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Biomolecules
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Sex Differences in Biomedical Research
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Sex Differences in Biomedical Research

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (15 January 2024) | Viewed by 16729

Special Issue Editor

Dr. Marion Korach-André

E-Mail Website
Guest Editor
Science for Life Laboratory, Department of Gene Technology, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), KTH Royal Institute of Technology, Karolinska Institute Science Park, SE-171 21 Solna, Sweden
Interests: lipid metabolism; lipidomic; sex differences; sex hormones; nutrition; metabolic syndrome
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Until recently, instructions or guidance on the effect of sex on basic and preclinical research were rare. Based on recent human and animal research over the past decade, it is now widely accepted that both biological and physiological functions in health and disease are influenced by sex-based differences. Some effort has recently been made to better represent women in clinical trials and to accept sex as a biological variable in biomedical research. Sex has been recognized as an important basic human variable that should be considered when planning studies in biomedical and health-related research, but much effort must still be made. For example, premenopausal women seem to have a natural protection to various disorders, probably due to circulating estrogen, since this protection disappears after menopause. However, the mechanism by which circulating estrogen would protect females from metabolic dysfunctions is still largely unknown. Importantly, the existence of sex differences in health implies that one sex has a specific factor or process that protects from disease. If that factor can be modulated, either directly or by modifying its downstream pathways, then disease development and/or progression may be tempered. Every cell in our bodies has a sex, which means that women and men are also different at the cellular level. This implies that diseases, nutrients, pollutants, and treatments may impact women and men differently. Therefore, we cannot continue to ignore sex differences in biomedical research, and considering sex as a biological variable is fundamental to perform good and efficient science. 

The purpose of this Special Issue is to introduce a sex-biased approach in biomedical research. To develop more effective diagnostic, treatment, and prevention strategies, it is crucial to elucidate the molecular and cellular mechanisms and the causes underlying sex-dependent biological response in human disease.

Dr. Marion Korach-André
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sex differences
  • metabolism
  • obesity
  • diet
  • nutrition
  • cancer
  • metabolic syndrome
  • type-2 diabetes
  • inflammation
  • liver steatosis
  • appetite
  • cytokines
  • adipokines

Published Papers (5 papers)

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Research

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20 pages, 6943 KiB  
Article
Ex Vivo 13C-Metabolic Flux Analysis of Porcine Circulating Immune Cells Reveals Cell Type-Specific Metabolic Patterns and Sex Differences in the Pentose Phosphate Pathway
by Melanie Hogg, Eva-Maria Wolfschmitt, Ulrich Wachter, Fabian Zink, Peter Radermacher and Josef Albert Vogt
Biomolecules 2024, 14(1), 98; https://0-doi-org.brum.beds.ac.uk/10.3390/biom14010098 - 12 Jan 2024
Viewed by 971
Abstract
In general, females present with stronger immune responses than males, but scarce data are available on sex-specific differences in immunometabolism. In this study, we characterized porcine peripheral blood mononuclear cell (PBMC) and granulocyte energy metabolism using a Bayesian 13C-metabolic flux analysis, which [...] Read more.
In general, females present with stronger immune responses than males, but scarce data are available on sex-specific differences in immunometabolism. In this study, we characterized porcine peripheral blood mononuclear cell (PBMC) and granulocyte energy metabolism using a Bayesian 13C-metabolic flux analysis, which allowed precise determination of the glycolytic, pentose phosphate pathway (PPP), and tricarboxylic acid cycle (TCA) fluxes, together with an assessment of the superoxide anion radical (O2•−) production and mitochondrial O2 consumption. A principal component analysis allowed for identifying the cell type-specific patterns of metabolic plasticity. PBMCs displayed higher TCA cycle activity, especially glutamine-derived aspartate biosynthesis, which was directly related to mitochondrial respiratory activity and inversely related to O2•− production. In contrast, the granulocytes mainly utilized glucose via glycolysis, which was coupled to oxidative PPP utilization and O2•− production rates. The granulocytes of the males had higher oxidative PPP fluxes compared to the females, while the PBMCs of the females displayed higher non-oxidative PPP fluxes compared to the males associated with the T helper cell (CD3+CD4+) subpopulation of PBMCs. The observed sex-specific differences were not directly attributable to sex steroid plasma levels, but we detected an inverse correlation between testosterone and aldosterone plasma levels and showed that aldosterone levels were related with non-oxidative PPP fluxes of both cell types. Full article
(This article belongs to the Special Issue Sex Differences in Biomedical Research)
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18 pages, 2235 KiB  
Article
Sex Differences in Comorbidity Combinations in the Swedish Population
by Laura Basso, Benjamin Boecking, Patrick Neff, Petra Brueggemann, Christopher R. Cederroth, Matthias Rose and Birgit Mazurek
Biomolecules 2022, 12(7), 949; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12070949 - 6 Jul 2022
Cited by 2 | Viewed by 2387
Abstract
High comorbidity rates, especially mental–physical comorbidity, constitute an increasing health care burden, with women and men being differentially affected. To gain an overview of comorbidity rates stratified by sex across a range of different conditions, this study examines comorbidity patterns within and between [...] Read more.
High comorbidity rates, especially mental–physical comorbidity, constitute an increasing health care burden, with women and men being differentially affected. To gain an overview of comorbidity rates stratified by sex across a range of different conditions, this study examines comorbidity patterns within and between cardiovascular, pulmonary, skin, endocrine, digestive, urogenital, musculoskeletal, neurological diseases, and psychiatric conditions. Self-report data from the LifeGene cohort of 31,825 participants from the general Swedish population (62.5% female, 18–84 years) were analyzed. Pairwise comorbidity rates of 54 self-reported conditions in women and men and adjusted odds ratios (ORs) for their comparison were calculated. Overall, the rate of pairwise disease combinations with significant comorbidity was higher in women than men (14.36% vs. 9.40%). Among psychiatric conditions, this rate was considerably high, with 41.76% in women and 39.01% in men. The highest percentages of elevated mental–physical comorbidity in women were found for musculoskeletal diseases (21.43%), digestive diseases (20.71%), and skin diseases (13.39%); in men, for musculoskeletal diseases (14.29%), neurological diseases (11.22%), and digestive diseases (10%). Implications include the need for integrating mental and physical health care services and a shift from a disease-centered to an individualized, patient-centered focus in clinical care. Full article
(This article belongs to the Special Issue Sex Differences in Biomedical Research)
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Review

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19 pages, 1507 KiB  
Review
The Next Frontier in Health Disparities—A Closer Look at Exploring Sex Differences in Glioma Data and Omics Analysis, from Bench to Bedside and Back
by Maria Diaz Rosario, Harpreet Kaur, Erdal Tasci, Uma Shankavaram, Mary Sproull, Ying Zhuge, Kevin Camphausen and Andra Krauze
Biomolecules 2022, 12(9), 1203; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12091203 - 30 Aug 2022
Cited by 2 | Viewed by 1950
Abstract
Sex differences are increasingly being explored and reported in oncology, and glioma is no exception. As potentially meaningful sex differences are uncovered, existing gender-derived disparities mirror data generated in retrospective and prospective trials, real-world large-scale data sets, and bench work involving animals and [...] Read more.
Sex differences are increasingly being explored and reported in oncology, and glioma is no exception. As potentially meaningful sex differences are uncovered, existing gender-derived disparities mirror data generated in retrospective and prospective trials, real-world large-scale data sets, and bench work involving animals and cell lines. The resulting disparities at the data level are wide-ranging, potentially resulting in both adverse outcomes and failure to identify and exploit therapeutic benefits. We set out to analyze the literature on women’s data disparities in glioma by exploring the origins of data in this area to understand the representation of women in study samples and omics analyses. Given the current emphasis on inclusive study design and research, we wanted to explore if sex bias continues to exist in present-day data sets and how sex differences in data may impact conclusions derived from large-scale data sets, omics, biospecimen analysis, novel interventions, and standard of care management. Full article
(This article belongs to the Special Issue Sex Differences in Biomedical Research)
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20 pages, 11617 KiB  
Review
Y It Matters—Sex Differences in Fetal Lung Development
by Mandy Laube and Ulrich H. Thome
Biomolecules 2022, 12(3), 437; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12030437 - 11 Mar 2022
Cited by 13 | Viewed by 3673
Abstract
Within this review, sex-specific differences in alveolar epithelial functions are discussed with special focus on preterm infants and the respiratory disorders associated with premature birth. First, a short overview about fetal lung development, the challenges the lung faces during perinatal lung transition to [...] Read more.
Within this review, sex-specific differences in alveolar epithelial functions are discussed with special focus on preterm infants and the respiratory disorders associated with premature birth. First, a short overview about fetal lung development, the challenges the lung faces during perinatal lung transition to air breathing and respiratory distress in preterm infants is given. Next, clinical observations concerning sex-specific differences in pulmonary morbidity of human preterm infants are noted. The second part discusses potential sex-specific causes of pulmonary complications, including pulmonary steroid receptors and local lung steroid metabolism. With regard to pulmonary steroid metabolism, it is important to highlight which steroidogenic enzymes are expressed at which stage during fetal lung development. Thereafter, we review the knowledge concerning sex-specific aspects of lung growth and maturation. Special focus is given to alveolar epithelial Na+ transport as a driver of perinatal lung transition and the sex differences that were noted in this process. Full article
(This article belongs to the Special Issue Sex Differences in Biomedical Research)
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27 pages, 431 KiB  
Review
Hormones and Sex-Specific Medicine in Human Physiopathology
by Maria Raza Tokatli, Leuconoe Grazia Sisti, Eleonora Marziali, Lorenza Nachira, Maria Francesca Rossi, Carlotta Amantea, Umberto Moscato and Walter Malorni
Biomolecules 2022, 12(3), 413; https://0-doi-org.brum.beds.ac.uk/10.3390/biom12030413 - 7 Mar 2022
Cited by 14 | Viewed by 6456
Abstract
A prodigious increment of scientific evidence in both preclinical and clinical studies is narrowing a major gap in knowledge regarding sex-specific biological responses observed in numerous branches of clinical practices. Some paradigmatic examples include neurodegenerative and mental disorders, immune-related disorders such as pathogenic [...] Read more.
A prodigious increment of scientific evidence in both preclinical and clinical studies is narrowing a major gap in knowledge regarding sex-specific biological responses observed in numerous branches of clinical practices. Some paradigmatic examples include neurodegenerative and mental disorders, immune-related disorders such as pathogenic infections and autoimmune diseases, oncologic conditions, and cardiovascular morbidities. The male-to-female proportion in a population is expressed as sex ratio and varies eminently with respect to the pathophysiology, natural history, incidence, prevalence, and mortality rates. The factors that determine this scenario incorporate both sex-associated biological differences and gender-dependent sociocultural issues. A broad narrative review focused on the current knowledge about the role of hormone regulation in gender medicine and gender peculiarities across key clinical areas is provided. Sex differences in immune response, cardiovascular diseases, neurological disorders, cancer, and COVID-19 are some of the hints reported. Moreover, gender implications in occupational health and health policy are offered to support the need for more personalized clinical medicine and public health approaches to achieve an ameliorated quality of life of patients and better outcomes in population health. Full article
(This article belongs to the Special Issue Sex Differences in Biomedical Research)
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