Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59
Filtrar
1.
Front Endocrinol (Lausanne) ; 15: 1379634, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601204

RESUMO

Purpose: Given the rising prevalence of high fasting plasma glucose (HFPG) over the past three decades, it is crucial to assess its global, national, and regional impact on chronic kidney disease (CKD). This study aims to investigate the burden of CKD attributed to HFPG and its distribution across various levels. Methods and materials: The data for this research was sourced from the Global Burden of Diseases Study 2019. To estimate the burden of CKD attributed to HFPG, we utilized DisMod-MR 2.1, a Bayesian meta-regression tool. The burden was measured using age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate. Correlation analysis was performed using the Spearman rank order correlation method. Temporal trends were analyzed by estimating the estimated annual percentage change (EAPC). Results: Globally in 2019, there were a total of 487.97 thousand deaths and 13,093.42 thousand DALYs attributed to CKD attributed to HFPG, which represent a substantial increase of 153.8% and 120%, respectively, compared to 1990. Over the period from 1990 to 2019, the burden of CKD attributable to HFPG increased across all regions, with the highest increases observed in regions with high socio-demographic index (SDI) and middle SDI. Regions with lower SDI exhibited higher ASMR and age-standardized DALYs (ASDR) compared to developed nations at the regional level. Additionally, the EAPC values, which indicate the rate of increase, were significantly higher in these regions compared to developed nations. Notably, high-income North America, belonging to the high SDI regions, experienced the greatest increase in both ASMR and ASDR over the past three decades. Furthermore, throughout the years from 1990 to 2019, males bore a greater burden of CKD attributable to HFPG. Conclusion: With an increasing population and changing dietary patterns, the burden of CKD attributed to HFPG is expected to worsen. From 1990 to 2019, males and developing regions have experienced a more significant burden. Notably, the EAPC values for both ASMR and ASDR were higher in males and regions with lower SDI (excluding high-income North America). This emphasizes the pressing requirement for effective interventions to reduce the burden of CKD attributable to HFPG.


Assuntos
Glicemia , Insuficiência Renal Crônica , Masculino , Humanos , Teorema de Bayes , Carga Global da Doença , Jejum , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/etiologia , Produtos Finais de Glicação Avançada
2.
Toxicol Appl Pharmacol ; 483: 116835, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38272317

RESUMO

Actin-interacting proteins are important molecules for filament assembly and cytoskeletal signaling within vascular endothelium. Disruption in their interactions causes endothelial pathogenesis through redox imbalance. Actin filament redox regulation remains largely unexplored, in the context of pharmacological treatment. This work focused on the peptidyl methionine (M) redox regulation of actin-interacting proteins, aiming at elucidating its role on governing antioxidative signaling and response. Endothelial EA.hy926 cells were subjected to treatment with salvianolic acid B (Sal B) and tert-butyl-hydroperoxide (tBHP) stimulation. Mass spectrometry was employed to characterize redox status of proteins, including actin, myosin-9, kelch-like erythroid-derived cap-n-collar homology-associated protein 1 (Keap1), plastin-3, prelamin-A/C and vimentin. The protein redox landscape revealed distinct stoichiometric ratios or reaction site transitions mediated by M sulfoxide reductase and reactive oxygen species. In comparison with effects of tBHP stimulation, Sal B treatment prevented oxidation at actin M325, myosin-9 M1489/1565, Keap1 M120, plastin-3 M592, prelamin-A/C M187/371/540 and vimentin M344. For Keap1, reaction site was transitioned within its scaffolding region to the actin ring. These protein M oxidation regulations contributed to the Sal B cytoprotective effects on actin filament. Additionally, regarding the Keap1 homo-dimerization region, Sal B preventive roles against M120 oxidation acted as a primary signal driver to activate nuclear factor erythroid 2-related factor 2 (Nrf2). Transcriptional splicing of non-POU domain-containing octamer-binding protein was validated during the Sal B-mediated overexpression of NAD(P)H dehydrogenase [quinone] 1. This molecular redox regulation of actin-interacting proteins provided valuable insights into the phenolic structures of Sal B analogs, showing potential antioxidative effects on vascular endothelium.


Assuntos
Actinas , Antioxidantes , Benzofuranos , Depsídeos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Actinas/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Vimentina/metabolismo , Estresse Oxidativo , Metionina , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução , Proteínas do Citoesqueleto/metabolismo , Miosinas/metabolismo , Miosinas/farmacologia
3.
IEEE J Biomed Health Inform ; 28(2): 881-892, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38048234

RESUMO

The segmentation of cardiac structure in magnetic resonance images (CMR) is paramount in diagnosing and managing cardiovascular illnesses, given its 3D+Time (3D+T) sequence. The existing deep learning methods are constrained in their ability to 3D+T CMR segmentation, due to: (1) Limited motion perception. The complexity of heart beating renders the motion perception in 3D+T CMR, including the long-range and cross-slice motions. The existing methods' local perception and slice-fixed perception directly limit the performance of 3D+T CMR perception. (2) Lack of labels. Due to the expensive labeling cost of the 3D+T CMR sequence, the labels of 3D+T CMR only contain the end-diastolic and end-systolic frames. The incomplete labeling scheme causes inefficient supervision. Hence, we propose a novel spatio-temporal adaptation network with clinical prior embedding learning (STANet) to ensure efficient spatio-temporal perception and optimization on 3D+T CMR segmentation. (1) A spatio-temporal adaptive convolution (STAC) treats the 3D+T CMR sequence as a whole for perception. The long-distance motion correlation is embedded into the structural perception by learnable weight regularization to balance long-range motion perception. The structural similarity is measured by cross-attention to adaptively correlate the cross-slice motion. (2) A clinical prior embedding learning strategy (CPE) is proposed to optimize the partially labeled 3D+T CMR segmentation dynamically by embedding clinical priors into optimization. STANet achieves outstanding performance with Dice of 0.917 and 0.94 on two public datasets (ACDC and STACOM), which indicates STANet has the potential to be incorporated into computer-aided diagnosis tools for clinical application.


Assuntos
Coração , Imageamento por Ressonância Magnética , Humanos , Coração/diagnóstico por imagem , Diagnóstico por Computador , Interpretação de Imagem Assistida por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos
4.
J Neuroinflammation ; 20(1): 293, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38062440

RESUMO

BACKGROUND: Depression is two-to-three times more frequent among women. The hypothalamus, a sexually dimorphic area, has been implicated in the pathophysiology of depression. Neuroinflammation-induced hypothalamic dysfunction underlies behaviors associated with depression. The lipopolysaccharide (LPS)-induced mouse model of depression has been well-validated in numerous laboratories, including our own, and is widely used to investigate the relationship between neuroinflammation and depression. However, the sex-specific differences in metabolic alterations underlying depression-associated hypothalamic neuroinflammation remain unknown. METHODS: Here, we employed the LPS-induced mouse model of depression to investigate hypothalamic metabolic changes in both male and female mice using a metabolomics approach. Through bioinformatics analysis, we confirmed the molecular pathways and biological processes associated with the identified metabolites. Furthermore, we employed quantitative real-time PCR, enzyme-linked immunosorbent assay, western blotting, and pharmacological interventions to further elucidate the underlying mechanisms. RESULTS: A total of 124 and 61 differential metabolites (DMs) were detected in male and female mice with depressive-like behavior, respectively, compared to their respective sex-matched control groups. Moreover, a comparison between female and male model mice identified 37 DMs. We capitalized on biochemical clustering and functional enrichment analyses to define the major metabolic changes in these DMs. More than 55% of the DMs clustered into lipids and lipid-like molecules, and an imbalance in lipids metabolism was presented in the hypothalamus. Furthermore, steroidogenic pathway was confirmed as a potential sex-specific pathway in the hypothalamus of female mice with depression. Pregnenolone, an upstream component of the steroid hormone biosynthesis pathway, was downregulated in female mice with depressive-like phenotypes but not in males and had considerable relevance to depressive-like behaviors in females. Moreover, exogenous pregnenolone infusion reversed depressive-like behaviors in female mice with depression. The 5α-reductase type I (SRD5A1), a steroidogenic hub enzyme involved in pregnenolone metabolism, was increased in the hypothalamus of female mice with depression. Its inhibition increased hypothalamic pregnenolone levels and ameliorated depressive-like behaviors in female mice with depression. CONCLUSIONS: Our study findings demonstrate a marked sexual dimorphism at the metabolic level in depression, particularly in hypothalamic steroidogenic metabolism, identifying a potential sex-specific pathway in female mice with depressive-like behaviors.


Assuntos
Depressão , Doenças Neuroinflamatórias , Humanos , Camundongos , Masculino , Feminino , Animais , Depressão/metabolismo , Lipopolissacarídeos/toxicidade , Lipopolissacarídeos/metabolismo , Hipotálamo/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Pregnenolona/metabolismo
5.
Toxicol Appl Pharmacol ; 472: 116571, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37269934

RESUMO

Bacterial lipopolysaccharide (LPS) is a toxic stimulant to macrophage inflammation. Inflammation intersects cell metabolism and often directs host immunopathogenesis stress. We aim here at pharmacological discovering of formononetin (FMN) action, to which anti-inflammatory signaling spans across immune membrane receptors and second messenger metabolites. In ANA-1 macrophage stimulated by LPS, and simultaneous treatment with FMN, results show the Toll-like receptor 4 (TLR4) and estrogen receptor (ER) signals, in concert with reactive oxygen species (ROS) and cyclic adenosine monophosphate (cAMP), respectively. LPS stimulates inactivation of the ROS-dependent nuclear factor erythroid 2-related factor 2 (Nrf2) by upregulating TLR4, but it does not affect cAMP. However, FMN treatment not only activates Nrf2 signaling by TLR4 inhibition, but also it activates cAMP-dependent protein kinase activities by upregulating ER. The cAMP activity gives rise to phosphorylation (p-) of protein kinase A, liver kinase B1 and 5'-AMP activated protein kinase (AMPK). Moreover, bidirectional signal crosstalk is amplified between p-AMPK and ROS, as FMN combinational validation with AMPK activator/inhibitor/target small-interfering RNA or ROS scavenger. The signal crosstalk is well positioned serving as the 'plug-in' knot for rather long signaling axis, and the immune-to-metabolic circuit via ER/TLR4 signal transduction. Collectively, convergence of the FMN-activated signals drives significant reduction of cyclooxygenase-2, interleukin-6 and NLR family pyrin domain-containing protein 3, in LPS-stimulated cell. Although anti-inflammatory signaling is specifically related to the immune-type macrophage, the p-AMPK antagonizing effect arises from FMN combination with ROS scavenger H-bond donors. Information of our work assists in predictive traits against macrophage inflammatory challenges, using phytoestrogen discoveries.


Assuntos
Proteínas Quinases Ativadas por AMP , Receptor 4 Toll-Like , Humanos , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Lipopolissacarídeos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais , Macrófagos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Anti-Inflamatórios/farmacologia
6.
Heliyon ; 9(6): e16539, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37303514

RESUMO

The population of China is aging, and the demand for healthy elderly care is expanding. There is an urgent need to develop a market-oriented elderly care industry and cultivate a number of high-quality elderly care bases. The geographical environment is an important condition affecting the health of elderly individuals and the suitability of elderly care. Research on this topic has important guiding significance for the layout of elderly care bases and the choice of elderly care locations. In this study, a spatial fuzzy comprehensive evaluation was conducted to construct an evaluation index system based on the following standard layers: climatic conditions, topography, surface vegetation, atmospheric environment, traffic conditions, economy and population, elderly-friendly urban environments, elderly care service capabilities, and wellness and recreation resources. The index system analyzes the suitability of elderly care in 4 municipalities and 333 prefecture-level administrative regions in China, and development and layout suggestions are proposed. The results show the following: (1) The three concentrated areas with a highly suitable geographical environment for elderly care in China are the Yangtze River Delta, the Yunnan-Guizhou-Sichuan region and the Pearl River Delta. The areas with the most concentrated unsuitable areas are the southern Xinjiang and Qinghai-Tibet areas. (2) In areas with a geographical environment that is highly suitable for elderly care, high-end elderly care industries can be deployed, and national-level elderly care demonstration bases can be built. Areas with a highly suitable temperature in Central and Southwest China can develop characteristic elderly care bases for people with cardiovascular and cerebrovascular diseases. Scattered areas with a highly suitable temperature and humidity can develop characteristic elderly care bases for people with rheumatic and respiratory diseases.

7.
ACS Appl Mater Interfaces ; 15(23): 28491-28502, 2023 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-37256265

RESUMO

The accuracy of data collected by optical instruments can be greatly impacted by radar band electromagnetic waves (EM) and scattered visible light. Traditional electromagnetic-wave-absorbing (EMA) materials face challenges in effectively attenuating electromagnetic waves within the visible light spectrum. To address this issue, a structural engineering-based assembly strategy was developed to construct PVDF/Ti3CNTx@PPyNF composites with multiple heterogeneous interfaces, inspired by snake scales. And through the self-doping of N elements and the coating process, the material finally exhibits excellent microwave and visible light absorption properties. This approach generates multiple polarization losses of electromagnetic waves, enabling the material to exhibit excellent electromagnetic wave absorption performance. Specifically, the PVDF/Ti3CNTx@PPyNF composite, containing 5 wt % Ti3CNTx@PPyNFs, demonstrates exceptional microwave absorption performance, with a minimum reflection loss of -65.5 dB and an effective absorption bandwidth of up to 6.95 GHz. Additionally, the composite coating exhibits 97.4% visible light absorption performance, providing a promising solution to the challenges of protecting against complex electromagnetic environments.

8.
Food Chem Toxicol ; 171: 113513, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36436616

RESUMO

Mitochondrion-related cardiotoxicity due to cardiotoxin stimuli is closely linked to abnormal activities of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), followed by co-inactivation of nuclear respiratory factor-1(NRF1). Pharmacological interventions targeting mitochondria may be effective for developing agents against cardiotoxicity. Herein, in triptolide-treated H9C2 cardiomyocytes, we observed defective mitochondrial biogenesis and respiration, characterized by depletion of mitochondrial mass and mitochondrial DNA copy number, downregulation of mitochondrial respiratory chain complexes subunits, and disorders of mitochondrial membrane potential and mitochondrial oxidative phosphorylation. Dysregulation of mitochondria led to cardiac pathological features, such as myocardial fiber fracture, intercellular space enlargement, and elevation of serum aspartate aminotransferase, creatine kinase isoenzyme, lactate dehydrogenase, and cardiac troponin I. However, following calycosin treatment, an active compound from Astragali Radix, the mitochondrion-related disorders at both cell and tissue levels were significantly ameliorated, which was facilitated by the activation of PGC-1α via deacetylation, followed by NRF1 co-activation. Calycosin-enhanced PGC-1α deacetylation is impelled by increasing sirtuin-1 expression and NAD+/NADH ratio. PGC-1α/NRF1 signaling in calycosin-mediated mitochondrial biogenesis protection was further confirmed by NRF1 knockdown and PGC-1α inhibition with SR18292. We conclude that calycosin ameliorated triptolide-induced cardiotoxicity by protecting PGC-1α/NRF1-dependent cardiac mitochondrial biogenesis and respiration, which is the druggable pathway for cardiotoxicity mitigation.


Assuntos
Cardiotoxicidade , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Biogênese de Organelas , Fosforilação Oxidativa , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6378-6386, 2023 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-38211994

RESUMO

This paper aims to investigate the protective effect and mechanism of Astragalus membranaceus and Angelica sinensis before and after compatibility against triptolide(TP)-induced hepatotoxicity. The experiment was divided into a blank group, model group, Astragalus membranaceus group, Angelica sinensis group, and compatibility groups with Astragalus membranaceus/Angelica sinensis ratio of 1∶1, 2∶1, and 5∶1. TP-induced hepatotoxicity model was established, and corresponding drug intervention was carried out. The levels of alanine transaminase(ALT), aspartate transaminase(AST), and alkaline phosphatase(ALP) in serum were detected. Pathological injuries of livers were detected by hematoxylin-eosin(HE) staining. The levels of malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and reduced glutathione(GSH) in the liver were measured. Wes-tern blot method was used to detect the expression of nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(Keap1), peroxisome proliferator-activated receptor gamma, coactivator-1 alpha(PGC-1α), heme oxygenase-1(HO-1), and NAD(P)H quinone dehydrogenase 1(NQO1) in livers. Immunofluorescence was used to detect the expression of Nrf2 and PGC-1α in livers. The results indicated that Astragalus membranaceus/Angelica sinensis ratio of 2∶1 and 5∶1 could significantly reduce the levels of serum AST, ALT, and ALP, improve the pathological damage of liver tissue, increase the levels of GSH and GSH-Px, and reduce the content of MDA in liver tissue. Astragalus membranaceus/Angelica sinensis ratio of 1∶1 and 2∶1 could significantly improve the level of SOD. Astragalus membranaceus and Angelica sinensis before and after compatibility significantly increased the protein expression of HO-1 and NQO1, improved the protein expression of Nrf2 and PGC-1α, and decreased the protein expression of Keap1 in liver tissue. The above results confirmed that the compatibility of Astragalus membranaceus and Angelica sinensis had antioxidant effects by re-gulating Keap1/Nrf2/PGC-1α, and the Astragalus membranaceus/Angelica sinensis ratio of 2∶1 and 5∶1 had stronger antioxidant effect and significantly reduced TP-induced hepatoto-xicity.


Assuntos
Angelica sinensis , Doença Hepática Induzida por Substâncias e Drogas , Diterpenos , Fenantrenos , Humanos , Astragalus propinquus , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Superóxido Dismutase/metabolismo , Estresse Oxidativo , Compostos de Epóxi
10.
Front Pharmacol ; 13: 925489, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225562

RESUMO

Renal fibrosis is an incurable disorder characterised by an imbalance of the extracellular matrix (ECM) favouring excess production over degradation. The identification of actionable pathways and agents that promote ECM degradation to restore ECM homeostasis may help mitigate renal fibrosis. In this study, we identified 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (LM49), a compound we previously synthesised, as a small-molecule inducer of ECM degradation. LM49 administration efficiently reduced ECM deposition in renal tissue of diabetic nephropathy rats and in transforming growth factor ß-treated renal fibroblast cells. LM49 promoted the cytosol-to-nucleus translocation of transcription factor EB (TFEB) to increase lysosome biogenesis, leading to lysosome-based degradation of the ECM. TFEB-mediated lysosome biogenesis was induced by LM49 directly inhibiting the activity of glycogen synthase kinase 3ß (GSK3ß) rather than mammalian target of rapamycin complex 1. LM49 inhibited GSK3ß kinase activity concentration-dependently via competing with ATP. Direct binding between LM49 and GSK3ß was confirmed by the bio-layer interferometry assay, cellular thermal shift assay, and drug affinity responsive target stability. A molecular docking and molecular dynamic simulation revealed that LM49 occupied the ATP pocket of GSK3ß, which was consistent with the kinase activity assay. In summary, LM49 enhances TFEB-mediated lysosome biogenesis by directly inhibiting GSK3ß, leading to the degradation of the ECM by lysosomes. The enhancement of GSK3ß-dependent lysosome biogenesis to rebalance the ECM may be a novel strategy to counteract renal fibrosis, and LM49 may be a viable clinical candidate for treating this disorder.

11.
Food Funct ; 13(21): 11236-11248, 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36222424

RESUMO

Ginger (Rhizoma zingiberis, RZ) has been used as a food, spice, supplement, flavoring agent, and as an edible herbal medicine. It is characterized by its pungency and aroma, and is rich in nutrients with remarkable pharmacological effects. It is used in traditional medicine clinics to treat diseases and symptoms, such as colds, headache, and primary dysmenorrhea (PD). In China, a variety of processed products of RZ are used as herbal medicines, such as baked ginger (BG) or ginger charcoal (GC) to treat different diseases and symptoms. However, the molecular mechanism of the therapeutic effect of RZ and its processed products (RZPPs, including BG or GC) against PD has not been well characterized. Moreover, whether the transient receptor potential (TRP) ion channels are involved in this process is not clear. In the present study, UHPLC-Q-TOF MS was adopted to analyse the differential quality markers (DQMs) between RZ and RZPPs. In addition, differential metabolomics (DMs) was acquired between RZ- and RZPPs-treated estradiol valerate coupled with an oxytocin-induced PD mouse uterus using untargeted metabolomics (UM). A correlation analysis between DQMs and DMs was also conducted. Benzenoids, lipids, and lipid-like molecules were the main DQMs between RZ and RZPPs. RZ and RZPPs were found to improve the pathological status of the uterus of a PD mouse, with significantly decreased serum levels of E2, PGF2α, TXB2 and remarkably increased levels of PROG and 6-keto-PGF1α. Moreover, RZ and RZPPs alleviated PD in mice via regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway. Our results indicate that the therapeutic effect of RZ and RZPPs against PD may be mediated by regulating the TRP ion channel-mediated ERK1/2/NF-κB signaling pathway, and provide a reference for the development of new dietary supplements or medicines.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Zingiber officinale , Humanos , Feminino , Camundongos , Animais , Dismenorreia/tratamento farmacológico , Dismenorreia/metabolismo , Ocitocina/metabolismo , Ocitocina/uso terapêutico , NF-kappa B/genética , NF-kappa B/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Estradiol , Transdução de Sinais , Canais Iônicos/metabolismo , Canais Iônicos/uso terapêutico , Prostaglandinas F/uso terapêutico
13.
BMC Neurol ; 22(1): 243, 2022 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-35788208

RESUMO

BACKGROUND: Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal, and distal limb muscle involvement. Recent research showed that GGC repeat expansions in the NOTCH2NLC gene were observed in a proportion of OPDM patients, and these patients were designated as having OPDM type 3 (OPDM3). Heterogeneous neuromuscular manifestations have been described previously in studies of OPDM3; however, kidney involvement in this disease has rarely been reported. CASE PRESENTATION: Here, we report the case of a 22-year-old Chinese patient with typical manifestations of OPDM complicated with focal segmental glomerular sclerosis (FSGS). This patient with sporadic FSGS exhibited distal motor neuropathy and rimmed vacuolar myopathy in clinical and pathological examinations. An expansion of 122 CGG repeats located in the 5' untranslated region (UTR) of the NOTCH2NLC gene was identified as the causative mutation in this patient. The clinical and histopathological findings fully met the criteria for the diagnosis of OPDM3. In addition, intranuclear inclusions were detected in the renal tubule epithelial cells of this patient, indicating that the kidney may also be impaired in NOTCH2NLC-related GGC repeat expansion disorders (NREDs). CONCLUSIONS: Our case report demonstrated the clinicopathological cooccurrence of sporadic FSGS and OPDM3 in a patient, which highlighted that the kidney may show inclusion depositions in OPDM3, thus expanding the clinical spectrum of NREDs.


Assuntos
Glomerulosclerose Segmentar e Focal , Distrofias Musculares , Adulto , Humanos , Distrofias Musculares/patologia , Linhagem , Esclerose/complicações , Adulto Jovem
14.
Artigo em Inglês | MEDLINE | ID: mdl-35895657

RESUMO

In this work, we address the task of few-shot medical image segmentation (MIS) with a novel proposed framework based on the learning registration to learn segmentation (LRLS) paradigm. To cope with the limitations of lack of authenticity, diversity, and robustness in the existing LRLS frameworks, we propose the better registration better segmentation (BRBS) framework with three main contributions that are experimentally shown to have substantial practical merit. First, we improve the authenticity in the registration-based generation program and propose the knowledge consistency constraint strategy that constrains the registration network to learn according to the domain knowledge. It brings the semantic-aligned and topology-preserved registration, thus allowing the generation program to output new data with great space and style authenticity. Second, we deeply studied the diversity of the generation process and propose the space-style sampling program, which introduces the modeling of the transformation path of style and space change between few atlases and numerous unlabeled images into the generation program. Therefore, the sampling on the transformation paths provides much more diverse space and style features to the generated data effectively improving the diversity. Third, we first highlight the robustness in the learning of segmentation in the LRLS paradigm and propose the mix misalignment regularization, which simulates the misalignment distortion and constrains the network to reduce the fitting degree of misaligned regions. Therefore, it builds regularization for these regions improving the robustness of segmentation learning. Without any bells and whistles, our approach achieves a new state-of-the-art performance in few-shot MIS on two challenging tasks that outperform the existing LRLS-based few-shot methods. We believe that this novel and effective framework will provide a powerful few-shot benchmark for the field of medical image and efficiently reduce the costs of medical image research. All of our code will be made publicly available online.

15.
BMC Complement Med Ther ; 22(1): 32, 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35101002

RESUMO

BACKGROUND: The incidence rate of invasive candidiasis is high, its treatment is difficult, and the prognosis is poor. In this study, an immunosuppressive mouse model of invasive Candida albicans (C. albicans) infection was constructed to observe the effects of cinnamaldehyde (CA) on the C. albicans cell wall structure and cell wall (1,3)-ß-D-glucan contents. This study provides a theoretical basis for CA treatment to target invasive C. albicans infection. METHODS: Immunosuppressed mice with invasive C. albicans infection were given an oral dosage of CA (240 mg.kg- 1.d- 1) for 14 days. Then, mouse lung tissue samples were collected for detection of the levels of (1,3)-ß-D-glucan and transmission electron microscopy observations, using fluconazole as a positive control and 2% Tween 80 saline as a negative control. RESULTS: The immunosuppressive mouse model of invasive C. albicans infection was successfully established. The levels of (1,3)-ß-D-glucan in the CA treatment group, fluconazole positive control group, invasive C. albicans infection immunosuppressive mouse model group, and 2% Tween 80 normal saline control group were 86.55 ± 126.73 pg/ml, 1985.13 ± 203.56 pg/ml, 5930.57 ± 398.67 pg/ml and 83.36 ± 26.35 pg/ml, respectively. Statistically, the CA treatment group, fluconazole positive control group and invasive C. albicans infection immunosuppressive mouse model group were compared with each other (P < 0.01) and compared with the 2% Tween 80 saline group (P < 0.01), showing that the differences were very significant. Comparison of the CA treatment group with the fluconazole positive control group (P < 0.05) displayed a difference as well. Electron microscopy showed that CA destroyed the cell wall of C. albicans, where the outer layer of the cell wall fell off and became thinner and the nuclei and organelles dissolved, but the cell membrane remained clear and intact. CONCLUSION: CA destroys the cell wall structure of C. albicans by interfering with the synthesis of (1,3)-ß-D-glucan to kill C. albicans. However, CA does not affect the cell membrane. This study provides a theoretical basis for CA treatment to target invasive C. albicans infection.


Assuntos
Acroleína/análogos & derivados , Candidíase/tratamento farmacológico , Glucanos/metabolismo , Acroleína/farmacologia , Animais , Candida albicans , Parede Celular/efeitos dos fármacos , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Masculino , Camundongos , Camundongos Endogâmicos BALB C
16.
ACS Appl Mater Interfaces ; 14(4): 6005-6015, 2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35050593

RESUMO

Fast and safe electric heating is highly needed in extreme climates or thermal therapy. Herein, porous activated carbon derived from silk waste is prepared by a simple method. Various porous activated carbons are obtained using different types and concentrations of activator (KOH, KCl, and KHCO3). The effect of the microstructure on the electric heating performance of these carbons is investigated carefully. The type, activator concentration, and carbonization temperature play key roles in the regulation of electric heating properties. The porous carbon activated by 0.05 M KHCO3 at 800 °C demonstrates larger specific surface area (3077 m2 g-1), higher graphitization degree, and lower resistance (2.4 Ω cm), which synergistically contribute greatly to its higher electrothermal efficiency and better electric heating performance. The equilibrium temperature could reach 73 °C in 2 min under a safe voltage of 12 V, proving the better pore-forming capacity and activating function of KHCO3. An electric heating cotton@carbon composite fabric with quite good electric heating property and stability is also prepared, which could reach 38 °C in 2 min under 12 V safe voltage and maintain a temperature 10 °C higher than the ambient temperature even when bent at an angle of 55°. This activated carbon derived from waste protein using a simple and cheap process has great potential in practical applications.

17.
Nanotechnology ; 33(15)2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-34983037

RESUMO

Macroscopic conformation of individual graphene sheets serves as the backbone of translating their intrinsic merits towards multifunctional practical applications. However, controllable and continuous assemblies of graphene-based nanomaterials to create stable macroscopic structural components are always in face of great challenge. We have developed a scalable converging-flow assisted wet-spinning methodology for continuously fabricating hollow graphene fibers (HGFs, the newest variation of solid graphene fibers) with high quality. The degradable silk thread is selectively utilized as the continuous hollow structure former that holds the coaxially stacked graphene sheets aligned through the converging-flow modulating process. For the first time, we have created the longest freestanding HGF in length of 2.1 m. The continuous HGFs are in an average diameter of 180µm and with 4-8µm adjustable wall thicknesses. The optimal HGF demonstrates an average tensile strength of 300 MPa and modulus of 2.49 GPa (comparable to typical solid graphene fibers, but the highest among the reported HGFs in literature) and an exceptional failure elongation of 10.8%. Additionally, our continuous HGFs exhibit spontaneous resistive response to thermal and strain stimuli (in form of large deformations and human motions), offering great potential for developing multifunctional sensors. We envision that this work demonstrates an effective and well-controlled macroscopic assembly methodology for the scaled-up mass production of HGFs.

18.
IEEE J Biomed Health Inform ; 26(5): 2264-2275, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34699378

RESUMO

The accurate 3D left ventricular (LV) myocardium segmentation in short-axis (SAX) view of cardiac magnetic resonance (CMR) is challenged by the sparse spatial structure of CMR. The strategy of multi-view CMR fusion can provide fine-grained spatial structure for accurate segmentation. However, the large information misalignment and lack of dense 3D CMR as fusion target in multi-view CMR fusion, and the different spatial resolution between the fusion result and the ground truth in segmentation limit the strategy. In this study, we propose a multi-view spatial-aware adversarial network (MVSGAN). It studies the perception of fine-grained cardiac structure for accurate segmentation by the spatialaware multi-view CMR fusion. It consists of three modules: (1) A residual adversarial fusion (RAF) module takes inter-slices deep correlation and anatomical prior to refine the spatial structures by residual supplement and adversarial optimization. (2) A structural perception-aggregation (SPA) module establishes the spatial correlation between the dense cardiac model and sparse label for accurate CMR LV myocardium segmentation. (3) A joint training strategy utilizes the dense SAX volume as explicit and implicit goals to jointly optimize the framework. The experiments are applied on a public dataset and a clinical dataset to evaluate the performance of MVSGAN. The average Dice and Jaccard score of LV myocardium segmentation obtained by MVSGAN are highest among seven existing state-of-the-art methods, which are up to 0.92 and 0.75. It is concluded that the spatial-aware multi-view CMR fusion can provide meaningful spatial correlation for accurate LV myocardium segmentation.


Assuntos
Ventrículos do Coração , Imageamento por Ressonância Magnética , Coração , Ventrículos do Coração/diagnóstico por imagem , Humanos , Espectroscopia de Ressonância Magnética , Miocárdio
19.
Int J Biol Macromol ; 193(Pt B): 1685-1693, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34748788

RESUMO

With the increasingly serious plastic pollution, people's demand for the multi-functional biodegradable plastics is becoming more and more urgent. Inspired by the crosslinked shape memory polymers, the crosslinked starch films were synthesized by inducing the decomposition of benzophenone into free radical and depriving hydrogen on starch macromolecules under UV irradiation, in order to gain a high shape memory performance. The results showed that a three-dimensional crosslinking network between starch macromolecule chains was formed. Compared with the uncrosslinked starch films, the photo-crosslinked films not only had higher mechanical property (tensile strength increased by 154%), but also had better water resistance (water contact angle from 60° to 87°) due to the reduction of free hydroxyl groups. In addition, the stable covalent bonds serving as netpoints endow photo-crosslinked films with great improvement in shape memory property, with nearly 180° bending recovery. More importantly, the maximum shape memory fixity ratio (Rf) and shape memory recovery ratio (Rr) under stretch deformation were 96.5% and 99.8%, respectively. And the Rf and Rr could reach 94.6% and 79.8% even at higher strain. In all, the excellent shape memory performance and good degradability crosslinked starch films, which have great potential application in disposable heat-shrinkable packaging materials.


Assuntos
Plásticos Biodegradáveis/química , Embalagem de Alimentos , Membranas Artificiais , Materiais Inteligentes/química , Amido/química
20.
Aging Dis ; 12(4): 954-963, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34221541

RESUMO

Dementia is a complex syndrome with various presentations depending on the underlying pathologies. Low emission of transcranial near-infrared (tNIR) light can reach human brain parenchyma and be beneficial to a number of neurological and neurodegenerative disorders. We hereby examined the safety and potential therapeutic benefits of tNIR light stimulations in the treatment of dementia. Patients of mild to moderate dementia were randomized into active and sham treatment groups at 2:1 ratio. Active treatment consisted of low power tNIR light stimulations with an active photobiomodulation for 6 min twice daily during 8 consequent weeks. Sham treatment consisted of same treatment routine with a sham device. Neuropsychological battery was obtained before and after treatment. Analysis of variance (ANOVA) was used to analyze outcomes. Sixty subjects were enrolled. Fifty-seven subjects completed the study and had not reported health or adverse side effects during or after the treatment. Three subjects dropped out from trial for health issues unrelated to use of tNIR light treatment. Treatment with active device resulted in improvements of cognitive functions and changes were: an average increase of MMSE by 4.8 points; Logical Memory Tests I and II by ~3.0 points; Trail Making Tests A and B by ~24%; Boston Naming Test by ~9%; improvement of both Auditory Verbal Learning Tests in all subtest categories and overall time of performance. Many patients reported improved sleep after ~7 days of treatment. Caregivers noted that patients had less anxiety, improved mood, energy, and positive daily routine after ~14-21 days of treatment. The tNIR light treatments demonstrated safety and positive cognitive improvements in patients with dementia. Developed treatment protocol can be conveniently used at home. This study suggests that additional dementia treatment trials are warranted with a focus on mitigating caregivers' burden with tNIR light treatment of dementia patients.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...