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1.
Food Chem ; 368: 130736, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34399179

RESUMO

To systematically identify and quantify the γ- and δ-lactones in Cheddar cheeses, 20 samples from three sources (Ireland, the UK and the USA) were analysed by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), aroma extract dilution analysis, aroma recombination analysis, and aroma addition/omission analysis. Nine lactones were detected in these samples, and one of these lactones, γ-undecalactone, was identified in Cheddar cheese for the first time. The quantitative results showed that the concentration of lactones in these cheeses usually increased as the length of their maturity period increased. γ-Octalactone, γ-undecalactone, γ-dodecalactone, δ-octalactone, δ-decalactone and δ-dodecalactone were identified as aroma-active substances based on their odour activity values and aroma extract dilution analysis, with flavour dilution factors ranging from 2 to 128. Aroma recombination and omission experiments based on a newly developed deodorised Cheddar matrix further validated the important contributions of these lactones to the overall aroma of Cheddar cheeses. The addition of each lactone to aroma recombination models reduced the aroma intensity of sour and rancid properties to various extents and improved the acceptability of the overall flavour.


Assuntos
Queijo , Compostos Orgânicos Voláteis , Queijo/análise , Cromatografia Gasosa-Espectrometria de Massas , Lactonas , Odorantes/análise , Olfatometria , Extratos Vegetais , Compostos Orgânicos Voláteis/análise
2.
J Colloid Interface Sci ; 606(Pt 2): 1140-1152, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492457

RESUMO

Understanding the microstructural parameters of amphiphilic copolymers that control the formation and structure of aggregated colloids (e.g., micelles) is essential for the rational design of hierarchically structured systems for applications in nanomedicine, personal care and food formulations. Although many analytical techniques have been employed to study such systems, in this investigation we adopted an integrated approach using non-interfering techniques - diffusion nuclear magnetic resonance (NMR) spectroscopy, dynamic light scattering (DLS) and synchrotron small-angle X-ray scattering (SAXS) - to probe the relationship between the microstructure of poly(ethylene glycol-b-caprolactone) (PEG-b-PCL) copolymers [e.g., block molecular weight (MW) and the mass fraction of PCL (fPCL)] and the structure of their aggregates. Systematic trends in the self-assembly behaviour were determined using a large family of well-defined block copolymers with variable PEG and PCL block lengths (number-average molecular weights (Mn) between 2 and 10 and 0.5-15 kDa, respectively) and narrow dispersity (Ð < 1.12). For all of the copolymers, a clear transition in the aggregate structure was observed when the hydrophobic fPCL was increased at a constant PEG block Mn, although the nature of this transition is also dependent on the PEG block Mn. Copolymers with low Mn PEG blocks (2 kDa) were observed to transition from unimers and loosely associated unimers to metastable aggregates and finally, to cylindrical micelles as the fPCL was increased. In comparison, copolymers with PEG block Mn of between 5 and 10 kDa transitioned from heterogenous metastable aggregates to cylindrical micelles and finally, well-defined ellipsoidal micelles (of decreasing aspect ratios) as the fPCL was increased. In all cases, the diffusion NMR spectroscopy, DLS and synchrotron SAXS results provided complementary information and the grounds for a phase diagram relating copolymer microstructure to aggregation behaviour and structure. Importantly, the absence of commonly depicted spherical micelles has implications for applications where properties may be governed by shape, such as, cellular uptake of nanomedicine formulations.


Assuntos
Poliésteres , Polietilenoglicóis , Caproatos , Lactonas , Micelas , Espalhamento a Baixo Ângulo , Difração de Raios X
3.
Molecules ; 26(21)2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34770855

RESUMO

In the last two years, nucleosides analogues, a class of well-established bioactive compounds, have been the subject of renewed interest from the scientific community thanks to their antiviral activity. The COVID-19 global pandemic, indeed, spread light on the antiviral drug Remdesivir, an adenine C-nucleoside analogue. This new attention of the medical community on Remdesivir prompts the medicinal chemists to investigate once again C-nucleosides. One of the essential building blocks to synthetize these compounds is the D-(+)-ribono-1,4-lactone, but some mechanistic aspects linked to the use of different carbohydrate protecting groups remain unclear. Here, we present our investigations on the use of benzylidene as a ribonolactone protecting group useful in the synthesis of C-purine nucleosides analogues. A detailed 1D and 2D NMR structural study of the obtained compounds under different reaction conditions is presented. In addition, a molecular modeling study at the B3LYP/6-31G* level of theory with the SM8 solvation model for CHCl3 and DMSO to support the obtained results is used. This study allows for clarifying mechanistic aspects as the side reactions and structural rearrangements liked to the use of the benzylidene protecting group.


Assuntos
Compostos de Benzilideno/química , Lactonas/química , Nucleosídeos/síntese química , Ribose/análogos & derivados , Adenina/análogos & derivados , Antivirais/química , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Humanos , Lactonas/síntese química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Nucleosídeos/metabolismo , Nucleosídeos de Purina , Ribose/síntese química , Ribose/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Estereoisomerismo
4.
J Agric Food Chem ; 69(45): 13557-13567, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34726896

RESUMO

Metabolic reprogramming is critical for tumorigenesis. Pyruvate kinase M2 (PKM2) is overexpressed in lung carcinoma cells and plays a critical role in the Warburg effect, making the enzyme a research hotspot for anticancer drug development. Cynaropicrin (CYN), a natural sesquiterpene lactone compound from artichoke, has received increasing consideration due to its consumable esteem and pharmacological properties. Our data reveal that CYN not only inhibited the purified PKM2 activity but also decreased the cellular PKM2 expression in A549 cells. The inhibition of PKM2 leads to the upregulation of p53 and the downregulation of the DNA repair enzyme poly (ADP-ribose) polymerase (PARP), and subsequently causes the cell cycle arrest. Additionally, CYN inhibits the interaction of PKM2 and Nrf2, resulting in the impairment of cellular antioxidant capacity, induction of oxidative stress, and mitochondrial damages. Overexpression of PKM2 attenuates the CYN-induced DNA damage, mitochondrial fission, and cell viability. Thus, targeting PKM2 provides an original mechanism for understanding the pharmacological impact of CYN and assists in the further development of CYN as an anticancer agent.


Assuntos
Piruvato Quinase , Sesquiterpenos , Células A549 , Apoptose , Pontos de Checagem do Ciclo Celular , Dano ao DNA , Humanos , Lactonas/farmacologia , Dinâmica Mitocondrial , Piruvato Quinase/genética , Sesquiterpenos/farmacologia
5.
J Agric Food Chem ; 69(41): 12230-12240, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34633804

RESUMO

Ginkgolide B (GB) is one of the main bioactive components of Ginkgo biloba leaf extracts with neuroprotective activity. However, the neuroprotective mechanism link between the anti-Alzheimer's disease (AD) efficiency of GB and gut microbiota have remained elusive. Here, we elucidated the effect and possible mechanism of GB against cognitive impairment in mice. Male mice were induced with d-galactose and aluminum chloride to establish an AD animal model, and then intragastrically treated with GB. Cognitive function was assessed by an object recognition test and an open-field test. Amyloid deposition and neuropathological change were detected. The levels of receptor for advanced glycation end products (RAGE), Bcl-2, and Bax were detected. Moreover, microbial compositions were measured by 16s rRNA sequencing. Our results showed that GB significantly alleviated cognitive dysfunction, neurodegeneration, and neuropathological changes in AD model mice. Moreover, GB treatment remarkably reduced the levels of RAGE and Bax and increased the level of Bcl-2 in AD model mice. GB treatment reversed the decreased abundance of Lactobacillus and the increased abundance of Bacteroidales, Muribaculaceae, and Alloprevotella, which led to reconstruction of gut microbiota. These findings demonstrated the neuroprotective effects of GB in AD mice, which were partly mediated by modulating gut dysbiosis, indicating that GB might be a potentially active supplement to alleviate AD.


Assuntos
Disfunção Cognitiva , Microbioma Gastrointestinal , Animais , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/genética , Ginkgolídeos , Lactonas , Masculino , Camundongos , RNA Ribossômico 16S
6.
Int J Mol Sci ; 22(19)2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34639057

RESUMO

Ferula penninervis Regel & Schmalh. is a perennial plant used in Kazakh traditional folk medicine to treat epilepsy, neurosis, rheumatism, gastroduodenal ulcers, dyspepsia, wounds, abscesses or tumors. The aim of this work was to isolate series of sesquiterpene lactones from a crude methanolic root extract and investigate their in vitro cytotoxic potential against androgen-dependent prostate cancer LNCaP and epithelial prostate PNT2 cells, as well as to evaluate their melanin production inhibitory effects in murine melanoma B16F10 cells stimulated with α-melanocyte-stimulating hormone (αMSH). Two new (penninervin P and penninervin Q) and five known (olgin, laferin, olgoferin, oferin and daucoguainolactone F) guaiane-type sesquiterpene lactones were isolated with the use of a simple and fast liquid-liquid chromatography method. Olgin and laferin showed the most promising cytotoxic effects in LNCaP cells (IC50 of 31.03 and 23.26 µg/mL, respectively). Additionally, olgin, laferin, olgoferin, and oferin (10 µg/mL) potently impaired melanin release (40.67-65.48% of αMSH + cells) without influencing the viability of B16F10 cells. In summary, our findings might indicate that guaiane-type sesquiterpene lactones from F. penninervis could be regarded as promising candidates for further research in discovering new therapeutic agents with anti-prostate cancer and skin depigmentation properties.


Assuntos
Cromatografia Líquida , Ferula/química , Lactonas/isolamento & purificação , Lactonas/farmacologia , Melaninas/antagonistas & inibidores , Sesquiterpenos de Guaiano/isolamento & purificação , Sesquiterpenos de Guaiano/farmacologia , Animais , Antineoplásicos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida/métodos , Relação Dose-Resposta a Droga , Humanos , Lactonas/química , Melanoma Experimental , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Raízes de Plantas/química , Sesquiterpenos de Guaiano/química , Análise Espectral
7.
Acta Cir Bras ; 36(8): e360802, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34644770

RESUMO

PURPOSE: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. METHODS: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). RESULTS: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. CONCLUSIONS: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.


Assuntos
Amidoidrolases/antagonistas & inibidores , Proteína Forkhead Box O1/antagonistas & inibidores , Lesão Pulmonar , Sepse , Sesquiterpenos , Animais , Apoptose , Proteínas Ligadas por GPI/antagonistas & inibidores , Lactonas , Camundongos , Sepse/complicações , Sepse/tratamento farmacológico , Sesquiterpenos/farmacologia
8.
Elife ; 102021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34632981

RESUMO

Gut enzymes can metabolize plant defense compounds and thereby affect the growth and fitness of insect herbivores. Whether these enzymes also influence feeding preference is largely unknown. We studied the metabolization of taraxinic acid ß-D-glucopyranosyl ester (TA-G), a sesquiterpene lactone of the common dandelion (Taraxacum officinale) that deters its major root herbivore, the common cockchafer larva (Melolontha melolontha). We have demonstrated that TA-G is rapidly deglucosylated and conjugated to glutathione in the insect gut. A broad-spectrum M. melolontha ß-glucosidase, Mm_bGlc17, is sufficient and necessary for TA-G deglucosylation. Using cross-species RNA interference, we have shown that Mm_bGlc17 reduces TA-G toxicity. Furthermore, Mm_bGlc17 is required for the preference of M. melolontha larvae for TA-G-deficient plants. Thus, herbivore metabolism modulates both the toxicity and deterrence of a plant defense compound. Our work illustrates the multifaceted roles of insect digestive enzymes as mediators of plant-herbivore interactions.


Assuntos
Besouros/enzimologia , Glucosídeos/metabolismo , Herbivoria , Proteínas de Insetos/metabolismo , Lactonas/metabolismo , Sesquiterpenos/metabolismo , Taraxacum/metabolismo , beta-Galactosidase/metabolismo , Animais , Besouros/embriologia , Besouros/genética , Digestão , Glucosídeos/toxicidade , Glutationa/metabolismo , Hidrólise , Inativação Metabólica , Proteínas de Insetos/genética , Lactonas/toxicidade , Larva/enzimologia , Larva/genética , Metabolismo Secundário , Sesquiterpenos/toxicidade , Taraxacum/toxicidade , beta-Galactosidase/genética
9.
Int J Mol Sci ; 22(19)2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34638673

RESUMO

Steroid-associated osteonecrosis (SAON) is a chronic disease that leads to the destruction and collapse of bone near the joint that is subjected to weight bearing, ultimately resulting in a loss of hip and knee function. Zn2+ ions, as an essential trace element, have functional roles in improving the immunophysiological cellular environment, accelerating bone regeneration, and inhibiting biofilm formation. In this study, we reconstruct SAON lesions with a three-dimensional (3D)-a printed composite made of poly (epsilon-caprolactone) (PCL) and nanoparticulate Willemite (npW). Rabbit bone marrow stem cells were used to evaluate the cytocompatibility and osteogenic differentiation capability of the PCL/npW composite scaffolds. The 2-month bone regeneration was assessed by a Micro-computed tomography (micro-CT) scan and the expression of bone regeneration proteins by Western blot. Compared with the neat PCL group, PCL/npW scaffolds exhibited significantly increased cytocompatibility and osteogenic activity. This finding reveals a new concept for the design of a 3D-printed PCL/npW composite-based bone substitute for the early treatment of osteonecrosis defects.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Fêmur/efeitos dos fármacos , Nanopartículas/administração & dosagem , Osteogênese/efeitos dos fármacos , Poliésteres/farmacologia , Tecidos Suporte/química , Animais , Caproatos/farmacologia , Diferenciação Celular/efeitos dos fármacos , Lactonas/farmacologia , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteonecrose/tratamento farmacológico , Impressão Tridimensional , Coelhos , Silicatos/farmacologia , Engenharia Tecidual/métodos , Microtomografia por Raio-X/métodos , Compostos de Zinco/farmacologia
10.
Int J Oral Maxillofac Implants ; 36(5): 1024-1031, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34698730

RESUMO

PURPOSE: To describe the postoperative complications following lateral wall sinus augmentation using (poly L-lactideco-ε-caprolactone; PLCL) and natural polysaccharides polymers-coated bovine bone (PBB). The secondary aims were to examine histologic findings and to propose complication management alternatives. MATERIALS AND METHODS: This retrospective study included 61 subjects who underwent 67 lateral wall sinus augmentation procedures using PBB in the standard protocol. In cases that presented complications, treatment included additional antibiotic therapy, implant removal, or sinus reentry and total removal of the grafting material. In three cases, biopsy specimens were taken from the sinuses, and histologic analyses were performed. RESULTS: The prevalence of postoperative complications was 32.8% (22 of 67 cases) in 18 of the patients (29.5%). The most prevalent symptoms were persistent pain (68.2%), swelling (63.6%), and oroantral fistula (54.5%). Radiographic signs appeared in 45.5% of the complications. A total of 24 implants failed; thus, an overall 80.3% survival rate was established at 19 months. The vast majority of complications (86.4%) were treated eventually with reentry surgery and revealed that the sinus was full with granulation tissue surrounding pieces of a nonossified rubber-like material. In cases where implants were placed, nonosseointegrated implants were surrounded by soft tissue. The sinus was cleaned thoroughly; the graft material remnants were removed together with inflamed parts of the sinus membrane, followed by chlorhexidine and saline lavages. In the biopsy specimens taken from the sinus cavity, there were no histologic features of new bone formation around the grafted material. CONCLUSION: Lateral wall maxillary sinus augmentation using PBB was associated with an acute sinus infection histologic appearance and with a 7-times-higher failure rate compared with previous reports. This serious adverse event suggests that PBB cannot be recommended for maxillary sinus augmentations.


Assuntos
Substitutos Ósseos , Implantes Dentários , Levantamento do Assoalho do Seio Maxilar , Animais , Substitutos Ósseos/efeitos adversos , Transplante Ósseo , Caproatos , Bovinos , Implantação Dentária Endo-Óssea/efeitos adversos , Implantes Dentários/efeitos adversos , Dioxanos , Humanos , Lactonas , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/cirurgia , Estudos Retrospectivos , Levantamento do Assoalho do Seio Maxilar/efeitos adversos
11.
Molecules ; 26(20)2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34684837

RESUMO

In the context of an aging population, unhealthy Western lifestyle, and the lack of an optimal surgical treatment, deep osteochondral defects pose a great challenge for the public health system. Biodegradable, biomimetic scaffolds seem to be a promising solution. In this study we investigated the biocompatibility of porous poly-((D,L)-lactide-ε-caprolactone)dimethacrylate (LCM) scaffolds in contrast to compact LCM scaffolds and blank cell culture plastic. Thus, morphology, cytotoxicity and metabolic activity of human mesenchymal stromal cells (MSC) seeded directly on the materials were analyzed after three and six days of culturing. Further, osteoclastogenesis and osteoclastic activity were assessed using reverse-transcriptase real-time PCR of osteoclast-specific genes, EIA and morphologic aspects after four, eight, and twelve days. LCM scaffolds did not display cytotoxic effects on MSC. After three days, metabolic activity of MSC was enhanced on 3D porous scaffolds (PS) compared to 2D compact scaffolds (CS). Osteoclast activity seemed to be reduced at PS compared to cell culture plastic at all time points, while no differences in osteoclastogenesis were detectable between the materials. These results indicate a good cytocompatibility of LCM scaffolds. Interestingly, porous 3D structure induced higher metabolic activity of MSC as well as reduced osteoclast activity.


Assuntos
Células-Tronco Mesenquimais/citologia , Osteoclastos/citologia , Tecidos Suporte/química , Materiais Biocompatíveis/química , Caproatos/química , Diferenciação Celular/fisiologia , Células Cultivadas , Feminino , Humanos , Lactonas/química , Masculino , Pessoa de Meia-Idade , Osteogênese/fisiologia , Porosidade
12.
Environ Monit Assess ; 193(11): 727, 2021 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-34655328

RESUMO

Twenty-nine surface sediments from Chaohu Lake in China and from its six main tributaries were sampled to investigate the concentrations of two important polycyclic musks (PCMs), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran (galaxolide, HHCB) and 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (tonalide, AHTN), as well as the concentration of 4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta(g)-2-benzopyran-1-one (galaxolidon, HHCB-lactone), which is the main degradation product of HHCB. Except for the high concentrations of AHTN and HHCB measured in the Nanfei River (879 ng/g dw and 5,513 ng/g dw, respectively), the levels of AHTN and HHCB in the river sediments were 7.08-44.9 ng/g dw and 20.6-268 ng/g dw, respectively, which are slightly lower than those documented in various areas worldwide. The concentrations of AHTN and HHCB in the sediments of Chaohu Lake were one or two orders of magnitude lower than those in the tributary rivers and showed a clear regional distribution. The concentrations of HHCB-lactone were comparable to those of HHCB and presented a significant positive correlation with the concentrations of HHCB, suggesting that the HHCB-lactone originated directly from the degradation of HHCB in wastewater treatment plants (WWTPs) or in the natural environment. The diagnostic ratios of HHCB/AHTN and HHCB-lactone/HHCB and the enantiomeric fractions (EFs) of these PCMs showed that the direct origins of the target PCMs in the study area were municipal and industrial wastewaters discharged from adjacent cities or point sources and that the HHCB-lactone in sediment originated from the natural degradation of HHCB in the rivers and the lake. The results of the risk assessment showed that the PCMs in the watershed sediments were unlikely to pose a threat to aquatic species. However, the effluents of industrial and municipal wastewaters that are discharged into the Nanfei River should be investigated in future research.


Assuntos
Lagos , Poluentes Químicos da Água , Benzopiranos/análise , China , Monitoramento Ambiental , Lactonas , Rios , Poluentes Químicos da Água/análise
13.
Ecotoxicol Environ Saf ; 227: 112909, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34673414

RESUMO

Wilforine, a compound of sesquiterpene alkaloids isolated from Tripterygium wilfordii, exhibits excellent insecticidal activity against Mythimna separata. In order to clarify the action mechanism of wilforine, the plasma membrane calcium transporting ATPase (PMCA) and inositol 1,4,5-trisphosphate receptor (IP3R) from M. separata were studied. Results showed that the open reading frame of MsIP3R and MsPMCA were 8118 bp and 3438 bp in length, as well as encoded 2706 and 1146 amino acids, respectively. Multiple sequence alignment and phylogenetic analysis revealed that the MsIP3R and MsPMCA had high homology with the IP3R and PMCA of other insects, but had low similarity with those of mammals, which means the IP3R and PMCA have potential to be the novel targets of insecticides with high selectivity between mammals and insects. Both MsIP3R and MsPMCA genes existed throughout the life cycle of M. separata, and were all predominantly expressed in somatic muscle of fifth-instar larvae and the adults. The susceptibilities of PMCA-silenced M. separata to wilforine were significantly lower than that of the normal M. separata, which illustrates that PMCA could be one of the targets of wilforine. However, the susceptibilities of IP3R-silenced M. separata to wilforine did not change significantly compared with the susceptibilities of normal M. separata, which shows that wilforine may not interact with the IP3R protein. These findings provide clues for elucidating the insecticidal mechanism of wilforine.


Assuntos
Inseticidas , Mariposas , Animais , Inativação Gênica , Inositol , Receptores de Inositol 1,4,5-Trifosfato/genética , Inseticidas/toxicidade , Lactonas , Larva/genética , Mariposas/genética , Filogenia , ATPases Transportadoras de Cálcio da Membrana Plasmática , Piridinas , Interferência de RNA
14.
Vet Res ; 52(1): 127, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34600565

RESUMO

Mammary pathogenic Escherichia coli (MPEC) is an important causative agent of mastitis in dairy cows that results in reduced milk quality and production, and is responsible for severe economic losses in the dairy industry worldwide. Oxidative stress, as an imbalance between reactive oxygen species (ROS) and antioxidants, is a stress factor that is common in most bacterial habitats. The presence of ROS can damage cellular sites, including iron-sulfur clusters, cysteine and methionine protein residues, and DNA, and may cause bacterial cell death. Previous studies have reported that Autoinducer 2 (AI-2) can regulate E. coli antibiotic resistance and pathogenicity by mediating the intracellular receptor protein LsrR. This study explored the regulatory mechanism of LsrR on the H2O2 stress response in MPEC, showing that the transcript levels of lsrR significantly decreased under H2O2 stress conditions. The survival cell count of lsrR mutant XW10/pSTV28 was increased about 3080-fold when compared with that of the wild-type WT/pSTV28 in the presence of H2O2 and overexpression of lsrR (XW10/pUClsrR) resulted in a decrease in bacterial survival rates under these conditions. The ß-galactosidase reporter assays showed that mutation of lsrR led to a remarkable increase in expression of the promoters of ahpCF, katG and oxyR, while lsrR-overexpressing significantly reduced the expression of ahpCF and katG. The electrophoretic mobility shift assays confirmed that LsrR could directly bind to the promoter regions of ahpCF and katG. These results revealed the important role played by LsrR in the oxidative stress response of MPEC.


Assuntos
Doenças Mamárias/veterinária , Doenças dos Bovinos/fisiopatologia , Proteínas de Escherichia coli/genética , Homosserina/análogos & derivados , Peróxido de Hidrogênio/farmacologia , Lactonas/metabolismo , Percepção de Quorum , Proteínas Repressoras/genética , Animais , Sequência de Bases , Doenças Mamárias/microbiologia , Doenças Mamárias/fisiopatologia , Bovinos , Doenças dos Bovinos/microbiologia , DNA Bacteriano/análise , Proteínas de Escherichia coli/metabolismo , Feminino , Homosserina/metabolismo , Glândulas Mamárias Animais/microbiologia , Proteínas Repressoras/metabolismo , Alinhamento de Sequência/veterinária , Estresse Fisiológico
15.
J Agric Food Chem ; 69(36): 10486-10495, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34478295

RESUMO

Strigolactones (SLs) are plant hormones that play various roles in plant physiology, including provoking the germination of parasitic weeds Orobanche and Striga. A family of α/ß-hydrolases have been proposed to be the SL receptor proteins. Effective assays for measuring the activity of SL receptors could promote the development of SL-related biology and chemistry. In this study, we developed a new approach called pharmacophore-linked probe virtual screening (PPVS). Its application yielded an effective "off-on" probe named Xilatone Red (XLR). This probe showed a broad spectrum and excellent sensitivity toward SL receptors, including ShD14 (Striga D14), for which the detection limit was determined to be in the micromolar range, outperforming that of the commercial fluorogenic agonist Yoshimulactone Green (YLG). Upon hydrolysis by SL receptors, XLR provided fluorogenic and colorimetric signaling responses. Furthermore, XLR could induce germination of Phelipanche aegyptiaca seeds and prevent Arabidopsis max4-1 branching defects at micromolar concentrations. Our molecular simulations revealed the essential factors in the molecular perception of XLR. We anticipate that this study can prompt the discovery of high-performance SL agonists/antagonists to combat parasitic weeds.


Assuntos
Orobanche , Striga , Germinação , Compostos Heterocíclicos com 3 Anéis , Lactonas
16.
J Org Chem ; 86(19): 13371-13380, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34533324

RESUMO

Herein we described an access to biaryl lactones from ortho-aryl benzoic acids via intramolecular O-H/C-H oxidative coupling with the commonly used cerium ammonium nitrate (CAN) as the one-electron oxidant under a thermal condition. The radical interrupting experiment suggested a radical process, while the kinetic isotope effect (KIE) showed that the C-H cleavage likely was not involved in the rate-determining step. Competitive reactions, especially the strikingly different ρ values of Hammett equations, indicated that the reaction rate was more sensitive to the electronic properties on the aryl moiety rather than the carboxylic moiety, which corresponded to the first single electron transfer (SET) step. In addition, the quite negative ρ values (-4.7) of the aryl moiety unveiled the remarkable electrophilic nature of the second intramolecular radical addition process, which was also consistent with product yields and regioselectivity. Moreover, control experiments disclosed that the single electron in the third step was also transferred to CeIV instead of molecular oxygen. Besides, the possible role of co-solvents trifluoroethanol (TFE) and its influences on the CeIV species were discussed. This work elucidated the possible mechanism by proposing the step that had more effects on the total reaction rate and the species that was responsible for the last single electron transfer.


Assuntos
Compostos de Amônio , Cério , Lactonas , Nitratos , Oxirredução
17.
J Org Chem ; 86(19): 13572-13582, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34547199

RESUMO

A full account of our efforts toward the stereoselective total synthesis of sesquiterpenoid-derived natural products (±)-pleurospiroketals A and B is described. Commercially available 3-methyl-2-cyclohexenone and 2,2-dimethyloxirane were used as key building blocks, and the substrate-controlled stereoselection was exploited to access the entire stereochemistry of these natural products. Initially, a planned synthetic route involving a [6,5]-bicyclic lactone intermediate was found to be insurmountable, and the later strategy comprising OsO4-NMO-mediated dihydroxylation of 3-methyl-2-cyclohexenone, followed by Luche reduction, Eschenmoser methylenation, and Brønsted acid-induced spiroketalization steps, was ultimately identified as the reliable strategy.


Assuntos
Produtos Biológicos , Lactonas
18.
Toxicon ; 202: 60-66, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34562495

RESUMO

A new guaianolide sesquiterpene lactone with cytotoxic properties was isolated from Euphorbia microsphaera Boiss. To determine the highest active fraction and isolate bioactive compounds, a bioassay guided fractionation approach was used. The general toxicity properties of the plant's extracts and fractions (fr1-10) were assessed against Artemia salina, Oryzeaphilus mercator, and Tribolium castaneum. Cytotoxic activities were investigated against normal human foreskin fibroblasts and two malignant cell lines, including human breast cancer (MCF-7) and human fibrosarcoma cells (HT1080) using the MTT assay at different time points of 24, 48, and 72 h. Single crystal X-ray diffraction (SC-XRD) and mass spectrometry data were used to determine the structure of the active guaianolide sesquiterpene lactone (3aR,4S,4aS,5R,7aS,9aS)-5-hydroxy-5,8-dimethyl-3-methylene-2-oxo-2,3,3a,4,4a,5,6,7,7a, 9a decahydroazuleno [6,5-b] furan-4-yl acetate (named aryanin). Chloroformic fraction 7 (fr7, LC50 = 93.50 µg/mL for general toxicity) had the highest toxicity result, with a mortality rate of more than 50% for both insect species after 12 h at 15 mg/mL. The highest cytotoxicity of aryanin was observed on 24 h treated MCF-7 with an IC50 of 13.81 µg/mL. After 24 h, the inhibition of MCF-7 cell proliferation was 92%-94% at concentrations of 25-50 µg/mL, respectively. On MCF-7, the IC50 was found to be 49.35 µg/mL after 72 h. This compound had a considerable cytotoxicity (IC50 ≤ 12.5 µg/mL, 24 h) on human foreskin fibroblasts. In contrast to the MCF-7 cell line, the proliferation of human foreskin fibroblasts was increased after 72 h.


Assuntos
Antineoplásicos Fitogênicos , Neoplasias da Mama , Euphorbia , Fibrossarcoma , Sesquiterpenos , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Lactonas , Células MCF-7
19.
Nat Commun ; 12(1): 5279, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489434

RESUMO

Chiral bridged [2,2,1] bicyclic lactones are privileged structural units in pharmaceutics and bioactive nature products. However, the synthetic methods for these compounds are rare. Here we report an efficient method for enantioselective construction of bridged [2,2,1] bicyclic lactones bearing a quaternary stereocenter via Rh-catalyzed asymmetric hydroformylation/intramolecular cyclization/pyridium chlorochromate (PCC) oxidation. By employing a hybrid phosphine-phosphite chiral ligand, a series of cyclopent-3-en-1-ols are transformed into corresponding γ-hydroxyl aldehydes with specific syn-selectivity. Then, hemiacetals form in situ and oxidation with PCC in one-pot affords bridged [2,2,1] bicyclic lactones in high yields and excellent enantiomeric excess. Replacing the hydroxyl group by an ester group, cyclopentanecarbaldehydes with a chiral all-carbon quaternary stereocenter in the γ-position can be generated efficiently.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Formiatos/química , Lactonas/síntese química , Fenazopiridina/química , Água/química , Aldeídos/química , Ciclização , Ciclopentanos/química , Humanos , Oxirredução , Fosfinas/química , Fosfitos/química , Estereoisomerismo
20.
J Food Biochem ; 45(10): e13919, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34486135

RESUMO

Marine pharaoh cuttlefish Sepia pharaonis (family Sepiidae) is regarded as an economically important class of cephalopod in the coastal Mediterranean and Asian regions. Bioassay-guided chromatographic purification of solvent extract of S. pharaonis led to the identification of a trans-decalin based spirolactone, spiropharanone, which was characterized as 1-hydroxy-7-(4'-methoxy-3-methylbut-2-enyl)-3,9,15-trimethyl-8-oxo-octahydro-5H-spiro[furan-8,9-naphtho]-8-yl-acetate by spectroscopic techniques. Spiropharanone exhibited significantly greater anti-inflammatory activity by attenuating pro-inflammatory 5-lipoxygenase (IC50 1.02 mM) than the non-steroidal drug ibuprofen (IC50 4.61 mM, p ≤ .05). Superior antioxidant properties of spiropharanone against free radicals (EC50 ~1.20 mM) and other oxidants (hydroxyl [EC50 0.97 mM] and superoxide [EC50 1.47 mM] scavenging) also reinforced its promising anti-inflammatory activity. The studied spiropharanone also exhibited significant attenuation toward insulin secretion regulating enzyme dipeptidyl peptidase-4 (IC50 0.92 mM) recognizing its anti-hyperglycemic potential. Significantly higher electronic properties (topological polar surface area ~100) combined with balanced hydrophilic-lipophilic properties (partition coefficient of logarithmic octanol-water ~3) and lesser docking parameters of spiropharanone demonstrated that the compound could be utilized as an important bioactive lead against oxidative stress, inflammation, and hyperglycemic-related ailments. PRACTICAL APPLICATIONS: Nutritionally rich edible marine pharaoh cuttlefish Sepia pharaonis occupies a prominent place among seafood fisheries owing to the presence of bioactive nutrients and functional food ingredients. These marine cuttlefish are widely distributed along the Asian and Mediterranean coasts, and consumed as culinary delicacy for decades. An undescribed trans-decalin spirolactone, spiropharanone was isolated from the organic extract of S. pharaonis based on bioactivity-assisted sequential chromatographic fractionation. Spiropharanone displayed promising antioxidant potential along with attenuation properties against inducible pro-inflammatory 5-lipoxygenase and insulin secretion regulating enzyme dipeptidyl peptidase-4. This study established the ameliorating potential of a naturally derived marine food constituent against inflammatory and diabetic ailments, and thus anticipated as functional food lead in pharmaceutical formulations towards inflammation and maintaining glucose homeostasis.


Assuntos
Sepia , Animais , Antioxidantes/farmacologia , Araquidonato 5-Lipoxigenase , Decapodiformes , Lactonas , Lipoxigenase , Naftalenos , Alimentos Marinhos , Serina Proteases
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