
In late 2019, the new Coronavirus has been identified in the city of Wuhan (China) then COVID-19 spreads like wildfire in the rest of the world. Pregnant women represent a risk category for increased abortion rates and vertical transmission with adverse events on the newborns has been recently confirmed. The scientific world is struggling for findi...
Article
Objective: The inhibition of the metastatic capability of cancer cells is a pivotal aim of current anticancer strategies. We investigated herein the anti-migrating and anti-invasive properties of Zebrafish embryo extracts (SL) - an integrative formula comprising morphogenetic factors extracted from zebrafish embryos - alone or in association with...
Article
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Metazoan living cells exposed to microgravity undergo dramatic changes in morphological and biological properties, which ultimately lead to apoptosis and phenotype reprogramming. However, apoptosis can occur at very different rates depending on the experimental model, and in some cases, cells seem to be paradoxically protected from programmed cell...
Article
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Objective: D-chiro-Inositol has been widely used in clinical practice to induce ovulation in women with polycystic ovary syndrome. Only recent evidence established that this molecule acts through two different mechanisms, with potentially different outcomes. On the one hand, under a metabolic perspective, D-chiro-Inositol improves insulin signalin...
Article
In late 2019, the new Coronavirus has been identified in the city of Wuhan then COVID-19 spreads like wildfire in the rest of the world infecting circa 23 million people with about 1,000,000 deaths up today. Pregnant women represent a risk category for increased abortion rates and vertical transmission with adverse events on the newborns has been r...
Article
Full-text available
Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promo...
Article
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COVID-19 pandemic in Italy displayed a spatial distribution that made the tracking of its time course quite difficult. The most relevant anomaly was the marked spatial heterogeneity of COVID-19 diffusion. Lombardia region accounted for around 60% of fatal cases (while hosting 15% of Italian population). Moreover, 86% of fatalities concentrated in f...
Article
Introduction: Obstetric history and maternal body composition and lifestyle may be associated with serious complications both for the mother, such as gestational diabetes mellitus (GDM), and for the fetus, including congenital malformations such as neural tube defects (NTDs). Areas covered: In view of the recent knowledge, changes in nutritional an...
Article
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Overactivation of the c‐MET/HGF system is a feature of many cancers. We previously reported that type II testicular germ cell tumor (TGCT) cells express the c‐MET receptor, forming non‐seminomatous lesions that are more positive compared with seminomatous ones. Notably, we also demonstrated that NT2D1 non‐seminomatous cells (derived from an embryon...
Article
To date, the spread of SARS-CoV-2 infection is increasing worldwide and represents a primary healthcare emergency. Although the infection can be asymptomatic, several cases develop severe pneumonia and acute respiratory distress syndrome (ARDS) characterized by high levels of pro-inflammatory cytokines, primarily interleukin (IL)-6. Based on availa...
Article
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The presence of abnormal ovarian ratios of myo-inositol (MI) to D-chiro-inositol (DCI) is a recurrent feature in PCOS. Available evidence suggests that MI and DCI may modulate steroid biosynthesis, likely in an opposite manner. Specifically, MI seems to induce estrogen production, while DCI has a role in the synthesis of androgens. Elevated insulin...
Article
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Inositol and its phosphate metabolites play a pivotal role in several biochemical pathways and gene expression regulation: inositol pyrophosphates (PP-IPs) have been increasingly appreciated as key signaling modulators. Fluctuations in their intracellular levels hugely impact the transfer of phosphates and the phosphorylation status of several targ...
Article
Breast cancer is the most common cancer among women and its metastasis which generally observed at the last stage is the major cause of breast cancer-related death. Therefore, the agents that have the potential to prevent metastatic and invasive nature of breast cancer can open up new therapeutic strategies. Melatonin, a major hormone of pineal gla...
Article
Several studies have shown that cancer cells can be “phenotypically reversed”, thus achieving a “tumor reversion”, by losing malignant hallmarks as migrating and invasive capabilities. These findings suggest that genome activity can switch to assume a different functional configuration, i.e. a different Gene Regulatory Network pattern. Indeed, once...
Article
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The “magic” word complexity evokes a multitude of meanings that obscure its real sense. Here we try and generate a bottom-up reconstruction of the deep sense of complexity by looking at the convergence of different features shared by complex systems. We specifically focus on complexity in biology but stressing the similarities with analogous featur...
Article
The ongoing worldwide pandemic of Coronavirus disease 2019 (COVID-19), raised the urgency to address knowledge gaps and to establish evidence for improving management and control of this viral infection. Throughout a keen analysis of the World Health Organization (WHO) most updated data, a gender-specific difference in the occurrence of infection w...
Preprint
Full-text available
COVID-19 pandemic in Italy had a spatial distribution that made the tracking of its time course quite difficult. The most relevant anomaly was the marked spatial heterogeneity of pandemics. Lombardia region accounted for around 60% of fatal cases (while hosting 15% of Italian population); moreover, 86% of fatalities concentrated in four Northern It...
Article
Full-text available
The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic cells. Using the model of murine MC3T3-E1 os...
Article
It is well known that myo-inositol (MI) and D-chiro-inositol (DCI) are insulin-sensitizing agents, and MI is of proven utility in polycystic ovary syndrome (PCOS). In addition, MI plays a pivotal role in the physiology of reproduction, and has beneficial effects on the development of oocytes, spermatozoa, and embryos. By contrast, DCI has little ef...
Chapter
Current network-based models, their heuristic and epistemological value notwithstanding, only partially explain the unfathomable complexity behind the outbreak of a disease, as they are habitually centered on an integrated representation of the cell biochemical and genetic pathways, and, as such, they discard the contribution of non-genetic factors...
Article
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Gravity is a constitutive force that influences life on Earth. It is sensed and translated into biochemical stimuli through the so called “mechanosensors”, proteins able to change their molecular conformation in order to amplify external cues causing several intracellular responses. Mechanosensors are widely represented in the human body with impor...
Article
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Introduction: This Experts’ opinion aims to offer an updated scientific support for the therapeutic use of Inositols in Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM), providing a practical support for gynecologists, obstetricians, endocrinologists, nutritionists, developmental and system biologists, n...
Article
Most drugs have a natural compound ‘ancestor’ acting as the lead molecule. Classic pharmacology does not explicitly take into consideration the peculiarities of natural origin compounds, the mechanism of action of which is interpreted by the same target-specific mode of action used for synthetic molecules. Over the past few decades, this approach h...
Article
The outbreak of Sars-CoV-2 (COVID-19) poses serious challenges to people's health worldwide. The management of the disease is mostly supportive, and respiratory failure from acute respiratory distress syndrome is the leading cause of death in a significant proportion of affected patients. Preliminary data point out that dramatic increase in IL-6 an...
Article
Studies performed in absence of gravitational constraint show that a living system is unable to choose between two different phenotypes, thus leading cells to segregate into different, alternative stable states. This finding demonstrates that the genotype does not determine by itself the phenotype but requires additional, physical constraints to fi...
Article
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Oxygenation conditions are crucial for growth and tumor progression. Recent data suggests a decrease in cancer cell proliferation occurring after exposure to normobaric hyperoxia. Those changes are associated with fractal dimension. The purpose of this research was to study the impact of hyperoxia on apoptosis and morphology of leukemia cell lines....
Article
The widely recognized problems of pharmacological strategies based on killing cancer cells demand a rethink of therapeutic approaches. Tumor reversion strategies that aim to shift cancer cells to a healthy differentiated state are a promising alternative. Although many studies have firmly demonstrated the possibility of reverting cancer to a normal...
Book
This volume – for pharmacologists, systems biologists, philosophers and historians of medicine – points to investigate new avenues in pharmacology research, by providing a full assessment of the premises underlying a radical shift in the pharmacology paradigm. The pharmaceutical industry is currently facing unparalleled challenges in developing inn...
Article
Graphs are powerful structures able to capture topological and semantic information from data, hence suitable for modelling a plethora of real-world (complex) systems. For this reason, graph-based pattern recognition gained a lot of attention in recent years. In this paper, a general-purpose classification system in the graphs domain is presented....
Article
Full-text available
Cells in simulated microgravity undergo a reversible morphology switch, causing the appearance of two distinct phenotypes. Despite the dramatic splitting into an adherent-fusiform and a floating-spherical population, when looking at the gene-expression phase space, cell transition ends up in a largely invariant gene transcription profile characteri...
Article
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The fall of reductionist approaches to explanation leaves biology with an unescapable challenge: how to decipher complex systems. This entails a number of very critical questions, the most basic ones being: “What do we mean by ‘complex’?” and “What is the system we should look for?” In complex systems, constraints belong to a higher level that the...
Article
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Some yet unidentified factors released by both oocyte and embryonic microenvironments demonstrated to be non-permissive for tumor development and display the remarkable ability to foster cell/tissue reprogramming, thus ultimately reversing the malignant phenotype. In the present study we observed how molecular factors extracted from Zebrafish embry...
Article
In the above article, the name of the first author was spelled incorrectly. This has been corrected in the HTML and PDF versions of the article.
Article
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The presence of microgravity conditions deeply affects the human body functions at the systemic, organ and cellular levels. This study aimed to investigate the effects induced by simulated-microgravity on non-stimulated Jurkat lymphocytes, an immune cell phenotype considered as a biosensor of the body responses, in order to depict at the cellular l...
Article
What does it mean to say that event X caused outcome Y in biology? Explaining the causal structure underlying the dynamic function of living systems is a central goal of biology. Transformative advances in regenerative medicine and synthetic bioengineering will require efficient strategies to cause desired system-level outcomes. We present a perspe...
Article
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Abstract Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cul...
Article
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Tumor glycolysis is a self-organized nonlinear mechanism that can exhibit oscillations under certain conditions. Experimental evidence suggests that glycolytic oscillations may give certain advantages to cancer, including resistance to therapies. A previously developed oscillating glycolysis model was modified with the objective of theoretically ev...
Article
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: c-MET pathway over-activation is the signature of malignancy acquisition or chemotherapy resistance of many cancers. We recently demonstrated that type II Testicular Germ Cell Tumours (TGCTs) express c-MET receptor. In particular, we elucidated that the non-seminoma lesions express c-MET protein at higher level, compared with the seminoma ones. I...
Article
Full-text available
In the past decades, both the importance of inositol for human health and the complex interaction between glucose and inositol have been the subject of increasing consideration. Glucose has been shown to interfere with cellular transmembrane transport of inositol, inhibiting, among others, its intestinal absorption. Moreover, intracellular glucose...
Article
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Mice exposed to continuous light undergo functional and histological changes that mimic those of human Polycystic Ovary Syndrome (PCOS). We herein induced the syndrome by exposing 30‐day‐old females to 10 weeks of permanent light. Ovarian morphology and histology, as well as reproductive parameters (time of observed pregnancy/delivery) were investi...
Article
Full-text available
Type II testicular germ cell tumors (TGCTs) represent the most frequent malignancy in Caucasian males (20–40 years). Even if diagnosed with disseminated disease, >80% of patients are cured; however, a small percentage of cases progress and result in death. It is commonly accepted that these cancers arise from a disturbed testicular embryonic niche...
Article
Objective: Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of anticancer agents. Yet, CIPN pathophysiology is poorly understood, and there is a lack of well-tolerated pharmacological remedies helpful to prevent or treat it. Therefore, new s...
Article
Herewith we discuss a network model of the epithelial–mesenchymal transition (EMT) based on our previous proposed framework. The EMT appears as a “first order” phase transition process, analogous to the transitions observed in the chemical–physical field. Chiefly, EMT should be considered a transition characterized by a supercritical Andronov–Hopf...
Article
Through activation of the ERK pathway nicotine, in both normal MCF-10A and low malignant breast cancer cells (MCF7), promotes increased motility and invasiveness. Melatonin antagonizes both these effects by inhibiting almost completely ERK phosphorylation. As melatonin has no effect on not-stimulated cells, it is likely that melatonin can counterac...
Preprint
Full-text available
Manned space flight has been the greatest human and technological adventure of the past half-century. Putting people into places and situations unprecedented in history is stirred the imagination while the human experience was expanding and redefining. Yet, space exploration compels humans to confront a hostile environment of cosmic radiations, rad...
Article
Data obtained by studying mammalian cells in absence of gravity strongly support the notion that cell fate specification cannot be understood according to the current molecular model. A paradigmatic case in point is provided by studying cell populations growing in absence of gravity. When the physical constraint (gravity) is 'experimentally removed...