Circulating miRNA as potential biomarkers for diabetes mellitus type 2: should we focus on searching for sex differences?

microRNAs are non-coding molecules, approximately 22 nucleotides in length, that regulate various cellular processes. A growing body of evidence has suggested that their dysregulated expression is involved in the pathogenesis of diverse diseases, including diabetes mellitus type 2 (DM2). Early onset of this chronic and complex metabolic disorder is frequently undiagnosed, leading to the development of severe diabetic complications. Notably, DM2 prevalence is rising globally and an increasing number of articles demonstrate that DM2 susceptibility, development, and progression differ between males and females. Therefore, this paper discusses the role of microRNAs as a source of novel diagnostic biomarkers for DM2 and aims to underline the importance of sex disparity in biomarkers research. Taking into account an urgent need for the development of sex-specific diagnostic strategies in DM2, recent results have shown that circulating miRNAs are promising candidates for sex-biased biomarkers.

Host Sex Steroids Interact With Virus Infection: New Insights Into Sex Disparity in Infectious Diseases

Sex hormones are steroid hormones synthesized from the gonads of animals and tissues such as the placenta and adrenocortical reticular zone. The physiological functions of sex hormones are complex. Sex hormones are not only pathologically correlated with many diseases of the reproductive system, but are etiological factors in some viral infectious diseases, including disease caused by infections of coronaviruses, herpesviruses, hepatitis viruses, and other kinds of human viruses, which either exhibit a male propensity in clinical practice, or crosstalk with androgen receptor (AR)-related pathways in viral pathogenesis. Due to the global pandemic of coronavirus disease 2019 (COVID-19), the role of androgen/AR in viral infectious disease is highlighted again, majorly representing by the recent advances of AR-responsive gene of transmembrane protease/serine subfamily member 2 (TMPRSS2), which proteolytically activates the receptor-mediated virus entry by many coronaviruses and influenza virus, along with the role of androgen-mediated signaling for the transcription of hepatitis B virus (HBV), and the role of sex hormone responsive genes during Zika virus (ZIKV) pathogenesis, et al. Collectively, we propose to provide a comprehensive overview of the role of male sex hormones during multiple phases in the life cycle of different human viruses, which may be partly responsible for the sex-specific prevalence, severity and mortality of some diseases, therefore, may provide clues to develop more efficient prevention and treatment strategies for high-risk populations.

Sex-Disparity in the Association Between Birthweight and Cardiovascular Parameters in 4-Year-Old Children: A Chinese Cohort Study

Background: Sex-related differences in cardiovascular parameters have been well documented in adults, and the impact of birthweight on cardiovascular health in later life has been acknowledged. However, data was limited regarding the association between birthweight and cardiovascular outcomes at an early age, and the sex-disparity in the association remained unclear.Objective: To investigate the association between birthweight and cardiovascular parameters in 4-year-old children. Furthermore, to explore whether sex-disparity exist in this association or in cardiovascular risk.Methods: Follow-up data from the Shanghai Birth Cohort (SBC) was analyzed. Detailed perinatal information including both maternal and offspring datum were recorded. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 4-year-old children. Linear regression models were used to analyze the association between birthweight and left ventricle (LV) structure and function changes in each sex and birthweight category. Multivariable logistic regression models were used to compare risk of left ventricular hypertrophy (LVH) in different birthweight subgroups.Results: Overall, macrosomia was significantly associated with thickened LV posterior wall thickness in systole [LVPWs, (β = 0.26, 95% CI: 0.06, 0.45)] and diastole [LVPWd, (β = 0.18, 95% CI: 0.06, 0.30)], and thickened interventricular septal thickness in diastole [IVSd, (β = 0.16, 95% CI: 0.05, 0.28)]. Boys with macrosomia showed a higher left ventricle mass index [LVMI, (β = 1.29, 95% CI: 0.14, 2.43)], thickened LVPWs (β = 0.30, 95% CI: 0.05, 0.56) and LVPWd (β = 0.21, 95% CI: 0.06, 0.36), and thickened IVSd (β = 0.23, 95% CI: 0.09, 0.36). However, no significant association of structural changes was found in girls. Furthermore, an increased risk of LVH was found solely in macrosomic boys (OR = 2.79, 95% CI: 1.17, 6.63).Conclusion: Children with macrosomia developed cardiovascular changes as early as 4 years of age. Macrosomia was associated with LV structural changes and higher LVH risk in pre-school-aged boys, while no association was found in girls.

Sex-differences in COVID-19 associated excess mortality is not exceptional for the COVID-19 pandemic

Europe experienced excess mortality from February through June, 2020 due to the COVID-19 pandemic, with more COVID-19-associated deaths in males compared to females. However, a difference in excess mortality among females compared to among males may be a more general phenomenon, and should be investigated in none-COVID-19 situations as well. Based on death counts from Eurostat, separate excess mortalities were estimated for each of the sexes using the EuroMOMO model. Sex-differential excess mortality were expressed as differences in excess mortality incidence rates between the sexes. A general relation between sex-differential and overall excess mortality both during the COVID-19 pandemic and in preceding seasons were investigated. Data from 27 European countries were included, covering the seasons 2016/17 to 2019/20. In periods with increased excess mortality, excess was consistently highest among males. From February through May 2020 male excess mortality was 52.7 (95% PI: 56.29; 49.05) deaths per 100,000 person years higher than for females. Increased male excess mortality compared to female was also observed in the seasons 2016/17 to 2018/19. We found a linear relation between sex-differences in excess mortality and overall excess mortality, i.e., 40 additional deaths among males per 100 excess deaths per 100,000 population. This corresponds to an overall female/male mortality incidence ratio of 0.7. In situations with overall excess mortality, excess mortality increases more for males than females. We suggest that the sex-differences observed during the COVID-19 pandemic reflects a general sex-disparity in excess mortality.

A global cancer data integrator reveals principles of synthetic lethality, sex disparity and immunotherapy

Background Advances in cancer biology are increasingly dependent on integration of heterogeneous datasets. Large-scale efforts have systematically mapped many aspects of cancer cell biology; however, it remains challenging for individual scientists to effectively integrate and understand this data. Results We have developed a new data retrieval and indexing framework that allows us to integrate publicly available data from different sources and to combine publicly available data with new or bespoke datasets. Our approach, which we have named the cancer data integrator (CanDI), is straightforward to implement, is well documented, and is continuously updated which should enable individual users to take full advantage of efforts to map cancer cell biology. We show that CanDI empowered testable hypotheses of new synthetic lethal gene pairs, genes associated with sex disparity, and immunotherapy targets in cancer. Conclusions CanDI provides a flexible approach for large-scale data integration in cancer research enabling rapid generation of hypotheses. The CanDI data integrator is available at https://github.com/GilbertLabUCSF/CanDI.

Lack of Sex Disparity in Oral Anticoagulation in Atrial Fibrillation Patients Presenting with Ischemic Stroke in a Rural Population

Various studies on oral anticoagulants (OAC) use among atrial fibrillation (AF) patients have shown high rates of undertreatment and the presence of sex disparity. This study used the ‘Geisinger Neuroscience Ischemic Stroke’ (GNSIS) database to examine sex differences in OAC treatment among ischemic stroke patients with the pre-event diagnosis of AF in rural Pennsylvania between 2004 and 2019. We examined sex disparities in OAC undertreatment and associated risks based on age group and ischemic stroke year. A total of 1062 patients were included in the study and 1015 patients (96%) had CHA2DS2-VASc score ≥ 2, of which 549 (54.1%) were women. Undertreatment rates were not statistically significant between men and women in the overall cohort (50.0% vs. 54.5%, p = 0.18), and male sex was not found to be a significant factor in undertreatment (OR 0.82, 95% CI 0.62–1.09, p = 0.17). The result persisted even when patients were divided into four age groups and two groups based on the study time period. The undertreatment rates in both sex groups remained consistent following the introduction of novel oral anticoagulants. In conclusion, there was no evidence of sex disparity with respect to OAC treatment, even after stratifying the cohort by age and ischemic stroke year.

Association of Daytime Napping with chronic diseases among Tibetan people in China: a cross-sectional study

Background Obesity, diabetes, and hypertension, as three of the most prevalent chronic diseases, remain a daunting health challenge. However, to our knowledge, no study has made a thorough examination of the association between the three chronic diseases and daytime napping, a widely accepted behavior in many countries. This is especially necessary among Tibetan populations, whose lifestyles and health outcomes may be unique, yet patterns of chronic diseases and napping are under-examined. Thus, we sought to explore the aforementioned association in the Tibetan population of China. Methods A total of 2902 participants aged 45–79 in 2019 were included. Multivariate logistic regressions were conducted in 2020. The sex disparity was examined through interaction and stratified analyses. Results Hypertension (40.7%) was more prevalent than obesity (20.2%) and diabetes (21.6%). Comparing to non-nappers, those who napped were more likely to have any conditions (OR = 1.30, 95% CI = 1.04–1.62 for 1–59 min/day group and OR = 1.40, 95% CI = 1.10–1.80 for ≥60 min/day group). Participants who had 1–59 min/day of napping were more likely to develop obesity (OR = 1.37, 95% CI = 1.07–1.75), and ≥ 60 min/day of napping was associated with diabetes (OR = 1.33, 95% CI = 1.01–1.74). The interactions between napping and sex were not statistically significant in the models. Conclusions The study revealed napping was unfavorably associated with obesity, diabetes, and any conditions in Tibetan people living on the Tibetan Plateau. Future interventions regarding the three chronic diseases may pay more attention to napping. Trial registration Not applicable.