Flavia Franconi

Istituto Nazionale Biostrutture e Biosistemi · National Laboratory Gender Pharmacology and Medicine

Ionizing radiation (IR) can induce some associated pathological conditions due to numerous cell damages. The influence of sex is scarcely known, and even less known is whether the effect of antioxidants is sex-dependent. Given the increased use of IR, we investigated whether male human umbilical vein endothelial cells (MHUVECs) and female human umb...

The influence of sex combined with smoking and combined oral contraceptives (COC) use on atherogenic indexes is scarcely studied. Thus, traditional lipid parameters were measured, and non-traditional atherogenic indexes were calculated in a young and healthy population of men, COC-free women, and COC users. Total cholesterol (TChol), low-density li...

Type 2 diabetes mellitus is a widespread and a chronic disease associated with micro- and macrovascular complications and is a well-established risk factor for cardiovascular disease, which are among the most important causes of death in diabetic patients. This disease is strongly affected by sex and gender: sex-gender differences have been reporte...

Background The sexual dimorphism represents one of the triggers of the metabolic disparities between the organisms, advising about wild implications in research or diagnostics contexts. Despite the mounting recognition of the importance of sex consideration in the biomedical fields, the identification of male- and female-specific metabolic signatur...

AimsTo investigate whether fetal sex affects the impact of classical GDM risk factors on the diagnosis of gestational diabetes (GDM) as well as on related adverse pregnancy outcomes.Methods This retrospective observational study concerned 206,917 singleton live births born to 170,126 women aged 15–45 over the years 2010–2018 in Tuscany, Italy. GDM...

There is an urgent need to optimize pharmacology therapy with a consideration of high interindividual variability and economic costs. A sex–gender approach (which considers men, women, and people of diverse gender identities) and the assessment of differences in sex and gender promote global health, avoiding systematic errors that generate results...

Sardinia is an Italian island in the Mediterranean characterized by secular isolation and the singular genetic characteristics of its inhabitants. Findings obtained in populations with diverse genetic make-up and cultural background indicate gender differences and/or similarities in drinking characteristics of patients with alcohol use disorder (AU...

Many pieces of evidence have accumulated over time suggesting sex-and-gender differences in type 2 diabetes, the most relevant being the greater excess risk of cardiovascular diseases in women with diabetes than in men. Drugs available for the treatment of diabetes have, meanwhile, increased in number and effectiveness over the last 20 years. Nonet...

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. In addition, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we gen...

Vaccines constitute a strategy to reduce the burden of COVID-19, but the treatment of COVID-19 is still a challenge. The lack of approved drugs for severe COVID-19 makes repurposing or repositioning of approved drugs a relevant approach because it occurs at lower costs and in a shorter time. Most preclinical and clinical tests, including safety and...

Monocytes play a critical role in inflammation and immune response, their activity being sex-dependent. However, the basis of sex differences is not well understood. Therefore, we investigated the lipopolysaccharide (LPS) effects on tumor necrosis factor-α (TNF-α) release, autophagy, and chemotaxis in freshly isolated monocytes from healthy young m...

Individual response to drugs is highly variable and largely influenced by genetic variants and gene-expression profiles. Also, it has been shown that response to drugs is strongly sex-dependent, both in terms of efficacy and toxicity. To expand current knowledge on sex differences in the expression of genes relevant for drug response, we generated...

In humans, the combination of all sex-specific genetic, epigenetic, and hormonal influences of biologic sex produces different in vivo environments for male and female cells. We dissect how these influences of sex modify the pharmacokinetics and pharmacodynamics of multiple drugs and provide examples for common drugs acting on specific organ system...

Prematurity is the leading cause of neonatal deaths and high economic costs; it depends on numerous biological and social factors, and is highly prevalent in males. Several factors can affect the metabolome of premature infants. Accordingly, the aim of the present study was to analyze the role played by gestational age (GA), parenteral nutrition (P...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Biological differences between sexes should be considered in all stages of research, as sexual dimorphism starts in utero leading to sex-specific fetal programming. In numerous biomedical fields, there is still a lack of stratification by sex despite primary cultured cells retaining memory of the sex and of the donor. The sex of donors in biological...

the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...

Little information is available on the influence of sex in combination with smoking habits and combined oral contraceptives (COC) use on cellular inflammatory indexes such as neutrophil/lymphocyte ratio (NLR), derived NRL (dNLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), mean platelet volume/platelet count (MPV/PLT), aggrega...

Diabetic foot disease (DFD) is a complication of diabetes mellitus, characterized by multiple pathogenetic factors and bearing a very high burden of disability as well as of direct and indirect costs for individuals or healthcare systems. A further characteristic of DFD is that it is associated with a marked risk of subsequent hospitalizations for...

Background: Sex-gender medicine focuses on differences and similarities in health and disease between men and women. The present study focused on the existence of male and female phenotypes when routine demographic, biochemical and haematological data are considered and aimed to determine the influence of smoking on phenotypes and evaluate the rol...

Noncommunicable diseases are long-lasting and slowly progressive and are the leading causes of death and disability. They include cardiovascular diseases (CVD) and diabetes mellitus (DM) that are rising worldwide, with CVD being the leading cause of death in developed countries. Thus, there is a need to find new preventive and therapeutic approache...

The characterization of urinary metabolome, which provides a fingerprint for each individual, is an important step to reach personalized medicine. It is influenced by exogenous and endogenous factors; among them, we investigated sex influences on 72 organic acids measured through GC-MS analysis in the urine of 291 children (152 males; 139 females)...

There are conflicting results about sex differences in the response to opioids for pain control and the role of potential influencing factors of these differences has not been investigated. We meta-analyzed differences and similarities between men and women in opioid response for pain control and investigated the potential influence of baseline pai...

Phenols are a wide family of phytochemicals that are characterized by large chemical diversity and are considered to bioactive molecules of foods, beverages, and botanicals. Although they have a multitude of biological actions, their beneficial effects are rarely evidenced in clinical practice. This may occur due to the presence of numerous confoun...

There is a clear sex–gender gap in the prevention and occurrence of diseases, and in the outcomes and treatments, which is relevant to women in the majority of cases. Attitudes concerning the enrollment of women in randomized clinical trials have changed over recent years. Despite this change, a gap still exists. This gap is linked to biological fa...

Introduction: The influence of sex and gender is particularly relevant in cardiovascular diseases (CVD) as well as in several aspects of drug pharmacodynamics and pharmacokinetics. Anatomical and physiological differences between the sexes may influence the activity of many drugs, including the possibility of their interaction with other drugs, bi...

Sex differences affect several diseases and are organ-and parameter-specific. In humans and animals, sex differences also influence the metabolism and homeostasis of amino acids and fatty acids, which are linked to the onset of diseases. Thus, the use of targeted metabolite profiles in tissues represents a powerful approach to examine the intermedi...

Purpose To investigate whether the hospitalization rate for bacterial infections was modified by statin therapy in a population retrospectively followed up, over years 2011 to 2015. Methods By using administrative databases, the 5‐year hospitalization rate due to bacterial infections in population living in Tuscany, Italy exposed to statin therapy...

Women and men, female and male animals and cells are biologically different, and acknowledgement of this fact is critical to advancing medicine. However, incorporating concepts of sex-specific analysis in basic research is largely neglected, introducing bias into translational findings, clinical concepts and drug development. Research funding agenc...

Diabetes is a chronic disease associated with micro- and macrovascular complications and is a well-established risk factor for cardiovascular disease. Cardiovascular complications associated with diabetes are among the most important causes of death in diabetic patients. Interestingly, several sex-gender differences have been reported to significan...

It is important to remember that gender health and illness should not to be conflated with women's health and illness. Turshen1 reports that numerous studies with ‘gender’ in the title use the word gender as a synonym for ‘women’ and as a result, men's gender-specific needs are missed. In addition, in reporting demographic characteristics of the st...

Background: Among individuals with Type 2 diabetes (T2DM), cardiovascular disease (CVD) is the leading cause of morbidity and mortality. Sex and gender differences (SGDs) in the cardiovascular consequences of T2DM are relevant suggesting the need for a more aggressive CVD preventive strategy in diabetic women as they lose the so-called "female adv...

Background: Alcohol use disorder (AUD) is a common and disabling mental disorder associated with a significant burden of medical consequences and high socioeconomic costs. Although a growing number of studies support the existence of sex differences in several aspects of alcohol consumption and AUD, the majority of investigations have been conduct...

The influence of sex has been largely described in cardiovascular diseases. Atherosclerosis is a complex process that involves many cell types such as vessel cells, immune cells and endothelial progenitor cells; however, many, if not all, studies do not report the sex of the cells. This review focuses on sex differences in human cells involved in t...

Sex is one of several factors influencing pharmacological responses, but research on its effects on pharmacokinetics and pharmacodynamics, although emerging remarkably, remains poor and contains many methodological issues. In this review, the current state of knowledge about sex differences in pharmacokinetics and some hints to pharmacogenomics wer...

Objective: Women with diabetes have a greater excess risk for cardiovascular diseases (CVD) than men. This study was aimed at clarifying whether this effect is lifelong or more evident in some life-periods. Methods: The effect of diabetes and gender on the risk of first ever hospitalization for acute myocardial infarction (AMI), ischemic stroke...

Sex has largely been neglected in cell studies. Therefore, we investigated the occurrence of sexual dimorphism in human umbilical artery smooth muscle cells (HUASMCs). In particular, we investigated the existence of sex differences in basal and in drug-induced autophagy, a process involved in cardiovascular diseases.

While in non-diabetic people the risk for cardiovascular disease is higher in men, diabetes completely reverts this sex-gender difference conferring to women a greater burden of cardiovascular complications. Additionally, all risk factors associated with cardiovascular disease appear to be more active in diabetic females than in their male counterp...

Immune function, inflammation and atherosclerosis display sex differences and are influenced by 17β-estradiol through estrogen receptors subtypes ERα and ERβ. Male tissues express active ERs, but their possible involvement in inflammation in males has never been assessed. Macrophages express both ERα and ERβ and offer the opportunity to evaluate th...

Hypertension is a major risk factor for cardiovascular disease and outcomes in women, and antihypertensive therapy is not always successful in achieving control over the blood pressure (BP). Nonoptimal control of BP remains a crucial risk factor for cardiovascular mortality, and in women, it could be related to sex-specific factors. Historically, w...

Although sex differences in several aspects of substance use disorders (SUDs) have been identified, less is known about the importance of possible sex differences in side effects induced by substances of abuse or by medications used to treat SUDs. In the SUD field, the perception of certain subjective effects are actively sought, while all other ma...

Purpose: The existence of gender differences in the management of statin therapy among patients with chronic heart failure (HF) is still poorly investigated. We aimed at exploring the effect of gender on statin prescription rates and adequacy of dosing and on the association between statin therapy and all-cause 1-year mortality, after HF hospitali...

Background: Endothelial progenitor cells (EPCs) are key elements in vascular homeostasis. Their function is regulated by estrogens and estrogen receptors (ERs), but the effect of estrogenic compounds such as bisphenol A (BPA; an agonist of ER-β and agonist and antagonist of ER-α) and (R,R)-5,11-diethyl-5,6,11,12-tetrahydro-2,8-chrysenediol (THC; a...

Background: Gender medicine requires a global analysis of an individual's life. Menopause and ageing induce variations of some cardiometabolic parameters, but, it is unknown if this occurs in a sex-specific manner. Here, some markers of oxidative stress, systemic inflammation, and endothelial dysfunction are analysed in men younger and older than 4...

Background: Taurine transporter gene expression (RNA-TauT) has a role in retinal cell function and is modulated in vitro and in vivo by hyperglycemia and/or oxidative stress. This study was aimed at testing whether RNA-TauT gene expression is modified in blood mononuclear peripheral cells (MPCs) of type 1 diabetic patients, is related to plasma ma...

Negli ultimi anni la comunità scientifica ha dichiarato che le differenze biologiche tra uomini e donne sono importanti determinanti della salute e, a differenza del passato, non è più possibile continuare a prendere in considerazione solo il sesso maschile come punto di riferimento per la ricerca medica e per la pratica clinica. Diversi studi ha...

Background: In basal conditions, vascular smooth muscle cells freshly isolated from aortas of male and female rats display marked sex differences in terms of redox balance and susceptibility to ultraviolet radiation-induced cell death. In particular, in the same experimental conditions, cells from male rats are more susceptible to oxidative stress...

Prevalences of patients receiving statin prescriptions in the study population, stratified by gender and age class

In the vast majority of cardiovascular diseases (CVDs), there are well-described differences between women and men in epidemiology, pathophysiology, clinical manifestations, effects of therapy, and outcomes.1–3 These differences arise on one hand from biological differences among women and men, which are called sex differences. They are due to diff...

The aim of this study was to evaluate whether the number of women recruited for studies to establish the efficacy of medications approved for treatment of alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to reveal possible gender differences in the response to these medications and in suggesting the use of different do...

A sex-gender approach in laboratory medicine is scarce; furthermore, the influence of sex on acylcarnitines and amino acids levels at birth has not been thoroughly investigated, even if sex impacts on newborn screening. We aimed to establish the influence of sex on amino acids and acylcarnitines levels in male and female newborns. Amino acids and a...

Background Incidence of ischemic stroke (IS) and associated in-hospital mortality are decreasing in Western populations, while the prevalence of diabetes, a well-known risk factor for IS, is progressively rising. Since whether the declining trend of IS occurs in diabetic patients as well is matter of debate, this study was aimed at evaluating the e...

Atrial fibrillation (AF), one of the most prevalent supra-ventricular arrhythmia in adults, is related to a substantial increase in the risk of thromboembolic events requiring tailored preventive strategy. In AF, antithrombotic therapy should be individualized according to a careful decision-making process, taking in account the likely concomitant...

Background: The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson's disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena. Methods: Patients on dopaminergic treatment fo...

HUVECs are worldwide used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. The present work characterised the phenotype of HUVECs in terms of morphology, proliferative and migratory capacity and in the gene expression of oestrogen and androgen receptors and...

Sex has largely been neglected in cellular studies. Autophagy is a sophisticatedly reg- ulated homeostatic mechanism, which ensures cell’s constituent turnover. Under physiological conditions, autophagy levels are usually low (constitutive autophagy), but can be induced by numerous cellular stresses such as starvation. The influence of sex on autop...

To evaluate the effect of diabetes by gender on the peak-risk of first-ever-ischemic stroke and its recurrence. Administrative datasets including all hospital discharges for ischemic stroke (N=43,332) in the diabetic (N=207,568) and non-diabetic (N=2,808,554) population of the Tuscany region, Italy were used to calculate Hazard ratios (HR) after Co...

Human umbilical endothelial cells (HUVECs) are widely used to study the endothelial physiology and pathology that might be involved in sex and gender differences detected at the cardiovascular level. This study evaluated whether HUVECs are sexually dimorphic in their morphological, proliferative and migratory properties and in the gene and protein...

Ischemic heart disease is the single leading cause of death and a significant cause of morbidity among women in industrialized countries. Current guidelines recommend antiplatelet therapy as the main cornerstone for the prevention and treatment of cardiovascular disease. Unfortunately, evidence is emerging that the response to antiplatelet drugs di...

Many international organisations encourage studies in a sex-gender perspective. However, research with a gender perspective presents a high degree of complexity, and the inclusion of sex-gender variable in experiments presents many methodological questions, the majority of which are still neglected. Overcoming these issues is fundamental to avoid e...

Background: the SMILE studies proved the prognostic benefit of zofenopril vs. placebo or other ACE-inhibitors (ACEIs) in post-acute myocardial infarction (AMI). In this retrospective pooled analysis of these studies we assessed whether the zofenopril effect is influenced by gender. Methods: the four double-blind, randomized, parallel-group SMILE st...

Aim: Considering that the effects of sex and oral contraceptives (OCs) on blood metabolites have been scarcely studied and the fact that protocol designs for clinical trials emphasise the use of contraception for women of childbearing potential, we examined if OCs and sex affect the serum levels of the physiologically relevant amino acids, carniti...

Food and beverage intake is the only behavior that animals, including human beings, must continually repeat in order to provide energy and chemical materials to the body. Recent epidemiological findings are poised to usher the science of nutrition into in a new era in which the consumption of specific whole foods, now called functional foods, is st...

Sex steroid hormones differently control the major physiological processes in male and female organisms. In particular, their effects on vascular smooth muscle cells (VSMCs) migration are at the root of sex/gender-related differences reported in the cardiovascular system. Several exogenous substances, defined endocrine disruptor chemicals (EDCs), c...

Patient sex is known to influence the response to general and regional anaesthesia and recovery after surgery. However, most studies come from analyses carried out on middle-aged patients. As most of the patients admitted to the post-anaesthesia recovery room in our institution are elderly, we took the opportunity to investigate the association bet...