Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 180
Filtrar
1.
Ann Anat ; 247: 152049, 2023 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-36690044

RESUMO

Ischemia-reperfusion (I/R) injury is a common pathological mechanism in many retinal diseases, which can lead to cell death via mitochondrial dysfunction. Voltage-dependent anion channel 1 (VDAC1), which is mainly located in the outer mitochondrial membrane, is the gatekeeper of mitochondria. The permeability of mitochondrial membrane can be regulated by controlling the oligomerization of VDAC1. However, the functional mechanism of VDAC1 in retinal I/R injury was unclear. Our results demonstrate that oxygen-glucose deprivation and re-oxygenation (OGD/R) injury leads to apoptosis, necroptosis, and mitochondrial dysfunction of R28 cells. The OGD/R injury increases the levels of VDAC1 oligomerization. Inhibition of VDAC1 oligomerization by VBIT-12 rescued mitochondrial dysfunction by OGD/R and also reduced apoptosis/necroptosis of R28 cells. In vivo, the use of VBIT-12 significantly reduced aHIOP-induced neuronal death (apoptosis/necroptosis) in the rat retina. Our findings indicate that VDAC1 oligomers may open and enlarge mitochondrial membrane pores during OGD/R injury, leading to the release of death-related factors in mitochondria, resulting in apoptosis and necroptosis. This study provides a potential therapeutic strategy against ocular diseases caused by I/R injury.

2.
Biochim Biophys Acta Mol Cell Res ; 1870(3): 119433, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36706922

RESUMO

Ischemia/reperfusion (I/R) injury is one of the most common etiologies in many diseases. Retinal I/R leads to cytokine storm, resulting in tissue damage and cell death. Pyroptosis, a novel type of regulated cell death, occurs after cellular I/R injury. In this study, we established an oxygen glucose deprivation (OGD/R) cellular model (R28) to simulate retinal I/R injury. We conducted an LDH assay, and EthD-III and PI staining procedures to confirm pyroptosis. Mass spectrometry and bioinformatics analysis were used to identify the possible proteins interacting with NLRP3. Co-IP and various molecular biology techniques were used to investigate the possible modes regulating NLRP3 by DTX3L. EthD-III, PI staining and LDH assays demonstrated pyroptosis induced by OGD/R injury, mediated via NLRP3 pathway. Mass spectrometry and bioinformatics analysis screened out three candidate proteins interacting with NLRP3, and further Co-IP experiment indicated that DTX-3L may interact with NLRP3 to regulate its protein levels after injury. Co-IP experiments and various molecular biology methods demonstrated that DTX3L ubiquitinates NLRP3 resulting in pyroptosis after R28 OGD/R injury. Further, NLRP3 LRR and DTX3L RING domains interact with each other. Our study demonstrated that DTX3L may ubiquitinate NLRP3 to regulate OGD/R-induced pyroptosis globally in R28 cells.

3.
Transl Stroke Res ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36631632

RESUMO

Subarachnoid hemorrhage (SAH) is a type of stroke with high morbidity and mortality. Netrin-1 (NTN-1) can alleviate early brain injury (EBI) following SAH by enhancing peroxisome proliferator-activated receptor gamma (PPARγ), which is an important transcriptional factor modulating lipid metabolism. Ferroptosis is a newly discovered type of cell death related to lipid metabolism. However, the specific function of ferroptosis in NTN-1-mediated neuroprotection following SAH is still unclear. This study aimed to evaluate the neuroprotective effects and the possible molecular basis of NTN-1 in SAH-induced EBI by modulating neuronal ferroptosis using the filament perforations model of SAH in mice and the hemin-stimulated neuron injury model in HT22 cells. NTN-1 or a vehicle was administered 2 h following SAH. We examined neuronal death, brain water content, neurological score, and mortality. NTN-1 treatment led to elevated survival probability, greater survival of neurons, and increased neurological score, indicating that NTN-1-inhibited ferroptosis ameliorated neuron death in vivo/in vitro in response to SAH. Furthermore, NTN-1 treatment enhanced the expression of PPARγ, nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPX4), which are essential regulators of ferroptosis in EBI after SAH. The findings show that NTN-1 improves neurological outcomes in mice and protects neurons from death caused by neuronal ferroptosis. Furthermore, the mechanism underlying NTN-1 neuroprotection is correlated with the inhibition of ferroptosis, attenuating cell death via the PPARγ/Nrf2/GPX4 pathway and coenzyme Q10-ferroptosis suppressor protein 1 (CoQ10-FSP1) pathway.

4.
Int J Biol Sci ; 19(2): 658-674, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36632450

RESUMO

The discovery of the necroptosis, a form of regulated necrosis that is mediated by receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like pseudokinase (MLKL), represents a major breakthrough that has dramatically altered the conception of necrosis - traditionally thought of as uncontrolled cell death - in various human diseases. Retinal cell death is a leading cause of blindness and has been identified in most retinal diseases, e.g., age-related macular degeneration, glaucoma, retinal detachment, retinitis pigmentosa, etc. Increasing evidence demonstrates that retinal degenerative diseases also share a common mechanism in necroptosis. Exacerbated necroptotic cell death hinders the treatment for retinal degenerative diseases. In this review, we highlight recent advances in identifying retinal necroptosis, summarize the underlying mechanisms of necroptosis in retinal degenerative diseases, and discuss potential anti-necroptosis strategies, such as selective inhibitors and chemical agents, for treating retinal degenerative diseases.


Assuntos
Proteínas Quinases , Doenças Retinianas , Humanos , Proteínas Quinases/metabolismo , Necrose , Apoptose , Morte Celular , Doenças Retinianas/tratamento farmacológico
5.
Front Cell Neurosci ; 16: 1025708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582214

RESUMO

Subarachnoid haemorrhage (SAH) is a common cerebrovascular disease with high disability and mortality rates worldwide. The pathophysiological mechanisms involved in an aneurysm rupture in SAH are complex and can be divided into early brain injury and delayed brain injury. The initial mechanical insult results in brain tissue and vascular disruption with hemorrhages and neuronal necrosis. Following this, the secondary injury results in diffused cerebral damage in the peri-core area. However, the molecular mechanisms of neuronal death following an aneurysmal SAH are complex and currently unclear. Furthermore, multiple cell death pathways are stimulated during the pathogenesis of brain damage. Notably, particular attention should be devoted to necrosis, apoptosis, autophagy, necroptosis, pyroptosis and ferroptosis. Thus, this review discussed the mechanism of neuronal death and its influence on brain injury after SAH.

6.
Br J Ophthalmol ; 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36385002

RESUMO

AIMS: To investigate longitudinal choroid and ganglion cell-inner plexiform layer (GCIPL) changes in type 2 diabetes mellitus (T2DM) patients and healthy populations across 2 years. METHODS: This prospective cohort study included T2DM patients and healthy controls. T2DM patients were divided into mild non-proliferative diabetic retinopathy (NPDR) or non-DR (NDR) groups. Macular choroidal and GCIPL thickness was measured using swept-source optical coherence tomography at baseline and follow-up after 2 years. A linear-mixed effect model compared rates of change in choroidal and GCIPL thicknesses between the three groups. RESULTS: 895 T2DM patients (770 in the NDR group and 125 in the NPDR group) and 847 healthy controls were included. Following 2 years, choroidal thinning occurred at a rate of -7.7±9.2 µm/year, -8.1±8.7 µm/year and -5.2±8.1 µm/year in NDR, NPDR and control groups, respectively (p<0.001). GCIPL loss occurred quickest in NPDR patients (-0.97±0.97 µm/year), followed by NDR (-0.91±0.89 µm/year) and the control group (-0.04±0.55 µm/year) (p<0.001). Following multivariate adjustment, choroidal thinning was -2.04 µm/year (95% CI: -4.05 to -0.03; p=0.047) and -1.95 µm/year (95% CI: -3.14 to -0.75; p=0.001) faster in NPDR and NDR groups than in the control group, respectively, and GCIPL thinning was -1.02 µm/year (95% CI: -1.19 to -0.84; p<0.001) and -0.88 µm/year (95% CI: -0.98 to -0.78; p<0.001) faster in the NPDR and NDR groups than in the control group, respectively. CONCLUSION: Progressive choroidal and GCIPL thinning occurs in healthy individuals and T2DM patients; however, T2DM undergoes accelerated choroidal and GCIPL loss in NPDR patients.

7.
Front Surg ; 9: 1025557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338621

RESUMO

Background: Biochemical processes involved in complex skin diseases (skin cancers, psoriasis, and wound) can be identified by combining proteomics analysis and bioinformatics tools, which gain a next-level insight into their pathogenesis, diagnosis, and therapeutic targets. Methods: Articles were identified through a search of PubMed, Embase, and MEDLINE references dated to May 2022, to perform system data mining, and a search of the Web of Science (WoS) Core Collection was utilized to conduct a visual bibliometric analysis. Results: An increased trend line revealed that the number of publications related to proteomics utilized in skin diseases has sharply increased recent years, reaching a peak in 2021. The hottest fields focused on are skin cancer (melanoma), inflammation skin disorder (psoriasis), and skin wounds. After deduplication and title, abstract, and full-text screening, a total of 486 of the 7,822 outcomes met the inclusion/exclusion criteria for detailed data mining in the field of skin disease tooling with proteomics, with regard to skin cancer. According to the data, cell death, metabolism, skeleton, immune, and inflammation enrichment pathways are likely the major part and hotspots of proteomic analysis found in skin diseases. Also, the focuses of proteomics in skin disease are from superficial presumption to depth mechanism exploration within more comprehensive validation, from basic study to a combination or guideline for clinical applications. Furthermore, we chose skin cancer as a typical example, compared with other skin disorders. In addition to finding key pathogenic proteins and differences between diseases, proteomic analysis is also used for therapeutic evaluation or can further obtain in-depth mechanisms in the field of skin diseases. Conclusion: Proteomics has been regarded as an irreplaceable technology in the study of pathophysiological mechanism and/or therapeutic targets of skin diseases, which could provide candidate key proteins for the insight into the biological information after gene transcription. However, depth pathogenesis and potential clinical applications need further studies with stronger evidence within a wider range of skin diseases.

8.
BMC Pulm Med ; 22(1): 402, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344945

RESUMO

BACKGROUND: Radiotherapy is an important treatment for patients with stage III/IV non-small cell lung cancer (NSCLC), and due to its high incidence of radiation pneumonitis, it is essential to identify high-risk people as early as possible. The present work investigates the value of the application of different phase data throughout the radiotherapy process in analyzing risk of grade ≥ 2 radiation pneumonitis in stage III/IV NSCLC. Furthermore, the phase data fusion was gradually performed with the radiotherapy timeline to develop a risk assessment model. METHODS: This study retrospectively collected data from 91 stage III/IV NSCLC cases treated with Volumetric modulated arc therapy (VMAT). Patient data were collected according to the radiotherapy timeline for four phases: clinical characteristics, radiomics features, radiation dosimetry parameters, and hematological indexes during treatment. Risk assessment models for single-phase and stepwise fusion phases were established according to logistic regression. In addition, a nomogram of the final fusion phase model and risk classification system was generated. Receiver operating characteristic (ROC), decision curve, and calibration curve analysis were conducted to internally validate the nomogram to analyze its discrimination. RESULTS: Smoking status, PTV and lung radiomics feature, lung and esophageal dosimetry parameters, and platelets at the third week of radiotherapy were independent risk factors for the four single-phase models. The ROC result analysis of the risk assessment models created by stepwise phase fusion were: (area under curve [AUC]: 0.67,95% confidence interval [CI]: 0.52-0.81), (AUC: 0.82,95%CI: 0.70-0.94), (AUC: 0.90,95%CI: 0.80-1.00), and (AUC:0.90,95%CI: 0.80-1.00), respectively. The nomogram based on the final fusion phase model was validated using calibration curve analysis and decision curve analysis, demonstrating good consistency and clinical utility. The nomogram-based risk classification system could correctly classify cases into three diverse risk groups: low-(ratio:3.6%; 0 < score < 135), intermediate-(ratio:30.7%, 135 < score < 160) and high-risk group (ratio:80.0%, score > 160). CONCLUSIONS: In our study, the risk assessment model makes it easy for physicians to assess the risk of grade ≥ 2 radiation pneumonitis at various phases in the radiotherapy process, and the risk classification system and nomogram identify the patient's risk level after completion of radiation therapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Pneumonia , Pneumonite por Radiação , Radioterapia de Intensidade Modulada , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Pneumonite por Radiação/etiologia , Estudos Retrospectivos , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Pulmonares/complicações , Medição de Risco , Pneumonia/complicações
9.
Heliyon ; 8(10): e10874, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36276718

RESUMO

Background: Rosacea is a common and complex chronic inflammatory skin disorder, the pathophysiology and etiology of which remain unclear. Recently, significant new insights into rosacea pathogenesis have enriched and reshaped our understanding of the disorder. A systematic analysis based on current studies will facilitate further research on rosacea pathogenesis. Objective: To establish an international core outcome and knowledge system of rosacea pathogenesis and develop a challenge, trend and hot spot analysis set for research and clinical studies on rosacea using bibliometric analysis and data mining. Methods: A search of the WoS, and PubMed, MEDLINE, Embase and Cochrane collaboration databases was conducted to perform visual bibliometric and data analysis. Results: A total of 2,654 studies were used for the visualization and 302 of the 6,769 outcomes for data analysis. It reveals an increased trend line in the field of rosacea, in which its fast-growing pathogenesis attracted attention closely related to risk, comorbidity and therapeutic strategies. The rosacea pathogenesis has undergone the great development on immunology, microorganisms, genes, skin barriers and neurogenetics. The major of studies have focused on immune and microorganisms. And keyword visualization and data analyses demonstrated the cross-talk between cells or each aspect of pathogenesis, such as gene-gene or gene-environment interactions, and neurological mechanisms associated with the rosacea phenotype warrant further research. Limitations: Inherent limitations of bibliometrics; and reliance on research and retrospective studies. Conclusions: The understanding of rosacea's pathogenesis has been significantly enhanced with the improved technology and multidisciplinary integration, but high-quality, strong evidence in favor of genomic and neurogenic requires further research combined with a better understanding of risks and comorbidities to guide clinical practice.

10.
Am J Ophthalmol ; 246: 96-106, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36240858

RESUMO

PURPOSE: To investigate the association of body mass index (BMI) and waist-to-hip ratio (WHR) with macular vessel density (VD) and foveal avascular zone (FAZ), using optical coherence tomography angiography (OCTA), in healthy Chinese adults. DESIGN: Cross-sectional study. METHODS: A total of 1555 Chinese adults aged ≥ 50 years with no history of ocular disease were recruited from communities in Guangzhou, China. The OCTA was performed with a 6 × 6 mm macular angiography model. The FAZ of the superficial capillary plexus (SCP), and VD of SCP and deep capillary plexus (DCP) were calculated. Univariable and multivariable linear regression analyses were used to evaluate the effect of BMI and WHR on VD and FAZ. RESULTS: The VD of the SCP increased as BMI increased, with average measurements of 39.30 ± 2.14 for normal, 39.52 ± 2.07 for overweight, and 39.76 ± 2.03 for obesity (P = .001). The VD of the DCP also increased with increasing BMI (P = .009). Multiple regression models confirmed a positive association between generalized obesity and superficial VD in the whole image (ß = 0.350, P = .008), inner circle (ß = 0.431, P = .032), and outer circle (ß = 0.368, P = .005). After adjusting for confounders, tertile 3 of the WHR level was positively associated with superficial VD (ß = 0.472, P = .033) and deep VD (ß = 0.422, P = .034) only in the inner circle. CONCLUSIONS: Generalized obesity was associated with increased superficial VD, while abdominal obesity was associated with increased superficial and deep VD only in the inner circle. Different manifestations of the retinal microvasculature may reflect distinct roles of body composition on macular vessel alterations and disease occurrence.

11.
Front Physiol ; 13: 950086, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36160840

RESUMO

Remote ischemic preconditioning (RIPC) may improve exercise performance. However, the influence of RIPC on aerobic performance and underlying physiological mechanisms during hypobaric hypoxia (HH) exposure remains relatively uncertain. Here, we systematically evaluated the potential performance benefits and underlying mechanisms of RIPC during HH exposure. Seventy-nine healthy participants were randomly assigned to receive sham intervention or RIPC (4 × 5 min occlusion 180 mm Hg/reperfusion 0 mm Hg, bilaterally on the upper arms) for 8 consecutive days in phases 1 (24 participants) and phase 2 (55 participants). In the phases 1, we measured the change in maximal oxygen uptake capacity (VO2max) and muscle oxygenation (SmO2) on the leg during a graded exercise test. We also measured regional cerebral oxygenation (rSO2) on the forehead. These measures and physiological variables, such as cardiovascular hemodynamic parameters and heart rate variability index, were used to evaluate the intervention effect of RIPC on the changes in bodily functions caused by HH exposure. In the phase 2, plasma protein mass spectrometry was then performed after RIPC intervention, and the results were further evaluated using ELISA tests to assess possible mechanisms. The results suggested that RIPC intervention improved VO2max (11.29%) and accelerated both the maximum (18.13%) and minimum (53%) values of SmO2 and rSO2 (6.88%) compared to sham intervention in hypobaric hypoxia exposure. Cardiovascular hemodynamic parameters (SV, SVRI, PPV% and SpMet%) and the heart rate variability index (Mean RR, Mean HR, RMSSD, pNN50, Lfnu, Hfnu, SD1, SD2/SD1, ApEn, SampEn, DFA1and DFA2) were evaluated. Protein sequence analysis showed 42 unregulated and six downregulated proteins in the plasma of the RIPC group compared to the sham group after HH exposure. Three proteins, thymosin ß4 (Tß4), heat shock protein-70 (HSP70), and heat shock protein-90 (HSP90), were significantly altered in the plasma of the RIPC group before and after HH exposure. Our data demonstrated that in acute HH exposure, RIPC mitigates the decline in VO2max and regional oxygenation, as well as physiological variables, such as cardiovascular hemodynamic parameters and the heart rate variability index, by influencing plasma Tß4, HSP70, and HSP90. These data suggest that RIPC may be beneficial for acute HH exposure.

12.
Eye (Lond) ; 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008530

RESUMO

BACKGROUND: To evaluate the risk of AAC and intraocular pressure (IOP) changes in diabetic patients after pupil dilation. METHODS: This cross-sectional study enrolled 2,287 diabetic patients among community residents in Guangzhou, China. All participants underwent routine pupil dilation unless they had a history of glaucoma. IOP was measured using a non-contact tonometer before and one hour after pupil dilation with tropicamide 0.5% and phenylephrine 0.5% eye drop. The proportion of AAC and changes in IOP after pupil dilation were evaluated. RESULTS: Only one of the 2,287 participants (0.04%) with diabetes developed post-dilation AAC. The mean pre and post-dilation IOP in the right was 16.1 ± 2.7 and 16.5 ± 2.8 mmHg (P < 0.001); mean pre and post-dilation IOP in the left was 16.5 ± 2.7 and 16.8 ± 2.8 mmHg (P < 0.001). Sixty-one participants (2.7%) showed an increase in IOP ≥ 5 mmHg and 25 participants (1.1%) showed a post-dilation IOP > 25 mmHg, including 11 participants (0.5%) who had both an increase in IOP ≥ 5 mmHg and post-dilation IOP > 25 mmHg. Lower pre-dilation IOP (OR = 0.827; 95% CI, 0.742-0.922; P = 0.001) and shallower anterior chamber depth (ACD) (OR = 0.226; 95% CI, 0.088-0.585; P = 0.002) were significant risk factors for an increase in IOP ≥ 5 mmHg in multivariate logistic regression analysis. CONCLUSIONS: The risk of developing AAC after pupil dilation in diabetic patients was very low. Lower pre-dilation IOP and shallower ACD are risk factors for increased post-dilation IOP.

13.
Am J Ophthalmol ; 245: 164-173, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35863493

RESUMO

PURPOSE: To determine the predictive value of the microcirculation of the optic nerve head by swept-source optical coherence tomography angiography for identifying individuals with high risk of diabetic retinopathy (DR) progression and diabetic macular edema (DME) development. DESIGN: Prospective observational cohort study. METHODS: A total of 946 patients (1879 eyes) with type 2 diabetes mellitus were recruited who had no DR or mild nonproliferative DR at baseline, and no DME. All subjects underwent 3 × 3 mm swept-source optical coherence tomography angiography centered on the optic nerve head to generate angiograms in 4 layers: radial peripapillary plexus, superficial retinal capillary plexus (SCP), deep retinal capillary plexus, and choriocapillaris (CC). The CC flow deficit percentage (CC FD%), vessel density (VD), and perfusion density (PD) were quantified. RESULTS: During the 3 consecutive years of follow-up, 312 eyes (16.60%) experienced DR progression and 115 eyes (6.12%) developed DME. The DR progression was related to a lower VD of the SCP (relative risk per standard deviation decrease, 95% confidence interval): 1.30, 1.14-1.48; P < .001), a lower PD of the SCP (1.41, 1.24-1.60; P < .001), a lower VD of the radial peripapillary plexus (1.23, 1.08-1.40; P = .002), and an elevated CC FD% (1.62, 1.40-1.88; P < .001). The DME occurrence was associated with a lower VD of SCP (1.35, 1.09-1.66; P = .005), a lower PD of SCP (1.29, 1.05-1.59; P = .016), and a higher CC FD% (1.29, 1.03-1.61; P < .001). The CC FD% significantly improved the predictive power, with the increase of the C-statistic for DR progression and DME occurrence by 3.83% (P = .002) and 5.24% (P < .001), respectively. CONCLUSIONS: This study provides the first longitudinal evidence suggesting that peripapillary CC FD% can improve the prediction of DR progression and DME development beyond traditional risk factors.

14.
Am J Ophthalmol ; 243: 19-27, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35850252

RESUMO

PURPOSE: To examine the associations of peripapillary microvascular metrics with diabetic retinopathy (DR) incidence and development using swept-source optical coherence tomography angiography (SS-OCTA). DESIGN: Prospective cohort study. METHODS: A total of 1033 eyes from 1033 patients with type 2 diabetes mellitus (T2DM) were included, with 2-year follow-up. The peripapillary microvascular metrics at the superficial capillary plexus (SCP) were measured by SS-OCTA at the baseline, including peripapillary vascular density (pVD) and peripapillary vascular length density (pVLD). The DR incidence and progression were evaluated with 7 standard fields of stereoscopic color fundus photographs. The associations were tested with logistic regression models after adjusting for established risk factors and confounding factors. The prediction value of OCTA metrics was examined with the elevation of area under the receiver operating characteristic curve (AUROC). RESULTS: The 2-year incidence of diabetic retinopathy (DR) was 25.1% (n = 222) in non-DR (NDR) eyes, 7.4% DR progression (n = 11) in DR eyes, and 4.17% RDR eyes (n = 43) in all eyes. After adjusting for established factors, lower whole-image pVD (wi-pVD) (relative risk [RR] = 0.81; 95% CI = 0.68-0.96; P = .015), circular pVD (circ-pVD) (RR = 0.79; 95% CI = 0.66-0.95; P = .013), whole-image pVLD (wi-pVLD) (RR = 0.79; 95% CI = 0.67-0.94; P = .008), and circular pVLD (circ-pVLD) (RR = 0.76; 95% CI = 0.63-0.91; P = .003) were significantly associated with increased risk of DR incidence; wi-pVD (RR = 0.48; 95% CI = 0.35-0.67; P < .001), circ-pVD (RR = 0.65; 95% CI = 0.45-0.94; P = .023), and wi-pVLD (RR = 0.46; 95% CI = 0.33-0.66; P < .001) were associated with incident risk of RDR. Both pVD and pVLD of SCP were not significantly associated with DR progression. The AUROC for the DR incidence risk prediction model increased from 0.631 to 0.658 (4.28%; P = .041) by circ-pVLD; the AUC of the RDR incidence risk prediction model increased from 0.631 to 0.752 by wi-pVD (19.18%; P = .009), to 0.752 by circ-pVD (19.18%; P=.009), and to 0.752 by wi-pVLD (19.18%; P = .009). CONCLUSION: Lower pVD and pVLD of SCP are associated with 2-year incident DR and RDR among the T2DM population. The peripapillary metrics imaged by SS-OCTA can provide additional value to the prediction of DR incidence and development.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/complicações , Tomografia de Coerência Óptica/métodos , Angiofluoresceinografia , Vasos Retinianos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Prospectivos , Incidência , Microvasos
15.
Transl Vis Sci Technol ; 11(6): 21, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35737377

RESUMO

Purpose: Identifying clinical associations causing attenuation in choroidal thickness (CT) among healthy Chinese adults. Methods: A 2-year longitudinal study was conducted in volunteers aged over 30 years from China. All participants had no history of eye disease or surgery. All subjects underwent swept-source optical coherence tomography to measure the CT in the macular region at baseline and at 2-year follow-up. The regression models were based on the generalized estimating equation. Results: A total of 603 eyes of 336 healthy participants were included in the final analysis (mean [SD] age, 58.88 [8.82] years; 74.70% female). Mean (SD) choroidal thickness (MCT) was reduced significantly from 206.62 (72.42) to 194.02 (72.08) µm (difference, -12.60 µm; 95% confidence interval [CI], -13.62 to -11.57). Among the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid, CT at the subfoveal sector showed the greatest 2-year reduction (difference, -14.55 µm; 95% CI, -15.87 to -13.22). The largest 2-year change was observed in the 50 to 59 years group (difference, -14.51 µm; 95% CI, -16.71 to -12.32). Multivariate regression showed female gender (ß = -2.85; 95% CI, -5.65 to -0.56) and baseline MCT (ß = -0.040; 95% CI, -0.056 to -0.024) were significantly and independently associated with greater 2-year CT decrease. Conclusions: These results indicated that CT among Chinese healthy adults decreased during the 2-year follow-up, and the greater choroidal thinning rate was significantly associated with female gender and larger baseline MCT. Translational Relevance: Longitudinal CT data of healthy adults provide a reference range when evaluating pathologic variations, especially for the age-related retinal-choroidal disorders.


Assuntos
Doenças da Coroide , Corioide , Adulto , Idoso , China , Corioide/diagnóstico por imagem , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Tomografia de Coerência Óptica/métodos
16.
Front Microbiol ; 13: 913023, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35756031

RESUMO

Enterococcus faecalis is a common gram-positive non-spore-forming bacterium in nature and is found in the upper respiratory tract, intestine, and mouth of healthy people. E. faecalis is also one of the common pathogens causing nosocomial infections and is resistant to several antibiotics commonly used in practice. Thus, treating drug-resistant E. faecalis with antibiotics is challenging, and new approaches are needed. In this study, we isolated a bacteriophage named EFap02 that targets E. faecalis strain EFa02 from sewage at Southwest Hospital. Phage EFap02 belongs to the Siphoviridae family with a long tail of approximately 210 nm, and EFap02 can tolerate a strong acid and alkali environment and high temperature. Its receptor was identified as the capsular polysaccharide. Phage-resistant mutants had loss-of-function mutations in glycosyltransferase (gtr2), which is responsible for capsular polysaccharide biosynthesis, and this caused the loss of capsular polysaccharide and interruption of phage adsorption. Although phage-resistant mutants against EFap02 can be selected, such mutants are impaired in biofilm formation due to the loss of capsular polysaccharide, which compromises its virulence. Therefore, this study provided a detailed description of the E. faecalis EFap02 phage with the potential for treating E. faecalis infection.

17.
BMJ Open ; 12(5): e056332, 2022 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-35589355

RESUMO

INTRODUCTION: Although obesity is one of the established risk factors of diabetes mellitus, the relationship between obesity and diabetic retinopathy (DR) remains unclear in different studies. This study aimed to investigate the association of DR with four obesity-related indexes, including body mass index (BMI), waist to hip ratio (WHR), waist to height ratio (WHtR) and body adiposity index (BAI) in patients with diabetes. RESEARCH DESIGN AND METHODS: We prospectively enrolled 2305 patients with diabetes (2305 eyes) in the Guangzhou Diabetic Eye Study between November 2017 and December 2019 to investigate the prevalence and the association of different types of obesity with DR using BMI, WHR, WHtR and BAI. DR, diabetic macular oedema (DME) and vision-threatening DR (VTDR) were selected as primary outcomes. BMI was categorised as normal (18.5-22.9 kg/m2), overweight (23.0-25.0 kg/m2) and obese (>25.0 kg/m2); WHR, WHtR and BAI were categorised into quarters. RESULTS: A total of 336 (14.58%), 93 (4.03%) and 98 (4.25%) developed DR, DME and VTDR, respectively. The prevalence of DR, DME and VTDR was higher in patients with higher BMI/WHR or lower WHtR/BAI. In the univariate regression model, WHR correlated positively with DR, while WHtR and BAI correlated negatively with DR, DME and VTDR. The association remained independent of age, sex and lipid metabolism parameters. In the multivariate model, obese presented as a protective factor for DME and VTDR, while the second quarter of WHtR(Q2-WHtR) presented as a risk factor. CONCLUSIONS: As high as 67.8% of patients with diabetes were overweight or obese. Obese presented as a significant protective factor of VTDR, while Q2-WHtR presented as a significant risk factor. Therefore, more attention should be paid to centripetal obesity as well as general obesity. Further research is also needed to focus on the improvement of sex-specific weight management in patients with diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/etiologia , Feminino , Humanos , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso , Fatores de Risco , Circunferência da Cintura , Relação Cintura-Quadril
19.
Curr Med Sci ; 42(2): 237-248, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35391618

RESUMO

Ischemic stroke is a serious cerebrovascular disease with high morbidity and mortality. As a result of ischemia-reperfusion, a cascade of pathophysiological responses is triggered by the imbalance in metabolic supply and demand, resulting in cell loss. These cellular injuries follow various molecular mechanisms solely or in combination with this disorder. Mitochondria play a driving role in the pathophysiological processes of ischemic stroke. Once ischemic stroke occurs, damaged cells would respond to such stress through mitophagy. Mitophagy is known as a conservatively selective autophagy, contributing to the removal of excessive protein aggregates and damaged intracellular components, as well as aging mitochondria. Moderate mitophagy may exert neuroprotection against stroke. Several pathways associated with the mitochondrial network collectively contribute to recovering the homeostasis of the neurovascular unit. However, excessive mitophagy would also promote ischemia-reperfusion injury. Therefore, mitophagy is a double-edged sword, which suggests that maximizing the benefits of mitophagy is one of the direction of future efforts. This review emphasized the role of mitophagy in ischemic stroke, and highlighted the crosstalk between mitophagy and apoptosis/necroptosis.


Assuntos
AVC Isquêmico , Traumatismo por Reperfusão , Apoptose , Humanos , Mitofagia/fisiologia , Necroptose , Traumatismo por Reperfusão/metabolismo
20.
Br J Ophthalmol ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459692

RESUMO

PURPOSE: To report the 6-year incidence, causes and risk factors for vision loss (visual impairment (VI) and blindness), among elderly adults in rural southern China. METHODS: Population-based, cohort study. Initiated in 2014, the study recruited participants aged 50 and older using random cluster sampling from Yangxi County. All eligible participants were invited to attend interviews and comprehensive eye examinations at the 6-year follow-up between November 2020 and March 2021. The WHO categories of vision loss were used to define incident cases of VI (3/60≤VA <6/12), moderate-to-severe VI (MSVI) (3/60≤VA<6/18) and blindness (VA <3/60) in the better-seeing eye. RESULTS: Among the 5825 baseline participants, 3187 (64.4%) of 4946 surviving subjects participated in the 6-year follow-up. Based on presenting and best-corrected VA, respectively, the crude incidence rate of blindness was 0.8% (95% CI 0.5% to 1.1%) vs 0.3% (95% CI 0.1% to 0.5%), for MSVI 6.7% (95% CI 5.7% to 7.6%) vs 4.6% (95% CI 3.8% to 5.4%) and for any VI 16.1% (95% CI 14.5% to 17.6%) vs 12.9% (95% CI 11.6% to 14.1%). Cataract (48.3%) and refractive errors (44.4%) were the most common causes of vision loss. Factors significantly associated with greater incident vision loss were older age, female sex, less education, living alone and longer axial length (all p<0.05). CONCLUSIONS: Substantial work is still required to reduce avoidable vision loss in rural China. Screening outreach and efforts to improve awareness which target the poorer and less educated are urgently needed to reduce the growing unmet need for eye care due to ageing.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...