Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Artigo em Inglês | MEDLINE | ID: mdl-32601216

RESUMO

The application of pressure can achieve novel structures and exotic phenomena in condensed matters. However, such pressure-induced transformations are generally reversible and useless for engineering materials for ambient-environment applications. Here, we report comprehensive high-pressure investigations on a series of Dion-Jacobson (D-J) perovskites A'A n-1Pb n I3n+1 [A' = 3-(aminomethyl) piperidinium (3AMP), A = methylammonium (MA), n = 1, 2, 4]. Our study demonstrates their irreversible behavior, which suggests pressure/strain engineering could viably improve light-absorber material not only in situ but also ex situ, thus potentially fostering the development of optoelectronic and electroluminescent materials. We discovered that the photoluminescence (PL) intensities are remarkably enhanced by one order of magnitude at mild pressures. Also, higher pressure significantly changes the lattices, boundary conditions of electronic wave functions, and possibly leads to semiconductor-metal transitions. For (3AMP)(MA)3Pb4I13, permanent recrystallization from 2D to three-dimensional (3D) structure occurs upon decompression, with dramatic changes in optical properties.

2.
Nat Chem Biol ; 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601486

RESUMO

Membraneless organelles formed by liquid-liquid phase separation of proteins or nucleic acids are involved in diverse biological processes in eukaryotes. However, such cellular compartments have yet to be discovered or created synthetically in prokaryotes. Here, we report the formation of liquid protein condensates inside the cells of prokaryotic Escherichia coli upon heterologous overexpression of intrinsically disordered proteins such as spider silk and resilin. In vitro reconstitution under conditions that mimic intracellular physiologically crowding environments of E. coli revealed that the condensates are formed via liquid-liquid phase separation. We also show functionalization of these condensates via targeted colocalization of cargo proteins to create functional membraneless compartments able to fluoresce and to catalyze biochemical reactions. The ability to form and functionalize membraneless compartments may serve as a versatile tool to develop artificial organelles with on-demand functions in prokaryotes for applications in synthetic biology.

3.
FASEB J ; 34(6): 8558-8573, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32359008

RESUMO

Mounting evidence has linked dietary capsaicin (CAP) consumption to the improvement of glucose homeostasis; however, the underlying mechanisms still need to be further elucidated. Male mice were fed a high-fat diet (HFD) with CAP administration for 8 weeks, gut microbiota, bile acid (BA) profiles and markers for BA, and glucose metabolism were investigated. CAP improved glucose homeostasis partially by enhancing the secretion of glucagon-like peptide 1 (GLP-1). The gut microbiota was remodeled by CAP and was characterized by the increased abundance of Bacteroides genera, which is related with lithocholic acid (LCA) production. LCA is an endogenous agonist of Takeda G-protein coupled receptor 5 (TGR5); it may enhance GLP-1 secretion in intestinal L cells. Meanwhile, antibiotics experiment abolished the effects of CAP on glucose homeostasis and microbiota transplantation experiments demonstrated that the CAP-induced beneficial effects were transferable, indicating that the effects of CAP on glucose homeostasis were largely dependent on the gut microbiota. Additionally, we further identified that the improvements induced by CAP were attenuated by the antagonist of GLP-1 receptor, indicating that the activation of GLP-1 signaling contributes to the CAP-induced improvement in glucose homeostasis.

4.
Glycoconj J ; 37(3): 373-394, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32103424

RESUMO

Currently, the definitive diagnosis in breast cancer requires biopsy and histopathology, such the most effective markers are tissue-based. However, the advantages of saliva in collection and storage make it possible for assessing human pathology and contributing to the development of cancer-related biomarkers for clinical application. The present study validated alteration of salivary protein glycopatterns recognized by Bandeiraea simplicifolia lectin I (BS-I) in the saliva of patients with breast diseases using saliva microarrays, and the N/O-glycan profiles of their salivary glycoproteins isolated by the BS-I-magnetic particle conjugates from 259 female subjects (66 healthy volunteers (HV), 65 benign breast cyst or tumor patients (BB), 66 patients with breast cancer in stage I (BC-I) and 62 patients with breast cancer in stage II (BC-II)) were analyzed by MALDI-TOF/TOF-MS. The results showed that the expression level of galactosylated glycans recognized by BS-I was significantly increased in patients with breast cancer compared with HV (p < 0.05). Totally, there were 11/10, 10/19, 7/24 and 7/9 galactosylated N-/O-linked glycans were identified and annotated from the pooled salivary samples of HV, BB, BC-I and BC-II, respectively. One galactosylated N-glycan peak (m/z 2773.977), and 4 galactosylated O-glycan peaks (m/z 868.295, 882.243, 884.270 and 1030.348) were found only in BC-I. These findings could provide pivotal information on galactosylated N/O-linked glycans related to breast cancer, and promote the study of biomarkers for early-stage breast cancer based on precise alterations of galactosylated N/O-glycans in saliva.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32109044

RESUMO

Heteromolecular bilayers of π-conjugated organic molecules on metals, considered as model systems for more complex thin film heterostructures, are investigated with respect to their structural and electronic properties. By exploring the influence of the organic-metal interaction strength in bilayer systems, we determine the molecular arrangement in the physisorptive regime for copper-hexadecafluorophthalocyanine (F16CuPc) on Au(111) with intermediate layers of 5,7,12,14-pentacenetetrone and perylene-3,4,9,10-tetracarboxylic diimide. Using the X-ray standing wave technique to distinguish the different molecular layers, we show that these two bilayers are ordered following their deposition sequence. Surprisingly, F16CuPc as the second layer within the heterostructures exhibits an inverted intramolecular distortion compared to its monolayer structure.

6.
Nanotechnology ; 31(20): 205403, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000156

RESUMO

As a substitute of Pt-based catalysts, MoS2-based catalysts have been widely used in hydrogen evolution reaction, but the inherent low conductivity, limited active edges, self-stacking and agglomeration still hinder their activities. In this work, Mn-doped MoS2 nanosheets were vertically anchored on carbon nanotubes (CNTs) by the one-step hydrothermal reaction, in which Mn-O-C/Mo-O-C was considered as a bridge between Mn-MoS2 and CNTs. The doping of the Mn element enables the spreading of MoS2 on CNTs and the rapid escape of hydrogen bubbles from the electrode, while conductive CNTs with hydrophilicity can accelerate the electron transport process between the electrolyte and the material. With an overpotential of 150 mV at a current density of -10 mA cm-2 and a Tafel slope of 39 mV dec-1, this material exhibited excellent catalytic hydrogen evolution activity, which could open the path for designing commercial electrocatalysts.

7.
Clin Nutr ; 39(4): 1264-1275, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31189495

RESUMO

BACKGROUND & AIMS: This study aims to investigate the ameliorative effects of resveratrol (RSV) in a high-fat diet (HFD)-induced non-alcoholic steatohepatitis (NASH) rat model, focusing on the gut endocannabinoid system (ECS), regulated by RSV, in the maintenance of gut barrier integrity and inhibition of gut inflammation. METHODS AND RESULTS: Male Sprague-Dawley (SD) rats were fed HFD with or without RSV for 6 weeks. The HFD caused increase in body weight, liver index, hepatic lipid accumulation, and inflammation, which was inhibited by RSV. RSV also attenuated gut microbial dysbiosis, with an increase in Akkermansia muciniphila, Ruminococcaceae, and Lachnospiraceae, and a decrease in Desulfovibrio. Moreover, RSV led to a reduction of metabolic endotoxemia and colon inflammation in HFD-fed rats. This was indicated by a decrease in bacterial invasion and translocation along with up-regulation of the mRNA levels of occludin, ZO1, claudin1, and down-regulation of FAK, MyD88, and IRAK4 in the distal colon. Furthermore, RSV inhibited HFD-induced elevation in the expression of cannabinoid receptor type 1 (CB1) mRNA and suppressed CB2 mRNA levels in the colon. The RSV-induced benefits regarding enhanced gut barrier integrity and reduced intestinal permeability were abrogated with a CB1 agonist, ACEA, whereas the inhibitory effect of RSV on the intestinal inflammation was abolished by a CB2 antagonist, AM630. Moreover, microbiota depletion using a cocktail of antibiotics was sufficient to block RSV-induced reduction in intestinal permeability and gut inflammation, as well as the altered mRNA expressions of CB1 and CB2 in the distal colon. CONCLUSIONS: These data indicate that the ECS, particularly the expressions of CB1 and CB2, appears to play a crucial role in the RSV induced anti-NASH effect by maintaining the gut barrier integrity and inhibiting gut inflammation.

8.
Biochem Biophys Res Commun ; 521(1): 64-71, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31627897

RESUMO

Rosacea is a chronic inflammatory cutaneous disease which mainly affects central face, leading to cosmetic disfigurement and compromised social psychology in billions of rosacea patients. Though the exact etiology of rosacea remains elusive, accumulating evidence has highlighted the dysfunction of innate immunity and inflammation in rosacea pathogenesis. Disintegrin Metalloprotease ADAM-like Decysin-1 (ADAMDEC1) is an orphan ADAM-like metalloprotease which is believed to be closely related to inflammation. Here for the first time, we reported that Adamdec1 expression was significantly increased in the skin lesions of rosacea patients and LL37-induced rosacea-like mouse models. Immunofluorescence analysis revealed co-localization of ADAMDEC1 and macrophages in patient and mouse biopsies. In cellular experiment, the expression of ADAMDEC1 was prominently elevated in M1 but not M2 macrophages. Knocking down of ADAMDEC1 significantly blunted M1 polarization in macrophages induced from human monocytes and THP-1 cell lines. Furthermore, silencing of Adamdec1 in LL-37-induced mouse model also suppressed the expression of M1 signature genes such as IL-6, iNOS and TNF-α, resulting in attenuated rosacea-like phenotype and inflammation. Taken together, our results demonstrate that ADAMDEC1 plays a pro-inflammatory role in rosacea via modulating the M1 polarization of macrophages.

9.
Cell Death Dis ; 10(11): 859, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719519

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

10.
Theranostics ; 9(22): 6468-6484, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588230

RESUMO

Identification of novel targets for triple-negative breast cancer (TNBC) is an urgent task as targeted therapies have increased the lifespans of Oestrogen Receptor +/ Progesterone Receptor + and HER2+ cancer patients. Methods: genes involved in protein processing in the endoplasmic reticulum, which have been reported to be key players in cancer, were used in loss-of-function screening to evaluate the oncogenic roles of these genes to identify candidate target genes in TNBC. In vitro and in vivo function assays as well as clinical prognostic analysis were used to study the oncogenic role of the gene. Molecular and cell based assays were further employed to investigate the mechanisms. Results: B Cell Receptor Associated Protein 31 (BCAP31), the expression of which is correlated with early recurrence and poor survival among patients, was identified an oncogene in our assay. In vitro studies further suggested that BCAP31 acts as a key oncogene by promoting TNBC development. We also showed that BCAP31 interacts with epidermal growth factor receptor (EGFR) and serves as an inhibitor of ligand-independent EGFR recycling, sustaining EGFR autophosphorylation and activation of downstream signalling. Conclusion: These findings reveal the functional role of BCAP31, an ER-related protein, in EGFR dysregulation and TNBC development.

11.
ACS Appl Mater Interfaces ; 11(41): 37833-37841, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31538760

RESUMO

Perovskite solar cells (PSCs) have demonstrated encouraging progress in recent years. Additive engineering, where diverse additives are incorporated into the perovskite layer, has been widely adopted to tune the perovskite grains, reduce defect density and charge recombination. Here, we observe a universal phenomenon that organic chloride additives enhance the open circuit voltage (VOC) and power conversion efficiencies (PCEs) of direct PSCs but decrease the VOC, short-circuit current (JSC), and PCE of inverted PSCs, regardless of the choice of charge transport materials. The polyTPD-based direct device incorporating trimethylammonium chloride (TACl) additive delivery improved PCE from 17.8 to 20.0%, arising from the enhanced VOC from 1.03 to 1.12 V. With the same content of TACl, the best PCE of the polyTPD-based inverted device decreased from 20.2 to 18.5% because of the reduced VOC (1.05-1.01 V) and JSC (23.2-22.5 mA/cm2). Our investigation confirms that organic chloride will p-dope perovskites and elevate the work functions, which lead to favorable/unfavorable charge transfer between perovskite films and its upper transport layers in direct and inverted devices. This work provides an insight into the rational design of the device structure when applying additives which can dope the perovskite to affect charge transfer at the perovskite/charge transport layer interface.

12.
Mol Nutr Food Res ; 63(23): e1900608, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31539192

RESUMO

SCOPE: Previous studies have linked dietary capsaicin (CAP) intake to improved glucose homeostasis and insulin sensitivity. However, the underlying mechanisms remain unclear. METHODS AND RESULTS: Type 2 diabetic db/db mice are fed a chow diet with or without CAP treatment for 8 weeks. CAP administration markedly improves glucose tolerance and insulin sensitivity through decreasing gluconeogenesis and increasing glycogen synthesis in the liver. Furthermore, CAP inhibits the increase in abundance of the genus Lactobacillus and its bile salt hydrolase (BSH) activity compared with levels in chow-fed mice, thereby leading to the accumulation of tauro-ß-muricholic acid (TßMCA), a natural antagonist of the farnesoid X receptor (FXR) that is involved in the regulation of BA and glucose metabolism. CAP-induced suppression of enterohepatic FXR-fibroblast growth factor 15 (FGF15) signaling contributes to the increased BA pool size, followed by increases in the expression of cholesterol 7α-hydroxylase (CYP7A1) and hepatic BA synthesis. Additionally, depleting gut microbiota by antibiotics administration abolishes the beneficial effects of CAP on BA metabolism and glucose homeostasis. CONCLUSIONS: CAP-induced improvements in BA and glucose metabolism are partially mediated by the gut microbiota-BA-enterohepatic FXR axis in db/db mice.

13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 44(7): 725-730, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31413209

RESUMO

OBJECTIVE: To detemine the expression pattern of mTOR complex subunits Raptor and Rictor in the hair follicles of mice at different hair follicle stages, and to explore its significance. 
 Methods: Immunostaining of Ki-67, a proliferative marker, was used to determine the precise hair follicle stages of mouse dorsal skin at different postnatal time points. Real-time PCR was used to detect the mRNA expression of Raptor and Rictor in mouse dorsal skin at 43 days after birth (P43, early telogen), 56 days after birth (P56, mid-telogen), 69 days after birth (P69, late telogen) and 74 days after birth (P74, early anagen). The expression intensity and localization of Raptor and Rictor at different stages of hair cycle were tested by co-immumostaining.
 Results: Ki-67 immunostaining showed that the time points (P43, P56, P69, P74) and hair follicle stages (early telogen, mid-telogen, late telogen, early anagen) of the dorsal skin were consistent with each other. The results of real-time PCR and immunostaining were consistent, showing that the expression of Raptor and Rictor did not changed in the early-, mid-, late telogen, and early anagen. However, Raptor was specifically expressed in the bulge where hair follicle stem cells (HFSCs) are residing in, and Rictor was mainly detected in inner root sheath (IRS) cells. 
 Conclusion: The expression of Raptor and Rictor does not altered in the hair follicles at different hair follicle stages, but Raptor and Rictor are specifically expressed in the HFSCs and IRS cells, respectively, indicating that Raptor might be a molecular marker for HFSCs, and Rictor might be involved in the maintenance of IRS and formation of hair shaft.


Assuntos
Folículo Piloso , Aves Predatórias , Animais , Cabelo , Camundongos , Proteína Companheira de mTOR Insensível à Rapamicina , Pele , Serina-Treonina Quinases TOR
14.
Ultrasound Med Biol ; 45(11): 3005-3017, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31421866

RESUMO

Eukaryotic cells can survive sonoporation and repair their plasma membrane wounds. However, it is not clear how the repaired plasma membranes will differ from the intact ones. To answer this question, we used high-resolution confocal microscopy and scanning electron microscopy to study plasma membrane lipid alterations induced by sonoporation. First, we found that the wound-induced increase in membrane lipid content was not limited to the sonoporation sites. The degree of lipid increase was dependent on pore distance, calcium influx and pore size. Second, we observed interesting lipid striation patterns on the sonoporated plasma membranes. This patterning effect was reversible in the cell subjected to small-scale sonoporation and could be recognized using digital image orientation analysis. Third, we showed that actin stress fibers underneath the plasma membrane hindered the addition and the protrusion of lipids to produce the patterning effect. Our findings demonstrated that the sonoporated and repaired plasma membranes have distinct lipid distribution characteristics.

15.
Front Oncol ; 9: 636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31355147

RESUMO

Aberrant glycosylation is not only a feature of malignant cell transformation, but also plays an important role in metastasis. In the present study, an integrated strategy combining the lectin microarrays and lectin cytochemistry was employed to investigate and verify the altered glycopatterns in gastric cancer (GC) cell lines as well as resected tumor specimens from matched tissue sets of 46 GC patients. Subsequently, lectin-mediated affinity capture glycoproteins, and MALDI-TOF/TOF-MS were employed to further acquire precise structural information of the altered glycans. According to the results, the glycopatterns recognized by 10 (e.g., ACA, MAL-I, and ConA) and 3 lectins (PNA, MAL-I, and VVA) showed significantly variations in GC cells and tissue compared to their corresponding controls, respectively. Notably, the relative abundance of Galß-1,4GlcNAc (LacNAc) recognized by MAL-I exhibited a significant increase in GC cells (p < 0.001) and tissue from patients at stage II and III (p < 0.05), and a significant increase in lymph node positive tumor cases, compared with lymph node negative tumor cases (p < 0.05). More LacNAc contained N-glycans were characterized in tumor sample with advanced stage compared to corresponding control. Moreover, there were 10 neo-LacNAc-contained N-glycans (e.g., m/z 1625.605, 1803.652, and 1914.671) only presented in GC tissue with advanced stage. Among these, six N-glycans were modified with sialic acid or fucose based on LacNAc to form sialylated N-glycans or lewis antigens, respectively. Our results revealed that the aberrant expression of LacNAc is a characteristic of GC, and LacNAc may serve as a scaffold to be further modified with sialic acid or fucose. Our findings provided useful information for us to understand the development of GC.

16.
Int J Mol Sci ; 20(12)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226870

RESUMO

Plants undergo several but very precise molecular, physiological, and biochemical modulations in response to biotic stresses. Mitogen-activated protein kinase (MAPK) cascades orchestrate multiple cellular processes including plant growth and development as well as plant responses against abiotic and biotic stresses. However, the role of MAPK kinases (MAPKKs/MKKs/MEKs) in the regulation of plant resistance to herbivores has not been extensively investigated. Here, we cloned a rice MKK gene, OsMKK3, and investigated its function. It was observed that mechanical wounding, infestation of brown planthopper (BPH) Nilaparvata lugens, and treatment with methyl jasmonate (MeJA) or salicylic acid (SA) could induce the expression of OsMKK3. The over-expression of OsMKK3 (oe-MKK3) increased levels of jasmonic acid (JA), jasmonoyl-L-isoleucine (JA-Ile), and abscisic acid (ABA), and decreased SA levels in rice after BPH attack. Additionally, the preference for feeding and oviposition, the hatching rate of BPH eggs, and BPH nymph survival rate were significantly compromised due to over-expression of OsMKK3. Besides, oe-MKK3 also augmented chlorophyll content but impaired plant growth. We confirm that MKK3 plays a pivotal role in the signaling pathway. It is proposed that OsMKK3 mediated positive regulation of rice resistance to BPH by means of herbivory-induced phytohormone dynamics.


Assuntos
Hemípteros/fisiologia , Herbivoria , MAP Quinase Quinase 3/metabolismo , Oryza/fisiologia , Proteínas de Plantas/metabolismo , Ácido Abscísico/metabolismo , Animais , Ciclopentanos/metabolismo , Isoleucina/análogos & derivados , Isoleucina/metabolismo , Oxilipinas/metabolismo , Reguladores de Crescimento de Planta/metabolismo
17.
Biomed Pharmacother ; 116: 109011, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132668

RESUMO

BACKGROUND: Rosacea is a chronic inflammatory skin disorder of uncertain etiology. Evidence suggests the underlying pathogenesis is modulated by abnormal inflammatory and vascular responses. Thalidomide is a synthetic derivative acid with anti-inflammatory and anti-angiogenic properties. However, its effects on rosacea remain unknown. OBJECTIVES: To investigate the effects of thalidomide on the lesional alterations and molecular mechanisms in rosacea. METHODS: Mice were intradermally injected with LL37 to induce rosacea-like features and intraperitoneally administered with thalidomide. The severity of skin inflammation was evaluated. The mRNA levels of cytokines and chemokines associated with rosacea were assessed by qPCR. The number of CD4 positive infiltrated T helper cells and CD31 positive microvessels, and related-genes were measured by immunofluorescence, qPCR and ELISA. Moreover, the effect of thalidomide on inhibiting NF-κB activation was determined by immunofluorescence and western blot. RESULTS: Our results showed that thalidomide significantly alleviated erythema and reduced inflammatory cell infiltration in dermis of LL37-induced rosacea-like mice. The production of cytokines and chemokines induced by LL37 was decreased by thalidomide in mice skin and HaCaT keratinocytes. Particularly, we showed thalidomide reduced CD4+ T helper cell infiltration and downregulated Th1- and Th17-polarizing genes. In addition, thalidomide treatment lowered the microvessel density and vascular endothelial growth factor (VEGF) expression. We further demonstrated that thalidomide suppressed NF-κB activation in LL37-treated skin and in TNF-α-stimulated HaCaT keratinocytes in vitro. CONCLUSIONS: Our findings suggest thalidomide attenuates the inflammation and represses NF-κB activation in skin, which leads to assumptions that thalidomide may be a new therapeutic agent for rosacea.


Assuntos
Inflamação/tratamento farmacológico , Queratinócitos/metabolismo , Queratinócitos/patologia , NF-kappa B/metabolismo , Rosácea/tratamento farmacológico , Rosácea/metabolismo , Pele/patologia , Talidomida/uso terapêutico , Animais , Peptídeos Catiônicos Antimicrobianos , Linhagem Celular , Quimiocinas/biossíntese , Humanos , Inflamação/complicações , Inflamação/metabolismo , Queratinócitos/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Neovascularização Fisiológica/efeitos dos fármacos , Rosácea/complicações , Rosácea/imunologia , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Pele/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia , Talidomida/farmacologia
18.
Cancer Med ; 8(6): 2840-2857, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31016890

RESUMO

BACKGROUND: To evaluate the significance and benefit of radiotherapy (RT) in young early-stage breast cancer patients according to different molecular subtypes. METHODS: We conducted a retrospective cohort study utilizing the Surveillance, Epidemiology, and End Results database with known hormone receptor (HoR) and human epidermal growth factor receptor 2 (HER2) status. Female patients aged 18-45, received RT treatment, and diagnosed with stage T1-3, N0-3, M0 primary breast cancer between 2010 and 2013 were identified. RESULTS: Of all the 23 148 included patients, 14 708 (63.54%), 3385 (14.62%), 1225 (5.29%), and 3830 (16.55%) were diagnosed with luminal-A (HoR + HER2-), luminal-B (HoR + HER2+), HER2-enriched (HoR-HER2+), and triple-negative (HoR-HER2-) breast cancer, respectively. RT was significantly correlated with improved overall survival (OS, HR: 0.295; 95% CI:0.138-0.63, P = 0.002) and breast cancer-specific survival (BCSS, HR: 0.328; 95% CI: 0.153-0.702, P = 0.004) in HER2-enriched patients. In addition, a significantly prolonged OS was also observed when RT was given to luminal-A (HR: 0.696; 95% CI: 0.538-0.902, P = 0.006) and luminal-B (HR: 0.385; 95% CI:0.199-0.744, P = 0.005) breast cancer patients compared to those without RT. Multivariable-adjusted analyses showed that HER2 was a significant favorable factor for RT benefit in breast cancer patients. CONCLUSIONS: RT could offer significant survival benefit in luminal-A, luminal-B, and especially HER2-enriched young early-stage breast cancer female patients. The results enabled clinicians to predict the benefits of RT and improve evidence-based treatment for breast cancer patients.

19.
Front Microbiol ; 10: 444, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30923517

RESUMO

Isovaleryl-CoA dehydrogenase (IVD), a member of the acyl-CoA dehydrogenase (ACAD) family, is a key enzyme catalyzing the conversion of isovaleryl-CoA to ß-methylcrotonyl-CoA in the third reaction of the leucine catabolism pathway and simultaneously transfers electrons to the electron-transferring flavoprotein (ETF) for ATP synthesis. We previously identified the ETF ortholog in rice blast fungus Magnaporthe oryzae (MoETF) and showed that MoETF was essential for fungal growth, conidiation and pathogenicity. To further investigate the biological function of electron-transferring proteins and clarify the role of leucine catabolism in growth and pathogenesis, we characterized MoIVD (M. oryzae isovaleryl-CoA dehydrogenase). MoIvd is highly conserved in fungi and its expression was highly induced by leucine. The Δmoivd mutants showed reduced growth, decreased conidiation and compromised pathogenicity, while the conidial germination and appressorial formation appeared normal. Consistent with a block in leucine degradation, the Δmoivd mutants accumulated isovaleric acid, grew more slowly, fully lacked pigmentation and completely failed to produce conidia on leucine-rich medium. These defects were largely rescued by raising the extracellular pH, suggesting that the accumulation of isovaleric acid contributes to the growth and conidiation defects. However, the reduced virulence of the mutants was probably due to their inability to overcome oxidative stress, since a large amount of ROS (reactive oxygen species) accumulated in infected host cell. In addition, MoIvd is localized to mitochondria and interacted with its electron receptor MoEtfb, the ß subunit of MoEtf. Taken together, our results suggest that MoIVD functions in leucine catabolism and is required for the vegetative growth, conidiation and full virulence of M. oryzae, providing the first evidence for IVD-mediated leucine catabolism in the development and pathogenesis of plant fungal pathogens.

20.
Bioorg Med Chem Lett ; 29(7): 890-895, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30765188

RESUMO

Allatostatins (AST) are neuropeptides originally described as inhibitors of juvenile hormone (JH) synthesis in insects. Consequently, they have been considered as potential lead compounds for the discovery of new insect growth regulators (IGRs). In the present work, receptor-based three-dimensional quantitative structure-activity relationship (3D-QSAR) was studied with 48 AST analogs, and a general approach for novel potent bioactive AST analogs is proposed. Hence, six novel AST analogs were designed and synthesized. Bioassays indicated that the majority novel analogs exhibited potent JH inhibitory activity, especially analog A6 (IC50: 3.79 nmol/L), which can be used as lead compound to develop new IGRs.


Assuntos
Proteínas de Insetos/química , Hormônios Juvenis/química , Neuropeptídeos/química , Animais , Sítios de Ligação , Baratas/química , Proteínas de Insetos/síntese química , Proteínas de Insetos/metabolismo , Hormônios Juvenis/antagonistas & inibidores , Hormônios Juvenis/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Neuropeptídeos/síntese química , Neuropeptídeos/metabolismo , Ligação Proteica , Relação Quantitativa Estrutura-Atividade , Receptores de Neuropeptídeos/química , Receptores de Neuropeptídeos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA