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1.
J Immunol ; 211(3): 462-473, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37326485

RESUMO

Cell spreading is an initial and critical step in neutrophil adhesion and migration, leading to neutrophil recruitment to inflammatory tissues. Sideroflexin (Sfxn) family proteins are metabolite transporters located in the mitochondrial membrane. Recombinant SFXN5 protein is a citrate transporter in vitro; however, whether Sfxn5 regulates any cellular behavior or function remains unknown. In this study, we found that small interfering RNA transfection or morpholino injection achieving Sfxn5 deficiency in neutrophils significantly decreased neutrophil recruitment in mice and zebrafish, respectively. Sfxn5 deficiency impaired neutrophil spreading and spreading-associated cellular phenotypes, such as cell adhesion, chemotaxis, and ROS production. Actin polymerization is critical for neutrophil spreading, and we found that actin polymerization in spreading neutrophils was partially inhibited by Sfxn5 deficiency. Mechanistically, we observed that the levels of cytosolic citrate and its downstream metabolic products, acetyl-CoA and cholesterol, were decreased in Sfxn5-deficient neutrophils. The levels of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a mediator for the regulation of actin polymerization by cholesterol, were reduced in the plasma membrane of Sfxn5-deficient neutrophils. Exogenous supplementation with citrate or cholesterol partially reversed the reduction in PI(4,5)P2 levels, defective neutrophil actin polymerization, and cell spreading. Altogether, we demonstrated that Sfxn5 maintains cytosolic citrate levels and ensures the synthesis of sufficient cholesterol to promote actin polymerization in a PI(4,5)P2-dependent manner during neutrophil spreading, which is essential for the eventual inflammatory recruitment of neutrophils. Our study revealed the importance of Sfxn5 in neutrophil spreading and migration, thus identifying, to our knowledge, for the first time, the physiological cellular functions of the Sfxn5 gene.


Assuntos
Actinas , Neutrófilos , Animais , Camundongos , Actinas/metabolismo , Neutrófilos/metabolismo , Ácido Cítrico/metabolismo , Peixe-Zebra/metabolismo , Polimerização , Colesterol/metabolismo
2.
Small ; 20(30): e2312019, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38389179

RESUMO

The growing interest in so-called interface coupling strategies arises from their potential to enhance the performance of active electrode materials. Nevertheless, designing a robust coupled interface in nanocomposites for stable electrochemical processes remains a challenge. In this study, an epitaxial growth strategy is proposed by synthesizing sulfide rhenium (ReS2) on exfoliated black phosphorus (E-BP) nanosheets, creating an abundance of robust interfacial linkages. Through spectroscopic analysis using X-ray photoelectron spectroscopy and X-ray absorption spectroscopy, the authors investigate the interfacial environment. The well-developed coupled interface and structural stability contribute to the impressive performance of the 3D-printed E-BP@ReS2-based micro-supercapacitor, achieving a specific capacitance of 47.3 mF cm-2 at 0.1 mA cm-2 and demonstrating excellent long-term cyclability (89.2% over 2000 cycles). Furthermore, density functional theory calculations unveil the positive impact of the strongly coupled interface in the E-BP@ReS2 nanocomposite on the adsorption of H+ ions, showcasing a significantly reduced adsorption energy of -2.17 eV. The strong coupling effect facilitates directional charge delocalization at the interface, enhancing the electrochemical performance of electrodes and resulting in the successful construction of advanced micro-supercapacitors.

3.
Macromol Rapid Commun ; : e2400379, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940242

RESUMO

Creating bionic intelligent robotic systems that emulate human-like skin perception presents a considerable scientific challenge. This study introduces a multifunctional bionic electronic skin (e-skin) made from polyacrylic acid ionogel (PAIG), designed to detect human motion signals and transmit them to robotic systems for recognition and classification. The PAIG is synthesized using a suspension of liquid metal and graphene oxide nanosheets as initiators and cross-linkers. The resulting PAIGs demonstrate excellent mechanical properties, resistance to freezing and drying, and self-healing capabilities. Functionally, the PAIG effectively captures human motion signals through electromechanical sensing. Furthermore, a bionic intelligent sorting robot system is developed by integrating the PAIG-based e-skin with a robotic manipulator. This system leverages its ability to detect frictional electrical signals, enabling precise identification and sorting of materials. The innovations presented in this study hold significant potential for applications in artificial intelligence, rehabilitation training, and intelligent classification systems.

4.
J Environ Manage ; 365: 121531, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38909582

RESUMO

Exploring the ecological utility of cultivated land's carbon metabolism offers policy insights for ensuring its healthy operation and promote the dual carbon goals (carbon peak and carbon neutrality). We employed ecological network analysis (ENA) and kernel density estimation to conduct an empirical study, taking Hubei Province from 2000 to 2020 as an example. The results revealed apparent negative effects of carbon metabolic flow on regional carbon balance. Specifically, cultivated land conversion into transportation and industrial land contributed significantly to the harmful carbon flow. Ecological relationships showed fierce competition for carbon storage, leading to overall adverse ecological effects. The ecological utility indicated detrimental impacts on the orderly functioning of land-use carbon metabolism. Cultivated land's carbon metabolism will be essential in achieving land-use carbon neutrality. Therefore, territorial spatial low-carbon optimization should be implemented to realize its green and sustainable development.


Assuntos
Carbono , China , Carbono/metabolismo , Ecossistema , Ecologia , Conservação dos Recursos Naturais , Agricultura
5.
J Am Chem Soc ; 145(39): 21387-21396, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37728869

RESUMO

The electrocatalytic nitrate (NO3-) reduction reaction (eNITRR) is a promising method for ammonia synthesis. However, its efficacy is currently limited due to poor selectivity, largely caused by the inherent complexity of the multiple-electron processes involved. To address these issues, oxygen-vacancy-rich LaFe0.9M0.1O3-δ (M = Co, Ni, and Cu) perovskite submicrofibers have been designed from the starting material LaFeO3-δ (LF) by a B-site substitution strategy and used as the eNITRR electrocatalyst. Consequently, the LaFe0.9Cu0.1O3-δ (LF0.9Cu0.1) submicrofibers with a stronger Fe-O hybridization, more oxygen vacancies, and more positive surface potential exhibit a higher ammonia yield rate of 349 ± 15 µg h-1 mg-1cat. and a Faradaic efficiency of 48 ± 2% than LF submicrofibers. The COMSOL Multiphysics simulations demonstrate that the more positive surface of LF0.9Cu0.1 submicrofibers can induce NO3- enrichment and suppress the competing hydrogen evolution reaction. By combining a variety of in situ characterizations and density functional theory calculations, the eNITRR mechanism is revealed, where the first proton-electron coupling step (*NO3 + H+ + e- → *HNO3) is the rate-determining step with a reduced energy barrier of 1.83 eV. This work highlights the positive effect of cation substitution in promoting eNITRR properties of perovskites and provides new insights into the studies of perovskite-type electrocatalytic ammonia synthesis catalysts.

6.
Am J Pathol ; 192(6): 876-886, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35337837

RESUMO

Diabetes leads to intestinal barrier dysfunction. 5-Hydroxytryptamine 4 receptor (5-HT4R) is distributed in the colonic mucosa, but little is known about the role of its activation in diabetes-evoked colonic barrier dysfunction. This study investigates whether activation of 5-HT4Rs on goblet cells (GCs) protects the colon from commensal bacterial translocation in diabetic mice. Expression of 5-HT4R detected inside the colonic epithelium by RNAscope in situ hybridization was further observed within the mucin 2 (MUC2)-immunoreactive GCs. In diabetic mice, neither 5-HT4R transcription nor protein levels were altered compared with those in nondiabetic mice. Bacterial translocation was characterized by 16S rRNA RNAscope in situ hybridization and manifested in both crypts and lamina propria of the colon in diabetic mice. Mucin production and MUC2 expression were significantly decreased in diabetic mice. Furthermore, the loss of mitochondrial cristae of GCs and the down-regulation of mitofilin, the core protein maintaining mitochondrial homeostasis, were observed in diabetic mice. Long-term treatment with 5-HT4R agonist in diabetic mice not only prevented bacterial penetration of the whole colonic mucosa but also promoted mucin production and MUC2 expression. Markedly, 5-HT4R agonist also restored the mitochondrial cristae of GCs and up-regulated mitofilin. However, co-administration of 5-HT4R antagonist abolished the effects of 5-HT4R agonist on diabetic mice. These findings indicate that 5-HT4R in colonic mucosa is an effective target for the treatment of diabetes-induced colonic mucous barrier dysfunction.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Animais , Colo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Camundongos , Mucina-2/metabolismo , Mucinas/metabolismo , RNA Ribossômico 16S/metabolismo , Receptores 5-HT4 de Serotonina/metabolismo , Serotonina/metabolismo , Serotonina/farmacologia
7.
Plant Dis ; 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37923979

RESUMO

Ampelopsis grossedentata, commonly known as "Vine Tea" and well-recognized for its rich flavonoid content, is mainly distributed in the southern regions of the Yangtze River basin in China. These regions include Hunan, Hubei, Jiangxi, and Guizhou provinces. Vine Tea is mainly consumed as an herbal tea and has garnered attention for its reported health benefits, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and neuroprotective properties. It has been used to alleviate coughs and sore throats (Zhang et al., 2021; Wang et al., 2017; Gao et al., 2009). In the Zhangjiajie region of Hunan province alone, the Vine Tea planting area reached 7,670.5 hectares and produced commercial goods worth 1.417 billion RMB in 2022. In May 2021, leaf margins and veins fading to yellowing mottling, and crumpling of leaf blades in the shape of a boat symptoms were found in ~16% of Vine Tea plants in the Sanjiakuan Township, Yongding District, Zhangjiajie region (29°15'E, 110°30' N) (Figure 1a, b, c). (Figure 1a, b, c). Phytoplasma-like microbial cells (small oval shaped bacterial cells, around 1000 nm in size) were observed in sieve tube cells in the phloem of diseased leaves using transmission electron microscopy. No such cell was observed in the phloem of healthy leaves (Figure 2a, b). To investigate the potential association between phytoplasma and the observed symptoms of the diseased plants, total DNA was isolated from ten diseasedeaves and compared with ten healthy leaves from the same field using SteadyPure Plant Genomic DNA Extraction Kit. The isolated DNAs were analyzed first in a direct PCR using universal phytoplasma primer pair R16mF2/R16mR1 targeting the 16S rRNA gene (Gundersen and Lee 1996) and specific pair rpF1/rpR1 (Lee et al. 1998) targeting the DNA fragment encoding partial ribosomal proteins (rp) L22 (complete) and S3 and S19 (partial). The initial amplified products were used as templates and further amplified by nested PCR respectively with primer pair R16F2n/R16R2 for the 16S rRNA gene (Lee et al. 1998) and the rpF2/rpR2 primer pair for the rp gene (Martini et al. 2007). No amplification was obtained with DNA from healthy leaf samples using any of the four primer pairs. The amplified fragments from diseased leaves by nested PCR were cloned and sequenced (Qingke Biotech, China). The obtained sequences have been deposited in GenBank with accession numbers OR282806 for the 16S rRNA gene and GenBank OR353012 for the rp gene. BLASTn analysis revealed that the partial 16S rRNA gene sequence in our sample shared 99.4% nucleotide sequence identity with 'Candidatus Phytoplasma sp.' (MW364378) and 'Peony yellows phytoplasma' (KY814723) of the 16SrI group. Similarly, our rp gene sequence shared 99.6% nucleotide identity with the rpI group of phytoplasma such as the 'Balsamine virescence phytoplasma' (JN572890) and 'Paulownia witches'-broom phytoplasma' (HM146079). Phylogenetic analysis of the 16S rRNA and rp sequences using MEGA version 7.0 revealed that the phytoplasma strain associated with A. grossedentata yellow leaf syndrome in our study site belonged to the 16SrI (Candidatus Phytoplasma asteris) group of phytoplasma (Figure 3a, b). Using the interactive online phytoplasma classification tool iPhyClassifier (Zhao et al., 2009), virtual restriction fragment length polymorphism (RFLP) analysis of the 16S rRNA gene sequences showed our strain having a distinct RFLP map but was closest to that of the onion yellow phytoplasma 16SrI-B subgroup (GenBank accession number: AP006628), with a similarity coefficient of 0.94 (Figure 4a, b). To confirm phytoplasma transmission, healthy plants were inoculated with three scions of infected plants of A. grossedentata. After 16 days, the new leaves of the inoculated A. grossedentata showed yellow leaf symptoms (Figure 5a, b, c), akin to the symptoms originally observed in the field, and the outer contour of the leaf margin appeared chlorotic. After 26 days, primer pairs R16mF2/R16R1 and R16F2n/R16R2 were used for nested PCR detection of phytoplasma in symptomatic A. grossedentata leaves. Phytoplasma was detected in the first and second leaves of symptomatic branches and leaves while negative control showed no amplification. Sequencing of the amplified fragments showed 100% nucleotide identity to the strain from the grafting source. Our results indicated that the pathogen and the disease can be transmitted by tissue grafting, consistent with the biological characteristics of phytoplasma, and further confirmed that the phytoplasma was the pathogen of yellow leaf syndrome of A. grossedentata. Toour knowledge, this is the first report of phytoplasma of group 16SrI affecting A. grossedentata.

8.
Mol Imaging ; 2022: 2679260, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35330799

RESUMO

[18F]tetrafluoroborate (TFB) has been introduced as the 18F-labeled PET imaging probe for the human sodium iodide symporter (NIS). Noninvasive NIS imaging using [18F]TFB has received much interest in recent years for evaluating various NIS-expressing tumors. Cancers are a global concern with enormous implications; therefore, improving diagnostic methods for accurate detection of cancer is extremely important. Our aim was to investigate the PET imaging capabilities of [18F]TFB in NIS-transfected lung cell line A549 and endogenous NIS-expressing tumor cells, such as thyroid cancer K1 and gastric cancer MKN45, and broaden its application in the medical field. Western blot and flow cytometry were used to assess the NIS expression level. Radioactivity counts of [18F]TFB, in vitro, in the three tumor cells were substantially higher than those in the KI inhibition group in the uptake experiment. In vivo PET imaging clearly delineated the three tumors based on the specific accumulation of [18F]TFB in a mouse model. Ex vivo biodistribution investigation showed high [18F]TFB absorption in the tumor location, which was consistent with the PET imaging results. These results support the use of NIS-transfected lung cell line A549 and NIS-expressing tumor cells MKN45 and K1, to investigate probing capabilities of [18F]TFB. We also demonstrate, for the first time, the feasibility of [18F]TFB in diagnosing stomach cancer. In conclusion, this study illustrates the promising future of [18F]TFB for tumor diagnosis and NIS reporter imaging.


Assuntos
Neoplasias , Simportadores , Animais , Linhagem Celular , Linhagem Celular Tumoral , Camundongos , Tomografia por Emissão de Pósitrons/métodos , Simportadores/genética , Simportadores/metabolismo , Distribuição Tecidual
9.
Plant Biotechnol J ; 18(3): 756-769, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31469486

RESUMO

Nonspecific lipid transfer proteins (nsLTPs) play critical roles in plant development and response to abiotic stresses. Here, we found that a rice lipid transfer protein, OsLTPL159, was associated with cold tolerance at the early seedling stage. Overexpression of an OsLTPL159IL112 allele from the cold-tolerant introgression line IL112 in either the japonica variety Zhonghua17 (ZH17) or the indica variety Teqing background dramatically enhanced cold tolerance. In addition, down-regulation of the expression of OsLTPL159 in the japonica variety ZH17 by RNA interference (RNAi) significantly decreased cold tolerance. Further transcriptomic, physiological and histological analysis showed that the OsLTPL159IL112 allele likely enhanced the cold tolerance of rice at the early seedling stage by decreasing the toxic effect of reactive oxygen species, enhancing cellulose deposition in the cell wall and promoting osmolyte accumulation, thereby maintaining the integrity of the chloroplasts. Notably, overexpression of another allele, OsLTPL159GC2 , from the recipient parent Guichao 2 (GC2), an indica variety, did not improve cold tolerance, indicating that the variations in the OsLTPL159 coding region of GC2 might disrupt its function for cold tolerance. Further sequence comparison found that all 22 japonica varieties surveyed had an OsLTPL159 haplotype identical to IL112 and were more cold-tolerant than the surveyed indica varieties, implying that the variations in OsLTPL159 might be associated with differential cold tolerance of japonica and indica rice. Therefore, our findings suggest that the OsLTPL159 allele of japonica rice could be used to improve cold tolerance of indica rice through a molecular breeding strategy.


Assuntos
Proteínas de Transporte/fisiologia , Temperatura Baixa , Oryza/fisiologia , Proteínas de Plantas/fisiologia , Estresse Fisiológico , Perfilação da Expressão Gênica , Plântula/fisiologia
10.
Mediators Inflamm ; 2020: 7835284, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922208

RESUMO

Asthma is associated with innate and adaptive immunity mediated by immune cells. T cell or macrophage dysfunction plays a particularly significant role in asthma pathogenesis. Furthermore, crosstalk between them continuously transmits proinflammatory or anti-inflammatory signals, causing the immune cell activation or repression in the immune response. Consequently, the imbalanced immune microenvironment is the major cause of the exacerbation of asthma. Here, we discuss the role of T cells, macrophages, and their interactions in asthma pathogenesis.


Assuntos
Asma/metabolismo , Macrófagos/metabolismo , Linfócitos T/metabolismo , Animais , Asma/fisiopatologia , Humanos , Imunidade Inata/fisiologia , Macrófagos/fisiologia , Linfócitos T/fisiologia
11.
J Cell Mol Med ; 23(5): 3097-3107, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30825266

RESUMO

BACKGROUND: Complement C3 has been shown to be highly expressed in cutaneous squamous cell carcinoma (cSCC) tumour tissues and is correlated with tumour cell growth. This study aimed to investigate the mechanism of C3 in cSCC malignant transformation. METHODS: C3 expression was analysed in cSCC cell lines A431, Tca8113, SCC13, HSC-5 and HSC-1 and in immortalized HaCaT keratinocytes. Proliferation and migration of cSCC were determined after C3a exposure. Expression of cyclin D1, cyclin E, vascular endothelial growth factor (VEGF), pro-matrix metalloproteinase 1 (pro-MMP1), pro-matrix metalloproteinase 2 (pro-MMP2), stemness factors, GSK-3ß, and ß-catenin were analyzed. Tumour growth was examined in a murine xenograft model. RESULTS: C3 expression was much more highly expressed in all cSCC cell lines than in HaCaT cells. C3a treatment significantly promoted cSCC cell proliferation and migration and upregulated cyclin D1, cyclin E, VEGF, pro-MMP1 and pro-MMP2 expression, which were impeded by the C3aR antagonist. Moreover, the expression of stemness factors Sox-2, Nanog, Oct-4, c-Myc and CD-44 was stimulated by C3a and slowed by C3aR disruption. Knockdown of Sox-2 by siRNA transfection suppressed cell proliferation and migration, constrained VEGF secretion and inhibited pro-MMP1 and pro-MMP2 expression. C3a also activated the Wnt and ß-catenin pathway in cSCC cells. Disruption of C3aR expression dampened tumour growth and the expression of Wnt-1, ß-catenin and Sox-2 in the xenograft model. CONCLUSIONS: C3a enhanced cell proliferation, migration and stemness in cSCC, and this activity was correlated with activation of the Wnt and ß-catenin pathway.


Assuntos
Carcinoma de Células Escamosas/genética , Proliferação de Células/genética , Complemento C3a/genética , Neoplasias Cutâneas/genética , Animais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Xenoenxertos , Humanos , Camundongos , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Transdução de Sinais , Neoplasias Cutâneas/patologia , Proteína Wnt1/genética , beta Catenina/genética
12.
Appl Opt ; 58(6): 1522-1529, 2019 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-30874042

RESUMO

The large normal dispersion of the fundamental mode (TEn=1 mode) in the whispering gallery modes (WGM) microsphere is detrimental to the visible comb generation. Herein, we demonstrate that this fundamental limitation can be removed by considering the high-order radial modes (TEn=2 mode) of the hybrid microsphere cavity (HMC). The studied HMC consists of a high-refractive-index coating (TiO2 or HfO2) and silica microsphere. The simulated electric field energy distribution and measured Q value in our experiment show that optical confinement of the coating effectively excites the TEn=2 mode and reduces the free spectral range (FSR) and modal dispersion. In addition, the observed redshift of WGM and decreased trend of FSR are in accordance with simulations. The zero-dispersion wavelength can be linearly shifted to a shorter wavelength or even into the visible region with the reduction of coating thickness or refractive index and larger microcavity, which advances the visible comb generation.

13.
Appl Opt ; 56(27): 7572-7576, 2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-29047733

RESUMO

We report an experimental realization of five-order Stokes stimulated Raman scattering lasing in silica microspheres pumped by a 1030 nm continuous-wave laser. The wavelength of the Stokes Raman laser is extended to 1348.55 nm, which is located in the second low loss window of the optical fiber. It has potential applications in the wavelength converter and Raman amplifier in O-waveband optical communication. The minimum pump power is about 50 µW when the first-order Stokes Raman laser can be observed.

14.
Zhongguo Zhong Yao Za Zhi ; 41(3): 451-455, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28868863

RESUMO

Rosa roxburghii, a kind of the medical and edible plants belonging to the Rosaceae family, is widely distributed in the southwest districts of China, especially Guizhou province. Now, by reason of the extensive bioactivities, the plant is widely used in the field of food, health product, drug, and so on. In the course of our continuing search for the bioactive constituents, thirteen compounds were isolated from R. roxburghii, and their structures were determined on the basis of physicochemical property, spectroscopic data and comparison with the literatures, as 2-oxo pomolic acid(1), 1ß-hydroxyeuscaphic acid(2), euscaphic acid(3), arjunic acid(4), tormentic acid(5), kaiiichigeside F1(6), rosamultin(7), arjunetin(8), 2ɑ, 3ɑ, 19ɑ-trihydroxy-olean-12-en-28-oic acid 28-O-ß-D-glucopyranoside(9), 2α, 3α, 19α, 24-tetrahydroxyolean-12-en-28-oic-acid 28-O-ß-D-glucopyranosyl ester(10), pyrogallic acid (11), daucosterol(12), and 1, 2-decanediol(13). Compounds 9 and 10 were firstly obtained from Rosaceae family, and compounds 1,4,5,9-11,13 were isolated from this plant for the first time.


Assuntos
Extratos Vegetais/química , Rosa/química , China , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Plantas Comestíveis/química , Espectrometria de Massas por Ionização por Electrospray
15.
J Cell Mol Med ; 19(6): 1197-207, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25786906

RESUMO

Hirschsprung's disease (HSCR) is a rare congenital disease caused by impaired proliferation and migration of neural crest cells. We investigated changes in expression of microRNAs (miRNAs) and the genes they regulate in tissues of patients with HSCR. Quantitative real-time PCR and immunoblot analyses were used to measure levels of miRNA, mRNAs, and proteins in colon tissues from 69 patients with HSCR and 49 individuals without HSCR (controls). Direct interactions between miRNAs and specific mRNAs were indentified in vitro, while the function role of miR-218-1 was investigated by using miR-218 transgenic mice. An increased level of miR-218-1 correlated with increased levels of SLIT2 and decreased levels of RET and PLAG1 mRNA and protein. The reductions in RET and PLAG1 by miR-218-1 reduced proliferation and migration of SH-SY5Y cells. Overexpression of the secreted form of SLIT2 inhibited cell migration via binding to its receptor ROBO1. Bowel tissues from miR-218-1 transgenic mice had nerve fibre hyperplasia and reduced numbers of gangliocytes, compared with wild-type mice. Altered miR-218-1 regulation of SLIT2, RET and PLAG1 might be involved in the pathogenesis of HSCR.


Assuntos
Proteínas de Ligação a DNA/genética , Doença de Hirschsprung/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Proteínas Proto-Oncogênicas c-ret/genética , Receptores Imunológicos/genética , Animais , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Colo/metabolismo , Colo/patologia , Proteínas de Ligação a DNA/metabolismo , Feminino , Expressão Gênica , Doença de Hirschsprung/metabolismo , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Ligação Proteica , Proteínas Proto-Oncogênicas c-ret/metabolismo , Receptores Imunológicos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/genética , Proteínas Roundabout
16.
J Cell Mol Med ; 18(8): 1580-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24974861

RESUMO

Hirschsprung's disease (HSCR), a congenital gastrointestinal disorder, is one of the most common causes of neonatal bowel obstruction. Without an early screening and diagnosis, some patients develop serious complications, such as toxic megacolon or acute enterocolitis. We sought to identify specific serum microRNAs (miRNAs) that can serve as novel early, non-invasive screening signature and then to test their specificity and sensitivity in diagnosing Hirschsprung's disease. We obtained serum samples from 95 HSCR cases and 104 matched controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR arranged in the training and a two-stage validation set. Additional double-blind testing was performed in 23 patients with clinically suspected HSCR to evaluate the diagnostic value and accuracy of the serum miRNA profile in predicting HSCR. Following a multi-stage evaluation approach, five miRNAs were significantly increased in HSCR cases compared with controls. The areas under the receiver operating characteristic (ROC) curve of this five-serum miRNA signature were 0.895, 0.893 and 0.925 in training set and two validation sets, respectively. The accuracy rate of the five-miRNA profile as HSCR signature was 82.6%, which, in the double-blind testing set, was markedly higher than that of contrast enema (70%), the most commonly used test performed to diagnose HSCR. Our results indicate that a five-serum miRNA signature may be linked to HSCR, representing a potential, novel, non-invasive diagnostic approach for early screening of HSCR.


Assuntos
Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Doença de Hirschsprung/sangue , Doença de Hirschsprung/diagnóstico , MicroRNAs/genética , Estudos de Casos e Controles , Método Duplo-Cego , Feminino , Doença de Hirschsprung/genética , Humanos , Lactente , Masculino , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
17.
Foods ; 13(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38890950

RESUMO

The global demand for protein is on an upward trajectory, and peanut protein powder has emerged as a significant player, owing to its affordability and high quality, with great future market potential. However, the industry currently lacks efficient methods for rapid quality testing. This research paper addressed this gap by introducing a portable device with employed near-infrared spectroscopy (NIR) to quickly assess the quality of peanut protein powder. The principal component analysis (PCA), partial least squares (PLS), and generalized regression neural network (GRNN) methods were used to construct the model to further enhance the accuracy and efficiency of the device. The results demonstrated that the newly established NIR method with PLS and GRNN analysis simultaneously predicted the fat, protein, and moisture of peanut protein powder. The GRNN model showed better predictive performance than the PLS model, the correlation coefficient in calibration (Rcal) of the fat, the protein, and the moisture of peanut protein powder were 0.995, 0.990, and 0.990, respectively, and the residual prediction deviation (RPD) were 10.82, 10.03, and 8.41, respectively. The findings unveiled that the portable NIR spectroscopic equipment combined with the GRNN method achieved rapid quantitative analysis of peanut protein powder. This advancement holds a significant application of this device for the industry, potentially revolutionizing quality testing procedures and ensuring the consistent delivery of high-quality products to fulfil consumer desires.

18.
Front Oncol ; 14: 1334631, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38496762

RESUMO

The 3D culture of intestinal organoids entails embedding isolated intestinal crypts and bone marrow mesenchymal stem cells within a growth factor-enriched matrix gel. This process leads to the formation of hollow microspheres with structures resembling intestinal epithelial cells, which are referred to as intestinal organoids. These structures encompass various functional epithelial cell types found in the small intestine and closely mimic the organizational patterns of the small intestine, earning them the name "mini-intestines". Intestinal tumors are prevalent within the digestive system and represent a significant menace to human health. Through the application of 3D culture technology, miniature colorectal organs can be cultivated to retain the genetic characteristics of the primary tumor. This innovation offers novel prospects for individualized treatments among patients with intestinal tumors. Presently established libraries of patient-derived organoids serve as potent tools for conducting comprehensive investigations into tissue functionality, developmental processes, tumorigenesis, and the pathobiology of cancer. This review explores the origins of intestinal organoids, their culturing environments, and their advancements in the realm of precision medicine. It also addresses the current challenges and outlines future prospects for development.

19.
Chin J Integr Med ; 30(4): 322-329, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37861963

RESUMO

OBJECTIVE: To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) and celastrol combination treatment (TCCT) in glioblastoma cells. METHODS: Cell counting kit-8 was used to detect the effects of different concentrations of celastrol (0-16 µmol/L) and TRAIL (0-500 ng/mL) on the cell viability of glioblastoma cells. U87 cells were randomly divided into 4 groups, namely control, TRAIL (TRAIL 100 ng/mL), Cel (celastrol 0.5 µmol/L) and TCCT (TRAIL 100 ng/mL+ celastrol 0.5 µmol/L). Cell proliferation, migration, and invasion were detected by colony formation, wound healing, and Transwell assays, respectively. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition (EMT) markers (zona occludens, N-cadherin, vimentin, zinc finger E-box-binding homeobox, Slug, and ß-catenin). Wnt pathway was activated by lithium chloride (LiCl, 20 mol/L) and the mechanism for action of TCCT was explored. RESULTS: Celastrol and TRAIL synergistically inhibited the proliferation, migration, invasion, and EMT of U87 cells (P<0.01). TCCT up-regulated the expression of GSK-3ß and down-regulated the expression of ß-catenin and its associated proteins (P<0.05 or P<0.01), including c-Myc, Cyclin-D1, and matrix metalloproteinase (MMP)-2. In addition, LiCl, an activator of the Wnt signaling pathway, restored the inhibitory effects of TCCT on the expression of ß-catenin and its downstream genes, as well as the migration and invasion of glioblastoma cells (P<0.05 or P<0.01). CONCLUSIONS: Celastrol and TRAIL can synergistically suppress glioblastoma cell migration, invasion, and EMT, potentially through inhibition of Wnt/ß-catenin pathway. This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.


Assuntos
Glioblastoma , Triterpenos Pentacíclicos , Via de Sinalização Wnt , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Ligantes , Linhagem Celular Tumoral , Apoptose , Fatores de Necrose Tumoral/farmacologia , Proliferação de Células , Movimento Celular , Transição Epitelial-Mesenquimal
20.
Cell Physiol Biochem ; 32(6): 1655-67, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24334875

RESUMO

BACKGROUND: MiR-141 has been confirmed to be associated with various human diseases. However, whether miR-141 is involved in the pathogenesis of Hirschsprung's disease (HSCR) remains unknown. Here, we design the experiment to reveal the relationship between miR-141 and HSCR. METHODS: Quantitative real-time PCR and Western blot were used to detect the expression levels of miR-141 and its potential genes in 70 tissues of HSCR compared with 60 controls. Bisulfite sequencing PCR (BSP) assay was applied to explain the possible mechanism of the aberrant expression level of miR-141. We employed a dual-luciferase reporter assay to validate the regulation relation between miR-141 and CD47/CUL3. Cell migration, proliferation, apoptosis, and cell cycle progression were examined by transwell assay, MTT assay, and flow cytometry, respectively. RESULTS: MiR-141 was down-regulated whereas CD47 and CUL3 expression was increased in colon tissues from patients with HSCR compared with control group, The increased level of CD47 and CUL3 induced by miR-141 reduced proliferation and migration of 293T and SH-SY5Y cells. Furthermore, this suppression was reversed by reducing of CD47 and CUL3. Hypermethylation of a CpG Island in the promoter region of miR-141 gene was confirmed in HSCR tissues. CONCLUSION: Aberrant reduction of miR-141 may play an important role in the pathogenesis of HSCR with the inhibiting affection on cell migration and proliferation abilities. The present study demonstrates for the first time the role of miR-141 and its target genes in the occurrence of HSCR, and provides us a new direction for the study of the pathogenesis of Hirschsprung's disease.


Assuntos
Proteínas Culina/metabolismo , Doença de Hirschsprung/patologia , MicroRNAs/metabolismo , Sequência de Bases , Antígeno CD47/química , Antígeno CD47/genética , Antígeno CD47/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Colo/metabolismo , Proteínas Culina/antagonistas & inibidores , Proteínas Culina/genética , Metilação de DNA , Regulação para Baixo , Feminino , Células HEK293 , Doença de Hirschsprung/metabolismo , Humanos , Lactente , Masculino , Regiões Promotoras Genéticas , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Regulação para Cima
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