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1.
Sci Rep ; 14(1): 16199, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39003312

RESUMO

Sustainable multi-story building designs are gaining increasing attention in light of the green development of the building industry. Recently, many studies have been conducted to determine the optimized embodied energy considering size of structural members and materials strength using a single objective function. In this context, the current study adopted a multi-objective function based on cost and Embodied Energy (EE) for the sustainable design of the entire multi-story building. A BuildingEnergy computer program is used to assess the energy consumption performance of a multi-story reinforcement cement concrete building. Based on the proposed method, an analysis is carried out to compare the optimal solutions for multi-story building. Furthermore, a detailed parametric study was conducted to explore the main factors for energy-efficient column and beam design. The results revealed that with a comparison of the most "carbon-friendly" and "cost-friendly" solutions, an added cost of 6-7% can contribute up to a 13% emission reduction. The sectional dimensions, steel rebar, concrete strengths, cost ratio, building height, and eccentricity remarkably influence sustainable design, cost optimization, and minimum carbon emission. Overall, this study could help to define cost-effective and energy-efficient structural members. Eventually, the EE is confirmed to be a feasible parameter for designing more sustainable multi-story RCC buildings.

2.
Sci Rep ; 14(1): 5666, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454024

RESUMO

Low computational efficiency and non-linearity behaviour make the simulation of the overall building structure problematic to attain with a single dynamic or static method. Thus, this paper uses a plastic deformation (PD) method based on concrete plasticity theory (CPT) for comparative analysis of multi-storey reinforcement cement concrete (RCC) and composite buildings under common and rare earthquake loads. For this purpose, a 15-storey tall building was selected for analysis using ABAQUS software. At first, a possible building model was created and then plastic deformation analysis was performed using the new PD method under both common and rare earthquakes. After that, a nonlinear time history analysis was conducted, and the results of plastic strain distribution, lateral displacement, peak acceleration, storey stiffness, shear force, storey drift, normalised shear, and top deflection of the RCC and composite buildings were studied deeply. The fundamental time period of the RCC model was found to be 5.2 s while the fundamental time period of the composite model was 6 s. Under common and rare earthquake leads, the peak acceleration of the RCC building was 19% and 22% higher than composite buildings, respectively. Under common and rare seismic loads, the top deflections of the composite building were 33% and 36% higher than those of RCC buildings, respectively. In the case of the RCC building, it was found in this study that higher peak acceleration (PA) of the ground motion led to higher storey top displacement, storey drift, shear force and top deflection under both ground motions. Numerical results suggested that the use of composite structure is more durable than RCC structure. It was also concluded that the PD method could also be effectively used for the analysis of RCC and composite buildings under dynamic loads.

3.
J Neurochem ; 168(7): 1359-1373, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38382918

RESUMO

Ferroptosis has been implicated in several neurological disorders and may be therapeutically targeted. However, the susceptibility to ferroptosis varies in different cells, and inconsistent results have been reported even using the same cell line. Understanding the effects of key variables of in vitro studies on ferroptosis susceptibility is of critical importance to facilitate drug discoveries targeting ferroptosis. Here, we showed that increased cell seeding density leads to enhanced resistance to ferroptosis by reducing intracellular iron levels. We further identified iron-responsive protein 1 (IRP1) as the key protein affected by cell density, which affects the expression of ferroportin or transferrin receptor and results in altered iron levels. Such observations were consistent across different cell lines, indicating that cell density should be tightly controlled in studies of ferroptosis. Since cell densities vary in different brain regions, these results may also shed light on selective regional vulnerability observed in neurological disorders.


Assuntos
Ferroptose , Homeostase , Proteína 1 Reguladora do Ferro , Ferro , Ferro/metabolismo , Ferroptose/fisiologia , Homeostase/fisiologia , Humanos , Proteína 1 Reguladora do Ferro/metabolismo , Proteína 1 Reguladora do Ferro/genética , Contagem de Células , Animais , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Camundongos
4.
Adv Sci (Weinh) ; 11(15): e2306399, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38348540

RESUMO

Traumatic brain injury (TBI) leads to progressive neurodegeneration that may be caused by chronic traumatic encephalopathy (CTE). However, the precise mechanism remains unclear. Herein, the study identifies a crucial protein, axonemal dynein light intermediate polypeptide 1 (DNALI1), and elucidated its potential pathogenic role in post-TBI neurodegeneration. The DNALI1 gene is systematically screened through analyses of Aging, Dementia, and TBI studies, confirming its elevated expression both in vitro and in vivo. Moreover, it is observed that altered DNALI1 expression under normal conditions has no discernible effect. However, upon overexpression, DNALI1 inhibits autophagosome-lysosome fusion, reduces autophagic flux, and exacerbates cell death under pathological conditions. DNALI1 silencing significantly enhances autophagic flux and alleviates neurodegeneration in a CTE model. These findings highlight DNALI1 as a potential key target for preventing TBI-related neurodegeneration.


Assuntos
Lesões Encefálicas Traumáticas , Encefalopatia Traumática Crônica , Humanos , Autofagossomos/metabolismo , Autofagossomos/patologia , Lesões Encefálicas Traumáticas/complicações , Encefalopatia Traumática Crônica/etiologia , Encefalopatia Traumática Crônica/patologia , Autofagia , Lisossomos/metabolismo
5.
J Neurol ; 271(1): 457-471, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37755462

RESUMO

BACKGROUND: The glymphatic system is reportedly involved in Parkinson's disease (PD). Based on previous studies, we aimed to confirm the correlation between the glymphatic system and PD progression by combining two imaging parameters, diffusion tensor image analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). METHODS: Fifty-one PD patients and fifty healthy control (HC) were included. Based on the Hoehn-Yahr scale, the PD group was divided into early-stage and medium-to late-stage. All PD patients were scored using the Unified PD Rating Scale (UPDRS). We assessed the DTI-ALPS indices in the bilateral hemispheres and EPVS numbers in bilateral centrum semiovale (CSO), basal ganglia (BG), and midbrain. RESULTS: The DTI-ALPS indices were significantly lower bilaterally in PD patients than in the HC group, and EPVS numbers in any of the bilateral CSO, BG, and midbrain were significantly higher, especially for the medium- to late-stage group and the BG region. In PD patients, the DTI-ALPS index was significantly negatively correlated with age, while the BG-EPVS numbers were significantly positively correlated with age. Furthermore, the DTI-ALPS index was negatively correlated with UPDRS II and III scores, while the BG-EPVS numbers were positively correlated with UPDRS II and III scores. Similarly, the correlation was more pronounced in the medium- to late-stage group. CONCLUSION: The DTI-ALPS index and EPVS numbers (especially in the BG region) are closely related to age and PD progression and can serve as non-invasive assessments for glymphatic dysfunction and its interventions in clinical studies.


Assuntos
Sistema Glinfático , Doença de Parkinson , Humanos , Imageamento por Ressonância Magnética , Doença de Parkinson/diagnóstico por imagem , Sistema Glinfático/diagnóstico por imagem , Gânglios da Base , Progressão da Doença
6.
Acta Pharmaceutica Sinica ; (12): 476-481, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1016640

RESUMO

Based on the long bud stage phenotype of a new Lonicera japonica Flos variety "Huajin 6", using "Huajin 6" and "Da Mao Hua" as materials, probing the mechanism of its phenotype formation. Detection of endogenous Jasmonic acid hormones (JAs) content; the genes related to jasmonic acid (JA) synthesis were identified by transcriptome analysis of Lonicera japonica; flower buds and flowers of "Huajin 6" and "Da Mao Hua" were collected at different periods, and the qRT-PCR (quantitative real-time PCR) technique was used to analyze the trend of the expression of synthesis-related enzyme genes in Lonicera japonica Flos during the bud stage. The study found that the content of JAs in "Huajin 6" Lonicera japonica Flos was significantly lower than that in "Da Mao Hua"; applying exogenous methyl-jasmonate (MeJA) to "Huajin 6" can restore its flowering phenotype, making it close to wild type Lonicera japonica Flos; there are significant differences in the expression of two allene oxide synthase genes (AOS), three lipoxygenase genes (LOX), and two allene oxide cyclase genes (AOC) in the flowers and buds of "Huajin 6" and "Da Mao Hua" at different periods. It is hypothesized that the low expression of JA synthesis-related enzyme genes in " Huajin 6" leads to the blockage of JA synthesis, which causes the formation of the long bud phenotype. This study laid a certain foundation for the genetic breeding of Lonicera japonica, provided a new idea for the improvement of Lonicera japonica varieties, and provided a reference for the study of JAs in plant flower organs.

7.
Chinese Pharmacological Bulletin ; (12): 162-170, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013611

RESUMO

Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.

8.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1013370

RESUMO

ObjectiveTo explore the policy framework, theoretical system and principles of educational placement for children with special needs based on the International Classification of Functioning, Disability and Health (ICF) for the multi-faceted educational placement services and methods for these children. MethodsBased on ICF theory and methods, public policy research techniques, and educational policy analysis, this study systematically investigated the policy architecture and theoretical underpinnings for the educational placement of children with special needs, focusing on an inclusive education-oriented system of multiple placements. ResultsThe study analyzed educational policies, emphasizing the rights to education under the United Nations Convention on the Rights of Persons with Disabilities (CRPD) and UNESCO's guidelines on ensuring inclusivity and equity in education which encourage the provision of individualized educational support services and reasonable accommodations to enable the effective participation of students with disablities in education. China, the European Union (EU) and the United States (US) have enacted laws and policies promoting inclusive education, integrating children with disablities into the general education system, and providing them with the same educational opportunities as other children. The development of special education focuses on tailored educational services for those children who need additional support and resources. Policies underscore the need to evaluate the specific needs of children with disablities and provide individualized educational plan based on these needs. ConclusionBased on core content from the CRPD, UNESCO's guidelines, and relevant policies from China, the EU, and the US regarding the education and educational placement services for children with special needs, the theoretical framework and principles of educational placement for children with special needs based on ICF are discussed, proposing contents and methods for constructing a multi-faceted educational placement service system for children with special needs.

9.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1010333

RESUMO

BACKGROUND@#The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results.@*OBJECTIVE@#To identify factors and their impact on the treatment effect of acupuncture in different outcomes.@*METHODS@#Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects.@*RESULTS@#The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01).@*CONCLUSIONS@#High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.


Assuntos
Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Acupuntura/métodos , Dor , Manejo da Dor , China
10.
Int Wound J ; 21(3): e14532, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38012097

RESUMO

Psoriasis and chronic ulcers not only significantly impair quality of life but also pose a challenge in dermatological treatment. This study aimed to identify new therapeutic targets and biomarkers for psoriasis and chronic ulcers by comparing their gene expression profiles. The gene expression profiles of psoriatic, wound and chronic ulcer patients, as well as healthy controls, were determined via RNA extraction and next-generation sequencing of biopsies. In order to identify biomarkers, functional enrichment, differential expression analysis and machine learning algorithms were implemented. It is worth mentioning that the genes IL17A, TNF, KRT16, MMP9, and CD44 exhibited substantial correlations with the pathogenesis of the conditions being studied. As evidenced by their AUC-ROC values approaching 0.90, machine learning models accurately identified these biomarkers. The differential gene expression was consequently validated via qRT-PCR, which highlighted the increased expression of matrix remodelling enzymes and inflammatory cytokines. Additionally, genes essential for maintaining epidermis integrity and facilitating wound healing exhibited downregulation. These insights into the molecular mechanisms of psoriasis and chronic ulcers pave the way for the development of targeted therapies, offering hope for improved treatment strategies.

11.
MedComm (2020) ; 4(6): e429, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38020716

RESUMO

Mutations in LRRK2 (encoding leucine-rich repeat kinase 2 protein, LRRK2) are the most common genetic risk factors for Parkinson's disease (PD), and increased LRRK2 kinase activity was observed in sporadic PD. Therefore, inhibition of LRRK2 has been tested as a disease-modifying therapeutic strategy using the LRRK2 mutant mice and sporadic PD. Here, we report a newly designed molecule, FL090, as a LRRK2 kinase inhibitor, verified in cell culture and animal models of PD. Using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mice and SNCA A53T transgenic mice, FL090 ameliorated motor dysfunctions, reduced LRRK2 kinase activity, and rescued loss in the dopaminergic neurons in the substantia nigra. Notably, by RNA-Seq analysis, we identified microtubule-associated protein 1 (MAP1B) as a crucial mediator of FL090's neuroprotective effects and found that MAP1B and LRRK2 co-localize. Overexpression of MAP1B rescued 1-methyl-4-phenylpyridinium induced cytotoxicity through rescuing the lysosomal function, and the protective effect of FL090 was lost in MAP1B knockout cells. Further studies may be focused on the in vivo mechanisms of MAP1B and microtubule function in PD. Collectively, these findings highlight the potential of FL090 as a therapeutic agent for sporadic PD and familial PD without LRRK2 mutations.

12.
J Tradit Chin Med ; 43(6): 1160-1167, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37946478

RESUMO

OBJECTIVE: To investigate whether Hetong decoction (, HTT) alleviates constipation via regulating AQPs expression. METHODS: Constipation in rats was induced by loperamide, and rats were randomly assigned into model (saline), HHT-low (95 g/kg), HTT-medium (190 g/kg), HTT-high (380 g/kg) and positive control (mosapride) groups. Then the defecation function, the concentration of serum arginine vasopressin (AVP) and cyclic adenosine monophosphate (cAMP), and the expression of AQP3 and AQP8 in colon tissues were assessed. NCM460 colon cells with AQP3 and AQP8 knockdown or overexpression were exposed to serum from rats that received low or high dose of HTT, followed by detection of AQP3 and AQP8 expression. RESULTS: The model group showed lower fecal weight and water content, weaker intestinal transit, higher serum concentration of AVP and cAMP, increased proximal and distal AQP8 expression, increased proximal but decreased distal AQP3 expression. However, these trends were reversed in both the HTT group (low, medium and high dose) and the positive control group. In NCM460 cells, HTT dose-dependently stabilized AQP3 and AQP8 expression under AQP3/8 plasmid interference or overexpression. CONCLUSIONS: HTT relieves constipation in rats through regulating AQP3 and AQP8 expression.


Assuntos
Aquaporinas , Loperamida , Ratos , Animais , Loperamida/efeitos adversos , Loperamida/metabolismo , Constipação Intestinal/induzido quimicamente , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/genética , Aquaporinas/genética , Aquaporinas/metabolismo , Colo/metabolismo , Intestinos , AMP Cíclico/genética , AMP Cíclico/metabolismo
14.
Mol Psychiatry ; 28(9): 3982-3993, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37735502

RESUMO

Tau protein is implicated in the pathogenesis of Alzheimer's disease (AD) and other tauopathies, but its physiological function is in debate. Mostly explored in the brain, tau is also expressed in the pancreas. We further explored the mechanism of tau's involvement in the regulation of glucose-stimulated insulin secretion (GSIS) in islet ß-cells, and established a potential relationship between type 2 diabetes mellitus (T2DM) and AD. We demonstrate that pancreatic tau is crucial for insulin secretion regulation and glucose homeostasis. Tau levels were found to be elevated in ß-islet cells of patients with T2DM, and loss of tau enhanced insulin secretion in cell lines, drosophila, and mice. Pharmacological or genetic suppression of tau in the db/db diabetic mouse model normalized glucose levels by promoting insulin secretion and was recapitulated by pharmacological inhibition of microtubule assembly. Clinical studies further showed that serum tau protein was positively correlated with blood glucose levels in healthy controls, which was lost in AD. These findings present tau as a common therapeutic target between AD and T2DM.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Insulina/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Secreção de Insulina , Proteínas tau/metabolismo , Pâncreas/metabolismo , Pâncreas/patologia , Glucose/metabolismo , Doença de Alzheimer/metabolismo
15.
Int J Gen Med ; 16: 2383-2391, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333878

RESUMO

Objective: To explore the potential value of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI) in the diagnosis of hepatocellular carcinoma (HCC) in LR-3/4 lesions by adding computed tomography (CT) delayed images based on the Liver Imaging Reporting And Data System (LI-RADS). Methods: The differences in clinical and imaging characteristics between hepatocellular carcinoma and non-HCC were compared, and logistic regression was used to analyze the imaging risk factors for the diagnosis of HCC. Based on the main and HCC-specific auxiliary features of Gd-EOB-DTPA MRI, the HCC diagnostic model 1 was established, and the diagnostic efficacy was analyzed. Based on model 1, delayed phase CT images were added to establish model 2 to find reliable predictors of HCC diagnosis. Receiver operating characteristic (ROC) analysis and the DeLong test were used to compare the two models. Results: There was a significant difference in serum AFP between HCC and non-HCC (P = 0.008). Based on main and HCC-specific auxiliary features of Gd-EOB-DTPA MRI, enhancing capsule (OR = 0.197, 95% CI = 0.06-0.595, P = 0.005) and washout (OR = 10.345, 95% CI = 3.460-30.930, P < 0.001) were independent risk factors in Model 1. After adding CT delayed-phase images to build model 2, enhancing capsule (OR = 0.132, 95% CI = 0.139-0.449, P = 0.001), MRI and (or) CT washout (OR = 0.052, 95% CI = 0.016-0.172, P < 0.001) were reliable predictors for HCC diagnosis. The AUC of model 1 was 0.808, sensitivity was 63.46%, and specificity was 85.00%. The AUC of model 2 was 0.854, the sensitivity was 71.20%, and the specificity was 85.00%. DeLong test (P = 0.040) demonstrated the diagnostic efficacy of model 2 significantly superior than model 1. Conclusion: Tumor washout and enhanced capsule are reliable factors for the diagnosis of HCC. Gd-EOB-DTPA MRI with delayed phase CT images can improve the sensitivity and diagnostic efficiency of HCC in LR-3/4 lesions on the premise of maintaining high specificity. Future studies are required to reinforce our finding.

16.
J Neurochem ; 165(4): 487-520, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36908209

RESUMO

Over 30 million people suffer from the consequences of ischemic stroke. The precise molecular mechanism of neuronal damage during ischemic stroke remains unclear; therefore, the effective treatment of post-ischemic stroke remains a critical challenge. Recently, iron has emerged as a crucial factor in post-reperfusion injuries, participating in cell peroxidation, excitotoxicity, and a distinctive cell death pathway, namely, ferroptosis. Since iron is tightly regulated in the brain and important for brain functions, the imbalance of its metabolism, including its overload and deficiency, has been shown to impact ischemic stroke outcomes. This review summarizes the current understanding of pathological events associated with iron in ischemic stroke and discusses relevant drug development.


Assuntos
Ferroptose , Sobrecarga de Ferro , AVC Isquêmico , Humanos , Ferro/metabolismo , Ferroptose/fisiologia , Morte Celular , Sobrecarga de Ferro/patologia , Peroxidação de Lipídeos
17.
Hum Mol Genet ; 32(9): 1466-1482, 2023 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-36519761

RESUMO

Abnormal lipid homeostasis has been observed in the brain of Parkinson's disease (PD) patients and experimental models, although the mechanism underlying this phenomenon is unclear. Notably, previous studies have reported that the PD-linked protein Parkin functionally interacts with important lipid regulators, including Sterol Regulatory Element-Binding Proteins (SREBPs) and cluster of differentiation 36 (CD36). Here, we demonstrate a functional relationship between Parkin and lipoprotein lipase (LPL), a triglyceride lipase that is widely expressed in the brain. Using a human neuroblastoma cell line and a Parkin knockout mouse model, we demonstrate that Parkin expression level positively correlates with neuronal LPL protein level and activity. Importantly, our study identified SREBP2, a major regulator of sterol and fatty acid synthesis, as a potential mediator between Parkin and LPL. Supporting this, SREBP2 genetic ablation abolished Parkin effect on LPL expression. We further demonstrate that Parkin-LPL pathway regulates the formation of intracellular lipid droplets, and that this pathway is upregulated upon exposure to PD-linked oxidative stress induced by rotenone. Finally, we show that inhibition of either LPL or SREBP2 exacerbates rotenone-induced cell death. Taken together, our findings reveal a novel pathway linking Parkin, SREBP2 and LPL in neuronal lipid homeostasis that may be relevant to the pathogenesis of PD.


Assuntos
Lipase Lipoproteica , Doença de Parkinson , Proteína de Ligação a Elemento Regulador de Esterol 2 , Ubiquitina-Proteína Ligases , Animais , Humanos , Camundongos , Homeostase , Metabolismo dos Lipídeos/genética , Metabolismo dos Lipídeos/fisiologia , Lipase Lipoproteica/genética , Lipase Lipoproteica/metabolismo , Camundongos Knockout , Neurônios/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Rotenona/efeitos adversos , Transdução de Sinais , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
18.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-996990

RESUMO

@#Implantable left ventricular assist device (LVAD) has become an essential treatment for end-stage heart failure, and its effect has been continuously improved. In the world, magnetic levitation LVAD has become mainstream and is increasingly used as a destination treatment. China has also entered the era of ventricular assist device. The continuous improvement of the ventricular assist device will further improve the treatment effect. This article reviews the current situation and development trend of LVAD treatment in China and abroad.

19.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-994314

RESUMO

Objective:To explore the association between dietary patterns and the incidence of type 2 diabetes mellitus(T2DM), so as to provide insights for the prevention and management of T2DM.Methods:Participants were recruited from the " The Tianjin Chronic Inflammation and Health Cohort Study(TCLSIH)" cohort study from 2013 to 2018, who had completed the modified semiquantitative food frequency questionnaire(FFQ) and blood glucose testing( n=26 425), free of cardiovascular disease, cancer, or diabetes at baseline. The relevant information collected includes food frequency, blood glucose concentration, and other confounding factors. In this study, the correlation between dietary patterns and T2DM was tested using Cox proportional risk regression model, and the gender stratification analysis and body mass index stratification analysis of different gender groups were carried out. All statistical analysis was performed using SAS 9.3 software. Results:The age of all participants was (41.0±11.5)years, and the cumulative incidence was 3.84% for T2DM. The cumulative incidence of T2DM in male population was 5.29%, while that in female population was 2.16%. There were significant differences in the incidence of T2DM among different genders( P <0.001). The multivariable-adjusted hazard ratios( HR) and corresponding 95% CI of T2DM across the plant-based dietary pattern score were 1.09(95% CI 0.91-1.31), 0.80(95% CI 0.66-0.97), and 0.76(95% CI 0.62-0.94; Ptrend =0.010). Moreover, no statistically significant differences were observed between animal and traditional northern Chinese diets with the incidence of T2DM. Conclusions:The plant-based dietary patterns were associated with substantially lower risk of developing T2DM, and there were no significant association between animal and traditional northern Chinese dietary patterns with T2DM. Plant-based dietary patterns characterized by a variety of fruit, leeks, onions, seaweed may be beneficial to the prevention and control of T2DM.

20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993646

RESUMO

Objective:To investigate the prevalence and related factors of chronic kidney disease (CKD).Methods:A total of 42 223 subjects who received annual physical examination from January to December 2019 were selected as the research objects, a cross-sectional study was conducted. They were divided into CKD patients and healthy control groups. The basic information of the subjects was collected by questionnaire, including age, sex, marital status, education level, smoking history, drinking history, physical exercise and previous disease history, etc. The height, weight, waist circumference and blood pressure of the subjects were measured through physical examination, and laboratory indicators including fasting blood glucose, total cholesterol, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, blood uric acid, creatinine and urine routine were collected. The influencing factors of CKD were analyzed by logistic regression.Results:A total of 42 223 subjects were included in the study. The prevalence of CKD was 5.62%, with 7.77% in males and 3.39% in females. The prevalence of CKD increased with age. The prevalence of CKD was the highest in ≥80 years old (25.84%), followed by 70-79 years old (13.08%), the prevalence of CKD in males was higher than that in females in all age groups. Most of the detected CKD patients were in the early stage (stage 1-2), and the total prevalence of early CKD was 5.13%, and the total prevalence of stage 3-5 was 0.49%. Multivariate logistic regression analysis showed that age 70-79 years old ( OR: 1.63, 95% CI: 1.17-2.27),≥80 years old ( OR: 0.82, 95% CI: 2.61-5.91), male ( OR: 1.55, 95% CI: 2.61-5.91), high diastolic blood pressure ( OR: 1.014, 95% CI: 1.007-1.021), high fasting blood glucose level ( OR: 1.22, 95% CI: 1.17-1.27), SUA ( OR: 1.001, 95% CI: 1.000-1.002), hypertension ( OR: 1.44, 95% CI: 1.23-1.68), coronary heart disease ( OR: 1.36, 95% CI: 1.10-1.69) and stroke ( OR: 1.63, 95% CI: 1.09-2.43) were independent risk factors for CKD (all P<0.05); Physical activity 15-30 min/day ( OR: 0.81, 95% CI: 0.71-0.93),>60 min/day ( OR: 0.82, 95% CI: 0.70-0.96) was a protective factor for the prevalence of CKD (all P<0.05) Conclusion:The prevalence of CKD in the health check-up population is low, and most of them are in the early stage of the disease. The prevalence of CKD is related to male, old age, physical exercise, elevated diastolic blood pressure, elevated blood glucose, elevated blood uric acid, hypertension, coronary heart disease, and stroke.

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