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Sex and Gender Medicine—Physiology: A New Horizon in Human Physiology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (20 April 2026) | Viewed by 2306

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Department of Biosciences, Biotechnologies and Environment, University of Bari Aldo Moro, 70125 Bari, Italy
Interests: sex gender physiology; neurological diseases; bioactive compounds; drug delivery system; in vitro toxicology; metal toxicity
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Special Issue Information

Dear Colleagues,

In recent years, the analysis of the biological and sociocultural differences between sexes has gained increasing relevance in medical and scientific research. It is now well established that sex, the set of biological and physiological characteristics that distinguish individuals, and gender, a sociocultural construct defining the roles and social expectations associated with different sexes, profoundly influence the physiological mechanisms underlying health and disease. This has significant implications for prevention, diagnosis, and therapeutic strategies.

The scientific literature has extensively documented how factors such as hormonal profiles, immune responses, enzymatic activity, and gene regulation can differ significantly between sexes. These variables influence not only the onset and progression of diseases but also individual responses to pharmacological treatments, suggesting that sex can play a crucial role in pharmacology and personalized medicine.

This Special Issue aims to examine the molecular, cellular, and systemic mechanisms underlying the physiological differences observed between the sexes across, for example, the cardiovascular, respiratory, endocrine, immune, neurophysiological, gastrointestinal, and musculoskeletal systems. The topics to be explored include the following:

  • The fundamental role of sexual hormones in the development and regulation of various biological systems, with a particular focus on their long-term effects on health;
  • Sex-specific differences in gene regulation, including an analysis of the epigenetic mechanisms that may modulate gene expression in response to environmental factors;
  • Comparative neurophysiology, highlighting differences between males and females in terms of cognitive and behavioral functions;
  • The impact of sex on responses to oxidative stress and inflammatory processes, which may have important long-term health consequences;
  • The examination of the pathophysiology of chronic diseases through a sex and gender lens to identify more targeted therapeutic approaches.

Additionally, proposals will be presented for the development of more effective prevention and treatment strategies based on sex-specific evidence. We warmly invite the scientific community to contribute their original articles, systematic reviews, experimental studies, and prospective research, with the shared goal of enriching our understanding of human physiology and promoting the advancement of medicine that is increasingly personalized, equitable, and grounded in solid scientific evidence.

Dr. Rosanna Mallamaci
Guest Editor

Manuscript Submission Information

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Keywords

  • sex and gender
  • personalized medicine
  • sex-specific evidence
  • sex-specific differences

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Published Papers (2 papers)

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Research

23 pages, 4142 KB  
Article
Sex-Specific Salivary Biochemical Composition in a Healthy Population
by Elena A. Sarf, Kirill S. Yunkind, Denis V. Solomatin and Lyudmila V. Bel’skaya
Int. J. Mol. Sci. 2026, 27(5), 2214; https://doi.org/10.3390/ijms27052214 - 26 Feb 2026
Viewed by 484
Abstract
The high potential of saliva for use in the non-invasive diagnosis of a number of diseases raises a number of questions regarding the substantiation of normal and abnormal salivary composition criteria. Factors that must be considered when forming patient cohorts include age, hormonal [...] Read more.
The high potential of saliva for use in the non-invasive diagnosis of a number of diseases raises a number of questions regarding the substantiation of normal and abnormal salivary composition criteria. Factors that must be considered when forming patient cohorts include age, hormonal status, and circadian variability. However, the influence of sex remains controversial. The aim of this study was to investigate the influence of sex on the biochemical composition of normal saliva, including amino acid and lipid profiles, cytokine levels, and electrolytes. The study involved 120 healthy volunteers (75 females and 45 males). The amounts of electrolytes (NH4+, K+, Na+, Mg2+, Ca2+, Cl, SO42−, NO2, NO3, F, PO43−), amino acids (Arg, Lys, Tyr, Phe, His, Leu+Ile, Met, Val, Pro, Thr, Ser, Ala, Gly), cytokines (VEGF, MCP-1, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, INF-α, INF-γ), and biochemical parameters (protein, urea, total content of α-amino acids, imidazole compounds, lipid peroxides) were analyzed. Lipid content was determined based on the intensity of absorption bands at 1396, 1458, 2853, 2923, and 2957 cm−1 in the IR spectra of salivary lipid extracts. A clear sex correlation was found for amino acid and lipid content in saliva. For electrolytes and biochemical parameters, median differences were demonstrated in some cases; however, the range of variation for all parameters overlapped. Although overall cytokine profiles did not show clear multivariate separation, significant differences between sexes were observed for individual cytokines (IL-1β and IL-10). A comprehensive assessment of all parameters (amino acids, lipids, cytokines, etc.) allows for the formation of a sex-associated metabolic profile of saliva. Therefore, it is recommended to avoid the use of mixed cohorts when analyzing the amino acid and lipid profiles of saliva. Full article
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12 pages, 537 KB  
Article
Sex-Independent Upregulation of miR-146a-5p in Parkinson’s Disease Patients: A Longitudinal Study
by Annamaria Vallelunga, Tommaso Iannitti, Giovanna Dati, Julio César Morales-Medina, Marina Picillo, Marianna Amboni, Calogero Edoardo Cicero, Roberto Cilia, Rosa De Micco, Anna De Rosa, Alessio Di Fonzo, Roberto Eleopra, Augusta Giglio, Giulia Lazzeri, Alessandra Nicoletti, Claudio Pacchetti, Andrea Soricelli, Alessandro Tessitore, Roberta Zangaglia, Paolo Barone and Maria Teresa Pellecchiaadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2025, 26(21), 10315; https://doi.org/10.3390/ijms262110315 - 23 Oct 2025
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Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The absence of reliable fluid biomarkers continues to hinder early diagnosis and effective monitoring of disease progression. Circulating microRNAs (cmiRNAs) are potential candidates, given their stability in biofluids and [...] Read more.
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. The absence of reliable fluid biomarkers continues to hinder early diagnosis and effective monitoring of disease progression. Circulating microRNAs (cmiRNAs) are potential candidates, given their stability in biofluids and their ability to mirror pathological processes. We conducted a longitudinal study in 30 early-stage levodopa-naive PD patients (22 men, 8 women). Serum samples were collected at baseline (T0) and at a follow-up time point two years later (T2). A panel of MicroRNAs (miRNAs) (miR-146a-5p, miR-34a-5p, miR-155-5p, miR-29a-3p, miR-106a-5p) were quantified by quantitative real-time PCR. Data were expressed as relative expression (2^−ΔCt), and statistical analyses included sex-stratified comparisons and paired tests for longitudinal changes. At baseline, no significant differences were found in the expression of the miRNAs between male and female PD patients. In contrast, longitudinal within-subject analysis revealed a highly significant upregulation in miR-146a-5p expression from T0 to T2 in both sexes (p < 0.0001). No other miRNAs in the panel exhibited significant changes over time. CmiR-146a-5p levels rise markedly over time in PD patients, independent of sex, suggesting that this miRNA could be a dynamic biomarker of disease progression. Full article
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