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1.
Angew Chem Int Ed Engl ; 63(3): e202313591, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38011010

RESUMEN

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) are emerging as a unique subclass of layer-stacked crystalline coordination polymers that simultaneously possess porous and conductive properties, and have broad application potential in energy and electronic devices. However, to make the best use of the intrinsic electronic properties and structural features of 2D c-MOFs, the controlled synthesis of hierarchically nanostructured 2D c-MOFs with high crystallinity and customized morphologies is essential, which remains a great challenge. Herein, we present a template strategy to synthesize a library of 2D c-MOFs with controlled morphologies and dimensions via insulating MOFs-to-c-MOFs transformations. The resultant hierarchically nanostructured 2D c-MOFs feature intrinsic electrical conductivity and higher surface areas than the reported bulk-type 2D c-MOFs, which are beneficial for improved access to active sites and enhanced mass transport. As proof-of-concept applications, the hierarchically nanostructured 2D c-MOFs exhibit a superior performance for electrical properties related applications (hollow Cu-BHT nanocubes-based supercapacitor and Cu-HHB nanoflowers-based chemiresistive gas sensor), achieving over 225 % and 250 % improvement in specific capacity and response intensity over the corresponding bulk type c-MOFs, respectively.

2.
Respir Res ; 24(1): 21, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36670409

RESUMEN

BACKGROUND: Receptor for Advanced Glycated Endproducts (RAGE) plays a major role in the inflammatory response to infectious and toxin induced acute lung injury. We tested the hypothesis that a RAGE blocking antibody when administered after the onset of injury can reduce lung inflammation compared to control antibody. METHODS: Male and female C57BL/6 (WT) mice were used. Forty-six received lipopolysaccharide (LPS) and 26 PBS by nasal instillation on day one, repeated on day three. On day 2, 36 mice receiving LPS were divided into two groups of 18, one treated with 200 µg of non-immune isotype control IgG and the second group treated with 200 µg of anti-RAGE Ab, each dose divided between IV and IP. Ten of the 46 were not treated. On day 4, before euthanasia, mice were injected with fluorescein isothiocyanate (FITC) labelled albumen. BALF and serum samples were collected as well as lung tissue for immunohistochemistry (IHC). BALF was analyzed for cell (leukocyte) counts, for FITC BALF/serum ratios indicating pulmonary vascular leak, and for cytokines/chemokines using bead based multiplex assays. Quantitative IHC was performed for MPO and RAGE. RESULTS: Ten LPS mice showed minimal inflammation by all measures indicating poor delivery of LPS and were excluded from analysis leaving n = 11 in the LPS + IgG group and n = 12 in the LPS + anti-RAGE group. BALF cell counts were low in the PBS administered mice (4.9 ± 2.1 × 105/ml) and high in the LPS injured untreated mice (109 ± 34) and in the LPS + IgG mice (91 ± 54) while in comparison, LPS + anti-RAGE ab mice counts were significantly lower (51.3 ± 18 vs. LPS + IgG, P = 0.03). The BALF/serum FITC ratios were lower for the LPS + anti-RAGE mice than for the LPS + IgG mice indicating less capillary leakiness. Quantitative IHC RAGE staining was lower in the LPS + anti-RAGE ab mice than in the LPS + IgG treated mice (P = 0.02). CONCLUSIONS: These results describe a four-day LPS protocol to sustain lung injury and allow for treatment and suggests that treatment aimed at blocking RAGE when given after onset of injury can reduce lung inflammation.


Asunto(s)
Lesión Pulmonar Aguda , Neumonía , Femenino , Masculino , Animales , Ratones , Lipopolisacáridos/toxicidad , Fluoresceína-5-Isotiocianato/metabolismo , Ratones Endogámicos C57BL , Lesión Pulmonar Aguda/tratamiento farmacológico , Pulmón/metabolismo , Inflamación/metabolismo , Neumonía/inducido químicamente , Neumonía/metabolismo , Inmunoglobulina G/metabolismo
3.
Int Wound J ; 20(3): 678-686, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35945908

RESUMEN

Receptor for Advanced Glycated End-products (RAGE) is highly expressed in diabetes and impairs wound healing. We proposed that administering an antibody that blocks RAGE will hasten the healing of dorsal wounds in diabetic pigs compared with a non-immune IgG. Two purpose-bred diabetic (D) Yucatan minipigs (Sinclair, Auxvasse MO) each underwent 12 2 × 2 cm full thickness dorsal wounds: four wounds received decellularized porcine skin patches (Xylyx Bio, Bklyn NY): four anti-RAGE Ab (CR-3) infused patches, four saline infused patches and four wounds were left open. One pig received anti-RAGE Ab (CR-3) 1 mg/kg IM q 10 days and other received non-immune IgG. Wounds were measured at 2 and 4 weeks followed by euthanasia and wound harvesting. At 2 weeks few of the patches appeared to be incorporated into the wound. By 4 weeks all patches in pigs treated systemically with CR-3 were detached and the wounds almost healed. For all 24 wounds for both pigs regardless of presence of patch or type of patch, the average IgG treated pig wound size at 4 weeks was 69.2 ± 14.6% of initial size and the average CR-3 treated pig wound size was 40.9 ± 11.3% of initial size (P = 0.0002). Quantitative immunohistology showed greater staining for collagen in the CR-3 treated wounds compared with IgG treated. Staining was positive for RAGE, Mac, and IL-6 in the IgG treated wounds and negative in the CR-3 treated wounds. From these pilot experiments, we conclude that a RAGE blocking antibody given parenterally improved wound healing in a diabetic pig while patches were not effective.


Asunto(s)
Diabetes Mellitus , Cicatrización de Heridas , Porcinos , Animales , Porcinos Enanos , Colágeno , Inmunoglobulina G
4.
Langmuir ; 36(13): 3471-3481, 2020 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-32162927

RESUMEN

Thermotropic ionic liquid crystals of polyoxometalate (POM)-based ionic liquids (POM-based ILs), which are formed by a POM, K7PW11O39, and cationic surfactants, tetra-n-alkylammonium bromide ((CnH2n+1)4N+Br-, n = 6 and 7), are first proposed. As a model system, the cubic phase structure of a POM-based IL, {(C7H15)4N+}7PW11O39, was determined to form in a wide range of temperatures, exhibiting good thermostability, excellent mechanical strength, and high viscosity. Furthermore, the lyotropic ionic liquid crystals formed by {(C7H15)4N+}7PW11O39 in solvents such as chloroform or toluene still maintained a cubic structure. These cubic ionic liquid crystals (CILCs) were used as anticorrosion coatings both in acidic and neutral environments. The electrochemical measurements of Cu and Fe surfaces coated by CILCs showed an excellent ability of anticorrosion, indicating that the metals can be perfectly protected by the CILC coatings with high resistance and low capacitance. We assume that the CILCs may serve as barriers to stop oxygen diffusing to metals and interrupt the electron tunnels between the metal surfaces and the electrolyte solutions. Such environmentally friendly CILCs of POMs-based ILs are convenient for coating and removal, being vital to versatile industrial and academic applications.

5.
Langmuir ; 35(26): 8806-8815, 2019 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-31244259

RESUMEN

Biomineralization is a typical methodology developed by nature to produce calcium-based materials. A method mimicking this process has nowadays become popular for the preparation of artificial organic-inorganic hybrids. Here, Cu3(PO4)2 crystals with a flowerlike morphology have been prepared using water-soluble derivatives of fullerene C60 as templates. In a typical system, flowerlike crystals of Cu3(PO4)2 (denoted FLCs-Cu) were obtained by simply dropping an aqueous solution of CuSO4 into phosphate-buffered saline (PBS) containing a highly water-soluble multiadduct of C60 (fullerenol). The best condition for the preparation of FLCs-Cu appeared at 0.20 mg·mL-1 fullerenol and 0.10 mol·L-1 PBS. During the formation of FLCs-Cu, fullerenol acts as a template and its content in FLCs-Cu is trace (less than 5% by atom) as confirmed by scanning electron microscopy mapping and thermogravimetric analysis. This feature makes fullerenol reusable, and the FLCs-Cu can be prepared repeatedly using the same fullerenol aqueous solution at least 10 times without a noticeable change in the morphology. The N2 adsorption/desorption isotherm showed that the doping of fullerenol increased the specific surface area of the Cu3(PO4)2 crystal. When fullerenol was replaced by C60 monoadducts that are cofunctionalized with a pyrrolidine cation and oligo(poly(ethylene oxide)) chains, FLCs-Cu can form as well, indicating that the strategy of using water-soluble C60 derivative as a template to get FLCs-Cu is universal. As a typical example of practical applications, the photocatalytic activity of the FLCs-Cu was investigated toward the degradation of dyes including rhodamine B and rhodamine 6G. In both cases, efficient photodegradation has been confirmed.

6.
Chemistry ; 24(59): 15912-15920, 2018 Oct 22.
Artículo en Inglés | MEDLINE | ID: mdl-30033525

RESUMEN

A series of EuIII complexes with thenoyltrifluoroacetone (tta) as the ligands were synthesized, which are balanced with imidazolium cations bearing naphthyl and branched alkyl chains. The complex with the longest alkyl chain (1Eu(tta)4 ) shows aggregation behavior in ethanol and water mixtures. It exists as individuals at low water percentages (VH2O ), and form particles with solid interiors at VH2O ≥50 % the sizes of which decrease with the increase of VH2O . At VH2O =90 %, vesicles were observed. The aggregation of 1Eu(tta)4 in ethanol and water binary mixtures induced changes of the photoluminescence (PL) properties where an abrupt increase in PL intensity, quantum yield, and lifetime were noticed above VH2O =50 %. This PL enhancement can be explained by the encapsulation of 1Eu(tta)4 inside the aggregates, preventing it from quenching by the active hydroxyls of water molecules. Contrary to the aggregation-induced emission (AIE) of the Eu complex, the naphthyl group in the imidazolium cation exhibited an aggregation-caused quenching (ACQ) effect. When the length of the alkyl chain in the imidazolium cation is reduced, no PL enhancement can be observed owing to the difficulty in forming the aggregates.

7.
Chemistry ; 23(43): 10413-10422, 2017 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-28580665

RESUMEN

Self-assembly exploits noncovalent interactions to offer a facile and effective method for the construction of soft materials with multifunctionalities and diversity. In this work, fluorescence carbon quantum dots coordinated by Ce3+ ions (CQDCe) have been synthesized and exploited as building blocks to generate a series of hierarchical structures through the ionic self-assembly of CQDCe and biomolecules, namely DNA, myoglobin (Mb), and hyaluronic acid (HA). In particular, vesicles can be constructed by the simple mixing of oppositely charged CQDCe and DNA in water. The formation of unusual vesicles can be explained by the self-assembly of CQDCe with a rearranged structure and the rigid DNA biomolecular scaffolds. This facile noncovalent self-assembly method has inspired the innovative use of virgin DNA as a building block to construct vesicles rather than resorting to a sophisticated synthesis. The self-assembly of CQDCe-biopolymers was accompanied by aggregation-induced photoluminescence (PL) quenching. The biosensing platform was designed to detect polypeptides and deoxyribonuclease I through competitive binding of CQDCe and enzymatic hydrolysis of the DNA backbone, respectively. We believe that the integrative self-assembly of CQDCe and DNA will enrich the theoretical study of vesicle formation by DNA molecules and extend the application of fluorescence carbon quantum dots in the biological field.


Asunto(s)
Técnicas Biosensibles/métodos , Carbono/química , Cerio/química , ADN/química , Puntos Cuánticos/química , Desoxirribonucleasa I/análisis , Fluorescencia , Hidrólisis , Espectroscopía de Resonancia Magnética/métodos , Microscopía Electrónica de Transmisión/métodos , Tamaño de la Partícula , Péptidos/análisis , Espectrofotometría Ultravioleta/métodos , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Propiedades de Superficie
8.
Chemistry ; 23(30): 7278-7286, 2017 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-28370495

RESUMEN

Honeycomb-structured films represent an intriguing class of two-dimensional porous materials. Specifically, polyoxometalate (POM) macroanions can be introduced into these films by complexing with oppositely charged, double-tailed surfactants. Here highly-ordered honeycomb structures are reported that can be constructed by the complexes between POMs and a room temperature ionic liquid (IL1) having an imidazolium moiety in the middle and a naphthyl unit and a branched aliphatic chain at the ends. The complexes can be produced through phase transfer between an aqueous solution of POMs (typically {Mo72 Fe30 }) and a CS2 (or chloroform) solution of IL1. Based on the intrinsic properties of {Mo72 Fe30 } and the functional groups of the IL1, the honeycomb structures show multiple functions with bright photoluminescence and rich electrochemical properties. This work shows that by simply engineering the organic ligands involved in the POM-based inorganic-organic complexes, supramolecular structures with improved properties and wide applications can be obtained.

9.
Chemistry ; 22(18): 6286-93, 2016 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-26929087

RESUMEN

Obtaining π-conjugated room temperature ionic liquids (RTILs) is difficult because of the relatively strong π-π interaction among the π-moieties. Existing strategies by using bulky counterions greatly hindered further property optimization and potential applications of these intriguing functional fluids through simple ion exchange. Herein, four naphthalene-functionalized, π-conjugated RTILs with small counterions (Br(-) ) have been facilely synthesized with high yields. Our strategy is to attach branched alkyl chains to the cationic backbone of the target compounds (2 a-d), which effectively tune inter- and intramolecular interactions. Compounds 2 a-d have satisfactory thermal stability (up to 300 °C) and low melting points (<-19 °C). Rheological measurements revealed the fluid character of 2 a-d, whose viscosity decrease with the increase of the alkyl chain length and temperature. The presence of the π-conjugated naphthalene moiety imparts 2 a-d photoluminescent properties in bulk solutions. Moreover, the absence of strong π-π stacking among the naphthalene units in solvent-free states enables them to be used as a new generation of photoluminescent inks.

10.
Vasc Med ; 20(3): 212-8, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25808570

RESUMEN

We investigated treatment with a receptor for advanced glycation endproduct (RAGE) blocking antibody on angiogenic response to hind limb ischemia in diabetic mice. Streptozotocin treated C57BL/6 mice received either murine monoclonal anti-RAGE F(ab')2 intraperitoneally (n=10) or saline (n=9) for 9 weeks. Diabetic plus 10 non-diabetic C57BL/6 mice underwent left femoral artery ligation and 5 days later angiogenesis imaging with (99m)Tc-Arg-Gly-Asp (RGD) nanoSPECT/CT. Twenty-four days later, hind limb blood flow was measured with ultrasound, the mice were euthanized, and tissue was taken for immunohistochemistry. The angiogenic imaging signal in ischemic limbs was higher in RAGE-ab treated versus saline treated mice at day 5 (3.1±1.4 vs 1.68±0.35, p=0.02) and blood flow was higher at day 24 (1.49±0.5 vs 0.61±0.39, p=0.04). Immunohistochemistry of ischemic muscles showed greater capillary density in the RAGE-ab treated group versus the vehicle-treated group (p<0.001) (NS from non-diabetic mice). In conclusion, treatment with anti-RAGE F(ab')2 in diabetic mice improves neovascularization in the ischemic leg.


Asunto(s)
Anticuerpos/uso terapéutico , Miembro Posterior/irrigación sanguínea , Isquemia/tratamiento farmacológico , Neovascularización Fisiológica/efectos de los fármacos , Receptor para Productos Finales de Glicación Avanzada/inmunología , Animales , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1/complicaciones , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/etiología , Arteria Femoral , Ligadura , Masculino , Ratones , Ratones Endogámicos C57BL
11.
Proc Natl Acad Sci U S A ; 109(22): 8705-9, 2012 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-22586099

RESUMEN

In extensive bone defects, tissue damage and hypoxia lead to cell death, resulting in slow and incomplete healing. Human embryonic stem cells (hESC) can give rise to all specialized lineages found in healthy bone and are therefore uniquely suited to aid regeneration of damaged bone. We show that the cultivation of hESC-derived mesenchymal progenitors on 3D osteoconductive scaffolds in bioreactors with medium perfusion leads to the formation of large and compact bone constructs. Notably, the implantation of engineered bone in immunodeficient mice for 8 wk resulted in the maintenance and maturation of bone matrix, without the formation of teratomas that is consistently observed when undifferentiated hESCs are implanted, alone or in bone scaffolds. Our study provides a proof of principle that tissue-engineering protocols can be successfully applied to hESC progenitors to grow bone grafts for use in basic and translational studies.


Asunto(s)
Huesos/fisiología , Células Madre Embrionarias/citología , Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Reactores Biológicos , Trasplante Óseo/métodos , Huesos/citología , Huesos/metabolismo , Diferenciación Celular , Células Cultivadas , Células Madre Embrionarias/trasplante , Femenino , Humanos , Células Madre Mesenquimatosas/citología , Ratones , Ratones SCID , Osteogénesis/fisiología , Reproducibilidad de los Resultados , Factores de Tiempo
12.
Proc Natl Acad Sci U S A ; 108(19): 7974-9, 2011 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-21508321

RESUMEN

Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-ß promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.


Asunto(s)
Infarto del Miocardio/terapia , Miocardio/química , Ingeniería de Tejidos/métodos , Andamios del Tejido , Animales , Modelos Animales de Enfermedad , Matriz Extracelular/química , Fibrina , Humanos , Hidrogeles , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/fisiología , Infarto del Miocardio/patología , Infarto del Miocardio/fisiopatología , Neovascularización Fisiológica , Ratas , Ratas Desnudas , Factor de Crecimiento Transformador beta/farmacología , Trasplante Heterólogo , Función Ventricular Izquierda
13.
Mol Med Rep ; 26(2)2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35703348

RESUMEN

Sepsis­induced cardiac dysfunction is one of the most common types of organ dysfunction in sepsis; its pathogenesis is highly complex and not yet fully understood. Cardiomyocytes serve a key role in the pathophysiology of cardiac function; due to the limited ability of cardiomyocytes to regenerate, their loss contributes to decreased cardiac function. The activation of inflammatory signalling pathways affects cardiomyocyte function and modes of cardiomyocyte death in sepsis. Prevention of cardiomyocyte death is an important therapeutic strategy for sepsis­induced cardiac dysfunction. Thus, understanding the signalling pathways that activate cardiomyocyte death and cross­regulation between death modes are key to finding therapeutic targets. The present review focused on advances in understanding of sepsis­induced cardiomyocyte death pathways, including apoptosis, necroptosis, mitochondria­mediated necrosis, pyroptosis, ferroptosis and autophagy. The present review summarizes the effect of inflammatory activation on cardiomyocyte death mechanisms, the diversity of regulatory mechanisms and cross­regulation between death modes and the effect on cardiac function in sepsis to provide a theoretical basis for treatment of sepsis­induced cardiac dysfunction.


Asunto(s)
Cardiopatías , Sepsis , Apoptosis , Autofagia , Cardiopatías/metabolismo , Humanos , Miocitos Cardíacos/metabolismo , Sepsis/metabolismo
14.
J Phys Chem Lett ; 13(39): 8999-9006, 2022 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-36149259

RESUMEN

Artificial light-harvesting systems (ALHSs), which are closely related to Förster resonance energy transfer (FRET), are among the most attractive scientific topics during the past few decades. Specifically, binary ALHSs that are composed of a fluid donor and acceptor have a simplified composition and high number density of the donor units. However, largely due to the difficulty in obtaining a fluid donor, investigation of these systems is still quite limited, especially for the ionic systems. Herein, we report a new type of binary ALHS using an ionic naphthalimide (NPI) derivative as a donor, which shows greatly improved photoluminescence for its bicontinuous liquid structure. When blending with an acceptor such as rhodamine 6G or trans-4-[4-(dimethylamino)styryl]-methylpyridinium iodide, efficient FRET was confirmed by both experimental results and molecular dynamics simulations, with an energy transfer efficiency up to ∼90%. Tunable color, including white-light emission, was achieved by tuning the acceptor/donor ratio, opening the door for a variety of applications such as light-emitting diodes and photoluminescent inks.


Asunto(s)
Yoduros , Naftalimidas , Transferencia Resonante de Energía de Fluorescencia , Iones , Luz
15.
JCI Insight ; 7(2)2022 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-34905515

RESUMEN

Acute cardiac injury is prevalent in critical COVID-19 and associated with increased mortality. Its etiology remains debated, as initially presumed causes - myocarditis and cardiac necrosis - have proved uncommon. To elucidate the pathophysiology of COVID-19-associated cardiac injury, we conducted a prospective study of the first 69 consecutive COVID-19 decedents at CUIMC in New York City. Of 6 acute cardiac histopathologic features, presence of microthrombi was the most commonly detected among our cohort. We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak erythrocyte sedimentation rate and C-reactive protein were independently associated with increased odds of microthrombi, supporting an immunothrombotic etiology. Using single-nuclei RNA-sequencing analysis on 3 patients with and 4 patients without cardiac microthrombi, we discovered an enrichment of prothrombotic/antifibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling among cardiac fibroblasts in microthrombi-positive, relative to microthrombi-negative, COVID-19 hearts. Non-COVID-19, nonfailing hearts were used as reference controls. Our study identifies a specific transcriptomic signature in cardiac fibroblasts as a salient feature of microthrombi-positive COVID-19 hearts. Our findings warrant further mechanistic study as cardiac fibroblasts may represent a potential therapeutic target for COVID-19-associated cardiac microthrombi.


Asunto(s)
COVID-19 , Lesiones Cardíacas , RNA-Seq , SARS-CoV-2/metabolismo , Trombosis , Adulto , Anciano , Anciano de 80 o más Años , COVID-19/genética , COVID-19/metabolismo , COVID-19/patología , Femenino , Lesiones Cardíacas/genética , Lesiones Cardíacas/metabolismo , Lesiones Cardíacas/patología , Humanos , Masculino , Persona de Mediana Edad , Miocardio/metabolismo , Miocardio/patología , Estudios Prospectivos , Trombosis/genética , Trombosis/metabolismo , Trombosis/patología
16.
J Am Heart Assoc ; 10(1): e016696, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33327730

RESUMEN

Background Expression of receptor for advanced glycation end products (RAGE) plays an important role in diabetic peripheral artery disease. We proposed to show that treatment with an antibody blocking RAGE would improve hind limb perfusion and muscle viability in diabetic pig with femoral artery (FA) ligation. Methods and Results Purpose-bred diabetic Yucatan minipigs with average fasting blood sugar of 357 mg/dL on insulin to maintain a glucose range of 300 to 500 mg/dL were treated with either a humanized monoclonal anti-RAGE antibody (CR-3) or nonimmune IgG. All pigs underwent intravascular occlusion of the anterior FA. Animals underwent (201Tl) single-photon emission computed tomography/x-ray computed tomography imaging on days 1 and 28 after FA occlusion, angiogenesis imaging with [99mTc]dodecane tetra-acetic acid-polyethylene glycol-single chain vascular endothelial growth factor (scVEGF), muscle biopsies on day 7, and contrast angiogram day 28. Results showed greater increases in perfusion to the gastrocnemius from day 1 to day 28 in CR-3 compared with IgG treated pigs (P=0.0024), greater uptake of [99mTc]dodecane tetra-acetic acid-polyethylene glycol-scVEGF (scV/Tc) in the proximal gastrocnemius at day 7, confirmed by tissue staining for capillaries and vascular endothelial growth factor A, and less muscle loss and fibrosis at day 28. Contrast angiograms showed better reconstitution of the distal FA from collaterals in the CR-3 versus IgG treated diabetic pigs (P=0.01). The gastrocnemius on nonoccluded limb at necropsy had higher 201Tl uptake (percentage injected dose per gram) and reduced RAGE staining in arterioles in CR-3 treated compared with IgG treated animals (P=0.04). Conclusions A novel RAGE-blocking antibody improved hind limb perfusion and angiogenesis in diabetic pigs with FA occlusion. Contributing factors are increased collaterals and reduced vascular RAGE expression. CR-3 shows promise for clinical treatment in diabetic peripheral artery disease.


Asunto(s)
Inductores de la Angiogénesis/farmacología , Anticuerpos Monoclonales/farmacología , Angiopatías Diabéticas , Enfermedad Arterial Periférica , Receptor para Productos Finales de Glicación Avanzada , Angiografía/métodos , Animales , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/metabolismo , Angiopatías Diabéticas/tratamiento farmacológico , Angiopatías Diabéticas/metabolismo , Descubrimiento de Drogas/métodos , Productos Finales de Glicación Avanzada/metabolismo , Miembro Posterior/irrigación sanguínea , Músculo Esquelético/irrigación sanguínea , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/etiología , Enfermedad Arterial Periférica/metabolismo , Receptor para Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Receptor para Productos Finales de Glicación Avanzada/inmunología , Porcinos , Porcinos Enanos , Resultado del Tratamiento
17.
bioRxiv ; 2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34341789

RESUMEN

Cardiac injury is associated with critical COVID-19, yet its etiology remains debated. To elucidate the pathogenic mechanisms of COVID-19-associated cardiac injury, we conducted a single-center prospective cohort study of 69 COVID-19 decedents. Of six cardiac histopathologic features, microthrombi was the most commonly detected (n=48, 70%). We tested associations of cardiac microthrombi with biomarkers of inflammation, cardiac injury, and fibrinolysis and with in-hospital antiplatelet therapy, therapeutic anticoagulation, and corticosteroid treatment, while adjusting for multiple clinical factors, including COVID-19 therapies. Higher peak ESR and CRP during hospitalization were independently associated with higher odds of microthrombi. Using single nuclei RNA-sequence analysis, we discovered an enrichment of pro-thrombotic/anti-fibrinolytic, extracellular matrix remodeling, and immune-potentiating signaling amongst cardiac fibroblasts in microthrombi-positive COVID-19 hearts relative to microthrombi-negative COVID-19. Non-COVID-19 non-failing hearts were used as reference controls. Our cumulative findings identify the specific transcriptomic changes in cardiac fibroblasts as salient features of COVID-19-associated cardiac microthrombi.

18.
J Cardiovasc Pharmacol ; 56(5): 506-12, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20881614

RESUMEN

BACKGROUND: It has been reported that erythropoietin (EPO) attenuates ischemia-induced damage in a variety of tissues. It is unknown whether EPO alters the left ventricular (LV) remodeling process after ischemic insult. Accordingly, we tested the potential benefits of carbamylated EPO (CEPO) on LV remodeling in rats with myocardial infarction (MI). METHODS: MI was induced by coronary artery ligation in adult male Sprague-Dawley rats. One hour after surgery, rats were randomly assigned to 1 of 2 groups: MI plus placebo injections (placebo, n = 21) and MI plus CEPO injection (CEPO, n = 22). CEPO (10 µg/kg) or placebo was given via tail vein in a blinded fashion daily for the first 3 days, followed by twice a week subcutaneous injection for 6 weeks. Sham surgery was performed in another group of rats (n = 18) without coronary artery ligation. Cardiac function was assessed by echocardiography, hemodynamic, and in vivo and ex vivo LV pressure-volume relationship measurements 6 weeks after MI. RESULTS: In comparison to placebo-treated rats, CEPO significantly improved LV geometry (LV end systolic dimension: 8.6 ± 0.8 vs. 9.6 ± 1.0 mm; LV end systolic volume: 404 ± 83 vs. 516 ± 122 µL, both P < 0.05). CEPO therapy also reduced the decline of systolic function (fractional shortening: -3.7% ± 1.7% vs. -10.9% ± 2.3%; Emax 0.46 ± 0.20 vs. 0.25 ± 0.08 mm Hg/s, both P < 0.05). Passive diastolic properties of the LV were minimally improved by leftward shift in the ex vivo end diastolic pressure-volume relationship. CONCLUSIONS: CEPO administration 1 hour after acute MI improves systolic performance and may attenuate the LV remodeling process. Further studies to determine the mechanism of CEPO responsible for its beneficial effects and optimize dosing and timing regimens are warranted.


Asunto(s)
Eritropoyetina/análogos & derivados , Insuficiencia Cardíaca/tratamiento farmacológico , Infarto del Miocardio/tratamiento farmacológico , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Animales , Esquema de Medicación , Ecocardiografía , Eritropoyetina/administración & dosificación , Eritropoyetina/farmacología , Eritropoyetina/uso terapéutico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Ratas , Ratas Sprague-Dawley
19.
ACS Appl Bio Mater ; 3(1): 358-368, 2020 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-35019452

RESUMEN

Fullerene C60 (refers to C60 hereafter) has a unique three-dimensional architecture and intriguing physicochemical properties. It has great potential applications in materials chemistry and life science. However, a big obstacle for the widespread application of C60 lies in the limited strategies to make supramolecular structures with diverse morphologies and functions. Herein, we report a strategy to prepare C60-based, magnetic microcapsules which can be used as external antioxidants to effectively attenuate oxidative stress. The microcapsules are composed of fullerenol, a highly water-soluble C60 multiadduct, and iron ions (Fe3+) released from a rusty nail. They can be easily obtained through coordination between the hydrophilic functional groups in fullerenol and Fe3+ with polystyrene microspheres as templates. The fullerenol/Fe3+ microcapsules have good colloidal stability both in water and serum. Their biocompatibility has been confirmed by in vitro tests on HEK293 and Hela cells. Electron spin resonance measurements indicate that the fullerenol/Fe3+ microcapsules can effectively scavenge hydroxyl radicals (OH·-) produced by H2O2, which greatly improves the living environment of the cells. The fullerenol/Fe3+ microcapsules exhibit ferromagnetic properties and can respond to the external magnetic field, enabling magnetic manipulation, and/or separation in practical applications.

20.
J Phys Chem B ; 124(22): 4651-4660, 2020 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-32383605

RESUMEN

We report the assembly of four imidazolium bromides, each of which bears a naphthyl on one side of the imidazolium cation and a branched alkyl chain on the other. This design creates a new type of amphiphilic ionic liquid with an apolar-polar-apolar structure and a low melting point (mp, <-20 °C), which has not been achieved by reported counterparts bearing linear alkyl chains. In solvent-free states, microphase segregation occurs where polar and apolar domains arrange bicontinuously as proved by molecular dynamics (MD) simulations. When dispersed in water, self-stabilized giant aggregates formed with ultrahigh colloidal stability (up to years). MD simulations provide clues of discrete bicontinuous phases within the giant aggregates. These newly discovered self-assemblies provide a heterogeneous reservoir that can accommodate guest molecules including the highly apolar fullerene C60, paving the way for a wide range of potential applications.

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