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1.
Small ; 20(23): e2309793, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38148305

RESUMO

The nerve guidance conduits incorporated with stem cells, which can differentiate into the Schwann cells (SCs) to facilitate myelination, shows great promise for repairing the severe peripheral nerve injury. The innovation of advanced hydrogel materials encapsulating stem cells, is highly demanded for generating supportive scaffolds and adaptive microenvironment for nerve regeneration. Herein, this work demonstrates a novel strategy in regulating regenerative microenvironment for peripheral nerve repair with a biodegradable conductive hydrogel scaffold, which can offer multifunctional capabilities in immune regulation, enhancing angiogenesis, driving SCs differentiation, and promoting axon regrowth. The biodegradable conductive hydrogel is constructed by incorporation of polydopamine-modified silicon phosphorus (SiP@PDA) nanosheets into a mixture of methacryloyl gelatin and decellularized extracellular matrix (GelMA/ECM). The biomimetic electrical microenvironment performs an efficacious strategy to facilitate macrophage polarization toward a pro-healing phenotype (M2), meanwhile the conductive hydrogel supports vascularization in regenerated tissue through sustained Si element release. Furthermore, the MSCs 3D-cultured in GelMA/ECM-SiP@PDA conductive hydrogel exhibits significantly increased expression of genes associated with SC-like cell differentiation, thus facilitating the myelination and axonal regeneration. Collectively, both the in vitro and in vivo studies demonstrates that the rationally designed biodegradable multifunctional hydrogel significantly enhances nerve tissues repair.


Assuntos
Hidrogéis , Regeneração Nervosa , Hidrogéis/química , Animais , Regeneração Nervosa/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Gelatina/química , Polímeros/química , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Células de Schwann/citologia , Células de Schwann/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Camundongos , Alicerces Teciduais/química , Células-Tronco/citologia , Condutividade Elétrica , Indóis/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Metacrilatos
2.
J Nanobiotechnology ; 22(1): 378, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943185

RESUMO

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.


Assuntos
Valvas Cardíacas , Hidrogéis , Ratos Sprague-Dawley , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Animais , Alicerces Teciduais/química , Anisotropia , Ratos , Hidrogéis/química , Materiais Biocompatíveis/química , Próteses Valvulares Cardíacas , Poliésteres/química , Células Cultivadas , Humanos , Matriz Extracelular/química , Masculino
3.
Clin Oral Investig ; 28(3): 194, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38441677

RESUMO

OBJECTIVES: This study aims to comprehensively investigate the potential genetic link between periodontitis and adverse pregnancy outcomes using a two-sample Mendelian Randomization approach. MATERIALS AND METHODS: We employed robust genetic instruments for chronic periodontitis as exposure data from the FinnGen database. Data encompassing various pregnancy stage outcomes, including pre-pregnancy conditions (irregular menstruation, endometriosis, abnormal reproductive bleeding, and female infertility), pregnancy complications (hemorrhage, spontaneous miscarriage, and abnormalities in products), and post-pregnancy factors (single spontaneous delivery, labor duration, and birth weight of the child), were obtained from the UK Biobank. The random-effects inverse-variance weighted (IVW) method was utilized to compute primary estimates while diligently assessing potential directional pleiotropy and heterogeneity. RESULTS: Our findings indicate a negative association between periodontitis and labor duration (odds ratio [OR] = 0.999; 95% confidence interval [CI]: 0.999 to 1.000; P = 0.017). Individuals with periodontitis are more likely to deliver lower-weight infants (OR = 0.983; 95% CI: 0.972 to 0.995; P = 0.005). We found no evidence of pleiotropy or heterogeneity in aforementioned two associations. We did not observe casual links with pre-pregnancy conditions and pregnancy complications. CONCLUSIONS: This Mendelian Randomization study underscores the genetic influence of periodontitis on specific adverse pregnancy outcomes, particularly concerning labor duration and lower birth weight deliveries. CLINICAL RELEVANCE: Our study emphasizes the critical importance of maintaining periodontal health during pregnancy and offers genetic evidence supporting these associations. Further investigation is required to delve deeper into the specific underlying mechanisms.


Assuntos
Periodontite Crônica , Complicações na Gravidez , Criança , Lactente , Gravidez , Humanos , Feminino , Peso ao Nascer/genética , Análise da Randomização Mendeliana , Biobanco do Reino Unido
4.
BMC Oral Health ; 24(1): 284, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418977

RESUMO

BACKGROUND: Investigating the molecular biology underpinning the early-stage of traumatic temporomandibular joint (TMJ) ankylosis is crucial for discovering new ways to prevent the disease. This study aimed to explore the dynamic changes of transcriptome from the intra-articular hematoma or the newly generated ankylosed callus during the onset and early progression of TMJ ankylosis. METHODS: Based on a well-established sheep model of TMJ bony ankylosis, the genome-wide microarray data were obtained from samples at postoperative Days 1, 4, 7, 9, 11, 14 and 28, with intra-articular hematoma at Day 1 serving as controls. Fold changes in gene expression values were measured, and genes were identified via clustering based on time series analysis and further categorised into three major temporal classes: increased, variable and decreased expression groups. The genes in these three temporal groups were further analysed to reveal pathways and establish their biological significance. RESULTS: Osteoblastic and angiogenetic genes were found to be significantly expressed in the increased expression group. Genes linked to inflammation and osteoclasts were found in the decreased expression group. The various biological processes and pathways related to each temporal expression group were identified, and the increased expression group comprised genes exclusively involved in the following pathways: Hippo signaling pathway, Wnt signaling pathway and Rap 1 signaling pathway. The decreased expression group comprised genes exclusively involved in immune-related pathways and osteoclast differentiation. The variable expression group consisted of genes associated with DNA replication, DNA repair and DNA recombination. Significant biological pathways and transcription factors expressed at each time point postoperatively were also identified. CONCLUSIONS: These data, for the first time, presented the temporal gene expression profiling and reveal the important process of molecular biology in the early-stage of traumatic TMJ bony ankylosis. The findings might contributed to identifying potential targets for the treatment of TMJ ankylosis.


Assuntos
Anquilose , Transtornos da Articulação Temporomandibular , Articulação Temporomandibular , Animais , Ovinos/genética , Côndilo Mandibular , Anquilose/genética , Perfilação da Expressão Gênica , Hematoma
5.
Med Sci Monit ; 28: e934511, 2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35301274

RESUMO

BACKGROUND The aims of the study were to comprehensively compare the morphology, immunophenotype, proliferation, migration, and regeneration potential of normal dental pulp stem cells (DPSCs) versus inflammatory dental pulp stem cells (iDPSCs). MATERIAL AND METHODS Healthy pulp or inflamed pulp tissue was used to isolate and culture DPSCs and iDPSCs, respectively. These cell populations were characterized by flow cytometry, colony formation assay, transwell assay, and multi-directional differentiation in vitro. RESULTS No difference was observed in the morphology, cell-surface markers, or cell migration between DPSCs and iDPSCs. DPSCs showed a higher colony-forming capacity, proliferative viability, and osteo/dentinogenesis ability compared with iDPSCs. However, iDPSCs demonstrated enhanced neurogenesis, angiogenesis, adipogenesis, and chondrogenesis capacities in comparison to DPSCs. CONCLUSIONS Our data revealed the differences of biological properties between DPSCs and iDPSCs. The highly angiogenic and neurogenic potential of iDPSCs indicate their possible use in the regeneration of the dentin-pulp complex and support the critical role of angiogenesis and neurogenesis in pulp regeneration.


Assuntos
Polpa Dentária/fisiologia , Osteogênese/fisiologia , Células-Tronco/citologia , Adulto , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Imunofenotipagem , Masculino , Estudos Retrospectivos , Adulto Jovem
6.
Nano Lett ; 21(21): 8999-9004, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34665629

RESUMO

Ubiquitous petrochemical-based plastics pose a potential threat to ecosystems. In response, bioderived and degradable polymeric materials are being developed, but their mechanical and thermal properties cannot compete with those of existing petrochemical-based plastics, especially those used as structural materials. Herein, we report a biodegradable plant cellulose nanofiber (CNF)-derived polymeric structural material with high-density reversible interaction networks between nanofibers, exhibiting mechanical and thermal properties better than those of existing petrochemical-based plastics. This all-green material has substantially improved flexural strength (∼300 MPa) and modulus (∼16 GPa) compared with those of existing petrochemical-based plastics. Its average thermal expansion coefficient is only 7 × 10-6 K-1, which is more than 10 times lower than those of petrochemical-based plastics, indicating its dimension is almost unchanged when heated, and thus, it has a thermal dimensional stability that is better than those of plastics. As a fully bioderived and degradable material, the all-green material offers a more sustainable high-performance alternative to petrochemical-based plastics.


Assuntos
Celulose , Nanofibras , Celulose/química , Ecossistema , Nanofibras/química , Plásticos , Polímeros
7.
Nano Lett ; 21(2): 952-958, 2021 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-33401909

RESUMO

Hydrogel materials with high water content and good biocompatibility are drawing more and more attention now, especially for biomedical use. However, it still remains a challenge to construct hydrogel fibers with enough strength and toughness for practical applications. Herein, we report a bio-inspired lotus-fiber-mimetic spiral structure hydrogel bacterial cellulose fiber with high strength, high toughness, high stretchability, and energy dissipation, named biomimetic hydrogel fiber (BHF). The spiral-like structure endows BHF with excellent stretchability through plastic deformation and local failure, assisted by the breaking-reforming nature of the hydrogen bonding network among cellulose nanofibers. With the high strength, high stretchability, high energy dissipation, high hydrophilicity, porous structure, and excellent biocompatibility, BHF is a promising hydrogel fiber for biomedicine. The outstanding stretchability and energy dissipation of BHF allow it to absorb energy from the tissue deformation around a wound and effectively protect the wound from rupture, which makes BHF an ideal surgical suture.


Assuntos
Lotus , Nanofibras , Celulose , Hidrogéis , Porosidade
8.
Macromol Rapid Commun ; 42(7): e2000703, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33543518

RESUMO

For polymer semiconductors, the backbone structure plays an essential role in determining their physicochemical properties and charge transport behaviors. In this work, two donor-acceptor-type polymers (P-BDF and P-NDF) based on benzodifuranone (BDF) and naphthodifunarone (NDF) as electron-deficient moieties and indaceno-dithiophene as electron-rich groups are designed, synthesized and, for the first time, applied in organic field-effect transistor. P-BDF and P-NDF differ from their backbone structures while P-BDF has a more planar backbone conformation due to its smaller conjugated core size and P-NDF features a perpendicular-extended main chain structure. As a result, P-BDF polymer exhibits bathochromic optical absorption, deeper molecular orbital energy levels, and more importantly, closer π-stacking and stronger aggregation in the solid state and thus affords a more promising hole mobility of up to 0.85 cm2 V-1 s-1 in OFET devices, while that of the P-NDF-based devices is only 0.55 cm2 V-1 s-1 . The results suggest the great potential of BDF/NDF-type chromophores in constructing novel organic semiconductors and also indicate that the main chain coplanarity of polymer semiconductors is more essential than the sole extension of π-conjugations (especially at the perpendicular direction of polymer main chains) for the design of high-performance OFET materials.


Assuntos
Polímeros , Transistores Eletrônicos , Conformação Molecular , Semicondutores
9.
BMC Oral Health ; 21(1): 668, 2021 12 28.
Artigo em Inglês | MEDLINE | ID: mdl-34961493

RESUMO

BACKGROUND: Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles. MATERIAL/METHODS: Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR. RESULTS: We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-ß), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction. CONCLUSIONS: Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.


Assuntos
Anquilose , Hemartrose , Animais , Anquilose/genética , Côndilo Mandibular , Análise em Microsséries , Osteogênese , Ovinos , Articulação Temporomandibular
10.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054063

RESUMO

Sweet cherry (Prunus avium L.) is a delicious nutrient-rich fruit widely cultivated in countries such as China, America, Chile, and Italy. However, the yield often drops severely due to the frequently-abnormal fruitlet abscission, and few studies on the metabolism during its ripening process at the proteomic level have been executed so far. To get a better understanding regarding the sweet cherry abscission mechanism, proteomic analysis between the abscising carpopodium and non-abscising carpopodium of sweet cherry was accomplished using a newly developed Liquid chromatography-mass spectrometry/mass spectrometry with Tandem Mass Tag (TMT-LC-MS/MS) methodology. The embryo viability experiments showed that the vigor of the abscission embryos was significantly lower than that of retention embryo. The activity of cell wall degrading enzymes in abscising carpopodium was significantly higher than that in non-abscising carpopodium. The anatomy results suggested that cells in the abscission zone were small and separated. In total, 6280 proteins were identified, among which 5681 were quantified. It has been observed that differentially accumulated proteins (DAPs) influenced several biological functions and various subcellular localizations. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that plenty of metabolic pathways were notably enriched, particularly those involved in phytohormone biosynthesis, cell wall metabolism, and cytoskeletal metabolism, including 1-aminocyclopropane-1-carboxylate oxidase proteins which promote ethylene synthesis, and proteins promoting cell wall degradation, such as endoglucanases, pectinase, and polygalacturonase. Differential expression of proteins concerning phytohormone biosynthesis might activate the shedding regulation signals. Up-regulation of several cell wall degradation-related proteins possibly regulated the shedding of plant organs. Variations of the phytohormone biosynthesis and cell wall degradation-related proteins were explored during the abscission process. Furthermore, changes in cytoskeleton-associated proteins might contribute to the abscission of carpopodium. The current work represented the first study using comparative proteomics between abscising carpopodium and non-abscising carpopodium. These results indicated that embryo abortion might lead to phytohormone synthesis disorder, which effected signal transduction pathways, and hereby controlled genes involved in cell wall degradation and then caused the abscission of fruitlet. Overall, our data may give an intrinsic explanation of the variations in metabolism during the abscission of carpopodium.


Assuntos
Proteínas de Plantas/metabolismo , Prunus avium/embriologia , Prunus avium/metabolismo , Lignina/metabolismo , Redes e Vias Metabólicas , Reguladores de Crescimento de Plantas/metabolismo , Biossíntese de Proteínas , Proteômica , Prunus avium/ultraestrutura , Sementes/embriologia , Sementes/metabolismo , Sementes/ultraestrutura
11.
Macromol Rapid Commun ; 40(23): e1900394, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31702099

RESUMO

Diketopyrrolopyrrole (DPP)-based copolymers have received considerable attention as promising semiconducting materials for high-performance organic thin-film transistors (OTFTs). However, these polymers typically exhibit p-type or ambipolar charge-transporting characteristics in OTFTs due to their high-lying highest occupied molecular orbital (HOMO) energy levels. In this work, a new series of DPP-based n-type polymers have been developed by incorporating fused bithiophene imide oligomers (BTIn) into DPP polymers. The resulting copolymers BTIn-DPP show narrow band gaps as low as 1.27 eV and gradually down-shifted frontier molecular orbital energy levels upon the increment of imide group number. Benefiting from the coplanar backbone conformation, well-delocalized π-system, and favorable polymer chain packing, the optimal polymer in the series shows promising n-type charge transport with an electron mobility up to 0.48 cm2 V-1 s-1 in OTFTs, which is among the highest values for the DPP-based n-type polymers reported to date. The results demonstrate that incorporating fused bithiophene imide oligomers into polymers can serve as a promising strategy for constructing high-performance n-type polymeric semiconductors.


Assuntos
Imidas/química , Cetonas/química , Polímeros/síntese química , Pirróis/química , Tiofenos/química , Teoria da Densidade Funcional , Estrutura Molecular , Polímeros/química , Semicondutores , Transistores Eletrônicos
12.
J Nanobiotechnology ; 16(1): 1, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-29321058

RESUMO

BACKGROUND: The results showed that the deciding factor is the culture medium in which the bacteria and the graphene oxide (GO) are incubated at the initial manipulation step. These findings allow better use of GO and GO-based materials more and be able to clearly apply them in the field of biomedical nanotechnology. RESULTS: To study the use of GO sheets applied in the field of biomedical nanotechnology, this study determines whether GO-based materials [GO, GO-polyoxyalkyleneamine (POAA), and GO-chitosan] stimulate or inhibit bacterial growth in detail. It is found that it depends on whether the bacteria and GO-based materials are incubated with a nutrient at the initial step. This is a critical factor for the fortune of bacteria. GO stimulates bacterial growth and microbial proliferation for Gram-negative and Gram-positive bacteria and might also provide augmented surface attachment for both types of bacteria. When an external barrier that is composed of GO-based materials forms around the surface of the bacteria, it suppresses nutrients that are essential to microbial growth and simultaneously produces oxidative stress, which causes bacteria to die, regardless of whether they have an outer-membrane-Gram-negative-bacteria or lack an outer-membrane-Gram-positive-bacteria, even for high concentrations of biocompatible GO-POAA. The results also show that these GO-based materials are capable of inducing reactive oxygen species (ROS)-dependent oxidative stress on bacteria. Besides, GO-based materials may act as a biofilm, so it is hypothesized that they suppress the toxicity of low-dose chitosan. CONCLUSION: Graphene oxide is not an antimicrobial material but it is a general growth enhancer that can act as a biofilm to enhance bacterial attachment and proliferation. However, GO-based materials are capable of inducing ROS-dependent oxidative stress on bacteria. The applications of GO-based materials can clearly be used in antimicrobial surface coatings, surface-attached stem cells for orthopedics, antifouling for biocides and microbial fuel cells and microbial electro-synthesis.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/crescimento & desenvolvimento , Grafite/farmacologia , Polímeros/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/ultraestrutura , Contagem de Colônia Microbiana , Fluorescência , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espectroscopia Fotoeletrônica , Espécies Reativas de Oxigênio , Espectrofotometria Ultravioleta
13.
Heliyon ; 10(2): e24366, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38288023

RESUMO

Objective: This study aims to identify the periodontitis factor that activates excessive autophagy in pancreatic ß cells, resulting in organic lesions of pancreatic islet tissues and diminished insulin secretion, thereby accelerating the progression of diabetes mellitus (DM). Methods: Sprague-Dawley (SD) rats were induced with periodontitis (PD), type 2 diabetes mellitus (T2DM), or the combination of T2DM and PD (DP) through a high-sugar/high-fat diet and ligation of the tooth neck with silk thread. Alveolar bone resorption was assessed using Micro-CT, blood glucose levels were measured with a blood glucose meter, pancreatic tissue pathology was examined through HE staining, and the expression of autophagy-related proteins Beclin1 and LC3II/LC3I was analyzed using Western blotting. Results: Micro-CT results revealed more pronounced alveolar bone resorption and root bifurcation exposure in the PD and DP groups compared to the control group, with the DP group exhibiting the most severe condition. HE staining demonstrated the formation of periodontal pockets, severe alveolar bone destruction, and abnormal pancreatic islet tissue morphology in the PD and DP groups. The serum levels of IL-6, TNF-α, and IL-1ß increased sequentially in the control, DM, PD, and DP groups (P < 0.05). Relative expressions of GCK and GLUT-2 mRNA decreased in the PD group compared to the control group (P > 0.05), while the mRNA expressions in the DP and DM groups increased (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Western blot results indicated increased expression levels of autophagy proteins Beclin1 and LC3II/LC3I in the DM and DP groups compared to the control group (P < 0.05), with the DP group exhibiting higher levels than the DM group (P < 0.05). Conclusion: The findings demonstrate that periodontal inflammatory factors may promote the enhancement of pancreatic cell autophagy in diabetic rats.

14.
Adv Sci (Weinh) ; 11(2): e2306230, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37953442

RESUMO

Combined chemotherapy and targeted therapy holds immense potential in the management of advanced gastric cancer (GC). GC tissues exhibit an elevated expression level of protein kinase B (AKT), which contributes to disease progression and poor chemotherapeutic responsiveness. Inhibition of AKT expression through an AKT inhibitor, capivasertib (CAP), to enhance cytotoxicity of paclitaxel (PTX) toward GC cells is demonstrated in this study. A cathepsin B-responsive polymeric nanoparticle prodrug system is employed for co-delivery of PTX and CAP, resulting in a polymeric nano-drug BPGP@CAP. The release of PTX and CAP is triggered in an environment with overexpressed cathepsin B upon lysosomal uptake of BPGP@CAP. A synergistic therapeutic effect of PTX and CAP on killing GC cells is confirmed by in vitro and in vivo experiments. Mechanistic investigations suggested that CAP may inhibit AKT expression, leading to suppression of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway. Encouragingly, CAP can synergize with PTX to exert potent antitumor effects against GC after they are co-delivered via a polymeric drug delivery system, and this delivery system helped reduce their toxic side effects, which provides an effective therapeutic strategy for treating GC.


Assuntos
Paclitaxel , Neoplasias Gástricas , Humanos , Inibidores da Angiogênese , Catepsina B , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases , Polímeros , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Neoplasias Gástricas/tratamento farmacológico
15.
ACS Nano ; 18(17): 11323-11334, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38635335

RESUMO

Expounding bioaccumulation pathways of nanoplastics in organisms is a prerequisite for assessing their ecological risks in the context of global plastic pollution. Invertebrate uptake preference toward nanoplastics is a key initial step of nanoplastic food chain transport that controls their global biosafety, while the biological regulatory mechanism remains unclear. Here, we reveal a preferential uptake mechanism involving active avoidance of nanoplastics by Caenorhabditis elegans and demonstrate the relationship between the uptake preference and nanoplastic characteristics. Nanoplastics with 100 nm in size or positive surface charges induce stronger avoidance due to higher toxicity, causing lower accumulation in nematodes, compared to the 500 nm-sized or negatively charged nanoplastics, respectively. Further evidence showed that nematodes did not actively ingest any types of nanoplastics, while different nanoplastics induced defense responses in a toxicity-dependent manner and distinctly stimulated the avoidance behavior of nematodes (ranged from 15.8 to 68.7%). Transcriptomics and validations using mutants confirmed that the insulin/IGF signaling (IIS) pathway is essential for the selective avoidance of nanoplastics. Specifically, the activation of DAF-16 promoted the IIS pathway-mediated defense against nanoplastics and stimulated the avoidance behavior, increasing the survival chances of nematodes. Considering the genetical universality of this defense response among invertebrates, such an uptake preference toward certain nanoplastics could lead to cascaded risks in the ecosystem.


Assuntos
Caenorhabditis elegans , Animais , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/metabolismo , Aprendizagem da Esquiva/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Nanopartículas/química , Plásticos/química , Tamanho da Partícula , Comportamento Animal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Microplásticos/toxicidade
16.
Adv Healthc Mater ; 13(10): e2304207, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38175149

RESUMO

Myocardial infarction (MI) results in cardiomyocyte necrosis and conductive system damage, leading to sudden cardiac death and heart failure. Studies have shown that conductive biomaterials can restore cardiac conduction, but cannot facilitate tissue regeneration. This study aims to add regenerative capabilities to the conductive biomaterial by incorporating human endometrial mesenchymal stem cell (hEMSC)-derived exosomes (hEMSC-Exo) into poly-pyrrole-chitosan (PPY-CHI), to yield an injectable hydrogel that can effectively treat MI. In vitro, PPY-CHI/hEMSC-Exo, compared to untreated controls, PPY-CHI, or hEMSC-Exo alone, alleviates H2O2-induced apoptosis and promotes tubule formation, while in vivo, PPY-CHI/hEMSC-Exo improves post-MI cardiac functioning, along with counteracting against ventricular remodeling and fibrosis. All these activities are facilitated via increased epidermal growth factor (EGF)/phosphoinositide 3-kinase (PI3K)/AKT signaling. Furthermore, the conductive properties of PPY-CHI/hEMSC-Exo are able to resynchronize cardiac electrical transmission to alleviate arrythmia. Overall, PPY-CHI/hEMSC-Exo synergistically combines the cardiac regenerative capabilities of hEMSC-Exo with the conductive properties of PPY-CHI to improve cardiac functioning, via promoting angiogenesis and inhibiting apoptosis, as well as resynchronizing electrical conduction, to ultimately enable more effective MI treatment. Therefore, incorporating exosomes into a conductive hydrogel provides dual benefits in terms of maintaining conductivity, along with facilitating long-term exosome release and sustained application of their beneficial effects.


Assuntos
Quitosana , Exossomos , Células-Tronco Mesenquimais , Infarto do Miocárdio , Humanos , Polímeros/metabolismo , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Pirróis , Exossomos/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Preparações de Ação Retardada/farmacologia , Peróxido de Hidrogênio/metabolismo , Infarto do Miocárdio/terapia , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/metabolismo , Miócitos Cardíacos/metabolismo
17.
mSystems ; : e0008924, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940519

RESUMO

The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs. IMPORTANCE: Our study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

18.
J Huazhong Univ Sci Technolog Med Sci ; 33(5): 754-758, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24142732

RESUMO

The purpose of this study was to develop docetaxel-poly (lactide-co-glycolide) (PLGA) loaded nanoparticles by using nanoprecipitation method and optimize the relative parameters to obtain nanoparticles with higher encapsulation efficiency and smaller size. The physicochemical characteristics of nanoparticles were studied. The optimized parameters were as follows: the oil phase was mixture of acetone and ethanol, concentration of tocopheryl polyethylene glycol succinate (TPGS) was 0.2%, the ratio of oil phase to water phase was 1:5, and the theoretical drug concentration was 5%. The optimized nanoparticles were spherical with size between 130 and 150 nm. The encapsulation efficiency was (40.83±2.1)%. The in vitro release exhibited biphasic pattern. The results indicate that docetaxel-PLGA nanoparticles were successfully fabricated and may be used as the novel vehicles for docetaxel, which would replace Taxotere® and play great roles in future.


Assuntos
Precipitação Fracionada/métodos , Ácido Láctico/química , Nanopartículas/química , Nanotecnologia/métodos , Ácido Poliglicólico/química , Taxoides/química , Acetona/química , Antineoplásicos/química , Antineoplásicos/farmacocinética , Cromatografia Líquida de Alta Pressão , Docetaxel , Composição de Medicamentos/métodos , Etanol/química , Microscopia Eletrônica de Varredura , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Succinatos/química , Propriedades de Superfície , Taxoides/farmacocinética
19.
Zookeys ; 1166: 121-139, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333897

RESUMO

Siphlonurusdongxi Li & Tong, sp. nov. from Shangri-La City, Yunnan Province, China, is described based on egg, nymph, and winged stages. The new species is closely related to S.davidi (Navás, 1932), and can be distinguished by the colour of the imago, the forking point of MP, the penis, posterolateral spines of tergum IX of imagoes, and first abdominal terga nymph, as well as the structure of the egg. The new species and S.davidi have the same morphological and structural characteristics, such as the long cubital area with many intercalaries, cross veins between C, Sc, RA, and RSa1 surrounded with distinct pigments, the strong curvature of vein CuP in the forewing, the broad expansion of the hindwing, the membranous penis lobes fused without teeth, supporting the proposition of a new species complex, the Siphlonurusdavidi group. The structures of the penis and the egg of the new species could help understand the origin and evolution of the genus Siphlonurus.

20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 41(6): 694-700, 2023 Dec 01.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-38597035

RESUMO

OBJECTIVES: This study aims to explore the status quo of health literacy and quality of life in elderly patients with chronic periodontitis and determine their correlation to understand the influencing factors of health literacy and quality of life. METHODS: A total of 150 elderly patients with chronic periodontitis were investigated using the general information questionnaire, Oral Health Literacy-Adult Questionnaire, and Oral Health Impact Profile for Chronic Periodontitis. RESULTS: The total scores of health literacy and quality of life of elderly patients with chronic periodontitis were 6.59±4.11 and 29.25±9.42, respectively. The total score of health literacy was negatively correlated with the total score of quality of life (r=-0.234, P<0.01). Regression analysis showed that age, place of residence, education level, and disease understanding were the influencing factors of health literacy. Family history, smoking, and education level were the influencing factors of quality of life. CONCLUSIONS: The health literacy level of elderly patients with chronic periodontitis is insufficient, and their quality of life needs to be improved. Improving the health literacy of patients is an effective way to improve their quality of life. Nursing staff must formulate corresponding health education strategies to improve the health literacy of patients and improve their quality of life.


Assuntos
Periodontite Crônica , Letramento em Saúde , Adulto , Humanos , Idoso , Qualidade de Vida , Saúde Bucal , Inquéritos e Questionários
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