Search Results (9,815)

Pancreatic ductal adenocarcinoma (PDAC) has earned a notorious reputation as one of the most formidable and deadliest malignant tumors. Within the tumor microenvironment, cancer cells have acquired the capability to maintain incessant expansion and increased proliferation in response to hypoxia via metabolic reconfiguration, leading to elevated levels of lactate within the tumor surroundings. However, there have been limited studies specifically investigating the association between hypoxia and lactic acid metabolism-related lactylation in PDAC. In this study, multiple machine learning approaches, including LASSO regression analysis, XGBoost, and Random Forest, were employed to identify hub genes and construct a prognostic risk signature. The implementation of the CERES score and single-cell analysis was used to discern a prospective therapeutic target for the management of PDAC. CCK8 assay, colony formation assays, transwell, and wound-healing assays were used to explore both the proliferation and migration of PDAC cells affected by CENPA. In conclusion, we discovered two distinct subtypes characterized by their unique hypoxia and lactylation profiles and developed a risk score to evaluate prognosis, as well as response to immunotherapy and chemotherapy, in PDAC patients. Furthermore, we indicated that CENPA may serve as a promising therapeutic target for PDAC. Full article

The cornea is a vital component of the visual system, and its integrity is crucial for optimal vision. Damage to the cornea resulting from trauma, infection, or disease can lead to blindness. Corneal regeneration using mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) offers a promising alternative to corneal transplantation. MSCs are multipotent stromal cells that can differentiate into various cell types, including corneal cells. They can also secrete a variety of anti-inflammatory cytokines and several growth factors, promoting wound healing and tissue reconstruction. This review summarizes the current understanding of the molecular and cellular mechanisms by which MSCs and MSC-EVs contribute to corneal regeneration. It discusses the potential of MSCs and MSC-EV for treating various corneal diseases, including corneal epithelial defects, dry eye disease, and keratoconus. The review also highlights finalized human clinical trials investigating the safety and efficacy of MSC-based therapy in corneal regeneration. The therapeutic potential of MSCs and MSC-EVs for corneal regeneration is promising; however, further research is needed to optimize their clinical application. Full article

Plants are able to perceive diverse environmental factors and form an appropriate systemic functional response. Systemic responses are induced by stimulus-specific long-distance signals that carry information about the stimulus. Variation potential is proposed as a candidate for the role of such a signal. Here, we focus on the mechanisms that determine the specificity of the variation potential under the action of different local stimuli. Local stimuli such as heating, burning and wounding cause variation potential, the parameters of which differ depending on the type of stimulus. It was found that the stimulus-specific features of the hydraulic signal monitored by changes in leaf thickness and variation potential, such as a greater amplitude upon heating and burning and a significant amplitude decrement upon burning and wounding, were similar. The main features of these signals are the greater amplitude upon heating and burning, and a significant amplitude decrement upon burning and wounding. Together with the temporal correspondence of signal propagation, this evidence indicates a role for the hydraulic signal in the induction of stimulus-specific variation potential. Experiments using mechanosensitive channel inhibitors have demonstrated that the hydraulic signal contributes more to the induction of the variation potential in the case of rapidly growing stimuli, such as burning and wounding, than in the case of gradual heating. For thermal stimuli (gradual heating and burning), a greater contribution, compared to wounding, of the chemical signal related to reactive oxygen species to the induction of the variation potential was demonstrated. Thus, the specificity of the parameters of the variation potential is determined by the different contributions of hydraulic and chemical signals. Full article

This study explores the recent advances of and functional insights into hydrogel composites, materials that have gained significant attention for their versatile applications across various fields, including contemporary dentistry. Hydrogels, known for their high water content and biocompatibility, are inherently soft but often limited by mechanical fragility. Key areas of focus include the customization of hydrogel composites for biomedical applications, such as drug delivery systems, wound dressings, and tissue engineering scaffolds, where improved mechanical properties and bioactivity are critical. In dentistry, hydrogels are utilized for drug delivery systems targeting oral diseases, dental adhesives, and periodontal therapies due to their ability to adhere to the mucosa, provide localized treatment, and support tissue regeneration. Their unique properties, such as mucoadhesion, controlled drug release, and stimuli responsiveness, make them ideal candidates for treating oral conditions. This review highlights both experimental breakthroughs and theoretical insights into the structure–property relationships within hydrogel composites, aiming to guide future developments in the design and application of these multifunctional materials in dentistry. Ultimately, hydrogel composites represent a promising frontier for advancing materials science with far-reaching implications in healthcare, environmental technology, and beyond. Full article

Background: Diabetes ranks high among worldwide global health problems, and diabetic foot ulcer syndrome (DFU) is considered as one of its most serious complications. The purpose of this study was to evaluate the impact of local ozone therapy procedures on the wound healing process in patients with two DFU types: neuropathic and ischemic. Material and Methods: In the retrospective study reported here, the treatment outcomes of 90 patients were analyzed: 44 males (48.8%) and 46 females (51.2%), in the age range between 38 and 87 years of age, with neuropathic (group 1) and ischemic (group 2) diabetic foot ulcers treated by means of local ozone therapy. The assessment of therapeutic effects in both groups of patients included an analysis of the rate of ulcer healing using planimetry and an analysis of the intensity of pain associated with ulcers performed using the VAS scale. Results: After the application of ozone therapy procedures, a statistically significant decrease in the surface area of the ulcers was obtained in both groups of patients, respectively: in group 1 from 7 (6–7.5) cm² to 3 (2–3.5) cm² and in group 2 from 7.5 (6.5–8) cm² to 5 (4.5–5.5) cm² (p < 0.001), with a complete healing of ulcers not observed in any patients from groups 1 and 2. After treatment, the surface area of the assessed ulcers was smaller in the neuropathic group. The intensity of pain experienced after treatment also decreased with statistical significance in both groups (p < 0.001). Conclusions: Short-term local ozone therapy was effective in promoting wound healing and alleviating pain in patients with DFUs of both neuropathic and ischemic etiology. The effectiveness of therapy in the neuropathic type of DFUs was significantly higher than in the ischemic type, in which patients had a higher incidence of risk factors and more advanced lesions, characterized by a larger initial ulcer area and greater intensity of pain. Full article

Electrospun membranes (EMs) have a wide range of applications, including use as local delivery systems. In this study, we manufactured a polyurethane Tecoflex™ EM loaded with bismuth-based lipophilic nanoparticles (Tecoflex™ EMs-BisBAL NPs). The physicochemical and mechanical characteristics, along with the antitumor and bactericidal effects, were evaluated using a breast cancer cell line and methicillin-susceptible and resistant Staphylococcus aureus (MRSA). Drug-free Tecoflex™ EMs and Tecoflex™ EMs-BisBAL NPs had similar fiber diameters of 4.65 ± 1.42 µm and 3.95 ± 1.32 µm, respectively. Drug-free Tecoflex™ EMs did not negatively impact a human fibroblast culture, indicating that the vehicle is biocompatible. Tecoflex™ EMs-BisBAL NPs increased 94% more in size than drug-free Tecoflex™ EMs, indicating that the BisBAL NPs enhanced hydration capacity. Tecoflex™ EMs-BisBAL NPs were highly bactericidal against both methicillin-susceptible S. aureus and MRSA clinical isolates, inhibiting their growth by 93.11% and 61.70%, respectively. Additionally, Tecoflex™ EMs-BisBAL NPs decreased the viability of MCF-7 tumor cells by 86% after 24 h exposure and 70.1% within 15 min. Regarding the mechanism of action of Tecoflex™ EMs-BisBAL NPs, it appears to disrupt the tumor cell membrane. In conclusion, Tecoflex™ EMs-BisBAL NPs constitute an innovative low-cost drug delivery system for human breast cancer and postoperative wound infections. Full article

Mineralization is a key biological process that is required for the development and repair of tissues such as teeth, bone and cartilage. Exosomes (Exo) are a subset of extracellular vesicles (~50–150 nm) that are secreted by cells and contain genetic material, proteins, lipids, nucleic acids, and other biological substances that have been extensively researched for bone and oral tissue regeneration. However, Exo-free biomaterials or exosome treatments exhibit poor bioavailability and lack controlled release mechanisms at the target site during tissue regeneration. By encapsulating the Exos into biomaterials like hydrogels, these disadvantages can be mitigated. Several tissue engineering approaches, such as those for wound healing processes in diabetes mellitus, treatment of osteoarthritis (OA) and cartilage degeneration, repair of intervertebral disc degeneration, and cardiovascular diseases, etc., have been exploited to deliver exosomes containing a variety of therapeutic and diagnostic cargos to target tissues. Despite the significant efficacy of Exo-laden hydrogels, their use in mineralized tissues, such as oral and bone tissue, is very sparse. This review aims to explore and summarize the literature related to the therapeutic potential of hydrogel-encapsulated exosomes for bone and oral tissue engineering and provides insight and practical procedures for the development of future clinical techniques. Full article

Jujube (Ziziphus jujuba Mill.), native to Southern Asia, stands out for its significant nutritional and therapeutic properties. Its adaptability and resilience have enabled its global cultivation, highlighting the necessity for comprehensive scientific research to fully harness its potential. Rich in bioactive compounds like flavonoids, polyphenols, vitamin C, polysaccharides, tannins, and saponins, jujube extracts exhibit notable antioxidant, anti-inflammatory, antimicrobial, and wound healing properties. These qualities have made jujube a popular ingredient in various skin and hair care formulations. The versatility of jujube extracts, along with their synergy with other herbal active ingredients, enables the development of targeted personal care solutions. These solutions address a range of concerns, including anti-aging, UV protection, brightening, moisturizing, and calming effects, as well as promoting hair health. Despite its potential, research on the cosmetic applications of Z. jujuba is still in its early stages, with only one clinical trial to date focusing on its skin-brightening effects. This review aims to consolidate the current and emerging research on the applications of jujube in conventional and medical cosmetics, highlighting its potential in enhancing skin and hair wellness. By providing a comprehensive overview, it seeks to pave the way for further studies and innovations in utilizing jujube for personal care. Full article

The study addresses the challenge of temperature sensitivity in pristine gelatin hydrogels, widely used in biomedical applications due to their biocompatibility, low cost, and cell adhesion properties. Traditional gelatin hydrogels dissolve at physiological temperatures, limiting their utility. Here, we introduce a novel method for creating stable hydrogels at 37 °C using pristine gelatin through photopolymerization without requiring chemical modifications. This approach enhances consistency and simplifies production and functionalization of the gelatin with bioactive molecules. The stabilization mechanism involves the partial retention of the triple-helix structure of gelatin below 25 °C, which provides specific crosslinking sites. Upon activation by visible light, ruthenium (Ru) acts as a photosensitizer that generates sulphate radicals from sodium persulphate (SPS), inducing covalent bonding between tyrosine residues and “locking” the triple-helix conformation. The primary focus of this work is the characterization of the mechanical properties, swelling ratio, and biocompatibility of the photopolymerized gelatin hydrogels. Notably, these hydrogels supported better cell viability and elongation in normal human dermal fibroblasts (NHDFs) compared to GelMA, and similar performance was observed for human pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). As a proof of concept for functionalization, gelatin was modified with selenous acid (GelSe), which demonstrated antioxidant and antimicrobial capacities, particularly against E. coli and S. aureus. These results suggest that pristine gelatin hydrogels, enhanced through this new photopolymerization method and functionalized with bioactive molecules, hold potential for advancing regenerative medicine and tissue engineering by providing robust, biocompatible scaffolds for cell culture and therapeutic applications. Full article

Objective: to investigate how body mass index (BMI) affects the outcome in patients treated surgically for infective endocarditis (IE). Methods: This is a single-center observational analysis of consecutive patients treated surgically for IE. We divided the cohort into six groups, according to the WHO classification of BMI, and performed subsequent outcome analysis. Results: The patient population consisted of 17 (2.6%) underweight, 249 (38.3%) normal weight, 252 (38.8%) overweight, 83 (12.8%) class I obese, 28 (4.3%) class II obese, and 21 (3.8%) class III, or morbidly obese, patients. The median age of the entire cohort was 64.5 [52.5–73.6] years. While only 168 (25.9%) patients were female, women significantly more often exhibited extremes in regards to BMI, including underweight (47.1%) and morbid obesity (52.4%), p = 0.026. Class II and III obese patients displayed more postoperative acute kidney injury (47.9%), p = 0.003, more sternal wound infection (12.9%), p < 0.001, worse 30-day survival (20.4%), p = 0.031, and worse long-term survival, p = 0.026, compared to the results for the other groups. However, the multivariable analysis did not identify obesity as an independent risk factor for 30-day mortality, with an odds ratio of 1.257 [0.613–2.579], p = 0.533. Rather, age > 60, reduced LVEF < 30%, staphylococcal infection, and prosthetic valve endocarditis correlated with mortality. While BMI showed poor discrimination in predicting 30-day mortality on the ROC curve (AUC = 0.609), it showed a fair degree of discrimination in predicting sternal wound infection (AUC = 0.723). Conclusions: Obesity was associated with increased comorbidities, complications, and higher postoperative mortality in IE patients, but it is not an independent mortality risk factor. While BMI is a poor predictor of death, it is a good predictor of sternal wound infections. Full article

Background and Objectives: Complex wounds in the hand and distal lower extremities pose challenges in reconstructive surgery, often involving critical structures like tendons. Tendon injuries, prevalent in such wounds, necessitate optimal repair methods for functional recovery. This study investigates the impact of vascularised and nonvascularised adipofascial tissue on tendon repair, focusing on early healing stages, mobilisation, and scintigraphic evaluation of flap vascularity. Materials and Methods: Wistar Albino rats were divided into groups undergoing primary tendon repair, vascularised adipofascial flap application, or nonvascularised flap application. Scintigraphic evaluation and histopathological assessment were performed to analyse healing processes. Results: Pedicle-free flaps support healing in tendon injuries without negatively affecting medium-term outcomes. Vascularised flaps exhibit faster healing. The scintigraphic analysis showed that the static measurements of the late phase were statistically significantly higher in the group with the non-vascularised adipofascial flap (p = 0.038). The mean perfusion reserve was higher in the vascularised pedicled adipofascial flap group than the non-vascularised adipofascial flap group. Scintigraphic analysis highlights the viability of pedicle-free flaps. Conclusions: Pedicle-free adipofascial flaps support the healing of the tendon without complicating the results, while vascularised flaps show accelerated healing. These findings provide valuable insights into optimising tendon repair strategies using adipofascial flaps, with implications for enhancing functional recovery in complex wounds. Full article

Background: This study aimed to analyse the variability in the incidence of the pharyngocutaneous fistula (PCF), the most common complication following a total laryngectomy (TLE), and to identify the underlying causes for fluctuations in incidence rates. Methods: In the retrospective study, the annual PCF incidence data and comprehensive clinicopathologic data from 540 patients who underwent TLE between January 2004 and December 2022 were reviewed. Distinct peri ods of both high and low PCF incidence were identified. Within these periods, patients were categorized into groups with PCF (study groups) and without it (control groups). These groups were statistically compared based on potential risk factors for PCF development. The high-incidence periods were specially analysed for recurring risk factors and the corresponding corrective measures were reviewed. Results: The analysis revealed four high-incidence periods with an overall PCF incidence of 37.61%, along with three low-incidence periods in between with an overall incidence of 19.38%. Surgical wound infection (SWI) and a history of head and neck cancer alongside their related treatments were repeatedly identified as independent risk factors during high-incidence periods, with SWI being the most consistent predictor of PCF development. Conclusions: Continuous monitoring of PCF incidence is crucial, as it allows for the identification of emerging risk factors and the immediate implementation of corrective measures to mitigate these newly identified risk factors. Full article

Urinary bladder wound healing shares many features with skin healing, involving several molecular players, including microRNAs (miRs). This study investigated the role of miR-132 in urothelial cells. We analyzed miR-132 expression in rat bladder using in situ hybridization and conducted gain and loss of miR-132 function assays in primary human urothelial cells (HUCs). These assays included cell proliferation and migration studies. To explore the regulation of miR-132 expression, cells were treated with wound-healing-related factors such as interleukin 6 (IL-6), interleukin 10 (IL-10), and transforming growth factor beta-1 (TGF-β1). Predictive bioinformatics and a literature review identified potential miR-132 targets, which were validated through real-time polymerase chain reaction (RT-PCR) and Western blot analysis. miR-132 was found to promote cellular proliferation and migration during the early stages of urothelial wound repair. Its expression was modulated by key cytokines such as IL-6, IL-10, and TGF-β1. miR-132 played a crucial role in urothelial wound healing by enhancing cell proliferation and migration, regulated by cytokines, suggesting its action within a complex regulatory network. These findings highlight the therapeutic potential of targeting miR-132 in bladder injury repair, offering new insights into bladder repair mechanisms. Full article

Background/Objectives: Wound healing relies on a coordinated process with the participation of different mediators. Natural products are a source of active compounds with healing potential. Isoorientin is a natural flavone recognized as having several pharmacological properties, such as anti-inflammatory effects, making it a potential treatment for wounds. We investigated the effect of isoorientin on the healing of excisional skin wounds. Methods: Male Swiss mice were subjected to the induction of excisional skin wounds (6 mm diameter) and treated with a vehicle (2% dimethyl sulfoxide in propylene glycol) or 2.5% isoorientin applied topically once a day for 14 days. The wound area was measured on days 0, 3, 7, and 14. Histopathological analyses were performed on the cicatricial tissue after 14 days. The myeloperoxidase activity and the interleukin-1β, tumoral necrosis factor (TNF)-α, and interleukin-6 concentrations were determined on the third day. Results: We observed that 3 days after the topical application of isoorientin, the lesion area was significantly smaller when compared to those of the vehicle (p < 0.01) and control (p < 0.05) groups. No difference was observed after 7 and 14 days of induction. Despite this, on day 14, histological analysis of cicatricial tissue from the animals treated with isoorientin showed reduced epidermal thickness (p < 0.001) and increased collagen deposition (p < 0.001). These effects were accompanied by decreased myeloperoxidase activity and interleukin-1β concentration on the third day of induction, without alteration in TNF-α and interleukin-6. Conclusions: The treatment with isoorientin promoted better tissue repair in excisional wounds in mice, which may be linked to the modulation of the early inflammatory response. Full article

Calcium phosphate bone cement (CPC) is a popular material for bone remodeling, and nanohydroxyapatite (nHA) represents a breakthrough that has a wide range of clinical applications. During the early stages of bone repair, antibacterial and angiogenesis effects are essential to remodel new bone tissues. In this study, an antibacterial effect was achieved by incorporating Cu²⁺-doped nano-hydroxyapatite (Cu–nHA) synthesized through hydrothermal methods into CPC, and the impact of various amounts of Cu–nHA addition on the antibacterial and mechanical properties of CPC hybridization was evaluated. Moreover, the effects of Cu–nHA/CPC composites on the proliferation and mineralization of mouse progenitor osteoblastic cells (D1 cells) were characterized; the cell migration and angiogenesis ability of vascular endothelial cells (HUVECs) were also studied. Results indicated that incorporating 5 wt.% and 10 wt.% Cu–nHA into CPC led to a practical short-term antibacterial effect on S. aureus but not on E. coli. These Cu–nHA/CPC slurries remained injectable, anti-disintegrative, and non-toxic. Furthermore, compared with pure CPC, these Cu–nHA/CPC slurries demonstrated positive effects on D1 cells, resulting in better proliferation and mineralization. In addition, these Cu–nHA/CPC slurries were more effective in promoting the migration and angiogenesis of HUVECs. These findings indicate that 10 wt.% Cu–nHA/CPC has great application potential in bone regeneration. Full article