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1.
Nat Immunol ; 17(3): 250-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26642356

RESUMO

The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1ß (IL-1ß) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.


Assuntos
Proteínas de Transporte/imunologia , Macrófagos/imunologia , Mitose/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Animais , Apoptose , Proteínas Reguladoras de Apoptose , Proteínas Adaptadoras de Sinalização CARD , Proteínas de Transporte/genética , Caspase 1 , Cromatografia em Gel , Ensaio de Unidades Formadoras de Colônias , Citocinas , Proteínas do Citoesqueleto , Células Dendríticas , Encefalomielite Autoimune Experimental/imunologia , Feminino , Citometria de Fluxo , Células HEK293 , Humanos , Imunoprecipitação , Técnicas In Vitro , Inflamassomos/genética , Inflamassomos/imunologia , Macrófagos Peritoneais/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitocôndrias/metabolismo , Monócitos , Quinases Relacionadas a NIMA , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteínas Serina-Treonina Quinases/genética , Espécies Reativas de Oxigênio , Medula Espinal/imunologia
2.
Phys Chem Chem Phys ; 26(3): 2463-2471, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38167684

RESUMO

In this paper, a novel type of tunable ultra-wide band and double-narrow band artificial electromagnetic absorption device is studied. This work uses a titanium nitride-titanium-tungsten (TiN-Ti-W) composite ring array, a TiN reflector layer, and a silver-titanium dioxide-silver (Ag-TiO2-Ag) three layer composite structure to prepare the absorption layer. The simulation results illustrate that the absorption rate can reach 96.6% when the absorption wavelength is 300-2800 nm. When the light source is backward incidence, ultra-narrow band absorption can occur at specific wavelengths of 465 nm and 932 nm. This proves that the absorber is in good agreement with the impedance matching theory. The research results of this work will provide a theoretical basis for the design and application of solar thermal energy conversion.

3.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34290146

RESUMO

Many endogenous molecules, mostly proteins, purportedly activate the Toll-like receptor 4 (TLR4)-myeloid differentiation factor-2 (MD-2) complex, the innate immune receptor for lipopolysaccharide (LPS) derived from gram-negative bacteria. However, there is no structural evidence supporting direct TLR4-MD-2 activation by endogenous ligands. Sulfatides (3-O-sulfogalactosylceramides) are natural, abundant sulfated glycolipids that have variously been shown to initiate or suppress inflammatory responses. We show here that short fatty acid (FA) chain sulfatides directly activate mouse TLR4-MD-2 independent of CD14, trigger MyD88- and TRIF-dependent signaling, and stimulate tumor necrosis factor α (TNFα) and type I interferon (IFN) production in mouse macrophages. In contrast to the agonist activity toward the mouse receptor, the tested sulfatides antagonize TLR4-MD-2 activation by LPS in human macrophage-like cells. The agonistic and antagonistic activities of sulfatides require the presence of the sulfate group and are inversely related to the FA chain length. The crystal structure of mouse TLR4-MD-2 in complex with C16-sulfatide revealed that three C16-sulfatide molecules bound to the MD-2 hydrophobic pocket and induced an active dimer conformation of the receptor complex similar to that induced by LPS or lipid A. The three C16-sulfatide molecules partially mimicked the detailed interactions of lipid A to achieve receptor activation. Our results suggest that sulfatides may mediate sterile inflammation or suppress LPS-stimulated inflammation, and that additional endogenous negatively charged lipids with up to six lipid chains of limited length might also bind to TLR4-MD-2 and activate or inhibit this complex.


Assuntos
Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Antígeno 96 de Linfócito/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Sulfoglicoesfingolipídeos/farmacologia , Receptor 4 Toll-Like/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/genética , Animais , Linhagem Celular , Feminino , Humanos , Antígeno 96 de Linfócito/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Simulação de Dinâmica Molecular , Fator 88 de Diferenciação Mieloide/genética , Sulfoglicoesfingolipídeos/química , Receptor 4 Toll-Like/genética
4.
Proc Natl Acad Sci U S A ; 118(28)2021 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-34260399

RESUMO

Forward genetic studies use meiotic mapping to adduce evidence that a particular mutation, normally induced by a germline mutagen, is causative of a particular phenotype. Particularly in small pedigrees, cosegregation of multiple mutations, occasional unawareness of mutations, and paucity of homozygotes may lead to erroneous declarations of cause and effect. We sought to improve the identification of mutations causing immune phenotypes in mice by creating Candidate Explorer (CE), a machine-learning software program that integrates 67 features of genetic mapping data into a single numeric score, mathematically convertible to the probability of verification of any putative mutation-phenotype association. At this time, CE has evaluated putative mutation-phenotype associations arising from screening damaging mutations in ∼55% of mouse genes for effects on flow cytometry measurements of immune cells in the blood. CE has therefore identified more than half of genes within which mutations can be causative of flow cytometric phenovariation in Mus musculus The majority of these genes were not previously known to support immune function or homeostasis. Mouse geneticists will find CE data informative in identifying causative mutations within quantitative trait loci, while clinical geneticists may use CE to help connect causative variants with rare heritable diseases of immunity, even in the absence of linkage information. CE displays integrated mutation, phenotype, and linkage data, and is freely available for query online.


Assuntos
Mutação em Linhagem Germinativa/genética , Leucócitos/metabolismo , Aprendizado de Máquina , Meiose/genética , Algoritmos , Animais , Automação , Feminino , Citometria de Fluxo , Masculino , Camundongos Endogâmicos C57BL , Fenótipo , Probabilidade , Reprodutibilidade dos Testes , Software
5.
Phys Chem Chem Phys ; 25(14): 10136-10142, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-36974981

RESUMO

In this paper, we design a solar absorber based on the Si3N4-W-Ti-SiO2 insulator-metal-insulator structure and demonstrate it using the finite difference time domain (FDTD) method. The absorption rate of the absorber consisting of a multi-layer structure with cross etching is over 90% in the bandwidth of 500 nm to 2995 nm with an average absorption rate of 98.3%. There are three peaks at 620 nm, 1002 nm and 1761 nm with peak heights of 99.8%, 99.8% and 99.0%, respectively. By analyzing the distribution of electric and magnetic fields in different sections of the absorber, it is found that the physical mechanism of the structure with high absorptivity is due to the interaction of propagating surface plasmon resonance and local surface plasma resonance. The effects of different structural parameters and the angle of incidence of a light source on the absorber absorption are discussed. The absorber can be used in solar thermal systems, thermal photovoltaics and thermoelectronic devices.

6.
Proc Natl Acad Sci U S A ; 117(15): 8563-8572, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32220963

RESUMO

The small GTPase RABL3 is an oncogene of unknown physiological function. Homozygous knockout alleles of mouse Rabl3 were embryonic lethal, but a viable hypomorphic allele (xiamen [xm]) causing in-frame deletion of four amino acids from the interswitch region resulted in profound defects in lymphopoiesis. Impaired lymphoid progenitor development led to deficiencies of B cells, T cells, and natural killer (NK) cells in Rabl3xm/xm mice. T cells and NK cells exhibited impaired cytolytic activity, and mice infected with mouse cytomegalovirus (MCMV) displayed elevated titers in the spleen. Myeloid cells were normal in number and function. Biophysical and crystallographic studies demonstrated that RABL3 formed a homodimer in solution via interactions between the effector binding surfaces on each subunit; monomers adopted a typical small G protein fold. RABL3xm displayed a large compensatory alteration in switch I, which adopted a ß-strand configuration normally provided by the deleted interswitch residues, thereby permitting homodimer formation. Dysregulated effector binding due to conformational changes in the switch I-interswitch-switch II module likely underlies the xm phenotype. One such effector may be GPR89, putatively an ion channel or G protein-coupled receptor (GPCR). RABL3, but not RABL3xm, strongly associated with and stabilized GPR89, and an N-ethyl-N-nitrosourea (ENU)-induced mutation (explorer) in Gpr89 phenocopied Rabl3xm.


Assuntos
Linfócitos B/imunologia , Linfopoese , Proteínas Mutantes/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Linfócitos T/imunologia , Proteínas rab de Ligação ao GTP/química , Proteínas rab de Ligação ao GTP/fisiologia , Animais , Linfócitos B/metabolismo , Linfócitos B/patologia , Cristalografia por Raios X , Feminino , Infecções por Herpesviridae/imunologia , Infecções por Herpesviridae/virologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muromegalovirus/imunologia , Proteínas Mutantes/química , Proteínas Mutantes/genética , Mutação , Conformação Proteica , Linfócitos T/metabolismo , Linfócitos T/patologia
7.
Mol Cell ; 54(1): 133-146, 2014 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-24703947

RESUMO

Programmed necrotic cell death induced by the tumor necrosis factor alpha (TNF-α) family of cytokines is dependent on a kinase cascade consisting of receptor-interacting kinases RIP1 and RIP3. How these kinase activities cause cells to die by necrosis is not known. The mixed lineage kinase domain-like protein MLKL is a functional RIP3 substrate that binds to RIP3 through its kinase-like domain but lacks kinase activity of its own. RIP3 phosphorylates MLKL at the T357 and S358 sites. Reported here is the development of a monoclonal antibody that specifically recognizes phosphorylated MLKL in cells dying of this pathway and in human liver biopsy samples from patients suffering from drug-induced liver injury. The phosphorylated MLKL forms an oligomer that binds to phosphatidylinositol lipids and cardiolipin. This property allows MLKL to move from the cytosol to the plasma and intracellular membranes, where it directly disrupts membrane integrity, resulting in necrotic death.


Assuntos
Membrana Celular/enzimologia , Proteínas Quinases/metabolismo , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Anticorpos Monoclonais/imunologia , Sítios de Ligação , Cardiolipinas/metabolismo , Membrana Celular/patologia , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Células HT29 , Células HeLa , Humanos , Membranas Intracelulares/enzimologia , Membranas Intracelulares/patologia , Fígado/enzimologia , Fígado/patologia , Lipídeos de Membrana/metabolismo , Necrose , Fosforilação , Conformação Proteica , Proteínas Quinases/genética , Proteínas Quinases/imunologia , Transporte Proteico , Interferência de RNA , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Transdução de Sinais , Especificidade por Substrato , Fatores de Tempo , Transfecção
8.
Proc Natl Acad Sci U S A ; 115(37): E8698-E8706, 2018 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-30150374

RESUMO

Successful cancer immunotherapy entails activation of innate immune receptors to promote dendritic cell (DC) maturation, antigen presentation, up-regulation of costimulatory molecules, and cytokine secretion, leading to activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs). Here we screened a synthetic library of 100,000 compounds for innate immune activators using TNF production by THP-1 cells as a readout. We identified and optimized a potent human and mouse Toll-like receptor (TLR)1/TLR2 agonist, Diprovocim, which exhibited an EC50 of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages. In mice, Diprovocim-adjuvanted ovalbumin immunization promoted antigen-specific humoral and CTL responses and synergized with anti-PD-L1 treatment to inhibit tumor growth, generating long-term antitumor memory, curing or prolonging survival of mice engrafted with the murine melanoma B16-OVA. Diprovocim induced greater frequencies of tumor-infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti-PD-L1 treatment.


Assuntos
Adjuvantes Imunológicos/farmacologia , Anticorpos Monoclonais/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Melanoma Experimental/terapia , Receptor 1 Toll-Like/agonistas , Receptor 2 Toll-Like/agonistas , Animais , Anticorpos Monoclonais/imunologia , Antígeno B7-H1/imunologia , Linhagem Celular Tumoral , Células Cultivadas , Sinergismo Farmacológico , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Melanoma Experimental/genética , Melanoma Experimental/imunologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ovalbumina/imunologia , Células THP-1 , Receptor 1 Toll-Like/genética , Receptor 1 Toll-Like/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo
9.
Proc Natl Acad Sci U S A ; 114(26): E5197-E5206, 2017 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-28607088

RESUMO

The recessive N-ethyl-N-nitrosourea-induced phenotype toku is characterized by delayed hair growth, progressive hair loss, and excessive accumulation of dermal cholesterol, triglycerides, and ceramides. The toku phenotype was attributed to a null allele of Gk5, encoding glycerol kinase 5 (GK5), a skin-specific kinase expressed predominantly in sebaceous glands. GK5 formed a complex with the sterol regulatory element-binding proteins (SREBPs) through their C-terminal regulatory domains, inhibiting SREBP processing and activation. In Gk5toku/toku mice, transcriptionally active SREBPs accumulated in the skin, but not in the liver; they were localized to the nucleus and led to elevated lipid synthesis and subsequent hair growth defects. Similar defective hair growth was observed in kinase-inactive GK5 mutant mice. Hair growth defects of homozygous toku mice were partially rescued by treatment with the HMG-CoA reductase inhibitor simvastatin. GK5 exists as part of a skin-specific regulatory mechanism for cholesterol biosynthesis, independent of cholesterol regulation elsewhere in the body.


Assuntos
Glicerol Quinase/metabolismo , Lipídeos/biossíntese , Processamento de Proteína Pós-Traducional , Pele/metabolismo , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Animais , Glicerol Quinase/genética , Lipídeos/genética , Camundongos , Camundongos Knockout , Domínios Proteicos , Sinvastatina/farmacologia , Proteínas de Ligação a Elemento Regulador de Esterol/genética
10.
J Sci Food Agric ; 100(3): 936-944, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31487041

RESUMO

BACKGROUND: This study investigates the efficacy of short peptides secreted by Bacillus subtilis for fungal inhibition in fresh-cut pumpkin and for maintaining its shelf life. RESULTS: Low-molecular-weight filtrate (LC < 1000 Da) of B. subtilis culture (BC) significantly lowered the total number of molds on fresh-cut pumpkin compared with the untreated control and a BC group after storage. Low-molecular-weight filtrate prevented the deterioration of sensory quality in a pumpkin incision, and reduced pectinase activity. It also inhibited the growth of Phytophthora capsici and Penicillium chrysogenum, and the activity of ß-1,3-glucan synthase (GS) secreted by both molds. Fifty-seven GS-inhibiting peptides were screened from 95 LC peptides with two to five amino acid residues. The two most potent peptides, AWYW and HWWY, had strongly suppressive effects on the growth of P. capsici and P. chrysogenum. CONCLUSION: Our study demonstrated that short peptides present in B. subtilis culture can play an important role in the maintenance of fresh-cut pumpkin by suppressing fungal growth. © 2019 Society of Chemical Industry.


Assuntos
Bacillus subtilis/química , Cucurbita/microbiologia , Fungos/efeitos dos fármacos , Fungicidas Industriais/farmacologia , Peptídeos/farmacologia , Bacillus subtilis/metabolismo , Frutas/microbiologia , Fungos/crescimento & desenvolvimento , Fungicidas Industriais/química , Fungicidas Industriais/metabolismo , Penicillium chrysogenum/efeitos dos fármacos , Penicillium chrysogenum/crescimento & desenvolvimento , Peptídeos/química , Peptídeos/metabolismo , Phytophthora/efeitos dos fármacos , Phytophthora/crescimento & desenvolvimento , Doenças das Plantas/microbiologia
11.
Proc Natl Acad Sci U S A ; 113(7): E884-93, 2016 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-26831104

RESUMO

Structurally disparate molecules reportedly engage and activate Toll-like receptor (TLR) 4 and other TLRs, yet the interactions that mediate binding and activation by dissimilar ligands remain unknown. We describe Neoseptins, chemically synthesized peptidomimetics that bear no structural similarity to the established TLR4 ligand, lipopolysaccharide (LPS), but productively engage the mouse TLR4 (mTLR4)/myeloid differentiation factor 2 (MD-2) complex. Neoseptin-3 activates mTLR4/MD-2 independently of CD14 and triggers canonical myeloid differentiation primary response gene 88 (MyD88)- and Toll-interleukin 1 receptor (TIR) domain-containing adaptor inducing IFN-beta (TRIF)-dependent signaling. The crystal structure mTLR4/MD-2/Neoseptin-3 at 2.57-Å resolution reveals that Neoseptin-3 binds as an asymmetrical dimer within the hydrophobic pocket of MD-2, inducing an active receptor complex similar to that induced by lipid A. However, Neoseptin-3 and lipid A form dissimilar molecular contacts to achieve receptor activation; hence strong TLR4/MD-2 agonists need not mimic LPS.


Assuntos
Lipopolissacarídeos/farmacologia , Antígeno 96 de Linfócito/agonistas , Peptidomiméticos/farmacologia , Receptor 4 Toll-Like/agonistas , Animais , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais
12.
J Am Chem Soc ; 140(43): 14440-14454, 2018 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-30272974

RESUMO

A screen conducted with nearly 100000 compounds and a surrogate functional assay for stimulation of an immune response that measured the release of TNF-α from treated human THP-1 myeloid cells differentiated along the macrophage line led to the discovery of the diprovocims. Unique to these efforts and of special interest, the screening leads for this new class of activators of an immune response came from a compound library designed to promote cell-surface receptor dimerization. Subsequent comprehensive structure-activity relationship studies improved the potency 800-fold over that of the screening leads, providing diprovocim-1 and diprovocim-2. The diprovocims act by inducing cell-surface toll-like receptor (TLR)-2 dimerization and activation with TLR1 (TLR1/TLR2 agonist), bear no structural similarity to any known natural or synthetic TLR agonist, and are easy to prepare and synthetically modify, and selected members are active in both human and murine systems. The most potent diprovocim (3, diprovocim-1) elicits full agonist activity at extraordinarily low concentrations (EC50 = 110 pM) in human THP-1 cells, being more potent than the naturally derived TLR1/TLR2 agonist Pam3CSK4 or any other known small molecule TLR agonist.


Assuntos
Antineoplásicos/farmacologia , Melanoma Experimental/tratamento farmacológico , Receptor 1 Toll-Like/agonistas , Receptor 2 Toll-Like/agonistas , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Melanoma Experimental/patologia , Camundongos , Conformação Molecular , Células THP-1
13.
Worldviews Evid Based Nurs ; 15(5): 386-393, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30098111

RESUMO

BACKGROUND: Nonpharmacological interventions are often used to promote sleep among preterm infants in the neonatal intensive care unit (NICU). However, there is a lack of synthesis in the evidence of their effectiveness. AIM: To synthesize the evidence on the effectiveness of nonpharmacological interventions on NICU preterm infants' sleep during hospital stay. METHODS: Seven databases were searched, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Wan-fang database, China National Knowledge Infrastructure, China Biological Medicine Database, and VIP Journal Integration Platform from their inceptions to August 2017. Randomized controlled trials examining the effects of nonpharmacological interventions on preterm infants' sleep were included. RESULTS: This review included 36 studies. Nonpharmacological interventions included the Newborn Individualized Developmental Care and Assessment Program (NIDCAP), music, non-nutritive sucking, touch, cycled light, cobedding, rocking, oral sucrose, remolding mattresses, and family nurturing. The meta-analysis results showed that 1. the NIDCAP had no significant effect on total sleep time efficiency (TST%; p = .34); 2. mattress interventions had significant effects on TST% (p < .001); and active sleep efficiency (AS%; p = .006) but no significant effect on quiet sleep efficiency (QS%; p = .75); 3. cycled light increased TST (p = .02); and 4. cobedding had no significant effects on QS% and AS% (p = .63 and p = .88, respectively). LINKING EVIDENCE TO ACTION: Remolding mattresses and cycled light had significant effects on sleep promotion in preterm infants, but the quality of the evidence was very low. Further high-quality studies are needed to strengthen this evidence.


Assuntos
Recém-Nascido Prematuro , Transtornos do Sono do Ritmo Circadiano/terapia , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal/organização & administração , Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Musicoterapia/normas
14.
Intensive Crit Care Nurs ; 82: 103632, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38290221

RESUMO

OBJECTIVES: To explore the differences in post-intensive care unit memory and posttraumatic stress disorder symptoms between patients with and without delirium, and assess the correlations between the two. DESIGN: Prospective cohort observation study. SETTING: A cardiac intensive care unit of a tertiary hospital in China. We enrolled 318 consecutive patients after cardiac surgery between December 2017 and March 2019. MAIN OUTCOME MEASURES: Delirium was assessed using the Confusion Assessment Method for the ICU from intensive care unit admission to discharge. Intensive care unit memory was assessed using the ICU-Memory Tool through face-to-face interviews one week after discharge. Posttraumatic stress disorder was measured telephonically using the Impact of Events Scale-revised questionnaire at three months post-discharge. RESULTS: Eighty patients each in the delirium and non-delirium groups were enrolled for follow-up interviews. Patients with delirium had vaguer memories of pre-intensive care unit admission and of their stay, and recollected more memories of feelings (vs. without delirium). Posttraumatic stress disorder was diagnosed in 14 patients with and in seven without delirium, with non-significant differences between groups. Delirium did not influence post-intensive care unit factual, feeling, and delusional memories, nor posttraumatic stress disorder and hyperarousal, intrusion, and avoidance. The memories of feelings were positively correlated with the last three (r = 0.285, r = 0.390 and r = 0.373, respectively). CONCLUSION: Patients with delirium had vague intensive care unit memories. Memories of feelings were positively correlated with symptoms of hyperarousal, intrusion, and avoidance. Delirium did not influence factual, feeling, or delusional memories nor posttraumatic stress disorder incidence and symptoms. IMPLICATIONS FOR CLINICAL PRACTICE: Interventions are needed to reduce the impact of vague memory in patients with post-intensive care unit delirium. Memories of feelings should be focused on because of their correlation with hyperarousal, intrusion, and avoidance. Delirium prevention and early recognition measures are suggested.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Delírio , Transtornos de Estresse Pós-Traumáticos , Humanos , Assistência ao Convalescente , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cuidados Críticos , Delírio/complicações , Unidades de Terapia Intensiva , Alta do Paciente , Estudos Prospectivos , Transtornos de Estresse Pós-Traumáticos/complicações
15.
J Cell Sci ; 124(Pt 4): 657-68, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21266468

RESUMO

Alveolar epithelium is composed of alveolar epithelial cells of type I (AEC I) and type II (AEC II). AEC II secrete lung surfactant by means of exocytosis. P2X(7) receptor (P2X(7)R), a P2 purinergic receptor, has been implicated in the regulation of synaptic transmission and inflammation. Here, we report that P2X(7)R, which is expressed in AEC I but not AEC II, is a novel mediator for the paracrine regulation of surfactant secretion in AEC II. In primary co-cultures of AEC I and AEC II benzoyl ATP (BzATP; an agonist of P2X(7)R) increased surfactant secretion, which was blocked by the P2X(7)R antagonist Brilliant Blue G. This effect was observed in AEC II co-cultured with human embryonic kidney HEK-293 cells stably expressing rat P2X(7)R, but not when co-cultured with AEC I in which P2X(7)R was knocked down or in co-cultures of AEC I and AEC II isolated from P2X(7)R(-/-) mice. BzATP-mediated secretion involved P2Y(2) receptor signaling because it was reduced by the addition of the ATP scavengers apyrase and adenosine deaminase and the P2Y(2) receptor antagonist suramin. However, the stimulation with BzATP might also release other substances that potentially increase surfactant secretion as a greater stimulation of secretion was observed in AEC II incubated with BzATP when co-cultured with E10 or HEK-293-P2X(7)R cells than with ATP alone. P2X(7)R(-/-) mice failed to increase surfactant secretion in response to hyperventilation, pointing to the physiological relevance of P2X(7)R in maintaining surfactant homeostasis in the lung. These results suggest that the activation of P2X(7)R increases surfactant secretion by releasing ATP from AEC I and subsequently stimulating P2Y(2) receptors in AEC II.


Assuntos
Apoproteínas/metabolismo , Pulmão/metabolismo , Comunicação Parácrina , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Células Cultivadas , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Células HEK293 , Humanos , Pulmão/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2X7/genética
16.
Heart Lung ; 59: 139-145, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36801548

RESUMO

BACKGROUND: Delirium is common in postoperative critically ill patients and may affect by intraoperative events. Biomarkers are vital indicators in the development and prediction of delirium. OBJECTIVES: This study aimed to investigate the associations between various plasma biomarkers and delirium. METHODS: We performed a prospective cohort study on cardiac surgery patients. Delirium assessment was performed twice daily using the confusion assessment method for the intensive care unit (ICU), and the Richmond Agitation Sedation Scale was used to assess the depth of sedation and agitation. Blood samples were collected on the day after ICU admission, and the concentrations of cortisol, interleukin (IL)-1ß, IL-6, tumor necrosis factor α, soluble tumor necrosis factor receptor-1 (sTNFR-1), and sTNFR-2 were measured. RESULTS: Delirium in the ICU was noted in 93 (29.2%, 95% CI 24.2-34.3) out of 318 patients (mean age 52 years, SD 12.0). The longer duration of cardiopulmonary bypass, aortic clamping and surgery, and higher plasma, erythrocytes, and platelet transfusion requirements were among the significant differences in intraoperative events between patients with and without delirium. Median levels of IL-6 (p = 0.017), TNF-α (p = 0.048), sTNFR-1 (p < 0.001), and sTNFR-2 (p = 0.001) were significantly higher in patients with delirium than in those without it. After adjusting for demographic variables and intraoperative events, only sTNFR-1 (odds ratio 6.83, 95% CI: 1.14-40.90) was associated with delirium. CONCLUSIONS: Plasma IL-6, TNF-α, sTNFR-1, and sTNFR-2 levels were higher in ICU-acquired delirium patients after cardiac surgery. sTNFR-1 was a potential indicator of the disorder.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Delírio , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fator de Necrose Tumoral alfa , Interleucina-6 , Delírio/diagnóstico , Delírio/etiologia , Estado Terminal , Biomarcadores , Unidades de Terapia Intensiva , Procedimentos Cirúrgicos Cardíacos/efeitos adversos
17.
Biochem Biophys Res Commun ; 422(4): 586-9, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22595456

RESUMO

P2X7 receptor (P2X7R) is a purinergic ion-channel receptor. We have previously shown that the activation of P2X7R in alveolar type I cells stimulates surfactant secretion in alveolar type II cells. In this study, we determined whether miR-150 regulates P2X7R-mediated surfactant secretion. The miR-150 expression level in alveolar type II cells was much higher than alveolar type I cells, which was inversely correlated with the P2X7R protein level. An adenovirus expressing miR-150 significantly reduced the P2X7R protein expression in E10 cells, an alveolar type I cell line. Furthermore, pre-treatment of E10 cells with the adenovirus reduced the surfactant secretion induced by E10 cell conditioned medium. Our study demonstrates that miR-150 regulates surfactant secretion through P2X7R.


Assuntos
MicroRNAs/fisiologia , Alvéolos Pulmonares/metabolismo , Proteínas Associadas a Surfactantes Pulmonares/metabolismo , Receptores Purinérgicos P2X7/biossíntese , Mucosa Respiratória/metabolismo , Animais , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Humanos , Masculino , MicroRNAs/genética , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2X7/genética
18.
Food Chem ; 384: 132422, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35193017

RESUMO

This study aimed to improve the emulsifying properties of microcrystalline cellulose by carboxylating (CC) and bridging to hydrophobic oat globule peptides (HP) via Ca2+ (CC-Ca-HP). FTIR and XRD spectra analysis proved the successful attachment of HP to CC through a salt bridge. The Ca2+-bridging significantly changed the particle characteristics of CC-Ca-HP, including particle size, ζ-potential, and wettability. The Ca2+-bridged composite CC-Ca-HP demonstrated remarkable emulsifying stability compared with the nonbridged blend (CC-HP). Further analysis of the steady flow characteristics and dynamic viscoelastic properties revealed a network structure formed in the CC-Ca-HP emulsion. Moreover, the CC-Ca-HP emulsion showed a marked release of free fatty acids, increased bioaccessibility of zeaxanthin in the simulated gastrointestinal digestion, and less oil oxidation under the accelerated oxidation condition, indicating that the stable structure of CC-Ca-HP imparted by Ca2+-bridging prevented the aggregation of oil droplets as collision occurred under the harsh gastric conditions.


Assuntos
Cálcio , Celulose , Cálcio da Dieta , Emulsificantes , Emulsões/química , Tamanho da Partícula , Peptídeos
19.
Cell Metab ; 34(11): 1860-1874.e4, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36228616

RESUMO

Using random germline mutagenesis in mice, we identified a viable hypomorphic allele (boh) of the transcription-factor-encoding gene Ovol2 that resulted in obesity, which initially developed with normal food intake and physical activity but decreased energy expenditure. Fat weight was dramatically increased, while lean weight was reduced in 12-week-old boh homozygous mice, culminating by 24 weeks in massive obesity, hepatosteatosis, insulin resistance, and diabetes. The Ovol2boh/boh genotype augmented obesity in Lepob/ob mice, and pair-feeding failed to normalize obesity in Ovol2boh/boh mice. OVOL2-deficient mice were extremely cold intolerant. OVOL2 is essential for brown/beige adipose tissue-mediated thermogenesis. In white adipose tissues, OVOL2 limited adipogenesis by blocking C/EBPα engagement of its transcriptional targets. Overexpression of OVOL2 in adipocytes of mice fed with a high-fat diet reduced total body and liver fat and improved insulin sensitivity. Our data reveal that OVOL2 plays dual functions in thermogenesis and adipogenesis to maintain energy balance.


Assuntos
Adipogenia , Resistência à Insulina , Camundongos , Animais , Adipogenia/genética , Tecido Adiposo Marrom/metabolismo , Termogênese/genética , Tecido Adiposo Branco/metabolismo , Obesidade/metabolismo , Dieta Hiperlipídica , Resistência à Insulina/genética , Metabolismo Energético/genética , Mutação , Camundongos Endogâmicos C57BL
20.
PLoS One ; 16(9): e0257816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555101

RESUMO

BACKGROUND: Inadvertent intraoperative hypothermia is frequent during open surgeries; however, few studies on hypothermia during laparoscopic abdominal surgery have been reported. We aimed to investigate the incidence and risk factors for hypothermia in patients undergoing laparoscopic abdominal surgery. METHODS: This single-center prospective cohort observational study involved patients undergoing laparoscopic surgery between October 2018 and June 2019. Data on core body temperature and potential variables were collected. A multivariate logistic regression analysis was performed to identify the risk factors associated with hypothermia. A Cox regression analysis was used to verify the sensitivity of the results. RESULTS: In total, 690 patients were included in the analysis, of whom 200 (29.0%, 95% CI: 26%-32%) had a core temperature < 36°C. The core temperature decreased over time, and the incident hypothermia increased gradually. In the multivariate logistic regression analysis, age (OR = 1.017, 95% CI: 1.000-1.034, P = 0.050), BMI (OR = 0.938, 95% CI: 0.880-1.000; P = 0.049), baseline body temperature (OR = 0.025, 95% CI: 0.010-0.060; P < 0.001), volume of irrigation fluids (OR = 1.001, 95% CI: 1.000-1.001, P = 0.001), volume of urine (OR = 1.001, 95% CI: 1.000-1.003, P = 0.070), and duration of surgery (OR = 1.010, 95% CI: 1.006-1.015, P < 0.001) were significantly associated with hypothermia. In the Cox analysis, variables in the final model were age, BMI, baseline body temperature, volume of irrigation fluids, blood loss, and duration of surgery. CONCLUSIONS: Inadvertent intraoperative hypothermia is evident in patients undergoing laparoscopic surgeries. Age, BMI, baseline body temperature, volume of irrigation fluids, and duration of surgery are significantly associated with intraoperative hypothermia.


Assuntos
Hipotermia/epidemiologia , Complicações Intraoperatórias/epidemiologia , Laparoscopia/efeitos adversos , Adulto , Índice de Massa Corporal , Feminino , Humanos , Hipotermia/etiologia , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
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