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1.
Talanta ; 236: 122877, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34635257

RESUMO

A covalent organic framework (named as TpDq) linked by ß-ketoamine was prepared by imine condensation reaction with 1,3,5-triformylphloroglucinol (TFP) and 2,6-diaminoanthraquinone (DAAQ) as building blocks. Via employing a functionalized modification strategy, a new lanthanide complex Eu3+-ß-diketone functionalized covalent organic framework hybrid material, Eu-TTA@TpDq (TTA = 2-thenoyltrifluoroacetone), has been synthesized. After post-synthetic modification (PSM), the shape and structure of the parent framework is well preserved and the modified material shows remarkable luminescence properties. Based on this, we designed it as a fluorescent probe and tried to use it to sense common aldehydes. The results indicate that Eu-TTA@TpDq exhibits a turn-off response toward glutaraldehyde which can distinguish from other common aldehydes. The fluorescent probe has the advantages of reusability, pH stability (4.50-8.52), fast luminescence response (<1 min) and low detection limit. The linear range of this method was 0-100 µM; the detection limit was 4.55 µM; the relative standard deviation was 2.16%. Furthermore, it has broad application prospect in both practical sensing of glutaraldehyde in water environment and simple detection of glutaraldehyde vapor. In addition, we preliminarily discussed the possible sensing mechanism.


Assuntos
Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Glutaral , Cetonas , Luminescência
3.
World J Surg Oncol ; 19(1): 324, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34775950

RESUMO

BACKGROUND: In the Response Evaluation Criteria for Solid Tumors (RECIST) diagnostic criteria, the concepts of progression by preexisting disease (PPL) and progression by new metastases (PNM) have been proposed to distinguish between the progression types of cancer refractory to treatment. According to the tumor biology of cancer progression forms, the "PPL" form indicates invasion, and the "PNM" form indicates metastasis. On the other hand, recent studies have focused on the clinical importance of inflammatory markers as indicators of the systemic tumor immune response. In particular, absolute lymphocyte count (ALC) is an indicator of the host's immune response. Thus, we developed a new measure that combined progression form with ALC. In this study, we clinically validated the combined assessment of progression form and ALC in eribulin chemotherapy. METHODS: From August 2011 to April 2019, a total of 486 patients with locally advanced or metastatic breast cancer (MBC) underwent treatment. In this study, only 88 patients who underwent chemotherapy using eribulin were included. The antitumor effect was evaluated based on the RECIST criteria, version 1.1. To measure ALC, peripheral blood samples collected before eribulin treatment were used. The cut-off value for ALC in this study was 1500/µl, based on previous studies. RESULTS: The PPL group (71 patients, 80.7%) had significantly longer progression-free survival (PFS) (p = 0.022, log-rank) and overall survival (OS) (p < 0.001, log-rank) than the PNM group (17 patients, 19.3%). In the 51 patients with ALC < 1500/µl, the PPL group had a significantly better prognosis than the PNM group (PFS: p = 0.035, OS: p < 0.001, log-rank, respectively). On the other hand, in the 37 patients with ALC ≥ 1500/µl, the PPL group had a better OS compared with the PNM group (p = 0.055, log-rank), but there was no significant difference in PFS between the two groups (p = 0.541, log-rank). Furthermore, multivariate analysis that validated the effect of OS showed that high ORR and "high-ALC and PPL" were factors for a good prognosis (p < 0.001, HR = 0.321; p = 0.036, HR = 0.290). CONCLUSIONS: The progression form of PNM had a worse prognosis than PPL in patients treated with eribulin. In breast cancer patients with eribulin chemotherapy, good systemic immune status, such as ALC ≥ 1500/µl, was associated with less progression, particularly metastasis, and better prognosis. Furthermore, the biomarker "high-ALC (ALC ≥ 1500/µl) and PPL" was particularly useful as a prognostic marker following eribulin chemotherapy.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/tratamento farmacológico , Intervalo Livre de Doença , Feminino , Furanos/uso terapêutico , Humanos , Cetonas , Contagem de Linfócitos , Prognóstico , Estudos Retrospectivos
4.
J Indian Prosthodont Soc ; 21(4): 412-419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34810370

RESUMO

Aim: The aim of this study is to assess the surface roughness and shear bond characteristics of pol-ether-ether-ketone after different surface treatments. Setting and Design: An in vitro, prospective. Materials and Methods: One hundred and twenty disc-shaped samples of 10 mm diameter and 2 mm thickness were milled and subjected to following surface treatments: 110 µm alumina particles, 98% concentrated sulfuric acid, and 10-20 µm synthetic diamond particles. Surface characteristics of treated sample were studied under SEM with ×500 and ×1000 magnification. Shear bond strength (SBS) with composite resin discs embedded in acrylic blocks after luting with self-etch resin cement and resin-modified glass ionomer cement (RMGIC) was evaluated using the universal testing machine (Instron®, Massachusetts U. S. A). Statistical Analysis Used: The data collected were evaluated using the Analysis of variance and Tukey's honest significant difference post hoc test. Results: Highest SBS and SR were noted with self-etch resin cement in the given order: 98% sulfuric acid (2.106 ± 0.186 µm), followed by alumina particles (1.706 ± 0.160 µm) and synthetic diamond particles (1.101 ± 0.167 µm). Conclusion: The SBS of self-etch resin cement was higher compared to RMGIC for all three surface treatments done on test samples. Hundred percent samples treated by all three surface treatment methods showed mixed type of failure.


Assuntos
Éter , Cetonas , Cimentos de Ionômeros de Vidro , Teste de Materiais , Estudos Prospectivos
5.
Acta Orthop Belg ; 87(3): 521-527, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34808727

RESUMO

A variety of different plate designs and materials are available to treat distal radius fractures. This study evaluates clinical results with a carbon fibre- reinforced (CFR)-polyether ether ketone (PEEK) plate in comparison to a standard titanium plate. Thirty-one distal radius fractures were included in this randomised controlled trial. Five fractures were classified as type A, 6 as type B and 20 as type C, in accordance with the AO classification. Patients were randomly allocated into two groups : 15 patients for titanium palmar plating (TPP) and 16 patients for PEEK palmar plating (PPP). Follow-up examinations were set at 2 weeks, 6 weeks, 3 months, 6 months and 3 years postop. In terms of wrist range of motion, radiological evaluation (alignment and fracture healing), DASH score (Disabilities of Arm, Shoulder and Hand), and VAS (visual analogue scale), no statistically significant differences were detected between the two groups, at all follow-up intervals. PEEK palmar plating and titanium plates give equivalent clinical and radiological outcomes up to 3 years follow-up.


Assuntos
Fraturas do Rádio , Titânio , Benzofenonas , Placas Ósseas , Seguimentos , Fixação Interna de Fraturas , Humanos , Cetonas , Polímeros , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular , Resultado do Tratamento
6.
Anticancer Res ; 41(10): 5007-5014, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34593449

RESUMO

BACKGROUND/AIM: In our previous study, first-line eribulin (ERI) showed 25 weeks of progression-free survival (PFS). This study investigated the efficacy and safety of ERI re-administration in metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: HER2-negative MBC patients who had never received chemotherapy for MBC received first-line ERI for 18 weeks if they did not have disease progression, and then one cycle of S-1 before ERI re-administration. RESULTS: Twelve patients received ERI re-administration. The PFS of re-administered ERI was 13 weeks. Total duration of ERI use was 30 weeks. The incidence and severity of adverse events were consistent with previous reports. CONCLUSION: In the first-line setting, the total PFS of eribulin was extended by S-1 administration before disease progression, compared with that of our previous report.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/metabolismo , Adulto , Idoso , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Furanos/administração & dosagem , Humanos , Cetonas/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Retratamento , Taxa de Sobrevida
7.
In Vivo ; 35(6): 3107-3110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34697141

RESUMO

BACKGROUND/AIM: Primary osteosarcoma of the mammary gland is a very rare disease, accounting for less than 1% of all mammary malignancies. There is no established first-line treatment and the prognosis is poor compared to normal breast cancer. We previously established the first patient tumor-derived animal model of this disease, grown subcutaneously in nude mice. In the present study, we established a patient derived orthotopic xenograft (PDOX) model of osteosarcoma of the breast and investigated the efficacy of cisplatinum (CDDP) and eribulin (ERB). MATERIALS AND METHODS: PDOX models of primary osteosarcoma of the breast were divided into 3 groups (5-6 mice per group): untreated control; CDDP treatment; ERB treatment. The tumor volume in the 3 groups was compared after 2 weeks. RESULTS: There were significant differences between control and CDDP, and control and ERB (p=0.036, 0.046, respectively). However, there was no significant difference between CDDP and ERB (p=0.964). CONCLUSION: CDDP and ERB are candidates for first-line clinical therapy of primary osteosarcoma of the breast.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Animais , Neoplasias Ósseas/tratamento farmacológico , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos , Furanos , Xenoenxertos , Humanos , Cetonas , Camundongos , Camundongos Nus , Osteossarcoma/tratamento farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Mater Sci Eng C Mater Biol Appl ; 130: 112451, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34702530

RESUMO

Long carbon fiber reinforced polyether ether ketone (LCFRPEEK) is fabricated using a three-dimensional (3D) needle-punched method in our previous work, which is considered as a potential orthopedic implant due to its high mechanical strength and isotropic properties, as well as having an elastic modulus similar to human cortical bone. However, the LCFRPEEK has inferior integration with bone tissue, limiting its clinical application. Thus, a facile surface modification method, using gelatin methacrylate/polyacrylamide composite hydrogel coating (GelMA/PAAM) loading with dexamethasone (Dex) on our newly-developed LCFRPEEK composite via concentrated sulfuric acid sulfonating and ultraviolet (UV) irradiation grafting methods, has been developed to tackle the problem. The results demonstrate that the GelMA/PAAM/Dex coating modified sulfonated LCFRPEEK (SCP/GP/Dex) has a hydrophilicity surface, a long-term Dex release capability and forms more bone-like apatite nodules in SBF. The SCP/GP/Dex also displays enhanced cytocompatibility and osteogenic differentiation in terms of rat bone marrow mesenchymal stem cells (rBMSCs) responses in vitro assay. The in vivo rat cranial defect assay confirms that SCP/GP/Dex boosts bone regeneration/osseointegration, which significantly improves osteogenic fixation between the implant and bone tissue. Therefore, the newly-developed LCFRPEEK modified via GelMA/PAAM/Dex bioactive coating exhibits improved biocompatibility and osteogenic integration capability, which has the basis for an orthopedic implant for clinical application.


Assuntos
Hidrogéis , Osteogênese , Animais , Fibra de Carbono , Proliferação de Células , Éteres , Cetonas/farmacologia , Ratos
9.
Molecules ; 26(20)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684840

RESUMO

Fresh roselle are high in moisture and deteriorate easily, which makes drying important for extending shelf-life and increasing availability. This study investigated the influence of different drying methods (oven-drying, freeze-drying, vacuum-drying, and sun-drying) on the quality of roselle calyx expressed as physicochemical properties (moisture content, water activity, soluble solids, color), volatile compounds, and microstructure. Oven-drying and freeze-drying reduced moisture content most while vacuum-drying and sun-drying were not as efficient. All drying methods except sun-drying resulted in water activities low enough to ensure safety and quality. Vacuum-drying had no impact on color of the dry calyx and only small impact on color of water extract of calyx. Drying reduced terpenes, aldehydes, and esters but increased furans. This is expected to reduce fruity, floral, spicy, and green odors and increase caramel-like aroma. Sun-drying produced more ketones, alcohols, and esters. Scanning electron microscopy revealed that freeze-drying preserved the cell structure better, and freeze-dried samples resembled fresh samples most compared to other drying techniques. The study concludes that freeze-drying should be considered as a suitable drying method, especially with respect to preservation of structure.


Assuntos
Flores/química , Hibiscus/química , Odorantes/análise , Compostos Orgânicos Voláteis/química , Álcoois/química , Aldeídos/química , Dessecação/métodos , Ésteres/química , Liofilização/métodos , Frutas/química , Cetonas/química , Extratos Vegetais/química , Terpenos/química
10.
Molecules ; 26(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684796

RESUMO

The unique fruity aroma of strawberries, a popular fruit of high economic value, is closely related to all the volatile organic compounds (VOCs) contained within them. Despite extensive studies on the identification of VOCs in strawberries, systematic studies on fruit-aroma-related VOCs are few, resulting in a lack of effective standards for accurately distinguishing aroma types. In the present study, solid-phase micro extraction and gas chromatography-mass spectrometry were used to analyze and identify VOCs in the ripe fruit of each of the 16 strawberry varieties at home and abroad and to explore their characteristic aroma components and the classification of such varieties by aroma type. The results suggested remarkable variations in the types and contents of VOCs in different strawberry varieties, of which esters were dominant. The principal volatile components, consisting of four esters, three alcohols, one aldehyde, and one ketone, in 16 strawberry varieties were detected based on the absolute and relative contents of VOCs in the fruit. The characteristic aroma components in strawberries, containing nine esters, six aldehydes, and one alcohol, were determined based on the aroma values of different VOCs, and the characteristic aroma components were divided into five types further based on aroma descriptions. Sixteen strawberry varieties were finally divided into four aroma types, namely, peachy, pineapple, fruity, and floral, based on the contributions of different types. The results provided a basis and standard for classifying strawberries by aroma type, studying the hereditary regularity of the fruity aroma of strawberries, and improving aroma quality.


Assuntos
Fragaria/química , Fragaria/classificação , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Álcoois/análise , Aldeídos/análise , Ésteres/análise , Frutas/química , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Cetonas/análise , Microextração em Fase Sólida , Especificidade da Espécie , Compostos Orgânicos Voláteis/química
11.
J Physiol ; 599(21): 4763-4778, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34605026

RESUMO

Adults with obesity are at increased risk of neurocognitive impairments, partly as a result of reduced cerebral blood flow and brain-derived neurotrophic factor (BDNF). Ketone supplements containing ß-hydroxybutyrate (ß-OHB) are a purported therapeutic strategy for improving brain health in at-risk populations. We tested the hypothesis that short-term ß-OHB supplementation will elevate cerebral blood flow and BDNF, as well as improve cognition in adults with obesity. In a placebo-controlled double-blind, cross-over design, 14 adults with obesity (10 females; aged 56 ± 12 years; body mass index = 33.8 ± 6.9 kg m-2 ) consumed 30 mL (12 g) of ß-OHB or placebo thrice-daily for 14 days. Blood flow (Q) and cerebrovascular conductance (CVC) were measured in the common carotid (CCA), internal carotid (ICA) and vertebral (VA) arteries by duplex ultrasound. BDNF was measured by an enzyme-linked immunosorbent assay. Cognition was assessed by the digit-symbol substitution (DSST), Stroop and task-switching tests. Following 14 days of ketone supplementation, we observed significant improvements in cerebrovascular outcomes including QCCA (+12%), QVA (+11%), VACVC (+12%) and VA shear rate (+10%). DSST performance significantly improved following ketone supplementation (+2.7 correct responses) and improved DSST performance was positively associated improvements in cerebrovascular outcomes including QCCA , CCACVC , QVA and VACVC . By contrast to one hypothesis, ß-OHB did not impact fasting serum and plasma BDNF. ß-OHB supplementation improved cognition in adults with obesity, which may be partly facilitated by improvements in cerebral blood flow. ß-OHB supplementation was well-tolerated and appears to be safe for cerebrovascular health, suggesting potential therapeutic benefits of ß-OHB in a population at risk of neurocognitive impairment. KEY POINTS: People with obesity are at increased risk of neurocognitive dysfunction, partly as a result of -induced reductions in cerebral blood flow (CBF) and brain-derived neurotrophic factor (BDNF). Ketone supplements containing ß-hydroxybutyrate (ß-OHB) reduce postprandial hyperglycaemia, which may increase CBF and BDNF, thereby protecting against obesity-related cognitive dysfunction. We show for the first time that 14 days of thrice-daily ß-OHB supplementation improves aspects of cognition and increases cerebrovascular flow, conductance and shear rate in the extracranial arteries of adults with obesity. Our preliminary data indicate a significant positive relationship between elevated CBF and improved cognition following ß-OHB supplementation. This trial provides a foundation for the potential non-pharmacological therapeutic application of ß-OHB supplementation in patient groups at risk of hyperglycaemic cerebrovascular disease and cognitive dysfunction.


Assuntos
Circulação Cerebrovascular , Cetonas , Adulto , Cognição , Estudos Cross-Over , Suplementos Nutricionais , Feminino , Humanos , Obesidade/complicações
12.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641285

RESUMO

A library of bile-acid-appended triazolyl aryl ketones was synthesized and characterized by detailed spectroscopic techniques such as 1H and 13C NMR, HRMS and HPLC. All the synthesized conjugates were evaluated for their cytotoxicity at 10 µM against MCF-7 (human breast adenocarcinoma) and 4T1 (mouse mammary carcinoma) cells. In vitro cytotoxicity studies on the synthesized conjugates against MCF-7 and 4T1 cells indicated one of the conjugate 6cf to be most active against both cancer cell lines, with IC50 values of 5.71 µM and 8.71 µM, respectively, as compared to the reference drug docetaxel, possessing IC50 values of 9.46 µM and 13.85 µM, respectively. Interestingly, another compound 6af (IC50 = 2.61 µM) was found to possess pronounced anticancer activity as compared to the reference drug docetaxel (IC50 = 9.46 µM) against MCF-7. In addition, the potent compounds (6cf and 6af) were found to be non-toxic to normal human embryonic kidney cell line (HEK 293), as evident from their cell viability of greater than 86%. Compound 6cf induces higher apoptosis in comparison to 6af (46.09% vs. 33.89%) in MCF-7 cells, while similar apoptotic potential was observed for 6cf and 6af in 4T1 cells. The pharmacokinetics of 6cf in Wistar rats showed an MRT of 8.47 h with a half-life of 5.63 h. Clearly, these results suggest 6cf to be a potential candidate for the development of anticancer agents.


Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/síntese química , Ácidos e Sais Biliares/química , Cetonas/administração & dosagem , Cetonas/síntese química , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Humanos , Cetonas/química , Cetonas/farmacocinética , Células MCF-7 , Masculino , Camundongos , Estrutura Molecular , Ratos , Ratos Wistar , Relação Estrutura-Atividade
13.
Molecules ; 26(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34641289

RESUMO

The dihydropyranoindole structures were previously identified as promising scaffolds for improving the anti-cancer activity of histone deacetylase inhibitors. This work describes the synthesis of related furoindoles and their ability to synergize with suberoylanilide hydroxamic acid (SAHA) against neuroblastoma and breast cancer cells. The nucleophilic substitution of hydroxyindole methyl esters with α-haloketones yielded the corresponding arylether ketones, which were subsequently cyclized to tricyclic and tetracyclic furoindoles. The furoindoles showed promising individual cytotoxic efficiency against breast cancer cells, as well as decent SAHA enhancement against cancer cells in select cases. Interestingly, the best IC50 value was obtained with the non-cyclized intermediate.


Assuntos
Neoplasias da Mama/enzimologia , Inibidores de Histona Desacetilases/farmacologia , Cetonas/síntese química , Neuroblastoma/enzimologia , Vorinostat/farmacologia , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Compostos Heterocíclicos/síntese química , Compostos Heterocíclicos/química , Compostos Heterocíclicos/farmacologia , Humanos , Cetonas/química , Cetonas/farmacologia , Células MCF-7 , Neuroblastoma/tratamento farmacológico
14.
Mater Sci Eng C Mater Biol Appl ; 128: 112333, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474884

RESUMO

Polyetheretherketone (PEEK) was widely applied into fabricating of orthopaedic implants, benefitting its excellent biocompatibility and similar mechanical properties to native bones. However, the inertness of PEEK hinders its integration with the surrounding bone tissue. Here PEEK scaffolds with a series of hydroxyapatite (HA) contents in gradient were manufactured via fused filament fabrication (FFF) 3D printing techniques. The influence of the pore size, HA content and printing direction on the mechanical properties of the PEEK/HA scaffolds was systematically evaluated. By adjusting the pore size and HA contents, the elastic modulus of the PEEK/HA scaffolds can be widely tuned in the range of 624.7-50.6 MPa, similar to the variation range of natural cancellous bone. Meanwhile, the scaffolds exhibited higher Young's modulus and lower compressive strength along Z printing direction. The mapping relationship among geometric parameters, HA content, printing direction and mechanical properties was established, which gave more accurate predictions and controllability of the modulus and strength of scaffolds. The PEEK/HA scaffolds with the micro-structured surface could promote cell attachment and mineralization in vitro. Therefore, the FFF-printed PEEK/HA composites scaffolds can be a good candidate for bone grafting and tissue engineering.


Assuntos
Durapatita , Cetonas , Benzofenonas , Polietilenoglicóis , Polímeros , Porosidade , Impressão Tridimensional , Tecidos Suporte
15.
Nat Commun ; 12(1): 5563, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34548479

RESUMO

Immune checkpoint inhibitors (ICIs) have minimal therapeutic effect in hormone receptor-positive (HR+ ) breast cancer. We present final overall survival (OS) results (n = 88) from a randomized phase 2 trial of eribulin ± pembrolizumab for patients with metastatic HR+ breast cancer, computationally dissect genomic and/or transcriptomic data from pre-treatment tumors (n = 52) for molecular associations with efficacy, and identify cytokine changes differentiating response and ICI-related toxicity (n = 58). Despite no improvement in OS with combination therapy (hazard ratio 0.95, 95% CI 0.59-1.55, p = 0.84), immune infiltration and antigen presentation distinguished responding tumors, while tumor heterogeneity and estrogen signaling independently associated with resistance. Moreover, patients with ICI-related toxicity had lower levels of immunoregulatory cytokines. Broadly, we establish a framework for ICI response in HR+ breast cancer that warrants diagnostic and therapeutic validation. ClinicalTrials.gov Registration: NCT03051659.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Furanos/uso terapêutico , Cetonas/uso terapêutico , Adulto , Idoso , Apresentação do Antígeno/genética , Antígeno B7-H1/metabolismo , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Citocinas/sangue , Citocinas/imunologia , Resistencia a Medicamentos Antineoplásicos/genética , Estrogênios/metabolismo , Feminino , Perfilação da Expressão Gênica , Heterogeneidade Genética , Genoma Humano/genética , Genômica , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Transdução de Sinais/genética , Taxa de Sobrevida , Resultado do Tratamento
16.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576025

RESUMO

Aziridination reactions represent a powerful tool in aziridine synthesis. Significant progress has been achieved in this field in the last decades, whereas highly functionalized aziridines including 3-arylated aziridine-2-carbonyl compounds play an important role in both medical and synthetic chemistry. For the reasons listed, in the current review we have focused on the ways to obtain 3-arylated aziridines and on the recent advances (mainly since the year 2000) in the methodology of the synthesis of these compounds via aziridination.


Assuntos
Aziridinas/química , Cetonas/química , Aziridinas/síntese química , Ácidos Carboxílicos/química , Iminas/química , Estrutura Molecular , Estereoisomerismo
17.
J Mech Behav Biomed Mater ; 124: 104811, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34500354

RESUMO

The control of interfacial interaction between polymers and fillers is essential for the fabrication of high-performance polymer composites. In this work, poly(ether-ether-ketone)/silica (PEEK/SiO2) and PEEK/SiO2/graphene oxide (GO) composite were prepared by ball milling-ultrasonic dispersion combined with melt extrusion injection molding. GO nanosheets were introduced as the interfacial enhancer to improve interfacial binding between SiO2 and PEEK. Mechanical tests showed that the incorporation of SiO2 and GO greatly optimized the modulus, strength, and fracture toughness of the composites. The tensile strength and Young's modulus of the PEEK/SiO2 composites increases with the increase of SiO2 content. The maximum tensile strength and Young's modulus of the PEEK/SiO2 composites are approximate 95.9 ± 0.6 MPa and 4.007 ± 0.005 GPa at 30 wt% of SiO2, an increase of 6.4% and 21.2% than that of pure PEEK. The maximum tensile strength and Young's modulus of the PEEK/SiO2/GO composite are further improved to approximate 101.5 ± 0.7 MPa and 4.62 ± 0.08 GPa at a GO content of 1.5% wt, which is 12.6% and 39.4% higher than that of pure PEEK. In addition, SEM images show that numerous HA formed on the surface of the PEEK/SiO2/GO composite after immersion in SBF for 7 days, and the HA layer becomes gradually thicker after 14 days, implying the good osteogenic activity of PEEK/SiO2/GO composites. Therefore, these results suggest that the use of GO as a novel filler surface modifier for the preparation of high-performance composites may become a novel interfacial design strategy for the development of high-performance composites.


Assuntos
Cetonas , Dióxido de Silício , Éter , Éteres , Grafite , Polietilenoglicóis
18.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500600

RESUMO

Carbon-carbon bond forming reactions, such as aldol reaction and condensation, belong to extremely desired transformations as manifested by >25,000 entries in SciFinder. Their stereoselective variant requires the use of an appropriate catalyst with a strictly defined structure. Hence, chiral 2-azabicycloalkane-based catalysts were designed, synthesized and tested in a stereoselective aldol reaction between cyclic/acyclic ketone and p-nitrobenzaldehyde both in organic and aqueous media. Among catalysts containing a chiral bicyclic backbone, amide based on 2-azabicyclo[3.2.1]octane and pyrrolidine units showed the best catalytic activity and afforded aldol product in excellent chemical yields (up to 95%) and good diastereo- and enantioselectivity (dr 22:78, ee up to 63%).


Assuntos
Aminoácidos/química , Cicloparafinas/química , Poliaminas/química , Amidas/química , Carbono/química , Catálise , Cetonas/química , Pirrolidinas/química , Estereoisomerismo
19.
Aerosp Med Hum Perform ; 92(7): 556-562, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34503629

RESUMO

BACKGROUND: During hypoxia an operators cognitive performance may decline. This decline is linked to altered brain metabolism, resulting in decreased adenosine triphosphate (ATP) production. Ketone bodies are an alternative substrate to glucose for brain metabolic requirements; previous studies have shown that the presence of elevated ketone bodies in the blood maintains brain ATP levels and reduces cerebral glycolysis during hypoxia. Thus, ketones may be a strategy to mitigate cognitive decline in hypoxia. Ketone ester (KE) consumption allows rapid elevation of blood ketone levels; therefore, we investigated the effects of consuming a KE drink on cognitive performance during hypoxia. Here, we report results of a pilot study.METHODS: There were 11 subjects who completed a cognitive performance test battery under conditions of normoxia and hypoxia following consumption of a KE drink and a placebo control drink.RESULTS: Significant hypoxia effects (O2 saturation minimum was found to range between 63 and 88 in subjects) were found for blink duration (Ph2 0.665) and blink rate (Ph2 0.626), indicating that the hypoxia condition was associated with longer blink durations and lower blink rates. Significant hypoxia effects were likewise observed for a code substitution task (Ph2 0.487), indicating that performance on the task was significantly disrupted by the hypoxia stressor. KE consumption had a significant effect on blink duration (Ph2 0.270) and the code substitution task (Ph2 0.309).DISCUSSION: These finding suggest that some effects of acute hypoxia can be mitigated by nutritional ketosis.Coleman K, Phillips J, Sciarini M, Stubbs B, Jackson O, Kernagis D. A metabolic intervention for improving human cognitive performance during hypoxia. Aerosp Med Hum Perform. 2021; 92(7):556562.


Assuntos
Cetose , Cognição , Humanos , Hipóxia , Cetonas , Projetos Piloto
20.
Molecules ; 26(18)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34576900

RESUMO

The conversion of ribonucleosides to 2'-deoxyribonucleosides is catalyzed by ribonucleoside reductase enzymes in nature. One of the key steps in this complex radical mechanism is the reduction of the 3'-ketodeoxynucleotide by a pair of cysteine residues, providing the electrons via a disulfide radical anion (RSSR•-) in the active site of the enzyme. In the present study, the bioinspired conversion of ketones to corresponding alcohols was achieved by the intermediacy of disulfide radical anion of cysteine (CysSSCys)•- in water. High concentration of cysteine and pH 10.6 are necessary for high-yielding reactions. The photoinitiated radical chain reaction includes the one-electron reduction of carbonyl moiety by disulfide radical anion, protonation of the resulting ketyl radical anion by water, and H-atom abstraction from CysSH. The (CysSSCys)•- transient species generated by ionizing radiation in aqueous solutions allowed the measurement of kinetic data with ketones by pulse radiolysis. By measuring the rate of the decay of (CysSSCys)•- at λmax = 420 nm at various concentrations of ketones, we found the rate constants of three cyclic ketones to be in the range of 104-105 M-1s-1 at ~22 °C.


Assuntos
Biomimética , Dissulfetos , Cetonas , Radical Hidroxila/química , Cinética , Água
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