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1.
Heart Fail Rev ; 29(1): 113-123, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37823952

RESUMEN

The progression of heart failure is reported to be strongly associated with homeostatic imbalance, such as mitochondrial dysfunction and abnormal autophagy, in the cardiomyocytes. Mitochondrial dysfunction triggers autophagic and cardiac dysfunction. In turn, abnormal autophagy impairs mitochondrial function and leads to apoptosis or autophagic cell death under certain circumstances. These events often occur concomitantly, forming a vicious cycle that exacerbates heart failure. However, the role of the crosstalk between mitochondrial dysfunction and abnormal autophagy in the development of heart failure remains obscure and the underlying mechanisms are mainly elusive. The potential role of the link between mitochondrial dysfunction and abnormal autophagy in heart failure progression has recently garnered attention. This review summarized recent advances of the interactions between mitochondria and autophagy during the development of heart failure.


Asunto(s)
Insuficiencia Cardíaca , Enfermedades Mitocondriales , Humanos , Insuficiencia Cardíaca/metabolismo , Autofagia/fisiología , Mitocondrias/metabolismo , Miocitos Cardíacos/metabolismo , Enfermedades Mitocondriales/metabolismo
2.
BMC Neurol ; 24(1): 199, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38872077

RESUMEN

BACKGROUND: Process approach is valuable for memory assessment in Alzheimer's disease (AD) and mild cognitive impairment (MCI), yet its underlying mechanisms remain elusive. This study aims to synergize the process approach with brain structure analysis to explore both the discriminative capacity and potential mechanisms underlying the process approach. METHODS: 37 subjects of MCI, 35 subjects of AD and 38 subjects of healthy control (HC) were included. The process approach in Auditory Verbal Learning Test (AVLT), including discriminability (A'), response bias (B"D), semantic clustering (LBCsem) and serial clustering (LBCser) was performed. The gray matter volume (GMV) was analyzed by voxel-based morphometry. Receiver operating characteristic (ROC) analysis and partial correlations were conducted to explore the value of the process approach and investigate the relationship between the process approach, traditional indices of AVLT and GMV. RESULTS: ROC analysis showed the value of A', B"D and LBCser in differentiating MCI and AD. Combining AVLT-Immediately Recall (AVLT-IR) and LBCser showed a higher value in diagnosing MCI. Partial correlations revealed that in the MCI group, A' and B"D were mainly positively associated with GMV of the hippocampus and temporal lobe. CONCLUSION: This study indicated that the process approach is a promising cognitive biomarker to detect MCI and AD.


Asunto(s)
Enfermedad de Alzheimer , Biomarcadores , Disfunción Cognitiva , Sustancia Gris , Imagen por Resonancia Magnética , Humanos , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico , Masculino , Femenino , Anciano , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Anciano de 80 o más Años , Pruebas Neuropsicológicas/estadística & datos numéricos
3.
BMC Ophthalmol ; 24(1): 210, 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38741065

RESUMEN

BACKGROUND: Parry-Romberg syndrome (PRS) is a rare progressive degenerative disorder of unknown etiology. Here we report a rare case of PRS combined with lens subluxation in Eye and ENT hospital of Fudan University, Shanghai. To our knowledge, it is the first reported case of PRS combined with lens subluxation that has been managed surgically with phacoemulsification and CTR placement and IOL implantation in Shanghai. CASE PRESENTATION: A 60-year-old woman was referred for "right visual blur for 2 years" and had persistent right facial paralysis of unknown etiology since the age 12. She had right facial muscle atrophy and paralysis. Eye examination also showed the right eyelid pseudoptosis, enophthalmos, age-related cataract combined with lens subluxation existed in the right eye. The patient was diagnosed as age-related cataract and lens subluxation in the right eye and progressive hemifacial atrophy (Parry-Romberg syndrome). We conducted a combined phacoemulsification, IOL and CTR implantation and pupilloplasty surgery for the patient under general anesthesia and the postoperative UCVA was 20/30 and remained for 1 year's follow up. CONCLUSIONS: Here we reported a rare case of PHA combined with lens subluxation in China. After appropriate eye surgery, the patient achieved satisfying vision result in the right eye.


Asunto(s)
Hemiatrofia Facial , Subluxación del Cristalino , Facoemulsificación , Humanos , Femenino , Hemiatrofia Facial/complicaciones , Hemiatrofia Facial/diagnóstico , Hemiatrofia Facial/cirugía , Persona de Mediana Edad , Subluxación del Cristalino/cirugía , Subluxación del Cristalino/diagnóstico , Subluxación del Cristalino/etiología , Implantación de Lentes Intraoculares , Agudeza Visual/fisiología
4.
Opt Lett ; 48(7): 1790-1793, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37221767

RESUMEN

We report an all-fiber 2.8-µm ultra-short pulse master oscillator power amplifier (MOPA) system seeded by a soliton self-frequency shift from a mode-locked thulium-doped fiber laser. This all-fiber laser source delivers 2.8-µm pulses with an average power of 3.42 W, a pulse width of 115 fs, and a pulse energy of 45.4 nJ. We demonstrate, to the best of our knowledge, the first femtosecond watt-level all-fiber 2.8-µm laser system. A 2.8-µm pulse seed was obtained via the soliton self-frequency shift of 2-µm ultra-short pulses in a cascaded silica and passive fluoride fiber. A novel, to the best of our knowledge, high-efficiency and compact home-made end-pump silica-fluoride fiber combiner was fabricated and used in this MOPA system. Nonlinear amplification of the 2.8-µm pulse was realized, and soliton self-compression was observed accompanied by spectral broadening.

5.
Diabetes Obes Metab ; 25(3): 664-674, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36314246

RESUMEN

AIM: To assess the efficacy and safety of liraglutide to reduce visceral and ectopic fat in adults with or without type 2 diabetes mellitus (T2DM). METHODS: Four databases were searched up to 6 May 2022 for randomized clinical trials assessing the effect of liraglutide on visceral and ectopic fat. The mean and standard deviation of the values of visceral fat, ectopic fat and body mass index were calculated. Subgroup analyses were performed based on the type of disease (T2DM or non-T2DM), duration of intervention, dosage of liraglutide and whether life interventions were added to liraglutide therapy. We extracted and integrated the safety assessments reported in each article. RESULTS: Sixteen randomized clinical trials with, in total, 845 participants were included in the meta-analysis. Liraglutide could significantly decrease visceral fat [standard mean difference (SMD) = -0.72, 95% confidence interval (CI; -1.12, -0.33)], liver fat [SMD = -0.78, 95% CI (-1.24, -0.32)] and body mass index [weighted mean difference = -1.44, 95% CI (-1.95, -0.92)] in adult patients with or without T2DM when compared with the control group. However, reduction of epicardial fat by liraglutide [SMD = -0.74, 95% CI (-1.82, 0.34)] was not statistically significant. Subgroup analysis revealed that an adequate dosage (≥1.8 mg/day) and appropriate duration of treatment (ranging from 16 to 40 weeks) were the decisive factors for liraglutide to reduce visceral fat effectively. Mild gastrointestinal reactions were the main adverse event of liraglutide. CONCLUSIONS: Liraglutide significantly and safely reduces visceral and ectopic liver fat irrespective of T2DM status, and reduces visceral fat provided adequate dosage and duration of therapy are ensured.


Asunto(s)
Diabetes Mellitus Tipo 2 , Liraglutida , Adulto , Humanos , Liraglutida/efectos adversos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/inducido químicamente , Hígado , Índice de Masa Corporal , Tejido Adiposo , Hipoglucemiantes/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto
6.
J Cardiovasc Pharmacol ; (0)2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-38113918

RESUMEN

ABSTRACT: Studies have examined the therapeutic effect of levosimendan on cardiovascular diseases such as heart failure, perioperative cardiac surgery, and septic shock, but the specific mechanism in mice remains largely unknown. This study aimed to investigate the relaxation mechanism of levosimendan in the thoracic aorta smooth muscle of mice. Levosimendan-induced relaxation of isolated thoracic aortic rings that were precontracted with norepinephrine (NE) or KCl was recorded in an endothelium-independent manner. Vasodilatation by levosimendan was not associated with the production of the endothelial relaxation factors NO and PGI2. The voltage-dependent K+ channel (KV) blocker (4-aminopyridine) and selective KCa blocker (tetraethylammonium) had no effect on thoracic aortas treated with levosimendan, indicating that KV and KCa channels may not be involved in the levosimendan-induced relaxation mechanism. Although the inwardly rectifying K+ channel (Kir) blocker (barium chloride) and the KATP channel blocker (glibenclamide) significantly inhibited levosimendan-induced vasodilation in the isolated thoracic aorta, barium chloride had a much stronger inhibitory effect on levosimendan-induced vasodilation than glibenclamide, suggesting that levosimendan-induced vasodilation may be mediated by Kir channels. The vasodilation effect and expression of Kir 2.1 induced by levosimendan were further enhanced by the PKC inhibitor staurosporine. Extracellular calcium influx was inhibited by levosimendan without affecting intracellular Ca2+ levels in the isolated thoracic aorta. These results suggest that Kir channels play a more important role than KATP channels in regulating vascular tone in larger arteries and that the activity of the Kir channel is enhanced by the PKC pathway.

7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 571-580, 2023 Aug.
Artículo en Zh | MEDLINE | ID: mdl-37654137

RESUMEN

Objective To investigate the changes in plasma amyloid-ß (Aß) level and their relationship with white matter microstructure in the patients with amnesic mild cognitive impairment(aMCI) and vascular mild cognitive impairment (vMCI).Methods A total of 36 aMCI patients,20 vMCI patients,and 34 sex and age matched healthy controls (HC) in the outpatient and inpatient departments of the First Affiliated Hospital of Anhui Medical University were enrolled in this study.Neuropsychological scales,including the Mini-Mental State Examination,the Montreal Cognitive Assessment,and the Activity of Daily Living Scale,were employed to assess the participants.Plasma samples of all the participants were collected for the measurement of Aß42 and Aß40 levels.All the participants underwent magnetic resonance scanning to obtain diffusion tensor imaging (DTI) data.The DTI indexes of 48 white matter regions of each individual were measured (based on the ICBM-DTI-81 white-matter labels atlas developed by Johns Hopkins University),including fractional anisotropy (FA) and mean diffusivity (MD).The cognitive function,plasma Aß42,Aß40,and Aß42/40 levels,and DTI index were compared among the three groups.The correlations between the plasma Aß42/40 levels and DTI index of aMCI and vMCI patients were analyzed.Results The Mini-Mental State Examination and the Montreal Cognitive Assessment scores of aMCI and vMCI groups were lower than those of the HC group (all P<0.001).There was no significant difference in the Activity of Daily Living Scale score among the three groups (P=0.654).The plasma Aß42 level showed no significant difference among the three groups (P=0.227).The plasma Aß40 level in the vMCI group was higher than that in the HC group (P=0.014),while it showed no significant difference between aMCI and HC groups (P=1.000).The plasma Aß42/40 levels in aMCI and vMCI groups showed no significant differences from that in the HC group (P=1.000,P=0.105),while the plasma Aß42/40 level was lower in the vMCI group than in the aMCI group (P=0.016).The FA value of the left anterior limb of internal capsule in the vMCI group was lower than those in HC and aMCI groups (all P=0.001).The MD values of the left superior corona radiata,left external capsule,left cingulum (cingulate gyrus),and left superior fronto-occipital fasciculus in the vMCI group were higher than those in HC (P=0.024,P=0.001,P=0.003,P<0.001) and aMCI (P=0.015,P=0.004,P=0.019,P=0.001) groups,while the MD values of the right posterior limb of internal capsule (P=0.005,P=0.001) and left cingulum (hippocampus) (P=0.017,P=0.031) in the aMCI and vMCI groups were higher than those in the HC group.In the aMCI group,plasma Aß42/40 level was positively correlated with FA of left posterior limb of internal capsule (r=0.403,P=0.015) and negatively correlated with MD of the right fonix (r=-0.395,P=0.017).In the vMCI group,plasma Aß42/40 level was positively correlated with FA of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=0.575,P=0.008;r=0.639,P=0.002),while it was negatively correlated with MD of the right superior cerebellar peduncle and the right anterior limb of internal capsule (r=-0.558,P=0.011;r=-0.626,P=0.003).Conclusions Plasma Aß levels vary differently in the patients with aMCI and vMCI.The white matter regions of impaired microstructural integrity differ in the patients with different dementia types in the early stage.The plasma Aß levels in the patients with aMCI and vMCI are associated with the structural integrity of white matter,and there is regional specificity between them.


Asunto(s)
Disfunción Cognitiva , Sustancia Blanca , Humanos , Imagen de Difusión Tensora , Sustancia Blanca/diagnóstico por imagen , Pacientes Ambulatorios , Cognición , Péptidos beta-Amiloides
8.
BMC Ophthalmol ; 22(1): 71, 2022 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-35151265

RESUMEN

BACKGROUND: To investigate the associations between anterior segment biometry and high axial myopia in cataractous eyes in the Chinese population. METHODS: Data on 3438 eyes from 3438 subjects were analyzed in this cross-sectional study. Anterior segment biometry, axial length measurements, and intraocular pressure evaluation were implemented using an Oculus Pentacam HR, a Zeiss IOLMaster 500, and a Nidek TonoRef II, respectively. A multivariate-adjusted logistic model and a multivariate-adjusted linear model were used for statistical analysis. RESULTS: The mean age of the subjects was 62.2 ± 10.6 years, and 56.4% were female. There were 2665 subjects with high axial myopia (axial length, ≥26.50 mm) and 773 without (axial length, < 26.50 mm). The characteristics independently associated with high axial myopia included lower total corneal refractive power, a more negative Q value, greater total corneal astigmatism, greater white-to-white corneal diameter, greater anterior chamber depth, and higher intraocular pressure (all P <  0.05). In addition, greater axial length correlated with a thicker temporal cornea and a thinner nasal cornea (both P <  0.001). CONCLUSIONS: For cataractous eyes, high axial myopia was associated with corneal flattening, increased total corneal astigmatism, anterior segment enlargement, and intraocular pressure elevation. The findings may inform the choice of intraocular lenses and the calculation of their power, help improve the surgical practice of refractive cataract procedures, and provide useful information on the centration and stability of intraocular lenses.


Asunto(s)
Biometría , Miopía , Anciano , China/epidemiología , Córnea , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Miopía/diagnóstico , Miopía/epidemiología , Refracción Ocular
9.
Ophthalmology ; 128(11): 1580-1591, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-33940045

RESUMEN

TOPIC: To provide updated estimates on the global prevalence and number of people with diabetic retinopathy (DR) through 2045. CLINICAL RELEVANCE: The International Diabetes Federation (IDF) estimated the global population with diabetes mellitus (DM) to be 463 million in 2019 and 700 million in 2045. Diabetic retinopathy remains a common complication of DM and a leading cause of preventable blindness in the adult working population. METHODS: We conducted a systematic review using PubMed, Medline, Web of Science, and Scopus for population-based studies published up to March 2020. Random effect meta-analysis with logit transformation was performed to estimate global and regional prevalence of DR, vision-threatening DR (VTDR), and clinically significant macular edema (CSME). Projections of DR, VTDR, and CSME burden were based on population data from the IDF Atlas 2019. RESULTS: We included 59 population-based studies. Among individuals with diabetes, global prevalence was 22.27% (95% confidence interval [CI], 19.73%-25.03%) for DR, 6.17% (95% CI, 5.43%-6.98%) for VTDR, and 4.07% (95% CI, 3.42%-4.82%) for CSME. In 2020, the number of adults worldwide with DR, VTDR, and CSME was estimated to be 103.12 million, 28.54 million, and 18.83 million, respectively; by 2045, the numbers are projected to increase to 160.50 million, 44.82 million, and 28.61 million, respectively. Diabetic retinopathy prevalence was highest in Africa (35.90%) and North American and the Caribbean (33.30%) and was lowest in South and Central America (13.37%). In meta-regression models adjusting for habitation type, response rate, study year, and DR diagnostic method, Hispanics (odds ratio [OR], 2.92; 95% CI, 1.22-6.98) and Middle Easterners (OR, 2.44; 95% CI, 1.51-3.94) with diabetes were more likely to have DR compared with Asians. DISCUSSION: The global DR burden is expected to remain high through 2045, disproportionately affecting countries in the Middle East and North Africa and the Western Pacific. These updated estimates may guide DR screening, treatment, and public health care strategies.


Asunto(s)
Costo de Enfermedad , Retinopatía Diabética/epidemiología , Predicción , Retinopatía Diabética/economía , Estudios de Seguimiento , Salud Global , Humanos , Prevalencia , Factores de Riesgo
10.
Molecules ; 26(17)2021 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-34500671

RESUMEN

Fumonisin B1 (FB1), belonging to the member of fumonisins, is one of the most toxic mycotoxins produced mainly by Fusarium proliferatum and Fusarium verticillioide. FB1 has caused extensive contamination worldwide, mainly in corn, rice, wheat, and their products, while it also poses a health risk and is toxic to animals and human. It has been shown to cause oxidative stress, endoplasmic reticulum stress, cellular autophagy, and apoptosis. This review focuses on the current stage of FB1 contamination, its toxic effects of acute toxicity, immunotoxicity, organ toxicity, and reproductive toxicity on animals and humans. The potential toxic mechanisms of FB1 are discussed. One of the main aims of the work is to provide a reliable reference strategy for understanding the occurrence and toxicity of FB1.


Asunto(s)
Fumonisinas/análisis , Animales , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Fumonisinas/farmacología , Fusarium/química , Humanos
11.
Nanomedicine ; 17: 119-123, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30677499

RESUMEN

Corneal neovascularization (CNV) leads to the loss of corneal transparency and vision impairment, and can ultimately cause blindness. Topical corticosteroids are the first line treatment for suppressing CNV, but poor ocular bioavailability and rapid clearance of eye drops makes frequent administration necessary. Patient compliance with frequent eye drop application regimens is poor. We developed biodegradable nanoparticles (NP) loaded with dexamethasone sodium phosphate (DSP) using zinc ion bridging, DSP-Zn-NP, with dense coatings of poly(ethylene glycol) (PEG). DSP-Zn-NP were safe and capable of providing sustained delivery of DSP to the front of the eye following subconjunctival (SCT) administration in rats. We reported that a single SCT administration of DSP-Zn-NP prevented suture-induced CNV in rats for two weeks. In contrast, the eyes receiving SCT administration of either saline or DSP solution developed extensive CNV in less than 1 week. SCT administration of DSP-Zn-NP could be an effective strategy in preventing and treating CNV.


Asunto(s)
Neovascularización de la Córnea/prevención & control , Preparaciones de Acción Retardada/química , Dexametasona/análogos & derivados , Glucocorticoides/administración & dosificación , Zinc/química , Animales , Dexametasona/administración & dosificación , Dexametasona/uso terapéutico , Glucocorticoides/uso terapéutico , Nanopartículas/química , Polietilenglicoles/química , Ratas
12.
Clin Exp Ophthalmol ; 46(4): 371-379, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-28842942

RESUMEN

IMPORTANCE: Cataract risk factors data will provide epidemic evidence for cataract prevention. BACKGROUND: This study aimed to study the risk factors for age-related cataract in a Chinese adult population. DESIGN: This is a population-based, cross-sectional study. PARTICIPANTS: A total of 10 234 eligible subjects ≥45 years old (response rate: 78.1%) were included in the study. METHODS: We conducted detailed eye examinations including presenting visual acuity, best-corrected visual acuity, slit lamp examination of lens opacities and fundus examination. Questionnaires about lifestyle were administered. Measurements of blood pressure, heart rate and body mass index were collected. Serological metabolic indicators, including fasting blood glucose, triglycerides, cholesterol, lipoprotein, were also evaluated. We used stepwise multivariate logistic regression model to evaluate the association of these risk factors with any cataract and subtypes of cataract. MAIN OUTCOME MEASURES: Odds ratios of risk factors for cataract were calculated. RESULTS: For any cataract, we found age, gender (female), increased outdoor activity, no outdoor eye protection, high myopia, high low-density lipoprotein, low high-density lipoprotein, lower education level and increased pickled food intake were independent risk factors. When further examined the risk factors of different subtypes of cataract, we found that these risk factors also existed, but there were slight differences among different subtypes. In addition, for cortical cataract, lower annual family income and high diastolic pressure were additional independent risk factors. CONCLUSIONS AND RELEVANCE: Reduced outdoor activity, outdoor eye protection, prevention of high myopia, higher education level, controlled blood pressure, improved high-density lipoprotein and low-density lipoprotein levels and reduced pickled food intake may help to reduce the risk of age-related cataract development.


Asunto(s)
Catarata/epidemiología , Estilo de Vida , Vigilancia de la Población/métodos , Medición de Riesgo/métodos , Población Rural , Agudeza Visual , Distribución por Edad , Anciano , Catarata/etiología , China/epidemiología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Prevalencia , Pronóstico , Factores de Riesgo , Distribución por Sexo
13.
BMC Ophthalmol ; 17(1): 196, 2017 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-29078747

RESUMEN

BACKGROUND: To report a case for repair of cyclodialysis after trabeculectomy with Cionni-modified capsular tension ring. CASE PRESENTATION: A 64-year-old man who had undergone trabeculectomy of his left eye 3 months earlier visited our clinic owing to blurred vision. His visual acuity was 20/2000 and the intraocular pressure (IOP) was 6 mmHg. Slit-lamp examination showed a shallow anterior chamber and dense cataract. Ultrasound biomicroscopy revealed 360 ° detachment of the ciliary body and suspected cyclodialysis of the trabeculectomy incision. Choroidal detachment was confirmed by B-scan ultrasonography and optical coherence tomography. Phacoemulsification was performed in which a foldable intraocular lens (IOL) was implanted in the capsular bag and a Cionni-modified capsular tension ring (MCTR) was inserted into the ciliary sulcus. The maximum focal point of the MCTR was rotated to the site of the most severe cyclodialysis and the MCTR was sutured to the sclera through its two eyelets. The patient's best-corrected visual acuity improved to 30/50 and the IOP increased to 16 mmHg after surgery. Gonioscopy and ultrasound biomicroscopy confirmed closure of the cyclodialysis and resolution of choroidal detachment. CONCLUSIONS: Phacoemjulsification with implantation of an intraocular lens combined with insertion of an MCTR into the ciliary sulcus appears to be a relatively safe, effective, minimally invasive method for repairing cyclodialysis in cataract patients. Although the technique yielded good results and appeared to be safe in one patient, further studies are necessary to validate the findings on more patients and with a long-term follow-up.


Asunto(s)
Catarata/etiología , Enfermedades de la Coroides/cirugía , Cuerpo Ciliar/patología , Implantación de Lentes Intraoculares/métodos , Lentes Intraoculares , Complicaciones Posoperatorias/cirugía , Trabeculectomía/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
14.
Cell Physiol Biochem ; 39(5): 1813-1826, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27744453

RESUMEN

BACKGROUND/AIMS: Oxidative stress plays a critical role in the development of cataracts, and glutaredoxins (Grxs) play a major protective role against oxidative stress in the lens. This study aimed to reveal the global regulatory network of Grx1. METHODS: Stable isotope labeling by amino acids in cell culture (SILAC) was used in a proteome-wide quantitative approach to identify the Grx1 regulatory signaling cascades at a subcellular resolution in response to oxidative stress. RESULTS: A total of 1,291 proteins were identified to be differentially expressed, which were further categorized into a variety of signaling cascades including redox regulation, apoptosis, cell cycle control, glucose metabolism, protein synthesis, DNA damage response, protein folding, proteasome and others. Thirteen key signaling node molecules representing each pathway were verified. Notably, the subunits of proteasome complexes, which play a pivotal role in preventing cytotoxicity via the degradation of oxidized proteins, were highly enriched by Grx1. By data-dependent network analysis, we found global functional links among these signaling pathways which elucidate how Grx1 integrates the operation of these regulatory networks in an interconnected way for H2O2-induced response. CONCLUSION: Our data provide a system-wide insight into the function of Grx1 and provide a basis for further mechanistic investigation of Grx1 in antioxidant responses in the lens.


Asunto(s)
Antioxidantes/metabolismo , Células Epiteliales/efectos de los fármacos , Redes Reguladoras de Genes , Glutarredoxinas/genética , Peróxido de Hidrógeno/farmacología , Complejo de la Endopetidasa Proteasomal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Ciclo Celular/genética , Línea Celular , Células Epiteliales/citología , Células Epiteliales/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Vectores Genéticos/química , Vectores Genéticos/metabolismo , Glutarredoxinas/metabolismo , Células HEK293 , Humanos , Cristalino/citología , Cristalino/efectos de los fármacos , Cristalino/metabolismo , Lentivirus/genética , Lentivirus/metabolismo , Oxidación-Reducción , Estrés Oxidativo , Complejo de la Endopetidasa Proteasomal/metabolismo , Mapeo de Interacción de Proteínas , Transducción de Señal , Transcripción Genética
15.
Mol Vis ; 22: 589-98, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27307692

RESUMEN

PURPOSE: This study aimed to investigate the genetic effects underlying non-familial sporadic congenital cataract (SCC). METHODS: We collected DNA samples from 74 patients with SCC and 20 patients with traumatic cataract (TC) in an age-matched group and performed genomic sequencing of 61 lens-related genes with target region capture and next-generation sequencing (NGS). The suspected SCC variants were validated with MassARRAY and Sanger sequencing. DNA samples from 103 healthy subjects were used as additional controls in the confirmation examination. RESULTS: By filtering against common variants in public databases and those associated with TC cases, we identified 23 SCC-specific variants in 17 genes from 19 patients, which were predicted to be functional. These mutations were further confirmed by examination of the 103 healthy controls. Among the mutated genes, CRYBB3 had the highest mutation frequency with mutations detected four times in four patients, followed by EPHA2, NHS, and WDR36, the mutation of which were detected two times in two patients. We observed that the four patients with CRYBB3 mutations had three different cataract phenotypes. CONCLUSIONS: From this study, we concluded the clinical and genetic heterogeneity of SCC. This is the first study to report broad spectrum genotyping for patients with SCC.


Asunto(s)
Pueblo Asiatico/genética , Catarata/genética , Cristalinas/genética , Mutación Missense , Polimorfismo de Nucleótido Simple , Catarata/congénito , Niño , Preescolar , China/epidemiología , Análisis Mutacional de ADN , Proteínas del Ojo/genética , Femenino , Heterogeneidad Genética , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Lactante , Recién Nacido , Masculino , Proteínas de la Membrana , Proteínas Nucleares/genética , Receptor EphA2/genética , Cadena B de beta-Cristalina/genética
16.
Ophthalmology ; 122(7): 1480-8, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25986897

RESUMEN

PURPOSE: To study the current prevalence and causes of low vision and blindness in an adult Chinese population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: We used a random cluster sampling method and evaluated 10 234 eligible subjects ≥45 years old (response rate, 78.1%) in the Taizhou Eye Study. METHODS: Examinations were performed from July 2012 through December 2013. Participants underwent a detailed examination, including uncorrected visual acuity, best-corrected visual acuity (BCVA), intraocular pressure, axial length, slit-lamp, and fundus examinations to evaluate the prevalence and primary causes of visual impairment (VI). MAIN OUTCOME MEASURES: We defined low vision and blindness according to the World Health Organization (WHO) criteria (low vision: BCVA, <20/63-≥20/400; blindness: BCVA, <20/400 in the better eye) and United States criteria (low vision: BCVA, <20/40-≥20/200; blindness: BCVA, <20/200 in the better eye). RESULTS: Using the WHO BCVA criteria, the standardized prevalence of bilateral low vision and blindness were 5.1% and 1.0%, respectively. Using the United States BCVA criteria, the standardized prevalence were 12.8% and 1.5%, respectively. Using the WHO criteria, the primary causes of bilateral low vision and blindness were cataract (59.1% and 48.5%, respectively), myopic macular degeneration (17.6% and 17.2%, respectively), and age-related macular degeneration (11.6% and 10.1%, respectively). The primary causes of monocular low vision were cataract (55.6%), age-related macular degeneration (12.6%), and myopic macular degeneration (8.9%), whereas those of monocular blindness were cataract (46.8%), atrophy of eyeball or prosthetic eye (10.2%), and cornea opacity (7.3%). A further analysis revealed that in adults 45-59 years old, myopic macular degeneration (59.6% and 27.2%, respectively) and cataract (13.8% and 23.4%, respectively) were the leading causes of bilateral and monocular VI. In adults ≥60 years old, cataract (66.8% and 61.2%, respectively) and age-related macular degeneration (12.6% and 11.8%, respectively) were the primary causes of bilateral and monocular VI. CONCLUSIONS: The prevalence of low vision and blindness in Chinese adults remains a severe public health problem. In the Taizhou Eye Study, cataract was the leading cause of low vision and blindness. Myopic macular degeneration and cataract were the primary causes of VI in adults 45-59 years and ≥60 years old, respectively.


Asunto(s)
Pueblo Asiatico/etnología , Ceguera/etnología , Baja Visión/etnología , Personas con Daño Visual/estadística & datos numéricos , Distribución por Edad , Anciano , Anciano de 80 o más Años , Longitud Axial del Ojo , Ceguera/etiología , Catarata/epidemiología , China/epidemiología , Estudios Transversales , Femenino , Humanos , Presión Intraocular/fisiología , Degeneración Macular/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Distribución por Sexo , Baja Visión/etiología , Agudeza Visual/fisiología
17.
Gels ; 10(5)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38786244

RESUMEN

Polyimide (PI) aerogels, renowned for their nano-porous structure and exceptional performance across a spectrum of applications, often encounter significant challenges during fabrication, primarily due to severe shrinkage. In this study, we innovatively incorporated ceramic fibers of varying diameters into the PI aerogel matrix to enhance the shape stability against shrinkage. The structure of the resulting ceramic fiber-reinforced PI (CF-PI) aerogel composites as well as their performance in thermal decomposition, thermal insulation, and compression resistance were characterized. The results revealed that the CF-PI aerogel composites dried by supercritical ethanol achieved greatly reduced shrinkage as low as 5.0 vol.% and low thermal conductivity ranging from 31.2 mW·m-1·K-1 to 35.3 mW·m-1·K-1, showcasing their excellent performance in shape stability and thermal insulation. These composites also inherited the superior residue-forming ability of ceramic fibers and the robust mechanical attributes of PI, thereby exhibiting enhanced thermal stability and compression resistance. Besides, the effects of different drying conditions on the structure and properties of CF-PI aerogels were also discussed. The coupling use of supercritical ethanol drying with the addition of ceramic fibers is preferred. This preferred condition gives birth to low-shrinkage CF-PI aerogel composites, which also stand out for their integrated advantages include high thermal stability, low thermal conductivity, and high mechanical strength. These advantages attribute to CF-PI aerogel composites substantial potential for a wide range of applications, particularly as high-performance thermal insulation materials for extreme conditions.

18.
Asia Pac J Ophthalmol (Phila) ; 13(1): 100002, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38383074

RESUMEN

PURPOSE: To investigate the current prevalence and causes of moderate and severe visual impairment (MSVI) and blindness in elderly people in suburban Shanghai, China. METHODS: A cross-sectional study based on the population was conducted, which involved 5846 individuals (11,692 eyes) aged 65 years or older. Thorough eye examinations were performed to assess the prevalence and leading factors of MSVI (BCVA <20/63 to ≥20/400) and blindness (BCVA <20/400). RESULTS: The standardized prevalence of bilateral MSVI and blindness was 3.3% and 0.6%, correspondingly. The standardized prevalence of monocular MSVI and blindness was 7.4% and 2.0%, correspondingly. Cataract (47.9% and 20.7%, correspondingly) and myopic macular degeneration (MMD, 25.7% and 31.1%, correspondingly) were the principal causes of bilateral MSVI and blindness. As for monocular MSVI, the primary causes were cataract (39.4%), age-related macular degeneration (AMD, 16.6%), and MMD (16.6%). The primary causes of monocular blindness were other posterior segment eye diseases (30.1%) and MMD (14.2%). In adults aged 65-74 years, MMD was the foremost factor causing bilateral vision impairment. Conversely, cataract was identified as the primary cause of bilateral and monocular vision impairment among adults aged ≥ 75 years. AMD accounts for a significant proportion of individuals across all age groups. CONCLUSIONS: The significant prevalence of MSVI and blindness among Chinese adults represents a critical public health issue. In addition to cataract, the vision impairment caused by MMD and AMD become an important issue in the elderly Chinese people.


Asunto(s)
Ceguera , Catarata , Pueblos del Este de Asia , Degeneración Macular , Trastornos de la Visión , Baja Visión , Anciano , Humanos , Ceguera/epidemiología , Ceguera/etiología , Catarata/complicaciones , Catarata/epidemiología , China/epidemiología , Estudios Transversales , Degeneración Macular/complicaciones , Degeneración Macular/epidemiología , Prevalencia , Trastornos de la Visión/epidemiología , Trastornos de la Visión/etiología , Baja Visión/epidemiología , Baja Visión/etiología
19.
J Alzheimers Dis ; 98(3): 907-923, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38489180

RESUMEN

Background: The hippocampus consists of histologically and functionally distinct subfields, which shows differential vulnerabilities to Alzheimer's disease (AD)-associated pathological changes. Objective: To investigate the atrophy patterns of the main hippocampal subfields in patients with mild cognitive impairment (MCI) and AD and the relationships among the hippocampal subfield volumes, plasma biomarkers and cognitive performance. Methods: This cross-sectional study included 119 patients stratified into three categories: normal cognition (CN; N = 40), MCI (N = 39), and AD (N = 40). AD-related plasma biomarkers were measured, including amyloid-ß (Aß)42, Aß40, Aß42/Aß40 ratio, p-tau181, and p-tau217, and the hippocampal subfield volumes were calculated using automated segmentation and volumetric procedures implemented in FreeSurfer. Results: The subiculum body, cornu ammonis (CA) 1-head, CA1-body, CA4-body, molecular_layer_HP-head, molecular_layer_HP-body, and GC-ML-DG-body volumes were smaller in the MCI group than in the CN group. The subiculum body and CA1-body volumes accurately distinguished MCI from CN (area under the curve [AUC] = 0.647-0.657). The subiculum-body, GC-ML-DG-body, CA4-body, and molecular_layer_HP-body volumes accurately distinguished AD from MCI (AUC = 0.822-0.833) and AD from CN (AUC = 0.903-0.905). The p-tau 217 level served as the best plasma indicator of AD and correlated with broader hippocampal subfield volumes. Moreover, mediation analysis demonstrated that the subiculum-body volume mediated the associations between the p-tau217 and p-tau181 levels, and the Montreal Cognitive Assessment and Auditory Verbal Learning Test recognition scores. Conclusions: Hippocampal subfields with distinctive atrophy patterns may mediate the effects of tau pathology on cognitive function. The subiculum-body may be the most clinically meaningful hippocampal subfield, which could be an effective target region for assessing disease progression.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/patología , Estudios Transversales , Imagen por Resonancia Magnética , Hipocampo/diagnóstico por imagen , Hipocampo/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/patología , Atrofia/patología , Biomarcadores
20.
Artículo en Inglés | MEDLINE | ID: mdl-38908503

RESUMEN

BACKGROUND: Low folate intake and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism have been suggested to increase the risk of Alzheimer's disease (AD). However, the synergistic effects and their impact on brain structure and perfusion remain unclear. METHODS: This study explored the effects of dietary and genetic deficiencies in folate metabolism on the volume of the hippocampal subregions, cerebral perfusion, and cognitive decline in 71 cognitively unimpaired (CU) individuals and 102 patients with mild cognitive impairment (MCI) due to AD or AD. All participants underwent magnetic resonance imaging, laboratory examinations, and neuropsychological assessments. The hippocampal subfields were segmented using Freesurfer, and arterial spin labeling was used to measure the cerebral blood flow. RESULTS: We found a significant group-by-MTHFR interaction effect on folate. Patients with AD and the 677 T allele showed hypoperfusion in the left precuneus compared to patients without this mutation, which mediated the relationship between low folate level and cognitive decline in patients carrying the 677 T allele. Moreover, a synergistic effect was observed for the combination of decreased folate concentrations and the presence of the MTHFR 677 T allele on the atrophy of specific hippocampal subregions in patients with AD. CONCLUSIONS: In addition to offering insights into the neuronal mechanism underlying gene-dependent folate-induced cognitive impairment in AD, these findings may have clinical significance for the allocation of auxiliary folate supplementation therapy in patients with AD with low folate levels and carrying the MTHFR 677 T allele and may eventually promote the selection of early individualized AD drug therapy.

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