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1.
Food Chem ; 371: 131050, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34537615

RESUMO

Vitamin B3, derived primarily from plant sources, is an essential nutrient for humans. Torreya grandis is rich in vitamin B3, however, the mechanism underlying the biosynthesis and regulation of vitamin B3 in T. grandis remains unclear. A systematic transcriptomic investigation was thus conducted to identify the gene expression pattern of vitamin B3 biosynthesis in 10 T. grandis cultivars. The findings suggest that biosynthesis occurs mainly via the aspartate pathway. Expression and correlation analyses indicate that aspartate oxidase (AOX) and quinolinate synthase (QS) may play important roles in vitamin B3 accumulation. Furthermore, co-expression network and ethephon treatments indicate that the ethylene response factor (ERF) may be involved in the regulation of vitamin B3 biosynthesis in T. grandis nuts. Our findings not only help to elucidate the biosynthesis of vitamin B3, but also provide valuable resource material for future genomic research and molecular-assisted breeding to develop genotypes with higher vitamin B3 levels.


Assuntos
Nozes , Taxaceae , Etilenos , Expressão Gênica , Regulação da Expressão Gênica de Plantas , Humanos , Nozes/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Vitaminas
2.
J Ethnopharmacol ; 284: 114829, 2022 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763041

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Natural bear bile powder (NBBP) is a traditional Chinese medicine used for treating liver dysfunction. Cultured bear bile powder (CBBP), which is produced using biotransformation of chicken bile, acts as an appropriate substitute for NBBP when treating cholestatic liver injury. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the hepatoprotective effects of CBBP in an α-naphthylisothiocyanate (ANIT)-induced cholestatic mouse model. MATERIALS AND METHODS: Cholestatic mice were pretreated with CBBP or NBBP via oral gavage once a day for two weeks. Their blood biochemistry and liver histopathology were then evaluated using standard protocols. Western blot analyses, real-time polymerase chain reaction, and immunohistochemistry were used to evaluate changes in the protein levels and gene expression profiles of factors associated with hepatic inflammation and apoptosis in cholestatic mice. RESULTS: CBBP significantly decreased the serum indices of liver injury, and ameliorated neutrophil infiltration and hepatocyte necrosis within liver tissue of cholestatic mice. Expression of the inflammatory factors, such as tumor necrosis factor-α, interleukin-1ß (IL-1ß), IL-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule 1, was significantly reduced in CBBP-treated cholestatic mice. Moreover, proteins involved in the toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B (TLR4/Myd88/NF-κB) signaling pathway, such as CD14, TLR4, Myd88, and NF-κB, that were increased in cholestatic mice, were downregulated by CBBP. Meanwhile, increased expression of the apoptosis-related proteins, caspase-3 and Bax, in cholestatic mice was reversed by CBBP treatment. CONCLUSION: CBBP treatment alleviates ANIT-induced cholestasis and liver injury by reducing hepatocyte inflammation and apoptosis.

3.
Food Chem ; 368: 130836, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34411862

RESUMO

The postharvest ripening stage is necessary for Torreya grandis (T. grandis) nuts to complete aromatic synthesis, which requires appropriate temperature and relative humidity (RH). Currently, scarce information is available regarding the changes in aroma profiles in T. grandis nuts and the relationship with their response to different environmental conditions. Therefore, the interaction of temperature (20 °C or 30 °C) and relative humidity (70% RH or 90% RH) was investigated on aromatic substances after harvest. The results showed that 56 aromatic components were detected by a gas chromatography-mass spectrometer (GC-MS) and mainly divided into five categories, among which terpenes were the most abundant (56.2-86.7%). Principal component analysis (PCA) showed that both temperature and humidity can affect the aroma composition, and terpenes were mainly influenced by humidity. Specifically, d-limonene occupied the largest proportion of terpenes (63.0-90.8%) and was significantly upregulated by high humidity.


Assuntos
Nozes , Taxaceae , Umidade , Odorantes , Temperatura
4.
Food Chem ; 368: 130819, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34411865

RESUMO

Squalene and ß-sitosterol are health-benefit compounds due to their nutritional and medicinal properties. It has been reported that the content of these bioactive compounds is relatively high in Torreya grandis nuts. However, it is not yet known what changes in squalene and ß-sitosterol accumulation occur during the special post-ripening process of T. grandis nuts and the effect of the well-known ripening hormone ethylene on the regulatory mechanism of their biosynthetic pathways. Thus, we performed transcriptome and metabolite analyses. The results showed that ethylene not only promoted the post-ripening process but also enhanced the accumulation of squalene by inducing gene expression in the mevalonate pathway. At the same time, ethylene treatment also promoted the accumulation of other sterols but inhibited gene expression in the ß-sitosterol biosynthesis pathway. In addition, co-expression and correlation analysis suggested a framework for the transcriptional regulation of squalene and ß-sitosterol biosynthesis genes under ethylene treatment.


Assuntos
Nozes , Taxaceae , Etilenos , Frutas , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Sitosteroides , Esqualeno
5.
J Mater Chem B ; 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34842264

RESUMO

The non-invasive treatment of glioblastoma (GBM) is of great significance and can greatly reduce the complications of craniotomy. Sonodynamic therapy (SDT) is an emerging tumor therapeutic strategy that overcomes some fatal flaws of photodynamic therapy (PDT). Different from PDT, SDT has deep tissue penetration and can be applied in the non-invasive treatment of deep-seated tumors. However, effective sonosensitizers that can be used for SDT of GBM are still very rare. Herein, we have prepared a suitable assembly based on a hypocrellin derivative (CTHB) with good biocompatibility. Excitedly, the hypocrellin-based assembly (CTHB NPs) can effectively produce reactive oxygen species under ultrasound stimulation. The inherent fluorescence and photoacoustic imaging characteristics of the CTHB NPs are conducive to the precise positioning of the tumors. It has been proved both in subcutaneous and in intracranial tumor models that CTHB NPs can be used as an effective sonosensitizer to inhibit tumor growth under ultrasound irradiation. This hypocrellin-based assembly has a good clinical prospect in the non-invasive treatment of GBM.

6.
Front Neurosci ; 15: 758887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720868

RESUMO

In recent years, an increasing number of people have myopia in China, especially the younger generation. Common myopia may develop into high myopia. High myopia causes visual impairment and blindness. Parapapillary atrophy (PPA) is a typical retinal pathology related to high myopia, which is also a basic clue for diagnosing high myopia. Therefore, accurate segmentation of the PPA is essential for high myopia diagnosis and treatment. In this study, we propose an optimized Unet (OT-Unet) to solve this important task. OT-Unet uses one of the pre-trained models: Visual Geometry Group (VGG), ResNet, and Res2Net, as a backbone and is combined with edge attention, parallel partial decoder, and reverse attention modules to improve the segmentation accuracy. In general, using the pre-trained models can improve the accuracy with fewer samples. The edge attention module extracts contour information, the parallel partial decoder module combines the multi-scale features, and the reverse attention module integrates high- and low-level features. We also propose an augmented loss function to increase the weight of complex pixels to enable the network to segment more complex lesion areas. Based on a dataset containing 360 images (Including 26 pictures provided by PALM), the proposed OT-Unet achieves a high AUC (Area Under Curve) of 0.9235, indicating a significant improvement over the original Unet (0.7917).

7.
Front Plant Sci ; 12: 761139, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745193

RESUMO

Torreya grandis 'Merrillii' is a famous nut with great nutritional value and high medicinal value. Aril cracking is an important process for seed dispersal, which is also an indicator of seed maturation. However, the cracking mechanism of T. grandis aril during the maturation stage remains largely unknown. Here, we provided a comprehensive view of the physiological and molecular levels of aril cracking in T. grandis by systematically analyzing its anatomical structure, physiological parameters, and transcriptomic response during the cracking process. These results showed that the length of both epidermal and parenchymatous cell layers significantly increased from 133 to 144 days after seed protrusion (DASP), followed by a clear separation between parenchymatous cell layers and kernel, which was accompanied by a breakage between epidermal and parenchymatous cell layers. Moreover, analyses of cell wall composition showed that a significant degradation of cellular wall polysaccharides occurred during aril cracking. To examine the global gene expression changes in arils during the cracking process, the transcriptomes (96 and 141 DASP) were analyzed. KEGG pathway analysis of DEGs revealed that 4 of the top 10 enriched pathways were involved in cell wall modification and 2 pathways were related to ethylene biosynthesis and ethylene signal transduction. Furthermore, combining the analysis results of co-expression networks between different transcription factors, cell wall modification genes, and exogenous ethylene treatments suggested that the ethylene signal transcription factors (ERF11 and ERF1A) were involved in aril cracking of T. grandis by regulation of EXP and PME. Our findings provided new insights into the aril cracking trait in T. grandis.

8.
Food Chem ; : 131558, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34794838

RESUMO

The kernel of Torreya grandis (T. grandis) is a rare nut with a variety of bioactive compounds. Flavonoids are a very important class of bioactive compounds with high antioxidant activity in T. grandis kernels. However, the flavonoid compositions which mainly contribute to antioxidant capacity and the molecular basis of flavonoid biosynthesis in T. grandis remain unclear. Here, transcriptome sequencing and metabolomics analysis for kernels were performed. In total, 124 flavonoids were identified. Among them, 9 flavonoids were highly correlated with antioxidant activity. Furthermore, unigenes encoding CHS, DFR and ANS showed significant correlation with the 9 flavonoids. Transient overexpression of TgDFR1 in tobacco leaves resulted in increased antioxidant activity. Moreover, several transcription factors from MYB, bHLH and bZIP families were identified by co-expression assay, suggesting that they may regulate flavonoid biosynthesis. Our findings provide a molecular basis and new insights into the flavonoid biosynthesis in T. grandis kernels.

9.
ACS Omega ; 6(40): 26575-26582, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34661012

RESUMO

The design and synthesis of single-molecule amphiphilic and multifunctional phototherapeutic agents are important to cancer diagnosis and therapy. In this work, we developed three amphiphilic diketopyrrolopyrrole derivatives (TPADPP, DTPADPP, and TPADDPP) with different donor-acceptor structures and poly(ethylene glycol) side chains. The corresponding nanoparticles (NPs) were obtained via a self-assembly from three amphiphilic DPP derivatives and used as smart phototherapeutic agents for tumor diagnosis and treatment. The three amphiphilic DPP NPs exhibited near-infrared (NIR) emissions and good biocompatibility. Thus, they could be used as fluorescence (FL) imaging agents for guided therapy. DTPADPP NPs and TPADDPP NPs also displayed excellent photothermal performance and high accumulation in the tumor. Owing to these beneficial features, the DTPADPP NPs and TPADDPP NPs synthesized herein are suitable for NIR FL imaging and effective photothermal therapy against the tumor in vivo.

10.
Hortic Res ; 8(1): 196, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34465767

RESUMO

Studies have shown that melatonin regulates the expression of various elements in the biosynthesis and catabolism of plant hormones. In contrast, the effects of these different plant hormones on the biosynthesis and metabolism of melatonin and their underlying molecular mechanisms are still unclear. In this study, the melatonin biosynthesis pathway was proposed from constructed metabolomic and transcriptomic libraries from hickory (Carya cathayensis Sarg.) nuts. The candidate pathway genes were further identified by phylogenetic analysis, amino-acid sequence alignment, and subcellular localization. Notably, most of the transcription factor-related genes coexpressed with melatonin pathway genes were hormone-responsive genes. Furthermore, dual-luciferase and yeast one-hybrid assays revealed that CcEIN3 (response to ethylene) and CcAZF2 (response to abscisic acid) could activate melatonin biosynthesis pathway genes, a tryptophan decarboxylase coding gene (CcTDC1) and an N-acetylserotonin methyltransferase coding gene (CcASMT1), by directly binding to their promoters, respectively. Our results provide a molecular basis for the characterization of novel melatonin biosynthesis regulatory mechanisms and demonstrate for the first time that abscisic acid and ethylene can regulate melatonin biosynthesis.

11.
Crit Rev Food Sci Nutr ; : 1-23, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397288

RESUMO

Though the knowledge on delta 5-unsaturated-polymethylene-interrupted fatty acids (Δ5-UPIFAs) is being updated, the issue of their integration still exists within the field. Thus, this review systematically summarizes the sources, biosynthesis and metabolism, analytical methods, preparation, and health-promoting roles of Δ5-UPIFAs. In plants, the content of Δ5-UPIFAs is higher, which is an ideal source. In animals, although the content of Δ5-UPIFAs is not high, there are many species, which is the possible source of some special Δ5-UPIFAs. At present, although the extraction of Δ5-UPIFAs is mainly from plants, the fermentation by organisms, especially for genetically modified microorganisms engineering maybe be a substitue of pepration of Δ5-UPIFAs. Δ5-UPIFAs have been proved to possess multi-beneficial effects, such as lipid lowering, anti-inflammation and so on, so it has a certain potential application value. However, related knowledge of the underlying molecular mechanisms regarding Δ5-UPIFAs limited, and how Δ5-UPIFAs work is not clear. Further clinical and human studies about Δ5-UPIFAs are also needed. Studies on tapping new resources, developing structured lipide rich in Δ5-UPIFA and enhancing delivery were quite deficient. This review emphasizes the further directions on Δ5-UPIFAs with scientific suggestions to pay more attention to the applications of Δ5-UPIFAs in food, pharmaceutical and cosmetic industries.

12.
Biomolecules ; 11(8)2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34439825

RESUMO

Among abiotic stressors, drought and salinity seriously affect crop growth worldwide. In plants, research has aimed to increase stress-responsive protein synthesis upstream or downstream of the various transcription factors (TFs) that alleviate drought and salinity stress. TFs play diverse roles in controlling gene expression in plants, which is necessary to regulate biological processes, such as development and environmental stress responses. In general, plant responses to different stress conditions may be either abscisic acid (ABA)-dependent or ABA-independent. A detailed understanding of how TF pathways and ABA interact to cause stress responses is essential to improve tolerance to drought and salinity stress. Despite previous progress, more active approaches based on TFs are the current focus. Therefore, the present review emphasizes the recent advancements in complex cascades of gene expression during drought and salinity responses, especially identifying the specificity and crosstalk in ABA-dependent and -independent signaling pathways. This review also highlights the transcriptional regulation of gene expression governed by various key TF pathways, including AP2/ERF, bHLH, bZIP, DREB, GATA, HD-Zip, Homeo-box, MADS-box, MYB, NAC, Tri-helix, WHIRLY, WOX, WRKY, YABBY, and zinc finger, operating in ABA-dependent and -independent signaling pathways.


Assuntos
Ácido Abscísico/metabolismo , Adaptação Fisiológica/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Plantas/genética , Fatores de Transcrição/genética , Secas , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Proteínas de Plantas/classificação , Proteínas de Plantas/metabolismo , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Plantas/metabolismo , Plantas Geneticamente Modificadas , Espécies Reativas de Oxigênio/metabolismo , Salinidade , Transdução de Sinais , Estresse Fisiológico/genética , Fatores de Transcrição/classificação , Fatores de Transcrição/metabolismo
13.
Food Sci Nutr ; 9(5): 2508-2516, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34026067

RESUMO

The aim of this study was to identify the locations and harvest months in Guizhou province, China, producing the most suitable red dragon fruit (Hylocereus polyrhizus) for winemaking. Fruit from Guanling, Luodian and Zhenfeng counties was harvested separately from successive fruit cycles in August, September and October, respectively. The key traits measured were fruit weight, pulp yield, soluble solids content, and titratable acid. Wine characteristics measured were alcohol content, total carbohydrates, titratable acidity, volatile acidity, and betacyanin content. The overall suitability of fruit from each location for winemaking was evaluated using a multi-factor, unweighted, scorecard. On that basis, fruit from Guanling county harvested in August was the most suitable. Fruit from Luodian, and Zhenfeng was most suitable when harvested in August and September, and September, respectively. These results provide a preliminary guide for the sourcing of red dragon fruit from Guizhou for wine production.

14.
Chemistry ; 27(43): 11195-11204, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-33960049

RESUMO

Hydrophobic photosensitizers greatly affect cell permeability and enrichment in tumors, but they cannot be used directly for clinical applications because they always aggregate in water, preventing their circulation in the blood and accumulation in tumor cells. As a result, amphiphilic photosensitizers are highly desirable. Although nanomaterial-based photosensitizers can solve water solubility, they have the disadvantages of complicated operation, poor reproducibility, low drug loading, and poor stability. In this work, an efficient synthesis strategy is proposed that converts small molecules into nanoparticles in 100 % aqueous solution by molecular assembly without the addition of any foreign species. Three photosensitizers with triphenylphosphine units and ethylene glycol chains of different lengths, TPP-PPh3 , TPP-PPh3 -2PEG and TPP-PPh3 -4PEG, were synthesized to improve amphiphilicity. Of the three photosensitizers, TPP-PPh3 -4PEG is the most efficient (singlet oxygen yield: 0.89) for tumor photodynamic therapy not only because of its definite constituent, but also because its amphiphilic structure allows it to self-assemble in water.


Assuntos
Nanopartículas , Fotoquimioterapia , Porfirinas , Linhagem Celular Tumoral , Fármacos Fotossensibilizantes/uso terapêutico , Reprodutibilidade dos Testes
15.
Chem Commun (Camb) ; 57(41): 5036-5039, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33881054

RESUMO

A new method is introduced to prepare hydrogen-substituted graphdiynes (HsGDYs) via the dehalogenative homocoupling of terminal alkynyl bromides. Compared with previous synthetic strategies, the reaction conditions are moderate and the time is shortened. HsGDYs exhibit porous structures and hydrogen/oxygen evolution reaction (HER/OER) catalytic activity, endowing applications in electrochemical catalysis.

16.
Chem Asian J ; 16(10): 1221-1224, 2021 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-33881805

RESUMO

Peroxalate CL as an energy source to excite photosensitizers has attracted tremendous attention in photodynamic therapy (PDT). In this work, peroxyoxalate CPPO and hypocrellin B (HB)-based nanoparticles (CBNPs) for ultrasound (US)-enhanced self-exciting PDT were designed and prepared. CBNPs showed an excellent therapeutic effect against cancer cells with the assistance of US. This US-enhanced-chemiluminescence system avoids the dependence on external light and provides an example for inspiring more effective and precise strategies for cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Estruturas Metalorgânicas/farmacologia , Perileno/análogos & derivados , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Quinonas/farmacologia , Ondas Ultrassônicas , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/química , Modelos Moleculares , Tamanho da Partícula , Perileno/química , Perileno/farmacologia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Quinonas/química
17.
Phytomedicine ; 84: 153513, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33647776

RESUMO

BACKGROUND: Huangqi decoction (HQD) has been used to treat chronic liver diseases since the 11th century, but the effective components in HQD against liver fibrosis have not been definitively clarified. PURPOSE: To investigate and identify multiple effective components in HQD against liver fibrosis using a pharmacokinetics-based comprehensive strategy. METHODS: The absorbed representative components in HQD and their metabolites were detected in human plasma and urine using high-resolution mass spectrometry combined with a database-directed method, and then pharmacokinetics in multiple HQD components in human plasma was analyzed by ultra-performance liquid chromatography coupled with triple-quadruple mass spectrometry. Furthermore, the anti-fibrotic effect of potential effective HQD components was studied in LX-2 cells and that of a multi-component combination of HQD (MCHD) was verified in a mouse CCl4-induced hepatic fibrosis model. RESULTS: Twenty-four prototype components in HQD and 17 metabolites were identified in humans, and the pharmacokinetic characteristics of 14 components were elucidated. Among these components, astragaloside IV, cycloastragenol, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, and isoliquiritigenin downregulated the mRNA expression of α-SMA; cycloastragenol, calycosin-7-O-ß-D-glucoside, formononetin, glycyrrhetinic acid, liquiritin, and isoliquiritin downregulated the mRNA expression of Col I; and calycosin, liquiritigenin, isoliquiritigenin, cycloastragenol, and glycyrrhetinic accelerated the apoptosis of LX-2 cells. MCHD reduced serum aminotransferase activity and hepatic collagen fibril deposition in mice with CCl4-induced hepatic fibrosis. CONCLUSION: Using the pharmacokinetics-based comprehensive strategy, we revealed that multiple effective HQD components act together against liver fibrosis.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Cirrose Hepática/tratamento farmacológico , Adolescente , Adulto , Animais , Chalcona/análogos & derivados , Chalcona/farmacocinética , Cromatografia Líquida , Medicamentos de Ervas Chinesas/química , Flavanonas/farmacocinética , Glucosídeos/farmacocinética , Ácido Glicirrízico/farmacocinética , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Espectrometria de Massas , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Saponinas/farmacocinética , Triterpenos/farmacocinética , Adulto Jovem
18.
J Pharm Biomed Anal ; 198: 113986, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690095

RESUMO

Cholestasis is characterized by obstruction of bile flow and can lead to serious liver injury. With sustained damage, cholestasis can progress to cholestatic liver fibrosis (CLF), and cirrhosis. Non-invasive, predictive, and reliable metabolites based on the early and progressive stages of CLF are urgently needed. Based on the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced CLF mouse model, serum metabolic profiling via a time-series strategy with ultra-performance liquid chromatography-LTQ-Orbitrap-based metabolomics, combined with histological progression, was used to find CLF-specific metabolites, and explore their dynamic changes in progressive stages of CLF. Compared to those in the control group, DDC-induced groups showed a substantial elevation in cholestatic liver injury and fibrosis indices. Next, 21 differential serum metabolites were selected and identified between the normal (control) and DDC groups, and 12 of them were greatly altered over time. Among these, taurocholic acid, tauromuricholic acid, LysoPE (20:2), sulfoglycolithocholic acid, and taurohyodeoxycholic acid were associated with the progression of the hepatocyte injury index, alanine aminotransferase. More importantly, docosahexaenoic acid, arachidonic acid, proline, leucine, and linoleic acid were associated with the progression of liver fibrosis index, liver hydroxyproline. Moreover, the differential metabolites that were related to hepatocyte injury and liver fibrosis were further validated in DDC-induced mice at weeks 4 and 8. Overall, this work provides data on differential metabolites for the progressive pathology of CLF.


Assuntos
Colestase , Animais , Colestase/patologia , Modelos Animais de Doenças , Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Metabolômica , Camundongos , Camundongos Endogâmicos C57BL , Piridinas
19.
Infect Drug Resist ; 14: 483-487, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603412

RESUMO

Voriconazole has been widely used in clinical practice for nearly 20 years. The adverse reactions caused by voriconazole have been reported gradually, such as visual impairment, hepatotoxicity, skin rash. At present, there are few reports about triazole antifungal drugs causing the increase of triglyceride and total cholesterol. Thus, the present study reported a case of chronic pulmonary aspergillosis with significantly increased blood lipids after treatment with voriconazole. In this case, the patient's total cholesterol was normal, and triglyceride was 2.64 times of the upper limit of the reference value at the time of admission. On the 30th day after oral administration of voriconazole 200mg q12h, triglyceride and total cholesterol were 4.55 times and 3.31 times of the baseline levels, respectively, with the trough concentration of voriconazole of 6.6 µ g/mL. After 28 days of voriconazole withdrawal and itraconazole administration, triglyceride decreased to 1.45 times of baseline level and total cholesterol decreased to the normal range. After another 24 days of treatment with voriconazole 200mg q12h, triglyceride increased again to 3.25 times of the baseline level and cholesterol was within the normal range. At the same time, the trough concentration of voriconazole was 3.2 µ g/mL. After 14 days of treatment with voriconazole 100mg q12h, the triglyceride level recovered to the baseline level, with the trough concentration of voriconazole of 1.5 µ g/mL. The Naranjo's rating scale was used, the final score was 10 points, indicating that the causal relationship between voriconazole and dyslipidemia was positive, which was likely to be related to the trough concentration of voriconazole.

20.
J Ethnopharmacol ; 267: 113544, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33152436

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gut microbiome dysbiosis is closely associated with cholestatic liver disease. Huangqi decoction (HQD), a traditional herbal formula, has protection against cholestatic liver injury. However, the effect of HQD on gut microbiome remains unknown. AIM OF THE STUDY: To investigate the effect of HQD on 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) induced cholestatic liver injury and its effect on the gut microbiome profiles. MATERIALS AND METHODS: Mice with DDC-induced cholestatic liver injury were treated with low and high doses of HQD for 8 weeks. Fecal samples were analyzed by 16 S ribosomal DNA sequencing. Barrier function as well as intestinal and hepatic inflammation was analyzed by real-time PCR and western blotting. RESULTS: HQD treatment ameliorated the DDC-induced liver injury and collagen deposition around hepatic bile ducts. Moreover, decreased diversity, reduced richness, and abnormal composition of intestinal microbiota of cholestatic mice were remarkably attenuated by HQD supplementation. Differences in bacterial abundance, including levels of Prevotellaceae_NK3B31_group, Alistipes, and Gordonibacter, were increased in DDC-induced mice, as compared with control mice, and were decreased after HQD treatment. Moreover, intestinal dysbiosis promoted disruption of the intestinal barrier in cholestatic mice. However, HQD treatment alleviated intestinal barrier dysfunction. Importantly, increased hepatic expression of pro-inflammatory factors and the NLRP3 inflammasome, which have a positive correlation with differential bacteria, were characteristics found in DDC-induced cholestatic mice that were alleviated upon treatment with HQD. CONCLUSION: HQD treatment alleviated gut microbiota dysbiosis, ameliorated the intestinal barrier dysfunction, inhibited liver inflammation, and protected against DDC-induced cholestatic liver injury.


Assuntos
Bactérias/efeitos dos fármacos , Colestase/tratamento farmacológico , Colo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fármacos Gastrointestinais/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hepatopatias/prevenção & controle , Fígado/efeitos dos fármacos , Animais , Bactérias/crescimento & desenvolvimento , Colestase/metabolismo , Colestase/microbiologia , Colestase/patologia , Colo/metabolismo , Colo/microbiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Disbiose , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Hepatopatias/metabolismo , Hepatopatias/microbiologia , Hepatopatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Permeabilidade
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