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1.
Talanta ; 207: 120287, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594575

RESUMO

The three-dimensional (3D) DNA nanostructure has been got much attention due to its excellent biocompatibility, enhanced structural stability, highly programmable and perfect cell-delivery performance. Here, a novel 3D DNA tetrahedron amplifier (DTA) has been developed for rapid and efficient mRNA imaging in living cells using target catalyzing spatial-confinement hairpin DNA assembly cascade reaction inside the DNA nanostructure. The DTA was constructed by assembling a DNA tetrahedron with four DNA strands at first, and then by assembling two metastable DNA hairpins H1 (Cy5) and H2 (Cy3) at specific locations of the DNA tetrahedron. In the presence of target mRNA, the catalyzed hairpin assembly (CHA) reaction on the DTA could be triggered and a H1-H2 duplexes nanostructure could be formed, which would obtain a significant fluorescence resonance energy transfer (FRET) signal, and release the target mRNA could trigger next H1-H2 duplexes formation. Due to the 3D DNA tetrahedral spatial-confinement effect, the circular reaction of DTA could achieve rapid and efficient amplification detection of target mRNA in living cells. Moreover, the DTA show excellent structural stability and non-cytotoxicity. This strategy presents a versatile method for the ultrasensitive detection of biomarkers in living system and gains a deeper development of the DNA nanostructures in biomedical functions.

2.
J Phys Condens Matter ; 32(7): 075101, 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-31574494

RESUMO

Producing nanopores from hexagonal lyotropic liquid crystals (LLCs) templates requires not only retaining phase morphology of the templates but also precisely controlling structural dimensions of unit cells. In this study, SAXS and 2H NMR are used to investigate dimensional evolutions of ternary systems consisting of polymerizable species, (ethylene glycol) diacrylate (PEGDA) and/or 2-hydroxyethyl methacrylate (HEMA), in a LLCs template of hexagonally packed cylinders formed from dodecyl trimethylammonium bromide (DTAB) and water. With the addition of those polymerizable species, the system rearranges into a new hexagonal system with a smaller aggregation number, smaller pores and a thicker pore wall thickness. The hexagonal system will coexist with an aqueous-rich phase containing isotropically distributed DTAB if sufficient PEGDA is applied but the single hexagonal system could be restored by partially replacing the PEGDA with HEMA. The mobility of DTAB molecules within the aggregates varies depending on monomer compositions. The changes in structural dimensions of the unit cells and phase behaviors after adding polymerizable monomers allow dimensional control of mesochannels and potentially enable the control of selectivity and robustness of polymerized nanomaterials via molecular design.

3.
Chem Commun (Camb) ; 55(92): 13904-13907, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31681914

RESUMO

A novel kind of bottlebrush cellulose-graft-diblock copolymer thermoplastic elastomer (Cell-g-PBA-b-PMMA) was synthesized by grafting from cellulose backbones via surface-initiated atom transfer radical polymerization (ATRP). The mechanical properties of the bottlebrush copolymer elastomers can be adjusted by controlling the block lengths and composition of the side chains.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31696427

RESUMO

Recently, there has been increased studies in noise-induced hearing loss (NIHL). We aimed to make an overview of research trends and genetic polymorphisms for NIHL from 2009 to 2018 with VOSviewer software. A total of 2391 papers were identified for research trends analysis in NIHL and 33 studies identified for a brief review of genetic polymorphisms in human NIHL. The number of publications has been increasing over the past decade. The journal Hearing Research published the most articles (218). The USA contributed the largest number of papers (1042; 43.58%), with the most citations (18,987) and the highest H-index (60). The University of Washington was the most contributive institution. Liberman MC published the most articles (32), and Kujawa SG possessed the highest co-citations (584). Except for high-frequency keywords identified by the software, "prevalence," "oxidative stress," "hair cells," and "cochlear implant" were also the latest research frontiers. HSPA1A rs1043618, HSPA1L rs2227956, PON2 rs12026 and rs7785846, SOD2 rs2855116, KCNE1 rs2070358, KCNQ4 rs34287852, GJB2 rs3751385, PCDH15 rs7095441 and rs11004085, GRHL2 rs1981361, ITGA8 rs10508489, MYH14 rs667907, and POU4F3 rs891969 were the research hotspots and were replicated in independent samples. Inflammation response underlying NIHL has emerged and should be considered as a pioneering field in the future for the prevention of NIHL and conservation of hearing.

5.
Autophagy ; : 1-21, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31696776

RESUMO

Macroautophagy/autophagy plays key roles in development, oncogenesis, and cardiovascular and metabolic diseases. Autophagy-specific class III phosphatidylinositol 3-kinase complex I (PtdIns3K-C1) is essential for autophagosome formation. However, the regulation of this complex formation requires further investigation. Here, we discovered that STYK1 (serine/threonine/tyrosine kinase 1), a member of the receptor tyrosine kinases (RTKs) family, is a new upstream regulator of autophagy. We discovered that STYK1 facilitated autophagosome formation in human cells and zebrafish, which was characterized by elevated LC3-II and lowered SQSTM1/p62 levels and increased puncta formation by several marker proteins, such as ATG14, WIPI1, and ZFYVE1. Moreover, we observed that STYK1 directly binds to the PtdIns3K-C1 complex as a homodimer. The binding with this complex was promoted by Tyr191 phosphorylation, by means of which the kinase activity of STYK1 was elevated. We also demonstrated that STYK1 elevated the serine phosphorylation of BECN1, thereby decreasing the interaction between BECN1 and BCL2. Furthermore, we found that STYK1 preferentially facilitated the assembly of the PtdIns3K-C1 complex and was required for PtdIns3K-C1 complex kinase activity. Taken together, our findings provide new insights into autophagy induction and reveal evidence of novel crosstalk between the components of RTK signaling and autophagy.Abbreviations: AICAR: 5-aminoimidazole-4-carboxamide ribonucleotide; AMPK: adenosine 5'-monophosphate (AMP)-activated protein kinase; ATG: autophagy related; ATP: adenosine triphosphate; BCL2: BCL2 apoptosis regulator; BECN1: beclin 1; Bre A: brefeldin A; Co-IP: co-immunoprecipitation; CRISPR: clustered regularly interspaced short palindromic repeats; DAPI: 4',6-diamidino-2-phenylindole; EBSS: Earle's balanced salt solution; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; GSEA: gene set enrichment analysis; MAP1LC3/LC3, microtubule associated protein 1 light chain 3; MAPK8/JNK1: mitogen-activated protein kinase 8; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; MTT: 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PIK3R4: phosphoinositide-3-kinase regulatory subunit 4; qRT-PCR: quantitative reverse transcription PCR; RACK1: receptor for activated C kinase 1; RUBCN: rubicon autophagy regulator; siRNA: small interfering RNA; SQSTM1: sequestosome 1; STYK1/NOK: serine/threonine/tyrosine kinase 1; TCGA: The Cancer Genome Atlas; Ub: ubiquitin; ULK1: unc-51 like autophagy activating kinase 1; UVRAG: UV radiation resistance associated; WIPI1: WD repeat domain, phosphoinositide interacting 1; ZFYVE1: zinc finger FYVE-type containing 1.

6.
Arch Pharm Res ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31701373

RESUMO

Arsenic is a potent chemotherapeutic drug that is applied as a treatment for cancer; it exerts its functions through multiple pathways, including angiogenesis inhibition. As angiogenesis is a critical component of the progression of many diseases, arsenic is a feasible treatment option for patients with other angiogenic diseases, including rheumatoid arthritis and psoriasis, among others. However, arsenic is also a well-known carcinogen, demonstrating a pro-angiogenesis effect. This review will focus on the dual effects of arsenic on neovascularization and the relevant mechanisms underlying these effects, aiming to provide a rational understanding of arsenic treatment. In particular, we expect to provide a comprehensive overview of the current knowledge of the mechanisms by which arsenic influences angiogenesis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31733833

RESUMO

Myocardial infarction (MI) is known as a serious global problem, which has a high mortality rate and cause severe heart damage. Mounting evidence has suggested that exercise provides direct endogenous cardiac protection against various cardiovascular diseases including MI. However, the underlying mechanism of exercise's cardioprotective effect against MI has not been fully understood. Here, we found that a 4-wk swim training exerted protective effects against MI in C57 mice, as evidenced by increased cardiac function and decreased cardiac apoptosis. A plasma miRNA profiling assay was then performed, and 10 differentially expressed miRNAs were detected. Among them, miR-1192 was increased after exercise, and it exerted significant protective effect against hypoxia in cultured neonatal cardiomyocytes. In addition, intramyocardially injection of agomiR-1192 exerted similar cardioprotective effect as exercise, and inhibition of miR-1192 using antgomiR-1192 abolished the cardioprotective effect of exercise in MI mice, suggesting that exercise exerted cardioprotection against MI through upregulation of miR-1192. Furthermore, we found that miR-1192 exerted cardioprotective effect via targeting caspase 3 in cardiomyocytes. These findings suggested that exercise protects the heart against MI through upregulation of miR-1192, and miR-1192 is a novel exerkine in exercise-induced cardioprotection against MI.

8.
Zhongguo Zhen Jiu ; 39(11): 1173-6, 2019 Nov 12.
Artigo em Chinês | MEDLINE | ID: mdl-31724352

RESUMO

OBJECTIVE: To compare the clinical efficacy of needle-knife and hydroxychloroquine sulfate in the treatment of dry mouth and eyes symptoms of primary Sjögren's syndrome. METHODS: A total of 60 patients with primary Sjögren's syndrome were randomly divided into an observation group and a control group, 30 cases in each group. In the observation group, needle-knife was used in the range of 2 cm and 2-3 cm below the occipital protuberance, the left and right lateral bone edges of the C2 spinous process, between and within the range of 1.5-3 cm beside the C3 and C4 spinous processes, points between the left and right mandibular angle and the mastoid, the treatment was given 1 time a week for 8 times. The hydroxychloroquine sulfate was applied 0.2 g each time, 2 times daily, 4 weeks as a course and a total of 2 courses in the control group. The changes of salivary flow rate, tear volume, serum immunoglobulin IgG, IgA, IgM contents and Chinese medicine symptom score were observed before and after treatment in the two groups, and the efficacy was evaluated. RESULTS: The total effective rate in the observation group was 86.7% (26/30), which was better than 70.0% (21/30) in the control group (P<0.05). The salivary flow rates, tear volume, serum IgG contents and Chinese medicine symptom scores in the two groups were significantly improved after treatment (all P<0.05), and the improvement degree in the observation group was better than the control group (all P<0.05). There was no significant difference in IgA and IgM between the two groups and before and after treatment (all P>0.05). CONCLUSION: Needle-knife is superior to hydroxychloroquine sulfate in improving dry mouth and eyes symptoms and reducing serum IgG content in patients with primary Sjögren's syndrome.


Assuntos
Terapia por Acupuntura , Síndrome de Sjogren , Humanos , Hidroxicloroquina/uso terapêutico , Síndrome de Sjogren/terapia , Lágrimas , Resultado do Tratamento
9.
Med Sci Monit ; 25: 8306-8314, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31685789

RESUMO

BACKGROUND Long noncoding RNAs play important roles in the development of various diseases. This study aimed to evaluate the effects and mechanism of VIM antisense RNA 1 (VIM-AS1) in the development of preeclampsia. MATERIAL AND METHODS HTR-8/SVneo cells were divided into normal control (NC), Model, Blank, and VIM-AS1 groups. These groups were analyzed for their VIM-AS1 gene expressions by RT-PCR, HTR-8/SVneo cell invasion was assessed by transwell and migration by wound healing, cell morphology was assessed by microscopy examination, and E-cadherin, Snail, and Vimentin genes expressions were assessed by RT-PCR and WB assay. RESULTS VIM-AS1 gene expression was significantly different among normal placenta tissue, mild preeclampsia tissues, and severe preeclampsia tissues (P<0.001 or P<0.01). VIM-AS1 gene expressions, cell invasions, and wound healing rates in the Model and Blank groups were significantly suppressed compared with that of NC group (P<0.001, all). With VIM-AS1 supplementation, VIM-AS1 gene expression, cell invasion, and wound healing rate in the VIM-AS1 group were significantly increased compared with that in the Model group (P<0.001). RT-PCR and WB assay showed that E-cadherin gene and protein expressions in Model and Blank groups were significantly upregulated compared with the NC group (P<0.001); Snail and Vimentin gene and protein expressions in the Model and Blank groups were significantly downregulated compared with the NC group (P<0.001). With VIM-AS1 supplementation, E-cadherin, Snail, and Vimentin gene and proteins expression levels in the VIM-AS1 group were significantly different compared with that in the Model group (P<0.001). CONCLUSIONS VIM-AS1 promotes preeclampsia via inducing epithelial-to-mesenchymal transition (EMT).

10.
J Cell Mol Med ; 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31680420

RESUMO

Hypoxia-inducible factor 1α (HIF-1α) plays a critical role in the apoptotic process during cardiac ischaemia/reperfusion (I/R) injury. This study aimed to investigate whether post-treatment with dexmedetomidine (DEX) could protect against I/R-induced cardiac apoptosis in vivo and in vitro via regulating HIF-1α signalling pathway. Rat myocardial I/R was induced by occluding the left anterior descending artery for 30 minutes followed by 6-hours reperfusion, and cardiomyocyte hypoxia/reoxygenation (H/R) was induced by oxygen-glucose deprivation for 6 hours followed by 3-hours reoxygenation. Dexmedetomidine administration at the beginning of reperfusion or reoxygenation attenuated I/R-induced myocardial injury or H/R-induced cell death, alleviated mitochondrial dysfunction, reduced the number of apoptotic cardiomyocytes, inhibited the activation of HIF-1α and modulated the expressions of apoptosis-related proteins including BCL-2, BAX, BNIP3, cleaved caspase-3 and cleaved PARP. Conversely, the HIF-1α prolyl hydroxylase-2 inhibitor IOX2 partly blocked DEX-mediated cardioprotection both in vivo and in vitro. Mechanistically, DEX down-regulated HIF-1α expression at the post-transcriptional level and inhibited the transcriptional activation of the target gene BNIP3. Post-treatment with DEX protects against cardiac I/R injury in vivo and H/R injury in vitro. These effects are, at least in part, mediated via the inhibition of cell apoptosis by targeting HIF-1α signalling.

11.
Adv Ther ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31728826

RESUMO

BACKGROUND: This study evaluates the clinical effects of the stepwise anterior vitrectomy on the prevention of positive vitreous pressure (PVP) during penetrating keratoplasty (PKP). METHODS: PKP in conjunction with stepwise anterior vitrectomy was performed on 15 eyes of 15 patients under retrobulbar anesthesia. A preset vitrectomy trocar-cannula was inserted into the vitreous cavity before PKP. During the opening of the anterior chamber, intermittent vitrectomy and corneal incision expansion were performed alternately to keep the lens or artificial intraocular lens (IOL) and iris flat until the entirety of the pathological cornea had been dissected. The main outcome measures include visual acuity, crystalline lens rise (CLR), corneal curvature and diopter, and corneal endothelial cell loss. RESULTS: All surgical procedures were performed successfully without any PVP-related intraoperative complications. The mean time of the stepwise vitrectomies was 3.1 ± 0.7 s, the duration of each vitrectomy was 8.1 ± 5.3 s, and the duration of the total surgery was 60.5 ± 5.3 min. The anterior segment reaction was mild and the shape of the pupil remained normal 1 day after surgery. The mean preoperative and mean 3-month postoperative CLR values were 0.48 ± 0.09 mm and - 0.16 ± 0.04 mm, respectively (p < 0.0001). The mean preoperative endothelial cell density in donor buttons was 2570 ± 171 cells/mm2, and the mean 6- and 12-month postoperative endothelial cell density in donor buttons was 2207 ± 127 cells/mm2 and 2000 ± 198 cells/mm2, respectively. CONCLUSIONS: The novel and stabilized PKP procedure, performed in conjunction with the stepwise anterior vitrectomy, effectively avoided the PVP during open-sky surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900021227.

12.
Biosci Rep ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729531

RESUMO

Colorectal cancer (CRC) remains the candidate for one of the typical type ofmalignant tumors of in gastrointestinal tract all around the world, which leads to tremendous death and ranks as the top leading death of cancer. Recently, microRNAs have emerged as double-edged sword in numerous cancers. This investigation aims to discuss the regulative role of microRNA-574-3p (miR-574-3p), elucidating its molecular mechanism and clinical significance in CRC. Herein, it revealed to us that miR-574-3p was lowly expressed in CRC tissues in comparison with the matched para-carcinoma tissues.  In addition, transfection of SW480 and HT29 cells with miR-574-3p mimics prohibited the posttranscriptional expression of Cyclin D2 (CCND2), which then significantly blocked cell growth and cell migration, yet triggered cell apoptosis. Also, dual-luciferase reporter assays proved the role of CCND2 as the targeted gene for miR-574-3p. miR-574-3p overexpression prohibited the activity of CCND2 in SW480 and HT29 cells. Silencing of CCND2 in SW480 and HT29 CRC cell lines leading to reduced cell proliferative and migrative rates, and enhanced apoptotic rate. The suppressive effects of elevation of miR-574-3p on the proliferation of the human CRC cells and promotive effects on cell apoptosis by targeting CCND2 was further illustrated in the in vitro studies. Thus, we hypothesize that miR-574-3p may be served as a prospective therapeutic candidate for CRC.

13.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1089-1093, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753090

RESUMO

OBJECTIVE: To study the application value of surface electromyography in children with dysphagia. METHODS: A total of 20 children with dysphagia were enrolled as the observation group, and 20 healthy children, matched for sex and age, were enrolled as the control group. Surface electromyography was used to record the electromyography integral values of the submental and infrahyoid muscle groups in the resting state and the state after water swallowing. The two groups were compared in terms of the electromyography integral values of the submental and infrahyoid muscle groups in the resting state and the state after swallowing 5 mL water. The observation group was observed in terms of the changes in the electromyography integral values of the submental and infrahyoid muscle groups after 1 month of rehabilitation treatment. A Spearman correlation analysis was used to evaluate the correlation of the degree of dysphagia with the electromyography integral values of the submental and infrahyoid muscle groups in the observation group. RESULTS: There was no significant difference between the two groups in the electromyography integral values of the submental and infrahyoid muscle groups in the resting state (P>0.05), while after water swallowing, the observation group had significantly higher electromyography integral values than the control group (P<0.05). The observation group had significant improvements in the clinical symptoms of dysphagia after treatment, with significant reductions in the electromyography integral values of the submental and infrahyoid muscle groups (P<0.05). The severity of dysphagia was positively correlated with the electromyography integral values of the submental and infrahyoid muscle groups (P<0.01). CONCLUSIONS: Surface electromyography is useful in the diagnosis and therapeutic effect evaluation for dysphagia in children.


Assuntos
Transtornos de Deglutição , Criança , Deglutição , Eletromiografia , Humanos
14.
J Genet Genomics ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31771824

RESUMO

Identifying approaches for treating neurodegeneration is a thorny task but is important for a growing number of patients. Researchers have focused on discovering the underlying molecular mechanisms of reprogramming and optimizing the technologies for acquiring neurons. Direct conversion is one of the most important processes for treating neurological disorders. Induced neurons derived from direct conversion, which bypass the pluripotency stage, are more effective, more quickly obtained, and are safer than those produced via induced pluripotent stem cells (iPSCs). Based on iPSC strategies, scientists have derived methods to obtain functional neurons by direct conversion, such as neuron-related transcriptional factors, small molecules, microRNAs, and epigenetic modifiers. In this review, we discuss the present strategies for direct conversion of somatic cells into functional neurons and the potentials of direct conversion for producing functional neurons and treating neurodegeneration.

15.
Anal Chim Acta ; 1089: 66-77, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31627820

RESUMO

The dehydration reaction of tetraamino porphyrin and 4,4'-biphenyldicarboxaldehyde was performed for the synthesis of a novel covalent organic framework (COF), which was decorated on magnetic Fe3O4 to obtain core-shell structured Fe3O4@COFs nanospheres for the first time, for effective extraction and enrichment of sulfonamides (SAs). The morphology and structure of the synthesized nanospheres were characterized through various methods. The extraction conditions for six SAs including sulfadiazine, sulfamerazine, sulfamethazine, sulfamonomethoxine, sulfamethoxazole, sulfadimethoxine were systematically optimized. Fe3O4@COFs nanospheres were evaluated for magnetic solid-phase extraction. By coupling with high-performance liquid chromatography, a facile and sensitive method was established for the quantitation analysis of six SAs. The method showed good linearity ranging from 1 to 500 ng mL-1 with R2 > 0.99, high sensitivity with LODs in the range of 0.2-1 ng mL-1, and high precision with RSDs≤6.3%. This method was further applied into determination of SAs in environmental water and food samples, with recoveries in the range of 65.3%-107.3% and RSDs≤6.7%. These successful applications suggest that the core-shell structured Fe3O4@COFs nanospheres could be used as a potential adsorbent for efficient extraction and analysis of trace SAs.

16.
J Biol Chem ; 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615894

RESUMO

Rational design-guided improvement of protein thermostability typically requires identification of residues or regions contributing to instability and introduction of mutations into these residues or regions. One popular method, B-FIT, utilizes B-factors to identify unstable residues or regions and combines them with other strategies, such as directed evolution. Here, we performed structure-based engineering to improve the thermostability of the subtilisin E-S7 (SES7) peptidase. The B-value of each residue was redefined in a normalized B-factor calculation, which was implemented with a refined bioinformatics analysis strategy to identify the critical area (loop 158-162) related to flexibility and to screen for suitable thermostable motif sequences in the PDB database that can act as transplant loops. In total, we analyzed 445 structures and identified 29 thermostable motifs as candidates. Using these motifs as a starting point, we performed iterative homologous modeling to obtain a desirable chimera loop and introduced five different mutations into this loop to construct thermostable SES7 proteins. Differential scanning fluorimetry (DSF) revealed increases of 7.3°C in the melting temperature of an SES7 variant designated M5 compared with the wild-type. The X-ray crystallographic structure of this variant was resolved at 1.96 Å resolution. The crystal structure disclosed that M5 forms more hydrogen bonds than the wild-type protein, consistent with design and molecular dynamics simulations (MDS) results. In summary, the modified B-FIT strategy reported here has yielded a subtilisin variant with improved thermostability and promising industrial applications, supporting the notion that this modified method is a powerful tool for protein engineering.

17.
Chem Commun (Camb) ; 55(84): 12699-12702, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31588456

RESUMO

A ligand-free iron-catalyzed method for the oxygenation of benzylic sp3 C-H bonds by molecular oxygen (1 atm) using a thiyl radical as a cocatalyst has been developed. This transformation provides a facile access to amides, esters and ketones from readily accessible corresponding amines, ethers and alkanes. It features high regioselectivity, mild oxidative conditions and excellent functional group compatibility, providing good opportunities to the site-selective functionalization of complex molecules. Preliminary mechanistic studies suggest that this reaction may not undergo a benzylic cation intermediate pathway and the carbonyl oxygen atom in the products may be derived from molecular oxygen.

18.
Drug Des Devel Ther ; 13: 3137-3149, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564830

RESUMO

Purpose: Intracellular calcium ([Ca2+]i) overload is a major cause of cell injury during myocardial ischemia/reperfusion (I/R). Dexmedetomidine (DEX) has been shown to exert anti-inflammatory and organ protective effects. This study aimed to investigate whether pretreatment with DEX could protect H9c2 cardiomyocytes against oxygen-glucose deprivation/reoxygenation (OGD/R) injury through regulating the Ca2+ signaling. Methods: H9c2 cardiomyocytes were subjected to OGD for 12 h, followed by 3 h of reoxygenation. DEX was administered 1 h prior to OGD/R. Cell viability, lactate dehydrogenase (LDH) release, level of [Ca2+]i, cell apoptosis, and the expression of 12.6-kd FK506-binding protein/ryanodine receptor 2 (FKBP12.6/RyR2) and caspase-3 were assessed. Results: Cells exposed to OGD/R had decreased cell viability, increased LDH release, elevated [Ca2+]i level and apoptosis rate, down-regulated expression of FKBP12.6, and up-regulated expression of phosphorylated-Ser2814-RyR2 and cleaved caspase-3. Pretreatment with DEX significantly blocked the above-mentioned changes, alleviating the OGD/R-induced injury in H9c2 cells. Moreover, knockdown of FKBP12.6 by small interfering RNA abolished the protective effects of DEX. Conclusion: This study indicates that DEX pretreatment protects the cardiomyocytes against OGD/R-induced injury by inhibiting [Ca2+]i overload and cell apoptosis via regulating the FKBP12.6/RyR2 signaling. DEX may be used for preventing cardiac I/R injury in the clinical settings.

19.
J BUON ; 24(4): 1673-1678, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31646824

RESUMO

PURPOSE: To explore the influence of postoperative enteral nutrition combined with adjuvant radiotherapy on inflammatory response, nutrition, healing and prognosis in patients undergoing radical surgery for esophageal carcinoma. METHODS: A total of 114 patients with esophageal carcinoma receiving radical surgery from January 2016 to July 2017 composed the observation group and randomly divided into control group (n=57) and study group (n=57). Patients in the control group were given routine nutritional support after surgery, while those in the study group received enteral nutrition after surgery. The changes in inflammatory response and nutritional level, healing and prognosis in the two groups of patients before and after treatment were compared and analyzed. RESULTS: After treatment, the levels of serum hypersensitive C-reactive protein (hs-CRP) and prostaglandin E (PGE) of patients were decreased in both the control group and study group, and they were lower in the study group than those in the control group, while the levels of serum pro-albumin (PA) and albumin (ALB) of patients in the study group were higher than those in the control group (p<0.05). The postoperative wound healing time, total length of hospital stay, postoperative first exhaust time and defecation time in the study group were shorter than those in the control group (p<0.05). The total incidence rate of postoperative complications of patients in the study group was lower than that in the control group (p<0.05). CONCLUSION: The application of postoperative enteral nutrition combined with adjuvant radiotherapy in patients subjected to radical surgery for esophageal carcinoma can suppress systemic inflammatory response, improve the nutritional condition, promote postoperative wound healing and improve prognosis and therefore it is worthy of promotion in clinical practice.

20.
Life Sci ; : 116985, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31647949

RESUMO

BACKGROUND: The infiltration and activation of macrophages play key roles in arterial restenosis, providing a promising strategy for the treatment of restenosis caused by intimal hyperplasia. Although miR-150 has been implicated in cardiovascular diseases, the individual effect of miR-150 on intimal hyperplasia remains unclear. METHODS AND RESULTS: We observed that the expression of miR-150 was robustly reduced in proinflammatory M1 macrophages and reversely induced in resolving M2 macrophages. An in vitro experiment demonstrated that miR-150 deficiency promoted extensive upregulation of the expression of M1 markers but attenuated the expression of M2 macrophage markers. MiR-150 enhanced the proliferation and migration of vascular smooth muscle cells (VSMCs) when co-cultured with conditioned medium from polarized macrophages upon LPS or IL-4 stimulation. Mechanistically, the bioinformatics analysis and luciferase assay results showed that miR-150 directly targeted STAT1 and STAT1 was required for the effect of miR-150 knockout on macrophage polarization. More importantly, we showed that knockout of miR-150 accelerated neointima formation, accompanied by the activation of M1 macrophages and the inactivation of M2 macrophages. Furthermore, miR-150 deficiency in marrow-derived cell accelerated neointima formation. CONCLUSION: Our research demonstrated that miR-150 deficiency promoted intimal hyperplasia with high ratios of M1 to M2 macrophages and subsequently increased VSMCs proliferation and migration, which were partially mediated by directly targeting to STAT1. Collectively, these results suggested that miR-150 may act as a novel therapeutic target for arterial restenosis.

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