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1.
Small ; 19(26): e2207995, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36942859

RESUMO

Effectively interfering energy metabolism in tumor cells and simultaneously activating the in vivo immune system to perform immune attacks are meaningful for tumor treatment. However, precisely targeted therapy is still a huge challenge. Herein, a mitochondrial-targeting phototheranostic system, FE-T nanoparticles (FE-T NPs) are developed to damage mitochondria in tumor cells and change the tumor immunosuppressive microenvironment. FE-T NPs are engineered by encapsulating the near-infrared (NIR) absorbed photosensitizer IR-FE-TPP within amphiphilic copolymer DSPE-SS-PEG-COOH for high-performing with simultaneous mitochondrial-targeting, near-infrared II (NIR-II) fluorescence imaging, and synchronous photothermal therapy (PTT) /photodynamic therapy (PDT) /immune therapy (IMT). In tumor treatment, the disulfide in the copolymer can be cleaved by excess intracellular glutathione (GSH) to release IR-FE-TPP and accumulate in mitochondria. After 808 nm irradiation, the mitochondrial localization of FE-T NPs generated reactive oxygen species (ROS), and hyperthermia, leading to mitochondrial dysfunction, photoinductive apoptosis, and immunogenic cell death (ICD). Notably, in situ enhanced PDT/PTT in vivo via mitochondrial-targeting with FE-T NPs boosts highly efficient ICD toward excellent antitumor immune response. FE-T NPs provide an effective mitochondrial-targeting phototheranostic nanoplatform for imaging-guided tumor therapy.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Terapia Combinada , Fármacos Fotossensibilizantes , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Polímeros , Mitocôndrias , Fotoquimioterapia/métodos , Linhagem Celular Tumoral , Fototerapia/métodos , Microambiente Tumoral
2.
J Periodontal Res ; 58(6): 1315-1325, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37715968

RESUMO

BACKGROUND AND OBJECTIVE: Neutrophils-derived exosomes have been shown to cause tissue inflammation in many diseases, but their role in periodontitis, a neutrophil-mediated disease, is unknown. Here, we investigated the effect of neutrophil-like cells derived exosomes on osteogenic dysfunction of periodontal ligament stem cells (PDLSCs) in periodontitis. METHODS: Neutrophil-like cells were derived from HL-60 cells by dimethylsulfoxide stimulation. Exosomes were isolated by ultracentrifugation and characterized using transmission electron microscopy, nanoflow cytometry and western blot. MicroRNA-223 (miR-223) expression were analyzed by real-time PCR. Western blot, alkaline phosphatase (ALP), and alizarin red staining were conducted to assess whether exosomes could affect the osteogenic differentiation of PDLSCs. The expression of miR-223 was inhibited in PDLSCs by transfecting with miR-223 inhibitor. Cyclic guanosine monophosphate (cGMP) expression was determined by enzyme-linked immunosorbent assay. RESULTS: We found that miR-223 was significantly increased in neutrophils and neutrophil-like cells derived exosomes. Treatment with exosomes derived from neutrophil-like cells upregulated miR-223 expression and inhibited the osteogenic differentiation of PDLSCs, while transfection with miR-223 inhibitor significantly promoted PDLSCs osteogenic differentiation. In addition, co-treatment with KT5823, a cGMP-PKG pathway inhibitor, markedly abrogated the rescue effects of miR-223 inhibitor on the osteogenic differentiation of PDLSCs. CONCLUSIONS: Our findings suggest that neutrophil-like cells derived exosomes might inhibit osteogenic differentiation of PDLSCs by transporting miR-223 and regulating the cGMP-PKG signaling pathway.


Assuntos
MicroRNAs , Periodontite , Humanos , Osteogênese/fisiologia , Neutrófilos/metabolismo , Ligamento Periodontal , Células-Tronco , Diferenciação Celular/fisiologia , Transdução de Sinais/fisiologia , Periodontite/metabolismo , Células Cultivadas , MicroRNAs/metabolismo
3.
J Transl Med ; 20(1): 465, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221121

RESUMO

BACKGROUND: MicroRNA (miRNA) is accepted as a critical regulator of cell differentiation. However, whether microRNA-223 (miR-223) could affect the osteogenic differentiation of periodontal ligament (PDL)-derived cells is still unknown. The aim of this study was to explore the mechanisms underlying the roles of miR-223 in the osteogenesis of PDL-derived cells in periodontitis. METHODS: Microarray analysis and real-time polymerase chain reaction (RT-PCR) were used to identify difference in miR-223 expression pattern between healthy and inflamed gingival tissue. The target genes of miR-223 were predicted based on Targetscan and selected for enrichment analyses based on Metascape database. The gain-and loss-of-function experiments were performed to discuss roles of miR-223 and growth factor receptor genes in osteogenic differentiation of PDL-derived cells. The target relationship between miR-223 and growth factor receptor genes was confirmed by a dual luciferase assay. Osteogenic differentiation of PDL-derived cells was assessed by Alizarin red staining, RT-PCR and western blot detection of osteogenic markers, including osteocalcin (OCN), osteopontin (OPN) and runt-related transcription factor 2 (Runx2). RESULTS: MiR-223 was significantly increased in inflamed gingival tissues and down-regulated in PDL-derived cells during osteogenesis. The expression of miR-223 in gingival tissues was positively correlated with the clinical parameters in periodontitis patients. Overexpression of miR-223 markedly inhibited PDL-derived cells osteogenesis, which was evidenced by reduced Alizarin red staining and osteogenic markers expressions. Furthermore, two growth factor receptor genes, including fibroblast growth factor receptor 2 (FGFR2) and transforming growth factor beta receptor 2 (TGFßR2), were revealed to be direct targets of miR-223 and shown to undergo up-regulation in PDL-derived cells during osteogenesis. Moreover, suppression of FGFR2 or TGFßR2 dramatically blocked PDL-derived cells osteogenic differentiation. CONCLUSIONS: Our study provides novel evidence that miR-223 can be induced by periodontitis and acts as a negative regulator of PDL-derived cells osteogenesis by targeting two growth factor receptors (TGFßR2 and FGFR2).


Assuntos
MicroRNAs , Periodontite , Antraquinonas , Diferenciação Celular/genética , Células Cultivadas , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/metabolismo , Ligamento Periodontal , Periodontite/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento Transformadores beta
4.
Artif Organs ; 46(6): 1097-1106, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35060136

RESUMO

BACKGROUND: Fecal incontinence caused by sphincter dysfunction is a difficult medical problem that has not been fully resolved. The artificial anal sphincter provides a new therapeutic strategy for fecal incontinence. In order to solve the biomechanical compatibility problem between the artificial anal sphincter and intestinal tissue in clinical application, a design of constant force artificial anal sphincter was assessed in this paper. METHODS: The constant force properties and safety of this novel device were evaluated by an experiment conducted in pig intestines with various thicknesses. The constant force characteristic of the device was evaluated by the intestinal pressure of the pig intestine. The safety of the device was evaluated by the surface contact stress of the pig intestine clamped by an artificial anal sphincter. RESULTS: The average measured value of the intestinal pressure of the pig intestines with three thicknesses is about 55.3 mm Hg, the maximum pressure difference is 1 mm Hg, and the fluctuation error of constant clamping load is about 1.8%. The constant clamping load fluctuation error of the four measuring points of the pig intestines with three thicknesses is less than 2%. Even if the thickness of the pig intestines is changed, the measured contact stress value is lower than 10 kPa, which may avoid bit damage for the intestinal tissue. CONCLUSIONS: This study demonstrates that the novel artificial sphincter has constant force properties and safety, which prevent ischemic necrosis of soft tissues caused by excessive pressure. Therefore, this study raises the possibility of the long-term efficacy of artificial anal sphincter.


Assuntos
Órgãos Artificiais , Incontinência Fecal , Canal Anal/cirurgia , Animais , Incontinência Fecal/etiologia , Incontinência Fecal/cirurgia , Desenho de Prótese , Ligas de Memória da Forma , Suínos
5.
Cell Tissue Bank ; 22(1): 11-24, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32808143

RESUMO

Accurate determination of the biomedical properties of connective tissue such as tendons and ligaments is dependent on the accurate measurement of their cross-sectional area (CSA). To date, techniques for determining cross-sectional areas of ligaments and tendons have been less than ideal due to their complex geometries and their deformations under external load. A novel non-destructive technique has been developed for determining the cross-sectional area of tendon by locating the tendon rupture, in which aqueous rapid curing alginate dental molding materials, digital photography and computerized image analysis are utilized. This technique marks tendons and alginate molds at 1 cm interval and then tendons are taken out for tensile test. Real-time video is recorded to locate the position of tendon rupture. The corresponding alginate slice is found and then analysis through computer image processing software to obtain a more accurate CSA at tendon rupture, which can be used to calculate the stress and young's modulus of tendon. The accuracy of this technique has been investigated and comparisons have been made with the alginate un-localization molding technique and ellipse estimation technique. Results show this technique can provide accurate CSA values (within 2%) and great reproducibility (coefficient of variation = 0.8%). The technique is non-destructive, can obtain morphological information of soft tissue and can detect cavities.


Assuntos
Traumatismos dos Tendões , Alginatos , Fenômenos Biomecânicos , Humanos , Reprodutibilidade dos Testes , Tendões
6.
Alzheimers Dement ; 15(2): 217-231, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30321504

RESUMO

INTRODUCTION: Altered cell cycle reentry has been observed in Alzheimer's disease (AD). Denticleless (DTL) was predicted as the top driver of a cell cycle subnetwork associated with AD. METHODS: We systematically investigated DTL expression in AD and studied the molecular, cellular, and behavioral endophenotypes triggered by DTL overexpression. RESULTS: We experimentally validated that CDT2, the protein encoded by DTL, activated cyclin-dependent kinases through downregulating P21, which induced tau hyperphosphorylation and Aß toxicity, two hallmarks of AD. We demonstrated that cyclin-dependent kinases inhibition by roscovitine not only rescued CDT2-induced cognitive defects but also reversed expression changes induced by DTL overexpression. RNA-seq data from the DTL overexpression experiments revealed the molecular mechanisms underlying CDT2 controlled cell cycle reentry in AD. DISCUSSION: These findings provide new insights into the molecular mechanisms of AD pathogenesis and thus pave a way for developing novel therapeutics for AD by targeting AD specific cell cycle networks and drivers.


Assuntos
Doença de Alzheimer/patologia , Ciclo Celular/fisiologia , Proteínas Nucleares/metabolismo , Animais , Regulação para Baixo , Humanos , Camundongos , Fosforilação/fisiologia , Proteínas tau/metabolismo
7.
J Hazard Mater ; 470: 134175, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574662

RESUMO

Emerging organic photoelectrochemical transistors (OPECTs) with inherent amplification capabilities, good biocompatibility and even self-powered operation have emerged as a promising detection tool, however, they are still not widely studied for pollutant detection. In this paper, a novel OPECT dual-mode aptasensor was constructed for the ultrasensitive detection of di(2-ethylhexyl) phthalate (DEHP). MXene/In2S3/In2O3 Z-scheme heterojunction was used as a light fuel for ion modulation in sensitive gated OPECT biosensing. A transistor system based on poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) converted biological events associated with photosensitive gate achieving nearly a thousand-fold higher current gain at zero bias voltage. This work quantified the target DEHP by aptamer-specific induction of CRISPR-Cas13a trans-cutting activity with target-dependent rolling circle amplification as the signal amplification unit, and incorporated the signal changes strategy of biocatalytic precipitation and TMB color development. Combining OPECT with the auxiliary validation of colorimetry (CM), high sensitivity and accurate detection of DEHP were achieved with a linear range of 0.1 pM to 200 pM and a minimum detection limit of 0.02 pM. This study not only provides a new method for the detection of DEHP, but also offers a promising prospect for the gating and application of the unique OPECT.


Assuntos
Técnicas Biossensoriais , Dietilexilftalato , Técnicas Eletroquímicas , Transistores Eletrônicos , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Sistemas CRISPR-Cas , Dietilexilftalato/química , Dietilexilftalato/análise , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico , Poliestirenos/química , Tiofenos , Poluentes Químicos da Água/análise
8.
Int J Biol Macromol ; 263(Pt 2): 130350, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38403226

RESUMO

In this study, the organosilane nanoparticles as additive and crosslinker were prepared and incorporated into sodium alginate to fabricate a series of alginate-based multi-crosslinked biomembranes at different thermal treatment temperature without the usage of another crosslinking agent. The effects of treatment temperature on the stability of biomembranes including dimensional, oxidative, hydrolytic and mechanical stability were investigated in detail. As a whole, the stability of biomembranes exhibited increasing tendency with the increment of treatment temperature due to the formation of more compact internal network structure. The electrochemical performance of biomembranes in respect to their potential as proton exchange membranes for direct methanol fuel cell application were also investigated based on the treatment temperature. The results revealed that the biomembranes possessed excellent methanol resistance and the methanol diffusion coefficient decreased with the increment of treatment temperature. The biomembrane with 120 °C heat-treatment showed the optimal selectivity (14.30 × 105 Ss cm-3), which was about 1.77 and 68.10 times of that and of M-80 (8.09 × 105 Ss cm-3) and Nafion@117 (0.21 × 105 Ss cm-3), respectively. Fuel cell performance measurements showed that M-120 possessed higher maximum power density and cell stability compared with M-80 and Nafion@117, indicating its best adaptability for use in direct methanol fuel cell.


Assuntos
Polímeros de Fluorcarboneto , Temperatura Alta , Metanol , Temperatura , Alginatos
9.
Ir J Med Sci ; 192(3): 1041-1049, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35829909

RESUMO

OBJECTIVE: Pyrotinib is a novel EGFR/HER2 dual tyrosine kinase inhibitor developed in China, while its role in neoadjuvant therapy of HER2-positive (HER2+) breast cancer lacks evidence. The current study aimed to explore the efficacy and safety of neoadjuvant pyrotinib plus docetaxel/liposomal doxorubicin/cyclophosphamide (TAC) for HER2+ breast cancer. METHODS: A total of 27 HER2+ breast cancer patients received neoadjuvant pyrotinib plus TAC for 6 cycles, then surgery was performed. The clinical and pathological responses, and adverse events were evaluated. RESULTS: Complete response rate, objective response rate, and disease control rate were 0.0%, 44.4% and 100.0% after 2 treatment cycles; 0.0%, 37.0%, and 100.0% after 4 treatment cycles; 37.0%, 37.0%, and 96.3% after 6 treatment cycles; as well as 37.0%, 44.4%, and 100.0% based on the best clinical response. Regarding pathological response, there were 1 (2.7%), 3 (11.1%), 8 (29.6%), 5 (18.5%), and 10 (37.0%) patients realizing Miller-Payne grade (G) 1, G2, G3, G4, and G5, respectively; besides, 10 (37.0%) patients achieved total pathological complete response (pCR), 10 (37.0%) patients realized pCR in breast, and 23 (85.2%) patients achieved pCR in lymph node. Additionally, adverse events included diarrhea (81.5%), dental ulcer (7.4%), and hand-foot syndrome (3.7%); meanwhile, grade 3-4 adverse event consisted of only diarrhea (11.1%). CONCLUSION: Neoadjuvant pyrotinib plus TAC treatment is efficient and safe in HER2+ breast cancer patients, while further validation is needed.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Docetaxel/uso terapêutico , Terapia Neoadjuvante , Ciclofosfamida/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor ErbB-2
10.
Biomater Sci ; 11(5): 1840-1852, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36655904

RESUMO

Antimicrobial resistance is a global challenge owing to the lack of discovering effective antibiotic agents. Antimicrobial polymers containing the cationic groups and hydrophobic groups which mimic natural host-defense peptides (HDPs) show great promise in combating bacteria. Herein, we report the synthesis of lipidated polycarbonates bearing primary amino groups and hydrophobic moieties (including both the terminal long alkyl chain and hydrophobic groups in the sequences) by ring-opening polymerization. The hydrophobic/hydrophilic group ratios were adjusted deliberately and the lengths of the alkyl chains at the end of the polymers were modified to achieve the optimized combination for the lead polymers, which exhibited potent and broad-spectrum bactericidal activity against a panel of Gram-positive and Gram-negative bacteria. The polymers only showed very limited hemolytic activity, demonstrating their excellent selectivity. Comprehensive analyses using biochemical and biophysical assays revealed the strong interaction between the polymers and bacteria membranes. Moreover, the polymers also showed strong biofilm inhibition activity and did not readily induce antibiotic resistance. Our results suggest that lipidated polycarbonates could be a new class of antimicrobial agents.


Assuntos
Antibacterianos , Anti-Infecciosos , Antibacterianos/química , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Anti-Infecciosos/farmacologia , Bactérias , Polímeros/farmacologia , Polímeros/química , Testes de Sensibilidade Microbiana
11.
Nat Commun ; 14(1): 4169, 2023 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-37443360

RESUMO

Although considerable research achievements have been made to address the plastic crisis using enzymes, their applications are limited due to incomplete degradation and low efficiency. Herein, we report the identification and subsequent engineering of BHETases, which have the potential to improve the efficiency of PET recycling and upcycling. Two BHETases (ChryBHETase and BsEst) are identified from the environment via enzyme mining. Subsequently, mechanism-guided barrier engineering is employed to yield two robust and thermostable ΔBHETases with up to 3.5-fold enhanced kcat/KM than wild-type, followed by atomic resolution understanding. Coupling ΔBHETase into a two-enzyme system overcomes the challenge of heterogeneous product formation and results in up to 7.0-fold improved TPA production than seven state-of-the-art PET hydrolases, under the conditions used here. Finally, we employ a ΔBHETase-joined tandem chemical-enzymatic approach to valorize 21 commercial post-consumed plastics into virgin PET and an example chemical (p-phthaloyl chloride) for achieving the closed-loop PET recycling and open-loop PET upcycling.


Assuntos
Hidrolases , Polietilenotereftalatos , Hidrolases/genética , Hidrolases/metabolismo , Plásticos/metabolismo , Polietilenotereftalatos/metabolismo , Reciclagem
12.
Bioresour Technol ; 360: 127516, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35764282

RESUMO

Lignocellulosic biomass is an abundant and sustainable raw material, but its conversion into ethanol fuel has not yet achieved large-scale industrialization and economic benefits. Integrated biorefineries have been widely identified as the key to achieving this goal. Here, four promising routes were summarized to assemble the new industrial plants for cellulose-based fuels and chemicals, including 1) integration of cellulase production systems into current cellulosic ethanol processes; 2) combination of processes and facilities between cellulosic ethanol and first-generation ethanol; 3) application of enzyme-free saccharification processes and computational approaches to increase the bioethanol yield and optimize the integration process; 4) production of multiple products to maximize the value derived from the lignocellulosic biomass. Finally, the remaining challenges and perspectives of this field are also discussed.


Assuntos
Etanol , Lignina , Biocombustíveis , Biomassa , Fermentação , Desenvolvimento Industrial , Lignina/metabolismo
13.
J Hazard Mater ; 421: 126685, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34332485

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are toxic and recalcitrant pollutants, with an urgent need for bioremediation. Systematic biodegradation studies show that surfactant-mediated bioremediation is still poorly understood. Here, we investigated a comprehensive cellular response pattern of the PAH degrading strain B. subtilis ZL09-26 to (non-)green surfactants at the cellular and proteomic levels. Eight characteristic cellular factor investigations and detailed quantitative proteomics analyses were performed to understand the highly enhanced phenanthrene (PHE) degradation efficiency (2.8- to 3-fold improvement) of ZL09-26 by humic acid (HA) or Tween80. The commonly upregulated pathway and proteins (Arginine generation, LacI-family transcriptional regulator, and Lactate dehydrogenase) and various metabolic pathways (such as phenanthrene degradation upstream pathway and central carbon metabolism) jointly govern the change of cellular behaviors and improvement of PHE transport, emulsification, and degradation in a network manner. The obtained molecular knowledge empowers engineers to expand the application of surfactants in the biodegradation of PAHs and other pollutants.


Assuntos
Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Biodegradação Ambiental , Substâncias Húmicas , Hidrocarbonetos Policíclicos Aromáticos/análise , Polissorbatos , Proteômica
14.
Oxid Med Cell Longev ; 2022: 9728172, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36148415

RESUMO

Methods: The differentially expressed genes (DEGs) were identified using periodontitis-related microarray from the GEO database, and OS-genes were extracted from GeneCards database. The intersection of the OS-genes and the DEGs was considered as oxidative stress-related DEGs (OS-DEGs) in periodontitis. The Pearson correlation and protein-protein interaction analyses were used to screen key OS-genes. Gene set enrichment, functional enrichment, and pathway enrichment analyses were performed in OS-genes. Based on key OS-genes, a risk score model was constructed through logistic regression, receiver operating characteristic curve, and stratified analyses. Results: In total, 74 OS-DEGs were found in periodontitis, including 65 upregulated genes and 9 downregulated genes. Six of them were identified as key OS-genes (CXCR4, SELL, FCGR3B, FCGR2B, PECAM1, and ITGAL) in periodontitis. All the key OS-genes were significantly upregulated and associated with the increased risk of periodontitis. Functional enrichment analysis showed that these genes were mainly associated with leukocyte cell-cell adhesion, phagocytosis, and cellular extravasation. Pathway analysis revealed that these genes were involved in several signaling pathways, such as leukocyte transendothelial migration and osteoclast differentiation. Conclusion: In this study, we screened six key OS-genes that were screened as risk factors of periodontitis. We also identified multiple signaling pathways that might play crucial roles in regulating oxidative stress damage in periodontitis. In the future, more experiments need to be carried out to validate our current findings.


Assuntos
Perfilação da Expressão Gênica , Periodontite , Biologia Computacional , Humanos , Análise em Microsséries , Estresse Oxidativo/genética , Periodontite/genética
15.
Biosensors (Basel) ; 12(9)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36140089

RESUMO

Covalent organic frameworks (COFs) are gaining growing interest owing to their various structures and versatility. Since their specific physical-chemical characteristics endow them great usage potentiality in biosensing, we herein have synthesized spherical COFs with regular shape and good dispersion, which are further used for the design of a novel nanoprobe by modifying Histostar on the surface of the COFs. Moreover, we have applied a nanoprobe for the fabrication of an electrochemical biosensor to detect exosomes. Since Histostar is a special polymer, conjugated with many secondary antibodies (IgG), and HRP can increase the availability of HRP at the antigenic site, the biosensor can have a strong signal amplification ability. Meanwhile, since COFs with high porosity can be loaded with a huge amount of Histostar, the sensitivity of the biosensor can be further improved. With such a design, the proposed biosensor can achieve a low exosomes detection limit of 318 particles/µL, and a wide linear detection range from 103 particles/µL to 108 particles/µL. So, this work may offer a promising platform for the ultrasensitive detection of exosomes.


Assuntos
Técnicas Biossensoriais , Exossomos , Estruturas Metalorgânicas , Técnicas Eletroquímicas , Exossomos/química , Imunoglobulina G/análise , Limite de Detecção , Estruturas Metalorgânicas/química , Polímeros
16.
Biosens Bioelectron ; 217: 114668, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36108585

RESUMO

Covalent organic frameworks (COFs) are an emerging type of porous crystalline polymers that are built by light elements (typically H, B, C, N, O and Si) via organic covalent bonds. Currently, COFs have been exploited for biomedical application due to their unique properties, such as structural diversity, intrinsic stability, ordered porosity, tailor-made functions, and excellent adsorption features. In particular, COFs are increasingly popular in the construction of biosensors for the detection of various disease biomarkers, and have been extended to the clinical applicability for early diagnostics, medication instruction and prognostic monitoring of diseases. In this review, we mainly summarize the recent advances on COFs-based biosensors for the assay of disease biomarkers with clinical applications. According to the features of molecular structure, disease biomarkers are classified into four categories, including small biological ions/molecules, proteins, nucleic acids, and cancer cells/exosomes. Impressively, COFs-based biosensors present a bright prospect in clinical diagnosis of diseases in both hospital-end and household-end utilization.


Assuntos
Técnicas Biossensoriais , Estruturas Metalorgânicas , Ácidos Nucleicos , Biomarcadores , Estruturas Metalorgânicas/química , Polímeros/química
17.
J Microbiol Methods ; 203: 106622, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36384173

RESUMO

Although electroporation technique has been mostly used to transform Bacillus thuringiensis (Bt), this method is not readily applicable to strains other than the one for which it was optimized. Polyethylenimine (PEI) is a golden standard non-viral vector that interacts with plasmids to form compact polymeric nanoparticles (PNPs) via electrostatic interactions. This PNPs system is very attractive because they are easily prepared, able to carry large nucleic acid constructs, and show low toxicity. In this study, PEI/pBTdsSBV-VP1 PNPs were successfully prepared at various N/P ratios which is positively-chargeable polymer amine (N = nitrogen) groups to negatively-charged nucleic acid phosphate (P) groups, and the internalization of the complexes into Bt 4Q7 was confirmed by confocal laser scanning microscopy. The PEI-mediated transformation showed similar efficiency comparable to that of electroporation method, suggesting that the method of PNPs will be an effective alternative for transformation of Bt strains.


Assuntos
Bacillus thuringiensis , Nanopartículas , Ácidos Nucleicos , Polietilenoimina , Bacillus thuringiensis/genética , Polímeros , Plasmídeos/genética , DNA
18.
Cartilage ; 13(3): 19476035221113959, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36040157

RESUMO

OBJECTIVE: Intervertebral disk degeneration is a prevalent postoperative complication after discectomy, underscoring the need to develop preventative and bioactive treatment strategies that decelerate degeneration and seal annulus fibrosus (AF) defects. Human mesenchymal stem cell-derived exosomes (MSC-Exos) hold promise for cell-free bioactive repair; however, their ability to promote AF repair is poorly understood. The objective of this study was to evaluate the ability of MSC-Exos to promote endogenous AF repair processes and integrate MSC-Exos within a biomaterial delivery system. DESIGN: We characterize biophysical and biochemical properties of normoxic (Nx) and hypoxic (Hx) preconditioned MSC-Exos from young, healthy donors and examine their effects on AF cell proliferation, migration, and gene expression. We then integrate a poly(lactic-co-glycolic acid) microsphere (PLGA µSphere) delivery platform within an interpenetrating network hydrogel to facilitate sustained MSC-Exo delivery. RESULTS: Hx MSC-Exos led to a more robust response in AF cell proliferation and migration than Nx MSC-Exos and was selected for a downstream protection experiment. Hx MSC-Exos maintained a healthy AF cell phenotype under a TNFα challenge in vitro and attenuated catabolic responses. In all functional assays, AF cell responses were more sensitive to Hx MSC-Exos than Nx MSC-Exos. PLGA µSpheres released MSC-Exos over a clinically relevant timescale without affecting hydrogel modulus or pH upon initial embedment and µSphere degradation. CONCLUSIONS: This MSC-Exo treatment strategy may offer benefits of stem cell therapy without the need for exogenous stem cell transplantation by stimulating cell proliferation, promoting cell migration, and protecting cells from the degenerative proinflammatory microenvironment.


Assuntos
Anel Fibroso , Exossomos , Células-Tronco Mesenquimais , Exossomos/genética , Exossomos/metabolismo , Glicóis/metabolismo , Humanos , Hidrogéis , Células-Tronco Mesenquimais/metabolismo , Microesferas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo
19.
Integr Zool ; 16(1): 128-135, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33136309

RESUMO

Although it has been suggested that olfaction is closely interconnected with hippocampal systems, whether olfaction regulates spatial memory strategy remains never known. Furthermore, no study has examined how olfaction mediates spatial memory established on the external objects, for example, caches made by scatter-hoarding animals. Here, we experimentally induced nondestructive and reversible olfaction loss of a scatter-hoarding animal Leopoldamys edwardsi, to test whether and how olfaction regulates spatial memory to mediate cache recovery and pilferage. Our results showed that the normal L. edwardsi preferred to pilfer caches of others rather than to recover their own using accurate spatial memory (35.7% vs. 18.6%). Anosmic L. edwardsi preferred to recover the caches they made prior to olfaction loss rather than to pilfer from others relied on spatial memory (54.2% vs. 36.0%). However, L. edwardsi with anosmia showed no preference either to the caches they established after olfaction loss or caches made by others (25.8% vs. 29.1%). These collectively indicate that olfaction loss has a potential to affect new memory formation but not previously established spatial memory on caches. Our study first showed that olfaction modified spatial memory strategy in cache recovery and pilferage behaviors of scatter-hoarding animals. We suggest that future studies pay more attention to the evolution of olfaction and its relationship with spatial memory strategy.


Assuntos
Comportamento Alimentar/fisiologia , Murinae/fisiologia , Olfato/fisiologia , Memória Espacial , Animais , Anosmia/induzido quimicamente , Comportamento Animal/fisiologia , Feminino , Masculino , Octoxinol/administração & dosagem
20.
Bioresour Technol ; 337: 125465, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34320745

RESUMO

Modificated lignins can affect enzymatic hydrolysis efficiency (EHE) because of changing physicochemical properties of lignin. In this study, carboxylated and quaternized lignin (CQL) and hydroxymethylated lignin (HML) were prepared to explore the effect of lignin modification on cellulase adsorption and EHE of p-toluenesulfonic acid treated corn stover (PCS). The results showed that CQL enhanced EHE of PCS due to the higher ß-glucosidase (ß-GL) activity, resulting from the formation of CQL-ß-GL complexes with a lower binding free energy and the improvement of ß-GL conformation made by the binding of CQL and ß-GL. However, the drop in EHE due to the addition of HML was consequent on ß-GL deactivation that was because the binding site of HML and ß-GL overlapped with the carbohydrate binding domain of ß-GL, causing the decrease in ß-GL activity compared with CQL. This study would help deeply elucidate the effect of modified lignins on EHE and cellulase adsorption.


Assuntos
Celulase , Lignina , Adsorção , Benzenossulfonatos , Hidrólise
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