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Frontiers in Immunology 2024Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options...
Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.
Topics: Humans; Male; Doxorubicin; Hemangioendothelioma, Epithelioid; Nivolumab; Prostatic Neoplasms; Programmed Cell Death 1 Receptor; Antineoplastic Combined Chemotherapy Protocols; Immunotherapy; Immune Checkpoint Inhibitors; Ipilimumab; Treatment Outcome; Polyethylene Glycols; Middle Aged
PubMed: 38947327
DOI: 10.3389/fimmu.2024.1384111 -
International Journal of Nanomedicine 2024To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the...
PURPOSE
To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.
MATERIALS AND METHODS
In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.
RESULTS
The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors.
CONCLUSION
This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.
Topics: Animals; Photothermal Therapy; Reactive Oxygen Species; Nanoparticles; Cell Line, Tumor; Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Mice; Indoles; Tumor Hypoxia; Radiation-Sensitizing Agents; Mice, Inbred BALB C; Mitochondria; Neoplasms; Nanomedicine
PubMed: 38946887
DOI: 10.2147/IJN.S450124 -
International Journal of Nanomedicine 2024It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery...
BACKGROUND
It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research.
METHODS
First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo.
RESULTS
CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 μg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent.
CONCLUSION
Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.
Topics: Flavanones; Animals; Osteoclasts; Bone Regeneration; Silicon Dioxide; Hydrogen-Ion Concentration; Nanoparticles; Rats; Mice; Rats, Sprague-Dawley; Chitosan; Male; Drug Liberation; Porosity; Drug Carriers; Bone Resorption; RAW 264.7 Cells; Drug Delivery Systems; Cell Differentiation
PubMed: 38946884
DOI: 10.2147/IJN.S456545 -
International Journal of Nanomedicine 2024Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin...
PURPOSE
Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations. The overarching objective of this study was to exploit strontium-doped mesoporous silicon particles (PSiSr) to impart multifunctionality to poly(lactic-co-glycolic acid)/gelatin (PG)-based fibrous dressings (PG@PSiSr) for excisional wound management.
METHODS
Mesoporous silicon particles (PSi) and PSiSr were synthesized using a chemo-synthetic approach. Both PSi and PSiSr were incorporated into PG fibers using electrospinning. A series of structure, morphology, pore size distribution, and cumulative pH studies on the PG@PSi and PG@PSiSr membranes were performed. Cytocompatibility, hemocompatibility, transwell migration, scratch wound healing, and delineated angiogenic properties of these composite dressings were tested in vitro. The biocompatibility of composite dressings in vivo was assessed by a subcutaneous implantation model of rats, while their potential for wound healing was discerned by implantation in a full-thickness excisional defect model of rats.
RESULTS
The PG@PSiSr membranes can afford the sustained release of silicon ions (Si) and strontium ions (Sr) for up to 192 h as well as remarkably promote human umbilical vein endothelial cells (HUVECs) and NIH-3T3 fibroblasts migration. The PG@PSiSr membranes also showed better cytocompatibility, hemocompatibility, and significant formation of tubule-like networks of HUVECs in vitro. Moreover, PG@PSiSr membranes also facilitated the infiltration of host cells and promoted the deposition of collagen while reducing the accumulation of inflammatory cells in a subcutaneous implantation model in rats as assessed for up to day 14. Further evaluation of membranes transplanted in a full-thickness excisional wound model in rats showed rapid wound closure (PG@SiSr vs control, 96.1% vs 71.7%), re-epithelialization, and less inflammatory response alongside skin appendages formation (eg, blood vessels, glands, hair follicles, etc.).
CONCLUSION
To sum up, we successfully fabricated PSiSr particles and prepared PG@PSiSr dressings using electrospinning. The PSiSr-mediated release of therapeutic ions, such as Si and Sr, may improve the functionality of PLGA/Gel dressings for an effective wound repair, which may also have implications for the other soft tissue repair disciplines.
Topics: Gelatin; Animals; Strontium; Wound Healing; Bandages; Polylactic Acid-Polyglycolic Acid Copolymer; Skin; Porosity; Rats; Humans; Silicon; Rats, Sprague-Dawley; Mice; Human Umbilical Vein Endothelial Cells; Male; Biocompatible Materials
PubMed: 38946883
DOI: 10.2147/IJN.S460177 -
RSC Advances Jun 2024Halogen-halogen interactions play a pivotal role in the formation and stability of supramolecular assemblies. Herein, we investigate the assembly dynamics and...
Halogen-halogen interactions play a pivotal role in the formation and stability of supramolecular assemblies. Herein, we investigate the assembly dynamics and dissociation pathways of linear supramolecular polymers based on pillar[5]arene-mediated by guest halogen-halogen interactions (C-X × X-C) in both the solution and solid states. The structure of the solid-state supramolecular assembly was determined by single-crystal X-ray diffraction analysis. The binding affinities of four different 1,4-dihalobutane guests with pillar[5]arene were investigated by H NMR spectroscopic titration and isothermal titration calorimetry (ITC). The formation of the halogen-bonded linear supramolecular polymer in solution was demonstrated using diffusion-ordered spectroscopy (DOSY) and ITC. Our findings highlight the dependence of the dissociation process on halogen nature within the encapsulated guest, revealing that the process is entropically driven (Δ = 27.12 kJ mol) and enthalpically disfavored (Δ = 9.99 kJ mol). Moreover, the disassembly of supramolecular polymers promoted by N-containing compounds was investigated using H NMR spectroscopy and ITC, revealing that the process is driven both enthalpically (Δ = -2.64 kJ mol) and entropically (Δ = 15.70 kJ mol). Notably, the data suggest the formation of N⋯I bonding interactions at both ends of the inclusion guest, elucidating the intricate interplay of halogen interactions and host-guest chemistry in supramolecular polymer systems.
PubMed: 38946765
DOI: 10.1039/d4ra03769c -
Physiological Reports Jul 2024The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl)-induced...
Oral administration of encapsulated catechin in chitosan-alginate nanoparticles improves cognitive function and neurodegeneration in an aluminum chloride-induced rat model of Alzheimer's disease.
The present study aimed to investigate the effect of catechin-loaded Chitosan-Alginate nanoparticles (NPs) on cognitive function in an aluminum chloride (AlCl)-induced rat model of Alzheimer's disease (AD). The Catechin-loaded Chitosan-Alginate nanocarriers were synthesized through ionotropic gelation (IG) method. Physio-chemical characterization was conducted with the Zetasizer Nano system, the scanning electron microscope, and the Fourier transform infrared spectroscopy. The experiments were performed over 21 days on six groups of male Wistar rats. The control group, AlCl treated group, Catechin group, nanocarrier group, treatment group 1 (AlCl + Catechin), and treatment group 2 (AlCl + nanocarrier). A behavioral study was done by the Morris water maze (MWM) test. In addition, the level of oxidative indices and acetylcholine esterase (AChE) activity was determined by standard procedures at the end of the study. AlCl induced a significant increase in AChE activity, along with a significant decrease in the level of Catalase (CAT) and total antioxidant capacity (TAC) in the hippocampus. Moreover, the significant effect of AlCl was observed on the behavioral parameters of the MWM test. Both forms of Catechin markedly improved AChE activity, oxidative biomarkers, spatial memory, and learning. The present study indicated that the administration of Catechin-loaded Chitosan-Alginate NPs is a beneficial therapeutic option against behavioral and chemical alteration of AD in male Wistar rats.
Topics: Animals; Catechin; Aluminum Chloride; Chitosan; Alginates; Male; Rats, Wistar; Alzheimer Disease; Rats; Nanoparticles; Administration, Oral; Cognition; Acetylcholinesterase; Maze Learning; Hippocampus; Disease Models, Animal; Antioxidants; Oxidative Stress; Drug Carriers
PubMed: 38946616
DOI: 10.14814/phy2.16095 -
Journal of Indian Prosthodontic Society Jul 2024Studies have not been done to evaluate the peri-implant stress exerted by materials(like PEEK and resin matrix ceramics) in different osseointegration conditions. To...
AIM
Studies have not been done to evaluate the peri-implant stress exerted by materials(like PEEK and resin matrix ceramics) in different osseointegration conditions. To investigate the effect of different occlusal materials on peri-implant stress distribution with different osseointegration condition using finite element analysis.
SETTINGS AND DESIGN
Eighteen different 3D FEA models of implant fixed with abutment were created involving 6 different occlusal materials (Heat cured temporary acrylic resin (PMMA), Bis-GMA, PEEK, Lithium disilicate, Resin matrix ceramics and translucent Zirconia) and different osseointegrated conditions (50%, 75%, 100%).
MATERIALS AND METHODS
Models were subjected to loading vertically and obliquely followed by evaluation of stress distribution.
STATISTICAL ANALYSIS USED
The results of the simulation obtained were analysed in terms of Von mises, maximum principal and minimal principal stresses using descriptive stastistics.
RESULTS
PMMA (40.14 MPa on vertical loading and 66 MPa on oblique loading) resulted in the highest stresses and lithium disilicate (24 MPa on vertical loading and 52.40 MPa on oblique loading) resulted in least stresses among all the crown materials. Upon oblique loading, von Mises stress increases except for translucent zirconia and lithium disilicate (52.444 MPa on 50%, 47.733 MPa on 75%, and 43.973 MPa on 100% osseointegration). Minimal principal stress values decreased with increase in osseointegration upon oblique loading for PMMA, BisGMA, and PEEK.
CONCLUSION
Translucent zirconia and lithium disilicate offer a better stress transmission. Minimal principal stress values of PEEK and BisGMA decreased with increasing osseointegration.
Topics: Finite Element Analysis; Osseointegration; Dental Materials; Dental Implants; Zirconium; Humans; Dental Porcelain; Ceramics; Materials Testing; Stress, Mechanical; Dental Stress Analysis; Polymethyl Methacrylate; Polymers
PubMed: 38946514
DOI: 10.4103/jips.jips_424_23 -
Journal of Indian Prosthodontic Society Jul 2024The aim of this study was to evaluate the effect of proanthocyanidin and C. sinensis-polyphenols on microtensile bonding properties of prepared teeth with resin-modified... (Comparative Study)
Comparative Study
Comparison of microtensile bond strength of prepared teeth treated with proanthocyanidin, Camellia sinensis - Polyphenols, and metal crowns luted with resin-modified glass ionomer cement: An in vitro study.
AIM
The aim of this study was to evaluate the effect of proanthocyanidin and C. sinensis-polyphenols on microtensile bonding properties of prepared teeth with resin-modified glass ionomer cement (GIC).
SETTING AND DESIGN
This was an in vitro study.
MATERIALS AND METHODS
Seventy-eight maxillary premolars were selected and mounted into auto-polymerizing acrylic resin blocks. The samples were prepared and metal crowns were fabricated. The samples were randomly divided into three groups. Samples under Group 1 were not treated with any of the extracts and followed conventional bonding protocol. Samples under Group 2 and Group 3 were treated with proanthocyanidin and C. sinensis-polyphenols, respectively. After dentin treatment, these samples were luted to metal crowns using resin-modified GIC. Universal testing machine was used to measure the load at which the crowns were debonded and microtensile bond strength in MPa was calculated.
STATISTICAL ANALYSIS
The results were statistically analyzed using one-way ANOVA and post hoc Tukey HSD.
RESULTS
Samples treated with C. sinensis polyphenols (Group 3) had maximum bond strength followed by Group 2, where the samples were treated with proanthocyanidin.
CONCLUSION
C. sinensis polyphenols due to their anti-proteolytic and antioxidant properties showed improved bond strength compared to proanthocyanidin, a cross-linking agent, followed by conventional bonding protocol.
Topics: Proanthocyanidins; Tensile Strength; Glass Ionomer Cements; Polyphenols; Humans; Crowns; Dental Bonding; Camellia sinensis; In Vitro Techniques; Resin Cements; Plant Extracts; Dental Stress Analysis
PubMed: 38946512
DOI: 10.4103/jips.jips_127_24 -
Journal of Indian Prosthodontic Society Jul 2024Occurrence of denture stomatitis and prosthesis breakage are common problems faced by elderly people wearing removable dentures. To overcome this, several attempts are...
AIM
Occurrence of denture stomatitis and prosthesis breakage are common problems faced by elderly people wearing removable dentures. To overcome this, several attempts are made to improve the denture material by addition of antimicrobials without compromising original properties. The aim of the study was to evaluate flexural strength and microhardness of self-cured polymethyl methacrylate (PMMA) denture base resin after addition of Vaccinium macrocarpon (commonly called as cranberry), extract as antimicrobial, at varying proportions.
STUDY SETTING AND DESIGN
Experimental in vitro study.
MATERIALS AND METHODS
Frozen cranberry fruits were subjected to extraction process in the presence of aqueous solvents. Lyophilized extract was added in proportions of 0, 0.5, 1.0, 1.5, and 2.0 dry wt/wt % into polymer of self-cure PMMA denture base resin. Based on cranberry inclusion, the study comprised one control (0%) and four test groups (0.5%-2%) with total of 100 samples. A three-point bending test for flexural strength was done for fifty study samples (n = 10). Surface of fractured samples was analyzed using a scanning electron microscope (SEM). Microhardness was determined using Vickers hardness test.
STATISTICAL ANALYSIS USED
One-way statistical ANOVA test was done to find the difference between groups, followed by Tukey's post hoc test for multiple pairwise comparison.
RESULTS
Flexural strength ranged from 66.80 to 69.28 MPa, and a statistically insignificant difference was observed between groups (P > 0.05). SEM evaluation showed uniformly dispersed strands of cranberry extract in PMMA matrix. With higher concentration, less voids were seen. Vickers microhardness value significantly decreased from 15.96 in the control group to 14.57 with 2% cranberry addition (P < 0.05).
CONCLUSION
Incorporation of cranberry extract into self-cure PMMA denture base resin, up to 2 dry wt %, did not decline the flexural strength. However, there was a significant decrease in Vickers microhardness values when compared against the control group (0% cranberry inclusion).
Topics: Polymethyl Methacrylate; Hardness; Flexural Strength; Vaccinium macrocarpon; Plant Extracts; Materials Testing; Humans; Denture Bases; Dental Materials; Anti-Infective Agents; In Vitro Techniques
PubMed: 38946510
DOI: 10.4103/jips.jips_25_24 -
Journal of Indian Prosthodontic Society Jul 2024This study investigates the interaction of zirconia and polyetheretherketone (PEEK) with indirect composite in fixed dental prostheses. This investigation aimed to... (Comparative Study)
Comparative Study
Comparative evaluation of bond strength and color stability of polyetheretherketone and zirconia layered with indirect composite before and after thermocycling: An in vitro study.
AIM
This study investigates the interaction of zirconia and polyetheretherketone (PEEK) with indirect composite in fixed dental prostheses. This investigation aimed to assess the shear bond strength (SBS) and color stability of zirconia and PEEK before and after aging, addressing critical concerns in dental restorative applications.
SETTINGS AND DESIGN
The current in vitro study used 96 samples, 48 of which were divided into two groups, zirconia and PEEK, before and after thermocycling. A dual-axis chewing simulator was used for thermocycling. SBS was measured using a universal testing machine, and color stability was checked using a reflective spectrophotometer.
MATERIALS AND METHODS
Ninety-six samples were categorized into zirconia and PEEK groups, each with subgroups undergoing thermocycling. Samples were prepared using computer-aided design/computer-aided manufacturing milling and veneered with composite resin. Thermocycling involved 10,000 cycles, simulating stress levels equivalent to approximately 1 year of clinical use. SBS was assessed using standardized tests. Stereomicroscopic analysis was performed to evaluate the type of failure. Color stability of the core materials with indirect composite was done using a spectrophotometer before and after aging.
STATISTICAL ANALYSIS USED
Statistical analysis included paired t-tests and independent t-tests in SPSS software.
RESULTS
The results revealed that SBS values for composite on PEEK decreased from 13.86 ± 0.164 MPa before thermocycling to 13.46 ± 0.185 MPa after thermocycling, with a significant difference (P < 0.005). However, both pre- and postthermocycling values for PEEK were higher than zirconia. The t-test confirmed the lower bond strength of composite to zirconia, with a noteworthy improvement after aging. Stereomicroscopic images revealed adhesive failure for the zirconia group and mixed (adhesive and cohesive) failure for the PEEK group. ΔE values were 3.21 ± 0.127 and 2.93 ± 0.142 for zirconia and PEEK groups, respectively (P < 0.005).
CONCLUSION
Within the limitations of this study, it can be deduced that PEEK is a feasible substitute for zirconia when used in conjunction with indirect composite for the fabrication of dental prostheses.
Topics: Benzophenones; Zirconium; Ketones; Polyethylene Glycols; Polymers; Composite Resins; In Vitro Techniques; Dental Bonding; Color; Materials Testing; Shear Strength; Dental Materials; Dental Stress Analysis; Humans
PubMed: 38946508
DOI: 10.4103/jips.jips_36_24