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1.
Org Biomol Chem ; 17(33): 7715-7722, 2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31402357

RESUMO

A simple and efficient BPO-promoted free radical-based cascade reaction of biaryl vinyl ethers with easily available unactivated alkanes has been developed. A series of 6-alkyl-6H-benzo[c]chromenes have been successfully obtained in moderate to high yields under transition-metal-free conditions. This method can also be utilized to synthesize 6-alkyl-6H-benzo[c]thiochromenes from the corresponding biaryl vinyl thioethers.

2.
Sci Total Environ ; 695: 133912, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31425993

RESUMO

Polluted air is as harmful as polluted water sources to public health. As air living organisms, the research on microbial consortia under haze stress with different PM2.5 levels in a mountainous environment remains very limited. This study investigated the dynamic changes in bacterial cell counts, apoptosis, human pathogens, consortia characteristics, metabolic pathways, and the biochemical functions under haze conditions with various degrees of pollution (leading pollutant PM2.5) from August to December 2017 in a typical mountainous terrain of Jinan, China. Samples were evaluated with flow cytometry and 16S rRNA gene amplicon sequencing. Results indicated that cell counts ranged from 6.83 × 105 ±â€¯1.27 × 104 (non-polluted air, NP) to 2.32 × 106 ±â€¯3.56 × 104 (heavily polluted air, HP) cell m-3 air. The proportion of viable apoptotic and necrotic cells were positively correlated to PM2.5. Burkholderia cenocepacia (36.6%) was the most abundant human pathogen found in HP; this gram-negative bacterium is associated with potentially lethal respiratory infections in cystic fibrosis patients. The relative abundance of the phylum Proteobacteria (63.8%) in NP first decreased in lightly polluted (LP) (41.3%) and moderately polluted air (MP) (26.3%) then increased in HP (81.0%). Cupriavidus (22.9%) and BTEX-degrading bacteria (0.6%, Pseudomonas) were found in HP. Metabolic pathways with significant differences included cell motility and endocrine and immune diseases that exhibited increasing relative abundance as pollution levels increased. The diversity of biochemical functions was found to be decreased in hazy air.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31369714

RESUMO

Lysophosphatidic acid (LPA) is an important lipid molecule for signal transduction in cell proliferation. Although the effects of LPA on vascular smooth muscle (VSM) cell growth have been reported previously, the underlying mechanisms of its action are not fully understood. The present study was undertaken to investigate the effects of some inhibitors of different protein kinases and other molecular targets on LPA-induced DNA synthesis as well as gene expression in the aortic VSM cells. The DNA synthesis was studied by [3H]-thymidine incorporation method and the gene expression was investigated by real time PCR technique. It was observed that the LPA-induced DNA synthesis was attenuated by inhibitors of protein kinase C (PKC; staurosporine, calphostin C and bisindolylmaleimide), phosphoinositide 3-kinase (PI3K; wortmannin, and LY294002), and ribosomal p70S6 kinase (p70S6K; rapamycin). The inhibitors of guanine protein coupled receptors (GPCR; pertussis toxin), phospholipase C (PLC; U73122 and D609), and sodium-hydrogen exchanger (NHE; amiloride and dimethyl amiloride) were also shown to depress the LPA-induced DNA synthesis. Furthermore, gene expressions for PLC ß1 isoform, PKC δ and ε isoforms, casein kinase II ß isoform and endothelin-1A receptors were elevated by LPA. These results suggest that the LPA-induced proliferation of VSM cells is mediated through the activation of GPCR and multiple protein kinases as well as gene expressions of their some specific isoforms.

4.
Cancer Med ; 2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31373147

RESUMO

BACKGROUND: Endocrine therapy is the preferred treatment for patients with hormone receptor -positive metastatic breast cancer (MBC). While visceral metastasis is a negative prognostic factor, few studies have distinguished between the prognoses of patients with metastases at different visceral sites. PATIENTS AND METHODS: In total, 398 patients receiving fulvestrant 500 mg at a single center over a 6-year period were analyzed. Logistic regression models were used to identify the prognostic factors associated with progression-free survival (PFS). Kaplan-Meier analysis was used to compare the PFS of patients with lung and liver metastases. RESULTS: Baseline visceral metastases were present in 233 patients, including 138 with lungw/o liver metastases (lung metastases without liver involvement), 51 with liverw/o lung metastases (liver metastases without lung involvement) and 41 with lung and liver metastases. The median PFS was 6.8 months (5.6 and 9.2 months for visceral and nonvisceral metastases, respectively, P = .028). PFS was longer in patients with lungw/o liver metastases than in those with liverw/o lung metastases or lung and liver metastases (9.6, 3.7 and 3.2 months, respectively, P < .001; liverw/o lung vs. lungw/o liver hazard ratio (HR) 1.70; lung and liver vs. lungw/o liver HR 2.85). Patients with liver metastases experienced significantly worse PFS than those without liver involvement (3.7 vs. 9.2 months, P < .001). PFS benefits were observed in patients with longer disease-free intervals, no liver metastases, and no previous chemotherapy. CONCLUSION: Fulvestrant treatment benefited patients with lungw/o liver or nonvisceral metastases. When treating hormone receptor-positive/HER2-negative MBC patients with endocrine therapy, it is important to differentiate patients with lung metastases from those with liver metastases.

5.
Langmuir ; 35(29): 9584-9592, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31287700

RESUMO

New designer biofluorophores are being increasingly used in the investigation of complex cellular processes. In this study, we utilized new derivatives of pyrene (Py), i.e., 2-n-alkyl-pyrenes (Py-C4 and Py-C8), in order to probe different regions inside the hydrophobic tail of n-dodecyl ß-d-maltoside (ßMal-C12) in two different phases (cubic ↔ lamellar). Although the sensitivity to the local environment is reduced compared to that of Py, attaching C4 and C8 at the 2-position of Py can provide a possible means to probe the local hydrophobicity in different parts of the tail region. The absence of excimer fluorescence and the ratio of the vibronic fluorescence peak intensities (I1/I3) in a lipid environment indicate the existence of Py as monomers in the hydrophobic region, similar to hydrophobic solvation, yet close to the headgroup region. When Py is replaced by Py-C4 and Py-C8, there is a small increase in hydrophobicity (reduction in I1/I3) as the Py moiety is pulled deeper inside the tail region of both cubic and lamellar phases. The larger space of the tail region in the lamellar phase is reflected as more local hydrophobicity measured by the probes which can penetrate deep inside, whereas the curved structure of the cubic phase limits the available space for the probes. Three fluorescence lifetime components were measured in lipid, indicating the heterogeneous nature of the hydrophobic region. In the lamellar phase, a large reduction in the average lifetime value, led by the long decay component, was measured for Py-C4 (reduction by 25%) and Py-C8 (45%) compared to that of the parent Py. This observation suggests the presence of a mechanism of interaction more collisional than static between the Py moiety and the tail region of the bilayer unit due to the ample space provided by the lamellar phase as the probe is buried deeper inside the hydrophobic region. A much smaller effect was observed in the cubic phase and was correlated with the tight environment around the probes, which stems from the increased curvature of the cubic phase. The current results provide a deeper understanding of the hydrophobic region during phase transition of lipid self-assembly which is important for better control during the process of membrane-protein crystallization.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31326579

RESUMO

OBJECTIVE: Cannabis consumption during adolescence has been reported as a risk-factor for psychotic-like experiences (PLEs) and schizophrenia. However, brain developmental processes associated with cannabis-related PLEs are still ill-described. METHOD: 706 adolescents from the general population that were recruited by the IMAGEN consortium had structural MRI scans both at 14 and 19 years-old. We used deformation-based morphometry to map voxel-wise brain changes between the two time points, using the pairwise algorithm in SPM12b. We used an a-priori region of interest (ROI) approach focusing on the hippocampus/parahippocampus to perform voxel-wise linear regressions. Life time cannabis consumption was assessed using the European School Survey Project on Alcohol and other Drugs (ESPAD) and PLEs were assessed with the Comprehensive Assessment Psychotic-like experiences (CAPE). We first tested whether hippocampus/para-hippocampus development was associated with PLEs. Then, we formulated and tested an a-priori simple mediation model where uncus development mediates the association between lifetime cannabis consumption and PLEs. RESULTS: We found that PLEs was associated with reduced expansion within a specific region of the right hippocampus/para-hippocampus formation, the uncus (p=0.002 at the cluster level, p=0.018 at the peak-level). The partial simple mediation model revealed a significant total effect from lifetime cannabis consumption to PLEs (b=0.069 95CI [0.04-0.1], p=2 x 10-16), as well as a small yet significant, indirect effect of right uncus development (0.004, 95IC [0.0004-0.01], p=0.026). CONCLUSION: We show here that the uncus development is involved in the cerebral basis of PLEs in a population-based sample of healthy adolescents.

7.
Int J Biol Macromol ; 138: 125-134, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31279884

RESUMO

Carboxypeptidase A4 (CPA4) is a novel cancer-related gene that is aberrantly expressed in various malignant tumors. However, the roles and mechanisms of CPA4 have not been explored in colorectal cancer (CRC). In this study, we investigated the functions and mechanisms by which CPA4 promotes CRC progression. Quantitative real-time PCR (qRT-PCR) and western blot showed that CPA4 mRNA and CPA4 protein levels were up-regulated in CRC compared to levels in adjacent normal tissue. Immunohistochemistry (IHC) results indicating high CPA4 levels were positively associated with poor prognoses. In addition, Cell Counting Kit-8 (CCK-8), colony formation, flow cytometry, and transwell assays demonstrated that CPA4 overexpression facilitated the growth of CRC cells, whereas CPA4 knockdown resulted in decreased proliferation, G1/S phase transition arrest, and apoptosis. Subcutaneous tumorigenesis was performed in nude mice to confirm the tumor-promoting effects of CPA4 in vivo. Western blot revealed that activation of the STAT3 and ERK pathways is one of the oncogenic functions of CPA4 in CRC. Accordingly, CPA4 promotes CRC cell growth via activating the STAT3 and ERK pathways and may be a prognostic factor or therapeutic target for CRC.

8.
Adv Mater ; 31(36): e1903499, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31338908

RESUMO

Electrocatalysis has emerged as an attractive way for artificial CO2 fixation to CH3 OH, but the design and development of metal-free electrocatalyst for highly selective CH3 OH formation still remains a key challenge. Here, it is demonstrated that boron phosphide nanoparticles perform highly efficiently as a nonmetal electrocatalyst toward electrochemical reduction of CO2 to CH3 OH with high selectivity. In 0.1 m KHCO3 , this catalyst achieves a high Faradaic efficiency of 92.0% for CH3 OH at -0.5 V versus reversible hydrogen electrode. Density functional theory calculations reveal that B and P synergistically promote the binding and activation of CO2 , and the rate-determining step for the CO2 reduction reaction is dominated by *CO + *OH to *CO + *H2 O process with free energy change of 1.36 eV. In addition, CO and CH2 O products are difficultly generated on BP (111) surface, which is responsible for the high activity and selectivity of the CO2 -to-CH3 OH conversion process.

9.
Infect Dis Poverty ; 8(1): 59, 2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31253202

RESUMO

BACKGROUND: Scrub typhus is a life-threatening disease caused by Orientia tsutsugamushi, and specific antimicrobial medicine is available. Early and accurate diagnosis is essential for reducing the risk of severe complications and death. In this study, we aimed to evaluate the case diagnosis situation among medical care institutions and geographical regions in China, and the results will benefit both clinical practice and the disease surveillance system. METHODS: We extracted individual scrub typhus case data 2006-2016 from a national disease surveillance system in China. The diagnosis category and interval time from illness onset to diagnosis were compared among three levels of medical care institutions and provinces. The descriptive analysis method was performed in our study. RESULTS: During the 11-year study period, 93 481 scrub typhus cases, including 57 deaths, were recorded in the nationwide surveillance system. The overall proportion of laboratory-confirmed cases was only 4.7%, and this proportion varied greatly among primary medical centres (2.8%), county level hospitals (4.2%), and city level hospitals (6.3%). Notably, the proportion of laboratory-confirmed cases has consistently decreased from 16.3% in 2006 to 2.6% in 2016, and the same decreasing trend was found among all three levels of medical care institutions. The interval from illness onset to case diagnosis (Tdiag) for all cases was 5 days (interquartile range [IQR]: 2-9 days) and decreased from 7 days (IQR: 3-11 days) in 2006 to 5 days (IQR: 2-8 days) in 2016. The risk of death for patients with a Tdiag of > 7 days was 2.2 times higher (OR = 2.21, 95% CI: 1.05-5.21) than that of patients with a Tdiag of < 2 days. CONCLUSIONS: The interval time from illness onset to diagnosis for scrub typhus cases decreased greatly in China; however, the diagnosis rate of cases with laboratory-confirmed results must be increased among all levels of medical care institutions to reduce both the risk of death and the misuse of antibiotics associated with scrub typhus.

10.
Chemosphere ; 233: 132-139, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31170583

RESUMO

Oil sludge is one kind of toxic and persistent contamination to ecology system from petroleum industry. In order to recycle contaminated sands and reduce environmental impacts at a lower operating cost, enzyme cocktail 21/CbFDH including NADH regeneration system for oily sludge bioremediation was constructed for the first time. The intracellular enzymes of oil-degrading strain Acinetobacter calcoaceticus 21 were prepared and the formate dehydrogenase gene Cbfdh from Candida boidinii was cloned and functionally expressed in E.coli BL21 induced by lactose. The activity and stability of CbFDH was enhanced through self-induction medium optimization using Box-Behnken design. The CbFDH activity was 12.2 times increased and was only decreased 3.9% upon storage at 30 °C for 5 d. The CbFDH increased the degradation rate of oil in high concentration. For the sludge with 10% oil (w/w), the degradation rate achieved 35.6% after 12 h using enzyme 21/CbFDH with the protein ratio of 1:4. The results will provide novel perspectives for creation and operation of petroleum-degrading enzymes involving formate dehydrogenase with higher efficiency and lower cost comparing to current microbial strains or consortium.

11.
Chemistry ; 25(42): 9840-9845, 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31155772

RESUMO

A bis(benzobuta)tetraazapentacene derivative was reduced to its radical anion and its dianion, using potassium [18]crown-6 anthracenide in THF. Both reduced species were characterized by UV/Vis spectroscopy of the isolated species and by spectroelectrochemistry. Two distinct single-crystal structures of the dianion and an EPR spectrum of the radical anion were obtained. Contrary to other azaacenes, the lowest energy absorption in the UV/Vis spectrum of the dianion is redshifted in comparison to that of the neutral compound.

12.
Chem Commun (Camb) ; 55(52): 7546-7549, 2019 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31188371

RESUMO

Using electrocatalytic N2 reduction to make NH3 is considered to be an attractive environmentally-friendly alternative to the Haber-Bosch process, which is rather energy-intensive and has heavy CO2 emissions. However, only limited success has been achieved in identifying metal oxides as effective electrocatalysts for the N2 reduction reaction (NRR) under alkaline conditions. In this communication, we report that a K2Ti4O9 nanobelt is able to effectively electrocatalyze the ambient NRR for N2-to-NH3 fixation at alkaline pH. When tested in 0.1 M KOH, a high NH3 yield of 22.88 µg h-1 mg-1cat. and a faradaic efficiency of 5.87% were attained. Moreover, K2Ti4O9 also demonstrates good selectivity and high electrochemical stability for NH3 formation.

13.
Nanoscale ; 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31215588

RESUMO

The Haber-Bosch process for industrial-scale NH3 production suffers from harsh conditions and serious CO2 release. Electrochemical N2 reduction is an alternative approach to synthesize NH3 under ambient conditions, but it requires highly-efficient electrocatalysts for the N2 reduction reaction (NRR). In this Communication, we demonstrate that WO3 nanosheets rich in oxygen vacancies (R-WO3 NSs) exhibit greatly enhanced NRR performances. In 0.1 M HCl, such R-WO3 NSs achieve a large NH3 yield of 17.28 µg h-1 mgcat.-1 and a high faradaic efficiency of 7.0% at -0.3 V vs. a reversible hydrogen electrode, much superior to the WO3 nanosheets deficient in oxygen vacancies (6.47 µg h-1 mgcat.-1 and 1.02%). Remarkably, R-WO3 NSs also show high electrochemical stability.

14.
Chem Asian J ; 14(15): 2724-2730, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31188545

RESUMO

TiO2 nanotubes were successfully co-doped with sulfur and Ti3+ states using a facile annealing treatment in H2 /H2 S gas mixture. The obtained nanotubes were investigated for their photocatalytic performance and characterized by SEM, XRD, XPS, EPR, IPCE, IMPS and Mott-Schottky measurements. The synthesized co-doped TiO2 nanotubes show an enhanced photocatalytic hydrogen production rate compared to tubes that were treated only in pure H2 or H2 S atmosphere-this without the presence of any co-catalyst. It was found that sulfur in co-doped TiO2 exists in the form of S2- and a small quantity of S4+ /S6+ , which leads to a narrowing of the band gap. However, the enhanced absorption of light in the visible range is not the key reason for the improved photocatalytic performance. We ascribe the enhanced photocatalytic activity to a synergetic effect of S mid-gap states and disordered Ti3+ defects that facilitate photo generated electron transfer.

15.
Chemistry ; 25(46): 10845-10857, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31210396

RESUMO

The synthesis and characterization of 10-(dimesitylboryl)-N,N-di-p-tolylbenzo[c]phenanthren-4-amine (3-B(Mes)2 -[4]helix-9-N(p-Tol)2 1) and 13-(dimesitylboryl)-N,N-di-p-tolyldibenzo[c,g]phenanthren-8-amine (3-B(Mes)2 -[5]helix-12-N(p-Tol)2 2) are reported herein. Their electrochemical and photophysical properties have been studied experimentally and theoretically. The donor and acceptor-substituted helicene derivatives exhibit moderate fluorescence quantum yields in THF (Φf =0.48 and 0.61 for 1 and 2, respectively), which are higher than unsubstituted ones (Φf =0.18 for [4]helicene; Φf <0.05 for [n]helicenes (n≥5)). In the solid state, the Φf values are higher (Φf =1.00 and 0.55 for 1 and 2, respectively) than those in solution, most likely due to the restrictions of molecular motions. The S1 ←S0 transitions of 1 and 2 are predominately HOMO→LUMO transitions. Upon excitation with UV light, the interplanar angle between the two terminal aryl rings of the [5]helix core of 2 decreases (S1 state compared with S0 state), which is similar to placing a spring under an external force.

16.
J Pharm Biomed Anal ; 174: 367-375, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31202879

RESUMO

Fufang Danshen Dripping Pill (FDDP) and Clopidogrel Bisulfate Tablet (CBT) are usually combined for treatment of coronary artery diseases in clinical. To investigate the pharmacokinetic interaction between FDDP and CBT after oral administration of FDDP, CBT and their combination in rats, a novel LC-MS method with segmented scan modes (multiple reaction monitoring and selected ion monitoring) and polarity (positive and negative ionization) was developed. Clopidogrel and the main active ingredients of FDDP, with different chemical and ionization properties, were simultaneously quantified in plasma in a single run. The method was validated in terms of specificity, linearity, precision, accuracy, recovery, matrix effect and stability. As a result, co-administration of FDDP and CBT significantly altered the pharmacokinetic parameters of danshensu, ginsenoside Rb1, dihydrotanshinone I, tanshinone I and tanshinone IIA of FDDP, as well as clopidogrel. Mechanism studies suggested that induction of liver cytochrome P450 isozymes CYP2C11 and CYP3A1 by co-administration, as well as inhibition of carboxyl esterase 1, was partly responsible for FDDP-CBT pharmacokinetic interactions. The developed LC-MS method could be used to simultaneously quantify different types of in vivo analytes in a single run, and the results could be used for clinical medication guidance of FDDP and CBT.

17.
J Am Chem Soc ; 141(23): 9165-9169, 2019 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-31141357

RESUMO

The fast-ionic-conducting ceramic electrolyte is promising for next-generation high-energy-density Li-metal batteries, yet its application suffers from the high interfacial resistance and poor interfacial stability. In this study, the compatible solid-state electrolyte was designed by coating Li1.4Al0.4Ti1.6(PO4)3 (LATP) with polyacrylonitrile (PAN) and polyethylene oxide (PEO) oppositely to satisfy deliberately the disparate interface demands. Wherein, the upper PAN constructs soft-contact with LiNi0.6Mn0.2Co0.2O2, and the lower PEO protects LATP from being reduced, guaranteeing high-voltage tolerance and improved stability toward Li-metal anode performed in one ceramic. Moreover, the core function of LATP is amplified to guide homogeneous ions distribution and hence suppresses the formation of a space-charge layer across interfaces, uncovered by the COMSOL Multiphysics concentration field simulation. Thus, such a bifunctional modified ceramic electrolyte integrates the respective superiority to render Li-metal batteries with excellent cycling stability (89% after 120 cycles), high Coulombic efficiency (exceeding 99.5% per cycle), and a dendrite-free Li anode at 60 °C, which represents an overall design of ceramic interface engineering for future practical solid battery systems.

18.
Chem Commun (Camb) ; 55(45): 6401-6404, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31094366

RESUMO

The synthesis of NH3 heavily relies on the Haber-Bosch process suffering from a large amount of CO2 emission and energy consumption. Possessing eco-friendly and sustainable characteristics, electrochemical reduction is considered as a promising candidate for artificial N2 fixation under ambient conditions, but efficient electrocatalysts are crucial for the N2 reduction reaction (NRR). In this communication, we report that perovskite La2Ti2O7 nanosheets behave as an efficient NRR electrocatalyst with excellent selectivity under ambient conditions. In 0.1 M HCl, this catalyst achieves a high NH3 yield rate of 25.15 µg h-1 mgcat.-1 with a faradaic efficiency of 4.55% at -0.55 V vs. a reversible hydrogen electrode. Notably, it also shows high electrochemical stability.

19.
J Cell Mol Med ; 23(8): 5200-5210, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144439

RESUMO

Colorectal cancer (CRC) is one of the leading causes of cancer-associated death globally. Long non-coding RNAs (lncRNAs) have been identified as micro RNA (miRNA) sponges in a competing endogenous RNA (ceRNA) network and are involved in the regulation of mRNA expression. This study aims to construct a lncRNA-associated ceRNA network and investigate the prognostic biomarkers in CRC. A total of 38 differentially expressed (DE) lncRNAs, 23 DEmiRNAs and 27 DEmRNAs were identified by analysing the expression profiles of CRC obtained from The Cancer Genome Atlas (TCGA). These RNAs were chosen to develop a ceRNA regulatory network of CRC, which comprised 125 edges. Survival analysis showed that four lncRNAs, six miRNAs and five mRNAs were significantly associated with overall survival. A potential regulatory axis of ADAMTS9-AS2/miR-32/PHLPP2 was identified from the network. Experimental validation was performed using clinical samples by quantitative real-time PCR (qRT-PCR), which showed that expression of the genes in the axis was associated with clinicopathological features and the correlation among them perfectly conformed to the 'ceRNA theory'. Overexpression of ADAMTS9-AS2 in colon cancer cell lines significantly inhibited the miR-32 expression and promoted PHLPP2 expression, while ADAMTS9-AS2 knockdown had the opposite effects. The constructed novel ceRNA network may provide a comprehensive understanding of the mechanisms of CRC carcinogenesis. The ADAMTS9-AS2/miR-32/PHLPP2 regulatory axis may serve as a potential therapeutic target for CRC.

20.
J Am Chem Soc ; 141(18): 7235-7239, 2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31010287

RESUMO

The morphology controlled molecular assemblies play vital roles in biological systems. Here we present endogenous reactive oxygen species (ROS)-triggered morphology transformation of polymer-peptide conjugates (PPCs) for cooperative interaction with mitochondria, exhibiting high tumor therapeutic efficacy. The PPCs are composed of (i) a ß-sheet-forming peptide KLVFF conjugated with poly(ethylene glycol) through ROS-cleavable thioketal, (ii) a mitochondria-targeting cytotoxic peptide KLAK, and (iii) a poly(vinyl alcohol) backbone. The self-assembled PPCs nanoparticles can enter cells and target mitochondria. Because of overgenerated ROS around mitochondria in most cancer cells, the thioketal linker can be cleaved, leading to transformation from nanoparticles to fibrous nanostructures. As a result, the locational nanofibers with exposure of KLAK exhibit enhanced multivalent cooperative interactions with mitochondria, which causes selective cytotoxicity against cancer cells and powerful tumor suppression efficacy in vivo. As the first example of ROS-triggered intracellular transformation, the locational assembly strategy in vivo may provide a new insight for disease diagnosis and therapy through enhanced interaction with targeting site.

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