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2.
ACS Appl Mater Interfaces ; 16(28): 37183-37196, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38963398

RESUMO

Here, we explored a new manufacturing strategy that uses the mask laser interference additive manufacturing (MLIAM) technique, which combines the respective strengths of laser interference lithography and mask lithography to efficiently fabricate across-scales three-dimensional bionic shark skin structures with superhydrophobicity and adhesive reduction. The phenomena and mechanisms of the MLIAM curing process were revealed and analyzed, showing the feasibility and flexibility. In terms of structural performance, the adhesive force on the surface can be tuned based on the growth direction of the bionic shark skin structures, where the maximum rate of the adhesive reduction reaches about 65%. Furthermore, the evolution of the directional diffusion for the water droplet, which is based on the change of the contact angle, was clearly observed, and the mechanism was also discussed by the models. Moreover, no-loss transportations were achieved successfully using the gradient adhesive force and superhydrophobicity on the surface by tuning the growth direction and modifying by fluorinated silane. Finally, this work gives a strategy for fabricating across-scale structures on micro- and nanometers, which have potential application in bioengineering, diversional targeting, and condenser surface.


Assuntos
Lasers , Tubarões , Pele , Animais , Interações Hidrofóbicas e Hidrofílicas , Propriedades de Superfície , Biônica
3.
J Ethnopharmacol ; 332: 118286, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-38723919

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Di-Long (Pheretima vulgaris) is a classic animal sourced traditional Chinese medicine. It has been used for the treatment of joint inflammation and arthralgia for over two thousand years due to its effects of Tong-Luo-Zhi-Tong (dredging collaterals and alleviating pain). Our previous study showed that Chinese medicine Di-Long has significant anti-rheumatoid arthritis (RA) effects. AIM OF THE STUDY: Considering Di-Long as a potential source of active compounds with specific anti-RA therapeutic effects, this research was to obtain the anti-RA target-specific active fraction from Di-Long extracts (DL), and to further explore the chemical basis and verify the anti-RA mechanism of this active fraction. MATERIALS AND METHODS: Transcriptomic was applied to obtain the main anti-RA targets of DL on human RA fibroblast-like synoviocytes (FLS) and validated by qPCR. The target-corresponding active fraction was isolated from DL by ethanol precipitation and gel chromatography, and analyzed by nanoliter chromatography-mass spectrometry. Anti-RA effects of this active fraction was investigated by collagen-induced arthritis (CIA) in mice, and anti-RA mechanisms were verified in cocultured model of rat FLS and peripheral blood lymphocytes. RESULTS: We confirmed that CXCL10/CXCR3 was the main anti-RA target of DL. The active fraction - A (2182 - 890 Da) was isolated from DL based on its CXCL10 inhibiting effects in RA-FLS. Fraction A contains 195 peptides (192 were newly discovered), 26 of which might be bioactive and were considered to be the chemical basis of its anti-RA effects. Fraction A significantly ameliorated the joint destruction and overall inflammation in CIA mice, and downregulated CXCR3 expression in mice joint. Fraction A inhibited the chemotaxis of Th-cells in rat peripheral blood lymphocytes towards the TNF-α-induced rat FLS through CXCL10/CXCR3 pathway. CONCLUSIONS: Our work indicated that active fraction from DL containing small peptides exhibits promising therapeutic effects for RA through inhibiting CXCL10/CXCR3 chemotaxis.


Assuntos
Antirreumáticos , Artrite Experimental , Artrite Reumatoide , Quimiocina CXCL10 , Quimiotaxia , Receptores CXCR3 , Membrana Sinovial , Animais , Receptores CXCR3/metabolismo , Quimiocina CXCL10/metabolismo , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Masculino , Antirreumáticos/farmacologia , Antirreumáticos/isolamento & purificação , Ratos , Humanos , Quimiotaxia/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo
4.
J Ginseng Res ; 48(1): 77-88, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38223829

RESUMO

Background: Lung inflammation occurs in many lung diseases, but has limited effective therapeutics. Ginseng and its derivatives have anti-inflammatory effects, but their unstable physicochemical and metabolic properties hinder their application in the treatment. Panaxadiol (PD) is a stable saponin among ginsenosides. Inhalation administration may solve these issues, and the specific mechanism of action needs to be studied. Methods: A mouse model of lung inflammation induced by lipopolysaccharide (LPS), an in vitro macrophage inflammation model, and a coculture model of epithelial cells and macrophages were used to study the effects and mechanisms of inhalation delivery of PD. Pathology and molecular assessments were used to evaluate efficacy. Transcriptome sequencing was used to screen the mechanism and target. Finally, the efficacy and mechanism were verified in a human BALF cell model. Results: Inhaled PD reduced LPS-induced lung inflammation in mice in a dose-dependent manner, including inflammatory cell infiltration, lung tissue pathology, and inflammatory factor expression. Meanwhile, the dose of inhalation was much lower than that of intragastric administration under the same therapeutic effect, which may be related to its higher bioavailability and superior pharmacokinetic parameters. Using transcriptome analysis and verification by a coculture model of macrophage and epithelial cells, we found that PD may act by inhibiting TNFA/TNFAR and IL7/IL7R signaling to reduce macrophage inflammatory factor-induced epithelial apoptosis and promote proliferation. Conclusion: PD inhalation alleviates lung inflammation and pathology by inhibiting TNFA/TNFAR and IL7/IL7R signaling between macrophages and epithelial cells. PD may be a novel drug for the clinical treatment of lung inflammation.

5.
J Ethnopharmacol ; 323: 117669, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38159828

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Thrombus generation is one of the leading causes of death in human, and vascular endothelial dysfunction is a major contributor to thrombosis. Pheretima guillemi (Michaelsen), a traditional medicinal animal known as "Dilong", has been utilized to cure thrombotic disorders for many years. DPf3, a group of functional proteins extracted from P. guillemi, has been characterized and identified to possess antithrombotic bioactivity via in vitro and ex vivo experiments. AIM OF THE STUDY: This study is aimed to investigate the vascular-protection activity and related mechanism of antithrombotic protein DPf3 purified from Pheretima guillelmi systematically. MATERIALS AND METHODS: The antithrombotic activity and vascular endothelium protection effect of DPf3 was explored in vivo using ponatinib-induced vascular endothelial injury zebrafish thrombus model. Then, (hi) ox-LDL-induced HUVECs was applied to investigate the protection mechanism of DPf3 against the injury of vascular endothelium. In addition, TMT-based proteomics analysis was used to study the biomarkers, biological processes and signal pathways involved in the antithrombotic and vascular protective effects of DPf3 holistically. RESULTS: DPf3 exerted robust in vivo antithrombosis and vascular endothelial protection ability. DPf3 was identified to prevent HUVECs from damage by reducing ROS production, and to reduce monocyte adhesion by decreasing the protein content of adhesion factor VCAM 1. DPf3 was also observed to weaken the migration ability of injured cells and inhibit abnormal angiogenesis. The mechanism of DPf3's antithrombotic and vascular protective activity was mainly related to the regulation of lipid metabolism, energy metabolism, complement and coagulation system, ECM receptor interaction, MAPK signal pathway, etc. CONCLUSIONS: This study demonstrates that DPf3 has strong antithrombotic and endothelial protective effects. The endothelial protective ability and related mechanisms of DPf3 provide a scientific reference for the traditional use of earthworms in the treatment of thrombosis.


Assuntos
Imidazóis , Oligoquetos , Piridazinas , Trombose , Doenças Vasculares , Animais , Humanos , Peixe-Zebra , Células Endoteliais da Veia Umbilical Humana , Oligoquetos/metabolismo , Proteômica , Fibrinolíticos/farmacologia , Lipoproteínas LDL/metabolismo , Doenças Vasculares/metabolismo , Fatores de Transcrição/metabolismo , Trombose/induzido quimicamente , Trombose/tratamento farmacológico , Trombose/prevenção & controle
7.
Eur J Pharmacol ; 955: 175902, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37422119

RESUMO

Allergic rhinitis (AR) is a nasal mucosal disease with sneezing and nasal itching as the main symptoms. Although AR treatment continues to improve, there remains a lack of effective drugs. There are still controversies regarding whether anticholinergic drugs can effectively and safely relieve the symptoms of AR and reduce inflammation in the nasal mucosa. Here, we synthesized 101BHG-D01, which is a novel anticholinergic drug that mainly targets the M3 receptor and may reduce the adverse effects of other anticholinergic drugs on the heart. We evaluated the effects of 101BHG-D01 on AR and investigated the potential molecular mechanism of anticholinergic therapy for AR. We found that 101BHG-D01 effectively alleviated AR symptoms, reduced the infiltration of inflammatory cells and attenuated the expression of inflammatory factors (IL-4, IL-5, IL-13, etc.) in various AR animal models. In addition, 101BHG-D01 reduced the activation of mast cells and the release of histamine from rat peritoneal mesothelial cells (RPMCs) challenged by IgE. Moreover, 101BHG-D01 reduced the expression of MUC5AC in IL-13-challenged rat nasal epithelial cells (RNECs) and human nasal epithelial cells (HNEpCs). Furthermore, IL-13 stimulation significantly increased JAK1 and STAT6 phosphorylation, which was suppressed by 101BHG-D01. We demonstrated that 101BHG-D01 reduced mucus secretion and inflammatory cell infiltration in the nasal mucosa, which may occur through a reduction in activation of the JAK1-STAT6 signaling pathway, indicating that 101BHG-D01 is a potent and safe anticholinergic therapy for AR.


Assuntos
Interleucina-13 , Rinite Alérgica , Humanos , Ratos , Animais , Camundongos , Interleucina-13/metabolismo , Imunoglobulina E , Modelos Animais de Doenças , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/metabolismo , Mucosa Nasal , Camundongos Endogâmicos BALB C , Ovalbumina/farmacologia , Citocinas/metabolismo
8.
J Inflamm Res ; 16: 2907-2928, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37465344

RESUMO

Background: Centromere protein I (CENPI) has been shown to affect the tumorigenesis of breast and colorectal cancers. However, its biological role and prognostic value in other kinds of cancer, especially adrenocortical carcinoma (ACC), remained to be further investigated. Methods: Various bioinformatics tools were adopted for exploring the significance of differential expression of CENPI in several malignant tumors from databases such as Depmap portal, GTEx, and TCGA. ACC was selected for further analyzed, and information such as clinicopathological features, the prognostic outcome of diverse subgroups, differentially expressed genes (DEGs), co-expression genes, as well as levels of tumor-infiltrating immune cells (TIIC), was extracted from multiple databases. To verify the possibility of CENPI as a therapeutic target in ACC, drug sensitivity assay and si-RNA mediate knockdown of CENPI were carried out. Results: The pan-cancer analyses showed that the CENPI mRNA expression levels differed significantly among most cancer types. Additionally, a high precision in cancer prediction and close relation with cancer survival indicated that CENPI could be a potential candidate biomarker to diagnose and predict cancer prognosis. In ACC, CENPI was closely related to multiple clinical characteristics, such as pathological stage and primary therapy outcome. High CENPI levels predicted poor overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) of ACC patients, particularly for different clinical subgroups. Moreover, the expression of CENPI showed positive relationship to Th2 cells but negatively related to most of the TIICs. Furthermore, drug sensitivity assay showed that vorinostat inhibit CENPI expression and ACC cell growth. Additionally, si-RNA mediated knockdown of CENPI inhibited ACC cell growth and invasion and showed synergistic anti-proliferation effect with AURKB inhibitor barasertib. Conclusion: Pan-cancer analysis demonstrated that CENPI is a potential diagnostic and prognostic biomarker in various cancers as well as an anti-ACC therapeutic target.

9.
Funct Integr Genomics ; 23(1): 53, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36717477

RESUMO

Olverembatinib represents the third-generation breakpoint cluster region protein-Abelson-murine leukemia 1 (BCR-ABL1) tyrosine kinase inhibitor with oral bioavailability, which can be used to overcome the T315I mutation in Philadelphia chromosome-positive (Ph +) leukemia. BCR-ABL-independent resistance to olverembatinib has been reported among patients in various clinical cases. However, the mechanism of olverembatinib resistance has rarely been reported. This study has illustrated bone marrow cell transcriptome and metabolome profiles among Ph + acute lymphoblastic leukemias (ALL) cases pre- and post-olverembatinib resistance. The transcriptome studies demonstrated that PI3K/AKT, purine metabolism, and other signaling pathways could play a vital role in olverembatinib resistance. As suggested by metabolomics, olverembatinib resistance in Ph + ALL was associated with purine metabolism alterations. Subsequently, high-performance liquid chromatography along with real-time quantitative PCR was utilized to measure purine metabolism-related mRNA levels and metabolism expression levels between olverembatinib resistance and sensitive cell lines. Our results elucidate the mechanism of olverembatinib resistance in Ph + ALL at transcriptome and metabolome levels, which facilitate a better understanding of olverembatinib resistance and hence may prove crucial in identifying novel drugs to tackle this conundrum.


Assuntos
Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metaboloma , Mutação , Fosfatidilinositol 3-Quinases/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Inibidores de Proteínas Quinases/farmacologia , Purinas , Transcriptoma
10.
Int J Neurosci ; 133(5): 555-566, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-34082664

RESUMO

OBJECTIVE: Children with ADHD are reported to accompany by various degrees of recognition memory cognitive deficits. We aimed to investigate age-related changes of the amplitude in event-related potential recordings on recognition memory in Chinese children with ADHD and to provide theoretical basis of neuro-electrophysiology for the cognition development of children. METHOD: ERP and behavioral data of 6- to -10-year-old children with ADHD (n = 94) and typically developing controls (TD, n = 96) were collected while the children performed a classical visual study-test paradigm task. RESULTS: Children with ADHD have defects in pictures recognition and showed a significantly smaller P2 component than that of TD children. The development of P2 and P3 component were different between the two groups. Moreover, the TD children showed the frontal old/new effect (N2) taken as a correlate of familiarity at 6 years old, and a parietal old/new effect (P3) taken as a correlate of recollection at 9 years old, while children with ADHD showed a parietal old/new effect (P3) only at 6 years old. CONCLUSION: Our study provided the novel evidence that recognition memory follow different developmental trajectories at the age of 6-10 between TD and ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtornos Cognitivos , Humanos , Criança , Potenciais Evocados/fisiologia , Reconhecimento Psicológico/fisiologia , Cognição , Eletroencefalografia
11.
Front Mol Biosci ; 10: 1281141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38161382

RESUMO

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder with an unpredictable prognosis. Ferroptosis, the iron-dependent cell death program, could serve as an alternative for overcoming drug resistance. However, its effect on AML remains largely unclear. Methods: We collected RNA sequencing data and relevant clinical information of AML patients from The Cancer Genome Atlas to construct a prognosis prediction model. Risk score was calculated with eight prognosis-related ferroptosis genes (PRFGs) discovered through univariate analysis and Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression. A nomogram was constructed by incorporating LASSO risk score, age, and cytogenetic risk based on univariate/multivariate Cox regression. Results: Of the 33 AML PRFGs identified from the TCGA-derived dataset, 8 genes were used to construct a gene signature to predict AML prognosis. Principal component analysis and heatmap showed significant differences between the low and high risk score groups. Next, LASSO risk score, age, and cytogenetic risk were incorporated into the nomogram to predict the overall survival (OS) of AML patients. According to survival analysis, patients with a low risk score had markedly increased OS as compared to those with a high risk score. Based on the results of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, the differences between the two risk groups showed a close relationship with immune-related pathways and membrane transportation. The analysis of tumor-infiltrating immune cells and immune checkpoints revealed that the immunosuppressive tumor microenvironment possibly facilitated different prognostic outcomes between the two groups. Gene expression analyses showed that the mRNA expression levels of PARP1 and PARP3 (PARPs) were closely related to the different clinical subgroups and the analyzed OS in AML patients. Finally, the PARP inhibitor talazoparib and the ferroptosis inducer erastin exerted a synergistic anti-proliferative effect on AML cells. Conclusion: We constructed a nomogram by incorporating PRFGs, and the constructed nomogram showed a good performance in AML patient stratification and prognosis prediction. The combination of PARP inhibitors with ferroptosis inducers could be a novel treatment strategy for treating AML patients.

12.
Front Immunol ; 13: 1040442, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36439114

RESUMO

Monkey disease models, which are comparable to humans in terms of genetic, anatomical, and physiological characteristics, are important for understanding disease mechanisms and evaluating the efficiency of biological treatments. Here, we established an A.suum-induced model of asthma in cynomolgus monkeys to profile airway inflammation and remodeling in the lungs by single-cell RNA sequencing (scRNA-seq). The asthma model results in airway hyperresponsiveness and remodeling, demonstrated by pulmonary function test and histological characterization. scRNA-seq reveals that the model elevates the numbers of stromal, epithelial and mesenchymal cells (MCs). Particularly, the model increases the numbers of endothelial cells (ECs), fibroblasts (Fibs) and smooth muscle cells (SMCs) in the lungs, with upregulated gene expression associated with cell functions enriched in cell migration and angiogenesis in ECs and Fibs, and VEGF-driven cell proliferation, apoptotic process and complement activation in SMCs. Interestingly, we discover a novel Fib subtype that mediates type I inflammation in the asthmatic lungs. Moreover, MCs in the asthmatic lungs are found to regulate airway remodeling and immunological responses, with elevated gene expression enriched in cell migration, proliferation, angiogenesis and innate immunological responses. Not only the numbers of epithelial cells in the asthmatic lungs change at the time of lung tissue collection, but also their gene expressions are significantly altered, with an enrichment in the biological processes of IL-17 signaling pathway and apoptosis in the majority of subtypes of epithelial cells. Moreover, the ubiquitin process and DNA repair are more prevalent in ciliated epithelial cells. Last, cell-to-cell interaction analysis reveals a complex network among stromal cells, MCs and macrophages that contribute to the development of asthma and airway remodeling. Our findings provide a critical resource for understanding the principle underlying airway remodeling and inflammation in a monkey model of asthma, as well as valuable hints for the future treatment of asthma, especially the airway remodeling-characterized refractory asthma.


Assuntos
Remodelação das Vias Aéreas , Asma , Animais , Humanos , Remodelação das Vias Aéreas/genética , Macaca fascicularis , Transcriptoma , Células Endoteliais/metabolismo , Asma/metabolismo , Inflamação/patologia , Pulmão/patologia
13.
In Vitro Cell Dev Biol Anim ; 58(10): 886-897, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36378269

RESUMO

Mandibular distraction osteogenesis (MDO) is an endogenous tissue engineering technology in which bone marrow mesenchymal stem cells (BMSC) play a key role in MDO-related osteogenesis. Activating transcription factor 4 (ATF4) is involved in osteogenesis through activation of PERK (Protein kinase R-like endoplasmic reticulum kinase) in endoplasmic reticulum stress (ERS) condition under hypoxia. However, the specific role of ATF4 in MDO with BMSC remains unknown. The aim of this study was to explore the effects of ATF4 in MDO with BMSC under hypoxia. Briefly, canine BMSCs were cultured in a hypoxic chamber, and effects of hypoxia were evaluated using cell migration assay and Alizarin Red S staining. Expression levels of protein kinase R-like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2α, ATF4, osteocalcin, and bone sialoprotein were evaluated using quantitative polymerase chain reaction and western blotting. BMSCs were transduced with the ATF4-small interfering RNA lentivirus. The effects were evaluated using all the aforementioned experiments. The results showed that hypoxia promoted migration, osteoblast differentiation, and ATF4 expression in BMSC. ATF4 knockdown in BMSC significantly inhibited migration and osteoblast differentiation abilities, while hypoxia reversed these effects to some extent. In addition, the molecular mechanism partly depended on the ERS signaling pathway, with ATF4 as the key factor. In summary, we presented a novel mechanism of ATF4-mediated regulation of BMSC under hypoxia.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Animais , Cães , Osteogênese/genética , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , eIF-2 Quinase/genética , eIF-2 Quinase/metabolismo , eIF-2 Quinase/farmacologia , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 2 em Eucariotos/farmacologia , Transdução de Sinais , Estresse do Retículo Endoplasmático , Hipóxia/metabolismo
14.
Front Mol Biosci ; 9: 959738, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046602

RESUMO

Targeted therapy for acute myeloid leukemia (AML) is an effective strategy, but currently, there are very limited therapeutic targets for AML treatment. Ferroptosis is strongly related to drug resistance and carcinogenesis. However, there are few reports about ferroptosis in AML. This article explores the relationship between ferroptosis-related gene (FRG) expression and prognosis in AML patients from the FerrDb and the Cancer Genome Atlas (TCGA) databases. The ferroptosis-related gene ARNTL was observed to have high expression and poor prognosis in AML. Receiver operating characteristic curve (ROC) analysis revealed the predictive accuracy of the signature. The area under the time-dependent ROC curve (AUC) was 0.533 at one year, 0.619 at two years, and 0.622 at three years within the training cohort. Moreover, we found that the ARNTL expression is closely associated with tumor-infiltrating immune cells like the macrophages and NK cells. Inhibiting the ARNTL expression suppressed colony formation and induced ferroptosis in AML cells. Overall, the survival prediction model constructed based on ARNTL accurately predicted the survival in AML patients, which could be a potential candidate for diagnosing and treating AML.

16.
Acta Histochem ; 124(6): 151913, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35759812

RESUMO

Distraction osteogenesis (DO) is a widely used surgical technique to repair bone defects, partly owing to its high efficiency in inducing osteogenesis; however, the process of osteogenesis is complex, and the precise mechanism is still unclear. Among the factors identified for an effective DO procedure, well-controlled inflammation is essential. We aimed to explore how microRNA(miR)-146a, a negative regulator of inflammation, influences osteogenesis in DO. First, we established canine right mandibular DO and bone fracture models to evaluate the expression level of miR-146a in response to these procedures. Second, bone marrow mesenchymal stem cells (BMSCs) were isolated from healthy puppies and cultured with lipopolysaccharide (LPS) to observe how inflammation affects osteogenesis. Finally, the osteogenesis activity of BMSCs transfected with lentiviral vector either overexpressing (miR-146a-up) or inhibited for miR-146a expression was evaluated. miR-146a-up-transfected BMSCs were injected locally into the distraction gaps of the DO model canines. On days 42 and 56 post-surgery, the bone volume/tissue volume and bone mineral density values were evaluated via using micro-computed tomography, and newly formed tissues were harvested and evaluated via histological staining. The expression of miR-146a in both the DO canine model and LPS-stimulated BMSCs increased. Overexpression of miR-146a enhanced cell proliferation, migration, and osteogenic differentiation. Additionally, the newly formed callus was improved in canine mandibles injected with miR-146a-up-transfected BMSCs. In summary, miR-146a regulates mandibular DO by improving osteogenesis, and can serve as a potential target to shorten the therapy period of DO.


Assuntos
Células-Tronco Mesenquimais , MicroRNAs , Osteogênese por Distração , Animais , Células da Medula Óssea , Diferenciação Celular , Células Cultivadas , Cães , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , MicroRNAs/metabolismo , Osteogênese , Microtomografia por Raio-X
17.
Cancer Invest ; 40(3): 282-292, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34797742

RESUMO

Despite high remission rates following chimeric antigen receptor T cell (CAR-T) cell therapy in B-cell acute lymphoblastic leukemia (B-ALL), relapse due to loss of the targeted antigen is increasingly recognized as a mechanism of immune escape. We hypothesized that simultaneous targeting of CD19 and CD22 may improve the CAR-T effect. The in vitro and in vivo leukemia model was established, and the anti-tumor effects of BiCAR-T, CD19 CAR-T, CD22 CAR-T, and LoopCAR6 cells were observed. We found that the BiCAR-T cells showed significant cytotoxicity in vitro and in vivo. The CD19/CD22 bivalent CAR provides an opportunity to test whether simultaneous targeting may reduce the risk of antigen loss.


Assuntos
Antígenos CD19/imunologia , Imunoterapia Adotiva/métodos , Leucemia Experimental/terapia , Receptores de Antígenos Quiméricos/imunologia , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/imunologia , Animais , Antígenos CD19/genética , Feminino , Humanos , Células K562 , Lentivirus/genética , Camundongos , Lectina 2 Semelhante a Ig de Ligação ao Ácido Siálico/genética
18.
Nanotechnology ; 33(11)2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34844231

RESUMO

The micro-stripe structure was prepared by laser interference induced forward transfer technique, composed of Ag nano-particles (NPs). The effects of the film thickness with the carbon nano-particles mixed polyimide (CNPs@PI), Ag film thickness, and laser fluence were studied on the transferred micro-stripe structure. The periodic Ag micro-stripe with good resolution was obtained in a wide range of CNPs@PI film thickness from âˆ¼0.5 to âˆ¼1.0µm for the Ag thin film âˆ¼20 nm. The distribution of the Ag NPs composing the micro-stripe was compact. Nevertheless, the average size of the transferred Ag NPs was increased from âˆ¼41 to âˆ¼197 nm with the change of the Ag donor film from âˆ¼10 to âˆ¼40 nm. With the increase of the laser fluence from 102 to 306 mJ·cm-2per-beam, the transferred Ag NPs became aggregative, improving the resolution of the corresponding micro-stripe. Finally, the transferred Ag micro-stripe exhibited the significant surface enhanced Raman scattering (SERS) property for rhodamine B (RhB). While the concentration of the RhB reached 10-10mol·L-1, the Raman characteristic peaks of the RhB were still observed clearly at 622, 1359 and 1649 cm-1. These results indicate that the transferred Ag micro-stripe has potential application as a SERS chip in drug and food detection.

19.
Front Oncol ; 11: 734593, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778046

RESUMO

Chimeric antigen receptor T (CAR-T) cells are not effective in solid tumor treatment due to reduced invasion and expansion, and short survival time. This study aimed to explore whether interleukin (IL)-7 and CCR2b expression could improve GD2-CAR-T cell survival and infiltration in neuroblastoma and melanoma treatment. IL-7 and CCR2b were inserted into the classical second-generation CAR structure to construct 7×2b CAR. The 7×2b CAR-T cell phenotypes were evaluated by flow cytometry and the chemokine levels by ELISA. The 7×2b CAR-T cell migration and anti-tumor abilities were detected by Transwell assay and animal experiments in vivo. We report that compared with that of CAR-T cells, 7×2b CAR-T cell IL-7 secretion and CCR2b expression did not affect the T cell surface expression of CAR or CAR-T specificity and efficacy against tumor cells. The 7×2b CAR-T cells could induce IFN-γ secretion in GD2-positive tumor cells, killing them as well as conventional CAR-T cells. Moreover, IL-7 and CCR2b co-expression enhanced the 7×2b CAR-T cell survival and migration. Similar to conventional CAR-T, 7×2b CAR-T cells could also inhibit tumor growth and increase IFN-γ, Gzms-B, and IL-2 expression. Finally, unlike in mice injected with CAR-T cells, CD3 expression was the most abundant in the spleen and tumor tissues in mice injected with 7×2b CAR-T cells. Our study demonstrates that IL-7 and CCR2b co-expression in GD2-CAR-T cells exhibit stronger anti-tumor activity than classical second-generation CAR-T cells, shedding light on the potential novel GD2-positive neuroblastoma and melanoma treatment approach.

20.
Front Mol Biosci ; 8: 754936, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746238

RESUMO

Acute myeloid leukemia (AML) represents a frequently occurring adulthood acute leukemia (AL). Great progresses have been achieved in the treatment of AML, but its pathogenic mechanism remains unclear. This study reported the biological functions of lncRNA DUBR in AML pathogenic mechanism. As a result, lncRNA DUBR showed high expression level within AML, resulting in poor prognosis, especially in M4 AML. In vitro studies elucidated that knockdown of DUBR with small interfering RNA (siRNA) resulted in the suppression of survival and colony formation ability, as well as induction of apoptosis, in AML cells. RNA pull-down assay and computational revealed that DUBR could sponge with miRNA-142-3P and interact with FUS protein. MiRNA-142-3P have a negative correlation with DUBR and overexpression of miRNA-142-3P inhibited cell growth in AML. Meanwhile, DUBR promoted the expression of FUS protein, targeting inhibition of FUS significantly promoted cell apoptosis in AML cell lines. In conclusion, these results revealed new mechanism of lncRNA DUBR in AML malignant behavior, and suggested that the manipulation of DUBR expression could serve as a potential strategy in AML therapy.

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