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Objective: Insulin resistance (IR) represents an independent risk factor for metabolic, cardiovascular, and neoplastic disorders. Preventing/attenuating IR is a major objective to be reached to preserve population health. Because many insulin-sensitizing drugs have shown unwanted side effects, active harmless compounds are sought after. Dietary anthocyanins have been demonstrated to ameliorate hyperglycemia and insulin sensitivity. This study aimed at investigating whether cyanidin-3-O-β-glucoside (C3G) and its metabolite protocatechuic acid (PCA) might have a role in glucose transport activation in human omental adipocytes and 3T3-L1 cells.Research Design and Methods: In cells treated with 50 µmol/L C3G and 100 µmol/L PCA, [(3)H]-2-deoxyglucose uptake, GLUT4 translocation by immunoblotting, adiponectin secretion, and peroxisome proliferator-activated receptor-γ (PPARγ) activation by enzyme-linked immunosorbent assay kits were evaluated. Parallel experiments were carried out in murine adipocyte 3T3-L1. To define the role of PPARγ in modulating polyphenol effects, small interfering RNA technique and PPARγ antagonist were used to inhibit transcription factor activity.Results: C3G and PCA increased adipocyte glucose uptake (P < 0.05) and GLUT4 membrane translocation (P < 0.01). Significant increases (P < 0.05) in nuclear PPARγ activity, as well as in adiponectin and GLUT4 expressions (P < 0.01), were also shown. It is interesting that PPARγ inhibition counteracted the polyphenol-induced adiponectin and GLUT4 upregulations, suggesting a direct involvement of PPARγ in this process.Conclusions: Our study provides evidence that C3G and PCA might exert insulin-like activities by PPARγ activation, evidencing a causal relationship between this transcription factor and adiponectin and GLUT4 upregulation. Dietary polyphenols could be included in the preventive/therapeutic armory against pathological conditions associated with IR. [ABSTRACT FROM AUTHOR]

Aside from being an integral protein involved in the synthesis and hydrolysis of ATP, Ecto-F1-ATPase plays a role in cholesterol homeostasis. We demonstrated the presence of autoantibodies to ecto-F1-ATPase (ASabs) in sera and cerebrospinal fluids from patients with Alzheimer's disease (AD). Herein we show that ASabs, unlike irrelevant antibodies, can increase cellular uptake of HDL, a risk factor for the development of AD, via a mechanism involving the prototypical function of ecto-F1-ATPase: the generation of ADP due to the hydrolysis of ATP. Piceatannol, a specific inhibitor ecto-F1-ATPase, completely hindered these effects. We hypothesize that ASabs could exert a pathogenetic role in AD. [ABSTRACT FROM AUTHOR]

Leptospirosis has a complex transmission, involving rodents and many species of domestic and wild animals. Carrier animals spread leptospires, contaminating soil and water, the main sources of human infection. The risk of infection is modulated by socio-economic factors, environment and host animals and has changed, historically linked to agriculture but now prevalent in recreational environments. Leptospirosis also reveal gender-specific exposure patterns that determine infection risks. Emphasizing the interconnectedness of humans, animals, and the environment, the One Health approach highlights the ecosystem dynamics through which leptospires interact with hosts and abiotic factors, ensuring their survival and transmission. We advocate for integrating gender considerations into the ecosystem dynamics of complex zoonoses, such as leptospirosis, through a One Health perspective. This approach, yet to be fully explored, may enhance our understanding of the infection and its modulating factors. A scoping review of the literature was conducted across Embase and Pubmed databases to collect information on sex and gender-specific drivers, sources of infections, environmental drivers, and related risks of leptospirosis. Quantitative data were extracted from the articles selected according to a list of criteria, and analyzed to discern sex and gender disparities and identify primary drivers of leptospirosis. We confirmed that the excess of male leptospirosis cases described in many parts of the world is also present in Europe. Furthermore, we identified environmental and sociocultural drivers and hypothesized their interactions between and within human, animal, and environmental sectors. These interactions modulate direct and indirect exposure to Leptospira , heightening infection risks across the ecosystem. Based on our findings, utilizing leptospirosis as a model, we advocate for integrating One Health and gender approaches in public health practices to better plan and implement more effective and timely intervention measures., Competing Interests: None., (© 2024 The Authors.)

Obesity represents an important public health concern, being one of the leading causes of death worldwide. It is a multifactorial disease with many underlying intertwined causes, including genetic, environmental and behavioral factors. Notably, metabolism-disrupting chemicals (MDCs) can alter the set point control of metabolism, affecting the development and function of the adipose tissue. Epidemiological studies have reported associations between human exposure to MDCs and several altered metabolic endpoints. It is also noteworthy that sex and gender represent important risk factors in the development of obesity. Different sex-related biological and physiological characteristics influence individual susceptibility, whereas gender represents a critical component in determining the different exposure scenarios. Although some advancements in the treatment of obesity have been achieved in preclinical and clinical studies, the obesity pandemic continues to increase worldwide. The present study performed a systematic review of recent studies considering the effects of MDCs on obesity, with a specific focus on sex- and gender-related responses. This review highlighted that MDCs could differently affect men and women at different stages of life even though the number of studies evaluating the association between obesity and MDC exposure in relation to sex and gender is still limited. This evidence should urge researchers to carry out studies considering sex and gender differences. This is essential for developing sex-/gender-tailored prevention strategies to improve public health policies and reduce exposure.

The human-animal-environment interface is where the emergence of new infectious diseases can occur as a result of many complex reasons, including its alteration due to intensive farming and agriculture, increased human encroachment into wildlife habitats, international travel networks, and urbanization. The One Health approach to zoonoses is a holistic approach that considers environmental sustainability, animal health, and human health together. Gender-specific social and domestic roles can modulate (increase or decrease) an individual's risk of exposure to various hazards, including infectious diseases and zoonoses. The two scenarios presented here, one on avian influenza and the other on leptospirosis, clearly highlight the influence of gender, demonstrating that women's roles at the human-animal-environment interface are not the same as men's. Integrating the gender aspect into cross-sectoral interventions defined according to the One Health perspective could help reduce the risks of exposure to infections for humans and animals and the possible consequent economic losses. We suggest supplementing the One Health perspective with a gender analysis to study the influence of social norms, activities and risk behavior on exposure to infections, chemical pollution and the consequences of climate change., Competing Interests: None., (© 2023 The Authors.)

MaestraNatura (MN) is a nutrition education program developed to both enhance awareness about the importance of healthy eating behaviour and skills on food and nutrition in primary school students. The level of knowledge about food and nutritional issues was assessed by a questionnaire administered to 256 students (9-10 years old) attending the last class of primary school and was compared with that of a control group of 98 students frequenting the same schools that received traditional nutrition education based on curricular science lessons and one frontal lesson conducted by an expert nutritionist. The results indicated that students in the MN program showed a higher percentage of correct responses to the questionnaire when compared with the control group (76 ± 15.4 vs. 59 ± 17.7; p < 0.001). Furthermore, the students attending the MN program were requested to organise a weekly menu before (T0) and when finished (T1) the MN program. The results evidenced an overall significant improvement in the score obtained at T1 with respect to those at T0 ( p < 0.001), indicating a strong improvement in the ability to translate the theoretical concepts of nutrition guidelines in practice. In addition, the analysis revealed a gender gap between boys and girls, with boys showing a worse score at T0 that was ameliorated after the completion of the program ( p < 0.001). Overall, MN program is effective in improving nutrition knowledge amongst 9-10-year-old students. Furthermore, students showed an increased ability to organise a weekly dietary plan after completing the MN program, a result which also bridged gender gaps. Thus, preventive nutrition education strategies specifically addressed to boys and girls, and involving both the school and family, are needed to make children aware of the importance of a healthy lifestyle and to correct inadequate eating habits.

Several factors including gender, age groups, cultures and social conditions may affect significantly the risk of diseases and their clinical evolution. Unfortunately, little research has been carried out on these aspects and, consequently few guidelines or interventions have been implemented. In particular, gender is considered a main determinant of inequalities in living conditions, access to health services and, thus, in health protection. Focusing on the gender gap, we propose an ecological approach to find relationships between quantitative indicators of the gender gap dimension, the environmental performance index and the life expectancy at birth as summary of human health index in 155 countries. We speculated on the consequences of wider gender gaps to the population and environmental health. We further explore these relationships considering gender gap and environmental aspect subindexes, to identify determinants that should be addressed to maximize the One Health effect. We found that the gender gap in educational attainment followed by the political empowerment were strongly correlated with life expectancy, environmental health, and ecosystem vitality. Addressing gender issues, particularly the education attainment and political empowerment, can provide positive impact beyond the social dimension and the population health, and gender should be component of the One Health approach. We recommend gender targeted interventions that integrate these aspects into One Health national policies., Competing Interests: None., (© 2023 The Authors.)

Introduction: Coronavirus disease 19 (COVID-19) is an infectious disease caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). To date, few data on clinical features and risk factors for disease severity and death by gender are available., Aim: The current study aims to describe from a sex/gender perspective the characteristics of the SARS-CoV-2 cases occurred in the Italian population from February 2020 until October 2021., Method and Results: We used routinely collected data retrieved from the Italian National Surveillance System. The highest number of cases occurred among women between 40 and 59 years, followed by men in the same age groups. The proportion of deaths due to COVID-19 was higher in men (56.46%) compared to women (43.54%). Most of the observed deaths occurred in the elderly. Considering the age groups, the clinical outcomes differed between women and men in particular in cases over 80 years of age; with serious or critical conditions more frequent in men than in women., Conclusions: Our data clearly demonstrate a similar number of cases in women and men, but with more severe disease and outcome in men, thus confirming the importance to analyse the impact of sex and gender in new and emerging diseases.

Accumulating evidence indicates that regular consumption of extra virgin olive oil (EVOO), the main source of fat in the Mediterranean diet, is associated with beneficial health effects and a reduced risk of developing chronic degenerative disorders. The beneficial effects of EVOO can be attributed to its unique composition in monounsaturated fats and phenolic compounds that provide important antioxidant, anti-inflammatory, and immune-modulating activities. On the other hand, it is well known that the gut microbiota has several important roles in normal human physiology, and its composition can be influenced by a multitude of environmental and lifestyle factors, among which dietary components play a relevant role. In the last few years, the two-way interaction between polyphenols, including those in EVOO, and the gut microbiota, i.e., the modulation of the microbiota by polyphenols and that of polyphenol metabolism and bioavailability by the microbiota, has attracted growing attention, being potentially relevant to explain the final effects of polyphenols, as well as of the microbiota profile. Furthermore, sex and gender can affect dietary habits, polyphenol intake, and nutrient metabolism. Lastly, it has been recently suggested that differences in gut microbiota composition could be involved in the unequal incidence of metabolic diseases observed between women and men, due to sex-dependent effects on shaping gut microbiota profiles according to diet. This review summarizes the most recent studies on the relationship between EVOO polyphenols and the gut microbiota, taking into account possible influences of sex and gender in modulating such an interaction.

Promoting a healthy diet, mainly in youths, is the most effective action to prevent and fight dietary excesses and nutritional imbalance in the population. MaestraNatura (MN) is an innovative nutritional education program aimed at promoting a healthy lifestyle in first-level secondary school students. The study evaluated the effectiveness of the MN program in improving knowledge in students following the MN program (MN group) with respect to a control group (CO group) undergoing a “traditional” nutritional education path. To this end, the nutrition knowledge of the two groups was assessed by three multi-choice questionnaires. The results showed a significant improvement in knowledge (p < 0.001) in the MN group with respect to the CO group for all the questionnaires. Furthermore, the students’ ability to transfer the principles of nutrition guidelines to the real context of daily meals was determined by asking the MN group to create a weekly food plan before (T0) and after (T1) the completion of the MN program. The MN group demonstrated improved performance in organizing the weekly menu plan at T1 with respect to T0 (p = 0.005). In conclusion, the MN nutritional education program appears to be an effective tool for improving knowledge and skills on nutritional issues, especially in those students with a lower starting level of knowledge and ability.

In the era of personalized medicine, fetal sex-specific research is of utmost importance for comprehending the mechanisms governing pregnancy and pregnancy-related complications. In recent times, noncoding RNAs (ncRNAs) have gained increasing attention as critical players in gene regulation and disease pathogenesis, and as candidate biomarkers in human diseases as well. Different types of ncRNAs, including microRNAs (miRNAs), piwi-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in every step of pregnancy progression, although studies taking into consideration fetal sex as a central variable are still limited. To date, most of the available data have been obtained investigating sex-specific placental miRNA expression. Several studies revealed that miRNAs regulate the (patho)-physiological processes in a sexually dimorphic manner, ensuring normal fetal development, successful pregnancy, and susceptibility to diseases. Moreover, the observation that ncRNA profiles differ according to cells, tissues, and developmental stages of pregnancy, along with the complex interactions among different types of ncRNAs in regulating gene expression, strongly indicates that more studies are needed to understand the role of sex-specific ncRNA in pregnancy and associated disorders.

Gestational diabetes mellitus (GDM) is associated with immune metabolic changes that increase women's risk of developing metabolic disorders later in life. Nutritional intervention is a crucial component in reducing the burden of these pathological features. We examined whether protocatechuic acid (PCA), a major metabolite of anthocyanins abundant in plant food, is able to exert insulin-mimetic activity and modulate inflammation in the visceral adipose tissue (VAT) obtained at delivery, from pregnant women with GDM or normal glucose tolerance (NGT). PCA stimulated glucose uptake in the VAT from both GDM and NGT women. This capability was associated with increased phosphorylation of p38 mitogen-activated protein kinase (p38MAPK), as further demonstrated by the inhibitory effect of SB203580, a p38MAPK inhibitor, on PCA-induced glucose uptake. The GDM-VAT expressed lower adiponectin levels and PCA stimulated adiponectin release in the NGT-VAT and, albeit to a lower extent, in the GDM-VAT. Higher levels of IL6 and TNFα were secreted by the GDM-VAT compared with the NGT one, and PCA had no effects on them. PCA reduced the overexpression of vasoactive intestinal peptide receptor 2 (VPAC2) in the GDM-VAT. Further studies are needed to establish whether and how anthocyanins and food rich in these compounds may contribute to prevent or delay metabolic disorders in women with GDM.

Colorectal cancer (CRC) is among the major threatening diseases worldwide, being the third most common cancer, and a leading cause of death, with a global incidence expected to increase in the coming years. Enhanced adiposity, particularly visceral fat, is a major risk factor for the development of several tumours, including CRC, and represents an important indicator of incidence, survival, prognosis, recurrence rates, and response to therapy. The obesity-associated low-grade chronic inflammation is thought to be a key determinant in CRC development, with the adipocytes and the adipose tissue (AT) playing a significant role in the integration of diet-related endocrine, metabolic, and inflammatory signals. Furthermore, AT infiltrating immune cells contribute to local and systemic inflammation by affecting immune and cancer cell functions through the release of soluble mediators. Among the factors introduced with diet and enriched in AT, fatty acids (FA) represent major players in inflammation and are able to deeply regulate AT homeostasis and immune cell function through gene expression regulation and by modulating the activity of several transcription factors (TF). This review summarizes human studies on the effects of dietary FA on AT homeostasis and immune cell functions, highlighting the molecular pathways and TF involved. The relevance of FA balance in linking diet, AT inflammation, and CRC is also discussed. Original and review articles were searched in PubMed without temporal limitation up to March 2021, by using fatty acid as a keyword in combination with diet, obesity, colorectal cancer, inflammation, adipose tissue, immune cells, and transcription factors.