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1.
Artigo em Inglês | MEDLINE | ID: mdl-31932451

RESUMO

Stem cells are capable of sensing and processing environmental inputs, converting this information to output a specific cell lineage through signaling cascades. Despite the combinatorial nature of mechanical, thermal, and biochemical signals, these stimuli have typically been decoupled and applied independently, requiring continuous regulation by controlling units. We employ a programmable polymer actuator sheet to autonomously synchronize thermal and mechanical signals applied to mesenchymal stem cells (MSCs). Using a grid on its underside, the shape change of polymer sheet, as well as cell morphology, calcium (Ca2+) influx, and focal adhesion assembly, could be visualized and quantified. This paper gives compelling evidence that the temperature sensing and mechanosensing of MSCs are interconnected via intracellular Ca2+ Up-regulated Ca2+ levels lead to a remarkable alteration of histone H3K9 acetylation and activation of osteogenic related genes. The interplay of physical, thermal, and biochemical signaling was utilized to accelerate the cell differentiation toward osteogenic lineage. The approach of programmable bioinstructivity provides a fundamental principle for functional biomaterials exhibiting multifaceted stimuli on differentiation programs. Technological impact is expected in the tissue engineering of periosteum for treating bone defects.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31814187

RESUMO

The MCP-1 -2518G/A polymorphism has been reported to be inconsistently associated with systemic lupus erythematosus (SLE)1-4 . To generate large-scale evidence on whether MCP-1 -2518G/A polymorphism is associated with SLE and lupus nephritis (LN) susceptibility. A comprehensive search of the literature was performed in the Medline, EMBASE, CNKI, WanFang, and Cochrane Library databases saved up to June 2018. Two investigators independently assessed the articles for inclusion and consensus was achieved for all data5-10 (see Tables 1 and 2). It is a summary on previous studies and would provide important clues for future studies.

3.
Hortic Res ; 6: 131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814984

RESUMO

Rose (Rosa hybrida) plants are major ornamental species worldwide, and their commercial value greatly depends on their open flowers, as both the quality of fully open petals and long vase life are important. Petal senescence can be started and accelerated by various hormone signals, and ethylene is considered an accelerator of petal senescence in rose. To date, however, the underlying mechanism of signaling crosstalk between ethylene and other hormones such as JA in petal senescence remains largely unknown. Here, we isolated RhMYB108, an R2R3-MYB transcription factor, which is highly expressed in senescing petals as well as in petals treated with exogenous ethylene and JA. Applications of exogenous ethylene and JA markedly accelerated petal senescence, while the process was delayed in response to applications of 1-MCP, an ethylene action inhibitor. In addition, silencing of RhMYB108 alter the expression of SAGs such as RhNAC029, RhNAC053, RhNAC092, RhSAG12, and RhSAG113, and finally block ethylene- and JA-induced petal senescence. Furthermore, RhMYB108 was identified to target the promoters of RhNAC053, RhNAC092, and RhSAG113. Our results reveal a model in which RhMYB108 functions as a receptor of ethylene and JA signals to modulate the onset of petal senescence by targeting and enhancing senescence-associated gene expression.

4.
Onco Targets Ther ; 12: 10299-10309, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31819514

RESUMO

Purpose: High metastasis is a leading risk factor for the survival of non-small cell lung cancer (NSCLC) and epithelial-mesenchymal transition (EMT) is a vital step of metastasis. The expression of novel oncogene with kinase domain (NOK) has been observed in some human malignancies, including non-small cell lung cancer (NSCLC); however, the biological function of NOK in NSCLC remains unclear. In the study, we explored the function of NOK in NSCLC, with an aim to elucidate the relevant underlying mechanisms. Patients and methods: We investigate the expression of NOK, p-Akt, p-GSK-3ß, E-cadherin and N-cadherin expression by immunohistochemical analysis using tissue microarrays of 72 paired NSCLC samples of cancerous and adjacent normal tissues. The associations between NOK expression and clinicopathological factors, overall survival, other proteins were assessed. Immunofluorescence analysis of NSCLC tissues was performed to study the location of NOK, Akt and GSK-3ß. Up or down-regulated of NOK were conducted in two NSCLC cell lines to analyze its impact on AKT/GSK3ß pathway. Results: Statistical analysis revealed NOK expression increased in NSCLC tissues compared with normal tissues (P<0.05). It also showed that low NOK expression were associated with a higher possibility of non-lymphatic metastasis, an early pN stage and clinical stage (P<0.05). Moreover, NOK expression was positively correlated with the expression of oncogene p-Akt (Thr308), p-GSK-3ß (Ser9) and N-cadherin (P<0.05). Immunofluorescence analysis of NSCLC tissues revealed that NOK is co-located with Akt and GSK-3ß. Further study in NSCLC cell lines revealed that NOK overexpression can activate the AKT/GSK3ß pathway. Conversely, knockdown of NOK can suppress the AKT/GSK3ß pathway. Conclusion: Our results suggest that NOK overexpression correlated significantly with lymphatic metastasis, advanced pN and clinical stage in NSCLC. And NOK may promote EMT by activating the AKT/GSK3ß/N-cadherin pathway in NSCLC.

5.
Sci Total Environ ; 709: 136109, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31884272

RESUMO

An unmanned aerial vehicle (UAV) equipped with miniature monitors was used to study the vertical profiles of PM2.5 (particulate matter with a ≤2.5-µm diameter) and black carbon (BC) in Macau, China, from the surface to 500 m above ground level (AGL). Twelve- and 11-day measurements were conducted during February and March 2018, respectively. In total, 46 flights were conducted between 05:00 and 06:00 AM Local Time (LT). The average concentrations of PM2.5 and BC were significantly lower in March (40.1 ± 17.9 and 2.3 ± 2.0 µg m-3, respectively) when easterly winds prevailed, compared with those in February (69.8 ± 35.7 and 3.6 ± 2.0 µg m-3, respectively) when northerly winds dominated. In general, PM2.5 concentrations decreased with height, with a vertical decrement of 0.2 µg m-3 per 10 m. BC concentrations exhibited diverse vertical profiles with an overall vertical decrement of 0.1 µg m-3 per 10 m. Meteorological analyses including back-trajectory analysis and atmospheric stability categorization revealed that both advection and convection transports may have notable influences on the vertical profiles of PM pollutants. The concentration of PM pollutants above the boundary layer was lower than that within the layer, thus exhibiting a sigmoid profile in some cases. In addition, the lighting of firecrackers and fireworks on February 16 (first day of the Chinese New Year) resulted in the elevated concentrations of PM2.5 and BC within 150 m AGL. The takeoff of a civil flight on February 10 may have resulted in a substantial increase in the PM2.5 concentrations from 80.8 (±2.1) µg m-3 at the ground level to 119.2 (±9.3) µg m-3 at a height of 330 m. Although the results are confined to a height of 500 m AGL, the current study provides a useful dataset for PM vertical distributions, complementing the spatiotemporal variations by ground-based measurements.

7.
Biofabrication ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31756727

RESUMO

After surgical resection for bone tumor, the uncleared bone tumor cells can multiply and cause recurrence of bone tumor. It is worthwhile to design a scaffold that kills the remaining bone tumor and repairs bone defects that were given rise to by surgical resection. Additionally, it is extremely important to consider the function of angiogenesis at the process of bone regeneration because the newly-formed blood vessel can offer the nutrients for bone regeneration. In this work, a novel scaffold that is metal-organic framework Cu-TCPP nanosheets interface-structured ß-tricalcium phosphate (TCP) scaffold (Cu-TCPP-TCP) was successfully prepared through integrating 3D printing technique with in situ growth method in a solvothermal system. Owing to the excellent photothermal effect of Cu-TCPP nanosheets, Cu-TCPP-TCP scaffolds that were illuminated by near infrared (NIR) light demonstrated photothermal performance, which was well regulated through varying the contents of Cu-TCPP nanosheets, ambient humidity and power density of NIR light. When cultured with osteosarcoma cells, Cu-TCPP-TCP scaffolds significantly killed osteosarcoma cells through the released heat energy. Similarly, Cu-TCPP-TCP scaffolds ablated the subcutaneous bone tumor tissues at the backs of naked mice and suppressed their growth because of transformed heat energy from NIR light. The in vitro studies found that Cu-TCPP-TCP scaffolds well supported the attachments of both human bone marrow stromal cells (HBMSCs) and human umbilical vein endothelial cells (HUVECs), and significantly stimulated expressions of osteogenesis differentiation-related genes in HBMSCs and angiogenesis differentiation-related genes in HUVECs. After implanting Cu-TCPP-TCP scaffolds into the bone defects of rabbits, they effectively promoted bone regeneration. Thus, the integration of the bone-forming bioactivity of TCP scaffolds with the photothermal property of Cu-TCPP nanosheets and angiogenesis activity of Cu ions awards Cu-TCPP-TCP scaffolds with multifunctions, representing a new horizon to develop biomaterials for simultaneously curing bone tumor and repairing bone defects.

8.
Free Radic Biol Med ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31770582

RESUMO

Corticosteroid insensitivity is a feature of airway inflammation in chronic obstructive pulmonary disease (COPD). Erythromycin exhibits anti-inflammatory activity in COPD, but the concrete mechanism is still unclear. This study aimed to investigate the effects of erythromycin on corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) and U937 cells (a human monocytic cell line). PBMCs were collected from non-smokers, healthy smoker volunteers, and COPD subjects. U937 cells were incubated with or without erythromycin and stimulated with TNF-α in the presence or absence of cigarette smoke extract (CSE). The dexamethasone (Dex) concentration required to achieve 50% inhibition of TNF-α-induced interleukin (IL)-8 production was determined and the mitogen-activated protein kinase (MAPK)/Activator protein-1 (AP-1) pathway was also evaluated. Erythromycin improved corticosteroid sensitivity in PBMCs obtained from COPD patients and CSE-treated U937 cells. This improvement in corticosteroid sensitivity was associated with reduced c-Jun expression, which resulted from the inhibition of P38 Mitogen-activated protein kinase (P38MAPK), extracellular signal-regulated protein kinase (ERK)1/2, and c-Jun N-terminal kinase (JNK) phosphorylation. Erythromycin had no effects on the phosphorylated and total protein expression levels of P38MAPK and ERK; however, it induced inhibition of the phosphorylated and total protein expression levels of JNK. This study provides evidence that erythromycin restores corticosteroid sensitivity in PBMCs and U937 cells. JNK inhibition by erythromycin restores corticosteroid sensitivity via the inhibition of c-Jun expression. Thus, JNK/c-Jun is a potential novel therapeutic target for COPD.

9.
ACS Chem Biol ; 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31742988

RESUMO

Affinity-based protein profiling has proven to be a powerful method in target identification of bioactive molecules. Here, this technology was applied in two photoreactive anticancer inhibitors, arenobufagin and HM30181. Using UV irradiation, these photoreactive reagents can covalently cross-link to target proteins, leading to a covalent binding with target proteins. Moreover, the cellular on/off targets of these two molecules, including ATP1A1, MDR1, PARP1, DDX5, NOP2, RAB6A, and ERGIC1 were first identified by affinity-based protein profiling and bioimaging approaches. The protein hit, PARP1, was further validated to be involved in the function of the anticancer effects.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31743992

RESUMO

Microfibers with a core-shell structure can be produced by co-axial electrospinning, allowing for the functionalization of the outer layer with bioactive molecules. In this study, a thermoplastic, degradable polyesteretherurethane, consisting of poly(p-dioxanone) (PPDO) and poly(ɛ-caprolactone) (PCL) segments with different PPDO to PCL weight ratios, were processed into fiber meshes by co-axial electrospinning with gelatin. The prepared PEEU fibers have a diameter of 1.3±0.5 µm and an elastic modulus of around 5.1±1.0 MPa as measured by tensile testing in a dry state at 37°C, while the PEEU/Gelatin core-shell fibers with a gelatin content of 12±6 wt% and a diameter of 1.5±0.5 µm possess an elastic modulus of 15.0±1.1 MPa in a dry state at 37 °C but as low as 0.7±0.7 MPa when hydrated at 37 °C. Co-axial electrospinning allowed for the homogeneous distribution of the gelatin shell along the whole microfiber. Gelatin with conjugated FITC remained stable on the PEEU fibers after 7 days incubation in PBS at 37 °C. The gelatin coating on PEEU fibers lead to enhanced human adipose tissue derived mesenchymal stem cell (hADSC) attachment and a proliferation rate 81.7±34.1 % higher in cell number in PEEU50/Gelatin fibers after 7 days of cell culture when compared to PEEU fibers without coating. In this work, we demonstrate that water-soluble gelatin can be incorporated as the outer shell of a polymer fiber via molecular entanglement, with a sustained presence and role in enhancing stem cell attachment and proliferation.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31683471

RESUMO

BACKGROUND: The behavior of endothelial cell is remarkably influenced by the physical and biochemical signals from their surrounding microenvironments. OBJECTIVE: Here, the elasticity of fiber meshes was studied as a design parameter of substrates for endothelial cells in order to modulate angiogenesis. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured on electrospun fiber meshes made from polyetheresterurethane (PEEU), differing in their elasticity. Cell morphology, proliferation, migration and angiogenesis of endothelial cells on the degradable substrates meshes were characterized. RESULTS: The aspect ratio of HUVECs cultured on the fiber meshes from PEEU materials increased with increasing stiffness of the materials. HUVECs cultured on fiber meshes with high stiffness (Young's modulus E = 4.5±0.8 MPa) presented a higher proliferation rate and significantly faster migration velocity, as well as higher tube formation capability than the cells cultured on fiber meshes with low stiffness (E = 2.6±0.8 MPa). CONCLUSIONS: These results suggested that tuning the fiber meshes' elasticity might be a potential strategy for modulating of the formation or regeneration of blood vessels.

12.
Environ Sci Technol ; 53(22): 13257-13264, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31589819

RESUMO

Characteristic particle size, fluorescence intensity, and fluorescence spectra are important features to detect and categorize bioaerosols. A prototype size-resolved single-particle fluorescence spectrometer (S2FS) was developed to simultaneously measure aerodynamic diameters and fluorescence spectra. Emission spectra are dispersed in 512 channels from 370 to 610 nm, where a major portion of biological fluorescence emission occurs. The S2FS consists of an aerodynamic particle sizer and a fluorescence spectrometer with a 355 nm laser excitation source and an intensified charge-coupled device as the detector. Highly fluorescent particles, such as Ambrosia artemisiifolia pollen and Olea europaea pollen, can be distinguished by the S2FS on a single-particle level. For weakly fluorescent particles, fluorescence spectra can only be obtained by averaging multiple particles (between 100 and 3000) of the same kind. Preliminary ambient measurements in Mainz (Germany, central Europe) show that an emission peak at ∼440 nm was frequently observed for fluorescent fine particles (0.5-1 µm). Fluorescent fine particles accounted for 2.8% on average based on the number fraction in the fine mode. Fluorescent coarse particles (>1 µm) accounted for 8.9% on average based on the number fraction, with strongest occurrence observed during a thunderstorm and in the morning.


Assuntos
Laboratórios , Aerossóis , Europa (Continente) , Alemanha , Tamanho da Partícula , Espectrometria de Fluorescência
13.
Artigo em Inglês | MEDLINE | ID: mdl-31609494

RESUMO

BACKGROUND AND AIM: We aim to investigate the risk factors of de novo hepatitis B virus (HBV) infection in pediatric liver transplantation recipients receiving hepatitis B core antibody positive grafts and to evaluate the efficacy of our prophylactic strategies. METHODS: One hundred thirty-nine pediatric recipients receiving hepatitis B core antibody positive grafts operated from September 2016 to September 2018 were retrospectively enrolled, and all the patients received prophylactic treatment to prevent de novo HBV infection. Donor and recipient features, operative information along with graft, and recipient outcomes were compared between recipients with or without de novo HBV infection. Univariate and multivariate analyses were applied to identify the risk factors of de novo HBV infection. RESULTS: The mean follow-up time was 23.5 ± 15.7 months, and the overall incidence of de novo HBV infection was 3.6%. Recipients with de novo HBV infection showed equal graft and recipient outcome compared with the recipients without de novo HBV infection during the follow-up time. Recipient preoperative hepatitis B surface antibody titer of < 1000 IU/L (odds ratio [OR] = 9.652, P = 0.024), graft HBV DNA of > 1000 copies (OR = 9.050, P = 0.032), and intraoperative fresh-frozen plasma transfusion of > 400 mL (OR = 10.462, P = 0.023) were identified as independent risk factors for de novo HBV infection. CONCLUSION: Hepatitis B core antibody positive grafts can safely be used in pediatric liver transplantation under rational prophylactic therapy.

14.
Biochem Biophys Res Commun ; 520(1): 211-217, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31587872

RESUMO

NQDI-1, an inhibitor of ASK1, has been reported to have protective effects in several experimental human disease models. However, the role of NQDI-1 in acute pancreatitis (AP) has not been reported. In this study, we found that NQDI-1 could attenuate histological damage of pancreatic tissue as well as the levels of serum amylase and lipase in a mouse model of AP induced by caerulein. Moreover, the production of reactive oxygen species (ROS) and the expression of necrosis-related proteins (RIP3 and p-MLKL) were also reduced after NQDI-1 administration. Correspondingly, we elucidated the effect of NQDI-1 in vitro and found that NQDI-1 protected against pancreatic acinar cells necrosis via decreasing the ROS production and RIP3 and p-MLKL expression. In addition, we identified the protective effect of NQDI-1 on AP through two other mouse models induced by l-arginine and pancreatic duct ligation. Taken together, these findings showed that NQDI-1 could reduce the acinar cells necrosis and alleviate the severity of AP, which may afford a new therapeutic target on pancreatic necrosis in AP clinically.

15.
Am J Transplant ; 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31597001

RESUMO

The experience of using pediatric donors in split liver transplant is exceedingly rare. We aim to investigate the outcomes of recipients receiving split pediatric grafts. Sixteen pediatric recipients receiving split liver grafts from 8 pediatric donors < 7 years were enrolled. The donor and recipient characteristics, perioperative course, postoperative complications, and graft and recipient survival rates were evaluated. The mean follow-up time was 8.0 ± 2.3 months. The graft and recipient survival rates were 100%. The liver function remained in the normal range at the end of the follow-up time in all recipients. No life-threatening complications were seen in these recipients, and the only surgery-related complication was portal vein stenosis in 1 recipient. Cytomegalovirus infection was the most common complication (62.5%). The transaminase level was significant higher in extended right lobe recipients in the early postoperative days, but the difference vanished at the end of first week; postoperative complications and graft and recipient survival rates did not differ between left and right graft recipients. Notably, the youngest split donor graft (2.7 years old) was associated with ideal recipient outcomes. Split liver transplant using well-selected pediatric donors is a promising strategy to expand pediatric donor source in well-matched recipients.

16.
Invest Ophthalmol Vis Sci ; 60(13): 4503-4510, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31661551

RESUMO

Purpose: MicroRNA-34a (miR-34a) has been implicated in many biological processes. It is downregulated in uveal melanoma, and introduction of miR-34a inhibits the proliferation and migration of uveal melanoma cells. Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4) is a novel target of miR-34a identified first in retinal pigment epithelial cells. In this study, we sought to evaluate the interaction of miR-34a and LGR4 in uveal melanoma and its downstream mechanisms. Methods: The expression of LGR4, epithelial-mesenchymal transition (EMT)-associated factors, and matrix metalloproteinase 2 (MMP2) in uveal melanoma cells was assessed by immunoblotting and immunofluorescence analysis. MicroRNA-34a mimic molecules, LGR4 small interfering RNA (siRNA), or MMP2-specific siRNA were transiently transfected into uveal melanoma cells. In vitro scratch and Transwell assays were used to evaluate the migratory and invasive potential of the resultant uveal melanoma cells. Results: LGR4 is upregulated in uveal melanoma cells. Introduction of miR-34a significantly decreased the expression level of LGR4. Transfection with miR-34a or knockdown of LGR4 attenuated the aggressiveness of uveal melanoma cells. In addition, there was a decrease in the expression of mesenchymal markers N-cadherin, vimentin, and Snail following miR-34a introduction or knockdown of LGR4. Finally, MMP2 was found to be a downstream effector for miR-34a and LGR4 that regulates the migration and invasion of uveal melanoma cells. Conclusions: MicroRNA-34a negatively controls LGR4, thereby inhibiting the migration and invasion of uveal melanoma cells. Ultimately, both miR-34a and LGR4 impact the aggressiveness of uveal melanoma with alterations in the markers of the EMT. MMP2 is a downstream effector that influences the metastasis seen with uveal melanoma cells.

17.
Sheng Wu Gong Cheng Xue Bao ; 35(9): 1686-1697, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31559750

RESUMO

Translationally controlled tumor proteins (TCTP) and SNF1- related protein kinase (SnRK1) are conserved and widely present in eukaryotic cells. TCTP regulates cell division, plant growth and development, and mediates plant resistance against pathogen infection. SnRK1 participates in a range of physiological processes including sugar metabolism and resistance to abiotic and biotic stresses. Previous work in our laboratory demonstrated that wheat TCTP can respond to Puccinia triticina infection and induce host defense responses. In order to further investigate the mechanism of TaTCTP in wheat resistance to Puccinia triticina infection, we used TAP (tandem affinity purification) and mass spectrometry to screen the potential interactants of TaTCTP. A SNF1- related protein kinase (SnRK1) was identified as a potential interacting protein of TaTCTP. The results of yeast two-hybrid assay showed that TCTP could interact with SnRK1 in yeast, and the yeast carrying TCTP and SnRK1 could grow on SD/-Leu/-Trp/-His/-Ade (SD/-LWHA) medium. The fluorescence signal of the interaction between TCTP and SnRK1 was found to be distributed in the cytoplasm in the Bi-fluorescense complementation experiment. Co-IP experiments further showed that TCTP and SnRK1 could interact in plant cells. This study lays an important foundation for further studying the mechanism of TaTCTP in the interaction between wheat and Puccinia triticina, and it play a great influence on further improving the molecular mechanism of wheat resistant to Puccinia triticina.


Assuntos
Basidiomycota , Triticum , Humanos , Neoplasias , Biossíntese de Proteínas , Proteínas Serina-Treonina Quinases
18.
Clin Hemorheol Microcirc ; 73(1): 229-236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31561331

RESUMO

The mechanical properties of electrospun fiber meshes typically are measured by tensile testing at the macro-scale without precisely addressing the spatial scale of living cells and their submicron architecture. Atomic force microscopy (AFM) enables the examination of the nano- and micro-mechanical properties of the fibers with potential to correlate the structural mechanical properties across length scales with composition and functional behavior. In this study, a polyesteretherurethane (PEEU) polymer containing poly(p-dioxanone) (PPDO) and poly(ɛ-caprolactone) (PCL) segments was electrospun into fiber meshes or suspended single fibers. We employed AFM three point bending testing and AFM force mapping to measure the elastic modulus and stiffness of individual micro/nanofibers and the fiber mesh. The local stiffness of the fiber mesh including the randomized, intersecting structure was also examined for each individual fiber. Force mapping results with a set point of 50 nN demonstrated the dependence of the elasticity of a single fiber on the fiber mesh architecture. The non-homogeneous stiffness along the same fiber was attributed to the intersecting structure of the supporting mesh morphology. The same fiber measured at a point with and without axial fiber support showed a remarkable difference in stiffness, ranging from 0.2 to 10 nN/nm respectively. For the region, where supporting fibers densely intersected, the stiffness was found to be considerably higher. In the region where the degrees of freedom of the fibers was not restricted, allowing greater displacement, the stiffness were observed to be lower. This study elucidates the relationship between architecture and the mechanical properties of a micro/nanofiber mesh. By providing a greater understanding of the role of spatial arrangement and organization on the surface mechanical properties of such materials, we hope to provide insight into the design of microenvironments capable of regulating cell functionality.

19.
Clin Hemorheol Microcirc ; 73(1): 237-247, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31561334

RESUMO

Laminin-5 (Ln-5), an important extracellular matrix (ECM) protein, plays a critical role in regulating the growth and differentiation of mesodermal tissues, including bone. Ln-5 can be secreted by the mesenchymal stem cells (MSCs), and Ln-5 promotes MSCs osteogenic differentiation. It has been demonstrated that a substrate's surface topography could regulate MSC secretion and differentiation. A better understanding of the mechanism of how Ln-5 and surface roughness regulate MSC osteogenic differentiation would guide the design of surface topography and coatings of orthopedic implants and cell culture substrates. However, few studies have investigated the relationship between surface roughness and the secretion of Ln-5 in MSC osteogenic differentiation. Whether substrate surface topography regulates MSC differentiation via regulating Ln-5 secretion and how surface topography contributes to the secretion of Ln-5 are still not known. In this study, the influence of microscale roughness at different levels (R0, R1 and R2) on the secretion of Ln-5 of human bone marrow MSCs (hBMSCs) and subsequent osteogenic differentiation were examined. hBMSCs spreading, distribution and morphology were greatly affected by different roughness levels. A significantly higher level of Ln-5 secretion was detected on R2, which correlated to the local cell density regulated by the rough surface. Ln-5 binding integrins (α2 and α3) were strongly activated on R2. In addition, the results from hBMSCs on R0 inserts with different cell densities further confirmed that local cell density regulated Ln-5 secretion and cell surface integrin activation. In addition, the mineralization level of MSCs on R2 was remarkably higher than that on R0 and R1. These results suggest that hBMSC osteogenic differentiation level on R2 roughness was enhanced via increased Ln-5 secretion that was attributed to rough surface regulated local cell density. Thus, the microroughness could serve as effective topographical stimulus in cell culture devices and bone implant materials.

20.
Clin Hemorheol Microcirc ; 73(1): 219-228, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31561335

RESUMO

Electrospinning has attracted significant attention as a method to produce cell culture substrates whose fibrous structure mimics the native extracellular matrix (ECM). In this study, the influence of E-modulus of fibrous substrates on the lineage commitment of human adipose-derived stem cells (hADSCs) was studied using fiber meshes prepared via the electrospinning of a polyetheresterurethane (PEEU) consisting of poly(ρ-dioxanone) (PPDO) and poly(ɛ-caprolactone) (PCL) segments. The PPDO: PCL weight ratio was varied from 40:60 to 70:30 to adjust the physiochemical properties of the PEEU fibers. The cells attached on stiffer PEEU70 (PPDO:PCL,= 70:30) fiber meshes displayed an elongated morphology compared to those cultured on softer fibers. The nuclear aspect ratio (width vs. length of a nucleus) of hADSCs cultured on softer PEEU40 (PPDO:PCL = 40:60) fibers was lower than on stiffer fibers. The osteogenic differentiation of hADSCs was enhanced by culturing on stiffer fibers. Compared to PEEU40, a 73% increase of osteocalcin expression and a 34% enhancement of alkaline phosphatase (ALP) activity was observed in cells on PEEU70. These results demonstrated that the differentiation commitment of stem cells could be regulated via tailoring the mechanical properties of electrospun fibers.

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