Search Results (2,159)

This study aimed to investigate the effect of enamel matrix derivatives (EMD) on the early healing biomarkers’ expression following flapless treatment. Thirty-eight patients with residual deep intrabony defects after steps 1 and 2 of periodontal therapy were randomly assigned to the test (flapless with EMD) or control group (flapless alone). Periodontal parameters were recorded at baseline and 6 months after treatment. Gingival crevicular fluid (GCF) was collected at baseline and 2 weeks after treatment to quantify the levels of biomarkers related to epithelial healing (epidermal growth factor, EGF), connective tissue healing (matrix metalloproteinase-8 [MMP-8], fibroblast growth factor [FGF], transforming growth factor-β [TGF-β]), and bone formation (osteoprotegerin [OPG]). The test group showed a significant reduction in MMP-8 levels (p = 0.039), along with significant increases in EGF (p < 0.01), FGF (p < 0.01), and OPG (p < 0.01). The control group demonstrated a significant decrease in MMP-8 (p = 0.010). No significant changes in TGF-β levels were observed in either group. At 6 months, the test group exhibited significantly greater reductions in probing pocket depth and clinical attachment level compared to the control group. This study is the first to characterize the biochemical changes following flapless treatment with EMD. These preliminary findings suggest that EMD may enhance early wound healing by modulating the expression of key regenerative biomarkers. 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

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

Polynucleotide (PN), a high-molecular-weight DNA fragment derived from salmon and other fish sources, shows promising anti-aging and regenerative effects on the skin. This study investigated how PN enhances collagen synthesis, focusing on its effect on phosphoenolpyruvate carboxykinase 1 (PCK1) in senescent macrophages and its downstream effects on fibroblasts. Using in vitro senescent cell models and in vivo aged animal models, PN significantly upregulated the adenosine 2A receptor (A2AR), adenylate cyclase (AC), cyclic AMP (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) in senescent macrophages. This led to increased PCK1 expression, which reduced oxidative stress and promoted M2 macrophage polarization, associated with elevated levels of interleukin-10 and tumor growth factor-β. Conditioned media from PN-treated macrophages enhanced SMAD family member 2 and signal transducer and activator of transcription 3 phosphorylation in senescent fibroblasts, increasing collagen I and III synthesis and reducing nuclear factor-κB activity. In vivo, PN administration elevated expression of the A2AR/AC/PKA/CREB/PCK1 pathway, reduced oxidative stress, increased M2 macrophage markers, and significantly improved collagen density and skin elasticity over time. Use of a PCK1 inhibitor attenuated these effects, highlighting the pivotal role of PCK1. Overall, PN modulates macrophage-fibroblast interactions via the CREB/PCK1 axis, enhancing collagen synthesis and counteracting age-related skin changes. PN has emerged as a promising therapeutic agent for skin rejuvenation by targeting cellular senescence and promoting extracellular matrix restoration. Full article

We investigated the impact of liver damage on systemic inter-organ communication in an extensive observational case–control study of 923 patients with severe obesity and biopsy-confirmed metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH) undergoing bariatric surgery. Using a comprehensive panel of circulating organokines, including fibroblast growth factor (FGF) 19, FGF21, adiponectin, galectin-3, irisin, and leptin, along with choline metabolites, we characterized metabolic signaling patterns associated with liver disease severity. Compared to controls, patients with MASLD/MASH exhibited significantly lower levels of FGF19, choline, and trimethylamine, while FGF21, galectin-3, irisin, and leptin were elevated. Sex-specific alterations in leptin and adiponectin were observed in patients with severe obesity but not in controls. Network analysis revealed a complex and individualized interplay among organokines, shaped by age, sex, and anthropometric factors. Despite this complexity, a dysregulation of the FGF21–adiponectin axis was associated with more advanced liver involvement. The large cohort and comprehensive organokine profiling studied provide valuable insights into the role of the FGF21–adiponectin axis on systemic metabolic alterations in severe obesity and their potential clinical implications. Full article

Background/Objectives: Hypertriglyceridemia (HTG) is a common multifactorial metabolic disorder often with genetic predisposition. Multiple lines of evidence support a causal role of triglyceride-rich lipoproteins (TRLs) in atherosclerotic cardiovascular disease (ASCVD), with severe HTG leading to pancreatitis and hepatic steatosis. This review covers TRL metabolism, causes and consequences of HTG, current management, and emerging TRL-targeted therapies. Methods: A narrative review was conducted. Results: Pharmacologic therapy with fibrates and omega-3 fatty acids remains the standard treatment for HTG but its efficacy in preventing pancreatitis and ASCVD is limited. Genetic studies have identified apolipoprotein C-III (ApoC-III) and angiopoietin-like 3 (ANGPTL3), both inhibitors of lipoprotein lipase, as potential therapeutic targets for reducing TG levels and ASCVD risk. Monoclonal antibodies and RNA-based therapies have enabled the development of inhibitors of ApoC-III and ANGPTL3, with promising results in phase 2 and small phase 3 trials. Angiopoietin-like 4 inhibitors and Fibroblast growth factor 21 analogs are in early-stage clinical development. Conclusions: Current pharmacologic therapies exhibit notable limitations in effectively managing severe HTG and in reducing the risk of ASCVD. Emerging therapies targeting TRLs metabolism showed favourable results in initial clinical trials. Full article

Voltage-gated Na⁺ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na⁺ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the α-subunit coded by each of the nine isoforms can sufficiently confer transient Na⁺ currents (I_Na), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein–protein interaction (PPI), and probes developed from iFGF/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated I_Na⁺. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177’s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress I_Na in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies. Full article

Background: Aberrant hepatic lipid metabolism is a key predisposing factor for dairy cow ketosis, with genetic factors playing a pivotal role in disease pathogenesis. However, systematic screening and functional validation of candidate genes for bovine ketosis remain limited. In this study, we aimed to identify genetic markers associated with clinical ketosis and explore their potential functional mechanisms underlying disease susceptibility. Methods: We conducted simplified genome sequencing (SuperGBS), genome-wide association studies (GWAS), and Sanger sequencing on Chinese Holstein cows, both healthy and with ketosis. Results: We reported that mitogen-activated protein kinase 1 (MAPK1) was significantly associated with clinical ketosis. Further investigation revealed concurrent upregulation of MAPK1 protein and disrupted hepatic lipid homeostasis in hepatocytes from in vivo and in vitro models. Critically, siRNA-mediated knockdown of MAPK1 reversed lipid metabolism processes and reduced lipid accumulation in β-Hydroxybutyric acid (BHB)-exposed bovine hepatocytes, thereby establishing MAPK1 activation as a driver of lipotoxicity in dairy cow ketosis. Additionally, we identified that supplementation of fibroblast growth factor 21 (FGF21) fusion protein not only reduced MAPK1 expression but also normalized hepatic lipid metabolism in BHB-exposed bovine hepatocytes. Conclusions: FGF21–MAPK1 imbalance is a reason for hepatic lipid metabolic dysfunction, providing a potential intervention approach to mitigate dairy cows’ ketosis. Full article

In recent years, the bidirectional regulatory mechanism of the bone-brain axis has become a hotspot for interdisciplinary research. In this paper, we systematically review the anatomical and functional links between bone and the central nervous system, focusing on the regulation of brain function by bone-derived signals and their clinical translational potential. At the anatomical level, the blood–brain barrier permeability mechanism and the unique structure of the periventricular organs establish the anatomical basis for bone-brain information transmission. Innovative discoveries indicate that the bone cell network (bone marrow mesenchymal stem cells, osteoblasts, osteoclasts, and bone marrow monocytes) directly regulates neuroplasticity and the inflammatory microenvironment through the secretion of factors such as osteocalcin, lipid transporter protein 2, nuclear factor κB receptor-activating factor ligand, and fibroblast growth factor 23, as well as exosome-mediated remote signaling. Clinical studies have revealed a bidirectional vicious cycle between osteoporosis and Alzheimer’s disease: reduced bone density exacerbates Alzheimer’s disease pathology through pathways such as PDGF-BB, while AD-related neurodegeneration further accelerates bone loss. The breakthrough lies in the discovery that anti-osteoporotic drugs, such as bisphosphonates, improve cognitive function. In contrast, neuroactive drugs modulate bone metabolism, providing new strategies for the treatment of comorbid conditions. Additionally, whole-body vibration therapy shows potential for non-pharmacological interventions by modulating bone-brain interactions through the mechano-osteoclast signaling axis. In the future, it will be essential to integrate multiple groups of biomarkers to develop early diagnostic tools that promote precise prevention and treatment of bone-brain comorbidities. This article provides a new perspective on the mechanisms and therapeutic strategies of neuroskeletal comorbidities. Full article

Electroactive biomaterials are a key emerging technology for the treatment of neural damage. Conducting polymer-coated carbon microfibers are particularly useful for this application because they provide directional support for cell growth and tissue repair and simultaneously allow for ultrasensitive recording and stimulation of neural activity. Here, we report in vitro experiments investigating the biology of Schwann cells (SCs), a major player in peripheral nerve regeneration, on electroconducting microfibers. The optimal molecular composition of the cell substrate and cell culture medium was studied for SCs dissociated from rat and pig peripheral nerves. The substrate molecules were then attached to carbon microfibers coated with poly (3,4-ethylenedioxythiophene) doped with poly [(4-styrenesulfonic acid)-co-(maleic acid)] (PCMFs), which served as an electroactive scaffold for culturing nerve explants. Biphasic electrical stimulation (ES) was applied through the microfibers, and its effects on cell proliferation and migration were assessed in different cell culture media. Rodent and porcine SCs avidly migrated on PCMFs functionalized with a complex of poly-L-lysine, heparin, basic fibroblast growth factor, and fibronectin. Serum and forskolin/heregulin increased, by two-fold and four-fold, the number of SCs on PCMFs, respectively, and ES further doubled cell numbers without favoring fibroblast proliferation. ES additionally increased SC migration. These results provide a baseline for using biofunctionalized PCMFs in peripheral nerve repair. Full article

Hair follicles are essential to hair formation and cyclic regeneration, experiencing growth and degeneration, and quiescence phases involving complex signaling pathways. Among these, fibroblast growth factors (FGFs) play a critical role in follicular morphogenesis, but the role of FGF receptor signaling in hair follicle development remains underexplored. Current treatments for hair loss, such as medical, surgical, light-based, and nutraceutical interventions, are often expensive, require long-term commitment, and are associated with substantial side effects. This review discusses the mechanisms and biological functions of the FGF signaling pathway within the hair follicle growth cycle, providing an overview of how these elements influence hair follicle dynamics and the pathogenesis of alopecia. Manipulating the FGF signaling pathway could offer new therapeutic options for androgenetic alopecia and other hair loss conditions, potentially exceeding current treatment modalities in efficacy and safety. Full article

Facial aging is a multifactorial process involving changes in bone, fat compartments, ligaments, muscles, and skin. Collagen biostimulators, including synthetic agents and autologous platelet concentrates, have gained attention for facial rejuvenation. Injectable platelet-rich fibrin (i-PRF), a second-generation autologous concentrate, has shown promising regenerative properties due to its natural composition and growth factors. Cosmetic peptides, such as palmitoyl pentapeptide-4 (Matrixyl) and Tetrapeptide-21 (GEKG), are also studied for their ability to stimulate collagen synthesis and remodel the extracellular matrix. This in vitro study examined the potential synergistic effects of i-PRF combined with Matrixyl or GEKG on human dermal fibroblast viability, proliferation, and ECM-related gene expression. Fibroblasts were cultured under six conditions: control, i-PRF alone, Matrixyl alone, GEKG alone, i-PRF + Matrixyl, and i-PRF + GEKG. Viability and proliferation were assessed via MTT, crystal violet, and RealTime-Glo™ assays. Gene expression of COL1A1, FN1, and HAS1 was measured using RT-qPCR. The combinations, especially i-PRF + GEKG, led to increased cell viability and upregulated ECM-related genes at 72 h. These effects were stronger than the individual treatments, suggesting synergistic effects, especially with GEKG. These findings highlight the clinical potential of combining autologous platelet concentrates with bioactive peptides for dermal regeneration. Further preclinical and clinical studies are warranted. Full article

Fibroblast growth factors (FGFs) play a key role in lung development by mediating complex interactions between epithelial and mesenchymal cells, which are central to processes such as branching morphogenesis, epithelial differentiation, and alveolarization. The findings regarding this interplay highlight the complexity of FGF signaling, as different FGFs contribute to various aspects of lung formation and maturation. Understanding the role of FGF proteins in shaping the lung is crucial for gaining insight into the biology of its development. Furthermore, FGFs orchestrate complex signaling pathways that regulate lung regeneration in adulthood. Therapeutic strategies targeting FGF-dependent pathways appear promising for repairing and improving lung function in diverse pulmonary diseases. In this review, we describe the current perception of the role of FGF proteins in lung development and regeneration, together with an overview of emerging therapeutic strategies aiming at FGF signaling in lung-related disorders. Full article

The low predictability of the effects of autologous platelet-rich plasma (PRP) in regenerative therapy for patients with type 1 and type 2 diabetes mellitus (DM) underscores the need for further research assessing the reparative effects of PRP based on the type of DM. The aim of this study was to evaluate the regenerative potential of PRP from young donors (30–40 years old) with DM1 and DM2 in vitro, specifically its effects on human dermal fibroblast cell culture. The in vitro effects of PRP from patients with type 1 and type 2 DM were investigated using a culture of human dermal fibroblasts (hTERT-HDFa) to evaluate metabolic activity, migration, proliferation of the cells, and their ability to release growth factors and exosomes. The study of the biological effects of PRP from donors with DM on hTERT-HDFa revealed a decrease in proliferative effects, an increase in prooxidant action, and toxic influences of PRP from patients, characterized by reduced metabolic activity and cell viability in culture, along with an increase in the percentage of necrosis. These effects were most pronounced in type 1 DM. The secretory response of hTERT-HDFa upon stimulation with PRP varied depending on the type of DM. Correlations indicated the differing significance of PAI-1, TGFB-1, PDGF, VEGF, and IL-6 in assessing the reparative potential across different types of DM. Full article

Wound management is a fundamental skill for veterinarians, requiring a systematic approach to wound care and a deep understanding of the biological principles underlying healing. Sucralfate, widely known as a mucoprotective agent for gastroduodenal ulcers, has recently shown promising topical effects in human skin lesions by binding and protecting growth factors from proteolytic degradation, thereby enhancing their local availability. This action promotes angiogenesis, chemotaxis and cell proliferation, while reducing oxidative stress and exerting bacteriostatic and bactericidal effects against common pathogens. However, the veterinary-specific literature on topical sucralfate is extremely limited, with most available data derived from experimental studies in rodent and porcine models, rather than clinical studies in common veterinary species. Nonetheless, these preliminary studies suggest a potential role for sucralfate in accelerating the healing process through improved collagen synthesis, neovascularization and fibroblast activity. Given the species-specific challenges in veterinary wound healing—especially in horses and cats, prone to delayed healing and exuberant granulation tissue—sucralfate represents a promising, cost-effective and safe candidate for clinical use. This narrative review synthetizes current evidence on sucralfate’s mechanisms and therapeutic benefits across human and veterinary contexts, highlighting the need for controlled, multidisciplinary veterinary studies. Validating sucralfate’s efficacy in clinical settings could enable the growing owner demand for advanced care to be satisfied, shorten recovery times, reduce complications and improve animal welfare. Full article