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1.
J Cell Mol Med ; 28(18): e70103, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39334527

RESUMO

Colorectal cancer (CRC) represents a significant malignancy within the digestive system, characterized by high incidence and mortality rates. In recent years, molecular targeted therapy has been introduced as a supplementary strategy in CRC management, complementing traditional modalities such as surgery, radiation and chemotherapy. The identification of novel therapeutic targets for CRC remains critically important. Ferroptosis, a unique form of programmed cell death distinct from apoptosis and necrosis, is characterized by cellular damage resulting from iron-induced lipid peroxidation, leading to cell death. This study utilizes a combination of bioinformatics analysis and clinical specimen validation to demonstrate that the long non-coding RNA (lncRNA) ALMS1-IT1 is significantly upregulated in CRC tissues and strongly associated with ferroptosis. Through a series of experimental investigations, we have determined that ALMS1-IT1 negatively regulates ferroptosis in CRC cells, thereby promoting cancer growth and metastasis, acting as an oncogenic factor. Furthermore, we explored the molecular interactions of ALMS1-IT1, revealing its role in activating STAT3 protein phosphorylation. This activation enhances the immune evasion capabilities of CRC cells. Rescue experiments indicated that STAT3 activation is essential for ALMS1-IT1's suppression of ferroptosis, immune evasion and oncogenic behaviour in CRC. Our findings underscore the critical biological role of ALMS1-IT1 in the progression of CRC and suggest its potential as a target for drug development.


Assuntos
Neoplasias Colorretais , Ferroptose , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante , Fator de Transcrição STAT3 , Ferroptose/genética , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , RNA Longo não Codificante/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Linhagem Celular Tumoral , Animais , Camundongos , Proliferação de Células , Evasão da Resposta Imune
2.
J Cell Mol Med ; 28(10): e18398, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38785203

RESUMO

Behçet's disease (BD) is a complex autoimmune disorder impacting several organ systems. Although the involvement of abdominal aortic aneurysm (AAA) in BD is rare, it can be associated with severe consequences. In the present study, we identified diagnostic biomarkers in patients with BD having AAA. Mendelian randomization (MR) analysis was initially used to explore the potential causal association between BD and AAA. The Limma package, WGCNA, PPI and machine learning algorithms were employed to identify potential diagnostic genes. A receiver operating characteristic curve (ROC) for the nomogram was constructed to ascertain the diagnostic value of AAA in patients with BD. Finally, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were conducted. The MR analysis indicated a suggestive association between BD and the risk of AAA (odds ratio [OR]: 1.0384, 95% confidence interval [CI]: 1.0081-1.0696, p = 0.0126). Three hub genes (CD247, CD2 and CCR7) were identified using the integrated bioinformatics analyses, which were subsequently utilised to construct a nomogram (area under the curve [AUC]: 0.982, 95% CI: 0.944-1.000). Finally, the immune cell infiltration assay revealed that dysregulation immune cells were positively correlated with the three hub genes. Our MR analyses revealed a higher susceptibility of patients with BD to AAA. We used a systematic approach to identify three potential hub genes (CD247, CD2 and CCR7) and developed a nomogram to assist in the diagnosis of AAA among patients with BD. In addition, immune cell infiltration analysis indicated the dysregulation in immune cell proportions.


Assuntos
Aneurisma da Aorta Abdominal , Síndrome de Behçet , Biomarcadores , Biologia Computacional , Análise da Randomização Mendeliana , Humanos , Síndrome de Behçet/genética , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/complicações , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/diagnóstico , Biologia Computacional/métodos , Curva ROC , Redes Reguladoras de Genes , Predisposição Genética para Doença , Mapas de Interação de Proteínas/genética , Nomogramas , Receptores CCR7
3.
Biomacromolecules ; 25(2): 890-902, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38180887

RESUMO

Both biochemical and mechanical cues could regulate the function of stem cells, but the interaction mechanism of their signaling pathway remains unclear, especially in the three-dimensional (3D) culture mode. Higher matrix stiffness promotes osteogenic differentiation of stem cells, and bone morphogenic protein-2 (BMP-2) has been clinically applied to promote bone regeneration. Here, the crosstalk of extracellular mechanical signals on BMP-2 signaling was investigated in rat bone marrow stromal cells (rMSCs) cultured inside cryogels with interconnective pores. Stiff cryogel independently promoted osteogenic differentiation and enhanced the autocrine secretion of BMP-2, thus stimulating increased phosphorylation levels of the Smad1/5/8 complex. BMP-2 mimetic peptide (BMMP) and high cryogel stiffness jointly guided the osteogenic differentiation of rMSCs. Inhibition of rho-associated kinase (ROCK) by Y-27632 or inhibition of nonmuscle myosin II (NM II) by blebbistatin showed that osteogenesis induction by BMP-2 signaling, as well as autocrine secretion of BMP-2 and phosphorylation of the Smad complex, requires the involvement of cytoskeletal tension and ROCK pathway signaling. An interconnective microporous cryogel scaffold promoted rMSC osteogenic differentiation by combining matrix stiffness and BMMP, and it accelerated critical cranial defect repair in the rat model.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Pargilina/análogos & derivados , Ratos , Animais , Criogéis , Gelatina , Diferenciação Celular , Proteína Morfogenética Óssea 2/farmacologia , Proteína Morfogenética Óssea 2/metabolismo , Células da Medula Óssea/metabolismo , Células Cultivadas
4.
IUBMB Life ; 75(8): 659-672, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36961205

RESUMO

Colorectal cancer (CRC) ranks as the most common gastrointestinal solid carcinoma globally. Substantial evidence has established a pivotal role for circular RNAs (circRNAs) in CRC progression. In this study, differentially expressed circRNAs were analyzed based on a public dataset (GSE126094) and elevated expression of circCASK (hsa_circ_0001917) was validated in CRC. Moreover, increased circCASK was also confirmed in CRC patients. Functionally, circCASK knockdown led to a significant decrease in CRC cell growth and attenuated cell migration and invasion. Similarly, circCASK knockdown markedly attenuated tumor growth in vivo. Mechanistically, circCASK sponged miR-1271-5p and enhanced sine oculis homeobox homolog 1 (SIX1) expression. More importantly, both SIX1 overexpression and miR-1271-5p knockdown could reverse the cellular behavior inhibition induced by circCASK knockdown. Furthermore, SIX1 was most strongly and positively linked with Wnt/ß-catenin signaling pathways, circCASK triggered Wnt/ß-catenin signaling through the miR-1271-5p/SIX1 axis, and FOXC2 transcriptionally induced circCASK expression. In conclusion, circCASK induced by FOXC2 accelerated CRC progression through the miR-1271-5p/SIX1 axis, thus providing an interesting insight into CRC tumorigenesis.


Assuntos
Neoplasias Colorretais , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , RNA Circular/genética , beta Catenina/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Proliferação de Células/genética , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo
5.
Sensors (Basel) ; 23(6)2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36992068

RESUMO

Fire remains a pressing issue that requires urgent attention. Due to its uncontrollable and unpredictable nature, it can easily trigger chain reactions and increase the difficulty of extinguishing, posing a significant threat to people's lives and property. The effectiveness of traditional photoelectric- or ionization-based detectors is inhibited when detecting fire smoke due to the variable shape, characteristics, and scale of the detected objects and the small size of the fire source in the early stages. Additionally, the uneven distribution of fire and smoke and the complexity and variety of the surroundings in which they occur contribute to inconspicuous pixel-level-based feature information, making identification difficult. We propose a real-time fire smoke detection algorithm based on multi-scale feature information and an attention mechanism. Firstly, the feature information layers extracted from the network are fused into a radial connection to enhance the semantic and location information of the features. Secondly, to address the challenge of recognizing harsh fire sources, we designed a permutation self-attention mechanism to concentrate on features in channel and spatial directions to gather contextual information as accurately as possible. Thirdly, we constructed a new feature extraction module to increase the detection efficiency of the network while retaining feature information. Finally, we propose a cross-grid sample matching approach and a weighted decay loss function to handle the issue of imbalanced samples. Our model achieves the best detection results compared to standard detection methods using a handcrafted fire smoke detection dataset, with APval reaching 62.5%, APSval reaching 58.5%, and FPS reaching 113.6.

6.
J Microencapsul ; 36(1): 21-31, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30757946

RESUMO

The purpose of this study was to investigate the influences of drying methods on the risperidone (RIS) release profiles of RIS-loaded PLGA microspheres. These microspheres were fabricated with an O/W emulsion solvent evaporation method. The wet microspheres were dried with freeze drying and vacuum drying methods. The microspheres were mono-dispersed spheres with an average diameter of 100 µm. Studies found that drying methods had great influence on the porosity, morphology, and release profiles of RIS-loaded PLGA microspheres. Specifically, the freeze-dried microspheres had higher porosity (78.46 ± 1.64%) than those vacuum-dried ones (52.45 ± 2.68%), and they showed higher RIS release rates (p < 0.05). In the accelerated release tests (45 °C), these microspheres dried under the pressures of 700 mmHg and 200 mmHg gave faster release rates than those ones dried under the pressure of 450 mmHg. Importantly, the accelerated release test (45 °C) had a high correlation with the real-time test (37 °C) (R2 > 0.99). These studies exhibited a significance in the precise preparation of RIS-loaded PLGA microspheres.


Assuntos
Portadores de Fármacos/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Risperidona/química , Antagonistas da Serotonina/química , Dessecação , Composição de Medicamentos , Liberação Controlada de Fármacos , Liofilização , Cinética , Porosidade , Risperidona/administração & dosagem , Antagonistas da Serotonina/administração & dosagem
7.
J Mater Sci Mater Med ; 26(8): 224, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26271217

RESUMO

Phosphate glass fibers (PGF) have emerged as promising building blocks for constructing bone scaffolds. In this study, fibrous scaffolds (PGFS) were fabricated using a facile binding method at room temperature. PGFS exhibited an extracellular matrix-like morphology and were composed of PGF as matrix and chitosan as the natural binding glue. They showed an interconnected porous structure with a porosity of ~87% and pore size of 100-500 µm. PGFS exhibited the typical compressive stress-strain behaviour of highly porous, low-density, open-cell scaffolds. Their yield stress and modulus were ~0.38 and ~2.84 MPa, respectively, with the strength being higher than the lower bound of the compressive strength of cancellous bone. PGFS were degradable and the weight loss was about 25% after immersion in stimulated body fluid (SBF) for 28 days. In addition, the yield stress and the modulus decreased with increasing immersion time in SBF. Apatite formation could be detected on the surface of PGFS within 7 days of immersion in SBF. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay indicated that PGFS were non-cytotoxic against bone marrow stromal cells (bMSCs) after culture for up to 72 h. These results suggest that PGFS could be promising scaffolds for bone regeneration applications.


Assuntos
Regeneração Óssea , Substitutos Ósseos/química , Quitosana/química , Vidro/química , Alicerces Teciduais/química , Implantes Absorvíveis , Materiais Biocompatíveis/química , Fenômenos Biomecânicos , Líquidos Corporais , Calcificação Fisiológica , Humanos , Técnicas In Vitro , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Microscopia Eletrônica de Varredura , Fosfatos/química , Propriedades de Superfície
8.
Chem Biodivers ; 12(11): 1718-24, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26567949

RESUMO

One new diketopiperazine alkaloid amauromine B (1), along with three known meroterpenoids, austalide B (2), austalides N and O (3 and 4), and two known steroids (5 and 6), was isolated and identified from the culture broth of the fungus Aspergillus terreus 3.05358. Their structures were elucidated by extensive spectroscopic techniques, including 2D-NMR and MS analysis, the absolute configuration of 1 was unambiguously established by single crystal X-ray diffraction analysis. All the isolates were evaluated for their inhibitory effects on α-glucosidase. Amauromine B (1) and austalide N (3) exhibited more potent α-glucosidase inhibitory activities than the positive control acarbose.


Assuntos
Aspergillus/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Glucosidases/metabolismo , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Inibidores de Glicosídeo Hidrolases/química , Humanos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
9.
Mol Biotechnol ; 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37812330

RESUMO

Although gemcitabine (GEM) is the first­line drug for advanced pancreatic adenocarcinoma (PAAD), the development of GEM resistance severely limits the effectiveness of this chemotherapy. This study investigated the mechanisms of ecotropic viral integration site 2 A (EVI2A) for resistance to GEM and immune evasion in PAAD. GEM resistance-related biomarkers were predicted using GEO datasets, and GEM-resistant PAAD cells were generated. EVI2A was found expressed highly in GEM-resistant PAAD cells. Gain-of-function analyses revealed that EVI2A encouraged the proliferation and motility of GEM-resistant cells and prevented apoptosis. In addition, EVI2A reduced T cell effector activation. SMYD2 was overexpressed in GEM-resistant cells, and SMYD2 enhanced H3K36me2 modification of EVI2A, thereby promoting EVI2A expression. SMYD2 reduced the sensitivity of GEM-resistant cells, which was reversed by EVI2A knockdown. SMYD2 increased the amount of M2 macrophages (co-cultured with PAAD cells) and decreased T cell effector activation (co-cultured with macrophage supernatant), and the number of M2 macrophages was decreased and T cell effectors were activated following EVI2A knockdown. Our findings indicate that EVI2A, manipulated by the SMYD2-H3K36me2 epigenetic axis, promoted GEM resistance and M2 macrophage-mediated immune evasion in PAAD. Therefore, EVI2A might represent a therapeutic target for overcoming GEM resistance and immunosuppressive environment in PAAD.

10.
Materials (Basel) ; 16(5)2023 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-36903027

RESUMO

Traditional research and development (R&D) on biomedical materials depends heavily on the trial and error process, thereby leading to huge economic and time burden. Most recently, materials genome technology (MGT) has been recognized as an effective approach to addressing this problem. In this paper, the basic concepts involved in the MGT are introduced, and the applications of MGT in the R&D of metallic, inorganic non-metallic, polymeric, and composite biomedical materials are summarized; in view of the existing limitations of MGT for R&D of biomedical materials, potential strategies are proposed on the establishment and management of material databases, the upgrading of high-throughput experimental technology, the construction of data mining prediction platforms, and the training of relevant materials talents. In the end, future trend of MGT for R&D of biomedical materials is proposed.

11.
Biomater Adv ; 154: 213585, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37591050

RESUMO

Implant instability and bacterial infection are the two main reasons for the failure of bone implantation. Herein, a porous biocomposite containing polyimide (PI) and 40 w% molybdenum disulfide (MoS2) nanosheets (PM40) was fabricated, and quercetin (QT) was loaded onto the porous surface of PM40 (PMQT). Incorporation of MoS2 nanosheets into PI remarkably increased the compressive strength, water absorption and protein absorption of PM40. PM40 exhibited good antibacterial capability owing to presence of MoS2, while PMQT displayed the further enhancement of antibacterial capability because of loading of QT. PM40 with MoS2 significantly stimulated the osteoblastic differentiation of bone mesenchymal stem cells in vitro, and PMQT with QT displayed further enhancement. In comparison with PI and PM40, PMQT significantly inhibited the osteoclastic differentiation thanks to the sustained-release of QT that suppressed the formation of osteoclasts and expression of osteoclastic genes. Moreover, PM40 with MoS2 accelerated osteogenesis and bone-bonding in vivo, and PMQT with QT displayed further enhancement. In summary, the cooperative effect of MoS2 and QT significantly improved osteoblastic differentiation and ameliorated bone-bonding in vivo. Accordingly, PMQT displayed marvelous osteogenic and antibacterial effects, which would have the potential for repair of load-bearing bone.


Assuntos
Molibdênio , Quercetina , Molibdênio/farmacologia , Quercetina/farmacologia , Porosidade , Antibacterianos/farmacologia , Diferenciação Celular
12.
J Mater Chem B ; 11(42): 10218-10233, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37869981

RESUMO

Polymer-based composites are considered promising candidates for bone repair as they possess some outstanding advantages over ceramic/metallic/polymeric biomaterials. Tantalum (Ta)/polyimide (PI) biocomposites (PT) containing 20 v% (PT20) and 40 v% (PT40) Ta nanoparticles were fabricated, and luteolin (LU) was loaded on PT40 (LUPT40). Compared with PT20 and PI, PT40 with a high Ta content displayed high surface behaviors (e.g., roughness, surface energy, and hydrophilicity). PT40 remarkably improved cell adhesion and multiplication, and LUPT40 with LU displayed further enhancement in vitro. Moreover, LUPT40 evidently boosted osteoblastic differentiation while suppressing osteoclastic differentiation. Furthermore, LUPT40 exhibited good antibacterial effects because of the slow release of LU. The in vivo results confirmed that PT40 markedly promoted bone formation and LUPT40 further enhanced bone formation/bone bonding. In brief, the incorporation of Ta particles improved the surface behaviors of PT40, which stimulated cell response/bone formation. Moreover, the slow release of LU from LUPT40 not only promoted cell response/bone formation but also enhanced bone bonding. The synergistic effects of Ta and LU release from LUPT40 enhanced bone formation/bone bonding. Therefore, LUPT40 would have great potential for the repair of bear-loading bone.


Assuntos
Osteogênese , Tantálio , Tantálio/farmacologia , Luteolina/farmacologia , Osso e Ossos , Diferenciação Celular , Polímeros/farmacologia
13.
Mater Horiz ; 10(11): 4662-4685, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37705440

RESUMO

Biomimetic cell culture, which involves creating a biomimetic microenvironment for cells in vitro by engineering approaches, has aroused increasing interest given that it maintains the normal cellular phenotype, genotype and functions displayed in vivo. Therefore, it can provide a more precise platform for disease modelling, drug development and regenerative medicine than the conventional plate cell culture. In this review, initially, we discuss the principle of biomimetic cell culture in terms of the spatial microenvironment, chemical microenvironment, and physical microenvironment. Then, the main strategies of biomimetic cell culture and their state-of-the-art progress are summarized. To create a biomimetic microenvironment for cells, a variety of strategies has been developed, ranging from conventional scaffold strategies, such as macroscopic scaffolds, microcarriers, and microgels, to emerging scaffold-free strategies, such as spheroids, organoids, and assembloids, to simulate the native cellular microenvironment. Recently, 3D bioprinting and microfluidic chip technology have been applied as integrative platforms to obtain more complex biomimetic structures. Finally, the challenges in this area are discussed and future directions are discussed to shed some light on the community.


Assuntos
Biomimética , Engenharia Tecidual , Técnicas de Cultura de Células , Microambiente Celular , Microfluídica
14.
Materials (Basel) ; 15(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35806535

RESUMO

An orbital enucleation implant is used to compensate for the orbital volume deficits in the absence of the globe. In this work, copper-doped bioactive glass in poly(ether-ether-ketone) (CuBG/PEEK) composite scaffolds as an orbital enucleation implant were designed and fabricated by cool-pressed sintering and particle-leaching techniques, the incorporation of copper-doped bioactive glass in poly(ether-ether-ketone) (CuBG/PEEK) was expected to significantly improve the biocompatibility of the PEEK implant. The consequences after implantation of the CuBG/PEEK composite scaffolds in experimental, eviscerated rabbits was observed and assayed in term of histopathological examination. In detail, 24 rabbits were randomly divided into three groups: Group A, PEEK scaffolds; Group B, 20% CuBG/PEEK composite scaffolds; Group C, 40% CuBG/PEEK composite scaffolds; the rabbits were sacrificed at week 4 and week 12, followed by histochemical staining and observation. As a result, the PEEK group exhibited poor material exposure and tissue healing, while the CuBG/PEEK scaffolds showed good biocompatibility, and the 40% CuBG/PEEK composite scaffold exhibited the best performance in angiogenesis and tissue repair. Therefore, this study demonstrates the potential of CuBG/PEEK composite scaffolds as an orbital enucleation implant.

15.
Biomater Sci ; 10(15): 4243-4256, 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35762466

RESUMO

Implanted materials with both osteogenic and antibacterial functions are promising for facilitating osteointegration and preventing infection for orthopedic applications. In this work, we synthesized flower-like molybdenum disulfide (fMD) submicro-spheres containing nanosheets, which were incorporated onto the microporous surface of polyimide (PI) via concentrated sulfuric acid, suspending fMD contents of 5 wt% (SPM1) and 10 wt% (SPM2). Compared with sulfonated polyimide (SPM0), both SPM1 and SPM2 with microporous surfaces containing fMD exhibited nano-submicro-microporous surfaces, which improved the surface roughness, wettability, and surface energy. Due to there being more fMD submicro-spheres on the microporous surface, SPM2 revealed a better antibacterial effect than SPM1. In addition, compared with SPM1 and SPM0, SPM2 with more fMD significantly promoted rat bone marrow-derived stromal cell response in vitro. Moreover, SPM2 remarkably enhanced new bone formation and osteointegration in vivo. In summary, the combination of fMD with the microporous surface of SPM2 resulted in a nano-submicro-microporous surface with optimized surface performance, which possessed not only osteogenic bioactivity but also an antibacterial effect. As a bone implant, SPM2 with osteogenic and antibacterial functions may have enormous potential as a bone tissue substitute.


Assuntos
Substitutos Ósseos , Células-Tronco Mesenquimais , Animais , Antibacterianos/farmacologia , Regeneração Óssea , Substitutos Ósseos/farmacologia , Dissulfetos , Molibdênio , Osteogênese , Ratos
16.
Artigo em Inglês | MEDLINE | ID: mdl-36508261

RESUMO

Background: Trigger transposable element-derived 1 (TIGD1) is a human-specific gene, but no studies have been conducted to determine its mechanism of action. Our aim is to ascertain the function and mode of action of TIGD1 in the development of colon cancer. Materials and Methods: We used bioinformatics to analyze the relationship between TIGD1 and the clinical characteristics of colon cancer, as well as its prognosis. A series of cell assays were conducted to assess the function of TIGD1 in the proliferation and migration of colon cancer, and flow cytometry was used to explore its effects on apoptosis and the cell cycle. Results: We discovered that the expression of TIGD1 was remarkably elevated in colon cancer. Clinical correlation analysis demonstrated that TIGD1 expression was elevated in the tissues of advanced-stage patients, and it was remarkably elevated in individuals with both lymph node and distant metastasis. Further, we found that individuals showing elevated TIGD1 expression levels had a shortened survival time. Univariate and multivariate Cox regression analyses revealed that TIGD1 was an independent prognostic factor. Overexpression of the TIGD1 gene remarkedly enhances the proliferation and metastasis of colon cancer cells and suppresses apoptosis. In addition, the overexpression of TIGD1 can enhance the transition of tumor cells from the G1 toward the S phase. Western blot results suggested that TIGD1 may promote the malignant activity of colon cancer cells via the Wnt/ß-catenin signaling pathway, Bcl-2, N-cadherin, BAX, E-cadherin, CDK6, and CyclinD1. Conclusions: TIGD1 may be an independent prognostic factor in the advancement of colon cancer, and therefore function as a therapeutic target.

17.
J Mater Chem B ; 10(42): 8719-8732, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36239238

RESUMO

Due to the lower regeneration capacity of the osteoporotic bone, the treatment of osteoporotic defects is extremely challenging in clinics. In this study, strontium-doped bioactive glass nanoparticles loaded with sodium alendronate (ALN), namely A-SrBG, were incorporated into the poly(ether-ether-ketone) matrix to fabricate a bioactive composite scaffold (ASP), which was expected to both inhibit bone resorption and promote bone regeneration. The results showed that such a composite scaffold with interconnected macropores (200-400 µm) could release Ca2+, Sr2+, and ALN in vitro. The proliferation, alkaline phosphatase (ALP) activity, expression of osteogenesis-related genes, and formation of calcified nodules of rat bone marrow stromal cells (rBMSCs) were clearly evidenced, and the reduction in the proliferation, tartrate-resistant acid phosphatase (TRAP) activity, cell fusion, and expression of osteoclastogenesis-related genes of osteoclasts was observed as well. In the presence of the ASP scaffold, enhanced osteogenesis along with inhibiting osteoclastogenesis was observed by modulating the osteoprotegerin (OPG)/receptor activator for nuclear factor κB ligand (RANKL) ratio. The efficacy of the composite scaffold in the regeneration of osteoporotic critical-sized cranial defect in a rat model was evaluated. Therefore, the bioactive composite scaffold with excellent biocompatibility and osteogenic potential could be a promising material for the repair of osteoporotic bone defects.


Assuntos
Nanocompostos , Osteoporose , Ratos , Animais , Osteoclastos/metabolismo , Cetonas/metabolismo , Éter/metabolismo , Osteoblastos/metabolismo , Osteoporose/tratamento farmacológico
18.
Front Genet ; 13: 995333, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072677

RESUMO

Background: ZEB2 is a protein-coding gene that is differentially expressed in tumors and can regulate the growth of tumor cells. This study investigated the specific regulatory mechanism of ZEB2 in COAD, a common cancer with high rates of morbidity and mortality. Methods: Multi-omics panoramic display of expression and function of ZEB2 in colon cancer. R software was used to study the expression of ZEB2 in 33 types of cancer. Furthermore, RT-PCR was used to detect the expression of ZEB2 in colon cancers and para-cancer tissues, as well as in colon cancer cells and normal cells. The ssGSEA was then used to explore the relationship between ZEB2 and immune cells, with UALCAN, EWAS and MEXPRESS applied to explore the methylation of ZEB2. The relationship between immunomodulators and chemokines (or receptors) based on expression data, copy number data, methylation data, and mutation data of ZEB2 was investigated using TISIDB. Finally, a protein interaction network of ZEB2 was constructed, and GO and KEGG analyses were performed on the differentially expressed genes. Results: ZEB2 is downregulated in most cancers, including COAD. The infiltration of the immune cells NK CD56 and Th17 cells was negatively correlated with ZEB2 expression, while the other 22 cells were positively correlated with ZEB2 expression. The DNA methylation of ZEB2 and the methylation of the ZEB2 protein on the EWAS website increased significantly. Analysis of the methylation levels and ZEB2 expression revealed that only the DNA methylation level and the expression of ZEB2 were significantly negatively correlated. The tumor-infiltrating lymphocytes positively correlated with the expression of ZEB2 but negatively correlated with the methylation of ZEB2. The same trend was observed for immunomodulators, chemokines, and receptors. The network showed that the protein performed certain biological functions, thereby affecting disease symptoms. Conclusion: These findings provide evidence that ZEB2-based therapy may represent a powerful treatment strategy for COAD.

19.
J Mater Chem B ; 10(26): 5058-5070, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35727102

RESUMO

Polymeric biocomposites display some advantages over metal or ceramic biomaterials, and are regarded as a promising candidate for artificial joint application. Herein, molybdenum disulfide (MD) nanosheets were prepared and incorporated into polyimide (PI) to form MD/PI composites with a MD content of 20 wt% (PM20) and 40 wt% (PM40). The results revealed that incorporation of MD nanosheets obviously improved the tribological performances, surface properties (e.g., roughness, wettability and surface energy) and protein absorption of the composites, which enhanced with the increase of MD content. In addition, the composites containing MD nanosheets exhibited antibacterial effects, and the antibacterial effects of PM40 were higher than those of PM20 and PI. PM40 significantly stimulated the cellular responses of rat bone mesenchymal stem cells in vitro, which was better than PM20 and PI. Furthermore, PM40 remarkably accelerated osteogenesis and osseointegration in vivo, which was better than PM20 and PI. In summary, the MD content in composites played pivotal roles in improving not only tribological performances, surface properties, antibacterial effects and cellular response in vitro but also osteogenesis and osseointegration in vivo. As a result, PM40 with high MD content exhibited excellent osteogenic bioactivity and antibacterial effects, which would have great potential for artificial joint applications.


Assuntos
Osseointegração , Osteogênese , Animais , Antibacterianos/farmacologia , Dissulfetos , Molibdênio , Ratos , Propriedades de Superfície
20.
Polymers (Basel) ; 14(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35160634

RESUMO

Composite materials composed of polylactide (PLA) and nano-hydroxyapatite (n-HA) have been recognized as excellent candidate material in bone repai The difference in hydrophilicity/hydrophobicity and poor interfacial compatibility between n-HA filler and PLA matrix leads to non-uniform dispersion of n-HA in PLA matrix and consequent poor reinforcement effect. In this study, an HA/PLA nanocomposite was designed based on the surface modification of n-HA with poly(D-lactide) (PDLA), which not only can improve the dispersion of n-HA in the poly(L-lactide) (PLLA) matrix but also could form a stereocomplex crystal with the matrix PLLA at the interface and ultimately lead to greatly enhanced mechanical performance The n-HA/PLA composites were characterized by means of scanning electron microscopy, Fourier transform infrared spectroscopy, X-Ray diffraction, thermal gravity analysis, differential scanning calorimetry, and a mechanical test; in vitro cytotoxicity of the composite material as well as its efficacy in inducing osteogenic differentiation of rat bone marrow stromal cells (rMSCs) were also evaluated. Compared with those of neat PLLA, the tensile strength, Young's modulus, interfacial shear strength, elongation at break and crystallinity of the composites increased by 34%, 53%, 26%, 70%, and 17%, respectively. The adhesion and proliferation as well as the osteogenic differentiation of rMSCs on HA/PLA composites were clearly evidenced. Therefore, the HA/PLA composites have great potential for bone repai.

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