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Nanogold-core Multifunctional Dendrimer for Pulsatile Chemo-, Photothermal- and Photodynamic- Therapy of Rheumatoid Arthritis
摘要： This investigation reports a novel nanoGold-core multifunctional dendrimer for pulsatile chemo-, photothermal- and photodynamic- therapy of rheumatoid arthritis (RA). Architecturally, the nanocomposites comprised of a nanoGold (Au) at the focal whose surface is functionalized by hydroxy-terminated thiolated-dendrons following Au-thiol bond formation to produce nanoGold-core multifunctional dendrimer (Au-DEN). The surface hydroxyl groups of Au-DEN were then conjugated with methotrexate (MTX; a disease-modifying first line anti-rheumatic drug; DMARD; 74.29±0.48 % loading) to form Au-DEN-MTX-NPs (Particle size: 100.15±28.36 nm; poly dispersibility index, PDI: 0.39±0.02; surface zeta potential, ζ: -22.45±1.06 mV). MTX was strategically selected to serve as an anti-rheumatic DMARD as well as a targeting ligand to attain selective localization of the formulation in arthritic tissue via folate receptors upregulated on arthritic tissues. The docking study was performed to confirm the viable binding efficiency of MTX towards β-folate receptors that are overexpressed on arthritic tissues taking folic acid as a reference standard. The IR780, a NIR active bioactive was also loaded in Au-DEN-MTX NPs to offer photothermal benefit upon irradiation with NIR laser (wavelength: 808 nm). The hypothesis was tested by elucidation of in vitro drug release profile, photothermal activity, cellular uptake (Fluorescence and confocal laser scanning microscopy; CLSM), cell viability assay (MTT protocol) and Intracellular reactive oxygen species (ROS) generation in mouse macrophage RAW264.7 cells and Lipopolysaccharide (LPS) activated RAW264.7 cells. Furthermore, the hemolytic toxicity and stability studies were also investigated to determine the blood compatibility as well as ideal storage condition of NPs. The outcome of this investigations presents developed multifunctional targeted NPs to be potential therapeutics for the improved treatment of RA. The approach can also be applied to other clinical interventions involving countering inflammatory conditions.
关键词： Rheumatoid arthritis,NanoGold-core multifunctional dendrimer,Methotrexate,Photothermal,Near-infrared,Dendron
更新于2025-11-21 11:24:58
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A Quantum Field Approach for Advancing Optical Coherence Tomography Part I: First Order Correlations, Single Photon Interference, and Quantum Noise
摘要： Optical coherence tomography has become an important imaging technology in cardiology and ophthalmology, with other applications under investigations. Major advances in optical coherence tomography (OCT) imaging are likely to occur through a quantum field approach to the technology. In this paper, which is the first part in a series on the topic, the quantum basis of OCT first order correlations is expressed in terms of full field quantization. Specifically first order correlations are treated as the linear sum of single photon interferences along indistinguishable paths. Photons and the electromagnetic (EM) field are described in terms of quantum harmonic oscillators. While the author feels the study of quantum second order correlations will lead to greater paradigm shifts in the field, addressed in part II, advances from the study of quantum first order correlations are given. In particular, ranging errors are discussed (with remedies) from vacuum fluctuations through the detector port, photon counting errors, and position probability amplitude uncertainty. In addition, the principles of quantum field theory and first order correlations are needed for studying second order correlations in part II.
关键词： Plaque,Quantum mechanics,Interferometry,Ophthalmology,Noise,Vacuum,Cardiology,Arthritis,Optical coherence tomography
更新于2025-09-23 15:22:29
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Imaging of anti-inflammatory effects of HNO <i>via</i> a near-infrared fluorescent probe in cells and in rat gouty arthritis model
摘要： Nitroxyl (HNO) plays a crucial role in anti-inflammatory effects via the inhibition of inflammatory pathways, but the details of the endogenous generation of HNO still remain challenging owing to the complex biosynthetic pathways, in which the interaction between H2S and NO simultaneously generates HNO and polysulfides (H2Sn) in mitochondria. Moreover, nearly all the available fluorescent probes for HNO are utilized for imaging HNO in cells and tissues, instead of the in situ real-time detection of the simultaneous formation of HNO and H2Sn in mitochondria and animals. Here, we have developed a mitochondria-targeting near-infrared fluorescent probe, namely, Mito-JN, to detect the generation of HNO in cells and a rat model. The probe consists of three moieties: Aza-BODIPY as a fluorescent signal transducer, a triphenylphosphonium cation as a mitochondria-targeting agent, and a diphenylphosphinobenzoyl group as an HNO-responsive unit. The response mechanism is based on an aza-ylide intramolecular ester aminolysis reaction with fluorescence emissions on. Mito-JN displays high selectivity and sensitivity for HNO over various other biologically relevant species. Mito-JN was successfully used for the detection of the endogenous generation of HNO, which is derived from the crosstalk between H2S and NO in living cells. The additional generation of H2Sn was also confirmed using our previous probe Cy-Mito. The anti-inflammatory effect of HNO was examined in a cell model of LPS-induced inflammation and a rat model of gouty arthritis. The results imply that our probe is a good candidate for the assessment of the protective effects of HNO in inflammatory processes.
关键词： H2S,fluorescent probe,HNO,polysulfides,gouty arthritis,anti-inflammatory,near-infrared,NO,mitochondria-targeting
更新于2025-09-19 17:15:36
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Physical exercise and low-level laser therapy on the nociception and leukocyte migration of Wistar rats submitted to a model of rheumatoid arthritis
摘要： Rheumatoid arthritis denotes hyperplasia and intense inflammatory process. Treatment involves exercise protocols and use of resources such as low-level laser therapy (LLLT) to modulate the inflammatory process and maintain physical capacity. The objective was to investigate whether treatment with LLLT and exercise modulates the inflammatory process and peripheral functionality. Sample is composed of 128 male rats, separated into three groups, control, treated and untreated, in the acute and chronic period of the disease with 64 animals in each group, divided into 8 subgroups with n = 8. The animals were immunized with injection at the base of the tail and 7 days after intra-articular injection with complete Freund adjuvant (CFA) for lesion groups, and saline solution for the controls. Joint disability was evaluated by PET (paw elevation time) and joint edema and treated with LLLT and/or resisted stair climbing exercise. Normality Shapiro-Wilk test, ANOVA mixed for the functional analyses, and ANOVA one-way for the variables of cellular differentiation, with Bonferroni post hoc, p = 5% were used. For the evaluations of joint disability and nociception, there was a significant difference between the evaluations, the groups, and the interaction groups-evaluations. The treated groups showed recovery of functionality; it is still verified that laser therapy increased the nociceptive threshold of the chronic inflammatory period, and the exercise reflected in significant functional improvement and modulation of the inflammatory process both in the acute and chronic periods. LLLT, resistance exercise, or a combination of treatments had a positive effect on the modulation of the inflammatory process, reducing the migration of leukocytes, in addition to helping the return of peripheral functionality by reducing joint disability in a model of rheumatoid arthritis induced by CFA in rats.
关键词： Neurogenic inflammation,Rheumatoid arthritis,Laser therapy,Exercise,Leukocyte count
更新于2025-09-16 10:30:52
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Photobiostimulation activity of different low-level laser dosage on masticatory muscles and temporomandibular joint in an induced arthritis rat model
摘要： This study aimed to investigate the anti-inflammatory effects of different dosage of low-level laser therapy (LLLT) in an experimental model of temporomandibular joint (TMJ) arthritis. One hundred male Wistar rats were used and divided into the following groups: CG, control group; AG, animals group with left TMJ arthritis induced by intra-articular injection of Complete Freund’s adjuvant - CFA; LG5, LG10 and LG20 - animals with arthritis and treated with LLLT at doses 5, 10, and 20 J/cm2, respectively. Morphological analysis was performed by TMJ histological sections stained with hematoxylin-eosin (HE), picrosirius (PSR), and toluidine blue (TB), as well as histomorphometric evaluation of cartilage, articular disc, and masticatory muscles. The amount of feed consumed within 3 weeks was evaluated, and biochemical analysis of TMJ tissues included measurement of sulfated glycosaminoglycans (GAGs), matrix metalloproteinases (MMPs) 2 and 9 zymography, and ELISA for cytokines IL-6, TNF-α, and IL-1β. Only the 20 J/cm2 dose promoted higher feed intake compared to AG. On the other hand, all LLLT doses promoted better organization of articular disc collagen fibers, greater number of proteoglycans in articular cartilage, increased area and diameter of left lateral pterygoid fibers, reduced latent and active MMP 9 and 2 activity, and lower IL-1β concentration compared to AG. Considering the study limitations, it was observed that LLLT treatments were effective in protecting and tissue cleansing joint structures, accelerating tissue repair, especially at lower doses.
关键词： Arthritis,Inflammation,Low-level laser therapy,Masticatory muscles,Temporomandibular joint disorders
更新于2025-09-12 10:27:22
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Capillary Electrophoresis with Laser Induced Fluorescence Detection for Study of the Association of HSP60 Gene Polymorphism with Gouty Arthritis
摘要： Background: Gout arthritis is a common inflammatory arthritis and it poses a major threat to human health. Objective: A method of capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) for the detection of HSP60 gene polymorphism has been developed and applied to the exploration of correlation between gouty arthritis and HSP60 gene polymorphism. Methods: The genomic deoxyribonucleic acid from 59 patients with gouty arthritis and 64 control subjects was extracted and the conservative fragment of HSP60 was amplified. The products were digested with restriction endonuclease NlaIII and then separated and detected by the proposed method. Results: In the case group, there were 7 cases of TT genotype, 29 cases of CC genotype, and 23 cases of CT genotype. In the control group, there were 4 cases of TT genotype, 6 cases of CC genotype, and 54 cases of CT genotype. The detection results of the samples were statistically analyzed by binary logistic regression and Spearman correlation analysis. After adjusting gender, age, and other compounding factors, the TT genotype and CT genotype of the HSP60 gene were found to affect gouty arthritis. Conclusions: When used for gene polymorphism research, the proposed CE-LIF method has the advantages of high efficiency, rapidity, sensitivity, and low sample consumption. A moderate correlation between gouty arthritis and HSP60 genotype distribution was discovered for the first time. Highlights: A new method using CE-LIF for the detection of HSP60 gene polymorphism of 59 patients with gouty arthritis and 64 control subjects in China. The correlation between gouty arthritis and HSP60 gene polymorphism was explored for the first time.
关键词： Gouty arthritis,Capillary electrophoresis,HSP60 gene polymorphism,Laser-induced fluorescence
更新于2025-09-12 10:27:22