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1.
Nano Lett ; 23(13): 5919-5926, 2023 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-37390368

RESUMO

Exerting forces on biomolecules inside living cells would allow us to probe their dynamic interactions in their native environment. Magnetic iron oxide nanoparticles represent a unique tool capable of pulling on biomolecules with the application of an external magnetic field gradient; however, their use has been restricted to biomolecules accessible from the extracellular medium. Targeting intracellular biomolecules represents an additional challenge due to potential nonspecific interactions with cytoplasmic or nuclear components. We present the synthesis of sulfobetaine-phosphonate block copolymer ligands, which provide magnetic nanoparticles that are stealthy and targetable in living cells. We demonstrate, for the first time, their efficient targeting in the nucleus and their use for magnetic micromanipulation of a specific genomic locus in living cells. We believe that these stable and sensitive magnetic nanoprobes represent a promising tool to manipulate specific biomolecules in living cells and probe the mechanical properties of living matter at the molecular scale.


Assuntos
Nanopartículas , Polímeros , Micromanipulação , Genômica , Nanopartículas Magnéticas de Óxido de Ferro , Fenômenos Magnéticos
2.
Biomacromolecules ; 24(12): 5698-5706, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-37945526

RESUMO

The development of cell-penetrating polymers with endocytosis-independent cell uptake pathways has emerged as a prominent strategy to enhance the transfection efficiency. Inspired by the rigid α-helical structure that endows polypeptides with cell-penetrating ability, we propose that a rigid backbone can facilitate the corresponding polymer vector's performance in gene delivery by bypassing the difficult endosomal escape process. Meanwhile, the installation of aromatic domains, as a way to promote gene transfection efficiency, is employed through the construction of a poly(benzyl ether) (PBE)-based scaffold in this work. We demonstrate that the direct membrane translocation capability of the synthesized PBE contributes to its enhanced transfection performance and excellent biocompatibility profile, rendering the imidazolium-functionalized PBE scaffold with higher activity and biocompatibility. Molecular details of the PBE-lipid interaction are also revealed in molecular dynamics simulations, indicating the important roles of individual structural elements on the polymeric scaffold in the membrane penetration process.


Assuntos
Técnicas de Transferência de Genes , Polímeros , Terapia Genética , Transfecção , Peptídeos/química
3.
Odontology ; 111(4): 982-992, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36773195

RESUMO

The aim of this study is to assess the relationship between somatosensory functional changes and inferior alveolar nerve (IAN) exposure after impacted mandibular third molars (M3M) removal. We recruited 35 patients who underwent impacted M3M extraction near the IAN. The M3Ms were extracted by combined endoscopy, piezosurgery, and contra-angle high-speed turbine handpiece. All IAN canal perforations and exposed regions were recorded and measured by endoscopy after extraction and on cone-beam computed tomography (CBCT) images before extraction. The patients were followed up 1, 7, and 35 days after surgery. A standardized quantitative sensory testing (QST) battery was performed on the lower lip skin. All of 35 cases had exposed IAN on CBCT images, 5 of which had no exposed IAN under endoscopy. For the other 30 cases, the endoscopy-measured IAN length and width were shorter than the CBCT measurements (P < 0.001). The warm and mechanical detection thresholds (MDT) on the operation side were significantly higher than the contralateral side after surgery (P < 0.05). Thermal sensory limen, MDT, and cold pain threshold were strongly correlated with the exposed IAN length and MDT also with the exposed IAN width one day after surgery. In conclusion, it was found that not all exposed IAN in CBCT images were real exposure after surgery. The intraoperative exposed IAN endoscopic measurements were smaller than by CBCT and strongly correlated with some QST parameters.


Assuntos
Dente Impactado , Traumatismos do Nervo Trigêmeo , Humanos , Dente Serotino/cirurgia , Mandíbula , Endoscopia , Extração Dentária/métodos , Dente Impactado/diagnóstico por imagem , Dente Impactado/cirurgia , Nervo Mandibular/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Radiografia Panorâmica/métodos
4.
AAPS PharmSciTech ; 24(8): 235, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37973629

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a progressive, fibrotic interstitial lung disease with unclear etiology and increasing prevalence. Pulmonary administration can make the drug directly reach the lung lesion location and reduce systemic toxic and side effects. The effectiveness of lenalidomide (Len) liposomal lung delivery in idiopathic pulmonary fibrosis was investigated. Len liposomes (Len-Lip) were prepared from soybean lecithin, cholesterol (Chol), and medicine in different weight ratios by thin film hydration method. The Len-Lip were spherical in shape with an average size of 226.7 ± 1.389 nm. The liposomes with a higher negative zeta potential of around - 34 mV, which was conducive to improving stability by repelling each other. The drug loading and encapsulation rate were 2.42 ± 0.07% and 85.47 ± 2.42%. Len-Lip had little toxicity at the cellular level and were well taken up by cells. At bleomycin-induced pulmonary fibrosis model mice, inhalation Len-Lip could improve lung function and decrease lung hydroxyproline contents, and alleviate pulmonary fibrosis state. Inhalation Len-Lip provided a reference for the treatment of idiopathic pulmonary fibrosis.


Assuntos
Fibrose Pulmonar Idiopática , Lipossomos , Camundongos , Animais , Lipossomos/farmacologia , Bleomicina/efeitos adversos , Lenalidomida/farmacologia , Lenalidomida/uso terapêutico , Pulmão , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/patologia
5.
Hum Mol Genet ; 29(15): 2471-2480, 2020 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-32592472

RESUMO

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy and shows clinical and genetic heterogeneity. Mutations in C1orf194 encoding a Ca2+ regulator in neurons and Schwann cells have been reported previously by us to cause CMT disease. In here, we further investigated the function and pathogenic mechanism of C1or194 by generating C1orf194 knockout (KO) mice. Homozygous mutants of C1orf194 mice exhibited incomplete embryonic lethality, characterized by differentiation abnormalities and stillbirth on embryonic days 7.5-15.5. Heterozygous and surviving homozygous C1orf194 KO mice developed motor and sensory defects at the age of 4 months. Electrophysiologic recordings showed decreased compound muscle action potential and motor nerve conduction velocity in the sciatic nerve of C1orf194-deficient mice as a pathologic feature of dominant intermediate-type CMT. Transmission electron microscopy analysis revealed demyelination and axonal atrophy in the sciatic nerve as well as swelling and loss of mitochondrial matrix and other abnormalities in axons and Schwann cells. A histopathologic examination showed a loss of motor neurons in the anterior horn of the spinal cord and muscle atrophy. Shorter internodal length between nodes of Ranvier and Schmidt-Lanterman incisures was detected in the sciatic nerve of affected animals. These results indicate that C1orf194 KO mice can serve as an animal model of CMT with a severe dominant intermediate CMT phenotype that can be used to investigate the molecular mechanisms of the disease and evaluate the efficacy of therapeutic strategies.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Deficiências do Desenvolvimento/genética , Fases de Leitura Aberta/genética , Natimorto/genética , Animais , Axônios/metabolismo , Doença de Charcot-Marie-Tooth/mortalidade , Doença de Charcot-Marie-Tooth/patologia , Deficiências do Desenvolvimento/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Knockout , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Mutação/genética , Bainha de Mielina/genética , Fenótipo , Células de Schwann/metabolismo , Células de Schwann/patologia , Nervo Isquiático/metabolismo , Nervo Isquiático/patologia
6.
Chem Biodivers ; 19(6): e202100753, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35560720

RESUMO

Aiming at the excellent killing effect of N-phenylmaleimide (N-PMI) on microorganisms, this article used structural simulation analysis, fluorescence analysis, confocal laser scanning microscope and SEM to find that the double bond in N-PMI could interact with the sulfur groups in the membrane protein, changing its conformation, rupturing the plasma membrane of the cell, leaking the contents, and ultimately causing the death of the microorganisms. Therefore, once the double bond participated in the polymerization, N-PMI lost its antimicrobial function. N-PMI could achieve azeotropic copolymerization with MMA through reactive extrusion polymerization. N-PMI with a content of 5 % can be evenly inserted into the PMMA chain segment during the copolymerization reaction, thereby increasing the Tg of pure PMMA by up to 15 °C, which provided the PMMA-co-PMI copolymer with resistance to boiling water sterilization advantageous conditions. In addition, N-PMI with a content of 5 % has little effect on the transparency of PMMA after participating in the copolymerization. Moreover, the trace amount of residual N-PMI made the material have excellent antimicrobial function, and the bacteriostatic zone is extremely small, which provided an excellent guarantee for the safety and durability of the material. As a medical biological material, the PMMA-co-PMI copolymer has a good industrialization application prospects.


Assuntos
Anti-Infecciosos , Polimetil Metacrilato , Antibacterianos/farmacologia , Maleimidas , Polímeros/química , Polímeros/farmacologia , Polimetil Metacrilato/química , Polimetil Metacrilato/farmacologia
7.
Ecotoxicology ; 30(8): 1632-1643, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33420883

RESUMO

While expanded polystyrene (EPS) microplastics have been widely recognized as one of the most important components of plastic litter in the intertidal zones of the global ocean, our understanding of their environmental fate on island beaches is insufficient. In this study, we intended to reveal that the latest EPS microplastic pollution status on 5 island beaches in the Pearl River Estuary, China, by comprehensively assessing the abundance, distribution, size, surface texture and carrying capacity of heavy metals (Cd, As, Cr, Ni, Cu, Pb, Mn, Fe, Al). High level of EPS microplastic abundance ranged from 328 to 82,276 particles m-2 was found, with the highest abundance at Guishan Island and the lowest at Dong'ao Island. Spatial distribution of EPS microplastic abundance was significantly different among different islands. EPS microplastics in the size range of 1-2 mm were the most abundant. The content of heavy metals in EPS microplastics collected on the beaches was greater than that in the new EPS products. The average concentrations of heavy metals in EPS microplastics from 5 islands are Cd (0.27 ± 0.19 µg g-1), As (5.50 ± 3.84 µg g-1), Cr (14.9 ± 8.25 µg g-1), Cu (15.0 ± 7.66 µg g-1), Ni (17.2 ± 17.6 µg g-1), Pb (24.8 ± 7.39 µg g-1), Mn (730 ± 797 µg g-1), Fe (8340 ± 4760 µg g-1), and Al (9624 ± 6187 µg g-1), respectively. The correlation between heavy metals in EPS microplastics and sediments was better than that between heavy metals in EPS microplastics and seawater. The study results indicated that EPS microplastics could act as a carrier for the transport of heavy metals, which might pose a threat to biological and human health.


Assuntos
Metais Pesados , Poluentes Químicos da Água , China , Conservação dos Recursos Naturais , Monitoramento Ambiental , Estuários , Sedimentos Geológicos , Humanos , Metais Pesados/análise , Microplásticos , Plásticos , Poliestirenos/análise , Rios , Poluentes Químicos da Água/análise
8.
Brain ; 142(8): 2215-2229, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31199454

RESUMO

Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy exhibiting great clinical and genetic heterogeneity. Here, the identification of two heterozygous missense mutations in the C1orf194 gene at 1p21.2-p13.2 with Charcot-Marie-Tooth disease are reported. Specifically, the p.I122N mutation was the cause of an intermediate form of Charcot-Marie-Tooth disease, and the p.K28I missense mutation predominately led to the demyelinating form. Functional studies demonstrated that the p.K28I variant significantly reduced expression of the protein, but the p.I122N variant increased. In addition, the p.I122N mutant protein exhibited the aggregation in neuroblastoma cell lines and the patient's peroneal nerve. Either gain-of-function or partial loss-of-function mutations to C1ORF194 can specify different causal mechanisms responsible for Charcot-Marie-Tooth disease with a wide range of clinical severity. Moreover, a knock-in mouse model confirmed that the C1orf194 missense mutation p.I121N led to impairments in motor and neuromuscular functions, and aberrant myelination and axonal phenotypes. The loss of normal C1ORF194 protein altered intracellular Ca2+ homeostasis and upregulated Ca2+ handling regulatory proteins. These findings describe a novel protein with vital functions in peripheral nervous systems and broaden the causes of Charcot-Marie-Tooth disease, which open new avenues for the diagnosis and treatment of related neuropathies.


Assuntos
Doença de Charcot-Marie-Tooth/genética , Animais , Cálcio/metabolismo , Técnicas de Introdução de Genes , Humanos , Camundongos , Camundongos Transgênicos , Mutação de Sentido Incorreto , Linhagem
9.
Soft Matter ; 15(18): 3655-3658, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31012474

RESUMO

We developed biocompatible ATP responsive DNA nanogels, by grafting DNA strands on carboxymethyl chitosan polymer chains, and then hybridizing with ATP aptamers to form core-shell nanogels. The DNA duplex structure could embed DOX in the G-C sequences, and realize simultaneous sol-gel transition and DOX release when suffering enrich ATP in tumor cells.


Assuntos
Trifosfato de Adenosina/metabolismo , Antineoplásicos/química , Materiais Biocompatíveis/química , DNA/química , Portadores de Fármacos/química , Nanoestruturas/química , Células A549 , Antineoplásicos/metabolismo , Transporte Biológico , Doxorrubicina/química , Doxorrubicina/metabolismo , Liberação Controlada de Fármacos , Géis , Humanos , Espaço Intracelular/metabolismo
10.
AAPS PharmSciTech ; 21(1): 6, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31754916

RESUMO

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.


Assuntos
Portadores de Fármacos/síntese química , Excipientes/síntese química , Impressão Tridimensional , Comprimidos/síntese química , Tecnologia Farmacêutica/métodos , Varredura Diferencial de Calorimetria/métodos , Portadores de Fármacos/farmacocinética , Liberação Controlada de Fármacos , Excipientes/farmacocinética , Álcool de Polivinil/síntese química , Álcool de Polivinil/farmacocinética , Propranolol/síntese química , Propranolol/farmacocinética , Comprimidos/farmacocinética , Difração de Raios X/métodos
11.
Guang Pu Xue Yu Guang Pu Fen Xi ; 37(3): 697-703, 2017 Mar.
Artigo em Zh, Inglês | MEDLINE | ID: mdl-30148547

RESUMO

In this work, regenerated cellulose films were prepared with an iced dissolution method, while the physical morphologies and crystal types of the products were systematically characterized with scanning electron microscope (SEM), Fourier transform infrared(FTIR), while X-Ray Diffraction (XRD). The results demonstrate that the as-prepared continuous and uniform films are indeed cellulose Ⅱ, whose morphology and crystal type are significantly different from those of the degreased cotton. Moreover, Terahertz time domain system (THz-TDS) and FTIR were employed to measure the THz spectra of the regenerated cellulose films. Accordingly, the THz characteristic peaks for the regenerated cellulose films are experimentally identified for the first time. In addition, the increase of the THz transmittance with the decrease of the wavenumber is attributed to the existence of amorphous components in the regenerated cellulose films. Although the shapes of Far-IR spectra in the range of 100~700 cm-1 are similar, the absorption peaks of the regenerated cellulose films move to lower wavenumbers (blue shift) compared with those of the degreased cotton. Based on this, we developed a new approach to distinguish the allomorphism of cellulose Ⅱ and cellulose Iß by Far-IR. Particularly, geometry optimization and IR calculation for the crystal structure of cellulose Ⅱ have been successfully processed by Density Functional Theory (DFT) using periodic boundary condition via CASTEP package. The calculated absorption peak positions are in good agreement with those experimentally measured. Consequently, the THz characteristic peaks of the regenerated cellulose films have been systematically and successfully assigned. Theoretical calculations reveal that the peaks at 42 and 54 cm-1 are assigned to the lattice vibration modes coupled with translational mode and rotational mode, respectively. Moreover, the absorption peaks in the range of 68~238 cm-1 are related with the torsion vibration of ­CH2OH group and deformation vibration of C­H bond and O­H bond, while those in the range of 351~583 cm-1 are assigned to the skeletal vibration of C­O­C bond and pyranoid ring, and those at 611 and 670 cm-1 are originated from the out-of-plane bending vibration of O­H bond. Each absorption peak is involved in more than single vibration mode. The THz spectra presented in this work, together with the theoretical simulations, indicate that the THz responses of regenerated cellulose are closely associated with both its chemical constituents and molecular structure. These results will be helpful not only for better understanding the relations between the molecular structure of the regenerated cellulose and its THz spectrum, but also for providing valuable information for future studies on the physical mechanisms of THz responses of other partially-crystalline polymers and organic biological macromolecules.


Assuntos
Celulose/química , Modelos Teóricos , Vibração , Difração de Raios X
12.
Beijing Da Xue Xue Bao Yi Xue Ban ; 46(1): 12-8, 2014 Feb 18.
Artigo em Zh | MEDLINE | ID: mdl-24535340

RESUMO

OBJECTIVE: To get the stem cells from the young permanent tooth apical papillae, and observe the osteogenic differentiation of the cells after cultured with acellular dermal matrix (ADM). METHODS: Young permanent tooth apical papillae were obtained by the oral surgeon. The cells from the apical papillae were isolated, cultured and analyzed through a flow cytometer. The cells in the experimental group were induced both osteogenic and adipogenic differentiation. The cells were not induced in the control group.Both groups were evaluated by staining and real-time polymerase chain reaction (real-time PCR) to examine the quantity of RNAs in the experimental group. The cells from apical papillae were also cultured with ADM. These cells were also induced both osteogenic and adipogenic differentiation in the experimental group, and not induced in the control group. The measures of staining and real-time PCR were also carried out. RESULTS: The cells from the apical papillae proliferated in a rapid rate. Of which 70.3% in cultures were positive for Stro-1, and 96% positive for CD105 according to flow cytometric analysis. After induction, the RNA level related to osteogenic and adipogenic differentiation expressed higher in the experimental group than those of the control group without induction obviously, such as osteocalcin (OCN), bone sialoprotein (BSP), liver X-recepter α (LXRα), lipoprotein lipase(LPL), peroxisome proliferator activated receptor γ (PPAR-γ), and scavenger receptor class B type 1(SR-B1). The cells cultured with ADM also had a fast proliferation, and grew attached to ADM. After induction, the RNA level of OCN and BSP had a higher expression than the control group (P > 0.05), and LPL also expressed higher (P < 0.05). CONCLUSION: The study approved that there were a big amount of stem cells in the young permanent tooth apical papilla obtained by oral surgery, which had significant osteogenic potential. The cells still proliferated well when they were cultured with ADM as a kind of collagen skelecton. The results showed that ADM could be performed as a base to support the stem cells to survive the environment, and it also could play a role in osteogenic differentiation of stem cells from apical papilla.


Assuntos
Derme Acelular , Diferenciação Celular , Papila Dentária/citologia , Osteogênese , Células-Tronco/citologia , Células Cultivadas , Citometria de Fluxo , Humanos , Sialoproteína de Ligação à Integrina/metabolismo , Lipase Lipoproteica/metabolismo , Receptores X do Fígado , Receptores Nucleares Órfãos/metabolismo , Osteocalcina/metabolismo , PPAR gama/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
13.
ACS Appl Mater Interfaces ; 16(36): 46947-46963, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39225271

RESUMO

Biomedical-device-associated infection (BAI) is undoubtedly a major concern and a serious challenge in modern medicine. Therefore, the development of biomedical materials that are capable of resisting or killing bacteria is of great importance. In this work, a croconaine-functionalized polymer with antifouling and near-infrared (NIR) photothermal bactericidal properties was prepared and facilely modified on polypropylene (PP) to combat medical device infections. Croconaine dye is elaborately modified as a "living" initiator, termed CR-4EBiB, for preparing amphiphilic block polymers by atom transfer radical polymerization (ATRP). In the formed polymer coating, the hydrophobic block can strongly adhere to the surface of the PP substrate, whereas the hydrophilic block is located on the outer layer by solvent-induced resistance to bacterial adhesion. Under the irradiation of an NIR laser (808 nm), the croconaine dye in the coating achieved maximum conversion of light to heat to effectively kill E. coli, S. aureus, and methicillin-resistant Staphylococcus aureus (MRSA). This work provides a facile and promising strategy for the development of implantable antibacterial biomedical materials.


Assuntos
Antibacterianos , Escherichia coli , Raios Infravermelhos , Staphylococcus aureus Resistente à Meticilina , Polipropilenos , Polipropilenos/química , Polipropilenos/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Propriedades de Superfície , Polímeros/química , Polímeros/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Incrustação Biológica/prevenção & controle
14.
Chin J Dent Res ; 27(1): 53-63, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546520

RESUMO

OBJECTIVE: To investigate FAM20A gene variants and histological features of amelogenesis imperfecta and to further explore the functional impact of these variants. METHODS: Whole-exome sequencing (WES) and Sanger sequencing were used to identify pathogenic gene variants in three Chinese families with amelogenesis imperfecta. Bioinformatics analysis, in vitro histological examinations and experiments were conducted to study the functional impact of gene variants, and the histological features of enamel, keratinised oral mucosa and dental follicle. RESULTS: The authors identified two nonsense variants c. 406C > T (p.Arg136*) and c.826C > T (p.Arg176*) in a compound heterozygous state in family 1, two novel frameshift variants c.936dupC (p.Val313Argfs*67) and c.1483dupC (p.Leu495Profs*44) in a compound heterozygous state in family 2, and a novel homozygous frameshift variant c.530_531insGGTC (p.Ser178Valfs*21) in family 3. The enamel structure was abnormal, and psammomatoid calcifications were identified in both the gingival mucosa and dental follicle. The bioinformatics and subcellular localisation analyses indicated these variants to be pathogenic. The secondary and tertiary structure analysis speculated that these five variants would cause structural damage to FAM20A protein. CONCLUSION: The present results broaden the variant spectrum and clinical and histological findings of diseases associated with FAM20A, and provide useful information for future genetic counselling and functional investigation.


Assuntos
Amelogênese Imperfeita , Proteínas do Esmalte Dentário , Humanos , Amelogênese Imperfeita/genética , Calcificação Fisiológica , Biologia Computacional , Esmalte Dentário , Proteínas do Esmalte Dentário/genética , População do Leste Asiático
15.
J Hazard Mater ; 477: 135275, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39053062

RESUMO

The abundance of biodegradable microplastics (BMPs) is increasing in soil due to the widespread use of biodegradable plastics. However, the influence of BMPs on soil metal biogeochemistry, especially arsenic (As), under different water regimes is still unclear. In this study, we investigated the effects of two types of BMPs (PLA-MPs and PBAT-MPs) on As fractionation in two types of soils (black soil and fluvo-aquic soil) under three water regimes including drying (Dry), flooding (FL), and alternate wetting and drying (AWD). The results show that BMPs had limited indirect effects on As fractionation by altering soil properties, but had direct effects by adsorbing and releasing As during their degradation. Enzyme degradation experiments show that the degradation of PLA-MPs led to an increased desorption of 4.76 % for As(III) and 15.74 % for As(V). Synchrotron-based X-ray fluorescence (µ-XRF) combined with micro-X-ray absorption near edge structure (µ-XANES) analysis show that under Dry and AWD conditions, As on the BMPs primarily bind with Fe hydrated oxides in the form of As(V). Conversely, 71.57 % of As on PBAT-MP under FL conditions is in the form of As(III) and is primarily directly adsorbed onto its surface. This study highlights the role of BMPs in soil metal biogeochemistry.


Assuntos
Arsênio , Microplásticos , Poluentes do Solo , Síncrotrons , Arsênio/química , Arsênio/análise , Poluentes do Solo/química , Poluentes do Solo/análise , Fracionamento Químico , Água/química , Solo/química , Biodegradação Ambiental , Plásticos Biodegradáveis/química , Adsorção
16.
iScience ; 27(5): 109818, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38766356

RESUMO

Allergic asthma is a chronic non-communicable disease characterized by lung tissue inflammation. Current treatments can alleviate the clinical symptoms to some extent, but there is still no cure. Recently, the transplantation of mesenchymal stem cells (MSCs) has emerged as a potential approach for treating allergic asthma. Gingival-derived mesenchymal stem cells (GMSCs), a type of MSC recently studied, have shown significant therapeutic effects in various experimental models of autoimmune diseases. However, their application in allergic diseases has yet to be fully elucidated. In this study, using an OVA-induced allergic asthma model, we demonstrated that GMSCs decrease CD11b+CD11c+ proinflammatory dendritic cells (DCs), reduce Th2 cells differentiation, and thus effectively diminish eosinophils infiltration. We also identified that the core functional factor, hepatocyte growth factor (HGF) secreted by GMSCs, mediated its effects in relieving airway inflammation. Taken together, our findings indicate GMSCs as a potential therapy for allergic asthma and other related diseases.

17.
Adv Healthc Mater ; 12(21): e2203386, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37016763

RESUMO

Aggregation caused quenching (ACQ) effect can severely inhibit the application of hydrophobic photosensitizers (PSs) bearing planar and rigid structures. Most of the reported cases utilized random-coiled polymers for the in vivo delivery of PSs, which would inevitably aggravate ACQ effect due to the flexible chains. In this work, the role of polymers' secondary structures (especially α-helical conformation) in overcoming the PSs' aggregation is systemically investigated based on the design of α-helical polypeptides bearing tetraphenylporphyrin (TPP) side chains. Atomistic molecular dynamics simulation, fluorescence quantum yield, and reactive oxygen species (ROS) generation yield are evaluated to demonstrate that α-helical polypeptide backbones can significantly boost both fluorescence quantum yield and ROS by suppressing the π-π stacking interaction between TPP units. The enhanced in vitro and in vivo phototoxicity for helical polypeptides also reveal functions of secondary structures in inhibiting ACQ and improving the membrane activity. Successful in vivo photodynamic therapy (PDT) results in mice bearing H22 tumors showed great potentials for further clinical applications.


Assuntos
Neoplasias , Fotoquimioterapia , Animais , Camundongos , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio , Fotoquimioterapia/métodos , Neoplasias/tratamento farmacológico , Polímeros/química , Peptídeos/farmacologia , Peptídeos/uso terapêutico
18.
Biomater Sci ; 11(2): 509-517, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36533394

RESUMO

Unimolecular micelles (UIMs) exhibit promising potential in the precise diagnosis and accurate treatment of tumor tissues, a pressing problem in the field of medical treatment, because of their perfect stability in the complex and variable microenvironment. In this study, porphyrin-based four-armed star-shaped block polymers with narrow molar mass dispersity (D = 1.34) were facilely prepared by photocontrolled bromine-iodine transformation reversible-deactivation radical polymerization (BIT-RDRP). A photothermal conversion dye, ketocyanine, was covalently linked onto the PEG and then introduced into the polymers through a "grafting onto" strategy to obtain polymeric nanomaterial, THPP-4PMMA-b-4P(PEGMA-co-APMA)@NIR-800, with dual PTT/PDT function. The resulting polymers could form monodispersed UIMs in the water below critical aggregation concentration, meanwhile maintaining the capacities of singlet oxygen release and photothermal conversion. Importantly, the UIMs displayed excellent biocompatibility while exerting superior PTT and/or PDT therapeutic effects under the irradiation of specific wavelengths of light, according to in vitro cellular experiments, which is expected to become a new hot spot for cancer therapy and anti-tumor research. Overall, stable and powerful UIMs with dual PTT/PDT function is provided, which are expected to be competitive candidates in cancer therapy.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes , Micelas , Polímeros/uso terapêutico , Bromo/uso terapêutico , Polimerização , Neoplasias/tratamento farmacológico , RNA Polimerase Dependente de RNA/uso terapêutico , Microambiente Tumoral
19.
Front Bioeng Biotechnol ; 11: 1273263, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38026896

RESUMO

Objective: This study presents an innovative articular fossa prosthesis generated by the envelope surface of condyle movement, and compares its mandible movements, muscle activities, and joint reaction forces with two temporomandibular joint (TMJ) prostheses using multibody musculoskeletal simulation. Methods: A healthy 23-year-old female was recruited for this study. Cone-beam computed tomographic (CBCT) was performed to reconstruct the mandibular bone geometry. A customized TMJ fossa prosthesis was designed based on the subject-specific envelope surface of condyle movement (ESCM). Mandibular kinematics and jaw-closing muscle electromyography (EMG) were simultaneously recorded during maximum jaw opening-closing movements. To validate our prosthesis design, a mandibular musculoskeletal model was established using flexible multibody dynamics and the obtained kinematics and EMG data. The Biomet fossa prosthesis and the ellipsoidal fossa prosthesis designed by imitating the lower limb prostheses were used for comparison. Simulations were performed to analyze the effects of different fossa prostheses on jaw opening-closing motions, mandibular muscle activation, and contact forces. Results: The maximum opening displacement for the envelope-based fossa prosthesis was greater than those for Biomet and ellipsoidal prostheses (36 mm, 35 mm, and 33 mm, respectively). The mandibular musculoskeletal model with ellipsoidal prosthesis led to dislocation near maximal jaw opening. Compared to Biomet, the envelope-based fossa reduced the digastric and lateral pterygoid activation at maximal jaw opening. It also reduced the maximal resistance to condylar sliding on the intact side by 63.2 N. Conclusion: A customized TMJ fossa prosthesis was successfully developed using the ESCM concept. Our study of musculoskeletal multibody modeling has highlighted its advantages and potential. The artificial fossa design successfully achieved a wider condylar range of motion. It also reduced the activation of jaw opening muscles on the affected side and resistance on the intact side. This study showed that an ESCM-based approach may be useful for optimizing TMJ fossa prostheses design.

20.
Environ Pollut ; 322: 121158, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36716949

RESUMO

In recent years, microplastics (MPs) as emerging carriers for environmental pollutants have attracted increasing worldwide attention. However, the adsorption of heavy metals on MPs, especially for biodegradable MPs, has been still poorly understood in estuarine environments. In this study, we investigated the aging of biodegradable and conventional MPs in the Pearl River Estuary after long-term exposure and their impacts on the adsorption of heavy metals from seawater. The results showed that the changes in surface characteristics were more prominent on biodegradable MPs than on conventional MPs after aging. Both biodegradable and conventional MPs could adsorb heavy metals, and their adsorption capacities fluctuated greatly on different MPs and different exposure times. The adsorption capacities of Cu, Pb, and As on biodegradable MPs were higher than those on conventional MPs, whereas Mn, Cr, and Co had lower adsorption on biodegradable MPs after 9-12 months by inductively coupled plasma-mass spectrometry (ICP-MS). The aging characteristics (CI, O/C, and Xc) of MPs accounted for a contribution of 51.0% on heavy metal adsorption, while the environmental factors (temperature, salinity, pH, and heavy metal concentration) only contributed to 13.2%. Therefore, the present study can provide important evidence on the environmental behaviors and ecological risks of biodegradable and conventional MPs in estuarine systems.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Microplásticos/química , Plásticos , Adsorção , Rios , Estuários , Poluentes Químicos da Água/análise , Metais Pesados/análise , China
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