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1.
Int J Biol Macromol ; 279(Pt 3): 135301, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233168

RESUMO

Management of diabetic wounds becomes increasingly challenging as bacterial infections intensify the inflammation. Employing polysaccharide hydrogels with inherent antibacterial qualities can significantly reduce the need for antibiotics to manage infections in diabetic wounds. The typical approach to achieving antibacterial outcomes with hydrogels relies on the penetration of bacteria into their porous architecture. Such penetration not only takes time but can also prolong inflammation, thus impeding the healing of wounds. Hence, the quick capture and eradication of bacteria are essential for optimizing the hydrogel's antibacterial performance. Herein, we introduce a multifunctional polysaccharide hydrogel dressing-designated as HAQ-created for managing bacterial infections in diabetic wounds. This dressing is based on hyaluronic acid, which is modified with methacrylic anhydride, and special functional groups are added to the modified hyaluronic acid matrix: phenylboronic acid for capturing bacteria and quaternary ammonium chitosan for bacterial destruction. As expected, the HAQ system exhibits robust antibacterial effectiveness against both methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa in vitro and in vivo. Consequently, HAQ stands as a promising hydrogel dressing with intrinsic antibacterial capabilities and offers significant potential for managing diabetic wounds infected by drug-resistant bacteria.

2.
bioRxiv ; 2024 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-39131371

RESUMO

The development of the human neocortex is a highly dynamic process and involves complex cellular trajectories controlled by cell-type-specific gene regulation1. Here, we collected paired single-nucleus chromatin accessibility and transcriptome data from 38 human neocortical samples encompassing both the prefrontal cortex and primary visual cortex. These samples span five main developmental stages, ranging from the first trimester to adolescence. In parallel, we performed spatial transcriptomic analysis on a subset of the samples to illustrate spatial organization and intercellular communication. This atlas enables us to catalog cell type-, age-, and area-specific gene regulatory networks underlying neural differentiation. Moreover, combining single-cell profiling, progenitor purification, and lineage-tracing experiments, we have untangled the complex lineage relationships among progenitor subtypes during the transition from neurogenesis to gliogenesis in the human neocortex. We identified a tripotential intermediate progenitor subtype, termed Tri-IPC, responsible for the local production of GABAergic neurons, oligodendrocyte precursor cells, and astrocytes. Remarkably, most glioblastoma cells resemble Tri-IPCs at the transcriptomic level, suggesting that cancer cells hijack developmental processes to enhance growth and heterogeneity. Furthermore, by integrating our atlas data with large-scale GWAS data, we created a disease-risk map highlighting enriched ASD risk in second-trimester intratelencephalic projection neurons. Our study sheds light on the gene regulatory landscape and cellular dynamics of the developing human neocortex.

3.
Nat Methods ; 21(7): 1298-1305, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38898094

RESUMO

Volumetric imaging of synaptic transmission in vivo requires high spatial and high temporal resolution. Shaping the wavefront of two-photon fluorescence excitation light, we developed Bessel-droplet foci for high-contrast and high-resolution volumetric imaging of synapses. Applying our method to imaging glutamate release, we demonstrated high-throughput mapping of excitatory inputs at >1,000 synapses per volume and >500 dendritic spines per neuron in vivo and unveiled previously unseen features of functional synaptic organization in the mouse primary visual cortex.


Assuntos
Sinapses , Transmissão Sináptica , Animais , Transmissão Sináptica/fisiologia , Camundongos , Sinapses/fisiologia , Ácido Glutâmico/metabolismo , Córtex Visual/fisiologia , Córtex Visual/citologia , Espinhas Dendríticas/fisiologia , Neurônios/fisiologia , Córtex Visual Primário/fisiologia , Córtex Visual Primário/diagnóstico por imagem , Camundongos Endogâmicos C57BL , Microscopia de Fluorescência por Excitação Multifotônica/métodos
4.
Bioact Mater ; 39: 562-581, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38883310

RESUMO

Oral ulcers can be managed using a variety of biomaterials that deliver drugs or cytokines. However, many patients experience minimal benefits from certain medical treatments because of poor compliance, short retention times in the oral cavity, and inadequate drug efficacy. Herein, we present a novel hydrogel patch (SCE2) composed of a biopolymer matrix (featuring ultraviolet-triggered adhesion properties) loaded with cuttlefish ink nanoparticles (possessing pro-healing functions). Applying a straightforward local method initiates the formation of a hydrogel barrier that adheres to mucosal injuries under the influence of ultraviolet light. SCE2 then demonstrates exceptional capabilities for near-infrared photothermal sterilization and neutralization of reactive oxygen species. These properties contribute to the elimination of bacteria and the management of the oxidation process, thus accelerating the healing phase's progression from inflammation to proliferation. In studies involving diabetic rats with oral ulcers, the SCE2 adhesive patch significantly quickens recovery by altering the inflamed state of the injured area, facilitating rapid re-epithelialization, and fostering angiogenesis. In conclusion, this light-sensitive hydrogel patch offers a promising path to expedited wound healing, potentially transforming treatment strategies for clinical oral ulcers.

5.
Blood Adv ; 8(13): 3388-3401, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38701351

RESUMO

ABSTRACT: Glycoprotein Ibα (GPIbα), the ligand-binding subunit of platelet GPIb-IX complex, interacts with von Willebrand factor (VWF) exposed at the injured vessel wall, initiating platelet adhesion, activation, hemostasis, and thrombus formation. The cytoplasmic tail of GPIbα interacts with 14-3-3ζ, regulating the VWF-GPIbα-elicited signal transduction and VWF binding function of GPIbα. However, we unexpectedly found that the GPIbα-14-3-3ζ association, beyond VWF-dependent function, is essential for general platelet activation. We found that the myristoylated peptide of GPIbα C-terminus MPαC, a potential GPIbα inhibitor, by itself induced platelet aggregation, integrin αIIbß3 activation, granule secretion, and phosphatidylserine (PS) exposure. Conversely, the deletion of the cytoplasmic tail of GPIbα in mouse platelets (10aa-/-) decreased platelet aggregation, integrin αIIbß3 activation, granule secretion, and PS exposure induced by various physiological agonists. Phosphoproteome-based kinase activity profiling revealed significantly upregulated protein kinase C (PKC) activity in MPαC-treated platelets. MPαC-induced platelet activation was abolished by the pan-PKC inhibitor and PKCα deletion. Decreased PKC activity was observed in both resting and agonist-stimulated 10aa-/- platelets. GPIbα regulates PKCα activity by sequestering 14-3-3ζ from PKCα. In vivo, the deletion of the GPIbα cytoplasmic tail impaired mouse hemostasis and thrombus formation and protected against platelet-dependent pulmonary thromboembolism. Therefore, our findings demonstrate an essential role for the GPIbα cytoplasmic tail in regulating platelet general activation and thrombus formation beyond the VWF-GPIbα axis.


Assuntos
Plaquetas , Ativação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Animais , Camundongos , Humanos , Plaquetas/metabolismo , Proteínas 14-3-3/metabolismo , Fator de von Willebrand/metabolismo , Trombose/metabolismo , Transdução de Sinais , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Camundongos Knockout , Agregação Plaquetária
6.
Nat Commun ; 15(1): 229, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172111

RESUMO

Large-scale functional networks have been characterized in both rodent and human brains, typically by analyzing fMRI-BOLD signals. However, the relationship between fMRI-BOLD and underlying neural activity is complex and incompletely understood, which poses challenges to interpreting network organization obtained using this technique. Additionally, most work has assumed a disjoint functional network organization (i.e., brain regions belong to one and only one network). Here, we employ wide-field Ca2+ imaging simultaneously with fMRI-BOLD in mice expressing GCaMP6f in excitatory neurons. We determine cortical networks discovered by each modality using a mixed-membership algorithm to test the hypothesis that functional networks exhibit overlapping organization. We find that there is considerable network overlap (both modalities) in addition to disjoint organization. Our results show that multiple BOLD networks are detected via Ca2+ signals, and networks determined by low-frequency Ca2+ signals are only modestly more similar to BOLD networks. In addition, the principal gradient of functional connectivity is nearly identical for BOLD and Ca2+ signals. Despite similarities, important differences are also detected across modalities, such as in measures of functional connectivity strength and diversity. In conclusion, Ca2+ imaging uncovers overlapping functional cortical organization in the mouse that reflects several, but not all, properties observed with fMRI-BOLD signals.


Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Camundongos , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Algoritmos , Neurônios
7.
Adv Mater ; 35(48): e2306632, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37803944

RESUMO

Current therapeutic protocols for diabetic foot ulcers (DFUs), a severe and rapidly growing chronic complication in diabetic patients, remain nonspecific. Hyperglycemia-caused inflammation and excessive reactive oxygen species (ROS) are common obstacles encountered in DFU wound healing, often leading to impaired recovery. These two effects reinforce each other, forming an endless loop. However, adequate and inclusive methods are still lacking to target these two aspects and break the vicious cycle. This study proposes a novel approach for treating DFU wounds, utilizing an immunomodulatory hydrogel to achieve self-cascade glucose depletion and ROS scavenging to regulate the diabetic microenvironment. Specifically, AuPt@melanin-incorporated (GHM3) hydrogel dressing is developed to facilitate efficient hyperthermia-enhanced local glucose depletion and ROS scavenging. Mechanistically, in vitro/vivo experiments and RNA sequencing analysis demonstrate that GHM3 disrupts the ROS-inflammation cascade cycle and downregulates the ratio of M1/M2 macrophages, consequently improving the therapeutic outcomes for dorsal skin and DFU wounds in diabetic rats. In conclusion, this proposed approach offers a facile, safe, and highly efficient treatment modality for DFUs.


Assuntos
Diabetes Mellitus Experimental , Pé Diabético , Hipertermia Induzida , Humanos , Ratos , Animais , Hidrogéis/uso terapêutico , Pé Diabético/terapia , Espécies Reativas de Oxigênio/uso terapêutico , Diabetes Mellitus Experimental/terapia , Glucose , Inflamação/terapia
8.
Res Sq ; 2023 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-37162818

RESUMO

Large-scale functional networks have been characterized in both rodent and human brains, typically by analyzing fMRI-BOLD signals. However, the relationship between fMRI-BOLD and underlying neural activity is complex and incompletely understood, which poses challenges to interpreting network organization obtained using this technique. Additionally, most work has assumed a disjoint functional network organization (i.e., brain regions belong to one and only one network). Here, we employed wide-field Ca2+ imaging simultaneously with fMRI-BOLD in mice expressing GCaMP6f in excitatory neurons. We determined cortical networks discovered by each modality using a mixed-membership algorithm to test the hypothesis that functional networks are overlapping rather than disjoint. Our results show that multiple BOLD networks are detected via Ca2+ signals; there is considerable network overlap (both modalities); networks determined by low-frequency Ca2+ signals are only modestly more similar to BOLD networks; and, despite similarities, important differences are detected across modalities (e.g., brain region "network diversity"). In conclusion, Ca2+ imaging uncovered overlapping functional cortical organization in the mouse that reflected several, but not all, properties observed with fMRI-BOLD signals.

9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(2): 483-488, 2023 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-37096523

RESUMO

OBJECTIVE: To explore the effects of Ena/VASP gene family on the expression of glycoprotein (GP) Ib-IX complex in human megakaryoblastic leukemia Dami cells. METHODS: SiRNAs targeting Ena/VASP gene family were designed and synthesized to interfere Enah, EVL and VASP gene expression. When the siRNAs were transfected into Dami cells by using LipofectamineTM 2000 for 48 h, the expression of GPIb-IX complex was detected by quantitative real-time PCR, Western blot and flow cytometry. RESULTS: We successfully established siVASP , siEVL and si Enah Dami cell lines. And it was found that the expression of GPIb-IX complex had no evident reduction in siEVL or siVASP Dami cells at both mRNA and protein level, while the total protein and membrane protein of GPIb-IX complex were obviously reduced when Enah was knocked down. CONCLUSION: Enah could affect the expression of GPIb-IX complex in human megakaryoblastic leukemia Dami cells, but the underlying mechanism still needs to be further explored.


Assuntos
Leucemia , Complexo Glicoproteico GPIb-IX de Plaquetas , Humanos , Linhagem Celular , Complexo Glicoproteico GPIb-IX de Plaquetas/genética , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Leucemia/metabolismo , Plaquetas/metabolismo
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(3): 919-923, 2022 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-35680827

RESUMO

OBJECTIVE: To explore the main factors of platelet spreading and provide the foundation for related research. METHODS: Platelets (2×107/ml) were draw from C57BL/6J mouse and kept at 22 ℃ for 1-2 hours. Platelets (2×107/ml) were were allowed to adhere and spread on the fibrinogen-coated slides, after staining F-actin in platelets, the platelets were observed with the confocal microscopy. The effects of different concentrations of fibrinogen (10 µg/ml, 30 µg/ml, 100 µg/ml) and kinds of agonists ï¼»thrombin(0.01,0.05,0.1 U/ml), ADP(5,10,20 µmol/L), U46619(0.125,0.25,0.5 µmol/L)] on platelets were analyzed. The platelet spreading was successful if the spreading rate was higher after treated with agonists. RESULTS: Compared to the group which coated with 10 µg/ml and 100 µg/ml fibrinogen, the platelet density is optimal when coated with 30 µg/ml fibrinogen. In addition, under the stimulation of thrombin, ADP and U46619, the spreading rate of platelets showed a certain concentration-dependent increasing. CONCLUSION: The platelet spreading is easily influenced by various factors, the platelet spreading can be induced successfully at 0.1 U/ml thrombin, 20 µmol/L ADP and 0.5 µmol/L U46619 on the slide coated with 30 µg/ml fibrinogen.


Assuntos
Plaquetas , Trombina , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Difosfato de Adenosina , Animais , Plaquetas/fisiologia , Fibrinogênio , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Adesividade Plaquetária/fisiologia , Trombina/farmacologia
11.
Cell Death Dis ; 12(11): 955, 2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34657146

RESUMO

Platelets are generated from the cytoplasm of megakaryocytes (MKs) via actin cytoskeleton reorganization. Zyxin is a focal adhesion protein and wildly expressed in eukaryotes to regulate actin remodeling. Zyxin is upregulated during megakaryocytic differentiation; however, the role of zyxin in thrombopoiesis is unknown. Here we show that zyxin ablation results in profound macrothrombocytopenia. Platelet lifespan and thrombopoietin level were comparable between wild-type and zyxin-deficient mice, but MK maturation, demarcation membrane system formation, and proplatelet generation were obviously impaired in the absence of zyxin. Differential proteomic analysis of proteins associated with macrothrombocytopenia revealed that glycoprotein (GP) Ib-IX was significantly reduced in zyxin-deficient platelets. Moreover, GPIb-IX surface level was decreased in zyxin-deficient MKs. Knockdown of zyxin in a human megakaryocytic cell line resulted in GPIbα degradation by lysosomes leading to the reduction of GPIb-IX surface level. We further found that zyxin was colocalized with vasodilator-stimulated phosphoprotein (VASP), and loss of zyxin caused diffuse distribution of VASP and actin cytoskeleton disorganization in both platelets and MKs. Reconstitution of zyxin with VASP binding site in zyxin-deficient hematopoietic progenitor cell-derived MKs restored GPIb-IX surface expression and proplatelet generation. Taken together, our findings identify zyxin as a regulator of platelet biogenesis and GPIb-IX surface expression through VASP-mediated cytoskeleton reorganization, suggesting possible pathogenesis of macrothrombocytopenia.


Assuntos
Plaquetas/metabolismo , Membrana Celular/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Zixina/metabolismo , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/ultraestrutura , Animais , Plaquetas/ultraestrutura , Medula Óssea/ultraestrutura , Moléculas de Adesão Celular/metabolismo , Diferenciação Celular , Linhagem Celular , Feminino , Fibrinogênio/farmacologia , Humanos , Lisossomos/metabolismo , Masculino , Megacariócitos/metabolismo , Megacariócitos/ultraestrutura , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Proteínas Mutantes/metabolismo , Fosfoproteínas/metabolismo , Contagem de Plaquetas , Ligação Proteica/efeitos dos fármacos , Proteólise , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Trombina/farmacologia , Trombocitopenia , Zixina/deficiência
12.
Science ; 373(6553)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437090

RESUMO

The ability to perceive and respond to environmental stimuli emerges in the absence of sensory experience. Spontaneous retinal activity prior to eye opening guides the refinement of retinotopy and eye-specific segregation in mammals, but its role in the development of higher-order visual response properties remains unclear. Here, we describe a transient window in neonatal mouse development during which the spatial propagation of spontaneous retinal waves resembles the optic flow pattern generated by forward self-motion. We show that wave directionality requires the same circuit components that form the adult direction-selective retinal circuit and that chronic disruption of wave directionality alters the development of direction-selective responses of superior colliculus neurons. These data demonstrate how the developing visual system patterns spontaneous activity to simulate ethologically relevant features of the external world and thereby instruct self-organization.


Assuntos
Fluxo Óptico , Retina/fisiologia , Células Ganglionares da Retina/fisiologia , Visão Ocular/fisiologia , Vias Visuais , Potenciais de Ação , Células Amácrinas/fisiologia , Animais , Animais Recém-Nascidos , Axônios/fisiologia , Proteínas do Citoesqueleto/genética , Camundongos , Movimento (Física) , Mutação , Piridazinas/farmacologia , Receptores de GABA-A/metabolismo , Retina/crescimento & desenvolvimento , Análise Espaço-Temporal , Colículos Superiores/fisiologia
14.
J Clin Lab Anal ; 35(6): e23791, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33955587

RESUMO

BACKGROUND: Tumor-educated platelets (TEPs) may enable blood-based cancer diagnosis. This study aimed to identify diagnostic TEPs genes involved in carcinogenesis. MATERIALS AND METHODS: The TEPs differentially expressed genes (DEGs) between healthy samples and early/advanced cancer samples were obtained using bioinformatics. Gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were used to identify the pathways and functional annotation of TEPs DEGs. Protein-protein interaction of these TEPs DEGs was analyzed based on the STRING database and visualized by Cytoscape software. The correlation analysis and diagnostic analysis were performed to evaluate the diagnostic value of TEPs mRNAs expression for early/advanced cancers. Quantitative real-time PCR (qRT-PCR) was applied to validate the role of DEGs in cancers. RESULTS: TEPs mRNAs were mostly involved in protein binding, extracellular matrix, and cellular protein metabolic process. RSL24D1 was negatively correlated to early-stage cancers compared to healthy controls and may be potentially used for early cancer diagnosis. In addition, HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to advanced cancer stages. Moreover, ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic cancers compared to healthy controls. Among the 12 selected DEGs, the expression of 7 DEGs, including RSL24D1, IFI27, CRYM, HBD, IFITM3, FCGR2A, and KLHDC8B, were verified by the qRT-PCR method. CONCLUSION: This study suggests that the 7-gene TEPs liquid-biopsy biomarkers may be used for cancer diagnosis and monitoring.


Assuntos
Biomarcadores Tumorais/genética , Plaquetas/metabolismo , Biologia Computacional/métodos , Neoplasias/diagnóstico , RNA Neoplásico/genética , Transcriptoma , Biomarcadores Tumorais/sangue , Plaquetas/patologia , Estudos de Casos e Controles , Proteínas de Ciclo Celular/genética , Proteínas de Ligação ao GTP/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Metástase Neoplásica , Neoplasias/sangue , Neoplasias/genética , Prognóstico , RNA Neoplásico/sangue , Receptores de IgG/genética
15.
Cancer Sci ; 112(6): 2140-2157, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33609307

RESUMO

Non-small-cell lung cancer (NSCLC), with its aggressive biological behavior, is one of the most diagnosed cancers. Tumor-associated inflammatory cells play important roles in the interaction between chronic inflammation and lung cancer, however the mechanisms involved are far from defined. In the present study, by developing an orthotopic NSCLC mouse model based on chronic inflammation, we proved that an inflammatory microenvironment accelerated the growth of orthotopic xenografts in vivo. Tumor-associated macrophages, the most abundant population of inflammatory cells, were identified. Treatment with macrophage-conditioned medium (MCM) promoted the growth and migration of NSCLC cells. Using bioinformatics analysis, we identified downregulated PP2Ac expression in NSCLC cells upon treatment with MCM. We further confirmed that this downregulation was executed in an NF-κB pathway-dependent manner. As IκB kinase (IKK) has been proved to be a substrate of PP2Ac, inhibition on PP2Ac could result in amplification of NF-κB pathway signaling. Overexpression of PP2Ac, or the dominant-negative forms of IKK or IκB, attenuated the acceleration of growth and metastasis by MCM. Using bioinformatics analysis, we further identified that CXCL1 and COL6A1 could be downstream of NF-κB/PP2Ac pathway. Luciferase assay and ChIP assay further confirmed the location of response elements on the promoter regions of CXCL1 and COL6A1. Elevated CXCL1 facilitated angiogenesis, whereas upregulated COL6A1 promoted proliferation and migration.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , NF-kappa B/metabolismo , Proteína Fosfatase 2/metabolismo , Macrófagos Associados a Tumor/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Quimiocina CXCL1/genética , Quimiocina CXCL1/metabolismo , Colágeno Tipo VI/genética , Colágeno Tipo VI/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Pessoa de Meia-Idade , Neovascularização Patológica , Proteína Fosfatase 2/genética , Transdução de Sinais
16.
Nat Methods ; 17(12): 1262-1271, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33139894

RESUMO

Achieving a comprehensive understanding of brain function requires multiple imaging modalities with complementary strengths. We present an approach for concurrent widefield optical and functional magnetic resonance imaging. By merging these modalities, we can simultaneously acquire whole-brain blood-oxygen-level-dependent (BOLD) and whole-cortex calcium-sensitive fluorescent measures of brain activity. In a transgenic murine model, we show that calcium predicts the BOLD signal, using a model that optimizes a gamma-variant transfer function. We find consistent predictions across the cortex, which are best at low frequency (0.009-0.08 Hz). Furthermore, we show that the relationship between modality connectivity strengths varies by region. Our approach links cell-type-specific optical measurements of activity to the most widely used method for assessing human brain function.


Assuntos
Mapeamento Encefálico/métodos , Proteínas de Ligação ao Cálcio/metabolismo , Córtex Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Animais , Gasometria , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Fluorescência , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Camundongos , Camundongos Transgênicos , Oxigênio/análise
17.
Neuron ; 104(4): 711-723.e3, 2019 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-31561919

RESUMO

Visual spatial perception in the mammalian brain occurs through two parallel pathways: one reaches the primary visual cortex (V1) through the thalamus and another the superior colliculus (SC) via direct projections from the retina. The origin, development, and relative function of these two evolutionarily distinct pathways remain obscure. We examined the early functional development of both pathways by simultaneously imaging pre- and post-synaptic spontaneous neuronal activity. We observed that the quality of retinal activity transfer to the thalamus and superior colliculus does not change across the first two postnatal weeks. However, beginning in the second postnatal week, retinal activity does not drive V1 as strongly as earlier wave activity, suggesting that intrinsic cortical activity competes with signals from the sensory periphery as the cortex matures. Together, these findings bring new insight into the function of the SC and V1 and the role of peripheral activity in driving both circuits across development.


Assuntos
Neurogênese/fisiologia , Colículos Superiores/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Feminino , Masculino , Camundongos Endogâmicos C57BL , Colículos Superiores/crescimento & desenvolvimento , Córtex Visual/crescimento & desenvolvimento , Vias Visuais/crescimento & desenvolvimento
18.
Oncol Lett ; 18(1): 571-580, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31289529

RESUMO

Colorectal cancer (CRC) represents the third most common malignancy worldwide. The aim of the present study was to investigate the predictive values of platelet-associated indicators, including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) in patients with resectable CRC. The current retrospective study included 153 patients who were pathologically diagnosed with resectable CRC. The patients were divided into two groups according to the median value of PLT, PCT, MPV or PDW. To evaluate the changes in PLT, PCT, MPV and PDW following resection and adjuvant chemotherapy, the concept of post-/pre-treatment PLT, PCT, MPV and PDW ratios was introduced, where <1 indicated decreased PLT, PCT, MPV and PDW values after treatment, and where ≥1 suggested stable or increased values. It was revealed that a low MPV prior to treatment correlated with a higher tumor stage. Surgery significantly decreased MPV, but had no impact on PLT, PCT or PDW. Adjuvant chemotherapy significantly decreased PLT and PCT, increased MPV and had no effect on PDW. After the whole course of treatment (surgery combined with adjuvant chemotherapy), PLT, PCT and PDW were significantly decreased. Kaplan-Meier plots illustrated that patients with a post-/pre-treatment MPV ratio <1 had poorer overall survival (OS), whereas the post-/pre-treatment ratios for PLT, PCT and PDW did not correlate with patient outcome. Multivariate Cox regression analysis revealed that sex, tumor size and the post-/pre-treatment MPV ratio were prognostic factors for OS. Therefore, the present results may suggest MPV as a potential prognostic factor in resectable CRC.

19.
Technol Cancer Res Treat ; 18: 1533033819837261, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30871415

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer death. Platelet-related indictors, including platelet count, plateletcrit, mean platelet volume, and platelet distribution width, not only associate with morphology and functions of platelet but also correlate with tumor development and metastasis. In the present study, we investigated the values of platelet-related indictors in the prognosis evaluation of resectable lung cancers. METHODS: In total, 101 patients with resectable lung cancer were recruited in this study. Patients were divided into 2 groups according to the median pretreatment values. To evaluate the individual value changes after treatment, we introduced the concept of post-/pretreatment ratio (≤1 indicated value was not increased after treatment, while >1 suggested increased value). RESULTS: The high pretreatment platelet count level was correlated with larger tumor size. High pretreatment plateletcrit level was associated with more lymph nodes metastasis. Patients with high pretreatment plateletcrit level had worse overall survival, whereas pretreatment platelet count, mean platelet volume, and platelet distribution width levels were not correlated with outcomes. Surgery had no impact on the values of platelet count, plateletcrit, mean platelet volume, or platelet distribution width. Adjuvant chemotherapy significantly decreased the values of platelet count and plateletcrit, whereas it had no effect on the values of mean platelet volume or platelet distribution width. Whole course of treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of platelet count and platelet distribution width, whereas it had no effect on the values of plateletcrit or mean platelet volume. Post-/pretreatment platelet count, plateletcrit, mean platelet volume, and platelet distribution width ratios were not correlated with outcomes. Univariate analyses demonstrated that American Joint Committee on Cancer stage and pretreatment plateletcrit level were significant risk factors for prognosis. Cox regression analysis revealed that no factor independently associated with worse survival. CONCLUSION: Pretreatment plateletcrit level could be a potential prognostic factor in resectable lung cancers.


Assuntos
Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/patologia , Carcinoma de Pequenas Células do Pulmão/secundário , Plaquetas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Volume Plaquetário Médio , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/metabolismo , Carcinoma de Pequenas Células do Pulmão/cirurgia , Taxa de Sobrevida
20.
Mol Med Rep ; 19(3): 2330-2340, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30664202

RESUMO

The count and classification of white blood cells (WBCs) may be used as prognostic markers in certain types of cancer. The present study investigated the prognostic potential of the counts of WBCs, including lymphocytes (LYs), monocytes (MOs), neutrophils (NEs), eosinophils (EOs) and basophils (BAs), in the prognosis of resectable colorectal cancer. The present study recruited 153 resectable colorectal cancer cases retrospectively, which were pathologically confirmed. All patients were divided into two groups, according to the median value of LY (low LY, ≤1.632x109/l or high LY, >1.632x109/l), MO (low MO, ≤0.330x109/l or high MO, >0.330x109/l), NE (low NE, ≤3.600x109/l or high NE, >3.600x109/l), EO (low EO, ≤0.085x109/l or high EO, >0.085x109/l), BA (low BA, ≤0.010x109/l or high BA, >0.010x109/l), or WBC (low WBC, ≤5.780x109/l or high WBC, >5.780x109/l). To evaluate the alterations in WBC counts following surgery and adjuvant chemotherapy; all samples received oxiplatin and capecitabine (XELOX) for 6­8 cycles or 5­fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) for 10­12 cycles. XELOX included oxaliplatin administered intravenously at a dose of 130 mg/m2 on day 1 and 850­1,250 mg/m2 capecitabine twice daily for days 1­14, repeated every 3 weeks. mFOLFOX6 included oxaliplatin administered intravenously at a dose of 85 mg/m2, 400 mg/m2 leucovorin and 400 mg/m2 5­FU on day 1 followed by 1,200 mg/m2/days continuous infusion for 2 days (in total, 2,400 mg/m2 over 46­48 h), repeated every 2 weeks. The present study investigated the post/pre­treatment of LY, MO, NE, EO, BA and WBC ratios (≤1 indicated that LY, MO, NE, EO, BA and WBC counts were not increased following therapy; whereas, >1 suggested increased counts). Kaplan­Meier curves were constructed to demonstrate overall survival (OS). A multivariate and univariate logistic regression analyses model was employed to identify the independent risk factors. Low pre­treatment BA counts were associated with larger tumor size (>5 cm); pre­treatment BA levels were positively associated with OS. Surgery significantly decreased the count of BAs and increased the count of EOs; whereas, no effect was observed on LYs, MOs, NEs or WBCs. Adjuvant chemotherapy markedly decreased the counts of LY, NE and WBC; whereas, no notable effects on MOs, EOs or BAs were observed. Whole course treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of LY, NE and WBC; however, increased the value of EO; no effects on the MO or BA counts were observed. An increased post­/pre­treatment NE ratio suggested poorer prognosis. Multivariate Cox regression analysis revealed that sex, tumor size, pre­treatment BA count and the post­/pre­treatment NE ratio were independent prognostic factors affecting OS. The results of the present study suggested that the pre­treatment BA count and post­/pre­treatment NE ratio may be potential prognostic factors for resectable colorectal cancer.


Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Contagem de Leucócitos , Prognóstico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Basófilos/efeitos dos fármacos , Capecitabina , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Eosinófilos/efeitos dos fármacos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Leucovorina/administração & dosagem , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Compostos Organoplatínicos/administração & dosagem , Oxaloacetatos
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