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1.
Photochem Photobiol Sci ; 23(5): 987-996, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38662174

RESUMEN

Pycnoporus sanguineus is a fungus of the phylum Basidiomycota that has many applications in traditional medicine, modern pharmaceuticals, and agricultural industries. Light plays an essential role in the metabolism, growth, and development of fungi. This study evaluated the mycelial growth and antioxidant and anti-inflammatory activities in P. sanguineus fermentation broth (PFB) cultured under different wavelengths of LED irradiation or in the dark. Compared to the dark cultures, the dry weight of mycelia in red- and yellow-light cultures decreased by 37 and 35% and the yields of pigments increased by 30.92 ± 2.18 mg and 31.75 ± 3.06 mg, respectively. Compared with the dark culture, the DPPH free radical scavenging ability, ABTS+ free radical scavenging capacity, and reducing power of yellow-light cultures increased significantly, and their total phenolic content peaked at 180.0 ± 8.34 µg/mL. However, the reducing power in blue-light cultures was significantly reduced, though the total phenol content did not vary with that of dark cultures. In LPS- and IFN-γ-stimulated RAW 264.7 cells, nitrite release was significantly reduced in the red and yellow light-irradiated PFB compared with the dark culture. In the dark, yellow-, and green-light cultures, TNF-α production in the inflamed RAW 264.7 cells was inhibited by 62, 46, and 14%, respectively. With red-, blue-, and white-light irradiation, TNF-α production was significantly enhanced. Based on these results, we propose that by adjusting the wavelength of the light source during culture, one can effectively modulate the growth, development, and metabolism of P. sanguineus.


Asunto(s)
Antioxidantes , Luz , Pycnoporus , Ratones , Animales , Antioxidantes/farmacología , Antioxidantes/química , Antioxidantes/metabolismo , Células RAW 264.7 , Pycnoporus/metabolismo , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Lipopolisacáridos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Picratos/antagonistas & inhibidores , Picratos/química , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Compuestos de Bifenilo/antagonistas & inhibidores , Compuestos de Bifenilo/química , Compuestos de Bifenilo/farmacología
2.
bioRxiv ; 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38586045

RESUMEN

Photoreceptor loss results in vision loss in many blinding diseases, and metabolic dysfunction underlies photoreceptor degeneration. So, exploiting photoreceptor metabolism is an attractive strategy to prevent vision loss. Yet, the metabolic pathways that maintain photoreceptor health remain largely unknown. Here, we investigated the dependence of photoreceptors on Gln catabolism. Gln is converted to glutamate via glutaminase (GLS), so mice lacking GLS in rod photoreceptors were generated to inhibit Gln catabolism. Loss of GLS produced rapid rod photoreceptor degeneration. In vivo metabolomic methodologies and metabolic supplementation identified Gln catabolism as critical for glutamate and aspartate biosynthesis. Concordant with this amino acid deprivation, the integrated stress response (ISR) was activated with protein synthesis attenuation, and inhibiting the ISR delayed photoreceptor loss. Furthermore, supplementing asparagine, which is synthesized from aspartate, delayed photoreceptor degeneration. Hence, Gln catabolism is integral to photoreceptor health, and these data reveal a novel metabolic axis in these metabolically-demanding neurons.

3.
Doc Ophthalmol ; 148(2): 121-128, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38265517

RESUMEN

PURPOSE: To report our findings of reduced full-field electroretinograms (ff-ERGs) and abnormal optical coherence tomographic (OCT) images in a patient with poor visual acuity after cataract surgery who was eventually diagnosed with vitamin A deficiency (VAD). METHODS: This was a clinical study of a patient who complained of blurred vision after cataract surgery. To determine the cause of the reduced vision, we recorded full-field electroretinograms (ff-ERGs) to determine the scotopic and photopic status of the retina. We also performed optical coherence tomography to assess the changes in the retinal structure. Serological tests were performed. RESULTS: A 74-year-old man presented with persistent corneal epithelial damages and reduced vision that developed after conventional cataract surgery. OCT showed an interrupted ellipsoid zone, and fundus autofluorescence (FAF) showed a severe hypofluorescence in the retina of the left eye. The scotopic ff-ERGs were severely reduced, and the photopic ff-ERGs were mildly reduced. Serological examinations revealed a vitamin A concentration < 7 IU/dL (normal, 97-316 IU/dL). Based on these findings, we diagnosed the patient with VAD and started treatment with oral vitamin A supplements. After three months, his visual acuity, ff-ERGs, and OCT findings recovered to normal levels. The amplitudes and implicit times of the RETeval flicker ERGs increased to be within the normal range, and the hypofluorescence of the left eye disappeared. The length of the photoreceptor outer segments increased after the vitamin A supplementation. CONCLUSION: Our findings indicate that the ERGs are helpful for diagnosing patients with VAD associated with persistent corneal epithelial damages.


Asunto(s)
Catarata , Baja Visión , Deficiencia de Vitamina A , Masculino , Humanos , Anciano , Electrorretinografía/métodos , Deficiencia de Vitamina A/diagnóstico , Deficiencia de Vitamina A/etiología , Vitamina A , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/etiología , Tomografía de Coherencia Óptica/métodos
4.
J Lasers Med Sci ; 14: e55, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38028864

RESUMEN

Introduction: Low-level laser therapy (LLLT), also called Photobiomodulation, has gained widespread acceptance as a mainstream modality, particularly in the form of photobiostimulation (PBM). Here in our review, we aim to present the application of LLLT to help with depression, explore potential action mechanisms and pathways, discuss existing limitations, and address the challenges associated with its clinical implementation. Methods: In biological systems, the visible light with a wavelength range of 400-700 nm activates photoreceptors involved in vision and circadian rhythm regulation. The near-infrared (NIR) light with a wavelength range of 800-1100 nm exhibits superior tissue penetration capabilities compared to the visible light, which enables the non-invasive application of LLLT to various tissues. Results: By enhancing adenosine triphosphate (ATP) production using the respiratory chain, LLLT is able to enhance blood flow, reduce inflammation, support repair and healing, and enhance stem cell growth and proliferation. Preclinical studies using animal models have shown promising neuroprotective effects of the LLLT method on central nervous system (CNS) diseases, suggesting potential improvements in brain function for patients suffering from Alzheimer's disease. In addition, it helps Parkinson's patients with their movement problems and ameliorates mental disorders in individuals with depression. Conclusion: patients' quality of life can be significantly enhanced. A comprehensive understanding of the protective effects and underlying mechanisms of LLLT will facilitate its therapeutic application in the future.

5.
BMC Plant Biol ; 23(1): 358, 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37442951

RESUMEN

BACKGROUND: GLutamate Receptor-like (GLR) channels are multimeric, ionotropic, ligand-gated plant transmembrane receptors. They are homologous to mammalian glutamate receptors, iGLuRs, which are critical to neuronal function. GLRs have been reported several times to play a role in photomorphogenesis. However, to date, no study has looked at the mechanism of their involvement in this process. Here we focused on examining the impact of GLRs on the regulation of early seedling growth in blue light, red light, and in the dark. RESULTS: Wild type and six photoreceptor mutant seedlings were grown on media supplemented with known iGLuR/GLR channel antagonists: MK-801, which non-competitively blocks NMDA channels in mammalian cells, and CNQX, known for competitive blocking of AMPA channels in mammalian cells. The lengths of hypocotyls and roots were measured in seedlings of phyA, phyB, phot1, phot2, cry1, and cry2 mutants after 7 days of in vitro culture. Changes in growth parameters, both in light and in darkness upon application of chemical antagonists, show that both types of GLR channels, NMDA-like and AMPA-like, are involved in the regulation of seedling growth irrespective of light conditions. Analysis of seedling growth of photoreceptor mutants indicates that the channels are influenced by signaling from phot1, phot2, and cry1. To extend our analysis, we also evaluated the elicitation of a calcium wave, which is likely to be partially driven by GLRs, in Arabidopsis seedlings. The changes in cellobiose-induced calcium waves observed after applying GLR inhibitors suggest that both types of channels likely cooperate in shaping Arabidopsis seedling growth and development. CONCLUSIONS: Our work provides the first experimental evidence that two types of GLR channels function in plants: NMDA-like and AMPA-like. We also demonstrate that the channels are involved in seedling growth and development, at least partially through modulation of calcium signaling, but they are unlikely to play a major role in photomorphogenesis.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Plantones/genética , Proteínas de Arabidopsis/genética , N-Metilaspartato , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico , Plantas , Mutación
6.
Phytomedicine ; 115: 154828, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37116386

RESUMEN

BACKGROUND: Retinitis pigmentosa (RP) refers to a group of progressive photoreceptor degenerative diseases. The activation of microglia has been reported to play an important role in the photoreceptor degeneration in RP retinal. Bujing Yishi tablets (BJYS), a Chinese herbal medicine, has been used to treat retinal diseases in China with desirable effect in improving visual function. However, the mechanisms underlying the efficacy of BJYS treatment in RP are not yet fully understood. PURPOSE: Based on the preliminary experiments, this study aimed to investigate the therapeutic mechanism involved in treating N-Methyl-N-Nitrosourea (MNU)-induced retinal degeneration of RP with BJYS. METHODS: To explore the efficacy of BJYS, a rat experimental RP model was established through intraperitoneal injection of MNU (50 mg/kg). Two experiment was carried out. After the treatment, we conducted H&E, TUNEL, retinal cytokine levels and IBA-1 expression in microglia to confirm the impact on RP model. The specific mechanism of action of BJYS tablet was assessed by western blot, real-time polymerase chain reaction (RT-PCR), and immunofluorescence to determine the mRNA and protein expression levels involved in clarifying the effectiveness of BJYS exerted through P2X7R/CX3CL1/CX3CR1 pathway. RESULTS: Significant alleviation of retinal morphological structure and photoreceptor degeneration by BJYS treatment was observed in the retinal of MNU-induced RP rats, BJYS prevented the reduction of ONL thickness and decreased the level of apoptotic cells in ONL. It also inhibited microglia overactivation and reduced retinal levels of IL-1ß, IL-6, TNF-α. In addition, BJYS decreased the protein expression and mRNA expression of P2X7, CX3CL1 and CX3CR1 and reduced the phosphorylation of p38 MAPK. CONCLUSION: In summary, this study suggested that BJYS treatment could alleviate photoreceptors degeneration of RP by inhibiting microglia overactivation and inflammation through the P2X7R/CX3CL1/CX3CR1 pathway. These effects suggest that BJYS tablets may serve as a promising oral therapeutic agent for RP.


Asunto(s)
Degeneración Retiniana , Retinitis Pigmentosa , Ratas , Animales , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/metabolismo , Células Fotorreceptoras/metabolismo , Retina , Degeneración Retiniana/inducido químicamente , Muerte Celular , Compuestos de Nitrosourea/efectos adversos , Compuestos de Nitrosourea/metabolismo , Apoptosis , Modelos Animales de Enfermedad , Quimiocina CX3CL1/efectos adversos , Quimiocina CX3CL1/metabolismo , Receptor 1 de Quimiocinas CX3C/metabolismo
7.
Pharmaceutics ; 15(2)2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36840007

RESUMEN

Retinitis pigmentosa (RP) is a heterogeneous group of hereditary diseases characterized by progressive degeneration of retinal photoreceptors leading to progressive visual decline. It is the most common type of inherited retinal dystrophy and has a high burden on both patients and society. This condition causes gradual loss of vision, with its typical manifestations including nyctalopia, concentric visual field loss, and ultimately bilateral central vision loss. It is one of the leading causes of visual disability and blindness in people under 60 years old and affects over 1.5 million people worldwide. There is currently no curative treatment for people with RP, and only a small group of patients with confirmed RPE65 mutations are eligible to receive the only gene therapy on the market: voretigene neparvovec. The current therapeutic armamentarium is limited to retinoids, vitamin A supplements, protection from sunlight, visual aids, and medical and surgical interventions to treat ophthalmic comorbidities, which only aim to slow down the progression of the disease. Considering such a limited therapeutic landscape, there is an urgent need for developing new and individualized therapeutic modalities targeting retinal degeneration. Although the heterogeneity of gene mutations involved in RP makes its target treatment development difficult, recent fundamental studies showed promising progress in elucidation of the photoreceptor degeneration mechanism. The discovery of novel molecule therapeutics that can selectively target specific receptors or specific pathways will serve as a solid foundation for advanced drug development. This article is a review of recent progress in novel treatment of RP focusing on preclinical stage fundamental research on molecular targets, which will serve as a starting point for advanced drug development. We will review the alterations in the molecular pathways involved in the development of RP, mainly those regarding endoplasmic reticulum (ER) stress and apoptotic pathways, maintenance of the redox balance, and genomic stability. We will then discuss the therapeutic approaches under development, such as gene and cell therapy, as well as the recent literature identifying novel potential drug targets for RP.

8.
Biosci Biotechnol Biochem ; 87(4): 378-388, 2023 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-36617234

RESUMEN

Blue light causes retinal damage that can lead to ocular diseases such as age-related macular degeneration. In this study, we determined the protective effect of blueberry stem extract (BStEx) and active components on blue light-emitting diode (LED) light-induced retinal photoreceptor cell damage in vitro. Photoreceptor cells cultured in the presence of BStEx or components were exposed to blue light to induce cell damage. BStEx, fractions of BStEx containing proanthocyanidins, chlorogenic acid, catechin, and epicatechin prevented the cell damage and/or inhibited the generation of reactive oxygen species (ROS). Furthermore, BStEx reduced apoptosis and cell death, and inhibited the phosphorylation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase leading to cellular apoptosis induced by blue light exposure. These findings suggest that BStEx and components exert a protective effect against blue light-induced photoreceptor cell damage through the inhibition of MAPK phosphorylation and ROS production.


Asunto(s)
Arándanos Azules (Planta) , Arándanos Azules (Planta)/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Retina , Apoptosis , Células Fotorreceptoras de Vertebrados/metabolismo , Luz , Extractos Vegetales/farmacología , Extractos Vegetales/metabolismo
9.
Biomolecules ; 12(12)2022 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-36551307

RESUMEN

UV-B and UV-A radiation are natural components of solar radiation that can cause plant stress, as well as induce a range of acclimatory responses mediated by photoreceptors. UV-mediated accumulation of flavonoids and glucosinolates is well documented, but much less is known about UV effects on carotenoid content. Carotenoids are involved in a range of plant physiological processes, including photoprotection of the photosynthetic machinery. UV-induced changes in carotenoid profile were quantified in plants (Arabidopsis thaliana) exposed for up to ten days to supplemental UV radiation under growth chamber conditions. UV induces specific changes in carotenoid profile, including increases in antheraxanthin, neoxanthin, violaxanthin and lutein contents in leaves. The extent of induction was dependent on exposure duration. No individual UV-B (UVR8) or UV-A (Cryptochrome or Phototropin) photoreceptor was found to mediate this induction. Remarkably, UV-induced accumulation of violaxanthin could not be linked to protection of the photosynthetic machinery from UV damage, questioning the functional relevance of this UV response. Here, it is argued that plants exploit UV radiation as a proxy for other stressors. Thus, it is speculated that the function of UV-induced alterations in carotenoid profile is not UV protection, but rather protection against other environmental stressors such as high intensity visible light that will normally accompany UV radiation.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Rayos Ultravioleta/efectos adversos , Arabidopsis/metabolismo , Carotenoides/metabolismo , Fotosíntesis , Proteínas de Arabidopsis/metabolismo , Proteínas Cromosómicas no Histona/metabolismo
10.
Molecules ; 27(14)2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35889503

RESUMEN

The availability of natural substances able to fulfill the role of antioxidants in a physiologic environment is important for the development of therapies against diseases associated with excessive production of reactive oxygen species and ensuing oxidative stress. Antioxidant properties have been reported episodically for sericin, a proteinaceous constituent of the silk thread in the cocoons generated by the larvae of the Lepidoptera order. We investigated the sericin fractions isolated from the cocoons spun by the domesticated (Bombyx mori) silkworm. Three fractions were isolated and evaluated, including two peptidoid fractions, the crude sericin and the purified (dialyzed) sericin, and the non-peptidoid methanolic extract of the crude fraction. When subjected to Trolox equivalent antioxidant capacity (TEAC) assay, the extract showed much higher antioxidant capacity as compared to the crude or purified sericin fractions. The three fractions were also evaluated in cultures of murine retinal photoreceptor cells (661 W), a cell line that is highly susceptible to oxidants and is crucially involved in the retinopathies primarily caused by oxidative stress. The extract displayed a significant dose-dependent protective effect on the cultured cells exposed to hydrogen peroxide. In identical conditions, the crude sericin showed a certain level of antioxidative activity at a higher concentration, while the purified sericin did not show any activity. We concluded that the non-peptidoid components accompanying sericin were chiefly responsible for the previously reported antioxidant capacity associated with sericin fractions, a conclusion supported by the qualitative detection of flavonoids in the extract but not in the purified sericin fraction.


Asunto(s)
Bombyx , Sericinas , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Bombyx/metabolismo , Ratones , Células Fotorreceptoras de Vertebrados/metabolismo , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Sericinas/farmacología , Seda/metabolismo
11.
Front Pharmacol ; 13: 904849, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35754507

RESUMEN

Cuscuta chinensis Lam. (CCL) is a medicinal herb widely used in traditional Chinese medicine for the treatment of ophthalmic diseases, including age-dependent vision-threatening retinal degenerative disorders that involve irreversible loss of the first-order retinal neurons, photoreceptors. However, evidence is lacking if CCL is pharmacologically active at protecting against loss of photoreceptors and photoreceptor degeneration-associated retinal structural and functional impairment. The current study thus evaluates the potential photoreceptor protective effects of CCL to better support its clinical applications in the prevention and treatment of photoreceptor degenerative diseases. Non-invasive full-retinal optical coherence tomography, electroretinography, histological examination, immunohistochemistry and real-time qPCR analysis were performed to assess the retinal protective effects of CCL in light-exposed BALB/c mice characterized by photooxidative stress-mediated photoreceptor loss and associated retinal morphological and functional impairment. The results showed that CCL treatment protected against light-induced degeneration of the photoreceptor structure and deterioration of the retinal function. Furthermore, CCL treatment increased the retinal expression of rhodopsin, S-opsin and M-opsin, supporting the protective effects of CCL in both rod and cone photoreceptors. CCL treatment suppressed photoreceptor cell death in the light-exposed retinas. The morphological integrity of the second-order retinal neurons was also preserved as a result of CCL treatment. In addition, CCL treatment attenuated light-induced reactive müller gliosis, microglial activation and inflammation in the retina. In conclusion, the current work demonstrates for the first time that CCL protects against photooxidative stress-mediated degeneration of photoreceptors and associated disturbance of structural, functional and immune homeostasis of the retina. The findings here thus provide novel experimental evidence supporting the clinical application of CCL in the prevention and treatment photoreceptor degenerative diseases.

12.
Int J Retina Vitreous ; 8(1): 40, 2022 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-35715832

RESUMEN

BACKGROUND: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes. Retinol and α-tocopherol of diabetic models prevent the damage of photoreceptor and retinal ganglion cells (RGC) caused by hyperglycemia. OBJECTIVE: This study aims to examine the effect of retinol and α-tocopherol on photoreceptor and RGC densities and the expression of caspase-3 and -7 on the retinal layers of the diabetic rat model. METHODS: Alloxan 150 mg/kg body weight single dose was used to develop animal models, which were separated into eight groups. These consist of one group without intervention (group 1), one positive control with only induced alloxan (group 2), and others receiving retinol (group 3 and 6), α-tocopherol (group 4 and 7), or their combination (group 5 and 8). Furthermore, histopathological examination was performed using Hematoxylin-Eosin staining to evaluate the photoreceptor and RGC densities, while immunohistochemistry staining evaluated the caspase-3 and -7 expressions. RESULTS: In the treatment group, the highest and lowest densities were identified in diabetic rats given α-tocopherol (group 7) and retinol (group 3) respectively. The caspase-3 and -7 expression showed that the group given α-tocopherol (group 7) had the lowest value. CONCLUSION: In diabetic rats, retinol and α-tocopherol compounds maintained densities and prevented photoreceptor and RGC death. However, α-tocopherol was more promising than retinol or combinations in the prevention of retinal cells apoptosis.

13.
Nutrients ; 14(8)2022 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-35458237

RESUMEN

Light-evoked retinal photodamage is considered an important factor contributing to functional vision deterioration and can even lead to light maculopathy or dry age-related macular degeneration. Loss of visual acuity (VA) and visual contrast sensitivity function (VCSF) are the major symptoms of retinal degenerative diseases. Cordyceps militaris is a carotenoid-rich Chinese medicinal fungus with antioxidant, anti-inflammatory, and immunomodulatory functions. C. militaris extract is a natural substance, and its bioactive constituents have been shown to confer health benefits, but their application in retinal tissue and functional vision protection in vivo remain incompletely understood. In the present study, we evaluated the influence of water-soluble, carotenoid-rich C. militaris extracts on the visual performance of light-damaged mouse retinas in vivo, using adult female CD-1® (ICR) albino mice. We showed that oral administration of this C. militaris extract (10 mg/kg, twice daily) protected the neural retina tissue against light-evoked photoreceptor cell death, reduced Müller cell hypertrophic gliosis, and elevated GSH levels and promoted the recovery of VA- and VCSF-thresholds, especially for high spatial frequency-characterized vision. These results suggest that, probably because of its water-soluble carotenoids, C. militaris extract has the potential to prevent or treat light-induced visual dysfunction.


Asunto(s)
Cordyceps , Animales , Carotenoides/metabolismo , Carotenoides/farmacología , Femenino , Ratones , Ratones Endogámicos ICR , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Agua/metabolismo
14.
Mol Biol Evol ; 39(4)2022 04 10.
Artículo en Inglés | MEDLINE | ID: mdl-35353898

RESUMEN

Functional classification of proteins from sequences alone has become a critical bottleneck in understanding the myriad of protein sequences that accumulate in our databases. The great diversity of homologous sequences hides, in many cases, a variety of functional activities that cannot be anticipated. Their identification appears critical for a fundamental understanding of the evolution of living organisms and for biotechnological applications. ProfileView is a sequence-based computational method, designed to functionally classify sets of homologous sequences. It relies on two main ideas: the use of multiple profile models whose construction explores evolutionary information in available databases, and a novel definition of a representation space in which to analyze sequences with multiple profile models combined together. ProfileView classifies protein families by enriching known functional groups with new sequences and discovering new groups and subgroups. We validate ProfileView on seven classes of widespread proteins involved in the interaction with nucleic acids, amino acids and small molecules, and in a large variety of functions and enzymatic reactions. ProfileView agrees with the large set of functional data collected for these proteins from the literature regarding the organization into functional subgroups and residues that characterize the functions. In addition, ProfileView resolves undefined functional classifications and extracts the molecular determinants underlying protein functional diversity, showing its potential to select sequences towards accurate experimental design and discovery of novel biological functions. On protein families with complex domain architecture, ProfileView functional classification reconciles domain combinations, unlike phylogenetic reconstruction. ProfileView proves to outperform the functional classification approach PANTHER, the two k-mer-based methods CUPP and eCAMI and a neural network approach based on Restricted Boltzmann Machines. It overcomes time complexity limitations of the latter.


Asunto(s)
Evolución Molecular , Proteínas , Secuencia de Aminoácidos , Bases de Datos de Proteínas , Filogenia , Extractos Vegetales , Proteínas/química , Proteínas/genética
15.
J Biol Chem ; 298(4): 101824, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35288190

RESUMEN

Glutathione peroxidase 4 (GPx4) is known for its unique function in the direct detoxification of lipid peroxides in the cell membrane and as a key regulator of ferroptosis, a form of lipid peroxidation-induced nonapoptotic cell death. However, the cytosolic isoform of GPx4 is considered to play a major role in inhibiting ferroptosis in somatic cells, whereas the roles of the mitochondrial isoform of GPx4 (mGPx4) in cell survival are not yet clear. In the present study, we found that mGPx4 KO mice exhibit a cone-rod dystrophy-like phenotype in which loss of cone photoreceptors precedes loss of rod photoreceptors. Specifically, in mGPx4 KO mice, cone photoreceptors disappeared prior to their maturation, whereas rod photoreceptors persisted through maturation but gradually degenerated afterward. Mechanistically, we demonstrated that vitamin E supplementation significantly ameliorated photoreceptor loss in these mice. Furthermore, LC-MS showed a significant increase in peroxidized phosphatidylethanolamine esterified with docosahexaenoic acid in the retina of mGPx4 KO mice. We also observed shrunken and uniformly condensed nuclei as well as caspase-3 activation in mGPx4 KO photoreceptors, suggesting that apoptosis was prevalent. Taken together, our findings indicate that mGPx4 is essential for the maturation of cone photoreceptors but not for the maturation of rod photoreceptors, although it is still critical for the survival of rod photoreceptors after maturation. In conclusion, we reveal novel functions of mGPx4 in supporting development and survival of photoreceptors in vivo.


Asunto(s)
Fosfolípido Hidroperóxido Glutatión Peroxidasa , Células Fotorreceptoras Retinianas Conos , Células Fotorreceptoras Retinianas Bastones , Animales , Supervivencia Celular/genética , Ratones , Mitocondrias/enzimología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Células Fotorreceptoras Retinianas Conos/citología , Células Fotorreceptoras Retinianas Conos/enzimología , Células Fotorreceptoras Retinianas Bastones/citología , Células Fotorreceptoras Retinianas Bastones/enzimología
16.
Nat Prod Res ; 36(12): 3022-3030, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34176391

RESUMEN

A new phenylethanoid, hebitol IV (1), along with fifteen known glycosides (2-16), were isolated from water extract of the flower buds of Buddleja officinalis. Their structures were elucidated on the basis of 1 D-NMR, 2 D-NMR and MS data. Molecular docking showed the potential activities of the natural products against VEGFR-2. Bioassay results revealed that the compounds 10 and 14 exhibited strong inhibitory activity against VEGFR-2 with IC50 values of 0.51 and 0.32 µM, respectively. Moreover, the potential retinal protective effects of 10 and 14 were then investigated in the mouse model featuring bright light-induced retinal degeneration. The results demonstrated remarkable photoreceptor protective activities of 10 and 14 in vivo.


Asunto(s)
Buddleja , Glicósidos , Células Fotorreceptoras , Retina , Animales , Buddleja/química , Glicósidos/química , Glicósidos/farmacología , Ratones , Simulación del Acoplamiento Molecular , Células Fotorreceptoras/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Retina/citología , Retina/efectos de los fármacos , Retina/efectos de la radiación , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores
17.
Chin J Integr Med ; 28(7): 620-626, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34755291

RESUMEN

OBJECTIVE: To study the protective effect of anthocyanins extracted from Vaccinium Uliginosum (VU) on retinal 661W cells against microwave radiation induced retinal injury. METHODS: 661W cells were divided into 6 groups, including control, model [661W cells radiated by microwave (30 mW/cm2, 1 h)] and VU groups [661W cells pretreated with anthocyanins extracted from VU (25, 50, 100 and 200 µg/mL, respectively) for 48 h, and radiated by microwave 30 mW/cm2, 1 h]. After treatment with different interventions, the cell apoptosis index (AI) was determined using Heochst staining; contents of malonaldehyde (MDA), glutataione (GSH), and activity of superoxide dismutase (SOD) were measured. mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1(HO-1) were detected by real time quantitative polymerase chain reaction, and the expression of HO-1 protein was examined by Western blot analysis. Nucleus and cytoplasm were separated and Nrf2 protein expression was further verified by Western blot analysis. RESULTS: There was significant difference in AI among the groups (F=322.83, P<;0.05). Compared with the control group, AI was significantly higher in the model group and was lower in 4 VU-pretreated groups (P<;0.05). Linear regression analysis showed the decline of AI was in a dose-dependent manner with VU treatment (r=0.8419, P<;0.05). The MDA and GSH contents of 661W cells in VU-treated groups were significantly lower than the model group (P<;0.05). Compared with the model group, the SOD activity in the VU-treated groups (50, 100 and 200 µg/mL) was significantly higher (all P<;0.05). The Nrf2 and HO-1 mRNA expressions were slightly increased after irradiation, and obviously increased in 100 µg/mL VU-treated group. After irradiation, the relative expressions of HO-1 and Nrf2 proteins in nucleus were slightly increased (P<;0.05), and the changes in cytoplasm were not obvious, whereas it was significantly increased in both nucleus and cytoplasm in the VU treatment groups. CONCLUSIONS: Anthocyanins extracted from VU could reduce apoptosis, stabilize cell membrane, and alleviate oxidant injury of mouse retinal photoreceptor 661W cells. The mechanism might be through activating Nrf2/HO-1 signal pathway and inducing HO-1 transcription and translation.


Asunto(s)
Arándanos Azules (Planta) , Factor 2 Relacionado con NF-E2 , Animales , Antocianinas/farmacología , Antocianinas/uso terapéutico , Arándanos Azules (Planta)/genética , Arándanos Azules (Planta)/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Ratones , Microondas , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , ARN Mensajero/metabolismo , Superóxido Dismutasa/metabolismo
18.
Artículo en Inglés | WPRIM | ID: wpr-939780

RESUMEN

OBJECTIVE@#To study the protective effect of anthocyanins extracted from Vaccinium Uliginosum (VU) on retinal 661W cells against microwave radiation induced retinal injury.@*METHODS@#661W cells were divided into 6 groups, including control, model [661W cells radiated by microwave (30 mW/cm2, 1 h)] and VU groups [661W cells pretreated with anthocyanins extracted from VU (25, 50, 100 and 200 µg/mL, respectively) for 48 h, and radiated by microwave 30 mW/cm2, 1 h]. After treatment with different interventions, the cell apoptosis index (AI) was determined using Heochst staining; contents of malonaldehyde (MDA), glutataione (GSH), and activity of superoxide dismutase (SOD) were measured. mRNA expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1(HO-1) were detected by real time quantitative polymerase chain reaction, and the expression of HO-1 protein was examined by Western blot analysis. Nucleus and cytoplasm were separated and Nrf2 protein expression was further verified by Western blot analysis.@*RESULTS@#There was significant difference in AI among the groups (F=322.83, P<;0.05). Compared with the control group, AI was significantly higher in the model group and was lower in 4 VU-pretreated groups (P<;0.05). Linear regression analysis showed the decline of AI was in a dose-dependent manner with VU treatment (r=0.8419, P<;0.05). The MDA and GSH contents of 661W cells in VU-treated groups were significantly lower than the model group (P<;0.05). Compared with the model group, the SOD activity in the VU-treated groups (50, 100 and 200 µg/mL) was significantly higher (all P<;0.05). The Nrf2 and HO-1 mRNA expressions were slightly increased after irradiation, and obviously increased in 100 µg/mL VU-treated group. After irradiation, the relative expressions of HO-1 and Nrf2 proteins in nucleus were slightly increased (P<;0.05), and the changes in cytoplasm were not obvious, whereas it was significantly increased in both nucleus and cytoplasm in the VU treatment groups.@*CONCLUSIONS@#Anthocyanins extracted from VU could reduce apoptosis, stabilize cell membrane, and alleviate oxidant injury of mouse retinal photoreceptor 661W cells. The mechanism might be through activating Nrf2/HO-1 signal pathway and inducing HO-1 transcription and translation.


Asunto(s)
Animales , Ratones , Antocianinas/uso terapéutico , Arándanos Azules (Planta)/metabolismo , Hemo-Oxigenasa 1/metabolismo , Microondas , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , ARN Mensajero/metabolismo , Superóxido Dismutasa/metabolismo
19.
Int J Mol Sci ; 22(19)2021 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-34638788

RESUMEN

Antimicrobial resistance is a global, mounting and dynamic issue that poses an immediate threat to human, animal, and environmental health. Among the alternative antimicrobial treatments proposed to reduce the external use of antibiotics is electromagnetic radiation, such as blue light. The prevailing mechanistic model is that blue light can be absorbed by endogenous porphyrins within the bacterial cell, inducing the production of reactive oxygen species, which subsequently inflict oxidative damages upon different cellular components. Nevertheless, it is unclear whether other mechanisms are involved, particularly those that can affect the efficacy of antimicrobial blue light treatments. In this review, we summarize evidence of inherent factors that may confer protection to a selected group of bacteria against blue light-induced oxidative damages or modulate the physiological characteristics of the treated bacteria, such as virulence and motility. These include descriptions of three major photoreceptors in bacteria, chemoreceptors, SOS-dependent DNA repair and non-SOS protective mechanisms. Future directions are also provided to assist with research efforts to increase the efficacy of antimicrobial blue light and to minimize the development of blue light-tolerant phenotypes.


Asunto(s)
Bacterias/genética , Reparación del ADN , Regulación Bacteriana de la Expresión Génica , Luz , Fototerapia , Bacterias/efectos de la radiación
20.
Membranes (Basel) ; 11(5)2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33946822

RESUMEN

Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid containing taurine conjugated with the ursodeoxycholic acid (UDCA), has been known and used from ancient times as a therapeutic compound in traditional Chinese medicine. TUDCA has recently been gaining significant interest as a neuroprotective agent, also exploited in the visual disorders. Among several mechanisms of TUDCA's protective action, its antioxidant activity and stabilizing effect on mitochondrial and plasma membranes are considered. In this work we investigated antioxidant activity of TUDCA and its impact on structural properties of model membranes of different composition using electron paramagnetic resonance spectroscopy and the spin labeling technique. Localization of TUDCA molecules in a pure POPC bilayer has been studied using a molecular dynamics simulation (MD). The obtained results indicate that TUDCA is not an efficient singlet oxygen (1O2 (1Δg)) quencher, and the determined rate constant of its interaction with 1O2 (1Δg) is only 1.9 × 105 M-1s-1. However, in lipid oxidation process induced by a Fenton reaction, TUDCA reveals substantial antioxidant activity significantly decreasing the rate of oxygen consumption in the system studied. In addition, TUDCA induces slight, but noticeable changes in the polarity and fluidity of the investigated model membranes. The results of performed MD simulation correspond very well with the experimental results.

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