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1.
Free Radic Biol Med ; 145: 223-236, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31580946

RESUMO

The intestine is a highly radiosensitive tissue that is susceptible to structural and functional damage due to systemic as well as localized radiation exposure. Unfortunately, no effective prophylactic or therapeutic agents are available at present to manage radiation-induced intestinal injuries. We observed that the vanillin derivative VND3207 improved the survival of lethally irradiated mice by promoting intestinal regeneration and increasing the number of surviving crypts. Pre-treatment with VND3207 significantly increased the number of Lgr5+ intestinal stem cells (ISCs) and their daughter cells, the transient Ki67+ proliferating cells. Mechanistically, VND3207 decreased oxidative DNA damage and lipid peroxidation and maintained endogenous antioxidant status by increasing the level of superoxide dismutase and total antioxidant capacity. In addition, VND3207 maintained appropriate levels of activated p53 that triggered cell cycle arrest but were not sufficient to induce NOXA-mediated apoptosis, thus ensuring DNA damage repair in the irradiated small intestinal crypt cells. Furthermore, VND3207 treatment restores the intestinal bacterial flora structures altered by TBI exposure. In conclusion, VND3207 promoted intestinal repair following radiation injury by reducing reactive oxygen species-induced DNA damage and modulating appropriate levels of activated p53 in intestinal epithelial cells.

2.
Nanotoxicology ; : 1-13, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31589482

RESUMO

Graphene quantum dots (GQDs) have gained significant attention in various biomedical applications. The physicochemical properties of these nanoparticles, including toxic effects, are largely determined by their surface modifications. Previous studies have demonstrated high in vitro cytotoxicity of the hydroxylated GQDs (OH-GQDs). The focus of this study was on the intestinal toxicity of OH-GQDs. Briefly, C57BL/6J mice were given daily oral gavage of 0.05, 0.5 or 5 mg/kg OH-GQD for 7 days, and the indices of intestinal damage were evaluated. Higher doses of the OH-GQDs caused significant intestinal injuries, such as enhanced intestinal permeability, shortened villi and crypt loss. The number of Lgr5+ intestinal stem cells also decreased dramatically upon OH-GQDs exposure, which also inhibited the Ki67+ proliferative progenitor cells. In addition, an increased number of crypt cells harboring the oxidized DNA base 8-OHdG and γH2AX foci were also detected in the intestines of OH-GQD-treated mice. Mechanistically, the OH-GQDs up-regulated both total and phosphorylated p53. Consistent with this, the average number of TUNEL+ and cleaved caspase-3+ apoptotic intestinal epithelial cells were significantly increased after OH-GQDs treatment. Finally, a 3-dimensional organoid culture was established using isolated crypts, and OH-GQDs treatment significantly reduced the size of the surviving intestinal organoids. Taken together, the intestinal toxicity of the OH-GQDs should be taken into account during biomedical applications.

3.
J Dent ; : 103210, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31600535

RESUMO

OBJECTIVES: The present study examined the effects of Na+→K+ ion-exchange on the wear performance of feldspathic veneering porcelain. METHODS: Bar and disk specimens were prepared using IPS classic as the feldspathic veneering porcelain. After ion-exchange by immersion of the specimens in melted KNO3 at two temperatures for different time-periods, the bars were tested for flexural strength and Vickers surface hardness. The disks were paired with zirconia antagonists and tested with a pin-on-disk tribometer with 10 N for 70☓104 wear cycles in artificial saliva. Wear analysis of the porcelain and zirconia was performed using 3D profilometer and analysed with one-way analysis of variance and Tukey's post-hoc pairwise comparison procedures. Worn surfaces were examined with scanning electron microscopy. RESULTS: The feldspathic veneering porcelain exhibited strong time-dependent wear behaviour, with typical running-in and steady wear stages. Ion-exchange treatments at 380 °C and 440 °C both enhanced the mechanical properties, decreased the wear rates of running-in wear and steady wear. The wear performance of porcelain treated by ion-exchange at lower temperature (380 °C) was improved significantly, especially reducing the wear rate of the running-in stage. CONCLUSION: A thicker ion-exchange layer with less stress relaxation may be obtained by ion-exchange at lower exchange temperature for a long processing time. Such a protocol improves the wear performance of the porcelain effectively. CLINICAL SIGNIFICANCE: Restorations with veneering porcelain may fail prematurely due to excessive wear. It important to improve the wear performance of the porcelain. Ion-exchange has the potential to strengthen dental veneering porcelain. Understanding the effect of ion-exchange on the wear performance of porcelain provides insight improving the wear performance of these restorations.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31542918

RESUMO

Selective isolation and enrichment of phosphoproteins play critical roles for identification of biomarkers in biological applications. Herein, a kind of polyoxometalate (P5W30)/polydopamine (PDA) composite microspheres is readily synthesized via an in situ polymerization way, followed by immobilization of Ti4+ on the surface of the microspheres to obtain P5W30/PDA-Ti4+. Due to metal affinity and π stacking interaction, this novel material exhibits high selectivity to ß-casein (ß-ca), and the theoretical maximum adsorption capacity is as high as 1250 mg g-1, fitting well with the Langmuir model. The captured ß-ca can be collected by using Britton-Robinson (B-R) buffer at pH 7.0, and a recovery of 81.5% is acquired. The enrichment factor is over 150 at a mass ratio of BSA/ß-ca = 100:1, indicating that phosphoproteins can be purified by P5W30/PDA-Ti4+. Moreover, the application of P5W30/PDA-Ti4+ as sorbent in real biological samples has been investigated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis, and the consequences show that this kind of material is able to selectively isolate phosphoproteins from complex samples such as drinking milk and chicken egg white.

5.
Front Immunol ; 10: 1861, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31481954

RESUMO

Fibrotic animal models are critical for the pathogenesis investigations and drug explorations in systemic sclerosis (SSc). The bleomycin (BLM)-induced mouse model is the classical and most widely used fibrosis model. However, traditional subcutaneous injection of BLM rarely induced diffuse skin and lung lesions. Hypochlorous acid (HOCl)-induced mice are a more representative model that have diffuse cutaneous lesions, lung fibrosis and renal involvement. However, the fibrotic and immunological features of this model are not fully elucidated. Here, we injected BALB/c mice subcutaneously with HOCl used at different concentrations of HOCl (1:55, 1:70, and 1:110 NaClO: KH2PO4, hereafter named HOCl55, HOCl70, and HOCl110, respectively) for 6 weeks to induce fibrosis, and also used HOCl110 at different time course (4, 5, and 6 weeks). Morphological changes were observed via HE and Masson's trichrome staining. Immunohistochemistry or real-time PCR was used to detect inflammatory infiltrates, important fibrosis pathways and pro-inflammatory mediator expression. Flow cytometry was used to detect the alteration of immune cells in mouse spleen. Skin and lung fibrosis were most obvious in the HOCl55 group compared to lower concentration groups. In the HOCl110 group, dominant inflammatory infiltrates were found after 5 weeks, and significant fibrosis was found after 6 weeks. Then we explored the fibrosis and immunological profiles in the HOCl110 (6 weeks) group. Important fibrosis pathway proteins such as TGF-ß, NF-κB, Smad3, p-Smad3, STAT3, and p-STAT3 were significantly elevated at week 6 in the HOCl110 group. Increased infiltration of CD4+T cells, CD8+T cells, CD20+B cells, and myofibroblasts was found both in skin and lung tissues. However, decreased CD4+T cells, CD8+T cells, monocytes and macrophages and increased CD19+B cells were found in the spleen tissues. The mRNA expression of fibrosis mediators such as IL-1ß, IL-6, IL-17, IL-33, TNF-α, and CTGF was also upregulated in skin and lung tissues. In conclusion, HOCl induced fibrosis mouse model displayed systemic immune cell infiltration, pro-inflammatory mediator release, vasculopathy and fibrosis, which better mimicked human SSc than BLM-induced mice.

6.
Org Lett ; 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31513413

RESUMO

We report a general and efficient approach to construct achiral and chiral gem-difluoroallylic amines from a masked difluorodiazo reagent (PhSO2CF2CHN2) and readily available imines. This facile protocol takes advantage of the phenylsulfonyl and diazo moieties as efficient activating and directing groups to assist difluoroalkyl incorporation and facilitate the chemodivergent and stereoselective formation of gem-difluoroallylic amines.

7.
Cell ; 179(1): 132-146.e14, 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31522887

RESUMO

Oligodendrocytes extend elaborate microtubule arbors that contact up to 50 axon segments per cell, then spiral around myelin sheaths, penetrating from outer to inner layers. However, how they establish this complex cytoarchitecture is unclear. Here, we show that oligodendrocytes contain Golgi outposts, an organelle that can function as an acentrosomal microtubule-organizing center (MTOC). We identify a specific marker for Golgi outposts-TPPP (tubulin polymerization promoting protein)-that we use to purify this organelle and characterize its proteome. In in vitro cell-free assays, recombinant TPPP nucleates microtubules. Primary oligodendrocytes from Tppp knockout (KO) mice have aberrant microtubule branching, mixed microtubule polarity, and shorter myelin sheaths when cultured on 3-dimensional (3D) microfibers. Tppp KO mice exhibit hypomyelination with shorter, thinner myelin sheaths and motor coordination deficits. Together, our data demonstrate that microtubule nucleation outside the cell body at Golgi outposts by TPPP is critical for elongation of the myelin sheath.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31478868

RESUMO

Constructing experiments to predict unknown miRNA-disease association is time-consuming, costly. Accordingly, new prediction model should be conducted to predict novel miRNA-disease associations. The performance of this method should be high and reliable. In this paper, a new computation model Logistic Weighted Profile-based Collaborative Matrix Factorization (LWPCMF) is put forward. In this method, weighted profile (WP) is combined with collaborative matrix factorization (CMF) to increase the performance of this model. And the neighbor information is considered. In addition, logistic function is applied to miRNA functional similarity matrix and disease semantic similarity matrix to extract valuable information. At the same time, by adding WP and logistic function, the known correlation can be protected. And Gaussian Interaction Profile (GIP) kernels of miRNAs and diseases are added to miRNA functional similarity network and disease semantic similarity network to augment kernel similarities. Then, a five-fold cross validation is implemented to evaluate the predictive ability of this method. Besides, case studies are conducted to view the experimental results. The final result contains not only known associations but also newly predicted ones. And the result proves that our method is better than other existing methods. This model is able to predict potential miRNA-disease associations.

9.
J Nat Prod ; 82(9): 2586-2593, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31532203

RESUMO

Eleven new nitrogenous meroterpenoids, cinerols A-K (1-11), were isolated from the marine sponge Dysidea cinerea collected in the South China Sea, and their structures were determined by detailed spectroscopic analysis. Cinerols A (1) and B (2) feature a rare 5H-pyrrolo[1,2a]benzimidazole moiety, while cinerols C-G (3-7) are examples of rare meroterpene benzoxazoles. The cinerols are noncytotoxic to human melanoma A375 cells at the concentration of 32 µM; however, selected cinerols exhibit moderate inhibitory activity against one or more of protein-tyrosine phosphatase 1B, ATP-citrate lyase, and SH2 domain-containing phosphatase-1 with IC50 values of 2.8-27 µM.

10.
Biosens Bioelectron ; 144: 111686, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31520966

RESUMO

In this communication, a paper-based 3D cell culture device integrated with electrochemical biosensor was applied to on-line monitoring of dopamine release from PC12 cell damage models induced by amyloid-beta peptide (Aß25-35) and cell intervene models protected by curcumin (Cur) and marrow mesenchymal stem cells (MSC) supernatant. The adhesion and proliferation of PC12 cells cultured on the paper scaffold was characterized by scanning electron microscopy and laser scanning confocal microscopy, which verify unique biocompatibility and 3D microarchitecture similar to human body microenvironment of paper substrate, so an artificial model simulating 3D microenvironment in vivo was constructed easily. The PC12 cells in paper-based devices consisted of four groups containing control group, Aß25-35 group, Aß25-35+Cur group and Aß25-35+MSC supernatant group. Under optimal conditions, this proposed device displayed a wide linear range from 0.05 to 1 µmol/L with a detection limit of 0.009 µmol/L (S/N = 3) and exhibited high sensitivity, good selectivity and excellent reproducibility. Furtherly, electrochemcial analysis and MTT assay gave a clue that the cell viability of Aß25-35+MSCs supernatant group was higher than that of Aß25-35+Cur group. Therefore, the detachable paper-based 3D device paves the way to a direct detection of exocytosis DA from neuron cells for on-line cell viability evaluation of neurodegenerative disease cell damage models.

11.
Analyst ; 144(20): 6055-6063, 2019 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-31517337

RESUMO

Unlike other extracellular vesicle (EV) subtypes such as exosomes, the lack of well-defined universal markers on the surface of microvesicles (MVs) has led to difficulty in the detection of the entire MV population. To design a universal MV detection method, we reported highly sensitive electrical detection of MVs using a reduced graphene oxide (RGO)-based field-effect transistor (FET) biosensor by the introduction of a membrane biotinylation strategy in this work. Biotinylated MVs (B-MVs) were obtained by supplying the culture medium with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[biotinyl(polyethylene glycol)-2000] (DSPE-PEG-biotin) while cultivating the cells. Excellent biotinylation efficiency of MVs (92.6%) was then realized. A streptavidin (SA) probe was subsequently modified onto the channel surface of the as-fabricated RGO-based FET device, which was capable of specifically recognizing B-MVs due to the high affinity between SA and biotin in a 1 : 4 recognition format. The results showed that the RGO-based FET biosensor could detect B-MVs in a wide range from 105 particles per mL to 109 particles per mL with a low detection limit down to 20 particles per µL, which was the lowest value compared with other previously reported results. This platform also allowed distinguishing B-MVs from other unbiotinylated EV types such as MVs and exosomes, exhibiting excellent specificity. Moreover, this FET biosensor demonstrated the capability of detecting B-MVs derived from different cell lines including cancer cells and normal cells, indicating its versatility and potential applications in the biomedical field.

12.
Chem Commun (Camb) ; 55(81): 12235-12238, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31552940

RESUMO

A new calixpyridinium-based light-responsive host-guest recognition motif was found in this work. This host-guest recognition motif was further discovered to be applied as a selective turn-on fluorescent sensor for lysine over other natural amino acids.

13.
Clin Genet ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31525260

RESUMO

Arrhythmogenic cardiomyopathy (ACM) is a familial cardiomyopathy featured by fibro-fatty replacement of cardiomyocytes. Responsible genetic factors are not discernible in approximately one third of ACM probands. To investigate this further, we performed whole genome sequencing (WGS) in 14 mutation-negative ACM probands who underwent cardiac transplantation, and we identified one ACM proband with a rare homozygous missense variant in PNPLA2 (c.245G>A, p.G82D), a rate-limiting enzyme that hydrolyzes triglycerides into fatty-acids and diacylglycerol. Bioinformatic analysis suggested that this missense variant may lead to loss-of-function and therefore impair lipid catabolism. Genetic screening in this proband's family also inferred that the homozygous variant co-segregated with disease. To validate the pathogenicity of this variant and confirm its association with ACM, we established a knock-in mouse model carrying the orthologous human homozygous PNPLA2 variant. Interestingly, mice with the homozygous variant presented with arrhythmias and significant cardiac dysfunction at 12-weeks, whereas heterozygous mice were not affected. Moreover, those homozygous mice suffered sudden death and/or heart failure by age of 14-weeks. Pathological examination showed that extensive lipogenesis in cardiomyocytes and cardiac fibrosis were prominent in the myocardium. Herein, our data demonstrated that the homozygous missense variant PNPLA2 (c.245G>A, p.G82D) associated with a recessive form of ACM. This article is protected by copyright. All rights reserved.

14.
Exp Gerontol ; 127: 110713, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31472256

RESUMO

BACKGROUND: Older adults with type 2 diabetes are prone to multiple metabolic abnormalities. However, data from these patients on comprehensive metabolic risk factors control are limited. METHODS: The present study included 2736 older adults aged 60 to 90 years with type 2 diabetes from 114 hospitals across 22 provinces in China. Metabolic abnormalities, including hypertension, dyslipidemia, hyperuricemia, and obesity, were recorded. Comprehensive metabolic risk factors control included the control of hemoglobin A1c (HbA1c) level, blood pressure, serum lipids level, serum uric acid level, and body mass index. The target glycemic control was defined as HbA1c <7%. RESULTS: The proportion of older adults who achieved the HbA1c target was 23.0%. The glycemic control rate increased with the number of metabolic abnormalities increased. The patients who had all four metabolic abnormalities had 4.05 times (95% confidence interval: 2.16, 7.61) the odd to meet glycemic target than those with none of metabolic abnormalities. However, only 4.6% of patients met the targets for all 5 metabolic risk factors. The comprehensive rate of all 5 factors in control decreased from 13.4% to 0% with the number of metabolic abnormalities increased. CONCLUSION: The glycemic control rate and the comprehensive metabolic risk factors control rate were 23.0% and 4.6%, respectively. As the number of metabolic abnormalities increased, the number of risk factor targets achieved decreased. Our findings suggest that a strategy for comprehensive control is urgently needed in older adults with type 2 diabetes, especially in those with co-existing metabolic abnormalities.

15.
Org Lett ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31456408

RESUMO

A highly efficient method for the enantioselective build of spiro[1-indanone-5,2'-γ-butyrolactones] has been developed through the tandem Michael/transesterification reaction of α-hydroxy-1-indanone and α,ß-unsaturated esters. A broad range of spiro(1-indanone-butyrolacones) with contiguous stereocenters have been synthesized with excellent stereoselectivities (up to >20:1 dr, up to >99% ee) under the catalysis of dinuclear zinc complex. Moreover, the reaction can be run on a gram scale without affecting its stereoselectivities. A possible mechanism is proposed.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31363874

RESUMO

A Gram-stain negative, aerobic bacterium, designated strain YIM 78456T, was isolated from a hot spring sediment, Ngamring county, Tibet, south-west China. The taxonomic position of the isolate was investigated by a polyphasic approach. The novel isolate was found to be aerobic and rod-shaped. Colonies were observed to be pale yellow and circular. The strain was found to grow at pH 7.0-8.0 (optimum, pH 7.0), 45-65 °C (optimum, 55 °C) and in the presence of up to 1.5% NaCl. Comparison of the 16S rRNA gene sequence of strain YIM 78456T and other members of the genus Thermus showed sequence similarities ranging from 90.3 to 97.3%, with strain YIM 78456T showing close sequence similarity to Thermus caliditerrae YIM 77925T (97.3%). The phylogenetic trees based on 16S rRNA gene sequences showed that strain YIM 78456T forms a distinct clade with T. caliditerrae YIM 77925T. The predominant menaquinone was identified as MK-8 and the DNA G+C content was determined to be 65.1 mol%. The major cellular fatty acids (> 10%) were identified as iso-C15:0, anteiso-C15:0 and iso-C17:0. The polar lipids were found to consist of an aminophospholipid, a phospholipid and glycolipids. On the basis of the morphological and chemotaxonomic characteristics, as well as genotypic data, it is proposed that strain YIM 78456T represents a novel species of the genus Thermus, for which the name Thermus caldilimi sp. nov. is proposed. The type strain is YIM 78456T (= KCTC 52948T = NBRC 113036T).

17.
Artigo em Inglês | MEDLINE | ID: mdl-31422138

RESUMO

OBJECTIVES: The aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics-based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia. BACKGROUND: A new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated. METHODS: A total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics-based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and "gray zone" lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed. RESULTS: Per vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p < 0.001 for all). No significant difference in diagnostic accuracy was observed in the "gray zone" range versus the other 2 lesion groups (FFR ≤0.75 and >0.80; p = 0.397) and in patients with "gray zone" versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and <400 (p = 0.393). CONCLUSIONS: This novel computational fluid dynamics-based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.

18.
Int J Mol Sci ; 20(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382526

RESUMO

Many Salicaceae s.l. plants are recognized for their important role in the production of products such as wood, oils, and medicines, and as a model organism in life studies. However, the difference in plastid sequence, phylogenetic relationships, and lineage diversification of the family Salicaceae s.l. remain poorly understood. In this study, we compare 24 species representing 18 genera of the family. Simple sequence repeats (SSRs) are considered effective molecular markers for plant species identification and population genetics. Among them, a total of 1798 SSRs were identified, among which mononucleotide repeat was the most common with 1455 accounts representing 80.92% of the total. Most of the SSRs are located in the non-coding region. We also identified five other types of repeats, including 1750 tandems, 434 forward, 407 palindromic, 86 reverse, and 30 complementary repeats. The species in Salicaceae s.l. have a conserved plastid genome. Each plastome presented a typical quadripartite structure and varied in size due to the expansion and contraction of the inverted repeat (IR) boundary, lacking major structural variations, but we identified six divergence hotspot regions. We obtained phylogenetic relationships of 18 genera in Salicaceae s.l. and the 24 species formed a highly supported lineage. Casearia was identified as the basal clade. The divergence time between Salicaceae s.l. and the outgroup was estimated as ~93 Mya; Salix, and Populus diverged around 34 Mya, consistent with the previously reported time. Our research will contribute to a better understanding of the phylogenetic relationships among the members of the Salicaceae s.l.

19.
Soft Matter ; 15(33): 6615-6625, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31406972

RESUMO

Self-healing materials (SHMs) have been a research hot topic in recent years owing to their greatly improved longevity and safety in practical applications. Recently, research on SHMs has gradually expanded from structural materials to functional materials. Functional materials with self-healing properties (FMSH) require simultaneous repairing not only of the mechanical properties but of the functionalities from damaged cracks or wounds. It is more challenging to introduce both self-healing properties and a particular functionality to materials owing to the difficulties of preparing the materials and their more complex healing mechanism. Herein, we summarize the recent progress that has been made in FMSH, put forward insights from the perspectives of material preparation and healing mechanisms and highlight future developments for FMSH.

20.
J Investig Med ; 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31431469

RESUMO

Hepatocellular Carcinoma (HCC) is one of the most common malignancies in the world, and is well-known for its bad prognosis. Potassium calcium-activated channel subfamily N member 4 (KCNN4) is a type of intermediate conductance calcium-activated potassium channel, and increasing evidence suggests that KCNN4 contributes to the regulation of invasion and metastasis in a number of cancers. However, its clinical significance and biological function remain unclear in the HCC disease process. In this study, the expression levels of KCNN4 in 86 HCC samples were compared with corresponding paracancerous tissues. sh-RNA was used to reduce the expression of KCNN4 in Hep3B HCC cells in vitro; this was confirmed by Real time-PCR and western blotting. Wound healing, transwell assays and high content analysis were performed to investigate the tumor-promoting characteristics of KCNN4 in Hep3B HCC cells. As results, KCNN4 expression was significantly associated with preoperative serum alpha-fetoprotein level (p=0.038) and TNM stage (p=0.039). Additionally, patients with high KCNN4 amplification in HCC tissue exhibited shorter disease-free survival, whereas there was no statistical significance between KCNN4 amplification and overall survival. Wound healing and transwell assays showed that knockdown of KCNN4 expression could reduce migration and invasion abilities of HCC cells. High content analysis result showed that down-regulated KCNN4 could inhibit the ability of HCC cell proliferation. The mitogen-activated protein kinase (MAPK) pathway is active in cell proliferation, differentiation, migration, senescence, and apoptosis. Matrix metallopeptidase 9 and extracellular signal regulated kinase 1/2 (ERK1/2) were important biomarkers of MAPK/ERK pathway, knockdown of KCNN4 reduced the expression of MMP9 and ERK1/2. These findings showed that KCNN4 promotes HCC invasion and metastasis through the MAPK/ERK pathway.

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