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1.
Food Chem ; 371: 131162, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34600368

RESUMO

The effects of combined treatment (PAL-U) of plasma-activated liquid (PAL) including plasma-activated water (PAW) and plasma-activated buffer solution (PABS) and ultrasound (U) for the degradation of chlorothalonil fungicide on tomato fruit was investigated. Distilled water and buffer solution were activated by radiofrequency plasma jet for durations of 1, 3, 5, and 10 min to obtain PAL1 to PAL10. Fruits were immersed in PAL for 15 min and also in distilled water with sonication for 15 min for individual treatments, and in PAL with sonication for 15 min for combined treatments. The maximum chlorothalonil fungicide residues were reduced by 89.28 and 80.23% for PAW10-U and PABS10-U, respectively. HPLC-MS characterization revealed chlorothalonil degradation pathway and formation of 2,4,5-trichloroisophthalonitrile, 2,4-dichloroisophthalonitrile, 4-chloroisophthalonitrile, isophthalonitrile and phenylacetonitrile as degradation products. Treatments also showed no negative effects on tomato quality. Therefore, PAL and PAL-U treatments could serve as effective methods for degrading pesticides on tomatoes.


Assuntos
Fungicidas Industriais , Lycopersicon esculentum , Resíduos de Praguicidas , Fungicidas Industriais/análise , Nitrilas/análise , Resíduos de Praguicidas/análise
2.
J Colloid Interface Sci ; 607(Pt 2): 1603-1612, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34592547

RESUMO

Crystalline carbon nitride is regarded as the new generation of emerging metal-free photocatalysts as opposed to polymeric carbon nitride (g-C3N4) because of its high crystalline structure and ultrahigh photocatalytic water splitting performance. However, further advances in crystalline g-C3N4 are significantly restricted by the sluggish separation of charge carriers and limited active sites. In this study, we demonstrate the successful synthesis of heptazine-triazine donor-acceptor-based ultrathin crystalline g-C3N4 nanosheets (UCCN) using a combined hot air exfoliation and molten salt (NaCl/KCl) copolymerization approach. The synergy of the donor-acceptor heterojunction and the ultrathin structure greatly accelerated the separation of the charge carriers and enriched the active sites. Accordingly, the superior hydrogen evolution activity and an ultrahigh apparent quantum efficiency of 73.6% at 420 nm under a natural photosynthetic environment were achieved by UCCN, positioning this material at the top among reported conjugated g-C3N4 materials. This study provides a novel paradigm for the development of donor-acceptor-based ultrathin crystalline layered materials.


Assuntos
Hidrogênio , Nitrilas , Água
3.
Sci Total Environ ; 802: 149938, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34525687

RESUMO

Deltamethrin (DM), a type II pyrethroid insecticide, is widely used to control agricultural pests. However, its excessive use exerts a detrimental effect on the ecological environment and human health, indicating the need to study its potential risks in detail. In the present study, zebrafish embryos were exposed to varying concentrations of DM (0.1, 1, 10, and 25 µg/L) for 96 h to assess the alterations in the transcript levels of proteins of the estrogenic and dopaminergic pathways. In addition, its effect on zebrafish locomotor activity was studied. The mRNA expression of cyp19a1b, erα, erß2, fshr, gnrh2, gnrhr3, vtg3, dat, and dr1 significantly changed after exposing the embryos to DM. Deltamethrin at 10 and 25 µg/L significantly reduced the average swimming speed of zebrafish larvae. In addition, embryos injected with zebrafish estrogen receptor α (erα) and ß (erß) morpholinos and co-exposed to 25 µg/L DM for 96 h showed reduced expression of vtg3 mRNA compared to embryos exposed to 25 µg/L DM only. The locomotor activity of erα and erß knockdown zebrafish following DM exposure was increased significantly when compared with that of larvae exposed to 25 µg/L DM only. Our results demonstrated that DM altered the locomotor activity of zebrafish larvae and the transcript levels of the components of estrogenic and dopaminergic pathways; erα and erß knockdown weakened these effects.


Assuntos
Piretrinas , Peixe-Zebra , Animais , Embrião não Mamífero , Humanos , Larva , Nitrilas , Piretrinas/toxicidade , Receptores de Estrogênio/genética
4.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120385, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536885

RESUMO

In this work, a strong blue-emitting fluorescent biosensor based on graphite carbon nitride nanoparticles (GCNNs) (Ex = 340 nm and Em = 435 nm) was synthesized by a facile one-step hydrothermal method. With the aid of hydrogen peroxide and horseradish peroxidase, pyrocatechol structure of dopamine (DA) was oxidized to o-quinone structure of polydopamine (PDA) by hydroxyl radical. PDA was able to rapidly and significantly quench fluorescence of GCNNs. In the meanwhile, oxidative self-polymerization from DA to PDA would be blocked by antioxidants, such as glutathione (GSH) and ascorbic acid (AA). Thus, the fluorescence of GCNNs@DA sensor would be recovered owing to the decrease of o-quinone. Based on above-mentioned dual recognition strategy of "turn-off" and "turn off-on", a fast, simple and ultrasensitive method was developed to measure DA and antioxidants. Under the optimal experimental conditions, the detection limits of DA, GSH and AA were 0.064 µmol L-1, 0.11 µmol L-1 and 0.16 µmol L-1 with relative standard deviations of 1.7%, 9.3% and 8.0%, respectively. As one of metal-free quantum dots, our GCNNs-based sensors were also successfully applied to the determination of DA as well as GSH and AA in human serum. The recoveries for the spiked samples were in the range of 93.8%-109% and 95.0%-110% of DA and antioxidants, which shows great promise to clinicalapplication.


Assuntos
Grafite , Pontos Quânticos , Antioxidantes , Carbono , Dopamina , Humanos , Limite de Detecção , Nitrilas , Soro
5.
Sci Total Environ ; 802: 149764, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461477

RESUMO

Intensive and indiscriminate use of insecticides in agroecosystems causes phytotoxic disturbances in non-target crops. However, the mechanisms by which plants reprogram cellular metabolites to resist and tolerate such agrochemicals remain unclear. Here, the interaction between lettuce plants with imidacloprid and fenvalerate was investigated by the complementary use of physiological and metabolomic analyses. Neither imidacloprid nor fenvalerate induced overt phytotoxicity in lettuce seedlings. The plant biomass, chlorophyll fluorescence, lipid peroxidation, and membrane integrity were not significantly affected by the selected insecticides. Flavonoid content decreased by 25% in lettuce leaves under fenvalerate exposure, whereas polyphenol and flavonoid contents were not significantly altered by imidacloprid. Although the content of most of the nutrient element in the leaves remained the same following pesticide treatment, iron content decreased by 28.1% under imidacloprid exposure but increased by 22.8% under fenvalerate exposure. Metabolomic analysis revealed that the selected insecticides induced extensive metabolic reprogramming in lettuce roots and shoots. Imidacloprid dramatically increased the metabolism of several amino acids (arginine, cysteine, homoserine, and 4-hydroxyisoleucine), whereas markedly decreased the metabolism of various carbohydrates (glucose, raffinose, maltotetraose, maltopentaose, and stachyose). Fenvalerate did not significantly alter amino acid metabolism but decreased carbohydrate metabolism. Additionally, the relative abundance of most organic acids and polyphenolic compounds decreased significantly after pesticide exposure. These results suggest that plants might program their primary and secondary metabolism to resist and tolerate insecticides. The findings of this study provide important information on how neonicotinoid and pyrethroid insecticides affect the health and physiological state of plants, which are ultimately associated with crop yield and quality.


Assuntos
Alface , Piretrinas , Neonicotinoides/toxicidade , Nitrilas , Nitrocompostos , Folhas de Planta , Piretrinas/toxicidade
6.
Anal Chim Acta ; 1187: 339143, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34753569

RESUMO

A novel methodology has been applied to generate a porous molecularly imprinted material for highly selective and sensitive recognition of Janus kinase inhibitor ruxolitinib (RUX). The porous material-based nucleobase-derivative functional monomer was developed by a photopolymerization method. The thymine methacrylate (ThyM) as a functional monomer was synthesized and copolymerized with 2-hydroxyethyl methacrylate (HEMA) in the presence of ethylene glycol dimethacrylate (EGDMA) onto the glassy carbon electrode [glassy carbon electrode/molecularly imprinted polymer@poly(2-hydroxyethyl methacrylate-co-thymine methacrylate), (GCE/MIP@PHEMA-ThyM)] for the first time. The presence of ThyM results in the functional groups in imprinting binding sites, while the presence of poly(vinyl alcohol) (PVA) allows to generate porous materials for sensitive sensing. The characterization of GCE/MIP@PHEMA-ThyM was investigated by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and impedance spectroscopy technique. Then, the porous MIP modified glassy carbon electrode was optimized with effecting parameters including removal agent, removal time, and incubation time to get a better response for RUX. Under well-controlled optimum conditions, the GCE/MIP@PHEMA-ThyM linearly responded to the RUX concentration up to 0.01 pM at the limit of detection (LOD) of 0.00191 pM. The non-imprinted polymer (NIP) was also prepared to serve as a control in the same way but without the template. The proposed method improves the accessibility of binding sites by generating the porous material resulting in highly selective and sensitive recognition of drugs in the pharmaceutical dosage form and synthetic human serum samples.


Assuntos
Antineoplásicos , Impressão Molecular , Humanos , Nitrilas , Porosidade , Pirazóis , Pirimidinas , Espectroscopia de Infravermelho com Transformada de Fourier
7.
BMJ Case Rep ; 14(11)2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725058

RESUMO

Ruxolitinib (RUX) is a kinase inhibitor used in the treatment of various medical conditions and its mechanism of action involves suppression of the immune system. While beneficial in treatment of polycythemia vera, myelofibrosis and other indications, it can also increase a patient's susceptibility to various infections, including bacterial, viral and fungal. We present a case of a patient being treated with RUX who presented with a disseminated fungal infection. This case emphasises the need for vigilance of endemic fungal infections in individuals who are on RUX therapy.


Assuntos
Blastomicose , Policitemia Vera , Mielofibrose Primária , Humanos , Nitrilas , Policitemia Vera/complicações , Policitemia Vera/tratamento farmacológico , Mielofibrose Primária/complicações , Mielofibrose Primária/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas
8.
Planta ; 254(6): 119, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34762174

RESUMO

MAIN CONCLUSION: Developmental and organ-specific expression of genes in dhurrin biosynthesis, bio-activation, and recycling offers dynamic metabolic responses optimizing growth and defence responses in Sorghum. Plant defence models evaluate the costs and benefits of resource investments at different stages in the life cycle. Poor understanding of the molecular regulation of defence deployment and remobilization hampers accuracy of the predictions. Cyanogenic glucosides, such as dhurrin are phytoanticipins that release hydrogen cyanide upon bio-activation. In this study, RNA-seq was used to investigate the expression of genes involved in the biosynthesis, bio-activation and recycling of dhurrin in Sorghum bicolor. Genes involved in dhurrin biosynthesis were highly expressed in all young developing vegetative tissues (leaves, leaf sheath, roots, stems), tiller buds and imbibing seeds and showed gene specific peaks of expression in leaves during diel cycles. Genes involved in dhurrin bio-activation were expressed early in organ development with organ-specific expression patterns. Genes involved in recycling were expressed at similar levels in the different organ during development, although post-floral initiation when nutrients are remobilized for grain filling, expression of GSTL1 decreased > tenfold in leaves and NITB2 increased > tenfold in stems. Results are consistent with the establishment of a pre-emptive defence in young tissues and regulated recycling related to organ senescence and increased demand for nitrogen during grain filling. This detailed characterization of the transcriptional regulation of dhurrin biosynthesis, bioactivation and remobilization genes during organ and plant development will aid elucidation of gene regulatory networks and signalling pathways that modulate gene expression and dhurrin levels. In-depth knowledge of dhurrin metabolism could improve the yield, nitrogen use efficiency and stress resilience of Sorghum.


Assuntos
Sorghum , Expressão Gênica , Glicosídeos , Nitrilas , Sorghum/genética
9.
Clin Neuropharmacol ; 44(6): 240-242, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34767326

RESUMO

OBJECTIVES: A case of perampanel-induced psychosis in a young woman is reported, a side effect that has only rarely been reported in the literature. METHODS: We describe a case of a young woman with epilepsy and no psychiatric history with perampanel-associated altered behavior and psychotic symptoms, requiring hospitalization in an acute psychiatry ward. We also provide a literature review on the possible neurobiological pathways implicated. RESULTS: Perampanel is believed to block a small proportion of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor current, retarding epileptiform discharges while sparing most normal synaptic transmission. Most common adverse events are related to central nervous system (including dizziness, drowsiness, blurred vision and imbalance) and psychiatric symptoms have been reported. CONCLUSIONS: The biological vulnerability to psychiatric and behavioral adverse reactions of antiepileptic drugs is multifactorial and different mechanisms and clinical predisposing factors may interact. For this reason, patients starting these antiseizure drugs need long-term and comprehensive clinical monitoring.


Assuntos
Transtornos Psicóticos , Piridonas , Anticonvulsivantes/efeitos adversos , Feminino , Humanos , Nitrilas , Transtornos Psicóticos/tratamento farmacológico , Piridonas/efeitos adversos , Resultado do Tratamento
10.
Pestic Biochem Physiol ; 179: 104969, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34802519

RESUMO

Carboxylesterases (CarEs) usually play critical roles in the detoxification of toxic chemicals and therefore may be involved in insecticide resistance in agricultural pests. Previous work has shown that CarE 001C from Helicoverpa armigera was able to metabolize the isomers of cypermethrin and fenvalerate. In this study, seven mutants of CarE 001C with single amino acid substitution were produced and expressed in the Escherichia coli. Enzyme kinetic analysis indicated that all seven mutations dramatically reduced enzymatic activities toward the generic substrate α-naphthyl acetate, but in vitro metabolism assay showed that two of the mutations, H423I and R322L, significantly improved hydrolase activities toward fenvalerate, with their recorded specific activities being 3.5 and 5.1 nM·s-1·mg -1 proteins, respectively. Further, thermostability assay showed that the stability of one mutant enzyme was enhanced. This study will help us better understand the potential of CarEs in insecticide detoxification and resistance in H. armigera.


Assuntos
Inseticidas , Mariposas , Piretrinas , Animais , Carboxilesterase/genética , Carboxilesterase/metabolismo , Hidrolases de Éster Carboxílico/genética , Resistência a Inseticidas/genética , Inseticidas/farmacologia , Cinética , Mariposas/genética , Mariposas/metabolismo , Mutação , Nitrilas
11.
Front Public Health ; 9: 686122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760859

RESUMO

Various control interventions have been effective in the control of arthropod vectors to a certain extent; still, sustained vector control is an existing problem globally. Insecticide-based formulations have been found to be useful, however the proper delivery of active molecules to target vectors is important. Currently, synthetic pyrethroid deltamethrin (DM) has been microencapsulated in the emulsion paint binder and evaluated for long-term effectiveness against dengue vector Aedes aegypti. Different compositions of emulsion binder were prepared by varying the content of monomer and DM. A selection was made for the composition yielding the best combination of properties like solid content, intrinsic viscosity, and DM content. Developed formulation was tested against laboratory-reared and pathogen-free Ae. aegypti mosquitoes. Encapsulation of DM in emulsion binder during polymerization showed a uniform distribution. The optimized formulation was stable and did not have a considerable plasticizing effect. Scanning electron microscopy revealed that grain-like micro crystals of DM and surfactant sodium lauryl sulfate (SDS) were uniformly distributed on the formulation surface. The best optimized formulation was highly effective against dengue vector Ae. aegypti and found to provide efficacy for up to 18 months of application. The knockdown time (KDT) values KDT10 and KDT50 were 7.4 min (95% CI: 5.6-9.1) and 22.1 min (95% CI: 19.7-24.3) respectively, whereas 24 h corrected mortality was 90% (95% CI: 82.5-97.5) after 18 months of application (T18). The probit model used to determine knockdown values did not deviate from the linearity and displayed normal distribution of knockdown % with time for different formulations (p ≥ 0.1). Presently developed DM microencapsulated emulsion binder was stable, smooth, and uniform. The binder displayed excellent anti-insect property and was capable of providing long-term effectiveness against dengue vectors Ae. aegypti. Such a formulation after field-scale evaluation could be very useful in attaining long-term protection from arthropod vectors.


Assuntos
Aedes , Dengue , Animais , Dengue/prevenção & controle , Emulsões , Resistência a Inseticidas , Mosquitos Vetores , Nitrilas , Pintura , Piretrinas
12.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 33(5): 501-504, 2021 Aug 24.
Artigo em Chinês | MEDLINE | ID: mdl-34791848

RESUMO

OBJECTIVE: To investigate the susceptibility of Anopheles sinensis to malathion, deltamethrin and lambda-cyhalothrin in Puyang City, Henan Province, so as to provide the scientific basis for local malaria vector control. METHODS: An. sinensis was captured from Puyang County, Puyang City of Henan Province in September 2018 and July 2020, and the susceptibility of field captured An. sinensis to malathion, deltamethrin and lambda-cyhalothrin was tested using the filter-paper bioassay recommended by WHO. The insecticide resistance level was assessed based on the WHO criteria. RESULTS: In 2018 and 2010, the half knock-down times (KT50) of malathion were 91.08 min and 40.95 min for An. sinensis, with knock-down rates of 37.50% and 60.87% 60 min post-exposure to malathion and 24-hour mortality rates of 90.91% and 100%, respectively, and the insecticide resistance levels were moderately resistant (M) and susceptible (S). The KT50 of deltamethrin were 415.56 min and 341.19 min for An. sinensis in 2018 and 2020, with knock-down rates of 22.92% and 16.98% 60 min post-exposure to malathion and 24-hour mortality rates of 22.92% and 16.98%, and the insecticide resistance levels were all resistant (R). The KT50 of lambda-cyhalothrin were 164.22 min and 236.22 min for An. sinensis in 2018 and 2020, with knock-down rates of 30.39% and 38.30% 60 min postexposure to malathion and 24 h mortality rates of 19.60% and 21.28%, respectively, and the insecticide resistance levels were all R. CONCLUSIONS: An. sinensis is relatively susceptible to malathion but has developed high-level resistance to deltamethrin and lambda-cyhalothrin in Puyang City, Henan Province..


Assuntos
Anopheles , Inseticidas , Malária , Piretrinas , Animais , Resistência a Inseticidas , Inseticidas/farmacologia , Controle de Mosquitos , Mosquitos Vetores , Nitrilas/farmacologia , Piretrinas/farmacologia
13.
J Agric Food Chem ; 69(45): 13425-13435, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34748318

RESUMO

Adaptation to phytochemicals in herbivorous insects can influence tolerance to insecticides. However, it is unclear how insects use phytochemicals as cues to activate their metabolic detoxification systems. In this study, we found that dietary exposure to xanthotoxin enhanced tolerance of Spodoptera litura larvae to λ-cyhalothrin. Xanthotoxin ingestion significantly elevated the mRNA levels of 35 detoxification genes as well as the transcription factors Cap 'n' collar isoform-C (CncC) and its binding factor small muscle aponeurosis fibromatosis isoform-K (MafK). Additionally, xanthotoxin exposure increased the levels of reactive oxygen species (ROS), while ROS inhibitor N-acetylcysteine (NAC) treatment blocked xanthotoxin-induced expression of CncC, MafK, and detoxification genes and also prevented xanthotoxin-enhanced larval tolerance to λ-cyhalothrin. The 20-hydroxyecdysone (20E) signaling pathway was effectively activated by xanthotoxin, while blocking of 20E signaling transduction prevented xanthotoxin-enhanced larval tolerance to λ-cyhalothrin. Application of 20E induced the expression of multiple xanthotoxin-induced detoxification genes and enhanced λ-cyhalothrin tolerance in S. litura. NAC treatment blocked xanthotoxin-induced 20E synthesis, while the CncC agonist curcumin activated the 20E signaling pathway. These results indicate that the ROS/CncC pathway controls the induction of metabolic detoxification upon exposure to xanthotoxin, at least in part, through its regulation of the 20E signaling pathway.


Assuntos
Ecdisterona , Inseticidas , Animais , Proteínas de Insetos/metabolismo , Inseticidas/farmacologia , Larva/genética , Larva/metabolismo , Metoxaleno , Nitrilas , Piretrinas , Espécies Reativas de Oxigênio , Transdução de Sinais , Spodoptera/genética , Spodoptera/metabolismo
15.
BMC Neurol ; 21(1): 410, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702211

RESUMO

BACKGROUND: When use of a single antiseizure medication (ASM) fails to induce seizure remission, add-on therapy is justified. Perampanel (PER) is approved in Europe as adjunctive therapy for focal, focal to bilateral tonic-clonic seizures and generalized tonic-clonic seizures. Aim of the study was to establish whether PER is suitable for first add-on use. METHODS: A Delphi methodology was adopted to assess consensus on a list of 39 statements produced by an Expert Board of 5 epileptologists. Using an iterative process, statements were finalized by a Delphi Panel of 84 Italian pediatric and adult neurologists. Each statement was rated anonymously to determine level of agreement on a 9-point Likert scale. Consensus was established as agreement by at least 80% of the panelists. The relevance of each statement was also assessed on a 3-point scale. RESULTS: Consensus was achieved for 37 statements. Characteristics of PER considered to justify its use as first add-on include evidence of a positive impact on quality of life based on long term retention data, efficacy, tolerability, and ease of use; no worsening of cognitive functions and sleep quality; a low potential for drug interactions; a unique mechanism of action. Potential unfavorable factors are the need for a relatively slow dose titration; the potential occurrence of behavioral adverse effects; lack of information on safety when used in pregnancy; limited access to plasma PER levels. CONCLUSION: Perampanel has many features which justify its use as a first add-on. Choice of an ASM as first add-on should be tailored to individual characteristics.


Assuntos
Anticonvulsivantes , Qualidade de Vida , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Consenso , Humanos , Itália , Nitrilas , Piridonas/uso terapêutico , Resultado do Tratamento
16.
BMJ Open ; 11(10): e052610, 2021 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-34697119

RESUMO

INTRODUCTION: This paper presents a study protocol for a comparative effectiveness evaluation of abiraterone acetate against enzalutamide in clinical practice, two cancer drugs given to patients suffering from advanced prostate cancer. METHOD AND ANALYSIS: The protocol designs a comparative-effectiveness analysis of abiraterone acetate against enzalutamide. With the substantial number of covariates a two-step procedure is suggested in choosing relevant covariates in the matching design. In the first step, an exploratory factor analysis reduces the dimension of a large set of continuous covariates to nine factors. In the second step, we reduce the dimension of the covariates, interactions and second order terms for the continuous covariates using propensity score estimation. The final design makes use of a genetic matching algorithm. The study protocol provides a detailed statistical analysis plan of the analysis sample derived from the matching design. The analysis will make use of linear regression and robust inference adjusted for multisignificance testing. DISCUSSION: As in a randomised experiment the focus is on the design of the assignment to treatment. This allows the publication of this preanalysis plan before having access to outcome data. This means that the p values will be correct if the maintained assumption of uncounfoundedness is valid. Given that is p-hacking is substantial problem in empirical research, this is a substantial strength of this study. However, while design yields, balance on the observed covariates one cannot discard the possibility that unobserved confounders are not balanced. For that reason, sensitivity tests for the maintained assumption of uncounfoundedness are presented. ETHICS AND DISSEMINATION: The study was approved by the Regional Ethical Review Board in Uppsala, Sweden (Dnr 2017/482). Results will be published in a peer-reviewed journal and distributed to relevant stakeholders in healthcare.


Assuntos
Acetato de Abiraterona , Neoplasias de Próstata Resistentes à Castração , Benzamidas , Humanos , Estudos Longitudinais , Masculino , Nitrilas , Feniltioidantoína , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Suécia , Resultado do Tratamento
17.
Molecules ; 26(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34641581

RESUMO

UV-Vis spectroscopy was used to investigate two new charge transfer (CT) complexes formed between the K+-channel-blocker amifampridine (AMFP) drug and the two π-acceptors 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tetracyanoethylene (TCNE) in different solvents. The molecular composition of the new CT complexes was estimated using the continuous variations method and found to be 1:1 for both complexes. The formed CT complexes' electronic spectra data were further employed for calculating the formation constants (KCT), molar extinction coefficients (εCT), and physical parameters at various temperatures, and the results demonstrated the high stability of both complexes. In addition, sensitive spectrophotometric methods for quantifying AMFP in its pure form were proposed and statistically validated. Furthermore, DFT calculations were used to predict the molecular structures of AMFP-DDQ and AMFP-TCNE complexes in CHCl3. TD-DFT calculations were also used to predict the electronic spectra of both complexes. A CT-based transition band (exp. 399 and 417 nm) for the AMFP-TCNE complex was calculated at 411.5 nm (f = 0.105, HOMO-1 → LUMO). The two absorption bands at 459 nm (calc. 426.9 nm, f = 0.054) and 584 nm (calc. 628.1 nm, f = 0.111) of the AMFP-DDQ complex were theoretically assigned to HOMO-1 → LUMO and HOMO → LUMO excitations, respectively.


Assuntos
Amifampridina/química , Benzoquinonas/química , Etilenos/química , Nitrilas/química , Fenômenos Químicos , Teoria da Densidade Funcional , Elétrons , Estrutura Molecular , Bloqueadores dos Canais de Potássio/química , Solventes/química , Espectroscopia de Infravermelho com Transformada de Fourier
18.
Biomacromolecules ; 22(11): 4618-4632, 2021 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-34647734

RESUMO

In recent years, polymers bearing reactive groups have received significant interest for biomedical applications. Numerous functional polymer platforms have been introduced, which allow for the preparation of materials with tailored properties via post-polymerization modifications. However, because of their reactivity, many functional groups are not compatible with the initial polymerization. The nitrile group is a highly interesting and relatively inert functionality that has mainly received attention in radical polymerizations. In this Article, a nitrile-functionalized 2-oxazoline monomer (2-(4-nitrile-butyl)-2-oxazoline, BuNiOx) is introduced, and its compatibility with the cationic ring-opening polymerization is demonstrated. Subsequently, the versatility of nitrile-functionalized poly(2-oxazoline)s (POx) is presented. To this end, diverse (co)polymers are synthesized and characterized by nuclear resonance spectroscopy, size-exclusion chromatography, and mass spectrometry. Amphiphilic block copolymers are shown to efficiently encapsulate the hydrophobic drug curcumin (CUR) in aqueous solution, and the anti-inflammatory effect of the CUR-containing nanostructures is presented in BV-2 microglia. Furthermore, the availability of the BuNiOx repeating units for post-polymerization modifications with hydroxylamine to yield amidoxime (AO)-functionalized POx is demonstrated. These AO-containing POx were successfully applied for the complexation of Fe(III) in a quantitative manner. In addition, AO-functionalized POx were shown to release nitric oxide intracellularly in BV-2 microglia. Thus nitrile-functionalized POx represent a promising and robust platform for the design of polymer therapeutics for a wide range of applications.


Assuntos
Nitrilas , Polímeros , Compostos Férricos , Oxazóis
19.
Gan To Kagaku Ryoho ; 48(10): 1259-1263, 2021 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-34657059

RESUMO

BACKGROUND: In step with the aging of the Japanese population, late recurrence of hormone receptor positive (HR+) breast cancer occurring especially beyond 20 years after the initial diagnosis has been recognized as not rare anymore, as it has been occurring at a constant rate lately. The administration of an aromatase inhibitor with a CDK4/6 inhibitor has become the gold standard in Japan for cases of recurring HR+ breast cancer without severe visceral metastasis. CASE: A 73- year-old woman was diagnosed by chance with late recurrence of HR+ breast cancer 21 years after undergoing radical resection followed by adjuvant anastrozole for 5 years for stage Ⅲb right breast cancer. Asymptomatic multiple bone metastases on her ribs and sternum with bilateral lung metastasis and malignant effusion all disappeared while she was on a year- long administration of anastrozole and an optimal dose of abemaciclib(100 mg bid). However, because of the Grade 3 digestive adverse event that occurred at approximately 1 year of treatment, she could only maintain the treatment for up to 13 months. After then, no recurrence has been detectable for 6 months so far. CONCLUSION: CDK4/6 inhibitors, in combination with anastrozole, will play a pivotal role in the initial approach to elderly patients with HR+ late recurrence as a chemotherapy- free strategy.


Assuntos
Neoplasias da Mama , Idoso , Aminopiridinas , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Benzimidazóis , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Feminino , Hormônios/uso terapêutico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Nitrilas/uso terapêutico
20.
Molecules ; 26(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684771

RESUMO

Excessive host inflammation following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with severity and mortality in coronavirus disease 2019 (COVID-19). We recently reported that the SARS-CoV-2 spike protein S1 subunit (S1) induces pro-inflammatory responses by activating toll-like receptor 4 (TLR4) signaling in macrophages. A standardized extract of Asparagus officinalis stem (EAS) is a unique functional food that elicits anti-photoaging effects by suppressing pro-inflammatory signaling in hydrogen peroxide and ultraviolet B-exposed skin fibroblasts. To elucidate its potential in preventing excessive inflammation in COVID-19, we examined the effects of EAS on pro-inflammatory responses in S1-stimulated macrophages. Murine peritoneal exudate macrophages were co-treated with EAS and S1. Concentrations and mRNA levels of pro-inflammatory cytokines were assessed using enzyme-linked immunosorbent assay and reverse transcription and real-time polymerase chain reaction, respectively. Expression and phosphorylation levels of signaling proteins were analyzed using western blotting and fluorescence immunomicroscopy. EAS significantly attenuated S1-induced secretion of interleukin (IL)-6 in a concentration-dependent manner without reducing cell viability. EAS also markedly suppressed the S1-induced transcription of IL-6 and IL-1ß. However, among the TLR4 signaling proteins, EAS did not affect the degradation of inhibitor κBα, nuclear translocation of nuclear factor-κB p65 subunit, and phosphorylation of c-Jun N-terminal kinase p54 subunit after S1 exposure. In contrast, EAS significantly suppressed S1-induced phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and Akt. Attenuation of S1-induced transcription of IL-6 and IL-1ß by the MAPK kinase inhibitor U0126 was greater than that by the Akt inhibitor perifosine, and the effects were potentiated by simultaneous treatment with both inhibitors. These results suggest that EAS attenuates S1-induced IL-6 and IL-1ß production by suppressing p44/42 MAPK and Akt signaling in macrophages. Therefore, EAS may be beneficial in regulating excessive inflammation in patients with COVID-19.


Assuntos
Asparagus (Planta)/química , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Asparagus (Planta)/metabolismo , Butadienos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Interleucina-1beta/genética , Interleucina-6/genética , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Nitrilas/farmacologia , Fosforilação/efeitos dos fármacos , Extratos Vegetais/química , Caules de Planta/química , Caules de Planta/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , Glicoproteína da Espícula de Coronavírus/farmacologia , Receptor 4 Toll-Like/metabolismo , Transcrição Genética/efeitos dos fármacos
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