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1.
Molecules ; 29(14)2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39064907

RESUMO

Caffeic acid (CA), a hydrophobic polyphenol with various pharmacological activities, exhibits a low aqueous solubility and sensitivity to light. In order to improve its chemical properties and overcome the limits in its application, the compound was loaded in P123 micelles (MCs) prepared using two polymer concentrations (10 and 20% w/w, MC10 and MC20). The micelles were characterised in terms of the size distribution, zeta potential, drug encapsulation efficiency, rheology, and cumulative drug release. Micellar formulations exhibited sizes in the range of 11.70 and 17.70 nm and a good polydispersion, indicating the formation of relatively small-sized micelles, which is favourable for drug delivery applications. Additionally, the stability and antioxidant profiles of the free CA and the CA loaded in micelles were studied. The results obtained on the free CA showed the formation of photodegradation products endowed with higher DPPH scavenging activity with respect to the pure compound. Instead, it was found that the incorporation of CA into the micelles significantly increased its solubility and decreased the photodegradation rate. Overall, the results indicate the successful formation of P123 micelles loaded with CA, with promising characteristics such as a small size, good encapsulation efficiency, sustained release profile, and improved light stability. These findings suggest the potentiality of these micelles as a delivery system for CA, thus enhancing its bioavailability.


Assuntos
Ácidos Cafeicos , Micelas , Polímeros , Solubilidade , Ácidos Cafeicos/química , Polímeros/química , Antioxidantes/química , Estabilidade de Medicamentos , Liberação Controlada de Fármacos , Composição de Medicamentos , Tamanho da Partícula , Portadores de Fármacos/química
2.
Molecules ; 28(15)2023 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-37570599

RESUMO

The control of alumina morphology is crucial yet challenging for its various applications. Unfortunately, traditional methods for preparing alumina particles suffer from several limitations such as irregular morphology, poor dispersibility, and restricted application areas. In this study, we develop a novel method for preparing spherical mesoporous alumina using chitin and Pluronic P123 as mixed templates. The effects of reaction temperature, time, and the addition of mixed templates on the phase structure, micromorphology, and optical absorption properties of the samples were investigated. The experimental results indicate that lower temperature and shorter reaction time facilitated the formation of spherical mesoporous alumina with excellent CO2 adsorption capacity. The periodic density functional theory (DFT) calculations demonstrate that both the (110) and (100) surfaces of γ-Al2O3 can strongly adsorb CO2. The difference in the amount of CO2 adsorbed by Al2O3 is mainly due to the different surface areas, which give different numbers of exposed active sites. This approach introduces a novel strategy for utilizing biological compounds to synthesize spherical alumina and greatly enhances mesoporous alumina's application efficiency in adsorption fields. Moreover, this study explored the electrochemical performance of the synthesized product using cyclic voltammetry, and improved loading of electrocatalysts and enhanced electrocatalytic activity were discovered.

3.
J Fluoresc ; 31(1): 17-27, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33037527

RESUMO

Drug delivery systems for the sustained and target delivery of doxorubicin to tumor cells are a topic of interest due to the efficacy of the doxorubicin in cancer treatment. The use of polymers such as Pluronic is being studied widely for the formulation of doxorubicin hydrochloride. However, the basic understanding of the physicochemical properties of pluronic micelles in presence of doxorubicin hydrochloride is a very essential topic of study. Doxorubicin hydrochloride is fluorescent; this helped us to study its sensitivity towards the Pluronic microenvironment using the fluorescence technique. In this work, the interaction and place of location of doxorubicin hydrochloride in Pluronic F127 and P123 micelles has been studied extensively using steady-state fluorescence intensity, dynamic fluorescence lifetime, quenching studies, dynamic light scattering, and zeta potential measurements, at different Pluronic concentrations. Using a fluorescence quenching experiment, doxorubicin hydrochloride was found to reside near the hydrophilic PEO corona region of the Pluronic micelles. For both the Pluronic, in the concentration range of study, the micellar size was found to be below 30 nm; this may have a greater advantage for various applications.


Assuntos
Antineoplásicos/química , Doxorrubicina/química , Micelas , Poloxaleno/química , Polietilenos/química , Polipropilenos/química , Fluorescência , Interações Hidrofóbicas e Hidrofílicas
4.
Int J Mol Sci ; 21(8)2020 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-32325870

RESUMO

Dementia with Lewy bodies (DLB) is the second most prevalent neurodegenerative dementia after Alzheimer's disease, and is pathologically characterized by formation of intracellular inclusions called Lewy bodies, the major constituent of which is aggregated α-synuclein (αS). Currently, neither a mechanistic etiology nor an effective disease-modifying therapy for DLB has been established. Although two missense mutations of ß-synuclein (ßS), V70M and P123H, were identified in sporadic and familial DLB, respectively, the precise mechanisms through which ßS mutations promote DLB pathogenesis remain elusive. To further clarify such mechanisms, we investigated transgenic (Tg) mice expressing P123H ßS, which develop progressive neurodegeneration in the form of axonal swelling and non-motor behaviors, such as memory dysfunction and depression, which are more prominent than motor deficits. Furthermore, cross-breeding of P123H ßS Tg mice with αS Tg mice worsened the neurodegenerative phenotype presumably through the pathological cross-seeding of P123H ßS with αS. Collectively, we predict that ßS misfolding due to gene mutations might be pathogenic. In this paper, we will discuss the possible involvement of amyloidogenic evolvability in the pathogenesis of DLB based on our previous papers regarding the P123H ßS Tg mice. Given that stimulation of αS evolvability by P123H ßS may underlie neuropathology in our mouse model, more radical disease-modifying therapy might be derived from the evolvability mechanism. Additionally, provided that altered ßS were involved in the pathogenesis of sporadic DLB, the P123H ßS Tg mice could be used for investigating the mechanism and therapy of DLB.


Assuntos
Proteínas Amiloidogênicas/genética , Proteínas Amiloidogênicas/metabolismo , Doença por Corpos de Lewy/etiologia , Doença por Corpos de Lewy/metabolismo , beta-Sinucleína/genética , beta-Sinucleína/metabolismo , Alelos , Substituição de Aminoácidos , Animais , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Expressão Gênica , Humanos , Doença por Corpos de Lewy/patologia , Doença por Corpos de Lewy/terapia , Camundongos , Camundongos Transgênicos , Mutação
5.
Am J Med Genet A ; 179(7): 1157-1172, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30980518

RESUMO

3M syndrome is characterized by severe pre- and postnatal growth retardation, typical facial features, and normal intelligence. Homozygous or compound heterozygous mutations in either CUL7, OBSL1, or CCDC8 have been identified in the etiology so far. Clinical and molecular features of 24 patients (23 patients and a fetus) from 19 unrelated families with a clinical diagnosis of 3M syndrome were evaluated and genotype-phenotype correlations were investigated with the use of DNA sequencing, chromosomal microarray, and whole exome sequencing accordingly. A genetic etiology could be established in 20 patients (n = 20/24, 83%). Eleven distinct CUL7 or OBSL1 mutations, among which eight was novel, were identified in 18 patients (n = 18/24, 75%). Ten patients had CUL7 (n = 10/18, 56%) while eight had OBSL1 (n = 8/18, 44%) mutations. Birth weight and height standard deviation scores at admission were significantly (p < 0.05) lower in patients with CUL7 mutation compared to that of patients with OBSL1 mutation. Two patients with a similar phenotype had a de novo 20p13p deletion involving BMP2. No genetic etiology could be established in four patients (n = 4/28, 17%). This study yet represents the largest cohort of 3M syndrome patients from a single center in Turkey. Microdeletions involving BMP2 may cause a phenotype similar to 3M syndrome with some distinctive features. Larger cohort of patients are required to establish genotype-phenotype correlations in 3M syndrome.


Assuntos
Proteína Morfogenética Óssea 2/genética , Proteínas Culina/genética , Proteínas do Citoesqueleto/genética , Nanismo/genética , Estudos de Associação Genética , Hipotonia Muscular/genética , Mutação , Coluna Vertebral/anormalidades , Adolescente , Sequência de Bases , Proteína Morfogenética Óssea 2/deficiência , Criança , Pré-Escolar , Cromossomos Humanos Par 20 , Estudos de Coortes , Proteínas Culina/metabolismo , Proteínas do Citoesqueleto/metabolismo , Nanismo/diagnóstico , Nanismo/metabolismo , Nanismo/patologia , Feminino , Feto , Expressão Gênica , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Hipotonia Muscular/diagnóstico , Hipotonia Muscular/metabolismo , Hipotonia Muscular/patologia , Fenótipo , Coluna Vertebral/metabolismo , Coluna Vertebral/patologia , Sequenciamento do Exoma
6.
Pharm Dev Technol ; 24(3): 338-347, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29799305

RESUMO

In tissue engineering, it is common to mix drugs that can control proliferation and differentiation of cells into polymeric solutions as part of composite to get bioactive scaffolds. However, direct incorporation of drugs might potentially result in undesired burst release. To overcome this problem, here we developed electrospun multilayer drug loaded poly-l-lactic acid/pluronic P123 (PLLA-P123) composite scaffolds. The drug was loaded into the middle layer. The surface, the mechanical and physiochemical properties of the scaffolds were evaluated. The drug release profiles were monitored. Finally, the osteogenic proliferation and differentiation potential were determined. The scaffolds fabricated here have appropriate surface properties, but with different mechanical strength and osteogenic proliferation and differentiation. Multi-layer scaffolds where the drug was in the middle layer and PLLA-plasma and PLLA-P123 with cover layer showed the best osteogenic proliferation and differentiation than the other groups of scaffolds. The drug release profiles of the scaffolds were completely different: single layer scaffolds showed burst release within the first day, while multilayer scaffolds showed controlled release. Therefore, the multilayer drug loaded scaffolds prepared have dual benefits can provide both better osteogenesis and controlled release of drugs and bioactive molecules at the implant site.


Assuntos
Dexametasona/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanofibras , Engenharia Tecidual/métodos , Adulto , Osso e Ossos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Química Farmacêutica/métodos , Dexametasona/farmacologia , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Humanos , Pessoa de Meia-Idade , Osteogênese/efeitos dos fármacos , Poloxaleno/química , Poliésteres/química , Adulto Jovem
7.
Biosci Biotechnol Biochem ; 82(2): 238-246, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29327653

RESUMO

Quercetin (QT) is a plant polyphenol with various pharmacological properties. However, the low water solubility limits its therapeutic efficacy. In the present study, QT-loaded sodium taurocholate-Pluronic P123 (QT-loaded ST/P123) mixed micelles were developed and characterized, and the effect of the formulation on improving the water solubility of QT was investigated. QT-loaded ST/P123 mixed micelles were prepared by thin film hydration-direct dissolution and optimized by uniform design. The optimal formulation possessed high drug loading (12.6%) and entrapment efficiency (95.9%) in small (16.20 nm) spherically-shaped micelles. A low critical micelle concentration indicated that the micelles were stable, and they showed a sustained release pattern, as determined in vitro in simulated gastric fluid and intestinal fluid. Pharmacokinetic evaluation showed the Cmax and AUC0-24 were 1.8-fold and 1.6-fold higher than the QT suspension. The present results indicate that QT-loaded ST/P123 micelles are potential candidates to improve the solubility and oral bioavailability of QT.


Assuntos
Portadores de Fármacos/química , Micelas , Quercetina/administração & dosagem , Quercetina/química , Administração Oral , Animais , Líquidos Corporais/metabolismo , Liberação Controlada de Fármacos , Poloxaleno/química , Quercetina/farmacocinética , Ratos , Ratos Wistar , Solubilidade , Ácido Taurocólico/química , Distribuição Tecidual
8.
Cleft Palate Craniofac J ; 55(6): 891-894, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-27500518

RESUMO

OBJECTIVE: The aim of this article is to publish a literature review and report on a new case of cleidocranial dysplasia syndrome with 6p21.1-p12.3 microdeletion. DESIGN: A PubMed search using "cleidocranial dysplasia syndrome (CCD)" or "6p microdeletion" was performed. Articles with information relevant to our case were obtained for review. A new case of cleidocranial dysplasia syndrome is presented to describe and discuss clinical manifestations, pathogenesis, clinical progression of cleidocranial dysplasia syndrome, and management. RESULTS: There were 22 articles with reports of cleidocranial dysplasia syndrome or 6p microdeletion. Cleidocranial dysplasia syndrome, a rare genetic disorder, documented to have an autosomal dominant inheritance pattern and caused by caused by mutations of the transcription factor RUNX2. RUNX2 has been mapped to chromosome 6p21. The anomalies in cleidocranial dysplasia syndrome can involve not only the clavicle and skull but the entire skeleton because the membranous as well as endochondral bone formation may be affected. Upon follow-up, our patient was found to have global developmental delay. CONCLUSIONS: We report a near-term neonate with characteristic features of cleidocranial dysplasia and a 6p21.1-p12.3 microdeletion. Cleidocranial dysplasia syndrome is a rare autosomal dominant skeletal dysplasia. The mutation of the RUNX2 gene results in cleidocranial dysplasia syndrome.


Assuntos
Cromossomos Humanos Par 6/genética , Displasia Cleidocraniana/genética , Displasia Cleidocraniana/diagnóstico por imagem , Feminino , Deleção de Genes , Humanos , Recém-Nascido , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único
9.
Am J Med Genet A ; 173(7): 1913-1918, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28436605

RESUMO

Chromosome 22q11.2 deletion is the most common chromosomal alteration associated with DiGeorge syndrome (DGS), even though this is not the only underlying cause of DGS. In rare patients, mutations in a single gene, TBX1, have been described resulting in a DGS phenotype. Recently, it has been reported that at least part of the TBX1 mutant phenotype is due to excessive bone morphogenetic proteins (BMP) signaling. Evidence suggests that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and Bmp-signaling. We report on a 7-year-old Caucasian male born to a mother affected with gestational diabetes (GDM) who had a 371Kb-interstitial deletion of 3p12.3 identified by array CGH, involving the ZNF717, MIR1243, and 4273 genes. The child presented with a DiGeorge anomaly (DGA) associated with unilateral renal agenesis and language delay. The immunological evaluation revealed a severe reduction and impairment of T lymphocytes. FISH analysis and TBX1 sequencing were negative. Among the miRNA-4273 predicted target genes, we found BMP3, which is involved in several steps of embryogenesis including kidney and lung organogenesis and in insulin gene expression. Since, DGA is not commonly found in newborns of diabetic mothers, we hypothesize that the pathogenesis of DGA associated with GDM is multifactorial, involving both genetic and/or epigenetic cofactors.

10.
Bioorg Med Chem ; 25(9): 2601-2608, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28341401

RESUMO

Pendred syndrome is the most common form of syndromic deafness. It is associated with a mutation in the SLC26A4 gene that encodes pendrin, which is thought to maintain the ion concentration of endolymph in the inner ear most likely by acting as a chloride/bicarbonate transporter. Mutations in the SLC26A4 gene are responsible for sensorineural hearing loss. In this study, we established a stable HEK293 cell line expressing P123S mutant pendrin and developed screening methods for compounds that show pharmacological chaperone activity by image analysis using CellInsight™. Morphological analysis of stained cells in each well of 96-well plates yielded six compounds in the compound library. Furthermore, fluorescence intensity analysis of the intracellular localization of P123S mutant pendrin in HEK293 cells using FLUOVIEW™ and cytotoxicity experiments revealed that (2-aminophenyl)methanol 8 is the most promising molecular chaperone to rescue P123S mutant pendrin: the plasma membrane (M)/cytoplasm (C) ratios are 1.5 and 0.9 at the concentrations of 0.3 and 0.1mM, respectively, and a sustained effect was observed 12h after removal of the compound from the cell medium. Because the M/C ratio of salicylate, which was previously discovered as a molecular chaperone of P123S mutant pendrin, was approximately 1 at 10mM concentration and a sustained effect was not observed even at 6h, (2-aminophenyl)methanol 8 was 100 times more potent and exhibited a longer sustained effect than salicylate. These findings suggest that (2-aminophenyl)methanol 8 is an attractive candidate for therapeutic agent for Pendred syndrome patients.


Assuntos
Álcoois Benzílicos/farmacologia , Proteínas de Membrana Transportadoras/metabolismo , Substituição de Aminoácidos , Álcoois Benzílicos/química , Álcoois Benzílicos/toxicidade , Membrana Celular/efeitos dos fármacos , Bócio Nodular/tratamento farmacológico , Células HEK293 , Perda Auditiva Neurossensorial/tratamento farmacológico , Humanos , Proteínas de Membrana Transportadoras/genética , Microscopia de Fluorescência , Salicilatos/farmacologia , Transportadores de Sulfato
11.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 73(10): 1028-1038, 2017.
Artigo em Japonês | MEDLINE | ID: mdl-29057774

RESUMO

PURPOSE: The N-Isopropyl-p-[123I] Iodoamphetamine (123I-IMP) SPECT imaging reduces the image quality and quantitative accuracy due to scatter and septal penetration occurred by radioactive uptake from outside of the field of view such as the lungs. We evaluated the influence of scatter and septal penetration using phantom-simulated radioactivity from outside of the field of view, and subsequently compared the effect of scatter and septal penetration corrections between the simulation-based effective scatter source estimation (ESSE) method and the multi-window method (ellipse approximation method). METHODS: We used the phantom filled with 10 and 25 kBq/mL for the brain and lung parts corresponding to radioactive concentration in the clinical study. The SPECT images were acquired with and without lung phantom using low-energy high-resolution (LEHR) and cardiac high-resolution (CHR) collimators. We quantitatively evaluated a brain phantom by count analysis and coefficient of variation as reference data without lung phantom simulated the radioactivity from outside of the field of view, and compared between two scatter corrections by each collimator. RESULTS: The brain count in cerebral base with the ESSE method using LEHR collimator was higher than that of the ellipse approximation method. The whole brain count with the ellipse approximation method using CHR collimator shows 28.8% lower than the ESSE method, so that it suggests that the ellipse approximation method for LEHR collimator and the ESSE method for CHR collimator was close to reference counts. The coefficient of variation of the ESSE method was lower than that of the ellipse approximation method for both two collimators. CONCLUSIONS: It was possible to correct the scatter and penetration from outside the field of view with high accuracy, by using the ellipse approximation method with LEHR collimator and the ESSE method with CHR collimator.


Assuntos
Encéfalo/irrigação sanguínea , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Circulação Cerebrovascular , Humanos , Inosina Monofosfato , Radioisótopos do Iodo , Imagens de Fantasmas
12.
Am J Med Genet A ; 167(6): 1315-22, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25847113

RESUMO

We detail here the clinical description and the family genetic study of a male patient with global developmental delay, disruptive and obsessive behaviors and minor dysmorphic features and a combination of two rare genetic variants: a maternally inherited 16p13.11-p12.3 duplication and a de novo 12p12.1 deletion affecting SOX5. The 16p13.11 microduplication has been implicated in several neurodevelopmental and behavioral disorders and is characterized by variable expressivity and incomplete penetrance. The causes of this variation in phenotypic expression are not fully clear, representing a challenge in genetic diagnosis and counseling. However, several authors have proposed the two-hit model as one of the underlying mechanisms for this phenotypic heterogeneity. Our data could also support this two-hit model in which the 16p13.11-p12.3 duplication might contribute to the phenotype, not only as a single event but also in association with the SOX5 deletion. The SOX5 gene plays important roles in various developmental processes and has been associated with several neurodevelopmental disorders, mainly intellectual disability, developmental delay and language and/or speech delay as well as with behavior problems and dysmorphic features. However, many of the physical features and behavioral manifestations as well as language deficiencies present in our patient are consistent with those previously reported for SOX5 deletions. Patients carrying multiple genomic variants, as the one presented here, illustrate the difficulty in analyzing genotypes when the contribution of each variant results in overlapping phenotypes and/or, alternatively, in the modification of the clinical manifestations defined by the coexisting variant.


Assuntos
Duplicação Cromossômica , Deficiências do Desenvolvimento/genética , Deleção de Genes , Transtornos do Desenvolvimento da Linguagem/genética , Comportamento Obsessivo/genética , Fatores de Transcrição SOXD/genética , Criança , Cromossomos Humanos Par 16 , Deficiências do Desenvolvimento/patologia , Deficiências do Desenvolvimento/fisiopatologia , Fácies , Genótipo , Humanos , Transtornos do Desenvolvimento da Linguagem/patologia , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Masculino , Modelos Genéticos , Comportamento Obsessivo/patologia , Comportamento Obsessivo/fisiopatologia , Linhagem , Fenótipo
13.
Int J Biol Macromol ; 259(Pt 1): 128788, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38154706

RESUMO

Polyurethane (PU) and poly(l-lactide) (PLLA) have attracted increasing attention in the development of shape memory polymers (SMPs) due to their good biocompatibility and degradability. Although Pluronic P123 can be used to tune polymeric surface hydrophilicity, its effect on SM performance is a mystery. In this study, a soluble cross-linked PU is synthesized as the switching phase and combined with PLLA and P123 to construct a hydrothermally responsive SM composite. The water contact angle of PU/PLLA/P123 decreases from 22.7° to 5.1° within 2 min. PU and P123 form the switching group, which enhances the SM behavior of the composite. The shape fixity (Rf) and shape recovery (Rr) of PU/PLLA/P123 are 94.4 % and 98 % in 55 °C water, respectively, and the shape recovery time is only 10 s. P123 plays the role of "turbine" in the SM process. PU/PLLA/P123 exhibits a balance between stiffness and elasticity, and good degradability. Furthermore, PU/PLLA/P123 is also biocompatible and beneficial to cell proliferation and growth. Therefore, it offers an alternative approach to developing hydrothermally responsive SM biocomposites based on P123, PU and PLLA for biomedical applications.


Assuntos
Poloxaleno , Poliuretanos , Poliésteres , Água , Materiais Biocompatíveis
14.
Gels ; 10(3)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38534599

RESUMO

BACKGROUND: This study aims to evaluate the percutaneous permeation profiles of caffeic acid (CA) from the cubic and hexagonal liquid crystalline phases of Pluronic P123/water mixtures. METHOD: The resulting drug-loaded mesophases were subjected to characterisation through deuterium nuclear magnetic resonance spectroscopy and polarised optical microscopy observations. These analyses aimed to evaluate the structural changes that occurred in the mesophases loading with CA. Additionally, steady and dynamic rheology studies were conducted to further explore their mechanical properties and correlate them to the supramolecular structure. Finally, CA release experiments were carried out at two different temperatures to examine the behaviour of the structured systems in a physiological or hyperthermic state. RESULTS: As the concentration of the polymer increases, an increase in the viscosity of the gel is noted; however, the addition of caffeic acid increases microstructure fluidity. It is observed that the temperature effect conforms to expectations. The increase in temperature causes a decrease in viscosity and, consequently, an increase in the rate of permeation of caffeic acid. CONCLUSIONS: The CA permeation profile from the prepared formulations is mostly dependent on the structural organisation and temperature. Cubic mesophase LLC 30/CA showed greater skin permeation with good accumulation in the skin at both tested temperatures.

15.
Eur J Med Genet ; 66(9): 104820, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37572998

RESUMO

BMP2 (bone morphogenic protein-2) is a member of the TGF-ß superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal. The recent report has characterized multiple patients with BMP2 haploinsufficiency, describing individuals with BMP2 sequence variants and deletions associated with short stature without endocrinological abnormalities, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease. However, due to a small number of reported patients with BMP2 haploinsufficiency, the genotype and phenotype correlations are not fully understood. We experienced a family of BMP2 haploinsufficiency with a novel frameshift variant NM_001200.4: c.231dup (p.Tyr78Leufs*38) which was predicted to be "pathogenic" by the American College of Genetics and Genomics (ACGM) criteria. In addition to short stature, impaired hearing ability and minor skeletal deformities, the proband exhibited isolated dextrocardia situs solitus without cardiac anomalies and abnormal locations of other visceral organs. Our study would shed light on the crucial role of BMP2 in determining the cardiac axis, and further studies are needed to assemble more cases to elucidate BMP2 role in human heart development.


Assuntos
Dextrocardia , Nanismo , Cardiopatias Congênitas , Camundongos , Animais , Humanos , Dextrocardia/diagnóstico por imagem , Dextrocardia/genética , Cardiopatias Congênitas/genética , Genótipo , Família , Fator de Crescimento Transformador beta/genética , Proteína Morfogenética Óssea 2/genética
16.
Ann Nucl Med ; 37(5): 280-288, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36805493

RESUMO

OBJECTIVE: The present prospective study aimed to determine whether the addition of 123I-iomazenil (IMZ) single-photon emission computed tomography (SPECT) to brain perfusion SPECT could improve the detection accuracy of misery perfusion on positron emission tomography (PET) in adult patients with ischemic moyamoya disease (MMD). METHODS: Oxygen extraction fraction (OEF) and brain perfusion were assessed using 15O gas PET and N-isopropyl-p-[123I]-iodoamphetamine (IMP) SPECT, respectively, in 137 patients. IMZ SPECT was also performed. Regions of interest (ROIs) were automatically placed in the five middle cerebral artery (MCA) territories ipsilateral to the symptomatic cerebral hemisphere and in the contralateral posterior cerebral artery territory using a three-dimensional stereotaxic ROI template. The radioactive count of the MCA ROI to the contralateral posterior cerebral artery ROI was calculated on IMP SPECT (relative SPECT-IMP uptake) and IMZ SPECT (relative SPECT-IMZ uptake). The relative SPECT-IMZ uptake to the relative SPECT-IMP uptake was also calculated (relative SPECT-IMZ/IMP uptake). Of the five MCA ROIs in the symptomatic cerebral hemisphere in each patient, the ROI with the highest PET-OEF value (one ROI per patient) was selected for analysis. RESULTS: Significant correlations were observed between the PET-OEF and relative SPECT-IMP uptake (correlation coefficient, - 0.683) and relative SPECT-IMZ/IMP uptake (correlation coefficient, 0.875). The area under the receiver operating characteristic curve for detecting misery perfusion (PET-OEF > 51.3%) was significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake (difference between areas, 0.080; p = 0.0004). The sensitivity, specificity, and positive- and negative-predictive values for the relative SPECT-IMZ/IMP uptake for detecting misery perfusion were 100%, 92%, 81%, and 100%, respectively. The specificity and positive-predictive value were significantly greater for the relative SPECT-IMZ/IMP uptake than for the relative SPECT-IMP uptake. CONCLUSIONS: The addition of IMZ SPECT to brain perfusion SPECT improves the detection accuracy of misery perfusion on PET in adult patients with ischemic MMD.


Assuntos
Doença de Moyamoya , Humanos , Adulto , Doença de Moyamoya/diagnóstico por imagem , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Perfusão , Circulação Cerebrovascular
17.
Mol Genet Metab Rep ; 34: 100960, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36846631

RESUMO

Primary triglyceride deposit cardiomyovasculopathy (P-TGCV), caused by a rare genetic mutation in PNPLA2 encoding adipose triglyceride lipase (ATGL), exhibits severe cardiomyocyte steatosis and heart failure. Here, we report the case of a 51-year-old man with P-TGCV homozygous for a novel PNPLA2 mutation (c.446C > G, P149R) in the catalytic domain of ATGL. Analyses of endomyocardial biopsy specimens and in vitro expression experiments showed mutant protein expression with conserved lipid binding, but reduced lipolytic activity, indicating mutation pathogenicity.

18.
Data Brief ; 41: 107841, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35146082

RESUMO

The data provided in this study are related to the fabrication of two light-responsive systems based on reduced graphene oxide (rGO) functionalized with the polymers Pluronic P123 (P123), rGO-P123, and polyethyleneimine (PEI), rGO-PEI, and loaded with amphotericin B (AmB), an antileishmanial drug. Here are described the experimental design to obtain the systems and characterization methods, such as Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman Spectroscopy, Powder X-Ray Diffraction, Transmission Electron Microscopy, Scanning Electron Microscopy and Thermogravimetric Analyses. Also, AmB spectroscopy studies are described. The materials rGO-P123 and rGO-PEI were loaded with AmB and the optimization of AmB and polymer fragments structures revealed several possible hydrogen bonds formed between the materials and the drug. The drug release was analyzed with and without Near-Infrared (NIR) light. In the studies conducted under NIR light irradiation for 10 min, an infrared lamp was disposed at 64 cm from the samples and an optical fiber thermometer was employed to measure the temperature variation. Cytotoxicity studies and antiproliferative assays against Leishmania amazonensis promastigotes were evaluated. The complete work data entitled Amphotericin-B-Loaded Polymer-Functionalized Reduced Graphene Oxides for Leishmania amazonensis Chemo-Photothermal Therapy have been published to Colloids and Surfaces B: Bionterfaces (https://doi.org/10.1016/j.colsurfb.2021.112169) [1].

19.
Materials (Basel) ; 15(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36556706

RESUMO

In this work, a series of micro/mesoporous SBA15 silica materials were synthesized using P123 and poly(vinyl alcohol) (PVA) as co-templates. The pore structure of the prepared SBA15 was observed to be a function of the PVA concentration. When the amount of PVA was relatively small, the specific surface area, micropore volume, and pore wall thickness of the synthesized SBA15 were considerably large. By contrast, when a large amount of PVA was added, the pore wall thickness was greatly reduced, but the mesopore volume and size increased. This is because the added PVA interacted with the polyethylene oxide (PEO) in the shells of the P123 micelles. Furthermore, when the amount of PVA was increased, the core polypropylene oxide (PPO) block also increased, owing to the enhanced aggregation of the P123/PVA mixed micelles. This research contributes to a basic comprehension of the cooperative interactions and formation process underlying porous silica materials, assisting in the rational design and synthesis of micro/mesoporous materials.

20.
Int J Biol Macromol ; 222(Pt B): 2670-2682, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36220402

RESUMO

Herein, we report a multifunctional hydrogel membrane with good mechanical properties, excellent antioxidant efficiency, and broad-spectrum antimicrobial activity. For this purpose, a series of chitosan-carboxymethyl cellulose-Pluronic P123 (CHT-CMC-P123) hydrogel membranes were prepared by blending various tetracycline hydrochloride (TCH) contents. The physicochemical and biological properties of CHT-CMC-P123 membranes were comprehensively investigated. With the increase of TCH content from 5 % to 20 %, hydrogel membranes presented a decreased water contact angle from 18.96° to 11.24°, and a decreased water vapor transmission rate from 171.8 to 156.1 g/m2 h. Besides, with the increase of TCH content (5-20 %), the tensile strength (0.31-0.11 MPa) and elongation at break (10.57-4.82 %) of hydrogel membranes decreased while their thickness increased (113.5-324.3 µm). The data show that the release of TCH reached equilibrium after 26 days, with a cumulative percentage of approximately 28 %-87 %. Moreover, the hydrogel membranes exhibited a high antioxidant capacity of ~92 % for DPPH radical. Importantly, the incorporation of TCH significantly (~2.3 fold) enhanced the antimicrobial activity of the hydrogel membranes against Gram-positive, and Gram-negative bacteria and yeast. Based on our findings, these hydrogel membranes with superior properties may serve as effective food packaging and wound healing materials.


Assuntos
Anti-Infecciosos , Quitosana , Tetraciclina/farmacologia , Tetraciclina/química , Quitosana/química , Carboximetilcelulose Sódica/química , Hidrogéis/química , Antioxidantes/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química
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