Search Results (972)

Beyond gas transport, red blood cells (RBCs) have emerging roles regarding innate immunity, regulating blood flow, and participating in nutrient transport, which can be engineered as drug delivery systems since they contribute to maintaining water homeostasis. Following extensive thermoanalytical studies of human blood plasma, our working group investigated the properties of RBCs, examining their role in healthy and in different disease states by using differential scanning calorimetry (DSC) and the deconvolution of the resulting thermal curve. In the first study, guinea pigs were treated with intraperitoneal chemotherapy. Cyclophosphamide treatment showed a dose-dependent difference between the thermal parameters of control and treated samples, indicating that DSC can be used in this area. Following deconvolution of the DSC studies, the changes can be attributed to the damaged compounds. In the second part of our study, a method for the thermal analysis and deconvolution of RBCs in patients with lower limb ischemia during a three-month cilostazol treatment was developed. The control DSC curve showed 5-6 distinct thermal domains, and in contrast to other drug treatments, this remained stable throughout the entire study period. No effects of stiffness or compact were caused by the anticancer drug cyclophosphamide were observed in the structure of RBCs. These preliminary results highlight the uniqueness of thermodynamic studies of RBCs and provide a fingerprint-like identification of a given individual or disease state. Full article

Objective: The aim of the study was to evaluate the dynamics of skin temperature at the injection points of botulinum toxin type A in the forehead area at different time stages as a marker of the vasomotor response and restoration of microcirculation after aesthetic botulinum therapy. Methods: The prospective study included 126 patients (19–59 years old, mean age 34.4 ± 1.2 years) who underwent injections of botulinum toxin type A at standard points of m. frontalis, m. procerus, and m. corrugator supercilii. Skin temperature was recorded with an infrared thermal imager at nine standardized points (P1–P9) at the following stages: before the procedure (T0), immediately after (T1), after 30 min (T2), after 14 (T14) and 30 (T30) days. The analysis was performed using analysis of variance with repeated measures and post hoc tests (p < 0.05). Results: A typical three-phase pattern of temperature response was revealed: an immediate decrease in temperature at all points immediately after injections (T1, −1.7–4.8% relative to the baseline, p < 0.001), subsequent reactive hyperemia after 30 min (T2, an increase of 2.35–5.8% at points P1, P2, P4–P7) and normalization of indicators by T14–T30. The most pronounced and stable changes were recorded at the interbrow points P7–P9, projecting to m. corrugator supercilii and m. procerus, which reflects their higher functional and vascular activity. Conclusions: Infrared thermography allows for objective recording of the phasic vasomotor response of the skin to injections of botulinum toxin type A, can be used to assess individual vascular response, and may aid in individualized treatment planning for aesthetic botulinum therapy. Full article

Background: The management of localized prostate cancer (PCa) suffers from the dilemma between the overtreatment associated with radical surgery and the uncertainty of active surveillance, highlighting a significant therapeutic gap specifically for intermediate-risk patients and selected low-risk patients. Focal therapy (FT) emerges as an advanced technological solution to balance rigorous oncological control with anatomical and functional preservation. Methods: A narrative review of the literature was conducted to analyze the physical principles underlying various ablative energies (thermal, cryogenic, and non-thermal) as well as radiation-based focal approaches. The review examines the oncological rationale of targeted ablation, recent innovations in imaging, and the expanding clinical scenarios for FT application. Results: Evidence supports the oncological rationale of “Index Lesion” ablation as a targeted curative strategy for clinically significant disease, rather than merely a palliative one. The review highlights the emerging concept of “pushing the disease” and demonstrates the valuable role of salvage focal therapy in the setting of radio-recurrent carcinoma. Furthermore, recent innovations in multiparametric magnetic resonance imaging (mpMRI) and fusion systems have significantly refined patient selection, rendering this minimally invasive approach highly targeted. Conclusions: The current barrier to the universal adoption of focal therapy is the lack of a standardized consensus on the definitions of therapeutic failure and the inadequacy of traditional PSA-based criteria. However, evidence suggests that FT represents a promising, organ-sparing alternative for carefully selected patients with localized PCa, though long-term comparative data are still required. Full article

Phage therapy has enormous potential in combating bacterial resistance in food animals. However, its application via the oral route remains limited due to challenges associated with the gastrointestinal tract (GIT) environment and a lack of rigorous clinical trial evidence. Therefore, we systematically searched in Google Scholar, PubMed, Scopus, and Web of Science databases following PRISMA guidelines and finally identified 111 articles on oral phage therapy in food animals from where we summarized the key physiological and chemical factors of the gut environment hindering the effectiveness of oral phage therapy (OPT), examined the methods used to evaluate phage stability in the GI environment, and highlighted potential strategies to mitigate these challenges. In addition, we performed quantitative analysis to visualize in vitro pH and thermal stability patterns of phages targeting bacteria isolated from food animals and variability in buffer and incubation period across stability studies. The GIT consists of several anatomically and functionally distinct segments, where complex interactions occur among digestive enzymes, gastric acids, electrolytes, commensal microbiota, and mucosal immune components. The acidic pH of the stomach is a major barrier to successful oral phage delivery. According to our analysis of pH stability testing data from the reviewed studies, most phages targeting antimicrobial-resistant bacteria in food animals remained stable at pH 5–9 and inactivated under highly acidic (pH ≤ 2) or highly alkaline (pH ≥ 11) conditions. In addition, phages are susceptible to high temperatures (above 60 °C), digestive enzymes (e.g., pepsin, trypsin, lipases), bile salts, and host immune responses. Several in vitro laboratory techniques are available to assess phage stability under simulated GI conditions, but variations occur in the assessment protocols. Microencapsulation using alginate and chitosan has been used to protect phages from the adverse GI environment. Additionally, enteric-coated capsules, antacids, co-encapsulation with acid-neutralizing agents, consumption of alkaline water, and daily phage administration are suggested to improve phage survival and efficacy. For the successful clinical implementation of OPT in food animals, future research should focus on elucidating the molecular and physicochemical determinants of phage stability, understanding the humoral immune response to OPT, standardizing laboratory protocol for assessing phage viability, improving the scalability of encapsulation methods, and exploring other potential delivery techniques. Full article

Light-based therapies are becoming increasingly = more mainstream, not only within the medical science space, but also within the fields of cosmetic dermatology and personal grooming. Intense Pulsed Light (IPL) harnesses the ability of the natural chromophore–melanin to absorb light energy, which is translated into heat energy and consequently results in targeted thermolysis of cells rich in melanin. This mechanistic pathway lends itself to a wide range of applications, including long-term hair removal, skin rejuvenation, the treatment of unwanted pigmentation, and the treatment of ophthalmic conditions. The development of home use devices (HUDs) for the delivery of IPL-mediated hair removal has facilitated the self-administration of photothermal treatments and reduced reliance on clinical settings. In this study, we demonstrate a pioneering approach to model aspects of IPL-induced thermal induction and selective thermolysis in a complex human skin tissue equivalent. Our approach utilised a deactivated HUD with disabled safety features that allowed for the exposure of tissue constructs to high-fluence IPL. We demonstrate an increase in biomarkers consistent with increased cellular temperature, induction of apoptosis, and increased pro-inflammatory cytokine release following extreme treatment regimens, all of which correlate with an increased fluence and/or increased number of IPL pulses delivered. This method allowed for the identification of cellular events evoked by increasing fluence and extreme-exposure regimes. Full article

Background/Objectives: Triptolide (TP), a potent natural diterpenoid, exhibits anti-glioma activity, but faces significant clinical translation challenges, including poor water solubility, systemic toxicity such as hepatotoxicity, and inadequate tumor targeting. This study aimed to develop a novel epidermal growth factor receptor (EGFR)-targeted liposomal formula-tion, designated as TP-CTX-Lip (where CTX denotes cetuximab), to enhance the deliv-ery efficiency and therapeutic window of TP. Methods: The formulation was optimized using a uniform design approach (four factors, six levels) and prepared via thin-film hydra-tion–ultrasonication. The encapsulation of TP was supported by Fourier transform in-frared spectroscopy (FTIR) and thermal analysis (DSC/TGA), which revealed molecu-lar interactions (e.g., hydrogen bonding) with lipid components and a marked en-hancement in thermal stability, consistent with successful incorporation into the lipo-somal bilayer. The physicochemical properties, including the size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and drug loading, were characterized. In vitro release kinetics were evaluated in phosphate buffer (pH 7.4), and cytotoxicity was assessed in high-EGFR (U87-MG) and low-EGFR (SW1088) glioma cells. In vivo efficacy and developmental toxicity were investigated using zebrafish models. The op-timized TP-CTX-Lip demonstrated favorable characteristics: size = 131.3 ± 4.5 nm, PDI = 0.24 ± 0.006, zeta potential = −23.37 ± 0.27 mV, encapsulation efficiency = 85.83% ± 1.81%, and drug loading = 13%. In vitro release followed first-order kinetics dominated by Higuchi diffusion (79.0% ± 4% at 24 h). After 48 h of treatment, TP-CTX-Lip exhib-ited significantly enhanced cytotoxicity in U87-MG cells (IC50 = 10.4 ± 0.2 nM), com-pared with IC50 values of 42.8 nM in SW1088 cells and 45.3 nM for non-targeted lipo-somes. In the 3T3-L1 non-cancerous cell line, the 48 h IC50 value of TP-CTX-Lip (8.433 ± 0.954µM) was higher than that of the TP solution (2.173 ± 0.181µM) but lower than that of TP-Lip (25.78 ± 2.691µM). Specifically, in 3T3-L1 cells, the 48 h IC50 of TP-CTX-Lip (8.43 µM) was approximately 4-fold higher than that of free TP (2.17 µM), confirming its substantially reduced cytotoxicity against non-cancerous cells. Results: In comparison to TP-Lip and free FITC solution, the uptake rate of TP-CTX-Lip in U87-MG cells exhibited a significantly higher level. Specifically, the uptake rate for the TP-CTX-Lip group (57.46 ± 5.44%) was statistically significantly higher than that of TP-Lip (13.7 ± 2.33%) and the free FITC solution group (20.97 ± 1.60%) (p < 0.01). In zebrafish, TP-CTX-Lip reduced developmental toxicity, with LC50 increased 1.26 times to 5.733 μg/mL, and suppressed orthotopic U87-MG xenograft growth (p < 0.001), in-dicating an improved therapeutic window as reflected by the LC50/IC50 ratio. Conclusions: the EGFR-targeted TP-CTX-Lip significantly enhances the tumor selectivity and safety of TP, providing a promising strategy for targeted glioma therapy. Full article

Background/Objectives: Thermal injuries represent a significant global health burden, often complicated by hypertrophic scarring, chronic inflammation, and delayed re-epithelialization. While Mesenchymal Stem Cell (MSC) transplantation has shown promise, its clinical translation is hindered by risks of tumorigenicity and immunological concerns. This study evaluates the efficacy of cell-free Extracellular Vesicle (EV) therapy—derived from both mammalian MSCs and plant sources (PDNVs)—as standardized, off-the-shelf alternatives. This study synthesizes evidence focusing on re-epithelialization velocity, angiogenic activity, and anti-fibrotic outcomes, while assessing the impact of second-generation delivery scaffolds on therapeutic durability. Methods: Conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420261305379), this review interrogated PubMed, Scopus, Embase, and Web of Science for studies published between 2015 and 2026. Eligible studies included in vivo animal models of thermal injury using purified vesicles from mammalian MSC sources or plant-derived nanovesicles compared with placebo, standard care, or untreated controls. Data were synthesized narratively; methodological quality was appraised using the SYRCLE risk of bias tool and compliance with MISEV guidelines. Results: Synthesis of 50 studies revealed that vesicle-based interventions consistently accelerate wound closure and improve histological healing. Mammalian ADSC-derived vesicles demonstrated superior anti-fibrotic effects via the miR-192-5p and miR-125b-5p axes, while hUC-MSC vesicles attenuated systemic inflammatory signaling via miR-181c. Plant-derived nanovesicles (PDNVs) showed potent antioxidant and re-epithelialization effects, with emerging potential as engineered genetic carriers. Crucially, advanced delivery systems, including bioactive hydrogels and microneedle patches, were repeatedly associated with improved local retention and more durable effects than bolus injections. Conclusions: Vesicle-based therapies show consistent pro-healing signals in preclinical models, suggesting source-dependent profiles: MSC-derived vesicles excel in immunomodulation and anti-fibrotic remodeling, while PDNVs provide a scalable, low-immunogenicity platform. As a cell-free strategy, these therapies circumvent the safety risks of live cell transplantation. This review identifies a critical shift toward second-generation delivery scaffolds to overcome the clearance crisis of topical applications, emphasizing the need for harmonized MISEV-aligned characterization in future clinical translation. Full article

Background/Objectives: Pulsed Electric Field (PEF) therapy is a non-thermal ablation technique that induces immunogenic cell death through high-voltage, short-duration electrical pulses. This may enhance antitumor immunity by releasing intact tumor antigens and potentially generating abscopal effects. We report early outcomes in 32 patients with primary lung cancer or lung oligometastases treated with PEF at a community hospital, with a median (IQR) follow-up of 180.5 (158–207) days. Methods: This retrospective study collected demographics, cancer type, treatment response, and outcomes for patients undergoing PEF ablation. Tumor response was assessed using Sum of Longest Dimensions per RECIST 1.1 to classify progressive disease, stable disease, partial response, or complete response. Volumetric changes were additionally analyzed using RECIST 1.1 percentage thresholds applied to change in volume. Results: At initial 3-month follow-up, 26 of 32 patients demonstrated stable disease, partial response, or complete response, suggesting an 81.25% disease control rate/clinical benefit rate among this cohort. Among patients with Stage III–IV disease, 27.6% (8/29) showed radiographic evidence of a possible abscopal response. At 6 months, 24 of 32 patients remained alive and evaluable, with 62.5% (20/32) maintaining stable disease, partial response, or complete response. Conclusions: Despite patients having progressive disease on systemic therapy before PEF, early outcomes post-ablation suggest favorable local control and potential immunologic benefit. Patients with early-stage disease not receiving systemic therapy also showed excellent local response. Patients tolerated therapy very well. Clinical benefit was observed in 81.25% of patients at 3 months and 62.5% at 6 months, with radiographic evidence of possible abscopal responses in 27.6% of advanced-stage patients, supporting further exploration of the immunogenic potential of PEF demonstrated in preclinical and emerging clinical studies. Full article

Dry eye disease, a multifactorial and symptomatic disease characterized by tear film instability and ocular surface dysfunction, has emerged as an increasingly pressing global health concern—particularly against the backdrop of increasing digital device usage and the widespread application of virtual learning. Traditional pharmacotherapies, such as artificial tears, yield only transient symptomatic relief. Compared with pharmacological agents, surgical treatments are further restricted in clinical application, primarily because of their invasiveness, technical complexity, postoperative complications, and high costs. Consequently, the development of novel therapeutic strategies has emerged as imperative. This review summarizes advances in pharmacotherapy, including nanomedicine and biological agents, as well as emerging physiotherapies, such as photobiomodulation, thermal pulsation, and neurostimulation. These innovative therapeutic approaches address the partial limitations of conventional treatments through three main molecular mechanisms: improved drug delivery, multitargeted pharmacology, and enhanced biocompatibility. Nevertheless, the clinical translation of many innovative therapies requires large-scale clinical trials to validate clinical efficacy, optimize dosage regimens, and assess long-term safety profiles. In the future, integrating lifestyle modifications, effective clinician–patient communication, and patient-centric diagnostic approaches will facilitate the establishment of therapeutic alliances and support the success of precision medicine. Full article

Background/Objectives: The oral administration of donepezil has been shown to have common side effects due to systemic drug delivery, with fluctuations in blood and brain donepezil concentrations. Therefore, we obtained nanostructured lipid carriers loaded with donepezil (donepezil–NLC) for nose-to-brain targeting. Methods: The obtained NLCs were characterized by measurements of particle size, the polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy, Differential Scanning Calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and in vitro release studies. Plasma and brain pharmacokinetic studies in Wistar rats were carried out to determine brain targeting. Results: Donepezil–NLC showed low polydispersity and nanometric size, high zeta potential, and high drug entrapment efficiency. Microscopy images showed spherical particles with regular surfaces. Thermal analysis, X-ray diffraction, and FTIR-ATR suggested the formation of an amorphous lipid matrix and the incorporation of donepezil molecularly dispersed within the lipid matrix. In vitro drug release studies demonstrated a biphasic drug release pattern with an initial burst followed by sustained release, with results better fitted to the Korsmeyer–Peppas model (n-value > 0.5). Following the nasal administration of donepezil–NLC, brain pharmacokinetic studies in Wistar rats demonstrated a significant improvement in bioavailability. Compared to the intravenous injection of donepezil, the AUC^0–ꝏ value was 10.5-fold higher. Drug targeting efficiency and direct transport percentage showed extremely higher values, suggesting nose-to-brain targeting after donepezil–NLC intranasal administration. Conclusions: Donepezil–NLC has proven to be an efficient drug delivery system for the nose to the brain, which may reduce systemic toxicity and improve Alzheimer’s therapy with low doses of donepezil and fewer adverse effects. Full article

Background/Objectives: The clinical management of bladder cancer is severely impeded by high recurrence rates and the rapid emergence of chemoresistance, necessitating the discovery of novel therapeutic agents with distinct mechanisms of action. Dehydrodiisoeugenol (DHE), a bioactive neolignan, exhibits potent anti-tumor efficacy, yet its direct molecular targets and mode of action remain elusive. Methods: To deconvolute the mechanism of DHE, we integrated a phenotypic screening approach using 2D cell lines and 3D patient-derived organoids with a chemoproteomics-based activity-based protein profiling (ABPP) strategy. We synthesized a functionalized photoaffinity probe to capture the specific interactome of DHE under physiological conditions and validated targets via cellular thermal shift assays (CETSA), quantitative mass spectrometry, and 100 ns molecular dynamics (MD) simulations. Results: DHE exhibited potent dose-dependent cytotoxicity in bladder cancer cells, with IC50 values of 39.23 μM in T24 and 34.58 μM in 5637 cells. In 3D patient-derived organoids, DHE significantly reduced viability (p < 0.0001). Using a dual-filtering ABPP strategy, we identified 65 high-confidence candidate targets, prioritizing PTPN1 (PTP1B) as the primary functional interactor. Comparative molecular docking and 100 ns MD analyses showed that multiple stereoisomers of DHE could adopt plausible PTPN1-binding modes. Mechanistically, organoid proteomics indicated that DHE engagement with PTPN1 disrupts ER membrane homeostasis, thereby modulating the PI3K-Akt signaling axes. Conclusions: These findings establish PTPN1 as a critical druggable vulnerability in bladder cancer and define the molecular basis for the therapeutic potential of DHE. This study highlights the power of combining chemoproteomics with physiological 3D models to accelerate the translation of natural products into precision cancer therapies. Full article

Background: Gastric cancer (GC) is characterized by aggressive invasion and early peritoneal dissemination, which are strongly driven by chronic inflammation and epithelial–mesenchymal transition (EMT). c-Jun N-terminal kinase (JNK), a stress-responsive serine/threonine kinase within the mitogen-activated protein kinase (MAPK) family, integrates inflammatory cues to promote EMT and metastasis. Huangjin Shuangshen granules (HJSS) is a multi-component traditional Chinese medicine (TCM) formula derived from Simiao Yong’an Decoction and clinically used as an adjuvant therapy for GC. However, whether HJSS restrains inflammation-driven metastasis through modulation of JNK-associated EMT signaling remains unclear. Methods: The anti-metastatic efficacy of HJSS was evaluated using integrated in vivo and in vitro models, combined with transcriptomics, network pharmacology and molecular validation. Results: HJSS markedly attenuated LPS-induced metastatic behavior and inflammatory activation. Multilevel analyses converged on MAPK8/JNK as a central regulatory node. HJSS reversed EMT progression and inhibited nuclear phosphorylation of JNK without affecting its upstream kinases. Thermal-shift assays and molecular docking supported potential target engagement of HJSS-derived constituents, including possible interactions with JNK-related signaling targets. Pharmacologic reactivation of JNK partially abrogated the inhibitory effects of HJSS, confirming JNK-dependent action. Conclusions: HJSS suppresses inflammation-driven GC metastasis primarily by attenuating JNK-associated EMT, potentially through modulation of JNK activation by its bioactive constituents. These findings provide mechanistic insight into HJSS as a low-toxicity anti-metastatic strategy and support further exploration of its active constituents. Full article

Chronic oxidative stress and lipid imbalance drive metabolic disorders such as obesity and non-alcoholic fatty liver disease, yet few therapies target the upstream redox imbalance in key tissues. Human carbonic anhydrase III (hCA III), a redox-associated enzyme enriched in liver and adipose tissue, has long remained pharmacologically elusive due to its low catalytic activity and lack of modulators. Here, we identify fragment-like nicotinic acid derivatives as non-sulfonamide hCA III modulators and evaluate their associated cellular effects. Using an esterase activity assay, we screened 25 analogues and identified two fragment-like hits, compound 17 (2-thioethyl) and compound 22 (6-morpholino), with IC₅₀ values of 487 and 361 µM, respectively. Orthogonal thermal shift analysis supported compound-protein interaction, and selected hits were subsequently evaluated in HepG2 cells. Both compounds were associated with reduced CA3 mRNA expression after treatment at 1 µM, while their cellular phenotypes diverged, with compound 22 increasing ROS under oxidative stress conditions and compound 17 affecting mitochondrial membrane potential. Taken together, these findings identify tractable nicotinic acid-derived fragment hits and associated cellular phenotypes that warrant further mechanistic investigation. These fragment-like hits provide a practical starting point for studying the redox-linked biology of hCA III. Full article

Due to its strong near-infrared (NIR) absorption and high thermal conductivity, graphene is considered an excellent nanophotothermal filler that can effectively improve the photothermal conversion performance of composites. In particular, graphene–polymer nanocomposites, new types of photothermal conversion materials, have broad application prospects in photothermal therapy, photothermal driving, and micro-/nanomachinery. Recent research results have shown that when the filling concentration of graphene nanosheets (GNSs) in the matrix reaches the percolation threshold, interface effects such as interface tunneling and Maxwell–Wagner–Sillars (MWS) polarization, the key factors affecting the photothermal conversion performance of such composites, will occur. Furthermore, graphene exhibits unique optical conductivity due to its strong interaction with light. To reveal how interface effects influence the photothermal conversion performance of these nanocomposites, the optical conductivity of graphene at near-infrared frequencies was introduced to modify the effective medium theory. By combining this with a photothermal conversion model, the photothermal conversion behaviors of GNS–polymer composites are discussed, taking into account the interface effects and optical conductivity characteristics of GNSs. Full article

Background/Objectives: Enteric drug forms are developed to delay drug release to avoid drug degradation in the acidic environment of the stomach or to prevent irritation of the stomach mucosa. The bioavailability of posaconazole (POS) after oral administration depends on stomach pH and food intake. Delayed-release tablets and unmodified oral suspension are the POS formulations currently available on the market. The oral suspension formulation is characterized by highly variable bioavailability, which may significantly affect therapy effectiveness. Methods: In this study, multi-unit drug forms with delayed and sustained POS release were designed. Polymeric microparticles consisting of sodium alginate (ALG), methacrylic acid–ethyl acrylate copolymer (EUD), or both, were prepared using the spray-drying technique. The formulations that met the pharmacopoeia enteric release standards in the in vitro dissolution test were subjected to further in vitro evaluation via swelling and mucoadhesion assays, an antifungal activity test, attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR), and thermal analysis. Results: It was shown that EUD formulations at concentrations of 5% and 6% provided enteric release, whereas ALG at 1.5% concentration exhibited a sustained, although not delayed, POS release profile. The optimal blended formulations (EAP15–EAP18), comprising 4% EUD with 1.5–2.0% ALG and either 1% or 4% POS, met the pharmacopoeia criteria for enteric dosage forms. Furthermore, these blends demonstrated the most favorable sustained-release profiles in the buffer phase, ranging from 2 to 3 h. The microparticles exhibited beneficial swelling and mucoadhesive properties, which are essential for prolonging contact with the intestinal mucosa; combined with antifungal properties. Conclusions: Obtained carrier may provide a promising preliminary basis for developing a multi-unit, sustained-release enteric dosage form for POS and future in vivo investigations. Full article