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BACKGROUND: Atherosclerosis is a chronic inflammatory disease causing a fatal plaque rupture, and its key aspect is a failure to resolve inflammation. We hypothesize that macrophage-targeted near-infrared fluorescence emitting photoactivation could simultaneously assess macrophage/lipid-rich plaques in vivo and facilitate inflammation resolution. METHODS: We fabricated a Dectin-1-targeted photoactivatable theranostic agent through the chemical conjugation of the near-infrared fluorescence-emitting photosensitizer chlorin e6 and the Dectin-1 ligand laminarin (laminarin-chlorin e6 [LAM-Ce6]). Intravascular photoactivation by a customized fiber-based diffuser after administration of LAM-Ce6 effectively reduced inflammation in the targeted plaques of atherosclerotic rabbits in vivo as serially assessed by dual-modal optical coherence tomography-near-infrared fluorescence structural-molecular catheter imaging after 4 weeks. RESULTS: The number of apoptotic macrophages peaked at 1 day after laser irradiation and then resolved until 4 weeks. Autophagy was strongly augmented 1 hour after the light therapy, with the formation of autophagolysosomes. LAM-Ce6 photoactivation increased the terminal deoxynucleotidyl transferase dUTP (deoxyuridine triphosphate) nick end labeling/RAM11 (rabbit monocyte/macrophage antibody)- and MerTK (c-Mer tyrosine kinase)-positive cells in the plaques, suggesting enhanced efferocytosis. In line with inflammation resolution, photoactivation reduced the plaque burden through fibrotic replacement via the TGF (transforming growth factor)-ß/CTGF (connective tissue growth factor) pathway. CONCLUSIONS: Optical coherence tomography-near-infrared fluorescence imaging-guided macrophage Dectin-1-targetable photoactivation could induce the transition of macrophage/lipid-rich plaques into collagen-rich lesions through autophagy-mediated inflammation resolution and TGF-ß-dependent fibrotic replacement. This novel strategy offers a new opportunity for the catheter-based theranostic strategy.
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Clorofilidas , Imagen Multimodal , Fármacos Fotosensibilizantes , Placa Aterosclerótica , Porfirinas , Tomografía de Coherencia Óptica , Animales , Placa Aterosclerótica/diagnóstico por imagen , Conejos , Imagen Multimodal/métodos , Tomografía de Coherencia Óptica/métodos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Macrófagos/metabolismo , Nanomedicina Teranóstica/métodos , Ratones , Masculino , Autofagia , Tirosina Quinasa c-Mer/metabolismo , ApoptosisRESUMEN
The activation of the anti-cancer immune system is an important strategy to control cancer. A new form of cancer phototherapy, near-infrared photoimmunotherapy (NIR-PIT), was approved for clinical use in 2020 and uses IRDye® 700DX (IR700)-conjugated antibodies and NIR light. After irradiation with NIR light, the antibody-IR700 conjugate forms water-insoluble aggregations on the plasma membrane of target cells. This aggregation causes lethal damage to the plasma membrane, and effectively leads to immunogenic cell death (ICD). Subsequently, ICD activates anti-cancer immune cells such as dendritic cells and cytotoxic T cells. Combination therapy with immune-checkpoint blockade has synergistically improved the anti-cancer effects of NIR-PIT. Additionally, NIR-PIT can eliminate immunosuppressive immune cells in light-irradiated tumors by using specific antibodies against regulatory T cells and myeloid-derived suppressor cells. In addition to cancer-cell-targeted NIR-PIT, such immune-cell-targeted NIR-PIT has shown promising results by activating the anti-cancer immune system. Furthermore, NIR-PIT can be used to manipulate the tumor microenvironment by eliminating only targeted cells in the tumor, and thus it also can be used to gain insight into immunity in basic research.
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Inmunoconjugados , Fototerapia , Línea Celular Tumoral , Fototerapia/métodos , Inmunoterapia/métodos , Inmunoconjugados/uso terapéuticoRESUMEN
The perfect integration of microbubbles for efficient ultrasound imaging and nanocarriers for intelligent tumor-targeting delivery remains a challenge in precise tumor theranostics. Herein, we exquisitely fabricated laser-activated and targeted polymersomes (abbreviated as FIP-NPs) for simultaneously encapsulating the photosensitizer indocyanine green (ICG) and the phase change agent perfluorohexane (PFH). The formulated FIP-NPs were nanosize and effectively accumulated into tumors as observed by ICG fluorescence imaging. When the temperature rose above 56 °C, the encapsulated PFH transformed from liquid to gas and the FIP-NPs underwent balloon-like enlargement without structure destruction. Impressively, the enlarged FIP-NPs fused with adjacent polymersomes to form even larger microparticles. This temperature-responsive "nano-to-micro" transformation and fusion process was clearly demonstrated, and FIP-NPs showed greatly improved ultrasound signals. More importantly, FIP-NPs achieved dramatic antitumor efficacy through ICG-mediated phototherapy. Taken together, the novel polymersomes achieved excellent ultrasound/fluorescence dual imaging-guided tumor phototherapy, providing an optimistic candidate for the application of tumor theranostics.
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Verde de Indocianina , Imagen Óptica , Fototerapia , Polímeros , Verde de Indocianina/química , Verde de Indocianina/uso terapéutico , Animales , Ratones , Fototerapia/métodos , Humanos , Imagen Óptica/métodos , Polímeros/química , Nanopartículas/química , Nanopartículas/uso terapéutico , Fluorocarburos/química , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Temperatura , Ultrasonografía/métodos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Nanomedicina Teranóstica/métodos , Microburbujas/uso terapéuticoRESUMEN
Ferroptosis is an iron-dependent and lipid peroxides (LPO)-overloaded programmed damage cell death, induced by glutathione (GSH) depletion and glutathione peroxide 4 (GPX4) inactivation. However, the inadequacy of endogenous iron and reactive oxygen species (ROS) restricts the efficacy of ferroptosis. To overcome this obstacle, a near-infrared photo-responsive FeP@PEG NPs is fabricated. Exogenous iron pool can enhance the effect of ferroptosis via the depletion of GSH and further regulate GPX4 inactivation. Generation of ·OH derived from the Fenton reaction is proved by increased accumulation of lipid peroxides. The heat generated by photothermal therapy and ROS generated by photodynamic therapy can enhance cell apoptosis under near-infrared (NIR-808 nm) irradiation, as evidenced by mitochondrial dysfunction and further accumulation of lipid peroxide content. FeP@PEG NPs can significantly inhibit the growth of several types of cancer cells in vitro and in vivo, which is validated by theoretical and experimental results. Meanwhile, FeP@PEG NPs show excellent T2-weighted magnetic resonance imaging (MRI) property. In summary, the FeP-based nanotheranostic platform for enhanced phototherapy/ferroptosis/chemodynamic therapy provides a reliable opportunity for clinical cancer theranostics.
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Ferroptosis , Fototerapia , Nanomedicina Teranóstica , Humanos , Ferroptosis/efectos de los fármacos , Fototerapia/métodos , Animales , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Hierro/química , Polietilenglicoles/química , Ratones , Fotoquimioterapia/métodosRESUMEN
Surface-enhanced Raman scattering (SERS) imaging integrating photothermal and photodynamic therapy (PTT/PDT) is a promising approach for achieving accurate diagnosis and effective treatment of cancers. However, most available Raman reporters show multiple signals in the fingerprint region, which overlap with background signals from cellular biomolecules. Herein, a 4T1 cell membrane-enveloped gold nanorods-manganese porphyrins system (GMCMs) is designed and successfully fabricated as a biomimetic theranostic nanoplatform. Manganese porphyrins are adsorbed on the surface of Au nanorods via the terminal alkynyl group. Cell membrane encapsulation protects the manganese porphyrins from falling off the gold nanorods. The biomimetic GMCMs confirm specific homologous targeting to 4T1 cells with good dispersibility, excellent photoacoustic (PA) imaging properties, and preferable photothermal and 1O2 generation performance. GMCMs exhibit distinct SERS signals in the silent region without endogenous biomolecule interference both in vitro and in vivo. Manganese ions could not only quench the fluorescence of porphyrins to enhance the SERS imaging effect but also deplete cellular GSH to increase 1O2 yield. Both in vitro and in vivo studies demonstrate that GMCMs effectively eradicate tumors through SERS/PA imaging-guided PTT/PDT. This study provides a feasible strategy for augmenting the Raman imaging effects of the alkynyl group and integrating GSH-depletion to enhance PTT/PDT efficacy.
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Pyroptosis, an inflammatory cell death, plays a pivotal role in activating inflammatory response, reversing immunosuppression and enhancing anti-tumor immunity. However, challenges remain regarding how to induce pyroptosis efficiently and precisely in tumor cells to amplify anti-tumor immunotherapy. Herein, a pH-responsive polydopamine (PDA) nanocluster, perfluorocarbon (PFC)@octo-arginine (R8)-1-Hexadecylamine (He)-porphyrin (Por)@PDA-gambogic acid (GA)-cRGD (R-P@PDA-GC), is rationally design to augment phototherapy-induced pyroptosis and boost anti-tumor immunity through a two-input programmed cascade therapy. Briefly, oxygen doner PFC is encapsulated within R8 linked photosensitizer Por and He micelles as the core, followed by incorporation of GA and cRGD peptides modified PDA shell, yielding the ultimate R-P@PDA-GC nanoplatforms (NPs). The pH-responsive NPs effectively alleviate hypoxia by delivering oxygen via PFC and mitigate heat resistance in tumor cells through GA. Upon two-input programmed irradiation, R-P@PDA-GC NPs significantly enhance reactive oxygen species production within tumor cells, triggering pyroptosis via the Caspase-1/GSDMD pathway and releasing numerous inflammatory factors into the TME. This leads to the maturation of dendritic cells, robust infiltration of cytotoxic CD8+ T and NK cells, and diminution of immune suppressor Treg cells, thereby amplifying anti-tumor immunity.
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The field of 2D materials has advanced significantly with the emergence of MBenes, a new material derived from the MAX phases family, a novel class of materials that originates from the MAX phases family. Herein, this article explores the unique characteristics and morphological variations of MBenes, offering a comprehensive overview of their structural evolution. First, the discussion explores the evolutionary period of 2D MBenes associated with the several techniques for synthesizing, modifying, and characterizing MBenes to tailor their structure and enhance their functionality. The focus then shifts to the defect chemistry of MBenes, electronic, catalytic, and photothermal properties which play a crucial role in designing multifunctional solar-driven hybrid systems. Second, the recent advancements and potentials of 2D MBenes in solar-driven hybrid systems e.g. photo-electro catalysis, hybrid solar evaporators for freshwater and thermoelectric generators, and phototherapy, emphasizing their crucial significance in tackling energy and environmental issues, are explored. The study further explores the fundamental principles that regulate the improved photocatalytic and photothermal characteristics of MBenes, highlighting their promise for effective utilization of solar energy and remediation of the environment. The study also thoroughly assesses MBenes' scalability, stability, and cost effectiveness in solar-driven systems. Current insights and future directions allow researchers to utilize MBenes for sustainable and varied applications. This review regarding MBenes will be valuable to early researchers intrigued with synthesizing and utilizing 2D materials for solar-powered water-energy-fuel and phototherapy systems.
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Precise integration of diverse therapeutic approaches into nanomaterials is the key to the development of multimodal synergistic cancer therapy. In this work, tadpole-like carbon nanotubes with Fe nanoparticle encapsulated at the head and Zn single-atom anchored on the body (Fe@CNT-Zn) is precisely designed and facilely prepared via one-pot carbonization. In vitro studies revealed the integration of chemotherapy (CT), chemodynamic therapy (CDT), photothermal therapy (PTT), and photodynamic therapy (PDT) in Fe@CNT-Zn as well as the near-infrared light (NIR)-responsive cascade therapeutic efficacy. Furthermore, in vivo studies demonstrated the NIR-triggered cascade-amplifying synergistic cancer therapy in a B16 tumor-bearing mouse model. The results not only showcased the Fe@CNT-Zn as a potential tetramodal therapeutic platform, but also demonstrated a proof-of-concept on metal-organic framework-based "one stone for multiple birds" strategy for in situ functionalization of carbon materials.
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Single-atom nanozymes (SAzymes) are emerging natural enzyme mimics and have attracted much attention in the biomedical field. SAzymes with MetalâNx sites designed on carbon matrixes are currently the mainstream in research. It is of great significance to further expand the types of SAzymes to enrich the nanozyme library. Single-atom alloys (SAAs) are a material in which single-atom metal sites are dispersed onto another active metal matrix, and currently, there is limited research on their enzyme-like catalytic performance. In this work, a biodegradable Pt1Pd SAA is fabricated via a simple galvanic replacement strategy, and for the first time reveals its intrinsic enzyme-like catalytic performance including catalase-, oxidase-, and peroxidase-like activities, as well as its photodynamic effect. Experimental characterizations demonstrate that the introduction of single-atom Pt sites contributes to enhancing the affinity of Pt1Pd single-atom alloy nanozyme (SAAzyme) toward substrates, thus exhibiting boosted catalytic efficiency. In vitro and in vivo experiments demonstrate that Pt1Pd SAAzyme exhibits a photo-controlled therapeutic effect, with a tumor inhibition rate of up to 100%. This work provides vital guidance for opening the research direction of SAAs in enzyme-like catalysis.
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Aleaciones , Aleaciones/química , Animales , Platino (Metal)/química , Humanos , Catálisis , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Ratones , Fototerapia/métodosRESUMEN
Current thrombolytic drugs exhibit suboptimal therapeutic outcomes and potential bleeding risks due to their limited circulation time, inadequate thrombus penetration, and off-target biodistribution. Herein, a photosensitizer-loaded, red cell membrane-encapsuled multiple magnetic nanoparticles aggregate is successfully developed for integrated mechanical/photothermal/photodynamic thrombolysis. Red cell membrane coating endows magnetic particles with prolonged blood circulation and superior biocompatibility. Under a preset rotating magnetic field (RMF), the aggregate with asymmetric magnetic distribution initiates rolling motion toward the blood clot interface, and because of magnetic dipole-dipole interactions, the aggregate tends to self-assemble into longer, flexible chain-like microrobotic swarm with powerful mechanical stir forces, thereby facilitating thrombus penetration and mechanical thrombolysis. Moreover, precise magnetic control enables targeted photosensitizer accumulation, allowing effective conversion of near-infrared (NIR) light into heat and reactive oxygen species (ROS) for thrombus phototherapy. In thrombolysis assays, the weight of thrombi is massively reduced by ≈90%. The work presents a safer and more promising combination of magnetic microrobotic technology and phototherapy for multi-modality thrombolysis.
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INTRODUCTION: Vitiligo is an autoimmune dermatosis that affects quality of life, which englobes sleep quality. Sleep regulates the immune system, including inflammatory cytokines, and other pathways, which may influence vitiligo pathogenesis. OBJECTIVES: To analyze levels of immune serum components (cytokines) in a vitiligo group, and assess whether there was any association with sleep. METHODS: This study comprised 30 vitiligo patients and 26 control individuals. Quality of life and sleep questionnaires were completed [Dermatology Life Quality Index (DLQI), Short-Form Health Survey (SF-36), Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI)]. Seven cytokines have been measured: IFN-γ, interleukin (IL)-4, IL-6, IL-10, IL-17A, IL-12 p40 and TNF-α. RESULTS: The mean age of the vitiligo group was 47.7 years-old, with prevalence of females (66.7 %). Mucosal (70 %), acral (60 %) and focal subtype (53.3 %) predominated. Signs of vitiligo activity were identified in 63.3 % of the disease sample. Total PSQI scores and scores for domain 4 (sleep efficiency) were statistically worse in vitiligo group. The SF-36 and ISI total scores were worse in the vitiligo group, although not statistically significant compared with controls. Four SF-36 domains were statistically worse in vitiligo sample, and the DLQI mean score was mild to moderate (5.57). Cytokine levels were not different between groups, or when associated with PSQI. Higher ISI scores (more severe insomnia) were related to increased IL-17A. Higher IL-4, IL-6 and IL-10 levels were associated with previous phototherapy. CONCLUSIONS: Poor sleep and impaired aspects of quality of life predominated in the vitiligo sample. Insomnia was related to IL-17A increase in vitiligo. Increased levels of IL-4, IL-6 and IL-10 were related to previous ultraviolet B narrow band (UVB-NB) phototherapy, suggesting an interaction of this treatment on immune system. Sleep disruption and the course of vitiligo may have common pathways in respect of circadian cytokines, which may represent an important subject in vitiligo management.
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Trastornos del Inicio y del Mantenimiento del Sueño , Vitíligo , Femenino , Humanos , Persona de Mediana Edad , Masculino , Citocinas , Interleucina-10 , Interleucina-17 , Interleucina-4 , Calidad de Vida , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Interleucina-6 , SueñoRESUMEN
Phototherapy is a useful treatment modality for atopic dermatitis (AD). This is a prospective randomised double-blind study comparing the clinical efficacy of combined ultraviolet-A (UVA)/narrowband ultraviolet-B (NBUVB) versus NBUVB phototherapy in the treatment of chronic AD. Patients with moderate-to-severe AD were randomised to receive either UVA/NBUVB or NBUVB phototherapy twice weekly over 12 weeks. At baseline, weeks 6 and 12, Eczema Area And Severity Index (EASI), itch score and adverse effects were assessed. At baseline and week 12, disease-related quality of life was evaluated using the Dermatology Life Quality Index (DLQI). Nine patients were randomised to receive UVA/NBUVB and 10 received NBUVB. At week 12, both groups showed significant improvement in EASI and itch scores (p < 0.05). Significant improvement in DLQI was seen in the UVA/NBUVB arm (p = 0.009) with a trend towards improvement in the NBUVB arm (p = 0.11). The efficacy of both modalities were comparable, as were reported adverse effects aside from skin dryness which was higher in the NBUVB arm (40% vs. 0%, p = 0.033). Combined UVA/NBUVB and NBUVB phototherapy have comparable clinical efficacy and safety in the treatment of chronic AD. NBUVB may induce greater skin dryness.
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Dermatitis Atópica , Eccema , Terapia Ultravioleta , Humanos , Dermatitis Atópica/radioterapia , Estudios Prospectivos , Método Doble Ciego , Calidad de Vida , Terapia Ultravioleta/efectos adversos , Fototerapia , Prurito/etiología , Prurito/radioterapia , Resultado del TratamientoRESUMEN
Near-Infrared-II (NIR-II) spans wavelengths between 1,000 to 1,700 nanometers, featuring deep tissue penetration and reduced tissue scattering and absorption characteristics, providing robust support for cancer treatment and tumor imaging research. This review explores the utilization of activatable NIR-II photodiagnosis and phototherapy based on tumor microenvironments (e. g., reactive oxygen species, pH, glutathione, hypoxia) and external stimulation (e. g., laser, ultrasound, photothermal) for precise tumor treatment and imaging. Special emphasis is placed on the advancements and advantages of activatable NIR-II nanomedicines in novel therapeutic modalities like photodynamic therapy, photothermal therapy, and photoacoustic imaging. This encompasses achieving deep tumor penetration, real-time monitoring of the treatment process, and obtaining high-resolution, high signal-to-noise ratio images even at low material concentrations. Lastly, from a clinical perspective, the challenges faced by activatable NIR-II phototherapy are discussed, alongside potential strategies to overcome these hurdles.
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Rayos Infrarrojos , Nanoestructuras , Neoplasias , Humanos , Nanoestructuras/química , Nanoestructuras/uso terapéutico , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Fototerapia/métodos , Animales , Microambiente Tumoral , Fotoquimioterapia , Técnicas Fotoacústicas/métodos , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéuticoRESUMEN
Hypoxia is a critical factor for restricting photodynamic therapy (PDT) of tumor, and it becomes increasingly severe with increasing tissue depth. Thus, the relief of deep tumor hypoxia is extremely important to improve the PDT efficacy. Herein, tumor microenvironment (TME)-responsive size-switchable hyaluronic acid-hybridized Ru nanoaggregates (HA@Ru NAs) were developed via screening reaction temperature to alleviate deep tumor hypoxia for improving the tumor-specific PDT by the artful integration multiple bioactivated chemical reactions inâ situ and receptor-mediated targeting (RMT). In this nanosystem, Ru NPs not only enabled HA@Ru NAs to have near infrared (NIR)-mediated photothermal/photodynamic functions, but also could catalyze endogenous H2O2 to produce O2 inâ situ. More importantly, hyaluronidase (HAase) overexpressed in the TME could trigger disassembly of HA@Ru NAs via the hydrolysis of HA, offering the smart size switch capability from 60 to 15â nm for enhancing tumor penetration. Moreover, the RMT characteristics of HA ensured that HA@Ru NAs could specially enter CD44-overexpressed tumor cells, enhancing tumor-specific precision of phototherapy. Taken together these distinguishing characteristics, smart HA@Ru NAs successfully realized the relief of deep tumor hypoxia to improve the tumor-specific PDT.
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In the category of 2D materials, MoS2 a transition metal dichalcogenide, is a novel and intriguing class of materials with interesting physicochemical properties, explored in applications ranging from cutting-edge optoelectronic to the frontiers of biomedical and biotechnology. MoS2 nanostructures an alternative to heavy toxic metals exhibit biocompatibility, low toxicity and high stability, and high binding affinity to biomolecules. MoS2 nanostructures provide a lot of opportunities for the advancement of novel biosensing, nanodrug delivery system, electrochemical detection, bioimaging, and photothermal therapy. Much efforts have been made in recent years to improve their physiochemical properties by developing a better synthesis approach, surface functionalization, and biocompatibility for their safe use in the advancement of biomedical applications. The understanding of parameters involved during the development of nanostructures for their safe utilization in biomedical applications has been discussed. Computational studies are included in this article to understand better the properties of MoS2 and the mechanism involved in their interaction with biomolecules. As a result, we anticipate that this combined experimental and computational studies of MoS2 will inspire the development of nanostructures with smart drug delivery systems, and add value to the understanding of two-dimensional smart nano-carriers.
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Nanoestructuras , Elementos de Transición , Molibdeno/química , Nanoestructuras/química , Sistemas de Liberación de MedicamentosRESUMEN
Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.
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Depresión , Lipopolisacáridos , Humanos , Ratones , Animales , Lipopolisacáridos/farmacología , Depresión/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Citocinas/metabolismo , Mesencéfalo/metabolismo , FormaldehídoRESUMEN
Carbon monoxide (CO) poisoning is a leading cause of poison-related morbidity and mortality worldwide. By binding to hemoglobin and other heme-containing proteins, CO reduces oxygen delivery and produces tissue damage. Prompt treatment of CO-poisoned patients is necessary to prevent acute and long-term complications. Oxygen therapy is the only available treatment. Visible light has been shown to selectively dissociate CO from hemoglobin with high efficiency without affecting oxygen affinity. Pulmonary phototherapy has been shown to accelerate the rate of CO elimination in CO poisoned mice and rats when applied directly to the lungs or via intra-esophageal or intra-pleural optical fibers. The extracorporeal removal of CO using a membrane oxygenator with optimal characteristic for blood exposure to light has been shown to accelerate the rate of CO illumination in rats with or without lung injury and in pigs. The development of non-invasive techniques to apply pulmonary phototherapy and the development of a compact, highly efficient membrane oxygenator for the extracorporeal removal of CO in humans may provide a significant advance in the treatment of CO poisoning.
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Intoxicación por Monóxido de Carbono , Fototerapia , Intoxicación por Monóxido de Carbono/terapia , Animales , Humanos , Fototerapia/métodos , Monóxido de CarbonoRESUMEN
In this account, we will highlight recent progress in the development of multichannel lanthanide-doped (MC-Ln) nanoprobes for highly efficient serodiagnosis and therapy, with a particular focus on our own work. First, we first provide a classification of the types of MC-Ln nanoprobes based on the contained type and number of signals. The merits of different types of nanoprobes and the reason using lanthanides are elucidated. Then, we provide an overview of the current uses of MC-Ln nanoprobes in serodiagnosis and therapy, focusing on the strategic exploration to improve the diagnostic and therapeutic performance from different perspectives. Finally, we present a prospective outlook on the future development and potential issues of next-generation MC-Ln nanoprobes. We hope that this timely account will update our understanding of MC-Ln and similar nanoprobes for bioapplications and provide helpful references for the state-of-the-art tools for serodiagnosis and therapy.
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Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.
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BACKGROUND: For people with atopic dermatitis (AD) refractory to topical therapies, treatment with phototherapy and systemic therapies can be considered. Multiple biologic therapies and Janus kinase (JAK)inhibitors have been approved since 2014 to treat AD. These guidelines update the 2014 recommendations for management of AD with phototherapy and systemic therapies. OBJECTIVE: To provide evidence-based recommendations on the use of phototherapy and systemic therapies for AD in adults. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 11 recommendations on the management of AD in adults with phototherapy and systemic agents, including biologics, oral JAK inhibitors, and other immunomodulatory medications. LIMITATIONS: Most randomized controlled trials of phototherapy and systemic therapies for AD are of short duration with subsequent extension studies, limiting comparative long-term efficacy and safety conclusions. CONCLUSIONS: We make strong recommendations for the use of dupilumab, tralokinumab, abrocitinib, baricitinib, and upadacitinib. We make conditional recommendations in favor of using phototherapy, azathioprine, cyclosporine, methotrexate, and mycophenolate, and against the use of systemic corticosteroids.