Search Results (225)

Background: Sarcopenia and metabolic deterioration are major health concerns in adults aged ≥ 75 years with type 2 diabetes (T2DM), a population characterized by anabolic resistance, reduced dietary intake, and limited renal reserve. Optimizing protein nutrition may support muscle maintenance in this high-risk group, but clinical evidence for individualized high-protein guidance in the oldest-old population remains limited. Objective: We investigated whether an 18-month dietary intervention improves muscle mass and strength in adults aged ≥ 75 years with T2DM and whether serum amino acid (AA) and hormonal profiles reflect these changes. Methods: In this 18-month, single-arm, prospective intervention study, 44 community-dwelling adults aged ≥ 75 years with T2DM received individualized, dietitian-led nutritional guidance targeting a protein intake of approximately 1.4 g/kg ideal body weight (IBW)/day. Assessments at baseline and every 6 months included body composition, muscle strength, renal function, and fasting serum amino acid and hormonal profiles. Longitudinal changes were analyzed using paired t-tests and linear mixed-effects models. This trial was registered in the UMIN Clinical Trials Registry (UMIN000044687). Results: Skeletal muscle index and grip strength showed significant improvements at specific time points during follow-up (both p < 0.05), while gait speed improved at 6 months. Renal function remained clinically stable (eGFRcreat slope: +0.18 mL/min/1.73 m²/year; eGFRcys slope: −2.97 mL/min/1.73 m²/year), with no significant increase in CKD stage. Changes in glucagon correlated positively and C-peptide negatively with changes in skeletal muscle index, whereas glucagon was inversely associated with grip strength. Serum fibroblast growth factor 21 (FGF21) levels decreased over time, suggesting metabolic adaptation to the intervention. Conclusions: Individualized high-protein nutritional guidance for 18 months improved sarcopenia-related parameters, including skeletal muscle index and grip strength, without clinically significant deterioration of renal function in adults aged ≥ 75 years with T2DM. These findings support the feasibility and safety of protein-focused dietary counseling as a strategy to preserve muscle health in advanced age. Full article

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors and COPD exacerbations over one year. Serum levels of eleven growth factors, including brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), and stem cell factor (SCF), were measured in COPD patients at baseline. Participants were followed prospectively for one year, and associations between these biomarkers and acute exacerbations (AE) and frequent acute exacerbations (Frequent AE) were assessed using statistical analyses and receiver operating characteristic (ROC) curves. Among the study population, 42 patients experienced at least one AE within the follow-up period. Lower serum FGF-2 levels were significantly associated with increased AE risk (adjusted odds ratio significant after covariate adjustment). ROC analysis identified FGF-2 ≤ 9.12 pg/mL as a predictor of AE (AUC = 0.614, sensitivity = 64.3%, specificity = 57.1%, p = 0.032). For Frequent AE, eight patients experienced multiple exacerbations and exhibited significantly lower levels of NGF, EGF, FGF-2, and LIF. After adjustment, NGF remained significantly predictive; NGF ≤ 25.23 pg/mL demonstrated strong discriminatory power for Frequent AE (AUC = 0.797, p < 0.001). However, interpretations are limited by the small Frequent AE subgroup. Serum growth factors, particularly FGF-2 and NGF, are associated with COPD exacerbation risk. Lower serum FGF-2 may indicate a higher likelihood of acute exacerbations, while lower NGF strongly predicts frequent exacerbations. Larger studies and longer follow-ups are needed to confirm these biomarkers’ predictive utility. Full article

The inflammatory and metabolic complexity of colitis necessitates therapies that act on multiple immune pathways. Using serum proteomic profiling, the present study evaluated the systemic immunomodulatory profile of Epilobium angustifolium lyophilized methanol-aqueous extract rich in oenothein B (EAE) in a dextran sulfate sodium (DSS)-induced mouse model of ulcerative colitis in a comparative manner to dexamethasone (DXM). DSS exposure triggered robust inflammatory activation, evidenced by elevated chemokines (CXCL9, CXCL10, CCL11), proinflammatory cytokines (IL-1α, IL-12, PAI-1, RAGE) and metabolic stress mediators (leptin, resistin, FGF-21). Treatment with EAE significantly attenuated this inflammatory profile, notably reducing Th2-skewed chemokines and eosinophil recruitment. In contrast to DXM, EAE uniquely normalized pro-thrombotic and tissue-remodeling markers, including PAI-1 and RAGE, both implicated in intestinal barrier dysfunction and chronic inflammation. Furthermore, EAE demonstrated superior modulation of inflammation-associated growth factors (IGFBP-5, HGF, Flt3L) and adipokines (leptin, resistin), indicating a broader therapeutic scope that includes metabolic dysfunctions. Collectively, our data reveal that EAE exerts a distinct immunoregulatory profile, modulating both innate and adaptive immune pathways while simultaneously addressing metabolic pathologies. These multifaceted actions underscore its promise as a phytotherapeutic candidate for the management of ulcerative colitis and other inflammatory conditions, with potential advantages over conventional steroid treatment. Full article

Background: Cardiovascular disease (CVD) is the leading cause of mortality in chronic kidney disease (CKD), driven by mechanisms distinct from the general population. Fibroblast Growth Factor 23 (FGF-23), a phosphaturic hormone elevated early in CKD, has been mechanistically linked to left ventricular hypertrophy, vascular dysfunction, and disordered mineral metabolism. This study examines the associations between FGF-23 and key renal, mineral, and cardiovascular parameters and its utility in risk stratification. Methods: We conducted a cross-sectional study of 60 adults with CKD stages 1–5. Serum FGF-23 was quantified using ELISA, alongside measures of iPTH, phosphorus, calcium, and eGFR (Estimated Glomerular Filtration Rate). Cardiovascular evaluation included transthoracic echocardiography and carotid intima-media thickness (CIMT). Associations were analyzed using Spearman correlations, ROC analysis, and multivariable logistic regression. Results: FGF-23 levels were significantly associated with declining eGFR (r = –0.288; p < 0.05), elevated iPTH (Intact Parathyroid Hormone) (r = 0.361; p < 0.05), and serum phosphorus (r = 0.335; p < 0.05). Patients with structural cardiac abnormalities (left atrial enlargement or left ventricular hypertrophy) exhibited higher FGF-23 concentrations (154 vs. 128 pg/mL; p = 0.027). FGF-23 alone predicted high cardiovascular risk with moderate accuracy (AUC 0.70; sensitivity 76%; specificity 67%). A composite model including iPTH and eGFR improved discriminatory power (AUC 0.76). Conclusions: FGF-23 correlates with subclinical cardiovascular remodeling and key mineral abnormalities in CKD. Its integration with iPTH and eGFR enhances cardiovascular risk stratification, supporting its potential as a multidimensional biomarker in early CKD. However, the cross-sectional design and modest correlation strengths limit causal inference and generalizability of the findings. Full article

Background: Hypophosphatemia is a frequently underestimated metabolic disorder, yet it can be one of the first biochemical findings in primary hyperparathyroidism (PHPT). Current diagnostic and surgical criteria for PHPT do not include serum phosphate, despite its potential value as an early marker. Methods: We report the case of a 79-year-old woman with type 2 diabetes mellitus, hypertension and osteoarthritis, followed since 2015 for persistent hypophosphatemia (0.8 mg/dL) and stress fractures. Results: Initial calcium and vitamin D levels were normal, but PTH was elevated. Bone scintigraphy revealed multiple stress fractures, while ultrasound and sestamibi scan were inconclusive. Despite cholecalciferol and calcitriol supplementation, hypophosphatemia persisted. From 2023, progressive hypercalcemia developed (10.9 mg/dL), with sustained hypophosphatemia (1.7 mg/dL), persistently high PTH (121 pg/mL) and markedly elevated FGF-23 (1694 kRU/L). Renal phosphate wasting was demonstrated, with reduced tubular reabsorption. An 18F-fluorocholine PET-CT performed in 2024 identified two right parathyroid adenomas, establishing the diagnosis of PHPT. The patient was referred for parathyroidectomy. Conclusions: Hypophosphatemia may serve as a complementary biomarker in the diagnostic and therapeutic approach to PHPT, but only after other potential causes of low phosphate levels have been excluded, as illustrated in this case. Its consideration could facilitate the early identification of PHPT and improve clinical decision-making, particularly in patients who do not meet classical surgical indications. Full article

Somatic cell preservation is an effective strategy for conserving the genetic potential of endangered species. To contribute to the conservation of the Milu deer (Elaphurus davidianus), this study aimed to establish and characterize an immortalized skin fibroblast cell line (ML-iSFC). The cell line is based on fibroblasts from the skin tissue of a male fawn of Milu deer. Optimal culture conditions were determined by supplementing the culture medium with different growth factors, and immortalization was achieved through simian virus 40 large T antigen (SV40T) transduction. Optimal culturing conditions for the cells were determined by adding a range of growth factors. The cellular morphology, growth characteristics, and marker expression of the cells were further evaluated. Cell cycle and proliferation were assessed by flow cytometry and CCK-8 assays, respectively. Chromosomes were determined by karyotype analysis. The highest cell growth rate was observed when the culture medium was supplemented with 3 ng/mL of FGF2. The fibroblast-specific marker vimentin (VIM) was expressed in both ML-SFC and ML-iSFC, while the epithelial marker keratin 18 (KRT18) was weakly expressed in ML-SFC cells. Cell proliferation and cell-cycle analysis revealed that ML-iSFC exhibited a higher growth rate and greater vitality compared to ML-SFC. Karyotype analysis showed that ML-iSFC maintained the same chromosome number and morphology as ML-SFC. In summary, this study reports the successful construction of an immortalized fibroblast cell line from Milu deer, which will serve as a valuable tool for Milu deer conservation. Full article

Fibroblast growth factor 21 (FGF21), a pleiotropic hormone, is a significant modulator of energy homeostasis. We evaluated serum FGF21 levels in patients with a deficiency of mitochondrial aminoacyl-tRNA synthetase (mt-aARSs). Six patients with mitochondrial aminoacyl tRNA synthetase deficiency and twelve healthy volunteers were included in this study. Whole-exome sequencing was used for molecular diagnosis. Serum FGF21 levels in the case group and healthy volunteers were analyzed using the enzyme-linked immunosorbent assay. Exome sequencing test revealed nine different pathogenic variants in the AARS2, EARS2, DARS2, SARS2, and WARS2 genes. A statistically significant difference was found between the serum FGF21 levels of the case and control groups: case group (n = 6), 882.49 ± 923.60 pg/mL; control group (n = 12), 20.89 ± 2.63 pg/mL (p < 0.001). The area under the ROC curve for FGF21 in the differential diagnosis of mitochondrial aminoacyl-tRNA synthetase deficiency was 1.000 (0.813–1.000). Sensitivity and specificity were 100%, and positive and negative predictive values were also 100% for an FGF21 cut-off value > 27.4 pg/mL. Assessment of FGF 21 levels as an indicator of mitochondrial damage in mt-aARSs deficiency may provide insight into the level of damage. Investigation of the biochemical mechanisms underlying the different levels of damage caused by different aminoacyl tRNA synthetases will be important in terms of elucidating clinical heterogeneity. Full article

Hypophosphatemia, defined as serum phosphate levels below 2.5 mg/dL, is a common yet underrecognized electrolyte disturbance in critically ill patients, with prevalence estimates reaching up to 80%. This review explores the intricate bidirectional relationship between hypophosphatemia and hyperventilation, emphasizing its profound implications for respiratory function and critical care management. Hypophosphatemia impairs oxygen delivery by depleting 2,3-diphosphoglycerate (2,3-DPG), disrupts central respiratory drive, and weakens respiratory muscles, leading to hyperventilation, ventilatory failure, and prolonged mechanical ventilation. Conversely, hyperventilation exacerbates hypophosphatemia through respiratory alkalosis, triggering intracellular phosphate shifts and metabolic cascades that rapidly deplete serum levels. This cycle creates significant challenges for ventilator weaning and increases morbidity and mortality. Underlying mechanisms include impaired ATP synthesis, altered chemoreceptor sensitivity, and systemic inflammatory responses. Hypophosphatemia-induced hyperventilation manifests as unexplained tachypnea and respiratory alkalosis, often misdiagnosed as anxiety or pain, while hyperventilation-induced hypophosphatemia contributes to diaphragmatic dysfunction and poor ventilatory performance. Common precipitating factors include refeeding syndrome, diabetic ketoacidosis, continuous renal replacement therapy, and malnutrition. Complications extend beyond respiratory dysfunction to include cardiac depression, immune dysfunction, prolonged ICU stays, and increased healthcare costs. Current diagnostic approaches rely on serum phosphate measurements, which poorly reflect total body stores due to significant intracellular shifts. Emerging biomarkers such as fibroblast growth factor 23 (FGF23) and advanced monitoring technologies, including continuous phosphate tracking, may enhance recognition. Treatment strategies emphasize targeted phosphate repletion based on severity, with intravenous supplementation and ventilatory support tailored to minimize complications. Preventive measures, including risk stratification, prophylactic supplementation, and ventilator management, are critical for high-risk populations. Despite advances, knowledge gaps persist in optimizing monitoring and repletion protocols, understanding genetic variations, and identifying ideal phosphate targets for improved respiratory outcomes. This review provides a comprehensive framework for recognizing and managing hypophosphatemia’s impact on respiratory dysfunction in critically ill patients. Adopting evidence-based interventions and leveraging emerging technologies can significantly improve clinical outcomes, reduce ICU complications, and enhance recovery in this vulnerable population. Full article

Background: Bone regeneration is a key therapeutic objective in periodontology, particularly in the treatment of alveolar defects caused by periodontal disease, dentoalveolar trauma, or surgical interventions. Among current regenerative strategies, collagen-enriched biomaterials have demonstrated an active role in modulating cellular behavior during bone repair. However, the specific effects of different collagen formulations on human dental pulp stem cells (hDPSCs) have not yet been fully characterized. Objective: To evaluate the impact of xenogeneic bone grafts with and without collagen—OsteoBiol^® Gen-Os^® (GO), OsteoBiol^® GTO^® (GTO), and Geistlich Bio-Oss^® (BO)—on cell viability, adhesion, migration, osteogenic differentiation, and mineralization potential of hDPSCs, and to explore the molecular mechanisms underlying their effects. Methods: In vitro assays were conducted to assess viability (MTT and fluorescence staining), adhesion (SEM), migration (wound healing assay), and mineralization (Alizarin Red S staining). Gene expression analyses (RT-qPCR) were performed for adhesion/migration markers (FN, SDF-1, COL1A1), angiogenic/proliferation markers (VEGF, FGF2), and osteogenic differentiation markers (RUNX2, ALP, COL1A1). Results: GO showed a higher early expression of genes associated with adhesion, migration, angiogenesis (FN, SDF-1, VEGF and FGF2: p < 0.05; COL1A1: p < 0.01), and osteogenic differentiation (7 days: COL1A1 and ALP (p < 0.001)); (14 days: RUNX2, ALP: p < 0.001; COL1A1: p < 0.05), indicating a sequential activation of molecular pathways and mineralization capacity comparable to the control group. GTO demonstrated the best biocompatibility, with significantly higher cell viability (p < 0.05), strong adhesion, and markedly increased mineralization at 21 days (p < 0.001), despite moderate early gene expression. BO showed reduced cell viability at 10 mg/mL (p < 0.05) and 20 mg/mL (p < 0.001), with mineralization levels similar to the control group. Conclusion: Collagen-based xenografts demonstrate favorable interactions with hDPSCs, enhancing viability and promoting osteogenic differentiation. Our findings suggest that beyond the presence of collagen, the specific formulation of these biomaterials may modulate their biological performance, highlighting the importance of material design in optimizing regenerative outcomes. Clinical Significance: The formulation of collagen in xenogeneic bone substitutes may be a determining factor in enhancing periodontal regenerative outcomes by modulating the early cellular response and osteogenic activity in stem cell-based tissue engineering. Full article

Several studies have shown an association of fibroblast growth factor-23 (FGF-23), 25-hydroxyvitamin D (25(OH)D), and asymmetric dimethylarginine (ADMA) with the pathogenesis of albuminuria. However, the direct relationship of these biomarkers with albuminuria independent of other risk factors for chronic kidney disease (CKD) remains controversial. FGF-23 and ADMA levels were associated with the progression of CKD, with a cutoff value of ≥100 RU/mL for FGF-23 and 0.69 μmol/L for ADMA. Background/Objectives: To analyze the correlation between FGF-23, 25(OH)D, and ADMA levels and albuminuria. Methods: This was an observational analytic study with a cross-sectional design conducted in patients with CKD with various disease stages (non-dialysis). The output is albuminuria. Statistical analysis was performed using multivariate logistic regression analysis. Results: This study included 107 patients with CKD stages 2–5 with an average age of 57.32 years. Their average FGF-23, vitamin D, ADMA, and uACR levels were 197.75 RU/mL, 23.44 ng/mL, 0.719 µmol/L, and 940 mg/g, respectively. FGF-23 was weakly correlated with uACR (r = 0.252; p = 0.009). Vitamin D was weakly correlated with uACR (r = −0.375; p = 0.000). ADMA was strongly correlated with uACR (r = 0.687; p = 0.00). Multivariate analysis showed an association of ADMA ≥ 0.69 µmol/L (p = 0.000) with albuminuria ≥ 300 mg/g (p = 0.003). Conclusions: ADMA was correlated with the presence of macroalbuminuria, strongly indicating its role in the progression of CKD. Full article

Ivermectin (IVM), a broad-spectrum anthelmintic agent, has anti-inflammatory properties, and affects cellular and humoral immune responses. We recently showed that multiple pro-inflammatory cytokines (e.g., FGF2, CCL5, CD40L) bind to the allosteric site (site 2) of integrins and activate them. 25-Hydroxycholesterol, a pro-inflammatory lipid mediator, is known to bind to site 2 and induce integrin activation and inflammatory signals (e.g., IL-6 and TNF secretion), suggesting that site 2 is critically involved in inflammation. We showed that two anti-inflammatory cytokines (FGF1 and NRG1) bind to site 2 and inhibit integrin activation by inflammatory cytokines. We hypothesized that ivermectin binds to site 2 and inhibits inflammatory signaling by pro-inflammatory cytokines. A docking simulation predicts that ivermectin binds to site 2. Ivermectin inhibits the integrin activation induced by inflammatory cytokines, suggesting that ivermectin is a site 2 antagonist. We showed that TNF, a major pro-inflammatory cytokine, binds to integrin site 2 and induces allosteric integrin activation like other pro-inflammatory cytokines, suggesting that site 2 binding and integrin activation is a potential mechanism of the pro-inflammatory action of these cytokines. Ivermectin suppressed the activation of soluble β3 integrins by TNF and other pro-inflammatory cytokines in a dose-dependent manner in cell-free conditions. Binding to site 2 and the inhibition of binding of inflammatory cytokines may be a potential mechanism of anti-inflammatory action of ivermectin. Full article

The COVID-19 pandemic has caused over 7 million deaths, but its legacy extends beyond mortality. SARS-CoV-2 infection induces immune alterations that persist post-recovery, manifesting not only in long COVID (LC) but also in healthy individuals. Cytokines serve as critical orchestrators of these processes. The goal of this study is to investigate post-pandemic immune remodeling through cytokine assessment in both patients with LC and healthy donor, and to compare the post-pandemic population with pre-pandemic controls to find changes in the immune responses and cytokine profiles. A panel of 47 immune mediators (cytokines, chemokines, and growth factors) was measured with the MAGPIX multiplex analysis. LC was characterized by an increase in IL-7, IL-8, IL-17F, IL-18, EGF, FGF-2, PDGF-AA, sCD40L, and MCP-3 and a decrease in IL-4, IL-13, IL-22, IL-27, and FLT-3L. Comparing post-pandemic recovered individuals with pre-pandemic healthy cohort, we saw an upregulation of IL-13 and MCP-3 and a downregulation of MDC, M-CSF, IL-12, and IL-17F. While LC is characterized by persistent immune imbalance—particularly in cytokine networks—our data emphasize the critical need to study healthy donors in both pre- and post-pandemic eras when analyzing and interpreting these changes. Full article

Myalgic encephalomyelitis (ME) and fibromyalgia (FM) are overlapping syndromes characterized by persistent fatigue, cognitive difficulties, and post-exertional malaise (PEM), yet they lack objective biomarkers for diagnosis and treatment. Fibroblast growth factor 21 (FGF-21), a stress-responsive metabolic hormone, may offer a promising avenue to distinguish subtypes within these patient populations. In this cross-sectional study, plasma FGF-21 levels were measured in 250 patients (FM = 47; ME = 99; ME + FM = 104) and 54 healthy controls. Participants were categorized based on FGF-21 levels into three groups: low (0–50 pg/mL), normal (51–200 pg/mL), and high (>200 pg/mL). Symptoms burden and cognitive function were assessed using validated questionnaires (SF-36, MFI-20, DSQ, DPEMQ) and the BrainCheck platform. A standardized mechanical provocation maneuver was used to induce PEM. Results showed that elevated FGF-21 levels were frequently observed in ME and ME + FM but varied widely across all groups. Stratification by circulating FGF-21 levels, rather than diagnosis alone, revealed distinct symptom and cognitive profiles. Low FGF-21 levels were linked to worsened PEM perception in FM, increased PEM severity and immune/autonomic symptoms in ME, and poorer mental health in ME + FM. Conversely, high FGF-21 levels correlated with better cognition in ME but greater fatigue in ME + FM. These findings suggest that FGF-21 may serve as a valuable biomarker for identifying clinically meaningful subtypes within ME and FM, supporting the development of personalized treatments. Furthermore, discrepancies between DSQ and DPEMQ highlight the need for objective PEM assessment tools. Overall, FGF-21 shows potential as a biomarker to guide precision medicine in these complex conditions. Full article

Novel therapeutic approaches for wound healing have included biomaterials from the Atlantic cod (Gadus morhua L.), with promising results in wound management. The use of extracellular vesicles (EVs), which can be isolated from cod biofluids, remains to be studied. EVs play key roles in cellular communication, and their use both as biomarkers and as therapeutic agents is widely reported in human pathologies, particularly with respect to mesenchymal stem cells. This pilot study characterized the total proteomic cargo content of EVs from cod serum and mucus and assessed the EVs’ potential for regenerative activity in wound-healing processes, using human and mouse fibroblast and keratinocyte in vitro scratch injury models. The pro-regenerative potential of both cod serum EVs and mucus EVs was identified, with differing capacities for accelerating wound closure in fibroblast and keratinocyte cells. This was further supported by varying effects of the cod serum EVs and mucus EVs on cellular vimentin and FGF-2 levels. The serum EV and mucus EV protein cargoes differed with respect to abundance of protein hits and associated enriched functional GO and KEGG pathways, but both were associated with immune, stress and wound-healing processes. Cod EVs may present as innovative therapeutic options for regenerative medicine applications, and our reported findings provide valuable insights for future in-depth studies. Full article

Background: Prolactin (PRL) is a key reproductive hormone that regulates follicular development through endocrine and paracrine mechanisms. However, its specific role in porcine follicular development remains unclear. Methods: In the in vivo experiments, follicular fluid and tissue cells were obtained from small (1–2 mm), medium (3–4 mm), and large (5–6 mm) porcine follicles. PRL levels in follicular fluid were measured by ELISA. The expression levels of genes and proteins related to follicular development were assessed using quantitative real-time PCR (RT-qPCR) and Western blotting (WB). In the in vitro experiments, CCK-8, RT-qPCR, and WB were used to detect the effects of different concentrations (0, 30, and 300 ng/mL) of recombinant porcine prolactin (prPRL) on granulosa cell (GC) proliferation, steroid hormone synthesis, and angiogenesis, and transcriptome sequencing was performed. Results: The PRL concentration was significantly higher in large follicles compared to small and medium follicles. During follicular development, expression levels of PRL, PRL receptor (PRLR), proteolytic enzymes (CTSD, MMP2, MMP14, and BMP-1), and angiogenic factors (VEGFA and FGF-2) increased and then decreased. Moreover, prPRL promoted GC proliferation, increased the expression of PCNA and cyclin D1, upregulated steroidogenesis-related genes CYP11A1 and 3β-HSD, and significantly enhanced the expression of key angiogenic factors VEGFA and FGF-2. RNA-seq analysis identified 226 differentially expressed genes (DEGs), which were mainly enriched in signaling pathways such as the Hippo, JAK/STAT, and Rap1 pathways. Conclusions: PRL may regulate porcine follicle development by affecting cell proliferation and angiogenesis in GCs through the Hippo, JAK/STAT and Rap1 signaling pathways. Full article