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1.
Food Chem ; 449: 139213, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38631134

ABSTRACT

This study took a novel approach to address the dual challenges of enhancing the ethanol content and aroma complexity in Laiyang pear wine. It focused on sorbitol as a pivotal element in the strategic selection of yeasts with specific sorbitol-utilization capabilities and their application in co-fermentation strategies. We selected two Saccharomyces cerevisiae strains (coded as Sc1, Sc2), two Metschnikowia pulcherrima (coded as Mp1, Mp2), and one Pichia terricola (coded as Tp) due to their efficacy as starter cultures. Notably, the Sc2 strain, alone or with Mp2, significantly increased the ethanol content (30% and 16%). Mixed Saccharomyces cerevisiae and Pichia terricola fermentation improved the ester profiles and beta-damascenone levels (maximum of 150%), while Metschnikowia pulcherrima addition enriched the phenethyl alcohol content (maximum of 330%), diversifying the aroma. This study investigated the efficacy of strategic yeast selection based on sorbitol utilization and co-fermentation methods in enhancing Laiyang pear wine quality and aroma.


Subject(s)
Fermentation , Flavoring Agents , Odorants , Pyrus , Saccharomyces cerevisiae , Sorbitol , Taste , Wine , Wine/analysis , Wine/microbiology , Pyrus/chemistry , Pyrus/microbiology , Pyrus/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/chemistry , Flavoring Agents/metabolism , Flavoring Agents/chemistry , Sorbitol/metabolism , Sorbitol/analysis , Odorants/analysis , Ethanol/metabolism , Ethanol/analysis , Pichia/metabolism , Metschnikowia/metabolism , Fruit/chemistry , Fruit/microbiology , Fruit/metabolism
2.
Food Res Int ; 184: 114256, 2024 May.
Article in English | MEDLINE | ID: mdl-38609234

ABSTRACT

Mycotoxins are important risk factors in beer. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to determine 10 mycotoxins in beer within 6 min. The method is fast, efficient, and has a simple and quick sample preparation. Validation was conducted based on the performance standards specified in Commission Decision 657/2002/EC, and the results demonstrated excellent linearity (R2 > 0.99), repeatability (RSD < 5 %), quantification limits (0.005-20.246 µg/L), and recovery rates (77 %-118 %). The prevalence of the 10 mycotoxins in 96 beers purchased from the Chinese market was analyzed, and the exposure of the Chinese population to mycotoxins through beer consumption was assessed. Deoxynivalenol (DON) was detected in 93.75 % of the beers, and the incidence of fumonisins (FBs) and zearalenone (ZEN) exceeded 50 %. Beer intake contributed significantly to the exposure of aflatoxins (AFs) and DON, especially in males. Correlation analysis between mycotoxin content in beer, raw materials, and the brewing process revealed that the brewing process significantly affected the content of DON (P < 0.001), while auxiliary materials also had a significant impact on the content of FBs and DON (P < 0.001). This study holds great significance in producing higher quality and safer beer.


Subject(s)
Aflatoxins , Mycotoxins , Male , Humans , Beer , Chromatography, Liquid , Tandem Mass Spectrometry
3.
Food Chem X ; 22: 101301, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38559440

ABSTRACT

In this study, liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to analyze the prevalence of 10 mycotoxins in 140 samples from the Chinese market, aiming to assess the exposure of Chinese individuals to these mycotoxins through the consumption of wine, baijiu, and huangjiu. Mycotoxins were detected in 98% of the samples, with fumonisins (FBs), deoxynivalenol (DON), and zearalenone (ZEN) exhibiting positive rates exceeding 50%. Regarding the exposure of the Chinese population to mycotoxins resulting from alcoholic beverage consumption, fruit wine intake made a relatively significant contribution to aflatoxin exposure, while baijiu showed a relatively significant contribution to ZEN exposure (1.84%). The analysis of the correlation between grape variety, wine region, and mycotoxin content demonstrated that FBs, ZEN, and DON were significantly influenced by grape variety and wine region. This research holds great significance in protecting human life and health, as well as in the production of safer alcoholic beverages.

4.
Molecules ; 29(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38675513

ABSTRACT

The mechanisms by which alcohol, alcoholic beverages, and their de-alcoholized derivatives affect animal physiology, metabolism, and gut microbiota have not yet been clarified. The polyphenol, monosaccharide, amino acid, and organic acid contents of four common alcoholic beverages (Chinese Baijiu, beer, Chinese Huangjiu, and wine) and their de-alcoholized counterparts were analyzed. The research further explored how these alcoholic beverages and their non-alcoholic versions affect obesity and gut microbiota, using a high-fat diet bee model created with 2% palm oil (PO). The results showed that wine, possessing the highest polyphenol content, and its de-alcoholized form, particularly when diluted five-fold (WDX5), markedly improved the health markers of PO-fed bees, including weight, triglycerides, and total cholesterol levels in blood lymphocytes. WDX5 treatment notably increased the presence of beneficial microbes such as Bartonella, Gilliamella, and Bifidobacterium, while decreasing Bombilactobacillus abundance. Moreover, WDX5 was found to closely resemble sucrose water (SUC) in terms of gut microbial function, significantly boosting short-chain fatty acids, lipopolysaccharide metabolism, and associated enzymatic pathways, thereby favorably affecting metabolic regulation and gut microbiota stability in bees.


Subject(s)
Alcoholic Beverages , Diet, High-Fat , Gastrointestinal Microbiome , Animals , Bees , Gastrointestinal Microbiome/drug effects , Diet, High-Fat/adverse effects , Alcoholic Beverages/analysis , Polyphenols/pharmacology , Polyphenols/analysis
5.
Food Microbiol ; 113: 104272, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37098424

ABSTRACT

The color of mulberry wine is difficult to maintain since the main chromogenic substances, anthocyanins, are severely degraded during fermentation and aging. This study selected Saccharomyces cerevisiae I34 and Wickerhamomyces anomalus D6, both displaying high hydroxycinnamate decarboxylase (HCDC) activity (78.49% and 78.71%), to enhance the formation of stable vinylphenolic pyranoanthocyanins (VPAs) pigments during mulberry wine fermentation. The HCDC activity of 84 different strains from eight regions in China was primarily screened via the deep well plate micro fermentation method, after which the tolerance and brewing characteristics were evaluated via simulated mulberry juice. The two selected strains and a commercial Saccharomyces cerevisiae were then inoculated individually or sequentially into the fresh mulberry juice, while the anthocyanin precursors and VPAs were identified and quantified via UHPLC-ESI/MS. The results showed that the HCDC-active strains facilitated the synthesis of stable pigments, cyanidin-3-O-glucoside-4-vinylcatechol (VPC3G), and cyanidin-3-O-rutinoside-4-vinylcatechol (VPC3R), highlighting its potential for enhancing color stability.


Subject(s)
Carboxy-Lyases , Morus , Wine , Anthocyanins/metabolism , Wine/analysis , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Fermentation , Morus/metabolism , Carboxy-Lyases/genetics , Carboxy-Lyases/metabolism
6.
Compr Rev Food Sci Food Saf ; 22(3): 1495-1516, 2023 05.
Article in English | MEDLINE | ID: mdl-36856535

ABSTRACT

Ethyl carbamate (EC) is a probable carcinogenic compound commonly found in fermented foods and alcoholic beverages and has been classified as a category 2A carcinogen by the International Agency for Research on Cancer (IARC). Alcoholic beverages are one of the main sources of EC intake by humans. Therefore, many countries have introduced a standard EC limit in alcoholic beverages. Wine is the second largest alcoholic beverage in the world after beer and is loved by consumers for its rich taste. However, different survey results showed that the detection rate of EC in wine was almost 100%, while the maximum content was as high as 100 µg/L, necessitating EC content regulation in wine. The existing methods for controlling the EC level in wine mainly include optimizing raw fermentation materials and processes, using genetically engineered strains, and enzymatic methods (urease or urethanase). This review focused on introducing and comparing the advantages, disadvantages, and applicability of methods for controlling EC, and proposes two possible new techniques, that is, changing the fermentation strain and exogenously adding phenolic compounds. In the future, it is hoped that the feasibility of this prospect will be verified by pilot-scale or large-scale application to provide new insight into the regulation of EC during wine production. The formation mechanism and influencing factors of EC in wine were also introduced and the analytical methods of EC were summarized.


Subject(s)
Vitis , Wine , Humans , Urethane/analysis , Wine/analysis , Alcoholic Beverages/analysis , Carcinogens/analysis
7.
Hortic Res ; 10(2): uhac261, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36778186

ABSTRACT

Proanthocyanidins (PAs) and anthocyanins are involved in the response of plants to various environmental stresses. However, the mechanism behind defense-induced PA biosynthetic regulation is still not completely elucidated, also in grapevine. This study performed a transcriptome sequencing analysis of grape berries infected with Colletotrichum gloeosporioides to highlight the induction of the VabHLH137 factor from the basic helix-loop-helix (bHLH) XII subfamily by the fungus, which appeared to be significantly co-expressed with PA-related genes. The functional analysis of VabHLH137 overexpression and knockdown in transgenic grape calli showed that it positively regulated PA and anthocyanin biosynthesis. Moreover, VabHLH137 overexpression in the grape calli significantly increased resistance to C. gloeosporioides. A yeast one-hybrid and electrophoretic mobility shift assay revealed that VabHLH137 directly bound to the VaLAR2 promoter, enhancing its activity and interacting with VaMYBPAR, a transcriptional activator of PA biosynthesis. Furthermore, transient experiments showed that although the VabHLH137 + VaMYBPAR complex activated VaLAR2 expression, it failed to further enhance VaLAR2 expression compared to VaMYBPAR alone. The findings indicated that VabHLH137 enhanced PA biosynthesis by activating of VaLAR2 expression, providing new insight into the transcriptional regulation of defense-induced PA biosynthesis in grapevine.

8.
Compr Rev Food Sci Food Saf ; 22(2): 1128-1147, 2023 03.
Article in English | MEDLINE | ID: mdl-36717374

ABSTRACT

Phenolic acids (PAs), a class of small bioactive molecules widely distributed in food and mainly found as secondary plant metabolites, present significant advantages such as antioxidant activity and other health benefits. The global epidemic of nonalcoholic fatty liver disease (NAFLD) is becoming a serious public health problem. Existing studies showed that gut microbiota (GM) dysbiosis is highly associated with the occurrence and development of NAFLD. In recent years, progress has been made in the study of the relationship among PA compounds, GM, and NAFLD. PAs can regulate the composition and functions of the GM to promote human health, while GM can increase the dietary sources of PAs and improve its bioavailability. This paper discussed PAs, GM, and their interrelationship while introducing several representative dietary PA sources and examining the absorption and metabolism of PAs mediated by GM. It also summarizes the effect and mechanisms of PAs in improving and regulating NAFLD via GM and their metabolites. This helps to better evaluate the potential preventive effect of PAs on NAFLD via the regulation of GM and expands the utilization of PAs and PA-rich food resources.


Subject(s)
Gastrointestinal Microbiome , Non-alcoholic Fatty Liver Disease , Humans , Gastrointestinal Microbiome/physiology , Diet , Dysbiosis
9.
Food Chem ; 404(Pt B): 134726, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36327504

ABSTRACT

The rising interest in craft beer urging for novel yeasts that provide diverse attributes. This research aimed to explore the potential of four non-Saccharomyces yeasts with high ß-glucosidase activity in beer fermentation. Fermentation ability, adverse environment resistance and carbohydrate affinity were measured via growth and physiochemical parameters and, based on these results, a Candida glabrata (D18) yeast was selected for subsequent sequential fermentations. Aroma analysis of the fermented beer was then performed using gas chromatography-mass spectrometry, demonstrated that some glucoside-binding terpenes had been significantly increased. In two D18 involved groups, geraniol content increased 51.5/11-fold in the single and mixed fermentations, respectively, while linalool increased 1.36-fold in the mixed fermentation, providing the final beer product with unique floral and fruity characteristics. Principal component analysis and sensory evaluation were also applied to further demonstrate these distinctions. Overall, D18 was found to be a potential yeast for beer fermentation with unique properties.


Subject(s)
Beer , Cellulases , Beer/analysis , Terpenes/analysis , Yeasts , Fermentation
10.
Food Chem ; 405(Pt A): 134861, 2023 Mar 30.
Article in English | MEDLINE | ID: mdl-36370563

ABSTRACT

This study evaluated the levels of eight biogenic amines in 59 craft beers of five styles and monitored the changes during beer fermentation, showing that putrescine and tryptamine were the most abundant at maximum values of 46.14 mg/L and 89.97 mg/L, respectively. This research indicated for the first time that dark beer, such as Stout/Porter, displayed the highest total biogenic amine content due to considerable tryptamine accumulation, with a maximum value of 116.95 mg/L. The total biogenic amine level increased gradually during the segmental saccharification and main fermentation stages, representing the two critical control points for their formation during beer fermentation. This study provides a theoretical basis and technical guidance for the safe and standardized production of craft beer and the formulation of biogenic amines limit standards, which is highly significant for protecting the health of consumers.


Subject(s)
Beer , Biogenic Amines , Beer/analysis , Fermentation , Biogenic Amines/analysis , Tryptamines/analysis , China
11.
Crit Rev Food Sci Nutr ; 63(23): 6379-6392, 2023.
Article in English | MEDLINE | ID: mdl-35125055

ABSTRACT

Gut microbiota (GM) is essential for host health, and changes in the GM are related to the development of various diseases. Recently, secretory immunoglobulin A (SIgA), the most abundant immunoglobulin isotype in the intestinal mucosa, has been found to play an essential role in controlling GM. SIgA dysfunction can lead to changes in the GM and is associated with the development of various GM-related diseases. Although in early stage, recent studies have shown that assorted dietary interventions, including vitamins, amino acids, fatty acids, polyphenols, oligo/polysaccharides, and probiotics, can influence the intestinal SIgA response and SIgA-GM interaction. Dietary intervention can enhance the SIgA response by directly regulating it (from top to bottom) or by regulating the GM structure or gene expression (from bottom to top). Furthermore, intensive studies involving the particular influence of dietary intervention on SIgA-binding to the GM and SIgA repertoire and the precise regulation of the SIgA response via dietary intervention are still exceedingly scarce and merit further consideration. This review summarizes the existing knowledge and (possible) mechanisms of the influence of dietary intervention on the SIgA-GM interaction. Key issues are considered, and the approaches in addressing these issues in future studies are also discussed.


Subject(s)
Gastrointestinal Microbiome , Immunoglobulin A, Secretory , Immunoglobulin A, Secretory/metabolism , Intestines , Intestinal Mucosa/metabolism , Diet
12.
Foods ; 13(1)2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38201134

ABSTRACT

The microbial community structure associated with wine in a wine-growing region is shaped by diverse ecological factors within that region, profoundly impacting the wine flavor. In wine fermentation, fungi contribute more sensory-active biochemical compounds than bacteria. In this study, we employed amplicon sequencing to measure samples from the spontaneous fermentation process of cabernet sauvignon wines from two wine-growing regions in China to study the diversity and structural evolution of fungi during spontaneous fermentation and analyze the correlation between fungi and volatile compounds. The results showed significant differences in fungal community structure and diversity in cabernet sauvignon musts from different geographical origins, and these differences affected the flavor quality of the wines. As alcoholic fermentation progressed, Saccharomyces became the dominant fungal genus and reshaped the fungal community structure, and the diversity of the fungal community decreased. However, the fungal communities of each wine-growing region remained distinct throughout the fermentation process. Furthermore, the correlation between the fungal community and volatile compounds indicated that wine is a product of fermentation involving multiple fungal genera, and the flavor is influenced by a variety of fungi. Our study enhances the comprehension of fungal communities in Chinese wine-growing regions, explaining the regulatory role of wine-related fungal microorganisms in wine flavor.

13.
Front Nutr ; 9: 1031594, 2022.
Article in English | MEDLINE | ID: mdl-36562039

ABSTRACT

Introduction: Indigenous yeasts are generally found in grapes, vineyards, and natural environments. Sequential inoculation and fermentation with non-Saccharomyces cerevisiae yeast (H30) and Saccharomyces cerevisiae (YT13) also improve the flavor of wine. Methods: This study sequentially inoculated fermented Petit Manseng and natural grape juice with native H30 and YT13 selected from vineyards in Yantai, China. Results and discussion: The sensory characteristics of Petit Manseng wine were evaluated by detecting the primary organic acids, phenolic acid compounds, and volatile ester compounds. The results showed that the lactic acid content of the natural wine fermented sequentially with H30 and YT13 increased by 490 µg/L compared with the control group, while the ferulic acid content was 1.4 times that of the single-yeast fermentation group. Furthermore, butyrolactone and anthocyanidin propionate were present in the mixed fermentation group, increasing the aroma complexity of Petit Manseng wine and providing high-quality yeast resources that increase the regional characteristics when producing dry white wine.

14.
Food Res Int ; 162(Pt A): 111923, 2022 12.
Article in English | MEDLINE | ID: mdl-36461187

ABSTRACT

Putrescine is abundant in wine and have toxicological risks for the health of consumers. Certain microbes with oxidative deamination activity are considered to be one of the most effective ways to degrade putrescine. The characterization and possible mechanism of putrescine degradation by Hanseniaspora uvarum FS35 were studied in this work. Hanseniaspora uvarum FS35 was selected from 111 yeast strains by UPLC analysis and exhibited the ability to eliminate > 44.5 mg/L of putrescine after 12 h of culture. Transcriptome analysis showed that by adding putrescine as a nitrogen source, the gene expression level of copper amine oxidase 1 (CuAO1) increased, leading to a coordinated response in the oxidative deamination of putrescine to 4-amino-butanal and subsequent dehydrogenation to 4-amino-butanoate. The purified recombinant protein CuAO1 could degrade 25.8 and 21.8 mg/L of putrescine in Marselan and Cabernet Sauvignon wines, respectively. H. uvarum FS35 was then inoculated sequentially with Saccharomyces cerevisiae into Cabernet Sauvignon grape juice, and the physiochemical indexes and aroma compounds were detected by HPLC and HS-SPME/GC-MS, respectively. wines produced from sequential inoculations showed significantly lower level of putrescine and higher amounts of glycerol, lactic acid, acetic acid, phenylethyl alcohol, ethyl acetate and ß-phenylethyl acetate compared with the control fermentation of commercial S. cerevisiae, which proved the potential of H. uvarum FS35 as a promising strategy to reduce biogenic amines in wines.


Subject(s)
Amine Oxidase (Copper-Containing) , Putrescine , Saccharomyces cerevisiae , Deamination , Oxidative Stress
15.
Front Nutr ; 9: 896021, 2022.
Article in English | MEDLINE | ID: mdl-36386906

ABSTRACT

Coconut oil (CO) and its main ingredients, medium-chain fatty acids (MCFA), present many benefits. Whether MCFA and CO play an equally valuable role in anti-obesity remains unclear. This study compared the anti-obesity effects of CO and MCFA [octanoic acid (C8:0) and decanoic acid (C10:0)] to gain insight into the underlying mechanism. Male C57BL/6J mice were fed either a low-fat diet (LFD) or high-fat diet (100% HFD) replaced with 2.5% MCFA (97.5% HFD + 2.5% MCFA) or 5% CO (95% HFD + 5% CO) for 17 weeks. CO and MCFA ameliorated the HFD-induced abnormal body and adipose depot weights, insulin sensitivity, and energy expenditure (EE), which was associated with brown adipose tissue (BAT) thermogenesis. Furthermore, CO enhanced the expression of thermogenesis markers in BAT, which was consistent with increased BAT activity. CO showed a better effect than MCFA in activating BAT to increase thermogenesis and energy metabolism to combat obesity, which may be attributed to the cooperation of MCFA and other substances in CO. This work provides evidence for the anti-obesity effects of CO, which could be a better alternative to lard in daily diet, rather than pure MCFA.

16.
Food Res Int ; 161: 111867, 2022 11.
Article in English | MEDLINE | ID: mdl-36192987

ABSTRACT

Ampelopsis grossedentata is a traditional medicinal and edible plant rich in bioactive compounds. This paper focus on the white powder on the surface of A. grossedentata, and the effects of processing technology and storage time on the composition of bioactive compounds in Ampelopsis grossedentata extracts (AMP). 33 compounds in AMP were identified and 30 compounds were reported for the first time compared with standards by UHPLC-Q-Orbitrap-MS. Organic acid, phenol, and flavonoids were detected in powder samples. Through comparing the mass spectrum data of three processing samples (traditional method, fermentation and drying-only), five compounds in fermentation samples were higher than other groups, and the content of most compounds of the traditional process was decreased compared with drying-only process. For the storage time research, the powder on the surface was found to be more unstable than leaf parts after 24 h, suggesting that sealing preservation is crucial in the process after powder precipitation.


Subject(s)
Ampelopsis , Flavonoids/pharmacology , Metabolomics , Phenols , Plant Extracts , Powders , Technology
17.
Molecules ; 27(20)2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36296484

ABSTRACT

Indigenous Saccharomyces cerevisiae, as a new and useful tool, can be used in fermentation to enhance the aroma characteristic qualities of the wine-production region. In this study, we used indigenous S. cerevisiae L59 and commercial S. cerevisiae FX10 to ferment Prince (a new hybrid variety from Lion Winery) wine, detected the basic physicochemical parameters and the dynamic changes of fungal communities during fermentation, and analyzed the correlations between fungal communities and volatile compounds. The results showed that the indigenous S. cerevisiae L59 could quickly adapt to the specific physicochemical conditions and microbial ecology of the grape must, showing a strong potential for winemaking. Compared with commercial S. cerevisiae FX10, the wine fermented by indigenous S. cerevisiae L59 contained more glycerol and less organic acids, contributing to a rounder taste. The results of volatile compounds indicated that the indigenous S. cerevisiae L59 had a positive effect on adding rosy, honey, pineapple and other sweet aroma characteristics to the wine. Overall, the study we performed showed that selection of indigenous S. cerevisiae from the wine-producing region as a starter for wine fermentation is conducive to improving the aroma profile of wine and preserving the aroma of the grape variety.


Subject(s)
Vitis , Wine , Saccharomyces cerevisiae , Vitis/chemistry , Glycerol , Wine/analysis , Fermentation
18.
Foods ; 11(16)2022 Aug 09.
Article in English | MEDLINE | ID: mdl-36010383

ABSTRACT

This study analyzed the interaction between copper and functional substances in wine under different drinking amounts on alcoholic liver injury in mice. When the daily drinking amount reached 500 mL/60 kg/day (14% abv) with just ethyl alcohol, the liver aspartate aminotransferase, alanine aminotransferase, and total triglyceride levels of mice were significantly increased to 130.71 U/L, 37.45 U/L, 2.55 U/L, the total antioxidant capacity, catalase, and glutathione level decreased significantly to 1.01 U/mL, 30.20 U/mgprot, and 2.10 U/mgprot, and the liver became gradually damaged. Wine could alleviate and reduce the damage caused by ethyl alcohol well. Low concentrations of copper (0.33, 0.66 mg/L) in wine hardly caused hepatic injury in mice and only significantly improved the aspartate aminotransferase values (109.21 U/L, 127.29 U/L) of serum. Combined with the staining evidence, in the case of medium and high intragastric doses (≥500 mL/60 kg/day), 0.99 mg/L copper (the maximum allowed by China's national standards) in wine began to damage the liver, indicating that under this concentration, the damage of copper to the liver had begun to exceed the protective effect of wine's functional substances on alcoholic hepatic injury. At all experimental doses, high concentrations (1.33 mg/L, 2.00 mg/L) of copper significantly aggravated alcoholic hepatic injury in mice, indicating that high concentrations of copper have a great toxicological risk. In the future, it is necessary to further strengthen the control of copper content in wine and the inspection of market wines in order to protect the health of consumers.

19.
Cell Death Dis ; 13(8): 708, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35970845

ABSTRACT

Breast cancer, the most common cancer in women, usually exhibits intrinsic insensitivity to drugs, even without drug resistance. MUC1 is a highly glycosylated transmembrane protein, overexpressed in breast cancer, contributing to tumorigenesis and worse prognosis. However, the molecular mechanism between MUC1 and drug sensitivity still remains unclear. Here, natural flavonoid apigenin was used as objective due to the antitumor activity and wide availability. MUC1 knockout (KO) markedly sensitized breast cancer cells to apigenin cytotoxicity in vitro and in vivo. Both genetical and pharmacological inhibition significantly enhanced the chemosensitivity to apigenin and clinical drugs whereas MUC1 overexpression conversely aggravated such drug resistance. Constitutively re-expressing wild type MUC1 in KO cells restored the drug resistance; however, the transmembrane domain deletant could not rescue the phenotype. Notably, further investigation discovered that membrane-dependent drug resistance relied on the extracellular glycosylated modification since removing O-glycosylation via inhibitor, enzyme digestion, or GCNT3 (MUC1 related O-glycosyltransferase) knockout markedly reinvigorated the chemosensitivity in WT cells, but had no effect on KO cells. Conversely, inserting O-glycosylated sites to MUC1-N increased the drug tolerance whereas the O-glycosylated deletant (Ser/Thr to Ala) maintained high susceptibility to drugs. Importantly, the intracellular concentration of apigenin measured by UPLC and fluorescence distribution firmly revealed the increased drug permeation in MUC1 KO and BAG-pretreated cells. Multiple clinical chemotherapeutics with small molecular were tested and obtained the similar conclusion. Our findings uncover a critical role of the extracellular O-glycosylation of MUC1-N in weakening drug sensitivity through acting as a barrier, highlighting a new perspective that targeting MUC1 O-glycosylation has great potential to promote drug sensitivity and efficacy.


Subject(s)
Breast Neoplasms , Mucin-1 , Apigenin/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Drug Resistance , Drug Tolerance , Female , Glycosylation , Humans , Mucin-1/genetics , Mucin-1/metabolism
20.
Molecules ; 27(13)2022 Jul 02.
Article in English | MEDLINE | ID: mdl-35807511

ABSTRACT

Mulberry extract has been proven to have the effect of resisting alcohol damage, but its mechanism is still unclear. In this study, the composition of mulberry ethanol extract (MBE) was identified by LC-MS/MS and the main components of MBE were ascertained by measuring. Gastric mucosal epithelial (GES-1) cells were used to elucidate the mechanism of MBE and rutin (the central part of MBE) helped protect against alcohol damage. The results revealed that phenolics accounted for the majority of MBE, accounting for 308.6 mg/g gallic acid equivalents and 108 substances were identified, including 37 flavonoids and 50 non-flavonoids. The treatment of 400 µg/mL MBE and 320 µM rutin reduced early cell apoptosis and the content of intracellular reactive oxygen species, malondialdehyde and increased glutathione. The qPCR results indicated that the MBE inhibits the expression of genes in the mitogen-activated protein kinase (MAPK) pathway, including p38, JNK, ERK and caspase-3; rutin inhibits the expression of p38 and caspase-3. Overall, MBE was able to reduce the oxidative stress of GES-1 cells and regulated apoptosis-related genes of the MAPK pathway. This study provides information for developing anti-ethanol injury drugs or functional foods.


Subject(s)
Morus , Rutin , Apoptosis , Caspase 3/metabolism , Chromatography, Liquid , Ethanol/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Morus/metabolism , Oxidative Stress , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Rutin/pharmacology , Tandem Mass Spectrometry , p38 Mitogen-Activated Protein Kinases/metabolism
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