Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 36.836
Filtrar
1.
Sci Total Environ ; 802: 149885, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474295

RESUMO

Chain elongation is an anaerobic biotechnological process that converts short chain carboxylates and an electron donor (e.g. ethanol, lactate) into more valuable medium chain carboxylates. Caproate production in lactate-based chain elongation is gaining popularity, however, the relation between lactate (electron donor) and acetate (electron acceptor) has not yet been fully elucidated. Herein, for the first time, the effect of an external acetate on the lactate-based chain elongation in a continuously-fed bioreactor was tested to verify how the external acetate would affect the product spectrum, gas production, as well as stability and efficiency of carboxylates production. Periodic fluctuations in caproate production were observed in bioreactor continuously fed with lactate as a sole carbon source due to the lack of an electron acceptor (acetate) and low chain elongation performance. The recovery of stable caproate production (68.9 ± 2.2 mmol C/L/d), total lactate consumption, and high hydrogen co-production (748 ± 76 mLH2/d) was observed as an effect of the addition of an external acetate. The lactate conversion with the external acetate in the second bioreactor ensured stable and dominant caproate production from the beginning of the process. Moreover, despite the continuous lactate overloading in the process with external acetate, stable caproate production was achieved (71.7 ± 2.4 mmol C/L/d) and previously unobserved hydrogen production occurred (213 ± 30 mLH2/d). Thus, external electron acceptor addition (i.e. acetate) was proposed as an effective method for stable lactate-based caproate production. Microbiological analysis showed the dominance of microbes closely related to Ruminococcaceae bacterium CPB6 and Acinetobacter throughout the process. Co-occurrence networks based on taxon abundances and process parameters revealed microbial sub-networks responding to lactate concentrations.


Assuntos
Reatores Biológicos , Ácido Láctico , Acetatos , Fermentação , Hidrogênio
2.
J Colloid Interface Sci ; 607(Pt 1): 848-856, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34536939

RESUMO

HYPOTHESIS: Cubosomes made from the inverse micellar cubic mesophase (I2) with Fd3m symmetry possess a unique structure of closely packed inverse micelles. These have prospective functionality in sustained drug release. In this study, we hypothesised that similar to fatty acids, various fatty acetate compounds can induce the formation of micellar Fd3m cubosomes in monoolein (MO) nanoparticles. They are different to micellar cubosomes made of MO and a fatty acid, which are pH responsive and can transition from an Fd3m phase to an inverse hexagonal phase (H2) as pH increases. We hypothesised that by co-doping a fatty acetate and fatty acid into MO, precise control of the Fd3m-H2 phase transition pH in nanoparticles can be achieved. EXPERIMENTS: Five unsaturated fatty acetates with hydrocarbon chain lengths between 18 and 24 were added to MO at a weight ratio of 0.45 - 0.60 to form nanoparticles. The nanoparticles were prepared using high-throughput formulation and characterised with synchrotron small angle X-ray scattering (SAXS). MO nanoparticles doped with vaccenyl acetate and vaccenic acid were used to demonstrate the fine control over Fd3m-H2 phase transition pH. FINDINGS: Micellar cubosomes (Fd3m phase) were found in MO nanoparticles doped with fatty acetates. The Fd3m structure was stable in a wide pH range of 2.6 - 8 and at temperatures up to 45 °C. In MO nanoparticles doped with the acetate/acid mixture, the Fd3m-H2 phase transition pH was tuned between pH 5 and pH 7 by adjusting the ratio of vaccenyl acetate and vaccenic acid. As a H2 phase generally offers faster drug release than an Fd3m phase, the pH responsive lipid nanoparticles developed here may find application in orally administrated formulation, where the vehicles must pass a low pH environment in the stomach before reaching neutral pH in the blood.


Assuntos
Cristais Líquidos , Nanopartículas , Acetatos , Ácidos Graxos , Glicerídeos , Concentração de Íons de Hidrogênio , Micelas , Estudos Prospectivos , Espalhamento a Baixo Ângulo , Difração de Raios X
3.
Sci Total Environ ; 804: 150147, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509840

RESUMO

Microbial conversion of methane to electricity, fuels, and liquid chemicals has attracted much attention. However, due to the low solubility of methane, it is not considered a suitable substrate for microbial fuel cells (MFCs). In this study, a conductive fiber membrane (CFM) module was constructed as the bioanode of methane-driven MFCs, directly delivering methane. After biofilm formation on the CFM surface, a steady voltage output of 0.6 to 0.7 V was recorded, and the CFM-MFCs obtained a maximum power density of 64 ± 2 mW/m2. Moreover, methane oxidation produced a high concentration of intermediate acetate (up to 7.1 mM). High-throughput 16S rRNA gene sequencing suggests that the microbial community was significantly changed after electricity generation. Methane-related archaea formed a symbiotic consortium with characterized electroactive bacteria and fermentative bacteria, suggesting a combination of three types of microorganisms for methane conversion into acetate and electricity.


Assuntos
Fontes de Energia Bioelétrica , Acetatos , Eletricidade , Eletrodos , Metano , RNA Ribossômico 16S/genética
4.
Food Chem ; 372: 131222, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34638059

RESUMO

Varietal thiols are important wine aroma compounds that are generally less abundant in red wines. Accentuated cut edges (ACE), known for accelerating phenolic extraction, was applied to Shiraz winemaking and compared with conventional crushing (NOACE) to examine the effects on varietal thiol precursor extraction and thiol formation. Water addition to grape must and skin contact time (SCT) during fermentation were also assessed. Although there was no difference for precursors in the must, ACE significantly decreased 3-S-glutathionylhexan-1-ol concentration during fermentation. 3-Sulfanylhexan-1-ol and ethyl esters were significantly influenced by crushing method and/or SCT, with NOACE or shorter SCT yielding higher concentrations. Acetates, higher alcohols, fatty acids, and isoprenoids differed according to the interaction of crushing method and SCT, with ACE and shorter SCT significantly enhancing all groups except acetates. Volatiles in Sauvignon blanc and Pinot noir wines produced at commercial scale with ACE were briefly evaluated, suggesting an impact of grape variety.


Assuntos
Vitis , Vinho , Acetatos/análise , Fermentação , Odorantes/análise , Fenóis/análise , Vinho/análise
5.
Chemosphere ; 287(Pt 1): 131794, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34438205

RESUMO

Halogenated disinfection byproducts (halo-DBPs) are drinking water contaminants of great public health concern. Nine haloaliphatic DBPs have been regulated by the U.S. Environmental Protection Agency and various halophenolic compounds have been identified as emerging DBPs. In this study, we evaluated the cytotoxic interactions of the regulated bromoacetic acid and three emerging bromophenolic DBPs, i.e., 2,4,6-tribromophenol, 3,5-dibromo-4-hydroxybenzoic acid, and 3,5-dibromo-4-hydroxybenzaldehyde. Cytotoxicity was measured for each DBP individually as well as each of their mixtures using in vitro human epithelial colorectal adenocarcinoma (Caco-2) and neuroblastoma (SH-SY5Y) cells. Concentration addition (CA) model and isobolographic analysis were employed to characterize the interactions among the DBPs. Our results show that the cytotoxicity of four bromo-DBPs against both cell-types followed the descending rank order of bromoacetic acid > 2,4,6-tribromophenol > 3,5-dibromo-4-hydroxybenzaldehyde > 3,5-dibromo-4-hydroxybenzoic acid. Compared with the toxicity data in literature, our finding that bromoacetic acid showed higher cytotoxicity than bromophenolic DBPs was consistent with the results from Chinese hamster ovary cells (a commonly used in vitro model of DBP toxicological studies); but different from the results obtained from in vivo biological models. Significantly, with CA model prediction, we found that mixtures of four bromo-DBPs exhibited synergistic cytotoxic effects on both human cell types. Isobolographic analysis of binary DBP mixtures revealed that, for Caco-2 cells, bromoacetic acid, 2,4,6-tribromophenol, and 3,5-dibromo-4-hydroxybenzoic acid induced synergism; for SH-SY5Y cells, bromoacetic acid induced synergism with all three bromophenolic DBPs. The production of reactive oxidative species (ROS) induced by DBP mixtures could be an important reason for the synergistic cytotoxicity.


Assuntos
Desinfetantes , Água Potável , Poluentes Químicos da Água , Purificação da Água , Acetatos , Animais , Células CHO , Células CACO-2 , Cricetinae , Cricetulus , Desinfetantes/toxicidade , Desinfecção , Halogenação , Humanos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
6.
Clin Drug Investig ; 41(12): 1075-1086, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34784011

RESUMO

OBJECTIVE: Since May 2018, a 6-year post­marketing surveillance (PMS) has been underway to evaluate the safety and effectiveness of letermovir for cytomegalovirus (CMV) prophylaxis in Japanese patients with allogenic hematopoietic stem-cell transplantation (allo-HSCT). The interim PMS data for 461 patients collected as of March 2021 are reported in this publication. METHODS: The case report forms (CRFs) were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT) using data elements in the Transplant Registry Unified Management Program (TRUMP) and sent to individual HSCT centers to decrease burden of reporting. These CRFs were completed by physicians in the respective HSCT centers and sent to MSD K.K., Tokyo, Japan. RESULTS: Allo-HSCT recipients prescribed with letermovir for CMV prophylaxis were included across 136 centers in Japan between May 2018 and March 2021. Safety and effectiveness were assessed for 460 and 373 patients, respectively. Of the patients in the safety analysis, 13.9 % experienced adverse drug reactions, the most frequent of which were renal impairment (2.2 %) and nausea (1.7 %). Among patients in the effectiveness analysis, the overall CMV antigen positivity rate was 21.2 % at Week 14 and 37.5 % at Week 24 after allo-HSCT. CONCLUSIONS: Interim data from this largest of real-world studies confirm the safety and effectiveness of letermovir for CMV prophylaxis in Japanese allo-HSCT recipients. Given the limited data on Asian patients for letermovir use, this survey will provide valuable information for medical decision-making in routine clinical practice, serving as a vital supplement to the results obtained from clinical trials.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Acetatos , Antivirais/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Japão , Vigilância de Produtos Comercializados , Quinazolinas
7.
Trials ; 22(1): 690, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34629091

RESUMO

BACKGROUND: Young children with sickle cell anaemia (SCA) often have slowed processing speed associated with reduced brain white matter integrity, low oxygen saturation, and sleep-disordered breathing (SDB), related in part to enlarged adenoids and tonsils. Common treatments for SDB include adenotonsillectomy and nocturnal continuous positive airway pressure (CPAP), but adenotonsillectomy is an invasive surgical procedure, and CPAP is rarely well-tolerated. Further, there is no current consensus on the ability of these treatments to improve cognitive function. Several double-blind, randomised controlled trials (RCTs) have demonstrated the efficacy of montelukast, a safe, well-tolerated anti-inflammatory agent, as a treatment for airway obstruction and reducing adenoid size for children who do not have SCA. However, we do not yet know whether montelukast reduces adenoid size and improves cognition function in young children with SCA. METHODS: The Study of Montelukast In Children with Sickle Cell Disease (SMILES) is a 12-week multicentre, double-blind, RCT. SMILES aims to recruit 200 paediatric patients with SCA and SDB aged 3-7.99 years to assess the extent to which montelukast can improve cognitive function (i.e. processing speed) and sleep and reduce adenoidal size and white matter damage compared to placebo. Patients will be randomised to either montelukast or placebo for 12 weeks. The primary objective of the SMILES trial is to assess the effect of montelukast on processing speed in young children with SCA. At baseline and post-treatment, we will administer a cognitive evaluation; caregivers will complete questionnaires (e.g. sleep, pain) and measures of demographics. Laboratory values will be obtained from medical records collected as part of standard care. If a family agrees, patients will undergo brain MRIs for adenoid size and other structural and haemodynamic quantitative measures at baseline and post-treatment, and we will obtain overnight oximetry. DISCUSSION: Findings from this study will increase our understanding of whether montelukast is an effective treatment for young children with SCA. Using cognitive testing and MRI, the SMILES trial hopes to gain critical knowledge to help develop targeted interventions to improve the outcomes of young children with SCA. TRIAL REGISTRATION: ClinicalTrials.gov NCT04351698 . Registered on April 17, 2020. European Clinical Trials Database (EudraCT No. 2017-004539-36). Registered on May 19, 2020.


Assuntos
Anemia Falciforme , Quinolinas , Acetatos/efeitos adversos , Anemia Falciforme/diagnóstico , Anemia Falciforme/tratamento farmacológico , Anti-Inflamatórios , Criança , Pré-Escolar , Ciclopropanos , Humanos , Quinolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sulfetos
8.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638573

RESUMO

13-lipoxygenases (13-LOX) catalyze the dioxygenation of various polyunsaturated fatty acids (PUFAs), of which α-linolenic acid (LeA) is converted to 13-S-hydroperoxyoctadeca-9, 11, 15-trienoic acid (13-HPOT), the precursor for the prostaglandin-like plant hormones cis-(+)-12-oxophytodienoic acid (12-OPDA) and methyl jasmonate (MJ). This study aimed for characterizing the four annotated A. thaliana 13-LOX enzymes (LOX2, LOX3, LOX4, and LOX6) focusing on synthesis of 12-OPDA and 4Z,7Z,10Z)-12-[[-(1S,5S)-4-oxo-5-(2Z)-pent-2-en-1yl] cyclopent-2-en-1yl] dodeca-4,7,10-trienoic acid (OCPD). In addition, we performed interaction studies of 13-LOXs with ions and molecules to advance our understanding of 13-LOX. Cell imaging indicated plastid targeting of fluorescent proteins fused to 13-LOXs-N-terminal extensions, supporting the prediction of 13-LOX localization to plastids. The apparent maximal velocity (Vmax app) values for LOX-catalyzed LeA oxidation were highest for LOX4 (128 nmol·s-1·mg protein-1), with a Km value of 5.8 µM. A. thaliana 13-LOXs, in cascade with 12-OPDA pathway enzymes, synthesized 12-OPDA and OCPD from LeA and docosahexaenoic acid, previously shown only for LOX6. The activities of the four isoforms were differently affected by physiologically relevant chemicals, such as Mg2+, Ca2+, Cu2+ and Cd2+, and by 12-OPDA and MJ. As demonstrated for LOX4, 12-OPDA inhibited enzymatic LeA hydroperoxidation, with half-maximal enzyme inhibition at 48 µM. Biochemical interactions, such as the sensitivity of LOX toward thiol-reactive agents belonging to cyclopentenone prostaglandins, are suggested to occur in human LOX homologs. Furthermore, we conclude that 13-LOXs are isoforms with rather specific functional and regulatory enzymatic features.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Lipoxigenase/metabolismo , Acetatos/metabolismo , Sequência de Aminoácidos , Ciclopentanos/metabolismo , Ácidos Graxos Insaturados/metabolismo , Regulação da Expressão Gênica de Plantas/fisiologia , Ácidos Linoleicos/metabolismo , Oxilipinas/metabolismo
9.
Molecules ; 26(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684788

RESUMO

It is known that Senna obtusifolia has been used in medicine since ancient times due to the content of many valuable compounds with a pro-health effect. One of them is betulinic acid, which is a pentacyclic triterpene with antimalarial, antiviral, anti-inflammatory and anticancer properties. In this work, a continuation of our previous research, an attempt was made to increase the level of betulinic acid accumulation by the cultivation of transgenic hairy roots that overexpress the squalene synthase gene in a 10 L sprinkle bioreactor with methyl jasmonate elicitation. We present that the applied strategy allowed us to increase the content of betulinic acid in hairy root cultures to the level of 48 mg/g dry weight. The obtained plant extracts showed a stronger cytotoxic effect on the U87MG glioblastoma cell line than the roots grown without elicitors. Additionally, the induction of apoptosis, reduction of mitochondrial membrane potential, chromosomal DNA fragmentation and activation of caspase cascades are demonstrated. Moreover, the tested extract showed inhibition of topoisomerase I activity.


Assuntos
Acetatos/farmacologia , Antineoplásicos Fitogênicos/metabolismo , Ciclopentanos/farmacologia , Oxilipinas/farmacologia , Triterpenos Pentacíclicos/metabolismo , Senna (Planta)/efeitos dos fármacos , Senna (Planta)/metabolismo , Células A549 , Antineoplásicos Fitogênicos/biossíntese , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Reatores Biológicos , Biotecnologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Fragmentação do DNA/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Reguladores de Crescimento de Plantas/farmacologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas Geneticamente Modificadas , Plantas Medicinais/efeitos dos fármacos , Plantas Medicinais/crescimento & desenvolvimento , Plantas Medicinais/metabolismo , Senna (Planta)/crescimento & desenvolvimento
10.
BMC Plant Biol ; 21(1): 450, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615468

RESUMO

BACKGROUND: Methyl jasmonate (MeJA), which has been identified as a lipid-derived stress hormone, mediates plant resistance to biotic/abiotic stress. Understanding MeJA-induced plant defense provides insight into how they responding to environmental stimuli. RESULT: In this work, the dynamic network analysis method was used to quantitatively identify the tipping point of growth-to-defense transition and detect the associated genes. As a result, 146 genes were detected as dynamic network biomarker (DNB) members and the critical defense transition was identified based on dense time-series RNA-seq data of MeJA-treated Arabidopsis thaliana. The GO functional analysis showed that these DNB genes were significantly enriched in defense terms. The network analysis between DNB genes and differentially expressed genes showed that the hub genes including SYP121, SYP122, WRKY33 and MPK11 play a vital role in plant growth-to-defense transition. CONCLUSIONS: Based on the dynamic network analysis of MeJA-induced plant resistance, we provide an important guideline for understanding the growth-to-defense transition of plants' response to environment stimuli. This study also provides a database with the key genes of plant defense induced by MeJA.


Assuntos
Acetatos/metabolismo , Arabidopsis/crescimento & desenvolvimento , Arabidopsis/genética , Ciclopentanos/metabolismo , Oxilipinas/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Estresse Fisiológico/genética , Estresse Fisiológico/fisiologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Estudo de Associação Genômica Ampla
11.
Drugs R D ; 21(4): 419-429, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34655050

RESUMO

OBJECTIVE: The aim of this study was to identify factors affecting blood concentrations of voriconazole following letermovir coadministration using population pharmacokinetic (PPK) analysis in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. METHODS: The following data were retrospectively collected: voriconazole trough levels, patient characteristics, concomitant drugs, and laboratory information. PPK analysis was performed with NONMEM® version 7.4.3, using the first-order conditional estimation method with interaction. We collected data on plasma voriconazole steady-state trough concentrations at 216 timepoints for 47 patients. A nonlinear pharmacokinetic model with the Michaelis-Menten equation was applied to describe the relationship between steady-state trough concentration and daily maintenance dose of voriconazole. After stepwise covariate modeling, the final model was evaluated using a goodness-of-fit plot, case deletion diagnostics, and bootstrap methods. RESULTS: The maximum elimination rate (Vmax) of voriconazole in patients coadministered letermovir and methylprednisolone was 1.72 and 1.30 times larger than that in patients not coadministered these drugs, respectively, resulting in decreased voriconazole trough concentrations. The developed PPK model adequately described the voriconazole trough concentration profiles in allo-HSCT recipients. Simulations clearly showed that increased daily doses of voriconazole were required to achieve an optimal trough voriconazole concentration (1-5 mg/L) when patients received voriconazole with letermovir and/or methylprednisolone. CONCLUSIONS: The development of individualized dose adjustment is critical to achieve optimal voriconazole concentration, especially among allo-HSCT recipients receiving concomitant letermovir and/or methylprednisolone.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Metilprednisolona , Acetatos , Antifúngicos , Humanos , Quinazolinas , Estudos Retrospectivos , Voriconazol
12.
PLoS One ; 16(10): e0258607, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648570

RESUMO

Staphylococcus aureus and Methicillin-resistant S. aureus (MRSA) remains one of the major concerns of healthcare associated and community-onset infections worldwide. The number of cases of treatment failure for infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, Acrophialophora levis, a thermophilous fungus species, showed antibacterial activity, namely against S. aureus and clinical MRSA strains. The ethyl acetate extract of culture filtrate was found to display significant activity against S. aureus and MRSA with a minimum inhibitory concentration (MIC) of 1 µg/mL and 4 µg/mL, respectively. Scanning electron micrographs demonstrated drastic changes in the cellular architecture of metabolite treated cells of S. aureus and an MRSA clinical isolate. Cell wall disruption, membrane lysis and probable leakage of cytoplasmic are hallmarks of the antibacterial effect of fungal metabolites against MRSA. The ethyl acetate extract also showed strong antioxidant activity using two different complementary free radicals scavenging methods, DPPH and ABTS with efficiency of 55% and 47% at 1 mg/mL, respectively. The total phenolic and flavonoid content was found to be 50 mg/GAE and 20 mg/CAE, respectively. More than ten metabolites from different classes were identified: phenolic acids, phenylpropanoids, sesquiterpenes, tannins, lignans and flavonoids. In conclusion, the significant antibacterial activity renders this fungal strain as a bioresource for natural compounds an interesting alternative against resistant bacteria.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Fatores Biológicos/farmacologia , Staphylococcus aureus Resistente à Meticilina/ultraestrutura , Sordariales/química , Acetatos/química , Antibacterianos/química , Antioxidantes/química , Fatores Biológicos/química , Flavonoides/isolamento & purificação , Hidroxibenzoatos/isolamento & purificação , Índia , Lignanas/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Sesquiterpenos/isolamento & purificação , Taninos/isolamento & purificação
14.
Phytomedicine ; 93: 153798, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34673348

RESUMO

BACKGROUND: NLRP3 inflammasome activation and pyroptosis play an important role in myocardial ischemia/reperfusion injury (MI/RI). Cinnamomi ramulus (CR), is an important folk medicinal plant in China, which derived from the dried twig of Cinnamomum cassia (L.) Presl, has function of "warming and tonifying heart yang", and traditionally utilized to treat the cold, blood-cold amenorrhea, phlegm, edema, arthralgia, and palpitations as well as improve blood circulation. The aqueous extract of C. ramulus was reported to show significant therapeutic potential for treating MI/RI. Whereas, there are no previous investigations in China or abroad has reported the cardioprotective effects and underlying mechanism of the ethyl acetate extract of C. ramulus (CREAE) and its bioactive substance cinnamic acid (CA) in triggering NLRP3 inflammasome activation and subsequent pyroptosis. PURPOSE: The present study aimed to assess the cardioprotective function of CREAE and CA against the MI/RI in rats and involved the underlying mechanisms. METHODS: The MI/RI model was established in male SD rats by occlusion of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min, respectively. The rats were intragastrically administered with CREAE (74 and 37 mg/kg) and CA (45 mg/kg) for 7 successive days before vascular ligation. The cardioprotective effects of CREAE and CA against myocardial injury of rats were detected by HE staining, TTC staining, echocardiograms, and myocardial enzymes detections. Serum levels of inflammatory factors, such as IL-6, IL-1ß, and TNF-α, were analyzed by ELISA kits to evaluate the effects of CREAE and CA. The protein and gene expression levels of NLRP3 and the pyroptosis-related factors in heart tissue were conducted by western blot and RT-qPCR. RESULTS: Our results showed that CREAE and CA decrease myocardial infarct size and improve cardiac function, mitigate myocardial damage, and repress inflammatory response in rats after I/R. Mechanistically, our results revealed that CREAE and CA can dramatically suppress the activation of NLRP3 inflammasome and subsequent cardiomyocyte pyroptosis in myocardial tissues that as evidenced by downregulating the protein and gene expressions of NLRP3, ASC, IL-1ß, caspase-1, gasdermin D, and N-terminal GSDMD. CONCLUSIONS: Our data indicated that CREAE and CA may attenuate MI/RI through suppression of NLRP3 inflammasome and subsequent pyroptosis-related signaling pathways.


Assuntos
Traumatismo por Reperfusão Miocárdica , Piroptose , Acetatos , Animais , Inflamassomos , Masculino , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Ratos Sprague-Dawley
15.
J Cosmet Dermatol ; 20(11): 3580-3585, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34648685

RESUMO

BACKGROUND: Acne is a chronic inflammatory skin disease which involves the pilosebaceous unit. Tissue inflammation isone of the crucial mechanisms, amongst others. Of the various cytokines, leukotriene B4 (LT-B4) is the most potentleucocyte chemotactic mediator. Montelukast is an antagonist of the LT-B4 receptor. Finasteride is an antiandrogen whichspecifically inhibits the 5α-reductase enzyme. AIMS: This study aimed at comparing the efficacy, tolerability and safety of montelukast versus finasteride in the treatmentof moderate acne in women. PATIENTS/METHOD: This randomized, single-blinded, prospective trial over 12 weeks recruited 65 female subjects with moderate acne vulgaris (Global Acne Grading System Scale) for evaluation. One group (n = 30) received oral montelukast (10 mg PO daily), while the second group (n = 25) received oral finasteride (2.5 mg PO daily) in combination with topical clindamycin 2% solution. Lesion count and acne severity were evaluated at time intervals of 0 (baseline), 4, 8, and 12 weeks. Adverse effects of the drugs were noted. RESULTS: Both lesion count and severity of acne decreased significantly after treatment in both the groups as compared to the baseline. The acne severity score reached from 33.93 in time zero to 20.6 in the 12th week and 35.71 at baseline to 16.43 at the end of treatment in the Montelukast and Finasteride groups, respectively. Side effects were noted in 3 patients and 2 patients in the monteleukast and finasteride group, respectively, which were transient and non-serious in nature proving the satisfactory tolerability and safety of these two drugs. CONCLUSION: The results of this study show that both montelukast and finasteride have good efficacy in the treatment of acne. Finasteride has more efficacy than montelukast for treating moderate acne in normo-androgenic women.


Assuntos
Acne Vulgar , Finasterida , Acetatos/efeitos adversos , Acne Vulgar/tratamento farmacológico , Ciclopropanos , Feminino , Finasterida/efeitos adversos , Humanos , Estudos Prospectivos , Quinolinas , Sulfetos
16.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3893-3899, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472265

RESUMO

To explore the protective effect and mechanism of ethyl acetate extract from Bidens bipinnata on hepatocyte damage induced by endoplasmic reticulum stress. Tunicamycin was used to establish the damage model in L02 cells. Methyl thiazolyl tetrazolium(MTT) colorimetric assay was used to investigate the survival rate of ethyl acetate extract from B. bipinnata in L02 cells injury induced by endoplasmic reticulum stress; the protein expressions of endoplasmic reticulum stress-related molecule glucose regulated protein 78(GRP78), PKR-like ER kinase(PERK), eukaryotic initiation factor-2(eIF2α), activating transcription factor 4(ATF4), C/EBP homologous protein(CHOP), B-cell CLL/lymphoma 2(Bcl-2), Bal-2 associated X apoptosis regulator(Bax) were examined by Wes-tern blot. The expressions of the above proteins were also detected after endoplasmic reticulum stress inhibitor(4-phenyl butyric acid) and CHOP shRNA-mediated knockdowns were added. The expressions of GRP78, PERK, CHOP in L02 cells were observed by immunofluorescence method. The results showed that ethyl acetate extract from B. bipinnata could significantly increase the survival rate of L02 cell injury caused by endoplasmic reticulum stress in a dose and time-dependent manner(P<0.05 or P<0.01). The expression levels of GRP78, PERK, eIF2α, ATF4, CHOP and Bax in the drug treatment groups were significantly down-regulated(P<0.05 or P<0.01), while Bcl-2 was significantly up-regulated(P<0.01). After endoplasmic reticulum stress inhibitor and CHOP shRNA-mediated knockdowns were added, the expression levels of GRP78, PERK, eIF2α, ATF4, CHOP, Bax in the drug treatment groups were significantly down-regulated(P<0.01), whereas Bcl-2 was significantly up-regulated(P<0.01). Immunofluorescence results showed that the expressions of GRP78, PERK, CHOP were consistent with the Western blot method. In conclusion, ethyl acetate extract from B. bipinnata has a significant protective effect on the damage of L02 cells caused by endoplasmic reticulum stress. The mechanism may be related to the inhibition of endoplasmic reticulum stress and the down-regulation of apoptosis in cells through the PERK/eIF2α/ATF4/CHOP signaling pathway.


Assuntos
Bidens , Estresse do Retículo Endoplasmático , Acetatos , Apoptose , Hepatócitos , Fator de Transcrição CHOP/genética , eIF-2 Quinase/genética
17.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500623

RESUMO

Lignans are the main secondary metabolites synthetized by Linum species as plant defense molecules. They are also valuable for human health, in particular, for their potent antiviral and antineoplastic properties. In this study, the adventitious root cultures of three Linum species (L. flavum, L. mucronatum and L. dolomiticum) were developed to produce aryltetralin lignans. The effect of two elicitors, methyl jasmonate and coronatine, on aryltetralin lignans production was also evaluated. The adventitious root cultures from L. dolomiticum were obtained and analyzed for the first time and resulted as the best producer for all the aryltetralins highlighted in this system: Podophyllotoxin, 6-methoxypodophyllotoxin and 6-methoxypodophyllotoxin-7-O-ß-glucoside, the last showing a productivity of 92.6 mg/g DW. The two elicitors differently affected the production of the 6-methoxypodophyllotoxin and 6-methoxypodophyllotoxin-7-O-ß-glucoside.


Assuntos
Linho/metabolismo , Lignanas/biossíntese , Raízes de Plantas/metabolismo , Acetatos/metabolismo , Aminoácidos/biossíntese , Ciclopentanos/metabolismo , Indenos , Oxilipinas/metabolismo , Podofilotoxina/análogos & derivados , Podofilotoxina/biossíntese
18.
J Enzyme Inhib Med Chem ; 36(1): 1996-2009, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34525898

RESUMO

Microtubule dynamics are crucial for multiple cell functions, and cancer cells are particularly sensitive to microtubule-modulating agents. Here, we describe the design and synthesis of a series of (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives and evaluation of their microtubule-modulating and anticancer activities in vitro. Proliferation assays identified I20 as the most potent of the antiproliferative compounds, with 50% inhibitory concentrations ranging from 7.0 to 20.3 µM with A549, PC-3, and HepG2 human cancer cell lines. Compound I20 also disrupted cancer A549 cell migration in a concentration-dependent manner. Immunofluorescence microscopy, transmission electron microscopy, and tubulin polymerisation assays suggested that compound I20 promoted protofilament assembly. In support of this possibility, computational docking studies revealed a strong interaction between compound I20 and tubulin Arg ß369, which is also the binding site for the anticancer drug Taxol. Our results suggest that (Z)-2-(5-benzylidene-4-oxo-2-thioxothiazolidin-3-yl)-N-phenylacetamide derivatives could have utility for the development of microtubule-stabilising therapeutic agents.


Assuntos
Acetatos/farmacologia , Amidas/farmacologia , Antineoplásicos/farmacologia , Descoberta de Drogas , Microtúbulos/efeitos dos fármacos , Rodanina/farmacologia , Moduladores de Tubulina/farmacologia , Células A549 , Acetatos/síntese química , Acetatos/química , Amidas/química , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Microtúbulos/metabolismo , Estrutura Molecular , Polimerização/efeitos dos fármacos , Rodanina/análogos & derivados , Rodanina/química , Relação Estrutura-Atividade , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/química
19.
BMC Infect Dis ; 21(1): 994, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556034

RESUMO

BACKGROUND: Human Cytomegalovirus (HCMV) still represents a crucial concern in solid organ transplant recipients (SOTRs) and the use of antiviral therapy are limited by side effects and the selection of viral mutations conferring antiviral drug resistance. CASE PRESENTATION: Here we reported the case of an HCMV seronegative patient with common variable immunodeficiency (CVID), multiple hepatic adenomatosis, hepatopulmonary syndrome and portal hypertension who received a liver transplant from an HCMV seropositive donor. The patient was treated with Valganciclovir (vGCV) and then IV Ganciclovir (GCV) at 5 week post-transplant for uncontrolled HCMV DNAemia. However, since mutation A594V in UL97 gene conferring resistance to ganciclovir was reported, GCV therapy was interrupted. Due to the high toxicity of Foscarnet (FOS) and Cidofovir (CDV), Letermovir (LMV) monotherapy at the dosage of 480 mg per day was administered, with a gradual viral load reduction. However, a relapse of HCMV DNAemia revealed the presence of mutation C325Y in HCMV UL56 gene conferring resistance to LMV. CONCLUSIONS: In conclusion, even if LMV is an effective and favorable safety molecule it might have a lower genetic barrier to resistance. A warning on the use of LMV monotherapy as rescue treatments for HCMV GCV-resistant infections in transplant recipients is warranted.


Assuntos
Infecções por Citomegalovirus , Transplante de Fígado , Acetatos , Antivirais/farmacologia , Antivirais/uso terapêutico , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Farmacorresistência Viral , Ganciclovir/uso terapêutico , Humanos , Mutação , Recidiva Local de Neoplasia/tratamento farmacológico , Quinazolinas
20.
Anal Chim Acta ; 1181: 338925, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34556226

RESUMO

An electrochemically synthetized nano-sensor based on molecularly imprinted polypyrrole (MIPPy) was successfully developed for the detection of 5-hydroxyindole-3-acetic acid (5-HIAA) in human biological fluids namely serum, urine, and plasma. The imprinted glassy carbon electrode was prepared by electropolymerisation of pyrrole via cyclic voltammetry (C.V). After completely leaching the imprinted molecules from the polymeric network, complementary cavities are created. The developed MIPPy sensor, under optimized conditions, shows a high sensitivity towards the target molecule (LOQ = 5 × 10-11 M). Moreover, it presents a wide linear response in the range of 5 × 10-11 - 5 × 10-5 M (R2 > 0.999) with a detection limit of 15 × 10-12 M. In order to evaluate the selectivity of the MIPPy film, several structural analogues and compounds forming the real matrices were tested. The obtained results show an excellent recovery rate (between 98.86 and 101.52%) proving the promising application of the proposed nano-sensor in the detection of 5-HIAA in human biological fluids without any significant interference recorded.


Assuntos
Tumor Carcinoide , Impressão Molecular , Acetatos , Biomarcadores Tumorais , Técnicas Eletroquímicas , Eletrodos , Humanos , Ácido Hidroxi-Indolacético , Indóis , Limite de Detecção , Polímeros , Pirróis
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...