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1.
BMC Genomics ; 25(1): 283, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500027

RESUMO

MYB transcription factors play an extremely important regulatory role in plant responses to stress and anthocyanin synthesis. Cloning of potato StMYB-related genes can provide a theoretical basis for the genetic improvement of pigmented potatoes. In this study, two MYB transcription factors, StMYB113 and StMYB308, possibly related to anthocyanin synthesis, were screened under low-temperature conditions based on the low-temperature-responsive potato StMYB genes family analysis obtained by transcriptome sequencing. By analyzed the protein properties and promoters of StMYB113 and StMYB308 and their relative expression levels at different low-temperature treatment periods, it is speculated that StMYB113 and StMYB308 can be expressed in response to low temperature and can promote anthocyanin synthesis. The overexpression vectors of StMYB113 and StMYB308 were constructed for transient transformation tobacco. Color changes were observed, and the expression levels of the structural genes of tobacco anthocyanin synthesis were determined. The results showed that StMYB113 lacking the complete MYB domain could not promote the accumulation of tobacco anthocyanins, while StMYB308 could significantly promote the accumulation involved in tobacco anthocyanins. This study provides a theoretical reference for further study of the mechanism of StMYB113 and StMYB308 transcription factors in potato anthocyanin synthesis.


Assuntos
Solanum tuberosum , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Antocianinas , Temperatura , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética
2.
BMC Plant Biol ; 24(1): 274, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605295

RESUMO

Temperature is one of the important environmental factors affecting plant growth, yield and quality. Moreover, appropriately low temperature is also beneficial for tuber coloration. The red potato variety Jianchuanhong, whose tuber color is susceptible to temperature, and the purple potato variety Huaxinyangyu, whose tuber color is stable, were used as experimental materials and subjected to 20 °C (control check), 15 °C and 10 °C treatments during the whole growth period. The effects of temperature treatment on the phenotype, the expression levels of structural genes related to anthocyanins and the correlations of each indicator were analyzed. The results showed that treatment at 10 °C significantly inhibited the potato plant height, and the chlorophyll content and photosynthetic parameters in the leaves were reduced, and the enzyme activities of SOD and POD were significantly increased, all indicating that the leaves were damaged. Treatment at 10 °C also affected the tuberization of Huaxinyangyu and reduced the tuberization and coloring of Jianchuanhong, while treatment at 15 °C significantly increased the stem diameter, root-to-shoot ratio, yield and content of secondary metabolites, especially anthocyanins. Similarly, the expression of structural genes were enhanced in two pigmented potatoes under low-temperature treatment conditions. In short, proper low temperature can not only increase yield but also enhance secondary metabolites production. Previous studies have not focused on the effects of appropriate low-temperature treatment during the whole growth period of potato on the changes in metabolites during tuber growth and development, these results can provide a theoretical basis and technical guidance for the selection of pigmented potatoes with better nutritional quality planting environment and the formulation of cultivation measures.


Assuntos
Solanum tuberosum , Temperatura , Solanum tuberosum/metabolismo , Antocianinas/metabolismo , Temperatura Baixa , Fotossíntese , Tubérculos/genética
3.
BMC Psychiatry ; 24(1): 232, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539137

RESUMO

BACKGROUND: Neurodevelopmental disorders (NDDs), such as Attention-Deficit/Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Tourette Syndrome (TS), have been extensively studied for their multifaceted impacts on social and emotional well-being. Recently, there has been growing interest in their potential relationship with fracture risks in adulthood. This study aims to explore the associations between these disorders and fracture rates, in order to facilitate better prevention and treatment. METHODS: Employing a novel approach, this study utilized Mendelian randomization (MR) analysis to investigate the complex interplay between ADHD, ASD, TS, and fractures. The MR framework, leveraging extensive genomic datasets, facilitated a systematic examination of potential causal relationships and genetic predispositions. RESULTS: The findings unveil intriguing bidirectional causal links between ADHD, ASD, and specific types of fractures. Notably, ADHD is identified as a risk factor for fractures, with pronounced associations in various anatomical regions, including the skull, trunk, and lower limbs. Conversely, individuals with specific fractures, notably those affecting the femur and lumbar spine, exhibit an increased genetic predisposition to ADHD and ASD. In this research, no correlation was found between TS and fractures, or osteoporosis.These results provide a genetic perspective on the complex relationships between NDDs and fractures, emphasizing the importance of early diagnosis, intervention, and a holistic approach to healthcare. CONCLUSION: This research sheds new light on the intricate connections between NDDs and fractures, offering valuable insights into potential risk factors and causal links. The bidirectional causal relationships between ADHD, ASD, and specific fractures highlight the need for comprehensive clinical approaches that consider both NDDs and physical well-being.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Fraturas Ósseas , Transtornos do Neurodesenvolvimento , Osteoporose , Síndrome de Tourette , Humanos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/psicologia , Análise da Randomização Mendeliana , Transtornos do Neurodesenvolvimento/genética , Transtorno do Deficit de Atenção com Hiperatividade/genética , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Osteoporose/genética , Fraturas Ósseas/genética , Predisposição Genética para Doença
4.
Small ; 19(34): e2300801, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37072877

RESUMO

Sub-10 nm nanoparticles are known to exhibit extraordinary size-dependent properties for wide applications. Many approaches have been developed for synthesizing sub-10 nm inorganic nanoparticles, but the fabrication of sub-10 nm polymeric nanoparticles is still challenging. Here, a scalable, spontaneous confined nanoemulsification strategy that produces uniform sub-10 nm nanodroplets for template synthesis of sub-10 nm polymeric nanoparticles is proposed. This strategy introduces a high-concentration interfacial reaction to create overpopulated surfactants that are insoluble at the droplet surface. These overpopulated surfactants act as barriers, resulting in highly accumulated surfactants inside the droplet via a confined reaction. These surfactants exhibit significantly changed packing geometry, solubility, and interfacial activity to enhance the molecular-level impact on interfacial instability for creating sub-10 nm nanoemulsions via self-burst nanoemulsification. Using the nanodroplets as templates, the fabrication of uniform sub-10 nm polymeric nanoparticles, as small as 3.5 nm, made from biocompatible polymers and capable of efficient drug encapsulation is demonstrated. This work opens up brand-new opportunities to easily create sub-10 nm nanoemulsions and advanced ultrasmall functional nanoparticles.

5.
Soft Matter ; 19(24): 4526-4535, 2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37306079

RESUMO

Collective cell migration plays a vital role in various physiological and pathological processes, such as embryonic development and tumor metastasis. Recent experiments have shown that different from isolated cells, the moving cell groups exhibit rich emerging motion modes in response to external geometrical constraints. By considering the interactions between neighboring cells and internal biomechanical processes of each cell (i.e., cell sociality and cell individuality), we develop an active vertex model to investigate the emerging modes of collective cell migration in microchannels. Single-cell polarization is propelled by continuous protrusion of its leading edge and retraction of the rear. We here introduce the contribution of continuous protrusions and retractions of lamellipodia, named the protrusion alignment mechanism, to the cell individuality. Using the present model, it is found that altering the width of channels can trigger the motion mode transitions of cell groups. When cells move in narrow channels, the protrusion alignment mechanism brings neighboring groups of coordinated cells into conflicts and in turn induces the caterpillar-like motion mode. As the channel width increases, local swirls spanning the channel in width first appear as long as the channel width is smaller than the intrinsic correlation length of cell groups. Then, only local swirls with a maximum diameter of the intrinsic correlation length are formed, when the channel is sufficiently wider. These rich dynamical modes of collective cells originate from the competition between cell individuality and sociality. In addition, the velocity of the cell sheet invading free spaces varies with the channel size-induced transitions of migration modes. Our predictions are in broad agreement with many experiments and may shed light on the spatiotemporal dynamics of active matter.


Assuntos
Movimento Celular , Movimento Celular/fisiologia , Movimento (Física)
6.
J Org Chem ; 88(1): 384-394, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36516991

RESUMO

The development of a convergent route to the NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. The synthesis relies on a key Miyaura borylation and a tandem Suzuki-Miyaura coupling between an iodoimidazole and an o-aminochloroarene, followed by acid-mediated cyclization to afford the aminoquinoline core. The subsequent Boc cleavage and regioselective acylation afford the target compound. Two routes to the iodoimidazole intermediate are presented, along with the synthesis of the o-aminochloroarene via Negishi coupling. The convergent six-step route leads to an 80% reduction in process mass intensity compared to the linear enabling synthesis.


Assuntos
Imidazóis , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ciclização , Acilação
7.
BMC Neurol ; 23(1): 447, 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38114953

RESUMO

BACKGROUND: Timely recognition of futile recanalization might enable a prompt response and an improved outcome in post-thrombectomy patients. This study aims to evaluate whether postoperative blood glucose increase (BGI) could act as an indicator of futile recanalization in patients receiving a successful thrombectomy. METHODS: This is a single-center, retrospective analysis of patients with anterior circulation large-vessel occlusion and successful thrombectomy between February 2019 and June 2022. BGI was defined as a higher level of blood glucose at the first postoperative morning than at admission. Futile recanalization was defined as patients with a modified Rankin Scale score of 3-6 at 90 days after onset. Multivariable binary logistic regression was used to assess the association of BGI with futile recanalization. RESULTS: A total of 276 patients were enrolled, amongst which 120 patients (43.5%) had BGI. Futile recanalization was more prevalent among patients with BGI compared to those without (70.0 vs. 49.4%, P = 0.001). After adjusting for potential confounders, BGI was associated with a higher likelihood of futile recanalization (adjusted OR: 2.97, 95%CI: 1.50-5.86, P = 0.002). This association was consistently observed regardless of diabetes history, occlusion site, time from symptom onset to groin puncture, or reperfusion status. CONCLUSION: Our findings support BGI serving as an indicator of futile recanalization in patients with anterior circulation large-vessel occlusion and successful thrombectomy.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Glicemia , Trombectomia/efeitos adversos , Isquemia Encefálica/etiologia , Procedimentos Endovasculares/efeitos adversos
8.
Acta Radiol ; 64(8): 2446-2454, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37551019

RESUMO

BACKGROUND: The optimal treatment for some symptomatic, benign osteopathy lesions is yet to be identified. PURPOSE: To investigate the clinical efficiency of cementoplasty in managing symptomatic, benign osteopathy. MATERIAL AND METHODS: Between June 2006 and January 2020, we retrospectively enrolled 31 patients (10 men, 21 women; mean age = 46.5 ± 16.6 years; age range = 20-85 years), accounting for 34 treatment sites, who underwent percutaneous osteoplasty (14 treatment sites) and percutaneous vertebroplasty (20 treatment sites) with digital subtraction angiography (DSA) or DSA combined with computed tomography (CT). All the participants experienced different degrees of clinical symptoms with benign osteopathy lesions. The technical success of the procedure and occurrence of complications were recorded. Follow-up examinations were conducted to assess the treatment outcome using the MacNab criteria. RESULTS: All the participants had a diagnosis of benign osteopathy lesions before or after the cementoplasty. Surgery was successfully completed in all patients. Cement distributions were diffuse and homogeneous, with the complication of cement leakage occurring in 17.6% (6 of 34) of the lesions. The leakage occurred in the intervertebral disc (n = 1), the intra-articular space (n = 1), and the surrounding soft tissue (n = 4). Analysis of the treatment outcome using the MacNab criteria revealed that all patients showed improvement in their clinical symptoms to some extent and in the quality of life. CONCLUSION: Cementoplasty is an effective treatment for symptomatic, benign osteopathy, with the advantage of favorable clinical outcomes, and low complication rate.


Assuntos
Doenças Ósseas , Cementoplastia , Masculino , Humanos , Feminino , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Qualidade de Vida , Cementoplastia/métodos , Cimentos Ósseos/uso terapêutico , Resultado do Tratamento
9.
Biophys J ; 121(10): 1931-1939, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35398343

RESUMO

Collective cell migration occurs in a wide range of physiological and pathological processes, such as wound healing and tumor metastasis. Experiments showed that many types of cells confined in circular islands can perform coherent angular rotation, yet the underlying mechanisms remain unclear. Here we propose a biomechanical model, including the membrane, microtubules, and nucleus, to study the spatiotemporal evolutions of small cell clusters in confined space. We show that cells can spontaneously transfer from "radial pattern" to "chiral pattern" due to fluctuations. For a pair of cells with identical chiral orientation, the cluster rotates in the opposite direction of the chiral orientation, and the fluctuations can reverse the cluster's rotational direction. Interestingly, during the persistent rotation, each cell rotates around its own centroid while it is revolving around the island center and shows a constant side to the island center, as tidal locking in astronomy. Furthermore, for a few more cells, coherent angular rotation also appears, and the emergence of a central cell can accelerate the cluster rotation. These findings shed light on collective cell migration in life processes and help to understand the spatiotemporal dynamics of active matter.


Assuntos
Microtúbulos , Modelos Biológicos , Movimento Celular/fisiologia , Rotação , Cicatrização
10.
J Cell Mol Med ; 25(17): 8312-8328, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34363438

RESUMO

The tumour-suppressive role of LINC00472 has been extensively reported in various human cancers such as lung, colon and ovarian cancers, yet its function in pancreatic cancer remains unidentified. Here, the current research aimed to explore the role and regulatory axis mediated by LINC00472 in the progression of pancreatic cancer. RT-qPCR was adopted to determine LINC00472 expression in the harvested pancreatic cancer tissues and adjacent normal tissues. Loss-of-function and gain-of-function experiments were performed to examine the effects of LINC00472 on proliferation and apoptosis in vitro and tumorigenesis in vivo. Immunoblotting was performed to detect the expression of several proliferation and apoptosis-related proteins. Bioinformatic analysis, dual-luciferase reporter assay and RNA pull-down were conducted to profile the relationships between LINC00472 and miR-23a-3p, between miR-23a-3p and FOXO3 and between FOXO3 and BID. The LINC00472 expression was down-regulated by ZEB1 in the pancreatic cancer cells and tissues. LINC00472 could competitively bind to miR-23a-3p to enhance the expression of FOXO3, which consequently could promote the BID expression, thereby suppressing proliferation and promoting the apoptosis of pancreatic cancer cells. Meanwhile, the inhibitory role of LINC00472 in tumorigenesis was validated in vivo, and the LINC00472-mediated miR-23a-3p/FOXO3/BID axis was also demonstrated in the nude mouse tumour formation model. The study substantiated the antitumour activity of LINC00472 in pancreatic cancer and proposed a regulatory axis in which LINC00472 competitively binds to miR-23a-3p to enhance the FOXO3 expression and promote BID expression. Consequently, these findings provide theoretical basis for developing potential targets for the treatment of pancreatic cancer.


Assuntos
Carcinogênese/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/metabolismo , RNA Longo não Codificante/fisiologia , Homeobox 1 de Ligação a E-box em Dedo de Zinco/fisiologia , Animais , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/metabolismo , Pessoa de Meia-Idade
11.
Eur Radiol ; 31(1): 411-422, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32749583

RESUMO

OBJECTIVE: To construct a MRI radiomics model and help radiologists to improve the assessments of pelvic lymph node metastasis (PLNM) in endometrial cancer (EC) preoperatively. METHODS: During January 2014 and May 2019, 622 EC patients (age 56.6 ± 8.8 years; range 27-85 years) from five different centers (A to E) were divided into training set, validation set 1 (351 cases from center A), and validation set 2 (271 cases from centers B-E). The radiomics features were extracted basing on T2WI, DWI, ADC, and CE-T1WI images, and most related radiomics features were selected using the random forest classifier to build a radiomics model. The ROC curve was used to evaluate the performance of training set and validation sets, radiologists based on MRI findings alone, and with the aid of the radiomics model. The clinical decisive curve (CDC), net reclassification index (NRI), and total integrated discrimination index (IDI) were used to assess the clinical benefit of using the radiomics model. RESULTS: The AUC values were 0.935 for the training set, 0.909 and 0.885 for validation sets 1 and 2, 0.623 and 0.643 for the radiologists 1 and 2 alone, and 0.814 and 0.842 for the radiomics-aided radiologists 1 and 2, respectively. The AUC, CDC, NRI, and IDI showed higher diagnostic performance and clinical net benefits for the radiomics-aided radiologists than for the radiologists alone. CONCLUSIONS: The MRI-based radiomics model could be used to assess the status of pelvic lymph node and help radiologists improve their performance in predicting PLNM in EC. KEY POINTS: • A total of 358 radiomics features were extracted. The 37 most important features were selected using the random forest classifier. • The reclassification measures of discrimination confirmed that the radiomics-aided radiologists performed better than the radiologists alone, with an NRI of 1.26 and an IDI of 0.21 for radiologist 1 and an NRI of 1.37 and an IDI of 0.24 for radiologist 2.


Assuntos
Neoplasias do Endométrio , Linfonodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/diagnóstico por imagem , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Radiologistas , Estudos Retrospectivos
12.
J Magn Reson Imaging ; 52(6): 1872-1882, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32681608

RESUMO

BACKGROUND: High- and low-risk endometrial cancer (EC) differ in whether lymphadenectomy is performed. Assessment of high-risk EC is essential for planning surgery appropriately. PURPOSE: To develop a radiomics nomogram for high-risk EC prediction preoperatively. STUDY TYPE: Retrospective. POPULATION: In all, 717 histopathologically confirmed EC patients (mean age, 56 years ± 9) divided into a primary group (394 patients from Center A), validation groups 1 and 2 (146 patients from Center B and 177 patients from Centers C-E). FIELD STRENGTH/SEQUENCE: 1.5/3T scanners; T2 -weighted imaging, diffusion-weighted imaging, apparent diffusion coefficient, and contrast enhancement sequences. ASSESSMENT: A radiomics nomogram was generated by combining the selected radiomics features and clinical parameters (metabolic syndrome, cancer antigen 125, age, tumor grade following curettage, and tumor size). The area under the curve (AUC) of the receiver operator characteristic was used to evaluate the predictive performance of the radiomics nomogram for high-risk EC. The surgical procedure suggested by the nomogram was compared with the actual procedure performed for the patients. Net benefit of the radiomics nomogram was evaluated by a clinical decision curve (CDC), net reclassification index (NRI), and integrated discrimination improvement (IDI). STATISTICAL TESTS: Binary least absolute shrinkage and selection operator (LASSO) logistic regression, linear regression, and multivariate binary logistic regression were used to select radiomics features and clinical parameters. RESULTS: The AUC for prediction of high-risk EC for the radiomics nomogram in the primary group, validation groups 1 and 2 were 0.896 (95% confidence interval [CI]: 0.866-0.926), 0.877 (95% CI: 0.825-0.930), and 0.919 (95% CI: 0.879-0.960), respectively. The nomogram achieved good net benefit by CDC analysis for high-risk EC. NRIs were 1.17, 1.28, and 1.51, and IDIs were 0.41, 0.60, and 0.61 in the primary group, validation groups 1 and 2, respectively. DATA CONCLUSION: The radiomics nomogram exhibited good performance in the individual prediction of high-risk EC, and might be used for surgical management of EC. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2 J. MAGN. RESON. IMAGING 2020;52:1872-1882.


Assuntos
Neoplasias do Endométrio , Nomogramas , Estudos de Coortes , Neoplasias do Endométrio/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos
14.
Acta Radiol ; : 284185119841988, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31042066

RESUMO

BACKGROUND: Disputes exist regarding whether the apparent diffusion coefficient (ADC) can differentiate the tumor grade, deep myometrial invasion and lymphovascular space invasion (LVSI) in endometrial cancer. The aim of this review was to assess the diagnostic performance of the ADC value in endometrial cancer. MATERIAL AND METHODS: The PubMed, Web of Science, Embase and Cochrane Library databases were searched for studies that used the ADC value to assess tumor grade, deep myometrial invasion and LVSI in endometrial cancer. We used forest plots to analyze the heterogeneity and generate the pooled sensitivity (SEN) and specificity (SPE). We used summary receiver operating characteristic (SROC) curves to work out the area under the SROC curve (AUC). Likelihood ratios (LRs) were also obtained. RESULTS: Of the 460 identified studies, 11 studies met our inclusion criteria and were included. Overall, nine studies (491 patients) aimed at differentiating high tumor grade had a pooled SEN, SPE and AUC of 77%, 73% and 81%, respectively; three studies (181 patients) for differentiating deep myometrial invasion had a pooled SEN, SPE and AUC of 71%, 67% and 77%, respectively; and two studies (106 patients) for differentiating LVSI had a pooled SEN and SPE of 66% and 74%, respectively. The positive and negative LRs were 2.77 and 0.35 for the tumor grade, 2.08 and 0.45 for deep myometrial invasion, and 2.48 and 0.45 for LVSI. CONCLUSION: This meta-analysis showed that the ADC value had a moderate diagnostic performance for the tumor grade, deep myometrial invasion and LVSI in endometrial cancer.

15.
Analyst ; 143(2): 374-391, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29200216

RESUMO

The last few decades have witnessed the development of many high-performance separation methods that use biologically related binding agents. The combination of HPLC with these binding agents results in a technique known as high performance affinity chromatography (HPAC). This review will discuss the general principles of HPAC and related techniques, with an emphasis on their use for the analysis of biological compounds and pharmaceutical agents. Various types of binding agents for these methods will be considered, including antibodies, immunoglobulin-binding proteins, aptamers, enzymes, lectins, transport proteins, lipids, and carbohydrates. Formats that will be discussed for these methods range from the direct detection of an analyte to indirect detection based on chromatographic immunoassays, as well as schemes based on analyte extraction or depletion, post-column detection, and multi-column systems. The use of biological agents in HPLC for chiral separations will also be considered, along with the use of HPAC as a tool to screen or study biological interactions. Various examples will be presented to illustrate these approaches and their applications in fields such as biochemistry, clinical chemistry, and pharmaceutical research.


Assuntos
Cromatografia de Afinidade , Cromatografia Líquida de Alta Pressão , Anticorpos/química , Carboidratos/química , Imunoensaio , Lipídeos/química , Preparações Farmacêuticas/análise , Proteínas/química
16.
Sheng Li Xue Bao ; 70(3): 335-341, 2018 Jun 25.
Artigo em Zh | MEDLINE | ID: mdl-29926076

RESUMO

The liver X receptors (LXRs) are members of the nuclear receptor superfamily. The activated LXRs have a variety of biological functions, for instance they can not only regulate the metabolism of cholesterol, fatty acids and glucose, but also play an important role in immune inflammatory response. Massive studies have shown that LXRs are involved in the occurrence and progress of inflammatory-related diseases, and can inhibit the inflammation of some inflammatory-related diseases in the nervous system, the respiratory system, and the cardiovascular system. In this review, we summarized the recent progress regarding LXRs in inflammatory-related diseases, including the structure, function and anti-inflammatory mechanism of LXRs, in order to provide new methods for preventing and treating inflammatory-related diseases.


Assuntos
Inflamação/metabolismo , Receptores X do Fígado/metabolismo , Animais , Colesterol/metabolismo , Ácidos Graxos/metabolismo , Glucose/metabolismo , Humanos
17.
Anal Bioanal Chem ; 408(21): 5745-5756, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27289464

RESUMO

An on-column approach for protein entrapment was developed to immobilize alpha1-acid glycoprotein (AGP) for drug-protein binding studies based on high-performance affinity chromatography. Soluble AGP was physically entrapped by using microcolumns that contained hydrazide-activated porous silica and by employing mildly oxidized glycogen as a capping agent. Three on-column entrapment methods were evaluated and compared to a previous slurry-based entrapment method. The final selected method was used to prepare 1.0 cm × 2.1 mm I.D. affinity microcolumns that contained up to 21 (±4) µg AGP and that could be used over the course of more than 150 sample applications. Frontal analysis and zonal elution studies were performed on these affinity microcolumns to examine the binding of various drugs with the entrapped AGP. Site-selective competition studies were also conducted for these drugs. The results showed good agreement with previous observations for these drug-protein systems and with binding constants that have been reported in the literature. The entrapment method developed in this study should be useful for future work in the area of personalized medicine and in the high-throughput screening of drug interactions with AGP or other proteins. Graphical abstract On-column protein entrapment using a hydrazide-activated support and oxidized glycogen as a capping agent.


Assuntos
Cromatografia de Afinidade/instrumentação , Cromatografia Líquida de Alta Pressão/instrumentação , Orosomucoide/metabolismo , Preparações Farmacêuticas/metabolismo , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/metabolismo , Cromatografia de Afinidade/métodos , Cromatografia Líquida de Alta Pressão/métodos , Desenho de Equipamento , Humanos , Orosomucoide/isolamento & purificação , Preparações Farmacêuticas/isolamento & purificação , Propranolol/isolamento & purificação , Propranolol/metabolismo , Ligação Proteica , Varfarina/isolamento & purificação , Varfarina/metabolismo
18.
Anal Chem ; 87(22): 11187-94, 2015 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-26484387

RESUMO

Ultrafast affinity extraction was used to study hormone-protein interactions in solution, using testosterone and its transport proteins human serum albumin (HSA) and sex hormone binding globulin (SHBG) as models. Both single column and two-dimensional systems based on HSA microcolumns were utilized to measure the free fraction of testosterone in hormone/protein mixtures at equilibrium or that were allowed to dissociate for various lengths of time. These data were used to determine the association equilibrium constants (Ka) or global affinities (nKa') and dissociation rate constants (kd) for testosterone with soluble HSA and SHBG. This method was also used to measure simultaneously the free fraction of testosterone and its equilibrium constants with both these proteins in physiological mixtures of these agents. The kd and Ka values obtained for HSA were 2.1-2.2 s(-1) and 3.2-3.5 × 10(4) M(-1) at pH 7.4 and 37 °C. The corresponding constants for SHBG were 0.053-0.058 s(-1) and 0.7-1.2 × 10(9) M(-1). All of these results gave good agreement with literature values, indicating that this approach could provide information on a wide range of rate constants and binding strengths for hormone-protein interactions in solution and at clinically relevant concentrations. The same method could be extended to alternative hormone-protein systems or other solutes and binding agents.


Assuntos
Albumina Sérica/análise , Albumina Sérica/química , Globulina de Ligação a Hormônio Sexual/análise , Globulina de Ligação a Hormônio Sexual/química , Testosterona/análise , Testosterona/química , Sítios de Ligação , Cromatografia Líquida de Alta Pressão/instrumentação , Humanos , Soluções
19.
Drug Discov Today Technol ; 17: 16-21, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26724332

RESUMO

Information on the kinetics of drug-protein interactions is of crucial importance in drug discovery and development. Several methods based on affinity chromatography have been developed in recent years to examine the association and dissociation rates of these processes. These techniques include band-broadening measurements, the peak decay method, peak fitting methods, the split-peak method, and free fraction analysis. This review will examine the general principles and applications of these approaches and discuss their use in the characterization, screening and analysis of drug-protein interactions in the body.


Assuntos
Preparações Farmacêuticas/metabolismo , Proteínas/metabolismo , Cromatografia de Afinidade , Humanos , Cinética , Ligação Proteica
20.
Cell Death Dis ; 15(7): 498, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997297

RESUMO

The tumor microenvironment is a complex space comprised of normal, cancer and immune cells. The macrophages are considered as the most abundant immune cells in tumor microenvironment and their function in tumorigenesis is interesting. Macrophages can be present as M1 and M2 polarization that show anti-cancer and oncogenic activities, respectively. Tumor-associated macrophages (TAMs) mainly have M2 polarization and they increase tumorigenesis due to secretion of factors, cytokines and affecting molecular pathways. Hepatocellular carcinoma (HCC) is among predominant tumors of liver that in spite of understanding its pathogenesis, the role of tumor microenvironment in its progression still requires more attention. The presence of TAMs in HCC causes an increase in growth and invasion of HCC cells and one of the reasons is induction of glycolysis that such metabolic reprogramming makes HCC distinct from normal cells and promotes its malignancy. Since M2 polarization of TAMs stimulates tumorigenesis in HCC, molecular networks regulating M2 to M1 conversion have been highlighted and moreover, drugs and compounds with the ability of targeting TAMs and suppressing their M2 phenotypes or at least their tumorigenesis activity have been utilized. TAMs increase aggressive behavior and biological functions of HCC cells that can result in development of therapy resistance. Macrophages can provide cell-cell communication in HCC by secreting exosomes having various types of biomolecules that transfer among cells and change their activity. Finally, non-coding RNA transcripts can mainly affect polarization of TAMs in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microambiente Tumoral , Macrófagos Associados a Tumor , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Macrófagos Associados a Tumor/imunologia , Animais , Macrófagos/metabolismo
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