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1.
Mater Today Bio ; 26: 100991, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38558773

RESUMO

Background: Effective communication is crucial for broad acceptance and applicability of alternative methods in 3R biomedical research and preclinical testing. 3D bioprinting is used to construct intricate biological structures towards functional liver models, specifically engineered for deployment as alternative models in drug screening, toxicological investigations, and tissue engineering. Despite a growing number of reviews in this emerging field, a comprehensive study, systematically assessing practices and reporting quality for bioprinted liver models is missing. Methods: In this systematic scoping review we systematically searched MEDLINE (Ovid), EMBASE (Ovid) and BioRxiv for studies published prior to June 2nd, 2022. We extracted data on methodological conduct, applied bioinks, the composition of the printed model, performed experiments and model applications. Records were screened for eligibility and data were extracted from included articles by two independent reviewers from a panel of seven domain experts specializing in bioprinting and liver biology. We used RAYYAN for the screening process and SyRF for data extraction. We used R for data analysis, and R and Graphpad PRISM for visualization. Results: Through our systematic database search we identified 1042 records, from which 63 met the eligibility criteria for inclusion in this systematic scoping review. Our findings revealed that extrusion-based printing, in conjunction with bioinks composed of natural components, emerged as the predominant printing technique in the bioprinting of liver models. Notably, the HepG2 hepatoma cell line was the most frequently employed liver cell type, despite acknowledged limitations. Furthermore, 51% of the printed models featured co-cultures with non-parenchymal cells to enhance their complexity. The included studies offered a variety of techniques for characterizing these liver models, with their primary application predominantly focused on toxicity testing. Among the frequently analyzed liver markers, albumin and urea stood out. Additionally, Cytochrome P450 (CYP) isoforms, primarily CYP3A and CYP1A, were assessed, and select studies employed nuclear receptor agonists to induce CYP activity. Conclusion: Our systematic scoping review offers an evidence-based overview and evaluation of the current state of research on bioprinted liver models, representing a promising and innovative technology for creating alternative organ models. We conducted a thorough examination of both the methodological and technical facets of model development and scrutinized the reporting quality within the realm of bioprinted liver models. This systematic scoping review can serve as a valuable template for systematically evaluating the progress of organ model development in various other domains. The transparently derived evidence presented here can provide essential support to the research community, facilitating the adaptation of technological advancements, the establishment of standards, and the enhancement of model robustness. This is particularly crucial as we work toward the long-term objective of establishing new approach methods as reliable alternatives to animal testing, with extensive and versatile applications.

2.
Int Orthop ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38580780

RESUMO

PURPOSE: The optimal choice of distal locking modes remains a subject due to limited available data, and therefore, this study aims to investigate the relationship between distal locking mode and postoperative mechanical complications in an intertrochanteric fracture (ITF) population who underwent closed reduction and intramedullary fixation with a PFNA-II. METHODS: Patients aged 65 years or older who underwent surgery with PFNA-II fixation in a university teaching hospital between January 2020 and December 2021 were potentially eligible. Based on the distal locking mode, patients were classified into static, dynamic, and limited dynamic groups, among which the differences were tested using univariate analysis. Multivariate logistic regression was used to examine whether the distal locking mode was independently associated with the risk of postoperative one year mechanical complications, adjusting for covariates and potential confounders. Subgroup analyses were performed to evaluate the robustness of the findings. RESULT: Among 507 eligible patients, 33 (6.5%) developed postoperative mechanical complications. In the univariate analysis, sex (P = 0.007), fracture type (P = 0.020), LAT Parker ratio (P = 0.023), and lateral femoral (P = 0.003) wall showed that the differences were significant. Compared to the static group, the limited dynamic group and the dynamic group showed higher odds of postoperative mechanical complications (OR = 3.314, 95% CI: 1.215-9.041; and OR = 3.652, 95% CI: 1.451-9.191, respectively). These associations were robust across a series of analyses, including adjusting for confounders and subgroup analyses. CONCLUSION: Using a distal non-static locking mode significantly increases the risk of postoperative mechanical complications, and static locking could be a preferable option when treating an intertrochanteric fracture.

3.
J Orthop Surg Res ; 19(1): 170, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38449033

RESUMO

BACKGROUND: No large cohort study has evaluated the surgical outcomes of THA between different stages of ONFH patients. This study aimed to compare the surgical outcomes of ONFH patients who underwent THA in ARCO stage III versus IV, in terms of operative parameters, one-year hip function assessments and postoperative at least five-year complications, to inform optimized management of ONFH. METHOD: From our prospectively collected database, 876 patients undergoing THA between October 2014 and April 2017 were analyzed and divided into ARCO stage III group (n = 383) and ARCO stage IV group(n = 493). Details of demographics, medical record information, adverse events and clinical scores of both groups were collected and compared. Proper univariate analysis was used for the analysis. RESULT: There were no statistically significant differences in baseline characteristics between the two groups. Compared to ARCO stage IV patients, ARCO stage III patients showed a shorter operative time (p < 0.01), less bleeding (p < 0.01), fewer one-year readmissions (p = 0.026) and complications (p = 0.040), and significantly higher HHS (p < 0.01) one year after THA. In addition, ARCO stage IV patients seem more likely to suffer prosthesis dislocation (p = 0.031). CONCLUSION: Although ARCO stage IV patients in the study cohorts appeared to suffer more one-year complications, no significant difference was observed at long-term follow-up. Enhanced clinical guidance on preventing early prosthesis dislocation may help improve the prognosis of final-stage ONFH patients.


Assuntos
Artroplastia de Quadril , Osteonecrose , Humanos , Seguimentos , Artroplastia de Quadril/efeitos adversos , Estudos de Coortes , Cabeça do Fêmur , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
4.
Int J Mol Sci ; 25(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38339088

RESUMO

Three-dimensional (3D) bioprinting is one of the most promising methodologies that are currently in development for the replacement of animal experiments. Bioprinting and most alternative technologies rely on animal-derived materials, which compromises the intent of animal welfare and results in the generation of chimeric systems of limited value. The current study therefore presents the first bioprinted liver model that is entirely void of animal-derived constituents. Initially, HuH-7 cells underwent adaptation to a chemically defined medium (CDM). The adapted cells exhibited high survival rates (85-92%) after cryopreservation in chemically defined freezing media, comparable to those preserved in standard medium (86-92%). Xeno-free bioink for 3D bioprinting yielded liver models with high relative cell viability (97-101%), akin to a Matrigel-based liver model (83-102%) after 15 days of culture. The established xeno-free model was used for toxicity testing of a marine biotoxin, okadaic acid (OA). In 2D culture, OA toxicity was virtually identical for cells cultured under standard conditions and in CDM. In the xeno-free bioprinted liver model, 3-fold higher concentrations of OA than in the respective monolayer culture were needed to induce cytotoxicity. In conclusion, this study describes for the first time the development of a xeno-free 3D bioprinted liver model and its applicability for research purposes.


Assuntos
Bioimpressão , Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Animais , Impressão Tridimensional , Engenharia Tecidual , Tecidos Suporte
5.
Environ Res ; 249: 118431, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38346481

RESUMO

Plant uptake, accumulation, and transformation of organophosphate esters (OPEs) play vital roles in their geochemical cycles and exposure risks. Here we reviewed the recent research advances in OPEs in plants. The mean OPE concentrations based on dry/wet/lipid weight varied in 4.80-3,620/0.287-26.8/12,000-315,000 ng g-1 in field plants, and generally showed positive correlations with those in plant habitats. OPEs with short-chain substituents and high hydrophilicity, particularly the commonly used chlorinated OPEs, showed dominance in most plant samples, whereas some tree barks, fruits, seeds, and roots demonstrated dominance of hydrophobic OPEs. Both hydrophilic and hydrophobic OPEs can enter plants via root and foliar uptake, and the former pathway is mainly passively mediated by various membrane proteins. After entry, different OPEs undergo diverse subcellular distributions and acropetal/basipetal/intergenerational translocations, depending on their physicochemical properties. Hydrophilic OPEs mainly exist in cell sap and show strong transferability, hydrophobic OPEs demonstrate dominant distributions in cell wall and limited migrations owing to the interception of Casparian strips and cell wall. Additionally, plant species, transpiration capacity, growth stages, commensal microorganisms, and habitats also affect OPE uptake and transfer in plants. OPE metabolites derived from various Phase I transformations and Phase II conjugations are increasingly identified in plants, and hydrolysis and hydroxylation are the most common metabolic processes. The metabolisms and products of OPEs are closely associated with their structures and degradation resistance and plant species. In contrast, plant-derived food consumption contributes considerably to the total dietary intakes of OPEs by human, particularly the cereals, and merits specifical attention. Based on the current research limitations, we proposed the research perspectives regarding OPEs in plants, with the emphases on their behavior and fate in field plants, interactions with plant-related microorganisms, multiple uptake pathways and mechanisms, and comprehensive screening analysis and risk evaluation.

6.
Int Orthop ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38286924

RESUMO

PURPOSE: This study aimed to investigate the mid- to long-term benefits of high tibial osteotomy in advanced age patients. METHODS: This retrospective study was conducted in our hospital from January 2017 to January 2021 with data prospectively collected, 47 patients with knee osteoarthritis who over 65 years old were included, and a 1:1 propensity score (PS) of patients < 65 years were matched according to gender, body mass index, and side. Patient demographics, intraooperative and postoperative variables, and patient self-reported outcomes were compared. A generalized linear model was used to screen possible risk factors. RESULTS: A total of 94 consecutive patients were included; the average age of advanced age group was 69.47 + 4.26 years and 57.87 + 5.51 years in the younger group. There were no statistically difference in K-L grade, smoke, drink, comorbidity, ASA, blood loss, operative duration, length of stay, surgical site infection, hinge fracture, DVT, and preooperative and postoperative aFTA; significantly statistical difference of the eFI was found between two groups (P < 0.05). Two groups had comparable VAS and MOMAC scores at one year postoperatively (P > 0.05), while the younger group had lower VAS and WOMAC scores than the advanced age group at the end of follow-up (P < 0.05). Generalized linear model showed both age and eFI were associated with WOMAC scores; there was a statistically significant difference in the effect of eFI on WOMAC scores at different ages (P > 0.05). CONCLUSIONS: Compared with younger patients, advanced age patients have similar short-term benefits, but less long-term benefits. We recommend that patients proposed for HTO be discriminated by eFI, and patients with higher scores should be cautiously selected.

7.
Environ Pollut ; 341: 122933, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37977360

RESUMO

Owing to their dominant wastewater origin, bioavailability, and toxicity, the occurrence and behavior of organophosphate esters (OPEs) in aquatic systems have attracted considerable attention over the past two decades. Aquatic plants can accumulate and metabolize OPEs in water, thereby playing an important role in their behavior and fate in waterbodies. However, their uptake, translocation and transformation mechanisms in plants remain incompletely characterized. We investigated the accumulation and transformation of OPEs in water hyacinth (Eichhornia crassipes) through a series of hydroponic experiments using three representative OPEs, tris(2-chloroethyl) phosphate (TCEP), tris(2-butoxyethyl) phosphate (TBEP), and triphenyl phosphate (TPP). These OPEs can not only be adsorbed onto and enter plant roots via passive diffusion pathways, which are facilitated by anion channels and/or aquaporins, but also can return to the solution when concentration gradients exist. After entry, hydrophilic TCEP showed a dominant distribution in the cell sap, strong acropetal transportability, and rapid translocation rate, whereas hydrophobic TPP was mostly retained in the root cell wall and therefore demonstrated weak acropetal transportability; TBEP with moderate hydrophilicity remained in the middle. All these OPEs can be transformed into diesters, which presented higher proportions in the cell sap and therefore have stronger acropetal transferability than their parent OPEs. TCEP exhibits the lowest biodegradability, followed by TPP and TBEP. These OPEs exerted apparent effects on plant growth, photosynthesis, and the diversity and composition of the rhizosphere microbial community.


Assuntos
Eichhornia , Retardadores de Chama , Hidroponia , Ésteres/metabolismo , Organofosfatos/metabolismo
8.
BMC Musculoskelet Disord ; 24(1): 845, 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884992

RESUMO

BACKGROUND: The primary objectives of this study were to focus on one - year unplanned readmissions after THA in ONFH patients and to investigate rates, causes, and independent risk factors. METHODS: Between October 2014 and April 2019, eligible patients undergoing THA were enrolled and divided into unplanned readmission within one year and no readmission in this study. All unplanned readmissions within 1 year of discharge were reviewed for causes and the rate of unplanned readmissions was calculated. Demographic information, ONFH characteristics, and treatment-related variables of both groups were compared and analysed. RESULTS: Finally, 41 out of 876 patients experienced unplanned readmission. The readmission rate was 1.83% in 30 days 2.63% in 90 days, and 4.68% in 1 year. Prosthesis dislocation was always the most common cause at all time points studied within a year. The final logistic regression model revealed that higher risks of unplanned readmission were associated with age > 60 years (P = 0.001), urban residence (P = 0.001), ARCO stage IV (P = 0.025), and smoking (P = 0.033). CONCLUSIONS: We recommend the introduction of a strict smoking cessation program prior to surgery and the development of comprehensive management strategies, especially for the elderly and end-stage ONFH patients, and pay more attention to preventing prosthesis dislocation in the early days after surgery.


Assuntos
Artroplastia de Quadril , Osteonecrose , Humanos , Idoso , Pessoa de Meia-Idade , Artroplastia de Quadril/efeitos adversos , Readmissão do Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Cabeça do Fêmur/cirurgia , Fatores de Risco , Osteonecrose/complicações , Estudos Retrospectivos
9.
Int J Surg ; 109(9): 2660-2671, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37226868

RESUMO

BACKGROUND: Malnutrition is significantly associated with unfavorable outcomes, but there is little high-level evidence to elucidate the association of malnutrition with losing walking independence (LWI) after hip fracture surgery. This study aimed to assess the association between preoperative nutritional status evaluated by the Controlling Nutritional Status (CONUT) score and walking independence at 180 days postoperatively in Chinese older hip fracture patients. METHODS: This prospective cohort study included 1958 eligible cases from the SSIOS database. The restricted cubic spline was used to assess the dose-effect relationship between the CONUT score and the recovery of walking independence. Propensity score matching was performed to balance potential preoperative confounders, and multivariate logistic regression analysis was applied to assess the association between malnutrition and LWI with perioperative factors for further adjustment. Furthermore, inverse probability treatment weighting and sensitivity analyses were performed to test the robustness of the results and the Fine and Gray hazard model was applied to adjust the competing risk of death. Subgroup analyses were used to determine potential population heterogeneity. RESULTS: The authors found a negative relationship between the preoperative CONUT score and recovery of walking independence at 180 days postoperatively, and that moderate-to-severe malnutrition evaluated by the CONUT score was independently associated with a 1.42-fold (95% CI, 1.12-1.80; P =0.004) increased risk of LWI. The results were overall robust. And in the Fine and Gray hazard model, the result was still statistically significant despite the apparent decrease in the risk estimate from 1.42 to 1.21. Furthermore, significant heterogeneities were observed in the subgroups of age, BMI, American Society of Anesthesiologists score, Charlson's comorbidity index, and surgical delay ( P for interaction < 0.05). CONCLUSION: Preoperative malnutrition is a significant risk factor for LWI after hip fracture surgery, and nutrition screening on admission would generate potential health benefits.


Assuntos
Fraturas do Quadril , Desnutrição , Humanos , Estado Nutricional , Avaliação Nutricional , População do Leste Asiático , Estudos Prospectivos , Desnutrição/etiologia , Desnutrição/complicações , Fraturas do Quadril/complicações , Fraturas do Quadril/cirurgia , Caminhada , Estudos Retrospectivos , Prognóstico
10.
Int J Biol Macromol ; 239: 124238, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37003386

RESUMO

Aerogels, especially bio-based ones, present a promising option for wound dressing; specifically, because of their low toxicity, high stability, bio-compatibility, and good biological performance. In this study, agar aerogel was prepared and evaluated as novel wound dressing material in an in vivo rat study. Agar hydrogel was prepared by thermal gelation, after that the water inside the gel was exchanged with ethanol, and finally the alcogel was dried by supercritical CO2. The textural and rheological properties of the prepared aerogel were characterized, showing that the prepared agar aerogels possess high porosity (97-98 %), high surface area (250-330 m2g-1) as well as good mechanical properties and easiness of removal from the wound site. The results of the in vivo experiments macroscopically demonstrate the tissue compatibility of the aerogels in dorsal interscapular injured rat tissue and a shorter wound healing time comparable to that of gauze-treated animals. The histological analysis underpins the reorganisation and healing of the tissue for the injured skin of rats treated with agar aerogel wound dressing within the studied time frame.


Assuntos
Bandagens , Cicatrização , Ratos , Animais , Ágar , Pele , Hidrogéis/farmacologia
11.
Int J Mol Sci ; 24(7)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37047045

RESUMO

Lung cancer still has one of the highest morbidity and mortality rates among all types of cancer. Its incidence continues to increase, especially in developing countries. Although the medical field has witnessed the development of targeted therapies, new treatment options need to be developed urgently. For the discovery of new drugs, human cancer models are required to study drug efficiency in a relevant setting. Here, we report the generation of a non-small cell lung cancer model with a perfusion system. The bioprinted model was produced by digital light processing (DLP). This technique has the advantage of including simulated human blood vessels, and its simple assembly and maintenance allow for easy testing of drug candidates. In a proof-of-concept study, we applied gemcitabine and determined the IC50 values in the 3D models and 2D monolayer cultures and compared the response of the model under static and dynamic cultivation by perfusion. As the drug must penetrate the hydrogel to reach the cells, the IC50 value was three orders of magnitude higher for bioprinted constructs than for 2D cell cultures. Compared to static cultivation, the viability of cells in the bioprinted 3D model was significantly increased by approximately 60% in the perfusion system. Dynamic cultivation also enhanced the cytotoxicity of the tested drug, and the drug-mediated apoptosis was increased with a fourfold higher fraction of cells with a signal for the apoptosis marker caspase-3 and a sixfold higher fraction of cells positive for PARP-1. Altogether, this easily reproducible cancer model can be used for initial testing of the cytotoxicity of new anticancer substances. For subsequent in-depth characterization of candidate drugs, further improvements will be necessary, such as the generation of a multi-cell type lung cancer model and the lining of vascular structures with endothelial cells.


Assuntos
Bioimpressão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Células Endoteliais/fisiologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Hidrogéis/química , Técnicas de Cultura de Células/métodos , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Tecidos Suporte/química
12.
Biofabrication ; 15(2)2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36645921

RESUMO

Additively manufactured hollow-strut bioceramic scaffolds present a promising strategy towards enhanced performance in patient-tailored bone tissue engineering. The channels in such scaffolds offer pathways for nutrient and cell transport and facilitate effective osseointegration and vascularization. In this study, we report an approach for the slurry based additive manufacturing of modified diopside bioceramics that enables the production of hollow-strut scaffolds with diverse cross-sectional forms, distinguished by different configurations of channel and strut geometries. The prepared scaffolds exhibit levels of porosity and mechanical strength that are well suited for osteoporotic bone repair. Mechanical characterization in orthogonal orientations revealed that a square outer cross-section for hollow struts in woodpile scaffolds gives rise to levels of compressive strength that are higher than those of conventional solid cylindrical strut scaffolds despite a significantly lower density. Finite element analysis confirms that this improved strength arises from lower stress concentration in such geometries. It was shown that hollow struts in bioceramic scaffolds dramatically increase cell attachment and proliferation, potentially promoting new bone tissue formation within the scaffold channel. This work provides an easily controlled method for the extrusion-based 3D printing of hollow strut scaffolds. We show here how the production of hollow struts with controllable geometry can serve to enhance both the functional and mechanical performance of porous structures, with particular relevance for bone tissue engineering scaffolds.


Assuntos
Engenharia Tecidual , Tecidos Suporte , Humanos , Estudos Transversais , Tecidos Suporte/química , Engenharia Tecidual/métodos , Osso e Ossos , Porosidade , Impressão Tridimensional
14.
Medicine (Baltimore) ; 101(33): e30111, 2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-35984135

RESUMO

BACKGROUND: To analyze the epidemiological characteristics and changing trends of lumbar fractures in Xingtai Orthopedic Hospital in the past 10 years, and to improve the prevention and treatment of lumbar fractures. METHODS: Using the hospital information system, data on patients with lumbar fractures in our hospital from 2009 to 2018 were collected regarding their age, gender, fracture time, injury mechanism, and the type of fracture. The epidemiological characteristics and trends of lumbar fractures for the period were summarized and analyzed. RESULTS: The age of male patients with a high incidence of lumbar fractures was 61 to 70 years, followed by 51 to 60 years. The age of female patients with the highest incidence rate was 61 to 70 years, followed by 51 to 60 years (19.22%). Lumbar fractures in group A were predominantly of men. The majority of lumbar fractures in group B were of women. In group A, the incidence rate was higher in young men (21-50 years) than in women and higher in women >51 years. Most of the affected individuals were women. In group B, there were more middle-aged and young men (21-50 years) than women; however, there were more women than men aged ≥51 years. Car accident injury was the main cause of fractures, but in group B women, low-energy injuries were the main cause of fractures. The periods of high incidence in groups A and B were 4 to 6 years and 7 to 9 years, respectively. The number of injuries in group A was the highest and burst fracture was the main fracture type. In group B, the number of fall injuries was the highest, followed by car accident injuries, and compression fracture was the main fracture type. CONCLUSION: The number of lumbar fractures in women caused by low-energy injuries showed an increasing trend. The type of compression fracture increased, which might be related to osteoporosis caused by the decrease in the estrogen level after menopause.


Assuntos
Fraturas por Compressão , Fraturas da Coluna Vertebral , Estudos Epidemiológicos , Feminino , Hospitais , Humanos , Pacientes Internados , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Fraturas da Coluna Vertebral/epidemiologia
15.
Hematology ; 27(1): 555-564, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35544695

RESUMO

OBJECTIVE: To determine the role of replication factor C subunit 5 (RFC5) in acute myeloid leukemia (AML) from four aspects: expression, prognosis, biological functions, and its effects on the immune system. METHODS: The RFC5 gene expression and survival analyses, biological function analyses including functional enrichment analysis of genes co-expressed with RFC5, RFC5-interacted gene network construction, gene set enrichment analysis (GSEA), and immune infiltration analysis were performed using data based on GDC TCGA and GEO. The CIBERSORT algorithm was employed to quantify immune cell fractions. All the statistical analyses were performed in SPSS software, GraphPad Prism, and R software. RESULTS: RFC5 expression was abnormally expressed in AML (P <0.05). Notably, differential RFC5 expression was observed among different FAB AML subtypes and hematopoietic lineages (all P <0.05). More importantly, high RFC5 expression served as an independent prognostic factor for the poor overall survival of AML patients (P <0.001). Enrichment analyses revealed that RFC5 was involved in cell cycle-related pathways in AML. CIBERSORT analysis showed high proportions of M2 macrophages in the high RFC5 expression group. CONCLUSIONS: RFC5 might serve as an effective and robust biomarker for the diagnosis and prognosis of AML. RFC5 might be involved in the AML progression via cell cycle regulation. Moreover, the correlation between RFC5 and immune cells might provide potential assistance for AML treatment.


Assuntos
Leucemia Mieloide Aguda , Proteína de Replicação C/metabolismo , Algoritmos , Redes Reguladoras de Genes , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Prognóstico , Proteína de Replicação C/genética
16.
Int J Mol Sci ; 23(1)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-35008547

RESUMO

Development of new anticancer drugs with currently available animal models is hampered by the fact that human cancer cells are embedded in an animal-derived environment. Neuroblastoma is the most common extracranial solid malignancy of childhood. Major obstacles include managing chemotherapy-resistant relapses and resistance to induction therapy, leading to early death in very-high-risk patients. Here, we present a three-dimensional (3D) model for neuroblastoma composed of IMR-32 cells with amplified genes of the myelocytomatosis viral related oncogene MYCN and the anaplastic lymphoma kinase (ALK) in a renal environment of exclusively human origin, made of human embryonic kidney 293 cells and primary human kidney fibroblasts. The model was produced with two pneumatic extrusion printheads using a commercially available bioprinter. Two drugs were exemplarily tested in this model: While the histone deacetylase inhibitor panobinostat selectively killed the cancer cells by apoptosis induction but did not affect renal cells in the therapeutically effective concentration range, the peptidyl nucleoside antibiotic blasticidin induced cell death in both cell types. Importantly, differences in sensitivity between two-dimensional (2D) and 3D cultures were cell-type specific, making the therapeutic window broader in the bioprinted model and demonstrating the value of studying anticancer drugs in human 3D models. Altogether, this cancer model allows testing cytotoxicity and tumor selectivity of new anticancer drugs, and the open scaffold design enables the free exchange of tumor and microenvironment by any cell type.


Assuntos
Antineoplásicos/farmacologia , Rim/efeitos dos fármacos , Neuroblastoma/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacos , Quinase do Linfoma Anaplásico/metabolismo , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Células HEK293 , Humanos , Rim/metabolismo , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/metabolismo , Panobinostat/farmacologia
17.
Mater Sci Eng C Mater Biol Appl ; 107: 110333, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761202

RESUMO

The mechanical environment of extracellular matrix (ECM) plays an important role in adjusting the behaviors of cells. Natural ECM are highly viscoelastic materials with stress-relaxion behavior. Hydrogel is considered as a promising and attractive material for cell carrier, but they are typically elastic serving as synthetic ECM. Double-network (DN) hydrogel has an interpenetrating network of special structure combining the advantages of both rigid and ductile components, due to which the mechanical properties of the system can be very different from that of the single-network ones, and some special biological properties can be obtained. In this study, GG/PEGDA DN hydrogel was prepared by combining gellan gum (GG) with polyethylene glycol diacrylate (PEGDA), and then the influence of the two individual networks on the viscoelasticity of the system were investigated. Furthermore, the effects of viscoelasticity of GG/PEGDA DN hydrogel on the biological behavior of bone mesenchymal stem cells (BMSCs) were explored in vitro and in vivo. The results indicate that the spreading of BMSCs was closely related to the relaxation behavior of the hydrogels. GG/PEGDA DN hydrogel shows excellent mechanical and relaxation properties which provide a favorable physical environment for cell proliferation and spreading, and induce chondrogenic differentiation. Our study demonstrates that this DN hydrogel has bright prospects in the fields of cell carrier and cartilage tissue engineering.


Assuntos
Condrogênese/fisiologia , Hidrogéis/química , Células-Tronco Mesenquimais/citologia , Implantes Absorvíveis , Animais , Fenômenos Biomecânicos , Osso e Ossos/citologia , Cartilagem/fisiologia , Diferenciação Celular , Células Cultivadas , Colágeno Tipo II/metabolismo , Masculino , Camundongos , Polissacarídeos Bacterianos/química , Regeneração , Reologia , Fator de Crescimento Transformador beta3/administração & dosagem , Fator de Crescimento Transformador beta3/metabolismo , Substâncias Viscoelásticas/química
18.
Carbohydr Polym ; 225: 115110, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31521272

RESUMO

Various functional active hydrogels have been widely applied in tissue regeneration, especially in fields of wound repair as they are similar to the natural extracellular matrix (ECM) and can maintain moist at the wound site. However, preparing a hydrogel with multifunctional properties including high mechanical properties, excellent biocompatibility and long-term antibacterial activity is still a challenge. Herein, we developed a series of double network hydrogels based on poly (ethylene glycol) diacrylate (PEGDA) and chitosan (CS) or thiolated chitosan (TCS). The hydrogels presented in situ forming properties, good mechanical strength, adhesiveness, antibacterial activity and biocompatibility. The sample with the optimal formula of 15 wt% of PEGDA and 2 wt% of CS or TCS showed excellent mechanical adhesiveness, sustained release of antibacterial peptide and plasmid DNA, and it significantly accelerated in vivo wound healing process in a full-thickness skin defect model by reducing the inflammation and promoting the angiogenesis, meaning that the prepared hydrogels are excellent candidates for wound dressing.


Assuntos
Curativos Hidrocoloides , Quitosana/farmacologia , Hidrogéis/farmacologia , Polietilenoglicóis/farmacologia , Cicatrização , Adesividade , Animais , Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Linhagem Celular , Ratos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos
19.
Colloids Surf B Biointerfaces ; 177: 496-505, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30807964

RESUMO

Excellent biocompatibility and inflammatory regulation ability are essential to bone repair materials. Herein, Rod-like HAP with a diameter of 0.1 µm and Flake-like HAP with a width of 0.5-1 µm were synthesized by hydrothermal method, and then combined with two kinds of biomolecules, Icariin and Kaempferol. Two kinds of HAPs have similar crystal structure, but different zeta potentials and specific surface area. Rod-like HAP possesses stronger loading capacity and internalization efficiency than Flake-like one. in vitro inflammation assay reveals that HAP particles up-regulate the expression of IL-1ß, TNF-α, IL-6, IL-10, IFN-γ and IL-2 cytokines. HAP particles loaded with Icariin or Kaempferol biomolecules up-regulate anti-inflammatory cytokines and down-regulate the expression of inflammatory cytokines.


Assuntos
Fluoresceína/química , Hidroxiapatitas/química , Inflamação/metabolismo , Ovalbumina/química , Caspases/química , Caspases/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Fluoresceína/metabolismo , Humanos , Hidroxiapatitas/farmacologia , Estrutura Molecular , Ovalbumina/metabolismo , Tamanho da Partícula , Propriedades de Superfície , Células THP-1 , Proteínas Quinases p38 Ativadas por Mitógeno/química , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
20.
Nanoscale ; 10(43): 20321-20328, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30375630

RESUMO

Living organisms have evolved functional structures for seeds dispersal in response to humidity changes. In this study, we construct moisture-responsive nanotubes by the supramolecular coordination of a peptide lipid with metal ions for potential applications in material delivery systems. These hydrophilic nanotubes can uptake atmospheric moisture and the water molecules are associated with unsaturated metal centers of the bis(lipid)-metal(ii) complex, thereby changing the molecular packing and inducing morphological transformation from nanotubes to sheets. The moisture responsivity of nanotubes depends on the hydration behavior of the metal ions. Co(ii)-coordinated nanotube shows higher moisture responsivity than that of the Zn(ii)-coordinated one since Co(ii) ion has stronger association with water molecules. These two nanotubes are self-assembled by the same molecular packings; however, they show different mechanisms in morphological changes. The Co(ii)-coordinated nanotube transforms into a sheet accompanied with the destruction of the complex and reverse molecular packing, whereas Zn(ii)-coordinated nanotube transforms into a sheet with a change in the complex geometry. Further, the Co(ii)-coordinated nanotubes exhibit reversible morphological changes between nanotubes and sheets, while Zn(ii)-coordinated nanotubes exhibit a one-way morphological change. These nanotubes also show potential applications in the release of fragrance oil under high humidity environments.

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