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15 pages, 492 KiB  
Systematic Review
Unveiling the Impact of COVID-19 on Ovarian Function and Premature Ovarian Insufficiency: A Systematic Review
by Charalampos Voros, Despoina Mavrogianni, Aspasia Minaoglou, Anthi-Maria Papahliou, Vasileios Topalis, Antonia Varthaliti, Dimitris Mathiopoulos, Panagiota Kondili, Menelaos Darlas, Agni Pantou, Sophia Sina, Antonia Athanasiou, Diamantis Athanasiou, Dimitrios Loutradis and Georgios Daskalakis
Biomedicines 2025, 13(2), 407; https://doi.org/10.3390/biomedicines13020407 - 7 Feb 2025
Viewed by 454
Abstract
Background/Objectives: Premature ovarian insufficiency (POI) is a disorder that affects women under the age of 40. It is characterized by decreased ovarian function, elevated gonadotropin levels, and decreased estradiol. SARS-CoV-2 disrupts ovarian function largely through oxidative stress, inflammation, and immunological dysregulation, which [...] Read more.
Background/Objectives: Premature ovarian insufficiency (POI) is a disorder that affects women under the age of 40. It is characterized by decreased ovarian function, elevated gonadotropin levels, and decreased estradiol. SARS-CoV-2 disrupts ovarian function largely through oxidative stress, inflammation, and immunological dysregulation, which are enhanced by its entrance into ovarian tissues via ACE2 receptors. The purpose of this comprehensive review was to investigate the molecular pathways that link SARS-CoV-2 infection to POI and analyze their consequences for ovarian reserve and fertility. Methods: We searched databases such as PubMed, Scopus, EMBASE, and Google Scholar for papers published between 2020 and 2024. Eligible studies investigated the effects of SARS-CoV-2 on ovarian function, including the hormonal indicators anti-Müllerian hormone (AMH) and follicle-stimulating hormone (FSH), oocyte quality, and ovarian reserve. The data were compiled into a complete examination of molecules and clinical findings. Increased inflammatory indicators, such as interleukin-6 and NLRP3 inflammasome activation, impaired ovarian homeostasis. Anti-SARS-CoV-2 antibodies in follicular fluid could have impaired oocyte quality. Observational studies showed transitory decreases in AMH and changed FSH levels following infection, with variable effects on antral follicle count and IVF results. Changes in lipid profiles and VEGF expression emphasized the virus’s influence on ovarian angiogenesis and the ovarian microenvironment. Conclusions: SARS-CoV-2 infection impairs ovarian function by causing oxidative stress, inflammation, and hormonal disruption, thereby increasing the incidence of POI. While most alterations are temporary, the long-term reproductive consequences remain unknown. Continuous monitoring and specific treatments are required to reduce the reproductive risks associated with COVID-19. Full article
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9 pages, 1428 KiB  
Communication
Acute Exposure to Ozone Affects Circulating Estradiol Levels and Gonadotropin Gene Expression in Female Mice
by Dustin Rousselle and Patricia Silveyra
Int. J. Environ. Res. Public Health 2025, 22(2), 222; https://doi.org/10.3390/ijerph22020222 - 5 Feb 2025
Viewed by 411
Abstract
Ozone, a critical air pollutant, has been shown to lead to systemic inflammation that can alter bodily functions, including hormone secretion, fertility, and the hypothalamic–pituitary–gonadal (HPG) axis. This study aimed to quantify changes in hormone production and follicle development after acute exposure to [...] Read more.
Ozone, a critical air pollutant, has been shown to lead to systemic inflammation that can alter bodily functions, including hormone secretion, fertility, and the hypothalamic–pituitary–gonadal (HPG) axis. This study aimed to quantify changes in hormone production and follicle development after acute exposure to ozone using an animal model to identify the potential mechanisms underlying the observed effects of air pollution exposures on fertility and hormone secretion. To accomplish this, regularly cycling 8-week-old female C57BL/6J mice were exposed to 2 ppm of ozone or filtered air (control) for 3 h on the day of proestrus. Blood, ovaries, brain tissues, and pituitary glands were collected at 4 h after exposure to evaluate hormone levels, ovarian follicle distribution, and gene expression. Ovaries were also harvested at 24 h post-exposure. We found that at 4 h after ozone exposure, mice had significantly higher (30%) circulating estradiol levels than mice exposed to filtered air. This effect was accompanied by a decrease in mRNA expression of gonadotropin genes (LH, FSH) and gonadotropin-releasing hormone in the pituitary gland. Analysis of ovarian tissue at 4 h and 24 h after exposure showed no significant changes in follicle composition or the expression of steroidogenesis genes. We conclude that acute ozone exposure affects sex hormone levels and disrupts the HPG axis. Future studies addressing chronic or long-term effects of air pollution exposure are needed to elucidate the mechanisms by which ambient ozone affects endocrine function. Full article
(This article belongs to the Special Issue Environmental Factors Impacting Reproductive and Perinatal Health)
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11 pages, 526 KiB  
Article
Preliminary Results of Microsurgical Sperm Retrieval in Azoospermic Patients: A Randomized Controlled Trial Comparing Operating Microscope vs. Surgical Loupes
by Mirko Preto, Luca Boeri, Lorenzo Cirigliano, Marco Falcone, Valentina Parolin, Federica Peretti, Ilaria Ferro, Natalia Plamadeala, Martina Scavone, Emanuele Zupo and Paolo Gontero
J. Clin. Med. 2025, 14(3), 970; https://doi.org/10.3390/jcm14030970 - 3 Feb 2025
Viewed by 388
Abstract
Objectives: To compare surgical outcomes and sperm retrieval rates (SRRs) between conventional microsurgical-assisted testicular sperm extraction (m-TeSE—Group A) and testicular sperm extraction performed with surgical loupes (l-TeSE—Group B) in adult males with non-obstructive azoospermia (NOA). Methods: A multicentric prospective randomized trial (ethics committee [...] Read more.
Objectives: To compare surgical outcomes and sperm retrieval rates (SRRs) between conventional microsurgical-assisted testicular sperm extraction (m-TeSE—Group A) and testicular sperm extraction performed with surgical loupes (l-TeSE—Group B) in adult males with non-obstructive azoospermia (NOA). Methods: A multicentric prospective randomized trial (ethics committee no. 202/2022) in accordance with the CONSORT guidelines was conducted from March 2022 to April 2024. Adult males with NOA without genetic alterations who signed the informed consent were enrolled. SRRs, intra- and postoperative complications (according to the Clavien–Dindo classification), and hormonal profile changes were considered as outcomes during the follow-up period. Results: A total of 42 NOA patients were enrolled. The median age was 35 years (IQR: 33–49). The preoperative median FSH was 16.5 mIU/mL (IQR: 11.6–22.5) and the total testosterone was 4.6 (3.5–5.6). Overall, the SRR was 22.6%, with sperm retrieved from 19 testes. Histopathological findings reported Sertoli cell-only syndrome (SCOS) in 46.4% (39 cases), hypospermatogenesis in 26.2%, and germ cell arrest in 26.2% of the patients. No intraoperative complications were recorded. The postoperative complications were minimal (Clavien–Dindo grade I), but no significant differences were recorded in-between the two surgical approaches. Considering the operative time of the testicular exploration alone, Group B seemed to be faster than the m-TeSE, with a median time saving of 8 min (p < 0.01). Conclusion: The use of surgical loupes was safe and comparable with m-TeSE in terms of the SRRs and complication rates. L-TeSE offered a reduction in the operative time compared with m-TeSE. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
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27 pages, 4544 KiB  
Systematic Review
Dietary Patterns, Oxidative Stress, and Early Inflammation: A Systematic Review and Meta-Analysis Comparing Mediterranean, Vegan, and Vegetarian Diets
by Sara Ilari, Stefania Proietti, Francesca Milani, Laura Vitiello, Carolina Muscoli, Patrizia Russo and Stefano Bonassi
Nutrients 2025, 17(3), 548; https://doi.org/10.3390/nu17030548 - 31 Jan 2025
Viewed by 616
Abstract
Background: Dietary habits influenced by lifestyle and cultural factors play a critical role in health by modulating oxidative stress and inflammation. While diets offer significant benefits, they may also pose risks, such as nutrient deficiencies, emphasizing the need for a balanced approach. Exploring [...] Read more.
Background: Dietary habits influenced by lifestyle and cultural factors play a critical role in health by modulating oxidative stress and inflammation. While diets offer significant benefits, they may also pose risks, such as nutrient deficiencies, emphasizing the need for a balanced approach. Exploring Mediterranean and plant-based diet effects on oxidative stress and inflammation biomarkers may help improve health outcomes and disease prevention strategies. Methods: This study analyzed 65 studies following PRISMA guidelines to evaluate the effects of Mediterranean and plant-based diets on biomarkers of oxidative stress and inflammation in healthy individuals. Results: The Mediterranean diet was weakly associated with reductions in oxidative stress markers, including MDA (ROM: 0.80; 95% CI: 0.57–1.13; p = 0.2092) and 8OHdG (ROM: 0.81; 95% CI: 0.59–1.11; p = 0.1847), as well as inflammation markers such as CRP (ROM: 0.72; 95% CI: 0.42–1.23; p = 0.1545) and IL-6 (ROM: 1.23; 95% CI: 0.97–1.55; p = 0.08). The vegetarian diet significantly reduced CRP (ROM: 0.82; 95% CI: 0.69–0.98; p = 0.0297), while the vegan diet showed a borderline reduction (ROM: 0.81; 95% CI: 0.56–1.17; p = 0.2544), suggesting lower systemic inflammation compared to omnivorous diets. Conclusions: Although all three diets demonstrate potential in reducing oxidative stress and inflammation, the antioxidant effects—especially for the Mediterranean diet—are lower than anticipated, indicating alternative mechanisms. Further research is essential to confirm these findings and clarify the underlying mechanisms to enhance preventive health strategies. Full article
(This article belongs to the Section Nutritional Epidemiology)
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31 pages, 5667 KiB  
Article
Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period
by R. Pavani, K. Venkaiah, P. Gnana Prakasam, Vijaya R. Dirisala, P. Gopi Krishna, B. Kishori and S. B. Sainath
Toxics 2025, 13(2), 111; https://doi.org/10.3390/toxics13020111 - 29 Jan 2025
Viewed by 454
Abstract
The antioxidant properties of resveratrol (RES) against oxidative toxicity induced by testicular toxicants are well documented. The current study aimed to investigate the probable beneficial role of RES on male reproduction in adult rats following prepubertal exposure to perfluorooctanoic acid (PFOA). Healthy rats [...] Read more.
The antioxidant properties of resveratrol (RES) against oxidative toxicity induced by testicular toxicants are well documented. The current study aimed to investigate the probable beneficial role of RES on male reproduction in adult rats following prepubertal exposure to perfluorooctanoic acid (PFOA). Healthy rats of the Wistar strain (23 days old) were allocated into four groups. Rats in group I did not receive any treatment, while rats in groups II, III, and IV received RES, PFOA, and RES + PFOA, respectively, between days 23 and 56 and were monitored for up to 90 days. Exposure to PFOA resulted in a significant reduction in spermiogram parameters, testicular 3β- and 17β-HSD activity levels, and circulatory levels of testosterone. A significant elevation in LPx, PCs, H2O2, and O2, associated with a concomitant reduction in SOD, CAT, GPx, GR, and GSH, was noticed in the testes, as well as region-specific changes in pro- and antioxidants in the epididymides of exposed rats compared to controls. A significant increase in serum FSH and LH, testicular cholesterol levels, and caspase-3 activity was observed in PFOA-exposed rats compared to controls. Histological analysis revealed that the integrity of the testes was deteriorated in PFOA-exposed rats. Transcriptomic profiling of the testes and epididymides revealed 98 and 611 altered genes, respectively. In the testes, apoptosis and glutathione pathways were disrupted, while in the epididymides, glutathione and bile secretion pathways were altered in PFOA-exposed rats. PFOA exposure resulted in the down-regulation in the testes of 17β-HSD, StAR, nfe2l2, ar, Lhcgr, and mRNA levels, associated with the up-regulation of casp3 mRNA, and down-regulation of alpha 1 adrenoceptor, muscarinic choline receptor 3, and androgen receptor in the epididymides of exposed rats compared to the controls. These events might lead to male infertility in PFOA-exposed rats. In contrast, restoration of selected reproductive variables was observed in RES plus PFOA-exposed rats compared to rats exposed to PFOA alone. Taken together, we postulate that prepubertal exposure to PFOA triggered oxidative damage and altered genes in the testes and epididymides, leading to suppressed male reproductive health in adult rats, while RES, with its steroidogenic, antiapoptotic, and antioxidant effects, restored PFOA-induced fertility potential in rats. Full article
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13 pages, 265 KiB  
Article
Hormones, Age, and Erectile Dysfunction: Should Routine Testing Be Part of the Initial Evaluation?
by Daniel Porav-Hodade, Raul Dumitru Gherasim, Irina Bianca Kosovski, Toader Septimiu Voidazan, Nicolae Crisan, Petrut Bogdan, Radu Galis, Bogdan Ovidiu Feciche, Mártha Orsolya Katalin Ilona and Ciprian Todea-Moga
Diagnostics 2025, 15(3), 294; https://doi.org/10.3390/diagnostics15030294 - 27 Jan 2025
Viewed by 562
Abstract
Background/Objectives: The aim of this study was to investigate the relationship between age, the severity of erectile dysfunction (ED), and the various hormones that may influence erectile function. Methods: A multicenter cross-sectional study was conducted between January 2015 and December 2023. [...] Read more.
Background/Objectives: The aim of this study was to investigate the relationship between age, the severity of erectile dysfunction (ED), and the various hormones that may influence erectile function. Methods: A multicenter cross-sectional study was conducted between January 2015 and December 2023. The study assessed age, sexual function using the IIEF-15 questionnaire, and the levels of total testosterone (TT), free testosterone (FT), FSH, LH, estradiol, prolactin (PRL), and SHBG. Results: A total of 411 patients were included in the study. The mean age of the patients was 63.19 years. The vast majority (91.73%) exhibited some degree of ED. The severity of ED increases with age, ranging from 56.26 years for patients without ED to 73.12 years for those with severe ED. A statistically significant negative correlation was observed between IIEF and age, while a positive correlation was observed between IIEF and serum levels of TT and FT (p < 0.05). Age was significantly correlated with all evaluated hormones (p < 0.01), except estradiol and prolactin. Total testosterone levels progressively decreased with the increase in the severity of erectile dysfunction, from a median of 7.05 ng/mL in patients with normal erectile function to 3.56 ng/mL in those with severe symptoms, remaining above the normal minimum threshold across all groups, whereas free testosterone (FT) levels also declined progressively. All erectile dysfunction groups had median FT levels below the normal minimum threshold. FSH, LH, and SHBG showed an increase with each progressive severity of erectile dysfunction. The multivariate linear regression revealed that IIEF scores are significantly associated with age, TT, and FT levels, while FSH did not present a statistically significant association in this model. Conclusions: Age shows a significant statistical correlation with both the severity of erectile dysfunction and the levels of total testosterone, free testosterone, LH, FSH, and SHBG. Total and free testosterone levels are significantly associated with the severity of erectile dysfunction, with free testosterone median values remaining above the normal minimum threshold in all patients with erectile dysfunction. Therefore, free testosterone should be considered a routine test, alongside total testosterone. In contrast, LH, estradiol, SHBG, and prolactin do not demonstrate any statistical correlation with erectile dysfunction and should not be recommended as routine investigations. Full article
(This article belongs to the Special Issue Exploring the Role of Diagnostic Biochemistry)
9 pages, 509 KiB  
Communication
Follicular Fluid Vanin-1 Levels in Patients Undergoing Ivf: A Preliminary Study
by Ákos Várnagy, Péter Mauchart, Gábor Nagy, József Bódis and Endre Sulyok
Antioxidants 2025, 14(2), 133; https://doi.org/10.3390/antiox14020133 - 23 Jan 2025
Viewed by 383
Abstract
This preliminary study was designed to determine follicular fluid (FF) vanin-1 levels, to assess their relation to serum vanin-1 and to reveal their potential to predict the outcome of in vitro fertilization (IVF). Eighteen unselected, consecutive women undergoing IVF were included. Serum and [...] Read more.
This preliminary study was designed to determine follicular fluid (FF) vanin-1 levels, to assess their relation to serum vanin-1 and to reveal their potential to predict the outcome of in vitro fertilization (IVF). Eighteen unselected, consecutive women undergoing IVF were included. Serum and pooled FF samples were obtained simultaneously during routine IVF procedures. Vanin-1 levels were measured by using commercially available ELISA kits. As most of the values were below 0.6 ng/mL, the data are given as optical density. It was found that vanin-1 can be detected in FF and that it is not significantly related to its maternal serum levels (p = 0.06). FF vanin-1 levels proved to be higher in non-pregnant as compared to pregnant women (p < 0.04). There are significant positive relationships between the FF to serum vanin-1 ratio and body mass index (BMI, p < 0.02), anti-Müllerian hormone (AMH, p < 0.02) and baseline serum estradiol (p < 0.01). Moreover, the FF/serum vanin-1 ratio tended to increase with cumulative FSH dose, but this increase did not reach statistical significance (p = 0.064). It may be concluded that FF vanin-1 may serve as a biomarker to predict IVF outcome. To confirm this contention, further studies are to be performed. Full article
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14 pages, 247 KiB  
Article
Hormonal Status and Quality of Life of Women Treated for Infertility Before and During COVID-19 Pandemic in Poland
by Kamila Wójtowicz, Justyna Kot, Marta Makara-Studzińska, Natalia Wdowiak, Michał Filip, Andrzej Wróbel, Jan Wróbel, Dorota Matuszyk, Melania Bojar, Joanna Bartosińska and Artur Wdowiak
J. Clin. Med. 2025, 14(3), 721; https://doi.org/10.3390/jcm14030721 - 23 Jan 2025
Viewed by 557
Abstract
Background/Objectives: Infertile people experience a lot of psychological stress due to the inability to conceive and achieve pregnancy. Studies on the quality of life (QoL) of people undergoing infertility treatment typically show a lower QoL for couples struggling with reproductive problems. In recent [...] Read more.
Background/Objectives: Infertile people experience a lot of psychological stress due to the inability to conceive and achieve pregnancy. Studies on the quality of life (QoL) of people undergoing infertility treatment typically show a lower QoL for couples struggling with reproductive problems. In recent years, a new factor that may have had a stressful impact on people treated for infertility is the COVID-19 pandemic. The aim of this study is to assess the impact of the COVID-19 pandemic on the QoL of Polish women treated for infertility and on the secretion of selected sex hormones. Methods: The study sample consisted of 600 women undergoing treatment due to infertility and 100 healthy women in a control group. The World Health Organization Quality of Life-BREF (WHOQOL-BREF) and the Polish version of the questionnaire Fertility Quality of Life (FertiQoL) were used for data collection. The levels of selected hormones were measured from blood samples. Results: The effects of the pandemic were visible primarily in the reduced QoL of patients. The QoL in terms of physical health, psychological health, social relationships, and environmental sphere was drastically reduced by COVID-19, especially among women treated with IVF (in vitro fertilization) and IUI (intrauterine insemination). The hormonal status of women treated for infertility during the pandemic significantly changed due to a decrease in FSH (follicle-stimulating hormone) and LH (luteinizing hormone) secretion and an increase in PRL (prolactin). Conclusions: The pandemic resulted in a decline in the QoL of women with reproductive problems. The quality of life was influenced by the type of therapy used during infertility treatment. The study also suggests a relationship between a decrease in the quality of life of persons treated for infertility during the pandemic and their hormonal status. Full article
(This article belongs to the Special Issue Clinical Updates in Reproductive Endocrinology)
20 pages, 1582 KiB  
Article
Androgens and Hirsutism in a Large Cohort of Portuguese Women
by Joana Pinto, Nicoletta Cera, Claudia Camerino, Jorge Beires and Duarte Pignatelli
J. Clin. Med. 2025, 14(3), 673; https://doi.org/10.3390/jcm14030673 - 21 Jan 2025
Viewed by 459
Abstract
Background/Objectives: Hirsutism is excessive male-patterned hair in postpubertal women with multifactorial etiology and is an indicator of hyperandrogenism associated with polycystic ovary syndrome (PCOS). Indeed, it can be caused by the enhanced peripheral conversion of androgen precursors to testosterone, as in idiopathic [...] Read more.
Background/Objectives: Hirsutism is excessive male-patterned hair in postpubertal women with multifactorial etiology and is an indicator of hyperandrogenism associated with polycystic ovary syndrome (PCOS). Indeed, it can be caused by the enhanced peripheral conversion of androgen precursors to testosterone, as in idiopathic hirsutism (IH). Moreover, hirsutism can be caused by hirsutism-related hyperandrogenic syndromes like non-classic congenital adrenal hyperplasia (NCAH) and idiopathic hyperandrogenism (IHA). Methods: In this study, we characterized a large cohort of Portuguese women referred for hirsutism and estimated the prevalence of PCOS, NCAH, IHA, and IH. The levels of androgens and gonadotropins and body mass index (BMI) were measured and compared with controls. The correlation between each variable was calculated. Results: In the cohort, we found a prevalence of PCOS of 56.2%, IH of 20.2%, IHA of 17.3%, and NCAH of 6.2%. Subjects with PCOS were the only ones showing a significant difference in BMI compared to the controls and had the lowest levels of sex hormone-binding globulin (SHBG). Those with NCAH were younger and more hirsute with higher levels of testosterone, among other androgens. Those with IH had lower luteinizing hormone (LH) and LH/follicle-stimulating hormone (FSH) ratios than those with PCOS. Those with IH had lower SHBG levels compared to the controls and a higher free androgen index (FAI). Those with IHA had higher androgens compared to those with IH, in particular, adrenal-derived androgens. Conclusions: The pathogenesis of hirsutism is complex, and the contributions of the pituitary gland, ovaries, adrenals, adipose tissue, and liver have to be ascertained to understand the clinical manifestations and delineate appropriate treatments. This study sheds new light on the fine hormonal regulation of these diseases. Full article
(This article belongs to the Special Issue Polycystic Ovary Syndrome (PCOS): State of the Art: 2nd Edition)
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17 pages, 1664 KiB  
Article
Binary Combinations of Essential Oils: Antibacterial Activity Against Staphylococcus aureus, and Antioxidant and Anti-Inflammatory Properties
by Clara Naccari, Giovanna Ginestra, Nicola Micale, Ernesto Palma, Benedetta Galletta, Rosaria Costa, Rossella Vadalà, Antonia Nostro and Mariateresa Cristani
Molecules 2025, 30(3), 438; https://doi.org/10.3390/molecules30030438 - 21 Jan 2025
Viewed by 507
Abstract
Background: The lack of new antimicrobial drugs and increased antimicrobial resistance has focused attention on the employment of essential oils (EOs) in human and veterinary medicine. The aim of this study was to test new binary associations between known and uncommon EOs. [...] Read more.
Background: The lack of new antimicrobial drugs and increased antimicrobial resistance has focused attention on the employment of essential oils (EOs) in human and veterinary medicine. The aim of this study was to test new binary associations between known and uncommon EOs. Methods: EOs from Origanum vulgare L., Juniperus communis L., Cistus ladaniferus L., Citrus aurantium L. var. amara were tested individually and in binary combinations to study, as follows: antibacterial activity against Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA) and Escherichia coli; antioxidant capacity via redox-based assays (DPPH, ABTS and FRAP); and anti-inflammatory activity via the bovine serum albumin denaturation inhibition assay. Results: O. vulgare L. showed good antibacterial activity against all strains (MIC = 0.03–0.12%, v/v), followed by C. ladaniferus L., and also had the best antioxidant and anti-inflammatory activities. Synergistic and additive effects were observed for the EO combinations O. vulgare L./C. ladaniferus L. and O. vulgare L./J. communis L. against S. aureus and MRSA, respectively. A reduction in biofilm was noted. Antioxidant and anti-inflammatory activities were also detected. Conclusions: The results suggest that EO combinations may be a promising strategy in veterinary settings for the treatment of infectious diseases caused by S. aureus, including drug-resistant and biofilm-forming strains accompanied by oxidative stress and inflammation. Full article
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9 pages, 577 KiB  
Review
Clinical Electrophysiology and Mathematical Modeling for Precision Diagnosis of Infertility
by Fernanda Carvalho Cavalari, Paola Sulis Mendes, Bruna Antunes Zaniboni, Carine Royer, Bárbara Ogliari Martins Taques, Karina Cesca, Marcela Aragón and Fátima Regina Mena Barreto Silva
Biomedicines 2025, 13(2), 250; https://doi.org/10.3390/biomedicines13020250 - 21 Jan 2025
Viewed by 457
Abstract
How can cellular electrophysiology measurements and mathematical modeling of ionic channels help to identify pivotal targets in disease-related cell signaling? The purpose of this review is to highlight the advantages and disadvantages of using both of these complementary techniques to determine molecular targets [...] Read more.
How can cellular electrophysiology measurements and mathematical modeling of ionic channels help to identify pivotal targets in disease-related cell signaling? The purpose of this review is to highlight the advantages and disadvantages of using both of these complementary techniques to determine molecular targets that may be structurally or functionally altered in a specific disease. In addition, both electrophysiology measurements and mathematical modeling may improve coordinated drug development, accelerate the prediction of new drugs, and facilitate repositioning of pharmacological agents. This review focuses on the data obtained from electrophysiology and mathematical model approaches, including intracellular recording, cellular patch clamp measurements, and the Hodgkin and Huxley equation, as key precision methodologies. To this end, seminiferous tubules, the Sertoli cell line (TM4), and/or primary cultures of Sertoli cells were used to explore the role of follicle-stimulating hormone (FSH), thyroid hormones, retinol, testosterone, and 1,25(OH)2 vitamin D3 in the coordinated activation or inhibition of ionic channels essential for male fertility. Based on the discussed data, Sertoli cells precisely regulate their biological activity by coordinating channel activity according to the hormonal environment and the nutritional requirements required for germ cell development. Full article
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12 pages, 264 KiB  
Review
The Clinical Use of Myo-Inositol in IVF-ET: A Position Statement from the Experts Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), the Polish Society of Andrology, and the International Scientific Association for the Support and Development of Medical Technologies
by Artur Wdowiak, Szymon Bakalczuk, Michał Filip, Antonio Simone Laganà and Vittorio Unfer
J. Clin. Med. 2025, 14(2), 558; https://doi.org/10.3390/jcm14020558 - 16 Jan 2025
Viewed by 815
Abstract
Background: Myo-inositol plays a vital role in human health, functioning as a second messenger of FSH and facilitating the transport of glucose into the cell. Consequently, myo-inositol is regularly utilized in the treatment of polycystic ovary syndrome (PCOS), wherein it acts upon metabolic [...] Read more.
Background: Myo-inositol plays a vital role in human health, functioning as a second messenger of FSH and facilitating the transport of glucose into the cell. Consequently, myo-inositol is regularly utilized in the treatment of polycystic ovary syndrome (PCOS), wherein it acts upon metabolic factors, improving insulin sensitivity and reducing total androgen levels. Patients with PCOS frequently suffer from infertility; thus, the use of myo-inositol has been explored in improving assistive reproductive technique (ART) procedures. This is by no means limited to patients with PCOS, as inositol has found applications in non-PCOS patient groups in addition to in male factor infertility. This joint statement from the Experts Group on Inositol in Basic and Clinical Research and on PCOS (EGOI-PCOS), the Polish Society of Andrology, and the International Scientific Association for the Support and Development of Medical Technologies discusses the latest evidence on this topic, with the aim of interrogating whether myo-inositol could be implemented in everyday ART patient care. Methods: The authors conducted a narrative review performed via an independent literature search between July and August 2024, using the search platforms PubMed, Web of Science, and Google Scholar. Results: In both non-PCOS and PCOS populations seeking IVF care, MI supplementation prior to ovarian stimulation may positively affect gonadotropin use and duration, oocyte and embryo quality, fertilization, and clinical pregnancy rates. Conclusions: This position statement recommends that myo-inositol be considered as a potential pretreatment strategy prior to ovarian hyperstimulation with gonadotropins. Full article
(This article belongs to the Section Reproductive Medicine & Andrology)
19 pages, 1716 KiB  
Review
Efficacy of N-Acetylcysteine in Polycystic Ovary Syndrome: Systematic Review and Meta-Analysis
by Isabel Viña, Juan R. Viña, Macarena Carranza and Gonzalo Mariscal
Nutrients 2025, 17(2), 284; https://doi.org/10.3390/nu17020284 - 14 Jan 2025
Viewed by 1268
Abstract
Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age and requires better treatment. N-acetylcysteine (NAC) is known to be beneficial under such conditions owing to its antioxidant potential and insulin-sensitizing properties. The effect of NAC [...] Read more.
Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age and requires better treatment. N-acetylcysteine (NAC) is known to be beneficial under such conditions owing to its antioxidant potential and insulin-sensitizing properties. The effect of NAC on the reproductive outcomes of PCOS patients was examined in this meta-analysis. Methods: In accordance with PRISMA standards, this meta-analysis included studies that compared N-acetylcysteine, metformin, clomiphene citrate, and a placebo in patients with POCS. The main indicators were follicular growth, endometrial thickness, and hormone level. The risk of bias was evaluated using the Cochrane ROB2 tool. Results: Twenty-two studies (n = 2515) were included. NAC was associated with a statistically significant increase in progesterone (SMD 0.95, 95% CI: 0.13–1.77, p = 0.02) and endometrial thickness (SMD 0.58, 95% CI: 0.10–1.06, p = 0.02) compared to the placebo and other drugs (SMD 0.71, 95% CI: 0.48–0.94, p < 0.0001). LH levels were significantly increased by NAC compared to metformin (SMD 0.67, 95% CI: 0.23–1.12, p = 0.003). However, no significant differences were observed in the estradiol, SHBG, or FSH levels. Conclusions: NAC had a major effect on progesterone, endometrial thickness, and LH levels in women with PCOS. Therefore, it may be a potential treatment option. Full article
(This article belongs to the Section Micronutrients and Human Health)
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17 pages, 559 KiB  
Article
Role of Vitamin D Status and Alterations in Gut Microbiota Metabolism in Fibromyalgia-Associated Chronic Inflammatory Pain
by Caterina Saija, Maria Paola Bertuccio, Alberto Scoglio, Vincenzo Macaione, Francesco Cacciola, Giuseppe Micalizzi, Daniela Caccamo, Carolina Muscoli and Monica Currò
Biomedicines 2025, 13(1), 139; https://doi.org/10.3390/biomedicines13010139 - 9 Jan 2025
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Abstract
Background/Objectives: Several studies suggest gut microbiota metabolites as important immuno-modulators in inflammatory pain. We aimed to investigate the relationship between vitamin D status and gut dysbiosis markers in fibromyalgia (FM)-associated chronic inflammation. Methods: Blood samples were collected from sixty-eight female FM [...] Read more.
Background/Objectives: Several studies suggest gut microbiota metabolites as important immuno-modulators in inflammatory pain. We aimed to investigate the relationship between vitamin D status and gut dysbiosis markers in fibromyalgia (FM)-associated chronic inflammation. Methods: Blood samples were collected from sixty-eight female FM patients (49.9 ± 12.35 years). Pain intensity was assessed by FIQ-R. The serum levels of the pro-inflammatory cytokines TNF-α, IL-1β, IL-6, IL-17, IFN-γ, as well as those of vitamin D (25(OH)D3) and the kynurenine/tryptophan ratio (Kyn/Trp) were determined by ELISA and HPLC, respectively. The plasma levels of the SCFAs acetate, butyrate, and propionate were detected by GC-MS. Results: A mean FIQ-R score indicated that the patients could be classified as having moderate FM. The mean levels of all cytokines, but IL-6 and IL-1β, were higher than the normal reference values. The highest concentrations of cytokines were observed in patients showing the highest FIQ-R scores and the lowest 25(OH)D3 levels. Deficient levels of acetate were found paralleled by an increase in Kyn/Trp. The highest acetate concentrations were detected in patients with the lowest FIQ-R scores and 25(OH)D3 levels. Significantly negative correlations were found between 25(OH)D3 concentrations and FIQ-R scores (p = 0.007) as well as IL-17 levels (p = 0.002) and between acetate and TNF-α (p = 0.040) as well as FIQ-R scores (p = 0.028), while significantly positive correlations were observed between Kyn/Trp and IL-17 (p = 0.027) as well as IFN-γ (p = 0.003). Conclusions: Our preliminary data suggest that the vitamin D status along with altered gut microbiota metabolism plays a major role in FM-related inflammatory pain. Replication of these findings in a larger cohort is required to provide additional insights. Full article
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Article
Cholecystokinin (CCK) Is a Mediator Between Nutritional Intake and Gonadal Development in Teleosts
by Hangyu Li, Hongwei Liang, Xiaowen Gao, Xiangtong Zeng, Shuo Zheng, Linlin Wang, Faming Yuan, Shaohua Xu, Zhan Yin and Guangfu Hu
Cells 2025, 14(2), 78; https://doi.org/10.3390/cells14020078 - 8 Jan 2025
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Abstract
Nutritional intake is closely linked to gonadal development, although the mechanisms by which food intake affects gonadal development are not fully understood. Cholecystokinin (CCK) is a satiety neuropeptide derived from the hypothalamus, and the present study observed that hypothalamic CCK expression is significantly [...] Read more.
Nutritional intake is closely linked to gonadal development, although the mechanisms by which food intake affects gonadal development are not fully understood. Cholecystokinin (CCK) is a satiety neuropeptide derived from the hypothalamus, and the present study observed that hypothalamic CCK expression is significantly influenced by food intake, which is mediated through blood glucose levels. Interestingly, CCK and its receptors were observed to exhibit a high expression in the hypothalamus–pituitary–gonad (HPG) axis of grass carp (Ctenopharyngodon idellus), suggesting that CCK is potentially involved in regulating fish reproduction through the HPG axis. Further investigations revealed that CCK could significantly stimulate the expression of gonadotropin-releasing hormone-3 (GnRH3) in the hypothalamus. In addition, single-cell RNA sequencing showed that cckrb was highly enriched in pituitary follicle-stimulating hormone (FSH) cells. Further study confirmed that CCK can significantly induce FSH synthesis and secretion in primary cultured pituitary cells. Additionally, with primary cultured ovary cells as a model, the in vitro experiment demonstrated that CCK directly induces the expression of lhr, fshr, and cyp19a1a mRNA. This indicates that hypothalamic CCK may act as a nutrient sensor involved in regulating gonadal development in teleosts. Full article
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