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1.
Stem Cell Res Ther ; 13(1): 314, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35841007

RESUMO

BACKGROUND: The biological activity and regenerative medicine of bone marrow mesenchymal stem cells (BMSCs) have been focal topics in the broad fields of diabetic wound repair. However, the molecular mechanisms are still largely elusive for other cellular processes that are regulated during BMSC treatment. Our previous studies have shown that hypoxia is not only a typical pathological phenomenon of wounds but also exerts a vital regulatory effect on cellular bioactivity. In this study, the beneficial effects of hypoxic BMSCs on the cellular behaviors of epidermal cells and diabetic wound healing were investigated. METHOD: The viability and secretion ability of hypoxic BMSCs were detected. The autophagy, proliferation and migration of HaCaT cells cultured with hypoxic BMSCs-derived conditioned medium were assessed by estimating the expression of autophagy-related proteins, MTS, EdU proliferation and scratch assays. And the role of the SMAD signaling pathway during hypoxic BMSC-evoked HaCaT cell autophagy was explored through a series of in vitro gain- and loss-of-function experiments. Finally, the therapeutic effects of hypoxic BMSCs were evaluated using full-thickness cutaneous diabetic wound model. RESULTS: First, we demonstrated that hypoxic conditions intensify HIF-1α-mediated TGF-ß1 secretion by BMSCs. Then, the further data revealed that BMSC-derived TGF-ß1 was responsible for the activation of epidermal cell autophagy, which contributed to the induction of epidermal cell proliferation and migration. Here, the SMAD signaling pathway was identified as downstream of BMSC-derived TGF-ß1 to regulate HaCaT cell autophagy. Moreover, the administration of BMSCs to diabetic wounds increased epidermal autophagy and the rate of re-epithelialization, leading to accelerated healing, and these effects were significantly attenuated, accompanied by the downregulation of Smad2 phosphorylation levels due to TGF-ß1 interference in BMSCs. CONCLUSION: In this report, we present evidence that uncovers a previously unidentified role of hypoxic BMSCs in regulating epidermal cell autophagy. The findings demonstrate that BMSC-based treatment by restoring epidermal cell autophagy could be an attractive therapeutic strategy for diabetic wounds and that the process is mediated by the HIF-1α/TGF-ß1/SMAD pathway.


Assuntos
Diabetes Mellitus , Subunidade alfa do Fator 1 Induzível por Hipóxia , Células-Tronco Mesenquimais , Proteínas Smad , Fator de Crescimento Transformador alfa , Cicatrização , Autofagia , Células da Medula Óssea/citologia , Células da Medula Óssea/metabolismo , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Diabetes Mellitus/terapia , Células Epidérmicas/citologia , Células Epidérmicas/metabolismo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador alfa/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Cicatrização/fisiologia
2.
Int J Med Sci ; 19(4): 669-680, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35582423

RESUMO

There is growing support for the notion that chronic inflammation contributes to lung tumorigenesis, but the molecular and cellular basis underlying the protumorigenic effects of inflammation remains to be explored. 3-Methylcholanthrene and diethylnitrosamine were intratracheally instilled into rats to induce multistep lung carcinogenesis, and the presence of pulmonary inflammation was observed in addition to precancerous lesions. By leveraging single-cell RNA sequencing, we sought to unravel the mechanism underlying the inflammatory process at a higher resolution. A total of 14 cell types were identified in chemically treated and control rats. Chemical intervention introduced heterogeneity in cell type composition and gene expression patterns. Nonimmune cells were found to be the most affected, and two subpopulations of endothelial cells with diverse roles were defined. Car4-high endothelial cells were mainly responsible for angiogenesis, whereas Car4-low endothelial cells were involved in neutrophil recruitment, and adhesion between Car4-low endothelial cells and neutrophils was verified in inflamed tissues. Our work unveiled the intricate process of pulmonary inflammation at the single-cell level and characterized a proinflammatory subpopulation of endothelial cells involved in neutrophil recruitment. The conditions provided by chronic inflammatory environment are prerequisites for neoplastic progression. Targeting the specific subsets or processes defined herein holds promise for the early prevention and therapeutic intervention of lung cancer through the manipulation of angiogenesis or the inflammatory response.


Assuntos
Células Endoteliais , Pneumonia , Animais , Células Endoteliais/patologia , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Infiltração de Neutrófilos , Neutrófilos/metabolismo , Pneumonia/induzido quimicamente , Pneumonia/genética , Ratos , Análise de Sequência de RNA
3.
Angew Chem Int Ed Engl ; 61(32): e202204899, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35639417

RESUMO

The structural diversity of three-dimensional (3D) covalent organic frameworks (COFs) are limited as there are only a few choices of building units with multiple symmetrically distributed connection sites. To date, 4 and 6-connected stereoscopic nodes with Td , D3h , D3d and C3 symmetries have been mostly reported, delivering limited 3D topologies. We propose an efficient approach to expand the 3D COF repertoire by introducing a high-valency quadrangular prism (D4h ) stereoscopic node with a connectivity of eight, based on which two isoreticular 3D imine-linked COFs can be created. Low-dose electron microscopy allows the direct visualization of their 2-fold interpenetrated bcu networks. These 3D COFs are endowed with unique pore architectures and strong molecular binding sites, and exhibit excellent performance in separating C2 H2 /CO2 and C2 H2 /CH4 gas pairs. The introduction of high-valency stereoscopic nodes would lead to an outburst of new topologies for 3D COFs.

4.
Anim Sci J ; 93(1): e13725, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35508764

RESUMO

In the process of modern breeding, high-concentrate diets are widely used to meet the high energy nutritional requirements of animals but change the form of access to energy and nutrients and the way the organism metabolizes them. Goat psoas major (PM) muscle is a hybrid skeletal muscle whose characteristics are important for the motility and meat quality of goats. However, there are few studies on the effects of high-concentrate diets on the muscle type and metabolic characteristics of PM in goats. In this study, two treatment groups were set up: high concentrate group (HC) and control group (C). The expression of genes related to muscle type and metabolism of the PM was examined by quantitative PCR. The results showed that high concentrate promoted the conversion of PM fibers from intermediate to slow type at the mRNA level, improved the absorption, transport, and oxidation of fat by PM, and upregulated the expression of calpain system. These changes may be regulated by the involvement of differential expression of MSTN, Myf-5, and IGF-2. These results suggest that high concentrate may exert a positive effect on skeletal muscle function, metabolism, and meat quality in goats by affecting the expression of muscle type and metabolism-related genes.


Assuntos
Dieta , Cabras , Animais , Dieta/veterinária , Cabras/fisiologia , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
6.
J Am Chem Soc ; 144(14): 6475-6482, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35377630

RESUMO

Two-dimensional (2D) covalent organic frameworks (COFs) possess designable pore architectures but limited framework topologies. Until now, 2D COFs adopting the kgd topology with ordered and rhombic pore geometry have rarely been reported. Here, an isoreticular series of 2D COFs with the kgd topology and controllable pore size is synthesized by employing a C6-symmetric aldehyde, i.e., hexa(4-formylphenyl)benzene (HFPB), and C3-symmetric amines i.e., tris(4-aminophenyl)amine (TAPA), tris(4-aminophenyl)trazine (TAPT), and 1,3,5-tris[4-amino(1,1-biphenyl-4-yl)]benzene (TABPB), as building units, referred to as HFPB-TAPA, HFPB-TAPT, and HFPB-TABPB, respectively. The micropore dimension down to 6.7 Å is achieved in HFPB-TAPA, which is among the smallest pore size of reported 2D COFs. Impressively, both the in-plane network and stacking sequence of the 2D COFs can be clearly observed by low-dose electron microscopy. Integrating the unique kgd topology with small rhombic micropores, these 2D COFs are endowed with both short molecular diffusion length and favorable host-guest interaction, exhibiting potential for drug delivery with high loading and good release control of ibuprofen.


Assuntos
Estruturas Metalorgânicas , Benzeno , Sistemas de Liberação de Medicamentos
7.
Nat Commun ; 13(1): 1239, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35264586

RESUMO

Riemann surfaces are deformed versions of the complex plane in mathematics. Locally they look like patches of the complex plane, but globally, the topology may deviate from a plane. Nanostructured graphitic carbon materials resembling a Riemann surface with helicoid topology are predicted to have interesting electronic and photonic properties. However, fabrication of such processable and large π-extended nanographene systems has remained a major challenge. Here, we report a bottom-up synthesis of a metal-free carbon nanosolenoid (CNS) material with a low optical bandgap of 1.97 eV. The synthesis procedure is rapid and possible on the gram scale. The helical molecular structure of CNS can be observed by direct low-dose high-resolution imaging, using integrated differential phase contrast scanning transmission electron microscopy. Magnetic susceptibility measurements show paramagnetism with a high spin density for CNS. Such a π-conjugated CNS allows for the detailed study of its physical properties and may form the base of the development of electronic and spintronic devices containing CNS species.

8.
J Cell Mol Med ; 26(7): 1918-1931, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35122390

RESUMO

Lymphocytes and neutrophils are involved in the immune response against cancer. This study aimed to investigate the relationship between lymphocyte percentage/neutrophil percentage and the clinical characteristics of lung cancer patients, and to explore whether they could act as valuable predictors to ameliorate lung cancer prognosis. A total of 1312 patients were eligible to be recruited. Lymphocyte percentage and neutrophil percentage were classified based on their reference ranges. Survival curves were determined using Kaplan-Meier method, and univariate and multivariate cox regression analyses were performed to identify the significant predictors. Decision curve analysis was used to evaluate the clinical benefit. The results of both training and validation cohorts indicated that lymphocyte percentage exhibited high correlation with clinical characteristics and metastasis of lung cancer patients. Both lymphocyte percentage and neutrophil percentage were closely associated with survival status (all p < 0.0001). Low lymphocyte percentage could act as an indicator of poor prognosis; it offered a higher clinical benefit when combined with the clinical characteristic model. Our findings suggested that pretreatment lymphocyte percentage served as a reliable predictor of lung cancer prognosis, and it was also an accurate response indicator in lung adenocarcinoma and advanced lung cancer. Measurement of lymphocyte percentage improved the clinical utility of patient characteristics in predicting mortality of lung cancer patients.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/patologia , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Contagem de Linfócitos , Linfócitos/patologia , Neutrófilos/patologia , Curva ROC , Estudos Retrospectivos
9.
Mater Horiz ; 9(1): 383-392, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34586118

RESUMO

Recent advances in wearable and implantable electronics have increased the demand for biocompatible integrated energy storage systems. Conducting polymers, such as polyaniline (PANi), have been suggested as promising electrode materials for flexible biocompatible energy storage systems, based on their intrinsic structural flexibility and potential polymer chain compatibility with biological interfaces. However, due to structural disorder triggering insufficient electronic conductivity and moderate electrochemical stability, PANi still cannot fully satisfy the requirements for flexible and biocompatible energy storage systems. Herein, we report a biocompatible physiological electrolyte activated flexible supercapacitor encompassing crystalline tetra-aniline (c-TANi) as the active electrode material, which significantly enhances the specific capacitance and electrochemical cycling stability with chloride electrochemical interactions. The crystallization of TANi endows it with sufficient electronic conductivity (8.37 S cm-1) and a unique Cl- dominated redox charge storage mechanism. Notably, a fully self-healable and biocompatible supercapacitor has been assembled by incorporating polyethylene glycol (PEG) with c-TANi as a self-healable electrode and a ferric-ion cross-linked sodium polyacrylate (Fe3+-PANa)/0.9 wt% NaCl as a gel electrolyte. The as-prepared device exhibits a remarkable capacitance retention even after multiple cut/healing cycles. With these attractive features, the c-TANi electrode presents a promising approach to meeting the power requirements for wearable or implantable electronics.


Assuntos
Compostos de Anilina , Cloretos , Capacitância Elétrica , Eletrodos , Eletrólitos
10.
Comput Intell Neurosci ; 2021: 2087438, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721562

RESUMO

In this paper, based on the HS method and a modified version of the PRP method, a hybrid conjugate gradient (CG) method is proposed for solving large-scale unconstrained optimization problems. The CG parameter generated by the method is always nonnegative. Moreover, the search direction possesses the sufficient descent property independent of line search. Utilizing the standard Wolfe-Powell line search rule to yield the stepsize, the global convergence of the proposed method is shown under the common assumptions. Finally, numerical results show that the proposed method is promising compared with two existing methods.


Assuntos
Algoritmos , Plasma Rico em Plaquetas , Resolução de Problemas
11.
Nat Commun ; 12(1): 5770, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34599160

RESUMO

Metal/oxide interface is of fundamental significance to heterogeneous catalysis because the seemingly "inert" oxide support can modulate the morphology, atomic and electronic structures of the metal catalyst through the interface. The interfacial effects are well studied over a bulk oxide support but remain elusive for nanometer-sized systems like clusters, arising from the challenges associated with chemical synthesis and structural elucidation of such hybrid clusters. We hereby demonstrate the essential catalytic roles of a nanometer metal/oxide interface constructed by a hybrid Pd/Bi2O3 cluster ensemble, which is fabricated by a facile stepwise photochemical method. The Pd/Bi2O3 cluster, of which the hybrid structure is elucidated by combined electron microscopy and microanalysis, features a small Pd-Pd coordination number and more importantly a Pd-Bi spatial correlation ascribed to the heterografting between Pd and Bi terminated Bi2O3 clusters. The intra-cluster electron transfer towards Pd across the as-formed nanometer metal/oxide interface significantly weakens the ethylene adsorption without compromising the hydrogen activation. As a result, a 91% selectivity of ethylene and 90% conversion of acetylene can be achieved in a front-end hydrogenation process with a temperature as low as 44 °C.

12.
Nanotechnology ; 32(50)2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34587602

RESUMO

Increasing requirements for wearable devices stimulate the development of flexible energy storage components. Herein, a flexible integrated electrode consisting of SnS2nanosheet arraysin situanchored on the functionalized carbon cloth was prepared via a facile one-step hydrothermal method. Through pretreatment of carbon cloth, rough morphology is appeared on the surface of carbon fiber, which is conducive to optimizing the accessible load of SnS2. The SnS2nanosheet arrays and the carbon fiber as conductive skeleton cooperate with each other to provide a highly open surface, leading to the enhancement in capacitance (194.4 mF cm-2) and the outstanding retention after long-term service (86.5% after 10 000 cycles). A quasi-solid-state asymmetric flexible supercapacitor was assembled to evaluate the practical application under various conditions, suggesting satisfactory electrochemical performance as a maximum energy density of 10.95µWh cm-2at the power density of 4.75 mW cm-2and mechanical stability under actual conditions.

13.
Front Immunol ; 12: 613365, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149681

RESUMO

Hyla annectans is a tree frog living in the southwestern plateau area of China where there is strong ultraviolet radiation and long duration of sunshine. So their naked skin may possess chemical defense components that protect it from acute photo-damage. However, no such peptide or components has been identified till to date. In the current work, two novel peptides (FW-1, FWPLI-NH2 and FW-2, FWPMI-NH2) were identified from the skin of the tree frog. Five copies of FW-1 and four copies of FW-2 are encoded by an identical gene and released from the same protein precursor, which possess 167 amino acid residues. FW-1 and -2 can exert significant anti-inflammatory functions by directly inhibiting Ultraviolet B irradiation (UVB)-induced secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). They may achieve this function by modulating the UV-induced stress signaling pathways such as Mitogen-activated protein kinases (MAPK) and Nuclear Factor Kappa B (NF-κB). Besides, FW-1 and -2 showed potential antioxidant effects on epidermis by attenuating the UVB-induced reactive oxygen species (ROS) production through an unknown mechanism. Considering small peptides' easy production, storage, and potential photo-protective activity, FW-1/2 might be exciting leading compounds or templates for the development of novel pharmacological agents for the suppression of UVB-induced skin inflammation. Moreover, this study might expand our knowledge on skin defensive mechanism of tree frog upon UVB irradiation.


Assuntos
Proteínas de Anfíbios/metabolismo , Anti-Inflamatórios/metabolismo , Queratinócitos/fisiologia , Peptídeos/metabolismo , Pele/metabolismo , Raios Ultravioleta/efeitos adversos , Proteínas de Anfíbios/genética , Animais , Antioxidantes , Anuros , China , Clonagem Molecular , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Peptídeos/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Pele/patologia , Fator de Necrose Tumoral alfa/metabolismo
14.
Adv Mater ; 33(29): e2006836, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34096113

RESUMO

Macromolecular films are crucial functional materials widely used in the fields of mechanics, electronics, optoelectronics, and biology, due to their superior properties of chemical stability, small density, high flexibility, and solution-processing ability. Their electronic and mechanical properties, however, are typically much lower than those of crystalline materials, as the macromolecular films have no long-range structural ordering. The state-of-the-art for producing highly ordered macromolecular films is still facing a great challenge due to the complex interactions between adjacent macromolecules. Here, the growth of textured macromolecular films on a designed graphene/high-index copper (Cu) surface is demonstrated. This successful growth is driven by a patterned potential that originates from the different amounts of charge transfer between the graphene and Cu surfaces with, alternately, terraces and step edges. The textured films exhibit a remarkable improvement in remnant ferroelectric polarization and fracture strength. It is also demonstrated that this growth mechanism is universal for different macromolecules. As meter-scale graphene/high-index Cu substrates have recently become available, the results open a new regime for the production and applications of highly ordered macromolecular films with obvious merits of high production and low cost.

15.
J Am Chem Soc ; 143(17): 6681-6690, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33887909

RESUMO

A bottom-up chemical synthesis of metal-organic frameworks (MOFs) permits significant structural diversity because of various combinations of metal centers and different organic linkers. However, fabrication generally complies with the classic hard and soft acids and bases (HSAB) theory. This restricts direct synthesis of desired MOFs with converse Lewis type of metal ions and ligands. Here we present a top-down strategy to break this limitation via the structural cleavage of MOFs to trigger a phase transition using a novel "molecular scalpel". A conventional CuBDC MOF (BDC = 1,4-benzenedicarboxylate) prepared from a hard acid (Cu2+) metal and a hard base ligand was chemically cleaved by l-ascorbic acid acting as chemical scalpel to fabricate a new Cu2BDC structure composed of a soft acid (Cu1+) and a hard base (BDC). Controlled phase transition was achieved by a series of redox steps to regulate the chemical state and coordination number of Cu ions, resulting in a significant change in chemical composition and catalytic activity. Mechanistic insights into structural cleavage and rearrangement are elaborated in detail. We show this novel strategy can be extended to general Cu-based MOFs and supramolecules for nanoscopic casting of unique architectures from existing ones.

16.
Sci Adv ; 7(13)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33762332

RESUMO

Metallic nanostructures are commonly densely packed into a few packing variants with slightly different atomic packing factors. The structural aspects and physicochemical properties related with the vacancies in such nanostructures are rarely explored because of lack of an effective way to control the introduction of vacancy sites. Highly voided metallic nanostructures with ordered vacancies are however energetically high lying and very difficult to synthesize. Here, we report a chemical method for synthesis of hierarchical Rh nanostructures (Rh NSs) composed of ultrathin nanosheets, composed of hexagonal close-packed structure embedded with nanodomains that adopt a vacated Barlow packing with ordered vacancies. The obtained Rh NSs exhibit remarkably enhanced electrocatalytic activity and stability toward the hydrogen evolution reaction (HER) in alkaline media. Theoretical calculations reveal that the exceptional electrocatalytic performance of Rh NSs originates from their unique vacancy structures, which facilitate the adsorption and dissociation of H2O in the HER.

17.
J Am Chem Soc ; 143(13): 5201-5211, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33764061

RESUMO

Noble metals manifest themselves with unique electronic structures and irreplaceable activity toward a wide range of catalytic applications but are unfortunately restricted by limited choice of geometric structures spanning single atoms, clusters, nanoparticles, and bulk crystals. Herein, we propose how to overcome this limitation by integrating noble metal atoms into the lattice of transition metal oxides to create a new type of hybrid structure. This study shows that iridium single atoms can be accommodated into the cationic sites of cobalt spinel oxide with short-range order and an identical spatial correlation as the host lattice. The resultant Ir0.06Co2.94O4 catalyst exhibits much higher electrocatalytic activity than the parent oxide by 2 orders of magnitude toward the challenging oxygen evolution reaction under acidic conditions. Because of the strong interaction between iridium and cobalt oxide support, the Ir0.06Co2.94O4 catalyst shows significantly improved corrosion resistance under acidic conditions and oxidative potentials. This work eliminates the "close-packing" limitation of noble metals and offers promising opportunity to create analogues with desired topologies for various catalytic applications.

18.
Angew Chem Int Ed Engl ; 60(19): 10614-10619, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33635599

RESUMO

The 3d-transition-metal (hydro)oxides belong to a group of highly efficient, scalable and inexpensive electrocatalysts for widespread energy-related applications that feature easily tailorable crystal and electronic structures. We propose a general strategy to further boost their electrocatalytic activities by introducing organic ligands into the framework, considering that most 3d-metal (hydro)oxides usually exhibit quite strong binding with reaction intermediates and thus compromised activity due to the scaling relations. Involving weakly bonded ligands downshifts the d-band center, which narrows the band gap, and optimizes the adsorption of these intermediates. For example, the activity of the oxygen evolution reaction (OER) can be greatly promoted by ≈5.7 times over a NiCo layered double hydroxide (LDH) after a terephthalic acid (TPA)-induced conversion process, arising from the reduced energy barrier of the deprotonation of OH* to O*. Impressively, the proposed ligand-induced conversion strategy is applicable to a series of 3d-block metal (hydro)oxides, including NiFe2 O4 , NiCo2 O4 , and NiZn LDH, providing a general structural upgrading scheme for existing high-performance electrocatalytic systems.

19.
Carcinogenesis ; 42(2): 243-253, 2021 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32808032

RESUMO

Apelin acts as a tumor promoter in multiple malignant tumors; however, its regulatory mechanism remains unclear. Previous studies have indicated that exosomes are pivotal to mediating tumor progression and metastasis. This study examined whether apelin enhances proliferation and invasion ability of lung cancer cells via exosomal microRNA (miRNA). Lung cancer A549 cells overexpressing apelin and control vector were generated by lentiviral transfection. Exosomes were isolated from the culture supernatant of each cell group and characterized. A-exo and V-exo were, respectively, cocultured with A549 cells, and assays of proliferation, apoptosis, colony formation and invasion were conducted. Exosomal miRNA sequencing (miRNA-seq) was performed on A-exo and V-exo to select a candidate miRNA. It was found that A549 cells absorbed more A-exo than V-exo, and A-exo could promote proliferation, colony formation, migration and invasion of A549 cells more than V-exo. Exosomal miRNA-seq data revealed that miR-15a-5p was markedly lower in A-exo compared with V-exo. Low expression of miR-15a-5p was also found in lung cancer tissues and cell lines, suggesting that miR-15a-5p may have an anti-tumor role. Overexpression of miR-15a-5p in A549 cells was associated with less cell proliferation, migration, invasion and suppressed cell cycle, and lower amounts of CDCA4 (cell division cycle-associated protein 4) indicated that it may be a potential target for miR-15a-5p. This study elucidated a novel regulatory mechanism that apelin may promote proliferation and invasion of lung cancer cells by inhibiting miR-15a-5p encapsulated in exosomes.


Assuntos
Apelina/metabolismo , Proteínas de Ciclo Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/antagonistas & inibidores , Células A549 , Apoptose/genética , Movimento Celular/genética , Proliferação de Células/genética , Técnicas de Cocultura , Regulação para Baixo , Exossomos/metabolismo , Humanos , Neoplasias Pulmonares/patologia , MicroRNAs/agonistas , MicroRNAs/metabolismo , RNA-Seq
20.
PLoS Negl Trop Dis ; 14(8): e0008660, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866199

RESUMO

Aedes mosquitoes can transmit dengue and several other severe vector-borne viral diseases, thereby influencing millions of people worldwide. Insects primarily control and clear the viral infections via their innate immune systems. Mitogen-Activated Protein Kinases (MAPKs) and antimicrobial peptides (AMPs) are both evolutionarily conserved components of the innate immune systems. In this study, we investigated the role of MAPKs in Aedes mosquitoes following DENV infection by using genetic and pharmacological approaches. We demonstrated that knockdown of ERK, but not of JNK or p38, significantly enhances the viral replication in Aedes mosquito cells. The Ras/ERK signaling is activated in both the cells and midguts of Aedes mosquitoes following DENV infection, and thus plays a role in restricting the viral infection, as both genetic and pharmacological activation of the Ras/ERK pathway significantly decreases the viral titers. In contrast, inhibition of the Ras/ERK pathway enhances DENV infection. In addition, we identified a signaling crosstalk between the Ras/ERK pathway and DENV-induced AMPs in which defensin C participates in restricting DENV infection in Aedes mosquitoes. Our results reveal that the Ras/ERK signaling pathway couples AMPs to mediate the resistance of Aedes mosquitoes to DENV infection, which provides a new insight into understanding the crosstalk between MAPKs and AMPs in the innate immunity of mosquito vectors during the viral infection.


Assuntos
Aedes/virologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Vírus da Dengue/imunologia , Quinases de Proteína Quinase Ativadas por Mitógeno/farmacologia , Mosquitos Vetores/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Linhagem Celular , Sistema Digestório/virologia , Feminino , Perfilação da Expressão Gênica , Técnicas de Silenciamento de Genes , Imunidade Inata , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Mosquitos Vetores/virologia , Carga Viral , Replicação Viral/efeitos dos fármacos
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