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1.
Bioorg Med Chem Lett ; 30(6): 126968, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32008907

RESUMO

Cysteine (Cys) is a semi-essential amino acid that exerts a vital role in numerous biological functions. A noninvasive method for in vivo imaging of cysteine could represent a valuable tool for research cysteine and its complex contributions in living organisms. Thus, we developed a turn-on bioluminescence probe (CBP) not only for detecting exogenous and endogenous cysteine in vitro and in vivo, but also for visualizing these cysteines in whole animal. The current applications may help shed light on the complex mechanisms of cysteine in miscellaneous physiological and pathological processes.

2.
Fish Shellfish Immunol ; 96: 152-160, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794843

RESUMO

C-type lectins are Ca2+-dependent carbohydrate-binding proteins containing one or more carbohydrate-recognition domains (CRDs). C-type lectins play crucial roles in innate immunity, including nonself-recognition and pathogen elimination. In the present study, two C-type lectins (designated ReCTL-1 and ReCTL-2) were identified from the shrimp Rimicaris exoculata which dwells in deep-sea hydrothermal vents. The open reading frames of ReCTL-1 and ReCTL-2 encoded polypeptides of 171 and 166 amino acids respectively, which were both composed of a signal peptide and a single CRD. The key motifs determining the carbohydrate binding specificity of ReCTL-1 and ReCTL-2 were respectively Glu-Pro-Ala (EPA) and Gln-Pro-Asn (QPN), which were firstly discovered in R. exoculata. ReCTL-1 and ReCTL-2 displayed similar pathogen-associated molecular pattern (PAMP) binding features and they bound three PAMPs-ß-glucan, lipopolysaccharide and peptidoglycan-with relatively high affinity. In addition, both could efficiently recognize and bind Gram-positive bacteria, Gram-negative bacteria and fungi. However, ReCTL-1 and ReCTL-2 exhibited different microbial agglutination activities: ReCTL-1 agglutinated Staphylococcus aureus and Saccharomyces cerevisiae, while ReCTL-2 agglutinated Micrococcus luteus, Vibrio parahaemolyticus and V. fluvialis. Both ReCTL-1 and ReCTL-2 inhibited the growth of V. fluvialis. All these results illustrated that ReCTL-1 and ReCTL-2 could function as important pattern-recognition receptors with broad nonself-recognition spectra and be involved in immune defense against invaders, but their specificities are not the same. In addition, the two ReCTLs possessed different carbohydrate binding specificities from each other and from the classical pattern: ReCTL-1 with an EPA motif bound d-galactose and l-mannose, while ReCTL-2 with a QPN motif bound d-fucose and N-acetylglucosamine.

3.
Cell Biol Int ; 44(2): 488-498, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31631456

RESUMO

Cardiomyocyte apoptosis contributes to the development of coxsackievirus B3 (CVB3)-induced myocarditis, but the mechanism for the apoptosis by CVB3 infection remains unclear. Here, we showed that CVB3-induced endoplasmic reticulum (ER) stress response and apoptosis in cultured H9c2 cardiomyocytes. We found that Ca2+ -calmodulin-dependent kinase II (CaMKII) was activated by ER stress-dependent intracellular Ca2+ overload in the CVB3-infected H9c2 cardiomyocytes. Treatment with an inhibitor of ER stress, 4-phenylbutyric acid (4-PBA), attenuated intracellular Ca2+ accumulation indirectly and reduced CaMKII activity. Inhibition of CaMKII with pharmacological inhibitor (KN-93) or short hairpin RNA reduced CVB3-induced H9c2 apoptosis and repressed cytochrome c release from mitochondria to cytoplasm; whereas overexpression of the activated mutant of CaMKII (CaMKII-T287D) enhanced CVB3-induced H9c2 apoptosis and mitochondrial cytochrome c release, which could be alleviated by blocking of mitochondrial Ca2+ uniporter or mitochondrial permeability transition pore. Further in vivo investigation revealed that blocking of CaMKII with KN-93 prevented cardiomyocytes apoptosis and improved cardiac contractile function in CVB3-infected mouse heart. Collectively, these findings provide a novel evidence that CaMKII plays a vital role in the promotion of CVB3-induced cardiomyocyte apoptosis, which links ER stress and mitochondrial Ca2+ uptake.

4.
J Exp Clin Cancer Res ; 38(1): 487, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822296

RESUMO

BACKGROUND: Arsenic sulfide was found to have potential anti-cancer activities, especially in gastric cancer. However, the underlying mechanism need to be further explored. This study was aimed to investigate the mechanism of arsenic compounds on gastric cancer. METHODS: Gastric cancer cell lines were infected with lentiviral vector carrying shNFATc3 and/or treated with arsenic sulfide. MTT assay were performed to assess cell growth. Flow cytometer assays were used to detect cell cycle and reactive oxygen species (ROS) level of gastric cancer cells. Western blot was carried out to detect nuclear factor of activated T-cells, cytoplasmic 3 (NFATc3), cell cycle markers, DNA damage pathway protein expression as well as other protein expression in gastric cancer cell lines. The expression of recombination activating gene 1 (RAG1) in gastric cancer cell lines was determined by RNA-sequencing analyses and Real-Time qPCR. The effect of NFATc3 on RAG1 were determined by CHIP-qPCR assay. The effect of arsenic sulfide on AGS cells was evaluated in vivo. RESULTS: We show that arsenic sulfide as well as knockdown of NFATc3 resulted in increased double-strand DNA damage in gastric cancer cells by increasing the expression of RAG1, an endonuclease essential for immunoglobulin V(D) J recombination. Overexpression of NFATc3 blocked the expression of RAG1 expression and DNA damage induced by arsenic sulfide. Arsenic sulfide induced cellular oxidative stress to redistribute NFATc3, thereby inhibiting its transcriptional function, which can be reversed by N-acetyl-L-cysteine (NAC). We show that NFATc3 targets the promoter of RAG1 for transcriptional inhibition. We further showed that NFATc3 upregulation and RAG1 downregulation significantly associated with poor prognosis in patients with gastric cancer. Our in vivo experiments further confirmed that arsenic sulfide exerted cytotoxic activity against gastric cancer cells through inhibiting NFATc3 to activate RAG1 pathway. CONCLUSION: These results demonstrate that arsenic sulfide targets NFATc3 to induce double strand DNA break (DSB) for cell killing through activating RAG1 expression. Our results link arsenic compound to the regulation of DNA damage control and RAG1 expression as a mechanism for its cytotoxic effect.

5.
J Gene Med ; : e3152, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830337

RESUMO

BACKGROUND: Troponin T1 (TNNT1) is a subunit of troponin that has been linked to neuromuscular disorder. Recently, it was reported that TNNT1 facilitates the proliferation of breast cancer cells. Interestingly, Cancer Genome Atlas data indicate that its overexpression is associated with an unfavorable prognosis of colorectal cancer (CRC) patients. The present study aimed to explore the expression, function and mechanism of dysregulation of TNNT1 in CRC. METHODS: Immunohistochemical staining and a real-time polymerase chain reaction were used to compare the expression level of TNNT1 in CRC tissues and adjacent tissues. Western blotting was used to detect the expression of TNNT1 in cell lines. Kaplan-Meier analysis and a chi-squared test were applied to evaluate the potential of TNNT1 to function as a cancer biomarker. RNA interference was used to inhibit TNNT1 expression in CRC cells, followed by detection of cell proliferation, apoptosis, migration and invasion. A luciferase reporter gene assay was used to determine the regulatory relationship between miR-873 and TNNT1. RESULTS: In the present study, we found that TNNT1 was significantly up-regulated in CRC samples and cell lines. The up-regulation of TNNT1 was also associated with several clinicopathologic features, and its high expression was correlated with an unfavorable prognosis of the patients. Knockdown of TNNT1 markedly arrested proliferation, migration and invasion, whereas it also promoted apoptosis. TNNT1 was identified as a target gene of miR-873, and there was a negative correlation among CRC samples. CONCLUSIONS: In conclusion, we have demonstrated that TNNT1, regulated by miR-873, is an oncogene of CRC associated with patient prognosis.

6.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671631

RESUMO

Tagetespatula L. is a widely cultivated herbal medicinal plant in China and other countries. In this study, two new 2, 3-dihydrobenzofuran glucosides (1, 2) and fourteen known metabolites (3-16) were isolated from the stems and leaves of T. patula (SLT). The chemical structures of the isolated compounds were characterized comprehensively based on one- and two-dimensional NMR spectroscopy and high resolution mass spectrometry. Absolute configurations of compounds 1 and 2 were determined by ECD calculations. Compounds 1 and 2 exhibited moderate in vitro inhibitory activities against human gastric cancer cell lines (AGS) with IC50 values of 41.20 µmol/L and 30.43 µmol/L, respectively. The fingerprint profiles of stems and leaves of T. patula with three color types of flowers (Janie Yellow Bright, Jinmen Orange, Shouyao Red and Yellow color) were established by high-performance liquid chromatography (HPLC). Ten different batches of stems and leaves were examined as follow: Shouyao Red and Yellow color (1, 2, 3), Janie Yellow Bright (4, 5, 6, 7) and Jinmen Orange (8, 9, 10). Twenty-two common peaks were identified with similarity values ranging from 0.910 to 0.977. Meanwhile, the average peak area of SLT in the three types of flowers was different and it was the highest in Janie Yellow Bright.

7.
Drug Des Devel Ther ; 13: 3037-3049, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31692505

RESUMO

Purpose: Gastric carcinogenesis is a multistep process and is the second-highest cause of cancer death worldwide with a high incidence of invasion and metastasis. MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Recent evidence has shown that miRNAs are involved in the cancer progression, including promoting cell-cycle, conferring resistance to apoptosis, and enhancing invasiveness and metastasis. Here, we aim to elucidate the roles of miRNAs, especially microRNA-4665-3p (miR-4665-3p), in the inhibitory effect of arsenic sulfide in gastric cancer (GC). Methods: The arsenic sulfide-induced miRNA expression alterations in AGS cells was determined by miRNA microarray. RT-PCR was used to further verify the arsenic sulfide-regulated miRNAs in GC tissues. The inhibition of miR-4665-3p on the migration and invasion of GC cells were determined by wound healing assay and transwell assay. Western blot analysis was used to detect the expression of EMT related proteins and the putative target of miR-4665-3p. Results: The miR-4665-3p was up-regulated by arsenic sulfide and showed inhibition upon the migration and invasion of GC cells. MiRBase and Western blotting indicated that miR-4665-3p directly down-regulated the oncoprotein GSE1. Morphological observation also indicated that the up-regulation of miR-4665-3p inhibits the EMT in GC cells. Conclusion: Our data demonstrates that the increased expression of miR-4665-3p induced by arsenic sulfide suppresses the cell invasion, metastasis and EMT of GC cells, and has the potential to be a novel therapeutic target in GC.

8.
Medicine (Baltimore) ; 98(40): e17126, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577702

RESUMO

BACKGROUND: The aim of this study was to investigate the role of n-acetyl cysteine (NAC) in the lipopolysaccharide (LPS)-mediated induction of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) synthesis by human periodontal ligament fibroblast cells (hPDLFs). In addition, we aimed to determine the involvement of the nuclear factor-kappa B (NF-κB) pathway in any changes in IL-1ß and TNF-α expression observed in response to LPS and NAC. METHODS: HPDLFs were obtained by primary culture. The culture medium used in this experiment was Dulbecco's Modified Eagle Medium (DMEM low-glucose). Cells were stimulated with various concentrations of NAC or LPS. Cell proliferation was measured at various time-points with the cell Counting Kit 8 (CCK-8) assay. mRNA levels of IL-1ß and TNF-α were determined by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Protein levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expression levels of NF-κB were measured by western blot and RT-qPCR. RESULTS: The results showed that LPS treatment in hPDLFs induced mRNA and protein expression of IL-1ß, TNF-α, and NF-κB. However, these effects were eliminated by pretreatment with NAC. Pretreatment with both NAC (1 mmol/L) and BAY11-7082 (10 µmol/L) significantly inhibited the NF-κB activity induced by LPS. CONCLUSION: NAC inhibits the LPS-mediated synthesis of tumor TNF-α and IL-1ß in hPDLFs, through the NF-κB pathway.


Assuntos
Acetilcisteína/farmacologia , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Humanos , Interleucina-1beta/biossíntese , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Ligamento Periodontal , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
9.
Sci Rep ; 9(1): 12309, 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444384

RESUMO

InN superconductivity is very special among III-V semiconductors, as other III-V semiconductors (such as GaAs, GaN, InP, InAs, etc.) usually lack strong covalent bonding and thus seldom show superconductivity at low temperatures. Here, we probe the different superconducting phase transitions in InN highlighted by its microstructure. Those chemical-unstable phase-separated inclusions, such as metallic indium or In2O3, are intentionally removed by HCl acid etching. The quasi-two-dimensional vortex liquid-glass transition is observed in the sample with a large InN grain size. In contrast, the superconducting properties of InN with a small grain size are sensitive to acid etching, showing a transition into a nonzero resistance state when the temperature approaches zero. Since the value of ξ0 (the zero-temperature-limit superconducting coherence length) is close to the grain size, it is suggested that individual InN grains and intergrain coupling should be responsible for the sample-dependent InN superconducting phase transition. Our work establishes a guideline for engineering superconductivity in III-nitride.

10.
Biomacromolecules ; 20(9): 3524-3534, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31381318

RESUMO

This work presents a salt-responsive interpenetrating network (IPN) hydrogel with effective antimicrobial properties and surface regeneration. The hydrogels were engineered using the double network strategy to form loosely cross-linked zwitterionic poly(sulfobetaine vinylimidazole) (pSBVI) networks into the highly cross-linked cationic poly((trimethylamino)ethyl methacrylate chloride) (pTMAEMA) framework via photopolymerization. The pTMAEMA/pSBVI hydrogel has strong mechanical properties, with a fracture stress 120× higher than single network pTMAEMA hydrogel. In addition, there is inverse correlation between elastic modulus and elastic strain of pTMAEMA/pSBVI hydrogels as a function of ionic strength. The cationic pTMAEMA and zwitterionic pSBVI show opposite swelling behaviors in salt solutions due to the polyelectrolyte effect and antipolyelectrolyte effect. Therefore, the pTMAEMA/pSBVI hydrogel elicits a significant interfacial transition in solutions with different ionic strengths. The IPN hydrogels have switchable lubrication and optical transmittance between deionized water and 1.0 M NaCl solution. The protein adsorption tests further confirmed the switchable interface of salt-responsive IPN hydrogels. In addition, bacterial attachment test on pTMAEMA/pSBVI hydrogels with Staphylococcus epidermidis (S. epidermidis) and Escherichia coli (E. coli) show bacterial killing rates of the IPN hydrogel over 80% for S. epidermidis and 90% for E. coli after incubating the hydrogels in the bacterial solutions for 24 h. The bacterial release rate from the IPN hydrogel reached 96% after washing with 1.0 M NaCl solution. Furthermore, the excellent reusability of the pTMAEMA/pSBVI hydrogels was demonstrated by the high bacterial killing and bacterial release rates after five kill/release cycles. The work presents a new stimuli-responsive IPN hydrogel with structural modulation, tunable antimicrobial properties, and surface regeneration by ionic strength. Integrating two salt-responsive polymers with mutually independent actions into a single material provides a new direction for smart materials with potential medical and industrial applications.

11.
J Am Geriatr Soc ; 67(11): 2298-2304, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31335969

RESUMO

OBJECTIVES: Whether early medication reconciliation and integration can reduce polypharmacy and potentially inappropriate medication (PIM) in the emergency department (ED) remains unclear. Polypharmacy and PIM have been recognized as significant causes of adverse drug events in older adults. Therefore, this pilot study was conducted to delineate this issue. DESIGN: An interventional study. SETTING: A medical center in Taiwan. PARTICIPANTS: Older ED patients (aged ≥65 years) awaiting hospitalization between December 1, 2017, and October 31, 2018 were recruited in this study. A multidisciplinary team and a computer-based and pharmacist-assisted medication reconciliation and integration system were implemented. MEASUREMENTS: The reduced proportions of major polypharmacy (≥10 medications) and PIM at hospital discharge were compared with those on admission to the ED between pre- and post-intervention periods. RESULTS: A total of 911 patients (pre-intervention = 243 vs post-intervention = 668) were recruited. The proportions of major polypharmacy and PIM were lower in the post-intervention than in the pre-intervention period (-79.4% vs -65.3%; P < .001, and - 67.5% vs -49.1%; P < .001, respectively). The number of medications was reduced from 12.5 ± 2.7 to 6.9 ± 3.0 in the post-intervention period in patients with major polypharmacy (P < .001). CONCLUSION: Early initiation of computer-based and pharmacist-assisted intervention in the ED for reducing major polypharmacy and PIM is a promising method for improving geriatric care and reducing medical expenditures. J Am Geriatr Soc 67:2298-2304, 2019.

12.
Int J Cancer ; 145(10): 2873-2883, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31044420

RESUMO

We analyzed the number of circulating tumor cells (CTCs) and Epstein-Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The levels of CTCs and EBV DNA were measured at baseline and after first-line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non-mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first-line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first-line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first-line chemotherapy was associated with significantly longer progression-free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first-line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first-line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.

13.
Front Pharmacol ; 10: 516, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31133861

RESUMO

Autophagy is fundamental to myocardial ischemia/reperfusion (I/R) injury. Antithrombin III (AT) has been shown to protect cardiomyocytes against I/R injury; however, it is unknown whether it modulates autophagy. The objective of this study was to investigate whether AT regulates autophagy during I/R injury and, if so, to identify the potential mechanism involved. Our study showed that AT attenuated I/R injury in vivo and hypoxia/reoxygenation (H/R) injury in vitro. Autophagy was increased both in H9C2 cardiomyocytes during H/R injury and in mouse hearts following I/R injury. The stimulation of autophagy by rapamycin attenuated the protective effect of AT against H9C2 cell injury, indicating that autophagy is involved in the protective role of AT. Furthermore, the cardioprotective effects of AT were abolished by A6730, a specific Akt inhibitor. This study shows that AT exhibits cardioprotective effects by modulating autophagy during I/R injury in a phosphoinositide 3-kinase/Akt-dependent manner.

15.
J Med Chem ; 62(6): 3163-3168, 2019 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-30816714

RESUMO

A bottleneck for developing CO-based therapeutics is the lack of a safe and controllable delivery form. Herein, we describe efforts toward organic CO prodrugs with dual-responsive endogenous triggers. One representative CO prodrug showed significant anti-inflammatory effects both in vitro and in a LPS-simulated systemic inflammation model. These results firmly establish such CO prodrugs as either research tools or candidate compounds for the treatment of systemic inflammation or inflammation related organ injuries.

16.
Bioinformatics ; 35(17): 3127-3132, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30668638

RESUMO

MOTIVATION: In recent years, several experimental studies have revealed that the microRNAs (miRNAs) in serum, plasma, exosome and whole blood are dysregulated in various types of diseases, indicating that the circulating miRNAs may serve as potential noninvasive biomarkers for disease diagnosis and prognosis. However, no database has been constructed to integrate the large-scale circulating miRNA profiles, explore the functional pathways involved and predict the potential biomarkers using feature selection between the disease conditions. Although there have been several studies attempting to generate a circulating miRNA database, they have not yet integrated the large-scale circulating miRNA profiles or provided the biomarker-selection function using machine learning methods. RESULTS: To fill this gap, we constructed the Circulating MicroRNA Expression Profiling (CMEP) database for integrating, analyzing and visualizing the large-scale expression profiles of phenotype-specific circulating miRNAs. The CMEP database contains massive datasets that were manually curated from NCBI GEO and the exRNA Atlas, including 66 datasets, 228 subsets and 10 419 samples. The CMEP provides the differential expression circulating miRNAs analysis and the KEGG functional pathway enrichment analysis. Furthermore, to provide the function of noninvasive biomarker discovery, we implemented several feature-selection methods, including ridge regression, lasso regression, support vector machine and random forests. Finally, we implemented a user-friendly web interface to improve the user experience and to visualize the data and results of CMEP. AVAILABILITY AND IMPLEMENTATION: CMEP is accessible at http://syslab5.nchu.edu.tw/CMEP.

17.
J Cell Physiol ; 234(4): 4726-4738, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30256405

RESUMO

The potential risk of arsenic-related neurodegeneration has been a growing concern. Arsenic exposure has been reported to disrupt neurite growth and neuron body integrity in vitro; however, its underlying mechanism remains unclear. Previously, we showed that arsenic sulfide (AS) exerted cytotoxicity in gastric and colon cancer cells through regulating nuclear factor of the activated T cells (NFAT) pathway. The NFAT pathway regulates axon path finding and neural development. Using neural crest cell line PC12 cells as a model, here we show that AS caused mitochondrial membrane potential collapse, reactive oxygen species production, and cytochrome c release, leading to mitochondria-mediated apoptosis via the AKT/GSK-3ß/NFAT pathway. Increased glycogen synthase kinase-3 beta (GSK-3ß) activation leads to the inactivation of NFAT and its antiapoptotic effects. Through inhibiting GSK-3ß activity, both nerve growth factor (NGF) and Tideglusib, a GSK-3ß inhibitor partially rescued the PC12 cells from the AS-induced cytotoxicity and restored the expression of NFATc3. In addition, overexpression of NFATc3 stimulated neurite outgrowth and potentiated the effect of NGF on promoting the neurite outgrowth. Collectively, our results show that NFATc3 serves as the downstream target of NGF and plays a key role in preventing AS-induced neurotoxicity through regulating the AKT/GSK-3ß/NFAT pathway in PC12 cells.

18.
Macromol Rapid Commun ; 40(3): e1800681, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30417474

RESUMO

Sequential deformations of patterned hydrogels into 3D configurations with multilevel structures are reported, which are realized for the first time in self-shaping materials. The periodically patterned single-layer hydrogels with different polymers are fabricated by multi-step photolithography. After swelling in water, the expansion of compartmentalized high-swelling gels is constrained by the dispersed non-swelling gels, resulting in out-of-plane buckling with high cooperativity and thus forming alternating concave-convex configuration. When the dispersed non-swelling gels are partly replaced by thermoresponsive ones, the preformed overall flat, yet locally undulant, hydrogel deforms further into dome-, saddle-, or sandglass-like configurations at elevated temperature. As such, multilevel 3D structures can be achieved via prebuilt mechanical/geometric cues in a sequentially controlled manner. This conceptual design and sequential deformation of patterned hydrogels to form 3D configurations with multilevel structures should enrich the deformation/functioning modes of morphing materials and broaden their applications in diverse areas.


Assuntos
Hidrogéis/química , Polímeros/química , Temperatura Ambiente , Água/química , Fenômenos Mecânicos , Modelos Moleculares , Conformação Molecular
19.
Nat Commun ; 9(1): 5196, 2018 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-30518919

RESUMO

Two dimensional layered organic-inorganic hybrid perovskites (2D perovskites) are potential candidates for next generation photovoltaic device. Especially, the out-of-plane surface perpendicular to the superlattice plane of 2D perovskites (layer-edge surface) has presented several exotic behaviors, such as layer-edge states which are found to be crucial for improving the efficiency of 2D perovskite solar cells. However, fundamental research on transport properties of layer-edge surface is still absent. In this report, we observe the electronic and opto-electronic behavior in layer-edge device of 2D perovskites. The dark and photo currents are demonstrated to strongly depend on the crystallographic orientation in layer-edge device, and such anisotropic properties, together with photo response, are related to the thickness of inorganic layers. Finally, due to the abundant hydroxyl groups, water molecules are easy to condense on the layer-edge surface, and the conductance is extremely sensitive to the humidity environment, indicating a potential application of humidity sensor.

20.
Drug Des Devel Ther ; 12: 3913-3927, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30532520

RESUMO

Purpose: Gastric and colon cancers have been the leading causes of cancer mortality in the world with limited therapy. Small molecules binding to bromodomains of bromodomain-containing protein 4 (BRD4) exert strong antitumor activities against hematological malignancies, while generally have limited efficacy in advanced solid tumors. Here, we found that the bromodomain and extra-terminal (BET)-bromodomain inhibitor JQ1, when combined with arsenic sulfide (As4S4, abbreviated as AS), synergistically decreased the expression of nuclear factor of activated T-cells (NFATs) as well as the downstream oncogene c-Myc and largely induced cell apoptosis via mitochondrial pathway in gastric and colon cancer cell lines. Methods: The synergistic cytotoxicity of AS and JQ1 in gastric and colon cancer cells was determined by MTT assay and verified by FACS assay. Western blot analysis and quantitative real-time PCR (qPCR) assay were used to detect the expression of NFATs and downstream apoptotic proteins. The mitochondrial transmembrane potential was determined by FACS assay, and the metastasis of cancer cells was detected by the wound-healing assay. Results: AS and JQ1 synergistically induced cell apoptosis in gastric and colon cancer cells by downregulating NFATs and upregulating apoptotic proteins. Combination of AS and JQ1 was associated with the decreased mitochondrial transmembrane potential, the cytochrome c release, and the subsequent caspase-3 activation. Conclusion: Thus, our data indicate that AS can effectively enhance the cytotoxicity of BET inhibitors in gastric and colon cancer cells through mitochondrial-mediated apoptosis induction.


Assuntos
Antineoplásicos/farmacologia , Arsenicais/farmacologia , Azepinas/farmacologia , Neoplasias do Colo/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Sulfetos/farmacologia , Triazóis/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Potenciais da Membrana/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Células Tumorais Cultivadas
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