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1.
Soft Matter ; 17(6): 1566-1573, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33346314

RESUMO

Microgel-reinforced (MR) hydrogels are tough hydrogels with dispersed rigid microgels embedded in a continuous soft matrix. MR gels have the great potential to provide not only mechanical toughness but also the desired functional matrix by incorporation of various functional microgels. Understanding the toughening mechanism of the MR hydrogels is critical for the rational design of the desired functionally tough MR gels. However, our current knowledge of the toughening mechanism of MR gels mainly comes from the MR hydrogels with both chemically crosslinked dispersed microgels and a continuous matrix. Little is known about the hybrid MR gels with physically crosslinked microgels embedded in a chemically crosslinked matrix. Herein, we synthesize such hybrid MR hydrogels with the ionic crosslinked calcium alginate microgels incorporated into the chemically crosslinked polyacrylamide (PAAm) matrix. The alginate microgels show strong size and modulus effects on the toughening enhancement: the larger microgels could toughen the MR gels more than the small ones, and the microgels with medium modulus could maximize the toughness of the MR gels. By comparison of the mechanical performances of the MR and the corresponding double network (DN) hydrogels, we have proposed that the hybrid MR gels may have the same toughening mechanism as the bulk DN gel. This work tries to better understand the structure-property relationships of both MR and DN gels and help in the design of more functionally tough MR gels with the desired properties.

2.
Dig Liver Dis ; 2020 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-33376073

RESUMO

BACKGROUND: Anti-tumour necrosis factor (TNF)-α drugs are used by increasing numbers of reproductive-age women. Although the neonatal outcomes have been described, there are concerns regarding the risk of infection in offspring following exposure to anti-TNF-α. METHODS: A literature search was conducted using Pubmed, EMBASE, and the Cochrane Database, from inception through August 2020. We evaluated the risk of infection in autoimmune disease (AID) offspring unexposed to anti-TNF-α compared to AID offspring exposed to anti-TNF-α, as well as to unexposed non-AID offspring. RESULTS: Our primary analysis showed that both AID offspring unexposed to anti-TNF-α [risk ratio (RR) 1.09; 95% confidence interval (CI), 1.03-1.16; I2=0%] and AID offspring exposed to anti-TNF-α (RR 1.39; 95% CI, 1.2-1.61; I2=0%] was associated with an increased risk of infection during the first year of life compared with the unexposed non-AID offspring. However, our secondary analysis demonstrated that AID offspring exposed to anti-TNF-α was not associated with an increased risk of infection when compared with AID offspring unexposed to anti-TNF-α (RR=1.1; 95% CI, 0.86-1.4). CONCLUSION: Our results suggest that in utero exposure to anti-TNF-α does not appear to increase the risk of infection during the first year of life in the offspring; however, AID itself was associated with a marked excess risk of infection in the children.

3.
Chem Commun (Camb) ; 56(89): 13731-13747, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33094746

RESUMO

Recently, numerous research studies have contributed to engineering hydrogels by soaking strategies to obtain designed properties, from mechanical strengthening to environmentally adapting. Hydrogels are three-dimensional hydrophilic polymer networks dispersed in water with widespread applications. However, most of the traditional hydrogels possess limited mechanical strength and poor temperature and environmental tolerance, which limits their applications. Due to their unique water-rich property, the physical and chemical properties of hydrogels can be post-engineered by facile soaking strategies. The soaking strategies can be divided into two categories: the first involves soaking salt solutions into the aqueous phase of the gel, and the second involves soaking in organic solvents to displace the water in the gel, forming organohydrogels. In this feature article, we aim to summarize the most recent progress in designing and engineering hydrogels using soaking strategies, including strengthening hydrogels with superior mechanical properties, and providing the hydrogels with environmentally adapting properties, such as anti-freezing and anti-dehydration. The first section summarizes some common design principles and fabrication methods to strengthen hydrogels by soaking, and then it introduces some successful applications of these soaking-induced tough hydrogels. In the second section, the soaking strategy to engineer hydrogels with environmentally adapting properties is discussed. In the end, a brief outlook is proposed based on current challenges and the pros and cons of the soaking strategy.

4.
Biosens Bioelectron ; 170: 112662, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33032198

RESUMO

Cancer cell enumeration and phenotyping can predict the prognosis and the therapy efficacy in patients, yet it remains challenging to detect the rare tumor cells. Herein, we report an octopus-inspired, bifunctional aptamer signal amplifier-based cytosensor (OApt-cytosensor) for sensitive cell analysis. By assembling high-affinity antibodies on an electrode surface, the target cells could be specifically captured and thus been sandwiched by the cell surface marker-specific DNA aptamers. These on-cell aptamers function as electrochemical signal amplifiers by base-selective electronic doping with methylene blue. Such a sandwich configuration enables highly sensitive cell detection down to 10 cells/mL (equal to ~1-2 cells at a sampling volume of 150 µL), even in a large excess of nontarget blood cells. This approach also reveals the cell-surface markers and tracks the cellular epithelial-to-mesenchymal transition induced by signaling regulators. Furthermore, the electron-doped aptamer shows remarkable cell fluorescent labeling that guides the release of the captured cells from electrode surface via electrochemistry. These features make OApt-cytosensor a promising tool in revealing the heterogeneous cancer cells and anticancer drug screening at the single-cell level.

5.
Int J Hyperthermia ; 37(1): 1159-1173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33003967

RESUMO

PURPOSE: To characterize temperature fields and tissue damage profiles of large-volume hyperthermia (HT) induced by magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU) in deep and superficial targets in vivo in a porcine model. METHODS: Nineteen HT sessions were performed in vivo with a commercial MRgHIFU system (Sonalleve® V2, Profound Medical Inc., Mississauga, ON, Canada) in hind leg muscles of eight pigs with temperature fields of cross-sectional diameter of 58-mm. Temperature statistics evaluated in the target region-of-interest (tROI) included accuracy, temporal variation, and uniformity. The impact of the number and location of imaging planes for feedback-based temperature control were investigated. Temperature fields were characterized by time-in-range (TIR, the duration each voxel stays within 40-45 °C) maps. Tissue damage was characterized by contrast-enhanced MRI, and macroscopic and histopathological analysis. The performance of the Sonalleve® system was benchmarked against a commercial phantom. RESULTS: Across all HT sessions, the mean difference between the average temperature (Tavg) and the desired temperature was -0.4 ± 0.5 °C; the standard deviation of temperature 1.2 ± 0.2 °C; the temporal variation of Tavg for 30-min HT was 0.6 ± 0.2 °C, and the temperature uniformity was 1.5 ± 0.2 °C. A difference of 2.2-cm (in pig) and 1.5-cm (in phantom) in TIR dimensions was observed when applying feedback-based plane(s) at different locations. Histopathology showed 62.5% of examined HT sessions presenting myofiber degeneration/necrosis within the target volume. CONCLUSION: Large-volume MRgHIFU-mediated HT was successfully implemented and characterized in a porcine model in deep and superficial targets in vivo with heating distributions modifiable by user-definable parameters.

6.
J Invest Surg ; : 1-6, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32865062

RESUMO

OBJECTIVE: To compare the efficacy and safety of iodine-125 seed interstitial brachytherapy and local chemotherapy perfusion in treatment of advanced pancreatic cancer. METHODS: The present open prospective randomized control study included a total of 165 cases of advanced pancreatic cancer patients who were admitted in our hospital during December 2016 to April 2019. All patients were randomized into two groups with 84 cases in iodine-125 group and 81 cases in chemotherapy perfusion group. Basic clinical characteristics and demographic data were collected. The main outcome was the tumor efficiency. The pain condition was measured by visual analogue scale (VAS) and the Karnofsky score was also measured at different time points, before the treatment, 1 d, 7 d, 14 d, 1 mon, 2 mon and 3 mon after treatment. Serum levels of CEA, CA19-9 and CA50 were measured by immunochemiluminescence. The overall survival was analyzed by K-M curve. RESULTS: The ratio of partial remission patients was significantly higher, and the ratio of stable disease (SD)+progressive disease patients was also remarkably lower in iodine-125 group than the chemotherapy perfusion group. The mean VAS scores decreased markedly after treatment and were significantly lower and the mean Karnofsky scores were remarkably higher in iodine-125 group than the chemotherapy perfusion group. The levels of CA19-9 and CA50 were remarkably lower in iodine-125 group, however no significant difference was found for CEA. The survival analysis by K-M curve showed the iodine-125 patients had longer overall survival time than the chemotherapy perfusion group. No infection, pancreatic fistula, biliary fistula, intestinal fistula, gastrointestinal obstruction or radiation enteritis was found in both groups. CONCLUSION: Iodine-125 seed interstitial brachytherapy could achieve better efficacy with no increased side complications than chemotherapy perfusion in advanced pancreatic cancer.

7.
ACS Appl Mater Interfaces ; 12(36): 40891-40900, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32805806

RESUMO

Gallium-based liquid metals (GLMs) exist as atypical liquid-phase metals at and near room temperature while being electrically and thermally conductive, enabling copious applications in soft electronics and thermal management systems. Yet, solid metals are affected by interfacing with GLMs, resulting in liquid metal embrittlement and device failure. To avert this issue, mechanically durable and electrically tunable diffusion barriers for long-term reliable liquid metal-solid metal interfacing based on the deposition of various diamond coatings are designed and synthesized, as they feature high chemical inertness and extraordinary mechanical resistance. The diamond coatings show superlyophobicity (GLM contact angle ≥ 155°) and are nonstick toward GLMs, thereby achieving high mobility of GLM droplets (sliding angle 8-12°). The excellent barrier and anti-adhesion performance of the diamond coatings are proven in long-term experiments (3 weeks) of coated titanium alloy (Ti) samples in contact with GLMs. The electrical performance of the conductive diamond coating deposited on Ti is reliable and stable over a period of 50 h. As proof-of-concept applications a switch and a thermal management device based on liquid metals are demonstrated, signifying that coating diamond films on metals is a potent means to achieve stable integration of solid metals with GLMs.

8.
PLoS One ; 15(6): e0234182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492056

RESUMO

The development of noninvasive approaches for brain tumor diagnosis and monitoring continues to be a major medical challenge. Although blood-based liquid biopsy has received considerable attention in various cancers, limited progress has been made for brain tumors, at least partly due to the hindrance of tumor biomarker release into the peripheral circulation by the blood-brain barrier. Focused ultrasound (FUS) combined with microbubbles induced BBB disruption has been established as a promising technique for noninvasive and localized brain drug delivery. Building on this established technique, we propose to develop FUS-enabled liquid biopsy technique (FUS-LBx) to enhance the release of brain tumor biomarkers (e.g., DNA, RNA, and proteins) into the circulation. The objective of this study was to demonstrate that FUS-LBx could sufficiently increase plasma levels of brain tumor biomarkers without causing hemorrhage in the brain. Mice with orthotopic implantation of enhanced green fluorescent protein (eGFP)-transfected murine glioma cells were treated using magnetic resonance (MR)-guided FUS system in the presence of systemically injected microbubbles at three peak negative pressure levels (0.59, 1.29, and 1.58 MPa). Plasma eGFP mRNA levels were quantified with the quantitative polymerase chain reaction (qPCR). Contrast-enhanced MR images were acquired before and after the FUS sonication. FUS at 0.59 MPa resulted in an increased plasma eGFP mRNA level, comparable to those at higher acoustic pressures (1.29 MPa and 1.58 MPa). Microhemorrhage density associated with FUS at 0.59 MPa was significantly lower than that at higher acoustic pressures and not significantly different from the control group. MRI analysis revealed that post-sonication intratumoral and peritumoral hyperenhancement had strong correlations with the level of FUS-induced biomarker release and the extent of hemorrhage. This study suggests that FUS-LBx could be a safe and effective brain-tumor biomarker release technique, and MRI could be used to develop image-guided FUS-LBx.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/metabolismo , Glioblastoma/metabolismo , Ultrassonografia de Intervenção/métodos , Animais , Biomarcadores Tumorais/sangue , Barreira Hematoencefálica , Neoplasias Encefálicas/diagnóstico por imagem , Linhagem Celular Tumoral , Meios de Contraste , Feminino , Glioblastoma/diagnóstico por imagem , Proteínas de Fluorescência Verde/sangue , Proteínas de Fluorescência Verde/genética , Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/patologia , Biópsia Líquida/métodos , Imagem por Ressonância Magnética , Camundongos , Ultrassonografia de Intervenção/efeitos adversos
9.
Cancer Cell Int ; 20: 158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425693

RESUMO

[This corrects the article DOI: 10.1186/s12935-019-1087-4.].

10.
Sci Rep ; 10(1): 7449, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366915

RESUMO

Although blood-based liquid biopsy is a promising noninvasive technique to acquire a comprehensive molecular tumor profile by detecting cancer-specific biomarkers (e.g. DNA, RNA, and proteins), there has been limited progress for brain tumor application partially because the low permeability of the blood-brain barrier (BBB) hinders the release of tumor biomarkers. We previously demonstrated focused ultrasound-enabled liquid biopsy (FUS-LBx) that uses FUS to increase BBB permeability in murine glioblastoma models and thus enhance the release of tumor-specific biomarkers into the bloodstream. The objective of this study was to evaluate the feasibility and safety of FUS-LBx in the normal brain tissue of a porcine model. Increased BBB permeability was confirmed by the significant increase (p = 0.0053) in Ktrans (the transfer coefficient from blood to brain extravascular extracellular space) when comparing the FUS-sonicated brain area with the contralateral non-sonicated area. Meanwhile, there was a significant increase in the blood concentrations of glial fibrillary acidic protein (GFAP, p = 0.0074) and myelin basic protein (MBP, p = 0.0039) after FUS sonication as compared with before FUS. There was no detectable tissue damage by T2*-weighted MRI and histological analysis. Findings from this study suggest that FUS-LBx is a promising technique for noninvasive and localized diagnosis of the molecular profiles of brain diseases with the potential to translate to the clinic.

11.
Materials (Basel) ; 13(10)2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32429161

RESUMO

The liquid metal lyophobicity of a rough substrate was, in previous articles, found to be rather independent on the surface wettability. In this article, we scrutinize the impact of surface wettability of a structured (rough) surface on the liquid metal wettability and adhesion. As a model system, a structured diamond coating was synthesized and modified by air plasma. We show that surface wettability (surface free energy) does not play a prominent role for static contact angle measurements and for the liquid metal repelling properties of the diamond coating in droplet impact experiments. In contrast, roll off angles and repeated deposition experiments illustrate that the increased hydrophilicity impacts the long-term liquid metal repellency of our coating. Liquid metal adhered after around 50 deposition/removal cycles on the hydrophilic diamond coating, while no liquid metal adhesion was visible after 100 cycles on the hydrophobic diamond coating, illustrating the fundamental role for the adhesion of liquid metal. The effect of repeated deposition in conjunction with gentle applied force was employed for coating the liquid metal lyophobic (hydrophilic) diamond coating with a thin liquid metal layer. The observed effect may find application in flexible electronics and thermal management systems as a means to improve interfacing of the liquid metal with conductive non-metal coatings.

12.
Hum Cell ; 33(3): 819-829, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32300960

RESUMO

Melanoma is a common skin cancer and it can lead to high mortality probably by early invasion and metastasis. LncRNA MIAT is involved in tumor proliferation, invasion and epithelial-to-mesenchymal transition (EMT). However, the roles of MIAT in melanoma still require further investigation. Thus, the aim of the study is to investigate the roles of MIAT in melanoma, especially the effects of MIAT on EMT of melanoma cancer cells. The results showed that the expression of MIAT was significantly upregulated in melanoma tissue and cells compared with the normal skin and normal melanocytes; moreover, miR-150 was confirmed as a target of MIAT. Furthermore, knockdown of MIAT inhibited cell proliferation and invasion in melanoma cancer cells and transfection of miR-150 inhibitors partial abrogated the anti-tumor effects of MIAT siRNA. In addition, MIAT siRNA also inhibited the EMT of melanoma cells, while miR-150 inhibitors can reverse the effects of MIAT siRNA. Finally, knockdown of MIAT also inhibited the carcinogenic effects of melanoma in vivo by targeting miR-150. In conclusion, we reported that MIAT promotes the proliferation, invasion and EMT of melanoma cells via targeting miR-150, which suggested that MIAT might be a therapeutic target for the treatment of melanoma.


Assuntos
Melanoma/genética , Melanoma/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/fisiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Humanos , Melanoma/terapia , Terapia de Alvo Molecular , Invasividade Neoplásica/genética , Neoplasias Cutâneas/terapia
13.
J Aerosol Med Pulm Drug Deliv ; 33(4): 194-204, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32176552

RESUMO

Background: Acute lung injury is a severe respiratory disorder characterized by overwhelming lung inflammation. Dipalmitoylphosphatidylcholine (DPPC) is the major lipid component of pulmonary surfactant, which here acts as a carrier delivery system for drugs, while also preserving surface tension in the lung. The clinical development of naringenin (NG) is limited by its low solubility and bioavailability. Methods: Novel NG-loaded DPPC phytosomes for dry powder inhalation (NPDPIs) were prepared by solvent evaporation and a freeze-drying method. The particle size, electric potential, in vitro release, and lung deposition were characterized. A rat model of acute lung injury was established and used for pharmacodynamic evaluations. Results: A mixture of NG/DPPC 1:2 (w/w) formed stable phytosomes with the addition of appropriate ethanol. The phytosomes had high complexation efficiency (92.1% ± 1.87%) with NG, a small mean size (150.8 ± 6.9 nm), and a high zeta potential (20.97 ± 0.55 mV). NPDPIs composed of mannitol/DPPC/NG (4:2:1, w/w/w) presented a satisfactory appearance, good fluidity, quick reconstitution to naringenin phytosomes (NGPs), and small (167.2 nm) reconstituted NGPs. The aerodynamic diameter (12.48 µm) and fine particle fraction (23.90%) were suitable for pulmonary delivery by inhalation. The in vivo NPDPIs demonstrated efficacy in a rat model of acute lung injury. NPDPIs significantly inhibited the phosphorylation of P38 in the mitogen-activated protein kinase pathway and suppressed oxidative stress. Surprisingly, the DPPC vehicle exhibited potential effects against acute lung injury by protecting respiratory function. Conclusions: NPDPIs were developed for sustained drug release, promoting pulmonary bioavailability of drug and protecting against acid-induced acute lung injury in rats by pulmonary delivery. NPDPIs are a promising dry powder inhaler for clinical application in acute lung injury.

14.
Emerg Microbes Infect ; 9(1): 332-340, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32037983

RESUMO

The seroprevalenc of autoimmune hepatitis (AIH)-related antibodies in patients, particularly Asians, with acute hepatitis E (AHE) is unclear. In this study, we investigated whether acute hepatitis E virus (HEV) infection is associated with the seroprevalence of AIH-related autoantibodies and assessed their impact on the disease characteristics. AIH-related autoantibodies were detected by indirect immunofluorescence in 198 AHE patients and 50 type 1 AIH patients. The positivity rates of against nuclear antigen (ANA) and smooth muscles antibody (SMA) in AHE patients were 37.4% and 22.7%, and the total positivity rate was 50%. Compared to those in AIH patients, the positivity rates of ANA-H and SMA-AA were significantly lower (35.1% vs. 82.1% and 4.4% vs. 88.4%). Female gender and the ALT level, but not immunosuppressive or antiviral drugs, were independently predictive of the presence of AIH-related autoantibodies in AHE patients. Fifty-two patients positive for AIH-related autoantibodies were followed up for 12 months. During this period, 33 of them became negative and 19 remained positive, albeit with significantly decreased titres. In conclusions, the seroprevalence of AIH-related autoantibodies in AHE patients was elevated, particularly in females, but their subspecificities and titres differed from those of type 1 AIH. Acute HEV infection may be related to AIH.Abbreviations: AIH: autoimmune hepatitis; AHE: acute hepatitis E; ANA: against nuclear antigen; SMA: smooth muscles antibody; ANA-H: ANA with homogeneous pattern; SMA-AA: SMA with anti-actin pattern; Anti-LKM1: anti- liver-kidney microsomes-1 antibody; ANCA: anti-neutrophil cytoplasmic antibody; AMA: anti-mitochondrial antibody; Anti-SLA: anti-soluble liver antigen; Anti-LC1: anti-liver cytoplasmic type 1 antibody; pANCA: perinuclear antineutrophil cytoplasmic antibody.


Assuntos
Autoanticorpos/sangue , Hepatite E/sangue , Hepatite Autoimune/sangue , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China , Feminino , Hepatite E/imunologia , Hepatite Autoimune/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Soroepidemiológicos
15.
Microb Cell Fact ; 19(1): 46, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093713

RESUMO

BACKGROUND: Escherichia coli is an important strain for L-threonine production. Genetic switch is a ubiquitous regulatory tool for gene expression in prokaryotic cells. To sense and regulate intracellular or extracellular chemicals, bacteria evolve a variety of transcription factors. The key enzymes required for L-threonine biosynthesis in E. coli are encoded by the thr operon. The thr operon could coordinate expression of these genes when L-threonine is in short supply in the cell. RESULTS: The thrL leader regulatory elements were applied to regulate the expression of genes iclR, arcA, cpxR, gadE, fadR and pykF, while the threonine-activating promoters PcysH, PcysJ and PcysD were applied to regulate the expression of gene aspC, resulting in the increase of L-threonine production in an L-threonine producing E. coli strain TWF001. Firstly, different parts of the regulator thrL were inserted in the iclR regulator region in TWF001, and the best resulting strain TWF063 produced 16.34 g L-threonine from 40 g glucose after 30 h cultivation. Secondly, the gene aspC following different threonine-activating promoters was inserted into the chromosome of TWF063, and the best resulting strain TWF066 produced 17.56 g L-threonine from 40 g glucose after 30 h cultivation. Thirdly, the effect of expression regulation of arcA, cpxR, gadE, pykF and fadR was individually investigated on L-threonine production in TWF001. Finally, using TWF066 as the starting strain, the expression of genes arcA, cpxR, gadE, pykF and fadR was regulated individually or in combination to obtain the best strain for L-threonine production. The resulting strain TWF083, in which the expression of seven genes (iclR, aspC, arcA, cpxR, gadE, pykF, fadR and aspC) was regulated, produced 18.76 g L-threonine from 30 g glucose, 26.50 g L-threonine from 40 g glucose, or 26.93 g L-threonine from 50 g glucose after 30 h cultivation. In 48 h fed-batch fermentation, TWF083 could produce 116.62 g/L L-threonine with a yield of 0.486 g/g glucose and productivity of 2.43 g/L/h. CONCLUSION: The genetic engineering through the expression regulation of key genes is a better strategy than simple deletion of these genes to improve L-threonine production in E. coli. This strategy has little effect on the intracellular metabolism in the early stage of the growth but could increase L-threonine biosynthesis in the late stage.


Assuntos
Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Treonina/biossíntese , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Fermentação , Genes Bacterianos , Engenharia Genética , Microbiologia Industrial , Microrganismos Geneticamente Modificados/genética , Microrganismos Geneticamente Modificados/metabolismo
16.
Stem Cell Res Ther ; 11(1): 26, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941556

RESUMO

BACKGROUND: Vitiligo is an acquired chronic and recurrent skin disease that causes a depigmentation disorder, resulting in selective destruction of melanocytes (MC). However, the mechanism that leads to melanocyte dysfunction and death remains unclear. METHODS: We performed RNA sequencing, immunohistochemistry, and immunoblotting to characterize the patterns of phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway activation in vitiligo. We also cocultured primary melanocytes with mesenchymal stem cells (MSCs) in a Transwell system to explore how MSCs inhibit the PTEN/PI3K/AKT pathway in melanocytes. RESULTS: We identified that vitiligo normal-lesional junction skin presented with high expression of PTEN, which led to the inhibition of AKT phosphorylation (p-AKT) at S-473. Furthermore, PTEN overexpression led to oxidative stress-induced apoptosis in melanocytes. Coculturing with MSCs enhanced the cell proliferation of human melanocytes and repressed PTEN expression, which inhibited oxidative stress-induced apoptosis. CONCLUSION: We report that vitiligo patients present with high PTEN expression, which may play a role in the impairment of melanocytes. Furthermore, our study provides evidence that MSCs target the PTEN/PI3K/AKT pathway to regulate cell proliferation and apoptosis in human melanocytes, indicating that MSCs may serve as a promising therapy for vitiligo.

17.
Cancer Cell Int ; 20: 12, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31938020

RESUMO

Background: Melanoma is the most aggressive type of skin cancer with high mortality rate and poor prognosis. lncRNA MEG3, a tumor suppressor, is closely related to the development of various cancers. However, the role of lncRNA MEG3 in melanoma has seldom been studied. Methods: RT-PCR was used to examine the expressions of lncRNA MEG3 and E-cadherin in melanoma patients and cell lines. Then, the biological functions of lncRNA MEG3 and E-cadherin were demonstrated by transfecting lncRNA MEG3-siRNA, lncRNA MEG3-overexpression, E-cadherin-siRNA and E-cadherin-overexpression plasmids in melanoma cell lines. Moreover, CCK8 assay and colony formation assay were utilized to assess the cell proliferation; Transwell assay was performed to evaluate the cell invasive ability; and tumor xenografts in nude mice were applied to test the tumor generation. Additionally, the target interactions among lncRNA MEG3, miR-21 and E-cadherin were determined by dual luciferase reporter assay. Finally, RT-PCR and WB were further conducted to verify the regulatory roles among lncRNA MEG3, miR-21 and E-cadherin. Results: The clinical data showed that lncRNA MEG3 and E-cadherin expressions were both declined in carcinoma tissues as compared with their para-carcinoma tissues. Moreover, lncRNA MEG3 and E-cadherin expressions in B16 cells were also higher than those in A375 and A2058 cells. Subsequently, based on the differently expressed lncRNA MEG3 and E-cadherin in these human melanoma cell lines, we chose B16, A375 and A2058 cells for the following experiments. The results demonstrated that lncRNA MEG3 could suppress the tumor growth, tumor metastasis and formation; and meanwhile E-cadherin had the same effects on tumor growth, tumor metastasis and formation. Furthermore, the analysis of Kaplan-Meier curves also confirmed that there was a positive correlation between lncRNA MEG3 and E-cadherin. Ultimately, dual luciferase assays were further used to verify that lncRNA MEG3 could directly target miR-21 which could directly target E-cadherin in turn. Additionally, the data of RT-PCR and WB revealed that knockdown of lncRNA MEG3 in B16 cells inhibited miR-21 expression and promoted E-cadherin expression, but overexpression of lncRNA MEG3 in A375 and A2058 cells presented completely opposite results. Conclusion: Our findings indicated that lncRNA MEG3 might inhibit the tumor growth, tumor metastasis and formation of melanoma by modulating miR-21/E-cadherin axis.

18.
J Integr Plant Biol ; 62(4): 403-420, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31001913

RESUMO

Low molecular weight secreted peptides have recently been shown to affect multiple aspects of plant growth, development, and defense responses. Here, we performed stepwise BLAST filtering to identify unannotated peptides from the Arabidopsis thaliana protein database and uncovered a novel secreted peptide family, secreted transmembrane peptides (STMPs). These low molecular weight peptides, which consist of an N-terminal signal peptide and a transmembrane domain, were primarily localized to extracellular compartments but were also detected in the endomembrane system of the secretory pathway, including the endoplasmic reticulum and Golgi. Comprehensive bioinformatics analysis identified 10 STMP family members that are specific to the Brassicaceae family. Brassicaceae plants showed dramatically inhibited root growth upon exposure to chemically synthesized STMP1 and STMP2. Arabidopsis overexpressing STMP1, 2, 4, 6, or 10 exhibited severely arrested growth, suggesting that STMPs are involved in regulating plant growth and development. In addition, in vitro bioassays demonstrated that STMP1, STMP2, and STMP10 have antibacterial effects against Pseudomonas syringae pv. tomato DC3000, Ralstonia solanacearum, Bacillus subtilis, and Agrobacterium tumefaciens, demonstrating that STMPs are antimicrobial peptides. These findings suggest that STMP family members play important roles in various developmental events and pathogen defense responses in Brassicaceae plants.

19.
Small ; 16(9): e1903841, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31573755

RESUMO

Motivated by the increasing demand of wearable and soft electronics, liquid metal (LM)-based microfluidics has been subjected to tremendous development in the past decade, especially in electronics, robotics, and related fields, due to the unique advantages of LMs that combines the conductivity and deformability all-in-one. LMs can be integrated as the core component into microfluidic systems in the form of either droplets/marbles or composites embedded by polymer materials with isotropic and anisotropic distribution. The LM microfluidic systems are found to have broad applications in deformable antennas, soft diodes, biomedical sensing chips, transient circuits, mechanically adaptive materials, etc. Herein, the recent progress in the development of LM-based microfluidics and their potential applications are summarized. The current challenges toward industrial applications and future research orientation of this field are also summarized and discussed.

20.
Int J Hyperthermia ; 36(1): 1147-1159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31752562

RESUMO

Purpose: To evaluate the feasibility and assess safety parameters of magnetic resonance-guided high-intensity focused ultrasound (MRgHIFU)-mediated hyperthermia (HT; heating to 40-45 °C) in various pelvic targets in a porcine model in vivo.Methods: Thirteen HT treatments were performed in six pigs with a commercial MRgHIFU system (Sonalleve V2, Profound Medical Inc., Mississauga, Canada) to muscle adjacent to the ventral/dorsal bladder wall and uterus to administer 42 °C (±1°) for 30 min (±5%) using an 18-mm target diameter and 100 W power. Feasibility was assessed using accuracy, uniformity, and MR-thermometry performance-based metrics. Safety parameters were assessed for tissues in the targets and beam-path by contrast-enhanced MRI, gross-pathology and histopathology.Results: Across all HT sessions, the mean difference between average temperature (Tavg) and the target temperature within the target region-of-interest (tROI, the cross-section of the heated volume at focal depth) was 0.51 ± 0.33 °C. Within the tROI, the temperature standard deviation averaged 1.55 ± 0.31 °C, the average 30-min Tavg variation was 0.80 ± 0.17 °C, and the maximum difference between Tavg and the 10th- or 90th-percentile temperature averaged 2.01 ± 0.44 °C. The average time to reach ≥41 °C and cool to ≤40 °C within the tROI at the beginning and end of treatment was 47.25 ± 27.47 s and 66.37 ± 62.68 s, respectively. Compared to unheated controls, no abnormally-perfused tissue or permanent damage was evident in the MR images, gross pathology or histological analysis.Conclusions: MRgHIFU-mediated HT is feasible and safety assessment is satisfactory for treating an array of clinically-mimicking pelvic geometries in a porcine model in vivo, implying the technique may have utility in treating pelvic targets in human patients.


Assuntos
Ablação por Ultrassom Focalizado de Alta Intensidade/métodos , Imagem por Ressonância Magnética/métodos , Pelve/patologia , Animais , Estudos de Viabilidade , Febre , Humanos , Suínos
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