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1.
Aging (Albany NY) ; 122020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32434960

RESUMO

Bone volume inadequacy is an emerging clinical problem impairing the feasibility and longevity of dental implants. Human bone marrow mesenchymal stem cells (HBMSCs) have been widely used in bone remodeling and regeneration. This study examined the effect of long noncoding RNAs (lncRNAs)-H19 on the human amnion-derived mesenchymal stem cells (HAMSCs)-droved osteogenesis in HBMSCs. HAMSCs and HBMSCs were isolated from abandoned amniotic membrane samples and bone marrow. The coculture system was conducted using transwells, and H19 level was measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR). The mechanism was further verified. We here discovered that osteogenesis of HBMSCs was induced by HAMSCs, while H19 level in HAMSCs was increased during coculturing. H19 had no significant effect on the proliferative behaviors of HBMSCs, while its overexpression of H19 in HAMSCs led to the upregulated osteogenesis of HBMSCs in vivo and in vitro; whereas its knockdown reversed these effects. Mechanistically, H19 promoted miR-675 expression and contributed to the competitively bounding of miR-675 and Adenomatous polyposis coli (APC), thus significantly activating the Wnt/ß-catenin pathway. The results suggested that HAMSCs promote osteogenic differentiation of HBMSCs via H19/miR-675/APC pathway, and supply a potential target for the therapeutic treatment of bone-destructive diseases.

2.
Epigenomics ; 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32408759

RESUMO

Aim: To investigate the associations between single nucleotide polymorphisms (SNPs) in miRNA regulome and nonsyndromic orofacial clefts. Materials & methods: The associations were evaluated by logistic regression model in stage I (504 cases and 455 controls) and stage II (1500 cases and 1386 controls). Functional experiments including luciferase activity assay, cell apoptosis and proliferation, serum miRNA expression, and mouse embryo RNA sequencing were performed. Results: Rs3830766 in the enhancer of hsa-miR-4260 was associated with cleft lip only (CLO) and enhancer activity. Hsa-miR-4260 expression decreased in the serum of CLO. Overexpression of miR-4260 inhibited cell proliferation and promoted cell apoptosis. UBB was the target gene of hsa-miR-4260. Conclusion: Rs3830766 in the hsa-miR-4260 enhancer that can interact with UBB was relevant to CLO.

3.
J Nanobiotechnology ; 18(1): 71, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404183

RESUMO

BACKGROUND: Although many therapeutic strategies for Alzheimer's disease (AD) have been explored, these strategies are seldom used in the clinic. Therefore, AD therapeutic research is still urgently needed. One major challenge in the field of nanotherapeutics is to increase the selective delivery of drugs to a targeted location. Herein, we devised and tested a strategy for delivery of nanoparticles to neurons to inhibit tau aggregation by directly targeting p-tau. RESULTS: Curcumin (CUR) is loaded onto red blood cell (RBC) membrane-coated PLGA particles bearing T807 molecules attached to the RBC membrane surface (T807/RPCNP). With the advantage of the suitable physicochemical properties of the PLGA nanoparticles and the unique biological functions of the RBC membrane, the RPCNP are stabilized and promote sustained CUR release, which provided improved biocompatibility and resulted in long-term presence in the circulation. Under the synergistic effects of T807, T807/RPCNP can not only effectively penetrate the blood-brain barrier (BBB), but they also possess high binding affinity to hyperphosphorylated tau in nerve cells where they inhibit multiple key pathways in tau-associated AD pathogenesis. When CUR was encapsulated, our data also demonstrated that CUR-loaded T807/RPCNP NPs can relieve AD symptoms by reducing p-tau levels and suppressing neuronal-like cells death both in vitro and in vivo. The memory impairment observed in an AD mouse model is significantly improved following systemic administration of CUR-loaded T807/RPCNP NPs. CONCLUSION: Intravenous neuronal tau-targeted T807-modified novel biomimetic nanosystems are a promising clinical candidate for the treatment of AD.

4.
Biomed Res Int ; 2020: 1276328, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32337219

RESUMO

Peroxiredoxin 2 (PRDX2), a member of the peroxiredoxin family of antioxidant enzymes, has been revealed to be an important player in cancer progression. However, the biological role of PRDX2 in the progression of non-small cell lung cancer (NSCLC) is poor reported. In the present study, the loss-of-function experiments were performed to investigate the specific role of PRDX2 in the growth and invasion of NSCLC. The results revealed that knockdown of PRDX2 by siRNA interference significantly suppressed the proliferation, migration, and invasion of A549 and H1299 cells, as well as diminished the activity of MMP9. Additionally, the decrease in PRDX2 expression significantly promoted apoptosis in NSCLC cells by downregulating expression of Bcl-2 and upregulating the expression of Bax, cleaved caspase 3 and cleaved caspase 9, but had no significant effect on the apoptosis of normal lung epithelial cells BEAS-2B. Moreover, PRDX2 inhibitor also inhibited the proliferation, migration, and invasion of A549 cells and promoted apoptosis. Further, our data demonstrated that silencing of PRDX2 markedly reduced the phosphorylation of Akt and mTOR and expression of downstream proteins Cyclin D1 and p70S6k. In conclusion, our findings indicate that PRDX2 exerts a prooncogenic role in the progression of NSCLC and might be a potential therapeutic target for NSCLC treatment.

5.
Acad Radiol ; 27(5): 614-617, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32276755

RESUMO

The COVID-19 epidemic, which is caused by the novel coronavirus SARS-CoV-2, has spread rapidly to become a world-wide pandemic. Chest radiography and chest CT are frequently used to support the diagnosis of COVID-19 infection. However, multiple cases of COVID-19 transmission in radiology department have been reported. Here we summarize the lessons we learned and provide suggestions to improve the infection control and prevention practices of healthcare workers in departments of radiology.


Assuntos
Infecções por Coronavirus/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Controle de Infecções/normas , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Serviço Hospitalar de Radiologia/normas , Radiologia/normas , Infecções por Coronavirus/classificação , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/transmissão , Desinfecção/normas , Humanos , Controle de Infecções/métodos , Pandemias/classificação , Isolamento de Pacientes , Pneumonia Viral/classificação , Pneumonia Viral/epidemiologia , Pneumonia Viral/transmissão , Saúde Pública/educação , Radiologia/educação
6.
Acta Biomater ; 108: 285-299, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32251785

RESUMO

Biomimetic nanotechnology represents a promising approach for the delivery of therapeutic agents for the treatment of complex diseases. Recently, neuronal mitochondria have been proposed to serve as a promising therapeutic target for sporadic Alzheimer's disease (AD). However, the efficient intravenous delivery of therapeutic agents to neuronal mitochondria in the brain remains a major challenge due to the complicated physiological and pathological environment. Herein, we devised and tested a strategy for functional antioxidant delivery to neuronal mitochondria by loading antioxidants into red blood cell (RBC) membrane-camouflaged human serum albumin nanoparticles bearing T807 and triphenylphosphine (TPP) molecules attached to the RBC membrane surface (T807/TPP-RBC-NPs). With the advantage of the suitable physicochemical properties of the nanoparticles and the unique biological functions of the RBC membrane, the T807/TPP-RBC-NPs are stabilized and promote sustained drug release, providing improved biocompatibility and long-term circulation. Under the synergistic effects of T807 and TPP, T807/TPP-RBC-NPs can not only penetrate the blood-brain barrier (BBB) but also target nerve cells and further localize in the mitochondria. After encapsulating curcumin (CUR) as the model antioxidant, the research data demonstrated that CUR-loaded T807/TPP-RBC-NPs can relieve AD symptoms by mitigating mitochondrial oxidative stress and suppressing neuronal death both in vitro and in vivo. In conclusion, the intravenous neuronal mitochondria-targeted biomimetic engineered delivery nanosystems provides an effective drug delivery platform for brain diseases. STATEMENT OF SIGNIFICANCE: The efficient intravenous delivery of therapeutic agents to neuronal mitochondria in the brain remains a major challenge for drug delivery due to the complicated physiological and pathological environment. To address this need, various types of nanovessels have been fabricated using a variety of materials in the last few decades. However, problems with the synthetic materials still exist and even cause toxicology issues. New findings in nanomedicine are promoting the development of biomaterials. Herein, we designed a red blood cell (RBC) membrane-coated human serum albumin nanoparticle dual-modified with T807 and TPP (T807/TPP-RBC-NPs) to accomplish these objectives. After encapsulating curcumin as the model drug, the research data demonstrated that the intravenous neuronal mitochondria-targeted biomimetic engineered delivery nanosystems are a promising therapeutic candidate for mitochondrial dysfunction in Alzheimer's disease (AD).

7.
World J Pediatr ; 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32232677

RESUMO

BACKGROUND: We aimed to explore predictive measures for intravenous immunoglobulin (IVIG) resistance in children with Kawasaki disease (KD). METHODS: Patients diagnosed with KD were enrolled in this study. Univariate analysis and multiple logistic regression were utilized to analyze the clinical features and laboratory results prior to IVIG-treatment of the two groups. Independent predictors of IVIG resistance were analyzed, and a predictive model for KD children with IVIG resistance was constructed. RESULTS: A total of 277 children with KD, 180 boys and 97 girls, aged 2-128 (median 23) months, were enrolled in the study. Compared with the IVIG-responsive group, the IVIG-resistant group had higher levels of the peripheral neutrophil count, mean platelet volume, mean platelet volume-to-lymphocyte ratio and C-reactive protein, and total serum bilirubin, but lower levels of peripheral lymphocyte count, serum albumin and serum prealbumin. Age (in months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin were independent indicators for IVIG resistance by multivariate logistic regression analysis. A logistic regression model and a scoring system were set up, where cut-off values of - 0.46 and 6.5 points yielded sensitivities of 83.9% and 77.4%, and specificities of 74.8% and 61.0%, respectively. The areas under the curve (AUC) were 0.808 in the logistic regression model, and 0.750 in the scoring system. CONCLUSION: Our model for predicting IVIG-resistant children with KD, involving age (months), peripheral neutrophil count, lymphocyte count and mean platelet volume and serum albumin prior to IVIG-treatment, is helpful for clinical prediction of children with IVIG-resistant KD.

8.
Phys Med Biol ; 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32325441

RESUMO

Positron emission tomography (PET) suffers from limited spatial resolution in current head and neck cancer management. We are building a dual-panel high-resolution PET system to aid the detection of tumor involvement in small lymph nodes (< 10 mm in diameter). The system is based on cadmium zinc Telluride (CZT) detectors with cross-strip electrode readout (1 mm anode pitch and 5 mm cathode pitch). One challenge of the dual-panel system is that the limited angular coverage of the imaging volume leads to artifacts in reconstructed images, such as the elongation of lesions. In this work, we leverage a penalized maximum-likelihood (PML) reconstruction for the limited-angle PET system. The dissimilarity between the image to be reconstructed and a prior image from a low-resolution whole-body scanner is penalized. An image-based resolution model is incorporated into the regularization. Computer simulations were used to evaluate the performance of the method. Results demonstrate that the elongation of the 6-mm and 8-mm diameter hot spheres is eliminated with the regularization strength being 0.02 or larger. The PML reconstruction yields higher contrast recovery coefficient of hot spheres compared to the maximum-likelihood reconstruction, as well as the low-resolution whole-body image, across all hot sphere sizes tested (3, 4, 6, and 8 mm). The method studied in this work provides a way to mitigate the limited-angle artifacts in the reconstruction from limited-angle PET data, making the high-resolution dual-panel dedicated head and neck PET system promising for head and neck cancer management.

9.
Abdom Radiol (NY) ; 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32146492

RESUMO

PURPOSE: This study aimed to explore the differences in VERDICT parameters for normal prostatic tissues among different regions and age groups. MATERIALS AND METHODS: In total, 31 male volunteers were included in the study. Vascular, extracellular and restricted diffusion for cytometry in tumors (VERDICT) model parameters (fIC, intracellular volume fraction; fEES, extracellular-extravascular space fraction; and fVASC, vascular fraction) were calculated based on the whole prostate volume and the peripheral zone (PZ), central gland (CG) and anterior fibromuscular stroma (AS) regions of interest (ROIs). Agreement between two readers was determined by calculating the intraclass correlation coefficient. Two-way ANOVA was used to identify significant differences among age groups and regions within the prostate. Age-related and area-related changes in these parameters were assessed using Spearman's correlation coefficients. RESULTS: There were differences in the parameters among regions of the prostate (P < 0.05). In the PZ, there was a negative correlation between age and fIC (r = - 0.66, P < 0.001, adjusted P < 0.001), and age was positively correlated with fEES (r = 0.69, P < 0.001, adjusted P < 0.001) but had no correlation with fVASC. In the CG ROI, there was a positive correlation between age and fEES (r = 0.56, P < 0.001, adjusted P < 0.001) but no correlation between age and fVASC, similar to the results for the PZ. There were no correlations between age and VERDICT parameters in the AS. CONCLUSION: VERDICT parameters vary among different regions of the prostate and correlate with age. These findings are in agreement with histological theory.

10.
Colloids Surf B Biointerfaces ; 190: 110930, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32146275

RESUMO

Multifunctional carbon dots (CDs) present enormous potential in numerous applications and have attracted widespread attention for various applications in the biomedical field. Bacterial infection is a common health issue; the development of antibacterial materials with low toxicity and good biocompatibility is becoming more important. In this work, we synthesized a new type of nitrogen co-doped carbon dots-genipin covalent conjugate (N-CDs-GP) via hydrothermal methods. The microstructure and chemical composition of the N-CDs-GP were characterized. The biocompatibility, stability, antibacterial activity, and fluorescence performance of the N-CDs-GP were assessed. The results revealed that N-CDs-GP possessed high biocompatibility, high light stability, and broad antibacterial activity. Additionally, selective Gram-positive bacterial imaging by N-CDs-GP provided a more rapid method of bacterial detection. The N-CDs-GP have the potential to be applied as bioimaging and antibacterial agents and for bacterial discrimination.

12.
Ground Water ; 58(1): 79-92, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30859561

RESUMO

Drawdown data from independent pumping tests have widely been used to validate the estimated hydraulic parameters from inverse modeling or hydraulic tomography (HT). Yet, the independent pumping test has not been clearly defined. Therefore, the goal of this paper is to define this independent pumping test concept, based on the redundant or nonredundant information about aquifer heterogeneity embedded in the observed heads during cross-hole pumping tests. The definition of complete, moderate redundancy and high nonredundancy of information are stipulated using cross-correlation analysis of the relationship between the head and heterogeneity. Afterward, data from numerical experiments and field sequential pumping test campaigns reinforce the concept and the definition.


Assuntos
Água Subterrânea , Calibragem , Modelos Teóricos , Tomografia , Tomografia Computadorizada por Raios X
13.
IUBMB Life ; 72(2): 296-304, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31509344

RESUMO

Human adipose-derived stem cells (HASCs) represent pluripotent cells capable of differentiating into the bone tissue. Meanwhile, human amnion-derived mesenchymal stem cells (HAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. This work assessed the osteogenic effects exerted by HAMSCs on the potential of HASCs to form bone cells. Cell growth was evaluated flow-cytometrically. Differentiation into osteoblasts and mineral formation were assessed by chromogenic alkaline phosphatase activity substrate assay and Alizarin red S staining. Adiponectin (APN), the adipocytokine secreted by adipocytes, was evaluated by enzyme-linked immunosorbent assay. In this study, HAMSCs concentration-dependently induced growth, osteoblastic differentiation, and APN excretion in HASCs. Mechanistically, immunofluorescence and immunoblot revealed HAMSCs promoted cytosolic translocation of leucine zipper motif (APPL1) from the nucleus and induced extracellular signaling-regulated kinase 1/2 (ERK1/2) phosphorylation in HASCs. Furthermore, HAMSC effects were markedly blunted by pretreatment with APPL1 siRNA and U0126, an ERK1/2 signaling inhibitor with high selectivity. These results suggested that APN excretion is not suppressed by APPL1 knockdown in HASCs, but by ERK1/2 inhibition. These findings collectively indicate that HAMSCs induce the osteogenesis of HASCs by promoting APN excretion through APPL1-ERK1/2 activation.

14.
Colloids Surf B Biointerfaces ; 185: 110596, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31707226

RESUMO

The rise of graphene has driven great revolution in various fields, e. g. electronics, device, energy, etc., owing to the well-researched understanding of its physical and chemical properties. In the very recent decade, scientists have poured significant efforts to explore the biological functions of graphene and expand its biomedical applications, including drug delivery, tumor therapy, and theranostics. Encouraged by the inspiring research results and promising contributions of graphene to biomedicine field, herein, we systematically summarize the recent advance of graphene for biomedical application. In this review, we introduce the development of graphene in biomedicine, from drug delivery, tumor therapy, to theranostics. We also demonstrate the surface engineering and multifunctional modification of graphene, and further present the active role of rational decoration in drug delivery, therapy, and theranostic application. In detail, we summarize the surface engineering, active-targeting modification, stimuli-responsive decoration, and their application in anticancer drugs delivery, multiple therapeutic approach, dual-model imaging guided therapy. On the basis of the systematic summary, in the final, we further present the development tendency of graphene in biomedicine, aiming to provide some valuable guidelines for further research.

15.
Biomed Pharmacother ; 123: 109745, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31855736

RESUMO

Colorectal cancer (CRC) is a malignant gastrointestinal cancer that seriously threatens human health. Its morbidity and mortality are in the forefront of tumors. Chemotherapy and radiotherapy play an important role in the treatment of CRC, which can improve the survival time and quality of life of patients, but the treatment progress is slow, and the treatment effect is not satisfactory. In recent years, immunotherapy has been a new direction in the field of colorectal cancer treatment after radiotherapy, chemotherapy and targeted therapy. Immune checkpoints play a vital role in the immunotherapy of cancer, and take part in the immune escape of cancer, which is closely related to the occurrence and development of cancer. This article reviews the research progress of immune checkpoints and their blockers in the field of CRC, in order to help better use of the immune system to treat cancer.

16.
Gene ; 730: 144316, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-31884109

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is widely known as the leading cause of death in patients with lung cancer. Extensive evidence has determined that microRNAs (miRNAs) exert critical effects on various biological processes in tumorigenesis. microRNA-147b (miR-147b) has been reported to serve as an oncogenic molecule in colorectal cancer and hepatocellular carcinoma, however, its prognostic value and biological effect in LUAD remain rare. MATERIALS AND METHODS: miR-147b and microfibril-associated glycoprotein 4 (MFAP4) data were collected from The Cancer Genome Atlas (TCGA) database to determine their expression levels in LUAD tissues. Kaplan-Meier method was used to plot the overall survival curves for the prognostic power of miR-147b and MFAP4 identification. Chi-square test was utilized to demonstrate the association between clinical characteristics and miR-147b or MFAP4 in LUAD. Luciferse reporter assay was implemented to identify the correlation between miR-147b and MFAP4. The mRNA and protein levels were detected by qRT-PCR and western blotting, respectively. To explore the effects of miR-147b and its potential mechanism in LUAD, cell counting kit 8 (CCK-8), colony formation and transwell assays were performed in LUAD cells with abnormal expression of miR-147b or/and MFAP4. RESULTS: Our results showed that miR-147b was up-regulated in LUAD tissues and cell lines, which induced poor outcome. Conversely, MFAP4, the putative target gene of miR-147b, was down-regulated in LUAD. The expression of MFAP4 in LUAD cells was negatively regulated by miR-147b. Results of experiments in vitro revealed that miR-147b could promote cell proliferation, colony formation, invasion and migration, while up-regulation of MFAP4 suppressed the impacts of miR-147b on cell malignant aggressiveness in A549 and Calu-3 cells. CONCLUSION: In conclusion, these findings determined that miR-147b contributed to the progression of LUAD via targeting MFAP4. Thus, understanding the potential mechanism of miR-147b/MFAP4 may improve the treatment of cancers, especially LUAD.


Assuntos
Adenocarcinoma de Pulmão/genética , Proteínas de Transporte/genética , Proteínas da Matriz Extracelular/genética , Glicoproteínas/genética , MicroRNAs/genética , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteínas de Transporte/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Bases de Dados Genéticas , Progressão da Doença , Proteínas da Matriz Extracelular/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Glicoproteínas/metabolismo , Humanos , Estimativa de Kaplan-Meier , Pulmão/metabolismo , Neoplasias Pulmonares/genética , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Prognóstico
17.
Front Neurosci ; 13: 1214, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780890

RESUMO

Purpose: To improve the metoprolol therapeutic effectiveness, we aimed to explore whether baseline heart rate variability (HRV) indicators before metoprolol treatment were useful for predicting its efficacy for postural tachycardia syndrome (POTS). Methods: We recruited 45 children with POTS who received metoprolol and 17 healthy controls. All children underwent a standing test or basic head-up tilt test and 24-h dynamic electrocardiography before treatment. After 3 months of metoprolol, therapeutic responsiveness was evaluated. The usefulness of baseline HRV parameters in predicting the effectiveness of metoprolol was studied and the long-term cumulative symptom rate was analyzed. Results: The baseline HRV frequency domain indicators for power, ultra-low frequency, very-low frequency, low frequency (LF), high frequency (HF), and total power (TP) as well as time domain indicators were significantly lower for responders than non-responders to metoprolol; however, low-frequency normalized units and LF/HF ratio were markedly greater for responders than non-responders. On series-parallel analysis, combined baseline triangular (TR) index ≤ 33.7 and standard deviation of all normal-to-normal intervals (SDNN) index ≤ 79.0 ms as cut-off values yielded sensitivity, specificity and accuracy of 85.3, 81.8, and 84.4%, respectively, to predict therapeutic responsiveness to metoprolol. On long-term follow-up, the cumulative symptom rate was significantly higher with TR index > 33.7 and SDNN index ≤ 79.0 ms, TR index ≤ 33.7 and SDNN index > 79.0 ms or TR index > 33.7 and SDNN index > 79.0 ms than TR index ≤ 33.7 and SDNN index ≤ 79.0 ms (P < 0.05). Conclusion: Combined TR index ≤ 33.7 and SDNN index ≤ 79.0 ms were useful preliminary measures to predict therapeutic response to metoprolol in pediatric POTS.

18.
Langmuir ; 35(47): 15275-15286, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31665888

RESUMO

Conventional drug delivery systems for natural clay materials still face critical challenges in their practical application, including multiple bacterial infections, combined infection of bacteria and fungi, and low sterilization efficiency. In this work, we address these challenges using the multifunctional montmorillonite nanosheet-based (MMT-based) drug nanoplatform, which involves the antibiotic 5-fluorocytosine (5-FC), antibacterial metal copper ions, and quaternized chitosan (QCS). Composite material QCS/MMT/5-FCCu can can strongly inhibit Staphylococcus aureus (a typical Gram-positive bacterium), Escherichia coli (a typical Gram-negative bacterium), and Candida albicans (a fungus) because 5-FC coordinates with copper ions in situ and due to the deposition of QCS. The subsequent drug release behavior of 5-FCCu was studied, and the results show an initial high concentration kills microorganisms and long-acting sustained release inhibition. Moreover, in vivo wound experiments and toxicity experiments show the promotion of wound healing and excellent biocompatibility. As a demonstration of the utility of the latter, we have shown that the MMT-based smart platform can be used for the treatment of mixed infections of wounds.

19.
Anal Chem ; 91(23): 15240-15247, 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31692334

RESUMO

Biochemical gradients across the intestinal epithelium play a major role in governing intestinal stem cell compartmentalization, differentiation dynamics, and organ-level self-renewal. However, scalable platforms that recapitulate the architecture and gradients present in vivo are absent. We present a platform in which individually addressable arrays of chemical gradients along the intestinal crypt long axis can be generated, enabling scalable culture of primary in vitro colonic epithelial replicas. The platform utilizes standardized well plate spacing, maintains access to basal and luminal compartments, and relies on a photopatterned porous membrane to act as diffusion windows while supporting the in vitro crypts. Simultaneous fabrication of 3875 crypts over a single membrane was developed. Growth factor gradients were modeled and then experimentally optimized to promote long-term health and self-renewal of the crypts which were assayed in situ by confocal fluorescence microscopy. The cultured in vitro crypt arrays successfully recapitulated the architecture and luminal-to-basal phenotypic polarity observed in vivo. Furthermore, known signaling regulators (e.g., butyrate and DAPT) produced measurable and predictable effects on the organized cell compartments, each decreasing crypt proliferation in the basal regions to negligible values. This platform is readily adaptable to the screening of tissue from individual patients to assay the impact of food and bacterial metabolites and/or drugs on colonic crypt dynamics. Importantly, the cassette is compatible with a wide range of sensing/detection modalities, and the developed fabrication methods should find applications for other cell and tissue types.

20.
Mol Biol Cell ; 30(26): 3104-3111, 2019 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-31693433

RESUMO

Recent studies indicate that adherent cells are keenly sensitive to external physical environment, such as substrate rigidity and topography, and internal physical states, such as cell shape and spreading area. Many of these responses are believed to involve coupled output and input of mechanical forces, which may constitute the key sensing mechanism to generate downstream regulatory signals for cell growth and differentiation. Here, we show that the state of cell migration also plays a regulatory role. Compared with migrating cells, stationary cells generate stronger, less dynamic, and more peripherally localized traction forces. These changes are coupled to reduced focal adhesion turnover and enhanced paxillin phosphorylation. Further, using cells migrating along checkerboard micropatterns, we show that the appearance of new focal adhesions directly in front of existing focal adhesions is associated with the down-regulation of existing focal adhesions and associated traction forces. Together, our results imply a mechanism where cell migration regulates traction forces by promoting dynamic turnover of focal adhesions, which may then regulate processes such as wound healing and embryogenesis where cell differentiation must coordinate with migration state and proper localization.

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