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1.
J Ethnopharmacol ; 282: 114654, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34537283

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Luteolin (Lut) was recently identified as the major active ingredient of Mosla scabra, which was a typical representative traditional Chinese medicine and had been used to treat pulmonary diseases for thousands of years. AIM OF THE STUDY: This study was to explore the effects and relative mechanisms of Lut in LPS-induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The main characteristic of ALI/ARDS is pulmonary edema, and epithelial sodium channel (ENaC) is a key factor in effective removal of excessive alveolar edematous fluid, which is essential for repairing gas exchange and minimizing damage to the peripheral tissues. However, whether the therapeutic effects of Lut on respiratory diseases are relative with ENaC is still unknown. MATERIALS AND METHODS: Alveolar fluid clearance was calculated in BALB/c mice and ENaC function was measured in H441 cells. Moreover, ENaC membrane protein and mRNA were detected by Western blot and real-time PCR, respectively. We also studied the involvement of cGMP/PI3K pathway during the regulation of Lut on ENaC during LPS-induced ALI/ARDS by ELISA method and applying cGMP/PI3K inhibitors/siRNA. RESULTS: The beneficial effects of Lut in ALI/ARDS were evidenced by the alleviation of pulmonary edema, and enhancement of both amiloride-sensitive alveolar fluid clearance and short-circuit currents. Lut could alleviate the LPS decreased expression levels of ENaC mRNA and membrane protein in H441 cells and mouse lung. In addition, cGMP concentration was increased after the administration of Lut in ALI/ARDS mice, while the inhibition of cGMP/PI3K pathway could abrogate the enhanced AFC and ENaC protein expression of Lut. CONCLUSION: These results implied that Lut could attenuate pulmonary edema via enhancing the abundance of membrane ENaC at least partially through the cGMP/PI3K pathway, which could provide a promising therapeutic strategy for treating ALI/ARDS.

2.
J Integr Neurosci ; 20(3): 529-539, 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34645086

RESUMO

Rab3a, a subtype protein in the Rab3 family amongst the small G proteins, is closely associated with the learning and memory formation process. Various neuronal stimuli can induce the expression of Rab3a; however, how DNA modification is involved in regulating its expression is not fully understood. Ten-eleven translocation (TET) proteins can oxidate methylcytosine to hydroxymethylcytosine, which can further activate gene expression. Previous studies reported that TET-mediated regulation of 5hmC induced by learning is involved in neuronal activation. However, whether Tet protein regulates Rab3a is unknown. To understand the role of TET-mediated 5hmC on Rab3a in neuronal activation, we adopted a KCl-induced depolarization protocol in cultured primary cortical neurons to mimic neuronal activity in vitro. After KCl treatment, Rab3a and Tet3 mRNA expression were induced. Moreover, we observed a decrease in the methylation level and an increase of hydroxymethylation level surrounding the CpG island near the transcription start site of Rab3a. Furthermore, recently, Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) has proven powerful in identifying open chromatin in the genome of various eukaryotes. Using FAIRE-qPCR, we observed a euchromatin state and the increased occupancy of Tet3, H3K4me3, and H3K27ac at the promoter region of Rab3a after KCl treatment. Finally, by using shRNA to knockdown Tet3 prior KCl treatment, all changes mentioned above vanished. Thus, our findings elucidated that the neuronal activity-induced accumulation of hydroxymethylation, which Tet3 mediates, can introduce an active and permissive chromatin structure at Rab3a promoter and lead to the induction of Rab3a mRNA expression.

3.
Adv Mater ; : e2105803, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34647376

RESUMO

Non-halogenated polymers have great potential in commercialization of organic photovoltaic (OPV) cells due to their advantage in low-cost preparation. However, non-halogenated polymers usually have high HOMO energy levels and inferior self-aggregation properties in solution, thus resulting in low power conversion efficiencies (PCEs). Herein, two non-halogenated polymers, PB1 and PB2, are prepared. When the polymers were used to fabricate OPV cells with the BTP-eC9, the PB1-based device only gave a PCE of 5.3%, while the PB2-based device showed an outstanding PCE of 17.7%. After the introduction of PBDB-TF as the third component, the PB2:PBDB-TF:BTP-eC9-based device with an optimal weight ratio of 0.5:0.5:1 achieved a PCE up to 18.4%. More importantly, PB2 exhibited good compatibility with various non-fullerene acceptors to achieve better PCEs than those of classical polymer (PBDB-T and PBDB-TF)-based devices. When PB2 was combined with wide bandgap electron acceptor (F-BTA3), this device showed the excellent PCE of 27.1% and 24.6% for 1 and 10 cm2 devices, respectively, under light intensity of 1000 lux light-emitting diode illumination. These results provide new insight in the rational design of novel non-halogenated polymer donors for further developing low-cost materials and broadening the application of OPV cells. This article is protected by copyright. All rights reserved.

4.
Adv Mater ; : e2106732, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34636085

RESUMO

Top-performance organic solar cells (OSCs) consisting of conjugated polymer donors and nonfullerene small molecule acceptors (NF-SMAs) deliver rapid increases in efficiencies. Nevertheless, many of the polymer donors exhibit high stiffness and small molecule acceptors are very brittle, which limit their applications in wearable devices. Here, a simple and effective strategy is reported to improve the stretchability and reduce the stiffness of high-efficiency polymer:NF-SMA blends and simultaneously maintain the high efficiency by incorporating a low-cost commercial thermoplastic elastomer, polystyrene-block-poly(ethylene-ran-butylene)-block-polystyrene (SEBS). The microstructure, mechanical properties, and photovoltaic performance of PM6:N3 with varied SEBS contents and the molecular weight dependence of SEBS on microstructure and mechanical properties are thoroughly characterized. This strategy for mechanical performance improvement exhibits excellent applicability in some other OSC blend systems, e.g., PBQx-TF:eC9-2Cl and PBDB-T:ITIC. More crucially, the elastic modulus of such complex ternary blends can be nicely predicted by a mechanical model. Therefore, incorporating thermoplastic elastomers is a widely applicable and cost-effective strategy to improve mechanical properties of nonfullerene OSCs and beyond.

5.
Artigo em Chinês | MEDLINE | ID: mdl-34628780

RESUMO

BACKGROUND: With the extensive development of minimally invasive surgery for pulmonary nodules, preoperative localization becomes more and more critical. There are some defects in traditional localization methods, so it is necessary to improve. The aim of this study was to compare and analyze the safety and effectiveness of two new methods, namely four-hook needle and memory alloy coil, in the localization of pulmonary nodules. METHODS: A retrospective analysis of 152 patients was performed. 76 cases were in four-hook needle group, 76 cases were in memory alloy coil group. Pulmonary nodules were located before operation, and then video-assisted wedge resection was performed. The average procedure time, localization complications and nodule resection time were counted. RESULTS: The target pulmonary nodules were successfully removed in both groups. In four-hook needle group, 76 patients found localization devices, all the pulmonary nodules were successfully removed, and one case was transferred to open the chest for wedge resection of pulmonary nodules due to severe thoracic adhesion. All 76 patients in memory alloy coil group were successfully resected with pulmonary nodules, and one patient underwent compromising enlarged resection because no lesion was found after the specimen was removed during the operation. There was no significant difference in the incidence of pneumothorax and pulmonary hemorrhage, the success rate of localization and nodule wedge resection time between the two groups. The average time of localization in four-hook needle group was (13.66±3.11) min lower than that of memory alloy coil group (15.51±3.65) min, and the difference was statistically significant (P=0.001). In memory alloy coil group, when the distance from the nodule to the pleura was ≥1.5 cm and <1.5 cm, the average localization time was (17.20±4.46) min and (14.91±3.15) min, respectively, and there was a statistical difference between the two (P=0.044). CONCLUSIONS: Four-hook needle and memory alloy coil have good safety and effectiveness, and the localization time of four-hook needle is shorter. When using memory alloy coil, the effect of the method is better for pulmonary nodules with a distance less than 1.5 cm to pleura.

6.
China CDC Wkly ; 3(19): 405-408, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-34594894

RESUMO

What is already known on this topic? Contact tracing and testing with isolated medical care of identified cases is a key strategy for interrupting chains of transmission of COVID-19 and reducing mortality associated with COVID-19. At the early phases of the COVID-19 pandemic, due to test capacity limitations, case finding often started from suspected cases. What is added by this report? The index patient infected 74 individuals who were close contacts that were identified through contact tracing, and exposed individuals were monitored in quarantine with daily polymerase chain reaction (PCR) testing. All individuals were asymptomatic initially, but all PCR-positive individuals eventually developed symptoms. Infectivity was documented up to 8 days before being confirmed as a symptomatic case, approximately 4 days before turning PCR positive. What are the implications for public health practice? During an outbreak, we suggest tracing close contacts from both PCR-positive individuals and suspected cases, rather than from suspected cases alone. Due to the long period of infectivity before turning PCR positive or developing symptoms, close contacts that had contact with a newly PCR positive case within 4 days should be judged as at risk of being infected; close contacts that had contact within 8 days of a newly symptomatic case should be judged as at risk being infected.

7.
J Am Chem Soc ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34618443

RESUMO

The exploration of chiral crystalline porous materials, such as metal-organic complexes (MOCs) or metal-organic frameworks (MOFs), has been one of the most exciting recent developments in materials science owing to their widespread applications in enantiospecific processes. However, achieving specific tight-affinity binding and remarkable enantioselectivity toward important biomolecules is still challenging. Perhaps most critically, the lack of adaptability, compatibility, and processability in these materials severely impedes practical applications in chemical engineering and biological technology. In this Perspective, artificial metal-peptide assemblies (MPAs), which are achieved by the assembly of peptides and metals with nanometer-sized cavities or pores, is a new development that could address the current bottlenecks of chiral porous materials. Bioinspired assembly of pore-forming MPAs is not foreign to biological systems and has granted scientists an unprecedented level of control over the chiral recognition sites, conformational flexibility, cavity sizes, and hydrophilic segments through ultrafine-tuning of peptide-derived linkers. We will specifically discuss exemplary MPAs including structurally well-defined metal-peptide complexes and highly crystalline metal-peptide frameworks. With insights from these structures, the peptide assembly and folding by the closer cooperation of metal coordination and noncovalent interactions can create adaptable protein-like nanocavities undergoing a myriad of conformational variations that is reminiscent of enzymatic pockets. We also consider challenges to advancing the field, where the deployment of side-chain groups and manipulation of amino acid sequences are more likely to access the programmable, genetically encodable peptide-mediated porous materials, thus contributing to the enhanced enantioselective recognition as well as enabling key biochemical processes in next-generation versatile biomimetic materials.

8.
Small ; : e2103497, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34622540

RESUMO

Layer-by-layer (LBL) deposition strategy enabling favorable vertical phase distributions has been regarded as promising candidates for constructing high-efficient organic photovoltaic (OPV) cells. However, solid additives with the merits of good stability and reproducibility have been rarely used to fine-tune the morphology of the LBL films for improved efficiency and stability. Herein, hierarchical morphology control in LBL OPV is achieved via a dual functional solid additive. Series of LBL devices are fabricated by introducing the solid additive individually or simultaneously to the donor or acceptor layer to clarify the functions of additives. Additive in the donor layer can facilitate the formation of preferable vertical component distribution, and that in the acceptor layer will enhance the molecular crystallinity for better charge transport properties. The optimized morphology ultimately contributed to high PCEs of 16.4% and 17.4% in the binary and quaternary LBL devices. This reported method provides an alternative way to controllably manipulate the morphology of LBL OPV cells.

10.
J Cell Mol Med ; 25(19): 9402-9410, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34472704

RESUMO

Apoptosis plays a key role in keloids. Growth arrest and DNA damage-inducible gene 153 (GADD153) is regulated by apoptosis. Botulinum toxin type A (BTXA) can induce apoptosis in keloid fibroblasts. This research aimed to explore the hypothesis that GADD153 mediates apoptosis in keloid fibroblasts exposed to BTXA. BTXA significantly induced GADD153 protein and mRNA expression in keloid fibroblasts. Treatment with c-Jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA) and tumour necrosis factor-alpha (TNF-α) antibodies reversed the BTXA-induced GADD153 expression. BTXA enhanced the transcriptional activity of GADD153, whereas the GADD153 mutant plasmid, JNK siRNA and anti-TNF-α antibody treatment abolished the BTXA-induced transcriptional activity of GADD153. The addition of TNF-α to keloid fibroblasts markedly increased GADD153 protein expression. The addition of GADD153 siRNA, SP600125 and anti-TNF-α antibodies reversed cell death and caspase 3 and 9 activity induced by BTXA.

11.
Adv Mater ; 33(43): e2103091, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34510580

RESUMO

The donor:acceptor heterojunction has proved as the most successful approach to split strongly bound excitons in organic solar cells (OSCs). Establishing an ideal architecture with selective carrier transport and suppressed recombination is of great importance to improve the photovoltaic efficiency while remains a challenge. Herein, via tailoring a hybrid planar/bulk structure, highly efficient OSCs with reduced energy losses (Eloss s) are fabricated. A p-type benzodithiophene-thiophene alternating polymer and an n-type naphthalene imide are inserted on both sides of a mixed donor:acceptor active layer to construct the hybrid heterojunction, respectively. The tailored structure with the donor near the anode and the acceptor near the cathode is beneficial for obtaining enhanced charge transport, extraction, and suppressed charge recombination. As a result, the photovoltaic characterizations suggest a reduced nonradiative Eloss by 25 meV, and the best OSC records a high efficiency of 18.5% (certified as 18.2%). This study highlights that precisely regulating the structure of donor:acceptor heterojunction has the potential to further improve the efficiencies of OSCs.

12.
Zool Res ; 42(5): 637-649, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34472225

RESUMO

The insect brain is the central part of the neurosecretory system, which controls morphology, physiology, and behavior during the insect's lifecycle. Lepidoptera are holometabolous insects, and their brains develop during the larval period and metamorphosis into the adult form. As the only fully domesticated insect, the Lepidoptera silkworm Bombyx mori experienced changes in larval brain morphology and certain behaviors during the domestication process. Hormonal regulation in insects is a key factor in multiple processes. However, how juvenile hormone (JH) signals regulate brain development in Lepidoptera species, especially in the larval stage, remains elusive. We recently identified the JH receptor Methoprene tolerant 1 ( Met1) as a putative domestication gene. How artificial selection on Met1 impacts brain and behavioral domestication is another important issue addressing Darwin's theory on domestication. Here, CRISPR/Cas9-mediated knockout of Bombyx Met1 caused developmental retardation in the brain, unlike precocious pupation of the cuticle. At the whole transcriptome level, the ecdysteroid (20-hydroxyecdysone, 20E) signaling and downstream pathways were overactivated in the mutant cuticle but not in the brain. Pathways related to cell proliferation and specialization processes, such as extracellular matrix (ECM)-receptor interaction and tyrosine metabolism pathways, were suppressed in the brain. Molecular evolutionary analysis and in vitro assay identified an amino acid replacement located in a novel motif under positive selection in B. mori, which decreased transcriptional binding activity. The B. mori MET1 protein showed a changed structure and dynamic features, as well as a weakened co-expression gene network, compared with B. mandarina. Based on comparative transcriptomic analyses, we proposed a pathway downstream of JH signaling (i.e., tyrosine metabolism pathway) that likely contributed to silkworm larval brain development and domestication and highlighted the importance of the biogenic amine system in larval evolution during silkworm domestication.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Bombyx/metabolismo , Proteínas de Insetos/metabolismo , Hormônios Juvenis/metabolismo , Sequência de Aminoácidos , Animais , Sequência de Bases , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Bombyx/crescimento & desenvolvimento , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Sistemas CRISPR-Cas , Deleção de Genes , Regulação da Expressão Gênica no Desenvolvimento , Genótipo , Proteínas de Insetos/genética , Tegumento Comum/fisiologia , Larva/crescimento & desenvolvimento , Larva/metabolismo , Filogenia , Conformação Proteica
13.
Thorac Cancer ; 12(19): 2614-2617, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34505347

RESUMO

Latent intracranial meningeal metastases (IMM) of lung cancer is difficult to determine, yet it is critical to do so given that it impacts the treatment agent. Studies on this disease are rare, thus necessitating further investigation. As a case study, we will explore the application of optic neuroimaging in IMM. A 62-year-old female patient was diagnosed with lung adenocarcinoma, which had progressed to osseous metastasis. During the course of chemotherapy, the patient had bilateral vision loss and paralysis of extraocular muscles. Ophthalmologists ruled out disease of the retina and suspected intracranial metastasis; however, brain-enhanced magnetic resonance angiography and magnetic resonance venography were normal. Given the patient's severe osteoarthropathy and poor physical condition, she refused to undergo a lumbar puncture examination. Optic neuro-ophthalmology imaging was ultimately used. Utilizing optical coherence tomography, we found that the basement membrane layer in the papilledema was protruding up towards the vitreous cavity. To assist in visualization, the optic nerve sheath was enhanced with optic magnetic resonance imaging. With these methods, the dural metastasis was identified, the treatment agent was changed for the patient, and she had a successful recovery. Thus, optic neuro-ophthalmology imaging should be recommended for patients who are in the latent course of dural metastasis, and it could also be used to evaluate therapeutic efficacy.

14.
J Healthc Eng ; 2021: 5790416, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34531966

RESUMO

Background: E2F transcription factors is a family of transcription factors, and lots of studies have shown that they play a key role in the occurrence and development of many tumors. However, the association between expression, prognostic value, and immune infiltration in the tumor microenvironment of the eight E2Fs members in ccRCC is still unclear. Method: s. We used online databases, such as ONCOMINE, UALCAN, Kaplan-Meier plotter, GEPIA, Metascape, TIMER, and cBioPortal, to analyze the effect of mRNA expression of E2Fs family members in ccRCC on the prognosis of patients and the relationship with immune infiltration. Results: Except for E2F5, other seven members of the family of E2Fs mRNA expression levels in ccRCC tissues were significantly higher than control tissues. And the high expression of E2Fs mRNA in ccRCC patients was related to cancer stage and tumor grade. Survival analysis results suggested that elevated mRNA expression levels of E2F1/2/3/4/7/8 were significantly related to the shorter overall survival (OS) in ccRCC patients (P = 3.9E - 06), while high mRNA expression of E2F6 is not related to OS (P = 0.061). Mutations of E2Fs were correlated with shorter OS of ccRCC patients (P = 7.094E - 5). In addition, mRNA expression of E2F1/2/3/4/7/8 was positively correlated with infiltration of six types of immune cells, including B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells. Conclusions: These results indicate that E2F1/2/3/4/7/8 may be used as a prognostic marker for the survival of ccRCC patients and laid the foundation for studying the immune infiltration role of E2Fs family members in tumors.

15.
J Am Chem Soc ; 143(36): 14869-14876, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34463501

RESUMO

Physical separation of C2H2 from CO2 on metal-organic frameworks (MOFs) has received substantial research interest due to the advantages of simplicity, security, and energy efficiency. However, that C2H2 and CO2 exhibit very close physical properties makes their separation exceptionally challenging. Previous work appeared to mostly focused on introducing open metal sites that aims to enhance the C2H2 affinity at desired sites, whereas the reticular manipulation of organic components has rarely been investigated. In this work, by reticulating preselected amino and hydroxy functionalities into isostructural ultramicroporous chiral MOFs-Ni2(l-asp)2(bpy) (MOF-NH2) and Ni2(l-mal)2(bpy) (MOF-OH)-we targeted efficient C2H2 uptake and C2H2/CO2 separation, which outperforms most benchmark materials. Explicitly, MOF-OH adsorbs substantial amount of C2H2 with record storage density of 0.81 g mL-1 at ambient conditions, which even exceeds the solid density of C2H2 at 189 K. In addition, MOF-OH gave IAST selectivity of 25 toward equimolar mixture of C2H2/CO2, which is nearly twice higher than that of MOF-NH2. Notably, the adsorption enthalpies for C2H2 at zero converge in both MOFs are remarkably low (17.5 kJ mol-1 for MOF-OH and 16.7 kJ mol-1 for MOF-NH2), which to our knowledge are the lowest among efficient rigid C2H2 sorbents. The efficiencies of both MOFs for the separation of C2H2/CO2 are validated by multicycle breakthrough experiments. DFT calculations provide molecular-level insight over the adsorption/separation mechanism. Moreover, MOF-OH can survive in boiling water for at least 1 week and can be easily scaled up to kilograms eco-friendly and economically, which is very crucial for potential industrial implementation.

16.
J Integr Plant Biol ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427970

RESUMO

Chloroplast biogenesis requires the coordinated expression of chloroplast and nuclear genes. Here, we show that EMB1270, a plastid-localized pentatricopeptide repeat (PPR) protein, is required for chloroplast biogenesis in Arabidopsis thaliana. Knockout of EMB1270 led to embryo arrest, whereas a mild knockdown mutant of EMB1270 displayed a virescent phenotype. Almost no photosynthetic proteins accumulated in the albino emb1270 knockout mutant. By contrast, in the emb1270 knockdown mutant, the levels of ClpP1 and photosystem I (PSI) subunits were significantly reduced, whereas the levels of photosystem II (PSII) subunits were normal. Furthermore, the splicing efficiencies of the clpP1.2, ycf3.1, ndhA, and ndhB plastid introns were dramatically reduced in both emb1270 mutants. RNA immunoprecipitation revealed that EMB1270 associated with these introns in vivo. In an RNA electrophoretic mobility shift assay (REMSA), a truncated EMB1270 protein containing the 11 N-terminal PPR motifs bound to the predicted sequences of the clpP1.2, ycf3.1, and ndhA introns. In addition, EMB1270 specifically interacted with CRM Family Member 2 (CFM2). Given that CFM2 is known to be required for splicing the same plastid RNAs, our results suggest that EMB1270 associates with CFM2 to facilitate the splicing of specific group II introns in Arabidopsis.

17.
Adv Mater ; 33(41): e2102420, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34464466

RESUMO

Improving power conversion efficiency (PCE) is important for broadening the applications of organic photovoltaic (OPV) cells. Here, a maximum PCE of 19.0% (certified value of 18.7%) is achieved in single-junction OPV cells by combining material design with a ternary blending strategy. An active layer comprising a new wide-bandgap polymer donor named PBQx-TF and a new low-bandgap non-fullerene acceptor (NFA) named eC9-2Cl is rationally designed. With optimized light utilization, the resulting binary cell exhibits a good PCE of 17.7%. An NFA F-BTA3 is then added to the active layer as a third component to simultaneously improve the photovoltaic parameters. The improved light unitization, cascaded energy level alignment, and enhanced intermolecular packing result in open-circuit voltage of 0.879 V, short-circuit current density of 26.7 mA cm-2 , and fill factor of 0.809. This study demonstrates that further improvement of PCEs of high-performance OPV cells requires fine tuning of the electronic structures and morphologies of the active layers.

18.
Front Bioeng Biotechnol ; 9: 640116, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368091

RESUMO

Background: One of the characteristics of acute lung injury (ALI) is severe pulmonary edema, which is closely related to alveolar fluid clearance (AFC). Mesenchymal stem cells (MSCs) secrete a wide range of cytokines, growth factors, and microRNA (miRNAs) through paracrine action to participate in the mechanism of pulmonary inflammatory response, which increase the clearance of edema fluid and promote the repair process of ALI. The epithelial sodium channel (ENaC) is the rate-limiting step in the sodium-water transport and edema clearance in the alveolar cavity; the role of bone marrow-derived MSC-conditioned medium (BMSC-CM) in edema clearance and how miRNAs affect ENaC are still seldom known. Methods: CCK-8 cell proliferation assay was used to detect the effect of BMSC-CM on the survival of alveolar type 2 epithelial (AT2) cells. Real-time polymerase chain reaction (RT-PCR) and western blot were used to detect the expression of ENaC in AT2 cells. The effects of miR-34c on lung fluid absorption were observed in LPS-treated mice in vivo, and the transepithelial short-circuit currents in the monolayer of H441 cells were examined by the Ussing chamber setup. Dual luciferase reporter gene assay was used to detect the target gene of miR-34c. Results: BMSC-CM could increase the viability of mouse AT2 cells. RT-PCR and western blot results showed that BMSC-CM significantly increased the expression of the γ-ENaC subunit in mouse AT2 cells. MiR-34c could restore the AFC and lung wet/dry weight ratio in the ALI animal model, and Ussing chamber assay revealed that miR-34c enhanced the amiloride-sensitive currents associated with ENaC activity in intact H441 cell monolayers. In addition, we observed a higher expression of miR-34c in mouse AT2 cells administrated with BMSC-CM, and the overexpression or inhibition of miR-34c could regulate the expression of ENaC protein and alter the function of ENaC. Finally, we detected that myristoylated alanine-rich C kinase substrate (MARCKS) may be one of the target genes of miR-34c. Conclusion: Our results indicate that BMSC-CM may alleviate LPS-induced ALI through miR-34c targeting MARCKS and regulate ENaC indirectly, which further explores the benefit of paracrine effects of bone marrow-derived MSCs on edematous ALI.

19.
Front Pharmacol ; 12: 732540, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393805

RESUMO

Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease that has a poor prognosis. Abnormal activation of transforming growth factor-ß1 (TGF-ß1) plays a crucial role in fibroblast differentiation. Mesenchymal stem cells (MSCs) are currently being considered for the treatment of PF, but the regulatory mechanisms are poorly understood. We co-cultured bone marrow-derived MSCs and mouse lung fibroblasts (MLg) in the presence of TGF-ß1, and studied the protein/mRNA expression of fibrosis markers and related signaling pathways. The effects of miR-130a-3p and TGF-ß receptor II (TGF-ßRII) on the differentiation of MLg induced by TGF-ß1 were studied using immunofluorescence assay, Western blot, and quantitative real-time PCR techniques, respectively. Our results showed that MSCs reversed the overexpression of fibrosis markers and TGF-ß1/Smad signaling pathway proteins and mRNAs after TGF-ß1 treatment and increased the level of miR-130a-3p. TGF-ßRII was identified as a target of miR-130a-3p and was evaluated by dual-luciferase reporter assay. The miR-130a-3p/TGF-ßRII axis could suppress the differentiation of lung fibroblasts via the TGF-ß1/Smad signaling pathway, thereby reducing the process of PF.

20.
Front Med (Lausanne) ; 8: 708644, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395483

RESUMO

Genetic testing is widely used in breast cancer and has identified a lot of susceptibility genes and single nucleotide polymorphisms (SNPs). However, for many SNPs, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are not in place. A recent genome-wide long non-coding RNA (lncRNA) association study in Chinese Han has verified a genetic association between rs12537 and breast cancer. This study is aimed at investigating the association between rs12537 and the phenotype. We collected the clinical information of 5,634 breast cancer patients and 6,308 healthy controls in the early study. And χ2 test was used for the comparison between different groups in genotype. The frequency of genotypic distribution among SNP rs12537 has no statistically significant correlation with family history (p = 0.8945), menopausal status (p = 0.3245) or HER-2 (p = 0.2987), but it is statistically and significantly correlated with ER (p = 0.004006) and PR (p = 0.01379). Most importantly, compared to the healthy control, rs12537 variant is significantly correlated with ER positive patients and the p-value has reached the level of the whole genome (p = 1.66E-08 <5.00E-08). Furthermore, we found rs12537 associated gene MTMR3 was lower expressed in breast cancer tissues but highly methylated. In conclusion, our findings indicate that rs12537 is a novel susceptibility gene in ER positive breast cancer in Chinese Han population and it may influence the methylation of MTMR3.

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