Search Results (314)

Background/Objectives: Different risk factors are involved in the initiation and progression of melanoma. In particular, genetic and epigenetic pathways are involved in all stages of melanoma and are exploited in therapeutic approaches. This study investigated the role of circular RNA circ_0001591 in melanoma cell migration. Methods: Three different melanoma cell lines were transfected with siRNA targeting circ_0001591 and with mimic or inhibitor molecules for miR-20a-3p and miR-34a-5p. Gene and protein expression levels were analyzed by RT-qPCR and Western blot, respectively. Dual luciferase reporter assays were performed to confirm the direct interaction of miR-20a-3p and miR-34a-5p with circ_0001591, as well as with the 3’UTRs of AXL (for both miRNAs) and FOSL1 (miR-34a-5p only). Wound healing assays were conducted to assess cell migration velocity. Results: The silencing of circ_0001591 significantly reduces the migration ability of melanoma cell lines. This downregulation was associated with an increased expression of miR-20a-3p and miR-34a-5p. Dual luciferase reporter assays confirmed the direct binding of both miRNAs to circ_0001591, supporting its role as a molecular sponge. The same assays also verified that miR-20a-3p directly targets the 3’UTR of AXL, while miR-34a-5p binds the 3’UTRs of both AXL and FOSL1. Western blot analysis showed that the modulation of this axis affects the expression levels of the AXL and FRA1 oncoproteins. Conclusions: Our findings demonstrate that circ_0001591 promotes melanoma migration by sponging miR-20a-3p and miR-34a-5p, thereby indirectly modulating the expression of AXL and FRA1 oncoprotein. Further investigations of this new regulatory network are needed to better understand its role in melanoma progression and to support the development of targeted therapies. Full article

Background/Objectives: During the repair of a wounded epithelium, keratinocytes become invasive via the epithelial-to-mesenchymal transition (EMT) process. Usually temporary and controlled, EMT persists in a chronically inflamed epithelium and is exacerbated in epithelial dysplasia and dysregulated in invasive carcinomas. Here we investigated the effects that IL-1 beta, IL-6, and IL-8, inflammatory cytokines expressed in specimens from OPMDs and OSCCs, have on NOKs and OSCC cells. Methods: AKT activation and EMT induction were assessed along with cellular invasiveness. Results: IL-1 beta, IL-6, and IL-8 induced EMT in NOKs, ex novo conferring them invasive capacity. The same cytokines exacerbated the constitutive EMT and invasiveness of OSCC cells. Since these phenomena were accompanied by AKT activation, we tested whether they could be influenced by RTV, a long-used anti-HIV drug that was previously found to block the activation of human AKT and exert antitumor effects. We observed that therapeutic amounts of RTV counteract all the above-mentioned tumorigenic activities of ILs. Finally, consistent with the key role that AKT and EMT play in OSCC radio-resistance, RTV increased OSCC cells’ sensitivity to therapeutic doses of ionizing radiation. Conclusions: These preliminary in vitro findings encourage the use of RTV to prevent the malignant evolution of OPMDs, reduce the risk of OSCC metastasis, and improve the outcomes of anti-OSCC radiotherapy. Full article

Objectives: This study sought to assess the impact of diabetes and hypertension on wound healing and recovery in orthopedic patients, with an emphasis on laboratory correlations. Materials and Methods: This study included 67 orthopedic patients, divided into a geriatric group (n = 49, ≥65 years) and a control group (n = 18). Clinical and laboratory assessments were performed at admission and discharge. Data were analyzed statistically. Results: Geriatric patients showed a higher triglyceride glucose-body mass index (TyG-BMI), glucose, cholesterol, C-reactive protein (CRP), interleukin-6 (IL-6), and leukocytes and lower hemoglobin and platelets (PLTs), with poorer healing and well-being. Elevated CRP, IL-6, and urea and decreased protein and hemoglobin persisted in this group. Diabetes improved outcomes in older adults, while hypertension worsened them in younger patients. Favorable outcomes correlated with higher triglycerides, fibrinogen, hemoglobin, and red blood cells (RBCs), while they did not correlate with elevated CRP, IL-6, leptin, urea, creatinine, and white blood cells (WBCs). Conclusions: Key predictors of healing and well-being included CRP, hemoglobin, RBC, and hematocrit in older patients and hypertension, CRP, hemoglobin, and leptin in younger individuals. Age-specific metabolic and inflammatory profiles influence recovery trajectories and may be used to predict problems in both recovery and patients’ well-being. Further research is required to better understand the correlations between these factors. Full article

Background/Objectives: Alectinib, a second-generation tyrosine kinase inhibitor indicated for the treatment of non-small-cell lung cancer (NSCLC), exhibits suboptimal oral bioavailability, primarily attributable to its inherently low aqueous solubility and limited dissolution kinetics. This study aimed to enhance Alectinib’s solubility and therapeutic efficacy by formulating a G4-NH2-PAMAM dendrimer complex. Methods: The complex was prepared using the organic solvent evaporation method and characterized by DSC, FTIR, dynamic light scattering (DLS), and zeta potential measurements. A validated high-performance liquid chromatography (HPLC) method quantified the Alectinib. In vitro drug release studies compared free Alectinib with the G4-NH2-PAMAM dendrimer complex. Cytotoxicity against NSCLC cell line A549 was assessed using MTT assays, clonogenic assay, and scratch-wound assay. Xenograft effect was investigated in the H460 lung cell line. Pharmacokinetic parameters were evaluated in rats using LC–MS/MS. Results: Alectinib exhibited an encapsulation efficiency of 59 ± 5%. In vitro release studies demonstrated sustained drug release at pH 6.8 and faster degradation at pH 2.5. Anticancer activity in vitro showed comparable efficacy to free Alectinib, with 98% migration inhibition. In vivo tumor suppression studies revealed near-complete tumor regression (~100%) after 17 days of treatment, compared to 75% with free Alectinib. Pharmacokinetic analysis indicated enhanced absorption (shorter Tmax), prolonged systemic circulation (longer half-life), and higher bioavailability (increased AUC) for the dendrimer-complexed drug. Conclusions: These findings suggest that the G4-NH2-PAMAM dendrimer system significantly improves Alectinib’s pharmacokinetics and therapeutic potential, making it a promising approach for NSCLC treatment. Full article

Background: Wound healing and scar management remain significant challenges in dermatology and aesthetic medicine. Recent advances in regenerative medicine have introduced plant-derived exosome-like nanoparticles (PDENs) as potential therapeutic agents due to their bioactive properties. This study examines the clinical application of rose stem cell exosomes (RSCEs) in combination with established treatments for managing different types of scars. Methods: A case series of four patients with different scar etiologies (dog bite, hot oil burn, forehead trauma, and facial laser treatment complications) was treated with RSCEs in combination with microneedling (Dermapen 4.0, 0.2–0.4 mm depth) and/or thulium laser therapy (Lutronic Ultra MD, 8–14 J), or as a standalone topical treatment. All cases underwent sequential treatments over periods ranging from two to four months, with comprehensive photographic documentation of the progression. The efficacy was assessed through clinical photography and objective evaluation using the modified Vancouver Scar Scale (mVSS) and the Patient and Observer Scar Assessment Scale (POSAS), along with assessment of scar appearance, texture, and coloration. Results: All cases demonstrated progressive improvement throughout the treatment course. The dog bite scar showed significant objective improvement, with a 71% reduction in modified Vancouver Scar Scale score (from 7/13 to 2/13) and a 61% improvement in Patient and Observer Scar Assessment Scale scores after four combined treatments. The forehead trauma case exhibited similar outcomes, with a 71% improvement in mVSS score and 55–57% improvement in POSAS scores. The hot oil burn case displayed the most dramatic improvement, with a 78% reduction in mVSS score and over 70% improvement in POSAS scores, resulting in near-complete resolution without visible scarring. The facial laser complication case showed a 75% reduction in mVSS score and ~70% improvement in POSAS scores using only topical exosome application without device-based treatments. Clinical improvements across all cases included reduction in elevation, improved texture, decreased erythema, and better integration with surrounding skin. No adverse effects were reported in any of the cases. Conclusions: This preliminary case series suggests that plant-derived exosome-like nanoparticles, specifically rose stem cell exosomes (RSCEs), may enhance scar treatment outcomes when combined with microneedling and laser therapy, or even as a standalone topical treatment. The documented objective improvements, measured by standardized scar assessment scales, along with clinical enhancements in scar appearance, texture, and coloration across different scar etiologies—dog bite, burn, traumatic injury, and iatrogenic laser damage—suggest that this approach may offer a valuable addition to the current armamentarium of scar management strategies. Notably, the successful treatment of laser-induced complications using only topical exosome application demonstrates the versatility and potential of this therapeutic modality. Full article

Background and Objectives: Postoperative pancreatic fistula and post-hepatectomy liver failure remain significant complications after HPB surgery; however, superficial surgical site infection (SSI) is the most frequent wound-related complication. Closed-incision negative-pressure wound therapy (ciNPWT) has been proposed to reduce superficial contamination, yet no liver-focused quantitative synthesis exists. We aimed to evaluate the effectiveness and safety of prophylactic ciNPWT after hepatopancreatobiliary (HPB) surgery. Methods: MEDLINE, Embase, and PubMed were searched from inception to 30 April 2025. Randomized and comparative observational studies that compared ciNPWT with conventional dressings after elective liver transplantation, hepatectomy, pancreatoduodenectomy, and liver resections were eligible. Two reviewers independently screened, extracted data, and assessed risk of bias (RoB-2/ROBINS-I). A random-effects Mantel–Haenszel model generated pooled risk ratios (RRs) for superficial SSI; secondary outcomes were reported descriptively. Results: Twelve studies (seven RCTs, five cohorts) encompassing 15,212 patients (3561 ciNPWT; 11,651 control) met the inclusion criteria. Device application lasted three to seven days in all trials. The pooled analysis demonstrated a 29% relative reduction in superficial SSI with ciNPWT (RR 0.71, 95% CI 0.63–0.79; p < 0.001) with negligible heterogeneity (I² 0%). Absolute risk reduction ranged from 0% to 13%, correlating positively with the baseline control-group SSI rate. Deep/organ-space SSI (RR 0.93, 95% CI 0.79–1.09) and 90-day mortality (RR 0.94, 95% CI 0.69–1.28) were unaffected. Seven studies documented a 1- to 3-day shorter median length of stay; only two reached statistical significance. Device-related adverse events were rare (one seroma, no skin necrosis). Conclusions: Prophylactic ciNPWT safely reduces superficial SSI after high-risk HPB surgery, with the greatest absolute benefit when baseline SSI risk exceeds ≈10%. Its influence on deep infection and mortality is negligible. Full article

Background/Objectives: Oral cavity wound recovery presents unique challenges due to constant moisture exposure and functional mechanical stresses. Nanoscale extracellular vesicles (exosomes) with regenerative properties offer promising therapeutic potential for tissue regeneration, contributing to improved health outcomes. This study evaluated human exosomal preparations in promoting oral mucosal regeneration. Methods: We established standardized full-thickness wounds in the buccal mucosa of SD rats and divided subjects into experimental (receiving 50 billion human exosomes) and control (receiving carrier solution only) groups. Comprehensive wound assessment occurred at predetermined intervals (days 0, 3, 7, and 10) through photographic documentation, histological examination, and quantitative measurement. Results: Exosomal-treated tissues demonstrated statistically significant acceleration in closure rates (p < 0.05), achieving 87.3% reduction by day 10 versus 64.1% in the controls. Microscopic analysis revealed superior epithelial development, reduced inflammatory infiltration, and enhanced collagen architectural organization in exosomal-treated specimens. Semi-quantitative evaluation confirmed consistently superior healing metrics in the experimental group across all assessment timepoints. Conclusions: These findings demonstrate that human exosome preparations significantly enhance oral mucosal regeneration in SD rats, suggesting potential clinical applications for accelerating recovery following oral surgical procedures. Full article

Background and Objectives: Cyanoacrylate (CA) tissue adhesives have gained increasing attention as alternatives to sutures in oral surgery and periodontology. The objective of this scoping review is to assess their clinical applications and effectiveness in wound closure and postoperative management. Materials and Methods: The review was conducted following the JBI methodology and PRISMA-ScR guidelines. A comprehensive search was performed in PubMed, Scopus, and Web of Science to identify randomized controlled trials published between 2015 and 2025 evaluating the use of CAs in oral surgery and periodontal procedures. Results: A total of 19 studies were included. Cyanoacrylate adhesives demonstrated comparable or superior outcomes to other wound healing strategies in terms of operative time, postoperative pain reduction, and early wound healing. Their use was particularly beneficial in free gingival grafts and palatal donor site management. However, the findings across studies were not always consistent, and some trials did not report statistically significant differences. The use of long-chain CA formulations is associated with minimal toxicological risk, though these adhesives demonstrate intrinsic hemostatic and antimicrobial effects. Conclusions: Cyanoacrylate tissue adhesives represent a valid alternative to sutures in several dental surgical contexts, especially in procedures involving mucogingival grafts. Further high-quality clinical studies are needed to clarify their long-term outcomes and broaden their indications in dentistry. Full article

Objective: Lower third impacted molar extraction, despite being a routinary procedure for oral and maxillo-facial surgeons, may often result in a significantly negative impact in patient’s post-operatory quality of life. Among others, treatments based on oxygen-enriched oils have been shown to provide valuable therapeutic benefits in promoting wound healing, and therefore improving the immediate post-operatory symptomatology. The aim of this triple-blinded randomized controlled study is to supplement the existing evidence in the scientific literature by assessing the effectiveness of NovoX^®-Drop (Moss S.p.A., Lesa, Novara), a specific type of oxygen enriched oil-based device in reducing pain and inflammatory stimulus of post-surgical wounds following the extraction of lower third impacted molars. Materials and methods: Seventy-one patients undergoing surgical extraction of a single lower third impacted molar were randomly assigned to receive either NovoX^®-Drop (Group A) or a glycerin-based gel (Group B). Additionally, both patient groups followed the same standard therapy with amoxicillin-clavulanic acid and ibuprofen. Data were collected preoperative (T0) and after three (T3) and seven (T7) days postoperative in order to assess the following outcomes: mean visual analogue scale (VAS) score during the seven days protocol treatment, total duration of nonsteroidal anti-inflammatory drug (NSAID) usage, trismus (maximum mouth opening) and facial oedema. Results: Group A (treatment group) reported significatively lower pain levels at T7 compared to group B (average VAS value during the week: Group A: 3.57 ± 0.39 cm; Group B: 4.47 ± 0.40 cm; p-value = 0.0014) despite a significatively shorter period of NSAID usage (average NSAID usage duration: Group A: 2.43 ± 0.38 days; Group B: 3.38 ± 0.44 days; p-value = 0.00001). Therefore, trismus seems to be better controlled in group A, although the difference between the groups did not reach the threshold for statistical significance. Conclusions: The results of this study suggest that application of NovoX^®-Drop is capable of significantly reducing the post-operatory pain as well as NSAID usage, representing a promising and effective option for third impacted molar extraction surgery management. Full article

Background: Scar formation and impaired wound healing represent significant challenges in dermatology and aesthetic medicine, with limited effective treatment options currently available. Objectives: To evaluate the efficacy and long-term outcomes of Damask rose stem-cell-derived exosome (RSCE) therapy in the management of diverse dermatological conditions, including traumatic wounds, surgical scars, and atrophic acne scars. Methods: We conducted a case series study from June 2023 to November 2024, documenting four cases with different types of skin damage treated with lyophilized RSCE products. Treatment protocols included a variety of delivery methods such as topical application, microneedling, and post-procedure care. Follow-up assessments were performed at intervals ranging from 7 days to 10 months. Results: All patients demonstrated significant improvements in scar appearance, skin elasticity, hydration, and overall tissue quality. In traumatic facial injury, RSCE therapy facilitated reduction in scar contracture and improved functional outcomes. For atrophic acne scars, comparative treatment of facial sides showed enhanced results with RSCE addition. Acute wounds exhibited accelerated healing with reduced inflammation, while chronic wounds demonstrated improved epithelialization and long-term scar quality. Conclusions: This case series provides preliminary evidence suggesting that RSCE therapy may offer significant benefits in wound healing and scar management. The observed improvements in tissue regeneration, inflammatory modulation, and long-term aesthetic outcomes warrant further investigation through controlled clinical trials. Full article

Background: Diabetic foot disease is a public health problem. The challenges of its management lie in the complexity of wound healing and, in particular, the high rate of lesion recurrence. Objectives: The primary objective of the study was to evaluate whether optimized post-healing follow-up by a multidisciplinary team can reduce the recurrence rate of foot ulcers in people living with diabetes. The secondary objectives were to assess patient needs in terms of hospitalization for recurrence, the number of amputations, pedicure care, and the use of adapted footwear. Participants: The study included 129 patients with diabetes presenting a healed foot ulcer. A total of 38 patients underwent an annual post-healing follow-up visit with a multidisciplinary team (optimized follow-up), while 91 had a visit every 2 years (minimum follow-up). Results: Of the 38 patients with optimal follow-up, 8 presented a wound recurrence (21.1%) compared with 38 out of 91 patients (41.8%) receiving minimum follow-up. The recurrence rate decreased significantly between the two groups (p < 0.05). The use of adapted shoes was also significantly better in the group with optimized follow-up (p = 0.02). Conclusions: Regular post-healing follow-up with a multidisciplinary team seems to be a contributing factor to reducing the recurrence of diabetic foot ulcers among people living with diabetes. Full article

Background/Objectives: Ketorolac is commonly used for pain management after orthopedic surgery, but concerns regarding its effects on postoperative complications remain. This study evaluates the impact of ketorolac use on short- and long-term outcomes in adult patients undergoing uncemented primary total hip arthroplasty (THA), where implant stability relies on biological fixation through bone ingrowth into a porous-coated prosthesis rather than bone cement. Methods: A retrospective cohort study was conducted using the TriNetX Research Network. Patients aged 18 years or older who underwent uncemented primary THA between 1 January 2004 and 1 January 2024 were included. Two cohorts were compared: those who received ketorolac on the day of or within one week of surgery and those who did not. Cohorts were propensity score-matched. Outcomes were assessed at 30 days, 1 year, and 5 years postoperatively. Results: At 30 days, ketorolac use was associated with significantly lower risks of transfusion (RR: 0.6, p < 0.01). However, it was linked to higher rates of acute posthemorrhagic anemia (RR: 1.2, p < 0.01) and periprosthetic fracture (RR: 1.4, p < 0.01). At 1 year, ketorolac use was associated with reduced risks of death (RR: 0.8, p < 0.01) and transfusion (RR: 0.7, p < 0.01), but increased risks of acute posthemorrhagic anemia (RR: 1.2, p < 0.01), deep surgical site infection (SSI) (RR: 1.8, p = 0.01), superficial SSI (RR: 1.9, p < 0.01), periprosthetic joint infection (RR: 1.1, p < 0.01), wound dehiscence (RR: 1.2, p < 0.01), periprosthetic mechanical complication (RR: 1.2, p < 0.01), and periprosthetic fracture (RR: 1.5, p < 0.01). Conclusions: Our findings highlight the complex risk profile of ketorolac in uncemented THA patients and suggest that clinicians should carefully consider individual patient factors and engage in shared decision-making when counseling patients on the use of ketorolac in the perioperative setting. Full article

Background/Objective: Laser therapy has gained attention in dental practice to minimize bleeding and enhance blood clot formation. This study aimed to explore the utilization and to compare the clinical efficacy of laser-mediated hemostasis for older patients receiving routine dental treatment. Methods: A prospective observational study was conducted across research networks between October 2023 and August 2024, involving 60 patients aged 50 years and older (average = 63.35 years) at risk of postoperative bleeding following dental treatments. Additionally, laser therapy for hemostasis was selected and provided among calibrated operators. A single researcher performed data collection. Before statistical analysis, data verification and clinical assessment were conducted by the operators and researcher. A clinical cut-off for hemostasis was set at 5 min. Two diode laser machines were used namely, an 810 nm and dual wavelengths of 635 nm and 980 nm. Results: There were 94 extraction sockets, 28 procedures of scaling and root planing and 18 procedures of minor oral surgery. Combining laser ablating sulcular fiber and photobiomodulation initiating blood clot formation was a preferable hemostatic technique for extraction socket, while photobiomodulation alone was a preferred technique for soft tissue hemostasis (p < 0.001). All operators confirmed that 97.86 percent of bleeding events achieved more rapid hemostasis. 61.43 percent of bleeding events clinically achieved hemostasis within 5 min by using laser-mediated hemostasis alone (p = 0.092). Full recovery of the extraction socket was significantly observed during the 2- to 4-week follow-up period (p = 0.005). No clinical complications were reported. Conclusions: Laser-mediated hemostasis effectively reduced hemostatic duration, prevented postoperative bleeding and promoted wound healing in older patients undergoing routine dental treatment. Full article

Background: Episiotomy-related morbidity remains a substantial challenge in postpartum recovery, often affecting maternal quality of life. Given the crucial role of local microbiota and wound environment in perineal healing, intravaginal lactic acid gel emerges as a promising adjunctive therapy. Objective: To evaluate the effectiveness and safety of intravaginal lactic acid gel (Canesbalance^®, Bayer) in enhancing scar healing and reducing pain following mediolateral episiotomy. Methods: In this single-center randomized controlled trial, 100 postpartum women with mediolateral episiotomy were allocated to either a treatment group receiving intravaginal lactic acid gel (Canesbalance^®, Bayer) or a standard care group. Scar healing was assessed at 7 and 40 days postpartum using POSAS, VAS, and NRS scores; hematological parameters were also monitored. Results: The lactic acid gel group demonstrated significantly greater reductions in scar severity and pain scores over time (p < 0.05), with no adverse hematological effects. Effect sizes (Cohen’s d) were moderate to high for scar healing (d = 0.76) and pain reduction (VAS: d = 0.83; NRS: d = 0.79), indicating clinical relevance beyond statistical significance. Conclusions: Intravaginal application of lactic acid gel may offer a safe and effective strategy to enhance perineal wound healing and pain relief after episiotomy. Further large-scale studies are warranted to validate these promising findings and explore underlying mechanisms. Full article

Background/Objectives: Rho-associated coiled-coil-containing protein kinase inhibitors (ROCKis) have now become known as modulators of corneal endothelial wound repair and cell survival. However, evidence remains fragmented across laboratory and clinical reports. We performed a systematic review to synthesize preclinical and clinical data on ROCKis in corneal disease, assess their efficacy and safety, and identify research gaps. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar (until May 2025) for English-language original studies evaluating ROCKis in corneal models or patients. Inclusion criteria encompassed in vitro, ex vivo, in vivo, and clinical trials reporting functional outcomes (endothelial cell density, wound closure, visual acuity). Results: Thirty-one studies met criteria: 14 preclinical studies and 17 clinical studies. Preclinical models (rabbit, porcine, human explants) uniformly showed ROCKis (Y-27632, Ripasudil, Netarsudil, H-1152) accelerate corneal endothelial cell proliferation, migration, and restoration of a hexagonal monolayer with improved barrier and pump function over days to weeks. In 17 clinical investigations, topical Ripasudil or Netarsudil and cultured cell injections achieved significant corneal thinning, endothelial cell density and central corneal thickness changes, and visual acuity improvements (≥2 lines) with minimal adverse events. Overall bias was moderate in non-randomized studies and low in the RCTs. Conclusions: ROCKis demonstrate consistent pro-regenerative effects on corneal endothelium in multiple models and show promising clinical efficacy in Fuchs endothelial dystrophy and pseudophakic endothelial failure. Future work should explore novel delivery systems and larger controlled trials to optimize dosing, safety, and long-term outcomes. Full article