Search Results (36)

Background/Objectives: Understanding the relationship between metabolism and eating behavior may improve how we treat and prevent obesity. Fibroblast growth factor 21 (FGF21) is a hormone secreted by the liver with a putative role in energy expenditure, energy intake, and weight regulation. In this secondary analysis, we studied how fasting FGF21 is correlated with eating behavior and decision making, as measured by the Three-Factor Eating Questionnaire (TFEQ) and the Iowa Gambling Task (IGT), respectively. Methods: Participants (n = 98; women = 19; white = 31) were medically healthy, between 18 and 55 years of age, weight-stable 6 months before admission, and had normal glucose regulation. Women were premenopausal and not pregnant. Pearson partial correlations were determined, accounting for age, sex, and body fat percentage. A mediation analysis examining whether the association between hunger and IGT score was mediated by FGF21 values was performed using general linear models. Results: In partial correlations adjusted for age, sex, and body fat percentage, we found that fasting FGF21 concentrations were positively correlated with hunger susceptibility (sum of internal and external cues) (partial r = 0.26, p = 0.02) and internal hunger (partial r = 0.22, p = 0.04), disinhibition (partial r = 0.27, p = 0.01), and better decision making (higher IGT scores) (partial r = 0.40, p = 0.0001). We also found a correlation between hunger susceptibility and better decision making, including the same covariates (partial r = 0.25, p = 0.03). However, this correlation was mediated (36%) by fasting FGF21. Conclusions: In this study, participants with greater susceptibility to hunger cues had higher IGT scores (better decision making) in the setting of higher fasting FGF21 concentrations. This provides further evidence of the role of FGF21 in the interplay between eating behavior and decision making. Further studying this topic may improve our understanding of the complex relationship between assessing energy requirements and cognitive processes related to eating behavior. 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

Vulvar lichen sclerosus (VLS) involves chronic inflammation, immune dysregulation, and abnormal extracellular matrix remodeling, involving extracellular matrix protein 1 (ECM1) and non-coding RNAs, particularly miR-155. Platelet-rich plasma (PRP) and adipose-derived mesenchymal stem cells (ADSCs) offer regenerative potential through the release of growth factors and cytokines that promote angiogenesis, fibroblast proliferation, collagen synthesis, and tissue repair, which could potentially compensate for the disordered matrix in VLS. This systematic review aimed to evaluate the current evidence on the efficacy and safety of PRP, ADSCs, and active substances administered through mesotherapy to adult women with VLS. A search of the PubMed, Scopus, and Web of Science databases identified 251 records, of which 13 studies met the inclusion criteria (RCTs and cohort studies involving women aged ≥ 18 years who were treated with PRP, ADSCs, or mesotherapy). The reviewed studies suggest that these therapies may improve clinical symptoms, quality of life, sexual function, and tissue quality. However, their application may be constrained by procedural invasiveness and potential immunologic risks. Moreover, the current evidence base is limited by small sample sizes, a lack of control groups, and short follow-up periods. Larger, well-designed randomized controlled trials with long-term follow-up are needed to confirm their therapeutic value and establish clear clinical guidelines. Full article

Diabetes is a common chronic disease. Untreated diabetes may lead to complications such as nephropathy, neuropathy, retinopathy, and macroangiopathies. The main goal in treating diabetes is to limit the development of vascular complications. The FGF (fibroblast growth factor) family, with its potential as a biomarker for diabetic complications, offers a promising avenue for future research and treatment. The study aimed to analyze and compare the concentrations of selected fibroblast growth factors, FGF-2, FGF-19, FGF-22, and FGF-23, in the plasma of patients with type 1 and type 2 diabetes with those of the control group. The study group consisted of 73 patients, including 33 people with type 1 diabetes (18 M and 15 W) aged 18 to 68 years and 40 with type 2 diabetes (20 M and 20 W) aged 25 to 90. The control group consisted of 41 healthy individuals (23 men and 18 women) aged 21 to 56. The FGF-2, FGF-19, FGF-22, and FGF-23 concentrations were measured using ELISA. The study observed a significant relationship between the levels of FGF19 and FGF22 in the serum of patients with type 1 and type 2 diabetes, as well as in the control group (p < 0.001; p < 0.001). Statistical analysis revealed a significant relationship between FGF-2 and FGF-22 concentrations and hypertension (p = 0.03; p = 0.01). A statistically significant difference was also found between the concentrations of FGF-19 and FGF-22 (p = 0.001; p < 0.001) in the serum of people with normal weight and people with overweight and obesity. A significant correlation was also observed between the concentrations of FGF-22 and FGF-23 and arthritis (p = 0.01; p = 0.02). FGF-2, FGF-19, FGF-22, and FGF-23 likely significantly impact diabetes and its complications. In the future, they could serve as biomarkers for diabetic complications, aiding in diagnosis, patient monitoring, and even predicting potential complications for individuals. However, more research in this area is necessary. Full article

Background: Blue light (BL) irradiation has been shown to induce photobiomodulation (PBM) in cells. Here, we investigate its influence on cell types involved in wound healing. Methods: Cellular responses of immortalized human keratinocytes (HaCaTs), normal human dermal fibroblasts (NHDFs), and human umbilical vein endothelial cells (HUVECs) after light treatment at 450 nm were analyzed by kinetic assays on cell viability, proliferation, ATP quantification, migration assay, and apoptosis assay. Gene expression was evaluated by transcriptome analysis. Results: A biphasic effect was observed on HaCaTs, NHDFs, and HUVECs. Low-fluence (4.5 J/cm²) irradiation stimulated cell viability, proliferation, and migration. mRNA sequencing indicated involvement of transforming growth factor beta (TGF-β), ErbB, and vascular endothelial growth factor (VEGF) pathways. High-fluence (18 J/cm²) irradiation inhibited these cellular activities by downregulating DNA replication, the cell cycle, and mismatch repair pathways. Conclusions: HaCaTs, NHDFs, and HUVECs exhibited a dose-dependent pattern after BL irradiation. These findings broaden the view of PBM following BL irradiation of these three cell types, thereby promoting their potential application in wound healing and angiogenesis. Our data on low-fluence BL at 450 nm indicates clinical potential for a novel modality in wound therapy. Full article

Obesity is considered a global pandemic. In Mexico, 7/10 adults, 4/10 adolescents, and 1/3 children are overweight or obese, and it is estimated that 90% of cases of type 2 diabetes (T2D) are attributable to these pathologies. Visceral adipose tissue (VAT) presents increased lipolysis, lower insulin sensitivity, and greater metabolic alterations. Glucagon-like peptide-1 (GLP-1) is a polypeptide incretin hormone that stimulates insulin secretion dependent on the amount of oral glucose consumed, reduces plasma glucagon concentrations, slows gastric emptying, suppresses appetite, improves insulin synthesis and secretion, and increases the sensitivity of β cells to glucose. Liraglutide is a synthetic GLP-1 analog that reduces VAT and improves the expression of Glucose transporter receptor type 4 (GLUT 4R), Mitogen-activated protein (MAP kinases), decreases Fibroblast growth factor type β (TGF-β), reactivates the peroxisome proliferator-activated receptor type ɣ (PPAR-ɣ) pathway, and decreases chronic inflammation. Currently, there are many studies that explain the decrease in VAT with these medications, but there are no studies that compare the decrease in patients with obesity and prediabetes vs. obesity and type 2 diabetes to know which population obtains a greater benefit from treatment with this pharmacological group; this is the reason for this study. The primary objective was to compare the difference in the determination of visceral adipose tissue in people with obesity and type 2 diabetes vs. obesity and prediabetes treated with liraglutide. Methods: A quasi-experimental, analytical, prolective, non-randomized, non-blinded study was conducted over a period of 6 months in a tertiary care center. A total of 36 participants were divided into two arms; group 1 (G1: Obesity and prediabetes) and group 2 (G2: Obesity and type 2 diabetes) for 6 months. Inclusion criteria: men and women ≥18 years with type 2 diabetes, prediabetes, and obesity. Exclusion criteria: Glomerular filtration rate (GFR) < 60 mL/min/1.73 m² elevated transaminases (>5 times the upper limit of normal), and use of non-weight-modifying antidiabetic agents. Conclusions: No statistically significant difference was found in the decrease in visceral adipose tissue when comparing G1 (OB and PD) with G2 (OB and T2D). When comparing intragroup in G2 (OB and T2D), greater weight loss was found [(−3.78 kg; p = 0.012) vs. (−3.78 kg; p = 0.012)], as well differences in waist circumference [(−3.9 cm; p = 0.049) vs. (−3.09 cm; p = 0.017)], and glucose levels [(−1.75 mmol/L; p = 0.002) vs. (−0.56 mmol/L; p = 0.002)], A1c% [(−1.15%; p = 0.001) vs. (−0.5%; p = 0.000)]. Full article

Background: Chronic wounds pose a significant public health challenge due to high treatment costs and the limited efficacy of current therapies. This study aims to evaluate the in vitro wound-healing activity and in silico interactions of two antimicrobial cationic peptides, derived from Galleria mellonella cecropin D, whose receptors are involved in tissue healing. Methods: Two peptides were tested: a long peptide (∆M2, 39 amino acids) and a short peptide (CAMP-CecD, 18 amino acids). Their cytotoxicity, as well as their effects on fibroblast proliferation and migration, were assessed using Detroit 551 cells. In parallel, molecular docking studies were conducted with AutoDock Vina to predict the binding affinities of these peptides to the key receptors involved in wound healing: the epidermal growth factor receptor (EGFR), the transforming growth factor beta receptor (TGFRβ2), and the vascular endothelial growth factor receptor (VEGFR). Results: In vitro assays showed that the short peptide exhibited lower cytotoxicity and significantly enhanced cell proliferation and migration, leading to a greater percentage of gap closure compared to the long peptide. A docking analysis revealed binding affinities of −6.7, −7.2, and −5.6 kcal/mol for VEGFR, EGFR, and TGFRβ2, respectively, with the RMSD values below 2 Å, indicating stable binding interactions. Conclusions: These findings suggest that the structure and cationic charge of the short peptide facilitate robust interactions with growth factor receptors, enhancing re-epithelialization and tissue regeneration. Consequently, this peptide is a promising candidate ligand for the treatment of chronic wounds and associated infections. Full article

The fibroblast growth factor (FGF) family includes 22 proteins in humans. Based on their mode of action, there are three families of FGFs: paracrine FGFs (FGF 1–10, 16, 17, 18, 20, and 22), intracrine FGFs (FGF 11–14), and endocrine FGFs (FGF 19, 21, and 23). FGF signaling plays critical roles in embryonic development, tissue repair, regeneration, angiogenesis, and metabolic regulation. They exert their cellular functions by binding, dimerization, and activation of transmembrane FGF receptors (FGFRs). Aberrant FGF signaling is associated with various human diseases. Thus, understanding the unique properties of FGF signaling will help to explore new therapeutic interventions against FGF-mediated pathological conditions. This review will discuss the differential expression and regulation of each FGF under normal human physiological and pathological conditions. Moreover, we will outline current therapeutics and treatment strategies that have been developed against FGF-related pathology. Full article

Human corneal fibrosis can lead to opacity and ultimately partial or complete vision loss. Currently, corneal transplantation is the only treatment for severe corneal fibrosis and comes with the risk of rejection and donor shortages. Sphingolipids (SPLs) are known to modulate fibrosis in various tissues and organs, including the cornea. We previously reported that SPLs are tightly related to both, transforming growth factor beta (TGF-β) signaling and corneal fibrogenesis. The aim of this study was to investigate the effects of sphingosine-1-phosphate (S1P) and S1P inhibition on specific TGF-β and SPL family members in corneal fibrosis. Healthy human corneal fibroblasts (HCFs) were isolated and cultured in EMEM + FBS + VitC (construct medium) on 3D transwells for 4 weeks. The following treatments were prepared in a construct medium: 0.1 ng/mL TGF-β1 (β1), 1 μM sphingosine-1-phosphate (S1P), and 5 μM Sphingosine kinase inhibitor 2 (I₂). Five groups were tested: (1) control (no treatment); rescue groups; (2) β1/S1P; (3) β1/I₂; prevention groups; (4) S1P/β1; and (5) I₂/β1. Each treatment was administered for 2 weeks with one treatment and switched to another for 2 weeks. Using Western blot analysis, the 3D constructs were examined for the expression of fibrotic markers, SPL, and TGF-β signaling pathway members. Scratch assays from 2D cultures were also utilized to evaluate cell migration We observed reduced fibrotic expression and inactivation of latent TGF-β binding proteins (LTBPs), TGF-β receptors, Suppressor of Mothers Against Decapentaplegic homologs (SMADs), and SPL signaling following treatment with I₂ prevention and rescue compared to S1P prevention and rescue, respectively. Furthermore, we observed increased cell migration following stimulation with I₂ prevention and rescue groups, with decreased cell migration following stimulation with S1P prevention and rescue groups after 12 h and 18 h post-scratch. We have demonstrated that I₂ treatment reduced fibrosis and modulated the inactivation of LTBPs, TGF-β receptors, SPLs, and the canonical downstream SMAD pathway. Further investigations are warranted in order to fully uncover the potential of utilizing SphK I₂ as a novel therapy for corneal fibrosis. Full article

Human skin is constantly exposed to various endogenous and exogenous factors, including UV radiation and vitamin deficiency, which can influence the earlier appearance of visible wrinkles and decrease skin firmness and elasticity. This process is related to decreased collagen I synthesis in the dermis. However, the use of retinol derivatives, synthetic molecules, and growth factors is associated with significant adverse effects, low bioavailability, and instability in dermatological products. Thus, our research was focused on the investigation of a novel plant-based combination for the stimulation of collagen I synthesis in deep skin layers and the prevention of accelerated skin ageing. Aloe barbadensis leaf extract, trimethylglycine, and panthenol were chosen as potential candidates using in silico modelling. A Way2Drug tool predicted anti-inflammatory, anti-psoriatic, and antioxidant activities beneficial for the prophylaxis of skin ageing. An in vitro study was conducted to determine collagen I synthesis in skin fibroblasts in the presence of single substances and their composition using a colorimetric analysis. It was revealed that the combination of Aloe barbadensis leaf extract, trimethylglycine, and panthenol in a specific mass ratio of 2:4:1 and at a concentration of 0.5% significantly increased the amount of collagen I in the skin fibroblasts by up to +18% within 24 h (p < 0.001). This effect was comparable to that of TGF-β1 (10 ng/mL), with a 37% collagen I increase (p < 0.001). The single compounds and the combination of Aloe barbadensis leaf extract and trimethylglycine showed a negative effect on collagen I synthesis, with an unpredictable decrease in this protein in fibroblasts. The combination of the compounds made it possible to achieve a synergistic effect, boosting the natural rejuvenation process in fibroblasts. Overall, the results indicate that the developed plant-based composition in the specific mass ratio and concentration given above could increase collagen I synthesis and can be considered a promising substance for dermatological products with reverse anti-ageing effects. Full article

Background: Vascular health is increasingly recognized for its roles in the pathogenesis and progression of Alzheimer’s disease (AD). The objective of this study was to investigate effects of exercise training, dose, and cardiorespiratory fitness (CRF) on neurotrophic factors in community-dwelling, older adults with mild-to-moderate AD dementia. Methods: This was a pilot blood ancillary study of the FIT-AD trial. Participants in the parent study were randomized to 6-month aerobic exercise (AEx) or stretching control. For this ancillary study, resting plasma brain-derived neurotrophic factor (BDNF), irisin, fibroblast growth factor-21 (FGF-21), and insulin-like growth factor-1 (IGF-1) biomarkers were assessed at baseline, 3, and 6 months. Estimates of within- and between- group effect sizes were calculated (Cohen’s d). Relationships of biomarker change with dose and CRF change were explored with multivariable linear regression and repeated measures correlations. Results: The sample (n = 26, 18 AEx/8 stretching) averaged 77.6 ± 6.9 years old, with the majority being male (65.4%), and non-Hispanic White (92.3%); between-group effect sizes were generally small except for irisin (d = −0.44)), AEx group relative to stretching group. Associations of dose and changes in CRF with changes in neurotrophic biomarker were weak (r² ≤ 0.025). Conclusions: The effects of exercise on BDNF, irisin, IGF-1, and FGF-21 were heterogeneous in AD. Our findings need validation in future, adequately powered exercise studies in AD. Full article

Fibroblast growth factor 21 (FGF21), a hormone predominantly released in the liver, has emerged as a critical endocrine signal of dietary protein intake, but its role in the control of estrous cyclicity by dietary protein remains uncertain. To investigated the role of FGF21 and hypothalamic changes in the regulation of estrous cyclicity by dietary protein intake, female adult Sprague-Dawley rats with normal estrous cycles were fed diets with protein contents of 4% (P4), 8% (P8), 13% (P13), 18% (P18), and 23% (P23). FGF21 liver-specific knockout or wild-type mice were fed P18 or P4 diets to examine the role of liver FGF21 in the control of estrous cyclicity. Dietary protein restriction resulted in no negative effects on estrous cyclicity or ovarian follicular development when the protein content was greater than 8%. Protein restriction at 4% resulted in decreased bodyweight, compromised Kiss-1 expression in the hypothalamus, disturbed estrous cyclicity, and inhibited uterine and ovarian follicular development. The disturbed estrous cyclicity in rats that received the P4 diet was reversed after feeding with the P18 diet. Liver Fgf21 mRNA expressions and serum FGF21 levels were significantly increased as dietary protein content decreased, and loss of hepatic FGF21 delayed the onset of cyclicity disruption in rats fed with the P4 diet, possibly due to the regulation of insulin-like growth factor-1. Collectively, severe dietary protein restriction results in the cessation of estrous cyclicity and ovarian follicle development, and hepatic FGF21 and hypothalamic Kiss-1 were partially required for this process. Full article

Most patients with end-stage renal disease (ESRD) and advanced chronic kidney disease (CKD) choose hemodialysis as their treatment of choice. Thus, upper-extremity veins provide a functioning arteriovenous access to reduce dependence on central venous catheters. However, it is unknown whether CKD reprograms the transcriptome of veins and primes them for arteriovenous fistula (AVF) failure. To examine this, we performed transcriptomic analyses of bulk RNA sequencing data of veins isolated from 48 CKD patients and 20 non-CKD controls and made the following findings: (1) CKD converts veins into immune organs by upregulating 13 cytokine and chemokine genes, and over 50 canonical and noncanonical secretome genes; (2) CKD increases innate immune responses by upregulating 12 innate immune response genes and 18 cell membrane protein genes for increased intercellular communication, such as CX3CR1 chemokine signaling; (3) CKD upregulates five endoplasmic reticulum protein-coding genes and three mitochondrial genes, impairing mitochondrial bioenergetics and inducing immunometabolic reprogramming; (4) CKD reprograms fibrogenic processes in veins by upregulating 20 fibroblast genes and 6 fibrogenic factors, priming the vein for AVF failure; (5) CKD reprograms numerous cell death and survival programs; (6) CKD reprograms protein kinase signal transduction pathways and upregulates SRPK3 and CHKB; and (7) CKD reprograms vein transcriptomes and upregulates MYCN, AP1, and 11 other transcription factors for embryonic organ development, positive regulation of developmental growth, and muscle structure development in veins. These results provide novel insights on the roles of veins as immune endocrine organs and the effect of CKD in upregulating secretomes and driving immune and vascular cell differentiation. Full article

Intra-articular injections of autologous platelet concentrates are considered capable to enhance the healing of cartilage lesions, alleviate joint inflammation, and relieve other musculoskeletal pathological conditions. The aim of this study was to analyze the soluble fractions obtained from platelet-rich plasma (pure- and leukocyte-PRP) to compare time- and preparation-dependent modifications of growth factor concentrations and the supporting activity of the two preparations on synovial fibroblast growth and hyaluronic acid (HA) production in vitro. The release kinetics of FGF-2, SDF-1, VEGF, HGF, EGF, PD GF-AB/BB, IGF-1, VCAM-1, and TGF-β isoforms were followed up to 168 h after PRP activation, and their amounts were determined by multiplex-beads immunoassay. Synovial cell growth and supernatant HA production were respectively analyzed by Alamar Blue assay and ELISA. Time-dependent modifications grouped molecules in three peculiar patterns: one reaching the highest concentrations within 18 h and decreasing afterwards, another progressively increasing up to 168 h, and the last peaking at the central time points. Synovial fibroblast growth in response to L-PRP and P-PRP revealed differences over time and among added concentrations. Both preparations displayed a preserved supporting capacity of HA synthesis. Full article

In tissue engineering, three key components are cells, biological/mechanical cues, and scaffolds. Biological cues are normally proteins such as growth factors and their derivatives, bioactive molecules, and the regulators of a gene. Numerous growth factors such as VEGF, FGF, and TGF-β are being studied and applied in different studies. The carriers used to release these growth factors also play an important role in their functioning. From the early part of the 1990s, more research has beenconductedon the role of fibroblast growth factors on the various physiological functions in our body. The fibroblast growth factor family contains 22 members. Fibroblast growth factors such as 2, 9, and 18 are mainly associated with the differentiation of osteoblasts and in bone regeneration. FGF-18 stimulates the PI3K/ERK pathway and smad1/5/8 pathway mediated via BMP-2 by blocking its antagonist, which is essential for bone formation. FGF-18 incorporated hydrogel and scaffolds had showed enhanced bone regeneration. This review highlights these functions and current trends using this growth factor and potential outcomes in the field of bone regeneration. Full article