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1.
Nature ; 585(7824): 221-224, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32908262

RESUMO

Platinum is a much used catalyst that, in petrochemical processes, is often alloyed with other metals to improve catalytic activity, selectivity and longevity1-5. Such catalysts are usually prepared in the form of metallic nanoparticles supported on porous solids, and their production involves reducing metal precursor compounds under a H2 flow at high temperatures6. The method works well when using easily reducible late transition metals, but Pt alloy formation with rare-earth elements through the H2 reduction route is almost impossible owing to the low chemical potential of rare-earth element oxides6. Here we use as support a mesoporous zeolite that has pore walls with surface framework defects (called 'silanol nests') and show that the zeolite enables alloy formation between Pt and rare-earth elements. We find that the silanol nests enable the rare-earth elements to exist as single atomic species with a substantially higher chemical potential compared with that of the bulk oxide, making it possible for them to diffuse onto Pt. High-resolution transmission electron microscopy and hydrogen chemisorption measurements indicate that the resultant bimetallic nanoparticles supported on the mesoporous zeolite are intermetallic compounds, which we find to be stable, highly active and selective catalysts for the propane dehydrogenation reaction. When used with late transition metals, the same preparation strategy produces Pt alloy catalysts that incorporate an unusually large amount of the second metal and, in the case of the PtCo alloy, show high catalytic activity and selectivity in the preferential oxidation of carbon monoxide in H2.

2.
Proc Natl Acad Sci U S A ; 119(15): e2121098119, 2022 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-35377803

RESUMO

The pathogenesis of lung fibrosis involves hyperactivation of innate and adaptive immune pathways that release inflammatory cytokines and growth factors such as tumor growth factor (TGF)ß1 and induce aberrant extracellular matrix protein production. During the genesis of pulmonary fibrosis, resident alveolar macrophages are replaced by a population of newly arrived monocyte-derived interstitial macrophages that subsequently transition into alveolar macrophages (Mo-AMs). These transitioning cells initiate fibrosis by releasing profibrotic cytokines and remodeling the matrix. Here, we describe a strategy for leveraging the up-regulation of the mannose receptor CD206 in interstitial macrophages and Mo-AM to treat lung fibrosis. We engineered mannosylated albumin nanoparticles, which were found to be internalized by fibrogenic CD206+ monocyte derived macrophages (Mo-Macs). Mannosylated albumin nanoparticles incorporating TGFß1 small-interfering RNA (siRNA) targeted the profibrotic subpopulation of CD206+ macrophages and prevented lung fibrosis. The findings point to the potential utility of mannosylated albumin nanoparticles in delivering TGFß-siRNA into CD206+ profibrotic macrophages as an antilung fibrosis strategy.


Assuntos
Linfotoxina-alfa , Macrófagos Alveolares , Nanopartículas , Fibrose Pulmonar , RNA Interferente Pequeno , Animais , Bleomicina/farmacologia , Modelos Animais de Doenças , Linfotoxina-alfa/genética , Macrófagos Alveolares/imunologia , Receptor de Manose , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/administração & dosagem , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/imunologia , Fibrose Pulmonar/terapia , RNA Interferente Pequeno/administração & dosagem , RNA Interferente Pequeno/genética
3.
Eur Spine J ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878173

RESUMO

PURPOSE: To evaluate the actual change in clinical hip pain and hip migration after operation for non-ambulatory flaccid neuromuscular (NM) scoliosis and investigate whether there is an association between hip migration and coronal/sagittal pelvic tilt (CO-PT/SA-PT). PATIENTS AND METHODS: This retrospective, single-center, observational study evaluated a total of 134 patients with non-ambulatory flaccid neuromuscular scoliosis who underwent surgery performed by a single surgeon between 2003 and 2020, with at least 2 years of follow-up period. Operation procedures were conducted in two stages, beginning with L5-S1 anterior release followed by posterior fixation. Radiologic parameters were measured at preoperative, immediate postoperative, and last follow-up periods with clinical hip pain and clinical hip dislocation events. RESULTS: The significant improvements occurred in various parameters after correction surgery for NM scoliosis, containing Cobb's angle of major curve and CO-PT. However, Reimer's hip migration percentage (RMP) was increased on both side of hip (High side, 0.23 ± 0.16 to 0.28 ± 0.21; Low side, 0.20 ± 0.14 to 0.23 ± 0.18). Hip pain and dislocation events were also increased (Visual analog scale score, 2.5 ± 2.3 to 3.6 ± 2.6, P value < 0.05; dislocation, 6-12). Logistic regression analysis of the interactions between ΔRMP(High) and the change of sagittal pelvic tilt (ΔSA-PT) after correction reveals a significant negative association. (95% CI 1.003-1.045, P value = 0.0226). CONCLUSIONS: In cases of non-ambulatory flaccid NM scoliosis, clinical hip pain, and subluxation continued to deteriorate even after correction of CO-PT. There was a relationship between the decrease in SA-PT, and an increase in hip migration percentage on high side, indicating the aggravation of hip subluxation.

4.
Angew Chem Int Ed Engl ; 62(27): e202303503, 2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37041117

RESUMO

We report a general synthetic strategy for post-encapsulation of metal nanoparticles within preformed zeolites using post-synthetic modification. Both anionic and cationic precursors to metal nanoparticle are supported on 8- and 10-membered ring zeolites and analogues during wet impregnation using 2-aminoethanethiol (AET) as a bi-grafting agent. Thiol groups are coordinated to metal centers, whereas amine moieties are dynamically attached to micropore walls via acid-base interactions. The dynamic acid-base interactions cause the even distribution of the metal-AET complex throughout the zeolite matrix. These processes encapsulate Au, Rh, and Ni precursors within the CHA, *MRE, MFI zeolite, and SAPO-34 zeolite analogues, for which small channel apertures preclude the post-synthesis impregnation of metal precursors. Sequential activation forms small and uniform nanoparticles (1-2.5 nm in diameter), as confirmed through electron microscopy and X-ray absorption spectroscopy. Containment within the small micropores protected the nanoparticles against harsh thermal sintering conditions and prevented the fouling of the metal surface by coke, thus resulting in a high catalytic performance in n-dodecane hydroisomerization and methane decomposition. The remarkable specificity of the thiol to metal precursors and the dynamic acid-base interaction make these protocols extendable to various metal-zeolite systems, suitable for shape-selective catalysts in challenging chemical environments.

5.
J Cell Sci ; 133(5)2020 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-31964705

RESUMO

The macrophage checkpoint receptor SIRPα signals against phagocytosis by binding CD47 expressed on all cells - including macrophages. Here, we found that inhibiting cis interactions between SIRPα and CD47 on the same macrophage increased engulfment ('eating') by approximately the same level as inhibiting trans interactions. Antibody blockade of CD47, as pursued in clinical trials against cancer, was applied separately to human-derived macrophages and to red blood cell (RBC) targets for phagocytosis, and both scenarios produced surprisingly similar increases in RBC engulfment. Blockade of both macrophages and targets resulted in hyper-phagocytosis, and knockdown of macrophage-CD47 likewise increased engulfment of 'foreign' cells and particles, decreased the baseline inhibitory signaling of SIRPα, and linearly increased binding of soluble CD47 in trans, consistent with cis-trans competition. Many cell types express both SIRPα and CD47, including mouse melanoma B16 cells, and CRISPR-mediated deletions modulate B16 phagocytosis, consistent with cis-trans competition. Additionally, soluble SIRPα binding to human CD47 displayed on Chinese hamster ovary (CHO) cells was suppressed by SIRPα co-display, and atomistic computations confirm SIRPα bends and binds CD47 in cis Safety and efficacy profiles for CD47-SIRPα blockade might therefore reflect a disruption of both cis and trans interactions.


Assuntos
Antígenos de Diferenciação , Antígeno CD47 , Animais , Antígeno CD47/genética , Células CHO , Cricetinae , Cricetulus , Macrófagos , Fagocitose , Receptores Imunológicos/genética
6.
Osteoporos Int ; 33(11): 2409-2416, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35925259

RESUMO

In this retrospective study, the effectiveness of short-term teriparatide with denosumab in reducing fragility fracture risk was determined in comparison with denosumab monotherapy. Administration of sequential teriparatide with denosumab showed excellent outcomes in suppressing the risk for fragility fractures compared with denosumab monotherapy. INTRODUCTION: To determine the effectiveness of short-term teriparatide with denosumab in reducing the risk of fragility fractures in comparison to denosumab monotherapy. METHODS: The data of postmenopausal patients treated with denosumab for > 2 years between August 2015 and October 2020 were retrospectively analyzed. One hundred sixty four postmenopausal women of a total 615 were excluded, since they did not undergo > 2 bone mineral density (BMD) tests, were lost to follow-up, or received long-term teriparatide therapy. Total 320 patients received denosumab monotherapy and 131 patients received teriparatide for ≥ 3 months followed by denosumab. The number of osteoporotic fractures, presence of back pain before and after treatment, and annual BMD during treatment were comparatively assessed using t-test, Chi-square test, and linear mixed model analysis. RESULTS: Before treatment, the denosumab monotherapy group had fewer osteoporotic fractures (mean ± standard deviation; 0.459 ± 0.689) than the sequential therapy group had (1.037 ± 0.871; p < 0.001). After treatment, the sequential therapy group had fewer osteoporotic fractures than the denosumab monotherapy group had (0.119 ± 0.348 versus 0.144 ± 0.385; p < 0.001). At 1 and 2 years after treatment, the increase in lumbar spine BMD was greater in the sequential therapy group than in the denosumab monotherapy group (p = 0.08, group × time). The difference between post and pre-treatment back pain visual analog scale score was significantly lower in the sequential therapy group than in the monotherapy group (3.246 ± 3.426 versus 1.734 ± 3.049; p < 0.001). CONCLUSION: Short-term teriparatide use before denosumab showed excellent outcomes in suppressing the risk of fragility fractures compared with denosumab monotherapy.


Assuntos
Conservadores da Densidade Óssea , Osteoporose Pós-Menopausa , Fraturas por Osteoporose , Densidade Óssea , Denosumab/uso terapêutico , Feminino , Humanos , Osteoporose Pós-Menopausa/induzido quimicamente , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/induzido quimicamente , Fraturas por Osteoporose/prevenção & controle , Estudos Retrospectivos , Teriparatida
7.
Proc Natl Acad Sci U S A ; 116(31): 15392-15397, 2019 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-31311862

RESUMO

Mesenchymal stem cell (MSC) therapies demonstrate particular promise in ameliorating diseases of immune dysregulation but are hampered by short in vivo cell persistence and inconsistencies in phenotype. Here, we demonstrate that biomaterial encapsulation into alginate using a microfluidic device could substantially increase in vivo MSC persistence after intravenous (i.v.) injection. A combination of cell cluster formation and subsequent cross-linking with polylysine led to an increase in injected MSC half-life by more than an order of magnitude. These modifications extended persistence even in the presence of innate and adaptive immunity-mediated clearance. Licensing of encapsulated MSCs with inflammatory cytokine pretransplantation increased expression of immunomodulatory-associated genes, and licensed encapsulates promoted repopulation of recipient blood and bone marrow with allogeneic donor cells after sublethal irradiation by a ∼2-fold increase. The ability of microgel encapsulation to sustain MSC survival and increase overall immunomodulatory capacity may be applicable for improving MSC therapies in general.


Assuntos
Encapsulamento de Células , Imunomodulação , Células-Tronco Mesenquimais/citologia , Alginatos/química , Animais , Células Cultivadas , Regulação da Expressão Gênica , Hematopoese/genética , Imunidade , Imunomodulação/genética , Camundongos Endogâmicos BALB C , Fatores de Tempo , Transplante Homólogo
8.
Curr Top Membr ; 86: 301-314, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33837697

RESUMO

The majority of Alzheimer's disease (AD) risk genes are highly and selectively expressed by microglia in the brain. Several of these genes are related to lipid and cholesterol metabolism, lipid synthesis, lipid transport, endocytosis, exocytosis and phagocytosis. Therefore, studying the roles of cellular membrane biophysics in microglial function should improve our understanding of the AD pathology. In this chapter, we discuss how lipid rafts and membrane-cytoskeleton adhesion impact microglial-mediated oxidative stress and clearance of amyloid-ß peptide (Aß). We also discuss potential roles of lipid membrane-bound extracellular vesicles as carriers of pathological factors to promote inflammation and cytotoxicity.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Microglia
9.
Molecules ; 25(23)2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33260680

RESUMO

Diverse harmful compounds can be emitted during the heating of tobacco sticks for heated tobacco products (HTPs). In this study, the generation of harmful compounds from the filter, instead of tobacco in tobacco sticks, was confirmed. The heat of a heated tobacco product device can be transferred to the tobacco stick filter, resulting in the generation of harmful compounds from the heated filter. Since the heating materials (tobacco consumable) of the tobacco sticks evaluated in this study were different depending on the brand, the harmful compounds emitted from the heated tobacco stick filters were examined by focusing on the carbonyl compounds, using three different tobacco stick parts. Acetaldehyde and propionaldehyde exhibited the highest concentrations in HTP aerosols produced by heating the tobacco consumable (conventional case) (63.5 ± 18.4 µg/stick and 1.71 ± 0.123 µg/stick, respectively). The aerosols produced by heating tobacco stick filters had higher formaldehyde and acrolein concentrations (0.945 ± 0.214 µg/stick and 0.519 ± 0.379 µg/stick) than the aerosols generated from heated tobacco consumable (0.641 ± 0.092 µg/stick and 0.220 ± 0.102 µg/stick). As such, formaldehyde and acrolein were produced by heating small parts of the mouthpiece of a tobacco stick, regardless of the heated tobacco product brand. In addition, acetone was only detected in the aerosols generated from heated filters (0.580 ± 0.305 µg/stick). Thus, safety evaluations of heated tobacco products should include considerations of the harmful compounds generated by heating tobacco stick mouthpieces for heated tobacco products in addition to those found in heated tobacco product aerosols.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Formaldeído/análise , Temperatura Alta , Nicotiana/química , Compostos Orgânicos/análise , Produtos do Tabaco/análise , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Humanos
10.
Proc Natl Acad Sci U S A ; 113(43): 12126-12131, 2016 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-27790998

RESUMO

Extracellular matrix stiffness influences biological functions of some tumors. However, it remains unclear how cancer subtypes with different oncogenic mutations respond to matrix stiffness. In addition, the relevance of matrix stiffness to in vivo tumor growth kinetics and drug efficacy remains elusive. Here, we designed 3D hydrogels with physical parameters relevant to hematopoietic tissues and adapted them to a quantitative high-throughput screening format to facilitate mechanistic investigations into the role of matrix stiffness on myeloid leukemias. Matrix stiffness regulates proliferation of some acute myeloid leukemia types, including MLL-AF9+ MOLM-14 cells, in a biphasic manner by autocrine regulation, whereas it decreases that of chronic myeloid leukemia BCR-ABL+ K-562 cells. Although Arg-Gly-Asp (RGD) integrin ligand and matrix softening confer resistance to a number of drugs, cells become sensitive to drugs against protein kinase B (PKB or AKT) and rapidly accelerated fibrosarcoma (RAF) proteins regardless of matrix stiffness when MLL-AF9 and BCR-ABL are overexpressed in K-562 and MOLM-14 cells, respectively. By adapting the same hydrogels to a xenograft model of extramedullary leukemias, we confirm the pathological relevance of matrix stiffness in growth kinetics and drug sensitivity against standard chemotherapy in vivo. The results thus demonstrate the importance of incorporating 3D mechanical cues into screening for anticancer drugs.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/tratamento farmacológico , Animais , Antineoplásicos/classificação , Linhagem Celular Tumoral , Matriz Extracelular/química , Matriz Extracelular/metabolismo , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/metabolismo , Dureza , Ensaios de Triagem em Larga Escala , Humanos , Hidrogéis/química , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Camundongos Endogâmicos NOD , Camundongos SCID , Proteína de Leucina Linfoide-Mieloide/antagonistas & inibidores , Proteína de Leucina Linfoide-Mieloide/genética , Proteína de Leucina Linfoide-Mieloide/metabolismo , Oligopeptídeos/farmacologia , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Ensaios Antitumorais Modelo de Xenoenxerto , Quinases raf/antagonistas & inibidores , Quinases raf/genética , Quinases raf/metabolismo
11.
Nat Mater ; 16(2): 236-243, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27798621

RESUMO

Existing techniques to encapsulate cells into microscale hydrogels generally yield high polymer-to-cell ratios and lack control over the hydrogel's mechanical properties. Here, we report a microfluidic-based method for encapsulating single cells in an approximately six-micrometre layer of alginate that increases the proportion of cell-containing microgels by a factor of ten, with encapsulation efficiencies over 90%. We show that in vitro cell viability was maintained over a three-day period, that the microgels are mechanically tractable, and that, for microscale cell assemblages of encapsulated marrow stromal cells cultured in microwells, osteogenic differentiation of encapsulated cells depends on gel stiffness and cell density. We also show that intravenous injection of singly encapsulated marrow stromal cells into mice delays clearance kinetics and sustains donor-derived soluble factors in vivo. The encapsulation of single cells in tunable hydrogels should find use in a variety of tissue engineering and regenerative medicine applications.


Assuntos
Hidrogéis/química , Nicho de Células-Tronco , Transplante de Células-Tronco/instrumentação , Células-Tronco/citologia , Engenharia Tecidual/instrumentação , Alicerces Teciduais , Animais , Células Cultivadas , Desenho de Equipamento , Humanos , Camundongos , Transplante de Células-Tronco/métodos , Células-Tronco/fisiologia , Engenharia Tecidual/métodos
12.
Environ Res ; 165: 267-273, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29734027

RESUMO

This study investigated the emission characteristics of glass particles resulting from smoking electronic cigarettes (ECs). First, the most suitable filter for the collection of glass particles was explored by examining the performance (reliability) of various types of filters. A polycarbonate filter was determined as the optimum choice to collect glass particles in EC aerosol. A cartomizer was filled with EC refill solution composed of an equal volume of propylene glycol (PG) and vegetable glycol (VG). To simulate the potential conditions for glass particle emission, EC vaped aerosols were collected at three distinctive puffing intervals: (1) 0-10 puffs, (2) 101-110 puffs, and (3) 201-210 puffs (flow rate of 1 L min-1, 2 s per puff, and 10 puffs per sample). Glass particles were observed as early as after 100 times puffing from certain products, while after 200 from others. Thus, glass particles were generated by increasing the number of puffs and usage of the EC cartomizer. The analysis of glass particles collected onto polycarbonate filters by scanning electron microscopy (SEM)/energy dispersive X-ray spectroscopy (EDS) confirmed the presence of glass particles in samples collected after puffing 100-200 times. The study demonstrated that the possibility of glass particle emissions from the EC device increased considerably with the increasing number of total puffs.


Assuntos
Poluentes Atmosféricos/análise , Sistemas Eletrônicos de Liberação de Nicotina , Vidro/análise , Vaping , Aerossóis/análise , Reprodutibilidade dos Testes
13.
Blood ; 125(3): 525-33, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25395423

RESUMO

Megakaryocyte ploidy and the generation of pre/proplatelets are both increased in culture by pharmacologic inhibition of myosin-II, but nonmuscle myosin-IIA (MIIA) mutations paradoxically cause MYH9-related diseases (MYH9-RD) that adversely affect platelets. In marrow, megakaryocytes extend projections into the microcirculation, where shear facilitates fragmentation to large pre/proplatelets, suggesting that fluid stresses and myosin-II activity somehow couple in platelet biogenesis. Here, in bulk shear, plateletlike particles generated from megakaryocytes are maximized at a shear stress typical of that in the microcirculation and after treatment with a myosin-II inhibitor. MIIA activity in static cells is naturally repressed through phosphorylation at Serine-1943, but shear decreases phosphorylation, consistent with MIIA activation and localization to platelet cortex. Micropipette aspiration of cells shows myosin-II accumulates at stressed sites, but its inhibition prevents such mechanoactivation and facilitates generation of CD41(+) fragments similar in size to pre/proplatelets. MYH9-RD mutants phenocopy inhibition, revealing a dominant negative effect. MIIA is diffuse in the large platelets of a MYH9-RD patient with macrothrombocytopenia and is also diffuse in normal pre/proplatelets treated with inhibitor that blocks in vitro division to small platelets. The findings explain the large platelets in MYH9-RD and the near-normal thrombocrit of patients. Myosin-II regulation thus controls platelet size and number.


Assuntos
Plaquetas/patologia , Megacariócitos/patologia , Proteínas Motores Moleculares/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Estresse Mecânico , Trombocitopenia/patologia , Plaquetas/metabolismo , Citometria de Fluxo , Imunofluorescência , Genes Dominantes , Humanos , Megacariócitos/metabolismo , Proteínas Motores Moleculares/genética , Mutação/genética , Cadeias Pesadas de Miosina/genética , Fosforilação , Resistência ao Cisalhamento , Trombocitopenia/genética , Trombocitopenia/metabolismo
14.
Bioessays ; 37(6): 633-42, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25810145

RESUMO

Clinical success with human hematopoietic stem cell (HSC) transplantation establishes a paradigm for regenerative therapies with other types of stem cells. However, it remains generally challenging to therapeutically treat tissues after engineering of stem cells in vitro. Recent studies suggest that stem and progenitor cells sense physical features of their niches. Here, we review biophysical contributions to lineage decisions, maturation, and trafficking of blood and immune cells. Polarized cellular contractility and nuclear rheology are separately shown to be functional markers of a hematopoietic hierarchy that predict the ability of a lineage to traffic in and out of the bone marrow niche. These biophysical determinants are regulated by a set of structural molecules, including cytoplasmic myosin-II and nuclear lamins, which themselves are modulated by a diverse range of transcriptional and post-translational mechanisms. Small molecules that target these mechanobiological circuits, along with novel bioengineering methods, could prove broadly useful in programming blood and immune cells for therapies ranging from blood transfusions to immune attack of tumors.


Assuntos
Diferenciação Celular , Núcleo Celular/fisiologia , Citoesqueleto/fisiologia , Animais , Fenômenos Biomecânicos , Linhagem da Célula , Movimento Celular , Reprogramação Celular , Módulo de Elasticidade , Eritrócitos/fisiologia , Hematopoese , Células-Tronco Hematopoéticas/fisiologia , Humanos , Leucócitos/fisiologia
15.
Clin Orthop Relat Res ; 475(11): 2795-2804, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28795294

RESUMO

BACKGROUND: Antibiotic-loaded bone cement is accepted as an effective treatment modality for musculoskeletal tuberculosis. However, comparative information regarding combinations and concentrations of second-line antimycobacterial drugs, such as streptomycin and amoxicillin and clavulanic acid, are lacking. QUESTIONS/PURPOSES: (1) In antibiotic-loaded cement, is there effective elution of streptomycin and Augmentin® (amoxicillin and clavulanic acid) individually and in combination? (2) What is the antibacterial activity duration for streptomycin- and amoxicillin and clavulanic acid -loaded cement? METHODS: Six different types of bone cement discs were created by mixing 40 g bone cement with 1 or 2 g streptomycin only, 0.6 g or 1.2 g Augmentin® (amoxicillin and clavulanic acid) only, and a combination of 1 g streptomycin plus 0.6 g amoxicillin and clavulanic acid and 2 g streptomycin plus 1.2 g amoxicillin and clavulanic acid. Five bone discs of each type were incubated in phosphate buffered saline for 30 days with renewal of the phosphate buffered saline every day. The quantity of streptomycin and/or amoxicillin and clavulanic acid in eluates were measured by a liquid chromatography-mass spectrometry system, and the antimycobacterial activity of eluates against Mycobacterium tuberculosis H37Rv, were calculated by comparing the minimal inhibitory concentration of each eluate with that of tested drugs using broth dilution assay on microplate. RESULTS: Streptomycin was detected in eluates for 30 days (in 1 g and 2 g discs), whereas 1.2 g amoxicillin and clavulanate eluted until Day 7 and 0.6 g amoxicillin and clavulanate until Day 3. All eluates in streptomycin-containing discs (streptomycin only, and in combination with amoxicillin and clavulanic acid) had effective antimycobacterial activity for 30 days, while amoxicillin and clavulanate-only preparations were only active until Day 14. The antimycobacterial activity of eluates of 2 g streptomycin plus 1.2 g amoxicillin and clavulanate were higher than those of discs containing 1 g streptomycin plus 0.6 g amoxicillin and clavulanate until Day 3, without differences (Day 3, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 17.5 ± 6.85 ug/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 32.5 ± 16.77 ug/mL; p = 0.109). After Day 7, however, values of the two combinations remained no different than that of Day 30 (Day 30, 1 g streptomycin plus 0.6 g amoxicillin and clavulanate: 0.88 ± 0.34 ug/mL; 2 g streptomycin plus 1.2 g amoxicillin and clavulanate: 0.59 ± 0.94 ug/mL; p = 0.107). CONCLUSIONS: Streptomycin, in the form of antibiotic-loaded bone cement, had effective elution characteristics and antimycobacterial effects during a 30-day period, whereas amoxicillin and clavulanate only had effective elution and antimycobacterial characteristics during the early period of this study. The two drugs did not interfere with each other during the elution test. CLINICAL RELEVANCE: This research revealed that combinations of streptomycin and amoxicillin and clavulanate mixed with bone cement are effective for 30 days. Further trials to determine various different combinations of drugs are necessary to improve the effectiveness of treatments for musculoskeletal tuberculosis.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Antituberculosos/farmacologia , Cimentos Ósseos/farmacologia , Portadores de Fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Estreptomicina/farmacologia , Tuberculose Osteoarticular/tratamento farmacológico , Combinação Amoxicilina e Clavulanato de Potássio/química , Antituberculosos/química , Cimentos Ósseos/química , Cromatografia Líquida de Alta Pressão , Liberação Controlada de Fármacos , Humanos , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/crescimento & desenvolvimento , Estreptomicina/química , Fatores de Tempo , Tuberculose Osteoarticular/microbiologia
16.
Microsc Microanal ; 23(6): 1107-1115, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29219802

RESUMO

We trace Sn nanoparticles (NPs) produced from SnO2 nanotubes (NTs) during lithiation initialized by high energy e-beam irradiation. The growth dynamics of Sn NPs is visualized in liquid electrolytes by graphene liquid cell transmission electron microscopy. The observation reveals that Sn NPs grow on the surface of SnO2 NTs via coalescence and the final shape of agglomerated NPs is governed by surface energy of the Sn NPs and the interfacial energy between Sn NPs and SnO2 NTs. Our result will likely benefit more rational material design of the ideal interface for facile ion insertion.

17.
Proc Natl Acad Sci U S A ; 115(34): 8472-8474, 2018 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-30093390
18.
Proc Natl Acad Sci U S A ; 110(47): 18892-7, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24191023

RESUMO

Hematopoietic stem and progenitor cells, as well as nucleated erythroblasts and megakaryocytes, reside preferentially in adult marrow microenvironments whereas other blood cells readily cross the endothelial barrier into the circulation. Because the nucleus is the largest organelle in blood cells, we hypothesized that (i) cell sorting across microporous barriers is regulated by nuclear deformability as controlled by lamin-A and -B, and (ii) lamin levels directly modulate hematopoietic programs. Mass spectrometry-calibrated intracellular flow cytometry indeed reveals a lamin expression map that partitions human blood lineages between marrow and circulating compartments (P = 0.00006). B-type lamins are highly variable and predominate only in CD34(+) cells, but migration through micropores and nuclear flexibility in micropipette aspiration both appear limited by lamin-A:B stoichiometry across hematopoietic lineages. Differentiation is also modulated by overexpression or knockdown of lamins as well as retinoic acid addition, which regulates lamin-A transcription. In particular, erythroid differentiation is promoted by high lamin-A and low lamin-B1 expression whereas megakaryocytes of high ploidy are inhibited by lamin suppression. Lamins thus contribute to both trafficking and differentiation.


Assuntos
Células-Tronco Adultas/citologia , Núcleo Celular/metabolismo , Eritropoese/fisiologia , Laminas/metabolismo , Trombopoese/fisiologia , Células-Tronco Adultas/fisiologia , Biofísica , Linhagem da Célula/fisiologia , Movimento Celular/fisiologia , Citometria de Fluxo/métodos , Humanos , Espectrometria de Massas/métodos , Reologia
19.
Nat Mater ; 13(10): 970-8, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24930031

RESUMO

In vitro models of normal mammary epithelium have correlated increased extracellular matrix (ECM) stiffness with malignant phenotypes. However, the role of increased stiffness in this transformation remains unclear because of difficulties in controlling ECM stiffness, composition and architecture independently. Here we demonstrate that interpenetrating networks of reconstituted basement membrane matrix and alginate can be used to modulate ECM stiffness independently of composition and architecture. We find that, in normal mammary epithelial cells, increasing ECM stiffness alone induces malignant phenotypes but that the effect is completely abrogated when accompanied by an increase in basement-membrane ligands. We also find that the combination of stiffness and composition is sensed through ß4 integrin, Rac1, and the PI3K pathway, and suggest a mechanism in which an increase in ECM stiffness, without an increase in basement membrane ligands, prevents normal α6ß4 integrin clustering into hemidesmosomes.


Assuntos
Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Matriz Extracelular/fisiologia , Glândulas Mamárias Humanas/patologia , Glândulas Mamárias Humanas/fisiopatologia , Alginatos/metabolismo , Membrana Basal/fisiologia , Materiais Biocompatíveis , Fenômenos Biofísicos , Linhagem Celular , Epitélio/patologia , Epitélio/fisiopatologia , Feminino , Ácido Glucurônico/metabolismo , Hemidesmossomos/fisiologia , Ácidos Hexurônicos/metabolismo , Humanos , Integrina alfa6beta4/metabolismo , Ligantes , Mecanotransdução Celular/fisiologia , Modelos Biológicos , Fenótipo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP/metabolismo
20.
Ann Surg Oncol ; 22(4): 1219-25, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25326398

RESUMO

BACKGROUND: Robotic surgery was developed to overcome the limitations of laparoscopic surgery and is increasingly used to treat low rectal cancer. In this study, we compared the operative, oncological, and functional outcomes of low rectal cancer patients who underwent robotic or laparoscopic intersphincteric resection (ISR). METHODS: Prospectively collected data from low rectal cancer patients who underwent laparoscopic or robotic ISR between September 2006 and August 2011 were retrospectively compared. The functional outcomes of patients followed up for ≥ 12 months after ileostomy closure were evaluated via questionnaire. RESULTS: Forty-four and 26 patients underwent robotic and laparoscopic ISR, respectively. The robotic group patients had a higher body mass index (BMI; 21.42 ± 3.13 vs. 24.13 ± 3.33 kg/m(2); p = 0.001), more advanced clinical N stage (p = 0.029), lower cancer location (3.71 ± 0.89 vs. 3.24 ± 0.78 cm; p = 0.023), more frequent chemoradiotherapy (26.9 vs. 54.5 %; p = 0.025), and longer operation time (286.77 ± 51.46 vs. 316.43 ± 65.11 min; p = 0.038). However, no intergroup differences were observed in the pathological details (except the number of retrieved lymph nodes), postoperative morbidity, 3-year overall survival, recurrence-free survival (RFS), local RFS, and functional outcomes. CONCLUSIONS: Robotic and laparoscopic ISR yielded similar operative, oncological, and functional outcomes in patients with low rectal cancer, despite differences in unfavorable outcome-affecting factors, including BMI, clinical N stage, cancer location, and chemoradiotherapy frequency. A randomized trial will provide more solid methodology for investigating the potential benefits of robotic ISR.


Assuntos
Adenocarcinoma/cirurgia , Canal Anal/cirurgia , Laparoscopia/métodos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Robótica/métodos , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Canal Anal/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Complicações Pós-Operatórias , Prognóstico , Estudos Prospectivos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia , Estudos Retrospectivos , Taxa de Sobrevida
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