Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 448
Filtrar
1.
Neural Plast ; 2019: 1247276, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582965

RESUMO

Background: Wnt/ß-catenin signaling has been reported to exert cytoprotective effects in a cellular model of Parkinson's disease (PD). Glutamate excitotoxicity has been suggested to contribute to the pathogenesis of PD, and excitatory amino acid transporters (EAATs) play a predominant role in clearing excessive glutamate. EAAT2 is mainly expressed in astrocytes, which are an important source of Wnt signaling in the brain. Methods: Wnt1-overexpressing U251 astrocytes were indirectly cocultured with dopaminergic SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Cell toxicity was determined by cell viability and flow cytometric detection. Glutamate level in the culture medium was determined by enzyme-linked immunosorbent assay (ELISA). Western blot analysis was used to detect the expression of Wnt1, ß-catenin, and EAAT2. Immunofluorescence was used to display the expression and translocation of NF-κB p65. Results: 6-OHDA treatment significantly decreased cell viability in both U251 cells and SH-SY5Y cells, inhibited the expression of Wnt1, ß-catenin, and EAAT2 in U251 cells, and increased the glutamate level in the culture medium. Coculture with Wnt1-overexpressing U251 cells attenuated 6-OHDA-induced apoptosis in SH-SY5Y cells. Overexpression of Wnt1 decreased the glutamate level in the culture media, upregulated ß-catenin, EAAT2, and NF-κB levels, and promoted the translocation of NF-κB from the cytoplasm to the nucleus in U251 cells. Conclusion: Wnt1 promoted EAAT2 expression and mediated the cytoprotective effects of astrocytes on dopaminergic cells. NF-κB might be involved in the regulation of EAAT2 by Wnt1.

2.
Neurosci Bull ; 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31531804

RESUMO

Emotional contagion, a primary form of empathy, is present in rodents. Among emotional contagion behaviors, social transmission of fear is the most studied. Here, we modified a paradigm used in previous studies to more robustly assess the social transmission of fear in rats that experienced foot-shock. We used resting-state functional magnetic resonance imaging to show that foot-shock experience enhances the regional connectivity of the anterior cingulate cortex (ACC). We found that lesioning the ACC specifically attenuated the vicarious freezing behavior of foot-shock-experienced observer rats. Furthermore, ablation of projections from the ACC to the mediodorsal thalamus (MDL) bilaterally delayed the vicarious freezing responses, and activation of these projections decreased the vicarious freezing responses. Overall, our results demonstrate that, in rats, the ACC modulates vicarious freezing behavior via a projection to the MDL and provide clues to understanding the mechanisms underlying empathic behavior in humans.

3.
Aging (Albany NY) ; 11(16): 6385-6397, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31454331

RESUMO

Hemorrhagic transformation (HT) is a severe complication occurring in acute ischemic stroke (AIS) patients. We explored the association between low triiodothyronine (T3) syndrome and HT in AIS patients. A total of 208 consecutive participants with HT and 208 age- and sex-matched stroke patients without HT were enrolled in this study. HT was diagnosed by follow-up imaging assessment, and was radiologically classified as hemorrhagic infarction (HI) type 1 or 2 or parenchymal hematoma (PH) type 1 or 2. HT was also classified into asymptomatic or symptomatic. The incidence of low T3 syndrome was significantly higher among patients who developed HT than among those without HT. Moreover, the more severe the HT, the lower the detected T3 levels. Multivariate-adjusted binary logistic regression showed that low T3 syndrome was an independent risk factor for HT and symptomatic HT in AIS patients. Low T3 syndrome was also significantly associated with a higher risk of PH, but not with the risk of HI. Thus, low T3 syndrome was independently associated with the risk of HT, symptomatic HT, and severe HT (PH) in AIS patients, which suggests monitoring T3 could be a useful means of preventing HT in patients with ischemic stroke.

5.
Genomics ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31376528

RESUMO

Cellular senescence is an irreversible cell cycle arrest process associated with aging and senescence-related diseases. DNA damage is an extensive feature of cellular senescence and aging. Different levels of DNA damage could lead to cellular senescence or transient cell-cycle arrest, but the genetic regulatory mechanisms determining cell fate are still not clear. In this work, high-resolution time course analysis of gene expression in DNA damage-induced cellular senescence and transient cell-cycle arrest was used to explore the transcriptomic differences between different cell fates after DNA damage response and to investigate the key regulatory factors affecting senescent cell fates. Pathways such as the cell cycle, DNA repair and cholesterol metabolism showed characteristic differential response. A number of key transcription factors were predicted to regulating cell cycle and DNA repair. Our study provides genome-wide insights into the molecular-level mechanisms of senescent cell fate decisions after DNA damage response.

6.
Pathol Res Pract ; 215(10): 152575, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31387807

RESUMO

The important role of LncRNA in the development of breast cancer is attracting more and more attention. In the previous study, we found that the expression level of LncRNA SNHG6 in breast cancer tissues and cells was significantly increased, but its mechanism in the development of breast cancer was still unclear. Our study found that knockdown of SNHG6 significantly inhibited the proliferation, migration and invasion of breast cancer cells MCF-7 and MDA-MB-231 cells. Further study showed that knockdown of SNHG6 significantly inhibited the expression level of VASP. More importantly, SNHG6 and VASP both can bind directly to miR-26a, suggesting that SNHG6 could act as a ceRNA to sponge miR-26a, thereby promoting the expression of VASP, which leading to activated proliferation, migration and invasion of breast cancer cells. Taken together, this study revealed the important role of the SNHG6/miR-26a/VASP regulatory network in the development of breast cancer, and provided a reference for exploring new pathogenesis and biomarkers of breast cancer.

7.
Pathol Res Pract ; 215(10): 152573, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31399258

RESUMO

The development of breast cancer is still a relatively unclear biological process, and there is currently no consensus on the occurrence of breast cancer and the process of tumor metastases. This study was to reveal a correlation between TRIM63 and the development of breast cancer. In this study, we found that the expression of TRIM63 was significantly increased in breast cancer tissues and closely related to pathological differentiation and TNM stage of breast cancer. Overexpression of TRIM63 could significantly promote proliferation and migration of breast cancer cells, while TRIM63 knockdown significantly inhibited the proliferation and migration of breast cancer cells. In addition, TRIM63 could activate Wnt/ß-catenin signaling pathway in breast cancer cells. Further study found that TRIM63 could regulate ß-catenin degradation by promoting GSK3ß phosphorylation. Our study revealed that TRIM63, as an oncogene, involved in breast cancer progression by activating the Wnt/ß-catenin signaling pathway, suggesting that the potential applicability of TRIM63 as a target for breast cancer treatment.

8.
Bone ; 127: 656-663, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31283994

RESUMO

OBJECTIVE: To investigate the protective effects of DAla2GIP against the apoptosis and inflammatory factor secretion in H2O2-induced chondrocyte, and explore the possible mechanisms of DAla2GIP underlying its protection. METHODS: The chondrocytes were divided into the following four groups: Control, 300 µM H2O2, 100 pM DAla2GIP and 300 µM H2O2 + 100 pM DAla2GIP. The apoptosis of chondrocyte was measured by using mitochondrial membrane potential assay kit (JC-1) and TUNEL assay, the inflammatory factor secretion were assessed by ELISA assay, and the cellular and molecular mechanisms of DAla2GIP protection were investigated by using Real time-PCR, flow cytometry, Non- invasive calcium detection and western blotting techniques. RESULTS: (1) DAPla2GIP prevents apoptosis of chondrocyte induced by H2O2. (2) DAla2GIP alleviated the inflammation of chondrocyte induced by H2O2. (3) DAla2GIP prevents chondrocyte apoptosis by inhibiting calcium influx of chondrocyte and regulating expression of Bcl-2 and Caspase-3induced by H2O2. (4) DAla2GIP inhibited the H2O2 mediated inflammation by up- regulating the expressions of Sox9 and Col2a1 and inhibiting PI3K/Akt/NF-κB pathway. CONCLUSION: Our experimental results revealed that DAla2GIP prevents chondrocyte apoptosis by inhibiting calcium influx of chondrocyte and induced regulating expression of Bcl-2 and Casp ase-3by H2O2. Further, molecular biology experiments confirmed that DAla2GIP inhibited the H2O2 mediated inflammation vis up-regulating the expressions of Sox9 and Col2a1 and inhibiting PI3K/Akt/NF-κB pathway. The results demonstrate that DAla2GIP has protective properties in H2O2-induced chondrocyte injury, this finding shows that novel GIP analogues have the potential as a novel therapeutic for osteoarthritis patients.

9.
Int Immunopharmacol ; 75: 105752, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310910

RESUMO

BACKGROUND: Downregulation of histone deacetylase-4 (HDAC4) contributes to cartilage degeneration in osteoarthritis (OA) because it promotes upregulation of runt-related transcription factor-2 (Runx-2) and osteoarthritis-related genes. The effect of HDAC4 upregulation on cartilage damage in OA remains unknown. METHODS: Rat chondrocytes were infected with Ad-GFP or Ad-HDAC4-GFP for 48 h, stimulated with interleukin-1ß (IL-1ß, 10 ng/mL) for 24 h, and then harvested for RT-qPCR. Male Sprague-Dawley rats in 3 groups were given anterior cruciate ligament transection (ACLT) or sham operation, and knee injections with different adenovirus (Ad) vectors at 48 h after surgery and every 3 weeks thereafter: ACLT+Ad-GFP (n = 17); ACLT+Ad-HDAC4-GFP (n = 20); and sham+Ad-GFP (n = 15). Three ACLT-Ad-HDAC4-GFP rats were sacrificed at different times to examine the expression of HDAC4. Two ACLT-Ad-GFP rats and two ACLT-Ad-HDAC4-GFP rats were euthanized at week-2; articular cartilage was harvested and expression of HDAC4 was determined by RT-qPCR. All other rats were euthanized at week-8. Cartilage damage and OA progression was assessed using radiography, fluorescence molecular tomography (FMT), histology, immunohistochemistry (IHC), ELISA, and RT-qPCR. RESULTS: Overexpression of HDAC4 in chondrocytes stimulated by IL-1ß reduced the levels of Runx-2, MMP-13, and Collagen X, but increased the levels of Collagen II and Aggrecan. Upregulation of HDAC4 reduced osteophyte formation and cartilage damage, and increased articular cartilage anabolism. CONCLUSION: HDAC4 attenuated articular cartilage damage by repression of Runx-2, MMP-13, and collagen X and induction of collagen II and ACAN in this rat model of OA. Upregulation of HDAC4 may provide chondroprotection in OA patients.

10.
Mol Med Rep ; 20(2): 1943-1951, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31257464

RESUMO

Saikosaponin b2 (SSb2) can be extracted from Bupleurum spp. roots (Radix Bupleuri), which belongs to the Umbelliferae family. The current study aimed to explore the effects of SSb2 on proliferation of breast cancer cells and to identify the mechanism by which SSb2 affects breast cancer cell migration. mRNA expression levels of STAT3 and vasodilator­stimulated phosphoprotein (VASP) were determined and increased expression was observed in 16 breast cancer tissues compared with the paracancerous tissues. MTT, wound healing, colony formation assays and western blot suggested that SSb2 inhibited MCF­7 proliferation and migration. It was further identified by western blot analysis that SSb2 treatment reduced levels of phosphorylated STAT3, VASP, matrix metallopeptidase (MMP) 2 and MMP9 in MCF­7 compared with the untreated cells. In addition, it was demonstrated that inhibition of STAT3 phosphorylation decreased VASP expression levels and induction of STAT3 phosphorylation increased VASP levels. Furthermore, it was observed that the treatment of Kunming mice with SSb2 at 30 mg/kg/day for 30 days induced no obvious changes in the liver or kidney tissues, as determined by haematoxylin and eosin staining. In conclusion, these results indicated that SSb2 may be a potential antitumor drug for the treatment of breast cancer, which acts by suppressing proliferation and migration by downregulating the STAT3 signalling pathway and inhibiting the expression of VASP, MMP2 and MMP9 expression.

11.
Fish Shellfish Immunol ; 92: 64-71, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31150764

RESUMO

The black-and-white traits on shells and mantle edges of the Pacific oyster, Crassostrea gigas, are inheritable and correlated, and black shells (melanin pigmentation) are usually found in the Pacific oysters. Based on differentially expressed genes from RNA-Seq and physiological characteristics, in this study, Black-shelled Pacific oysters (BSO) and White-shelled Pacific oysters (WSO) were selected to determine the molecular differences between oysters with obviously different melanin content. The differences in the process of immune recognition and modulation indicated that BSO may be more sensitive to the immune substances. There might have different modulation mode of apoptosis and phagocytosis between BSO and WSO, and caspase-3 might have played a key role in the apoptotic process of BSO. Different oxidation-related pathways were enriched in both BSO and WSO, suggesting the different response strategies of BSO and WSO to oxidative stress. The physiological evidences showed that, compared with WSO, in BSO, the tyrosinase content, the caspase-3 activity and the suppression of hydroxyl radical increased, and the reactive oxygen species concentration decreased. Therefore, immune-related molecular and physiological differences were found between BSO and WSO.

12.
Aging (Albany NY) ; 11(12): 4011-4031, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31219803

RESUMO

Cellular senescence is an important mechanism of autonomous tumor suppression, while its consequence such as the senescence-associated secretory phenotype (SASP) may drive tumorigenesis and age-related diseases. Therefore, controlling the cell fate optimally when encountering senescence stress is helpful for anti-cancer or anti-aging treatments. To identify genes essential for senescence establishment or maintenance, we carried out a CRISPR-based screen with a deliberately designed single-guide RNA (sgRNA) library. The library comprised of about 12,000 kinds of sgRNAs targeting 1378 senescence-associated genes selected by integrating the information of literature mining, protein-protein interaction network, and differential gene expression. We successfully detected a dozen gene deficiencies potentially causing senescence bypass, and their phenotypes were further validated with a high true positive rate. RNA-seq analysis showed distinct transcriptome patterns of these bypass cells. Interestingly, in the bypass cells, the expression of SASP genes was maintained or elevated with CHEK2, HAS1, or MDK deficiency; but neutralized with MTOR, CRISPLD2, or MORF4L1 deficiency. Pathways of some age-related neurodegenerative disorders were also downregulated with MTOR, CRISPLD2, or MORF4L1 deficiency. The results demonstrated that disturbing these genes could lead to distinct cell fates as a consequence of senescence bypass, suggesting that they may play essential roles in cellular senescence.

13.
J Immunother Cancer ; 7(1): 156, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221207

RESUMO

BACKGROUND: Efficient identification of neoantigen-specific T-cell responses in epithelial ovarian cancer (EOC) remains a challenge. Existing investigations of spontaneous T-cell response to tumor neoepitope in EOC have taken the approach of comprehensive screening all neoantigen candidates, with a validation rate of 0.5-2%. METHODS: Whole-exome and transcriptome sequencing analysis of treatment-naive EOC patients were performed to identify neoantigen candidates, and the immunogenicity of prioritized neoantigens was evaluated by analyzing spontaneous neoantigen-specfic CD4+ and CD8+ T-cell responses in the tumor and/or peripheral blood. The biological relevance of neoantigen-specific T-cell lines and clones were analyzed by evaluating the capacity of autologous ovarian tumor recognition. Genetic transfer of T-cell receptor (TCR) from these neoantigen-specific T-cell clones into peripheral blood T-cells was conducted to generate neoepitope-specific T-cells. The molecular signature associated with positive neoantigen T-cell responses was investigated, and the impacts of expression level and lymphocyte source on neoantigen identification were explored. RESULTS: Using a small subset of prioritized neoantigen candidates, we were able to detect spontaneous CD4+ and/or CD8+ T-cell responses against neoepitopes from autologous lymphocytes in half of treatment-naïve EOC patients, with a significantly improved validation rate of 19%. Tumors from patients exhibiting neoantigen-specific T-cell responses exhibited a signature of upregulated antigen processing and presentation machinery, which was also associated with favorable patient survival in the TCGA ovarian cohort. T-cells specific against two mutated cancer-associated genes, NUP214 and JAK1, recognized autologous tumors. Gene-engineering with TCR from these neoantigen-specific T-cell clones conferred neoantigen-reactivity to peripheral T-cells. CONCLUSIONS: Our study demonstrated the feasibility of efficiently identifying both CD4+ and CD8+ neoantigen-specific T-cells in EOC. Autologous lymphocytes genetically engineered with tumor antigen-specific TCR can be used to generate cells for use in the personalized adoptive T-cell transfer immunotherapy.

14.
J Am Chem Soc ; 141(28): 10962-10966, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31246448

RESUMO

Understanding the dynamics of covalent organic frameworks (COFs) is desirable for developing smart materials with coherent responses to external stimulus. Here we illustrate the structural determination of dynamics at atomic level by cryo-electron diffraction tomography (EDT) with single crystals of COF-300 having only submicrometer sizes. We observe and elucidate the crystal contraction upon H2O adsorption by ab initio structural solution of all non-hydrogen atoms of framework and unambiguous location of guest molecules in the pores. We also observe the crystal expansion of COF-300 upon inclusion of ionic liquid or polymer synthesized in the channels, whose conformational aspects of frameworks can be confirmed.

15.
Mult Scler Relat Disord ; 33: 70-74, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31158805

RESUMO

OBJECTIVES: To determine the differentiating features of autoimmune central nervous system (CNS) vasculitis and multiple sclerosis (MS) on susceptibility-weighted imaging (SWI). METHODS: Seventy-three patients (27 with autoimmune CNS vasculitis and 46 with MS) who underwent magnetic resonance imaging with SWI sequence were included. The features of lesions and distinct SWI findings were investigated in both diseases. RESULTS: On SWI, autoimmune CNS vasculitis presented with a higher prevalence of multiple microbleeds (48.1%), cortical superficial siderosis (70.4%), and tortuosity of the vascular route (59.3%) than were found in MS (p < 0.001, p < 0.001, and p = 0.001, respectively). Multivariable logistic analysis showed that multiple microbleeds and cortical superficial siderosis were associated with a much higher probability of a diagnosis of autoimmune CNS vasculitis than of MS (OR 19.09, 95% CI 1.13-321.18, p = 0.041; and OR 13.20, 95% CI 2.22-78.30, p = 0.005, respectively). The presence of more than eleven lesions was associated with a lower probability of a diagnosis of autoimmune CNS vasculitis than of MS (OR 0.14, 95% CI 0.03-0.73, p = 0.020). CONCLUSIONS: SWI may be a useful adjunct in distinguishing autoimmune CNS vasculitis from MS. The identification of multiple microbleeds and cortical superficial siderosis can point to a diagnosis of autoimmune CNS vasculitis.

16.
Arthritis Res Ther ; 21(1): 109, 2019 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046827

RESUMO

BACKGROUND: To determine if ipriflavone, a novel and safe inhibitor of Indian hedgehog (Ihh) signaling, can attenuate cartilage degeneration by blocking the Ihh pathway. METHODS: Human chondrocytes were used to evaluate Ihh signaling, cell proliferation, apoptosis, gene, and protein expression of chondrocytes by cell proliferation and apoptosis assays, real-time qPCR, and Western blotting at 48 h after ipriflavone treatment. Human cartilage explants were further used to validate the cell culture results. The effects of ipriflavone on cartilage degeneration in vivo were assessed using the rat ACLT OA model. Two-month-old male SD rats were randomized into 3 groups (n = 75): (1) sham, (2) ACLT alone, and (3) ACLT+ ipriflavone. Ipriflavone was administered intragastrically at 24 h after ACLT for 6 weeks. The extent of OA progression was evaluated by the OARSI score and immunohistochemistry at 12 weeks after surgery. The Ihh signaling pathway and OA-related genes were quantified by real-time PCR. RESULTS: Cell proliferation in the cells treated with ipriflavone was increased to 36.40% ± 1.32% (5 µM) and 28.54% ± 0.74% (10 µM) from 11.99% ± 0.35% (DMSO) (P < 0.001), and apoptosis was decreased to 12.64% ± 3.7% (5 µM) and 15.18% ± 3.13% (10 µM) from 25.76% ± 5.1% (DMSO) (P < 0.05). Ipriflavone blocked Runx-2 mainly through the Smo-Gli2 pathway. A similar result was found in the cartilage explant culture. Ihh signaling in vivo was inhibited in animals treated with ipriflavone. Safranin-O staining revealed a less cartilage damage with lower OARSI scores (P < 0.05) in the ipriflavone-treated animals compared with untreated animals. The gene expression of Smo and Gli2 was inhibited significantly by ipriflavone (P < 0.05). The OA-related gene and protein type X, MMP-13, and type II collagen-C fragment were reduced, while type II collagen and Agg were increased in the ipriflavone-treated animals (P < 0.05). CONCLUSIONS: Catabolic genes were disrupted by blocking the Ihh pathway. This finding suggests that disruption of Ihh signaling with ipriflavone provides chondral protection in rat posttraumatic OA.

17.
Nano Lett ; 19(6): 4035-4042, 2019 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-31082244

RESUMO

Extensive efforts have been devoted to construct a fiber-shaped energy-storage device to fulfill the increasing demand for power consumption of textile-based wearable electronics. Despite the myriad of available material selections and device architectures, it is still fundamentally challenging to develop eco-friendly fiber-shaped aqueous rechargeable batteries (FARBs) on a single-fiber architecture with high energy density and long-term stability. Here, we demonstrate flexible and high-voltage coaxial-fiber aqueous rechargeable zinc-ion batteries (CARZIBs). By utilizing a novel spherical zinc hexacyanoferrate with prominent electrochemical performance as cathode material, the assembled CARZIB offers a large capacity of 100.2 mAh cm-3 and a high energy density of 195.39 mWh cm-3, outperforming the state-of-the-art FARBs. Moreover, the resulting CARZIB delivers outstanding flexibility with the capacity retention of 93.2% after bending 3000 times. Last, high operating voltage and output current are achieved by the serial and parallel connection of CARZIBs woven into the flexible textile to power high-energy-consuming devices. Thus, this work provides proof-of-concept design for next-generation wearable energy-storage devices.

18.
Methods Mol Biol ; 1983: 3-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31087289

RESUMO

The dynamic nature of protein posttranslational modification (PTM) allows cells to rapidly respond to changes in their environment, such as nutrition, stress, or signaling. Lysine residues are targets for several types of modifications, including methylation, ubiquitination, and various acylation groups, especially acetylation. Currently, one of the best methods for identification and quantification of protein acetylation is immunoaffinity enrichment in combination with high-resolution mass spectrometry. As we are using a relatively novel and comprehensive mass spectrometric approach, data-independent acquisition (DIA), this protocol provides high-throughput, accurate, and reproducible label-free PTM quantification. Here we describe detailed protocols to process relatively small amounts of mouse liver tissue that integrate isolation of proteins, proteolytic digestion into peptides, immunoaffinity enrichment of acetylated peptides, identification of acetylation sites, and comprehensive quantification of relative abundance changes for thousands of identified lysine acetylation sites.

19.
Biomed Res Int ; 2019: 3235021, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011573

RESUMO

Background: Breast cancer (BC) is one of the most common malignant tumors in women around the world. Atorvastatin (ATO) was found to be associated with a decreased risk of recurrence and mortality in cancer. But the exact mechanism of its carcinostatic effects is unclear. The expression level of Ras homolog family member B (RhoB) in breast cancer cells was found to be upregulated after being treated with ATO. Thus, we conjecture that altered expression of RhoB induced by ATO may be decisive for the migration and progression of breast cancer. Methods: The effects of ATO on breast tumor cells in vivo and in vitro were detected by clone formation assay, CCK-8 assay, flow cytometry, wound healing, transwell assays, tumor xenograft model, and immunohistochemistry. Distribution of RhoB in different breast cancer tissues and its influence on prognosis were analyzed using the data from TCGA or GEO databases. The relationship between RhoB and PTEN/AKT pathway was detected by Western blotting and RT-qPCR. Results: ATO inhibits proliferation, invasion, EMT, and PTEN/AKT pathway and promotes apoptosis in breast tumor cells. In addition, ATO inhibits the volume and weight of breast tumor in tumor-bearing mice and upregulated RhoB in tumor tissues. The expression of RhoB in mRNA and protein level was upregulated in statin-treated breast cancer cells and downregulated in cancer tissues. Low expression of RhoB links with poor prognosis in patients with breast cancer (HR = 0.74[0.66-0.83], p =7e-8, log-rank test). Further research found that RhoB inhibits the proliferation, invasion, EMT, and PTEN/AKT signal pathway in breast tumor cells. Conclusions: The exact mechanism of ATO's carcinostatic effects in breast cancer is related to downregulating PTEN/AKT pathway via promoting RhoB. Our study also demonstrates the potential applicability of RhoB as a therapeutic target for breast cancer.


Assuntos
Atorvastatina/farmacologia , Neoplasias da Mama/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/efeitos dos fármacos , Proteína rhoB de Ligação ao GTP/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Recidiva Local de Neoplasia/genética , Prognóstico , Transdução de Sinais/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Ensaios Antitumorais Modelo de Xenoenxerto/métodos
20.
Inorg Chem ; 58(7): 4320-4327, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30848900

RESUMO

Thermal conductivity is an important physical parameter for the application of nonlinear optical single crystal materials. The underlying science of thermal transport behavior is not well established both experimentally and theoretically. In the present work, we have studied the microscopic picture of lattice thermal conductivity of ZnXP2 (X = Si, Ge, Sn), chalcopyrite ABC2 type infrared optical crystals, by using a harmonic and anharmonic lattice dynamic method and phonon Boltzmann transport equation based on first-principle calculations. With the mass of atom X increased, the phonon frequencies and phonon group velocities of ZnXP2 (X = Si, Ge, Sn) are shown not surprisingly to be decreased. Nevertheless, the phonon lifetime of ZnXP2 is unexpectedly increased, which is the governing mechanism for the increased thermal conductivity as 12.5 W/(m·k), 31.6 W/(m·k), and 35.4 W/(m·k), for ZnSiP2, ZnGeP2, and ZnSnP2, respectively, at 300 K. The contributions of optical phonons (with the frequency below 150 cm-1) to the total thermal conductivity are remarkable, reaching 18%, 31%, and 34% for three compounds, due to the significantly increased phonon lifetime in the frequency range 50-150 cm-1. To explore the physical insights of phonon lifetime and phonon anharmonicity, three-phonon scattering phase space and electronic localization function analysis of the X-P bond are provided. The results show that the covalent nature of X-P bonds is enhanced with the increased mass of atom X = Si, Ge, Sn, which induces the reduction of three-phonon scattering phase space in the frequency range 50-150 cm-1, leading to the enhancement of the phonon lifetime and thermal conductivity of ZnXP2.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA