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1.
Artículo en Inglés | MEDLINE | ID: mdl-38673397

RESUMEN

BACKGROUND: Globally, the prevalence of diabetes is increasing, especially in low- and middle-income countries (LMICs), including those in the sub-Saharan African region. However, the independent socioeconomic correlates of glycemic control as measured by hemoglobin A1C have yet to be identified. Therefore, the aim of this analysis was to understand the independent correlates of glycemic control in South Africa. METHODS: Data from the 2016 South Africa Demographic and Health Survey on adults with diabetes were used for this analysis. The dependent variable, glycemic control, was defined using hemoglobin A1c (HbA1c). Independent variables included: age, gender, ethnicity, marital status, region, urban/rural residence, ability to read, education, insurance, wealth, occupation, and employment in the last year. Analysis of variance was used to test for differences in mean HbA1c for each category of all independent variables, and a fully adjusted linear regression model was used to identify independent correlates of glycemic control (HbA1c). RESULTS: Among the 772 people included in this analysis, there were significant differences in mean HbA1c by age (p < 0.001), ethnicity (p < 0.001), place of residence (p = 0.024), wealth index (p = 0.001), and employment in the last year (p = 0.008). Independent correlates of HbA1c included age, ethnicity, and wealth index. CONCLUSIONS: This study used data from a large diverse population with a high prevalence of diabetes in sub-Saharan Africa and provides new evidence on the correlates of glycemic control and potential targets for interventions designed to lower HbA1c and improve diabetes-related health outcomes of adults in South Africa.


Asunto(s)
Diabetes Mellitus , Hemoglobina Glucada , Control Glucémico , Humanos , Masculino , Sudáfrica/epidemiología , Femenino , Persona de Mediana Edad , Adulto , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Hemoglobina Glucada/análisis , Control Glucémico/estadística & datos numéricos , Anciano , Factores Socioeconómicos , Adulto Joven , Adolescente
2.
Int J Nanomedicine ; 19: 2091-2112, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476278

RESUMEN

Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting system Xc-. Additionally, the article explores the potential of combined treatment strategies involving iron-induced cell death and bionanotechnology. Finally, the application prospects and challenges of iron-induced nanoagents for cancer treatment are discussed.


Asunto(s)
Ferroptosis , Neoplasias , Humanos , Terapia Combinada , Muerte Celular , Hierro , Peroxidación de Lípido
3.
Bioresour Technol ; 395: 130381, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38281545

RESUMEN

Biogas production via anaerobic digestion is highly attractive for microalgae. The technology of microalgae cultivation has profound impacts on biogas production system as it is the most energy-consuming process. However, a comprehensive evaluation of the environmental and economic benefits of different cultivation systems has yet to be sufficiently conducted. Here, life-cycle and economic assessments of open raceway ponds, photobioreactors and biofilm systems were investigated. Results showed greenhouse gas emissions of all systems were positive because more than two-thirds of carbon in fuel gas was lost and the fixed carbon in product gas and solid fertilizer was less than the emitted carbon during energy input. Particularly, biofilm system achieved the least greenhouse gas emissions (9.3 g CO2-eq/MJ), net energy ratio (0.7) and levelized cost of energy (0.9 $/kWh), indicating the optimum cultivation system. Open raceway ponds and photobioreactors failed to achieve positive benefits because of low harvesting efficiency and biomass concentration.


Asunto(s)
Gases de Efecto Invernadero , Microalgas , Biocombustibles/análisis , Dióxido de Carbono/análisis , Biomasa , Biopelículas , Carbono
4.
Int J Nanomedicine ; 19: 109-135, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38192633

RESUMEN

The tumor microenvironment (TME) plays an important role in various stages of tumor generation, metastasis, and evasion of immune monitoring and treatment. TME targeted therapy is based on TME components, related pathways or active molecules as therapeutic targets. Therefore, TME targeted therapy based on environmental differences between TME and normal cells has been widely studied. Biomimetic nanocarriers with low clearance, low immunogenicity, and high targeting have enormous potential in tumor treatment. This review introduces the composition and characteristics of TME, including cancer­associated fibroblasts (CAFs), extracellular matrix (ECM), tumor blood vessels, non-tumor cells, and the latest research progress of biomimetic nanoparticles (NPs) based on TME. It also discusses the opportunities and challenges of clinical transformation of biomimetic nanoparticles.


Asunto(s)
Fibroblastos Asociados al Cáncer , Neoplasias , Humanos , Biomimética , Microambiente Tumoral , Neoplasias/tratamiento farmacológico , Matriz Extracelular
6.
IEEE Trans Med Imaging ; 43(1): 203-215, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37432807

RESUMEN

Automated volumetric meshing of patient-specific heart geometry can help expedite various biomechanics studies, such as post-intervention stress estimation. Prior meshing techniques often neglect important modeling characteristics for successful downstream analyses, especially for thin structures like the valve leaflets. In this work, we present DeepCarve (Deep Cardiac Volumetric Mesh): a novel deformation-based deep learning method that automatically generates patient-specific volumetric meshes with high spatial accuracy and element quality. The main novelty in our method is the use of minimally sufficient surface mesh labels for precise spatial accuracy and the simultaneous optimization of isotropic and anisotropic deformation energies for volumetric mesh quality. Mesh generation takes only 0.13 seconds/scan during inference, and each mesh can be directly used for finite element analyses without any manual post-processing. Calcification meshes can also be subsequently incorporated for increased simulation accuracy. Numerous stent deployment simulations validate the viability of our approach for large-batch analyses. Our code is available at https://github.com/danpak94/Deep-Cardiac-Volumetric-Mesh.


Asunto(s)
Aprendizaje Profundo , Humanos , Fenómenos Biomecánicos , Simulación por Computador , Modelación Específica para el Paciente , Corazón/diagnóstico por imagen
7.
bioRxiv ; 2023 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-37986801

RESUMEN

Nuclear atypia, including altered nuclear size, contour, and chromatin organization, is ubiquitous in cancer cells. Atypical primary nuclei and micronuclei can rupture during interphase; however, the frequency, causes, and consequences of nuclear rupture are unknown in most cancers. We demonstrate that nuclear envelope rupture is surprisingly common in many human cancers, particularly glioblastoma. Using highly-multiplexed 2D and super-resolution 3D-imaging of glioblastoma tissues and patient-derived xenografts and cells, we link primary nuclear rupture with reduced lamin A/C and micronuclear rupture with reduced lamin B1. Moreover, ruptured glioblastoma cells activate cGAS-STING-signaling involved in innate immunity. We observe that local patterning of cell states influences tumor spatial organization and is linked to both lamin expression and rupture frequency, with neural-progenitor-cell-like states exhibiting the lowest lamin A/C levels and greatest susceptibility to primary nuclear rupture. Our study reveals that nuclear instability is a core feature of cancer, and links nuclear integrity, cell state, and immune signaling.

8.
Eur J Pharmacol ; 959: 176078, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37805133

RESUMEN

OBJECTIVE: The anti-tussive effect of gabapentin and its underlying neuromodulatory mechanism were investigated via a modified guinea pig model of gastroesophageal reflux-related cough (GERC). METHODS: Intra-esophageal perfusion with hydrochloric acid (HCl) was performed every other day 12 times to establish the GERC model. High-dose gabapentin (48 mg/kg), low-dose gabapentin (8 mg/kg), or saline was orally administered for 2 weeks after modeling. Cough sensitivity, airway inflammation, lung and esophagus histology, levels of substance P (SP), and neurokinin-1 (NK1)-receptors were monitored. RESULTS: Repeated intra-esophageal acid perfusion aggravated the cough sensitivity in guinea pigs in a time-dependent manner. The number of cough events was significantly increased after 12 times HCl perfusion, and the hypersensitivity period was maintained for 2 weeks. The SP levels in BALF, trachea, lung, distal esophagus, and vagal ganglia were increased in guinea pigs receiving HCl perfusion. The intensity of cough hypersensitivity in the GERC model was significantly correlated with increased SP expression in the airways. Both high and low doses of gabapentin administration could reduce cough hypersensitivity exposed to HCl perfusion, attenuate airway inflammatory damage, and inhibit neurogenic inflammation by reducing SP expression from the airway and vagal ganglia. CONCLUSIONS: Gabapentin can desensitize the cough sensitivity in the GERC model of guinea pig. The anti-tussive effect is associated with the alleviated peripheral neurogenic inflammation as reflected in the decreased level of SP.


Asunto(s)
Tos , Reflujo Gastroesofágico , Cobayas , Animales , Tos/tratamiento farmacológico , Tos/metabolismo , Inflamación Neurogénica/complicaciones , Inflamación Neurogénica/metabolismo , Gabapentina/farmacología , Pulmón/metabolismo , Reflujo Gastroesofágico/metabolismo , Ácido Clorhídrico/metabolismo , Sustancia P/metabolismo , Receptores de Neuroquinina-1/metabolismo , Perfusión
9.
Appl Opt ; 62(28): 7441-7446, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37855512

RESUMEN

Self-referenced spectral interferometry with extended time excursion (SRSI-ETE) is a powerful method for single-shot characterization of the temporal contrast of a high peak power laser, which has high temporal resolution but a low dynamic range. Here, a temporal contrast reduction method is proposed that uses the cascaded Kerr lens process in two thin glass plates. Combined with the SRSI-ETE method, the measurement dynamic range of the method is increased about two orders of magnitude while having a 20 fs temporal resolution and a 40 ps time window in single shot.

10.
Artículo en Inglés | MEDLINE | ID: mdl-37800098

RESUMEN

Objective: Joint stiffness results from the coupling of the nervous system and joint mechanics, and thus stiffness is a comprehensive representation of joint stability. It has been reported that moxibustion can alleviate general weakness and fatigue symptoms and subsequently may influence joint stiffness. This study investigated whether moxibustion could enhance knee joint stiffness in recreational athletes pre- and post-fatigue. Methods: Eighteen participants were randomized into intervention (5 males: 20.6 ± 1.5 yr; 4 females: 20.8 ± 1.5 yr) and control groups (5 males: 19.4 ± 0.9 yr; 4 females: 20.5 ± 0.6 yr). The intervention group received indirect moxibustion applied to acupoints ST36 (bilateral) and CV4 for 30 min every other day for 4 consecutive weeks. The control group maintained regular exercise without moxibustion. Peak torque (PT) of right knee extensor, relaxed and contracted muscle stiffness (MS) of vastus lateralis, and knee extensor musculoarticular stiffness (MAS) was assessed with an isokinetic dynamometer (IsoMed 2000), myometer, and free oscillation technique, respectively. Measurements were taken at three time points: pre-intervention, post-intervention/pre-fatigue, and post-fatigue. Results: MAS (P = 0.006) and PT (P = 0.007) in the intervention group increased more from pre-to post-intervention compared with the control group. Post-fatigue MAS (P = 0.016) and PT (P = 0.031) increased more in the intervention group than in the control group. Conclusion: Moxibustion enhanced PT and knee MAS, suggesting that this intervention could be used in injury prevention and benefit fatigue resistance in young recreational athletes.

12.
Eye Vis (Lond) ; 10(1): 22, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37121995

RESUMEN

BACKGROUND: Implantable collamer lens (ICL) has been widely accepted for its excellent visual outcomes for myopia correction. It is a new challenge in phakic IOL power calculation, especially for those with low and moderate myopia. This study aimed to establish a novel stacking machine learning (ML) model for predicting postoperative refraction errors and calculating EVO-ICL lens power. METHODS: We enrolled 2767 eyes of 1678 patients (age: 27.5 ± 6.33 years, 18-54 years) who underwent non-toric (NT)-ICL or toric-ICL (TICL) implantation during 2014 to 2021. The postoperative spherical equivalent (SE) and sphere were predicted using stacking ML models [support vector regression (SVR), LASSO, random forest, and XGBoost] and training based on ocular dimensional parameters from NT-ICL and TICL cases, respectively. The accuracy of the stacking ML models was compared with that of the modified vergence formula (MVF) based on the mean absolute error (MAE), median absolute error (MedAE), and percentages of eyes within ± 0.25, ± 0.50, and ± 0.75 diopters (D) and Bland-Altman analyses. In addition, the recommended spheric lens power was calculated with 0.25 D intervals and targeting emmetropia. RESULTS: After NT-ICL implantation, the random forest model demonstrated the lowest MAE (0.339 D) for predicting SE. Contrarily, the SVR model showed the lowest MAE (0.386 D) for predicting the sphere. After TICL implantation, the XGBoost model showed the lowest MAE for predicting both SE (0.325 D) and sphere (0.308 D). Compared with MVF, ML models had numerically lower values of standard deviation, MAE, and MedAE and comparable percentages of eyes within ± 0.25 D, ± 0.50 D, and ± 0.75 D prediction errors. The difference between MVF and ML models was larger in eyes with low-to-moderate myopia (preoperative SE > - 6.00 D). Our final optimal stacking ML models showed strong agreement between the predictive values of MVF by Bland-Altman plots. CONCLUSION: With various ocular dimensional parameters, ML models demonstrate comparable accuracy than existing MVF models and potential advantages in low-to-moderate myopia, and thus provide a novel nomogram for postoperative refractive error prediction and lens power calculation.

13.
Clin Exp Optom ; : 1-7, 2023 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-36794379

RESUMEN

CLINICAL RELEVANCE: Myopia has become a public health priority as its prevalence increases worldwide, and in clinical practice, the precise evaluation of refraction errors is necessary. BACKGROUND: This study aimed to compare objective and subjective refraction measured by a binocular wavefront optometer (BWFOM) in adults with conventional objective and subjective refractions measured by an optometrist. METHODS: This cross-sectional study included 119 eyes of 119 participants (34 men and 85 women; mean age:27.5 ± 6.3 years). Refractive errors were measured using BWFOM and conventional methods, with and without cycloplegia. The mean outcome measures were spherical power, cylindrical power, and spherical equivalence (SE). The agreement test was assessed using a two-tailed paired t-test and Bland - Altman plots. RESULTS: Under noncycloplegic conditions, there were no significant differences in the objective SE between BWFOM and Nidek. Significant differences in subjective SE were observed between BWFOM and conventional subjective refraction (-5.79 ± 1.86 vs -5.65 ± 1.75 D, P < 0.01). Under cycloplegic conditions, the mean objective SE was significantly different between BWFOM and Nidek (-5.70 ± 1.76 vs -5.50 ± 1.83 D, P < 0.001); the mean subjective SE was significantly different between BWFOM and conventional subjective refractions (-5.52 ± 1.77 vs -5.62 ± 1.79 D, P < 0.001). The Bland - Altman plots revealed mean percentages of 95.38% and 95.17% for the points within the limits of agreement between BWFOM and conventional measurements and those between noncycloplegic and cycloplegic refractions, respectively. CONCLUSION: The BWFOM is a new device that measures both objective and subjective refraction. It is more convenient and faster to obtain a proper prescription at a 0.05-D interval. The subjective refraction results of the BWFOM and the conventional subjective refraction were in good agreement.

14.
Cancer Lett ; 557: 216075, 2023 03 31.
Artículo en Inglés | MEDLINE | ID: mdl-36736530

RESUMEN

N6-methyladenosine (m6A) RNA methylation and its associated RNA-binding protein insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) are involved in tumor initiation and progression. Here, we explored the biological function and clinical significance of IGF2BP1 in intrahepatic cholangiocarcinoma (iCCA). We found that IGF2BP1 expression was upregulated by H3K27 acetylation enrichment of its promoter, which positively correlated with poor clinicopathological characteristics and survival. Gain- and loss-of-function experiments showed that IGF2BP1 overexpression (knockdown) enhanced (attenuated) iCCA growth and metastasis in vitro and in vivo. Mechanistically, IGF2BP1 not only regulated the c-Myc/p16 axis to promote iCCA growth and inhibit senescence, but also activated the ZIC2/PAK4/AKT/MMP2 axis to induce tumor metastasis. More importantly, BTYNB, a recently identified IGF2BP1 inhibitor, exerted promising anti-tumor efficacy in a patient-derived xenograft (PDX) model, and IGF2BP1 conditional knockout (cKO) reduced the tumor burden. These results demonstrate the crucial role of IGF2BP1 in iCCA progression via m6A-dependent modification, highlighting IGF2BP1 as a potential therapeutic target in iCCA.


Asunto(s)
Colangiocarcinoma , Humanos , Línea Celular Tumoral , Colangiocarcinoma/patología , Quinasas p21 Activadas
15.
Cell Rep Methods ; 3(1): 100372, 2023 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-36814844

RESUMEN

The development of protease-activatable drugs and diagnostics requires identifying substrates specific to individual proteases. However, this process becomes increasingly difficult as the number of target proteases increases because most substrates are promiscuously cleaved by multiple proteases. We introduce a method-substrate libraries for compressed sensing of enzymes (SLICE)-for selecting libraries of promiscuous substrates that classify protease mixtures (1) without deconvolution of compressed signals and (2) without highly specific substrates. SLICE ranks substrate libraries using a compression score (C), which quantifies substrate orthogonality and protease coverage. This metric is predictive of classification accuracy across 140 in silico (Pearson r = 0.71) and 55 in vitro libraries (r = 0.55). Using SLICE, we select a two-substrate library to classify 28 samples containing 11 enzymes in plasma (area under the receiver operating characteristic curve [AUROC] = 0.93). We envision that SLICE will enable the selection of libraries that capture information from hundreds of enzymes using fewer substrates for applications like activity-based sensors for imaging and diagnostics.


Asunto(s)
Endopeptidasas , Péptido Hidrolasas , Especificidad por Sustrato , Péptido Hidrolasas/metabolismo
16.
Innovation (Camb) ; 4(1): 100364, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36632190

RESUMEN

The generation of ectoderm, mesoderm, and endoderm layers is the most critical biological process during the gastrulation of embryo development. Such a differentiation process in human embryonic stem cells (hESCs) is an inherently nonlinear multi-stage dynamical process which contain multiple tipping points playing crucial roles in the cell-fate decision. However, the tipping points of the process are largely unknown, letting alone the understanding of the molecular regulation on these critical events. Here by designing a module-based dynamic network biomarker (M-DNB) model, we quantitatively pinpointed two tipping points of the differentiation of hESCs toward definitive endoderm, which leads to the identification of M-DNB factors (FOS, HSF1, MYCN, TP53, and MYC) of this process. We demonstrate that before the tipping points, M-DNB factors are able to maintain the cell states and orchestrate cell-fate determination during hESC (ES)-to-ME and ME-to-DE differentiation processes, which not only leads to better understanding of endodermal specification of hESCs but also reveals the power of the M-DNB model to identify critical transition points with their key factors in diverse biological processes, including cell differentiation and transdifferentiation dynamics.

17.
Cell Res ; 33(2): 147-164, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36670290

RESUMEN

Acute liver failure (ALF) is a life-threatening disease that occurs secondary to drug toxicity, infection or a devastating immune response. Orthotopic liver transplantation is an effective treatment but limited by the shortage of donor organs, the requirement for life-long immune suppression and surgical challenges. Stem cell transplantation is a promising alternative therapy for fulminant liver failure owing to the immunomodulatory abilities of stem cells. Here, we report that when transplanted into the liver, human endoderm stem cells (hEnSCs) that are germ layer-specific and nontumorigenic cells derived from pluripotent stem cells are able to effectively ameliorate hepatic injury in multiple rodent and swine drug-induced ALF models. We demonstrate that hEnSCs tune the local immune microenvironment by skewing macrophages/Kupffer cells towards an anti-inflammatory state and by reducing the infiltrating monocytes/macrophages and inflammatory T helper cells. Single-cell transcriptomic analyses of infiltrating and resident monocytes/macrophages isolated from animal livers revealed dramatic changes, including changes in gene expression that correlated with the change of activation states, and dynamic population heterogeneity among these cells after hEnSC transplantation. We further demonstrate that hEnSCs modulate the activation state of macrophages/Kupffer cells via cystatin SN (CST1)-mediated inhibition of interferon signaling and therefore highlight CST1 as a candidate therapeutic agent for diseases that involve over-activation of interferons. We propose that hEnSC transplantation represents a novel and powerful cell therapeutic treatment for ALF.


Asunto(s)
Fallo Hepático Agudo , Células Madre Pluripotentes , Animales , Humanos , Endodermo , Inflamación , Hígado , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/terapia , Cistatinas Salivales , Porcinos , Interferones/metabolismo
18.
J Liposome Res ; 33(3): 283-299, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36594207

RESUMEN

In this study, cantharidin(CTD), a bioactive terpenoid in traditional Chinese medicine cantharidin, was selected as a model component to construct novel nano liposome delivery systems for hepatocellular carcinoma therapy. Previous studies have shown that although cantharidin has definite curative effects on primary liver cancer, it is associated with numerous toxic and side effects. Therefore, based on the glycyrrhetinic acid (GA) binding site and the asialoglycoprotein receptor (ASGPR) on the hepatocyte membrane, the surface of CTD liposomes was modified with stearyl alcohol galactoside (SA-Gal) or/and the newly synthesized 3-succinic-30-stearyl deoxyglycyrrhetinic acid (11-DGA-Suc) ligands, and the physicochemical properties, pharmacokinetics, in vivo and in vitro anti-liver tumor activity and its mechanism of modified liposomes were investigated. Compared to CTD-lip, SA-Gal-CTD-lip, and 11-DGA-Suc + SA-Gal-CTD-lip, 11-DGA-Suc-CTD-lip showed stronger cytotoxicity and increased inhibition of HepG2 cell migration had the highest apoptosis rate. The cell cycle results indicated that HepG2 cells was arrested mainly at G0/G1phase and G2/M phase. The results of in vivo pharmacokinetic experiments revealed that the distribution of modified liposomes in the liver was significantly increased compared with that of unmodified liposome. In vivo tumor inhibition experiment showed that 11-DGA-Suc-CTD-lip had excellent tumor inhibition, and the tumor inhibition rates was 80.96%. The 11-DGA-Suc-CTD-lip group also displayed the strongest proliferation inhibition with the lowest proliferation index of 7% in PCNA assay and the highest apoptotic index of 49% in TUNEL assay. Taken together, our findings provide a promising solution for improving the targeting of nano liposomes and further demonstrates the encouraging potential of poor solubility and high toxicity drugs applicable to tumor therapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Liposomas , Cantaridina/farmacología , Cantaridina/química , Ligandos , Neoplasias Hepáticas/tratamiento farmacológico , Carcinoma Hepatocelular/tratamiento farmacológico
19.
IET Nanobiotechnol ; 17(3): 182-196, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36680386

RESUMEN

Alzheimer's disease (AD) is a neurodegenerative disease with high incidence and widespread attention. There is currently no clear clarification of the pathogenesis. However, ORMDL3 causes ferroptosis in AD, and the potential mechanisms remain unclear. So, this study explore the function of ORMDL3 on ferroptosis in AD and its potential regulatory mechanisms. APPswe/PS1dE9 mice and C57BL/6 mice were induced into the mice model. The murine microglial BV-2 cells also were induced into the vitro model. In serum samples of AD patients, ORMDL3 mRNA expression levels were upregulated. The serum ORMDL3 levels expression was positively related to the ADL score or MoCA score in AD patients. The serum ORMDL3 expression level was positively related to MMSE score or Hcy levels in AD patients. The mRNA expression of ORMDL3 in the hippocampal tissue of the mice model of AD was upregulated at one, four and eight months. The protein expression of ORMDL3 was upregulated in the mice model of AD. ORMDL3 promoted Alzheimer's disease, and increased oxidative response and ferroptosis in a model of AD. PERK/ATF4/HSPA5 pathway is one important signal pathway for the effects of ORMDL3 in a model of AD. Collectively, these data suggested that ORMDL3 promoted oxidative response and ferroptosis in a model of AD by the PERK/ATF4/HSPA5 pathway, which might be a novel target spot mechanism of ferroptosis in AD and may serve as a regulator of AD-induced ferroptosis.


Asunto(s)
Enfermedad de Alzheimer , Ferroptosis , Enfermedades Neurodegenerativas , Ratones , Animales , Enfermedad de Alzheimer/prevención & control , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , ARN Mensajero , Proteínas de la Membrana/genética
20.
Graefes Arch Clin Exp Ophthalmol ; 261(5): 1465-1472, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36527496

RESUMEN

PURPOSE: To compare school-age children's objective and subjective refraction using a binocular wavefront optometer (BWFOM) with autorefraction and retinoscopy before and after cycloplegia. METHODS: Eighty-six eyes from 86 children (6-15 years old) were enrolled in this cross-sectional study. BWFOM objective and subjective refractions were compared with autorefraction and retinoscopy under cycloplegia. BWFOM refraction was evaluated before and after cycloplegia. Measurements were compared using a paired t-test; agreement was assessed using Bland-Altman plots. RESULTS: Under cycloplegia, the sphere, spherical equivalence, and J45 were significantly more negative on BWFOM objective refraction than autorefraction (- 1.39 ± 2.20 D vs. - 1.28 ± 2.23 D, P = 0.003; - 1.84 ± 2.38 D vs. - 1.72 ± 2.43 D, P = 0.001; - 0.02 ± 0.17 D vs. 0.03 ± 0.21 D, P = 0.004). The subjective sphere of BWFOM was less myopic, and the cylinder and the J45 were more negative than those with retinoscopy (- 1.17 ± 2.09 D vs. - 1.25 ± 2.20 D, P = 0.02; - 0.91 ± 0.92 D vs. - 0.76 ± 0.92 D, P < 0.001; - 0.01 ± 0.15 D vs. 0.03 ± 0.21 D, P = 0.028). For both BWFOM objective and subjective refraction, sphere and spherical equivalence with noncycloplegia were more myopic than those with cycloplegia (objective: - 1.76 ± 2.10 D vs. - 1.39 ± 2.20 D, - 2.21 ± 2.30 D vs. - 1.84 ± 2.38 D, P < 0.001; subjective: - 1.57 ± 1.92 D vs. - 1.17 ± 2.09 D, - 2.01 ± 2.13 D vs. - 1.62 ± 2.27 D, P < 0.001). Bland-Altman plots showed good agreement in spherical equivalence between BWFOM objective refraction and autorefraction (mean difference = 0.12 D, 95% confidence interval [CI] - 0.52 to 0.76), subjective refraction with retinoscopy (mean difference = - 0.01 D, 95% CI - 0.65 to 0.64), and BWFOM refractions with or without cycloplegia (objective: mean difference = - 0.37 D, 95% CI - 1.31 to 0.57; subjective: mean difference = - 0.39 D, 95% CI - 1.30 to 0.51). The time cost by BWFOM was significantly less than the total time of autorefraction and retinoscopy (264.88 ± 90.67 s vs. 315.89 ± 95.31 s, P < 0.001). CONCLUSION: BWFOM is a new device that realizes both objective and subjective refraction. For children's refractive errors, it is more convenient and quicker to obtain the proper prescription at a 0.05-D interval, and it is more accurate than autorefraction and retinoscopy under cycloplegia.


Asunto(s)
Miopía , Presbiopía , Errores de Refracción , Niño , Humanos , Adolescente , Retinoscopía , Estudios Transversales , Pruebas de Visión , Refracción Ocular , Miopía/diagnóstico
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