Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
Mais filtros








Base de dados
Intervalo de ano de publicação
1.
Phys Rev Lett ; 132(8): 081601, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38457701

RESUMO

We consider a model of Parisi where a single particle hops on an infinite-dimensional hypercube, under the influence of a uniform but disordered magnetic flux. We reinterpret the hypercube as the Fock-space graph of a many-body Hamiltonian and the flux as a frustration of the return amplitudes in Fock-space. We will identify the set of observables that have the same correlation functions as the double-scaled Sachdev-Ye-Kitaev (DS-SYK) model, and hence the hypercube model is an equally good quantum model for near-AdS_{2}/near-CFT_{1} (NAdS_{2}/NCFT_{1}) holography. Unlike the SYK model, the hypercube Hamiltonian is not p local. Instead, the SYK model can be understood as a Fock-space model with similar frustrations. Hence we propose this type of Fock-space frustration as the broader characterization for NAdS_{2}/NCFT_{1} microscopics, which encompasses the hypercube and the DS-SYK models as two specific examples. We then speculate on the possible origin of such frustrations.

2.
Phytomedicine ; 128: 155521, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489891

RESUMO

BACKGROUND: The ancient Chinese herb Salvia miltiorrhiza Bunge (Danshen), plays the important role in cardiovascular and cerebrovascular disease. Furthermore, Danshen could also be used for curing carcinogenesis. Up to now, the anti-tumor effects of the main active constituents of Danshen have made great progress. However, the bioavailability of the active constituents of Danshen were restricted by their unique physical characteristics, like low oral bioavailability, rapid degradation in vivo and so on. PURPOSE: With the leap development of nano-delivery systems, the shortcomings of the active constituents of Danshen have been greatly ameliorated. This review tried to summarize the recent progress of the active constituents of Danshen based delivery systems used for anti-tumor therapeutics. METHODS: A systematic literature search was conducted using 5 databases (Embase, Google scholar, PubMed, Scopus and Web of Science databases) for the identification of relevant data published before September 2023. The words "Danshen", "Salvia miltiorrhiza", "Tanshinone", "Salvianolic acid", "Rosmarinic acid", "tumor", "delivery", "nanomedicine" and other active ingredients contained in Danshen were searched in the above databases to gather information about pharmaceutical decoration for the active constituents of Danshen used for anti-tumor therapeutics. RESULTS: The main extracts of Danshen could inhibit the proliferation of tumor cells effectively and a great deal of studies were conducted to design drug delivery systems to ameliorate the anti-tumor effect of the active contents of Danshen through different ways, like improving bioavailability, increasing tumor targeting ability, enhancing biological barrier permeability and co-delivering with other active agents. CONCLUSION: This review systematically represented recent progress of pharmaceutical decorations for the active constituents of Danshen used for anti-tumor therapeutics, revealing the diversity of nano-decoration skills and trying to inspire more designs of Danshen based nanodelivery systems, with the hope that bringing the nanomedicine of the active constituents of Danshen for anti-tumor therapeutics from bench to bedside in the near future.


Assuntos
Antineoplásicos Fitogênicos , Medicamentos de Ervas Chinesas , Salvia miltiorrhiza , Salvia miltiorrhiza/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacologia , Sistemas de Liberação de Medicamentos , Animais , Neoplasias/tratamento farmacológico , Sistemas de Liberação de Fármacos por Nanopartículas/química , Nanopartículas/química
3.
Nanotechnology ; 34(3)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36219885

RESUMO

The serious side effects of cisplatin hindered its clinical application and the nanotechnology might be the potential strategy to address the limitation. However, rapid clearance in the blood circulation and ineffective controlled drug release from nanocarriers hamper the therapeutic efficacy of the nano-delivery system. We constructed a tumor microenvironment and redox dual stimuli-responsive nano-delivery system PEG-c-(BPEI-SS-Pt) by cross-linking the disulfide-containing polymeric conjugate BPEI-SS-Pt with the dialdehyde group-modified PEG2000via Schiff base. After optimized the cross-linking time, 72 h was selected to get the nano-delivery system.1H NMR and drug release assays showed that under the acidic tumor microenvironment (pH 6.5-6.8), the Schiff base can be broken and detached the PEG cross-linked outer shells, displaying the capability to release the drugs with a sequential pH- and redox-responsive manner. Moreover, PEG-c-(BPEI-SS-Pt) showed more effective anti-tumor therapeutic efficacyin vivowith no significant side effects when compared with the drug of cisplatin used in the clinic. This strategy highlights a promising platform with the dual stimuli-responsive profile to achieve better therapeutic efficacy and minor side effects for platinum-based chemotherapy.


Assuntos
Nanopartículas , Neoplasias , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Microambiente Tumoral , Bases de Schiff , Nanopartículas/química , Polímeros/química , Sistemas de Liberação de Medicamentos , Oxirredução , Neoplasias/tratamento farmacológico , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral
4.
Phys Rev Lett ; 128(8): 081601, 2022 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-35275644

RESUMO

We show that, after ensemble averaging, the low temperature phase of a conjugate pair of uncoupled, quantum chaotic, non-Hermitian systems such as the Sachdev-Ye-Kitaev (SYK) model or the Ginibre ensemble of random matrices is dominated by saddle points that couple replicas and conjugate replicas. This results in a nearly flat free energy that terminates in a first-order phase transition. In the case of the SYK model, we show explicitly that the spectrum of the effective replica theory has a gap. These features are strikingly similar to those induced by wormholes in the gravity path integral which suggests a close relation between both configurations. For a nonchaotic SYK, the results are qualitatively different: the spectrum is gapless in the low temperature phase and there is an infinite number of second order phase transitions unrelated to the restoration of replica symmetry.

5.
Endocr J ; 69(2): 217-224, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35228410

RESUMO

Di-(2-ethylhexyl) phthalate (DEHP) is extensively used in many personal care and consumer products, which results in widespread human exposure. Limited studies have suggested that exposure to DEHP may affect thyroid function, but little is known about the effect and mechanisms of DEHP exposure on the hypothalamic-pituitary-thyroid axis (HPTA). The present study was conducted to elucidate the potential mechanisms underlying DEHP disrupting the function of the HPTA. DEHP was administered to Wistar rats by gavage at 0, 5, 50, and 500 mg/kg/day for consecutive 28 days and then the rats were sacrificed within 24 h following the last dose. The hormone levels of HPTA were quantified with radioimmunoassay and enzyme-linked immunosorbent assay, the protein levels of thyrotropin-releasing hormone receptor (TRHR) and thyroid-stimulating hormone receptor (TSHR) were analyzed by Western blot and immunohistochemistry, and the expression levels of TRHR and TSHR mRNA were measured by quantitative real-time PCR. The low dose of DEHP increased the body weights of rats. Serum levels of T3, T4, FT3 and FT4 as well as protein and mRNA levels of TSHR decreased in rats treated with 50 mg/kg or 500 mg/kg DEHP compared with those of controls. Although the protein levels of TRH in the hypothalamus or protein and mRNA levels of TRHR in pituitary were up-regulated, serum levels of TSH did not change statistically in rats treated with DEHP. Therefore, DEHP can produce thyroid toxicity and may interfere with the secretion of pituitary TSH. In conclusion, DEHP could interfere with the balance of HPTA of adolescent rats, and disturb the homeostasis of thyroid related hormones and the expression levels of receptors.

6.
Adv Healthc Mater ; 11(12): e2102479, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35182456

RESUMO

Primary tumor organoids (PTOs) growth in hydrogels have emerged as an important in vitro model that recapitulates many characteristics of the native tumor tissue, and have important applications in fundamental cancer research and for the development of useful therapeutic treatment. This paper begins with reviewing the methods of isolation of primary tumor cells. Then, recent advances on the instructive hydrogels as biomimetic extracellular matrix for primary tumor cell culture and construction of PTO models are summarized. Emerging microtechnology for growth of PTOs in microscale hydrogels and the applications of PTOs are highlighted. This paper concludes with an outlook on the future directions in the investigation of instructive hydrogels for PTO growth.


Assuntos
Matriz Extracelular , Hidrogéis , Técnicas de Cultura de Células , Microtecnologia , Organoides
7.
Mitochondrial DNA B Resour ; 5(1): 551-553, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33366642

RESUMO

The complete mitochondrial genome of the Annamanum lunulatum is 15,610 bp in length, which contains 13 protein-coding genes, 22 transfer RNAs, two ribosomal RNAs, and the A + T-rich region. The arrangement of genes is identical to all know longhorn beetles mitochondrial genomes. The overall AT content of the mitochondrial genome is 75.3%, whereas the AT content of A + T-rich region is 84.3%. In ML and BI phylogenetic analyses, A. lunulatum is a sister clade to Blepephaeus succinctor, and the monophyly of Lamiinae is supported.

8.
PeerJ ; 8: e9740, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879803

RESUMO

As a small order of Pterygota (Insecta), Ephemeroptera has almost 3,500 species around the world. Ephemerellidae is a widely distributed common group of Ephemeroptera. However, the relationship among Ephemerellidae, Vietnamellidae and Teloganellidae is still in dispute. In this study, we sequenced six complete mitogenomes of three genera from Ephemerellidae (Insecta: Ephemeroptera): Ephemerella sp. Yunnan-2018, Serratella zapekinae, Serratella sp. Yunnan-2018, Serratella sp. Liaoning-2019, Torleya grandipennis and T. tumiforceps. These mitogenomes were employed to reveal controversial phylogenetic relationships among the Ephemeroptera, with emphasis on the phylogenetic relationships among Ephemerellidae. The lengths of the six mayfly mitogenomes ranged from 15,134 bp to 15,703 bp. Four mitogenomes of Ephemerella sp. Yunnan-2018, Serratella zapekinae, Serratella sp. Yunnan-2018 and Serratella sp. Liaoning-2019 had 22 tRNAs including an inversion and translocation of trnI. By contrast, the mitogenomes of T. tumiforceps and T. grandipennis had 24 tRNAs due to an extra two copies of inversion and translocation of trnI. Within the family Ephemerellidae, disparate gene rearrangement occurred in the mitogenomes of different genera: one copy of inversion and translocation trnI in the genera Ephemerella and Serratella, and three repeat copies of inversion and translocation of trnI in the genus Torleya. A large non-coding region (≥200 bp) between trnS1 (AGN) and trnE was detected in T. grandipennis and T. tumiforceps. Among the phylogenetic relationship of the Ephemeroptera, the monophyly of almost all families except Siphlonuridae was supported by BI and ML analyses. The phylogenetic results indicated that Ephemerellidae was the sister clade to Vietnamellidae whereas Teloganellidae was not a sister clade of Ephemerellidae and Vietnamellidae.

9.
Nanotechnology ; 31(32): 325101, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32325436

RESUMO

Polyethylenimine (PEI), a kind of cationic non-viral gene delivery vector, is capable of stable and efficient transgene expression for gene delivery. However, low transfection efficiency in vivo along with high toxicity limited the further application of gene therapy in the clinic. To enhance gene transfection performance and reduce cytotoxicity of polyethylenimine, branched polyethylenimine-derived cationic polymers BPEI25 k-man-S/L/M/H with different grafting degree with mannitol moieties were prepared and the transfection efficiency was evaluated. Among them, BPEI25 k-man-L showed the best transfection efficiency, lower toxicity, and significantly enhanced long-term systemic transgene expression for 96 h in vivo even at a single-dose administration. The results of cellular uptake mechanism and western-blot experiments revealed that the mannitol modification of BPEI25 k induced and up-regulated the phosphorylation of caveolin-1 and thus enhanced the caveolae-mediated cellular uptake. This class of gene delivery system highlights a paradigmatic approach for the development of novel and safe non-viral vectors for gene therapy.


Assuntos
Caveolina 1/metabolismo , Vetores Genéticos/administração & dosagem , Manitol/química , Polietilenoimina/química , Animais , Células COS , Chlorocebus aethiops , Técnicas de Transferência de Genes , Vetores Genéticos/química , Células HEK293 , Células HeLa , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação , Transfecção
10.
Int J Pharm ; 580: 119190, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32151664

RESUMO

Cisplatin is one of the most widely used platinum-based anticancer chemotherapeutic drugs. However, its low solubility, serious side effects and the development of cisplatin resistance limit its further use in the clinic. Controlling the delivery and release of cisplatin at the targeted site efficiently is a meaningful way to overcome these undesirable side effects of cisplatin. Herein, a tumor targeted and stimuli responsive nano-delivery system for cisplatin was constructed using branched polyethyleneimine (BPEI) as the backbone, disulfide bond as the redox-responsive covalent linker and hyaluronic acid (HA) as targeting recognition unit which can bind selectively to the receptor of CD44, which is highly expressed on the A549 tumor cells. The cisplatin-polyethyleneimine conjugate BPEI-SS-Pt was prepared and the drug loading of cisplatin was up to 32.66 ± 0.06%. After optimized the coating weight ratio of HA and BPEI-SS-Pt, the nanoparticle delivery system HA-(BPEI-SS-Pt)-1/4 outperformed with smaller particle size of 159.0 ± 21.0 nm, narrow polydispersity index (PDI) of 0.069 ± 0.022 and higher cisplatin loading of 29.23 ± 0.18%, showing specific tumor-targeting ability and redox-responsive drug release manner. Moreover, for the treatment of cancer in vivo, it achieved more effective antitumor performance along with minor side effects and systemic toxicity compared with cisplatin which is of great significance for the chemotherapeutic drug in the clinic.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/administração & dosagem , Neoplasias/tratamento farmacológico , Células A549 , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cisplatino/química , Cisplatino/metabolismo , Relação Dose-Resposta a Droga , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanopartículas/química , Nanopartículas/metabolismo , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução/efeitos dos fármacos , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
11.
J Exp Clin Cancer Res ; 39(1): 42, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093760

RESUMO

BACKGROUND: We have previously described CLDN6 as a tumor suppressor gene in breast cancer. Here, a new finding is that CLDN6 was upregulated under hypoxia, a commonly recognized factor that promotes tumor metastasis. In this study, we aim to explain this confusing finding and delineate the role of CLDN6 in the breast cancer metastasis induced by hypoxia. METHODS: RNAi and ChIP assays were used to confirm that CLDN6 is transcriptional regulated by HIF-1α. mRNA seq and KEGG analysis were performed to define the downstream pathways of CLDN6. The roles of the CLDN6/SENP1/HIF-1α signaling on tumor metastasis were evaluated by function experiments and clinical samples. Finally, the possible transcription factor of SENP1 was suspected and then validated by ChIP assay. RESULTS: We demonstrated a previously unrecognized negative feedback loop exists between CLDN6 and HIF-1α. CLDN6 was transcriptionally up-regulated by HIF-1α under hypoxia. On the other hand, in cytoplasm CLDN6 combines and retains ß-catenin, a transcription factor of SENP1, causing ß-catenin degradation and preventing its nuclear translocation. This process reduced SENP1 expression and prevented the deSUMOylation of HIF-1α, ultimately leading to HIF-1α degradation and breast cancer metastasis suppression. CONCLUSIONS: Our data provide a molecular mechanistic insight indicating that CLDN6 loss may lead to elevated HIF-1α-driven breast cancer metastasis in a SUMOylation-dependent manner.


Assuntos
Neoplasias da Mama/patologia , Claudinas/genética , Claudinas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Hipóxia Celular , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Retroalimentação Fisiológica , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Proteólise , Transdução de Sinais/efeitos dos fármacos , Sumoilação
12.
Aging Dis ; 11(1): 44-59, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32010480

RESUMO

Many oncogenes are involved in the progression from low-grade squamous intraepithelial lesions (LSILs) to high-grade squamous intraepithelial lesions (HSILs); which greatly increases the risk of cervical cancer (CC). Thus, a reliable biomarker for risk classification of LSILs is urgently needed. The prolyl isomerase Pin1 is overexpressed in many cancers and contributes significantly to tumour initiation and progression. Therefore, it is important to assess the effects of cancer therapies that target Pin1. In our study, we demonstrated that Pin1 may serve as a biomarker for LSIL disease progression and may constitute a novel therapeutic target for CC. We used a the novel Pin1 inhibitor KPT-6566, which is able to covalently bind to Pin1 and selectively target it for degradation. The results of our investigation revealed that the downregulation of Pin1 by shRNA or KPT-6566 inhibited the growth of human cervical cancer cells (CCCs). We also discovered that the use of KPT-6566 is a novel approach to enhance the therapeutic efficacy of cisplatin (DDP) against CCCs in vitro and in vivo. We showed that KPT-6566-mediated inhibition of Pin1 blocked multiple cancer-driving pathways simultaneously in CCCs. Furthermore, targeted Pin1 treatment suppressed the metastasis and invasion of human CCCs, and downregulation of Pin1 reversed the epithelial-mesenchymal transition (EMT) of CCCs via the c-Jun/slug pathway. Collectively, we showed that Pin1 may be a marker for the risk of progression to HSIL and that inhibition of Pin1 has anticancer effects against CC.

13.
J Nanobiotechnology ; 18(1): 26, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005170

RESUMO

BACKGROUND: Gene therapy remains a significant challenge due to lots of barriers limiting the genetic manipulation technologies. As for non-viral delivery vectors, they often suffer insufficient performance due to inadequate cellular uptake and gene degradation in endosome or lysosome. The importance of overcoming these conserved intracellular barriers is increasing as the delivery of genetic cargo. RESULTS: A surface-functionalized non-viral vector involving the biomimetic mannitol moiety is initiated, which can control the cellular uptake and promote the caveolae-mediated pathway and intracellular trafficking, thus avoiding acidic and enzymatic lysosomal degradation of loaded gene internalized by clathrin-mediated pathway. Different degrees of mannitol moiety are anchored onto the surface of the nanoparticles to form bio-inspired non-viral vectors and CaP-MA-40 exhibits remarkably high stability, negligible toxicity, and significantly enhanced transgene expression both in vitro and in vivo. CONCLUSIONS: This strategy highlights a paradigmatic approach to construct vectors that need precise intracellular delivery for innovative applications.


Assuntos
Fosfatos de Cálcio/química , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Nanopartículas/química , Transgenes , Cavéolas/metabolismo , Linhagem Celular , Permeabilidade da Membrana Celular , Clatrina/metabolismo , Endossomos/metabolismo , Regulação Viral da Expressão Gênica , Técnicas de Transferência de Genes , Terapia Genética , Humanos , Lisossomos/metabolismo , Manitol/metabolismo , Transdução de Sinais , Propriedades de Superfície , Transdução Genética , Transfecção
14.
Mitochondrial DNA B Resour ; 5(3): 3079-3081, 2020 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-33458066

RESUMO

The mitochondrial genome sequence of Xanthomantis bimaculata (Mantodea: Iridopterygidae) from Yunnan, China is a circular molecule with the typical insect mitochondrial gene arrangement, which is 15,941 bp in length and contains 22 tRNAs, two rRNAs, 13 protein-coding genes, and one control region. The overall AT content of the mitogenome is 73.12% (A = 37.58%, T = 35.54%, C = 16.54%, G = 10.34%). In BI and ML phylogenetic analyses, X. bimaculata was a sister clade to Sceptuchus simplex. The monophyly of the families Iridopterygidae, Thespidae and Liturgusidae were supported.

15.
J Exp Clin Cancer Res ; 38(1): 354, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31412908

RESUMO

BACKGROUND: Estrogen receptor ß (ERß) has been reported to play an anti-cancer role in breast cancer, but the regulatory mechanism by which ERß exerts this effect is not clear. Claudin-6 (CLDN6), a tight junction protein, acts as a tumor suppressor gene in breast cancer. Our previous studies have found that 17ß-estradiol (E2) induces CLDN6 expression and inhibits MCF-7 cell migration and invasion, but the underlying molecular mechanisms are still unclear. In this study, we aimed to investigate the role of ERß in this process and the regulatory mechanisms involved. METHODS: Polymerase chain reaction (PCR) and western blot were used to characterize the effect of E2 on the expression of CLDN6 in breast cancer cells. Chromatin immunoprecipitation (ChIP) assays were carried out to confirm the interaction between ERß and CLDN6. Dual luciferase reporter assays were used to detect the regulatory role of ERß on the promoter activity of CLDN6. Wound healing and Transwell assays were used to examine the migration and invasion of breast cancer cells. Western blot, immunofluorescence and transmission electron microscopy (TEM) were performed to detect autophagy. Xenograft mouse models were used to explore the regulatory effect of the CLDN6-beclin1 axis on breast cancer metastasis. Immunohistochemistry (IHC) was used to detect ERß/CLDN6/beclin1 expression in breast cancer patient samples. RESULTS: Here, E2 upregulated the expression of CLDN6, which was mediated by ERß. ERß regulated CLDN6 expression at the transcriptional level. ERß inhibited the migration and invasion of breast cancer cells through CLDN6. Interestingly, this effect was associated with CLDN6-induced autophagy. CLDN6 positively regulated the expression of beclin1, which is a key regulator of autophagy. Beclin1 knockdown reversed CLDN6-induced autophagy and the inhibitory effect of CLDN6 on breast cancer metastasis. Moreover, ERß and CLDN6 were positively correlated, and the expression of CLDN6 was positively correlated with beclin1 in breast cancer tissues. CONCLUSION: Overall, this is the first study to demonstrate that the inhibitory effect of ERß on the migration and invasion of breast cancer cells was mediated by CLDN6, which induced the beclin1-dependent autophagic cascade.


Assuntos
Autofagia/genética , Neoplasias da Mama/genética , Claudinas/genética , Receptor beta de Estrogênio/genética , Animais , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Claudinas/metabolismo , Modelos Animais de Doenças , Receptor beta de Estrogênio/metabolismo , Feminino , Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos
16.
J Biomed Nanotechnol ; 15(8): 1654-1672, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31219018

RESUMO

Stimuli-responsive materials are promising paradigm applied to construct diagnostic and therapeutic intracellular controlled release vectors, while highlighting many challenges and opportunities. In this paper, six α-cyclodextrin-based supramolecular nanovectors were constructed and the efficacy of amine groups, stimuli-responsive profiles and endocytic mechanisms were investigated. The results indicated that the designed supermolecules can compact DNA to form stable complexes and display low cytotoxicity. Among them, PRPEI-2 with suitable PEI amine group exhibited enhanced transfecting performance, high dilution stability, nice serum compatibility, and good acid-responsive profiles to enable endosome escape, significantly higher than commercially available transfecting agent PEI25000, the most effective vector studied to date. The endocytic uptake mechanisms involved in the transfection was mainly through clathrin-mediated pathway, which is closely associated with and can be improved by endosome escape. Moreover, PRPEI-2/DNA polyplex can be effectively expressed in vivo even after 48 h via only single tail-vein injection, and the gene expression and main tissue distribution appeared in the testis, liver, brain and spleen. These excellent characteristics demonstrated that the supramolecular PRPEI-2 represents an excellent prospect as stimuli-responsive nanovectors for gene diagnosis and therapy.


Assuntos
Técnicas de Transferência de Genes , DNA , Endossomos , Polietilenoimina , Transfecção , alfa-Ciclodextrinas
17.
Cell Prolif ; 52(4): e12612, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31012189

RESUMO

OBJECTIVE: POU5F1 (OCT4) is implicated in cancer stem cell self-renewal. Currently, some studies have shown that OCT4 has a dual function in suppressing or promoting cancer progression. However, the precise molecular mechanism of OCT4 in breast cancer progression remains unclear. MATERIALS AND METHODS: RT-PCR and Western blot were utilized to investigate OCT4 expression in breast cancer tissues and cells. Cell proliferation assays and mouse models were applied to determine the effects of OCT4 on breast cancer cell proliferation. DNMT1 inhibitors, ChIP, CoIP, IHC and ERα inhibitors were used to explore the molecular mechanism of OCT4 in breast cancer. RESULTS: OCT4 was down-regulated in breast cancer tissues, and the overexpression of OCT4 promoted MDA-MB-231 cell proliferation and inhibited the proliferation of MCF-7 cells in vitro and in vivo, respectively. Two DNMT1 inhibitors (5-aza-dC and zebularine) suppressed OCT4-induced MDA-MB-231 cell proliferation through Ras/Raf1/ERK inactivation by targeting ISL1, which is the downstream of DNMT1. In contrast, OCT4 interacted with ERα, decreased DNMT1 expression and inactivated the Ras/Raf1/ERK signalling pathway in MCF-7 cells. Moreover, ERα inhibitor (AZD9496) reversed the suppression of OCT4-induced proliferation in MCF-7 cells via the activation of ERK signalling pathway. CONCLUSIONS: OCT4 is dependent on ERα to suppress the proliferation of breast cancer cells through DNMT1/ISL1/ERK axis.


Assuntos
Neoplasias da Mama/genética , Proliferação de Células/genética , DNA (Citosina-5-)-Metiltransferase 1/genética , Receptor alfa de Estrogênio/genética , Proteínas com Homeodomínio LIM/genética , Sistema de Sinalização das MAP Quinases/genética , Fator 3 de Transcrição de Octâmero/genética , Fatores de Transcrição/genética , Animais , Linhagem Celular Tumoral , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transdução de Sinais/genética
18.
Stem Cell Res Ther ; 10(1): 28, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646941

RESUMO

BACKGROUND: Self-renewal is dependent on an intrinsic gene regulatory network centered on OCT4 and on an atypical cell cycle G1/S transition, which is also regulated by OCT4. p21, a gene negatively associated with self-renewal and a senescence marker, is a member of the universal cyclin-dependent kinase inhibitors (CDKIs) and plays critical roles in the regulation of the G1/S transition. The expression of p21 can be regulated by OCT4-targeted DNA methyltransferases (DNMTs), which play distinct roles in gene regulation and maintaining pluripotency properties. The aim of this study was to determine the role of OCT4 in the regulation of self-renewal and senescence in human hair follicle mesenchymal stem cells (hHFMSCs) and to characterize the molecular mechanisms involved. METHODS: A lentiviral vector was used to ectopically express OCT4. The influences of OCT4 on the self-renewal and senescence of hHFMSCs were investigated. Next-generation sequencing (NGS) was performed to identify the downstream genes of OCT4 in this process. Methylation-specific PCR (MSP) analysis was performed to measure the methylation level of the p21 promoter region. p21 was overexpressed in hHFMSCsOCT4 to test its downstream effect on OCT4. The regulatory effect of OCT4 on DNMTs was examined by ChIP assay. 5-aza-dC/zebularine was used to inhibit the expression of DNMTs, and then self-renewal properties and senescence in hHFMSCs were detected. RESULTS: The overexpression of OCT4 promoted proliferation, cell cycle progression, and osteogenic differentiation capacity of hHFMSCs. The cell senescence of hHFMSCs was markedly suppressed due to the ectopic expression of OCT4. Through NGS, we identified 2466 differentially expressed genes (DEGs) between hHFMSCsOCT4 and hHFMSCsEGFP, including p21, which was downregulated. The overexpression of p21 abrogated the proliferation and osteogenic differentiation capacity of hHFMSCsOCT4 and promoted cell senescence. OCT4 enhanced the transcription of DNMT genes, leading to an elevation in the methylation of the p21 promoter. The inhibition of DNMTs reversed the OCT4-induced p21 reduction, depleted the self-renewal of hHFMSCsOCT4, and triggered cell senescence. CONCLUSIONS: OCT4 maintains the self-renewal ability of hHFMSCs and reverses senescence by suppressing the expression of p21 through the upregulation of DNMTs.


Assuntos
Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Metilases de Modificação do DNA/metabolismo , Folículo Piloso/citologia , Células-Tronco Mesenquimais/citologia , Fator 3 de Transcrição de Octâmero/metabolismo , Linhagem Celular , Senescência Celular/fisiologia , Regulação para Baixo , Células HEK293 , Folículo Piloso/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Fator 3 de Transcrição de Octâmero/biossíntese , Fator 3 de Transcrição de Octâmero/genética
19.
Mitochondrial DNA B Resour ; 4(2): 3797-3799, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-33366196

RESUMO

The complete mitochondrial genome of Mantis religiosa (Mantodea: Mantidae) from Canada was successfully sequenced. The mitochondrial genome was a circular molecule of 15,521 bp in length, containing 13 protein-coding genes, two rRNA genes, 23 tRNA genes (including an extra tRNAArg gene), and the control region. The AT content of the whole genome was 76.9% and the length of the control region was 636 bp with 81.9% AT content. The structure of the M. religiosa mitochondrial genome from Canada was almost identical to M. religiosa from China and their genetic distance was just 0.017. In Bayesian inference (BI) and maximum likelihood (ML) analyses, we found that M. religiosa was a sister clade to Statilia sp. and the monophyly of the genera Hierodula and Rhombodera was not supported.

20.
Mitochondrial DNA B Resour ; 5(1): 192-193, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-33366482

RESUMO

The phylogenetic relationship of Caenidae remains hotly debated within the Ephemeroptera. We sequenced the complete mitochondrial genome of Caenis sp. (Ephemeroptera: Caenidae) to discuss the phylogenetic relationships among the Caenidae. The mitochondrial genome of Caenis sp. collected from Jian'ou, Fujian province, China is a circular molecule of 15,392 bp in length containing 37 genes (13 protein-coding genes, 22 tRNAs, and two rRNAs), which showed the typical insect mitochondrial gene arrangement. In BI and ML phylogenetic trees using 23 species from 13 families, the monophyly of the families Caenidae, Heptageniidae, Isonychiidae, and Vietnamellidae was strongly supported. The clade of Caenidae is a sister clade to the clade of Teloganodidae and Baetidae.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA