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1.
Cancers (Basel) ; 13(21)2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34771735

RESUMO

BACKGROUND: Metastatic castration-resistant prostate cancer (CRPC) is the leading cause of death among prostate cancer patients. Here, our aim was to ascertain the immune regulatory mechanisms involved in CRPC development and identify potential immunotherapies against CRPC. METHODS: A CRPC model was established using Myc-CaP cells in immune-competent FVB mice following castration. The immune cell profile of the tumor microenvironment (TME) was analyzed during CRPC development. Different immunotherapies were screened in the CRPC tumor model, and their efficacies and underlying mechanisms were investigated in vitro and in vivo. RESULTS: During CRPC development, the proportion of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the TME increased. Among the immunotherapies tested, IFNα was more effective than anti-PD-L1, anti-CTLA-4, anti-4-1BB, IL-2, and IL-9 in reducing Myc-CaP CRPC tumor growth. IFNα reduced the number of G-MDSCs both in vitro during differentiation and in vivo in CRPC mice. Furthermore, IFNα reduced the suppressive function of G-MDSCs on T cell proliferation and activation. CONCLUSION: G-MDSCs are crucial to effective immunotherapy against CRPC. Treatment with IFNα presents a promising therapeutic strategy against CRPC. Besides the direct inhibition of tumor growth and the promotion of T cell priming, IFNα reduces the number and the suppressive function of G-MDSCs and restores T cell activation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34812603

RESUMO

Precisely tuning emission spectra through the component control of mixed halides has been proved to be an efficient method for procuring deep-blue perovskite LEDs (PeLEDs). However, the inferior color instability and lifetime attenuation, originated from vacancy- and trap-mediated mechanisms under an external field, remain an uninterruptedly formidable challenge for the commercial development of PeLEDs. Here, an ultrafast thermodynamics-induced injection enhancement strategy was employed to promote efficient carrier recombination within perovskite quantum dots (QDs), accompanied by less inefficient charge accumulation and trap generation, enabling deep-blue PeLEDs with improved thermal and spectral stability. The resultant PeLEDs feature an external quantum efficiency (EQE) of 3.66%, a max luminance of 2100 cd/m2 at the electroluminescence (EL) of 460 nm, and a halftime of 288 s. This work provides a general platform for promoting the EL performances and a deep insight into unraveling the degradation mechanism of blue PeLEDs.

3.
Nanoscale ; 13(43): 18010-18031, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34718363

RESUMO

All inorganic perovskites CsPbX3 (X = Cl, Br, I), rising stars of optical materials, have shown promising application prospects in optoelectronic and photovoltaic fields. However, some open issues still exist in these perovskites, like poor long-term stability, inevitable intrinsic defects and much nonradiative recombination, which greatly weakens their optical capability and seriously hinders their further development. The metal doping strategy, through the partial substitution of foreign ions for native ions, has gradually become an effective method for significantly enhancing the comprehensive properties of CsPbX3. Whereas some previous studies have reported the impressive properties of metal-doped CsPbX3, there is still a lack of a comprehensive review on the influences of metal doping on CsPbX3. In this review, we aim to provide a systematic review of the latest achievements in metal-doped CsPbX3, which focuses on their synthetic methods and the positive effects of metal doping on structure, optical properties, morphology control, carrier behavior and related optoelectronic and photovoltaic devices. Finally, we put forward a few opportunities and challenges about the further investigation of metal-doped perovskites, which may help researchers explore new research directions.

4.
Front Med (Lausanne) ; 8: 598182, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249954

RESUMO

Background: Inflammation might play a critical role in the pathogenesis and progression of Philadelphia-negative myeloproliferative neoplasms (Ph-MPNs) with elevated inflammatory cytokines in peripheral blood (PB). However, the inflammatory status inside the bone marrow (BM), which is the place of malignancy origin and important microenvironment of neoplasm evolution, has not yet been elucidated. Methods: Inflammatory cytokine profiles in PB and BM of 24 Ph-MPNs patients were measured by a multiplex quantitative inflammation array. Cytokines that correlated between PB and BM were selected and then validated by ELISA in a separate cohort of 52 MPN patients. Furthermore, a panel of cytokines was identified and examined for potential application as non-invasive markers for the diagnosis and prediction of fibrosis progress of MPN subtypes. Results: The levels of G-CSF, I-309, IL-1ß, IL-1ra, IL-12p40, IL-15, IL-16, M-CSF, MIG, PDGF-BB, and TIMP-1 in BM supernatants were significantly higher than those in PB (all p < 0.05). Linear correlations between BM and PB levels were found in 13 cytokines, including BLC, Eotaxin-2, I-309, sICAM-1, IL-15, M-CSF, MIP-1α, MIP-1δ, RANTES, TIMP-1, TIMP-2, sTNFRI, and sTNFRII (all R > 0.4 and p < 0.05). Levels of BLC, Eotaxin-2, M-CSF, and TIMP-1 in PB were significantly different from those in health controls (all p < 0.05). In PB, levels of TIMP-1 and Eotaxin-2 in essential thrombocythemia (ET) group were significantly lower than those in groups of prefibrotic primary myelofibrosis (pre-PMF) [TIMP-1: 685.2 (322.2-1,229) ng/ml vs. 1,369 (1,175-1,497) ng/ml, p = 0.0221; Eotaxin-2: 531.4 (317.9-756.6) pg/ml vs. 942.4 (699.3-1,474) pg/ml, p = 0.0393] and primary myelofibrosis (PMF) [TIMP-1: 685.2 (322.2-1229) ng/ml vs. 1,365 (1,115-1,681) ng/ml, p = 0.0043; Eotaxin-2: 531.4 (317.9-756.6) pg/ml vs. 1,010 (818-1,556) pg/ml, p = 0.0030]. The level of TIMP-1 in myelofibrosis (MF) >1 group was significantly higher than that in MF ≤ 1 group. Conclusion: Abnormal inflammatory status is present in MPN, especially in its BM microenvironment. Consistency between PB and BM levels was found in multiple inflammatory cytokines. Circulating cytokine levels of BLC, M-CSF, Eotaxin-2, and TIMP-1 reflected inflammation inside BM niche, suggesting potential diagnostic value for MPN subtypes and prognostic value for fibrosis progression.

5.
Nature ; 595(7868): 596-599, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34234347

RESUMO

Biomolecular condensates have emerged as an important subcellular organizing principle1. Replication of many viruses, including human respiratory syncytial virus (RSV), occurs in virus-induced compartments called inclusion bodies (IBs) or viroplasm2,3. IBs of negative-strand RNA viruses were recently shown to be biomolecular condensates that form through phase separation4,5. Here we report that the steroidal alkaloid cyclopamine and its chemical analogue A3E inhibit RSV replication by disorganizing and hardening IB condensates. The actions of cyclopamine and A3E were blocked by a point mutation in the RSV transcription factor M2-1. IB disorganization occurred within minutes, which suggests that these molecules directly act on the liquid properties of the IBs. A3E and cyclopamine inhibit RSV in the lungs of infected mice and are condensate-targeting drug-like small molecules that have in vivo activity. Our data show that condensate-hardening drugs may enable the pharmacological modulation of not only many previously undruggable targets in viral replication but also transcription factors at cancer-driving super-enhancers6.

6.
Int J Lab Hematol ; 43(6): 1510-1515, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34288423

RESUMO

INTRODUCTION: The current framework for risk stratification is still insufficient for highly heterogeneous intermediate-risk acute myeloid leukemia (IRC-AML), which lacks specific genomic abnormalities. METHODS: In order to incorporate novel biomarkers to refine current risk stratification strategies for patients with this subtype, we investigated pretreatment telomere length (TL), which is essential for maintaining genomic stability, in 204 adults with de novo AML (non-acute promyelocytic leukemia). RESULTS: We found that TL measured at diagnosis did not decrease with advancing age in 204 patients with AML (R2  = 0.001, P = .695). A multivariate analysis demonstrated that short TL was independently associated with an inferior relapse-free survival (hazard ratio [HR] 3.08, 95% confidence interval [CI] 1.48-6.41, P = .003); event-free survival (HR 2.14, 95% CI 1.12-4.08, P = .021); and overall survival (HR 2.26, 95% CI 1.09-4.67, P = .028) in IRC-AML patients. In addition, IRC-AML patients with short TL also exhibited an increased cumulative incidence of hematologic relapse (HR 2.32, 95% CI 1.08-5.26, P = .032). CONCLUSION: Short TL is an independent prognostic factor for poor prognosis in patients with IRC-AML and may represent a novel mechanism that links genomic stability and disease progression.

7.
J Am Soc Nephrol ; 32(10): 2634-2651, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34261756

RESUMO

BACKGROUND: Rare variants in gene coding regions likely have a greater impact on disease-related phenotypes than common variants through disruption of their encoded protein. We searched for rare variants associated with onset of ESKD in individuals with type 1 diabetes at advanced kidney disease stage. METHODS: Gene-based exome array analyses of 15,449 genes in five large incidence cohorts of individuals with type 1 diabetes and proteinuria were analyzed for survival time to ESKD, testing the top gene in a sixth cohort (n=2372/1115 events all cohorts) and replicating in two retrospective case-control studies (n=1072 cases, 752 controls). Deep resequencing of the top associated gene in five cohorts confirmed the findings. We performed immunohistochemistry and gene expression experiments in human control and diseased cells, and in mouse ischemia reperfusion and aristolochic acid nephropathy models. RESULTS: Protein coding variants in the hydroxysteroid 17-ß dehydrogenase 14 gene (HSD17B14), predicted to affect protein structure, had a net protective effect against development of ESKD at exome-wide significance (n=4196; P value=3.3 × 10-7). The HSD17B14 gene and encoded enzyme were robustly expressed in healthy human kidney, maximally in proximal tubular cells. Paradoxically, gene and protein expression were attenuated in human diabetic proximal tubules and in mouse kidney injury models. Expressed HSD17B14 gene and protein levels remained low without recovery after 21 days in a murine ischemic reperfusion injury model. Decreased gene expression was found in other CKD-associated renal pathologies. CONCLUSIONS: HSD17B14 gene is mechanistically involved in diabetic kidney disease. The encoded sex steroid enzyme is a druggable target, potentially opening a new avenue for therapeutic development.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33946141

RESUMO

The purpose of this study is to verify the influence of internet usage frequency on women's fertility intentions and to examine the mediating effects of gender role attitudes, under the influence of internet usage frequency that affects women's fertility intentions, combined with the specific Chinese cultural context. A cross-sectional secondary data analysis was conducted using a sample of 3113 women of childbearing age in the Chinese General Social Survey in 2017 (CGSS2017). The results of the negative binomial regression model showed that, under the premise of controlling individual characteristic variables, the higher the frequency of internet usage, the lower the fertility intention (p < 0.01). The results of the mediating effect model show that the more frequently women use the internet, the lower their fertility intentions, and the less they agree with Chinese traditional gender roles, which are "men work outside to support the family while women stay at home to take care of the family". These findings have implications in formulating public policies aimed at increasing the fertility rate; that is, it is not enough to increase women's fertility intentions under China's universal two-child policy. Moreover, public policy formulators need to consider gender role attitudes and the influence of the internet as a method for dissemination of information.


Assuntos
Papel de Gênero , Intenção , Atitude , Criança , Estudos Transversais , Feminino , Fertilidade , Humanos , Uso da Internet , Masculino
9.
Molecules ; 26(9)2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33946996

RESUMO

Respiratory syncytial virus (RSV) is a major pathogen that causes severe lower respiratory tract infection in infants, the elderly and the immunocompromised worldwide. At present no approved specific drugs or vaccines are available to treat this pathogen. Recently, several promising candidates targeting RSV entry and multiplication steps are under investigation. However, it is possible to lead to drug resistance under the long-term treatment. Therapeutic combinations constitute an alternative to prevent resistance and reduce antiviral doses. Therefore, we tested in vitro two-drug combinations of fusion inhibitors (GS5806, Ziresovir and BMS433771) and RNA-dependent RNA polymerase complex (RdRp) inhibitors (ALS8176, RSV604, and Cyclopamine). The statistical program MacSynergy II was employed to determine synergism, additivity or antagonism between drugs. From the result, we found that combinations of ALS8176 and Ziresovir or GS5806 exhibit additive effects against RSV in vitro, with interaction volume of 50 µM2% and 31 µM2% at 95% confidence interval, respectively. On the other hand, all combinations between fusion inhibitors showed antagonistic effects against RSV in vitro, with volume of antagonism ranging from -50 µM2 % to -176 µM2 % at 95% confidence interval. Over all, our results suggest the potentially therapeutic combinations in combating RSV in vitro could be considered for further animal and clinical evaluations.


Assuntos
Antivirais/farmacologia , Descoberta de Drogas , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Antivirais/química , Antivirais/uso terapêutico , Descoberta de Drogas/métodos , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Quinazolinas/química , Quinazolinas/farmacologia , Quinazolinas/uso terapêutico , RNA Polimerase Dependente de RNA/antagonistas & inibidores , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Bibliotecas de Moléculas Pequenas , Tiazepinas/química , Tiazepinas/farmacologia , Tiazepinas/uso terapêutico , Inibidores de Proteínas Virais de Fusão/química , Inibidores de Proteínas Virais de Fusão/farmacologia , Inibidores de Proteínas Virais de Fusão/uso terapêutico
10.
J Nanosci Nanotechnol ; 21(10): 5235-5240, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33875112

RESUMO

In Situ transformed carbon fibers/Al2O3 ceramic matrix nanocomposites with Cao-MgO-SiO2 sintering agent were prepared by hot-pressed sintering technology in vacuum. In the sintering process, pre-oxidized polyacrylonitrile fibers (below named as pre-oxidized PAN fibers) were used as the precursors of In Situ transformed carbon fibers. The micro/nanostructure of composites and interface between In Situ transformed carbon fibers and matrix were investigated, as well as the properties of composites. The results showed that the composites could be sintered well at a relatively low temperature of 1650 °C. During the sintering, the precursors, pre-oxidized PAN fibers, were In Situ transformed into carbon fibers, and the In Situ transformed carbon fibers had the graphitelike structure along the fiber axial direction. The carbon atoms arrangement in the surface layer of the fiber was more orderly than the core. A typical diffraction peak of carbon fiber at 26°, which corresponded to the (002) crystal plane, was observed, and the inter-planar spacing was approximately 0.34 nm. The CaO-MgO-SiO2 sintering agent formed MgAl2O4 and CaAl2Si2O8 phases in the interface between In Situ transformed carbon fibers and matrix, therefore improving the interface bonding, and thereby modifying the mechanical properties of the composites.

11.
Ann Palliat Med ; 10(4): 4375-4383, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33752436

RESUMO

BACKGROUND: Depression and anxiety are common psychological conditions in end-stage renal disease (ESRD) patients and contribute to poor quality of life and increased mortality. Six Sigma methodology is a novel method of hospital management. The aim of the present study was to determine whether Six Sigma methodology could reduce the incidence of depression and anxiety in ESRD patients. METHODS: ESRD patients undergoing hemodialysis from March 2018 to February 2020 were enrolled in the study. They were divided into the control group or study group according to whether they received conventional nursing care or Six Sigma methodology, respectively. Data on patients' demographic characteristics were retrospectively collected. The conditions of depression and anxiety were assessed by the Self-Rating Depression Scale and the Self-Rating Anxiety Scale, and the severity of depression and anxiety was defined according to the scores of the scales. Univariable and multivariable logistic regression analyses were used to determine the risk factors of depression and anxiety at discharge in ESRD patients and the effects of Six Sigma methodology on them. RESULTS: A total of 251 patients were retrospectively enrolled in the study, with 112 patients in the control group and 139 patients in the study group. There were no significant differences in the collected demographic characteristics between the two groups. Six Sigma methodology was shown to relieve mild and moderate depression and anxiety at discharge; however, severe depression and anxiety was hardly affected by Six Sigma methodology. The results from multivariable logistic regression analysis identified Six Sigma methodology as an important protective factor of psychological conditions at discharge. Depression and anxiety status at admission and older age are also independent risk factors for anxiety at discharge in ESRD patients. Marital status may also play a role in the incidence of depression. CONCLUSIONS: Six Sigma methodology is significantly useful to reduce the incidence of mild and moderate depression and anxiety at discharge, and should be extended to improve psychological conditions in ESRD patients.


Assuntos
Depressão , Falência Renal Crônica , Idoso , Ansiedade/etiologia , Humanos , Qualidade de Vida , Estudos Retrospectivos , Gestão da Qualidade Total
12.
Ann Transl Med ; 9(3): 222, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708849

RESUMO

Background: Primary immune thrombocytopenia (ITP) is an autoimmune-mediated disorder characterized by a decreased platelet count. Systemic lupus erythematosus (SLE) is also an autoimmune disease in which thrombocytopenia is a common hematologic manifestation. Interleukin (IL)-1 family cytokines are major proinflammatory and immunoregulatory mediators. This study aimed to investigate the role of IL-1 cytokines in patients with ITP and SLE and the potential pathophysiologic mechanism to differentiate SLE-associated thrombocytopenia (SLE-TP) from ITP. Methods: Multiplex cytokine assay and real-time polymerase chain reaction (RT-PCR) were used to measure IL-1 cytokines in 17 newly diagnosed ITP patients, 17 SLE-TP patients, 19 SLE patients without thrombocytopenia (SLE-NTP), and 10 healthy controls. Results: The serum levels of IL-1ß, IL-18, IL-36α, IL-36ß, IL-36γ, and IL-33 were decreased significantly in ITP patients compared with SLE-TP patients, SLE-NTP patients, and healthy controls (P<0.05). While there was no significant difference in the serum level of IL-37 between ITP and SLE-TP patients, there was a positive correlation between the platelet count and IL-37 level in ITP patients. Our data suggested that serum IL-1ß, IL-18, IL-36α, IL-36ß, IL-36γ, IL-33, and IL-37 could be considered biomarkers in the diagnosis of ITP. Conclusions: Serum IL-1ß, IL-18, IL-36α, IL-36ß, IL-36γ, and IL-33 could be considered biomarkers to differentiate SLE-TP from ITP patients.

14.
ACS Nano ; 15(2): 2707-2718, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33543923

RESUMO

The hierarchical ultrathin nanostructures are excellent electrode materials for supercapacitors because of their large surface area and their ability to promote ion and electron transport. Herein, we investigated nine l-amino acids (LAs) as inductive agents to synthesize a series of CoNi-OH/LAs materials for energy storage. With the different amino acids, the assembled CoNi-OH/LAs form a lamellar, flower-shaped, and bulk structure. Among all materials, the ultrathin flowerlike CoNi2-OH/l-asparagine (CoNi2-OH/l-Asn) exhibits an excellent specific capacity of 405.4 mAh g-1 (2608 F g-1) and a 100% retention rate after 3000 cycles. We also assembled asymmetrical supercapacitor CoNi2-OH/l-Asn//N-rGO devices, which demonstrated an energy density of 64.9 Wh kg-1 at 799.9 W kg-1 and superlong cycling stability (82.4% at 10 A g-1) over 5000 cycles.

15.
Biomater Sci ; 9(7): 2658-2669, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33595547

RESUMO

Visualization of cerebrovascular networks is crucial for understanding the pathogenesis of many neurological diseases. Recently developed optical clearing techniques offer opportunities in deep tissue imaging, and have been successfully applied in many research studies. The development of nanotechnology enables the labeling of brain vessels with functionalized micro/nanoparticles embedded with fluorescent dyes. We herein report an efficient method, named LIMPID (Labeled and Interlinked Micro/nanoparticles for Imaging and Delipidation), specific for the precise fluorescence imaging of vascular networks in clearing-treated tissues. This robust vessel labeling technique replaces conventional fluorescence dyes with functionalized polymer micro/nanoparticles that are able to cross-link with polyacrylamide to form dense hydrogels in vessels. LIMPID shows high-robustness during the clearing process without sacrificing fluorescence signals and clearing performance. LIMPID enables three dimension (3D) visualization of elaborate vascular networks in mouse brains and is compatible with other fluorescence-labeling techniques. We have successfully applied this method to acquire cortical vasculature images simultaneously with the neurons or microglia, as well as to evaluate vascular damage in a mouse model of stroke. The LIMPID method provides a novel tool for the precise analysis of vascular dysfunction and vascular diseases.


Assuntos
Sistema Cardiovascular , Imageamento Tridimensional , Animais , Encéfalo/diagnóstico por imagem , Corantes Fluorescentes , Camundongos , Microscopia de Fluorescência
16.
Nat Commun ; 12(1): 483, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33473132

RESUMO

Artificial photosynthesis of H2O2 from H2O and O2, as a spotless method, has aroused widespread interest. Up to date, most photocatalysts still suffer from serious salt-deactivated effects with huge consumption of photogenerated charges, which severely limit their wide application. Herein, by using a phenolic condensation approach, carbon dots, organic dye molecule procyanidins and 4-methoxybenzaldehyde are composed into a metal-free photocatalyst for the photosynthetic production of H2O2 in seawater. This catalyst exhibits high photocatalytic ability to produce H2O2 with the yield of 1776 µmol g-1h-1 (λ ≥ 420 nm; 34.8 mW cm-2) in real seawater, about 4.8 times higher than the pure polymer. Combining with in-situ photoelectrochemical and transient photovoltage analysis, the active site and the catalytic mechanism of this composite catalyst in seawater are also clearly clarified. This work opens up an avenue for a highly efficient and practical, available catalyst for H2O2 photoproduction in real seawater.

17.
Chemosphere ; 269: 128774, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33143890

RESUMO

The effects of water-saving patterns (Semi-dry water-saving, B; Shallow-wet control irrigation, Q; Traditional flooding irrigation, C; and Moistening irrigation, S) on the environmental fate of phenanthrene (Phe) and microbial responses in rhizosphere were investigated in paddy field system. Results showed the rice grain in Q treatment was more high production and safety with less Phe residue (up to 18%-49%) than other treatments, and the residual Phe in soil declined in the order: C (14.17%) > S (13.36%) > B (5.86%)>Q (2.70%), which proves the existence of optimal water conditions for PAHs degradation and rhizosphere effect during rice cultivation. Laccase (LAC) and dioxygenase (C23O) played important roles in Phe degradation, which were significantly positively correlated with Phe dissipation rate in soil (p < 0.01). Moreover, their activities in Q treatment, rhizosphere and subsoil were higher than those in C treatment, non-rhizoshere and upper layer soil. The introduction of Phe and rice into paddy field system decreased the microorganism diversity, and promoted the activities of enzymes and some PAHs degrading bacteria, such as Delftia, Serratia, Enterobacter, Pseudomonas, norank_f_Rhodospirillaceae, norank_f_Nitrosomonadaceae and so on. According to the cluster analysis, redundancy analysis and correlation analysis between bacterial community composition and environmental factors, water-saving patterns markedly impacted the relative abundance and bacterial community structure by the regulating and controlling on environmental conditions of paddy field. The dioxygenase activity, laccase activity, oxidation-reduction potential and conductivity were the main affecting factors on Phe dissipation during growth stage of rice.


Assuntos
Oryza , Fenantrenos , Rizosfera , Solo , Microbiologia do Solo , Água
18.
Breast Cancer ; 28(2): 424-433, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33113070

RESUMO

BACKGROUND: Long non-coding RNA (LncRNA) Breast cancer anti-estrogen resistance 4 (BCAR4) has been shown to participate in the biological progress of various cancers including breast cancer. Genetic Polymorphisms in BCAR4 may have an influence on the progress of breast cancer, but it is rarely studied. METHODS: In our epidemiology study, three tagging SNPs (rs4561483, rs11649623 and rs13334967) in lncRNA BCAR4 were selected for genotyping among 487 breast cancer cases and 489 healthy controls. And quantitative real-time PCR (qRT-PCR) was performed to evaluate the relative mRNA expression of BCAR4 in different genotypes of the significant locus rs13334967. RESULTS: We found that BCAR4 rs13334967 is associated with lower breast cancer risk both in codominant model (AT vs AA, OR 0.632, 95% CI 0.429-0.931, TT vs AA, OR 0.731, 95% CI 0.511-0.990) and dominant model (AT + TT vs AA, OR 0.798, 95% CI 0.571-0.970). The further results of qRT-PCR displayed that carriers with rs13334967 AT, TT genotype have lower BCAR4 mRNA expression compared with AA genotype. CONCLUSION: The research study implied that BCAR4 rs13334967 was correlated with the susceptibility to breast cancer and may impact the mRNA expression of BCAR4. LncRNA BCAR4 may be a potential biomarker and therapeutic target for breast cancer.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Adulto , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , China/epidemiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Loci Gênicos , Predisposição Genética para Doença/epidemiologia , Haplótipos , Humanos , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Estudos Retrospectivos , Fatores de Risco
19.
J Biomater Sci Polym Ed ; 32(2): 229-247, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32966753

RESUMO

There are intensive needs for scaffolds with new designs to meet the diverse requirements of bone repairing. Biodegradable microspheres are highlighted as injectable micro-scaffolds thanks to their advantages in filling irregular defects via a minimally invasive surgery. In this study, microspheres with surface micropores were made via the W1/O/W2 double emulsion method using amphiphilic triblock copolymers (PLLA-PEG-PLLA) composed of poly(L-lactide) (PLLA) and poly(ethylene glycol) (PEG) segments. When the PEG fraction was controlled as 10 wt.%, the microspheres demonstrated higher cell affinity than the smooth-surfaced PLLA microspheres. After being further functionalized with polydopamine coating and apatite deposition, the PLLA-PEG-PLLA microspheres could up-regulate the osteogenic differentiation of bone marrow mesenchymal stromal cells (BMSCs) significantly. Before subcutaneous implantation, bone morphogenetic protein-2 (BMP-2) was adsorbed onto the biomineralized microspheres by taking advantages of the strong affinity of apatite to BMP-2. The resulted microspheres induced ectopic osteogenesis efficiently without causing biocompatibility problems. In summary, this study provided a simple strategy to prepare functionalized microspheres with osteoconductivity and osteoinductivity, which showed great potential in promoting bone regeneration as injectable micro-scaffolds.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Apatitas , Regeneração Óssea , Microesferas , Tecidos Suporte
20.
Curr Probl Cancer ; 45(1): 100638, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32829957

RESUMO

INTRODUCTION: Esophageal cancer is the fourth most common cause of cancer death in China. Patients with esophageal cancer are more likely to suffer from malnutrition. The purpose of this study is to assess nutritional status of patients with esophageal cancer from multiple perspectives and analyze the risk factors. METHODS: A total of 1482 esophageal cancer patients were enrolled in the study. We investigated the Scored Patient Generated Subjective Global Assessment (PG-SGA) scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and laboratory indicators of patients. Unconditional logistic regression analysis was applied to identify the risk factors of nutritional status. RESULTS: PG-SGA (≥4) and NRS-2002 (≥3) showed the incidence of malnutrition were 76% and 50%, respectively. In the patients with PG-SGA score ≥4, the proportion of patients who did not receive any nutritional support was 60%. The incidence of malnutrition in females was significantly higher than that in males. Besides, abnormality rates of Red blood cell (P < 0.001), MAC (P = 0.037), and MAMC (P < 0.001) in males was significantly higher than that in females, while abnormality rates of TSF (P < 0.001) was lower than that in females. After adjusted with the other potential risk factors listed, unconditional logistic regression analysis indicated smoking (odds ratio: 2.868, 95% confidence interval: 1.660-4.954), drinking (OR: 1.726, 95% CI: 1.099-2.712), family history (OR: 1.840, 95% CI: 1.132-2.992), radiotherapy or chemotherapy (OR: 1.594, 95% CI: 1.065-2.387), and pathological stage (OR: 2.263, 95% CI: 1.084-4.726) might be the risk factors of nutritional status, while nutritional support can reduce the risk of malnutrition. CONCLUSION: Effective nutritional risk assessment methods and nutritional intervention measures can be adopted according to the research data to improve quality of life of esophageal cancer patients.

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