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1.
Artigo em Inglês | MEDLINE | ID: mdl-33803264

RESUMO

Urban riverfront space has diversified ecosystem services, but due to excessive changes in the geographical environment, such as drastic changes in land use, people gain social value at a great ecological cost. Obtaining benefits from the ecosystem in this way is not sustainable. Therefore, this paper uses the SolVES model to evaluate the social value of ecosystem services on the east bank of the Fenghe River, while also studying the contribution of different environmental variables to social value. The main results are as follows. (1) Environmental variables affect the spatial distribution characteristics of social value. The distance to water (DTW) means the social value was distributed in strips, and the distance to road (DTR) concentrated the social value along the road. The landscape type (LT) means the social value was concentrated in the landscape space. (2) When DTW, DTR, and LT were collectively used as environmental variables, the distribution characteristics of various social values were similar to when LT was used as the only environmental variable. (3) The results of MaxEnt show that LT made a greater contribution to the aesthetic, recreation, therapeutic, and historic values, and was the largest contribution factor to the aesthetic, therapeutic, and historic values, with contribution rates of 47.6, 50.5, and 80.0%, respectively. DTW is the factor that contributed the most to recreation, with a contribution rate of 43.1%. Improving social value based on the influence and contribution of environmental variables can reduce the damage to the ecological environment caused by changes in geographic factors. This is sustainable for both the ecosystem and the services it provides to mankind.

2.
Small ; : e2100762, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33817965

RESUMO

In this work, by combining the superiority of polyoxometalates (POMs) and catalytic single-metal site Co of metalloporphyrin, a series of mixed-valence POM-based metal-organic frameworks (MOFs) composites is synthesized by a post-modification method. The electron-transfer property of POM@PCN-222(Co) composite is significantly enhanced owing to the directional electron-transfer from POM to single-metal site Co in PCN-222(Co). In particular, H-POM@PCN-222(Co) gives a high Faradaic efficiency of 96.2% for electroreduction of CO2 into CO and good stability over 10 h. DFT calculations confirm that the directional electron transfer, which accelerates the multi-electron transfer from the electrode to active single-metal site Co, enriches the electron density of the Co center, and ultimately reduces the energy of the rate-determining step, thus increasing the catalytic activity of CO2 reduction reaction (CO2 RR). This work therefore suggests some new insight for the design of efficient electrocatalysts for CO2 RR.

3.
Clin Neurol Neurosurg ; 203: 106598, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33730617

RESUMO

OBJECTIVES: This study aimed to summarize the surgical strategies for subdural effusion secondary to decompressive craniectomy (SESDC) and discuss the applicable scenarios of effusion-peritoneal shunt (EP shunt). METHODS: A total of 53 consecutive patients with SESDC were screened out of 7569 cases. The SESDC was divided into five types, and the treatment methods of each type were analyzed and compared. According to the implementation strategy of cranioplasty (CP), patients were divided into CP-first and delayed-CP groups. The differences in surgical methods were compared between the two groups. RESULTS: All patients with SESDC in this cohort had undergone cranioplasty. Subcutaneous puncture and aspiration (SPAA) proved ineffective. Only 2/30 patients in the CP-first group used EP shunt, while 6/19 patients in the delayed-CP group used EP shunt; the difference was statistically significant (P = 0.03). A significant difference was found in the use of EP shunt among type 1, type 2, and type 5 SESDC (χ2 = 6.778, P = 0.034). CONCLUSIONS: CP combined with other treatments could cure most SESDC. EP shunt should be used preferentially in some specific scenarios in which CP cannot be performed first, rather than as a backup measure that can only be used when other preceding treatments fail.

4.
J Clin Pharm Ther ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537999

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The benefits and risks of restarting antiplatelet therapy (APT) for patients with spontaneous intracranial haemorrhage (ICH) remain controversial. This meta-analysis was performed to explore the efficacy and safety of restarting APT for these patients. METHODS: We followed the recommended PRISMA guidelines for systematic reviews. Studies from PubMed, Embase, Web of Science, CNKI and the Cochrane Library were systematically retrieved from the inception of each database to 31 July 2020. We also manually retrieved studies of reference. RESULTS AND DISCUSSION: In this study, seven cohort studies and one randomized controlled trial (RCT) with subjects were included. APT resumption after spontaneous ICH did not significantly increase the risk of major haemorrhagic events (HR 1.15; 95% CI: 0.70-1.89; p = .59). However, it did not significantly reduce the risk of a composite endpoint concerning occlusive/thromboembolic events (HR 0.98; 95% CI: 0.81-1.19; p = .83) and all-cause mortality (HR 0.93; 95% CI: 0.80-1.08; p = .35). WHAT IS NEW AND CONCLUSION: Restarting APT for patients with spontaneous ICH is generally safe. However, the benefits of reducing the risk of ischaemic vascular events and all-cause mortality were not apparent. More RCTs are required.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33540451

RESUMO

BACKGROUND: Organized chronic subdural hematoma (CSDH) is a special type of CSDH. However, the optimal surgical procedure has not been established. We present our experience here to discuss the surgical procedure in treatment of organized CSDH. METHODS: Thirty-three patients with organized CSDH were admitted between January 1, 2008 and January 1, 2018. Age, gender, clinical symptoms, imaging data, type of surgical procedure, Barthel index (BI), and postoperative complications were collected and retrospectively analyzed. The BI was assessed both pre and postoperatively (1 week and 1 month after surgery). RESULTS: Overall, 14 patients underwent large craniotomy and 19 patients underwent small craniotomy. No significant differences in gender, age, initial clinical symptoms, and preoperative BI were found between the groups (p > 0.05). Among the 14 patients who underwent large craniotomy, 2 patients developed epilepsy after the operation, while 1 patient had postoperative aphasia. None of the patients had recurrence in 6 months postoperatively. Among the 19 patients who underwent small craniotomy, 1 patient developed an acute subdural hematoma and 1 patient developed aphasia. No obvious complications were found in the remaining 18 patients and none of the 19 patients had recurrence in 6 months postoperatively. BI scores of the small craniotomy group were significantly better than those of the large craniotomy group at 1 week postoperatively (p < 0.05). However, there was no significant difference in the 1-month results (p > 0.05). CONCLUSION: According to our single-center experience, a small craniotomy for treating organized CSDH can be considered as an alternative to a larger craniotomy.

6.
Nat Commun ; 12(1): 1076, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33597535

RESUMO

Upstream open reading frames (uORFs) play widespread regulatory functions in modulating mRNA translation in eukaryotes, but the principles underlying the genomic distribution and evolution of uORFs remain poorly understood. Here, we analyze ~17 million putative canonical uORFs in 478 eukaryotic species that span most of the extant taxa of eukaryotes. We demonstrate how positive and purifying selection, coupled with differences in effective population size (Ne), has shaped the contents of uORFs in eukaryotes. Besides, gene expression level is important in influencing uORF occurrences across genes in a species. Our analyses suggest that most uORFs might play regulatory roles rather than encode functional peptides. We also show that the Kozak sequence context of uORFs has evolved across eukaryotic clades, and that noncanonical uORFs tend to have weaker suppressive effects than canonical uORFs in translation regulation. This study provides insights into the driving forces underlying uORF evolution in eukaryotes.


Assuntos
Eucariotos/genética , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Fases de Leitura Aberta/genética , Regiões 5' não Traduzidas/genética , Sequência de Aminoácidos , Códon de Iniciação/genética , Eucariotos/classificação , Evolução Molecular , Filogenia , Biossíntese de Proteínas/genética , Homologia de Sequência de Aminoácidos , Especificidade da Espécie
7.
Medicine (Baltimore) ; 100(1): e24198, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429809

RESUMO

BACKGROUND: With the outbreak of novel coronavirus, the treatment of respiratory diseases has been promoted. In particular, many traditional Chinese medicines, including Chinese patent medicines, have been found to be effective in the treatment of respiratory illness in China. chronic obstructive pulmonary disease (COPD) is one of most common respiratory condition. It is predicted that COPD will be become the third frequent cause of death by 2030. The aim of this study is to assess the efficacy and safety of Shufeng Jiedu Capsule in the treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). METHODS: According to the search strategy, randomized controlled trials (RCTs) of Shufeng Jiedu Capsule in the treatment of AECOPD were obtained from Cochrane Library, MEDLINE, Embase, CNKI, VIP, CBM, and WANGFANG. Studies were screened according to inclusion and exclusion criteria, and the Cochrane risk bias assessment tool was used to assess the quality of the study. Meta-analysis was performed using Revman 5.4 software. Finally, the evidence level of the results will be evaluated. RESULTS: The purpose of this study was to evaluate the efficacy and safety of Shufeng Jiedu Capsule in the treatment of AECOPD, and to provide basis for clinical rational drug use. CONCLUSION: Our research results of this study could provide reference for clinical decision-making and guiding development in the future COPD patient. INPLASY REGISTRATION NUMBER: INPLASY2020120062.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Projetos de Pesquisa , Cápsulas , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
8.
Artigo em Inglês | MEDLINE | ID: mdl-33511739

RESUMO

Multidimensional fabrication of metal-organic frameworks (MOFs) into multilevel channel integrated devices are in high demanded for Li-S separators. Such separators have advantages in pore-engineering that might fulfill requirements such as intercepting the diffusing polysulfides and improving the Li+ /electrolyte transfer in Li-S batteries. However, most reported works focus on the roles of MOFs as ionic sieves for polysulfides while offering limited investigation on the tuning of Li+ transfer across the separators. A photoinduced heat-assisted processing strategy is proposed to fabricate MOFs into multidimensional devices (e.g., hollow/Janus fibers, double-or triple-layer membranes). For the first time, a triple-layer separator with stepped-channels has been designed and demonstrated as a powerful separator with outstanding specific capacity (1365.0 mAh g-1 ) and cycling performance (0.03 % fading per cycle from 100th to 700th cycle), which is superior to single/double-layer and commercial separators. The findings may expedite the development of MOF-based membranes and extend the scope of MOFs in energy-storage technologies.

9.
J Neuroinflammation ; 18(1): 2, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402181

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI. METHODS: The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed. RESULTS: Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation. CONCLUSIONS: Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.

10.
Physiol Rep ; 9(1): e14636, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33369887

RESUMO

ATP is an important paracrine regulator of renal tubular water and urea transport. The activity of P2Y2 , the predominant P2Y receptor of the medullary collecting duct, is mediated by ATP, and modulates urinary concentration. To investigate the role of purinergic signaling in the absence of urea transport in the collecting duct, we studied wild-type (WT) and UT-A1/A3 null (UT-A1/A3 KO) mice in metabolic cages to monitor urine output, and collected tissue samples for analysis. We confirmed that UT-A1/A3 KO mice are polyuric, and concurrently observed lower levels of urinary cAMP as compared to WT, despite elevated serum vasopressin (AVP) levels. Because P2Y2 inhibits AVP-stimulated transport by dampening cAMP synthesis, we suspected that, similar to other models of AVP-resistant polyuria, purinergic signaling is increased in UT-A1/A3 KO mice. In fact, we observed that both urinary ATP and purinergic-mediated prostanoid (PGE2 ) levels were elevated. Collectively, our data suggest that the reduction of medullary osmolality due to the lack of UT-A1 and UT-A3 induces an AVP-resistant polyuria that is possibly exacerbated by, or at least correlated with, enhanced purinergic signaling.

11.
Mol Cancer ; 19(1): 168, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33261601

RESUMO

Hypoxic stress plays a pivotal role in cancer progression; however, how hypoxia drives tumors to become more aggressive or metastatic and adaptive to adverse environmental stress is still poorly understood. In this study, we revealed that CSN8 might be a key regulatory switch controlling hypoxia-induced malignant tumor progression. We demonstrated that the expression of CSN8 increased significantly in colorectal cancerous tissues, which was correlated with lymph node metastasis and predicted poor patient survival. CSN8 overexpression induces the epithelial-mesenchymal transition (EMT) process in colorectal cancer cells, increasing migration and invasion. CSN8 overexpression arrested cell proliferation, upregulated key dormancy marker (NR2F1, DEC2, p27) and hypoxia response genes (HIF-1α, GLUT1), and dramatically enhanced survival under hypoxia, serum deprivation, or chemo-drug 5-fluorouracil treatment conditions. In particular, silenced CSN8 blocks the EMT and dormancy processes induced by the hypoxia of 1% O2 in vitro and undermines the adaptive capacity of colorectal cancer cells in vivo. The further study showed that CSN8 regulated EMT and dormancy partly by activating the HIF-1α signaling pathway, which increased HIF-1α mRNA expression by activating NF-κB and stabilized the HIF-1α protein via HIF-1α de-ubiquitination. Taken together, CSN8 endows primary colorectal cancer cells with highly aggressive/metastatic and adaptive capacities through regulating both EMT and dormancy induced by hypoxia. CSN8 could serve as a novel prognostic biomarker for colorectal cancer and would be an ideal target of disseminated dormant cell elimination and tumor metastasis, recurrence, and chemoresistance prevention.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33375213

RESUMO

Lung cancer is the most commonly diagnosed cancer in China. The incidence trend and geographical distribution of lung cancer in southern China have not been reported. The present study explored the temporal trend and spatial distribution of lung cancer incidence in Shenzhen from 2008 to 2018. The lung cancer incidence data were obtained from the registered population in the Shenzhen Cancer Registry System between 2008 and 2018. The standardized incidence rates of lung cancer were analyzed by using the joinpoint regression model. The Moran's I method was used for spatial autocorrelation analysis and to further draw a spatial cluster map in Shenzhen. From 2008 to 2018, the average crude incidence rate of lung cancer was 27.1 (1/100,000), with an annual percentage change of 2.7% (p < 0.05). The largest average proportion of histological type of lung cancer was determined as adenocarcinoma (69.1%), and an increasing trend was observed in females, with an average annual percentage change of 14.7%. The spatial autocorrelation analysis indicated some sites in Shenzhen as a high incidence rate spatial clustering area. Understanding the incidence patterns of lung cancer is useful for monitoring and prevention.


Assuntos
Neoplasias Pulmonares , China/epidemiologia , Análise por Conglomerados , Feminino , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia , Masculino , Sistema de Registros , Análise Espaço-Temporal
13.
Oncoimmunology ; 9(1): 1773200, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32923131

RESUMO

Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results: For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions: Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.

15.
Cell Prolif ; 53(8): e12830, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32608556

RESUMO

OBJECTIVES: Skin serves as the major interface between the external environment and body which is liable to many kinds of injuries. Mesenchymal stem cell (MSC) therapy has been widely used and became a promising strategy. Pre-treatment with chemical agents, hypoxia or gene modifications can partially protect MSCs against injury, and the pre-treated MSCs show the improved differentiation, homing capacity, survival and paracrine effects regard to attenuating injury. The aim of this study was to investigate whether the exosomes from the educated MSCs contribute to accelerate wound healing process. MATERIALS AND METHODS: We extracted the exosomes from the two educated MSCs and utilized them in the cutaneous wound healing model. The pro-angiogenetic effect of exosomes on endothelial cells was also investigated. RESULTS: We firstly found that MSCs pre-treated by exosomes from neonatal serum significantly improved their biological functions and the effect of therapy. Moreover, we extracted the exosomes from the educated MSCs and utilized them to treat the cutaneous wound model directly. We found that the released exosomes from MSCs which educated by neonatal serum before had the more outstanding performance in therapeutic effect. Mechanistically, we revealed that the recipient endothelial cells (ECs) were targeted and the exosomes promoted their functions to enhance angiogenesis via regulating AKT/eNOS pathway. CONCLUSIONS: Our findings unravelled the positive effect of the upgraded exosomes from the educated MSCs as a promising cell-free therapeutic strategy for cutaneous wound healing.


Assuntos
Exossomos/metabolismo , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/fisiologia , Cicatrização/fisiologia , Animais , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Fibroblastos/metabolismo , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Camundongos Endogâmicos C57BL , Pele/citologia
17.
J Mater Chem B ; 8(18): 4046-4055, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32248212

RESUMO

A berberine 9-O-pyrazole alkyl derivative, a chemical compound (called B3) previously synthesized by our group, shows anti-cancer activity. However, B3 lacks targeting cytotoxicity to cancer cells, leading to obvious toxic side effects on normal cells. To solve this problem, here, we prepared a drug delivery system, namely, AS1411-GO/B3 for tumor targeting, in which nano-graphene oxide (GO) sheets were employed as the drug carrier, and the aptamer AS1411 was conjugated onto GO for tumor targeting. GO also had a photothermal effect, which helped the release of B3 from GO as well as the thermal cytotoxicity to cells. We found that the release of B3 could respond to acid conditions, indicating that the tumor intracellular environment could promote the release of B3, thus allowing it to perform chemotherapy effects. This system could also release B3 in response to photothermal heating, moreover, combined photothermal therapy and chemotherapy to improve the anticancer activity was achieved. This AS1411-GO/B3 platform with chemo-photothermal synergetic therapy provides a very promising treatment for tumors.

18.
Cancer Res ; 80(13): 2790-2803, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32169859

RESUMO

Long noncoding RNAs (lncRNA) have been shown to play critical roles in many diseases, including esophageal squamous cell carcinoma (ESCC). Recent studies have reported that some lncRNA encode functional micropeptides. However, the association between ESCC and micropeptides encoded by lncRNA remains largely unknown. In this study, we characterized a Y-linked lncRNA, LINC00278, which was downregulated in male ESCC. LINC00278 encoded a Yin Yang 1 (YY1)-binding micropeptide, designated YY1BM. YY1BM was involved in the ESCC progression and inhibited the interaction between YY1 and androgen receptor (AR), which in turn decreased expression of eEF2K through the AR signaling pathway. Downregulation of YY1BM significantly upregulated eEF2K expression and inhibited apoptosis, thus conferring ESCC cells more adaptive to nutrient deprivation. Cigarette smoking decreased m6A modification of LINC00278 and YY1BM translation. In conclusion, these results provide a novel mechanistic link between cigarette smoking and AR signaling in male ESCC progression. SIGNIFICANCE: Posttranscriptional modification of a micropeptide-encoding lncRNA is negatively impacted by cigarette smoking, disrupting negative regulation of the AR signaling pathway in male ESCC. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/13/2790/F1.large.jpg.See related commentary by Banday et al., p. 2718.


Assuntos
Fumar Cigarros , Neoplasias Esofágicas , RNA Longo não Codificante , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , RNA Longo não Codificante/genética , Transdução de Sinais/genética , Fumaça , Cromossomo Y
19.
Nat Commun ; 11(1): 497, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31980641

RESUMO

Efficient conversion of carbon dioxide (CO2) into value-added products is essential for clean energy research. Design of stable, selective, and powerful electrocatalysts for CO2 reduction reaction (CO2RR) is highly desirable yet largely unmet. In this work, a series of metalloporphyrin-tetrathiafulvalene based covalent organic frameworks (M-TTCOFs) are designed. Tetrathiafulvalene, serving as electron donator or carrier, can construct an oriented electron transmission pathway with metalloporphyrin. Thus-obtained M-TTCOFs can serve as electrocatalysts with high FECO (91.3%, -0.7 V) and possess high cycling stability (>40 h). In addition, after exfoliation, the FECO value of Co-TTCOF nanosheets (~5 nm) is higher than 90% in a wide potential range from -0.6 to -0.9 V and the maximum FECO can reach up to almost 100% (99.7%, -0.8 V). The electrocatalytic CO2RR mechanisms are discussed and revealed by density functional theory calculations. This work paves a new way in exploring porous crystalline materials in electrocatalytic CO2RR.

20.
J Exp Med ; 217(3)2020 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-31816634

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) with the most aggressive phenotype and poor overall survival. Using bioinformatics tools, we identified LINC00908 encoding a 60-aa polypeptide and differentially expressed in TNBC tissues. We named this endogenously expressed polypeptide ASRPS (a small regulatory peptide of STAT3). ASRPS expression was down-regulated in TNBCs and associated with poor overall survival. We showed that LINC00908 was directly regulated by ERα, which was responsible for the differential down-regulation of LINC00908 in TNBCs. ASRPS directly bound to STAT3 through the coiled coil domain (CCD) and down-regulated STAT3 phosphorylation, which led to reduced expression of VEGF. In human endothelial cells, a mouse xenograft breast cancer model, and a mouse spontaneous BC model, ASRPS expression reduced angiogenesis. In a mouse xenograft breast cancer model, down-regulation of ASRPS promoted tumor growth, and ASRPS acted as an antitumor peptide. We presented strong evidence that LINC00908-encoded polypeptide ASRPS represented a TNBC-specific target for treatment.


Assuntos
Neovascularização Patológica/genética , Peptídeos/genética , RNA Longo não Codificante/genética , Neoplasias de Mama Triplo Negativas/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Células Endoteliais/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Células MCF-7 , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Neovascularização Patológica/patologia , Fator de Transcrição STAT3/genética , Neoplasias de Mama Triplo Negativas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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