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Photobiomodulation at Multiple Wavelengths Differentially Modulates Oxidative Stress <i>In Vitro</i> and <i>In Vivo</i>
摘要： Photobiomodulation (PBM) is emerging as an effective strategy for the management of multiple inflammatory conditions, including oral mucositis (OM) in cancer patients who receive chemotherapy or radiotherapy. Still, the poor understanding of the mechanisms by which the light interacts with biological tissues and the heterogeneity of light sources and protocols employed worldwide significantly limits its applicability. Reactive oxygen species (ROS) are massively generated during the early phases of OM and play a major role in the pathogenesis of inflammation in general. Here, we report the results of a clinical and experimental study, aimed at evaluating the effect of laser light at different wavelengths on oxidative stress in vivo in oncologic patients suffering from OM and in vitro in two cell types abundantly present within the inflamed oral mucosa, neutrophil polymorphonuclear (PMN) granulocytes, and keratinocytes. In addition to standard ROS detection methods, we exploited a roGFP2-Orp1 genetically encoded sensor, allowing specific, quantitative, and dynamic imaging of redox events in living cells in response to oxidative stress and PBM. We found that the various wavelengths differentially modulate ROS production. In particular, the 660 nm laser light increases ROS production when applied either before or after an oxidative stimulus. In contrast, the 970 nm laser light exerted a moderate antioxidant activity both in the saliva of OM patients and in both cell types. The most marked reduction in the levels of ROS was detected in cells exposed either to the 800 nm laser light or to the combination of the three wavelengths. Overall, our study demonstrates that PBM exerts different effects on the redox state of both PMNs and keratinocytes depending on the used wavelength and prompts the validation of a multiwavelength protocol in the clinical settings.
关键词： Reactive oxygen species,Laser therapy,Photobiomodulation,Oxidative stress,Oral mucositis
更新于2025-09-04 15:30:14
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Radiation-responsive scintillating nanotheranostics for reduced hypoxic radioresistance under ROS/NO-mediated tumor microenvironment regulation
摘要： Abstract: Hypoxia-induced radioresistance is the primary reason for failure of tumor radiotherapy (RT). Changes within the irradiated tumor microenvironment (TME) including oxygen, reactive oxygen species (ROS) and nitric oxide (NO) are closely related to radioresistance. Therefore, there is an urgent need to develop new approaches for overcoming hypoxic radioresistance by incorporating TME regulation into current radiotherapeutic strategies. Methods: Herein, we explored a radiation-responsive nanotheranostic system to enhance RT effects on hypoxic tumors by multi-way therapeutic effects. This system was developed by loading S-nitrosothiol groups (SNO, a NO donor) and indocyanine green (ICG, a photosensitizer) onto mesoporous silica shells of Eu3+-doped NaGdF4 scintillating nanocrystals (NSC). Results: Under X-ray radiation, this system can increase the local dosage by high-Z elements, promote ROS generation by X-ray-induced photodynamic therapy, and produce high levels of NO to enhance tumor-killing effects and improve hypoxia via NO-induced vasodilation. In vitro and in vivo studies revealed that this combined strategy can greatly reinforce DNA damage and apoptosis of hypoxic tumor cells, while significantly suppressing tumor growth, improving tumor hypoxia and promoting p53 up-regulation and HIF1α down-regulation. In addition, this system showed pronounced tumor contrast performance in T1-weighted magnetic resonance imaging and computed tomography. Conclusion: This work demonstrates the great potential of scintillating nanotheranostics for multimodal imaging-guided X-ray radiation-triggered tumor combined therapy to overcome radioresistance.
关键词： X-ray induced photodynamic therapy,hypoxia-induced radioresistance,nanoscintillators,multimodal imaging,nitric oxide
更新于2025-09-04 15:30:14
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Central serous chorioretinopathy in elderly subjects: angiographic and tomographic characteristics
摘要： Purpose To investigate the angiographic, tomographic, and clinical characteristics of idiopathic central serous chorioretinopathy (CSC) in elderly patients. Methods The patients were divided into two groups according to a cutoff age of 60 years at baseline. Patients underwent spectral domain optical coherence tomography, fluorescein angiography, and indocyanine green angiography. Angiographic and tomographic features were compared between the two groups (young vs. elderly group). Results Of 176 patients, 26 patients (15.1%) were 60 years or older. Complete resolution of subretinal fluid after treatment was noted in 72.0% of the elderly group and 90.8% of the young group (P = 0.021). The elderly group showed worse baseline and final vision, more bilateral involvement, and lower male preponderance than the young group (P < 0.05, respectively). The elderly group was also associated with a higher frequency of retinal pigment epithelium depigmentation, foveal thinning, and double-layer sign compared with the young group (P < 0.05, respectively). Conclusion CSC in elderly patients was associated with a lower resolution of serous detachment, increased impairment of retinal pigment epithelial layers, foveal thinning, and worse visual outcome, suggesting a chronic insult to the choroidal vessels involving more severe damage to the outer retinal layers.
关键词： Pachychoroid,Polypoidal choroidal vasculopathy,Fluorescein angiography,Photo dynamic therapy,Imaging,Optical coherence tomography,Indocyanine green angiography,Central serous chorioretinopathy
更新于2025-09-04 15:30:14
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PRaVDA: The first solid-state system for proton computed tomography
摘要： Purpose: Proton CT is widely recognised as a beneficial alternative to conventional X-ray CT for treatment planning in proton beam radiotherapy. A novel proton CT imaging system, based entirely on solid-state detector technology, is presented. Compared to conventional scintillator-based calorimeters, positional sensitive detectors allow for multiple protons to be tracked per read out cycle, leading to a potential reduction in proton CT scan time. Design and characterisation of its components are discussed. An early proton CT image obtained with a fully solid-state imaging system is shown and accuracy (as defined in Section IV) in Relative Stopping Power to water (RSP) quantified. Method: A solid-state imaging system for proton CT, based on silicon strip detectors, has been developed by the PRaVDA collaboration. The system comprises a tracking system that infers individual proton trajectories through an imaging phantom, and a Range Telescope (RT) which records the corresponding residual energy (range) for each proton. A back-projection-then-filtering algorithm is used for CT reconstruction of an experimentally acquired proton CT scan. Results: An initial experimental result for proton CT imaging with a fully solid-state system is shown for an imaging phantom, namely a 75 mm diameter PMMA sphere containing tissue substitute inserts, imaged with a passively-scattered 125 MeV beam. Accuracy in RSP is measured to be 1.6% for all the inserts shown. Conclusions: A fully solid-state imaging system for proton CT has been shown capable of imaging a phantom with protons and successfully improving RSP accuracy. These promising results, together with system the capability to cope with high proton fluences (protons/s), suggests that this research platform could improve current standards in treatment planning for proton beam radiotherapy.
关键词： Proton therapy,Proton CT Elsevier,Solid state detectors
更新于2025-09-04 15:30:14
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A two-year study of diffused retinal pigment epitheliopathy treated with half-dose photodynamic therapy guided by simultaneous angiography and optical coherence tomography
摘要： Objectives Diffused retinal pigment epitheliopathy (DRPE) is not necessarily the same as chronic central serous chorioretinopathy (CSC), but a severe subgroup under the umbrella of chronic CSC. This study was to evaluate the efficacy and safety of half-dose PDT treating DRPE. Methods A retrospective case series design was used. Forty-eight consecutive patients (48 eyes) with DRPE treated with half-dose PDT underwent follow-up at baseline, 3 months, 6 months, 12 months and 24 months. Simultaneous FA, ICGA and OCT were used for the treatment and follow-up. The primary outcomes were the subretinal fluid and best-corrected visual acuity in optical coherence tomography. Results Complete fluid absorption was achieved in 95.8% of eyes at 3 months and 100.0% of eyes at 24 months. The baseline logarithm of the minimum angle of resolution (logMAR) BCVA, which was 0.51 ± 0.36, significantly improved to 0.43 ± 0.38 (p < 0.001) at 6 months. The boost continued to 0.29 ± 0.37 (p < 0.001) at 12 months and 0.19 ± 0.39 (p < 0.001) at 24 months. The integrities of the ellipsoid zone (EZ) and interdigitation zone (IZ) improved throughout. Regression analyses showed the BCVA in logMAR was inversely correlated with the EZ (p < 0.01) and IZ (p < 0.01). The recurrence rate was 6.3%. No severe complications were witnessed. Conclusions In 48 eyes with DRPE, simultaneous angiography and OCT facilitated a more comprehensive guidance for half-dose PDT treatment and follow-up. The BCVA improvement occurred at 6 months, which may be attributed to the restoration of the outer retinal structure.
关键词： chronic central serous chorioretinopathy,half-dose photodynamic therapy,Diffused retinal pigment epitheliopathy,angiography,CSC,optical coherence tomography,OCT,DRPE,PDT
更新于2025-09-04 15:30:14
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In Vitro antimicrobial photoinactivation with methylene blue in different microorganisms
摘要： Aim: To evaluate the in vitro antimicrobial effects of photodynamic therapy (PDT). Methods: The microorganism indicators were: Candida albicans, Pseudomonas aeruginosa,Enterococcus faecalis and Staphylococcus aureus. A microbial pool was prepared (108 cells/mL), from which aliquots were transferred to culture plates for carrying out the PDT using methylene blue (50 μM) and low-power laser (660 nm, 100 mW and 9 J).The effect of methylene blue alone, low power laser and the absence of treatments were evaluated. Then, aliquots of 1 μL were plated in a media culture, the number of colony forming units (CFU/mL) was obtained and the data submitted to the F test (ANOVA) with Tamhane’s comparisons. Results:The laser radiation in the presence of methylene blue was able to eliminate 74.90% of C. albicans, 72.41% of P. aeruginosa, 96.44% of E. faecalis and 95.42% of S. aureus, thus statistically significant differences were found among the groups (p<0.001). Conclusions: PDT was effective in reducing the number of viable cells in the studiedmicroorganisms, especially E. faecalis and S. aureus.
关键词： microbiology,Enterococcus faecalis,methylene blue,endodontics,photodynamic therapy
更新于2025-09-04 15:30:14
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Solar powered oxygen systems in remote health centers in Papua New Guinea: a large scale implementation effectiveness trial
摘要： Background Pneumonia is the largest cause of child deaths in Papua New Guinea (PNG), and hypoxaemia is the major complication causing death in childhood pneumonia, and hypoxaemia is a major factor in deaths from many other common conditions, including bronchiolitis, asthma, sepsis, malaria, trauma, perinatal problems, and obstetric emergencies. A reliable source of oxygen therapy can reduce mortality from pneumonia by up to 35%. However, in low and middle income countries throughout the world, improved oxygen systems have not been implemented at large scale in remote, difficult to access health care settings, and oxygen is often unavailable at smaller rural hospitals or district health centers which serve as the first point of referral for childhood illnesses. These hospitals are hampered by lack of reliable power, staff training and other basic services. Methods We report the methodology of a large implementation effectiveness trial involving sustainable and renewable oxygen and power systems in 36 health facilities in remote rural areas of PNG. The methodology is a before–and after evaluation involving continuous quality improvement, and a health systems approach. We describe this model of implementation as the considerations and steps involved have wider implications in health systems in other countries. Results The implementation steps include: defining the criteria for where such an intervention is appropriate, assessment of power supplies and power requirements, the optimal design of a solar power system, specifications for oxygen concentrators and other oxygen equipment that will function in remote environments, installation logistics in remote settings, the role of oxygen analyzers in monitoring oxygen concentrator performance, the engineering capacity required to sustain a program at scale, clinical guidelines and training on oxygen equipment and the treatment of children with severe respiratory infection and other critical illnesses, program costs, and measurement of processes and outcomes to support continuous quality improvement. Conclusions This study will evaluate the feasibility and sustainability issues in improving oxygen systems and providing reliable power on a large scale in remote rural settings in PNG, and the impact of this on child mortality from pneumonia over 3 years post–intervention. Taking a continuous quality improvement approach can be transformational for remote health services.
关键词： Pneumonia,Papua New Guinea,oxygen therapy,hypoxaemia,solar power,remote health centers
更新于2025-09-04 15:30:14
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Targeted Methotrexate Prodrug Conjugated With Heptamethine Cyanine Dye Improving Chemotherapy and Monitoring Itself Activating by Dual-Modal Imaging
摘要： Theranostic prodrug plays a vital role in reducing the side effects and evaluating the therapeutic efficiency of prodrug in vivo. In particular, small conjugate-based theranostic prodrugs have attracted much attention because of their clear and simple structures. In this work, we synthesized a novel tumor-targeting and glutathione-activated conjugate-based theranostic prodrug (Cy-SS-MTX). The prodrug was constructed by conjugating Cy (IR780) to methotrexate (MTX) via a disulfide bond. The Cy dye as targeting molecule bring prodrug to cancer cells and then the prodrug was activated by the high levels of glutathione in tumor. In cell experiments, the results showed the excellent ability of prodrug to target tumor. Meanwhile, the prodrug apparently improved the anti-tumor ability and hugely reduced toxicity of free MTX on normal cells. Furthermore, owing to intramolecular charge transfer between Cy and MTX, the Cy structure in the prodrug showed an absorption peak at 654 nm in UV-Vis spectroscopy. However, when the disulfide bond of prodrug was broken by glutathione, a new UV-Vis absorption peak at 802 nm of Cy structure in prodrug was arised. At the same time, the fluorescence (FL) emission peak at 750 nm (excitation at 640 nm) would turn into 808 nm (excitation at 745 nm). What’s more, the photoacoustic (PA) signal with excitation at 680 and 808 nm also changed. The experimental results in vivo showed that the prodrug has been successfully utilized for real-timely tracking MTX activation by FL and PA imaging upon near infrared laser excitation and cancer targeting therapy. Our studies further encourage application of small conjugate-based prodrug based on tumor-targeted heptamethine cyanine dye as reporter group for targeted therapy and real-timely tracking activation of drug.
关键词： small conjugate-based prodrug,heptamethine cyanine dye,dual-modal imaging,targeting therapy,monitoring prodrug activation,theranostic
更新于2025-09-04 15:30:14
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Designing of UCNPs@Bi@SiO2 Hybrid Theranostic Nanoplatforms for Simultaneous Multimodal Imaging and Photothermal Therapy
摘要： Herein, a novel multifunctional nanoplatform was designed towards multimodality imaging and photothermal therapy (PTT). It was found that Bi nanoparticles could grow in situ on the surface of NaYF4:20%Yb,2%Er@NaYF4:40%Yb@NaGdF4 core-shell nanoparticles (labeled as UCNPs). In this structure, UCNPs were mainly employed as upconversion luminescence (UCL) imaging agent, while the Bi nanoparticles worked as effective CT imaging and photothermal agent. Importantly, a dense SiO2 shell was employed to protect the Bi nanoparticles from oxidation, and it also endowed the nanoplatform with excellent hydrophilic ability. The effective UCL/CT imaging and PTT performances were emphasized by a series of in vivo experiments, which suggest that the integrated nanoplatform with imaging and therapy functions show great promise in the biomedical field.
关键词： Theranostic Nanoplatform,UCL imaging,CT imaging,Photothermal Therapy,UCNPs
更新于2025-09-04 15:30:14
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Nano-Assemblies from J-Aggregated Dyes: A Stimuli-Responsive Tool Applicable to Living Systems
摘要： Controlling the packing arrangements of dyes is a facile way of tuning their photophysical and/or photochemical properties, thus enabling new sensing mechanisms for photofunctional tools. Here, we present a general and robust strategy toward water-stable J-aggregated dye templated nano-assemblies by incorporating an amphiphilic diblock copolymer and a stimuli-responsive dye as the only two building components. An iodo-substituted boron dipyrromethene (BODIPY) was adopted as a template to direct the self-assembly of poly(ethylene glycol)-block-polycaprolactone (PEG-PCL), forming a core-shell nanoplate with slip-stacked BODIPYs as core surrounded by hydrophilic PEG shell. The self-assembled nanoplate is stable in cell culture medium and possesses a built-in stimuli-responsiveness that arises from BODIPY bearing meso-carboxylate protecting group, which is efficiently removed upon treatment with peroxynitrite. The resulting negative charges lead to rearrangement of dyes from J-stacking to non-stacking, which activates photoinduced singlet oxygen production from the nano-assemblies. The stimuli-activatable photosensitivity has been exploited for specific photodynamic ablation of activated RAW 264.7 cells with excessive endogenous peroxynitrite. In light of the generality of the sensing mechanism, the concept described herein will significantly expands the palette of design principles to develop diverse photofunctional tools for biological research and clinical needs.
关键词： J-aggregated dyes,PEG-PCL,photodynamic therapy,nano-assemblies,BODIPY,stimuli-responsive
更新于2025-09-04 15:30:14