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Fever is an evolutionarily conserved response that confers survival benefits during infection. However, the underlying mechanism remains obscure. Here, we report that fever promoted T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to α4 integrins, but not ß2 integrins, fever increased α4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the α4 tail and activated α4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two α4 tails, leading to dimerization and clustering of α4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-α4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-α4-integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.
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Fiebre/inmunología , Proteínas HSP90 de Choque Térmico/metabolismo , Integrina alfa4/metabolismo , Infecciones por Salmonella/inmunología , Salmonella typhimurium/inmunología , Linfocitos T/inmunología , Animales , Carga Bacteriana , Adhesión Celular , Movimiento Celular , Dimerización , Quinasa 1 de Adhesión Focal/metabolismo , Vigilancia Inmunológica , Integrina alfa4/genética , Activación de Linfocitos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Unión Proteica , Transducción de Señal , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
Among the environmental factors contributing to myopia, the role of correlated color temperature (CCT) of ambient light emerges as a key element warranting in-depth investigation. The choroid, a highly vascularized and dynamic structure, often undergoes thinning during the progression of myopia, though the precise mechanism remains elusive. The retinal pigment epithelium (RPE), the outermost layer of the retina, plays a pivotal role in regulating the transport of ion and fluid between the subretinal space and the choroid. A hypothesis suggests that variations in choroidal thickness (ChT) may be modulated by transepithelial fluid movement across the RPE. Our experimental results demonstrate that high CCT illumination significantly compromised the integrity of tight junctions in the RPE and disrupted chloride ion transport. This functional impairment of the RPE may lead to a reduction in fluid transfer across the RPE, consequently resulting in choroidal thinning and potentially accelerating axial elongation. Our findings provide support for the crucial role of the RPE in regulating ChT. Furthermore, we emphasize the potential hazards posed by high CCT artificial illumination on the RPE, the choroid, and refractive development, underscoring the importance of developing eye-friendly artificial light sources to aid in the prevention and control of myopia.
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Cloruros , Coroides , Transporte Iónico , Epitelio Pigmentado de la Retina , Epitelio Pigmentado de la Retina/metabolismo , Epitelio Pigmentado de la Retina/efectos de la radiación , Epitelio Pigmentado de la Retina/patología , Coroides/metabolismo , Coroides/efectos de la radiación , Coroides/patología , Animales , Transporte Iónico/efectos de la radiación , Cloruros/metabolismo , Iluminación/métodos , Temperatura , Color , Uniones Estrechas/metabolismo , Miopía/metabolismo , Miopía/patología , Miopía/etiologíaRESUMEN
A chemical investigation of Anthriscus sylvestris roots led to the isolation and characterization of two new nitrogen-containing phenylpropanoids (1-2) and two new phenol glycosides (8-9), along with fifteen known analogues. Structure elucidation was based on HRESIMS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD). In addition, compounds 3, 6, 9-10, 12, and 17 exhibited inhibitory effects against the abnormal proliferation of pulmonary arterial smooth muscle cells with IC50 values ranging from 10.7 ± 0.6 to 57.1 ± 1.1 µM.
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Proliferación Celular , Miocitos del Músculo Liso , Raíces de Plantas , Arteria Pulmonar , Raíces de Plantas/química , Proliferación Celular/efectos de los fármacos , Miocitos del Músculo Liso/efectos de los fármacos , Arteria Pulmonar/citología , Arteria Pulmonar/efectos de los fármacos , Animales , Estructura Molecular , Extractos Vegetales/farmacología , Extractos Vegetales/química , Glicósidos/farmacología , Glicósidos/química , Glicósidos/aislamiento & purificación , Ratas , Espectroscopía de Resonancia MagnéticaRESUMEN
Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.
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Medicamentos Herbarios Chinos , Úlceras Bucales , Ratas , Masculino , Animales , Medicamentos Herbarios Chinos/farmacología , Úlceras Bucales/tratamiento farmacológico , Interleucina-6 , Calor , Factor de Necrosis Tumoral alfa , Ratas Sprague-Dawley , Metabolómica/métodos , Cromatografía Líquida de Alta Presión , Superóxido Dismutasa , BiomarcadoresRESUMEN
BACKGROUND: X-linked retinoschisis (XLRS), due to mutations in the RS1 gene, is a common genetically determined form of macular degeneration. This report describes an unusual case of angle-closure glaucoma (ACG) with XLRS and discusses the treatment. CASE PRESENTATION: A 39-year-old Chinese man with an X chromosome-recessive inherited c.489G > A variant in the RS1 gene was diagnosed as XLRS and ACG, presenting with cystic macular lesions, shallow anterior chamber depth (ACD), and angle-closure with uncontrolled intraocular pressure (IOP). Malignant glaucoma occurred following trabeculectomy combining phacoemulsification with intraocular lens (IOL) implantation and goniosynechialysis. Subsequent anterior vitrectomy and irido-zonulo-hyaloid-vitrectomy (IZHV) effectively lowered IOP and deepened ACD, but the cystic cavity became larger. CONCLUSIONS: There is a potential risk of malignant glaucoma in ACG patients with XLRS after filtering surgery. Although anterior vitrectomy can effectively resolve aqueous misdirection, the macular retinoschisis may get worse. Awareness of this risk may aid in surgical planning and postoperative management in these patients.
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Extracción de Catarata , Glaucoma de Ángulo Cerrado , Glaucoma , Facoemulsificación , Retinosquisis , Masculino , Humanos , Adulto , Glaucoma de Ángulo Cerrado/complicaciones , Glaucoma de Ángulo Cerrado/genética , Glaucoma de Ángulo Cerrado/cirugía , Retinosquisis/diagnóstico , Retinosquisis/genética , Retinosquisis/cirugía , Implantación de Lentes Intraoculares/efectos adversos , Glaucoma/cirugía , Presión IntraocularRESUMEN
Scar formation resulting from overly active wound healing is a critical factor in the success rate of glaucoma filtration surgery (GFS). IL-6 and TGF-ß have been implicated in the pathogenesis of fibrogenesis. In addition, the signal transducer and activator of transcription 3 (STAT3) can be activated by numerous cytokines and growth factors, including IL-6 and TGF-ß1. Thus, STAT3 activation may integrate common profibrotic pathways to promote fibrosis. In this study, an increase in p-STAT3 was observed in activated HTFs. Inhibiting STAT3 in cultured HTFs by pharmacological inactivation reversed the fibrotic responses, such as fibroblast migration, the differentiation of resting fibroblasts into myofibroblasts and the deposition of ECM, mediated by IL-6 and TGF-ß1. Moreover, the expression of suppressor of cytokine signaling 3 (SOCS3) was decreased in HTFs cultured with IL-6 and TGF-ß1, and SOCS3 overexpression rescued ECM deposition, α-SMA expression and migration in IL-6- and TGF-ß1-stimulated HTFs by inactivating STAT3. Finally, S3I-201 treatment inhibited profibrotic gene expression and subconjunctival fibrosis in a rat model of GFS. In conclusion, our data suggests that STAT3 plays a central role in fibrosis induced by different profibrotic pathways and that STAT3 is a potential target for antifibrotic therapies following GFS.
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BACKGROUND: Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare fundus disease characterized by the presence of osteoblast-like pigment, atrophy of retinal pigment epithelium (RPE), and choroid deposition along the large retinal veins. CASE PRESENTATION: A 55-year-old Chinese female presented with right eye distention and bilateral vision loss. Osteocyte-like pigmentation and retinal choroidal atrophy distributed along the large retinal veins were seen in the fundus of bilateral eyes. The atrophy in the left eye was more severe compared to the right eye. The patient also presented with bilateral acute angle-closure glaucoma (AACG) and posterior subcapsular cataract (PSC) accompanied with anterior segmental manifestations, similar to the complications of retinitis pigmentosa (RP). The patient underwent ultrasound biomicroscopy (UBM), Humphrey field analyser (HFA), optical coherence tomography (OCT), fundus autofluorescence (FAF), fluorescein fundus angiography (FFA), electroretinogram (ERG), and electrooculography (EOG), all of which confirmed the aforementioned diagnose. CONCLUSION: PPRCA is a rare disease of unknown etiology. The patient in this case presented with complications similar to those of RP, and the two conditions may share a genetic basis. Further studies are needed to confirm this relationship.
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Catarata , Glaucoma de Ángulo Cerrado , Degeneración Retiniana , Retinitis Pigmentosa , Atrofia/patología , Catarata/diagnóstico , Catarata/patología , Coroides/patología , Enfermedades Hereditarias del Ojo , Femenino , Angiografía con Fluoresceína , Glaucoma de Ángulo Cerrado/diagnóstico , Glaucoma de Ángulo Cerrado/patología , Humanos , Persona de Mediana Edad , Degeneración Retiniana/diagnóstico , Retinitis Pigmentosa/genética , Tomografía de Coherencia Óptica/métodosRESUMEN
BACKGROUND: To identify the feasibility, safety, cosmetic outcomes and patient satisfaction of immediate prosthetic breast reconstruction after removal of Polyacrylamide Hydrogel (PAAG) through a small areolar incision assisted with an endoscope. METHODS: This was a retrospective study. Medical records of 87 patients who underwent PAAG removal were reviewed retrospectively from February 2010 to December 2019. These patients were dichotomized based on whether they accepted immediate prosthetic breast reconstruction after PAAG removal or not. A comprehensive analysis on the data was conducted to observe the surgical results, cosmetic outcomes, health-related quality of life (HRQOL) and patient satisfaction. RESULTS: Sixty-two patients underwent PAAG removal through a small areolar incision assisted with an endoscope, while another 25 patients underwent further immediate prosthetic breast reconstruction after PAAG removal. All the patients recovered smoothly after operation. In the immediate breast reconstructed group, most of the breasts were natural in appearance, but one patient had mild nipple and breast asymmetry, and another had mild breast asymmetry. Three patients had PAAG residual, and one of them accepted fine needle aspiration. The cosmetic satisfaction rate was 88% and 92% by surgeons and patients, respectively. In the other group, seven patients suffered from PAAG residual, one patient suffered from postoperative bleeding, and five patients suffered from skin laxity. The BREAST-Q scores revealed that patients who accepted immediate breast reconstruction had significant better outcomes in psychosocial well-being (p = 0.030), satisfaction with breasts (p = 0.021), when compared to patients who only accepted PAAG removal, while similar in sexual well-being (p = 0.081), physical well-being chest (p = 0.124), and satisfaction with outcomes (p = 0.068), and satisfaction with care (p = 0.077). CONCLUSION: Immediate prosthetic breast reconstruction after PAAG removal through a small areolar incision aided with an endoscope might be a viable and safe technique, with better psychosocial well-being and satisfaction with breasts.
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Mamoplastia , Resinas Acrílicas , Endoscopios , Femenino , Humanos , Mamoplastia/métodos , Pezones/cirugía , Calidad de Vida , Estudios RetrospectivosRESUMEN
Spiroaxillarone A, a novel and unique spirocyclic dinaphthalene natural product with significant antimalarial activity, was regioselectively synthesized from tetrahydrocurcumin in five steps with an overall 10% yield. Key features of the synthesis involved an oxidized free radical cycloaddition to build the spiro ring central skeleton and an oxidized dehydrogenation to introduce two double bonds via enol silicon ether from diketones.
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Antimaláricos , Compuestos de Espiro , Reacción de Cicloadición , Estructura MolecularRESUMEN
BACKGROUND: Excessive scarring of filtering blebs is the main cause of surgical failure in glaucoma. Previous studies have highlighted the role of chloride channels (ClCs) in scar formation, whereas the role of ClCs in scarring of filtering blebs has not been studied. OBJECTIVES: The objective of this study was to investigate the effects of the chloride channel 2 (ClC-2) on scar formation of filtering blebs after glaucoma filtering surgery. METHODS: ClC-2 siRNA-transfected human conjunctival fibroblasts (HConFs) were cultured in type 1 collagen gels in the presence of transforming growth factor (TGF)-ß1. Collagen gel contraction was evaluated based on the gel area. 3D-cultured HConFs were treated with the ClC blocker NPPB in the presence of TGF-ß1, and cell proliferation collagen synthesis and contractility were measured. The expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in HConFs were assessed by Western blotting and qPCR. RESULTS: TGF-ß1 induced cell proliferation, cell cycle progression, collagen synthesis, and collagen gel contraction in HConFs. TGF-ß1 increased MMP-2 and MMP-9 levels but inhibited the expression of TIMPs. NPPB and ClC-2 siRNA transfection inhibited TGF-ß2-induced cell proliferation, cell cycle progression, collagen synthesis, and collagen gel contraction, mediated by HConFs. TGF-ß2-induced increases in MMP-2 and MMP-9 were also inhibited by NPPB and ClC-2 siRNA transfection, but TIMP expression was increased by NPPB and ClC-2 siRNA transfection. CONCLUSIONS: These findings demonstrate that ClC-2 ClCs modulate TGF-ß1-induced cell proliferation, collagen synthesis, and collagen gel contraction of HConFs by attenuating MMP-2 and MMP-9 production and by stimulating TIMP1 production. NPPB may therefore prove to be of clinical value for the inhibition of scar formation of filtering blebs.
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Glaucoma , Humanos , Proliferación Celular , Células Cultivadas , Cicatriz/genética , Canales de Cloruro CLC-2/genética , Colágeno/metabolismo , Fibroblastos/metabolismo , Geles , Glaucoma/genética , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/genética , ARN Interferente Pequeño/genética , Factor de Crecimiento Transformador beta1/farmacología , Factor de Crecimiento Transformador beta2/farmacologíaRESUMEN
BACKGROUND: ß7 integrins are responsible for the efficient recruitment of lymphocytes from the blood and their retention in gut-associated lymphoid tissues. Integrin α4ß7 binds MAdCAM-1, mediating rolling adhesion of lymphocytes on blood vessel walls when inactive and firm adhesion when activated, thereby controlling two critical steps of lymphocyte homing to the gut. By contrast, integrin αEß7 mediates the adhesion of lymphocytes to gut epithelial cells by interacting with E-cadherin. Integrin ß7 blocking antibodies have shown efficacy in clinical management of inflammatory bowel disease (IBD); however, fully blocking ß7 function leads to the depletion of colonic regulatory T (Treg) cells and exacerbates dextran sulfate sodium (DSS)-induced colitis by evoking aberrant innate immunity, implying its potential adverse effect for IBD management. Thus, a better therapeutic strategy targeting integrin ß7 is required to avoid this adverse effect. RESULTS: Herein, we inhibited integrin α4ß7 activation in vivo by creating mice that carry in their integrin ß7 gene a mutation (F185A) which from structural studies is known to lock α4ß7 in its resting state. Lymphocytes from ß7-F185A knock-in (KI) mice expressed α4ß7 integrins that could not be activated by chemokines and showed significantly impaired homing to the gut. The ß7-F185A mutation did not inhibit αEß7 activation, but led to the depletion of αEß7+ lymphocytes in the spleen and a significantly reduced population of αEß7+ lymphocytes in the gut of KI mice. ß7-F185A KI mice were resistant to T cell transfer-induced chronic colitis, but did not show an increased susceptibility to DSS-induced innate colitis, the adverse effect of fully blocking ß7 function. CONCLUSIONS: Our findings demonstrate that specific inhibition of integrin α4ß7 activation is a potentially better strategy than fully blocking α4ß7 function for IBD treatment.
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Inmunidad Adaptativa , Colitis/genética , Integrinas/genética , Mutación , Animales , Colitis/inmunología , Femenino , Integrinas/metabolismo , Masculino , Ratones , Ratones TransgénicosRESUMEN
As a kind of serious, potentially sight-threatening corneal infections with poor prognosis, fungal keratitis can bring a heavy economic burden to patients and seriously affect the quality of life, especially those in developing countries where fungal keratitis is more prevalent. Typical clinical features include immune rings, satellite lesions, pseudopods, hypha moss, hypopyon and endothelial plaques. The ideal therapeutic effects could not be achieved by current treatments for many reasons. Therefore, under the current status, understanding the pathogenesis, early diagnosis and prevention strategies might be of great importance. Here, in this review, we discuss the recent progresses that may advance our understanding of pathogenesis, early diagnosis and prevention of fungal keratitis.
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Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Fúngicas del Ojo/microbiología , Infecciones Fúngicas del Ojo/prevención & control , Queratitis/diagnóstico , Queratitis/etiología , Queratitis/prevención & control , Biomarcadores , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Infecciones Fúngicas del Ojo/metabolismo , Interacciones Huésped-Patógeno , Humanos , Queratitis/metabolismo , Microscopía Confocal , Técnicas de Diagnóstico Molecular , Factores de Riesgo , TomografíaRESUMEN
Nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a regulator of many biological processes and plays an essential role in preventing oxidation, inflammation, and fibrosis. In the past 20 years, there has been increasing research on the role of Nrf2 and oxidative stress in human glaucoma, including the roles of inflammation, trabecular meshwork cells, retinal ganglion cells, Tenon's capsule, antioxidants, fibrosis, and noncoding RNAs. Studies have shown that the upregulation of Nrf2 can reduce damage from oxidative stress in the trabecular meshwork cells and the retinal ganglion cells, reduce fibrosis in Tenon's capsule fibroblasts, which may reduce the progression of fibrosis after surgery for glaucoma. The regulatory roles of Nrf2, microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and exogenous compounds on trabecular meshwork cells (TMCs) and retinal ganglion cells have also been studied. The use of Nrf2 agonists, including noncoding RNAs, control the expression of Nrf2 through signaling pathways that continue to be investigated to identify effective treatments to improve clinical outcome following surgery for glaucoma. This review of publications between 1999 and 2019 aims to focus on the potential mechanisms of Nrf2 in the occurrence and development of glaucoma and the prognosis following surgical treatment. Also, several factors that induce the expression of Nrf2 in trabecular meshwork cells, retinal ganglion cells, and human Tenon's capsule fibroblasts are discussed.
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Glaucoma/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Animales , Glaucoma/patología , Humanos , Estrés Oxidativo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Células Ganglionares de la Retina/metabolismo , Células Ganglionares de la Retina/patología , Malla Trabecular/patologíaRESUMEN
INTRODUCTION: Retinitis pigmentosa (RP) caused by the photoreceptor cell degeneration is currently incurable and leads to partial or complete blindness eventually. 3,5-dimethoxy-4-hydroxy myricanol (DM) is a novel compound isolated from the leaves of Micromelum integerrimum, with proliferative activities on NIH3T3 cells. This study was to investigate whether DM could mitigate retinal degeneration of rd10 mice, a well-characterized mouse model of RP. MATERIALS AND METHOD: Rd10 mice were treated with DM daily by intraperitoneal injection from postnatal day 12 (P12) to P26. Electroretinography (ERG) reflects the mass response of photoreceptor cells and was used to test the outer retinal function after DM treatment. Haematoxylin and Eosin staining was used to show the retinal morphology and evaluate the rod photoreceptor cell loss. TUNEL assay was used to detect the apoptosis-positive cells. Inflammatory factors were measured by ELISA to show the inflammatory response. Real-time PCR and western blot were applied to measure the gene and protein change to explore the underlying mechanisms. RESULTS: Results showed that DM significantly improved the retinal function by increasing the ERG amplitude, preserving the retinal morphology, reducing photoreceptor cell apoptosis, decreasing inflammatory response, and inhibiting endoplasmic reticulum stress in rd10 mice. CONCLUSION: This is the first time when the protective effects of DM against photoreceptor cell degeneration of rd10 mice have been demonstrated, providing scientific rationale to develop DM as a potential agent to treat RP.
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Antiinflamatorios/uso terapéutico , Diarilheptanoides/uso terapéutico , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Degeneración Retiniana/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Ratones MutantesRESUMEN
BACKGROUND: Light emitting diodes laser is emerging as an important source of light replacing conventional lights. It is widely used for illumination in the bar where young people love to go. But not everyone knows about the light damage to the eye especially to the macula. In this article, we report the case of a macular damage induced by LED-derived blue laser in a bar, studied with optical coherence tomography (OCT) to evaluate the retinal lesion and multifocal electroretinography (mfERG) to evaluate functional damage. CASE PRESENTATION: Four days after the photo injury to the right eye, the visual acuity was 0.5. Funduscopy revealed a round red lesion in the macula of the right eye. Fluorescein angiography (FA) revealed no leakage. OCT revealed a deficiency in the center of the fovea. MfERG revealed a reduction of the peak value in the right eye compared to the left eye. One month later, although the vision was 1.0 in the right eye, OCT revealed a hyporeflectivity of the ellipsoid zone. MfERG still showed a reduction of the peak value in the right eye compared to the left eye. CONCLUSION: We believe that general knowledge about laser injuries to the eye should be realized widely. We also think in cases of macular laser damage, the recovery of vision can not demonstrate the recovery of the function of photoreceptors.
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Quemaduras Oculares/diagnóstico , Rayos Láser/efectos adversos , Mácula Lútea/lesiones , Enfermedades de la Retina/diagnóstico , Tomografía de Coherencia Óptica/métodos , Adulto , Electrorretinografía , Quemaduras Oculares/complicaciones , Angiografía con Fluoresceína/métodos , Fondo de Ojo , Humanos , Mácula Lútea/patología , Masculino , Oftalmoscopía/métodos , Enfermedades de la Retina/etiología , Agudeza VisualRESUMEN
OBJECTIVE: To perform a meta-analysis to determine the effect of radiotherapy (RT) on nipple-areolar complex (NAC) and skin flap necrosis, and local recurrence in women who undergo nipple-sparing mastectomy (NSM) and immediate breast reconstruction. METHODS: Medline, PubMed, Cochrane, and Google Scholar databases were searched until October 16, 2015. Randomized-controlled-trials, prospective, retrospective, and cohort studies were included. The primary outcome was the NAC necrosis rate, and the secondary outcomes were the skin flap necrosis and local recurrence rates. RESULTS: Of 186 studies identified, 2 prospective and 5 retrospective studies including a total of 3692 patients were included in the meta-analysis. Five, 3, and 2 studies reported data of NAC necrosis (3461 breasts), skin flap necrosis (2490 breasts), and local recurrence (988 breasts), respectively. Pooled results showed no difference in the odds of NAC necrosis [odds ratio (OR) = 1.250, 95% confidence interval (CI) 0.481-3.247, P = 0.647], or local recurrence (OR = 0.564, 95% CI 0.056-5.710, P = 0.627) between patients who received and did not receive RT. Patients treated with RT had a higher likelihood of skin flap necrosis (OR = 2.534, 95% CI 1.720-3.735, P < 0.001). Significant heterogeneity, however, was noted in the analysis of NAC and local recurrence. CONCLUSIONS: Because of the limitations of the small number of studies and heterogeneity in the analysis, this study does not allow drawing any definitive conclusions and highlights the need of well-controlled trials to determine the effect of RT in patients undergoing NSM.
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Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Mastectomía/métodos , Recurrencia Local de Neoplasia , Pezones/patología , Tratamientos Conservadores del Órgano , Traumatismos por Radiación/patología , Colgajos Quirúrgicos/patología , Adulto , Neoplasias de la Mama/patología , Femenino , Humanos , Mamoplastia , Persona de Mediana Edad , Necrosis/etiología , Pezones/efectos de la radiación , Oportunidad Relativa , Evaluación de Resultado en la Atención de Salud , Radioterapia/efectos adversos , Sensibilidad y EspecificidadRESUMEN
Owing to a rapidly aging population, vision impairment caused by age-related cataract has become very common. Age-related cataract has also become one of the principal causes of blindness, and apoptosis of lens epithelial cells contributes to non-congenital cataract development. Previous studies have reported that microRNA let-7b (let-7b) is upregulated in cataractous lens epithelial cells, and the expression level of let-7b is positively associated with N, C and P cataract scores. However, the role of let-7b in the development of age-related cataract remains unclear. Here, we observed that the expression level of let-7b in the anterior lens capsules of age-related cataract was significantly higher than that in the normal anterior lens capsules. We performed ultraviolet (UV) irradiation to induce lens epithelial cell apoptosis. The results showed that the expression level of let-7b in lens epithelial cells which were treated by UV irradiation was significantly higher than that in the control, and let-7b promoted UV irradiation-induced apoptosis. Furthermore, we showed that leucine-rich repeat containing G protein-coupled receptor 4 (Lgr4) was a direct target of let-7b, and let-7b modulated lens epithelial cell apoptosis by directly targeting Lgr4. These findings will offer new insights into our understanding of the molecular mechanisms underlying the pathogenesis of cataract.
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Apoptosis/fisiología , Catarata/metabolismo , Células Epiteliales/metabolismo , Cristalino/metabolismo , Leucina/metabolismo , MicroARNs/fisiología , Anciano , Apoptosis/efectos de la radiación , Catarata/fisiopatología , Línea Celular , Regulación hacia Abajo , Células Epiteliales/efectos de la radiación , Femenino , Humanos , Cristalino/efectos de la radiación , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Receptores Acoplados a Proteínas G/metabolismo , Rayos Ultravioleta/efectos adversos , Regulación hacia ArribaRESUMEN
Recent evidence suggests that chloride channels are critical for cell proliferation, migration, and differentiation. We examined the effects of transforming growth factor (TGF)-ß1 on chloride channel expression and associations with human conjunctival fibroblast (HConF) biology. To investigate the potential role of chloride channel (CLC)-2 in migration, transition to myofibroblasts and extracellular matrix (ECM) synthesis of HconF, a small interfering RNA (siRNA) approach was applied. TGF-ß1-induced migration and transition of fibroblasts to myofibroblasts characterized by α-smooth muscle actin (α-SMA) expression, supported by increased endogenous expression of CLC-2 protein and mRNA transcripts. ECM (collagen I and fibronectin) synthesis in HConF was enhanced by TGF-ß1. CLC-2 siRNA treatment reduced TGF-ß1-induced cell migration, transition of fibroblasts to myofibroblasts, and ECM synthesis of HConF. CLC-2 siRNA treatment in the presence of TGF-ß1 inhibited phosphorylation of PI3K and Akt in HConF. These findings demonstrate that CLC-2 chloride channels are important for TGF-ß1-induced migration, differentiation, and ECM synthesis via PI3K/Akt signaling in HConF.
Asunto(s)
Diferenciación Celular , Movimiento Celular , Canales de Cloruro/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Sistemas de Mensajero Secundario , Actinas/genética , Actinas/metabolismo , Canales de Cloruro CLC-2 , Células Cultivadas , Canales de Cloruro/genética , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Conjuntiva/citología , Conjuntiva/metabolismo , Fibroblastos/citología , Fibroblastos/fisiología , Fibronectinas/genética , Fibronectinas/metabolismo , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
Exposure to reactive oxygen species (ROS) leads to the development and progression of retinal degenerative diseases. However, the exact mechanisms are not fully understood. In this article, the role of angiotensin II type 1 receptor (AT1R) signaling in H(2)O(2)-induced retinal damage was examined. Mouse photoreceptor-derived 661 W cells were treated with the AT1R blockers valsartan, losartan and candesartan before exposure to H(2)O(2). Cell viability, intracellular ROS level, mitochondrial membrane potential (MMP), cytochrome-c level, DNA fragmentation, caspase activity and gene expression were detected. Pre-treatment of 661 W cells with AT1R blockers significantly decreased H(2)O(2)-mediated toxicity and reduced the ROS level. In addition, apoptosis-related biochemical indicators showed that pre-incubation of AT1R blockers would elevate the MMP, decrease the release of cytochrome-c and formation of DNA fragmentation, and inhibit activities of caspase-3 and caspase-9 in exogenous H(2)O(2)-treated 661 W cells. Moreover, treatment with AT1R blockers suppressed the expression of Egr1, Fosl1 and Lox12. These results suggest that AT1R signaling mediates H(2)O(2)-induced apoptosis, at least partially through generating the ROS and increasing the levels of proapoptotic molecules in 661 W cells. AT1R blockade may provide a new therapeutic approach for preventing oxidative stress-induced retinal neural damage.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Peróxido de Hidrógeno/toxicidad , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Degeneración Retiniana/prevención & control , Animales , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Técnicas de Cultivo de Célula , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Citocromos c/metabolismo , Expresión Génica/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Células Fotorreceptoras de Vertebrados/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor de Angiotensina Tipo 1/genética , Degeneración Retiniana/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
PURPOSE: To explore the correlation between cardiovascular health (CVH) and ocular diseases, given their shared risk factors and biological mechanisms, this study utilizes the newly updated Life's Essential 8 (LE8) algorithm. DESIGN: A cross-sectional study. METHODS: This analysis, conducted from February 15 to April 1, 2024, in Changchun, includes data from 4146 participants aged 40 and above, drawn from the National Health and Nutrition Examination Survey database (2005-2008). It covers information on visual health status, dietary habits through interviews, and professional ophthalmological examinations. Participants' CVH status was assessed using the LE8 algorithm, and relationships with major ocular diseases such as retinopathy, cataracts, diabetic retinopathy, glaucoma, and age-related macular degeneration were explored through weighted logistic regression analysis, restricted cubic splines, stratified analysis, and sensitivity analysis. RESULTS: After multivariable adjustment, lower LE8 scores showed a significant positive relationship with any ocular disease (odds ratio [OR]: 2.03, 95% confidence interval [CI]: 1.39-2.96, P = .001), any objectively determined ocular disease (OR: 2.24, 95% CI: 1.48-3.38, P < .001), retinopathy (OR: 2.88, 95% CI: 1.89-4.41, P < .001), diabetic retinopathy (OR: 10.23, 95% CI: 3.11-33.61, P < .001), and glaucoma (OR: 2.76, 95% CI: 1.47-5.21, P = .003), with all trends significant (all P < .01). Additionally, lower scores in the behavioral subdomain were significantly correlated with an elevated risk of cataracts (OR: 1.45, 95% CI: 1.03-2.04). Subgroup analyses revealed more pronounced negative correlations between LE8 and retinopathy among females and those suffering from chronic kidney disease. CONCLUSIONS: A low CVH score was linked to an increased likelihood of ocular diseases in a US-populated-based study. This correlation supports the potential benefits of enhancing cardiovascular wellness to mitigate the development of ocular conditions.