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1.
J Food Biochem ; : e13672, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624852

RESUMO

Alcoholic liver disease (ALD) is characterized by dyslipidemia, hepatic steatosis, steatohepatitis, edema, necrosis, etc. Studies have reported that some dietary nutrition factors have beneficial effects in improving ALD. Red yeast rice (RYR), a traditional herbal supplement, has been confirmed to lower cholesterol mainly due to its component monacolin K. However, the effect of RYR on ALD has not been investigated. In this study, mice were supplemented with a daily oral gavage of 4 g/kg 50% ethanol for 8 weeks to induce a chronic ALD. RYR (150 mg kg-1  day-1 ) was supplied to ALD mice in treatment group. The results showed that RYR supplementation significantly attenuated hyperlipidemia, elevated circulating inflammatory cytokines, hepatic structural damage, and oxidative stress in mice supplemented with alcohol with no effects on body weight. Moreover, RYR significantly suppressed alcohol-induced hepatic NF-κB activation and apoptosis. Our results suggest that RYR is capable of preventing ALD mainly by attenuating hepatic oxidative stress and inflammatory response. PRACTICAL APPLICATIONS: RYR was known for cholesterol-lowering effect through its main component monacolin K. The current study revealed that RYR was capable of ameliorating ALD, which is characterized by profound dyslipidemia, hepatic steatosis, steatohepatitis, edema, etc. Our results indicated that the protective effect of RYR on ALD is largely achieved by regulating lipid metabolism, and closely related to the anti-inflammatory and antioxidant effects of RYR. This study provides research foundation for the development of RYR-related food or pharmaceutical products, especially targeting for ALD.

2.
Food Chem ; 346: 128895, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33421902

RESUMO

Bisphenols (BPs) are worldwide used organic compounds in plastics, belonging to the group of endocrine disrupting chemicals (EDCs) which exhibits endocrine disruption to beings. Migration of BPs from food contact materials like plastic containers, epoxy coatings in metal cans and thermal papers, would results in bioaccumulation of BPs in human beings, causing adverse health effects. Therefore, sensitive and selective determination of BPs in food is needed. Among different strategies have been explored for the detection of BPs, electrochemical sensors with relatively high sensitivity and fast response are promising. This paper is devoted to comprehensively review the developed electrochemical methods for BPs sensing in food, so that to find a direction for developing low cost, high accuracy and compatibility sensors toward the sensitive and selective detection of BPs. Different electrochemical technologies categorized by recognition agents, aptamers, enzymes, molecularly imprinted polymers and nanomaterials are discussed and summarized in their mechanisms, usages, merits and limitations. The challenges and further perspectives in the development of electrochemical sensors is also discussed.


Assuntos
Compostos Benzidrílicos/análise , Eletroquímica/métodos , Análise de Alimentos/métodos , Fenóis/análise , Disruptores Endócrinos/análise , Contaminação de Alimentos/análise , Humanos , Nanoestruturas/química
3.
Biomolecules ; 11(1)2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33418906

RESUMO

Royal jelly (RJ), a natural honeybee product, has a wide range of antibacterial activities. N-glycosylated major royal jelly protein 2 (N-MRJP2), purified from RJ, can inhibit the growth of Paenibacillus larvae (P. larvae, Gram-positive), a contagious etiological agent of the American foulbrood disease of honeybees. However, the inhibitory mechanism is largely unknown. Antibacterial assay and membrane proteome were conducted to investigate the inhibition capacity of RJ from different instar larvae and P. larvae treated by N-MRJP2, respectively. The similar antibacterial efficiency of RJ from different larval instar indicates that RJ is vital for the adaptive immune defense of small larvae. The killing of P. larvae by N-MRJP2 is achieved by disturbing the cell wall biosynthesis, increasing the permeability of cell membrane, hindering aerobic respiration, restraining cell division and inducing cell death. This demonstrates that RJ is critical for the passive immunity of immature larvae and N-MRJP2 can be used as natural antibiotic substance to resist P. larvae, even for other gram-positive bacteria. This constitutes solid evidence that RJ and N-MRJP2 have potentials as novel antibacterial agents.

4.
Food Res Int ; 139: 109974, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33509520

RESUMO

Royal jelly (RJ), a natural secretion of nurse bees, is a functional food with health-promoting properties. To investigate RJ quality changes with enhanced output and harvesting time, we compared metabolic profiles of RJ harvested at 24 h, 48 h, and 72 h after larval grafting into queen cells from Italian bees (ITBs) and high RJ-producing bees (RJBs) selected from ITBs. A total of 77 high-abundance compounds were identified with reverse-phase liquid chromatography- and hydrophilic interaction liquid chromatography-high-resolution mass spectrometry. Metabolite abundance, water content, and antibacterial activity were found largely unchanged between both bee strains, indicating that a similar RJ quality was achieved. Notably, the observed 10-hydroxy-2-decenoic acid content in RJBs (1.98%) and ITBs (2.41%) meet the standard for premium RJ in China. RJ harvested at 48 h and 72 h had similar metabolic profiles, indicating little influence of the two harvesting times on RJ quality. The harvesting at 24 h could lead to a higher RJ quality with higher abundance levels of many bioactive compounds and lower water content. Our data based mainly on RJ metabolic composition constitute evidence for mass production of high-quality RJ.

5.
J Cell Mol Med ; 25(2): 1198-1206, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33342045

RESUMO

Calcium/calmodulin-dependent protein kinase (CAMKs) can control a wide range of cancer-related functions in multiple tumour types. Herein, we explore the expressions and clinical significances of calcium/calmodulin-dependent protein kinase 1 (CAMK1) in pancreatic cancer (PC). The expression of CAMK1 in PC was analysed by Gene Expression Profiling Interactive Analysis 2 (GEPIA 2) database and the Oncomine database. For further validation, the protein level of CAMK1 in PC tissues was also detected in the Human Protein Atlas (HPA) database and the tissue microarray (TMA)-based immunohistochemistry (IHC). GEPIA 2 and Kaplan-Meier Plotter (KM Plotter) databases were used to explore the prognostic significances of CAMK1 in overall survival (OS) and disease-free survival (DFS) of PC at mRNA level. The relationship between CAMK1 expression and the clinicopathological characteristics of PC was further explored. Additionally, the Search Tool for the Retrieval of Interacting Genes (STRING) database was used to analyse protein-protein interactions (PPI). We found CAMK1 was highly expressed in PC both in bioinformatics analyses and TMA-IHC results. The prognostic analyses from the public databases also showed consistent results with follow-up data. The PPI network suggested that CALM1, CALM3, CREB1, CALM2, SYN1, NOS3, ATF1, GAPDH, PPM1F and FBXL12 were important significant genes associated with CAMK1. Our finding revealed CAMK1 has prognostic value in PC patients, suggesting that CAMK1 may has a distinct role in PC patients and can be used as a candidate marker for investigating clinical prognosis of PC.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33373323

RESUMO

Coronavirus disease 2019 (COVID-19) is a recently emerged pandemic caused by a novel virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is communicable and mainly affects the respiratory tract. The outbreak of this disease has greatly influenced human health and economic activities worldwide. The absence of any medication for this infection highlights the urgent need for the development of alternative methods for managing the spread of the disease. Our immune system operates based on a complex array of cells, processes, and chemicals that continuously protect our body from invading pathogens, including viruses, toxins, and bacteria. The present study was conducted to perform a comprehensive review of all dietary treatments for boosting immunity against viral infections. No study was found to explicitly support the use of any healthy foods or supplements to protect against COVID-19. However, this study offers details on well-researched functional foods and supplements that typically improve the immune response, which could be helpful against this newly emerged pandemic.

7.
Food Sci Nutr ; 8(8): 4565-4572, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32884736

RESUMO

Green tea, superfine green tea powder (SGTP), and tea extract were prepared to determine their chemical components and antioxidant activity. The nutrition and aroma challenges of green tea during traditional extract technique and superfine grinding were profiled in this study. The traditional extract technique took advantage over superfine grinding in L-theanine and glutamic acid (Glu) preservation, but not in other 16 essential amino acids. SGTP preserved a maximum of elements from green tea, whereas tea extract greatly changed the elements ratio. Tea extract contained higher VB2 and VC contents and doubled the tea polyphenol (TP) content in comparison with green tea and SGTP. Additionally, tea extract contained more favorable aroma compounds and maintained stronger antioxidant activity in comparison with green tea and SGTP. This study profiled an important basis for the comprehensive utilization of green tea resources by consumers and manufacturers.

8.
Mol Cell Proteomics ; 19(10): 1632-1648, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32669299

RESUMO

The neuronal basis of complex social behavior is still poorly understood. In honeybees, reproductive investment decisions are made at the colony-level. Queens develop from female-destined larvae that receive alloparental care from nurse bees in the form of ad-libitum royal jelly (RJ) secretions. Typically, the number of raised new queens is limited but genetic breeding of "royal jelly bees" (RJBs) for enhanced RJ production over decades has led to a dramatic increase of reproductive investment in queens. Here, we compare RJBs to unselected Italian bees (ITBs) to investigate how their cognitive processing of larval signals in the mushroom bodies (MBs) and antennal lobes (ALs) may contribute to their behavioral differences. A cross-fostering experiment confirms that the RJB syndrome is mainly due to a shift in nurse bee alloparental care behavior. Using olfactory conditioning of the proboscis extension reflex, we show that the RJB nurses spontaneously respond more often to larval odors compared with ITB nurses but their subsequent learning occurs at similar rates. These phenotypic findings are corroborated by our demonstration that the proteome of the brain, particularly of the ALs differs between RJBs and ITBs. Notably, in the ALs of RJB newly emerged bees and nurses compared with ITBs, processes of energy and nutrient metabolism, signal transduction are up-regulated, priming the ALs for receiving and processing the brood signals from the antennae. Moreover, highly abundant major royal jelly proteins and hexamerins in RJBs compared with ITBs during early life when the nervous system still develops suggest crucial new neurobiological roles for these well-characterized proteins. Altogether, our findings reveal that RJBs have evolved a strong olfactory response to larvae, enabled by numerous neurophysiological adaptations that increase the nurse bees' alloparental care behavior.

9.
Poult Sci ; 99(6): 3144-3157, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32475451

RESUMO

The effects of storage temperature (4°C, 25°C, and 35°C) on sensory quality, physicochemical properties, texture, molecular forces, flavor, and microbial indexes of preserved eggs were studied. The results showed that the sensory quality, weight loss rate, pH, and color of preserved eggs were significantly different at different storage temperatures (P < 0.05). Compared with high temperature and normal temperature storage, low temperature storage reduced weight loss rate by 55.15 and 64.1%, respectively, improved the sensory score (P < 0.05), inhibited the reduction of pH and the increase of total volatile base nitrogen (P < 0.05), and decreased the change of color (P < 0.05). During storage, there was no difference in the springiness of preserved egg white stored at different temperatures (P > 0.05). Hardness and chewiness at 3 different temperatures increased first and then decreased, and low temperature significantly inhibited the progress of these changes to a certain extent (P < 0.05). The content of ionic bond in egg white first decreased and then increased, and content of disulfide bond increased first and then decreased. Content of ionic bond in yolk decreased all the time, and high temperature could promote this change. Whatever the temperature was, the content of free amino acids in preserved egg white and yolk increased first and then decreased, and the total content of amino acids stored at different temperatures was significantly different (P < 0.05). The content of free fatty acids in yolk decreased. At the end of storage, no microorganisms were detected in 3 temperatures during the storage period of 84 D. The results showed that low temperature storage is more conducive for preservation of preserved eggs.

10.
Mol Med Rep ; 22(2): 828-840, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32468041

RESUMO

Molecular classifications of gastric cancer (GC) by the Asian Cancer Research Group (ACRG) and The Cancer Genome Atlas Consortium (TCGA) are useful for diagnosis and treatment of GC. However, their clinical significance is unknown. The present study aims to explore the associations between subtypes of GC and prognosis of patients with GC. Immunohistochemistry (IHC) was used in the ACRG molecular classification of GC, while next­generation sequencing technology was used in TCGA molecular classification. The results indicated that, out of a total of 65 cases of GC, some were classified as Epstein­Barr virus positive type (9.2%, 6 of 65), some as microsatellite instability (MSI) type (23.1%, 15 of 65), some as gene stable type (21.5%, 14 of 65) and some as chromosome instability type (46.2%, 30 of 65) according to TCGA typing standard. Of the total 65 GC cases, some were classified as MSI (21.5%, 14 of 65), some as microsatellite stable/epithelial­mesenchymal transition (MSS/EMT; 20.0%, 13 of 65), some as MSS/tumor protein 53 active (TP53+; 15.4%, 10 of 65) and some as MSS/TP53 inactive (43.1%, 28 of 65) according to ACRG typing standard. ARCG molecular subtype (P=0.010) and Lauren classification (P=0.011) were independently correlated with the overall survival of patients with GC. In conclusion, TCGA classification based on a Chinese population is the same as TCGA typing based on a European population in terms of proportion and clinical characteristics, but there are differences in gene amplification and gene mutation. ACRG molecular classification could be performed by IHC analysis and may be a valuable independent prognostic marker for patients with GC.

11.
Autophagy ; : 1-13, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32003282

RESUMO

Microglial activation-induced neuroinflammation is closely associated with the development of Parkinson disease (PD). Macroautophagy/autophagy regulates many biological processes, but the role of autophagy in microglial activation during PD development remains largely unclear. In this study, we showed that deletion of microglial Atg5 caused PD-like symptoms in mice, characterized by impairment in motor coordination and cognitive learning, loss of tyrosine hydroxylase (TH) neurons, enhancement of neuroinflammation and reduction in dopamine levels in the striatum. Mechanistically, we found that inhibition of autophagy led to NLRP3 (NLR family pyrin domain containing 3) inflammasome activation via PDE10A (phosphodiesterase 10A)-cyclic adenosine monophosphate (cAMP) signaling in microglia, and the sequential upregulation of downstream IL1B/IL-1ß in turn increased the expression of MIF (macrophage migration inhibitory factor [glycosylation-inhibiting factor]), a pro-inflammatory cytokine. Inhibition of NLRP3 inflammasome activation by administration of MCC950, a specific inhibitor for NLRP3, decreased MIF expression and neuroinflammatory levels, and rescued the loss of TH neurons in the substantial nigra (SN). Interestingly, we found that serum MIF levels in PD patients were significantly elevated. Taken together, our results reveal an important role of autophagy in microglial activation-driven PD-like symptoms, thus providing potential targets for the clinical treatment of PD.Abbreviations: ATG: autophagy related; cAMP: cyclic adenosine monophosphate; cKO: conditional knockout; NOS2/INOS: nitric oxide synthase 2, inducible; IL1B: interleukin 1 beta; ITGAM/CD-11b: integrin alpha M/cluster of differentiation molecule 11B; MAP1LC3: microtubule-associated protein 1 light chain 3; MIF: macrophage migration inhibitory factor (glycosylation-inhibiting factor); NLRP3: NLR family pyrin domain containing 3; PBS: phosphate-buffered saline; PD: parkinson disease; PDE10A: phosphodiesterase 10A; SN: substantial nigra; TH: tyrosine hydroxylase; TNF: tumor necrosis factor; WT: wild type.

12.
Expert Opin Ther Targets ; 24(3): 267-279, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32077781

RESUMO

Objectives: 10-hydroxydec-2-enoic acid (10-HDA), a unique component of royal jelly existing only in nature, has the potential to promote human health. Knowledge of 10-HDA in regulating immuno-activity, however, is lacking. The aim of our work is to gain a novel understanding of 10-HDA in promoting immunity.Methods: Immuno-suppressed mice were generated by cyclophosphamide injection, After 10-HDA supplementation to the mice to rescue their immunity, the proteomes of the thymus and spleen were analyzed.Results: The weight of the body, thymus, and spleen in cyclophosphamide-induced mice recovered by 10-HDA indicate its potential role in immuno-organ protection. In the thymus, the enhanced activity of pathways associated with DNA/RNA/protein activities may be critical for T-lymphocyte proliferation/differentiation, and cytotoxicity. In the spleen, the induced pathways involved in DNA/RNA/protein activities, and cell proliferative stimulation suggest their vital role in B-lymphocyte affinity maturation, antigen presentation, and macrophage activity. The up-regulated proteins highly connected in networks modulated by 10-HDA indicate that the mice may evolve tactics to respond to immuno-organ impairment by activating critical physiological processes.Conclusion: Our data constitute a proof-of-concept that 10-HDA is a potential agent to improve immunity in the thymus and spleen and offer a new venue for applying natural products to the therapy for hypoimmunity.

13.
Int J Mol Sci ; 21(2)2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31936187

RESUMO

Royal jelly (RJ) is a yellowish-white and acidic secretion of hypopharyngeal and mandibular glands of nurse bees used to feed young worker larvae during the first three days and the entire life of queen bees. RJ is one of the most appreciated and valued natural product which has been mainly used in traditional medicines, health foods, and cosmetics for a long time in different parts of the world. It is also the most studied bee product, aimed at unravelling its bioactivities, such as antimicrobial, antioxidant, anti-aging, immunomodulatory, and general tonic action against laboratory animals, microbial organisms, farm animals, and clinical trials. It is commonly used to supplement various diseases, including cancer, diabetes, cardiovascular, and Alzheimer's disease. Here, we highlight the recent research advances on the main bioactive compounds of RJ, such as proteins, peptides, fatty acids, and phenolics, for a comprehensive understanding of the biochemistry, biological, and pharmaceutical responses to human health promotion and life benefits. This is potentially important to gain novel insight into the biological and pharmaceutical properties of RJ.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Ácidos Graxos/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Abelhas/química , Abelhas/metabolismo , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Cosméticos , Ácidos Graxos/farmacologia , Humanos , Larva/metabolismo , Preparações Farmacêuticas/química
14.
Clin Pharmacol Drug Dev ; 9(2): 277-286, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31916418

RESUMO

Quizartinib is an oral, highly potent, and selective type II FMS-like tyrosine kinase 3 inhibitor in development for acute myeloid leukemia. This parallel-group study evaluated potential food effects on quizartinib absorption in healthy subjects who received a single 30-mg dose after overnight fasting (n = 34) or a high-fat, high-calorie meal (n = 30). Blood samples were collected through 504 hours after dosing, and pharmacokinetic parameters calculated were maximum observed concentration (Cmax ) and area under plasma concentration-time curve from time 0 to last quantifiable concentration (AUClast ) and from time 0 to infinity (AUCinf ). Mean quizartinib pharmacokinetic profiles were similar under fasted and fed conditions. The geometric least squares means ratios (%) for fed/fasted and associated 90% confidence intervals (CIs) for Cmax , AUClast , and AUCinf were 91.58 (82.15-102.08), 105.39 (90.79-122.35), and 108.39 (91.54-128.34), respectively. The 90%CI for the ratio fell within the 80% to 125% limits for Cmax and AUClast , with 90%CI for AUCinf slightly outside the limits (ie, 128%). Food delayed quizartinib time to Cmax by 2 hours. All adverse events were either mild or moderate; no discontinuations due to adverse events occurred. Based on these results, quizartinib can be administered without regard to food.

15.
J Sci Food Agric ; 100(4): 1418-1425, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31667852

RESUMO

BACKGROUND: Silkworm pupa oil polyunsaturated fatty acid (SPO PUFA) has been confirmed to have a cholesterol-lowering function. METHODS AND RESULTS: The effect of SPO PUFA and its main component, α-linolenic acid (ALA), on the metabolism of cholesterol and its regulation was investigated. The model of lipid denatured cells were constructed to carry out lipid accumulation, cholesterol metabolism and transformation. Real-time PCR and western blots were also used to analyze the expression levels of related genes and proteins to investigate the cholesterol efflux regulation mechanism. The data indicated that SPO PUFA and ALA dose-dependently decreased intracellular total cholesterol (TC) and enhanced total bile acid (TBA). They could also promote cholesterol removal by enhancing bile acid secretion and by upregulating genes LXRα, PPARγ, ABCA1, ABCG1, and CYP7A1, which were regulated by LXRα/PPARγ-ABCA1/ABCG1-CYP7A1 nuclear receptor signal pathways. CONCLUSIONS: This study is of great significance in maintaining the balance of cholesterol and lipid metabolism, and in reducing the risk of steatohepatitis. © 2019 Society of Chemical Industry.


Assuntos
Bombyx/química , Colesterol/metabolismo , Ácidos Graxos Insaturados/farmacologia , Hepatócitos/metabolismo , Pupa/química , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular , Colesterol 7-alfa-Hidroxilase/genética , Colesterol 7-alfa-Hidroxilase/metabolismo , Hepatócitos/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , PPAR gama/genética , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Sci Rep ; 9(1): 19092, 2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836821

RESUMO

The Trigonidiidae, a family of crickets, comprises 981 valid species with only one mitochondrial genome (mitogenome) sequenced to date. To explore mitogenome features of Trigonidiidae, six mitogenomes from its two subfamilies (Nemobiinae and Trigonidiinae) were determined. Two types of gene rearrangements involving a trnN-trnS1-trnE inversion and a trnV shuffling were shared by Trigonidiidae. A long intergenic spacer was observed between trnQ and trnM in Trigonidiinae (210-369 bp) and Nemobiinae (80-216 bp), which was capable of forming extensive stem-loop secondary structures in Trigonidiinae but not in Nemobiinae. The anticodon of trnS1 was TCT in Trigonidiinae, rather than GCT in Nemobiinae and other related subfamilies. There was no overlap between nad4 and nad4l in Dianemobius, as opposed to a conserved 7-bp overlap commonly found in insects. Furthermore, combined comparative analysis and transcript verification revealed that nad1 transcripts ended with a U, corresponding to the T immediately preceding a conserved motif GAGAC in the superfamily Grylloidea, plus poly-A tails. The resultant UAA served as a stop codon for species lacking full stop codons upstream of the motif. Our findings gain novel understanding of mitogenome structural diversity and provide insight into accurate mitogenome annotation.


Assuntos
Genoma Mitocondrial , Proteínas de Insetos/genética , Ortópteros/genética , Animais , Sequência de Bases , DNA Intergênico/genética , Ordem dos Genes , Rearranjo Gênico , Genes de Insetos , Proteínas de Insetos/metabolismo , Conformação de Ácido Nucleico , Fases de Leitura Aberta/genética , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Ribossômico/genética , RNA de Transferência/genética
17.
Food Funct ; 10(12): 8273-8285, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31720661

RESUMO

Recent studies have found that a high-fat diet (HFD) causes gut microbiota imbalance and colon tissue damage, resulting in increased intestinal permeability, which is one of the main reasons for the existence of constantly circulating low-grade inflammatory cytokines. Pomegranate extracts have been shown to protect from HFD-induced metabolic inflammation (e.g., colitis) and to promote the growth of beneficial bacteria in in vitro stool cultures. However, whether the beneficial effects of pomegranate extracts on the HFD-induced metabolic inflammation are achieved by acting on intestinal tissues has not yet been studied. In our present study, we found that pomegranate peel polyphenols (PPPs) alleviated HFD-induced obesity, elevated circulating pro-inflammatory cytokines, colonic tissue damage, and depressed colonic tight junction protein expression level in rats. Moreover, PPPs normalized the HFD-induced gut microbiota imbalance by increasing the abundance of beneficial bacteria in the colon. Furthermore, we also found that PPPs, punicalagin, and urolithin A (the main microbiota metabolites of pomegranate ellagitannins) all increased the LPS-induced decreased tight junction protein expression level and reversed the LPS-induced inflammatory response in Caco-2 cells. Urolithin A exhibited the best effects among the three pomegranate components. Our results suggested that the protective effects of PPPs in HFD-induced metabolic inflammation can be due to the recovery of colonic tissue damage and the regulation of gut microbiota and that urolithin A is the major component that contributes to the in vivo effects of PPPs.


Assuntos
Colite/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Polifenóis/administração & dosagem , Romã (Fruta)/química , Animais , Colite/etiologia , Colite/imunologia , Colite/microbiologia , Colo/imunologia , Colo/microbiologia , Cumarínicos/administração & dosagem , Cumarínicos/análise , Dieta Hiperlipídica/efeitos adversos , Frutas/química , Humanos , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/análise , Inflamação , Masculino , Extratos Vegetais/análise , Polifenóis/análise , Ratos , Resíduos/análise
18.
Int J Mol Sci ; 20(17)2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31480282

RESUMO

Advances in instrumentation and computational analysis in proteomics have opened new doors for honeybee biological research at the molecular and biochemical levels. Proteomics has greatly expanded the understanding of honeybee biology since its introduction in 2005, through which key signaling pathways and proteins that drive honeybee development and behavioral physiology have been identified. This is critical for downstream mechanistic investigation by knocking a gene down/out or overexpressing it and being able to attribute a specific phenotype/biochemical change to that gene. Here, we review how emerging proteome research has contributed to the new understanding of honeybee biology. A systematic and comprehensive analysis of global scientific progress in honeybee proteome research is essential for a better understanding of research topics and trends, and is potentially useful for future research directions.


Assuntos
Abelhas/metabolismo , Proteômica , Pesquisa , Animais , Hierarquia Social , Proteínas de Insetos/metabolismo , Proteoma/metabolismo
19.
Int J Biol Macromol ; 141: 553-563, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31499112

RESUMO

Honeybees communicate with members of their intra-species via pheromones. The volatile pheromones, ß-ocimene and allo-ocimene, are the primary signals of larvae to beg for the care from the nurses. Of the odorant binding proteins (OBPs)/chemosensory proteins (CSPs), CSP4 has the best affinity with ß-ocimene and allo-ocimene. To reveal the binding mechanism of CPS4 with them, fluorescent quenching, UV absorption spectra, circular dichroism (CD) spectra, isothermal titration calorimetry (ITC), molecular docking, molecular dynamic (MD) simulation, and site-directed mutagenesis were applied. The quenching constant Ksv decreased with temperature increase, and the interaction distance was 2.73 nm and 2.43 nm (<10 nm), indicating that ß-ocimene and allo-ocimene could form stable complexes with CSP4. The observed △H < 0 and △S > 0 of thermodynamics suggest the main driving forces are electrostatic or hydrophobic force. All above thermodynamics findings are in line with the results of ITC experiments. Furthermore, molecular docking, MD simulation and site-directed mutagenesis indicate the binding cavities are located at cavity 1 in C-terminal of CSP4, where Tyr98 and Asp67 are vital amino acids in maintaining the stable form of protein and larval pheromones, and electrostatic energies are the main driving forces. Our findings gain novel insight into the binding mechanism of chemosensory protein with volatile larval pheromones and are important for understanding olfactory interaction of honeybees.


Assuntos
Abelhas/química , Proteínas de Insetos/química , Simulação de Acoplamento Molecular , Feromônios/química , Animais , Abelhas/metabolismo , Proteínas de Insetos/metabolismo , Larva/química , Larva/metabolismo , Feromônios/metabolismo
20.
Cancer Chemother Pharmacol ; 84(4): 799-807, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31385001

RESUMO

PURPOSE: Quizartinib, a potent, selective FMS-like tyrosine kinase 3 (FLT3) inhibitor, is currently in phase 3 development for patients with FLT3-internal tandem duplication-mutated acute myeloid leukemia (AML). Acid-reducing agents (ARAs; e.g., proton pump inhibitors) are frequently used during AML treatment. Since quizartinib demonstrates pH-dependent solubility, the effect of lansoprazole coadministration on pharmacokinetics (PK) of quizartinib tablet formulation was assessed. METHODS: An open-label, parallel-group study randomized 64 healthy adults to single-dose quizartinib 30 mg alone (reference) or lansoprazole (60 mg once daily, days 1-5) + single-dose quizartinib 30 mg (day 5) (test). Plasma concentrations of quizartinib and its active metabolite, AC886, were measured to 504 h postdose; the effect of lansoprazole on quizartinib PK was assessed by analysis of variance. RESULTS: Quizartinib geometric mean ratios (test/reference) and 90% confidence intervals for maximum observed plasma concentration (Cmax), area under the concentration-time curve to last measurable drug concentration (AUClast), and AUC to infinity were 86.11% (78.4%, 94.6%), 93.96% (79.6%, 110.9%), and 95.30% (80.2%, 113.3%), respectively. Comparisons showed a modest decrease in quizartinib absorption when co-administered with lansoprazole, with lower limits for Cmax and AUClast just below 80-125% limits. Treatment-emergent adverse events were mild or moderate; the most frequent in either treatment group were headache [quizartinib alone: (n = 3) 10%], upper respiratory tract infection [quizartinib alone: (n = 2) 6.7%; lansoprazole + quizartinib: (n = 3) 9.1%], and muscle tightness [quizartinib alone: (n = 2) 6.7%]. CONCLUSIONS: Concomitant lansoprazole had minimal effect on quizartinib PK as a formulated tablet, indicating that quizartinib can be administered with ARAs.


Assuntos
Benzotiazóis , Lansoprazol , Compostos de Fenilureia , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Benzotiazóis/administração & dosagem , Benzotiazóis/efeitos adversos , Benzotiazóis/farmacocinética , Relação Dose-Resposta a Droga , Interações Medicamentosas , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Lansoprazol/administração & dosagem , Lansoprazol/efeitos adversos , Lansoprazol/farmacocinética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/farmacocinética , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/farmacocinética , Resultado do Tratamento , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores
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