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1.
Molecules ; 29(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38675698

RESUMO

The increasing demand for sustainable alternatives underscores the critical need for a shift away from traditional hydrocarbon-dependent processes. In this landscape, biomanufacturing emerges as a compelling solution, offering a pathway to produce essential chemical materials with significantly reduced environmental impacts. By utilizing engineered microorganisms and biomass as raw materials, biomanufacturing seeks to achieve a carbon-neutral footprint, effectively counteracting the carbon dioxide emissions associated with fossil fuel use. The efficiency and specificity of biocatalysts further contribute to lowering energy consumption and enhancing the sustainability of the production process. Within this context, cell-free synthesis emerges as a promising approach to accelerate the shift towards biomanufacturing. Operating with cellular machinery in a controlled environment, cell-free synthesis offers multiple advantages: it enables the rapid evaluation of biosynthetic pathways and optimization of the conditions for the synthesis of specific chemicals. It also holds potential as an on-demand platform for the production of personalized and specialized products. This review explores recent progress in cell-free synthesis, highlighting its potential to expedite the transformation of chemical processes into more sustainable biomanufacturing practices. We discuss how cell-free techniques not only accelerate the development of new bioproducts but also broaden the horizons for sustainable chemical production. Additionally, we address the challenges of scaling these technologies for commercial use and ensuring their affordability, which are critical for cell-free systems to meet the future demands of industries and fully realize their potential.


Assuntos
Sistema Livre de Células , Vias Biossintéticas , Biotecnologia/métodos , Biomassa , Produtos Biológicos/química
2.
Medicina (Kaunas) ; 60(5)2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38792920

RESUMO

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02-0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86-182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment.


Assuntos
Biomarcadores Tumorais , Neoplasias da Mama , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Biomarcadores Tumorais/análise , Idoso , Intervalo Livre de Doença , Quimioterapia Adjuvante/métodos , Prognóstico , Receptor ErbB-2/análise , Análise de Sobrevida
3.
Biochem Biophys Res Commun ; 652: 14-21, 2023 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-36806084

RESUMO

Lipocalin-2 (LCN2) is an acute phase protein used as a biomarker for acute lung injury (ALI). Although the innate immune functions of LCN2 have been studied, how LCN2 contributes to ALI induced by lipopolysaccharide (LPS) remains unknown. In this study, we investigated the effect of LCN2 deletion on LPS-induced ALI using RNA-sequencing. LPS-treated LCN2 knockout (KO) mice had a decreased histopathological score and reduced neutrophil and macrophage infiltration in lung tissue compared with LPS-treated WT mice. RNA-sequencing analysis identified 38 differentially expressed genes (DEGs), including Cxcl5, Cxcl13, Xcl1, Saa1, and Cd14. In particular, Gene Ontology analysis of DEGs revealed a significant reduction in the inflammatory response, neutrophil chemotaxis, and chemokine-mediated signaling in LPS-treated LCN2KO mice compared with LPS-treated WT mice. Thus, these results suggest that LCN2 deletion alleviates LPS-induced ALI and that LCN2 may be involved in chemotaxis-related gene expression.


Assuntos
Lipopolissacarídeos , Pneumonia , Animais , Camundongos , Lipocalina-2/genética , Lipopolissacarídeos/efeitos adversos , Quimiotaxia , RNA , Camundongos Endogâmicos C57BL , Inflamação/metabolismo , Camundongos Knockout
4.
Biochem Biophys Res Commun ; 667: 10-17, 2023 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-37201358

RESUMO

Type 2 diabetes is associated with a risk factor for Alzheimer's disease (AD). Activation of glial cells, such as microglia and astrocytes, is crucial for the development of neuroinflammation in both diabetes and AD. The role of amyloid-beta oligomer (AßO) in the hippocampus of diabetic mice has been investigated; however, the effect of galectin-3 and lipocalin-2 (LCN2) on amyloid toxicity-related glial activation in diabetic mice is not known. To fill this knowledge gap, we fed mice a high-fat diet (HFD) for 20 weeks to induce a diabetic state and then injected the hippocampus with AßO. Sholl analysis of iba-1-positive microglia showed retraction of microglial ramifications in the hippocampus of HFD-fed diabetic mice. AßO treatment caused more retraction of microglial process in HFD-fed mice. In particular, microglial galectin-3 levels and astrocytic LCN2 levels were increased in the hippocampus of HFD-fed mice with AßO treatment. These findings suggest that galectin-3 and LCN2 are involved in amyloid toxicity mechanisms, especially glial activation under diabetic conditions.


Assuntos
Doença de Alzheimer , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Camundongos , Animais , Microglia/metabolismo , Peptídeos beta-Amiloides/metabolismo , Galectina 3 , Astrócitos/metabolismo , Dieta Hiperlipídica/efeitos adversos , Lipocalina-2/farmacologia , Doença de Alzheimer/etiologia , Hipocampo/metabolismo
5.
Biotechnol Bioprocess Eng ; : 1-7, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36687336

RESUMO

Cell-free protein synthesis is emerging as a powerful tool to accelerate the progress of synthetic biology. Notably, cell-free systems that harness extracted synthetic machinery of cells can address many of the issues associated with the complexity and variability of living systems. In particular, cell-free systems can be programmed with various configurations of genetic information, providing great flexibility and accessibility to the field of synthetic biology. Empowered by recent progress, cell-free systems are now evolving into artificial biological systems that can be tailored for various applications, including on-demand biomanufacturing, diagnostics, and new materials design. Here, we review the key developments related to cell-free protein synthesis systems, and discuss the future directions of these promising technologies.

6.
Medicina (Kaunas) ; 59(6)2023 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-37374289

RESUMO

Background and Objectives: BRAF mutational status in resected non-small cell lung cancer (NSCLC) in the Korean population is poorly understood. We explored BRAF (particularly BRAF V600E) mutational status among Korean patients with NSCLC. Materials and Methods: This study included 378 patients with resected primary NSCLC who were enrolled from January 2015 to December 2017. The authors obtained formalin-fixed paraffin-embedded (FFPE) tissue blocks and performed peptide nucleic acid (PNA)-clamping polymerase chain reaction (PCR) for detecting BRAF V600, real-time PCR for detecting BRAF V600E, and immunohistochemical analyses using the mutation-specific Ventana VE1 monoclonal antibody. For positive cases in any methods mentioned above, direct Sanger sequencing was additionally performed. Results: The PNA-clamping method revealed the BRAF V600 mutation in 5 (1.3%) of the 378 patients. Among these five patients, real-time PCR, direct Sanger sequencing detected BRAF V600E mutations in three (0.8%) patients. Thus, two cases showed differences in their PNA-clamping and the others. Direct Sanger sequencing of PNA-clamping PCR product was performed for two cases showing negative results on direct Sanger sequencing; both contained BRAF mutations other than V600E. All patients harboring BRAF mutations had adenocarcinomas, and all patients with V600E mutation exhibited minor micropapillary components. Conclusions: Despite the low incidence of the BRAF mutation among Korean patients with NSCLC, lung adenocarcinoma patients with micropapillary components should be prioritized in terms of BRAF mutation testing. Immunohistochemical staining using Ventana VE1 antibody may serve as a screening examination for BRAF V600E.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas Proto-Oncogênicas B-raf/genética , Imuno-Histoquímica , Neoplasias Pulmonares/genética , Mutação , Reação em Cadeia da Polimerase em Tempo Real , Biomarcadores Tumorais/genética , República da Coreia
7.
Eur Radiol ; 32(11): 7843-7853, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35538263

RESUMO

OBJECTIVES: To investigate the pooled diagnostic yield of MR myelography in patients with newly diagnosed spontaneous intracranial hypotension (SIH). METHODS: A literature search of the MEDLINE/PubMed and Embase databases was conducted until July 25, 2021, including studies with the following inclusion criteria: (a) population: patients with newly diagnosed SIH; (b) diagnostic modality: MR myelography or MR myelography with intrathecal gadolinium for evaluation of CSF leakage; (c) outcomes: diagnostic yield of MR myelography or MR myelography with intrathecal gadolinium. The risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. DerSimonian-Laird random-effects modeling was used to calculate the pooled estimates. Subgroup analysis regarding epidural fluid collection and meta-regression were additionally performed. RESULTS: Fifteen studies with 643 patients were included. Eight studies used MR myelography with intrathecal gadolinium, and 11 used MR myelography. The overall quality of the included studies was moderate. The pooled diagnostic yield of MR myelography was 86% (95% CI, 80-91%) and that of MR myelography with intrathecal gadolinium was 83% (95% CI, 51-96%). There was no significant difference in pooled diagnostic yield between MR myelography and MR myelography with intrathecal gadolinium (p = 0.512). In subgroup analysis, the pooled diagnostic yield of the epidural fluid collection was 91% (95% CI, 84-94%). In meta-regression, the diagnostic yield was unaffected regardless of consecutive enrollment, magnet strength, or 2D/3D. CONCLUSIONS: MR myelography had a high diagnostic yield in patients with SIH. MR myelography is non-invasive and not inferior to MR myelography with intrathecal gadolinium. KEY POINTS: • The pooled diagnostic yield of MR myelography was 86% (95% CI, 80-91%) in patients with spontaneous intracranial hypotension. • There was no significant difference in pooled diagnostic yield between MR myelography and MR myelography with intrathecal gadolinium. • MR myelography is non-invasive and not inferior to MR myelography with intrathecal gadolinium.


Assuntos
Hipotensão Intracraniana , Mielografia , Humanos , Hipotensão Intracraniana/diagnóstico por imagem , Gadolínio/farmacologia , Imageamento por Ressonância Magnética , Vazamento de Líquido Cefalorraquidiano/diagnóstico por imagem
8.
Molecules ; 27(13)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35807366

RESUMO

In this study, thirty-eight isoflavone derivatives were comprehensively identified and quantified from the raw, steamed and fermented seeds of four selected soybean cultivars based on UPLC-DAD-QToF/MS results with reference to the previously reported LC-MS library and flavonoid database, and summarized by acylated group including glucosides (Glu), malonyl-glucosides (Mal-Glu), acetyl-glucosides (Ac-Glu), succinyl-glucosides (Suc-Glu) and phosphorylated conjugates (Phos) in addition to aglycones. Among them, Suc-Glu and Phos derivatives were newly generated due to fermentation by B. subtilis AFY-2 (cheonggukjang). In particular, Phos were characterized for the first time in fermented soy products using Bacillus species. From a proposed roadmap on isoflavone-based biotransformation, predominant Mal-Glu (77.5-84.2%, raw) decreased rapidly by decarboxylation and deesterification into Ac-Glu and Glu (3.5-8.1% and 50.0-72.2%) during steaming, respectively. As fermentation continued, the increased Glu were mainly succinylated and phosphorylated as well as gradually hydrolyzed into their corresponding aglycones. Thus, Suc-Glu and Phos (17.3-22.4% and 1.5-5.4%, 36 h) determined depending on cultivar type and incubation time, and can be considered as important biomarkers generated during cheonggukjang fermentation. Additionally, the changes of isoflavone profile can be used as a fundamental report in applied microbial science as well as bioavailability research from fermented soy foods.


Assuntos
Isoflavonas , Fermentação , Glucosídeos/metabolismo , Isoflavonas/metabolismo , Sementes/metabolismo , Glycine max/metabolismo
9.
J Org Chem ; 86(20): 14121-14130, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34505779

RESUMO

This report describes a method for the nucleophilic radiofluorination of (hetero)aryl chlorides, (hetero)aryl triflates, and nitroarenes using a combination of [18F]KF·K2.2.2 and Me4NHCO3 for the in situ formation of a strongly nucleophilic fluorinating reagent (proposed to be [18F]Me4NF). This method is applied to 24 substrates bearing diverse functional groups, and it generates [18F](hetero)aryl fluoride products in good to excellent radiochemical yields in the presence of ambient air/moisture. The reaction is applied to the preparation of 18F-labeled HQ-415 for potential (pre)clinical use.


Assuntos
Fluoretos , Radioisótopos de Flúor , Compostos de Amônio Quaternário , Compostos Radiofarmacêuticos
10.
Molecules ; 27(1)2021 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-35011337

RESUMO

Platycodon grandiflorum (PG) is known as a high-potential material in terms of its biological activity. The objective of this report is to provide chromatographic and mass fragment ion data of 38 simultaneously identified saponins, including novel compounds, by analyzing them through ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QToF/MS). In so doing, we investigated their diverse conditions, including morphological parts (stems, roots, buds, and leaves), peeling (or not), and blanching of PG. The total contents of individual saponins indicated an order of roots (containing peel, 1674.60 mg/100 g, dry weight) > buds (1364.05) > roots (without peel, 1058.83) ≈ blanched roots (without peel, 945.17) ≈ stems (993.71) ≈ leaves (881.16). When considering three types of aglycone, the platycodigenin group (55.04 ~ 68.34%) accounted for the largest proportion of the total content, whereas the platycogenic acid A group accounted for 17.83 ~ 22.61%, and the polygalacic acid group represented 12.06 ~ 22.35%. As they are classified as major compounds, novel saponins might be utilized for their role in healthy food for human consumption. Additionally, during blanching, the core temperature of PG was satisfied with the optimal condition, thus activating the enzymes related to biotransformation. Furthermore, through the use of this comprehensive data, additional studies related to buds, as well as roots or the characterization of individual saponins, can be conducted in a rapid and achievable manner.


Assuntos
Cromatografia Líquida de Alta Pressão , Platycodon/química , Saponinas/química , Saponinas/farmacologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Estrutura Molecular , Especificidade de Órgãos , Compostos Fitoquímicos/química , Relação Estrutura-Atividade
11.
Histopathology ; 76(6): 898-905, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31985086

RESUMO

AIMS: We sought to determine if non-terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. METHODS AND RESULTS: We reviewed whole-section images of 489 cases of lung adenocarcinoma from The Cancer Genome Atlas (TCGA). TCGA data were classified into 426 TRU type adenocarcinoma, 49 IMA and 14 unclassifiable. Their RNA sequencing data was analysed by DESeq2 and WGCNA R packages. Gene expression in patients' samples was measured by NanoString assay. Overexpression of genes including REG4, TFF2, MUCL3, FER1L6, B3GALT5, ANXA10 was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes, including ANXA10, FER1L6, HNF4a, MUC5AC, REG4, TFF1, TFF2 and VSIGI, was increased> 15-fold in IMA. Immunohistochemistry of ANXA10, TFF2 and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed a predominant expression in IMA, but are not in TRU type adenocarcinoma. CONCLUSION: Our results showed the level of genes expressed in stomach mucosa was increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help the understanding of the pathogenesis of IMA and discovery of therapeutic targets.


Assuntos
Adenocarcinoma Mucinoso/patologia , Biomarcadores Tumorais/análise , Mucosa Gástrica , Neoplasias Pulmonares/patologia , Transcriptoma , Diferenciação Celular/genética , Humanos , Fenótipo
12.
Pancreatology ; 20(7): 1486-1494, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32948429

RESUMO

OBJECTIVES: Venous invasion is a poor prognostic factor for pancreatic ductal adenocarcinoma (PDAC). However, our understanding of various features of venous invasion is limited. Our aim is to comprehensively evaluate various histopathologic features of venous invasion, including status, type (lymphatic or venous), number of invasion foci, and histologic pattern (pancreatic intraepithelial neoplasia [PanIN]-like, conventional) in PDACs. METHODS: Various features of venous invasion, including status, number of invasion foci, histologic patterns [pancreatic intraepithelial neoplasia (PanIN)-like, conventional], and size of involved vessels in 471 surgically resected PDACs were evaluated with all available hematoxylin and eosin (H&E)-stained slides. RESULTS: Venous invasion was observed in 319 cases (67.7%) and was more frequently associated with increased tumor size, extrapancreatic extension, resection margin involvement, diffuse tumor distribution, lymph node metastasis, and perineural invasion (all Ps < .05). High frequency (≥3 foci) of venous invasion was associated with shorter overall survival both in the entire group and in the early stage subgroup (stage I; all Ps < .05). Multivariate analysis indicated that a high frequency (≥3 foci) of venous invasion, large tumor size (>4 cm), higher histologic grade, and lymph node metastasis, were independent prognostic factors of worse overall survival (all Ps < .05). CONCLUSION: Precise evaluation of venous invasion status, including foci number of invasion, can provide additional prognostic information for patients undergoing surgical resection of PDAC, especially for those with early disease stage.


Assuntos
Carcinoma Ductal Pancreático/irrigação sanguínea , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/irrigação sanguínea , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/patologia , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/cirurgia , Prognóstico , Fluxo Sanguíneo Regional , Análise de Sobrevida , Veias/patologia
13.
Int J Obes (Lond) ; 43(10): 2057-2065, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30242240

RESUMO

CONTEXT: Adult extreme obesity (EO) is a growing health concern. The prevalence of known obesity associated co-morbidities namely cardio-metabolic and neuro-psychiatric disease in EO is not fully established. The contribution of pathogenic genetic variants, previously implicated in early childhood onset obesity, to adult EO is also not established. OBJECTIVE: We undertook phenotypic and genetic analysis of adult patients with extreme obesity (EO, BMI > 50). Specifically, we assessed the prevalence of eating disorders, cardio-metabolic, and neuro-psychiatric disease and the presence of pathogenic variants in known monogenic obesity genes. DESIGN: A total of 55 patients with EO from a single site bariatric surgery referral program were assessed for the presence of eating disorders, cardio-metabolic, and neuro-psychiatric disease. The 54 obese (O) patients with a BMI < 50 from the same program were identified for phenotypic comparison. The 45 EO patients underwent whole exome sequencing to identify deleterious variants in known monogenic obesity genes. OUTCOMES: (1) Presence of eating disorders, cardio-metabolic, and neuro-psychiatric disease in EO compared to O. (2) Onset of obesity in the EO group. (3) Presence of deleterious variants in genes previously implicated in monogenic obesity in the EO group. RESULTS: The EO group had higher prevalence of lifetime neuro-psychiatric disease (67.3% vs. 37%, p = 0.001) and sleep apnea (74.6% vs. 51.9%, p = 0.01) but lower prevalence of type 2 diabetes (30.1% vs. 50%, p = 0.045) compared to O. There were no significant differences in binge eating, dyslipidemia, hypertension, and cardiac disease. In the EO group, we found previously unreported singleton variants in NTRK2 (pS667W, bio-informatically predicted to be deleterious) and BDNF (pE23K). No previously confirmed loss of function variants in monogenic obesity genes were found. CONCLUSIONS: Adults with EO have significantly increased prevalence of neuro-psychiatric disease and a possibly lower burden of type 2 diabetes compared to less obese patients. Known monogenic causes of obesity were not highly prevalent in this cohort. Further studies are warranted to confirm these preliminary findings.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos/genética , Transtornos Mentais/genética , Obesidade Mórbida/genética , Índice de Massa Corporal , Fator Neurotrófico Derivado do Encéfalo , Estudos de Casos e Controles , Comorbidade , Transtornos da Alimentação e da Ingestão de Alimentos/psicologia , Feminino , Humanos , Masculino , Glicoproteínas de Membrana , Transtornos Mentais/complicações , Transtornos Mentais/fisiopatologia , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/psicologia , Fenótipo , Prevalência , Receptor trkB
14.
Diabetes Obes Metab ; 21(6): 1357-1364, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30740846

RESUMO

AIM: To assess the acute effects of 0.7 mg intranasal glucagon (ING) vs intranasal placebo (INP) on food intake and resting energy expenditure (REE). METHODS: A single-blind, crossover study was conducted in 19 overweight/obese adults (15 men, 4 women). REE was assessed by indirect calorimetry over 90 minutes, after which appetite was assessed using a visual analogue scale, and ad libitum caloric intake was assessed. Plasma samples were obtained at baseline and at 15-minute intervals post-treatment up to 90 minutes. RESULTS: ING increased total REE (INP 61.5 ± 1.2 kcal vs ING 69.4 ± 1.2 kcal; P = 0.027). There were no between-treatment differences in blood glucose, food intake and appetite. There were no adverse effects. CONCLUSION: ING acutely increases REE without increasing plasma glucose. Longer term studies with multiple daily dosing will establish whether this affects body weight.


Assuntos
Glicemia/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Glucagon/administração & dosagem , Glucagon/farmacologia , Sobrepeso/tratamento farmacológico , Administração Intranasal , Estudos Cross-Over , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Glucagon/sangue , Glucagon/uso terapêutico , Humanos , Hiperglicemia , Masculino , Pessoa de Meia-Idade , Obesidade/tratamento farmacológico
15.
Angew Chem Int Ed Engl ; 58(10): 3119-3122, 2019 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-30605563

RESUMO

A Cu-mediated ortho-C-H radiofluorination of aromatic carboxylic acids that are protected as 8-aminoquinoline benzamides is described. The method uses K18 F and is compatible with a wide range of functional groups. The reaction is showcased in the high specific activity automated synthesis of the RARß2 agonist [18 F]AC261066.


Assuntos
Aminoquinolinas/química , Benzamidas/química , Benzoatos/síntese química , Cobre/química , Radioisótopos de Flúor/química , Tiazóis/síntese química , Aminoquinolinas/síntese química , Benzamidas/síntese química , Benzoatos/química , Halogenação , Humanos , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Receptores do Ácido Retinoico/agonistas , Tiazóis/química
16.
Chemistry ; 24(26): 6848-6853, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29504637

RESUMO

The development of a convenient and rapid method to synthesize radiolabeled, enantiomerically pure amino acids (AAs) as potential positron emission tomography (PET) imaging agents for mapping various biochemical transformations in living organisms remains a challenge. This is especially true for the synthesis of carbon-11-labeled AAs given the short half-life of carbon-11 (11 C, t1/2 =20.4 min). A facile synthetic pathway to prepare enantiomerically pure 11 C-labeled l-asparagine was developed using a partially protected serine as a starting material with a four-step transformation providing a chiral five-membered cyclic sulfamidate as the radiolabeling precursor. Its structure and absolute configuration were confirmed by X-ray crystallography. Utilizing a [11 C]cyanide nucleophilic ring opening reaction followed by selective acidic hydrolysis and deprotection, enantiomerically pure l-[4-11 C]asparagine was synthesized. Further optimization of reaction parameters, including base, metal ion source, solvent, acid component, reaction temperature and reaction time, a reliable two-step method for synthesizing l-[4-11 C]asparagine was presented: within a 45±3 min (n=5, from end-of-bombardment), the desired enantiomerically pure product was synthesized with the initial nucleophilic cyanation yield of 69±4 % (n=5) and overall two-step radiochemical yield of 53±2 % (n=5) based on starting [11 C]HCN, and with radiochemical purity of 96±2 % (n=5).


Assuntos
Asparagina/química , Compostos Radiofarmacêuticos/química , Ácidos Sulfônicos/química , Asparagina/síntese química , Radioisótopos de Carbono/química , Cristalografia por Raios X , Conformação Molecular , Nitrilas/química , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos/síntese química , Estereoisomerismo
17.
Plant Physiol ; 172(2): 776-788, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27406166

RESUMO

The western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte) is a major pest of maize (Zea mays) that is well adapted to most crop management strategies. Breeding for tolerance is a promising alternative to combat WCR but is currently constrained by a lack of physiological understanding and phenotyping tools. We developed dynamic precision phenotyping approaches using 11C with positron emission tomography, root autoradiography, and radiometabolite flux analysis to understand maize tolerance to WCR Our results reveal that WCR attack induces specific patterns of lateral root growth that are associated with a shift in auxin biosynthesis from indole-3-pyruvic acid to indole-3-acetonitrile. WCR attack also increases transport of newly synthesized amino acids to the roots, including the accumulation of Gln. Finally, the regrowth zones of WCR-attacked roots show an increase in Gln turnover, which strongly correlates with the induction of indole-3-acetonitrile-dependent auxin biosynthesis. In summary, our findings identify local changes in the auxin biosynthesis flux network as a promising marker for induced WCR tolerance.


Assuntos
Besouros/fisiologia , Produtos Agrícolas/parasitologia , Raízes de Plantas/parasitologia , Zea mays/parasitologia , Aminoácidos/biossíntese , Animais , Transporte Biológico , Radioisótopos de Carbono/metabolismo , Produtos Agrícolas/genética , Produtos Agrícolas/metabolismo , Glutamina/metabolismo , Herbivoria/fisiologia , Interações Hospedeiro-Parasita , Ácidos Indolacéticos/metabolismo , Indóis/metabolismo , Fenótipo , Doenças das Plantas/genética , Doenças das Plantas/parasitologia , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Tomografia por Emissão de Pósitrons , Zea mays/genética , Zea mays/metabolismo
18.
World J Surg Oncol ; 15(1): 72, 2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28351362

RESUMO

BACKGROUND: Brenner tumors almost always develop in the ovary. Exceptionally, extraovarian Brenner tumors have been reported in the lower abdomen or pelvic organs. Here, we introduce a peculiar case of an extraovarian Brenner tumor arising in the omentum. CASE PRESENTATION: A 43-year-old woman presented with a palpable abdominal mass. Computed tomography (CT) scan revealed a 9.0-cm solid mass in the omentum. The tumor was not associated with pelvic structures, including the ovaries. It was excised under the clinical impression of an extragastrointestinal stromal tumor or neurogenic tumor. Grossly, the mass was a well-circumscribed solid tumor, with yellow-tan cut surface and minute cystic spaces. Microscopically, the tumor showed well-defined epithelial nests with variable cystic changes embedded in an abundant fibrous stroma. The cells within the nests were reminiscent of benign urothelial cells in that they had oval, frequently grooved nuclei. The epithelial cells focally showed a gradual transition into the surrounding stromal cells with short spindled features. The urothelium-like cells were positive for pancytokeratin, WT-1, p63, CK7, uroplakin-III, and GATA-3 but were negative for CD34, CD10, CK20, c-KIT, DOG-1, PAX-8, and calretinin. Morphological and immunohistochemical features of the tumor were the same as an ovarian Brenner tumor, and so it was diagnosed as an extraovarian Brenner tumor. CONCLUSIONS: Although the location of the tumor was very unusual, we could diagnose the tumor as an extraovarian Brenner tumor on the basis of the histologic and immunohistochemical findings. This is the first case of extraovarian Brenner tumor arising in the omentum near the stomach ever reported in the English literature.


Assuntos
Tumor de Brenner/patologia , Omento/patologia , Neoplasias Ovarianas/patologia , Células Estromais/patologia , Adulto , Tumor de Brenner/cirurgia , Feminino , Humanos , Omento/cirurgia , Neoplasias Ovarianas/cirurgia , Prognóstico
19.
Ann Diagn Pathol ; 31: 9-13, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29146062

RESUMO

Adrenocortical adenomas and carcinomas in other parenchyma are extremely rare, with few cases reported and because of the rarity of these tumors, they occasionally cause problems during diagnosis. Adrenal cortical neoplasms in liver parenchyma can be present in 3 forms, including direct invasion or adhesion to liver parenchyma, tumors arising in adrenohepatic fusion tissue or in ectopic adrenal gland tissue. We report 3 cases of adrenal cortical tumors that were misdiagnosed as hepatocellular carcinoma in the preoperative state. The first case involved an adrenocortical adenoma arising in adrenohepatic fusion tissue. The remaining 2 cases involved an adrenocortical carcinoma and an adrenocortical oncocytoma arising in ectopic adrenal tissue in the liver. We describe the clinical presentations, gross, microscopic findings, immunohistochemical findings with respect to each case, with emphasis on differential diagnosis from hepatocellular carcinoma.


Assuntos
Neoplasias do Córtex Suprarrenal/diagnóstico , Glândulas Suprarrenais , Carcinoma Hepatocelular/diagnóstico , Coristoma/patologia , Neoplasias Hepáticas/diagnóstico , Fígado/patologia , Neoplasias do Córtex Suprarrenal/patologia , Idoso , Carcinoma Hepatocelular/patologia , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade
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