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1.
Artigo em Inglês | MEDLINE | ID: mdl-34673249

RESUMO

Xanthotoxin (XAT) is widely present in many kinds of plants. Caenorhabditis elegans, a typical model organism, was used to study the effects of XAT on C. elegans developmental toxicity, neurotoxicity, reproductive toxicity induced under ultraviolet A (UVA), oxidative stress and apoptosis in C. elegans. The results showed that after XAT exposure treatment, the hatchability of C. elegans decreased significantly as the concentration increased; the body length and width increased markedly, the external morphology was swollen; the brood sizes had been decreased; and the frequencies of head thrashes and body bend decreased significantly. At 80 and 100 mg/L, XAT reduced the activities of mitochondrial complex enzymes I and III, resulting in the excessive production of ROS, and inhibited SOD and CAT so that the ROS could not be eliminated over time. ROS accumulation in the bodies further caused the contents of MDA, protein carbonyl and lipofuscin to increase significantly, the mitochondrial membrane potential to be severely damaged, apoptosis to occur, and the apoptosis genes ced-3 and ced-4 to be significantly upregulated. Thus, XAT showed photoactivated toxicity to C. elegans under UVA, which will help people to make full and rational use of plants containing XAT.

2.
Biosens Bioelectron ; 197: 113776, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34785492

RESUMO

In this work, a novel smartphone-based electroporation (EP) system integrated with 3D scalable and robust gold-coated silicon-nanopillar Electroporation (Au-Si NP-EP) chip using projection photolithography is developed, for the first time, for both EP and electric cell lysing (ECL) at low voltages. Au-SiNP-EP chip consists of silicon nanopillars fabricated by using ASML stepper, Deep Reactive Ion Etching (DRIE) process and coated with a gold microelectrode. The silicon nanopillars were optimized based on theoretical analysis and numerical simulations to enhance the electrical field intensity and mechanical strength. The fabricated Au-SiNP-EP chips are tested with both permeable (Acridine Orange (AO) and impermeable (Propidium Iodide (PI)) molecules for HeLa cells at different volts (1-8 V) and pulse duration (1-9 µs). The fabricated chip achieved an optimized EP efficiency of 84.3% and cell viability of 81.4% at a much smaller voltage (4.5V) than reported planar electroporation (PEP) devices (8-100V). Compared with nanostructures-based devices (2-20 V), our devices show both higher mechanical strength and fabrication yield. Besides, a smartphone app integrated with a low-cost open-source portable Arduino-based system is developed to provide optimized electrical protocols for both EP and ECL. The electric cell lysing with ECL efficiency of 97.0% at 7 V and pulse duration of 9 ms has been successfully demonstrated. The experimental results show that the proposed smartphone-based EP system with Au-SiNP EP chips is promising for various applications, including intracellular delivery of various biomolecules, drugs, and release of DNA/RNA molecules from biological cells.

3.
Mater Horiz ; 8(1): 234-243, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34821302

RESUMO

Novel applications of waste thermosetting resins are developed by facile mechanical crushing, and their excellent performances are demonstrated in oil-water separation, superhydrophobic coatings with diverse water adhesion, acid liquid/gas monitoring and information storage. This work provides new ideas for waste treatments and functional material design, as well as speeds up the transformation of waste resins from laboratory achievements to industrial applications. Moreover, it can also improve the utilization efficiency of non-renewable resources and meet the requirements of energy conservation and environmental protection.

4.
J Mater Chem B ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34821894

RESUMO

Phototheranostics has attracted great interest in cancer therapy. Small-molecule self-reporting photosensitizers, one kind of idea agent in phototheranostics, enables simultaneous photodynamic therapy (PDT) and feedback of therapeutic efficacy. However, previous such photosensitizers exclusively employed the change of single emission to monitor cell death, which can be disturbed by variations in photosensitizer concentration and the excitation intensity. Herein, we report a unique self-reporting photosensitizer TPA-3PyA+ constructed from a twisted triphenylamine unit (TPA), three benzene ring units and three cyanovinyl-pyridinium units (PyA) for PDT and its real-time monitoring in a dynamic dual-color mode. TPA-3PyA+ possesses a rotatable electron donor-π bridge-electron acceptor framework and exhibits high singlet oxygen quantum yield (124%) and a twisted intramolecular charge transfer (TICT) effect. TPA-3PyA+ not only enables effective staining of cancer cells with dual-color fluorescence due to the TICT effect but also shows excellent PDT performance. The simultaneous change in emission color, intensity and intracellular location of TPA-3PyA+ during cell death allows it to self-report cell death. Moreover, the change of dual-emission color allows distinguishing living and dead cells and effectively avoids interference in previous single-emission self-reporting photosensitizers. This work highlights the great potential of a self-reporting photosensitizer with dual-color emissions for efficient feedback of theranostics.

5.
Appl Opt ; 60(31): 10002-10008, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34807195

RESUMO

Large-scale optical fiber phased arrays (OFPAs) are capable of realizing high-power lasers and high-speed beam steering, which are widely used in long-distance detection and communication. However, dephasing occurring from optical fiber jitter and power amplifier noise can reduce beam quality and steering precision in applications. We demonstrate a two-dimensional 64-element OFPA system that employs a stochastic parallel gradient descent algorithm to synchronize the phases and thus achieve high-quality multi-beam output. Using multi-beam steering, the total scan time for covering a certain field of view can be shorter compared to single-beam steering. Moreover, an avalanche photodiode array is used to enhance the precision of the voltage for beam steering. Experimental results show that the peak sidelobe ratio of the main beam achieves 23.7 dB, and the speed of the beam steering between two discretionary angles is 128 kHz.

6.
Biomol Ther (Seoul) ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34815367

RESUMO

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 µM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

7.
Food Funct ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34806108

RESUMO

Hyperuricemia is a metabolic condition closely linked to xanthine oxidase (XOD) function, which is involved in the production of uric acid (UA). In this study, XOD was used as a target to construct an in vitro and in vivo activity screening and verification system. The XOD inhibition ability of the main components from the water extract of Sophorae Flos (WSF), an unopened dry flower bud of Sophora japonica, was screened by HPLC. Isorhamnetin (IRh) was identified as a major flavonoid XOD inhibitor from WSF, and we characterized its effects and potential mechanism in ameliorating UA levels and renal function in hyperuricemia model mice. Hyperuricemia was induced by oral administration of potassium oxonate (PO) and hypoxanthine to mice for 7 days. The biochemical index results showed that treatments with low, medium, and high doses of IRh (50, 100, and 150 mg kg-1) significantly reduced serum UA levels and inhibited XOD activity in serum and in the liver. Additionally, IRh effectively decreased the levels of serum creatinine and blood urea nitrogen, suggesting that it possessed nephroprotective effects in hyperuricemic mice. Furthermore, histopathological results showed that nuclear lesions and renal tubule dilatation in the kidneys of IRh-treated hyperuricemic mice were reduced, suggesting that IRh may alleviate renal injury. Molecular docking results showed that IRh combined well with XOD and is an effective XOD inhibitor. In conclusion, IRh from Sophora japonica may reduce the UA levels and alleviate renal injury by inhibiting XOD activity. It potentially functions as a therapeutic drug and dietary supplement to treat hyperuricemia.

8.
J Phys Chem Lett ; : 11578-11584, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807621

RESUMO

Scaling relations play a vital role in high-throughput screening of catalytic materials, and more and more attention is being paid to strain-based regulation of catalytic performance. Here we investigated the variation of several energetics, including adsorption energies in the initial state, transition state, and final state, reaction energies, and energy barriers with strain, by studying CO, BH, NH, CH, and NO adsorption and dissociation on M(111) (M = Cu, Ag, Ni, Pd, or Pt) surfaces. We show that energy barriers, reaction energies, and adsorption energies can vary either linearly or nonlinearly (quadratically) with strain. Systems with stronger adsorbate-substrate interaction and weaker atom-atom interaction in substrates are more likely to exhibit nonlinear relations. The well-known Brønsted-Evans-Polanyi relationships and transition state scaling relationships under strain were also examined, and both of them can be nonlinear under strain, in principle. The observed nonlinear relationships were satisfactorily rationalized with the equations derived from Mechanics of Solids.

9.
BMC Cancer ; 21(1): 1185, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742270

RESUMO

BACKGROUND: Various randomized trials have demonstrated that postmastectomy radiotherapy (RT) to the chest wall and comprehensive regional nodal areas improves survival in patients with axillary node-positive breast cancer. Controversy exists as to whether the internal mammary node (IMN) region is an essential component of regional nodal irradiation. Available data on the survival benefit of IMN irradiation (IMNI) are conflicting. The patient populations enrolled in previous studies were heterogeneous and most studies were conducted before modern systemic treatment and three-dimensional (3D) radiotherapy (RT) techniques were introduced. This study aims to assess the efficacy and safety of IMNI in the context of modern systemic treatment and computed tomography (CT)-based RT planning techniques. METHODS: POTENTIAL is a prospective, multicenter, open-label, parallel, phase III, randomized controlled trial investigating whether IMNI improves disease-free survival (DFS) in high-risk breast cancer with positive axillary nodes (pN+) after mastectomy. A total of 1800 patients will be randomly assigned in a 1:1 ratio to receive IMNI or not. All patients are required to receive ≥ six cycles of anthracycline and/or taxane-based chemotherapy. Randomization will be stratified by institution, tumor location (medial/central vs. other quadrants), the number of positive axillary nodes (1-3 vs. 4-9 vs. ≥10), and neoadjuvant chemotherapy (yes vs. no). Treatment will be delivered with CT-based 3D RT techniques, including 3D conformal RT, intensity-modulated RT, or volumetric modulated arc therapy. The prescribed dose is 50 Gy in 25 fractions or 43.5 Gy in 15 fractions. Tiered RT quality assurance is required. After RT, patients will be followed up at regular intervals. Oncological and toxilogical outcomes, especially cardiac toxicities, will be assessed. DISCUSSION: This trial design is intended to overcome the limitations of previous prospective studies by recruiting patients with pN+ breast cancer, using DFS as the primary endpoint, and prospectively assessing cardiac toxicities and requiring RT quality assurance. The results of this study will provide high-level evidence for elective IMNI in patients with breast cancer after mastectomy. TRIAL REGISTRATION: ClinicalTrails.gov , NCT04320979 . Registered 25 Match 2020, https://clinicaltrials.gov/ct2/show/NCT04320979.

10.
Soft Matter ; 17(43): 9866-9870, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34724018

RESUMO

6,6'-Dibromided tert-butyloxycarbonyl isoindigo (Br-TBOCII) has intense fluorescence in the solid state via excitation with aggregation-induced emission (AIE), contrary to the classic heavy-atom effect. The unique AIE mechanism is attributed to the Br-Br bonding joint restricting intramolecular motion. Furthermore, the water-soluble nanoparticles Br-TBOCII/Pluronic® 127, possess robust photostability, low toxicity and good cell imaging performance.


Assuntos
Corantes Fluorescentes , Nanopartículas , Fluorescência , Indóis
11.
ChemSusChem ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34747148

RESUMO

Plastic has now become a contradiction between civilization and pollution which human society has to resolve. The recycling of thermosetting plastics in waste plastics is even more a huge challenge since they are difficult to remold like thermoplastic plastics due to their high crosslinking density. Here, a new strategy is presented to achieve multicycling of anhydride-cured epoxy thermosets. The process consists of mild and high-efficiency alcoholysis catalyzed by potassium phosphate/low-boiling alcohol system, and subsequent fast hydrolysis to obtain degradation products rich of carboxyl groups. The degradation products are reused as curing agent to prepare new anhydride-cured epoxy thermosets without sacrifice of high strength and high stability. Moreover, the new epoxy thermosets can still be repeatedly recycled using the same protocol. The insoluble property of the potassium phosphate in the ethanol at room temperatures makes the separation and reuse of the catalyst more convenient. Meanwhile low-boiling alcohol not only allows high-efficiency degradation, but also enables easy separation from the degradation products. The excellent degradation performance is attribute to the improved swelling of the thermoset and the increased solubility of potassium phosphate induced by the small water in the alcohol. This research provides a recycling method that can reintegrate thermoset waste plastics into remodeling ones under the background of circular economy.

12.
J Phys Chem A ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34793164

RESUMO

To provide guiding information for developing efficient and stable catalysts for epoxide hydration, we investigated the mechanism of propylene oxide (PO) to 1,2-propylene glycol (PG) using density functional theory (DFT) calculations. The mechanism was identified to follow the cooperative bimetallic mechanism in which a metal-salen complex activated H2O attacks the middle carbon atom of a metal-salen complex activated PO from the oxygen side of three-membered ring. Analyses reveal that the distortion energy correlates linearly with the barrier, and the hydrogen bonding between H2O and PO increases from reaction precursors to transition states. A nice linear relationship exists between the ratio of square root of ionic potential to the square of the distance from the metal ion spherical surface to the oxygen atom center of PO. It is demonstrated that the substrates with larger polarizability tend to have lower hydration barriers and the influence of ligands is less than that of metal centers and substrates. Modifying metal ions is the first choice for developing metal-salen catalysts, and metal ions with more formal charges and larger radius are expected to exhibit high activity. These findings shed lights on the mechanism and provide guiding information for developing efficient metal-salen catalysts for epoxide hydration.

13.
Front Microbiol ; 12: 721426, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745029

RESUMO

Most isolated strains of Staphylococcus sciuri contain mecA1, the evolutionary origin of mecA, but are sensitive to ß-lactams (OS-MRSS, oxacillin-susceptible mecA1-positive S. sciuri). In order to improve the efficacy of antibiotic treatment, it is important to clarify whether the resistance of OS-MRSS to ß-lactams is an inducible phenotype. In this study, three OS-MRSS strains with oxacillin MIC = 1 µg/ml were isolated from 29 retail pork samples. The resistance of OS-MRSS to ß-lactams (MIC > 256 µg/ml) was found to be induced by oxacillin, and the induced resistance was observed to remain stable within a certain period of time. Interestingly, the induced ß-lactam resistance was not caused by mecA1, heterogeneous resistance, or any genetic mutation, but mainly due to increased wall teichoic acid (WTA) synthesis that thickened the cell wall. The induced strains also showed slower growth rate, as well as decreased adhesion ability and biofilm thickness. These phenotypes were found to be achieved through altered gene expression in associated pathways, such as the citrate cycle and pentose phosphate pathway. The results challenge the traditional antibiotic sensitivity test. In the presence of ß-lactam antibiotics, OS-MRSS that was initially sensitive to ß-lactams was observed to gradually develop ß-lactam resistance in several days. This often-neglected phenomenon in antibiotic sensitivity tests requires further research attention.

14.
J Ethnopharmacol ; : 114838, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34788645

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Keguan-1, a new traditional Chinese medicine (TCM) prescription contained seven Chinese herbs, is developed to treat coronavirus disease 19 (COVID-19). The first internationally registered COVID-19 randomised clinical trial on integrated therapy demonstrated that Keguan-1 significantly reduced the incidence of ARDS and inhibited the severe progression of COVID-19. AIM OF THE STUDY: To investigate the protective mechanism of Keguan-1 on ARDS, a lipopolysaccharide (LPS)-induced acute lung injury (ALI) model was used to simulate the pathological state of ARDS in patients with COVID-19, focusing on its effect and mechanism on ALI. MATERIALS AND METHODS: Mice were challenged with LPS (2 mg/kg) by intratracheal instillation (i.t.) and were orally administered Keguan-1 (low dose, 1.25 g/kg; medium dose, 2.5 g/kg; high dose, 5 g/kg) after 2 h. Bronchoalveolar lavage fluid (BALF) and lung tissue were collected 6 h and 24 h after i.t. LPS administration. The levels of inflammatory factors tumour necrosis factor α (TNF-α), interleukin (IL)-6, IL-1ß, keratinocyte-derived chemokine (KC or mCXCL1), macrophage inflammatory protein 2 (MIP2 or mCXCL2), angiotensin II (Ang II), and endothelial cell junction-associated proteins were analysed using ELISA or western blotting. RESULTS: Keguan-1 improved the survival rate, respiratory condition, and pathological lung injury; decreased the production of proinflammatory factors (TNF-α, IL-6, IL-1ß, KC, and MIP2) in BALF and the number of neutrophils in the lung tissues; and ameliorated inflammatory injury in the lung tissues of the mice with LPS-induced ALI. Keguan-1 also reduced the expression of Ang II and the adhesion molecule ICAM-1; increased tight junction proteins (JAM-1 and claudin-5) and VE-cadherin expression; and alleviated pulmonary vascular endothelial injury in LPS-induced ALI. CONCLUSION: These results demonstrate that Keguan-1 can improve LPS-induced ALI by reducing inflammation and pulmonary vascular endothelial injury, providing scientific support for the clinical treatment of patients with COVID-19. Moreover, it also provides a theoretical basis and technical support for the scientific use of TCMs in emerging infectious diseases.

15.
J Environ Sci (China) ; 110: 84-91, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34593197

RESUMO

The direct urea fuel cell (DUFC) is a low cost and competitive approach for contemporaneous urine or urea-contaminated wastewater treatment and electricity generation. However, the lack of efficient urea oxidation reaction (UOR) electrocatalysts and suitable electron acceptors remains a challenge for practical applications. Here, we developed a DUFC system using Ni2P@Ni foam as the anode and peroxymonosulfate (PMS) as the chemical oxidizers. The Ni2P@Ni foam anode showed a high oxidation activity for UOR with an onset potential of 0.30 V vs. Ag/AgCl and Tafel slope of 34.4 mV/dec. PMS with high theoretical potential improved the cell voltage to 1.43 V. A power density of DUFC up to 4.91 mW/cm2 was achieved using PMS at room temperature, which was approximately twice as high as using H2O2 (2.38 mW/cm2). NiII/NiIII was the redox active species on the Ni2P anode in the DUFC process, and NiII was electrochemically oxidized to NiIII, which reverted to NiII by urea reduction. When real human urine was used as the fuel, a power density of 4.46 mW/cm2 can be achieved at room temperature. This DUFC with high cell performance showed potential application in urea wastewater treatment.


Assuntos
Níquel , Ureia , Eletrodos , Humanos , Peróxido de Hidrogênio , Peróxidos
16.
J Cosmet Dermatol ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34619007

RESUMO

BACKGROUND: Xanthelasma palpebrarum is a type of human xanthoma that occurs on the skin of human eyelids and is a benign skin lesion. Pingyangmycin (also known as bleomycin A5) is one of the 13 components of bleomycin. The aim of this study was to explore the efficacy of intralesional bleomycin and pingyangmycin in the treatment of xanthoma based on histopathological observations in animal experimental research. METHODS: An animal model of xanthoma was established by feeding rabbits with a high-cholesterol diet. Pingyangmycin and bleomycin interfered with the skin xanthoma of the animal model. Skin tissue specimens were stained with hematoxylin-eosin and oil red O to evaluate the effect of the intervention. RESULTS: A xanthoma animal model was established. Pingyangmycin and bleomycin could reduce the abnormal lipid deposition in the lesion area of the skin xanthoma of the animal, via a local injection. In addition, pingyangmycin was more effective than bleomycin in eliminating lipid deposition in rabbit skin xanthoma.

17.
Entropy (Basel) ; 23(10)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34682018

RESUMO

Quantum dual-signature means that two signed quantum messages are combined and expected to be sent to two different recipients. A quantum signature requires the cooperation of two verifiers to complete the whole verification process. As an important quantum signature aspect, the trusted third party is introduced to the current protocols, which affects the practicability of the quantum signature protocols. In this paper, we propose a quantum dual-signature protocol without arbitrator and entanglement for the first time. In the proposed protocol, two independent verifiers are introduced, here they may be dishonest but not collaborate. Furthermore, strongly nonlocal orthogonal product states are used to preserve the protocol security, i.e., no one can deny or forge a valid signature, even though some of them conspired. Compared with existing quantum signature protocols, this protocol does not require a trusted third party and entanglement resources.

18.
Biomed Res Int ; 2021: 9957209, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631891

RESUMO

Thyroid transcription factor-1 (TTF-1/NKx2.1) is a member of the NKx2 tissue-specific transcription factor family, which is expressed in thyroid follicle, parathyroid gland, alveolar epithelium, and diencephalon which originated from ectoderm, and participates in the differentiation, development, and functional maintenance of the above organs. Recent studies have shown that the abnormal expression of TTF-1 is closely related to the occurrence of a variety of human diseases and can be used as a potential new target for the diagnosis and treatment of related diseases. In this article, in order to strengthen the systematic understanding of TTF-1 and promote the progress of related research, we reviewed the structure, expression regulation, biological functions of TTF-1, and its role in the occurrence and development of human-related clinical diseases. Meanwhile, we prospect the future research direction of TTF-1, which might ultimately contribute to the understanding of the pathogenesis of related clinical diseases and the development of new prevention and treatment strategies.

19.
iScience ; 24(10): 103213, 2021 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-34632326

RESUMO

The emergence of SARS-CoV-2 has led to a global health crisis that, in addition to vaccines and immunomodulatory therapies, calls for the identification of antiviral therapeutics. The papain-like protease (PLpro) activity of nsp3 is an attractive drug target as it is essential for viral polyprotein cleavage and for deconjugation of ISG15, an antiviral ubiquitin-like protein. We show here that 6-Thioguanine (6-TG), an orally available and widely available generic drug, inhibits SARS-CoV-2 replication in Vero-E6 cells with an EC50 of approximately 2 µM. 6-TG also inhibited PLpro-catalyzed polyprotein cleavage and de-ISGylation in cells and inhibited proteolytic activity of the purified PLpro domain in vitro. We therefore propose that 6-TG is a direct-acting antiviral that could potentially be repurposed and incorporated into the set of treatment and prevention options for COVID-19.

20.
Sci Rep ; 11(1): 21014, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697393

RESUMO

Cisplatin (CDDP) based chemotherapy is widely used as the first-line strategy in treating non-small cell lung cancer (NSCLC), especially lung squamous cell carcinoma (LUSC). However, secondary cisplatin resistance majorly undermines the cisplatin efficacy leading to a worse prognosis. In this respect, we have identified the role of the DLX6-AS1/miR-181a-5p/miR-382-5p/CELF1 axis in regulating cisplatin resistance of LUSC. qRT-PCR and Western blot analysis were applied to detect gene expression. Transwell assay was used to evaluate the migration and invasion ability of LUSC cells. CCK-8 assay was used to investigate the IC50 of LUSC cells. Flow cytometry was used to test cell apoptosis rate. RNA pull-down and Dual luciferase reporter gene assay were performed to evaluate the crosstalk. DLX6-AS1 was aberrantly high expressed in LUSC tissues and cell lines, and negatively correlated with miR-181a-5p and miR-382-5p expression. DLX6-AS1 expression was enhanced by H3K4me1 in cisplatin resistant LUSC cells. Besides, DLX6-AS1 knockdown led to impaired IC50 of cisplatin resistant LUSC cells. Furthermore, DLX6-AS1 interacted with miR-181a-5p and miR-382-5p to regulate CELF1 expression and thereby mediated the cisplatin sensitivity of cisplatin resistant LUSC cells. DLX6-AS1 induced by H3K4me1 played an important role in promoting secondary cisplatin resistance of LUSC through regulating the miR-181a-5p/miR-382-5p/CELF1 axis. Therefore, targeting DLX6-AS1 might be a novel way of reversing secondary cisplatin resistance in LUSC.

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