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1.
Macromol Rapid Commun ; : e2100510, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643989

RESUMO

To solve the issue of polymeric materials recycling, developing intrinsic self-healing materials containing dynamic bonds has attracted many researchers' highly concerning. However, the tradeoff between their mechanical strength and stretchability always doesn't avoid. Herein, to surmount the above tradeoff, metal-ligand (Cu2+ -S) interactions were introduced into the cross-linking polythiourethane covalent adaptable networks (PTU CANs) with three kinds of dynamic motifs (thiourethane, disulfide, and hydrogen bonds). When the molar ratio of Cu2+ to S is 6.37%, the break strength (9.41±0.34 MPa) and Young's modulus (26.02±0.55 MPa) of the metal-ligand coordination complex PTU (Cu2+ -PTU-3) dramatically increased, whereas the peak strain almost did not decline (454.44±3.95%). To conduct the repairing, Cu2+ -PTU-3 was further confirmed excellent repairing capability. Therefore, these new PTU CANs have significant potential for the new self-healing materials. This article is protected by copyright. All rights reserved.

2.
Int J Mol Sci ; 22(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34360850

RESUMO

Autophagy is a conserved degradation pathway for recycling damaged organelles and aberrant proteins, and its important roles in plant adaptation to nutrient starvation have been generally reported. Previous studies found that overexpression of autophagy-related (ATG) gene MdATG10 enhanced the autophagic activity in apple roots and promoted their salt tolerance. The MdATG10 expression was induced by nitrogen depletion condition in both leaves and roots of apple plants. This study aimed to investigate the differences in the growth and physiological status between wild type and MdATG10-overexpressing apple plants in response to nitrogen starvation. A hydroponic system containing different nitrogen levels was used. The study found that the reduction in growth and nitrogen concentrations in different tissues caused by nitrogen starvation was relieved by MdATG10 overexpression. Further studies demonstrated the increased root growth and the higher nitrogen absorption and assimilation ability of transgenic plants. These characteristics contributed to the increased uptake of limited nitrogen nutrients by transgenic plants, which also reduced the starvation damage to the chloroplasts. Therefore, the MdATG10-overexpressing apple plants could maintain higher photosynthetic ability and possess better growth under nitrogen starvation stress.


Assuntos
Proteínas Relacionadas à Autofagia/metabolismo , Malus/metabolismo , Nitrogênio/metabolismo , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Autofagia , Cloroplastos/metabolismo , Regulação da Expressão Gênica de Plantas , Raízes de Plantas/crescimento & desenvolvimento , Estresse Fisiológico
3.
Adv Drug Deliv Rev ; : 113917, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34384827

RESUMO

Natural small molecules derived from plants have fascinated scientists for centuries due to their practical applications in various fields, especially in nanomedicine. Some of the natural molecules were found to show intrinsic optical features such as fluorescence emission and photosensitization, which could be beneficial to provide spatial temporal information and help tracking the drugs in biological systems. Much efforts have been devoted to the investigation of optical properties and practical applications of natural molecules. In this review, optical properties of natural small molecules and their applications in fluorescence imaging, and theranostics will be summarized. First, we will introduce natural small molecules with different fluorescence emission, ranging from blue to near infrared emission. Second, imaging applications in biological samples will be covered. Third, we will discuss the applications of theranostic nanomedicines or drug delivering systems containing fluorescent natural molecules acting as imaging agents or photosensitizers. Finally, future perspectives in this field will be discussed.

4.
Bioconjug Chem ; 32(8): 1812-1822, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34264651

RESUMO

Strained alkenes and alkynes are the predominant dienophiles used in inverse electron demand Diels-Alder (IEDDA) reactions. However, their instability, cross-reactivity, and accessibility are problematic. Unstrained dienophiles, although physiologically stable and synthetically accessible, react with tetrazines significantly slower relative to strained variants. Here we report the development of potassium arylethynyltrifluoroborates as unstrained dienophiles for fast, chemically triggered IEDDA reactions. By varying the substituents on the tetrazine (e.g., pyridyl- to benzyl-substituents), cycloaddition kinetics can vary from fast (k2 = 21 M-1 s-1) to no reaction with an alkyne-BF3 dienophile. The reported system was applied to protein labeling both in the test tube and fixed cells and even enabled mutually orthogonal labeling of two distinct proteins.

5.
Nat Commun ; 12(1): 2772, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33986258

RESUMO

Reversible NIR luminescent probes with negligible photocytotoxicity are required for long-term tracking of cycling hypoxia in vivo. However, almost all of the reported organic fluorescent hypoxia probes reported until now were irreversible. Here we report a reversible arylazo-conjugated fluorescent probe (HDSF) for cycling hypoxia imaging. HDSF displays an off-on fluorescence switch at 705 nm in normoxia-hypoxia cycles. Mass spectroscopic and theoretical studies confirm that the reversible sensing behavior is attributed to the two electron-withdrawing trifluoromethyl groups, which stabilizes the reduction intermediate phenylhydrazine and blocks the further reductive decomposition. Cycling hypoxia monitoring in cells and zebrafish embryos is realized by HDSF using confocal imaging. Moreover, hypoxic solid tumors are visualized and the ischemia-reperfusion process in mice is monitored in real-time. This work provides an effective strategy to construct organic fluorescent probes for cycling hypoxia imaging and paves the way for the study of cycling hypoxia biology.


Assuntos
Hipóxia Celular/fisiologia , Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Análise de Célula Única/métodos , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Isquemia/diagnóstico por imagem , Células MCF-7 , Camundongos , Camundongos Endogâmicos ICR , Microscopia Confocal , Traumatismo por Reperfusão/diagnóstico por imagem , Peixe-Zebra/embriologia
6.
Chem Commun (Camb) ; 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33870390

RESUMO

A transition metal-free aldol condensation/[1+2+3] annulation reaction of isocyanoacetates with 8-(alkynyl)-1-naphthaldehydes has been developed for the general synthesis of azafluoranthenes. This domino reaction enables successive formation of three new bonds and two rings from readily accessible starting materials in a single operation. Furthermore, this methodology can also be utilized to construct chromeno[4,3-c]pyridines and benzo[c][2,6]naphthyridines in moderate yields.

7.
Angew Chem Int Ed Engl ; 60(15): 8174-8181, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33656228

RESUMO

Limited therapeutic efficacy to hypoxic and refractory solid tumors has hindered the practical application of photodynamic therapy (PDT). Two new benzothiophenylisoquinoline (btiq)-derived cyclometalated IrIII complexes, IrL1 and MitoIrL2, were constructed as potent photosensitizers, with the latter being designed for mitochondria accumulation. Both complexes demonstrated a type I PDT process and caused photoinduced ferroptosis in tumor cells under hypoxia. This ferroptosis featured lipid peroxide accumulation, mitochondria shrinkage, down-regulation of glutathione peroxidase 4 (GPX4), and ferrostatin-1 (Fer-1)-inhibited cell death. Upon photoirradiation under hypoxia, mitochondria targeting MitoIrL2 caused mitochondria membrane potential (MMP) collapse, ATP production suppression, and induced cell apoptosis. The synergetic effect of ferroptosis and apoptosis causes MitoIrL2 to outperform IrL1 in inhibiting the growth of MCF-7, PANC-1, MDA-MB-231 cells and multicellular spheroids. This study demonstrates the first example of ferroptosis induced by photosensitizing IrIII complexes. Moreover, the synergism of ferroptosis and apoptosis provides a promising approach for combating hypoxic solid tumors through type I PDT processes.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Ferroptose/efeitos dos fármacos , Irídio/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/química , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química
8.
Knee ; 29: 510-519, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33756261

RESUMO

BACKGROUND: The systems for precisely locating the joint line during primary and revision total knee arthroplasty are still controversial, and they should be better evaluated in the Chinese population. METHODS: A total of 451 standard anteroposterior knee radiographs from 451 healthy Chinese people (283 males and 168 females, the average age of 33.26 years, range 20-50 years) were included to measure the femoral width (FW) and the distances from the adductor tubercle (AT), the medial epicondyle (ME), the lateral epicondyle (LE), and the fibular head (FH) to the joint line (JL). Correlation between FW and distances from landmarks to the joint line was evaluated using Pearson correlation coefficient, and the ratios of ATJL, MEJL, LEJL, FHJL to FW were calculated. RESULTS: The average distances from the AT, the ME, the LE, the FH to the JL were 49.4 ± 5.0 mm, 28.3 ± 3.1 mm, 26.9 ± 2.9 mm, 20.0 ± 4.0 mm, respectively. An excellent linear correlation was found between FW and the distance from AT to the joint line (R = 0.836, R2 = 0.698); it was more reliable than the LE (R = 0.686, R2 = 0.471) and the ME (R = 0.672, R2 = 0.452). The average ratios of ATJL/FW, MEJL/FW, LEJL/FW were 0.553, 0.317, and 0.302, respectively. There were significant differences between our results and the studies based on the Western people. CONCLUSION: The AT can be used as a reliable landmark to locate the JL precisely by the formula (ATJL = 0.548 × FW in males; ATJL = 0.562 × FW in females) in the Chinese population. The LE and ME can be the second choices. Moreover, it may be better to use ratios from the research based on the same race.


Assuntos
Artroplastia do Joelho/métodos , Fêmur/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Adulto , Artroplastia do Joelho/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Feminino , Fêmur/cirurgia , Fíbula/diagnóstico por imagem , Fíbula/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reoperação , Adulto Jovem
9.
J Inorg Biochem ; 218: 111394, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33647541

RESUMO

Photodynamic therapy (PDT) has attracted extensive attention in cancer treatment because of its minimum trauma, less side effects, and so on. Photosensitizers, as one of the core elements of PDT, usually have to face problems such as poor water solubility and light stability, lack of targeting, and other problems, which seriously affect the therapeutic effect. In this work, two BODIPY (boron-dipyrromethene)-based monofunctional Pt (II) complexes, 1a and 2a, were designed and synthesized, and their PDT effect was studied. The Pt atom improved the singlet oxygen quantum yield (0.19 for 1a and 0.14 for 2a, respectively), which effectively improves the efficiency of PDT. MTT assay confirmed that the short time photo-irradiation distinctly promoted antitumor cytotoxicity of Pt (II) compounds against different cell lines. For 1a under irradiation, the IC50 value of cancer cell lines were 13.1 µM for HeLa cells and 7.6 µM for MCF-7 cells, while those of normal cell lines were 32.4 µM for HBL-100 cells and 48.6 µM for L02 cells. The results demonstrated that 1a showed specific phototoxicity to cancer cells. This specific selectivity could be attributed to the synergistic effect of increased cellular uptake (determined by ICP-MS) and higher ROS generation (detected by Cell ROX Deep Red) in cancer cells after irradiation. This study laid the foundation for the future design and synthesis of effective PDT photosensitizers.

10.
Plant Sci ; 306: 110850, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33775357

RESUMO

Autophagy is a major degradation pathway in plants for maintaining cellular homeostasis in response to various environmental stressors. ATG8 is one of a series of autophagy-related (ATG) proteins and plays a central role in both bulk and selective autophagy. Previously, we characterized MdATG8i in apple and demonstrated that it has a positive role in apple stress resistance. Although many ATG8-interacting proteins have been found in Arabidopsis, no protein has been reported to interact with MdATG8 in apple. Here, we identified MdHARBI1 as a MdATG8i-interacting protein in apple, however, the functions of HARBI1-like proteins have not been explored in plants. Expression analysis of MdHARBI1 and pro-MdHARBI1-GUS staining of transgenic Arabidopsis exposed to high temperature demonstrated that MdHARBI1 was significantly induced by heat stress. Moreover, heat-treated MdHARBI1-trangenic tomato plants maintained higher autophagic activity, accumulated fewer ROS, and displayed stronger chlorophyll fluorescence than wild-type plants. Because these phenotypes were consistent with those displayed by MdATG8i-overexpressing apple plants under high temperature, we concluded that the MdATG8i-interacting protein MdHARBI1 plays a critical role in the basal thermotolerance of plants, mainly by influencing autophagy pathways.


Assuntos
Proteínas Relacionadas à Autofagia/fisiologia , Autofagia/genética , Resposta ao Choque Térmico/genética , Malus/genética , Malus/fisiologia , Termotolerância/genética , Termotolerância/fisiologia , Autofagia/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Resposta ao Choque Térmico/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia
11.
Dalton Trans ; 50(10): 3516-3522, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33433537

RESUMO

Platinum-based anticancer drugs constitute the cornerstone of chemotherapy for various cancers. Although cytotoxic agents are considered to have immunosuppressive effects, increasing evidence suggests that some cytotoxic compounds can effectively stimulate the antitumor immune response by inducing a special type of apoptosis called immunogenic cell death (ICD). A platinum(iv) complex (DCP) modified with the derivative of synthetic capsaicin (nonivamide) was designed to elicit ICD. The complex exhibited high cytotoxicity against a panel of human cancer cell lines including pancreas (PANC-1), breast (MCF-7), and liver (HepG2) cancer cells, and osteosarcoma (MG-63) cells. In addition to causing DNA damage, DCP also triggered the translocation of calreticulin (CRT) as well as the release of ATP and HMGB1 protein in PANC-1 cells, thus manifesting an efficient ICD-inducing effect on cancer cells. Furthermore, the DCP-treated PANC-1 cell-conditioned culture medium promoted the release of IFN-γ and TNF-α to induce the immune response of human peripheral blood mononuclear cells, thereby increasing their cytotoxicity to cancer cells. Concurrently, the phagocytosis of PANC-1 cells by macrophages was also augmented by DCP. The results demonstrate that DCP is an effective inducer of ICD and a potential agent for chemoimmunotherapy of cancers.


Assuntos
Antineoplásicos/farmacologia , Capsaicina/farmacologia , Complexos de Coordenação/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Capsaicina/síntese química , Capsaicina/química , Bovinos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , DNA/química , DNA/efeitos dos fármacos , Dano ao DNA , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucócitos Mononucleares/imunologia , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química
12.
Nat Commun ; 12(1): 109, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397937

RESUMO

Zn2+ plays important roles in metabolism and signaling regulation. Subcellular Zn2+ compartmentalization is essential for organelle functions and cell biology, but there is currently no method to determine Zn2+ signaling relationships among more than two different organelles with one probe. Here, we report simultaneous Zn2+ tracking in multiple organelles (Zn-STIMO), a method that uses structured illumination microscopy (SIM) and a single Zn2+ fluorescent probe, allowing super-resolution morphology-correlated organelle identification in living cells. To guarantee SIM imaging quality for organelle identification, we develop a new turn-on Zn2+ fluorescent probe, NapBu-BPEA, by regulating the lipophilicity of naphthalimide-derived Zn2+ probes to make it accumulate in multiple organelles except the nucleus. Zn-STIMO with this probe shows that CCCP-induced mitophagy in HeLa cells is associated with labile Zn2+ enhancement. Therefore, direct organelle identification supported by SIM imaging makes Zn-STIMO a reliable method to determine labile Zn2+ dynamics in various organelles with one probe. Finally, SIM imaging of pluripotent stem cell-derived organoids with NapBu-BPEA demonstrates the potential of super-resolution morphology-correlated organelle identification to track biospecies and events in specific organelles within organoids.


Assuntos
Rastreamento de Células , Organelas/metabolismo , Zinco/metabolismo , Autofagossomos/metabolismo , Autofagia , Carbonil Cianeto m-Clorofenil Hidrazona/farmacologia , Sobrevivência Celular , Retículo Endoplasmático/metabolismo , Corantes Fluorescentes/metabolismo , Células HeLa , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Espaço Intracelular/metabolismo , Lisossomos/metabolismo , Sondas Moleculares/química , Sondas Moleculares/metabolismo , Naftalimidas/metabolismo , Organoides/metabolismo , Espectrometria de Fluorescência
13.
J Org Chem ; 86(1): 207-222, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33232152

RESUMO

A novel metal-free, efficient cascade reaction has been developed to construct 1,2,3-triazole-fused 1,4-diazepinone skeletons. Mechanism investigation indicated that sodium azide has not only served as a 1,3-dipoles synthon in [3 + 2] cycloaddition but also prompted C-N bond formation. Furthermore, the potential utility of this protocol was demonstrated by scale-up synthesis of 1,2,3-triazole-fused diazepinone derivatives and the derivatization of them.

14.
Cancer Gene Ther ; 28(5): 400-412, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33057139

RESUMO

Encouraging insight into novel underlying mechanisms targeting abnormal biological pathways in colorectal cancer (CRC) are currently under investigation, edging closer and closer to clinical use. Of note, basic leucine zipper ATF-like transcription factor 3 (BATF3) has been implicated with the tumorigenicity of CRC. The current study aimed to elucidate the oncogenic BATF3-mediated S1PR1/p-STAT3/miR-155-3p/WDR82 axis in CRC. Initially, clinical samples of CRC tissues as well as CRC cell lines were collected to evaluate the expression patterns of BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82. Dual luciferase assay was employed to assess the binding affinity between miR-155-3p and WDR82. Artificial modulation of BATF3 (down- and overexpression) was conducted to measure the malignant phenotypes of CRC cells, while tumor-bearing mice were examined to determine the in vivo effects. BATF3 facilitated the proliferative, migratory, and invasive potential of CRC cells by upregulating S1PR1. Besides, the stimulatory effect of S1PR1 was realized via restored p-STAT3 expression. Furthermore, p-STAT3 was evidenced to heighten the expression of miR-155-3p and subsequently restrict the expression of its target gene WDR82. The in vivo assays provided data further substantiating the in vitro findings that inactivation of the BATF3/S1PR1/p-STAT3/miR-155-3p/WDR82 axis suppresses CRC tumor growth. Collectively, the results of the present study emphasize the oncogenic function of BATF3 illustrated by the reinforcement the biological processes of proliferation, invasion, as well as the metastatic capacity of CRC cells through activating the S1PR1/p-STAT3/miR-155-3p/WDR82 axis.

15.
Dalton Trans ; 50(1): 304-310, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33300919

RESUMO

Topoisomerases are ubiquitous enzymes and important targets for DNA-oriented anticancer drugs. Two mitochondrion-targeted monofunctional platinum(ii) complexes, [Pt(ortho-PPh3CH2Py)(NH3)2Cl](NO3)2 (OPT) and [Pt(para-PPh3CH2Py)(NH3)2Cl](NO3)2 (PPT; PPh3 = triphenylphosphonium, Py = pyridine), show significant inhibition towards the activity of DNA topoisomerases in addition to their DNA binding and mitochondrial targeting capabilities. OPT exhibits strong cytotoxicity toward the human renal clear cell carcinoma 786-O and the murine prostate cancer RM-1 cell lines. The complex could bind to the minor groove of DNA, as well as DNA topoisomerases I and IIα, thereby acting as an inhibitor of topoisomerase I/IIα and causing DNA damage. The damage was evidenced by the enhanced expression of γ-H2AX, Chk1/2 phosphorylation, p53 and cell cycle arrest in the G2/M phase. In contrast, the inhibitory effect of PPT on DNA topoisomerases was largely limited to the isolated enzymes. The results demonstrate that the cellular inhibition of the complex towards the DNA topoisomerases positively correlated with its mitochondrial accumulation. Molecular docking provided more detailed structural insights into the interactions of OPT or PPT with DNA and topoisomerase I/IIα. The binding sites of OPT and PPT in topoisomerase-DNA complexes are different from each other. Aside from previously revealed DNA and mitochondrial targets, this study discovered new evidence that DNA topoisomerases may also serve as targets of monofunctional platinum(ii) complexes. For a multispecific platinum complex, strong DNA binding ability does not necessarily lead to potent cytotoxicity as other factors including the cell types, mitochondrial accumulation, and activity of DNA topoisomerases also affect the outcome of DNA damage.

16.
Nat Commun ; 11(1): 6290, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293545

RESUMO

Mitochondria-lysosome interactions are essential for maintaining intracellular homeostasis. Although various fluorescent probes have been developed to visualize such interactions, they remain unable to label mitochondria and lysosomes simultaneously and dynamically track their interaction. Here, we introduce a cell-permeable, biocompatible, viscosity-responsive, small organic molecular probe, Coupa, to monitor the interaction of mitochondria and lysosomes in living cells. Through a functional fluorescence conversion, Coupa can simultaneously label mitochondria with blue fluorescence and lysosomes with red fluorescence, and the correlation between the red-blue fluorescence intensity indicates the progress of mitochondria-lysosome interplay during mitophagy. Moreover, because its fluorescence is sensitive to viscosity, Coupa allowed us to precisely localize sites of mitochondria-lysosome contact and reveal increases in local viscosity on mitochondria associated with mitochondria-lysosome contact. Thus, our probe represents an attractive tool for the localization and dynamic tracking of functional mitochondria-lysosome interactions in living cells.


Assuntos
Microscopia Intravital/métodos , Lisossomos/metabolismo , Mitocôndrias/metabolismo , Mitofagia , Sondas Moleculares/química , Recuperação de Fluorescência Após Fotodegradação/métodos , Corantes Fluorescentes/química , Células HeLa , Humanos , Lisossomos/química , Microscopia de Fluorescência/métodos , Mitocôndrias/química , Técnicas de Sonda Molecular , Fotodegradação
17.
Metallomics ; 12(11): 1834-1840, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151228

RESUMO

Cisplatin and oxaliplatin are widely used anti-tumour chemotherapeutic agents with different spectra of activity. The therapeutic efficacy of such platinum-based drug is believed to, at least in part, result from formation of Pt-DNA adducts, followed by DNA damage response and ultimately apoptosis. However, it remains unclear whether these DNA lesions caused by cisplatin and oxaliplatin elicit distinct reactions in cellular signaling pathways. Here, a label-free comparative proteomic study was performed to profile the protein phosphorylation patterns using Pt-DNA probes with different ligand identities and geometries. Phosphorylated proteins recognizing different cisplatin- and oxaliplatin-DNA lesions were enriched and analyzed on LC-MS/MS. Proteomic analysis revealed that cisplatin mainly affected proteins involved in mRNA processing, while chromatin organization and rRNA processing are two major biological processes influenced by oxaliplatin. Changes to site-specific phosphorylation levels of two proteins YBX1 and UBF1 were also validated by Western blotting. In particular, platinum drug treatment in colon and liver cancer cell lines down-regulated S484 phosphorylation of UBF1, which is an essential transcription factor responsible for ribosomal DNA transcription activation, implying that inhibition of ribosome biogenesis might be involved in the cytotoxic mechanism of platinum drugs. Collectively, these results directly reflected distinct protein phosphorylation patterns triggered by cisplatin and oxaliplatin, and could also provide valuable resources for future mechanistic studies of platinum-based anti-tumour agents.

18.
Biochem Biophys Res Commun ; 533(4): 1039-1047, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-33012505

RESUMO

Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. In this study, we aimed to explore the role and mechanism of lncRNA ST8SIA6-AS1 in HCC. We found that ST8SIA6-AS1 was upregulated in HCC tissues and associated with poorer overall survival of HCC patients from TCGA. Moreover, ST8SIA6-AS1 was highly expressed in HCC in-house tissues and cells, and ST8SIA6-AS1 upregulation was related to aggressive tumor phenotypes and the poor overall survival of HCC patients. Downregulation of ST8SIA6-AS1 suppressed HCC cell proliferation, migration and invasion in vitro and restrained HCC tumorigenesis in vivo. In terms of mechanism, ST8SIA6-AS1 regulated melanoma-associated antigen (MAGE)-A3 (MAGEA3) and DDB1-and Cul4-associated factor 4-like 2 (DCAF4L2) expression, and rescue experiments verified that ST8SIA6-AS1 played a protumorigenic role in HCC via the regulation of MAGEA3 and DCAF4L2. ST8SIA6-AS1 partly directly bound to miR-129-5p and functioned as a competing endogenous RNA (ceRNA), subsequently facilitating the expression of the miR-129-5p target gene DCAF4L2 to play its role in HCC. In summary, our results identified ST8SIA6-AS1 as an oncogenic lncRNA predicting poor clinical outcomes of patients with HCC. These findings suggest that ST8SIA6-AS1 is a potential therapeutic target for HCC.


Assuntos
Antígenos de Neoplasias/metabolismo , Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Antígenos de Neoplasias/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Bases de Dados Genéticas , Progressão da Doença , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos SCID , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas de Neoplasias/genética , Prognóstico , RNA Longo não Codificante/genética , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Dalton Trans ; 49(40): 13954-13957, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33000850

RESUMO

Ru(ii) complexes have been recognized as excellent anticancer candidates. However, the poor cell uptake of these complexes has been the major obstacle in improving their anticancer efficacy. Along with the development of the knowledge on the anticancer nature of the Ru(ii) complexes, several strategies have been designed to increase the cellular accumulation of these complexes. Among them, the light-triggered drug uptake approach is most promising. In this study, a bioactive Ru(ii)-polypyridyl complex Ru-1 is constructed via incorporating a modified phenanthroline ligand into the enlarged conjugate structure. The modulation of the ligand makes Ru-1 powerful in generating singlet oxygen and effective in photodynamic therapeutic activity. Moreover, the cell uptake is improved during this photodynamic process and induces further chemotherapeutic effect, which act synergistically to enhance its anticancer activity. The photoinduced synergistic cytotoxicity of Ru-1 towards cancer cells offers an effective way to sensitize the antitumor activity of Ru(ii) complexes.

20.
ACS Appl Mater Interfaces ; 12(45): 50812-50822, 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33118819

RESUMO

Achieving a desirable combination of good mechanical properties and healing efficiency is a great challenge in the development of self-healing elastomers. Herein, a class of tough and strong self-healing polyacrylate elastomers (denoted as HPs) was developed simply by free-radical copolymerization of n-butyl acrylate (nBA) and tert-butyl acrylate (tBA) and a subsequent hydrolysis reaction rather than direct copolymerization of nBA and acrylic acid (AA). The tiny difference in reactivity between nBA and tBA makes the structural units of the copolymer easy to control. Precise regulation of molecular composition can be realized just by varying the relative monomer content, making its mechanical properties to vary from ductile to robust. Strikingly, when HP samples are cut off within the gauge length, they can heal into coherent and smooth samples and recover at least 79% of the original strength. Hydrogen bond interactions serve as physical cross-linking points, contributing to the high mechanical performance (fracture energy of up to 73.78 MJ·m-3 and tensile strength of up to 17.80 MPa) as well as shape memory function. Moreover, the HP samples emit strong fluorescence when exposed to a 365 nm UV lamp and exhibit an aggregation-enhanced emission effect in the state of dissolution.

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