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Introduction: Within normal variation, higher hemoglobin (Hb) levels are associated with poorer metabolic profile in population cohorts, underlying the link between oxygen delivery and cell metabolism. Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women and is commonly accompanied by metabolic derangements. In this study we sought to investigate Hb levels, and their metabolic associations, in women with PCOS., Material and Methods: We used data from Northern Finland Birth Cohort 1966 to evaluate Hb levels in women with or without PCOS at the ages of 31 and 46 years. Linear regression models were used to investigate associations between Hb levels and essential metabolic parameters in both groups., Results: Women with PCOS had higher Hb levels than controls at the age of 31 years but not at the age of 46 years. Hb levels were associated positively with most of the metabolic parameters tested (body mass index, waist circumference, fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR), blood pressure, inflammatory markers, and blood lipids), with stronger associations in women with PCOS than in non-PCOS controls. There were fewer associations at the age of 46 than at 31 years, and body mass index seemed to explain many, though not all, differences between the PCOS and non-PCOS groups., Conclusions: Women with PCOS have higher Hb levels at the age of 31 years. In both women with and without PCOS, Hb levels associate with poorer metabolic profile., (© 2024 The Author(s). Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Objective: To study ferritin levels, and potential factors influencing them, in women with polycystic ovary syndrome (PCOS), and to investigate potential associations between ferritin levels and other parameters in these women., Design: Longitudinal general population -based cohort study, including data from both questionnaires and clinical measurements., Subjects: The study was conducted with data from the participants of the Women's Health Study, including a total of 1918 Finnish women, around 35 years of age., Exposure: PCOS was defined according to the Rotterdam criteria by the presence of at least two of the following findings: oligo/amenorrhea, hyperandrogenism (clinical or biochemical), and polycystic ovarian morphology., Main Outcome Measures: Serum ferritin levels and other parameters were determined from the cohort data and the associations between ferritin levels and other investigated parameters were investigated with linear regression models., Results: Women with PCOS had significantly higher median ferritin levels than women without PCOS (51.43 μg/L vs 44.85 μg/L, p=0.020). Low ferritin levels were less common among women with PCOS who had oligo- or amenorrhea than in those who did not (1.5% vs 11.8%, p=0.024). Median ferritin levels were also found to be lower in hyperandrogenic women with PCOS than in those with normoandrogenemia (49.96 μg/L vs 73.50 μg/L, p=0.011). Women with PCOS had higher fasting insulin levels than women without PCOS (8.85 mU/L vs 7.60 mU/L), and a positive association between fasting insulin and ferritin levels was found in the whole population (effect size: 0.0619, 95% confidence intervals: 0.005; 0.119, p=0.034). Finally, associations between ferritin levels and history of infertility were investigated in both the total population and in women with PCOS, but no significant associations were found., Conclusion: Our results suggest that women with PCOS have higher ferritin levels than those without PCOS, and that both the decreased blood loss from irregular menstruation and elevated androgen levels can influence ferritin levels in women with PCOS. A metabolic connection was also found as serum insulin levels associated positively with serum ferritin levels in the total population, whereas history of infertility did not seem to associate with serum ferritin levels in any of the study groups., (Copyright © 2025. Published by Elsevier Inc.)

Global warming increases the risk of dangerous heat waves, which may have deleterious effects on humans and wildlife. Here, we have utilized zebrafish embryos as a model to analyze heat stress and effect of chemical compounds on responses to heat stress. The temperature adaptation limit of zebrafish embryos was 37 °C in behavioural test and 38 °C in cardiac test. Polyaromatic hydrocarbon phenanthrene completely blocked the behavioural adaptation to heat stress. Interestingly, the cardiotoxic effects of lapatinib, phenanthrene and paclitaxel were induced by heat stress. Taken together, our data indicates that motility and cardiac function of zebrafish embryos can be utilized as a model to analyze modulatory effects of compounds on heat stress., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Ilkka Paatero, Katri Vaparanta, Minna Ampuja reports financial support was provided by Finnish Foundation for Cardiovascular Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Polycystic ovary syndrome (PCOS) is a highly prevalent disorder in women that is commonly accompanied by metabolic syndrome. Activation of the hypoxia-inducible factor (HIF) pathway is known to alleviate metabolic defects. Hence, this study utilized a preclinical PCOS mouse model to investigate the effects of chemically induced HIF activation on the metabolic traits of PCOS. Prepubertal letrozole treatment was used to generate a PCOS mouse model in the C57Bl6/J strain, and PCOS mice were orally treated with vehicle or roxadustat for six weeks from age 12 weeks onwards to induce HIF activation. Although the PCOS mice showed impaired glucose tolerance, increased insulin resistance, elevated blood lipids, and reduced muscle glycogen content, there was no difference in histological evaluations of white adipose tissue (WAT) or liver or in organ weights. Roxadustat treatment resulted in significant improvement in glucose tolerance (27 % reduction in area under the curve (AUC) values, p < 0.0001), fasting glucose levels (4.59 ± 0.83 mmol/l vs 3.05 ± 0.62 mmol/l, p < 0.0001) and insulin resistance (46 % reduction in homeostasis model assessment-insulin resistance (HOMA-IR) values, 6.76 ± 3.72 vs 3.64 ± 2.44, p = 0.019) compared to vehicle-treated mice without altering the body weight. Gene expression analyses with real-time quantitative polymerase chain reaction (RT-qPCR) and RNA sequencing revealed significant differences in gene expression in the tissues of PCOS mice compared to control mice, whereas the transcriptomic effects of roxadustat were mainly transient. However, immunohistochemistry revealed increased uncoupling protein 1 (UCP1) expression in WAT, which may indicate WAT browning related to HIF pathway activation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Terhi T. Piltonen reports financial support was provided by Novo Nordisk Foundation. Terhi T. Piltonen and Peppi Koivunen reports financial support was provided by Sigrid Jusélius Foundation. Peppi Koivunen reports financial support was provided by Jane and Aatos Erkko Fundation. Terhi T. Piltonen and Peppi Koivunen reports financial support was provided by Research Council of Finland. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To test whether a musculoskeletal multifactorial and individualised hamstring muscle injury (HMI) risk reduction programme could reduce HMI risk in professional football., Methods: We conducted a prospective cohort study in Finnish premier football league teams, with the 2019 season used as a control and an intervention conducted in the 2021 season. Screening was conducted to provide individualised programmes and monitor progress. Cox regression with hazard ratio (HR) was used with HMI as outcome and season as explanatory variable, including all players for primary analysis and those who performed the two seasons for secondary analysis., Results: 90 players were included in the control and 87 in the intervention seasons; 31 players performed in the 2 seasons. Twenty HMIs were recorded during the control and 16 during the intervention seasons. Cox regression analyses revealed that HMI risk at any given time was not significantly different between control and intervention seasons (for all players: HR 0.77 (95% CI 0.39 to 1.51), p=0.444; for the 31 players: HR 0.32 (95% CI 0.01 to 1.29), p=0.110)). For the 31 players, the HMI burden was significantly reduced in the intervention compared with the control season (RR 0.67 (95% CI 0.53 to 0.85)). Higher compliance with knee strength training, maximal velocity exposure and lower performance reductions in maximal theoretical horizontal force and knee flexor force were associated with lower HMI incidence., Conclusions: Although the primary analysis did not reveal any significant effect of the intervention to reduce HMI risk in professional football, the programme was feasible, and additional secondary analyses showed a significant association between the intervention and lower HMI burden, incidence and risk., Competing Interests: Competing interests: PE is an Associate Editor for the British Journal of Sports Medicine and the BMJ Open Sports and Exercise Medicine., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Reports regarding the presence of bacteria in the fetal environment remain limited and controversial. Recently, extracellular vesicles secreted by the human gut microbiota have emerged as a novel mechanism for host-microbiota interaction. We aimed to investigate the presence of bacterial extracellular vesicles in the fetal environment during healthy pregnancies and determine whether extracellular vesicles derived from the gut microbiota can cross biological barriers to reach the fetus., Results: Bacterial extracellular vesicles were detectable in the amniotic fluid of healthy pregnant women, exhibiting similarities to extracellular vesicles found in the maternal gut microbiota. In pregnant mice, extracellular vesicles derived from human maternal gut microbiota were found to reach the intra-amniotic space., Conclusions: Our findings reveal maternal microbiota-derived extracellular vesicles as an interaction mechanism between the maternal microbiota and fetus, potentially playing a pivotal role in priming the prenatal immune system for gut colonization after birth. Video Abstract., (© 2023. The Author(s).)

Background: Bacterial extracellular vesicles (EVs) are more likely to cross biological barriers than whole-cell bacteria. We previously observed EV-sized particles by electron microscopy in the first-pass meconium of newborn infants. We hypothesized that EVs may be of bacterial origin and represent a novel entity in the human microbiome during fetal and perinatal periods., Methods: We extracted EVs from first-pass meconium samples of 17 newborn infants and performed bacterial 16S rRNA gene sequencing of the vesicles. We compared the EV content from the meconium samples of infants based on the delivery mode, and in vaginal delivery samples, based on the usage of intrapartum antibiotics., Results: We found bacterial EVs in all first-pass meconium samples. All EV samples had bacterial RNA. Most of the phyla present in the samples were Firmicutes (62%), Actinobacteriota (18%), Proteobacteria (10%), and Bacteroidota (7.3%). The most abundant genera were Streptococcus (21%) and Staphylococcus (17%). The differences between the delivery mode and exposure to antibiotics were not statistically significant., Conclusions: Bacterial EVs were present in the first-pass meconium of newborn infants. Bacterial EVs may represent an important novel feature of the gut microbiome during fetal and perinatal periods., Impact: We show that bacterial extracellular vesicles are present in the microbiome of first-pass meconium in newborn infants. This is a novel finding. To our knowledge, this is the first study to report the presence of bacterial extracellular vesicles in the gut microbiome during fetal and perinatal periods. This finding is important because bacterial extracellular vesicles are more likely to cross biological barriers than whole-cell bacteria. Thus, the early gut microbiome may potentially interact with the host through bacterial EVs., (© 2022. The Author(s).)

Body consciousness is associated with kinetic skills and various aspects of wellbeing. Physical activities have been shown to contribute to the development of body consciousness. Methodological studies are needed in improving the assessment of body consciousness in adults with distinct physical activity backgrounds. This study (1) examined whether dancers, athletes, and lightly physically active individuals differed regarding the level of their body consciousness, and (2) evaluated the usability of different methods in assessing body consciousness. Fifty-seven healthy adults (aged 20-37) were included in the study. Three experimental methods (aperture task, endpoint matching, and posture copying) and two self-report questionnaires (the Private Body Consciousness Scale, PBCS, and the Body Awareness Questionnaire, BAQ) were used in assessing body consciousness. Athletes outperformed the lightly physically active participants in the posture copying task with the aid of vision when copying leg postures. Dancers performed better than the athletes without the aid of vision when their back and upper body were involved, and better than the lightly active participants when copying leg postures. Dancers and athletes had higher self-reported cognitive and perceptual knowledge of their body than lightly physically active participants. To examine the role of different physical activities in developing body consciousness, experimental methods involving the use of the whole body might be most suitable. Subjective measures may provide complementary evidence for experimental testing., (© 2022. The Author(s).)

Background: Tumor microenvironment or stroma has the potency to regulate the behavior of malignant cells. Fibroblast-like cells are abundant in tumor stroma and they are also responsible for the synthesis of many extracellular matrix components. Fibroblast-cancer cell interplay can modify the functions of both cell types., Methods: We applied mass spectrometry and proteomics to unveil the matrisome in 3D spheroids formed by DU145 prostate cancer cells, PC3 prostate cancer cells, or prostate-derived fibroblasts. Similarly, DU145/fibroblast and PC3/fibroblast coculture spheroids were also analyzed. Western blot analysis and immunofluorescence were used to confirm the presence of specific proteins in spheroids. Cancer dissemination was studied by utilizing "out of spheroids" migration and invasion assays., Results: In the spheroid model cancer cell-fibroblast interplay caused remarkable changes in the extracellular matrix and accelerated the invasion of DU145 cells. Fibroblasts produced structural matrix proteins, growth factors, and matrix metalloproteinases. In cancer cell/fibroblast cocultures basement membrane components, including laminins (α3, α5, β2, and β3), heparan sulfate proteoglycan (HSPG2 gene product), and collagen XVIII accumulated in a prominent manner when compared with spheroids that contained fibroblasts or cancer cells only. Furthermore, collagen XVIII was intensively processed to different endostatin-containing isoforms by cancer cell-derived cathepsin L., Conclusions: Fibroblasts can promote carcinoma cell dissemination by several different mechanisms. Extracellular matrix and basement membrane proteins provide attachment sites for cell locomotion promoting adhesion receptors. Growth factors and metalloproteinases are known to accelerate cell invasion. In addition, cancer cell-fibroblast interplay generates biologically active fragments of basement membrane proteins, such as endostatin., (© 2020 The Authors. The Prostate Published by Wiley Periodicals, Inc.)

High expression level of integrin α2β1 is a hallmark of prostate cancer stem cell like cells. The role of this collagen receptor is controversial since it is down regulated in poorly differentiated carcinomas, but concomitantly proposed to promote metastasis. Here, we show that docetaxel resistant DU145 prostate cancer cells express high levels of α2β1 and that α2β1 High subpopulation of DU145 cells proliferates slower than the cells representing α2β1 Low subpopulation. To further study this initial observation we used Crispr/Cas9 technology to create an α2β1 negative DU145 cell line. Furthermore, we performed rescue experiment by transfecting α2 knockout cells with vector carrying α2 cDNA or with an empty vector for appropriate control. When these two cell lines were compared, α2β1 positive cells proliferated slower, were more resistant to docetaxel and also migrated more effectively on collagen and invaded faster through matrigel or collagen. Integrin α2β1 was demonstrated to be a positive regulator of p38 MAPK phosphorylation and a selective p38 inhibitor (SB203580) promoted proliferation and inhibited invasion. Effects of α2β1 integrin on the global gene expression pattern of DU145 cells in spheroid cultures were studied by RNA sequencing. Integrin α2β1 was shown to regulate several cancer progression related genes, most notably matrix metalloproteinase-1 (MMP-1), a recognized invasion promoting protein. To conclude, the fact that α2β1 decelerates cell proliferation may explain the dominance of α2β1 negative/low cells in primary sites of poorly differentiated carcinomas, while the critical role of α2β1 integrin in invasion stresses the importance of this adhesion receptor in cancer dissemination., Competing Interests: CONFLICTS OF INTEREST The authors disclose no potential conflicts of interest.