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1.
Artigo em Inglês | MEDLINE | ID: mdl-39003133

RESUMO

BACKGROUND AND AIM: The objective of our study was to examine the association between composite dietary antioxidant index (CDAI) and atherosclerotic cardiovascular disease (ASCVD) in adults. METHODS AND RESULTS: Data was gathered from the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018. To examine the connection between CDAI and ASCVD, multiple logistic regression analyses were performed. Restricted cubic splines were utilized to examine non-linear correlations, and the inflection point was identified using a two-piecewise linear regression approach. Subgroup analyses were performed to demonstrate stability of results. A total of 44,494 individuals were included in the study. The multivariate logistic regression model was fully adjusted and revealed an odds ratio of 0.968 (95% CI: 0.959-0.978; P < 0.001) for the correlation between CDAI and ASCVD. Furthermore, individuals in the highest quartile of CDAI exhibited a decreased risk of ASCVD compared to those in the lowest quartile [0.716 (0.652-0.787); P < 0.001]. Moreover, restricted cubic spline (RCS) analysis revealed non-linear relationship between CDAI and ASCVD, with inflection point at -0.387. The analysis of subgroups showed that the importance of CDAI remained consistent among various age, sex, race, body mass index (BMI), and physical activity. CONCLUSIONS: Our research revealed an inverse and non-linear relationship between CDAI and ASCVD in adults. The implications of these findings are significant for future studies and the formulation of dietary guidelines.

2.
Soc Sci Res ; 118: 102972, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38336423

RESUMO

Women are often considered more liberal than men on controversial social issues, but gender gaps in sociopolitical attitudes across different age groups have not been fully explored. This study challenges the taken-for-granted gender differences in public attitudes toward homosexuality by examining both between-gender gaps and within-gender changes across the life course. Using data from five waves of the World Values Survey in South Korea, we explore gender and age differences in Korean adults' attitudes toward homosexuality from 1996 to 2018. Consistent with previous research, people become more conservative as they get older, and in general, women are more accepting of homosexuality than men, accounting for sociodemographic covariates. However, this gender difference is conditioned by people's life stages. Only among young adults (aged 18-29) were female respondents more accepting of homosexuality than their male counterparts. For people aged 30 and older, there are no significant gender differences in attitudes, and for both women and men, homosexuality is mostly unacceptable during their mid (aged 50-59) and late adulthood (aged 60+). Further mediation investigation has shown gendered mechanisms behind age differences in homosexuality acceptability. For both women and men, traditional family/gender attitudes provide significant explanations about age differences in homosexuality, while for women, not for men, family status, especially the number of children, makes older women more conservative in homosexuality issues. We suggest that heteropatriarchal social structures may lead to a resistance to attitudinal changes in non-traditional family forms, such as homosexuality.


Assuntos
Atitude , Homossexualidade , Adulto , Idoso , Feminino , Humanos , Masculino , Adulto Jovem , Opinião Pública , República da Coreia , População do Leste Asiático , Pessoa de Meia-Idade
3.
Cell Commun Signal ; 21(1): 14, 2023 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-36670446

RESUMO

BACKGROUND: Cellular communication network factor 3 (CCN3) has been implicated in the regulation of osteoblast differentiation. However, it is not known if CCN3 can regulate valvular calcification. While macrophages have been shown to regulate valvular calcification, the molecular and cellular mechanisms of this process remain poorly understood. In the present study, we investigated the role of macrophage-derived CCN3 in the progression of calcific aortic valve disease. METHODS: Myeloid-specific knockout of CCN3 (Mye-CCN3-KO) and control mice were subjected to a single tail intravenous injection of AAV encoding mutant mPCSK9 (rAAV8/D377Y-mPCSK9) to induce hyperlipidemia. AAV-injected mice were then fed a high fat diet for 40 weeks. At the conclusion of high fat diet feeding, tissues were harvested and subjected to histologic and pathologic analyses. In vitro, bone marrow-derived macrophages (BMDM) were obtained from Mye-CCN3-KO and control mice and the expression of bone morphogenic protein signaling related gene were verified via quantitative real-time PCR and Western blotting. The BMDM conditioned medium was cocultured with human valvular intersititial cells which was artificially induced calcification to test the effect of the conditioned medium via Western blotting and Alizarin red staining. RESULTS: Echocardiography revealed that both male and female Mye-CCN3-KO mice displayed compromised aortic valvular function accompanied by exacerbated valve thickness and cardiac dysfunction. Histologically, Alizarin-Red staining revealed a marked increase in aortic valve calcification in Mye-CCN3-KO mice when compared to the controls. In vitro, CCN3 deficiency augmented BMP2 production and secretion from bone marrow-derived macrophages. In addition, human valvular interstitial cells cultured with conditioned media from CCN3-deficient BMDMs resulted in exaggerated pro-calcifying gene expression and the consequent calcification. CONCLUSION: Our data uncovered a novel role of myeloid CCN3 in the regulation of aortic valve calcification. Modulation of BMP2 production and secretion in macrophages might serve as a key mechanism for macrophage-derived CCN3's anti-calcification function in the development of CAVD. Video Abstract.


Assuntos
Estenose da Valva Aórtica , Calcinose , Masculino , Feminino , Humanos , Camundongos , Animais , Valva Aórtica/metabolismo , Valva Aórtica/patologia , Estenose da Valva Aórtica/metabolismo , Estenose da Valva Aórtica/patologia , Meios de Cultivo Condicionados , Calcinose/metabolismo , Calcinose/patologia , Células Cultivadas
4.
Proc Natl Acad Sci U S A ; 117(21): 11337-11343, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32398373

RESUMO

The study of topological materials possessing nontrivial band structures enables exploitation of relativistic physics and development of a spectrum of intriguing physical phenomena. However, previous studies of Weyl physics have been limited exclusively to semimetals. Here, via systematic magnetotransport measurements, two representative topological transport signatures of Weyl physics, the negative longitudinal magnetoresistance and the planar Hall effect, are observed in the elemental semiconductor tellurium. More strikingly, logarithmically periodic oscillations in both the magnetoresistance and Hall data are revealed beyond the quantum limit and found to share similar characteristics with those observed in ZrTe5 and HfTe5 The log-periodic oscillations originate from the formation of two-body quasi-bound states formed between Weyl fermions and opposite charge centers, the energies of which constitute a geometric series that matches the general feature of discrete scale invariance (DSI). Our discovery reveals the topological nature of tellurium and further confirms the universality of DSI in topological materials. Moreover, introduction of Weyl physics into semiconductors to develop "Weyl semiconductors" provides an ideal platform for manipulating fundamental Weyl fermionic behaviors and for designing future topological devices.

5.
Proc Natl Acad Sci U S A ; 117(30): 18018-18028, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32651278

RESUMO

CCN3 is a matricellular protein that promotes oligodendrocyte progenitor cell differentiation and myelination in vitro and ex vivo. CCN3 is therefore a candidate of interest in central nervous system (CNS) myelination and remyelination, and we sought to investigate the expression and role of CCN3 during these processes. We found CCN3 to be expressed predominantly by neurons in distinct areas of the CNS, primarily the cerebral cortex, hippocampus, amygdala, suprachiasmatic nuclei, anterior olfactory nuclei, and spinal cord gray matter. CCN3 was transiently up-regulated following demyelination in the brain of cuprizone-fed mice and spinal cord lesions of mice injected with lysolecithin. However, CCN3-/- mice did not exhibit significantly different numbers of oligodendroglia or differentiated oligodendrocytes in the healthy or remyelinating CNS, compared to WT controls. These results suggest that despite robust and dynamic expression in the CNS, CCN3 is not required for efficient myelination or remyelination in the murine CNS in vivo.


Assuntos
Sistema Nervoso Central/metabolismo , Doenças Desmielinizantes/etiologia , Regulação da Expressão Gênica , Proteína Sobre-Expressa em Nefroblastoma/genética , Remielinização/genética , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Imunofluorescência , Camundongos , Bainha de Mielina/metabolismo , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Oligodendroglia/metabolismo , Medula Espinal/metabolismo , Medula Espinal/patologia
6.
Aging Ment Health ; 27(2): 425-433, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-34951553

RESUMO

OBJECTIVE: This study examines the longitudinal association between the location of multiple children and depressive symptoms of older parents in rural China, where massive rural-to-urban migration has profoundly altered the family life of the aging population. METHODS: Using seven waves of panel data from the Longitudinal Study of Older Adults in Anhui Province (2001-2018, N = 8,253) and multilevel growth curve models, this study compares mental health trajectories of old parents across different compositions of local and migrant children over an 18-year time period. RESULTS: The results show that older parents with a greater share of adult children who had migrated away not only scored worse mental health on average, but also experienced a more rapid increase in depressive symptoms across ages, after accounting for other covariates. Further, older adults who had their most children migrated away for a longer period of time suffered from the steeper rate of increase in depressive symptoms as they got older. CONCLUSIONS: We suggest that it is not the geographic locality of a single child but the location of multiple children that matters for parental mental health in later life.


Assuntos
Depressão , Saúde Mental , Humanos , Idoso , Depressão/epidemiologia , Estudos Longitudinais , Envelhecimento/psicologia , População Rural , Pais/psicologia , China/epidemiologia
7.
Phytother Res ; 37(9): 4210-4223, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37253360

RESUMO

Type 2 diabetes mellitus (T2DM) and its complications have become a serious global health epidemic. Cardiovascular complications have considered as a major cause of high mortality in diabetic patients. Fucoidans from brown algae have diverse medicinal activities, however, few studies reported pharmacological activity of Sargassum. pallidum fucoidan (Sp-Fuc). Therefore, the aim of this study was to investigate the effects of Sp-Fuc on diabetic symptoms and cardiac injury in spontaneous diabetic db/db mice. SP-Fuc at 200 mg/(kg/d) was administered intragastrically to db/db mice for 8 weeks, the effects on hyperlipidemia, hyperglycemia, insulin resistance, and cardiac damage, as well as oxidative stress, inflammation, Nrf2/ARE, and NF-κB signaling pathways, were investigated. Our data demonstrated that Sp-Fuc significantly (p < 0.05) decreased body weights, hyperlipidemia, and hyperglycemia in db/db mice, along with improved insulin sensitivity. Additionally, Sp-Fuc significantly (p < 0.05) alleviated cardiac dysfunction and pathological morphology of cardiac tissue. Sp-Fuc also significantly (p < 0.05) decreased lipid peroxidation, increased antioxidant function, as well as reduced cardiac inflammation, possibly through Nrf2/ARE and NF-κB signaling. Sp-Fuc can ameliorate the metabolism disorders of glucose and lipid in diabetic mice by activating Nrf2/ARE antioxidant signaling, simultaneously reducing cardiac redox imbalance and inflammatory damage. The present findings provide a perspective on the therapy strategy for T2DM and its complications.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Hiperglicemia , Resistência à Insulina , Sargassum , Camundongos , Animais , Antioxidantes/farmacologia , NF-kappa B/metabolismo , Fígado , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Experimental/complicações , Fator 2 Relacionado a NF-E2/metabolismo , Globo Pálido/metabolismo , Estresse Oxidativo , Inflamação/tratamento farmacológico , Hiperglicemia/metabolismo
8.
Microvasc Res ; 140: 104302, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34919942

RESUMO

PURPOSE: Myocardial ischemia/reperfusion injury (MI/RI) is a major problem in the clinical treatment of ischemic cardiomyopathy, and its specific underlying mechanisms are complicated and still unclear. A number of studies have indicated that the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxidase-1(HO-1) signaling pathway might serve as an important target for the management of MI/RI. Catalpol is a kind of iridoid glucoside that has been found to exhibit diverse anti-inflammatory and antioxidant properties. This study was aimed at investigating the role of Catalpol in targeting MI/RI and its related mechanisms in an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro and a preclinical ischemia/reperfusion (I/R) model. METHODS: This study using both in vitro and in vivo models investigated the possible role and underlying mechanisms used by Catalpol for modulating of MI/RI. The potential effects of Catalpol on the viability of cardiomyocytes were measured by cell counting kit-8 (CCK-8) assays. The phenotypes of myocardial injury, oxidative stress and inflammation markers were measured by western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA) etc. Nrf2/HO-1 signaling pathway was detected by immunofluorescence and western blot analysis. RESULTS: We found that Catalpol significantly suppressed the process of MI/RI and protected OGD/R-treated cardiomyocytes by inhibiting the various markers of inflammation and suppressing oxidative stress. Additionally, mechanistically it was also demonstrated that Catalpol could effectively activate Nrf2/HO-1 signaling pathway to suppress the damage caused by inflammation and oxidative stress in MI/RI. CONCLUSION: In summary, the findings suggest that Catalpol exerted significant cardioprotective effects following myocardial ischemia, possibly through the activation of the Nrf2/HO-1 signaling pathway.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Heme Oxigenase-1/metabolismo , Glucosídeos Iridoides/farmacologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular , Linhagem Celular , Modelos Animais de Doenças , Glucose/deficiência , Humanos , Mediadores da Inflamação/metabolismo , Masculino , Proteínas de Membrana , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais
9.
Phys Rev Lett ; 128(9): 096601, 2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35302793

RESUMO

For solids, the dispersionless flat band has long been recognized as an ideal platform for achieving intriguing quantum phases. However, experimental progress in revealing flat-band physics has so far been achieved mainly in artificially engineered systems represented as magic-angle twisted bilayer graphene. Here, we demonstrate the emergence of flat-band-dominated anomalous transport and magnetic behaviors in CoSn, a paramagnetic kagome-lattice compound. By combination of angle-resolved photoemission spectroscopy measurements and first-principles calculations, we reveal the existence of a kagome-lattice-derived flat band right around the Fermi level. Strikingly, the resistivity within the kagome lattice plane is more than one order of magnitude larger than the interplane one, in sharp contrast with conventional (quasi-) two-dimensional layered materials. Moreover, the magnetic susceptibility under the out-of-plane magnetic field is found to be much smaller as compared with the in-plane case, which is revealed to be arising from the introduction of a unique orbital diamagnetism. Systematic analyses reveal that these anomalous and giant anisotropies can be reasonably attributed to the unique properties of flat-band electrons, including large effective mass and self-localization of wave functions. Our results broaden the already fascinating flat-band physics, and demonstrate the feasibility of exploring them in natural solid-state materials in addition to artificial ones.

10.
J Magn Reson Imaging ; 55(2): 518-527, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34184356

RESUMO

BACKGROUND: Renal hypoxia, which caused by a mismatch between oxygen delivery and oxygen demand, may be the primary pathophysiological pathway driving diabetic kidney disease (DKD). Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) could detect hypoxia, but can be limited in distinguishing increased oxygen consumption or decreased blood supply. PURPOSE: To explore multiparametric functional MRI in evaluating mechanism of the hypoxia changes in early stage of DKD. STUDY TYPE: Prospective. ANIMAL MODEL: Thirty-five New Zealand White rabbits were divided into control group (n = 5) and alloxan-induced diabetes mellitus (DM) groups (DM3 group: n = 15, DM7 group: n = 15). FIELD STRENGTH/SEQUENCE: 3 T MRI/BOLD, arterial spin labeling (ASL), and asymmetric spin-echo (ASE). ASSESSMENT: The renal oxygenation level (R2*), renal blood flow (RBF), and oxygen extraction fraction (OEF) were evaluated by BOLD, ASL, and ASE MRI, respectively. The regions of interest were manually drawn including cortex, outer stripes of outer medulla (OS), and inner stripes of outer medulla (IS). STATISTICAL TESTS: Analysis of variance, independent-sample t-test, and paired-sample t-test were applied for comparisons among groups, between groups, and within the same group. P < 0.05 was considered statistically significant. RESULTS: All renal regions of DM3 group at Day 3 after DM induction showed significantly higher R2* and OEF values compared to baseline. The RBF values showed no statistically significant difference (P = 0.62, 0.76, 0.09 in cortex, OS, and IS, respectively). For DM7 group at Day 7, R2*, OEF, and RBF values showed no statistically significant difference compared to baseline (P = 0.06, 0.05, 0.06 of R2*; 0.70, 0.64, 0.68 of OEF; and 0.33, 0.58, 0.48 of RBF in cortex, OS, and IS, respectively). DATA CONCLUSION: BOLD MRI could detect renal hypoxia in early stage of DKD rabbit model, which was mainly revealed by increased oxygen consumption, but not affected by renal blood flow change. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 1.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Animais , Nefropatias Diabéticas/diagnóstico por imagem , Hipóxia/diagnóstico por imagem , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , Oxigênio , Estudos Prospectivos , Coelhos
11.
Artigo em Inglês | MEDLINE | ID: mdl-35809333

RESUMO

Matrix metalloproteinase-9 (MMP-9) is a gelatinase, which is a member of the MMPs family. We know that MMP-9 is not only an important gelatinase to regulate the extracellular matrix balance, but also one of the most closely related proteases to the pathogenesis of intracranial aneurysm. The purpose of this study is to investigate the relationship between MMP-9 gene polymorphism and intracranial aneurysm. In this paper, 98 patients who were admitted to a hospital from 2018 to 2019 were selected as the experimental group and the control group according to the relevant standards of intracranial aneurysms. The MMP-9 positive and MMP-9 absorbance values between the two groups were compared, so as to determine the concentration of MMP-9 between the two groups. In addition, the gene distribution and gene frequency analysis of the C-1562T promoter region of MMP-9 were carried out. The results showed that in the control group, the gene distribution frequency of CC type was 67% that of CT type was 31% that of TT type was 2%, that of the experimental group was 52%, and that of CT type was 44%. The results showed that there was a correlation between MMP-9 gene polymorphism and intracranial aneurysm.


Assuntos
Aneurisma Intracraniano , Metaloproteinase 9 da Matriz , Gelatinases/genética , Frequência do Gene/genética , Humanos , Aneurisma Intracraniano/genética , Metaloproteinase 9 da Matriz/genética , Polimorfismo Genético
12.
Eur Heart J ; 42(42): 4373-4385, 2021 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-34534287

RESUMO

AIMS: Aortic aneurysm and dissection (AAD) are high-risk cardiovascular diseases with no effective cure. Macrophages play an important role in the development of AAD. As succinate triggers inflammatory changes in macrophages, we investigated the significance of succinate in the pathogenesis of AAD and its clinical relevance. METHODS AND RESULTS: We used untargeted metabolomics and mass spectrometry to determine plasma succinate concentrations in 40 and 1665 individuals of the discovery and validation cohorts, respectively. Three different murine AAD models were used to determine the role of succinate in AAD development. We further examined the role of oxoglutarate dehydrogenase (OGDH) and its transcription factor cyclic adenosine monophosphate-responsive element-binding protein 1 (CREB) in the context of macrophage-mediated inflammation and established p38αMKOApoe-/- mice. Succinate was the most upregulated metabolite in the discovery cohort; this was confirmed in the validation cohort. Plasma succinate concentrations were higher in patients with AAD compared with those in healthy controls, patients with acute myocardial infarction (AMI), and patients with pulmonary embolism (PE). Moreover, succinate administration aggravated angiotensin II-induced AAD and vascular inflammation in mice. In contrast, knockdown of OGDH reduced the expression of inflammatory factors in macrophages. The conditional deletion of p38α decreased CREB phosphorylation, OGDH expression, and succinate concentrations. Conditional deletion of p38α in macrophages reduced angiotensin II-induced AAD. CONCLUSION: Plasma succinate concentrations allow to distinguish patients with AAD from both healthy controls and patients with AMI or PE. Succinate concentrations are regulated by the p38α-CREB-OGDH axis in macrophages.


Assuntos
Aneurisma Aórtico , Animais , Biomarcadores , Dissecação , Humanos , Metabolômica , Camundongos , Ácido Succínico
13.
Pediatr Surg Int ; 38(3): 415-421, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34783877

RESUMO

PURPOSE: The feasibility of single-port video-assisted thoracic surgery (SPVATS) for pediatric lobectomy has not been clearly established. We compared the feasibilities of single-port (SP), multi-port (MP) VATS and open lobectomy (OL) for surgical treatment of children with lung disease. METHODS: In this study, we retrospectively analyzed and compared data for 22,19 and 30 pediatric lung disease patients who had been subjected to SP, MP and OL, respectively. These procedures were performed between March, 2012 and August, 2020 at the Second Affiliated Hospital of Wenzhou Medical University. Perioperative clinical indicators were analyzed. RESULTS: Compared to OL, SP was associated with lower intraoperative blood loss (p = 0.008), lower postoperative thoracic drainage volume (p = 0.041), shorter chest drainage duration (p = 0.002) and hospital stay (p = 0.001). Operation time (p = 0.437), volume of estimated blood loss (p = 0.979), conversion rate to thoracotomy (p = 0.861), total thoracic drainage volume (p = 0.824), duration of chest tube drainage (p = 0.543), length of hospital stay (p = 0.812) and incidences of postoperative complications were comparable in MP and SP groups. CONCLUSION: SPVATS is a safe and feasible approach for lobectomy in pediatrics, with comparable postoperative clinical outcomes to MPVATS and better outcomes relative to OL. However, studies with large sample sizes in multicenter should be performed to verify our findings.


Assuntos
Neoplasias Pulmonares , Cirurgia Torácica Vídeoassistida , Criança , Humanos , Tempo de Internação , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Estudos Retrospectivos , Toracotomia
14.
Nano Lett ; 21(5): 2033-2039, 2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33619963

RESUMO

Graphene has been the subject of much research, with structural engineering frequently used to harness its various properties. In particular, the concepts of graphene origami and kirigami have inspired the design of quasi-three-dimensional graphene structures, which possess intriguing mechanical, electronic, and optical properties. However, accurate controlling the folding process remains a big challenge. Here, we report the discovery of spontaneous folding growth of graphene on the h-BN substrate via adopting a simple chemical vapor deposition method. Folded edges are formed when two stacked graphene layers share a joint edge at a growth temperature up to 1300 °C. Using first-principles density functional theory calculations, the bilayer graphene with folded edges is demonstrated to be more stable than that with open edges. Utilizing this novel growth mode, hexagram bilayer graphene containing entirely sealed edges is eventually realized. Our findings provide a route for designing graphene devices with a new folding dimension.

15.
Clin Sci (Lond) ; 135(17): 2085-2097, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34402501

RESUMO

Although extremely important, the molecular mechanisms that govern aortic aneurysm (AA) formation and progression are still poorly understood. This deficit represents a critical roadblock toward the development of effective pharmaceutical therapies for the treatment of AA. While dysregulation of protein phosphatase 2A (PP2A) is thought to play a role in cardiovascular disease, its role in aortic aneurysm is unknown. The objective of the present study is to test the hypothesis that PP2A regulates abdominal aortic aneurysm (AAA) progression in a murine model. In an angiotensin II-induced AAA murine model, the PP2A inhibitor, LB-100, markedly accelerated AAA progression as demonstrated by increased abdominal aortic dilation and mortality. AAA progression was associated with elevated inflammation and extracellular matrix fragmentation, concomitant with increases in both metalloproteinase activity and reactive oxygen species production. Conversely, administration of a novel class of small molecule activators of PP2A (SMAPs) resulted in an antithetical effect. SMAPs effectively reduced AAA incidence along with the corresponding pathologies that were increased with LB-100 treatment. Mechanistically, modulation of PP2A activities in vivo functioned in part via alteration of the ERK1/2 and NFκB signaling pathways, known regulators of AAA progression. These studies, for the first time, demonstrate a role of PP2A in AAA etiology and demonstrate that PP2A activation may represent a novel strategy for the treatment of abdominal aortic aneurysms.


Assuntos
Aorta Abdominal/efeitos dos fármacos , Aneurisma da Aorta Abdominal/prevenção & controle , Ativadores de Enzimas/farmacologia , Proteína Fosfatase 2/metabolismo , Remodelação Vascular/efeitos dos fármacos , Regulação Alostérica , Angiotensina II , Animais , Aorta Abdominal/enzimologia , Aorta Abdominal/patologia , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/enzimologia , Aneurisma da Aorta Abdominal/patologia , Aneurisma da Aorta Torácica/enzimologia , Aneurisma da Aorta Torácica/patologia , Estudos de Casos e Controles , Dilatação Patológica , Modelos Animais de Doenças , Ativação Enzimática , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Masculino , Camundongos , Camundongos Knockout para ApoE , NF-kappa B/metabolismo , Células RAW 264.7
16.
Eur Radiol ; 31(7): 5021-5031, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33439313

RESUMO

OBJECTIVES: To develop a 3D U-Net-based deep learning model for automated segmentation of kidney and renal mass, and detection of renal mass in corticomedullary phase of computed tomography urography (CTU). METHODS: Data on 882 kidneys obtained from CTU data of 441 patients with renal mass were used to learn and evaluate the deep learning model. The CTU data of 35 patients with small renal tumors (diameter ≤ 1.5 cm) were used for additional testing. The ground truth data for the kidney, renal tumor, and cyst were manually annotated on corticomedullary phase images of CTU. The proposed segmentation model for kidney and renal mass was constructed based on a 3D U-Net. The segmentation accuracy was evaluated through the Dice similarity coefficient (DSC). The volume of the maximum 3D volume of interest of renal tumor and cyst in the predicted segmentation by the model was used as an identification indicator, while the detection performance of the model was evaluated by the area under the receiver operation characteristic curve. RESULTS: The proposed model showed a high accuracy in segmentation of kidney and renal tumor, with average DSC of 0.973 and 0.844, respectively. It performed moderately in the renal cyst segmentation, with an average DSC of 0.536 in the test set. Also, this model showed good performance in detecting renal tumor and cyst. CONCLUSIONS: The proposed automated segmentation and detection model based on 3D U-Net shows promising results for the segmentation of kidney and renal tumor, and the detection of renal tumor and cyst. KEY POINTS: • The segmentation model based on 3D U-Net showed high accuracy in segmentation of kidney and renal neoplasm, and good detection performance of renal neoplasm and cyst in corticomedullary phase of CTU. • The segmentation model based on 3D U-Net is a fully automated aided diagnostic tool that could be used to reduce the workload of radiologists and improve the accuracy of diagnosis. • The segmentation model based on 3D U-Net would be helpful to provide quantitative information for diagnosis, treatment, surgical planning, etc.


Assuntos
Processamento de Imagem Assistida por Computador , Tomografia Computadorizada por Raios X , Humanos , Rim/diagnóstico por imagem , Redes Neurais de Computação , Urografia
17.
Mar Drugs ; 19(4)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33806251

RESUMO

The von Willebrand factor type D (VWD) domain in vitellogenin has recently been found to bind tetrodotoxin. The way in which this protein domain associates with tetrodotoxin and participates in transporting tetrodotoxin in vivo remains unclear. A cDNA fragment of the vitellogenin gene containing the VWD domain from pufferfish (Takifugu flavidus) (TfVWD) was cloned. Using in silico structural and docking analyses of the predicted protein, we determined that key amino acids (namely, Val115, ASP116, Val117, and Lys122) in TfVWD mediate its binding to tetrodotoxin, which was supported by in vitro surface plasmon resonance analysis. Moreover, incubating recombinant rTfVWD together with tetrodotoxin attenuated its toxicity in vivo, further supporting protein-toxin binding and indicating associated toxicity-neutralizing effects. Finally, the expression profiling of TfVWD across different tissues and developmental stages indicated that its distribution patterns mirrored those of tetrodotoxin, suggesting that TfVWD may be involved in tetrodotoxin transport in pufferfish. For the first time, this study reveals the amino acids that mediate the binding of TfVWD to tetrodotoxin and provides a basis for further exploration of the molecular mechanisms underlying the enrichment and transfer of tetrodotoxin in pufferfish.


Assuntos
Proteínas de Peixes/metabolismo , Takifugu/metabolismo , Tetrodotoxina/metabolismo , Vitelogeninas/metabolismo , Fator de von Willebrand/metabolismo , Animais , Proteínas de Peixes/genética , Simulação de Acoplamento Molecular , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Vitelogeninas/genética , Fator de von Willebrand/genética
18.
Urol Int ; 105(3-4): 206-214, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33221793

RESUMO

INTRODUCTION: Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare disease that may coexist with prostate stromal sarcoma (PSS). We aimed to analyze the histological and clinical features of STUMP. METHODS: Twenty-three patients diagnosed with STUMP from 2008 to 2019 were included. Clinicopathological and follow-up information was collected. In the subgroup analysis, we divided the patients into a pure STUMP group (N = 18) and a mixed STUMP (STUMP coexisting with PSS) group (N = 5). Student's t test was used to compare the 2 groups. RESULTS: Patients had a mean age of 55.5 ± 19.4 years and an average follow-up time of 42.3 months. The mean prostate volume was 109.2 ± 73.5 cm3, and the mean prostate-specific antigen was 8.03 ± 10.5 ng/mL. In the subgroup analysis, 16.7% (2/12) of pure STUMP patients had disease progression, while 100% (3/3) of mixed STUMP patients suffered from recurrence. Compared with the pure STUMP group, the mixed STUMP group was younger (37.2 vs. 60.6 years, p = 0.013) and had lower expression of estrogen receptor and progesterone receptor (p = 0.004 and p < 0.001, respectively). CONCLUSION: STUMP is a rare disease with a relatively good prognosis. However, there is still a possibility of disease progression or coexistence with stromal sarcoma. Timely diagnosis and regular monitoring may be helpful in improving treatment outcomes.


Assuntos
Neoplasias da Próstata/patologia , Sarcoma/patologia , Adulto , Idoso , China , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
19.
J Appl Clin Med Phys ; 22(9): 332-338, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34347931

RESUMO

OBJECTIVE: To compare conventional method and compressed-sensing (CS) accelerated 3D balanced fast field echo imaging (bFFE) of inner ear. METHODS: Twenty patients with suspected inner ear disease underwent CS accelerated 3D-bFFE (CS-bFFE) and conventional 3D-bFFE (Con-bFFE) by a 3T MRI. The overall image quality, motion artifacts, and image quality of specific structures of inner ear were assessed on ordinal scales by three radiologists who were blinded to the scan protocols. Kendall W test was used to evaluate interobserver agreement and Wilcoxon test was performed to compare the image quality and motion artifacts between CS-bFFE and Con-bFFE. RESULTS: The acquisition duration of CS-bFFE (1 min 53 s) was 49% faster than Con-bFFE. Three radiologists had good inter-observer agreement of image quality (Kendall W value of 0.829 for CS-bFFE and 0.815 for Con-bFFE) and motion artifacts evaluation (Kendall W value of 0861 for CS-bFFE and 0.707 for Con-bFFE). The better overall image quality of CS-bFFE was assessed (4.93 ± 0.23 for CS-bFFE, 4.53 ± 0.70 for Con-bFFE, Z = -2.254, p = 0.024). The image quality score of facial and cochlear nerve gained higher in CS-bFFE (4.93 ± 0.23 for CS-bFFE, 4.58 ± 0.64 for Con-bFFE, Z = -2.094, p = 0.036). No significant difference of motion artifacts (p = 0.050) between CS-bFFE and Con-bFFE. CONCLUSIONS: The CS-bFFE improves image quality and reduces acquisition time significantly, and it is a feasible MRI protocol for inner ear imaging.


Assuntos
Orelha Interna , Imageamento por Ressonância Magnética , Artefatos , Orelha Interna/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Pressão
20.
Nano Lett ; 20(3): 2191-2196, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32059111

RESUMO

The typical polymer electrolyte matrix has been limited to the chains consisting of -C-C- or -C-O-C- or -Si-O- backbone with different solvating groups for decades. In this work, the polymeric sulfur consisting of -(S-S)n- backbone with a high sulfur content (up to 90 wt % S) was reported for the first time. The flexible -(S-S)n- chains with high S atom density create an intense "solvating" environment for Li+ conduction, achieving an excellent Li+ conductivity of 1.69 × 10-3 S cm-1 at 80 °C. Benefiting from its unique thermoplasticity, a hot-rolling process was also developed for fabricating the poly-S membrane. The symmetric solid-state Li cell using the membrane showed a high cycling stability over 300 h. The work offers a novel platform for chemists to design new polymer electrolytes that are quite different with conventional carbon-based polymer electrolytes.

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