Search Results (162)

Autologous serum (AS) tears are an effective therapeutic option for advanced DED, mimicking the biochemical composition of natural tears. However, the absence of universally accepted guidelines has resulted in variability in AS tear concentration, diluents, processing of collected blood, and storage conditions, raising questions regarding the optimal parameters for AS tear use. This perspective provides a framework to inform clinical implementation and to guide future research on AS tear therapy optimization. PubMed, Scopus, and the Cochrane Library were searched for English-language articles from January 2022 through September 2025 using the terms “autologous serum,” “dry eye disease,” “dry eye syndrome,” “dry eye,” and “DED.” Evidence suggests that AS tears diluted to 20% are widely used for moderate DED, whereas higher concentrations may provide faster, more pronounced and more durable improvements, particularly in severe cases. Levofloxacin-containing eye drops, artificial tears without emphasis on a specific component, sodium hyaluronate (SH)-containing eye drops, cyclosporine A (CsA)-containing ultra-nano emulsions, and methylcellulose have been investigated as alternatives to conventional diluents. Standardization of clotting, centrifugation and storage parameters is expected to enhance efficacy of AS tears and ensure stability of growth factors. Combination with estrogen replacement therapy in perimenopausal women or with topical insulin eye drops, as well as perioperative prophylactic use in patients with graft-versus-host disease (GVHD)-associated dry eye undergoing cataract surgery, represent emerging applications of AS tears that demonstrate potential to improve therapeutic outcomes. Overall, this perspective highlights the need for consensus protocols, supports severity-based concentration tailoring, and notes that diluents and processing methods require further refinement. Full article

Osteoporosis is a prevalent metabolic bone disorder characterized by reduced bone mass, compromised microarchitecture, and increased fracture risk. Its pathogenesis extends beyond simple bone mineral density (BMD) loss and reflects complex disruptions in bone remodeling governed by osteoblast–osteoclast coupling and systemic metabolic factors. This review lays particular emphasis on diabetes mellitus-related osteoporosis (DOP) and estrogen deficiency-induced osteoporosis (EDOP), discussing bone remodeling between osteoclastogenesis and osteoblast differentiation regulated by key signaling pathways, including the RANKL/RANK/OPG, Wnt/β-catenin, BMP–Smad, Hedgehog, and inflammatory cytokine networks. This review then explores how chronic hyperglycemia, insulin deficiency or resistance, oxidative stress, ferroptosis, advanced glycation end products, and low-grade inflammation disrupt bone homeostasis in diabetes, resulting in impaired bone quality and elevated fracture risk, particularly in type 2 diabetes. In parallel, we discuss the genomic and non-genomic actions of estrogen in maintaining skeletal integrity and elucidate how estrogen deficiency accelerates bone resorption and suppresses bone formation through altered cytokine signaling, oxidative stress, and impaired mechanotransduction. Advances in diagnostic strategies beyond BMD, including trabecular bone score, high-resolution peripheral quantitative computed tomography, and emerging biomarkers, are reviewed. Finally, this review summarizes current and emerging therapeutic approaches tailored to DOP and EDOP, emphasizing the need for mechanism-based, individualized management. A deeper understanding of these shared and distinct pathways may facilitate improved risk stratification and the development of targeted interventions for osteoporosis. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum from simple steatosis to steatohepatitis (MASH), including liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The 2023 EASL–EASD–EASO guidelines provide updated definitions and emphasize personalized management, yet do not explicitly address sex- and gender-related differences. This review highlights the impact of biological sex and gender on MASLD epidemiology, pathogenesis, clinical presentation, and therapeutic response. Men show earlier peak prevalence, greater visceral obesity, higher insulin resistance, and increased risk of fibrosis, HCC, and cardiovascular mortality. Women of childbearing age benefit from estrogen-mediated protection, which diminishes after menopause, leading to disease risk similar to men. Genetic variants (PNPLA3, TM6SF2), hormonal factors, platelet parameters, liver biomarkers, and environmental exposures contribute to sex-specific susceptibility and disease progression. Lifestyle interventions and pharmacological therapies exhibit differential efficacy across sexes, influenced by hormonal status. Integrating biological sex, gender identity, and sociocultural factors into diagnostic and therapeutic strategies is essential to optimize MASLD management and reduce its global burden. Full article

Background: Genetic studies have found that a germline BRCA1 gene mutation is the origin of highly increased cancer risk. Clinical studies have suggested that increased cancer risk in type-2 diabetes may be attributed to unhealthy lifestyle factors and bad habits. Purpose: Patients with either BRCA1 gene mutation or type-2 diabetes similarly exhibit increased cancer risk, insulin resistance, and fertility disorders. It was suggested that these three alterations derive from a common genomic failure, and its recognition may shed light on the unsolved secret of cancer. Results: (1) Germline mutations on ESR1, BRCA1, and CYP19A genes encoding estrogen receptor alpha (ERα), genome safeguarding BRCA1 protein, and CYP19 aromatase enzyme cause genomic instability. BRCA1 and ESR1 gene mutations specifically cause breast cancer, while error in the CYP19A gene leads to cancers in the endometrium, ovaries, and thyroid. (2) ERα, BRCA1, and CYP19 aromatase proteins are transcription factors creating the crucial DNA stabilizer circuit driven by estrogen regulation. Liganded ERα drives a second regulatory circuit to also control cell proliferation, in partnership with various growth factors. In a third regulatory circuit, liganded ERα drives cellular glucose supply in close interplay with insulin, IGF-1, and glucose transporters. (3) Impaired expression or activation of each transcription factor of the triad leads to defective estrogen signaling and endangers regular cell proliferation, insulin sensitivity, and fertility. (4) Impaired estrogen signaling caused by either genetic or lifestyle factors alarms the hypothalamus, which issues neural and hormonal commands throughout the body to restore estrogen signaling. (5) When the compensatory actions cannot restore estrogen signaling, the breakdown of genomic regulation leads to cancer initiation. (6) Lifestyle factors that upregulate estrogen signaling decrease cancer risk, while downregulating estrogen signaling increases it. Conclusions: Increased cancer risk, insulin resistance, and infertility all originate from defective estrogen signaling. Full article

Introduction: We previously showed that baboon offspring born to mothers deprived of estrogen during the second half of gestation exhibited insulin resistance prior to and after the onset of puberty. Moreover, the size of skeletal muscle myofibers and the number of microvessels important for delivery of insulin/glucose to myofibers were lower in near-term fetuses deprived of estrogen during pregnancy, and myofiber capillarization remained reduced in post-pubertal offspring deprived of estrogen in utero. However, it remains to be determined whether skeletal muscle size is restored to normal in animals deprived of estrogen in utero after the onset of puberty/gonadal estrogen production. Methods: To answer this question, the current study quantified the size and number of slow and fast fibers in biopsies of vastus lateralis skeletal muscle obtained from post-pubertal female baboon offspring 9–12 years old, born to mothers who were untreated (n = 7) or treated during the second half of gestation with letrozole (n = 6; suppressed maternal and fetal estrogen by >90%) or letrozole plus estradiol benzoate (n = 3). Results: Results indicated that skeletal muscle slow and fast fiber growth in female offspring appeared to occur by hypertrophy and that respective size of fibers after the onset of puberty was similar in offspring born to mothers who were untreated or deprived of estrogen in utero. Conclusions: Postnatal myofiber hypertrophy likely reflects the impact of the pubertal surge in and continued exposure of offspring myofibers to ovarian estrogen and is restored to normal in post-pubertal female offspring deprived of estrogen in utero. Full article

Obesity and menopausal hypoestrogenism interact in a way that worsens insulin resistance and increases the risk of metabolic diseases. This study evaluated the effects of a diet composed of liquid chickpea sprouts (CS) on these problems. Sixty-four female Wistar rats were assigned to four experimental groups: a control group (Ctrl); a hypoestrogenic (HE) group, induced by ovariotomy; an obese (Ob) group, fed a high-sucrose diet; and a hypoestrogenic-obese (HE-Ob) group. Each group was subdivided into animals treated with chickpea sprouts (CS, 0.9 g/kg/day) or with a vehicle for four weeks. The results showed that CS significantly improved glucose tolerance and restored insulin sensitivity, normalizing the HOMA-IR index in both the Ob and HE-Ob groups. In addition, CS reduced serum triglycerides, reversed hepatic steatosis, and caused a favorable redistribution of adipose tissue, leading to decreased mesenteric fat accumulation. In conclusion, chickpea sprouts have protective metabolic effects by improving glucose homeostasis, reducing blood lipids, and mitigating liver damage in an estrogen-deficient model of obesity. These findings support the potential of chickpea sprouts as a dietary intervention to help prevent metabolic complications in obese postmenopausal women. Full article

Background: Metabolic instability, encompassing fluctuations in body weight, glucose, insulin, and sex hormones, may create a pro-inflammatory and proliferative endometrial microenvironment even in women with normal BMI. Methods: A systematic literature review was performed in PubMed, Embase, and Google Scholar, including studies assessing the relationship between metabolic, endocrine, and inflammatory factors and the risk of endometrial cancer in non-obese women. Results: Variability in body weight and hormonal parameters was associated with chronic subclinical inflammation, altered leptin/adiponectin secretion, decreased sex hormone-binding globulin, and increased estrogen bioavailability. These changes disrupt the homeostatic rhythm of endometrial cell regeneration and increase the likelihood of neoplastic transformation. Conclusions: Metabolic instability represents a novel integrated risk factor for endometrial cancer among women without obesity and should be incorporated into future risk stratification and prevention models. Full article

In birds, light can penetrate the cranial bones and reach deep brain regions, where non-visual photoreceptors, especially in the hypothalamus, detect spectral and photoperiodic cues. Alongside retinal photoreception, deep-brain light sensing contributes to circadian entrainment and regulates melatonin secretion by the pineal gland. These light-driven pathways modulate endocrine activity, playing a key role in muscle development. This review explores how monochromatic light-emitting diode (LED) illumination, particularly green and blue wavelengths, affects the somatotropic axis (growth hormone-releasing hormone [GHRH]-growth hormone [GH]-insulin-like growth factor 1 [IGF-1]), the gonadal axis (gonadotropin-releasing hormone [GnRH]-luteinizing hormone [LH]/follicle-stimulating hormone [FSH]-sex steroids [testosterone, estrogen, progesterone]), the thyroid axis (thyrotropin-releasing hormone [TRH]-thyroid-stimulating hormone [TSH]-thyroxine [T₄]/triiodothyronine [T₃]), and the hypothalamic-pituitary-adrenal (HPA) axis (corticotropin-releasing hormone [CRH]-adrenocorticotropic hormone [ACTH]-corticosterone). Green light enhances early-stage muscle growth via GHRH and IGF-1 upregulation, while blue light supports later myogenic activity and oxidative balance. Light schedules also influence melatonin dynamics, which in turn modulate endocrine axis responsiveness to photic cues. Furthermore, variations in photoperiod and exposure to artificial lights at night (ALAN) affect thyroid activity and HPA axis reactivity, influencing metabolism, thermoregulation, and stress resilience. Together, ocular and intracranial photoreception form a complex network that links environmental light to hormonal regulation and muscle growth. These insights support the strategic use of LED lighting to optimize broiler performance and welfare. Full article

Background/Objectives: Conventional two-dimensional (2D) cell cultures offer valuable insights into cancer cell biology; however, they lack in replicating the complex interactions present in solid tumors. Therefore, research has shifted towards the development of three-dimensional (3D) cell models that recapitulate the dynamic cell–cell and cell–matrix interactions within the complex tumor microenvironment (TME), better resembling tumor growth and initial stages of dissemination. Extracellular matrix, a key component within the TME, regulates cell morphology and signaling, influencing key functional properties. Breast cancer remains the most frequently diagnosed cancer type in women and a leading cause of cancer-related mortality. Methods: The aim of the present study was the development of breast cancer cell-derived spheroids, utilizing two breast cancer cell lines with differential estrogen receptor (ER) expression profile, and their characterization in terms of morphology, functional properties, and expression of epithelial-to-mesenchymal transition (EMT) markers and matrix signatures implicated in breast cancer progression. To this end, the ERα-positive MCF-7, and ERβ-positive MDA-MB-231 breast cancer cell lines were utilized. Results: Our findings revealed notable phenotypic transitions between 2D and 3D cultures, which were further supported by differential EMT markers expression. Moreover, spheroids exhibited distinct expression profiles of key receptors [ERs, epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGF1R)] and matrix molecules (syndecans, and matrix metalloproteinases), accompanied by altered functional cell properties. Bioinformatic tools further emphasized the interplay between the studied matrix regulators and their prognostic relevance in breast cancer. Conclusions: Overall, this study introduces a simple yet informative 3D breast cancer model that captures key TME features to better predict cell behavior in vitro. Full article

Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder affecting 6–20% of women of reproductive age, manifesting through hyperandrogenism, ovulatory dysfunction, insulin resistance, and diverse metabolic derangements. Increasing evidence highlights the contribution of environmental factors, particularly endocrine-disrupting chemicals (EDCs), to PCOS susceptibility and severity. Sunscreen ultraviolet (UV) filters such as oxybenzone (benzophenone-3) and octinoxate (ethylhexyl methoxycinnamate) are widely used EDCs with established systemic absorption and biomonitoring evidence in human populations. Their endocrine-disrupting potential encompasses estrogenic and anti-androgenic activity, interference with steroidogenic enzymes, modulation of thyroid hormone, induction of oxidative stress, and epigenetic reprogramming, all of which are mechanistic pathways that overlap with PCOS pathophysiology. This evidence-based study critically appraises the evidence linking oxybenzone and octinoxate exposures to ovarian endocrinology, with a PCOS-specific focus. Human exposure patterns, pharmacokinetics, and regulatory perspectives are summarized alongside preclinical and in vitro data implicating these filters in ovarian dysfunction. Mechanistic intersections with PCOS include hyperandrogenism, disrupted folliculogenesis, oxidative stress-adipokine imbalance, and potential impairment of vitamin D signaling. Although epidemiological studies directly addressing PCOS outcomes remain sparse, the convergence of toxicological evidence with known endocrine vulnerabilities in PCOS underscores a need for targeted investigation. By mapping exposure pathways and mechanistic disruptions, this appraisal emphasizes the translational relevance of UV filter toxicity in the context of PCOS. It advocates for PCOS-specific biomonitoring cohorts, mechanistic studies, and regulatory consideration of reproductive endpoints while balancing the dermatological benefits of photoprotection against reproductive risks. Full article

Obesity is a major, modifiable driver of endometrial carcinogenesis. This review distills how excess adiposity promotes malignant change and synthesizes prevention strategies across the hyperplasia–cancer continuum. Three converging axes underpin risk: aromatase-mediated estrogen excess; insulin resistance with hyperinsulinemia activating PI3K–AKT–mTOR signaling; and adipokine-driven low-grade inflammation with downstream NF-κB/STAT3 activity. Within this framework, EIN is the key precursor in which these pathways coalesce. Risk can be attenuated through progestin-based therapy (levonorgestrel-releasing intrauterine system or continuous oral regimens), structured weight management, and metabolic adjuncts in selected phenotypes (e.g., metformin for insulin resistance; incretin-based anti-obesity agents as emerging options). Bariatric surgery produces substantial weight loss and favorable metabolic shifts, though evidence for cancer risk reduction is largely observational. Overall, a practical precision-prevention approach—combining progestins with durable weight control and metabolic optimization under guideline-concordant surveillance—appears feasible in routine gynecologic care. Future research should establish causal effects, durability, and optimal sequencing/combination of interventions in trials with endometrial endpoints. Full article

Adipocyte cell models are essential for investigating adipogenesis, yet methodological inconsistencies pose challenges to obtaining reproducible and physiologically relevant results. Murine cell lines, such as 3T3-L1 and OP9, are commonly utilized due to their established adipogenic capabilities. However, differences in its metabolic, genetic regulation, and receptor signaling raise concerns about their applicability to human adipose biology. Human-derived models, including mesenchymal stem cells (hMSCs) and preadipocyte cell lines, offer a closer approximation to in vivo adipogenesis but display significant variability in differentiation efficiency. This variability is often compounded by heterogeneous differentiation protocols, variations in cell confluence, and unstandardized pharmacological induction strategies. A pivotal factor influencing adipogenic potential is the receptor toolkit, which dictates cellular responses to differentiation stimuli. This study systematically evaluates key receptors—PPARγ, glucocorticoid receptors (GR), insulin receptor (IR), thyroid hormone receptors (TR), estrogen receptors (ER), and adenosine receptors (AR)—across commonly used adipocyte models to assess their roles in adipogenic regulation. Additionally, we examine the impact of pharmacological agents capable of inducing adipogenesis (adipogens) and the methodological inconsistencies that contribute to variations in adipocyte differentiation. By addressing these factors, we aim to elucidate the extent to which receptor variability influences experimental outcomes and propose a more structured approach to interpreting adipogenesis research. This critical assessment underscores the need for greater methodological transparency and receptor profiling to enhance the reliability of adipocyte models in metabolic research. Standardizing differentiation methodologies while accounting for receptor diversity will be essential for refining in vitro models and improving their translational potential in the study of obesity, diabetes, and other metabolic disorders. Full article

Pregnancy is a unique physiological state associated with profound hormonal, metabolic, and immunological changes that may affect ocular surface homeostasis. Among these changes, fluctuations in estrogen and progesterone are the most consistent factors contributing to the development or exacerbation of dry eye syndrome (DES), although insulin resistance and maternal immune tolerance may also play a role in modulating disease severity. Current evidence suggests that DES can affect between 20% and 50% of pregnant women, most commonly during the second and third trimesters. Symptoms are often mild and self-limiting, but they can negatively impact quality of life and adherence to prenatal care. Importantly, however, current consensus reports such as TFOS DEWS III emphasize that pregnancy has not been established as a confirmed risk factor for DES and the evidence remains inconclusive despite the biological plausibility of hormonal influences. This review summarizes the pathophysiological mechanisms underlying DES in pregnancy, highlights diagnostic approaches and safe management strategies tailored for pregnant women, and emphasizes the importance of awareness among obstetricians and ophthalmologists. Greater recognition of DES in pregnancy may improve patient comfort and prevent long-term ocular complications. Full article

Polycystic ovary syndrome (PCOS) is a systemic metabolic and endocrine disorder that significantly disrupts reproductive physiology and endometrial function. In this narrative review, we examine the molecular impact of metabolic and hormonal imbalances on the endometrium of women with PCOS. We investigate the specific mechanisms that delineate how hyperinsulinemia and insulin resistance, chronic low-grade inflammation, and estrogen/progesterone/androgen imbalance contribute to altered epigenetic, transcriptomic, metabolomic, and signaling profiles in a wide array of different cell types within endometrial tissues. The synergistic interplay between upregulated inflammatory cytokines (e.g., IL-1,2,6,8,17,18, and TNF-α), along with key changes in critical molecular pathways associated with hyperinsulinemia and insulin resistance (e.g., PI3K/AKT/MAPK, and Wnt/β-catenin), in addition to aberrant sex steroid hormone signaling (e.g., CYP19A1, COX-2, PGE₂, HOXA10, 11βHSD2), promotes deleterious changes within the endometrial microenvironment. These anomalies underpin a spectrum of clinical manifestations observed in women with PCOS at each stage of the life course, including abnormal uterine bleeding in reproductive-age women, impaired decidualization in pregnancy, and altered postmenopausal endometrial physiology. Clinically, these alterations are associated with abnormal uterine bleeding, subfertility, implantation failure, miscarriage, pregnancy complications, and postmenopausal endometrial hyperplasia and cancer. Overall, our review provides novel insights into the molecular mechanisms linking systemic metabolic and endocrine dysfunction with endometrial pathology in PCOS and has broader implications that apply to all women. Full article