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Purpose: Neuroinflammation is a characteristic feature of neurodegenerative diseases. Mesenchymal stem cell-derived exosomes (MSC-exo) have shown neuroprotective effects through immunoregulation, but the therapeutic efficacy remains unsatisfactory. This study aims to enhance the neuroprotective capacity of MSC-exo through IL-23 priming for treating retinal degeneration in mice. Methods: MSC were primed with IL-23 stimulation in vitro, and subsequently, exosomes (MSC-exo and IL-23-MSC-exo) were isolated and characterized. Two retinal degenerative disease models (NaIO3-induced mice and rd10 mice) received intravitreal injections of these exosomes. The efficacy of exosomes was assessed by examining retinal structural and functional recovery. Furthermore, exosomal microRNA (miRNA) sequencing was conducted, and the effects of exosomes on the M1 and M2 microglial phenotype shift were evaluated. Results: IL-23-primed MSC-derived exosomes (IL-23-MSC-exo) exhibited enhanced capability in protecting photoreceptor cells and retinal pigment epithelium (RPE) cells against degenerative damage and fostering the restoration of retinal neural function in both NaIO3-induced retinal degeneration mice and rd10 mice when compared with MSC-exo. The exosomal miRNA suppression via Drosha knockdown in IL-23-primed MSC would abolish the neuroprotective role of IL-23-MSC-exo, highlighting the miRNA-dependent mechanism. Bioinformatic analysis, along with further in vivo biological studies, revealed that IL-23 priming induced a set of anti-inflammatory miRNAs in MSC-exo, prompting the transition of M1 to M2 microglial polarization. Conclusions: IL-23 priming presents as a potential avenue for amplifying the immunomodulatory and neuroprotective effects of MSC-exo in treating retinal degeneration.
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Modelos Animales de Enfermedad , Exosomas , Interleucina-23 , Células Madre Mesenquimatosas , Ratones Endogámicos C57BL , Degeneración Retiniana , Animales , Exosomas/metabolismo , Exosomas/trasplante , Degeneración Retiniana/terapia , Degeneración Retiniana/metabolismo , Degeneración Retiniana/prevención & control , Ratones , Células Madre Mesenquimatosas/metabolismo , Interleucina-23/metabolismo , MicroARNs/genética , Inyecciones Intravítreas , Fármacos Neuroprotectores , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/patología , Yodatos/toxicidad , Células Cultivadas , Microglía/metabolismo , MasculinoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cordyceps cicadae (C.cicadae), named "Chan Hua", an anamorph of Isaria cicadae Miquel, is an entomogenous complex formed by fungi parasitizing on the larvae of cicadas and belongs to the Claviciptaceae family and the genus Codyceps, which traditionally holds a significant place in Chinese ethnopharmacology, specifically for eye clarity and as a remedy for age-related ocular conditions. The underlying mechanisms contributing to its eyesight enhancement and potential effectiveness against Age-related macular degeneration (AMD) remain unexplored. AIM OF THE STUDY: This study aims to elucidate the protective role of C.cicadae and its active ingredient, Myriocin (Myr), against AMD. MATERIALS AND METHODS: A chemical inducer was employed to make retinal pigment epithelium (RPE) damage in vitro and in vivo. The key ingredients of C.cicadae and their related mechanisms for anti-AMD were studied through bioinformatic analysis and molecular biological approaches. RESULTS: Myr was identified through high-performance liquid chromatography (HPLC) as an active ingredient in C.cicadae, and demonstrated a protective effect on RPE cells, reducing the structural damage and cell death induced by sodium iodate (SI). Further, Myr reduced eyelid secretions in AMD mice and restored their retinal structure and function. The differentially expressed genes (DEGs) in Myr treatment are primarily associated with TNF and Necroptosis signaling pathways. Molecular docking indicated a strong affinity between TNF and Myr. Myr inhibited the TNF signaling pathway thereby reducing the expression of inflammatory factors in ARPE-19 cells. Additionally, Myr had consistent action with the necroptosis inhibitor Necrostatin-1 (Nec-1), inhibited the RIPK1/RIPK3/MLKL pathway thereby protecting ARPE-19 cells. CONCLUSION: The findings present Myr, as a potent protector against SI-induced AMD, predominantly through modulation of the TNF-RIPK1/RIPK3/MLKL signaling pathway, offering the insights of therapeutic C.cicadae as viable candidates for AMD treatment.
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Cordyceps , Yodatos , Degeneración Macular , Epitelio Pigmentado de la Retina , Factor de Necrosis Tumoral alfa , Animales , Degeneración Macular/tratamiento farmacológico , Cordyceps/química , Ratones , Factor de Necrosis Tumoral alfa/metabolismo , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Línea Celular , Ratones Endogámicos C57BL , Proteína Serina-Treonina Quinasas de Interacción con Receptores/metabolismo , Masculino , Necroptosis/efectos de los fármacos , Ácidos Grasos MonoinsaturadosRESUMEN
Iodine is an essential trace element in the human diet because it is involved in the synthesis of thyroid hormones. Iodine deficiency affects over 2.2 billion people worldwide, making it a significant challenge to find plant-based sources of iodine that meet the recommended daily intake of this trace element. In this study, cabbage plants were cultivated in a hydroponic system containing iodine at concentrations ranging from 0.01 to 1.0 mg/L in the form of potassium iodide or potassium iodate. During the experiments, plant physiological parameters, biomass production, and concentration changes of iodine and selected microelements in different plant parts were investigated. In addition, the oxidation state of the accumulated iodine in root samples was determined. Results showed that iodine addition had no effect on photosynthetic efficiency and chlorophyll content. Iodide treatment did not considerably stimulate biomass production but iodate treatment increased it at concentrations less than 0.5 mg/L. Increasing iodine concentrations in the nutrient solutions increased iodine content in all plant parts; however, the iodide treatment was 2-7 times more efficient than the iodate treatment. It was concluded, that iodide addition was more favourable on the target element accumulation, however, it should be highlighted that application of this chemical form in nutrient solution decreased the concetrations of selected micoelement concentration comparing with the control plants. It was established that iodate was reduced to iodide during its uptake in cabbage roots, which means that independently from the oxidation number of iodine (+ 5, - 1) applied in the nutrient solutions, the reduced form of target element was transported to the aerial and edible tissues.
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Biofortificación , Brassica , Hidroponía , Yodatos , Yodo , Yodo/metabolismo , Yodo/análisis , Brassica/metabolismo , Brassica/crecimiento & desarrollo , Brassica/efectos de los fármacos , Yodatos/metabolismo , Biomasa , Raíces de Plantas/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/efectos de los fármacos , Fotosíntesis/efectos de los fármacos , Yoduro de Potasio/farmacología , Compuestos de Potasio/farmacología , Compuestos de Potasio/metabolismo , Clorofila/metabolismoRESUMEN
Extracellular iodate reduction by Shewanella spp. contributes to iodide generation in the biogeochemical cycling of iodine. However, there is a disagreement on whether Shewanella spp. use different extracellular electron transfer pathways with dependence on electron donors in iodate reduction. In this study, a series of gene deletion mutants of Shewanella oneidensis MR-1 were created to investigate the roles of dmsEFABGH, mtrCAB, and so4357-so4362 operons in iodate reduction. The iodate-reducing activity of the mutants was tested with lactate, formate, and H2 as the sole electron donors, respectively. In the absence of single-dms gene, iodate reduction efficiency of the mutants was only 12.9%-84.0% with lactate at 24 hours, 22.1%-85.9% with formate at 20 hours, and 19.6%-57.7% with H2 at 42 hours in comparison to complete reduction by the wild type. Progressive inhibition of iodate reduction was observed when the dms homolog from the so4357-so4362 operon was deleted in the single-dms gene mutants. This result revealed complementation of dmsEFABGH by so4357-so4362 at the single-gene level, indicating modularity of the extracellular electron transfer pathway encoded by dmsEFABGH operon. Under the conditions of all electron donors, significant inhibition of iodate reduction and accumulation of H2O2 were detected for ΔmtrCAB. Collectively, these results demonstrated that the dmsEFABGH operon encodes an essential and modular iodate-reducing pathway without electron donor dependence in S. oneidensis MR-1. The mtrCAB operon was involved in H2O2 elimination with all electron donors. The findings in this study improved the understanding of molecular mechanisms underlying extracellular iodate reduction.IMPORTANCEIodine is an essential trace element for human and animals. Recent studies revealed the contribution of microbial extracellular reduction of iodate in biogeochemical cycling of iodine. Multiple reduced substances can be utilized by microorganisms as energy source for iodate reduction. However, varied electron transfer pathways were proposed for iodate reduction with different electron donors in the model strain Shewanella oneidensis MR-1. Here, through a series of gene deletion and iodate reduction experiments, we discovered that the dmsEFABGH operon was essential for iodate reduction with at least three electron donors, including lactate, formate, and H2. The so4357-so4362 operon was first demonstrated to be capable of complementing the function of dmsEFABGH at single-gene level.
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Proteínas Bacterianas , Yodatos , Operón , Oxidación-Reducción , Shewanella , Shewanella/genética , Shewanella/metabolismo , Transporte de Electrón , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Yodatos/metabolismo , Formiatos/metabolismo , Eliminación de GenRESUMEN
BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people in the developed world, and the number of people affected is expected to almost double by 2040. The retina presents one of the highest metabolic demands in our bodies that is partially or fully fulfilled by mitochondria in the neuroretina and retinal pigment epithelium (RPE), respectively. Together with its post-mitotic status and constant photooxidative damage from incoming light, the retina requires a tightly-regulated housekeeping system that involves autophagy. The natural polyphenol Urolithin A (UA) has shown neuroprotective benefits in several models of aging and age-associated disorders, mostly attributed to its ability to induce mitophagy and mitochondrial biogenesis. Sodium iodate (SI) administration recapitulates the late stages of AMD, including geographic atrophy and photoreceptor cell death. METHODS: A combination of in vitro, ex vivo and in vivo models were used to test the neuroprotective potential of UA in the SI model. Functional assays (OCT, ERGs), cellular analysis (flow cytometry, qPCR) and fine confocal microscopy (immunohistochemistry, tandem selective autophagy reporters) helped address this question. RESULTS: UA alleviated neurodegeneration and preserved visual function in SI-treated mice. Simultaneously, we observed severe proteostasis defects upon SI damage induction, including autophagosome accumulation, that were resolved in animals that received UA. Treatment with UA restored autophagic flux and triggered PINK1/Parkin-dependent mitophagy, as previously reported in the literature. Autophagy blockage caused by SI was caused by severe lysosomal membrane permeabilization. While UA did not induce lysosomal biogenesis, it did restore upcycling of permeabilized lysosomes through lysophagy. Knockdown of the lysophagy adaptor SQSTM1/p62 abrogated viability rescue by UA in SI-treated cells, exacerbated lysosomal defects and inhibited lysophagy. CONCLUSIONS: Collectively, these data highlight a novel putative application of UA in the treatment of AMD whereby it bypasses lysosomal defects by promoting p62-dependent lysophagy to sustain proteostasis.
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Cumarinas , Animales , Ratones , Cumarinas/farmacología , Autofagia/efectos de los fármacos , Autofagia/fisiología , Degeneración Macular/metabolismo , Degeneración Macular/patología , Retina/metabolismo , Retina/efectos de los fármacos , Retina/patología , Mitofagia/efectos de los fármacos , Mitofagia/fisiología , Proteína Sequestosoma-1/metabolismo , Lisosomas/metabolismo , Lisosomas/efectos de los fármacos , Humanos , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Ratones Endogámicos C57BL , Yodatos/toxicidadRESUMEN
BACKGROUND: Iron-induced oxidative stress was thought to be the reason why the a-wave amplitude of the electroretinogram (ERG) dropped when iron ions were present. It is assumed that reactive oxygen species (ROS) are generated in the presence of iron ions, and this leads to a decrease in hyperpolarization of the photoreceptor. It is known that in age-related macular degeneration (AMD), sodium iodate can induce oxidative stress, apoptosis, and retinal damage, which mimic the effects of clinical AMD. Here, the reduction of the a-wave amplitude in mice with sodium iodate-induced age-related macular degeneration is explained. METHODS: The leading edge of the a-wave is divided into voltages developed by cones and rods. The same oxidative stress model is applied here since sodium iodate causes the creation of ROS in a manner similar to that caused by iron ions, with the exception that the retina is treated as a circuit of various resistances when computing the photoresponse. Moreover, sodium iodate also leads to apoptosis and, hence, may cause misalignment in cones (not in rods) during the initial stage of apoptosis in AMD. To include the effects of apoptosis and shortening in cones and rods, we have used a factor representing the fraction of total cones and rods that are alive. To include the effect of misalignment of cones on the reduction of the a-wave amplitude, we have used the Stiles-Crawford function to calculate the number of photoisomerizations occurring in a photoreceptor misaligned at an angle θ. The results are compared with experimental data. RESULTS: In sodium iodate-treated eyes, the ROS produced can attract calcium ions in the photoreceptor, which increases the calcium influx. In the case of the cones, the inclusion of the misalignment angle in the phototransduction process helps in determining the voltage and slope of the voltage vs. time graph.The smaller the fraction of active photoreceptors, the smaller the amplitude of the a-wave. The calcium influx, misaligned photoreceptors, and total photoreceptor loss all cause the amplitude of the a-wave to decrease, and at any time from the beginning of phototransduction cascade, the calcium influx causes the slope of the a-wave to increase. CONCLUSION: The reduction in the a-wave amplitude in the eyes of sodium iodate-treated mice is attributed to oxidative stress in both cones and rods and cone misalignment, which ultimately lead to apoptosis and vision loss in AMD.
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Electrorretinografía , Yodatos , Degeneración Macular , Estrés Oxidativo , Especies Reactivas de Oxígeno , Células Fotorreceptoras Retinianas Conos , Animales , Degeneración Macular/patología , Degeneración Macular/fisiopatología , Degeneración Macular/inducido químicamente , Ratones , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Células Fotorreceptoras Retinianas Conos/efectos de los fármacos , Células Fotorreceptoras Retinianas Conos/patología , Células Fotorreceptoras Retinianas Conos/metabolismo , Apoptosis/efectos de los fármacos , Células Fotorreceptoras Retinianas Bastones/efectos de los fármacos , Células Fotorreceptoras Retinianas Bastones/patología , Células Fotorreceptoras Retinianas Bastones/metabolismo , Modelos Animales de Enfermedad , Modelos BiológicosRESUMEN
Because the selective estrogen receptor modulator tamoxifen was shown to be retina-protective in the light damage and rd10 models of retinal degeneration, the purpose of this study was to test whether tamoxifen is retina-protective in a model where retinal pigment epithelium (RPE) toxicity appears to be the primary insult: the sodium iodate (NaIO3) model. C57Bl/6J mice were given oral tamoxifen (in the diet) or the same diet lacking tamoxifen, then given an intraperitoneal injection of NaIO3 at 25 mg/kg. The mice were imaged a week later using optical coherence tomography (OCT). ImageJ with a custom macro was utilized to measure retinal thicknesses in OCT images. Electroretinography (ERG) was used to measure retinal function one week post-injection. After euthanasia, quantitative real-time PCR (qRT-PCR) was performed. Tamoxifen administration partially protected photoreceptors. There was less photoreceptor layer thinning in OCT images of tamoxifen-treated mice. qRT-PCR revealed, in the tamoxifen-treated group, less upregulation of antioxidant and complement factor 3 mRNAs, and less reduction in the rhodopsin and short-wave cone opsin mRNAs. Furthermore, ERG results demonstrated preservation of photoreceptor function for the tamoxifen-treated group. Cone function was better protected than rods. These results indicate that tamoxifen provided structural and functional protection to photoreceptors against NaIO3. RPE cells were not protected. These neuroprotective effects suggest that estrogen-receptor modulation may be retina-protective. The fact that cones are particularly protected is intriguing given their importance for human visual function and their survival until the late stages of retinitis pigmentosa. Further investigation of this protective pathway could lead to new photoreceptor-protective therapeutics.
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Modelos Animales de Enfermedad , Electrorretinografía , Yodatos , Ratones Endogámicos C57BL , Degeneración Retiniana , Tamoxifeno , Tomografía de Coherencia Óptica , Animales , Yodatos/toxicidad , Ratones , Tomografía de Coherencia Óptica/métodos , Tamoxifeno/farmacología , Degeneración Retiniana/prevención & control , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/metabolismo , Degeneración Retiniana/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/patología , Rodopsina/metabolismo , Rodopsina/genética , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , ARN Mensajero/genética , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/metabolismo , Opsinas de Bastones/metabolismoRESUMEN
Organoiodine compounds (OICs) are the dominant iodine species in groundwater systems. However, molecular mechanisms underlying the geochemical formation of geogenic OICs-contaminated groundwater remain unclear. Based upon multitarget field monitoring in combination with ultrahigh-resolution molecular characterization of organic components for alluvial-lacustrine aquifers, we identified a total of 939 OICs in groundwater under reducing and circumneutral pH conditions. In comparison to those in water-soluble organic matter (WSOM) in sediments, the OICs in dissolved organic matter (DOM) in groundwater typically contain fewer polycyclic aromatics and polyphenol compounds but more highly unsaturated compounds. Consequently, there were two major sources of geogenic OICs in groundwater: the migration of the OICs from aquifer sediments and abiotic reduction of iodate coupled with DOM iodination under reducing conditions. DOM iodination occurs primarily through the incorporation of reactive iodine that is generated by iodate reduction into highly unsaturated compounds, preferably containing hydrophilic functional groups as binding sites. It leads to elevation of the concentration of the OICs up to 183 µg/L in groundwater. This research provides new insights into the constraints of DOM molecular composition on the mobilization and enrichment of OICs in alluvial-lacustrine aquifers and thus improves our understanding of the genesis of geogenic iodine-contaminated groundwater systems.
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Agua Subterránea , Yodo , Contaminantes Químicos del Agua , Yodatos , Contaminantes Químicos del Agua/análisis , Agua Subterránea/química , Agua , Monitoreo del AmbienteRESUMEN
Purpose: Geographic atrophy (GA) is an advanced form of dry age-related macular degeneration with multifactorial etiology and no well-established treatment. A model recapitulating the hallmarks would serve as a key to understanding the underlying pathologic mechanisms better. In this report, we further characterized our previously reported subretinal sodium iodate model of GA. Methods: Retinal degeneration was induced in rats (6-8 weeks old) by subretinal injections of NaIO3 as described previously. Animals were sacrificed at 3, 8 and 12 weeks after injection and eyes were fixed or cryopreserved. Some choroids were processed as flatmounts while other eyes were cryopreserved, sectioned, and immunolabeled with a panel of antibodies. Finally, some eyes were prepared for transmission electron microscopic (TEM) analysis. Results: NaIO3 subretinal injection resulted in a well-defined focal area of retinal pigment epithelium (RPE) degeneration surrounded by viable RPE. These atrophic lesions expanded over time. RPE morphologic changes at the border consisted of hypertrophy, multilayering, and the possible development of a migrating phenotype. Immunostaining of retinal sections demonstrated external limiting membrane descent, outer retinal tubulation (ORT), and extension of Müller cells toward RPE forming a glial membrane in the subretinal space of the atrophic area. TEM findings demonstrated RPE autophagy, cellular constituents of ORT, glial membranes, basal laminar deposits, and defects in Bruch's membrane. Conclusions: In this study, we showed pathologic features of a rodent model resembling human GA in a temporal order through histology, immunofluorescence, and TEM analysis and gained insights into the cellular and subcellular levels of the GA-like phenotypes. Translational Relevance: Despite its acute nature, the expansion of atrophy and the GA-like border in this rat model makes it ideal for studying disease progression and provides a treatment window to test potential therapeutics for GA.
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Atrofia Geográfica , Degeneración Retiniana , Humanos , Ratas , Animales , Retina , Epitelio Pigmentado de la Retina/patología , Yodatos , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/patologíaRESUMEN
In aquatic settings, radioactive iodine from nuclear waste can exist as iodate (IO3-). This study explored the efficiency and mechanism of IO3- adsorption by minimally modified anthocyanin-based adsorbents. Pomegranate peels and mangosteen pericarps were selected from an initial screening test and could remove over 70% of 10 mg/L IO3-. The adsorbents yielded adsorption capacity (q) of 9.59 mg/g and 2.31 mg/g, respectively, at room temperature. At 5 °C, q values increased to 14.5 and 5.13 mg/g, respectively. Pomegranate peels showed superior performance, with approximately 4 times the anthocyanin content of mangosteen pericarps. Both adsorbents took 120 min to reach adsorption equilibrium, and no desorption was observed after 8 days (I-131 half-time). Confirmation of physisorption was indicated by the fit of the pseudo-first-order reaction model, negative entropy (exothermic), and negative activation energy (Arrhenius equation). IO3- inclusion was confirmed through adsorbent surface modifications in scanning electron microscope images, the increased iodine content post-adsorption in energy-dispersive X-ray spectroscopy analysis, and alterations in peaks corresponding to anthocyanin-related functional groups in Fourier transform infrared spectroscopy analysis. X-ray absorption near-edge spectroscopy at 4564.54 eV showed that iodine was retained in the form of IO3-. Through the computational analysis, electrostatic forces, hydrogen bonds, and π-halogen interactions were deduced as mechanisms of IO3- adsorption by anthocyanin-based adsorbents. Anthocyanin-rich fruit wastes emerged as sustainable materials for eliminating IO3- from water.
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Antocianinas , Yodatos , Adsorción , Antocianinas/química , Antocianinas/aislamiento & purificación , Yodatos/química , Frutas/química , Radioisótopos de Yodo/química , Contaminantes Radiactivos del Agua/química , Purificación del Agua/métodosRESUMEN
Sodium iodate (NaIO3) is a commonly used model for age-related macular degeneration (AMD), but its rapid and severe induction of retinal pigment epithelial (RPE) and photoreceptor degeneration can lead to the premature dismissal of potentially effective therapeutics. Additionally, little is known about how sex and age affect the retinal response to NaIO3. This study aims to establish a less severe yet reproducible regimen by testing low doses of NaIO3 while considering age- and sex-related effects, enabling a broader range of therapeutic evaluations. In this study, young (3-5 months) and old (18-24 months) male and female C57Bl/6J mice were given an intraperitoneal (IP) injection of 15, 20, or 25 mg/kg NaIO3. Damage assessment one week post-injection included in vivo imaging, histological examination, and qRT-PCR analysis. The results revealed that young mice showed no damage at 15 mg/kg IP NaIO3, with varying degrees of damage observed at 20 mg/kg. At 25 mg/kg, most young mice displayed widespread retinal damage, with females exhibiting less retinal thinning than males. In contrast, older mice at 20 and 25 mg/kg displayed a more patchy degeneration pattern, outer retinal undulations, and greater variability in degeneration than the young mice. The most effective model for minimizing damage while maintaining consistency utilizes young female mice injected with 25 mg/kg NaIO3. The observed sex- and age-related differences underscore the importance of considering these variables in research, aligning with the National Institutes of Health's guidance. While the model does not fully replicate the complexity of AMD, these findings enhance its utility as a valuable tool for testing RPE/photoreceptor protective or replacement therapies.
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Degeneración Macular , Degeneración Retiniana , Femenino , Masculino , Ratones , Animales , Retina/patología , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/patología , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/patología , Yodatos/toxicidad , Ratones Endogámicos C57BL , Epitelio Pigmentado de la Retina/patología , Modelos Animales de EnfermedadRESUMEN
Age-related macular degeneration (AMD) is a global health challenge. AMD causes visual impairment and blindness, particularly in older individuals. This multifaceted disease progresses through various stages, from asymptomatic dry to advanced wet AMD, driven by various factors including inflammation and oxidative stress. Current treatments are effective mainly for wet AMD; the therapeutic options for dry AMD are limited. Photobiomodulation (PBM) using low-energy light in the red-to-near-infrared range is a promising treatment for retinal diseases. This study investigated the effects of multi-wavelength PBM (680, 780, and 830 nm) on sodium iodate-induced oxidatively damaged retinal tissue. In an in vivo rat model of AMD induced by sodium iodate, multi-wavelength PBM effectively protected the retinal layers, reduced retinal apoptosis, and prevented rod bipolar cell depletion. Furthermore, PBM inhibited photoreceptor degeneration and reduced retinal pigment epithelium toxicity. These results suggest that multi-wavelength PBM may be a useful therapeutic strategy for AMD, mitigating oxidative stress, preserving retinal integrity, and preventing apoptosis.
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Terapia por Luz de Baja Intensidad , Degeneración Macular Húmeda , Animales , Ratas , Yodatos/toxicidad , RetinaRESUMEN
Purpose: Inflammation and oxidative stress contribute to age-related macular degeneration (AMD) and other retinal diseases. We tested a cell-penetrating peptide from the kinase inhibitory region of an intracellular checkpoint inhibitor suppressor of cytokine signaling 3 (R9-SOCS3-KIR) peptide for its ability to blunt the inflammatory or oxidative pathways leading to AMD. Methods: We used anaphylatoxin C5a to mimic the effect of activated complement, lipopolysaccharide (LPS), and tumor necrosis factor alpha (TNFα) to stimulate inflammation and paraquat to induce mitochondrial oxidative stress. We used a human retinal pigment epithelium (RPE) cell line (ARPE-19) as proliferating cells and a mouse macrophage cell line (J774A.1) to follow cell propagation using microscopy or cell titer assays. We evaluated inflammatory pathways by monitoring the nuclear translocation of NF-κB p65 and mitogen-activated protein kinase p38. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot were used to evaluate the induction of inflammatory markers. In differentiated ARPE-19 monolayers, we evaluated the integrity of tight junction proteins through microscopy and the measurement of transepithelial electrical resistance (TEER). We used intraperitoneal injection of sodium iodate in mice to test the ability of R9-SOC3-KIR to prevent RPE and retinal injury, as assessed by fundoscopy, optical coherence tomography, and histology. Results: R9-SOCS3-KIR treatment suppressed C5a-induced nuclear translocation of the NF-kB activation domain p65 in undifferentiated ARPE-19 cells. TNF-mediated damage to tight junction proteins in RPE, and the loss of TEER was prevented in the presence of R9-SOCS3-KIR. Treatment with the R9-SOCS3-KIR peptide blocked the C5a-induced expression of inflammatory genes. The R9-SOCS3-KIR treatment also blocked the LPS-induced expression of interleukin-6, MCP1, cyclooxygenase 2, and interleukin-1 beta. R9-SOCS3-KIR prevented paraquat-mediated cell death and enhanced the levels of antioxidant effectors. Daily eye drop treatment with R9-SOCS3-KIR protected against retinal injury caused by i.p. administration of sodium iodate. Conclusions: R9-SOCS3-KIR blocks the induction of inflammatory signaling in cell culture and reduces retinal damage in a widely used RPE/retinal oxidative injury model. As this peptide can be administered through corneal instillation, this treatment may offer a convenient way to slow down the progression of ocular diseases arising from inflammation and chronic oxidative stress.
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Yodatos , Degeneración Macular , Enfermedades de la Retina , Humanos , Animales , Ratones , Lipopolisacáridos , Paraquat , Retina , Estrés Oxidativo , Péptidos , Inflamación , Proteínas de Uniones Estrechas , CitocinasRESUMEN
As soluções volumétricas são rotineiramente utilizadas nos laboratórios, principalmente nos processos de síntese de produtos e nas análises quantitativas de matéria-prima e/ou produto acabado, entretanto poucos são os estudos que abordam a estabilidade destas soluções. Considerando que a qualidade das soluções volumétricas pode afetar os procedimentos de análises químicas e consequentemente induzir a erros, e ainda que, a Farmacopeia Brasileira (2010) não cita tempo máximo de utilização dessas soluções padronizadas, a avaliação da estabilidade das mesmas é importante. Sendo assim, o objetivo do trabalho foi avaliar a estabilidadede 10 soluções volumétricas, empregadas rotineiramente em laboratórios de análises químicas, com o intuito de estabelecer o período que essas soluções permanecem estáveis, isto é, sem sofrer alteração na concentração. As metodologias de preparo e padronização das soluções volumétricas seguiram os métodos descritos na Farmacopeia Brasileira (2010), sendo as mesmas padronizadas no momento do preparo e a cada 20 dias, por um período de 180 dias. As soluções contendo ácidos e bases, bem como as soluções de iodato de potássio e nitrato de prata, permaneceram constantes durante o período de análises. As soluções de EDTA, iodo, nitrito de sódio, permanganato de potássio e tiossulfato de sódio apresentaram estabilidade inferior a 180 dias, tornando necessária a realização de padronização periódica. As soluções volumétricas utilizadas nos laboratórios apresentam diferentes estabilidades, o que ressalta a importância da determinação do período que as mesmas se mantêmcom as concentrações estáveis, evitando possíveis alterações de resultados nas análises químicas.
Volumetric solutions are routinely used in laboratories, mainly in product synthesis processes and in quantitative analyzes of raw materials and/or finished products, however there are few studies that address the stability of these solutions. Considering that the quality of volumetric solutions can affect chemical analysis procedures and consequently induce errors, and even though the Brazilian Pharmacopoeia (2010) does not mention the maximum time for using these standardized solutions, the evaluation of their stability is important. Therefore, the aim of this work was to evaluate the stability of 10 volumetric solutions, routinely used in chemical analysis laboratories, in order to establish the period that these solutions remain stable without changing their concentrations. The methodologies for preparing and standardizing the volumetric solutions followed the methods described in the Brazilian Pharmacopoeia (2010), being standardized at the time of preparation and every 20 days, for a period of 180 days. Solutions containing acids and bases, as well as potassium iodate and silver nitrate solutions, were stable during the analysis period. The solutions of EDTA, iodine, sodium nitrite, potassium permanganate and sodium thiosulfate showed stability less than 180 days, making it necessary to carry out periodic standardization of these solutions. The volumetric solutions used in the laboratories have different stabilities, which highlights the importance of determining the period in which they remain stable, avoiding possible changes in results in chemical analyzes.
Las soluciones volumétricas se utilizan de forma rutinaria en los laboratorios, principalmente en los procesos de síntesis de productos y en el análisis cuantitativo de materias primas y/o productos acabados. Sin embargo, existen pocos estudios que aborden la estabilidad de estas soluciones. Considerando que la calidad de las soluciones volumétricas puede afectar los procedimientos de análisis químico y consecuentemente inducir a errores, y también que, la Farmacopea Brasileña (2010) no menciona el tiempo máximo de uso de estas soluciones estandarizadas, la evaluación de su estabilidad es importante. Así, el objetivo del trabajo fue evaluar la estabilidad de 10 soluciones volumétricas, utilizadas rutinariamente en los laboratorios de análisis químico, con el fin de establecer el período en que estas soluciones permanecen estables, es decir, sin sufrir alteraciones en la concentración. Las metodologías de preparación y estandarización de las soluciones volumétricas siguieron los métodos descritos en la Farmacopea Brasileña (2010), siendo las mismas estandarizadas en el momento de la preparación y cada 20 días, por un período de 180 días. Las soluciones que contienen ácidos y bases, así como las soluciones de yodato de potasio y nitrato de plata, permanecieron constantes durante el periodo de análisis. Las soluciones de EDTA, yodo, nitrito de sodio, permanganato de potasio y tiosulfato de sodio fueron estables durante menos de 180 días, por lo que fue necesario realizar estandarizaciones periódicas. Las soluciones volumétricas utilizadas en los laboratorios presentan diferentes estabilidades, lo que pone de manifiesto la importancia de determinar el periodo que permanecen con concentraciones estables, evitando posibles cambios en los resultados en los análisis químicos.
Asunto(s)
Volumetría , Químicos de Laboratorio/análisis , Laboratorios Clínicos , Periodicidad , Permanganato de Potasio/análisis , Estándares de Referencia , Nitrato de Plata/análisis , Nitrito de Sodio/análisis , Tiosulfatos/análisis , Farmacopea Brasileña , Yodatos/análisisRESUMEN
One titrimetric and two spectrophotometric methods are proposed for the determination of diethylcarbamazine citrate (DEC) in bulk drug and in formulations using potassium iodate and potassium iodide as reagent. The methods employ the well-known analytical reaction between iodate and iodide in the presence of acid. In titrimetry (method A), the drug was treated with a measured excess of thiosulfate in the presence of unmeasured excess of iodate-iodide mixture and after a standing time of 10 min, the surplus thiosulfate was determined by back titration with iodine towards starch end point. Titrimetric assay is based on a 1:3 reaction stoichiometry between DEC and iodine and the method is applicable over 2.0-10.0 mg range. The liberated iodine is measured spectrophotometrically at 370 nm (method B) or the iodine-starch complex measured at 570 nm (method C). In both methods, the absorbance is found to be linearly dependent on the concentration of iodine, which in turn is related to DEC concentration. The calibration curves are linear over 2.5-50 and 2.5-30 µg mL-1 DEC for method B and method C, respectively. The calculated molar absorptivity and Sandell sensitivity values were 6.48×103 L mol-1 cm-1 and 0.0604 µg cm-2, respectively, for method B, and their respective values for method C are 9.96×103 L mol-1 cm-1 and 0.0393 µg cm-2. The intra-day and inter-day accuracy and precision studies were carried out according to the ICH guidelines. The methods were successfully applied to the analysis of DEC formulations.
Propõem-se titulação e dois métodos espectrofotométricos para a determinação de citrato de dietilcarbamazina (DEC) a granel e em suas formulações, usando iodato de potássio e iodeto de potássio como reagente. Os métodos utilizam a reação analítica conhecida entre iodato e iodeto, na presença de ácido. Na titulometria (Método A), o fármaco foi tratado com excesso medido de tiossulfato, na presença de excesso não medido de mistura iodato-iodeto e, depois de um tempo de repouso de 10 min, o excesso de tiossulfato foi determinado por titulação de retorno com iodo até o ponto final com amido. A titulação é baseada em reação com estequiometria 1:3 entre DEC e iodo e o método é aplicável na faixa de 2.0-10.0 mg. O iodo liberado é medido espectrofotometricamente a 370 nm (método B) ou o complexo de iodo-amido medido a 570 nm (método C). Em ambos os métodos, a absorvância é considerada linearmente dependente da concentração de iodo, a qual, por sua vez, está relacionada à concentração de DEC. As curvas de calibração são lineares para concentrações de DEC de 2.5-50 e 2.5-30 mg mL- 1 para o método B e para o método C, respectivamente. A absortividade molar calculada e os valores de sensibilidade Sandel foram 6.48×103 L mol-1 cm- 1 e 0.0604 ug cm-2, respectivamente, para o método B, e os seus respectivos valores para o método C são 9.96×103 L mol-1 cm-1 e 0.0393 mg cm-2. Os estudos de exatidão e precisão intra-dia e inter-dia foram realizados de acordo com as diretrizes da ICH. Os métodos foram aplicados com sucesso na análise de formulações de DEC.
Asunto(s)
Espectrofotometría , Dietilcarbamazina/análisis , Yodatos/análisis , Yoduros/análisis , Química Farmacéutica/clasificación , Volumetría/métodosRESUMEN
El propósito de este trabajo ha sido el de estimar por intermedio de la medición de la yoduria y la natriuria y ulterior cálculo de la saluresis, en 710 escolares entre 6 y 14 años, el efecto de la campaña ya citada en la región Suroccidental andina (SOA) y compararla con las de las regiones Central (C) y Nor Oriental Costera (NOC), donde no se efectuó tal campaña. La muestra de orina se mostró en 12 escuelas de la región andina y 5 de las otras regiones, en forma aleatoria de niños de uno y otro sexo, Graffar IV, y V. La yoduria se midió por una variante del método colorimétrico de oxidoreducción del cérico-arsenioso por el I. La natriuria se midió por potenciometría, con un electrodo específico de Na. La saluresis como NaCl, se calculó a partir de la natriuria. Se relacionaron además estas tres variables con la edad, sexo. Indice de Masa Corporal (IMC) y el número de habitantes de cada poblado estudiado. Se encontró una mayor y significativa diferencia en la excreción de I, Na y NaCl, en la región SOA, que en las C y NOC. Y no así al compararlas con las variables auxológicas, sexo o tamaño del poblado. Se encontraron yodurias bajas pero aceptables de acuerdo con la OMS, al igual que elevadas. No obstante el promedio de la saluresis fue de 9,32 ± 3,65 g/d en la región SOA y menor en las otras dos regiones, cifra que se estima elevada tratándose de niños, con el consecuente riesgo de que desarrollen a futuro hipertensión arterial, de habituarse a esta ingesta de sal. Se recomienda repetir estos estudios, con especial énfasis en el consumo de sal y de confirmarse, rediseñar la campaña educativa a favor del consumo de sal yodada a fin de lograr un consumo adecuado de yodo a la par que de sal
Asunto(s)
Humanos , Adolescente , Niño , Niño , Promoción de la Salud , Yodatos , Yodo , Deficiencia de Yodo , Natriuresis , Sodio , Cloruro de Sodio , Endocrinología , CienciaRESUMEN
Foi verificada a estabilidade do teor de iodo no sal refinado e moído, durante o tempo de prateleira, no período de dois anos, armazenado em condiçöes ambientais. Dezenove amostras recém-iodadas foram coletadas em usinas beneficiadoras de sal e analisadas a cada três meses. Constatou-se que o teor de iodo permaneceu inalterado. As amostras também foram analisadas após cocçäo com água, por uma e duas horas, no início e final do presente trabalho. Na dosagem do teor de iodo no sal foi utilizada a técnica indicada nas Normas Analíticas do Instituto Adolfo Lutz. A determinaçäo da estabilidade do iodo no sal é imprescindível para fixar o prazo de validade desse produto, uma vem que o sal iodado é o mais eficiente meio de profilaxia existente na ocorrência do bócio. E, por este trabalho, ficou constatada a estabilidade do teor de iodo no sal no período de dois anos nas condiçöes estabelecidas
Asunto(s)
Yodatos , Yodo , Cloruro de SodioRESUMEN
Se presenta la experiencia con 72 pacientes con diferentes patologías, en quienes se realizó tratamiento endovascular con embolización selectiva. Se discuten la técnica, diferentes materiales utilizados, resultados y complicaciones. Se concluye que la EE constituye una excelente alternativa terapéutica pre-quirúrgica, paliativa o definitiva, de fácil realización en centros especialmente entrenados
Asunto(s)
Humanos , Masculino , Femenino , Embolización Terapéutica/métodos , Aneurisma/terapia , Angiografía , Medios de Contraste , Embolización Terapéutica/efectos adversos , Embolización Terapéutica/instrumentación , Epistaxis/terapia , Esponja de Gelatina Absorbible/uso terapéutico , Hematuria/terapia , Hemoptisis/terapia , Yodatos , Neoplasias Renales/terapia , Metilcelulosa/uso terapéutico , Cuidados Paliativos , Varicocele/terapiaAsunto(s)
Yodatos/efectos adversos , Mala Praxis/tendencias , Radiografía/efectos adversos , Medios de Contraste/efectos adversos , Hipersensibilidad a las Drogas/prevención & control , Hipersensibilidad Inmediata/inducido químicamente , Seguro de Responsabilidad Civil/legislación & jurisprudencia , Seguro de Responsabilidad Civil/tendencias , Mala Praxis/legislación & jurisprudenciaRESUMEN
Con el propósito de determinar la factibilidad de realizar una preparación preoperatoria abreviada mediante el uso de dexametasona(Dex) e iodato de sodio(IS) en pacientes con EBG, se analizan prospectivamente 11 casos tratados entre febrero de 1985 y abril de 1987. Su hipertiroidismo se determinó por hallazgos clínicos y de laboratorio y se sometieron a tiroidectomía subtotal bilateral, una vez obtenido el eutiroidismo, al 4o día de iniciada la preparación. Durante la intervención se evaluó el comportamiento hemodinámico y las características de la glándula, con el fin de establecer los efectos de agresión anestésico quirúrgica, observándose estabilidad hemodinámica y moderada disminución de la hipervascularización glandular. Mediante microscopia óptica y electrónica de las glándulas extirpadas se evaluaron las alteraciones histológicas producidas por la Dex e IS. No se registró mortalidad y sólo 2 ,pacientes presentaron seroma de herida operatoria