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We theoretically show the asymmetric spin wave transmission in a coupled waveguide-skyrmion structure, where the skyrmion acts as an effective nanocavity allowing the whispering gallery modes for magnons. The asymmetry originates from the chiral spin wave mode localized in the circular skyrmion wall. By inputting two-tone excitations and mixing them in the skyrmion wall, we observe a unidirectional output magnon frequency comb propagating in the waveguide with a record number of teeth (>50). This coupled waveguide-cavity structure turns out to be a universal paradigm for generating asymmetric magnon frequency combs, where the cavity can be generalized to other magnetic structures that support the whispering gallery mode of magnons. Our results advance the understanding of the nonlinear interaction between magnons and magnetic textures and open a new pathway to exploring the asymmetric spin wave transmission and to steering the magnon frequency comb.
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RNA methylation is a widespread regulatory mechanism that controls gene expression in physiological processes. In recent years, the mechanisms and functions of RNA methylation under diseased conditions have been increasingly unveiled by RNA sequencing technologies with large scale and high resolution. In this review, the fundamental concept of RNA methylation is introduced, and the common types of transcript methylation and their machineries are described. Then, the regulatory roles of RNA methylation, particularly N6-methyladenosine and 5-methylcytosine, in the vascular lesions of ocular and cardiopulmonary diseases are discussed and compared. The ocular diseases include corneal neovascularization, retinopathy of prematurity, diabetic retinopathy, and pathologic myopia; whereas the cardiopulmonary ailments involve atherosclerosis and pulmonary hypertension. This review hopes to shed light on the common regulatory mechanisms underlying the vascular lesions in these ocular and cardiopulmonary diseases, which may be conducive to developing therapeutic strategies in clinical practice.
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BACKGROUND: G6PD deficiency is a common inherited disorder worldwide and has a higher incidence rate in southern China. Many variants of G6PD result from point mutations in the G6PD gene, leading to decreased enzyme activity. This study aimed to analyse the genotypic and phenotypic characteristics of G6PD deficiency in Guangzhou, China. METHODS: In this study, a total of 20,208 unrelated participants were screened from 2020 to 2022. G6PD deficiency was further analysed by quantitative enzymatic assay and G6PD mutation analysis. The unidentified genotype of the participants was further ascertained by direct DNA sequencing. RESULTS: A total of 12 G6PD mutations were identified. Canton (c.1376G>T) and Kaiping (c.1388G>A) were the most common variants, and different mutations led to varying levels of G6PD enzyme activity. Comparing the enzyme activities of the 6 missense mutations between the sexes, we found significant differences (P < 0.05) in the enzyme activities of both male hemizygotes and female heterozygotes. Two previously unreported mutations (c.1438A>T and c.946G>A) were identified. CONCLUSIONS: This study provided detailed genotypes of G6PD deficiency in Guangzhou, which could be valuable for diagnosing and researching G6PD deficiency in this area.
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Deficiência de Glucosefosfato Desidrogenase , Feminino , Humanos , Masculino , China/epidemiologia , Genótipo , Glucosefosfato Desidrogenase/genética , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , Heterozigoto , MutaçãoRESUMO
INTRODUCTION: Fibrosing mediastinitis (FM) is a rare disease characterized by excessive proliferation of fibrous tissue in the mediastinum and can cause bronchial stenosis, superior vena cava obstruction, pulmonary artery and vein stenosis, etc. CASE PRESENTATION: An aging patient with intermittent chest tightness and shortness of breath was diagnosed with FM associated pulmonary hypertension (FM-PH) by echocardiography and enhanced CT of the chest, and CT pulmonary artery (PA)/ pulmonary vein (PV) imaging revealed PA and PV stenosis. Selective angiography revealed complete occlusion of the right upper PV, and we performed endovascular intervention of the total occluded PV. After failure of the antegrade approach, the angiogram revealed well-developed collaterals of the occluded RSPV-V2b, so we chose to proceed via the retrograde approach. We successfully opened the occluded right upper PV and implanted a stent. CONCLUSIONS: This report may provide new management ideas for the interventional treatment of PV occlusion.
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Veias Pulmonares , Stents , Humanos , Resultado do Tratamento , Veias Pulmonares/diagnóstico por imagem , Veias Pulmonares/fisiopatologia , Veias Pulmonares/cirurgia , Doença Crônica , Pneumopatia Veno-Oclusiva/terapia , Pneumopatia Veno-Oclusiva/diagnóstico por imagem , Pneumopatia Veno-Oclusiva/fisiopatologia , Pneumopatia Veno-Oclusiva/etiologia , Estenose de Veia Pulmonar/diagnóstico por imagem , Estenose de Veia Pulmonar/terapia , Estenose de Veia Pulmonar/fisiopatologia , Estenose de Veia Pulmonar/etiologia , Mediastinite/diagnóstico , Mediastinite/terapia , Masculino , Flebografia , Angioplastia com Balão/instrumentação , Idoso , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/diagnóstico por imagem , Fibrose , Circulação Colateral , Circulação Pulmonar , FemininoRESUMO
Acute coronary syndrome (ACS) is a severe type of coronary heart disease (CHD) with increasing prevalence and significant challenges for prevention and treatment. Metabolomics is an emerging technology with intrinsic dynamics and flexibility to better delineate the phenotypic and metabolic alterations in organisms at the time of altered pathological states. It provides new insights into the complex pathological mechanisms of cardiovascular disease and contributes to the early detection, monitoring and evaluation of ACS. In this review, we analyze and summarize the literature related to ACS metabolomics which has contributed to the diagnosis and prevention of ACS.
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When a magnon passes through two-dimensional magnetic textures, it will experience a fictitious magnetic field originating from the 3×3 skew-symmetric gauge fields. To date, only one of the three independent components of the gauge fields has been found to play a role in generating the fictitious magnetic field, while the other two are perfectly hidden. In this Letter, we show that they are concealed in the nonlinear magnon transport in magnetic textures. Without loss of generality, we theoretically study the nonlinear magnon-skyrmion interaction in antiferromagnets. By analyzing the scattering features of three-magnon processes between the circularly polarized incident magnon and breathing skyrmion, we predict a giant Hall angle of both the confluence and splitting modes. Furthermore, we find that the Hall angle reverses its sign when one switches the handedness of the incident magnons. We dub this the nonlinear topological magnon spin Hall effect. Our findings are deeply rooted in the bosonic nature of magnons that the particle number is not conserved, which has no counterpart in low-energy fermionic systems and may open the door for probing gauge fields by nonlinear means.
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We report the experimental realization of a two-dimensional (2D) weak topological insulator (WTI) in spinless Su-Schrieffer-Heeger circuits with parity-time and chiral symmetries. Strong and weak Z2 topological indexes are adopted to explain the experimental findings that a Dirac semimetal (DSM) phase and four WTI phases emerge in turn when we modulate the centrosymmetric circuit deformations. In the DSM phase, it is found that the Dirac cone is highly anisotropic and that it is not pinned to any high-symmetry points but can widely move within the Brillouin zone, which eventually leads to the phase transition between WTIs. In addition, we observe a pair of flat-band domain wall states by designing spatially inhomogeneous node connections. Our work provides the first experimental evidence for 2D WTIs, which significantly advances our understanding of the strong and weak nature of topological insulators, the robustness of flat bands, and the itinerant and anisotropic features of Dirac cones.
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Pulmonary endarterectomy (PEA) is used to treat chronic thromboembolic pulmonary hypertension (CTEPH) patients, and it can effectively remove organized thrombotic materials and proliferative intima as well as improve hemodynamics. It has been reported that the levels of several inflammatory factors were altered in the peri-operative period of PEA. Even though their specific role remains unknown, this could have some relevance. In this study, we reviewed the recently published data addressing these factors in PEA, attempting to understand their potential implications.
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Quantization effects of the nonlinear magnon-vortex interaction in ferromagnetic nanodisks are studied. We show that the circular geometry twists the spin-wave fields with spiral phase dislocations carrying quantized orbital angular momentum (OAM). Meanwhile, the confluence and splitting scattering of twisted magnons off the gyrating vortex core (VC) generates a frequency comb consisting of discrete and equally spaced spectral lines, dubbed as twisted magnon frequency comb (TMFC). It is found that the mode spacing of the TMFC is equal to the gyration frequency of the VC and the OAM quantum numbers between adjacent spectral lines differ by one. By applying a magnetic field perpendicular to the plane of a thick nanodisk, we observe a magnonic Penrose superradiance inside the cone vortex state, which mimics the amplification of particles scattered from a rotating black hole. It is demonstrated that the higher-order modes of TMFC are significantly amplified while the lower-order ones are trapped within the VC gyrating orbit which manifests as the ergoregion. These results suggest a promising way to generate twisted magnons with large OAM and to drastically improve the flatness of the magnon comb.
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AIMS: This study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu's arteritis-associated pulmonary hypertension (TA-PH). METHODS AND RESULTS: We conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu's arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77-16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03-1.06), P < 0.001], and mean right atrial pressure [adjusted HR 1.07 (1.01-1.13), P = 0.015]. CONCLUSION: Patients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators' personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Arterite de Takayasu , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Estudos Retrospectivos , Arterite de Takayasu/complicações , Arterite de Takayasu/epidemiologiaRESUMO
Although balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) are effective in chronic thromboembolic pulmonary hypertension (CTEPH), the comparison of their efficacy and safety is still unclear. We identified studies through a systematic review of PubMed, Cochrane Library, and Embase and used a random effects meta-analysis model to synthesize estimates of weighted mean differences or combined effect size. In total, 54 studies were included in this meta-analysis. The survival rates at perioperative/in-hospital period, 2 years, and 3 years were 100%, 99%, and 97%, respectively, in BPA group and 93%, 90%, and 88%, respectively, in PEA group. The variation of 6-min walk distance was 141.80 m in BPA and 100.73 m in PEA when the follow-up was 1-6 months. At < 1-month, 1-6-month, and > 12-month follow-up, the changed results of mean pulmonary arterial pressure were - 18.31, - 17.00, and - 12.97 mmHg in BPA group and - 18.93, - 21.21, and - 21.35 mmHg in PEA group. At < 1-month and 1-6-month follow-up, the changed values of pulmonary vascular resistance were - 542.24 and - 599.77 dyneâ¢sâ¢cm-5 in PEA group and - 443.49 and - 280.00 dyneâ¢sâ¢cm-5 in BPA group. In addition, there was more wide variety of complications in PEA group than in BPA group. BPA might have higher survival rate (perioperative/in-hospital period, 2-year and 3-year follow-up) and fewer types of complications compared with PEA. The improvement in exercise capacity (1-6-month follow-up) in the BPA group might be more pronounced than in PEA group. Moreover, PEA might be superior in improvement of hemodynamic parameters (< 1-month, 1-6-month, and > 12-month follow-up).
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Angioplastia com Balão , Hipertensão Pulmonar , Embolia Pulmonar , Doença Crônica , Endarterectomia , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/cirurgia , Artéria Pulmonar/cirurgia , Embolia Pulmonar/complicações , Embolia Pulmonar/cirurgia , Resultado do TratamentoRESUMO
An optical frequency comb consists of a set of discrete and equally spaced frequencies and has found wide applications in the synthesis over a broad range of spectral frequencies of electromagnetic waves and precise optical frequency metrology. Despite the analogies between magnons and photons in many aspects, the analog of an optical frequency comb in magnonic systems has not been reported. Here, we theoretically study the magnon-skyrmion interaction and find that a magnonic frequency comb (MFC) can be generated above a threshold driving amplitude, where the nonlinear scattering process involving three magnons prevails. The mode spacing of the MFC is equal to the breathing-mode frequency of the skyrmion and is thus tunable by either electric or magnetic means. The theoretical prediction is verified by micromagnetic simulations, and the essential physics can be generalized to a large class of magnetic solitons. Our findings open a new pathway to observe frequency comb structures in magnonic devices that may inspire the study of fundamental nonlinear physics in spintronic platforms in the future.
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BACKGROUND: ST-segment elevation (STE) in lead aVR is a useful tool in recognizing patients with left main or left anterior descending coronary obstruction during acute coronary syndrome (ACS). The prognostic implication of STE in lead aVR on outcomes has not been established. METHODS: We performed a systematic search for clinical studies about STE in lead aVR in four databases including PubMed, EMBASE, Cochrane Library, and Web of Science. Primary outcome was in-hospital mortality. Secondary outcomes included in-hospital (re)infarction, in-hospital heart failure, and 90-day mortality. RESULTS: We included 7 studies with a total of 7,700 patients. The all-cause in-hospital mortality of patients with STE in lead aVR during ACS was significantly higher than that of patients without STE (OR: 4.37, 95% CI 1.63 to 11.68, p = .003). Patients with greater STE (>0.1 mV) in lead aVR had a higher in-hospital mortality when compared to lower STE (0.05-0.1 mV) (OR: 2.00, 95% CI 1.11-3.60, p = .02), However, STE in aVR was not independently associated with in-hospital mortality in ACS patients (OR: 2.72, 95% CI 0.85-8.63, p = .09). The incidence of in-hospital myocardial (re)infarction (OR: 2.77, 95% CI 1.30-5.94, p = .009), in-hospital heart failure (OR: 2.62, 95% CI 1.06-6.50, p = .04), and 90-day mortality (OR: 10.19, 95% CI 5.27-19.71, p < .00001) was also noted to be higher in patients STE in lead aVR. CONCLUSIONS: This contemporary meta-analysis shows STE in lead aVR is a poor prognostic marker in patients with ACS with higher in-hospital mortality, reinfarction, heart failure and 90-day mortality. Greater magnitude of STE portends worse prognosis. Further studies are needed to establish an independent predictive role of STE in aVR for these adverse outcomes.
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Síndrome Coronariana Aguda/diagnóstico por imagem , Síndrome Coronariana Aguda/fisiopatologia , Eletrocardiografia/métodos , Mortalidade Hospitalar , Humanos , PrognósticoRESUMO
Higher-order topological insulator (HOTI) represents a new phase of matter, the characterization of which goes beyond the conventional bulk-boundary correspondence and is attracting significant attention by the broad community. Using a square-root operation, it has been suggested that a square-root HOTI may emerge in a hybrid honeycomb-kagome lattice. Here, we report the first experimental realization of the square-root HOTI in topological LC circuits. We show theoretically and experimentally that the square-root HOTI inherits the feature of wave function from its parent with corner states pinned to nonzero energies. The topological feature is fully characterized by the bulk polarization. To directly measure the finite-energy corner modes, we introduce extra grounded inductors to each node, which shifts corner states to zero-energy without affecting their spatial distributions. Our results experimentally substantiate the emerging square-root HOTI and pave the way to realizing exotic topological phases that are challenging to observe in condensed matter physics.
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Wave fields with spiral phase dislocations carrying orbital angular momentum (OAM) have been realized in many branches of physics, such as for photons, sound waves, electron beams, and neutrons. However, the OAM states of magnons (spin waves)-the building block of modern magnetism-and particularly their implications have yet to be addressed. Here, we theoretically investigate the twisted spin-wave generation and propagation in magnetic nanocylinders. The OAM nature of magnons is uncovered by showing that the spin-wave eigenmode is also the eigenstate of the OAM operator in the confined geometry. Inspired by optical tweezers, we predict an exotic "magnetic tweezer" effect by showing skyrmion gyrations under twisted magnons in the exchange-coupled nanocylinder-nanodisk heterostructure, as a practical demonstration of magnonic OAM transfer to manipulate topological spin defects. Our study paves the way for the emerging magnetic manipulations by harnessing the OAM degree of freedom of magnons.
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BACKGROUND: Whether glutathione S-transferase (GST) null polymorphisms, namely GSTM1 null, GSTP1 null and GSTT1 null polymorphisms, influence the risk of coronary artery disease (CAD) or not remains unclear. Thus, the authors performed a meta-analysis to more robustly estimate associations between GST null polymorphisms and the risk of CAD by integrating the results of previous publications. METHODS: Medline, Embase, Wanfang, VIP and CNKI were searched comprehensively for eligible studies, and 45 genetic association studies were finally selected to be included in this meta-analysis. RESULTS: We found that GSTM1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.37, p = 0.003) and mixed population (OR = 1.61, p = 0.004), GSTP1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.23, p = 0.03), whereas GSTT1 null polymorphism was significantly associated with the risk of CAD in overall population (OR = 1.23, p = 0.02), Caucasians (OR = 1.23, p = 0.02) and East Asians (OR = 1.38, p < 0.0001). CONCLUSIONS: This meta-analysis demonstrated that GSTM1 null, GSTP1 null and GSTT1 null polymorphisms were all significantly associated with an increased risk of CAD.
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Pulmonary hypertension (PH) is a syndrome characterized by a persistent increase in pulmonary vascular resistance. Due to the lack of specificity in clinical manifestations, patients are usually diagnosed at the late stage of PH, which is hard to treat and often causes right heart failure and death. Furthermore, the regulation and pathogenesis of PH remain obscure. Recently, long noncoding RNAs (lncRNAs), a type of transcript longer than 200 nt that lacks protein-coding ability, have been found to substantially influence the incidence and progression of various diseases through regulating gene expression at the chromatin, transcriptional, post-transcriptional, translational, and even post-translational levels. The crucial roles of lncRNAs in PH have started to draw widespread attention. This review summarizes the regulatory, pathogenic, and diagnostic roles of lncRNAs in PH, in the hope to facilitate the search for early diagnostic markers of and effective therapeutic targets for this devastating disease.
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Programmed death receptor-1 (PD-1) and its ligand, PD-L1, as negative co-stimulatory molecules, are indispensable for regulating both physiological and pathological immune responses. The PD-1/PD-L1-mediated signaling pathway has been studied extensively in cancer research and has become a hotspot for biopharmaceuticals and immunotherapy. Furthermore, monoclonal antibodies to PD-1 have just been approved by the US Food and Drug Administration to treat certain types of malignancies. Recent research has unveiled a close association between the PD-1/PD-L1 system and eye diseases. This review describes the expression and physiological functions of PD-1 and its ligand in ocular tissues and summarizes the pathogenic, regulatory, and therapeutic roles of PD-1/PD-L1 system in eye diseases, including uveal melanoma, autoimmune uveitis, autoimmune dry eye, sympathetic ophthalmia, Graves' ophthalmopathy, diabetic retinopathy, herpes simplex keratitis, and trachoma, with the intent of highlighting the potential of PD-1/PD-L1 as novel therapeutic targets or biomarkers for these ocular diseases.
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Antígeno B7-H1/metabolismo , Oftalmopatias/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Animais , Doenças Autoimunes/metabolismo , Humanos , Modelos BiológicosRESUMO
BACKGROUND: Familial hypercholesterolemia (FH) can lead to premature coronary heart disease. Anticardiolipin antibody may be a contributor for thrombosis. Here, we report an adult with possible FH suffered from premature myocardial infarction that may be triggered by transient increased anticardiolipin antibody. CASE PRESENTATION: A 29-year-old male had presented with a history of 2-h chest pain and numbness of left upper arm before 5 days. The electrocardiogram (ECG) had demonstrated inferior wall myocardial infarction (MI). Five days later he was admitted to our hospital and diagnosed as acute MI and possible FH (premature coronary heart disease, low density lipoprotein cholesterol of 5.90 mmol/L) with increased anticardiolipin antibody (up to 120 RU/ml). Other auto-antibodies including ß2-glicoprotein antibodies IgM, IgA, IgG, lupus anticoagulant (LA), antinuclear antibodies, anti-myocardial antibody were normal. Coronary artery angiography (CAG) showed right coronary artery was total occlusion from the middle segment. Then he underwent percutaneous coronary intervention with a stent. Four days later, he was discharged with complete recovery. CAG showed intra-stent restenosis and anticardiolipin antibody level was normal and the patient had no any symptoms at 6-month follow-up. CONCLUSIONS: Transient elevated anticardiolipin antibody may be a trigger or biomarker of cardiac thrombotic events in younger atherosclerotic patients.
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Anticorpos Anticardiolipina/sangue , Oclusão Coronária/etiologia , Trombose Coronária/etiologia , Hiperlipoproteinemia Tipo II/complicações , Infarto do Miocárdio/etiologia , Adulto , Anticoagulantes/uso terapêutico , Biomarcadores/sangue , Oclusão Coronária/sangue , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Trombose Coronária/sangue , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/terapia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/diagnóstico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Masculino , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Intervenção Coronária Percutânea/instrumentação , Inibidores da Agregação Plaquetária/uso terapêutico , Stents , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND/AIMS: Blood-retinal barrier (BRB) breakdown and vascular leakage is the leading cause of blindness of diabetic retinopathy (DR). Hyperglycemia-induced oxidative stress and inflammation are primary pathogenic factors of this severe DR complication. An effective interventional modality against the pathogenic factors during early DR is needed to curb BRB breakdown and vascular leakage. This study sought to examine the protective effects of α-Melanocyte-stimulating hormone (α-MSH) on early diabetic retina against vascular hyperpermeability, electrophysiological dysfunction, and morphological deterioration in a rat model of diabetes and probe the mechanisms underlying the α-MSH's anti-hyperpermeability in both rodent retinas and simian retinal vascular endothelial cells (RF6A). METHODS: Sprague Dawley rats were injected through tail vein with streptozotocin to induce diabetes. The rats were intravitreally injected with α-MSH or saline at Week 1 and 3 after hyperglycemia. In another 2 weeks, Evans blue assay, transmission electron microscopy, electroretinogram (ERG), and hematoxylin and eosin (H&E) staining were performed to examine the protective effects of α-MSH in diabetic retinas. The expression of pro-inflammatory factors and tight junction at mRNA and protein levels in retinas was analyzed. Finally, the α-MSH's anti-hyperpermeability was confirmed in a high glucose (HG)-treated RF6A cell monolayer transwell culture by transendothelial electrical resistance (TEER) measurement and a fluorescein isothiocyanate-Dextran assay. Universal or specific melanocortin receptor (MCR) blockers were also employed to elucidate the MCR subtype mediating α-MSH's protection. RESULTS: Evans blue assay showed that BRB breakdown and vascular leakage was detected, and rescued by α-MSH both qualitatively and quantitatively in early diabetic retinas; electron microscopy revealed substantially improved retinal and choroidal vessel ultrastructures in α-MSH-treated diabetic retinas; scotopic ERG suggested partial rescue of functional defects by α-MSH in diabetic retinas; and H&E staining revealed significantly increased thickness of all layers in α-MSH-treated diabetic retinas. Mechanistically, α-MSH corrected aberrant transcript and protein expression of pro-inflammatory factor and tight junction genes in the diseased retinas; moreover, it prevented abnormal changes in TEER and permeability in HG-stimulated RF6A cells, and this anti-hyperpermeability was abolished by a universal MCR blocker or an antagonist specific to MC4R. CONCLUSIONS: This study showed previously undescribed protective effects of α-MSH on inhibiting BRB breakdown and vascular leakage, improving electrophysiological functions and morphology in early diabetic retinas, which may be due to its down-regulating pro-inflammatory factors and augmenting tight junctions. α-MSH acts predominantly on MC4R to antagonize hyperpermeability in retinal microvessel endothelial cells.