Search Results (10,391)

Lung adenocarcinoma (LUAD) remains the leading cause of cancer-related mortality worldwide, highlighting the urgent need for novel therapeutic targets. While the role of the somatostatin receptor (SSTR) family is well established in neuroendocrine tumors, their expression patterns, clinical significance, and therapeutic potential in LUAD are not fully understood. In this study, comprehensive analyses of publicly available databases, including TCGA, GSCA, and TIMER, revealed that SSTR4 transcriptional expression is significantly downregulated in LUAD tissues compared to adjacent normal lung tissues. Moreover, low SSTR4 expression correlates with advanced tumor stage, remodeling of the immune microenvironment, and decreased overall survival in patients with LUAD. Using the PRESTO-Tango system, we identified tangeretin (TAN) as a potential ligand for SSTR4. Functional assays demonstrated that SSTR4 knockdown markedly enhanced TAN-mediated proliferative, migratory, and survival inhibitory effects in LUAD cells. Subsequent RNA sequencing and pathway enrichment analyses revealed that the loss of SSTR4 altered the effects of TAN from extracellular matrix remodeling to disruption of calcium homeostasis and energy metabolism disorders, elucidating the mechanism underlying the enhanced antitumor activity. Collectively, these findings establish SSTR4 as a critical tumor suppressor and prognostic biomarker in LUAD and highlight the therapeutic potential of targeting the TAN–SSTR4 signaling axis. These results provide novel insights into the biological functions of SSTR family members in LUAD. Full article

Background/Objectives: Diabetic Foot Ulceration (DFU) is one of the most debilitating and costly complications of diabetes mellitus, representing a significant cause of morbidity, disability, and healthcare burden worldwide. Refractory non-healing ulcers that fail to respond to conventional therapies require novel adjuvant treatment modalities. This clinical audit aimed to evaluate the long-term clinical outcomes of an autologous, bioactive platelet-rich fibrin (PRF) matrix combined with topical gentamicin in patients with chronic, non-healing DFUs. Methods: A retrospective observational audit was conducted, involving eleven patients with refractory DFUs who underwent adjunctive treatment with a PRF matrix (Arthrozheal^®) and co-applied gentamicin. Patients were followed at three-week intervals using standardised wound imaging (Silhouette^® 3D) to assess healing parameters. Long-term follow-up data, evaluating healing durability and complications, is presented. Results: All patients completed the treatment protocol, with significant reductions in mean wound area (87.9%), perimeter, depth, and volume (all p < 0.05). Epithelialised tissue increased from 24.7% to 82.8%. At 12 months, 81.8% of patients maintained complete ulcer healing. Two patients experienced complications: one ulcer recurrence requiring surgical debridement and one unrelated amputation due to osteomyelitis. Conclusions: The combination of autologous PRF matrix and gentamicin demonstrated promising results in promoting sustained healing of refractory DFUs with minimal complications. These findings support further investigation in larger, controlled studies to validate this biologic-antimicrobial approach as a safe, effective, and durable therapy for complex diabetic wounds. Full article

Free flavin adenine dinucleotide (FAD) is metabolized to flavin mononucleotide (FMN) and adenine monophosphate (AMP) by hydrolases and to 4′,5′-cyclic phosphoriboflavin (cFMN) and AMP by the triose kinase FMN cyclase (TKFC). Yet, the lack of analytical standards for cFMN might have resulted in the incidence of cFMN in biological specimens being underreported. To address this shortcoming, cFMN was synthesized from either FMN or FAD. The optimization of the FAD to cFMN reaction conditions revealed that an equimolar ratio of ZnSO₄ and FAD yielded pure cFMN upon the precipitation of AMP-Zn salts. cFMN is stable to aqueous acidic and basic conditions and is readily extracted from biological samples for detection by liquid chromatography coupled with mass spectrometry. Although cFMN is hydrolyzed by liver tissue extracts to FMN and riboflavin, the mechanisms for this conversion remain elusive. Full article

Nanotechnology has emerged as a transformative tool in animal production, offering novel strategies to enhance productivity, health, and product quality. Among trace elements, selenium (Se) plays an essential role in antioxidant defence, immune regulation, and redox balance through its incorporation into selenoproteins. Selenium nanoparticles (SeNPs), synthesized via chemical, physical, or biological methods, have shown superior bioavailability, stability, and lower toxicity compared to traditional organic and inorganic selenium forms. This review explores the synthesis, physicochemical properties, and metabolic fate of SeNPs, emphasizing their advantages in poultry production systems. In poultry, SeNPs exhibit potent antioxidant and anti-stress effects by enhancing the activity of glutathione peroxidase, superoxide dismutase, and thioredoxin reductase, thereby mitigating lipid peroxidation and oxidative tissue damage. Their immunomodulatory effects are linked to improved lymphocyte proliferation, cytokine regulation, and increased immunoglobulin levels under normal and stress conditions. SeNP supplementation has been associated with enhanced growth performance, feed efficiency, carcass quality, and reproductive outcomes in broilers, layers, and quails. Furthermore, selenium nanoparticles have demonstrated therapeutic potential in preventing or alleviating chronic diseases such as cancer, diabetes, cardiovascular dysfunction, and neurodegenerative disorders. SeNPs also serve as biofortification agents, increasing selenium deposition in poultry meat and eggs, thus improving their nutritional value for human consumption. However, selenium’s narrow safety margin requires careful dose optimization to avoid potential toxicity. This review highlights the multifaceted benefits of selenium nanoparticles in poultry nutrition and health, while underscoring the need for further studies on grey SeNPs, long-term safety, and regulatory frameworks. Integrating SeNPs into poultry production represents a promising strategy to bridge animal health, food security, and public nutrition. Full article

Platelet-rich plasma (PRP) is a cornerstone of regenerative medicine, offering therapeutic potential across numerous clinical disciplines. Its efficacy relies on concentrated platelets and plasma components that release growth factors, cytokines, and extracellular vesicles to orchestrate tissue repair, immunomodulation, and angiogenesis. Recent findings have uncovered novel mechanisms, such as mitochondrial transfer from platelets to target cells and the delivery of bioactive microRNAs that regulate inflammation and metabolic reprogramming. However, despite its potential, PRP therapy is often limited by inconsistent results. In this review, we examine how patient-specific factors—including age, comorbidities, and lifestyle—and technical variables in preparation and storage, influence the biological quality of the final product. Therefore, standardizing protocols and accounting for individual biological variability are essential for achieving reproducible outcomes. In conclusion, PRP is a complex therapeutic agent whose success depends on both intrinsic bioactive content and extrinsic processing factors. Integrating these molecular insights with personalized patient assessment is crucial to optimizing PRP treatment procedures. Future research should focus on refining standardization to fully establish PRP as a precision medicine tool in regenerative therapy. Full article

Cancer remains a significant challenge in the field of medicine, primarily due to its inherent plasticity and the development of resistance to conventional therapeutic interventions. Genomic mutations and the activation of oncogenes enable cancer cells to resist senescence and apoptosis, leading to uncontrolled growth with harmful consequences. Small peptides are molecules with interesting anti-tumour properties and represent a valid alternative to conventional treatments. Our group has previously identified a class of small peptides bound to the DNA that can be extracted from the chromatin of various tissues, including wheat germ and trout. These peptide pools have been shown to possess interesting antiproliferative and apoptotic properties, and they are associated with cell cycle regulation. However, given the complexity of the extraction process, it is necessary to identify a substrate that will enable a more efficient extraction of these peptides, while also ensuring a composition that is simple to investigate. The present study developed a method for the extraction of this group of peptides from yeast, and the extract was then tested on cancer cells in order to confirm its anti-tumoral properties. The peptides were obtained from chromatin extracted from Saccharomyces cerevisiae cells through alkalisation and purification by gel filtration chromatography. The extract was tested on HeLa cells to verify its effects on vitality and the cell cycle. The data demonstrate that the chromatographic profile of this peptide extract indicates a more basic composition than the pool extracted from other tissues and exhibits comparable antiproliferative properties. The ability to rapidly obtain a biologically active, analytically accessible, and adequately purified fraction from the widely available substrate Saccharomyces cerevisiae represents a significant advance in the study of these DNA-binding peptides. Full article

Conductive polymers (CPs), such as polypyrrole (PPy), have shown promising properties for use as electro-responsive bioactive scaffolds for tissue regeneration. PPy can be synthesized by chemical electrosynthesis and doped with biomolecules such as hyaluronic acid (HA). Taking advantage of the electrochemical synthesis versatility, nanofibers for surface-modified indium tin oxide (ITO) electrodes can be used as templates to produce tridimensional HA-doped PPy scaffolds. In this study, polyvinyl alcohol/chitosan (PVA/CTS) electrospun nanofibers deposited on ITO electrodes were used as a 3D template for the in situ electrosynthesis of HA-doped PPy to produce a bioactive scaffold for tissue engineering. The final material gathers the advantages of each biopolymer, the porous morphology of the nanofiber, and the conductivity of the electrosynthetized polymer. Furthermore, the biological activity of the NF-PVA/CTS@PPy:HA composite was evaluated in NIH-3T3 fibroblasts by MTT, resulting in a cell viability of 146 ± 40% and wound-healing capacity of 97 ± 1.9% at 24 h of culture. Full article

Carotenoids are a class of C40 isoprenoid-derived fat-soluble pigments that play vital roles in plant physiology and human health and serve as precursors for several biologically critical regulatory molecules. Carotenoid cleavage dioxygenases (CCDs) are key enzymes that catalyze the selective oxidative cleavage of carotenoids into apocarotenoids, thereby significantly influencing plant development and responses to abiotic stress. Although extensive research has been conducted on many model species, comprehensive studies on the StCCD gene family in potato remain limited. In this study, we conducted a genome-wide analysis to identify and characterize the CCD gene family in potato. Phylogenetic and structural analyses classified the 17 StCCD genes into six distinct subfamilies, which are distributed across five chromosomes of the genome. Analysis of cis-acting regulatory elements revealed that the promoters of most StCCD genes contain various elements associated with light responsiveness, stress signaling, and phytohormone regulation. Molecular docking analysis indicated that CCD proteins exhibit distinct substrate specificity in their binding to carotenoids and intermediate products. The expression profiling of StCCD genes uncovered pronounced specificity in their expression, which was evident across tissues, throughout tuber maturation, and following exposure to abiotic stresses and hormonal applications. This specificity strongly implicates these genes in the regulation of developmental processes and stress adaptation mechanisms. This study provides a comprehensive genomic and transcriptomic overview of the CCD gene family in potato, establishing a foundation for functional characterization of individual genes in the future. Full article

Objective: This study compares the brain protective effects of L-borneolum and its main components (a combined application of L-borneol and L-camphor) on the rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). It also makes clear the intrinsic regulatory mechanisms that link the neuroprotective effects of these compounds on IS to the blood-brain barrier (BBB), based on network pharmacology predictions. Furthermore, the study investigates the relationship between these compounds and the Major Facilitator Superfamily Domain-containing Protein 2A (MFSD2A)/Caveolin-1 (Cav-1) signaling axis. Methods: The MCAO/R model in rats was established to evaluate the therapeutic effect of L-borneolum (200 mg/kg) and its main components combination of L-borneol and L-camphor (6:4 ratio, 200 mg/kg). Neurological scores, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and Nissl staining were performed to evaluate the neurological damage in the rats. Cerebral blood flow Doppler was applied to monitor the cerebral blood flow changes. Immunofluorescence analysis of albumin leakage and transmission electron microscopy (TEM) were conducted to evaluate blood-brain barrier (BBB) integrity. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the optimal drug concentration. Trans-epithelial electrical resistance (TEER) and horseradish peroxidase (HRP) assays were employed to confirm the successful establishment of an in vitro BBB co-culture model. Network pharmacology was utilized to predict the biological processes, molecular functions, and cellular components involved in the treatment of ischemic stroke (IS) by the main components of L-borneolum (L-borneol and L-camphor). Finally, immunofluorescence, real-time fluorescent quantitative PCR (RT-qPCR) and western blot analyses were performed to detect the expression of Major Facilitator Superfamily Domain Containing 2A (MFSD2A), caveolin-1 (CAV-1), sterol regulatory element-binding protein 1 (SREBP1) in brain tissue and hCMEC/D3 cells. Results: Network pharmacology prediction indicated that L-borneolum and its main components (L-borneol and L-camphor) in the treatment of IS are likely associated with vesicle transport and neuroprotection. Treatment of IS with L-borneolum and its main components significantly decreased neurological function scores and cerebral infarction area, while alleviating pathological morphological changes and increasing the number of Nissl bodies in the hippocampus. Additionally, it improved cerebral blood flow, reduced albumin leakage, and decreased vesicle counts in the brain. The trans-epithelial electrical resistance (TEER) of the co-culture model stabilized on the fifth day after co-culture, and the permeability to horseradish peroxidase (HRP) in the co-culture model was significantly lower than that of the blank chamber at this time. RT-qPCR and Western blot results demonstrated that, compared to the model group, the expression of SREBP1 and MFSD2A significantly increased, while the expression of Cav-1 decreased. Conclusions: L-borneolum and its main components combination (L-borneol/L-camphor, 6:4 ratio) may exert a protective effect in rats with IS by improving BBB transport function through modulation of the MFSD2A/Cav-1 signaling pathway. Full article

Titanium dioxide (TiO₂) nano- and submicrometric particles’ widespread use in different sectors raised concerns about human and environmental exposure. The validation of analytical methods is essential to ensure reliability in risk assessment studies. In this study, a single-particle inductively coupled plasma mass spectrometry (spICP-MS) method was validated for the detection, quantification, and dimensional characterization of TiO₂ particles in biological tissues. Tissue samples collected after exposure to TiO₂ particles underwent mild acidic digestion using a HNO₃/H₂O₂ mixture to achieve complete matrix decomposition while preserving particle integrity. The resulting digests were analyzed by ICP-MS operated in single-particle mode to quantify and size TiO₂ particles. Method validation was conducted according to ISO/IEC 17025:2017 and included linearity, repeatability, recovery, and detection limit assessments. The limit of detection for TiO₂ particles was 0.04 µg/g, and 55.7 nm was the size the detection limit. Repeatability was within 0.5–11.5% for both TiO₂ mass concentrations and particle size determination. The validated method was applied to tissues from inhalation-exposed subjects, showing TiO₂ levels of 80 ± 20 µg TiO₂/g and particle number concentrations of 5.0 × 10⁵ ± 1.2 × 10⁵ part. TiO₂/mg. Detected TiO₂ particles’ mean diameter ranged from 230 to 330 nm. The developed and validated spICP-MS method provides robust and sensitive quantification of TiO₂ particles in biological matrices, supporting its use in human biomonitoring and exposure assessment studies. Full article

Agrobacterium tumefaciens, a destructive pathogen causing crown gall disease, results in substantial agricultural losses. Traditional chemical and existing biocontrol methods are limited by environmental pollution, pesticide resistance, and low efficacy, while bacteriophages emerge as a promising alternative due to their high host specificity, environmental compatibility, and low resistance risk. In this study, we isolated and characterized a lytic phage (PAT-A) targeting A. tumefaciens, evaluating its biological traits, genomic features, and biocontrol potential. The host strain A. tumefaciens CL-1 was isolated from cherry crown gall tissue and identified by 16S rDNA sequencing. Phage PAT-A was recovered from orchard soil via the double-layer agar method, showing a tadpole-shaped morphology (60 nm head diameter, 30 nm tail length) under transmission electron microscopy (TEM). Nucleic acid analysis confirmed a double-stranded DNA genome, susceptible to DNase I but resistant to RNase A and Mung Bean Nuclease. PAT-A exhibited an optimal MOI of 0.01, tolerated wide pH and temperature ranges, but was sensitive to UV (titer declined after 15 min of irradiation) and chloroform (8% survival at a 5% concentration). Whole-genome sequencing revealed a 44,828 bp genome with a compact structure, and phylogenetic/collinearity analyses placed it in the Atuphduvirus genus (Autographiviridae). Biocontrol experiments on tobacco plants demonstrated that PAT-A significantly reduced crown gall incidence. Specifically, simultaneous inoculation of PAT-A and A. tumefaciens CL-1 resulted in the lowest tumor incidence (12.0%), while pre-inoculation of PAT-A 2 days before pathogen exposure achieved an incidence rate of 33.3%. In conclusion, PAT-A is a novel strictly lytic phage with favorable biological properties and potent biocontrol efficacy against A. tumefaciens, enriching phage resources for crown gall management and supporting phage-based agricultural biocontrol strategies. Full article

Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and many patients cannot undergo curative surgery due to frailty. Multimodal prehabilitation: combining exercise, nutrition, and psychological support improves functional readiness, but its biological impact on the PDAC tumor microenvironment (TME) is unclear. In this exploratory pilot study, we profiled resected PDAC tissues from prehabilitation-treated patients and matched controls using NanoString GeoMx Digital Spatial Profiling across immune, tumor, and stromal compartments (n = 4). Transcriptomic signatures were analyzed via differential expression, pathway enrichment, and MCP-counter deconvolution; protein-level validation used multiplex immunofluorescence (n = 8). Ligand–receptor modeling assessed cell–cell communication, and prognostic relevance was evaluated in TCGA-PDAC (n = 178). Prehabilitation was associated with increased NK-cell cytotoxicity, interferon response, and chemokine recruitment, as well as higher neutrophil signatures (p < 0.01) and reduced fibroblast signatures (p < 0.05). Tumor regions showed lower MAPK and PI3K/AKT activity, while stroma exhibited decreased TGF-β and Wnt signaling. Immunofluorescence confirmed neutrophil infiltration and reduced fibroblast density. TCGA analysis linked neutrophil-high/fibroblast-low profiles to longer survival (1044.6 vs. 458.7 days, p = 0.0052). These findings suggest prehabilitation may promote a more immune-active, less fibrotic TME in PDAC, resembling transcriptional states associated with improved survival. Prospective studies integrating biological and clinical endpoints are warranted. Full article

Objectives: The study examined tear and serum alterations using the ferning test and quantified the number of branches formed during the controlled drying of these biological fluids (tears and serum), in order to identify a potential diagnostic patterning test in individuals with obesity. Methods: A total of 61 patients aged between 25 and 72 years were enrolled (median age [interquartile range] = 39.0 [26] years). BMI values ranged from 19.1 to 47.5 kg/m², with a median BMI (interquartile range) of 29.3 (12.1) kg/m². Results: The Kruskal–Wallis test showed statistically significant differences among at least two Schirmer classes with respect to the number of branches observed in dried tears at a brightness threshold of 220 (H(2) = 8.485, p = 0.014). According to the Dunn post hoc test, Schirmer Class 1 showed a markedly lower number of branches compared with Classes 2 and 3 (p < 0.031 and p < 0.021), whereas no significant difference was found between Classes 2 and 3. The Kruskal–Wallis test further suggested the presence of statistically significant differences in the number of branches in dried serum, quantified using ImageJ2 at a brightness threshold of 190, across visceral fat classes (H(2) = 9.583, p = 0.008). Dunn’s post hoc tests revealed that the number of branches in serum analyzed at a brightness threshold of 190 was significantly higher in visceral fat class 3 compared to class 1 (p_holm = 0.006), while no statistically significant differences were observed between classes 1 and 2 or between classes 2 and 3 (p_holm > 0.05). Conclusions: In addition to other obesity-specific complications patients with obesity exhibit an increased risk of developing dry eye syndrome. The combined assessment of DPT in both the tear film and serum may represent a new method for analyzing obesity-associated biomarkers. Further studies are required to determine the sensitivity and specificity of these approaches in diagnosing systemic alterations induced by excess adipose tissue. Full article

Autologous fat grafting is the main surgical technique for soft tissue reconstruction. However, its clinical use with more extended volumes is limited by repeated procedures due to the little possibility of banking tissue, donor-site morbidity and unpredictable graft resorption rates. To overcome these problems, adipose tissue engineering has focused on developing injectable scaffolds. Most of them are hydrogels that closely mimic the biological, structural and mechanical characteristics of native adipose tissue. This review provides an overview of current injectable scaffolds designed to restore soft tissue volume defects, emphasizing their translational potential and future directions. Natural injectable scaffolds exhibit excellent biocompatibility but degrade rapidly and lack mechanical strength. Synthetic injectable scaffolds provide tunable elasticity and degradation rates but require biofunctionalization to support cell adhesion and tissue integration. Adipose extracellular matrix-derived injectable scaffolds are fabricated by decellularization of adipose tissue. Accordingly, they combine bio-mimetic structure with intrinsic biological cues that stimulate host-driven adipogenesis and angiogenesis, thus representing a translatable “off-the-shelf” alternative to autologous fat grafting. However, despite this broad spectrum of available injectable scaffolds, the establishment of clinically reliable soft tissue substitutes capable of supporting large-volume and long-lasting soft tissue reconstruction still remains an open challenge. Full article

Liver cancer, also known as hepatocellular carcinoma (HCC), remains a major global health concern, with high mortality driven by late-stage diagnosis, limited treatment efficacy, and frequent therapeutic resistance. Matrix metalloproteinases (MMPs), a large family of zinc-dependent endopeptidases, are central to the biological processes that drive liver tumor initiation and progression. By degrading and reorganizing extracellular matrix components, MMPs facilitate tumor expansion, tissue invasion, and metastatic dissemination. In addition, these enzymes regulate the availability of growth factors, cytokines, and chemokines, thereby influencing angiogenesis, inflammation, immune cell recruitment, and the development of an immunosuppressive tumor microenvironment. Aberrant expression or activity of multiple MMP family members is consistently associated with aggressive clinicopathologic features, including vascular invasion, increased metastatic potential, and reduced patient survival, highlighting their promise as prognostic markers and actionable therapeutic targets. Past attempts to modulate MMP activity were hindered by broad inhibition profiles and dose-limiting toxicities, underscoring the need for improved specificity and delivery strategies. Recent advances in molecular design, biologics engineering, and nanotechnology have revitalized interest in MMP targeting by enabling more selective, context-dependent modulation of proteolytic activity. Preclinical studies demonstrate that carefully tuned MMP inhibition can limit tumor invasion, enhance anti-angiogenic responses, and potentially improve the efficacy of existing systemic therapies, including immuno-oncology agents. This review synthesizes current knowledge on the multifaceted roles of MMPs in HCC pathobiology and evaluates emerging therapeutic strategies that may finally unlock the clinical potential of targeting these proteases. Full article