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Detection of lysozyme levels in ocular fluids is considered crucial for diagnosing and monitoring various health and eye conditions, including dry-eye syndrome. Hydrogel-based nanocomposites have been demonstrated to be one of the most promising platforms for fast and accurate sensing of different biomolecules. In this work, hydrogel, electrospun nanofibers, and plasmonic nanoparticles are combined to fabricate a sensitive and easy-to-use biosensor for lysozyme. Poly(L-lactide-co-caprolactone) (PLCL) nanofibers were covered with silver nanoplates (AgNPls), providing a stable plasmonic platform, where a poly(N-isopropylacrylamide)-based (PNIPAAm) hydrogel layer allows mobility and good integration of the biomolecules. By integrating these components, the platform can also exhibit a colorimetric response to the concentration of lysozyme, allowing for easy and non-invasive monitoring. Quantitative biosensing operates on the principle of localized surface plasmon resonance (LSPR) induced by plasmonic nanoparticles. Chemical, structural, thermal, and optical characterizations were performed on each platform layer, and the platform's ability to detect lysozyme at concentrations relevant to those found in tears of patients with dry-eye syndrome and other related diseases was investigated by colorimetry and UV-Vis spectroscopy. This biosensor's sensitivity and rapid response time, alongside the easy detection by the naked eye, make it a promising tool for early diagnosis and treatment monitoring of eye diseases.
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Resinas Acrílicas , Técnicas Biosensibles , Colorimetría , Muramidasa , Nanocompuestos , Plata , Resonancia por Plasmón de Superficie , Muramidasa/análisis , Muramidasa/metabolismo , Colorimetría/métodos , Plata/química , Nanocompuestos/química , Resinas Acrílicas/química , Humanos , Hidrogeles/química , Nanopartículas del Metal/química , Nanofibras/químicaRESUMEN
Polycaprolactone (PCL), a recognized biopolymer, has emerged as a prominent choice for diverse biomedical endeavors due to its good mechanical properties, exceptional biocompatibility, and tunable properties. These attributes render PCL a suitable alternative biomaterial to use in biofabrication, especially the electrospinning technique, facilitating the production of nanofibers with varied dimensions and functionalities. However, the inherent hydrophobicity of PCL nanofibers can pose limitations. Conversely, acrylamide-based hydrogels, characterized by their interconnected porosity, significant water retention, and responsive behavior, present an ideal matrix for numerous biomedical applications. By merging these two materials, one can harness their collective strengths while potentially mitigating individual limitations. A robust interface and effective anchorage during the composite fabrication are pivotal for the optimal performance of the nanoplatforms. Nanoplatforms are subject to varying degrees of tension and physical alterations depending on their specific applications. This is particularly pertinent in the case of layered nanostructures, which require careful consideration to maintain structural stability and functional integrity in their intended applications. In this study, we delve into the influence of the fiber dimensions, orientation and surface modifications of the nanofibrous layer and the hydrogel layer's crosslinking density on their intralayer interface to determine the optimal approach. Comprehensive mechanical pull-out tests offer insights into the interfacial adhesion and anchorage between the layers. Notably, plasma treatment of the hydrophobic nanofibers and the stiffness of the hydrogel layer significantly enhance the mechanical effort required for fiber extraction from the hydrogels, indicating improved anchorage. Furthermore, biocompatibility assessments confirm the potential biomedical applications of the proposed nanoplatforms.
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The shortage of face masks and the lack of antipathogenic functions has been significant since the recent pandemic's inception. Moreover, the disposal of an enormous number of contaminated face masks not only carries a significant environmental impact but also escalates the risk of cross-contamination. This study proposes a strategy to upgrade available surgical masks into antibacterial masks with enhanced particle and bacterial filtration. Plasmonic nanoparticles can provide photodynamic and photothermal functionalities for surgical masks. For this purpose, gold nanorods act as on-demand agents to eliminate pathogens on the surface of the masks upon near-infrared light irradiation. Additionally, the modified masks are furnished with polymer electrospun nanofibrous layers. These electrospun layers can enhance the particle and bacterial filtration efficiency, not at the cost of the pressure drop of the mask. Consequently, fabricating these prototype masks could be a practical approach to upgrading the available masks to alleviate the environmental toll of disposable face masks.
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Nanofibras , Nanopartículas , Nanotubos , Máscaras , FiltraciónRESUMEN
In this study, we introduce a novel family of symmetrical thiophene-based small molecules with a Donor-Acceptor-Donor structure. These compounds feature three different acceptor units: benzo[c][1,2,5]thiadiazole (Bz), thieno[3,4-b]pyrazine (Pz), and thieno[1,2,5]thiadiazole (Tz), coupled with electron donor units based on a carbazole-thiophene derivative. Using Density Functional Theory (DFT), we investigate how the molecular geometry and strength of the central acceptor unit impact the redox and spectroscopic properties. Notably, the incorporation of Pz and Tz moieties induces a significant redshift in the absorption and emission spectra, which extend into the near-infrared (NIR) region, simultaneously reducing their energy gaps (~1.4-1.6â eV). This shift is attributed to the increased coplanarity of the oligomeric inner core, both in the ground (S0 ) and excited (S1 ) states, due to the enhanced quinoidal character as supported by bond-length alternation (BLA) analysis. These structural changes promote better π-electron delocalization and facilitate photoinduced charge transfer processes in optoelectronic devices. Notably, we show that Pz- and Tz-containing molecules exhibit NIR electrochromic behavior and present ambivalent character in bulk heterojunction (BHJ) solar cells. Finally, theoretical calculations suggest that these molecules could serve as effective two-photon absorption (2PA) probes, further expanding their potential in optoelectronic applications.
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Cross-linking of poly(vinyl alcohol) (PVA) creates a three-dimensional network by bonding adjacent polymer chains. The cross-linked structure, upon immersion in water, turns into a hydrogel, which exhibits unique absorption properties due to the presence of hydrophilic groups within the PVA polymer chains and, simultaneously, ceases to be soluble in water. The properties of PVA can be adjusted by chemical modification or blending with other substances, such as polymers, e.g., conductive poly[3-(potassium-5-butanoate)thiophene-2,5-diyl] (P3KBT). In this work, PVA-based conductive semi-interpenetrating polymer networks (semi-IPNs) are successfully fabricated. The systems are obtained as a result of electrospinning of PVA/P3KBT precursor solutions with different polymer concentrations and then cross-linking using "green", environmentally safe methods. One approach consists of thermal treatment (H), while the second approach combines stabilization with ethanol and heating (E). The comprehensive characterization allows to evaluate the correlation between the cross-linking methods and properties of nanofibrous hydrogels. While both methods are successful, the cross-linking density is higher in the thermally cross-linked samples, resulting in lower conductivity and swelling ratio compared to the E-treated samples. Moreover, the H-cross-linked systems have better mechanical properties-lower stiffness and greater tensile strength. All the tested systems are biocompatible, and interestingly, due to the presence of P3KBT, they show photoresponsivity to solar radiation generated by the simulator. The results indicate that both methods of PVA cross-linking are highly effective and can be applied to a specific system depending on the target, e.g., biomedical or electronic applications.
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In neuroscience, the acquisition of neural signals from the brain cortex is crucial to analyze brain processes, detect neurological disorders, and offer therapeutic brain-computer interfaces. The design of neural interfaces conformable to the brain tissue is one of today's major challenges since the insufficient biocompatibility of those systems provokes a fibrotic encapsulation response, leading to an inaccurate signal recording and tissue damage precluding long-term/permanent implants. The design and production of a novel soft neural biointerface made of polyacrylamide hydrogels loaded with plasmonic silver nanocubes are reported herein. Hydrogels are surrounded by a silicon-based template as a supporting element for guaranteeing an intimate neural-hydrogel contact while making possible stable recordings from specific sites in the brain cortex. The nanostructured hydrogels show superior electroconductivity while mimicking the mechanical characteristics of the brain tissue. Furthermore, in vitro biological tests performed by culturing neural progenitor cells demonstrate the biocompatibility of hydrogels along with neuronal differentiation. In vivo chronic neuroinflammation tests on a mouse model show no adverse immune response toward the nanostructured hydrogel-based neural interface. Additionally, electrocorticography acquisitions indicate that the proposed platform permits long-term efficient recordings of neural signals, revealing the suitability of the system as a chronic neural biointerface.
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Encéfalo , Hidrogeles , Ratones , Animales , Hidrogeles/farmacología , Conductividad Eléctrica , Corteza CerebralRESUMEN
In recent times, the use of personal protective equipment, such as face masks or respirators, is becoming more and more critically important because of common pollution; furthermore, face masks have become a necessary element in the global fight against the COVID-19 pandemic. For this reason, the main mission of scientists has become the development of face masks with exceptional properties that will enhance their performance. The versatility of electrospun polymer nanofibers has determined their suitability as a material for constructing "smart" filter media. This paper provides an overview of the research carried out on nanofibrous filters obtained by electrospinning. The progressive development of the next generation of face masks whose unique properties can be activated in response to a specific external stimulus is highlighted. Thanks to additional components incorporated into the fiber structure, filters can, for example, acquire antibacterial or antiviral properties, self-sterilize the structure, and store the energy generated by users. Despite the discovery of several fascinating possibilities, some of them remain unexplored. Stimuli-responsive filters have the potential to become products of large-scale availability and great importance to society as a whole.
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COVID-19 , Máscaras , Humanos , Pandemias/prevención & control , COVID-19/prevención & control , Filtración , Nanotecnología , Antivirales , Antibacterianos , PolímerosRESUMEN
Sorbus aucuparia L. is a source of edible fruits appreciated for their nutritional and medicinal properties. In this work some bioactivity mechanisms were evaluated, which might be connected with the traditional application of rowanberries in cardiovascular complications of diabetes. With the use of a panel of chemical and biological in vitro models the rowanberry extracts were proved to significantly inhibit the formation of advanced glycation end products, neutralise multiple oxidants generated in vivo, increase the non-enzymatic antioxidant capacity of human plasma and protect plasma components (proteins and lipids) against oxidative/nitrative damage at in vivo-relevant levels (1-5 µg/mL). Moreover, the extracts were found safe in cytotoxicity tests on the peripheral blood mononuclear cells. The comprehensive phytochemical profiling of the extracts (RP/HILIC-UHPLC-PDA-ESI-MS3, HPLC-PDA, and UV-spectrophotometric methods) led to the identification of 51 phenolics, including caffeic and ferulic acids pseudodepsides (34 compounds, prevailing isomers of chlorogenic acid and cynarin, total content up to 269.4 mg/g), flavonols (mostly quercetin glycosides, up to 5.8 mg/g), flavan-3-ol derivatives (proanthocyanidin oligomers and polymers, up to 17.0 mg/g), and simple phenolic acids. The experiments on model constituents of the extracts and correlation studies were used to evaluate contribution of polyphenols to the observed effects. Taking into account the possible additive and synergistic effects, the co-occurrence of various compounds was indicated as partly responsible for biological activity of the fruits. Considering both the composition and activity parameters, the methanol-water (1:1, v/v) extract and its concentrated phenolic fractions appeared to be the most advantageous for biological application.
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Sorbus , Frutas , Humanos , Leucocitos Mononucleares , Estrés Oxidativo , Fitoquímicos/farmacología , Extractos Vegetales/farmacologíaRESUMEN
Purpose: The diagnosis of adult GH deficiency (AGHD) is challenging and often requires confirmation with a GH stimulation test (GHST). The insulin tolerance test (ITT) is considered the reference standard GHST but is labor intensive, can cause severe hypoglycemia, and is contraindicated for certain patients. Macimorelin, an orally active GH secretagogue, could be used to diagnose AGHD by measuring stimulated GH levels after an oral dose. Materials and Methods: The present multicenter, open-label, randomized, two-way crossover trial was designed to validate the efficacy and safety of single-dose oral macimorelin for AGHD diagnosis compared with the ITT. Subjects with high (n = 38), intermediate (n = 37), and low (n = 39) likelihood for AGHD and healthy, matched controls (n = 25) were included in the efficacy analysis. Results: After the first test, 99% of macimorelin tests and 82% of ITTs were evaluable. Using GH cutoff levels of 2.8 ng/mL for macimorelin and 5.1 ng/mL for ITTs, the negative agreement was 95.38% (95% CI, 87% to 99%), the positive agreement was 74.32% (95% CI, 63% to 84%), sensitivity was 87%, and specificity was 96%. On retesting, the reproducibility was 97% for macimorelin (n = 33). In post hoc analyses, a GH cutoff of 5.1 ng/mL for both tests resulted in 94% (95% CI, 85% to 98%) negative agreement, 82% (95% CI, 72% to 90%) positive agreement, 92% sensitivity, and 96% specificity. No serious adverse events were reported for macimorelin. Conclusions: Oral macimorelin is a simple, well-tolerated, reproducible, and safe diagnostic test for AGHD with accuracy comparable to that of the ITT. A GH cutoff of 5.1 ng/mL for the macimorelin test provides an excellent balance between sensitivity and specificity.
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Pruebas Diagnósticas de Rutina/métodos , Hormona de Crecimiento Humana/deficiencia , Hipopituitarismo/diagnóstico , Indoles/administración & dosificación , Pruebas de Función Hipofisaria/métodos , Triptófano/análogos & derivados , Administración Oral , Adolescente , Adulto , Edad de Inicio , Anciano , Estudios Cruzados , Pruebas Diagnósticas de Rutina/efectos adversos , Femenino , Humanos , Hipopituitarismo/sangre , Hipopituitarismo/epidemiología , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Pruebas de Función Hipofisaria/efectos adversos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Triptófano/administración & dosificación , Triptófano/efectos adversos , Adulto JovenRESUMEN
In this study we present a new series of phenantridine-based substituted difluoroboranyls. The effects of substitution and double benzannulation on their photophysical properties were examined with experimental techniques and compared with the results obtained for previously reported quinoline and isoquinoline derivatives. The experimental characterizations are supported by state-of-the-art quantum-chemical calculations. In particular, the theoretical calculations were performed to gain insights into the complex nature of the relevant excited-states. These calculations reveal that both the nature of the substituent and its position on the phenyl ring significantly impact the magnitude of the electronic charge transferred upon excitation. Additionally, vibrationally resolved spectra were determined allowing for the analysis of the key vibrations playing a role in the band shapes.
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Weak organic acids like sorbic and acetic acid are widely used to prevent growth of spoilage organisms such as Bacilli. To identify genes involved in weak acid stress tolerance we screened a transposon mutant library of Bacillus subtilis for sorbic acid sensitivity. Mutants of the rodZ (ymfM) gene were found to be hypersensitive to the lipophilic weak organic acid. RodZ is involved in determining the cell's rod-shape and believed to interact with the bacterial actin-like MreB cytoskeleton. Since rodZ lies upstream in the genome of the essential gene pgsA (phosphatidylglycerol phosphate synthase) we hypothesized that expression of the latter might also be affected in rodZ mutants and hence contribute to the phenotype observed. We show that both genes are co-transcribed and that both the rodZ::mini-Tn10 mutant and a conditional pgsA mutant, under conditions of minimal pgsA expression, were sensitive to sorbic and acetic acid. Both strains displayed a severely altered membrane composition. Compared to the wild-type strain, phosphatidylglycerol and cardiolipin levels were lowered and the average acyl chain length was elongated. Induction of rodZ expression from a plasmid in our transposon mutant led to no recovery of weak acid susceptibility comparable to wild-type levels. However, pgsA overexpression in the same mutant partly restored sorbic acid susceptibility and fully restored acetic acid sensitivity. A construct containing both rodZ and pgsA as on the genome led to some restored growth as well. We propose that RodZ and PgsA play intertwined roles in membrane homeostasis and tolerance to weak organic acid stress.
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INTRODUCTION: GJB2 mutations are the most frequent reason of genetic congenital hearing loss. The aim of the study was to assess the prevalence of GJB2 mutations in the deaf and profound hearing loss children. MATERIAL AND METHODS: The material of the study was a group of 61 patients divided into two groups. Group I - 35 deaf or with profound sensorineural hearing loss children (the pupils of the deaf and hard of hearing school), aged 5-17 years (average 9.2 years), 14 males, 21 females, II - control group comprised 26 normal hearing patients, aged 5-16 years (average 10.4years), 14 males, 12 females (patients of Department of Pediatric Otolaryngology, Audiology and Phoniatrics, Medical University of Lodz). In both groups, exon 2 sequencing of GJB2 gene was performed. RESULTS: In group I in 6 patients (17%) 35delG in GJB2 gene was found. The patients were homozygotes, with negative family history of hearing loss. No other mutations in GJB2 gene were found. In group II no mutations in GJB2 were observed. CONCLUSIONS: The most frequent cause of hearing impairment in the deaf and profound sensorineural hearing loss children was 35delG mutation in GJB2 gene. No other mutations in GJB2 gene were detected.
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Conexina 26/genética , Sordera/congénito , Sordera/genética , Pérdida Auditiva Sensorineural/congénito , Pérdida Auditiva Sensorineural/genética , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Mutación , PoloniaRESUMEN
Pleomorphic adenoma, the most common benign nonvascular tumor of the parotid gland in juveniles, should be differentiated from other extremely rare tumors, including schwannoma. In this article, we present a rare case of an intraparotid schwannoma in a juvenile, along with the patient history, a description of pathological features, and the results of ultrastructural and immunohistochemical examination. The respective labeling indexes of Ki-67 and MCM-3, i.e., the mean proportions of positive tumor cells out of 1000 tumoral cells counted in 10 microscopic fields at ×400 magnification, given as a percentage, were found to be 0.82% and 0.4%, respectively.
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Neurilemoma/diagnóstico , Neoplasias de la Parótida/diagnóstico , Adolescente , Biomarcadores de Tumor/análisis , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Antígeno Ki-67/biosíntesis , Masculino , Microscopía Electrónica de Transmisión , Componente 3 del Complejo de Mantenimiento de Minicromosoma/análisis , Componente 3 del Complejo de Mantenimiento de Minicromosoma/biosíntesis , Neurilemoma/patología , Neurilemoma/ultraestructura , Neoplasias de la Parótida/patología , Neoplasias de la Parótida/ultraestructuraRESUMEN
BACKGROUND & OBJECTIVES: The fat mass and obesity-associated (FTO) gene is known to be associated with obesity. However, no data are available on the relation between FTO rs9930506 polymorphism and obesity in Polish population. The aim of this study was to evaluate an association between rs9930506 variants of the FTO gene and obesity in Polish adults. METHODS: The study group consisted of 442 adults, aged 33.9 ±12.7 yr, with mean BMI 27.2 ± 5.4 kg/m2. The following variables were determined for each subject: fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides. Real-time PCR was used to detect the A/G alleles of the rs9939506 polymorphism in the FTO gene. An association between the rs9930506 polymorphism and obesity was determined using codominant, dominant, and recessive models. The odds ratio (OR) was calculated to determine the risk of obesity associated with this polymorphism. RESULTS: It was observed that the presence of FTO rs9939506 G allele was associated with increased risk for obesity and this association was found significant in both recessive (OR = 1.72, P = 0.014) and co-dominant (OR = 1.36, P = 0.031) models of inheritance. The FTO rs9939506 GG homozygotes had a significantly higher BMI than those with other genotypes. INTERPRETATION & CONCLUSIONS: This study shows that FTO rs9939506 GG genotype is related to higher BMI and is associated with obesity in Polish adults.
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Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Obesidad/genética , Adulto , Alelos , Índice de Masa Corporal , HDL-Colesterol , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Obesidad/patología , Polonia , Polimorfismo de Nucleótido SimpleRESUMEN
The unprecedented N-pyridin-2-yl substituted benzo(thio)amides were prepared and subsequently converted into the cyclic difluoroboranyl (BF2) derivatives. Mass spectrometry, multinuclear NMR, IR, and elemental analysis confirmed the structure of these compounds. UV/vis and fluorescence spectroscopy as well as first-principle calculations were used to study their properties. For the first time, the influence of both the O/S replacement and presence/absence of the BF2 moiety on the photophysical properties of compounds exhibiting charge transfer properties were examined experimentally and theoretically. We show that the sulfur-containing compound has a much smaller emission quantum yield than its oxygen counterpart. The fluorescence quantum yield is much higher upon formation of the difluoroboranyl complex.
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Despite the immense growth in interest in difluoroborate dyes, the nature of the interactions of the boron atom within the N-BF2 -O kernel is not yet fully understood. Herein, a set of real-space bonding indicators is used to quantify the electronic characteristics of the dative N-B bond in difluoroborate derivatives. The atoms-in-molecules (AIM) partitioning scheme is complemented by the electron localizability indicator (ELI-D) approach, and both were applied to experimental and theoretical electron-density distributions (X-ray constrained wavefunction fitting vs. DFT calculations). Additionally, Fermi orbital analysis was introduced for small DFT models to support and extend the findings for structures that contain BF2 .
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A series of difluoroboranyls derived from amides carrying a variable π-conjugated spacer between the electron-donating (D) and electron-accepting (A) groups was synthesized and characterized with (1)H, (11)B, (13)C, (15)N, and (19)F NMR, electronic absorption, fluorescence spectroscopies, and first-principle calculations. The D-to-A distance in the series varied from 1.5 to 4.5 Å, causing bathochromic shifts of both the absorption and fluorescence maxima by more than 120 and 213 nm, respectively. These trends are rationalized by quantum-mechanical calculations that allow for quantification of the charge-transfer distance. Theoretical calculations were also performed to determine the vibronic couplings and thus to reproduce the experimental band shapes.
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While Ki-67 expression is frequently used as an indicator of tumor cell proliferation, alternative markers have also been proposed. Possible alternative indicators of proliferation are the minichromosome maintenance (MCM) proteins, whose levels are inversely associated with tumor cell differentiation. The aim of this preliminary study was to compare the levels of Ki-67 and MCM-3 expression in major salivary gland epithelial tumors in all children and adolescents who underwent surgery in our department in the years 2009-2014. The histopathological diagnosis of the subjects was reviewed, as well as the expression of Ki-67 and MCM-3 in post-op specimens of the tumors. The normality of data was checked with the Shapiro-Wilk test. The t test for independent variables or the U test was used as appropriate to determine statistically significant differences in the expression of Ki-67 and MCM-3. Five cases of pleomorphic adenoma, one of myoepithelioma, one of basal cell adenoma and one of mucoepidermoid carcinoma were identified. Significantly greater MCM-3 than Ki-67 expression was observed in every case. The results of our preliminary study emphasize the need for future research on MCM-3 as a sensitive proliferation marker, providing an alternative to Ki-67, in cases of various major salivary gland epithelial tumors in children and adolescents.
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Biomarcadores de Tumor/análisis , Antígeno Ki-67/biosíntesis , Componente 3 del Complejo de Mantenimiento de Minicromosoma/biosíntesis , Neoplasias de las Glándulas Salivales/patología , Adenoma/metabolismo , Adenoma/patología , Adenoma Pleomórfico/metabolismo , Adenoma Pleomórfico/patología , Adolescente , Carcinoma Mucoepidermoide/metabolismo , Carcinoma Mucoepidermoide/patología , Niño , Femenino , Humanos , Inmunohistoquímica , Antígeno Ki-67/análisis , Masculino , Componente 3 del Complejo de Mantenimiento de Minicromosoma/análisis , Mioepitelioma/metabolismo , Mioepitelioma/patología , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/metabolismoRESUMEN
The identification of human broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem revitalized hopes of developing a universal influenza vaccine. Using a rational design and library approach, we engineered stable HA stem antigens ("mini-HAs") based on an H1 subtype sequence. Our most advanced candidate exhibits structural and bnAb binding properties comparable to those of full-length HA, completely protects mice in lethal heterologous and heterosubtypic challenge models, and reduces fever after sublethal challenge in cynomolgus monkeys. Antibodies elicited by this mini-HA in mice and nonhuman primates bound a wide range of HAs, competed with human bnAbs for HA stem binding, neutralized H5N1 viruses, and mediated antibody-dependent effector activity. These results represent a proof of concept for the design of HA stem mimics that elicit bnAbs against influenza A group 1 viruses.
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Glicoproteínas Hemaglutininas del Virus de la Influenza/química , Glicoproteínas Hemaglutininas del Virus de la Influenza/inmunología , Subtipo H1N1 del Virus de la Influenza A/inmunología , Subtipo H5N1 del Virus de la Influenza A/inmunología , Vacunas contra la Influenza/inmunología , Gripe Humana/prevención & control , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Humanos , Ratones , Multimerización de Proteína , Estructura Secundaria de ProteínaRESUMEN
Acute and chronic injuries are characterized by leukocyte infiltration into tissues. Although matrix metalloproteinase 9 (Mmp9) has been implicated in both conditions, its role in wound repair remains unclear. We previously reported a zebrafish chronic inflammation mutant caused by an insertion in the hepatocyte growth factor activator inhibitor gene 1 (hai1; also known as spint1) that is characterized by epithelial extrusions and neutrophil infiltration into the fin. Here, we performed a microarray analysis and found increased inflammatory gene expression in the mutant larvae, including a marked increase in mmp9 expression. Depletion of mmp9 partially rescued the chronic inflammation and epithelial phenotypes, in addition to restoring collagen fiber organization, as detected by second-harmonic generation imaging. Additionally, we found that acute wounding induces epithelial cell mmp9 expression and is associated with a thickening of collagen fibers. Interestingly, depletion of mmp9 impaired this collagen fiber reorganization. Moreover, mmp9 depletion impaired tissue regeneration after tail transection, implicating Mmp9 in acute wound repair. Thus, Mmp9 regulates both acute and chronic tissue damage and plays an essential role in collagen reorganization during wound repair.