Search Results (1,137)

Background/Objectives: Cardiac sarcoidosis (CS) is a challenging diagnosis due to its subclinical progression and the limitations of existing screening tools. Cardiac magnetic resonance (CMR) and PET/CT imaging have improved diagnosis and detection. Aldosterone, a hormone with known profibrotic effects, may offer additional diagnostic value. We therefore aimed to determine whether plasma aldosterone level is associated with myocardial fibrosis, independent of active inflammation, in CS. Methods: This observational study included 541 patients with biopsy-proven sarcoidosis and preserved left ventricular ejection fraction (LVEF ≥ 50%). All underwent CMR with extracellular volume (ECV) mapping and 18F-FDG PET/CT to assess myocardial fibrosis and inflammation, respectively. Plasma aldosterone levels were also measured. Results: Plasma aldosterone levels were significantly higher in patients with cardiac sarcoidosis (172 [IQR 106–235] pg/mL) compared to those without cardiac involvement (143 [100–205] pg/mL, p = 0.02). Aldosterone was independently associated with the presence of late gadolinium enhancement (LGE) on CMR (OR 1.002 per 1 pg/mL increase; 95% CI 1.001–1.004, p = 0.04) and with higher ECV values (β = 0.008 per 1 pg/mL, p = 0.001). Regression analysis showed that aldosterone is associated with ECV (b-0.009, CI: 0.002–0.016, p = 0.009) and there was no interaction according to LGE status indicating a relationship with diffuse myocardial fibrosis even in the absence of visible scarring. No association was observed with T1-, T2-, or PET/CT-defined inflammation. Conclusions: Plasma aldosterone is a robust marker of myocardial fibrosis in sarcoidosis, particularly in early or subclinical stages. Its correlation with ECV—but not with inflammatory imaging markers—suggests its link with myocardial diffuse fibrotic remodeling before, and independently of, overt scarring or inflammation. Full article

With increasing life expectancy driven by rapid biomedical science advancement, reproductive longevity has become a key concept in women’s health. Preventing reproductive senescence is important not only to extend fertility potential but also to preserve endocrine health, enhance quality of life, and promote healthy aging. The end of ovarian function and fertility is symbolized by menopause, as the most eminent index of reproductive aging. Hormone replacement therapy (HRT) remains the mainstay for managing menopausal symptoms. However, as the use of HRT is often limited, there is a need for safe and effective alternatives. This narrative review summarizes current and emerging approaches targeting different stages of reproductive aging. Both hormonal and non-hormonal therapies for vasomotor and genitourinary symptoms are discussed alongside developing fertility preservation techniques, including oocyte vitrification, ovarian tissue cryopreservation, in vitro follicle maturation, and artificial ovary engineering. Furthermore, evolving and experimental ovarian regenerative strategies, such as stem cell transplantation, intraovarian platelet-rich plasma (PRP) injections, antioxidants, metabolic modulators, telomerase activators, and stem cell-derived extracellular vesicles, offer new prospects for delaying or reversing ovarian aging. Overall, personalized regenerative strategies and innovative solutions may reshape the future of women’s reproductive health and longevity. Full article

The endocrine stress response is a valuable tool for evaluating how organisms cope with environmental challenges. However, selecting an appropriate matrix for measuring glucocorticoids (GCs) requires careful consideration of sample quality and accessibility. This study reveals that blood sampling affects plasma cortisol levels in the subterranean rodent Ctenomys talarum, with the effect being reversed shortly thereafter. To facilitate a non-invasive approach, an enzyme-linked immunosorbent assay (EIA) that had previously been validated for measuring plasma cortisol in C. talarum was evaluated to measure adrenocortical activity by analyzing fecal glucocorticoid metabolites (FGCs). Using this assay, we monitored the stress response during wild capture, transport to captivity, adrenocorticotropic hormone (ACTH) stimulation, and immobilization. This showed that FGC levels accurately reflect adrenal activation in these contexts. We also documented a relationship between reproductive seasonality and FGCs. Finally, we provide evidence for a relationship between adrenal activity and behavior. Our results suggest that when considering plasma GCs for the assessment of acute stress, it is crucial to understand the magnitude and timing of the effects of blood sampling on the stress state of organisms. The validation of FGC measurement in C. talarum provides a new option for advancing ecophysiological studies in both the wild and captivity. Full article

Follicle-stimulating hormone receptor (FSHR) is expressed on the plasma membrane of granulosa cells in the ovarian follicles. FSHR is involved in the development and maturation of Graafian follicles, along with granulosa proliferation and estrogen synthesis. There are two well-characterized non-synonymous single-nucleotide gene polymorphisms in the exon 10 of the human FSHR gene, namely rs6165 (c.919G>A, Ala307Thr) and rs6166 (c.2039A>G, Ser680Asn). Recent research clarifies the association of rs6165/rs6166 with susceptibility to infertility-associated ovarian diseases, ranging from polycystic ovarian syndrome, premature ovarian insufficiency, endometriosis, to ovarian cancer, along with response/resistance to ovulation induction/ovarian stimulation with clomiphene citrate, letrozole, metformin, FSH preparations, and adjunctive growth hormone in infertility treatment. This narrative review aims to update the knowledge on the relationship among rs6165/rs6166, infertility etiology, and differential responses to oral ovulation induction agents, FSH preparations, and adjunctive growth hormone. The re6165/rs6166 genotype-guided choice of individualized ovulation stimulation preparations has great potential to reduce unexpected poor or high ovarian responses in ovulation induction and ovarian stimulation and improve clinical outcomes in reproductive medicine. Current evidence is insufficient, and further studies are warranted to ascertain its potential for clinical implementation. Full article

Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disorder caused by fumarylacetoacetate hydrolase deficiency, leading to the accumulation of toxic metabolites such as fumarylacetoacetate (FAA) and succinylacetone (SA). We report an 11-year-old boy with poorly controlled HT1 who presented with a severe neurovisceral crisis after suboptimal adherence to nitisinone (NTBC) therapy, characterized by abdominal pain, hypertension, paralytic ileus, seizures, and profound hyponatremia. Biochemical evaluation revealed markedly elevated urinary δ-aminolevulinic acid (ALA), consistent with a porphyria-like metabolic decompensation, together with inappropriately increased plasma copeptin in the setting of hypotonic hyponatremia and clinical euvolemia, fulfilling diagnostic criteria for the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Optimization of NTBC therapy combined with tailored fluid management resulted in complete clinical and biochemical recovery. This case supports a pathophysiological link between acute disruption of the heme–porphyrin pathway and inappropriate antidiuretic hormone secretion. In HT1, this susceptibility may be further amplified by FAA- and SA-mediated oxidative stress, mitochondrial dysfunction, and heme depletion, with an additional contribution from SA-associated renal tubular impairment. Overall, our findings underscore SIADH as a potentially underrecognized cause of acute hyponatremia in HT1 and highlight the importance of strict NTBC adherence and early monitoring of urinary ALA during metabolic decompensation. Full article

Background. The aim of this study was to develop a predictive model of anticancer drug therapy toxicity in patients with gastric cancer. Methods. The retrospective study included 100 patients with stage II–IV gastric cancer who underwent 4 chemotherapy cycles. Initial significant toxicity factors included age, gender, height, body mass, body mass index, disease stage, skeletal muscle index (SMI), as well as plasma levels of trace elements (copper, zinc, selenium, manganese) and thyroid-stimulating hormone, cancer histology type and treatment regimen. The CTCAE v5.0 scale was employed to assess the severity of adverse events. Statistical analysis and building of mathematical neural network models were carried out in SPSS Statistics (v19.0). Results. Lower SMI values were associated with higher rates of toxicity-related complications of anticancer drug therapy (p < 0.05): leukopenia, hypoproteinemia, nausea, vomiting, cardiovascular events. Anemia, thrombocytopenia, hepatic cytolysis syndrome, nausea, diarrhea, constipation and stomatitis showed a weaker correlation with SMI. An increase in TSH was associated with higher rates of thrombocytopenia, nausea and vomiting. A decrease in Cu/Zn in plasma correlated with the severity of leukopenia and diarrhea, whereas Se/Mn showed an inverse correlation with the severity of anemia. Conclusions. Sarcopenia, abnormal thyroid status and imbalances in copper, zinc, selenium and manganese in blood plasma of patients with gastric cancer may be used as predictors of increased toxicity of anticancer drug therapy. Full article

Background: Oxytocin (OT) is a nonapeptide hormone produced in the hypothalamus, released into the brain and peripheral circulation, and plays a key role in social behavior. Recent studies indicate that complement component C4a is an OT-binding protein, which modulates plasma OT concentrations in mice. However, the role of C4a is unclear as to whether it contributes to consolation behavior. Methods: Social behavior, especially allogrooming, which is a form of empathy that depends on detecting the emotional states of others, was measured in wild-type or C4a/Slp knockout (Slp^−/−) male mice. Results: Observer mice of both genotypes exhibited comforting (allogrooming) behavior toward a cage-mate demonstrator during reunion after brief isolation of the demonstrator mice. When demonstrator mice experienced body restraint stress during isolation, the allogrooming behavior was significantly increased in both genotypes, with a markedly greater increase in Slp^−/− than in Slp^+/+ mice. Allogrooming behavior in observer Slp^−/− mice was significantly suppressed by an OT receptor antagonist. Furthermore, immunohistochemical analysis revealed that activation was significantly elevated in OT-positive hypothalamic neurons in observer Slp^−/− mice that interacted with stressed demonstrator mice. OT release from the isolated hypothalamus, stimulated via CD38 and TRPM2 channel activation, was greater in Slp^−/− mice than in Slp^+/+ mice. Conclusions: Our results highlight that the data are consistent with a potential role for C4a in modulating neural circuits, possibly via its peripheral action on OT bioavailability. Direct evidence for C4a’s action within the brain remains a hypothesis for future investigation, for example, via site-specific manipulations. Full article

Testosterone, an androgenic steroid hormone, regulates primary sexual characteristics and influences mood, cognition, social behavior, and sexual function. Deficiency, caused by factors such as aging and genetics, is linked to multiple disease conditions. However, current testosterone therapies are limited by extensive metabolism, poor solubility, and undesirable side effects. To address these limitations, we synthesized a four-armed star PEG-OH-linked testosterone (PEG-T). The in vitro release of testosterone from PEG-T was evaluated in buffer (pH 7.4) and mouse plasma. PEG-T was stable in the buffer, but released testosterone in plasma via esterase-mediated hydrolysis. Pharmacokinetics of testosterone and PEG-T were compared following intraperitoneal (IP) and subcutaneous (SC) administration. Following IP dosing, PEG-T exhibited a ~6-fold improvement in half-life compared to testosterone (1.18 h vs. 0.21 h), and a 54-fold increase in exposure (AUC_0-t = 36.0 μM·h vs. 0.67 μM·h) at equimolar doses; furthermore, following SC dosing, PEG-T showed a 4-fold improvement in both half-life (3.57 h vs. 0.91 h) and plasma exposure (11.5 μM·h vs. 3.1 μM·h). Additionally, PEG-T showed lower liver and kidney to plasma ratios, which could potentially result in reduced hepatotoxicity and nephrotoxicity. Overall, PEG-T provides sustained release pharmacokinetics, representing a promising candidate for safer testosterone replacement therapy. Full article

Background/Objectives: Spexin (SPX) is a bioactive peptide involved in the regulation of appetite, lipid metabolism, and glucose homeostasis. This systematic review and meta-analysis aimed to evaluate exercise-induced changes in SPX levels and their implications for metabolic health. Methods: This systematic review and meta-analysis aimed to synthesize evidence retrieved from PubMed, Web of Science, and Scopus databases, without restrictions on publication year, with the final literature search completed on 10 September 2024 and conducted in line with PRISMA 2020 reporting standards. The search strategy employed the keywords exercise, metabolic health, obesity, spexin and diabetes yielding 42 eligible records. Eligible studies included human or experimental animal populations exposed to acute or chronic exercise interventions. Exercise interventions included aerobic, resistance, combined, and high-intensity interval training protocols, with exercise intensity reported using heterogeneous metrics. The primary focus was on circulating SPX, alongside the assessment of related metabolic and endocrine parameters. Six studies satisfied the eligibility criteria and were included in the review. Results: The included studies were conducted in overweight or obese sedentary populations. Plasma SPX levels remained unchanged following acute (<3 weeks) aerobic exercise, whereas increased SPX levels were reported after chronic (≥3 weeks) exercise interventions. Elevated SPX concentrations were observed across different exercise modalities, including aerobic exercise, combined aerobic–resistance training, treadmill running, swimming, and HIIT. In addition to SPX, the included studies reported changes in metabolic and endocrine markers, including lipid-related variables, insulin-associated indices, adipokines, hormones, and selected metabolic proteins. Conclusions: This systematic review and meta-analysis indicate that exercise-related increases SPX are reported alongside changes in adiposity and metabolic–endocrine markers. Full article

VD (VD), a hormone-like, fat-soluble molecule, is essential for several biological processes, such as gene regulation, calcium balance, bone health, immune function, antiviral defense, and neuromuscular activity. Its deficiency is associated with various disorders, including chronic hypocalcemia and increased risk of severe diseases, such as COVID-19. Monitoring 25-hydroxyVD (25-OH-D) levels is vital, with serum 25-OH-VD being the standard marker. While chromatography and immunometric assays are well-established, innovative point-of-care (POC) platforms like AFIAS-1^® (Boditech & Menarini, Gangwon, Republic of Korea) are emerging as rapid and automated alternatives, particularly advantageous for decentralized settings such as pharmacies, general practitioners’ offices, and specialized hospital centers like intensive care units. This study compared AFIAS-1^® using whole blood with the gold standard UHPLC-MS/MS using plasma in 50 samples, showing a strong correlation and confirming AFIAS-1^® as a reliable method for measuring 25-OH-D levels. Full article

Late-night feeding, defined in the present review as feeding after 8:00 pm when evening insulin secretion and sensitivity are low, is increasingly prevalent in Western society and is recognized as a disruptor of metabolic homeostasis. Yet health problems related to late-night feeding are largely ignored in time-restricted feeding studies that generally do not extend past an 8:00 pm feeding window. This paper proposes a novel cascade linking late-night hyperglycemia with sleep disturbances and nasal congestion mediated by renal sodium retention, increased plasma osmolarity, and stress hormone release by hypothalamic–pituitary–adrenal axis activation. The narrative describes the circadian decline in insulin sensitivity, which amplifies postprandial glucose surges following late-night feeding. Elevated glucose levels drive renal glucose reabsorption via sodium–glucose cotransporters, promoting sodium retention independent of insulin. Increased sodium retention raises extracellular osmolarity, activating hypothalamic osmoreceptors and stimulating the hypothalamic–pituitary–adrenal axis. Cortisol release promotes alertness, while fluid retention and mucosal edema contribute to nasal congestion and early waking. Supine fluid redistribution during sleep further exacerbates airway narrowing, increasing the risk of sleep fragmentation and obstructive sleep apnea. The present paper fills a gap in current time-restricted feeding literature by integrating renal, osmotic, and neuroendocrine pathways that may be overlooked as underlying mechanisms of dysregulated glucose control and hormone dysfunction. Reviewed evidence suggests that symptoms such as nocturnal congestion and sleep disruption are not merely incidental to late-night feeding but frame late night feeding as a risk factor with underlying physiological stressors that could contribute to cardiometabolic risk. Full article

This study investigated the systemic metabolic effects of feeding a Fusarium-contaminated diet to early-lactation Holstein cows, with or without a mycotoxin-deactivating product (MDP; Mycofix^® Plus, BIOMIN Holding GmbH, Tulln, Austria). Thirty cows were divided into three dietary groups: a mildly contaminated control (CTR), a moderately contaminated diet containing zearalenone and deoxynivalenol (MTX), and the same contaminated diet supplemented with MDP. Plasma collected at 56 days in milk was analyzed by untargeted ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry (HRMS), and multivariate models identified discriminant metabolites and pathways. MTX-fed cows showed alterations in sphingolipid metabolism, including accumulation of ceramide (t18:0/16:0), lactosylceramide, and sphinganine 1-phosphate, consistent with ceramide synthase inhibition and lipid remodeling stress. Increases in estradiol, estrone, and cholesterol sulfate suggested endocrine disruption, while elevated 8-oxo-dGMP indicated oxidative DNA damage. MDP supplementation mitigated these alterations, reducing sphingolipid intermediates, modulating tryptophan and glycerophospholipid pathways, and lowering oxidative stress markers. Metabolites such as riboflavin, pipecolic acid, and N-acetylserotonin could be likely associated with an improved mitochondrial function and redox homeostasis, although future studies are required to confirm this hypothesis. Additionally, MDP-fed cows exhibited distinct shifts in pyrimidine and nucleotide metabolism. Overall, MDP effectively counteracted Fusarium-related metabolic disturbances, supporting its protective role in maintaining lipid balance, hormonal stability, oxidative control, and metabolic resilience. Full article

Background: Manganese (Mn) exposure is common in welding and metal-processing occupations and has been implicated in both thyroid disruption and endothelial dysfunction through oxidative and nitric-oxide–related pathways. However, endocrine and vascular biomarkers have rarely been examined together in occupational settings. Methods: In this cross-sectional study, 95 Mn-exposed workers and 95 non-exposed controls were evaluated. Whole-blood Mn, triiodothyronine (T3), thyroxine (T4), thyroid-stimulating hormone (TSH), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine and citrulline were measured using validated Inductively Coupled Plasma—Mass Spectrometer and chemiluminescent immunoassays. Group differences were assessed using independent samples t-tests, and exposure–biomarker associations were evaluated using Pearson correlations (p < 0.05). Results: Mn-exposed workers had significantly higher blood Mn levels than controls (19.82 ± 4.54 vs. 10.22 ± 3.07 µg/L; p < 0.001). Thyroid hormones (T3, T4, and TSH) were significantly lower among Mn workers, representing a non-classical hormonal pattern, including T3 (2.47 ± 0.31 vs. 3.14 ± 0.42 ng/L; p < 0.001), T4 (1.02 ± 0.13 vs. 1.21 ± 0.18 ng/L; p < 0.001), and TSH (1.75 ± 0.53 vs. 2.88 ± 0.37 mIU/L; p < 0.001). Endothelial biomarkers also differed: ADMA (0.26 ± 0.14 vs. 0.19 ± 0.08 µmol/L; p < 0.001) and SDMA (0.24 ± 0.06 vs. 0.20 ± 0.03 µmol/L; p < 0.001) were higher, while citrulline was lower (18.77 ± 10.23 vs. 22.82 ± 6.70 µmol/L; p = 0.002). In Mn workers, blood Mn showed negative correlations with T3 (r = –0.535, p < 0.01), T4 (r = –0.331, p < 0.01), and TSH (r = –0.652, p < 0.01), and positive correlations with ADMA (r = 0.205, p < 0.05) and SDMA (r = 0.193, p < 0.05). Conclusions: These findings indicate measurable differences in thyroid hormones and dimethylarginine-related endothelial markers among Mn-exposed workers. While the cross-sectional design precludes causal inference, the combined pattern suggests a possible unusual biological response involving both endocrine regulation and nitric-oxide–related pathways. Further longitudinal studies incorporating oxidative stress markers, co-exposure assessment, and functional endothelial testing are needed to clarify the biological relevance of these associations. Full article

Background/Objectives: Excessive sugar, fat, and salt intake heighten susceptibility to metabolic syndrome and other chronic metabolic conditions. Biofortification (i.e., enhancing the nutritional content of crops) emerges as a sustainable new approach to address dietary deficiencies. Methods: This study evaluated the impact of an acute nutritional intervention in a controlled, randomized, single-blind trial involving healthy adults aged 50–79 years, in late middle age and early older adulthood utilizing biofortified vegetables enriched with iodine and molybdenum, aimed to explore short-term biochemical responses to the consumption of iodine- and molybdenum-biofortified lettuce. The study was designed as a controlled dietary intervention including both a biofortified and a non-biofortified lettuce group, matched for handling and composition. It was powered to detect short-term biochemical responses, providing initial insights into the physiological impact of micronutrient biofortification. Dietary intake was carefully monitored throughout the 12-day period to control for confounding dietary effects. Results: The intervention was associated with decreased plasma levels of triglycerides, AST, and ALT, and increased plasma levels of HDL-cholesterol and the satiety hormone PYY, suggesting enhanced metabolic regulation. Conclusions: These biochemical markers reflect early metabolic adaptations that may inform future research on the metabolic impact of micronutrient biofortification. This study also highlights the potential of crop biofortification as a sustainable, strategy to enhance the nutrient density of vegetables within controlled dietary patterns. Full article

This study aimed to evaluate the efficacy of oregano essential oil (OEO) in improving the production performance, health, and welfare of late-phase laying hens raised under commercial farm conditions by analyzing its effect on performance metrics and metabolic and endocrine profiles. Daily performance data for approximately 7884 Hy-Line Brown layers divided into two commercial flocks, one consisting of 96-week-old hens (n = 3849) and the other of 79-week-old hens (n = 4035), were recorded before (Pre-OEO Tx), during (OEO Tx-Week) and one week (Post-OEO Tx Week) following the week of water supplementation with commercial oregano essential oil (5%) of Origanum heracleoticum containing carvacrol (79.75%) as the main component (300 mL of product/1000 L of water). The results show a significant improvement in hen-day egg production (HDEP) during treatment (p < 0.05), a significant decrease in daily mortality one week after the cessation of treatment, mainly in the youngest hens (p < 0.05), and a reduction in feed conversion rate (p < 0.05). The general model (GLM) analysis of data from blood samples collected before and after OEO addition showed a significant decrease in plasma levels of procalcitonin (PCT), calcium, albumin (p < 0.05), and aspartate aminotransferase (AST) (p < 0.01). In contrast, a significant increase in estradiol, total protein globulin (p < 0.01), and phosphorus levels (p < 0.05) was recorded. The changes in endocrine profiles were significantly related to a restoration of calcium–phosphorus balance and a decrease in hepatic activity of AST and gamma glutamyl transferase (GGT). These results reveal the investigative value of PCT, in conjunction with metabolic profiling and reproductive hormones, for evaluating the effectiveness of phytogenic additives. Further studies are suggested to determine whether essential oil components can improve health and production performances of laying hens by a potential concurrent modulation of their metabolism, inflammatory response, and reproductive axis function. Full article