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1.
Neurosci Bull ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38869703

RESUMO

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.

2.
Transl Neurodegener ; 13(1): 3, 2024 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191451

RESUMO

BACKGROUND: Microglia-mediated neuroinflammation in Alzheimer's disease (AD) is not only a response to pathophysiological events, but also plays a causative role in neurodegeneration. Cytoplasmic cysteinyl-tRNA synthetase (CARS) is considered to be a stimulant for immune responses to diseases; however, it remains unknown whether CARS is involved in the pathogenesis of AD. METHODS: Postmortem human temporal cortical tissues at different Braak stages and AD patient-derived serum samples were used to investigate the changes of CARS levels in AD by immunocytochemical staining, real-time PCR, western blotting and ELISA. After that, C57BL/6J and APP/PS1 transgenic mice and BV-2 cell line were used to explore the role of CARS protein in memory and neuroinflammation, as well as the underlying mechanisms. Finally, the associations of morphological features among CARS protein, microglia and dense-core plaques were examined by immunocytochemical staining. RESULTS: A positive correlation was found between aging and the intensity of CARS immunoreactivity in the temporal cortex. Both protein and mRNA levels of CARS were increased in the temporal cortex of AD patients. Immunocytochemical staining revealed increased CARS immunoreactivity in neurons of the temporal cortex in AD patients. Moreover, overexpression of CARS in hippocampal neurons induced and aggravated cognitive dysfunction in C57BL/6J and APP/PS1 mice, respectively, accompanied by activation of microglia and the TLR2/MyD88 signaling pathway as well as upregulation of proinflammatory cytokines. In vitro experiments showed that CARS treatment facilitated the production of proinflammatory cytokines and the activation of the TLR2/MyD88 signaling pathway of BV-2 cells. The accumulation of CARS protein occurred within dense-core Aß plaques accompanied by recruitment of ameboid microglia. Significant upregulation of TLR2/MyD88 proteins was also observed in the temporal cortex of AD. CONCLUSIONS: The findings suggest that the neuronal CARS drives neuroinflammation and induces memory deficits, which might be involved in the pathogenesis of AD.


Assuntos
Doença de Alzheimer , Humanos , Animais , Camundongos , Camundongos Endogâmicos C57BL , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Fator 88 de Diferenciação Mieloide , Doenças Neuroinflamatórias , Receptor 2 Toll-Like , Proteínas Adaptadoras de Transdução de Sinal , Citocinas
3.
Methods Mol Biol ; 2689: 107-118, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37430050

RESUMO

In mammals, it is believed that the intercellular coupling mechanism between neurons in the suprachiasmatic nucleus (SCN) confers circadian robustness and distinguishes the central clock from peripheral circadian oscillators. Current in vitro culturing methods mainly work with Petri dishes to study intercellular coupling by exogenous factors and invariably cause perturbations, such as simple exchanges of media. Here, a microfluidic device is designed to quantitatively study the intercellular coupling mechanism of circadian clock at the single-cell level and to demonstrate that the vasoactive intestinal peptide (VIP)-induced coupling in clock mutant Cry1-/- mouse adult fibroblasts (MAF), which are engineered to express the VIP receptor (i.e., VPAC2), is sufficient to synchronize, and maintain, robust circadian oscillations. This method provides a proof-of-concept strategy to reconstitute the intercellular coupling system of the central clock using uncoupled, single mouse adult fibroblast (MAF) cells in vitro and to mimic SCN slice cultures ex vivo and mouse behavior in vivo phenotypically. Such a versatile microfluidic platform may greatly facilitate the studies of intercellular regulation networks and provide new insights into the coupling mechanisms of the circadian clock.


Assuntos
Relógios Circadianos , Animais , Camundongos , Microfluídica , Dispositivos Lab-On-A-Chip , Neurônios , Núcleo Supraquiasmático , Mamíferos
4.
Clin Transl Med ; 13(6): e1289, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37264743

RESUMO

BACKGROUND: HCFC1 encodes transcriptional co-regulator HCF-1, which undergoes an unusual proteolytic maturation at a centrally located proteolysis domain. HCFC1 variants were associated with X-linked cobalamin metabolism disorders and mental retardation-3. This study aimed to explore the role of HCFC1 variants in common epilepsy and the mechanism underlying phenotype heterogeneity. METHODS: Whole-exome sequencing was performed in a cohort of 313 patients with idiopathic partial (focal) epilepsy. Functional studies determined the effects of the variants on the proteolytic maturation of HCF-1, cell proliferation and MMACHC expression. The role of HCFC1 variants in partial epilepsy was validated in another cohort from multiple centers. RESULTS: We identified seven hemizygous HCFC1 variants in 11 cases and confirmed the finding in the validation cohort with additional 13 cases and six more hemizygous variants. All patients showed partial epilepsies with favorable outcome. None of them had cobalamin disorders. Functional studies demonstrated that the variants in the proteolysis domain impaired the maturation by disrupting the cleavage process with loss of inhibition of cell growth but did not affect MMACHC expression that was associated with cobalamin disorder. The degree of functional impairment was correlated with the severity of phenotype. Further analysis demonstrated that variants within the proteolysis domain were associated with common and mild partial epilepsy, whereas those in the kelch domain were associated with cobalamin disorder featured by severe and even fatal epileptic encephalopathy, and those in the basic and acidic domains were associated with mainly intellectual disability. CONCLUSION: HCFC1 is potentially a candidate gene for common partial epilepsy with distinct underlying mechanism of proteolysis dysfunction. The HCF-1 domains played distinct functional roles and were associated with different clinical phenotypes, suggesting a sub-molecular effect. The distinct difference between cobalamin disorders and idiopathic partial epilepsy in phenotype and pathogenic mechanism, implied a clinical significance in early diagnosis and management.


Assuntos
Epilepsias Parciais , Epilepsia , Humanos , Proteólise , Epilepsia/genética , Vitamina B 12/genética , Vitamina B 12/metabolismo , Regulação da Expressão Gênica , Epilepsias Parciais/genética , Oxirredutases/genética , Oxirredutases/metabolismo
5.
ACS Omega ; 7(7): 5844-5852, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35224345

RESUMO

Heterostructuring, as a promising route to optimize the physical properties of 2D materials, has attracted great attention from the academic community. In this paper, we investigated the room-temperature in-plane and cross-plane phonon thermal transport in silicene/graphene van der Waals (vdW) heterostructures using molecular dynamics simulations. Our simulation results demonstrated that heat current along the graphene layer is remarkably larger than that along the silicene layer, which suggests that graphene dominates the thermal transport in silicene/graphene heterostructures. The in-plane phonon thermal conductivity of the silicene/graphene heterostructures could be a compromise between monolayer graphene and monolayer silicene. Heterostructuring can remarkably reduce the in-plane thermal conductivity of the graphene layer but increase the in-plane thermal conductivity of the silicene layer in heterobilayers compared with the freestanding monolayer counterparts because of their different structures. We also simulated the interlayer interaction strength effect on the in-plane phonon thermal conductivity and cross-plane interfacial thermal resistance of silicene/graphene heterostructures. Total in-plane phonon thermal conductivity and interfacial thermal resistance both decrease with the increase in the interlayer interaction strength in the silicene/graphene heterobilayers. In addition, the calculated interfacial thermal resistance shows the effect of the thermal transport direction across the interface. This study provides a useful reference for the thermal management regulation of 2D vdW heterostructures.

6.
Opt Express ; 29(16): 24804-24815, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34614828

RESUMO

In this work, we propose broadband and switchable terahertz (THz) polarization converters based on either graphene patch metasurface (GPMS) or its complementary structure (graphene hole metasurface, GHMS). The patch and hole are simply cross-shaped, composed of two orthogonal arms, along which plasmonic resonances mediated by Fabry-Perot cavity play a key role in polarization conversion (PC). An incidence of linear polarization will be converted to its cross-polarization (LTL) or circular polarization (LTC), as the reflected wave in the direction of two arms owning the same amplitude and π phase difference (LTL), or ±π/2 phase difference (LTC). Such requirements can be met by optimizing the width and length of two arms, thickness of dielectric layer, and Fermi level EF of graphene. By using GPMS, LTL PC of polarization conversion ratio (PCR) over 90% is achieved in the frequency range of 2.92 THz to 6.26 THz, and by using GHMS, LTC PC of ellipticity χ ≤ -0.9 at the frequencies from 4.45 THz to 6.47 THz. By varying the Fermi level, the operating frequency can be actively tuned, and the functionality can be switched without structural modulation; for instance, GPMS supports LTL PC as EF = 0.6 eV and LTC PC of χ ≥ 0.9 as EF = 1.0 eV, in the frequency range of 2.69 THz to 4.19 THz. Moreover, GHMS can be optimized to sustain LTL PC and LTC PC of |χ| ≥ 0.9, in the frequency range of 4.96 THz to 6.52 THz, which indicates that the handedness of circular polarization can be further specified. The proposed polarization converters of broad bandwidth, active tunability, and switchable functionality will essentially make a significant progress in THz technology and device applications, and can be widely utilized in THz communications, sensing and spectroscopy.

7.
Front Pharmacol ; 12: 671572, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122097

RESUMO

To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and in silico analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE (p = 0.002, p c = 0.04). HLA-B*38:02 was associated with CBZ-MPE (p = 0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE (p = 0.02 and p = 0.04, respectively). In silico analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE.

8.
Transl Psychiatry ; 11(1): 297, 2021 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-34011923

RESUMO

Genetic factors contribute to the susceptibility of anxiety disorders (ADs) and responses to associated cognitive-behavioral therapy (CBT). However, the type of brain cell affected by the related genes remains unclear. Previous studies have indicated various important brain neurons associated with psychiatric disorders, highlighting the necessity to study the cellular basis of anxiety. We assembled 37 AD-related genes and 23 CBT-related genes from recent large-scale genome-wide association studies, and then investigated their cell-type specificity in single-cell transcriptome data via an expression weighted cell type enrichment method. Additionally, to investigate the cellular differences between ADs and other psychiatric disorders, we excluded the genes associated with major depressive disorder, bipolar disorder, and neuroticism, resulting in 29 AD-specific genes. Remarkably, results indicate that serotonergic neurons are significantly associated with both AD-related and CBT-related genes, despite the two gene sets showing no overlap. These observations provide evidence that serotonergic neurons are involved in the etiology and therapygenetics of ADs. Moreover, results also showed that serotonergic neurons are associated with AD-specific genes, providing a supplementary finding that is in opposition to previous studies that found no evidence for the association between serotonergic neurons and psychiatric disorders via the same strategy. In summary, the current study found that serotonergic neurons are involved in the etiology and therapygenetics of ADs, providing insights into their genetic and cellular basis. Further, this cellular difference study may deepen our understanding of ADs and other psychiatric disorders.


Assuntos
Transtorno Depressivo Maior , Neurônios Serotoninérgicos , Transtornos de Ansiedade/genética , Transtornos de Ansiedade/terapia , Biologia Computacional , Estudo de Associação Genômica Ampla , Humanos
9.
Brain ; 144(10): 3050-3060, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-33876820

RESUMO

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), which is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of the UNC13B mutation in human disease is not known. In this study, we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. UNC13B variants were identified in 12 individuals affected by partial epilepsy and/or febrile seizures from eight unrelated families. The eight probands all had focal seizures and focal discharges in EEG recordings, including two patients who experienced frequent daily seizures and one who showed abnormalities in the hippocampus by brain MRI; however, all of the patients showed a favourable outcome without intellectual or developmental abnormalities. The identified UNC13B variants included one nonsense variant, two variants at or around a splice site, one compound heterozygous missense variant and four missense variants that cosegregated in the families. The frequency of UNC13B variants identified in the present study was significantly higher than that in a control cohort of Han Chinese and controls of the East Asian and all populations in the Genome Aggregation Database (gnomAD). Computational modelling, including hydrogen bond and docking analyses, suggested that the variants lead to functional impairment. In Drosophila, seizure rate and duration were increased by Unc13b knockdown compared to wild-type flies, but these effects were less pronounced than in sodium voltage-gated channel alpha subunit 1 (Scn1a) knockdown Drosophila. Electrophysiological recordings showed that excitatory neurons in Unc13b-deficient flies exhibited increased excitability. These results indicate that UNC13B is potentially associated with epilepsy. The frequent daily seizures and hippocampal abnormalities but ultimately favourable outcome under anti-epileptic therapy in our patients indicate that partial epilepsy caused by UNC13B variant is a clinically manageable condition.


Assuntos
Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/genética , Variação Genética/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Criança , Pré-Escolar , Drosophila , Epilepsias Parciais/fisiopatologia , Feminino , Humanos , Masculino , Resultado do Tratamento
10.
Nucl Med Commun ; 42(3): 244-252, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33306622

RESUMO

OBJECTIVE: Hip pain arising from implant instability is generally caused by repetitive stress injury, which subsequently leads to induction or exacerbation of abnormal metabolism of bone around the implant. single photon emission tomography/computed tomography (SPECT-CT) has advantages in localizing areas of increased tracer uptake that reflects such abnormal bone metabolism. Therefore, we investigated whether the application of SPECT/CT with stress analysis can be an effective practice in evaluating the instability of stem in noncemented hip arthroplasty or not. METHOD: In total 16 patients were collected for unexplained painful hip arthroplasties. When physical examination and blood tests were unremarkable, radiographs were inconclusive and bone scan indicated increased scintigraphic uptake at the proximal part and at the tip of the stem; SPECT/CT was performed. Stem stability was assessed by measuring whether there was consistency between the increased scintigraphic uptake and the direction of the stress around the implant along with the location of the prosthesis. RESULT: Among the 16 symptomatic hips, 9 hips showed the stability of the stem, 3 hips showed the stem instability and 4 hips showed the acetabular loosening with the stem stability. With the application of SPECT/CT with stress analysis, 15 out of 16 (93.7%) cases were found to have the change in the diagnoses, and managements were implemented in 11 out of 16 (68.7%) cases. When comparing before and after SPECT/CT, there was no significant association in clinical diagnosis and management (Pearson chi- square test = 4.61 and 1.33, P = 0.33 and 0.25). CONCLUSION: SPECT/CT combined with stress analysis can be a useful tool in early diagnosis of stem instability and can assist surgeons in subsequent management and decision implementation when other radiographic imagings are inconclusive.


Assuntos
Artroplastia de Quadril , Falha de Prótese , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único , Estresse Mecânico , Adulto , Idoso , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
11.
J Nanosci Nanotechnol ; 21(1): 788-794, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33213680

RESUMO

A central issue in the study of fault evolution is to identify shear weakening and its mechanism; currently, studies of fault weakening in narrow slip deformation zones, including those of various slipping planes such as schistosity, foliation, cleavage, joints and faults in rocks, are ongoing. To verify the nanoweakening in shear slipping, we carried out experiments: triaxial compression experiments on sandstones and uniaxial compression experiments on granites. Furthermore, on the basis of scanning electron microscopy (SEM) observations and experimental data analyses, we suggested three kinds of nanoweakening in terms of the corresponding strain stages: (1) The slip nanoweakening caused by the strain hardening deformation stage of the shear slip, which creates nanograins with dense coatings that may be due to the nanocoating on the shear planes, can result in rolling friction rather than with sliding friction, and the former is a principal mechanism of sliding nanoweakening. (2) The rheological nanoweakening caused by the strain softening deformation stage; in view of developing weakened deformation due to grain boundary migration (GBM), the flow of synkinematic minerals and melt coating phenomena lead to rheological nanoweakening. (3) The dynamic nanoweakening caused by thermal pressurization and fluid pressurization during the strain softening stage and strain degenerating stage. Thus, when these aspects are considered in defining the relationship between the nanoweakening at the slipping planes and the strain stages, the representative mechanism and its behavior rules can be obtained.

12.
Front Neurosci ; 14: 821, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848577

RESUMO

To explore the phenotype spectrum of DEPDC5 variants and the possible mechanisms underlying phenotypical variation, we performed targeted next-generation sequencing in 305 patients with focal epilepsies and 91 patients with generalized epilepsies. Protein modeling was performed to predict the effects of missense mutations. All previously reported epilepsy-related DEPDC5 variants were reviewed. The genotype-phenotype correlations with molecular sub-regional implications were analyzed. We identified a homozygous DEPDC5 mutation (p.Pro1031His) in a case with focal cortical dysplasia and eight heterozygous mutations in 11 families with mild focal epilepsies, including 13 patients in eight families with focal epilepsy with febrile seizures plus/febrile seizures (FEFS + /FS). The mutations included one termination codon mutation (p.Ser1601_Ter1604del_ext133), three truncating mutations (p.Val151Serfs∗27, p.Arg239∗, and p.Arg838∗), and four missense mutations (p.Tyr7Cys, p.Tyr836Cys, p.Pro1031His, and p.Gly1545Ser) that were predicted to affect hydrogen bonds and protein stability. Analysis on epilepsy-related DEPDC5 variants revealed that malformations of cortical development (MCDs) had a tendency of higher frequency of null mutations than those without MCD. MCD-associated heterozygous missense mutations were clustered in structural axis for binding arrangement (SABA) domain and close to the binding sites to NPRL2/NPRL3 complex, whereas those associated with FEFS + /FS were a distance away from the binding sites. Evidence from four aspects and one possible evidence from sub-regional implication suggested MCD and FEFS + /FS as phenotypes of DEPDC5 variants. This study suggested that the phenotypes of DEPDC5 variants vary from mild FEFS + /FS to severe MCD. Heterozygous DEPDC5 mutations are generally less pathogenic and commonly associated with mild phenotypes. Bi-allelic mutations and second hit of somatic mutations, together with the genotype-phenotype correlation and sub-regional implication of DEPDC5 variants, explain severe phenotypes.

13.
Lab Chip ; 20(7): 1204-1211, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32149320

RESUMO

In mammals, it is believed that the intercellular coupling mechanism between neurons in the suprachiasmatic nucleus (SCN) confers robustness and distinguishes the central clock from peripheral circadian oscillators. Current in vitro culturing methods used in Petri dishes to study intercellular coupling by exogenous factors invariably cause perturbations, such as simple media changes. Here, we design a microfluidic device to quantitatively study the intercellular coupling mechanism of circadian clock at the single cell level, and demonstrate that vasoactive intestinal peptide (VIP) induced coupling in clock mutant Cry1-/- mouse adult fibroblasts engineered to express the VIP receptor, VPAC2, is sufficient to synchronize and maintain robust circadian oscillations. Our study provides a proof-of-concept platform to reconstitute the intercellular coupling system of the central clock using uncoupled, single fibroblast cells in vitro, to mimic SCN slice cultures ex vivo and mouse behavior in vivo phenotypically. Such a versatile microfluidic platform may greatly facilitate the studies of intercellular regulation networks, and provide new insights into the coupling mechanisms of the circadian clock.


Assuntos
Relógios Circadianos , Animais , Ritmo Circadiano , Mamíferos , Camundongos , Microfluídica , Núcleo Supraquiasmático
14.
Arch Biochem Biophys ; 679: 108187, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31706880

RESUMO

Macrophages play a pivotal role in the defense response against harmful pathogens and stimuli by releasing various pro-inflammatory mediators. However, overproduction of pro-inflammatory mediators will do harm to the organism and cause inflammation-associated diseases. Omentin-1, which is a newly discovered adipokine, is specifically expressed in omental adipose tissue. Recent studies have found correlations between omentin-1 and insulin resistance, diabetes, obesity, inflammation, atherosclerosis, bone metabolism, and tumor cell proliferation. Some studies have shown that the association between omentin-1, insulin resistance, and inflammation might suggest that omentin-1 plays an important role in chronic inflammatory diseases. In this study, we found that omentin-1 inhibited LPS-induced expression of inflammatory mediators and pro-inflammatory cytokines in macrophages. Furthermore, omentin-1 inhibited activation of the NF-κB pathway by suppressing both nuclear p65 accumulation and transfected NFκB promoter activity. Importantly, omentin-1 increased nuclear translocation of Nrf2. Our findings demonstrate that omentin-1 exerts anti-inflammatory effects on LPS-induced macrophages and has potential implication in the treatment of inflammation-associated diseases.


Assuntos
Lectinas/farmacologia , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Células U937
15.
Appl Opt ; 58(14): 3712-3717, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31158186

RESUMO

We investigate magnetoplasmon resonances and their coupling effects in gyroelectric cylinders. In individual cylinders, the dipole plasmon can be excited by plane wave illumination, and the dipole plasmon splits into lower energy and higher energy rotational magnetoplasmons in the presence of an external magnetic field. With respect to the external magnetic field, the two magnetoplasmons carry either right-handed chirality or left-handed chirality. In addition, originally dark plasmons can also be excited as the magnetic field increases. They are lower-order bulk plasmons (such as the radial breathing mode). In cylindrical dimers, the optically bright modes are combinations of magnetoplasmons with the same chirality. If the magnetic fields are antiparallel, the absorption spectra will be different for light incident from two opposite directions. This asymmetry can be well understood by carrying out eigenstate analysis, where the eigenstate does not possess mirror symmetry respecting the dimer axis. The dark modes engineering and asymmetrical optical behavior could have potential for terahertz device applications.

16.
Sci Rep ; 9(1): 5201, 2019 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-30914749

RESUMO

Cephalopods have remarkable ability to change their body color across a wide range of wavelengths, yet the structural basis remains largely unknown. Reflectin, a protein family assumed to be responsible for structural color in cephalopods, has unique features of higher-order assembly that are tightly regulated by aromatic molecules. Here, we reconstructed the dynamic and reversible color change using purified reflectin protein and demonstrated how the conformational change and the status of assembly led to the change in optical properties. In addition, optical spectral and structural analyses indicated that the "cephalopod-blue" primarily resulted from wavelength-dependent light scattering rather than reflection. Our results suggest a possible role of reflectin in color dynamics. The in vitro reconstruction system we present here may serve as an initial step for designing bio-inspired optical materials based on reflectin protein.


Assuntos
Pigmentação , Proteínas/metabolismo , Animais , Cefalópodes , Cor , Simulação por Computador , Proteínas/química , Proteínas/ultraestrutura
17.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-816371

RESUMO

Standardization of ~(131)I treatment following thyroidectomy for DTC patients tends to be compulsory in clinical practice. However, many remains controversies concerning with the indications for ~(131)I treatment since it takes definitive effects mostly in parts of DTC patients with unresectable lesions or metastases. Standardization of ~(131)I treatment also requires proper management of radiation protection for in-patients taking high dose ~(131)I,objective and complete evaluation of treatment outcomes as well as side effects related with ~(131)I therapy, and above all, the establishment of long-term follow-up database.

18.
J Med Genet ; 55(5): 298-306, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29453195

RESUMO

Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) - a protein that functions in the Jak/ STAT pathway- are associated with ADNSHL Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. ConclusionIFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.


Assuntos
Predisposição Genética para Doença , Perda Auditiva Neurossensorial/genética , Receptores de Citocinas/genética , Receptores de Interferon/genética , Animais , Técnicas de Silenciamento de Genes , Ligação Genética , Perda Auditiva Neurossensorial/fisiopatologia , Heterozigoto , Humanos , Janus Quinase 1/genética , Camundongos , Morfolinas , Mutação de Sentido Incorreto/genética , Fator de Transcrição STAT3/genética , Transdução de Sinais , Sequenciamento do Exoma , Peixe-Zebra/genética
19.
J Mol Model ; 23(3): 79, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28210879

RESUMO

We investigate the molecular structure, vibrational and electronic absorption spectra, and electronic hyperpolarizabilities of trans and cis isomers of 4-hydroxyazobenzene (HOAB) via density functional theory. Results show that the azo dye exhibits a high third-order nonlinear optical response and good optical transparency. Both the basis set and the functional are important influences on the results obtained when calculating the absorption spectrum and NLO response. We also study the effect of the solvent on the electronic absorption spectrum to assess the ability of the functional to reproduce the experimental spectrum in combination with a suitable solvent model. Our calculations show that the SMD model of Truhlar et al. handles the electrostatic and the non-electrostatic effects of hydrogen-bonding solvents on the absorption spectrum better than the traditional polarizable continuum model does. In addition, our results indicate that the dye trans-HOAB exhibits a high second hyperpolarizability and excellent optical transparency. Also, although the second hyperpolarizability of cis-HOAB is much lower than that of trans-HOAB, it is non-negligible when calculating the optical nonlinearity of HOAB under an optical pump. We also examine the effect of frequency dispersion on second harmonic generation. This study provides the basis for further research on the spectroscopic and nonlinear optical properties of novel azo dyes and other π-conjugated compounds.

20.
Chin J Nat Med ; 15(11): 860-864, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29329613

RESUMO

Three new labdane diterpenoids, leojaponicone A (1), isoleojaponicone A (2) and methylisoleojaponicone A (3), were isolated from the herb of Leonurus japonicus. The chemical structures of these secondary metabolites were elucidated on the basis of 1D and 2D NMR, including HMQC, and HMBC spectroscopic techniques. All the new compounds were tested in vitro for their acetylcholinesterase and α-glucosidase inhibitory activity. Compounds 1-3 exhibited low inhibitory effects on α-glucosidase with respect to acarbose and exhibited high inhibitory effects on acetylcholinesterase with respect to huperzine A.


Assuntos
Acetilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Diterpenos/farmacologia , Leonurus/química , Extratos Vegetais/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Diterpenos/química , Diterpenos/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/química
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