RESUMO
The family of phosphatidylethanolamine-binding proteins (PEBPs) participates in various plant biological processes, mainly flowering regulation and seed germination. In cucurbit crops, several PEBP genes have been recognized to be responsible for flowering time. However, the investigation of PEBP family members across the genomes of cucurbit species has not been reported, and their conservation and divergence in structure and function remain largely unclear. Herein, PEBP genes were identified from seven cucurbit crops and were used to perform a comparative genomics analysis. The cucurbit PEBP proteins could be classified into MFT, FT, TFL, and PEBP clades, and further, the TFL clade was divided into BFT-like, CEN-like, and TFL1-like subclades. The MFT-like, FT-like, and TFL-like proteins were clearly distinguished by a critical amino acid residue at the 85th position of the Arabidopsis FT protein. In gene expression analysis, CsaPEBP1 was highly expressed in flowers, and its expression levels in females and males were 70.5 and 89.2 times higher, respectively, than those in leaves. CsaPEBP5, CsaPEBP6, and CsaPEBP7 were specifically expressed in male flowers, with expression levels 58.1, 17.3, and 15.7 times higher, respectively, than those of leaves. At least five CsaPEBP genes exhibited the highest expression during the later stages of corolla opening. Through clustering of time-series-based RNA-seq data, several potential transcription factors (TFs) interacting with four CsaPEBPs were identified during cucumber corolla opening. Because of the tandem repeats of binding sites in promoters, NF-YB (Csa4G037610) and GATA (Csa7G64580) TFs appeared to be better able to regulate the CsaPEBP2 and CsaPEBP5 genes, respectively. This study would provide helpful information for further investigating the roles of PEBP genes and their interacting TFs in growth and development processes, such as flowering time regulation in cucurbit crops.
Assuntos
Cucumis sativus , Gastrópodes , Feminino , Masculino , Animais , Cucumis sativus/genética , Reprodução , Hibridização Genômica Comparativa , Fatores de Tempo , Produtos Agrícolas , GenômicaRESUMO
The presence of the ozone hole increases the amount of UV radiation reaching a plant's surface, and UV-B radiation is an abiotic stress capable of affecting plant growth. Rhododendron chrysanthum Pall. (R. chrysanthum) grows in alpine regions, where strong UV-B radiation is present, and has been able to adapt to strong UV-B radiation over a long period of evolution. We investigated the response of R. chrysanthum leaves to UV-B radiation using widely targeted metabolomics and transcriptomics. Although phytohormones have been studied for many years in plant growth and development and adaptation to environmental stresses, this paper is innovative in terms of the species studied and the methods used. Using unique species and the latest research methods, this paper was able to add information to this topic for the species R. chrysanthum. We treated R. chrysanthum grown in a simulated alpine environment, with group M receiving no UV-B radiation and groups N and Q (externally applied abscisic acid treatment) receiving UV-B radiation for 2 days (8 h per day). The results of the MN group showed significant changes in phenolic acid accumulation and differential expression of genes related to phenolic acid synthesis in leaves of R. chrysanthum after UV-B radiation. We combined transcriptomics and metabolomics data to map the metabolic regulatory network of phenolic acids under UV-B stress in order to investigate the response of such secondary metabolites to stress. L-phenylalanine, L-tyrosine and phenylpyruvic acid contents in R. chrysanthum were significantly increased after UV-B radiation. Simultaneously, the levels of 3-hydroxyphenylacetic acid, 2-phenylethanol, anthranilate, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, α-hydroxycinnamic acid and 2-hydroxy-3-phenylpropanoic acid in this pathway were elevated in response to UV-B stress. In contrast, the study in the NQ group found that externally applied abscisic acid (ABA) in R. chrysanthum had greater tolerance to UV-B radiation, and phenolic acid accumulation under the influence of ABA also showed greater differences. The contents of 2-phenylethanol, 1-o-p-coumaroyl-ß-d-glucose, 2-hydroxy-3-phenylpropanoic acid, 3-(4-hydroxyphenyl)-propionic acid and 3-o-feruloylquinic ac-id-o-glucoside were significantly elevated in R. chrysanthum after external application of ABA to protect against UV-B stress. Taken together, these studies of the three groups indicated that ABA can influence phenolic acid production to promote the response of R. chrysanthum to UV-B stress, which provided a theoretical reference for the study of its complex molecular regulatory mechanism.
Assuntos
Glucose , Hidroxibenzoatos , Álcool Feniletílico , Fenilpropionatos , Rhododendron , Ácido Abscísico/metabolismo , Rhododendron/genética , Ácidos Cumáricos , Raios UltravioletaRESUMO
Background: Although the level of medical care has been improved in recent years, the probability of patients contracting pathogens has increased greatly, with a rising incidence of invasive fungal infections. Deep-seated fungi have become common pathogens of nosocomial infections. Objective: This study aims to systematically assess the effectiveness, mortality, survival rate, and adverse reactions (ARs) of high-dose (HD) liposomal amphotericin B (L-AMB) for human diseases. Methods: Ten articles (1661 patients) of randomized controlled trials (RCTs; whether randomized, single-blind, or double-blind) from January 1, 1960, to December 31, 2020, of HD-L-AMB treatment of diseases were retrieved from the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. The primary outcome measure was the overall therapeutic effect, and the secondary outcome measures were mortality, ≥10-week survival, and ARs. Data were meta-analyzed using RevMan 5.3. Results: Ten RCTs involving 1661 patients were included. HD-L-AMB did not show a significant therapeutic advantage in anti-infection treatment. In addition, HD-L-AMB treatment of invasive Aspergillus infection led to high mortality and low survival (≥10 weeks, OR = 0.57, 95%CI 0.34-0.94, P = .03). According to subgroup analysis, the incidence of ARs and the incidence of renal dysfunction associated with invasive fungal infection treatment were higher with HD-L-AMB than with regular-dose L-AMB. Conclusion: HD-L-AMB had no obvious advantage for the treatment of diseases and was accompanied by increased mortality, reduced long-term survival, and increased ARs (including renal insufficiency). Therefore, the use of HD-L-AMB to control infections is recommended with caution only when the preferred treatment is contraindicated.
RESUMO
BACKGROUND: There is a substantially increasing need for general practitioners (GPs) for future unpredictable pandemic crises, especially at the community-based health services (CBHS) level to protect the vast and varied grassroot-level population in China. Thus, it is crucial to understand the factors that affect Chinese medical students' GP career choices and commitments to CBHS. METHODS: Leveraging the self-administered data collected across the country, this study conducted logistic regressions with 3,438 medical students. First, descriptive statistics of outcome variables and independent variables were provided. Then, stepwise logistic regression models were built, starting from adding individual characteristics, and then familial and institutional characteristics. Last, post-estimation was conducted to further assess whether there were significant marginal effects. RESULTS: Results showed that women students were 24% less likely to choose GP careers but were 1.25 times more likely to commit to CBHS than their men peers, holding other individual, familial, and institutional characteristics constant. In addition, students who major in GP-orientated were more likely to choose GP careers and commit to CBHS, respectively, than those who major in clinical medicine. Furthermore, familial characteristics like annual income and mother's educational level only significantly predicted commitments to CBHS. Notably, sex-related differences in GP career choices and commitments to CBHS - by different regions - were observed. CONCLUSIONS: Understanding the factors that affect medical students' GP career choices sheds light on how medical education stakeholders can make informed decisions on attracting more medical students to GP-orientated majors, which in turn cultivates more GP professionals to meet the nation's demand for GPs. In addition, by understanding the factors that influence medical students' commitment to CBHS, policymakers could make beneficial policies to increase medical students' motivations to the grassroot-level health institutions, and devote to CBHS as gatekeepers for a large population of residents' health.
Assuntos
Educação Médica , Clínicos Gerais , Estudantes de Medicina , Masculino , Humanos , Feminino , Modelos Logísticos , Escolaridade , Escolha da ProfissãoRESUMO
PURPOSE: The formation of advanced plaques, which is characterized by the uninterrupted aggregation of macrophages with high expression of folate receptor-ß (FR-ß), is observed in several concomitant metabolic syndromes. The objective of this study was to develop a novel FR-ß-targeted single-photon emission computed tomography (SPECT) radiotracer and validate its application to the noninvasive detection of atherosclerosis (AS) plaque and non-alcoholic fatty liver (NAFL). METHODS: Two radioiodinated probes, [131I]IPBF and [131I]IBF, were developed, and cell uptake studies were used to identify their specific targets for activated macrophages. Biodistribution in normal mice was performed to obtain the pharmacokinetic information of the probes. Apolipoprotein E knockout (ApoE-/-) mice with atherosclerotic aortas were induced by a high-fat and high-cholesterol (HFHC) diet. To investigate the affinity of radiotracers to FR-ß, Kd values were determined using in vitro assays. In addition, the assessments of the aorta in the ApoE-/- mice at different stages were performed using in vivo SPECT/CT imaging, and the findings were compared by histology. RESULTS: Both [131I]IPBF and [131I]IBF were synthesized with > 95% radiochemical purity and up to 3 MBq/nmol molar activity. In vitro assay of [131I]IPBF showed a moderate binding affinity to plasma proteins and specific uptake in activated macrophages. The prolonged blood elimination half-life (t1/2z) of [131I]IPBF (8.14 h) was observed in a pharmacokinetic study of normal mice, which was significantly longer than that of [131I]IBF (t1/2z = 2.95 h). As expected, the Kd values of [131I]IPBF and [131I]IBF in the Raw 264.7 cells were 43.94 ± 9.83 nM and 61.69 ± 15.19 nM, respectively. SPECT imaging with [131I]IPBF showed a high uptake in advanced plaques and NAFL. Radioactivity in excised aortas examined by ex vivo autoradiography further confirmed the specific uptake of [131I]IPBF in high-risk AS plaques. CONCLUSIONS: In summary, we reported a proof-of-concept study of an albumin-binding folate derivative for macrophage imaging. The FR-ß-targeted probe, [131I]IPBF, significantly prolongs the plasma elimination half-life and has the potential for the monitoring of AS plaques and concomitant fatty liver.
Assuntos
Aterosclerose , Hepatopatia Gordurosa não Alcoólica , Compostos Radiofarmacêuticos , Tomografia Computadorizada de Emissão de Fóton Único , Albuminas , Animais , Macrófagos/metabolismo , Camundongos , Compostos Radiofarmacêuticos/farmacocinética , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único/métodosRESUMO
Overexpression of estrogen receptors (ERs) is one of the important characteristics of most breast cancers. We aim to develop a new type of ER-specific radioiodine-labeled estrogen derivative ([131I]IPBA-EE), which was modified with an albumin-specific ligand 4-(p-iodophenyl) butyric acid (IPBA) to improve the metabolic stability and enhance the ER-targeting ability of estrogen. [131I]IPBA-EE can effectively bind to albumin in vitro, and its dissociation constant (Kd = 0.31 µM) is similar to IPBA (Kd = 0.30 µM). The uptake of [131I]IPBA-EE in ER-positive MCF-7 cells (41.81 ± 3.41%) was significantly higher than that in ER-negative MDA-MB-231 cells (8.78 ± 2.37%, ***P < 0.0005) and could be significantly blocked (3.92 ± 0.35%, ***P < 0.0005). The uptakes of [131I]IPBA-EE in rat uterus and ovaries were 5.66 ± 0.34% ID/g and 5.71 ± 2.77% ID/g, respectively, at 1 h p.i., and these uptakes could be blocked by estradiol (uterus: 2.81 ± 0.41% ID/g, *P < 0.05; ovarian: 3.02 ± 0.08% ID/g, *P < 0.05). SPECT/CT imaging showed that ER-positive MCF-7 tumor uptake of [131I]IPBA-EE reached to 6.07 ± 0.20% ID/g at 7 h p.i., which was significantly higher than that of ER-negative MDA-MB-231 tumor (0.87 ± 0.08% ID/g, **P < 0.005) and could be blocked obviously with fulvestrant (1.65 ± 1.56% ID/g, *P < 0.05). In conclusion, a novel radioiodinated estradiol derivative, [131I]IPBA-EE with albumin-binding property and good metabolic stability, was developed to image the ER in breast cancer. This promising ER-targeted probe has the potential to warrant further preclinical investigations.
Assuntos
Neoplasias da Mama , Estradiol , Animais , Neoplasias da Mama/diagnóstico por imagem , Ácido Butírico , Estrogênios , Feminino , Humanos , Radioisótopos do Iodo , Ratos , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
This study focuses on the construction of novel diphenylacrylonitrile-connected BODIPY dyes with high fluorescence in both solution and an aggregated state by combining DRET and FRET processes in a single donor-acceptor system. The first BODIPY derivatives with one, two, or three AIE-active diphenylacrylonitrile groups were designed and synthesized in moderate yields. Strong fluorescence emissions were observed in the THF solution under excitation at the absorption wavelength of non-emissive diphenylacrylonitrile chromophores, implying the existence of the DRET process between the dark diphenylacrylonitrile donor and the emissive BODIPY acceptor. In the THF/H2O solution, the fluorescence intensity of the novel BODIPY derivatives gradually increased under excitation at the absorption wavelength of diphenylacrylonitrile chromophores, suggesting a FRET process between diphenylacrylonitrile and BODIPY moieties. A greater number of diphenylacrylonitrile units led to higher energy-transfer efficiencies. The pseudo-Stokes shift for both DRET and FRET processes was as large as 190 nm.
RESUMO
The symbiosis between endophytic fungi and plants can promote the absorption of potassium, nitrogen, phosphorus, and other nutrients by plants. Phosphorus is one of the indispensable nutrient elements for plant growth and development. However, the content of available phosphorus in soil is very low, which limits the growth of plants. Phosphorus-soluble microorganisms can improve the utilization rate of insoluble phosphorus. In this study, Talaromyces verruculosus (T. verruculosus), a potential phosphorus-soluble fungus, was isolated from Acer truncatum, a plant with strong stress resistance, and its phosphorus-soluble ability in relation to cucumber seedlings under different treatment conditions was determined. In addition, the morphological, physiological, and biochemical indexes of the cucumber seedlings were assessed. The results show that T. verruculosus could solubilize tricalcium phosphate (TCP) and lecithin, and the solubilization effect of lecithin was higher than that of TCP. After the application of T. verruclosus, the leaf photosynthetic index increased significantly. The photosynthetic system damage caused by low phosphorus stress was alleviated, and the root morphological indexes of cucumber seedlings were increased. The plant height, stem diameter, and leaf area of cucumber seedlings treated with T. verruculosus were also significantly higher than those without treatment. Therefore, it was shown that T. verruculosus is a beneficial endophytic fungus that can promote plant growth and improve plant stress resistance. This study will provide a useful reference for further research on endophytic fungi to promote growth and improve plant stress resistance.
RESUMO
Introduction: Phosphorus (P) readily forms insoluble complexes in soil, thereby inhibiting the absorption and utilization of this essential nutrient by plants. Phosphorus deficiency can significantly impede the growth of forage grass. While Trichoderma viride (T. viride) has been recognized for promoting the assimilation of otherwise unobtainable nutrients, its impact on P uptake remains understudied. Consequently, it is imperative to gain a more comprehensive insight into the role of T. viride in facilitating the uptake and utilization of insoluble P in forage grass. Methods: This research explored the influence of T. viride inoculation on P absorption and the growth of Chloris virgata (C. virgata) across various P sources. We treated plants with control P (P), tricalcium phosphate (TCP), calcium phytate (PHY), and low P (LP), with and without T. viride inoculation (P+T, TCP+T, PHY+T, LP+T). We analyzed photosynthesis parameters, growth indices, pigment accumulation, P content, leaf acid phosphatase activity. Results: Results demonstrated that T. viride inoculation alleviated inhibition of photosynthesis, reduced leaf acid phosphatase activity, and enhanced growth of C. virgata in the presence of insoluble P sources. Additionally, T. viride inoculation enabled the plants to extract more available P from insoluble P sources, as evidenced by a substantial increase in P content: shoot P content surged by 58.23 to 59.08%, and root P content rose by 55.13 to 55.2%. Biomass P-use efficiency (PUE) declined by 38% upon inoculation with T. viride compared to the non-inoculated insoluble P sources, paralleled by a reduction in photosynthetic P-use efficiency (PPUE) by 26 to 29%. Inoculation under insoluble P sources further triggered a lower allocation to root biomass (25 to 26%) and a higher investment in shoot biomass (74 to 75%). However, its application under low P condition curtailed the growth of C. virgata. Discussion: Our results suggest that T. viride inoculation represents an innovative approach for plants to acquire available P from insoluble P sources, thereby promoting growth amid environmental P limitations. This insight is crucial for comprehending the synergy among forage grass, P, and T. viride.
RESUMO
Total volatile basic nitrogen (TVB-N) is a vital indicator for assessing seafood freshness and edibility. Rapid on-site detection of volatile basic nitrogen (VBN) is of significant importance for food safety monitoring. In this study, highly luminescent self-assembled copper nanoclusters (Cu NCs@p-MBA), synthesized using p-mercaptobenzoic acid (p-MBA) as the ligand, were utilized for the sensitive detection of VBNs. Under acidic conditions, Cu NCs@p-MBA formed compact and well-organized nanosheets through noncovalent interactions, accompanied by intense orange fluorescence emission (651 nm). The benzene carboxylic acid part of Cu NCs@p-MBA provided the driving force for supramolecular assembly and exhibited a strong affinity for amines, particularly low-molecular-weight amines such as ammonia (NH3) and trimethylamine (TMA). The quantitative determination of NH3 and TMA showed the detection limits as low as 0.33 and 0.81 ppm, respectively. Cu NCs@p-MBA also demonstrated good responsiveness to putrescine and histamine. Through density functional theory (DFT) calculations and molecular dynamics (MD) simulations, the precise atomic structure, assembly structure, luminescent properties, and reaction processes of Cu NCs@p-MBA were studied, revealing the sensing mechanism of Cu NCs@p-MBA for highly sensitive detection of VBNs. Based on the self-assembled Cu NCs@p-MBA nanosheets, portable fluorescent labels were developed for semiquantitative, visual, and real-time monitoring of seafood freshness. Therefore, this study exemplified the high sensitivity of self-assembly induced emission (SAIE)-type Cu NCs@p-MBA for VBNs sensing, offering an efficient solution for on-site monitoring of seafood freshness.
Assuntos
Cobre , Nitrogênio , Cobre/química , Corantes Fluorescentes/química , Histamina , Alimentos MarinhosRESUMO
Ultraviolet-B (UV-B) radiation is a significant environmental factor influencing the growth and development of plants. MYBs play an essential role in the processes of plant responses to abiotic stresses. In the last few years, the development of transcriptome and acetylated proteome technologies have resulted in further and more reliable data for understanding the UV-B response mechanism in plants. In this research, the transcriptome and acetylated proteome were used to analyze Rhododendron chrysanthum Pall. (R. chrysanthum) leaves under UV-B stress. In total, 2348 differentially expressed genes (DEGs) and 685 differentially expressed acetylated proteins (DAPs) were found. The transcriptome analysis revealed 232 MYB TFs; we analyzed the transcriptome together with the acetylated proteome, and screened 4 MYB TFs. Among them, only RcMYB44 had a complete MYB structural domain. To investigate the role of RcMYB44 under UV-B stress, a homology tree was constructed between RcMYB44 and Arabidopsis MYBs, and it was determined that RcMYB44 shares the same function with ATMYB44. We further constructed the hormone signaling pathway involved in RcMYB44, revealing the molecular mechanism of resistance to UV-B stress in R. chrysanthum. Finally, by comparing the transcriptome and the proteome, it was found that the expression levels of proteins and genes were inconsistent, which is related to post-translational modifications of proteins. In conclusion, RcMYB44 of R. chrysanthum is involved in mediating the growth hormone, salicylic acid, jasmonic acid, and abscisic acid signaling pathways to resist UV-B stress.
Assuntos
Rhododendron , Rhododendron/genética , Proteoma/genética , Multiômica , Perfilação da Expressão Gênica , Transcriptoma/genéticaRESUMO
Background: One of the most common nasal external sites in extranodal Natural Killer/T-cell lymphoma (NKTCL) is in the gastrointestinal (GI) system. Despite this, reports on gastrointestinal-Natural Killer/T-cell lymphoma (GI-NKTCL) are very few. To obtain a better understanding of this manifestation of NKTCL, we conducted a retrospective study on GI-NKTCL to analyze its clinical features, genomic changes and immune infiltration. Methods: We retrospectively collected patients diagnosed with GI-NKTCL in the Sixth Affiliated Hospital of Sun Yat-sen University from 2010 to 2020. From this cohort we obtained mutation data via whole exome sequencing. Results: Genomic analysis from 15 patients with GI-NKTCL showed that the most common driving mutations were ARID1B(14%, 2/15), ERBB3(14%, 2/15), POT1(14%, 2/15), and TP53(14%, 2/15). In addition, we found the most common gene mutation in patients with GI-NKTCL to be RETSAT(29%, 4/15) and SNRNP70(21%, 3/15), and the most common hallmark pathway mutations to be G2M checkpoint pathway (10/15, 66.7%), E2F targets (8/15, 53.3%), estrogen response late (7/15, 46.7%), estrogen response early (7/15, 46.7%), apoptosis (7/15, 46.7%) and TNFA signaling via NFKB (7/15, 46.7%). In the ICIs-Miao cohort, SNRNP7-wild-type (WT) melanoma patients had significantly prolonged overall survival (OS) time compared with SNRNP7 mutant type (MT) melanoma patients. In the TCGA-UCEC cohort, the patients with RETSAT-MT or SNRNP7-MT had significantly increased expression of immune checkpoint molecules and upregulation of inflammatory immune cells. Conclusions: In this study, we explored GI-NKTCL by means of genomic analysis, and identified the most common mutant genes (RETSAT and SNRNP70), pathway mutations (G2M checkpoint and E2F targets) in GI-NKTCL patients. Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL.
RESUMO
Two novel PEGylated ethinylestradiol (PEG = poly(ethylene glycol)) estrogen receptor (ER) targeting probes [131I]EITE and [131I]MITE were synthesized and evaluated. Both probes had a nanomolar binding affinity to the ER receptor (36.47 nM for [131I]EITE and 61.83 nM for [131I]MITE). They showed high uptake in ER-positive MCF-7 cells and tumors, which could be significantly blocked by a coinjection of excess estradiol. Their ER specificities were further demonstrated by the low uptake in ER-negative MDA-MB-231 cells and tumors. The maximum tumor-to-muscle (T/M) ratios reach to 6.59 for [131I]EITE at 1 h postinjection (p.i.) and to 3.69 for [131I]MITE at 2 h p.i. in MCF-7 tumors. Among these two probes, [131I]EITE showed a faster tumor accumulation and a higher T/M ratio indicating it could be a better candidate for the potential diagnosis of ER-positive breast cancers.
RESUMO
Traditional radio monitoring and management largely depend on radio spectrum data analysis, which requires considerable domain experience and heavy cognition effort and frequently results in incorrect signal judgment and incomprehensive situation awareness. Faced with increasingly complicated electromagnetic environments, radio supervisors urgently need additional data sources and advanced analytical technologies to enhance their situation awareness ability. This paper introduces a visual analytics approach for electromagnetic situation awareness. Guided by a detailed scenario and requirement analysis, we first propose a signal clustering method to process radio signal data and a situation assessment model to obtain qualitative and quantitative descriptions of the electromagnetic situations. We then design a two-module interface with a set of visualization views and interactions to help radio supervisors perceive and understand the electromagnetic situations by a joint analysis of radio signal data and radio spectrum data. Evaluations on real-world data sets and an interview with actual users demonstrate the effectiveness of our prototype system. Finally, we discuss the limitations of the proposed approach and provide future work directions.
RESUMO
OBJECTIVE: Accurate evaluation of tumor programmed death ligand 1 (PD-L1) expression can assist in predicting whether a patient will respond to anti-PD-L1 therapy. In this study, we aimed to develop stable radioiodinated PD-L1 antibodies that can be used for PD-L1 targeted SPECT/PET imaging. METHODS: Radioiodination was accomplished via a prosthetic group ([131I]SIB or [124I]SIB) to give radioiodinated anti-human PD-L1 and anti-mouse PD-L1 antibody (anti-PD-L1 and anti-PD-L1M). MicroSPECT/PET imaging and biodistribution of radioiodinated antibodies were studied in two immune-competent murine models (B16F10 and 4T1 syngeneic tumor models) and patient-derived xenograft (PDX) model of lung adenocarcinoma to evaluate the feasibility of identifying tumor PD-L1 expression. RESULTS: Radioiodinated PD-L1 antibodies had high radiochemical purity (>99%) and favorable stability in vivo. There was high uptake of [131I]SIB-anti-PD-L1M in both 4T1 and B16F10 syngeneic tumors when injected with 5.5 MBq radiotracers containing 200 µg anti-mouse-PD-L1. The presence of excess unlabeled anti-PD-L1 antibody increased [131I]SIB-anti-PD-L1M uptake in tumors. The highly specific PD-L1-positive tumor uptake detected by SPECT imaging indicated that radioiodinated antibody could be used for PD-L1 expression imaging. In addition, PET imaging of the PDX model was performed with [124I]SIB-anti-PD-L1, which showed high signal intensity in tumors and optimal contrast between tumor and muscle (tumor-to-muscle ratios at 6 h p.i. and 24 h p.i. were 2.5 and 5.3, respectively). CONCLUSIONS: This study provides an efficient strategy for synthesizing stable radioiodinated PD-L1 antibodies with excellent pharmacokinetics to identify PD-L1 expression in tumors.
Assuntos
Adenocarcinoma de Pulmão/diagnóstico por imagem , Antígeno B7-H1/imunologia , Regulação Neoplásica da Expressão Gênica , Imunoconjugados/imunologia , Melanoma Experimental/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/metabolismo , Animais , Antígeno B7-H1/metabolismo , Transformação Celular Neoplásica , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Radioisótopos do Iodo/química , Melanoma Experimental/imunologia , Melanoma Experimental/metabolismo , Camundongos , Distribuição TecidualRESUMO
The terminal complement complex C5b-9 plays an important role in acute ischemic stroke (AIS) and carotid atherosclerosis. However, the associations between serum C5b-9, the severity and outcome of AIS, and the stability of carotid plaques have not been well investigated. In this clinical study, 70 patients with AIS and 70 healthy controls were enrolled. Serum C5b-9 levels at 72 h after stroke onset were measured by enzyme-linked immunosorbent assay (ELISA). Infarct size, the National Institutes of Health Stroke Scale (NIHSS), the 90-day modified Rankin Scale (mRS), and carotid plaque and stenosis were evaluated. Serum C5b-9 levels were significantly higher in AIS patients than in healthy controls (p < 0.001) and were correlated with infarction sizes (p = 0.045) and the NIHSS (P = 0.035). Furthermore, 90-day mRS analysis demonstrated that the patients with poor outcomes had higher serum C5b-9 levels than those with good outcomes (P < 0.001). Moreover, serum C5b-9 levels in AIS patients with unstable carotid plaques were much higher than in those with stable carotid plaques (P = 0.009). Multivariate logistic regression indicated that C5b-9 could be an independent risk factor for AIS (P < 0.001) and unstable carotid plaques (P = 0.015). Therefore, complement complex C5b-9 may be a potential biomarker in predicting the severity and outcome, as well as the stability of carotid plaques, in AIS patients.
Assuntos
Isquemia Encefálica/sangue , Estenose das Carótidas/sangue , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Acidente Vascular Cerebral/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Isquemia Encefálica/diagnóstico , Estenose das Carótidas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Studies of omega-3 supplementation in dialysis patients describe salutary effects on lipid profiles. However, study results have been inconsistent. The aim of this study was to evaluate the influence of omega-3 supplementation on serum lipids in chronic dialysis patients. METHODS: A systematic literature search was performed to identify the relevant randomized controlled trials (RCTs) that investigated the effects of omega-3 supplementation on dialysis patients. The outcomes included the levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and albumin. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated and heterogeneity was assessed with the I(2) test. RESULTS: A total of 678 patients from 14 trials were subjected to meta-analysis. Omega-3 supplementation could significantly decrease the levels of TG (MD, -34.8 mg/dL; 95% CI, -62.32 to -7.28) and LDL (MD, -7.15 mg/dL; 95% CI, -10.11 to -4.2). However, no statistically significant effects were observed for TC, HDL and albumin levels. In a subgroup meta-analysis, a statistically significant effect of omega-3 consumption on TG and LDL was observed in a short-term interventional duration and hemodialysis populations. CONCLUSION: Our findings indicate that omega-3 supplementation significantly reduced serum TG and LDL level in dialysis patients. However, there is no conclusive evidence that it can modulate the TC, HDL and albumin level.