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1.
Dis Markers ; 2022: 5653033, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531478

RESUMO

Background: Both malignant pleural effusion (MPE) and tuberculous pleural effusion (TPE) are common etiologies of pleural effusion; the present study was conducted to establish the diagnostic value of platelet parameters in the differential diagnosis of MPE and TPE. Methods: This retrospective study enrolled patients with lung adenocarcinoma-associated MPE and TPE. Platelet parameter data, including platelet count (PLT), mean platelet volume (MPV), plateletcrit (PCT), platelet distribution width (PDW), and platelet-larger cell ratio (P-LCR), were collected. Principal component analysis and multiple logistic regression modelling were carried out to assess the diagnostic value of these platelet parameters. Results: The MPE group and the TPE group enrolled 270 and 433 patients, respectively. Demographic characteristics of patients were more female and higher age in the MPE group. MPV, PDW, and P-LCR were significantly higher in MPE patients, while PLT and PCT were significantly higher in TPE patients. Principal component analysis generated two principal components (PCs) based on above platelet parameters. After adjusting for confounding factors including gender and age, multiple logistic regression showed positive association between PC1 and MPE. Conclusion: Platelet parameters were potential biomarkers in distinguishing lung adenocarcinoma-associated MPE from TPE. A patient with lower PLT and PCT and higher MPV, PDW, and P-LCR was more likely to be diagnosed as the former. Principal component analysis and multiple logistic regression performed well in improving multicollinearity, adjusting confounding factors, and identifying important risk factors for MPE.


Assuntos
Adenocarcinoma de Pulmão , Derrame Pleural Maligno , Derrame Pleural , Tuberculose , Adenocarcinoma de Pulmão/complicações , Adenocarcinoma de Pulmão/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Derrame Pleural/diagnóstico , Derrame Pleural Maligno/diagnóstico , Estudos Retrospectivos
2.
Plants (Basel) ; 11(9)2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35567204

RESUMO

Luculia yunnanensis (Rubiaceae), an evergreen shrub or small tree, is endemic to China and confined to Nujiang Prefecture, Yunnan Province. This plant is of high ornamental value owing to its attractive pink flowers, sweet fragrance, and long flowering period. Due to the influence of climate change and human factors, the distribution range of L. yunnanensis has exhibited a significant shrinking trend, and it has become a vulnerable species that is in urgent need of conservation and rational utilization research. In this study, the flower transcriptome sequencing of L. yunnanensis was conducted using an Illumina HiSeq platform. We designed and developed a series of EST-SSR primers based on the flower transcriptome data of L. yunnanensis. The results showed that 98,389 unigenes were obtained from the L. yunnanensis flower transcriptome, all of which were aligned with sequences in public databases. Nr, Nt, Pfam, KOG/COG, Swiss-Prot, KEGG, and GO annotated 31,859, 13,853, 22,684, 10,947, 21,416, 9722, and 23,390 unigenes, respectively. The MISA (Microsatellite) tool was used to identify SSR loci from all unigenes, and a total of 15,384 SSRs were identified. Repeat motifs were given priority with mononucleotides, dinucleotides, and trinucleotides. The 81 primer pairs were synthesized randomly, of which 44 pairs showed effective amplification. A total of 17 primers showed stable amplification, and rich polymorphism was observed in 6 populations. We concluded via genetic diversity analysis that the average effective number of alleles (Ne), Shannon's information index (I), and polymorphism information content (PIC) were 1.925, 0.837, and 0.403, respectively. In conclusion, 17 EST-SSR primers can be used for subsequent population genetic diversity analysis and molecular-marker-assisted breeding, which is of great significance for formulating resource conservation and utilization strategies for L. yunnanensis.

4.
Virol J ; 19(1): 74, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35459242

RESUMO

BACKGROUND: Selectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity. METHODS: Herein, we simultaneously constructed five "armed" oncolytic viruses (OVs), designated oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19. These OVs delete the ICP34.5 and ICP47 genes with the insertion of transgenes into the deleted ICP34.5 locus. The anti-tumor efficacy in vivo was tested in the syngeneic 4T1 and CT26 tumor-bearing mice model. RESULTS: The OVs showed comparable oncolytic capability in vitro. The combination therapy of oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19 exhibited the highest tumor inhibition efficacy compared with the treatment of single OV or two OVs combination. CONCLUSIONS: The OVs armed with different transgenes combination therapy also named 5-valent oHSV2 (also called cocktail therapy) might be an effective therapeutic strategy for solid tumors.


Assuntos
Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Animais , Vetores Genéticos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Herpesvirus Humano 2/genética , Interleucina-12/genética , Interleucina-15/genética , Interleucina-7/genética , Camundongos , Neoplasias/tratamento farmacológico , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética
5.
Artigo em Inglês | MEDLINE | ID: mdl-35409773

RESUMO

The Middle Route Project of the South-to-North Water Diversion is an artificially independent system that does not connect to other surface waters. Excessive periphyton proliferation causes a series of environmental problems in the canal. In this study, the periphyton community and environmental factors on the left and right banks of the canal in the algal growing area were investigated and sampled six times (June, September, and November of 2019 and 2020). The succession pattern of the attached organism community in the artificial canal was analyzed, and the key factors affecting the algal community were analyzed using RDA and GAM. The results showed that the seasonal variability of the environmental factors was more significant than the spatial variability. A total of 114 taxa of periphytic algae were found, belonging to seven phyla and 69 genera, and mainly composed of Bacillariophyta. Species richness was ranked as Bacillariophyta (60 taxa), Chlorophyta (31 taxa) and Cyanobacteria (15 taxa), and higher in autumn than in summer. The dominant taxa were Cymbella sp., Fragilaria sp., Navicula sp. and Diatoma sp. The abundance of periphytic algal varied from 0.07 × 105 to 8.99 × 105 ind./cm2, with trends similar to that of species richness. The redundancy analysis and generalized additive model showed that water temperature and nutrient concentration were the key factors influencing the structure of the algal community, followed by discharge rate and velocity, which were the determinants of the spatial and temporal patterns of the algal community. In view of the influence of discharge and velocity on the structure of algal communities, it is suggested that ecological scheduling could be used to regulate the structure of the algal community on the canal wall in the operation of later water division projects to ensure the safety of water division.


Assuntos
Cianobactérias , Diatomáceas , China , Monitoramento Ambiental/métodos , Fitoplâncton , Plantas , Estações do Ano , Água
6.
Plant Cell Environ ; 45(6): 1876-1890, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35312080

RESUMO

Nucleotide-binding leucine-rich repeat (NLR) proteins work as crucial intracellular immune receptors. N-terminal domains of NLRs fall into two groups, coiled-coil (CC) and Toll-interleukin 1 receptor domains, which play critical roles in signal transduction and disease resistance. However, the activation mechanisms of NLRs, and how their N-termini function in immune induction, remain largely unknown. Here, we revealed that the CC domain of a rice NLR Pit contributes to self-association. The Pit CC domain possesses three conserved hydrophobic residues that are known to be involved in oligomer formation in two NLRs, barley MLA10 and Arabidopsis RPM1. Interestingly, the function of these residues in Pit differs from that in MLA10 and RPM1. Although three hydrophobic residues are important for Pit-induced disease resistance against rice blast fungus, they do not participate in self-association or binding to downstream signalling molecules. By homology modelling of Pit using the Arabidopsis ZAR1 structure, we tried to clarify the role of three conserved hydrophobic residues and found that they are located in the predicted α2-helix of the Pit CC domain and involved in the plasma membrane localization. Our findings provide novel insights for understanding the mechanisms of NLR activation as well as the relationship between subcellular localization and immune induction.

8.
Microb Ecol ; 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35254501

RESUMO

Anaerobic digestion (AD) has been widely applied for the degradation of organic wastewater due to its advantages of high-load operation and energy recovery. However, some challenges, such as low treatment capacity and instability caused by the accumulation of volatile fatty acids, limit its further application. Here, S. wolfei and G. sulfurreducens were initially co-cultured in the anaerobic anode of bio-electrochemical system for degrading butyric acid. Butyrate degradation characteristics in different conditions were quantitatively described. Moreover, G. sulfurreducens simultaneously strengthened the consumption of H2 and acetic acid via direct interspecies electron transfer, thereby strengthening the degradation of butyric acid via a co-metabolic process. During butyrate degradation, the co-culture of S. wolfei and G. sulfurreducens showed more advantages than that of S. wolfei and methanogens. This present study provides a new perspective of butyrate metabolism, which was independent of methanogens in an AD process.

9.
Infect Genet Evol ; 99: 105249, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35183752

RESUMO

The Gyrovirus genus consists of nonenveloped, icosahedral viruses with small circular single-stranded DNA genomes. Gyroviruses have been detected in diverse hosts, including humans, chickens, rodents, and cats. Two Gyroviruses were detected in canine serum samples using PCR in this study. The results indicated that four serum samples were positive for CAV (0.28%, 2/700) or AGV2 (0.28%, 2/700). Additionally, recombination analysis showed that AGV2 and CAV might have originated from the recombination of viruses similar to those detected in chickens and humans. We detected a total of 14 mutations in CAV VP1 amino acid sequences and identified new mutations at positions 31, 388, 390, 399, and 421 for the first time. The identification of T390C, C912T, T1230C, and T1297C mutations in AGV2 VP1, R93C mutations in AGV2 VP2, and R58C mutations AGV2 VP3 indicated that the differences might be related to a transboundary movement among hosts, which requires further elucidation. To the best of our knowledge, this study is the first report of an AGV2-infected dog in China, suggesting that the cross-species transmission of viruses with circular single-stranded DNA genomes is a public health concern.


Assuntos
Vírus da Anemia da Galinha , Infecções por Circoviridae , Gyrovirus , Doenças das Aves Domésticas , Animais , Vírus da Anemia da Galinha/genética , Galinhas , Infecções por Circoviridae/veterinária , DNA de Cadeia Simples , Cães , Gyrovirus/genética
10.
Epidemiol Infect ; 150: e25, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35193716

RESUMO

The association between the ABO blood group and the risk of malaria during pregnancy has not been clearly established. The present study summarised relevant knowledge and reassessed the association through meta-analysis. Articles in MEDICINE and PubMed published before 30 November 2021 were searched. Five studies satisfied the inclusion criteria and were enrolled in the meta-analysis. It was shown that primiparae with different ABO blood group, multiparae with blood group A and non-A, AB and non-AB had a comparable risk of malaria. However, multiparae with blood group B had a significantly higher risk than non-B group [odds ratio (OR) = 1.23, 95% confidence interval (CI) was 1.01 to 1.50, P = 0.04], while multiparae with blood group O had a significantly lower risk than non-O group (OR = 0.78, 95% CI was 0.63 to 0.97, P = 0.03). Therefore, the ABO blood group may not result in a different risk of malaria in primiparae. Blood group B is potentially a risk factor while blood group O is a protective factor for multiparae.


Assuntos
Sistema ABO de Grupos Sanguíneos/fisiologia , Malária , Complicações Infecciosas na Gravidez , Feminino , Humanos , Malária/sangue , Malária/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/epidemiologia , Fatores de Risco
11.
Plants (Basel) ; 11(4)2022 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-35214804

RESUMO

Auxin-responsive genes AUX/IAA are important during plant growth and development, but there are few relevant reports in peanut. In this study, 44 AhIAA genes were identified from cultivated peanut, of which 31 genes were expressed in seed at varying degrees. AhIAA-3A, AhIAA-16A and AhIAA-15B were up-regulated, while AhIAA-11A, AhIAA-5B and AhIAA-14B were down-regulated with seed development and maturation. The expression patterns of seven genes, AhIAA-1A, AhIAA-4A, AhIAA-10A, AhIAA-20A, AhIAA-1B, AhIAA-4B and AhIAA-19B, were consistent with the change trend of auxin, and expression in late-maturing variety LM was significantly higher than that in early-maturing EM. Furthermore, allelic polymorphism analysis of AhIAA-1A and AhIAA-1B, which were specifically expressed in seeds, showed that three SNP loci in 3'UTR of AhIAA-1A could effectively distinguish the EM- and LM- type germplasm, providing a basis for breeding markers development. Our results offered a comprehensive understanding of Aux/IAA genes in peanut and provided valuable clues for further investigation of the auxin signal transduction pathway and auxin regulation mechanism in peanut.

13.
Chemosphere ; 297: 134063, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35192855

RESUMO

Organochlorine pesticides, especially lindane and endosulfan, have been demonstrated to be both biodegradable and frequently coexistent, but their inhibitory effect has never been studied. In this study, we investigated the effect of endosulfan coexistence on lindane degradation to a lindane-degrading isolate, Novosphingobium barchaimii strain LL02, and mixed enrichment cultures from two different inocula. Our results of the lindane degradation batch experiments demonstrated that endosulfan concentration above 20 mg L-1 causes significant inhibition to the lindane degradation efficiency of the strain LL02. Besides, the acidic conditions at pH 5.0 to 6.0 further decreased its lindane degradation rate constants by 57% compared to the neutral and alkaline conditions. For the mixed microbial cultures, the lindane degradation efficiency in the lindane/endosulfan co-contamination conditions decreased by 35.7%-50.7% compared to the lindane alone conditions. From our 16S rRNA amplicon sequencing results through the PacBio platform, most of the predominant bacteria in the lindane-enriched cultures were depressed in the lindane/endosulfan-enriched cultures. Moreover, bacteria of Burkholderia australis, Chujaibacter soli, Flavitalea flava, and one Rhodanobacteraceae bacterium were relatively highly abundant in the co-contamination enrichment cultures, suggesting their potential for lindane degradation under the endosulfan stress. Our results demonstrated that endosulfan coexistence causes inhibitory impacts on lindane biodegradation toward both lindane-degrading bacteria and mixed microbial cultures. The coexistence of multiple organochlorine pesticides on the biodegradation efficiencies should be carefully considered when applying bioremediation to remove organochlorine pesticide contamination.


Assuntos
Hidrocarbonetos Clorados , Inseticidas , Praguicidas , Sphingomonadaceae , Biodegradação Ambiental , Endossulfano/análise , Hexaclorocicloexano/análise , Inseticidas/metabolismo , Praguicidas/toxicidade , RNA Ribossômico 16S/genética , Microbiologia do Solo , Sphingomonadaceae/metabolismo
14.
Mol Ther Nucleic Acids ; 27: 200-210, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-34976438

RESUMO

Differentiation of preadipocytes into functional adipocytes could be a major target for repressing obesity-induced insulin resistance (IR). However, the molecular mechanisms involved in adipogenesis and the development of IR are unclear. We report, for the first time, that miR-574-5p, a novel miRNA, promotes adipogenesis to suppress IR. An increase in the level of miR-574-5p significantly induced the differentiation of preadipocytes into mature adipocytes. Conversely, reduction of miR-574-5p levels blocked the differentiation of preadipocytes in vitro. In a dual-luciferase reporter assay, it was shown that homeobox A5 (HOXA5) promoted the transcription of miR-574-5p to induce the differentiation of preadipocytes. Hdac9, a direct downstream target of miR-574-5p, was involved in the regulation of adipocyte differentiation. The overexpression of miR-574-5p also promoted adipogenesis in subcutaneous fat to alleviate IR in high-fat-diet-fed mice. Additionally, miR-574-5p expression was significantly higher in the subcutaneous adipose tissue of obese patients without type 2 diabetes than in those with type 2 diabetes. There was an increase in HOXA5 expression and a decrease in histone deacetylase 9 (HDAC9) expression in the subcutaneous fat of obese patients without type 2 diabetes. These results suggest that miR-574-5p may be a potential therapeutic target for combating obesity-related IR.

15.
Int Ophthalmol ; 42(2): 509-523, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34633608

RESUMO

BACKGROUND: It has been gradually recognized that circular RNAs (circRNAs) are important modulators in multiple malignancies. Here, we analyzed the function of circ_0075804 and explored its associated mechanism in regulating retinoblastoma (RB) progression. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were utilized to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell counting kit-8 (CCK8) assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion abilities were analyzed by wound healing assay and transwell invasion assay. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were applied to verify intermolecular target relations. Xenograft tumor model was used to analyze the role of circ_0075804 in tumor growth in vivo. RESULTS: Circ_0075804 expression was markedly up-regulated in RB tissues and cell lines. Circ_0075804 knockdown restrained the proliferation, migration and invasion whereas promoted the apoptosis of RB cells. Circ_0075804 acted as a molecular sponge for microRNA-138-5p (miR-138-5p), and circ_0075804 silencing-induced effects were partly reversed by miR-138-5p knockdown in RB cells. MiR-138-5p interacted with the 3' untranslated region (3'UTR) of paternally expressed 10 (PEG10). Circ_0075804 positively regulated PEG10 level by sponging miR-138-5p in RB cells. PEG10 overexpression largely overturned miR-138-5p overexpression-mediated effects in RB cells. Circ_0075804 knockdown blocked xenograft tumor growth in vivo. CONCLUSION: Circ_0075804 promoted RB progression via miR-138-5p-dependent regulation of PEG10, which provided new insight in RB therapy.


Assuntos
Proteínas Reguladoras de Apoptose , MicroRNAs , RNA Circular , Neoplasias da Retina , Retinoblastoma , Proteínas Reguladoras de Apoptose/metabolismo , Proliferação de Células , Proteínas de Ligação a DNA/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Proteínas de Ligação a RNA/metabolismo , Neoplasias da Retina/genética , Neoplasias da Retina/patologia , Retinoblastoma/genética , Retinoblastoma/patologia
16.
Am J Med Genet A ; 188(2): 540-547, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34741396

RESUMO

This study aimed to identify the disease-causing gene of three Chinese families with glaucoma. Whole exome sequencing was performed on the probands and detected three different variants (c.405C>A (p.Cys135Ter), c.851G>T (p.Ser284Ile), and c.392C>T (p.Ser131Leu)) in FOXC1 as a causative gene of glaucoma, and Sanger sequencing was performed for verification and cosegregation analysis. Three in silico tools all predicted these two missense variants to be probably disease-causing. Western blot analysis, immunofluorescence, and dual-luciferase assay were further used to evaluate the effect of FOXC1 missense variants, and demonstrated that the two variants resulted in decreased transactivation activity of FOXC1 although the variants had no effect on the protein amount and the nucleus subcellar localization of FOXC1 compared with the wild type, which implies that both of two variants may be probably pathogenic. In this study, we reported two novel FOXC1 variants as well as a reported variant and the phenotypes associated to these variants, which expands the spectrum and relevant phenotypes of FOXC1 variants. Additionally, the functional analysis of FOXC1 variants provides further insight into the possible pathogenesis of anterior segment anomaly related to FOXC1.


Assuntos
Anormalidades do Olho , Glaucoma , Segmento Anterior do Olho/anormalidades , China/epidemiologia , Anormalidades do Olho/genética , Fatores de Transcrição Forkhead/genética , Glaucoma/genética , Humanos , Mutação de Sentido Incorreto/genética
17.
Transl Res ; 240: 64-86, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34757194

RESUMO

Oncolytic virotherapy is a new and safe therapeutic strategy for cancer treatment. In our previous study, a new type of oncolytic herpes simplex virus type 2 (oHSV2) was constructed. Following the completion of a preclinical study, oHSV2 has now entered into clinical trials for the treatment of melanoma and other solid tumors (NCT03866525). Oncolytic viruses (OVs) are generally able to directly destroy tumor cells and stimulate the immune system to fight tumors. Natural killer (NK) cells are important components of the innate immune system and critical players against tumor cells. But the detailed interactions between oncolytic viruses and NK cells and these interaction effects on the antitumor immune response remain to be elucidated. In particular, the functions of activating surface receptors and checkpoint inhibitors on oHSV2-treated NK cells and tumor cells are still unknown. In this study, we found that UV-oHSV2 potently activates human peripheral blood mononuclear cells, leading to increased antitumor activity in vitro and in vivo. Further investigation indicated that UV-oHSV2-stimulated NK cells release IFN-γ via Toll-like receptor 2 (TLR2)/NF-κB signaling pathway and exert antitumor activity via TLR2. We found for the first time that the expression of a pair of checkpoint molecules, NKG2A (on NK cells) and HLA-E (on tumor cells), is upregulated by UV-oHSV2 stimulation. Anti-NKG2A and anti-HLA-E treatment could further enhance the antitumor effects of UV-oHSV2-stimulated NK92 cells in vitro and in vivo. As our oHSV2 clinical trial is ongoing, we expect that the combination therapy of oncolytic virus oHSV2 and anti-NKG2A/anti-HLA-E antibodies may have synergistic antitumor effects in our future clinical trials.


Assuntos
Herpesvirus Humano 2/efeitos da radiação , Inibidores de Checkpoint Imunológico/farmacologia , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Neoplasias/terapia , Vírus Oncolíticos/efeitos da radiação , Raios Ultravioleta , Inativação de Vírus/efeitos da radiação , Animais , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Citotoxicidade Imunológica/efeitos dos fármacos , Feminino , Herpesvirus Humano 2/efeitos dos fármacos , Antígenos de Histocompatibilidade Classe I/metabolismo , Humanos , Interferon gama/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Subfamília C de Receptores Semelhantes a Lectina de Células NK/metabolismo , Vírus Oncolíticos/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Receptor 2 Toll-Like/metabolismo , Inativação de Vírus/efeitos dos fármacos
18.
Int J Infect Dis ; 114: 175-177, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34758390

RESUMO

The global incidence of lung fluke disease is low, and the infection is a rare cause of pleural effusion in adults. This article reports a case of exudative pleural effusion accompanied by eosinophilia in a 19-year-old male which was finally proven to be caused by lung fluke infection through antibody testing. This case highlights that lung fluke infection is an easily overlooked cause of pleural effusion. Eosinophilia is a potential marker of infection, and serological tests could further confirm the diagnosis.


Assuntos
Eosinofilia , Derrame Pleural , Trematódeos , Adulto , Animais , Exsudatos e Transudatos , Humanos , Pulmão , Masculino , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/etiologia , Adulto Jovem
19.
Eur J Med Chem ; 227: 113968, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34752954

RESUMO

ß-Amyloid (Aß) plaques and Tau tangles are cognitive impairment markers vital for diagnosing and preventing Alzheimer's disease (AD). To systematically explore the relationship between the number or position of nitrogen atoms and their optical properties and biological properties, five series of new N, O-coordinated organo-difluoroboron probes were introduced as binding scaffolds for Aß plaques and Tau tangles. These probes exhibited suitable optical properties for near-infrared (NIR) imaging. Probe 4PmNO-2 (4-((1E,3E)-4-(1,1-difluoro-1H-1λ4,9λ4-pyrimido[1,6-c][1,3,5,2]oxadiazaborinin-3-yl)buta-1,3-dien-1-yl)-N,N-dimethylaniline) displayed the excellent emission maximum (716 nm in PBS), a high quantum yield (61.4% in CH2Cl2), and a high affinity for synthetic Aß1-42 (Kd = 23.64 ± 1.08 nM) and Tau (K18) aggregates (Kd = 26.38 ± 1.29 nM), as well as for native Aß plaques and NFTs in the brain tissue from AD patients. 4PmNO-2, with significantly enhanced fluorescence (Aß1-42, 136 fold; Tau (K18), 96 fold) and the highest initial brain uptake (11.57% ID/g at 2 min) in normal ICR mice, was evaluated further. In vivo NIR fluorescent imaging studies in living Aß and Tau transgenic mice revealed that it could differentiate healthy and diseased animals. Further ex vivo fluorescent staining studies showed that 4PmNO-2 specifically bound to Aß plaques and Tau tangles in transgenic mice. In summary, the probe 4PmNO-2 may be a useful near-infrared fluorescence (NIRF) probe for AD biomarkers.


Assuntos
Peptídeos beta-Amiloides/análise , Benzamidas/química , Corantes Fluorescentes/química , Proteínas tau/análise , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Benzamidas/síntese química , Corantes Fluorescentes/síntese química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Estrutura Molecular , Proteínas tau/metabolismo
20.
Radiat Oncol ; 16(1): 233, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34865626

RESUMO

BACKGROUND: The study aimed to compare the efficacy of osimertinib plus cranial radiotherapy (RT) with osimertinib alone in advanced non-small-cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations and brain metastases (BMs). METHODS: The clinical data of advanced NSCLC patients with BMs who received osimertinib were retrospectively collected. The patients were assigned to one of the two groups according to the therapeutic modality used: the osimertinib monotherapy group or the osimertinib plus RT group. RESULTS: This was a retrospective study and 61 patients were included from December 2015 to August 2020. Forty patients received osimertinib monotherapy, and twenty-one patients received osimertinib plus RT. Radiotherapy included whole-brain radiation therapy (WBRT, n = 14), WBRT with simultaneous integrated boost (WBRT-SIB, n = 5) and stereotactic radiosurgery (SRS, n = 2). The median number of prior systemic therapies in the two groups was one. Intracranial and systemic ORR and DCR were not significantly different between the two groups. No difference in iPFS was observed between the two groups (median iPFS: 16.67 vs. 13.50 months, P = 0.836). The median OS was 29.20 months in the osimertinib plus RT group compared with 26.13 months in the osimertinib group (HR = 0.895, P = 0.826). In the L858R mutational subgroup of 31 patients, the osimertinib plus RT group had a longer OS (P = 0.046). In the exon 19 deletion mutational subgroup of 30 patients, OS in the osimertinib alone group was longer than that in the osimertinib plus RT group (P = 0.011). The incidence of any-grade adverse events was not significantly different between the osimertinib plus RT group and the osimertinib alone group (47.6% vs. 32.5%, P = 0.762). However, six patients (28.5%) experienced leukoencephalopathy in the osimertinib plus RT group, and 50% (3/6) of the leukoencephalopathy was greater than or equal to grade 3. CONCLUSION: The therapeutic effect of osimertinib with RT was similar to that of osimertinib alone in EGFR-positive NSCLC patients with BM. However, for patients with the L858R mutation, osimertinib plus RT could provide more benefit than osimertinib alone.


Assuntos
Acrilamidas/uso terapêutico , Compostos de Anilina/uso terapêutico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/patologia , Quimiorradioterapia/mortalidade , Irradiação Craniana/mortalidade , Mutação , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
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