Search Results (8,071)

Background: Head and neck squamous cell carcinoma remains a highly aggressive malignancy with limited predictive biomarkers for prognosis and radiotherapy response. Increasing evidence indicates that pseudogenes are functionally active regulators of cancer biology, yet their clinical relevance in HNSCC is poorly defined. Methods: Using transcriptomic and clinical data from The Cancer Genome Atlas, we analyzed the expression and clinical significance of two pseudogenes, ANXA2P2 and PA2G4P4, in HNSCC. Associations with clinicopathological features, HPV status, tumor subtypes, survival, genomic instability, radiotherapy response, and immune landscape were assessed using bioinformatic tools. Results: Both pseudogenes were significantly upregulated in HNSCC compared to normal tissues. Higher expression levels correlated with adverse clinicopathological features, increased tumor proliferation and wound-healing capacity, and unfavorable TCGA molecular subtypes. High ANXA2P2 and PA2G4P4 expression was associated with reduced overall survival, while their combined low-expression signature identified patients with significantly improved overall and disease-free survival. Notably, lower expression of both pseudogenes was observed in patients responding to radiotherapy, whereas higher expression was linked to genomic instability parameters and enrichment of oncogenic pathways, including MYC, PI3K/AKT/mTOR, cell cycle regulation, and DNA repair. ANXA2P2 expression differed significantly by HPV status, showing reduced levels in HPV-positive tumors. Furthermore, pseudogene expression stratified distinct immune profiles, including immune subtypes, stromal and immune scores, and specific immune cell populations. Conclusions:ANXA2P2 and PA2G4P4 are clinically relevant pseudogenes associated with tumor aggressiveness, immune modulation, and radiotherapy response in HNSCC. These findings support their potential utility as prognostic and predictive biomarkers and provide a rationale for further functional validation in experimental models. Full article

Bacterial infections remain a major challenge to human health, especially in wound healing, where they can cause prolonged inflammation, delayed recovery, and severe complications. Current research is increasingly focused on developing innovative antimicrobial materials capable of overcoming the limitations of conventional antibiotics, whose effectiveness has declined due to the rise in bacterial resistance. Among the various alternatives, silver nanoparticles have gained particular attention for their broad-spectrum antibacterial properties and have already been successfully applied in the functionalization of commercial wound dressings. The aim of this study was to optimize the functionalization of commercial cotton gauzes based on in situ UV-assisted reduction of silver nanoparticles, reducing methanol usage and identifying the minimal silver nitrate precursor concentration to achieve antimicrobial efficacy while maintaining biocompatibility. Different precursor concentrations were then evaluated through cytocompatibility assays (MTT, Live/Dead, and scratch tests on fibroblasts) and antimicrobial analyses against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus (including an antibiotic-resistant strain), and Candida albicans. The results demonstrated that a 0.5% w/w silver nitrate concentration provided strong antimicrobial and antibiofilm activity without compromising textile properties or cytocompatibility. Furthermore, this optimized process reduced material waste, highlighting its potential for scalable production of antimicrobial wound dressings. Full article

This study addresses the critical need for advanced biomedical materials that possess both potent antimicrobial properties and high biocompatibility to prevent device-related infections and promote healing. To this end, we demonstrate the successful development and comprehensive characterization of functional composite materials based on a photopolymerizable acrylate resin modified with laser-ablated copper nanoparticles (Cu NPs). The synthesized Cu NPs exhibited a monomodal size distribution with a peak at 47 nm, a high zeta potential of −33 mV, and a spherical morphology. Incorporation of Cu NPs into the polymer matrix via Masked Stereolithography (MSLA) enabled the fabrication of complex structures that maintained high surface quality and optical transparency after polishing. Modification of photopolymer resin with Cu NPs significantly increased the strength of the resulting products and caused dose-dependent formation of reactive oxygen species (ROS). The resulting composite materials exhibited strong antibacterial activity against E. coli. Crucially, despite their potent antimicrobial efficacy, the materials showed no cytotoxicity towards human fibroblast cultures. These results highlight the potential of these composites for a new generation of biomedical applications, such as implantable devices and wound coatings, which combine programmable antimicrobial activity with high biocompatibility. Full article

Prostate cancer (PCa) metastasis is reliant on the activity of proteases, such as matrix metalloproteinase-2 (MMP-2). While increased extracellular heat shock protein 90α (eHSP90α) has been linked to increased MMP-2 activity, this has not been examined in the context of cellular stress. We examined stress-induced eHSP90α in human prostate cell lines by immunoblot. Fluorometric gelatin dequenching and zymography assays measured MMP activity. Wound healing and Matrigel drop invasion assays were used to quantify cell motility. HSP90α knockout (KO) cells were established with CRISPR/Cas9. Proteases were profiled with molecular inhibitors and protein arrays and validated by siRNA knockdown, immunoblot, and motility assays. Stress increased eHSP90 in four out of four human prostate cell lines examined. Surprisingly, it concurrently decreased MMP-2 activity. The functional relevance of this was demonstrated when conditioned media from stressed cells decreased the motility of non-stressed cells. Screening for protease inhibitors that would rescue stress-induced decreases in MMP-2 activity identified a single serine protease inhibitor: aprotinin. Yet rescue with aprotinin was lost in HSP90α KO cells. A protease array identified stress-induced increases in kallikrein-related peptidase 6 (KLK6). Knockdown of KLK6 rescued stress-induced MMP-2 activity and cell motility. In conclusion, we identify a novel stress-induced extracellular network that regulates MMP-2 activity and cell motility. We identified KLK6 as a stress-induced extracellular protease leading to decreased MMP-2 activity and cellular invasion, while eHSP90α is required for the rescue of MMP-2 activity once KLK6 is neutralized. Full article

Edible flowers have garnered increasing attention due to their high content of bioactive compounds, making them promising candidates for biomedical and functional food applications. This work evaluated the metabolomic data of fresh Rosa x hybrida petals, revealing seven types of metabolites, including amino acids, organic acids, vitamins, sugars, phenolic acids, and flavonoids. Notably, quercetin, kaempferol and their derivatives were the main flavonoids determined. Furthermore, in vitro studies were conducted to evaluate the potential antiproliferative effects against triple-negative breast cancer (TNBC). Thus, the methanolic extract derived from Rosa x hybrida petals demonstrated significant antitumoral activity against both sensitive and resistant TNBC cells, as evidenced by reduced MTT metabolization, colony formation, and wound healing activity. Furthermore, the cell death mechanism associated with the petal extract was studied. The antiproliferative activity was mediated by reactive oxygen species generation, triggering cell death mechanisms such as apoptosis and autophagy. In conclusion, these results propose Rosa x hybrida could be a new tool for nutraceuticals and functional food production. Full article

Background: Cancer-associated fibroblasts (CAFs) are key mediators of metastatic progression in non-small cell lung cancer (NSCLC). Fibroblast activation protein (FAP) serves as the hallmark of CAF activation. However, the upstream regulation of FAP remains elusive, limiting stroma-targeted therapy development. Methods: ⁶⁸Ga-FAP inhibitor (FAPI)-04 PET/CT imaging was performed on 61 NSCLC patients to evaluate the clinical significance of FAP. CAFs and normal fibroblasts (NFs) were isolated from patient tissues. Bioinformatic analysis and qRT-PCR were employed to screen and validate miRNAs. Functional assays (CCK-8, collagen contraction, wound healing, transwell co-culture) were utilized to investigate the role of miR-624-5p in regulating fibroblast activation and the effects on the metastatic potential of NSCLC cells. The targeting relationship between miR-624-5p and FAP was validated using FISH, dual-luciferase assay, and Western blotting. Results: ⁶⁸Ga-FAPI-04 uptake was higher in advanced NSCLC (p < 0.001) and correlated with tumor size, lymph node metastases, and distant metastases (p < 0.05). Isolated primary CAFs significantly enhanced the migration and invasion of A549 and PC9 cells compared to NFs (p < 0.001). We identified miR-624-5p as a significantly downregulated miRNA in CAFs (p < 0.001). Functionally, miR-624-5p overexpression inhibited CAF proliferation and collagen contraction (p < 0.01) and reduced the proliferation, migration, and invasion capabilities of A549 and PC9 cells (p < 0.001). Mechanistically, miR-624-5p bound to FAP mRNA and negatively regulated FAP expression (p < 0.001), thus suppressing CAF activation and tumor metastasis. Conclusions: Our findings establish miR-624-5p as a novel upstream regulator that suppresses FAP expression, consequently inhibiting CAF activation and its pro-metastatic function. Targeting the miR-624-5p/FAP axis represents a promising therapeutic strategy for NSCLC metastasis. Full article

Background/Objectives: War-related mandibular injuries result in extensive soft-tissue damage, severe comminution, and bone loss, and are associated with high rates of infection and delayed healing. No universally accepted management protocol exists for these injuries. External fixation is commonly used in this context, particularly when internal fixation is unavailable or contraindicated. This study aimed to analyze injury patterns, treatment outcomes, and complications of war-related mandibular fractures treated with external fixation as a primary and definitive stabilization method in a resource-limited setting in eastern Democratic Republic of Congo. Methods: A retrospective review was conducted of all patients who sustained war-related mandibular fractures and were treated with external fixation between January 2017 and December 2024 at the Hôpital Provincial Général de Référence de Bukavu. Demographic data, injury characteristics, treatment details, outcomes, and complications were collected. Factors associated with delayed union and fracture-related infection were evaluated using univariate analysis. Results: Ninety-one patients with severe mandibular war injuries were included. High-velocity gunshot wounds accounted for 94.5% of injuries. Clinical evidence of wound infection at admission was present in 29.7% of patients. The mean delay between injury and external fixation was 9.2 ± 6.6 days. Successful bone healing without secondary bone procedures was achieved in 71 patients (78.0%), with a mean healing time of 7.6 ± 3.0 weeks. Delayed bone grafting was required in 20 patients (22.0%), performed at a mean of 77.3 ± 30.5 days after initial fixation. The overall complication rate was 36.3%, with fracture-site infection being the most frequent complication (30.8%). Bone loss at presentation, clinical infection at admission, and the need for bone grafting were significantly associated with fracture-related infection (p < 0.05). Conclusions: War-related mandibular fractures in this series were characterized by severe comminution, bone loss, infection, and delayed presentation. Despite these challenges, external fixation provided acceptable fracture healing and functional outcomes. Small orthopedic external fixators represent a pragmatic and effective treatment option for complex mandibular war injuries in resource-limited settings. Full article

Dermatomyositis (DM) is an idiopathic inflammatory myopathy (IIM) characterized by distinctive chronic cutaneous manifestations. Although immune-mediated and microvascular mechanisms are well established, the role of metabolic dysfunction, particularly hyperglycemia, is underexplored in dermatological conditions. This review synthesizes mechanistic, clinical, and translational evidence to explore the relationship between dysglycemia and cutaneous disease severity in DM. Hyperglycemia is associated with oxidative stress, advanced glycation end-product formation, endothelial injury, and proinflammatory cytokine signaling. These processes may plausibly amplify DM-associated vasculopathy, impair wound healing, and worsen cutaneous inflammation. Limited DM-specific studies demonstrate increased insulin resistance and a higher prevalence of diabetes compared with healthy controls. Meanwhile, case reports suggest that poor glycemic control can exacerbate cutaneous disease. Evidence from other inflammatory dermatoses supports a biologically plausible role for dysglycemia in increasing flare frequency, infection risk, and delayed tissue repair. Dietary patterns characterized by high glycemic index and coexisting metabolic syndrome may further intensify systemic and cutaneous inflammation. Collectively, these findings suggest hyperglycemia as a biologically plausible contributor to cutaneous disease severity in DM that warrants further investigation. These observations highlight the need for future studies to evaluate whether metabolic screening, dietary patterns, and interdisciplinary care influence cutaneous disease activity and wound healing in DM. Prospective clinical investigation is needed to determine whether targeted glycemic optimization is associated with changes in cutaneous and systemic outcomes in DM. Full article

Jawbone cavitations have been described for decades under various terminologies, including neuralgia-inducing cavitational osteonecrosis (NICO) and fatty degenerative osteolysis of the jawbone (FDOJ). Their biological nature and clinical relevance remain controversial. The present review aimed to summarize the current understanding of jawbone cavitations, identify relevant research gaps, and propose a unified descriptive terminology. This narrative literature review was conducted using PubMed/MEDLINE, Google Scholar, and manual searches of relevant journals. The available evidence was qualitatively synthesized. The results indicate that most published data on jawbone cavitations are derived from observational, retrospective, and cohort studies, with etiological concepts largely based on histopathological findings. Recent three-dimensional radiological analyses suggest that intraosseous non-mineralized areas frequently observed at former extraction sites may represent a physiological outcome of socket collapse and incomplete ossification rather than a pathological condition. This review introduces Covered Socket Residuum (CSR) as a radiological descriptive term and clearly distinguishes it from pathological entities such as NICO and FDOJ. Recognition of CSR is clinically relevant, particularly in dental implant planning, where unrecognized non-mineralized areas may compromise primary stability. The findings emphasize the role of three-dimensional radiological assessment for diagnosis and implant planning and discuss preventive and therapeutic strategies, including Guided Open Wound Healing (GOWH^TM). Prospective controlled clinical studies are required to validate this concept and determine its clinical relevance. Full article

Cutaneous leishmaniasis is a zoonotic disease caused by Leishmania parasites and leads to chronic, non-healing skin lesions. Although current drugs can control the disease, their use is limited by systemic side effects, low efficacy, and inadequate lesion penetration. Therefore, innovative local delivery systems are required to enhance drug penetration and reduce systemic toxicity. To address these challenges, silver nanoparticles (AgNPs) were synthesized using propolis extract through a green synthesis approach, and a tri-layer wound dressing composed of polyvinyl alcohol and gelatin containing synthesized AgNPs and Glucantime was fabricated by electrospinning. Characterization (SEM-EDX, FTIR, TGA) confirmed uniform morphology, chemical structure, and thermal stability; the wound dressing exhibited hydrophilicity, antioxidant activity, and biphasic release. Biological evaluations against Leishmania tropica demonstrated significant antiparasitic activity. Promastigote viability decreased from 76.3% in neat fibers to 31.6% in nanofibers containing AgNPs and 7.9% in tri-layer nanofibers containing both AgNPs and Glucantime. Similarly, the amastigote infection index dropped from 410 in controls to 250 in neat nanofibers, 204 in AgNPs-containing nanofibers, and 22 in tri-layer nanofibers containing AgNPs and Glucantime. The tri-layer nanofibers demonstrated enhanced antileishmanial activity over AgNPs-containing fibers, confirming synergistic efficacy. All nanofibers were biocompatible, supporting their use as a safe platform for cutaneous leishmaniasis treatment. Full article

Background: Wound healing contributes to restoring skin integrity. However, scars affect soft tissue in all its layers, including the superficial and deep fascia; moreover, it has been demonstrated that the fibroblasts leading the scarring process develop from progenitors located in the superficial fascia. In the past, research into scar etiology has focused primarily on the dermal and epidermal layers, leaving the role of the fasciae largely overlooked. Many patients presenting with surgical or traumatic scars complain of the increased stiffness and thickness of the scar, reduced extensibility of the area surrounding it, and chronic pain persisting even after the healing process has been completed. The purpose of this systematic review is to investigate the non-invasive tools and methods employed for the objective evaluation of scars that involve fascial layers. Methods: A systematic literature search was conducted on PubMed and WOS. Registration DOI: 10.17605/OSF.IO/SDR3Q. Results: A total of 11 articles were selected; the etiologies of scars were surgical, traumatic, and other (keloids). The investigations were conducted using ultrasound, magnetic resonance imaging, strain elastography, and shear wave elastography on the visceral fasciae, superficial fascia, hypodermis, and musculoskeletal fasciae. Sliding of fasciae was assessed by ultrasound; thickness of fasciae was assessed by ultrasound and magnetic resonance imaging; stiffness was assessed by shear wave elastography and strain elastography; and the qualitative assessment was performed via ultrasound. Conclusions: Our literature review showed that ultrasound, magnetic resonance imaging, strain elastography, and shear wave elastography are currently adopted for investigating the sliding, thickness, stiffness, and qualitative features of scars involving fascial layers. Moreover, our research showed the existence of a gap in the scientific literature on this topic. Full article

Hard-to-heal wounds remain a significant challenge for healthcare professionals, particularly in aging populations. Although most chronic wounds are associated with diabetes or chronic venous insufficiency, rare etiologies should also be considered. One such cause is envenomation by Phoneutria spp. (native to South America, rare in Europe). Their venom contains potent neurotoxins. While systemic manifestations are more commonly reported, localized necrotic skin lesions may also occur. This case report presents a rare chronic wound following a suspected Phoneutria spider bite and highlights the importance of an individualized, multimodal treatment approach. A 61-year-old male patient with a progressive thigh wound following a spider bite sustained during work. Despite initial self-treatment and pharmacotherapy the wound deteriorated. The patient was admitted to the authors’ facility, where surgical treatment included necrosectomy and a sandwich graft using an acellular dermal matrix combined with a split-thickness skin graft. Adjunctive therapies included negative pressure wound therapy and hyperbaric oxygen therapy. After discharge, outpatient wound care was continued. Treatment was monitored with photographic documentation and serial microperfusion measurements. Complete wound closure was achieved after 4 months of specialized therapy. Management of chronic wounds requires a multidisciplinary and individualized approach with surgical intervention, advanced wound care and specialized outpatient follow-up. Full article

Background and Objectives: The treatment of duodenal injuries remains one of the most challenging issues in clinical surgery due to their high morbidity and mortality rates. The primary objective of this study was to evaluate the histopathology and other diagnostic outcomes of wound repair following surgical reconstruction of large experimental duodenal defects using synthetic (ePTFE, expanded polytetrafluoroethylene) or organic (JSP, jejunal serosal patch) materials. Materials and Methods: A total of 20 European rabbits were randomly divided into two equal groups (n = 10 each). A grade III defect covering over 50% of the duodenum’s circumference was created in the second part of the duodenum of the rabbits. The anesthesia, duodenal injury, postoperative care, and animal sacrifice protocols were identical for all experimental rabbits. The effectiveness of JSP and ePTFE patch repair techniques was investigated based on clinical, macroscopic, and microscopic assessments at two and four weeks postoperatively. Results: Survival rates were comparable between groups (p > 0.05). Remarkable mucosal regeneration was evident in all experimental animals by two weeks, showing complete coverage of the jejunal serosal and ePTFE patches by re-epithelialized mucosa with functional villus formation. While partial development of the underlying muscular and serosal layers was observed in both groups at four weeks, the JSP group achieved a significantly higher median histological score (19 vs. 14; p = 0.003). Conversely, the ePTFE group exhibited a major safety concern: a highly significant increase (p ≤ 0.001) in Grade 4 dense, inseparable adhesions throughout the abdominal cavity, which were entirely absent in the JSP group. Conclusions: Both JSP and ePTFE are viable for duodenal reconstruction, but the autologous JSP is superior in tissue healing and safety. Severe adhesions associated with ePTFE constitute a significant clinical concern, limiting its use to a second-line alternative. Consequently, JSP is the preferred option, while ePTFE requires further long-term safety validation. Full article

Background/Objectives: Dental implant placement protocols including immediate (IIP) and delayed implant placement (DIP) are likely to affect bone tissue repair and regeneration after the surgery. Despite many benefits of IIP, it has remained unclear whether IIP demonstrates comparable healing processes and outcomes to those observed in DIP. This review aims to summarize and compare biological and clinical outcomes of IIP and DIP, focusing on success and survival rates, periodontal status, esthetics and radiographic outcomes, and biochemical markers. Methods: A literature search of electronic databases was conducted using PubMed/MEDLINE, Embase, and the Scopus databases (January 1983–February 2025). 109 articles published in English, consisting of in vitro, in vivo, and clinical studies met the inclusion criteria. Results: This review shows that both IIP and DIP show similar implant survival rates, but IIP may lead to a higher risk of mid-facial recession in esthetic areas. DIP, on the other hand, can result in better soft tissue and bone healing. Histological and radiographic evidence shows comparable bone to implant contact (BIC) between the two methods, although peri-implant bone loss tends to be higher with IIP. Lastly, although specific molecular markers are well-established in all phases of osseointegration following DIP, there is no available literature comparing differences in biomarkers during healing periods between IIP and DIP. Conclusions: This review highlights the similarities and differences in the outcomes of IIP and DIP, as well as the knowledge gaps that require further investigation, providing valuable insights for predicting treatment outcomes and managing complications associated with dental implant placement. Full article

Background/Objectives: This 7-day rat tracheocutaneous fistula study considered the not-studied issues of tracheocutaneous fistula course, wound healing, and fistula in the NO-system relations. Therefore, we focused on fistulas’ severe course, tracheocutaneous fistula → air leak → compensatory diaphragmatic/abdominal “heaving”, NO-system failed relations, and therapy resolution. Stable gastric pentadecapeptide BPC 157 was proposed. Methods: Tracheocutaneous fistula rats received daily medication (/kg), alone or combined, BPC 157 therapy (10 µg, 10 ng, in drinking water or intraperitoneally) along with a triple NO-agent approach (L-NAME 5 mg, L-arginine 100 mg, and L-NAME+L-arginine, intraperitoneally). Results: Tracheocutaneous fistulas occurred as specific and NO-system-related as follows: NO system: blockade (L-NAME-aggravation) over-activity (L-arginine-amelioration) or immobilization (L-NAME+L-arginine oppose each other’s effects). Controls presented severe clinical signs of respiratory distress, failed healing, skin and tracheal defects, a not-healed and open, macro/microscopically, and fistulous tract that was well-formed and wide, tracheal shrinking below the fistula, and clinically, open-mouth breathing, “heaving abdomen”, cyanosis (bluish snout, ears, extremities), abundant secretion through the fistula, and weight loss. Fistula tissue NO level decreased, and the malondialdehyde (MDA) level increased. The BPC 157 therapy (both application routes) resulted in rapid recovery. Healing of defects (skin and trachea) and fistula closure, macro/microscopically, corresponded with clinical findings, avoiding observable clinical signs of dyspnea, reducing weight loss, and avoiding any sign of “heaving abdomen”. BPC 157-treated rats displayed regular breathing movements without observable signs of respiratory distress. Finally, when combined, BPC 157 therapy upgrades L-arginine amelioration, abolishes L-NAME-induced worsening, and restores full healing after NO immobilization (L-NAME+L-arginine). BPC 157 counteracted increase in NO level and counteracted increase in MDA level. Conclusions: Thus, first, acting systemically, BPC 157 reverses tracheocutaneous fistula course in rats. It acts through the NO system. Full article