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1.
Circ Res ; 133(4): 333-349, 2023 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-37462027

RESUMO

BACKGROUND: Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood. METHODS: We used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries. RESULTS: By studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction. CONCLUSIONS: Our results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.


Assuntos
Vasos Linfáticos , Proteínas Monoméricas de Ligação ao GTP , Camundongos , Animais , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Quilomícrons/metabolismo , Vasos Linfáticos/metabolismo , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Permeabilidade Capilar
2.
Small ; 20(22): e2310036, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38126916

RESUMO

Strain effect in the structurally defective materials can contribute to the catalysis optimization. However, it is challenging to achieve the performance improvement by strain modulation with the help of geometrical structure because strain is spatially dependent. Here, a new class of compressively strained platinum-iridium-metal zigzag-like nanowires (PtIrM ZNWs, M = nickel (Ni), cobalt (Co), iron (Fe), zinc (Zn) and gallium (Ga)) is reported as the efficient alkaline hydrogen evolution reaction (HER) and hydrogen oxidation reaction (HOR) catalysts. Particularly, the optimized PtIrNi ZNWs with 3% compressive strain (cs-PtIrNi ZNWs) can achieve the highest HER/HOR performances among all the catalysts investigate. Their HOR mass and specific activities are 3.2/14.4 and 2.6/32.7 times larger than those of PtIrNi NWs and commercial Pt/C, respectively. Simultaneously, they can exhibit the superior stability and high CO resistance for HOR. Further, experimental and theoretical studies collectively reveal that the compressive strain in cs-PtIrNi ZNWs effectively weakens the adsorption of hydroxyl intermediate and modulates the electronic structure, resulting in the weakened hydrogen binding energy (HBE) and moderate hydroxide binding energy (OHBE), beneficial for the improvement of HOR performance. This work highlights the importance of strain tuning in enhancing Pt-based nanomaterials for hydrogen catalysis and beyond.

3.
Small ; : e2403448, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38881353

RESUMO

Alcohol electrooxidation is pivotal for a sustainable energy economy. However, designing efficient electrocatalysts for this process is still a formidable challenge. Herein, palladium-selenium nanowires featuring distinct crystal phases: monoclinic Pd7Se2 and tetragonal Pd4.5Se for ethylene glycol electrooxidation reaction (EGOR) are synthesized. Notably, the supported monoclinic Pd7Se2 nanowires (m-Pd7Se2 NWs/C) exhibit superior EGOR activity, achieving a mass activity (MA) and specific activity (SA) of 10.4 A mgPd -1 (18.7 mA cm-2), which are 8.0 (6.7) and 10.4 (8.2) times versus the tetragonal Pd4.5Se and commercial Pd/C and surpass those reported in the literature. Furthermore, m-Pd7Se2 NWs/C displays robust catalytic activity for other alcohol electrooxidation. Comprehensive characterization and density functional theory (DFT) calculations reveal that the enhanced electrocatalytic performance is attributed to the increased formation of Pd0 on the high-index facets of the m-Pd7Se2 NWs, which lowers the energy barriers for the C─C bond dissociation in CHOHCHOH* and the CO* oxidation to CO2*. This study provides palladium-based alloy electrocatalysts exhibiting the highest mass activity reported to date for the electrooxidation of ethylene glycol, achieved through the crystalline phase engineering strategy.

4.
Chemistry ; : e202401847, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924258

RESUMO

Graphitic-carbon nitride (g-C3N4), a metal-free two-dimensional layered semiconductor material, holds great potential for energy conversion, environmental remediation, and sensing. However, the limited solubility of g-C3N4 in conventional solvents hinders its widespread application. Improving the dissolution of g-C3N4 in the liquid phase is highly desired but challenging. Herein, we report an innovative approach to dissolve g-C3N4 using ZnCl2 molten salt hydrates. The solubility of g-C3N4 in the solution reaches up to 200 mg mL-1. Density functional theory (DFT) results suggest that ZnCl+H2O is the key species that leads to charge redistribution on g-C3N4 surface and promotes the dissolution of carbon nitride in the solution. Furthermore, through dilution, the dissolved carbon nitride can be effectively recovered while maintaining its intrinsic chemical structure. The resultant regenerated C3N4 (r-C3N4) exhibits  nanobelt morphology and demonstrates a substantially improved photocatalytic activity in H2O2 production. The rate of H2O2 production over the r- C3N4 reaches 20,228 µmol g-1 h-1, which is 6.2 times higher than that of pristine g-C3N4. This green and efficient dissolution route of g-C3N4 offers an effective approach for its diverse applications.

5.
Cereb Cortex ; 33(13): 8523-8533, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37130822

RESUMO

The locus coeruleus (LC) is the site where tau accumulation is preferentially observed pathologically in Alzheimer's disease (AD) patients, but the changes in gray matter co-alteration patterns between the LC and the whole brain in the predementia phase of AD remain unclear. In this study, we estimated and compared the gray matter volume of the LC and its structural covariance (SC) with the whole brain among 161 normal healthy controls (HCs), 99 individuals with significant memory concern (SMC) and 131 patients with mild cognitive impairment (MCI). We found that SC decreased in MCI groups, which mainly involved the salience network and default mode network. These results imply that seeding from LC, the gray matter network disruption and disconnection appears early in the MCI group. The altered SC network seeding from the LC can serve as an imaging biomarker for discriminating the patients in the potential predementia phase of AD from the normal subjects.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Locus Cerúleo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo , Disfunção Cognitiva/diagnóstico por imagem , Substância Cinzenta/diagnóstico por imagem , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/psicologia
6.
Nano Lett ; 23(4): 1474-1480, 2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36779931

RESUMO

The electroreduction of carbon dioxide into high-value-added products is an effective approach to alleviating the energy crisis and pollution issues. However, there are still significant challenges for multicarbon (C2+) product production due to the lack of efficient catalysts with high selectivity. Herein, a Cu-rich electrocatalyst, where Cu2O nanoparticles are decorated on two-dimensional (2D) Cu-BDC metal-organic frameworks (MOFs) with abundant heterogeneous interfaces, is synthesized for highly selective CO2 electroreduction into C2+ products. A high C2+ Faradaic efficiency of 72.1% in an H-type cell and 58.2% in a flow cell are obtained, respectively. The heterogeneous interfaces of Cu2O/Cu-BDC can optimize the adsorption energy of reaction intermediates during CO2 electroreduction. An in situ infrared spectroscopy study indicates that the constructed interfaces can maintain the particular distribution of Cu valence states, where the C-C coupling is promoted to efficiently produce C2+ products owing to the stabilization of *CHO and *COH intermediates.

7.
Chemistry ; 29(46): e202301456, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37314829

RESUMO

Electrochemical carbon monoxide reduction reaction (CORR) is a potential way to obtain high-value multi-carbon (C2+ ) products. However, achieving high selectivity to acetate is still a challenge. Herein, we develop a two-dimensional Ag-modified Cu metal-organic framework (Ag0.10 @CuMOF-74) that demonstrates Faradaic efficiency (FE) for C2+ products up to 90.4 % at 200 mA cm-2 and an acetate FE of 61.1 % with a partial current density of 122.2 mA cm-2 . Detailed investigations show that the introduction of Ag on CuMOF-74 favors the generation of abundant Cu-Ag interface sites. In situ attenuated total reflection surface enhanced infrared absorption spectroscopy confirms that these Cu-Ag interface sites improve the coverage of *CO and *CHO and the coupling between each other and stabilize key intermediates *OCCHO and *OCCH2 , thus significantly promoting to the acetate selectivity on Ag0.10 @CuMOF-74. This work provides a high-efficiency pathway for CORR to C2+ products.

8.
Eur J Nutr ; 59(5): 2025-2037, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31312904

RESUMO

PURPOSE: Obesity, substantially increasing the risk of diseases such as metabolic diseases, becomes a major health challenge. In this study, we, therefore, investigated the effect of modified apple polysaccharide (MAP) on obesity. METHODS: Twelve male C57BL/6J mice were given a 45% high-fat diet (HFD) for 12 weeks to replicate an obesity model and six mice were given normal diet as control. Then, 1 g/kg MAP was administrated to six mice by gavage for 15 days. Illumina Miseq PE300 sequencing platform was used to analyze the microbial diversity of fecal samples. Flow cytometry was employed to investigate the effects of MAP on immune cells in adipose tissue. Bacterial culture and qPCR were used to assess the effects of MAP on the growth of whole fecal bacteria and representative microbiota in vitro. RESULTS: MAP could alleviate HFD-induced obesity and decrease body weight of mice effectively. The results of α diversity showed that Shannon index in HFD group was significantly lower than that in control group; Shannon index in MAP group was higher than that in HFD group. The results of ß diversity showed that the microbiota of MAP group was more similar to that of control group. HFD increased the number of T cells and macrophages in adipocytes; while MAP decreased the number of T cells and macrophages. MAP could promote the growth of fecal bacteria, and demonstrated a facilitated effect on the proliferation of Bacteroidetes, Bacteroides, Lactobacillus, and an inhibitory effect on Fusobacterium. CONCLUSIONS: MAP could reduce HFD-induced obesity of mice effectively. The possible mechanisms are that MAP restored HFD-induced intestinal microbiota disorder, downregulated the number of T cells and macrophages in adipose tissue.


Assuntos
Dieta Hiperlipídica , Malus , Animais , Dieta Hiperlipídica/efeitos adversos , Disbiose/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Polissacarídeos/farmacologia
9.
Entropy (Basel) ; 21(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33267134

RESUMO

This paper presents a nanofluid-based cooling method for a brushless synchronous generator (BLSG) by using Al2O3 lubricating oil. In order to demonstrate the superiority of the nanofluid-based cooling method, analysis of the thermal performance and efficiency of the nanofluid-based cooling system (NBCS) for the BLSG is conducted along with the modeling and simulation cases arranged for NBCS. Compared with the results obtained under the base fluid cooling condition, results show that the nanofluid-based cooling method can reduce the steady-state temperature and power losses in BLSG and decrease the temperature settling time and changing ratio, which demonstrate that both steady-state and transient thermal performance of NBCS are improved as nanoparticle volume fraction (NVF) in nanofluid increases. Besides, although the input power of cycling pumps in NBCS has ~30% increase when the NVF is 10%, the efficiency of the NBCS has a slight increase because the 4.1% reduction in power loss of BLSG is bigger than the total incensement of input power of the cycling pumps. The results illustrate the superiority of the nanofluid-based cooling method, and it indicates that the proposed method has a broad application prospect in the field of thermal control of onboard synchronous generators with high power density.

10.
Sensors (Basel) ; 17(5)2017 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-28481266

RESUMO

Metal roof sheathings are widely employed in large-span buildings because of their light weight, high strength and corrosion resistance. However, their severe working environment may lead to deformation, leakage and wind-lift, etc. Thus, predicting these damages in advance and taking maintenance measures accordingly has become important to avoid economic losses and personal injuries. Conventionally, the health monitoring of metal roofs mainly relies on manual inspection, which unavoidably compromises the working efficiency and cannot diagnose and predict possible failures in time. Thus, we proposed a novel damage monitoring scheme implemented by laying bend sensors on vital points of metal roofs to precisely monitor the deformation in real time. A fast reconstruction model based on improved Levy-type solution is established to estimate the overall deflection distribution from the measured data. A standing seam metal roof under wind pressure is modeled as an elastic thin plate with a uniform load and symmetrical boundaries. The superposition method and Levy solution are adopted to obtain the analytical model that can converge quickly through simplifying an infinite series. The truncation error of this model is further analyzed. Simulation and experiments are carried out. They show that the proposed model is in reasonable agreement with the experimental results.

11.
Small ; 11(34): 4385-93, 2015 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-26081741

RESUMO

The design of an ideal heterogeneous catalyst for hydrogenation reaction is to impart the catalyst with synergetic surface sites active cooperatively toward different reaction species. Herein a new strategy is presented for the creation of such a catalyst with dual active sites by decorating metal and metal oxide nanoparticles with ultrafine nanoclusters at atomic level. This strategy is exemplified by the design and synthesis of Ru nanoclusters supported on Ni/NiO nanoparticles. This Ru-nanocluster/Ni/NiO-nanoparticle catalyst is shown to exhibit ultrahigh catalytic activity for benzene hydrogenation reaction, which is 55 times higher than Ru-Ni alloy or Ru on Ni catalysts. The nanoclusters-on-nanoparticles are characterized by high-resolution transmission electron microscope, Cs-corrected high angle annular dark field-scanning transmission electron microscopy, elemental mapping, high-sensitivity low-energy ion scattering, and X-ray absorption spectra. The atomic-scale nanocluster-nanoparticle structural characteristics constitute the basis for creating the catalytic synergy of the surface sites, where Ru provides hydrogen adsorption and dissociation site, Ni acts as a "bridge" for transferring H species to benzene adsorbed and activated at NiO site, which has significant implications to multifunctional nanocatalysts design for wide ranges of catalytic reactions.

12.
Tumour Biol ; 35(7): 6397-404, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24671823

RESUMO

Vasoactive intestinal peptide (VIP) is a neurotransmitter that primarily functions as a vasodilator. VIP plays its role through binding to its receptors known as VIP/pituitary adenylate cyclase-activating peptide receptors (VPACs). In this study, we examined the expression of VPAC1 in human colon cancer tissues, analyzed the relationship between VPAC1 expression and cancer malignancy, and explored the possible mechanisms using immunohistochemistry and immunofluorescence double staining. The results showed that (1) poorly differentiated colon cancers have significantly higher VPAC1 expression than well-differentiated colon cancers do (p < 0.01); (2) phospho-epithelial growth factor receptor (EGFR) overexpression/activation in the cytoplasm of cancer cells is related to VPAC1 overexpression; (3) blood vessels surrounding colon cancer have significantly more VPAC1-positive than normal colon mucosa does; (4) tumor-associated macrophages (TAMs) of colon cancer have a higher level of VPAC1 expression than macrophages in normal colon mucosa do. These data suggest that VPAC1 overexpression is associated with poorer differentiation of colon cancer, which is likely caused by subsequent EGFR activation in cancer cells. In addition, VPAC1 overexpression in both blood vessels and macrophages in tumors may also play an important role in the development of aggressive cancer.


Assuntos
Diferenciação Celular/genética , Neoplasias do Colo/genética , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/genética , Adulto , Neoplasias do Colo/patologia , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Mensageiro/biossíntese , Receptores Tipo I de Polipeptídeo Intestinal Vasoativo/biossíntese , Peptídeo Intestinal Vasoativo/genética
13.
PLoS One ; 19(6): e0301226, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38875241

RESUMO

OBJECTIVES: To assess the efficacy of acceptance and commitment therapy (ACT) for patients with chronic pain. MATERIALS AND METHODS: The research conducted a systematic search of the Cochrane Library, Web of Science, PubMed, EMBASE, PsycINFO, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases following the PRISMA guidelines. The retrieval time limit was from the establishment of the database to October 2023. A meta-analysis was carried out for the randomized controlled trials (RCTs) that meet the inclusion and exclusion criteria by using RevMan 5.3. RESULTS: Twenty-one RCTs were included. At post-treatment, a significant medium effect size (ES) was found in measuring pain interference, functional impairment, pain acceptance, psychological inflexibility, and depression; Pain intensity, anxiety, and quality of life (QOL) had a small ES. At three months post-treatment, a large ES was found in measuring functional impairment, and a medium ES was found in the other indicators. CONCLUSION: The researchers provided evidence for the effectiveness of ACT as an intervention for patients with chronic pain, which can be applied by clinicians or nurses in practice. Future research should explore the applicability of ACT to different pain conditions and modalities. IMPLICATIONS FOR NURSING: Post-treatment data highlight the efficacy of ACT in moderating pain-related outcomes. Clinical nurses are encouraged to incorporate ACT into routine patient education and interventions, including promoting pain acceptance, promoting mindfulness practices, and using cognitive stress reduction techniques. Standardized follow-up after an ACT intervention for patients with chronic pain is critical, including regular assessment, feedback, and realignment of treatment strategies. Overall, ACT became an important tool for nurses to improve the lives of patients with chronic pain.


Assuntos
Terapia de Aceitação e Compromisso , Dor Crônica , Qualidade de Vida , Humanos , Dor Crônica/terapia , Dor Crônica/psicologia , Terapia de Aceitação e Compromisso/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Ansiedade/terapia , Ansiedade/psicologia
14.
Acad Radiol ; 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39054246

RESUMO

RATIONALE AND OBJECTIVES: The tumor-tropic properties of mesenchymal stem cells (MSCs) enable them to serve as appealing cellular vehicles for delivering therapeutic agents to treat malignant glioma. However, the exact engraftment status of MSCs in glioma via different administration routes remains unclear due to the lack of quantitative analysis. This study aimed to quantify the engraftment of MSCs in glioma after administration via different routes using non-invasive dual-modality magnetic resonance imaging (MRI) and bioluminescence imaging (BLI). MATERIALS AND METHODS: MSCs were transduced with a lentivirus overexpressing ferritin heavy chain (FTH) and firefly luciferase (FLUC) reporter genes to yield FTH- and FLUC-overexpressed MSCs (FTH-FLUC-MSCs). Wistar rats bearing intracranial C6 glioma received peritumoral, intratumoral, intra-arterial, and intravenous injection of FTH-FLUC-MSCs, respectively. MRI and BLI were performed to monitor FTH-FLUC-MSCs in vivo. RESULTS: FTH-FLUC-MSCs administered via peritumoral, intratumoral and intra-arterial routes migrated specially toward the intracranial glioma in vivo, as detected by MRI and BLI. As quantified by the BLI signal intensity, the percentages of FTH-FLUC-MSCs in the glioma were significantly higher with peritumoral injection (61%) and intratumoral injection (71%) compared to intra-arterial injection (30%) and intravenous injection (0%). Peritumorally injected FTH-FLUC-MSCs showed a gradual decline, with approximately 6% of FTH-FLUC-MSCs still retained within the tumor up to 11 days after injection. Meanwhile, the number of FTH-FLUC-MSCs injected via other routes dropped quickly, and none were detectable by day 11 post-injection. CONCLUSION: Peritumoral delivery of FTH-FLUC-MSCs offers robust engraftment and could be used as the optimal delivery route for treating malignant glioma.

15.
Cell Rep ; 43(2): 113799, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38367239

RESUMO

Schlemm's canal (SC) functions to maintain proper intraocular pressure (IOP) by draining aqueous humor and has emerged as a promising therapeutic target for glaucoma, the second-leading cause of irreversible blindness worldwide. However, our current understanding of the mechanisms governing SC development and functionality remains limited. Here, we show that vitronectin (VTN) produced by limbal macrophages promotes SC formation and prevents intraocular hypertension by activating integrin αvß3 signaling. Genetic inactivation of this signaling system inhibited the phosphorylation of AKT and FOXO1 and reduced ß-catenin activity and FOXC2 expression, thereby causing impaired Prox1 expression and deteriorated SC morphogenesis. This ultimately led to increased IOP and glaucomatous optic neuropathy. Intriguingly, we found that aged SC displayed downregulated integrin ß3 in association with dampened Prox1 expression. Conversely, FOXO1 inhibition rejuvenated the aged SC by inducing Prox1 expression and SC regrowth, highlighting a possible strategy by targeting VTN/integrin αvß3 signaling to improve SC functionality.


Assuntos
Glaucoma , Hipertensão , Doenças do Nervo Óptico , Humanos , Idoso , Integrina alfaVbeta3 , Canal de Schlemm , Macrófagos
16.
J Am Chem Soc ; 135(16): 6122-9, 2013 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-23550909

RESUMO

Mass spectrometry with desorption electrospray ionization (DESI) is demonstrated to be useful for probing the strength of hydrogen bonding, exemplified by various complexes of benzothiazoles and carboxylic acids in the solid state. Efficiencies for fragmentation of the complexes, quantified by collision-induced dissociation (CID) technology, correspond well with energies of the hydrogen bonds of O-H···N and N-H···O bridging each pair of benzothiazole and carboxylic acid. Linear correlations (with correlation factors of 0.8953 and 0.9928) have been established for the calibration curves of normalized collision energy at 100% fragmentation rate vs the length between donor and acceptor (in the hydrogen bond of O-H···N) as well as the slope of the fragmentation efficiency curve vs the average length difference between O-H···N and N-H···O in the complex. The mechanism responsible for determination of the hydrogen bonds is proposed on the basis of the experiments starting from the mixtures of the complexes as well as labeling with deuterium. As a complement of previously available methods (e.g., X-ray diffraction analysis), expectably, the proposed mass spectrometric method seems to be versatile for probing hydrogen bond energies.

17.
Tissue Cell ; 79: 101937, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36156375

RESUMO

This study aimed to determine the expression and investigate the role of chemokine 26 (CCL26) in colon cancer cells. The Cancer Genome Atlas (TCGA) analysis, qRT-PCR, and western blotting were used to detect CCL26 expression while the Kaplan-Meier plotter was used to analyze the survival of patients with colon cancer. Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and Transwell assays were performed to measure the viability, proliferation, apoptosis, and migration and invasion of colon cancer cells, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to analyze the signaling pathways regulated by CCL26. Western blotting, used to measure protein expression in this study, found overexpression of CCL26 in colon tumors. Low CCL26 levels were associated with better survival of patients as CCL26 siRNAs markedly reduced viability and proliferation, accelerated apoptosis, decreased migration and invasion, enhanced E-cadherin expression, and reduced N-cadherin and vimentin expression in cancer cells. The opposite results were obtained in CCL26-overexpressed colon cancer cells. In addition, CCL26 activated the epithelial-mesenchymal transition (EMT) pathway. CCL26 siRNAs suppressed the expression of tissue inhibitor matrix metalloproteinase 1 (TIMP1), nicotinamide N-methyltransferase (NNMT), and fibromodulin (FMOD), while CCL26 overexpression significantly increased the expression of all. EMT inhibition using the EMT inhibitor C19 eliminated the effect of CCL26 overexpression on colon cancer cells. In summary, CCL26 is involved in colon cancer progression through regulation of the EMT signaling pathway.


Assuntos
Neoplasias do Colo , Transição Epitelial-Mesenquimal , Humanos , Transição Epitelial-Mesenquimal/genética , Movimento Celular/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Transdução de Sinais/genética , Regulação Neoplásica da Expressão Gênica , Quimiocina CCL26/genética , Quimiocina CCL26/metabolismo
18.
Cell Oncol (Dordr) ; 45(3): 381-398, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35426084

RESUMO

BACKGROUND: Solute carrier family 26 member (SLC26A9) is a Cl- uniporter with very high expression levels in the gastric mucosa. Here, we describe morphological and molecular alterations in gastric mucosa of slc26a9-/- mice and in selective parietal cell-deleted slc26a9fl/fl/Atp4b-Cre mice and correlate SLC26A9 expression levels with morphological and clinical parameters in a cohort of gastric cancer (GC) patients. METHODS: The expression patterns of genes related to transport and enzymatic function, proliferation, apoptosis, inflammation, barrier integrity, metaplasia and neoplasia development were studied by immunohistochemistry (IHC), quantitative RT-PCR, in situ hybridization and RNA microarray analysis. SLC26A9 expression and cellular/clinical phenotypes were studied in primary human GC tissues and GC cell lines. RESULTS: We found that both complete and parietal cell-selective Slc26a9 deletion in mice caused spontaneous development of gastric premalignant and malignant lesions. Dysregulated differentiation of gastric stem cells in an inflammatory environment, activated Wnt signaling, cellular hyperproliferation, apoptosis inhibition and metaplasia were observed. Analysis of human gastric precancerous and cancerous tissues revealed that SLC26A9 expression progressively decreased from atrophic gastritis to GC, and that downregulation of SLC26A9 was correlated with patient survival. Exogenous expression of SLC26A9 in GC cells induced upregulation of the Cl-/HCO3- exchanger AE2, G2/M cell cycle arrest and apoptosis and suppressed their proliferation, migration and invasion. CONCLUSIONS: Our data indicate that SLC26A9 deletion in parietal cells is sufficient to trigger gastric metaplasia and the development of neoplastic lesions. In addition, we found that SLC26A9 expression decreases during human gastric carcinogenesis, and that exogenous SLC26A9 expression in GC cells reduces their malignant behavior.


Assuntos
Antiporters , Lesões Pré-Cancerosas , Neoplasias Gástricas , Transportadores de Sulfato , Animais , Antiporters/genética , Antiporters/metabolismo , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Imuno-Histoquímica , Metaplasia/metabolismo , Metaplasia/patologia , Camundongos , Lesões Pré-Cancerosas/patologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Transportadores de Sulfato/genética , Transportadores de Sulfato/metabolismo
19.
Adv Healthc Mater ; 11(23): e2201630, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36148580

RESUMO

Neural stem cells (NSCs) transplantation has been considered as a promising strategy for the treatment of ischemic stroke. However, the therapeutic prospect is limited by the poor control over the survival, migration, and maturation of transplanted NSCs. Upregulating hypoxia inducible factor (HIF)-1α expression in stem cells can improve the survival and migration of NSCs grafted for stroke therapy. Functional peptide drugs, which could inhibit endogenous HIF-1α ubiquitination, might be used to effectively upregulate the HIF-1α expression in NSCs, thereby to improve the therapeutic effect in ischemia stroke. Herein, a magnetic resonance imaging (MRI)-visible nanomedicine is developed to codeliver functional peptides and superparamagnetic iron oxide (SPIO) nanoparticles into NSCs. This nanomedicine not only promotes the survival and migration ability of NSCs but also allows an in vivo tracking of transplanted NSCs with MRI. The results demonstrate the great potential of the functional peptides-complexed multifunctional nanomedicine in boosting the therapeutic effect of stem cell-based therapy in stroke.


Assuntos
Células-Tronco Neurais , Acidente Vascular Cerebral , Humanos , Nanomedicina , Peptídeos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico
20.
Micromachines (Basel) ; 12(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34683230

RESUMO

To reduce the influence of internal residual stress on the processing deformation of thin-walled hydrogen-resistant steel components, combined aging cryogenic and high-temperature treatment was used to eliminate the residual stress, and the effect of cryogenic process parameters on the initial residual stress of the specimens was compared and analyzed based on the contour method. X-ray diffraction, electron backscatter diffraction, and transmission electron microscopy were used to research the mechanism of the effect of cryogenic treatment on the internal residual stress of the specimen. After forging, the internal residual stress distribution of the hydrogen-resistant steel specimens without aging was characterized by tensile stress on the core and compressive stress on both sides, with a stress amplitude of -350-270 MPa. After compound treatment of -130 °C for 10 h and 350 °C for 2 h, the internal residual stress distribution remained unchanged, and the stresses decreased to -150-100 MPa. The internal residual stresses were reduced by 57-63% compared with the untreated specimens. The cryogenic treatment did not cause phase transformation and carbide precipitation of the hydrogen-resistant steel material. Instead, grain refinement and dislocation density depletion were the main reasons for the reduction in internal residual stresses in the specimens.

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