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1.

1 Scope

Ursolic acid (UA) is a pentacyclicterpenoid carboxylic acid that is present in a wide variety of plant foods. There are many beneficial health effects that are attributed to the properties of UA. However, the specific cellular targets of UA and the mechanism underlying downstream signal transduction processes linked to the anti‐inflammation pathway have not been thoroughly elucidated to date.

2 Methods and results

Chemical biology strategies such as target fishing, click reaction synthesis of a UA probe and molecular imaging were used to identify potential target proteins of UA. Cysteinyl aspartate specific proteinase 3 (CASP3) and its downstream signaling pathway were verified as potential targets by molecular docking, intracellular enzyme activity evaluation and accurate pathway analysis. The results indicated that UA acted on CASP3, ERK1 and JNK2 targets, alleviated inflammation‐associated downstream multiple signal transduction factors, including ERK1, NF‐κB and STAT3, and exhibited anti‐inflammation activities.

3 Conclusion

As a natural dietary supplement, UA demonstrated anti‐inflammation activity via inhibition of CASP3 and shows the potential to improve the therapy effect of several inflammation‐associated diseases.  相似文献   

2.
ABSTRACT

Physiologically based pharmacokinetic (PBPK) models are scientific methods used to predict veterinary drug residues that may occur in food-producing animals, and which have powerful extrapolation ability. Quinocetone (QCT) and mequindox (MEQ) are widely used in China for the prevention of bacterial infections and promoting animal growth, but their abuse causes a potential threat to human health. In this study, a flow-limited PBPK model was developed to simulate simultaneously residue depletion of QCT and its marker residue dideoxyquinocetone (DQCT) in pigs. The model included compartments for blood, liver, kidney, muscle and fat and an extra compartment representing the other tissues. Physiological parameters were obtained from the literature. Plasma protein binding rates, renal clearances and tissue/plasma partition coefficients were determined by in vitro and in vivo experiments. The model was calibrated and validated with several pharmacokinetic and residue-depletion datasets from the literature. Sensitivity analysis and Monte Carlo simulations were incorporated into the PBPK model to estimate individual variation of residual concentrations. The PBPK model for MEQ, the congener compound of QCT, was built through cross-compound extrapolation based on the model for QCT. The QCT model accurately predicted the concentrations of QCT and DQCT in various tissues at most time points, especially the later time points. Correlation coefficients between predicted and measured values for all tissues were greater than 0.9. Monte Carlo simulations showed excellent consistency between estimated concentration distributions and measured data points. The extrapolation model also showed good predictive power. The present models contribute to improve the residue monitoring systems of QCT and MEQ, and provide evidence of the usefulness of PBPK model extrapolation for the same kinds of compounds.  相似文献   

3.

Scope

Lactic acid fermentation (LAF) modulates the composition of food, leading to changes in safety, sensory, and nutritional properties. The effects of lactic fermented pineapple juice (FJ) supplementation on energetic metabolism of high-fat diet (HFD) fed mice are compared with either water (control), sweetened water (SW), bacteria in SW, and pineapple juice (J) supplementation.

Methods and results

Drink consumption and body weight are measured during the 6 weeks of experiment, whereas glycemia and lipid content are determined at the beginning and at the end of the experiment. Total energy intake is similar between all groups though the volume of juice consumed is lower than that of SWs. Weight gain is higher for mice provided with sugary drinks (5.65 ± 1.32 to 7.74 ± 2.98 g) compared to water (4.68 ± 0.93 g). The FJ is less detrimental to blood carbohydrate regulation than other sugary drinks. Triglyceride (TG) and total cholesterol content are not modified following fermented juice or water consumption, contrarily to other sugary drinks. Whatever the drink, intestinal permeability is preserved. Lactic acid bacterium (LAB) population in feces is not affected by the beverage but species composition is modified.

Conclusion

From a health perspective, FJ is preferable to other sugary drinks to limit metabolic disorders related to HFD.  相似文献   

4.

Scope

Zinc and glutamine are well known to be essential for the function and polarization of immune cells. TH17 cells are more frequently induced during zinc deficiency and cover their energy requirement mainly through glutaminolysis. A dysregulation of TH17 cells can contribute to the development of autoimmune diseases. Both inhibition of glutaminolysis and zinc supplementation suppress experimental autoimmune encephalomyelitis in mice. Therefore, the aim of this study is to investigate whether zinc modulates glutaminolysis in T cells.

Methods and results

CD3/CD28 stimulation and mixed lymphocytes culture are used as in vitro models for T cell activation. Then, the glutaminolysis is investigated on mRNA, protein, and functional level. Zinc deficiency and glutaminase (GLS) inhibition decrease immune responses in vitro. Furthermore, extracellular zinc and glutamine levels both modulate glutaminolysis by changing the expression of glutamine transporters and key enzymes. Intriguingly, zinc directly interferes with the activity of GLS both in a cell free system and in the cytosol.

Conclusion

Besides T cell subset differentiation, zinc also impacts on the cellular metabolism by inhibiting glutaminolysis. This suggests that zinc deficiency can contribute to the development of autoimmune diseases whereas zinc supplementation can support their therapy.  相似文献   

5.

Scope

Modifying the composition of colostrum by external factors may provide opportunities to improve the infant's health. Here, we evaluated how fish oil and/or probiotics supplementation modify concentrations of colostrum immune mediators and their associations with perinatal clinical factors on mothers with overweight/obesity.

Methods and results

Pregnant women were randomized in a double-blind manner into four intervention groups, and the supplements were consumed daily from early pregnancy onwards. Colostrum samples were collected from 187 mothers, and 16 immune mediators were measured using bead-based immunoassays. Interventions modified colostrum composition; the fish oil+probiotics group had higher concentrations of IL-12p70 than probiotics+placebo and higher FMS-like tyrosine kinase 3 ligand (FLT-3L) than fish oil+placebo and probiotics+placebo (one-way analysis of variance, post-hoc Tukey's test). Although the fish oil+probiotics group had higher levels of IFNα2 compared to the fish oil+placebo group, these differences were not statistically significant after correction for multiple testing. Multivariate linear model revealed significant associations between several immune mediators and the perinatal use of medication.

Conclusion

Fish oil/probiotics intervention exerted a minor effect on concentrations of colostrum immune mediators. However, medication during the perinatal period modulated the immune mediators. These changes in colostrum's composition may contribute to immune system development in the infant.  相似文献   

6.

Scope

Western type of diets are characterized by high animal protein intake and are associated with various chronic inflammatory diseases. With a higher protein consumption, excess undigested protein will reach the colon and be subsequently metabolized by gut microbiota. Depending on the type of protein, fermentation in the colon generates different metabolites with varying biological effects. This study aims to compare the impact of protein fermentation products from different sources on gut health.

Methods and results

Three high protein diets (vital wheat gluten [VWG], lentil, or casein) are submitted to the in vitro model of colon. Fermentation of excess lentil protein for 72 h results in highest production of short-chain fatty acids and lowest production of branched-chain fatty acids. Exposure of Caco-2 monolayers or Caco-2 monolayers co-cultured with THP-1 macrophages to luminal extracts of fermented lentil protein results in less cytotoxicity of Caco-2 monolayers and less damage to barrier integrity, when compared to VWG and casein. Lowest induction of interleukin-6 is observed in THP-1 macrophages after treatment with lentil luminal extracts, which is identified to be regulated by aryl hydrocarbon receptor signaling.

Conclusion

The findings indicate that protein sources affect the health effects of high protein diet in the gut.  相似文献   

7.
Anthocyanins are one of the most widespread families of natural pigments in the plant kingdom. Their health beneficial effects have been documented in many in vivo and in vitro studies. This review summarizes the most recent literature regarding the health benefits of anthocyanins and their molecular mechanisms. It appears that several signaling pathways, including mitogen-activated protein kinase, nuclear factor κB, AMP-activated protein kinase, and Wnt/β-catenin, as well as some crucial cellular processes, such as cell cycle, apoptosis, autophagy, and biochemical metabolism, are involved in these beneficial effects and may provide potential therapeutic targets and strategies for the improvement of a wide range of diseases in future. In addition, specific anthocyanin metabolites contributing to the observed in vivo biological activities, structure–activity relationships as well as additive and synergistic efficacy of anthocyanins are also discussed.  相似文献   

8.

1 Scope

Known pharmacological activities of guava (Psidium guajava) include modulation of blood glucose levels. However, mechanistic details remain unclear in many cases.

2 Methods and results

This study investigated the effects of different guava leaf and fruit extracts on intestinal glucose transport in vitro and on postprandial glucose levels in vivo. Substantial dose‐ and time‐dependent glucose transport inhibition (up to 80%) was observed for both guava fruit and leaf extracts, at conceivable physiological concentrations in Caco‐2 cells. Using sodium‐containing (both glucose transporters, sodium‐dependent glucose transporter 1 [SGLT1] and glucose transporter 2 [GLUT2], are active) and sodium‐free (only GLUT2 is active) conditions, we show that inhibition of GLUT2 was greater than that of SGLT1. Inhibitory properties of guava extracts also remained stable after digestive juice treatment, indicating a good chemical stability of the active substances. Furthermore, we could unequivocally show that guava extracts significantly reduced blood glucose levels (≈fourfold reduction) in a time‐dependent manner in vivo (C57BL/6N mice). Extracts were characterized with respect to their main putative bioactive compounds (polyphenols) using HPLC and LC‐MS.

3 Conclusion

The data demonstrated that guava leaf and fruit extracts can potentially contribute to the regulation of blood glucose levels.  相似文献   

9.
Experimental results proved that the development of Colletotrichum capsici B4 is extremely sensitive to water‐soluble chitosan (WSC) and inhibitory effects increase with increasing concentrations of WSC. In the in vitro test, the results showed that the entire prevention of conidial germination and mycelial diameter development are recognized in a potato dextrose agar medium containing 0.4% and 0.8% WSC, respectively. WSC was more efficient in a potato dextrose broth where it absolutely prevented the mycelial development of C. capsici B4 at a concentration of 0.32%. WSC treatments considerably decreased disease prevalence and the lesion diameter of anthracnose disease on chilli pepper fruits in the in vivo experiments. Experiments in biochemistry indicated that the activities of the key defense‐related enzymes in peel, consisting of chitinase, β‐1,3‐glucanase and total phenolic content, were increased by both C. capsici B4 infection and C. capsici B4 treatment, and was further treated with a 0.5% WSC concentration.

Practical applications

From the present studies we conclude that water‐soluble chitosan (WSC) can directly inhibit the development of C. capsici B4 isolated from infected chili pepper fruits showing typical symptoms of anthracnose in in vitro and effectively control anthracnose in chili pepper fruit in in vivo with concentration‐dependent antifungal effects. These findings suggest that WSC may be recognized as a feasible effective alternative to artificial fungicides for postharvest disease control of chili pepper fruits.  相似文献   

10.

Scope

Micronutrients are in small amounts in foods, act in concert, and require variable amounts of time to see changes in health and risk for disease. These first principles are incorporated into an intervention study designed to develop new experimental strategies for setting target recommendations for food bioactives for populations and individuals.

Methods and results

A 6‐week multivitamin/mineral intervention is conducted in 9–13 year olds. Participants (136) are (i) their own control (n‐of‐1); (ii) monitored for compliance; (iii) measured for 36 circulating vitamin forms, 30 clinical, anthropometric, and food intake parameters at baseline, post intervention, and following a 6‐week washout; and (iv) had their ancestry accounted for as modifier of vitamin baseline or response. The same intervention is repeated the following year (135 participants). Most vitamins respond positively and many clinical parameters change in directions consistent with improved metabolic health to the intervention. Baseline levels of any metabolite predict its own response to the intervention. Elastic net penalized regression models are identified, and significantly predict response to intervention on the basis of multiple vitamin/clinical baseline measures.

Conclusions

The study design, computational methods, and results are a step toward developing recommendations for optimizing vitamin levels and health parameters for individuals.
  相似文献   

11.

Scope

The aim of the study is to investigate in Jurkat cells the possible beneficial effect of pumpkin (P) and fermented milk whey (FW) mixture against aflatoxin B1 (AFB1) and ochratoxin A (OTA) induced alterations in gene expression profile.

Methods and results

Human T cells are exposed for 7 days to digested bread extracts containing P-FW mixture along with AFB1 and OTA, individually and in combination. The results of RNA sequencing show that AFB1 P-FW exposure resulted in 34 differentially expressed genes (DEGs) while 3450 DEGs are found in OTA P-FW exposure and 3264 DEGs in AFB1-OTA P-FW treatment. Gene ontology analysis reveals biological processes and molecular functions related to immune system and inflammatory response. Moreover, PathVisio analysis points to eicosanoid signaling via lipoxygenase as the main pathway altered by AFB1 P-FW exposure whereas interferon signaling is the most affected pathway after OTA P-FW and AFB1-OTA P-FW treatments.

Conclusions

The mitigation of genes and inherent pathways typically associated with the inflammatory response suggest not only the anti-inflammatory and protective role of P-FW mixture but also their possible application in food industry to counteract AFB1 and OTA toxic effects on human and animal health.  相似文献   

12.

1 Scope

Cheonggukjang (CGJ) is a soybean‐based quick‐fermented food popular in Korea that contains a variety of biologically active compounds including isoflavones and saponins. Isoflavone bioavailability may be important for the bone health of postmenopausal women; therefore, the aim of this study is to evaluate the influence of fermentation on the isoflavone metabolite nutrikinetic profile after single dose CGJ or unfermented soybean administration in ovariectomized (OVX) and sham mice.

2 Methods and results

We identify 34 isoflavone metabolites using UPLC–QTOF‐MS and analyze their nutrikinetics at different time points (0.25, 0.5, 1, 2, 4, 8, 16, and 24 h) to understand their fermentation‐ and OVX‐mediated time‐dependent concentration changes. Nutrikinetics analysis shows that genistein, daidzein, genistein 4′‐sulfate, dihydrodaidzein sulfate, equol 4′‐sulfate, and equol‐7‐glucuronide are present at high concentrations in all groups based on area‐under‐the‐curve analysis. OVX mice appear to show lower isoflavone bioavailability than mice in the sham group. CGJ enhances various isoflavone metabolite bioavailability including genistein, 3‐hydroxygenistein, and equol 7‐glucuronide, compared to the unfermented soybean‐treated group. Among these metabolites, intact isoflavones, 3‐hydroxygenistein, genistein 4′‐sulfate, and equol 7‐glucuronide promote osteoblastogenesis and inhibit osteoclast formation.

3 Conclusions

CGJ has good isoflavone bioavailability and may be beneficial for the bone health of postmenopausal women.  相似文献   

13.
Tart cherries are increasingly popular due to purported health benefits. This Prunus cesarus species is cultivated worldwide, and its market has increased significantly in the last two decades due to improvements in agricultural practices and food processing technology. Tart cherries are rich in polyphenols, with a very specific profile combining anthocyanins and flavonols (berries-like) and chlorogenic acid (coffee-like). Tart cherries have been suggested to exert several potentially beneficial health effects including: lowering blood pressure, modulating blood glucose, enhancing cognitive function, protecting against oxidative stress and reducing inflammation. Studies focusing on tart cherry consumption have demonstrated particular benefits in recovery from exercise-induced muscle damage and diabetes associated parameters. However, the bioconversion of tart cherry polyphenols by resident colonic microbiota has never been considered, considerably reducing the impact of in vitro studies that have relied on fruit polyphenol extracts. In vitro and in vivo gut microbiota and metabolome studies are necessary to reinforce health claims linked to tart cherries consumption.  相似文献   

14.

Scope

The beneficial health effects of (poly)phenol-rich foods such as red grapes mainly depend on both the type and concentration of (poly)phenols. Since fruit (poly)phenol content is influenced by growing conditions, the study examines the seasonal effects of red grapes (Vitis vinifera L.), grown under various cultivation conditions, on metabolic markers of adipose tissue in healthy rats.

Methods and results

For this purpose, Fischer 344 rats are exposed into three different light-dark cycles and daily supplemented with 100 mg kg−1 of either conventionally or organically grown red grapes for 10 weeks (n = 6). Seasonal consumption of organic grapes (OGs), which are richer in anthocyanins, increases energy expenditure (EE) of animals exposed to long photoperiod and enhances uncoupling protein 1 (UCP1) protein expression in brown adipose tissue of animals under standard photoperiod. Additionally, red grape consumption affects the gene expression profile of white adipose tissue (WAT), upregulating browning markers of subcutaneous WAT in 12 h light (L12) and 18 h light (L18) photoperiods, and downregulating adipogenic and lipolytic markers of visceral WAT in 6 h light (L6) and L12 photoperiods.

Conclusions

These results clearly show that bioactive compounds of grapes can modulate the metabolic markers of white and brown adipose tissues in a photoperiod and depot-dependent manner, partly affecting EE when consumed out of season.  相似文献   

15.
Some studies have reported improved reproductive performance with dietary fat supplementation. This study examined effects of fatty acids with different lengths, or desaturation, or both, on metabolism of estradiol (E2) and progesterone (P4) in bovine liver slice incubations (experiments 1 and 2) and in vivo (experiment 3). In experiment 1, effects of fatty acids C16:0 (palmitic acid), C16:1 (palmitoleic acid), C18:1 (oleic acid), and C18:3 (linolenic acid) were evaluated at 30, 100, and 300 μM on P4 and E2 metabolism in vitro. In experiment 2, stearic acid (C18:0) and C18:3 were evaluated in the same incubation conditions. In experiment 1, all of the fatty acids had some significant inhibitory effect on metabolism of P4, E2, or both (300 μM C16:0 on E2; 100 μM C16:1 on E2; 300 μM C16:1 on both P4 and E2; 300 μM C18:1 on P4; and 100 and 300 μM C18:3 on both P4 and E2). In experiment 2, C18:3 (100 and 300 μM) but not C18:0 decreased P4 and E2 metabolism. Overall, the most profound increase (∼60%) in half-life of P4 and E2 was observed with incubations of 300 μM C18:3 in both in vitro experiments. Based on these in vitro results, in experiment 3 linseed oil (rich in C18:3) was supplemented into the abomasum and acute effects on metabolism of E2 and P4 were evaluated. Cows (n = 4) had endogenous E2 and P4 minimized (corpus luteum regressed, follicles aspirated) before receiving continuous intravenous infusion of E2 and P4 to analyze metabolic clearance rate for these hormones during abomasal infusion of saline (control) or 70 mL of linseed oil every 4 h for 28 h. Linseed oil infusion increased C18:3 in plasma by 46%; however, metabolic clearance rate for E2 and P4 were similar for control cows compared with linseed-treated cows. Thus, in vitro experiments indicated that E2 and P4 metabolism can be inhibited by high concentrations of C18:3. Nevertheless, in vivo, linseed oil did not acutely inhibit E2 and P4 metabolism, perhaps because insufficient C18:3 concentrations (increased to ∼8 μM) were achieved. Further research is needed to determine the mechanism(s) of fatty acid inhibition of P4 and E2 metabolism and to discover practical methods to mimic this effect in vivo.  相似文献   

16.
Hulls from dry edible beans are rich in phenolic compounds recognized as possessing antioxidant activity. The aim of this study was to characterize antioxidant properties of bean hull extract (BHE) and to determine whether BHE supplementation (at 400 or 800 mg/kg for 3 months) affects serum biochemical markers and bone structure in 12-month-old male C57BL/6 mice. Mice supplemented with 800 mg BHE/kg had lower serum tartrate-resistant acid phosphatase and parathyroid hormone concentrations than those on control diet or supplemented with 400 mg BHE/kg. BHE supplementation caused slight decrease in oxidized glutathione concentration in blood (P = 0.07). Compared to the control group, BHE supplementation at 800 mg/kg for 3 months improved bone structural indices, bone mineral density and trabecular thickness in the third lumbar vertebra. These results suggest that BHE supplementation may have beneficial effects on bone health in mice by decreasing bone resorption.  相似文献   

17.

Scope

We modeled red blood cell (RBC)‐folate response to supplementation and developed personalized folate supplementation concepts.

Methods and results

The changes of RBC‐folate were modeled in a time‐ (4 or 8 weeks) and dose‐ (400 or 800 μg d?1 folate) dependent manner. Post‐supplementation RBC‐folate levels were predicted from folate‐loading capacities (= measured RBC‐folate – [baseline RBC‐folate × RBC‐survival]). The prediction equations were validated in 119 participants. The median increase of RBC‐folate was higher in the 800 μg d?1 than in the 400 μg d?1 group (275 vs 169 nmol L?1 after 4 weeks, and 551 vs 346 nmol L?1 after 8 weeks). Medians (interquartile range) of RBC‐folate loading were (4 weeks: 299 (160) vs 409 (237) nmol L?1) and (8 weeks: 630 (134) versus 795 (187) nmol L?1) in the 400 and 800 μg d?1 group, respectively. The individual measured and predicted RBC‐folate values (after 4 weeks/400 μg d?1 = 25 + 1.27 × baseline RBC‐folate) and (after 4 weeks/800 μg d?1 = 65 + 1.41 × baseline RBC‐folate) did not differ significantly. The measured and predicted concentrations showed high agreement in the validation cohort.

Conclusions

The models can guide nutritional recommendations in women when baseline RBC‐folate concentrations are measured and the time to pregnancy between 4 and 8 weeks.
  相似文献   

18.
An in vitro cell culture model to assess the intestinal absorption of carotenoids is described. When supplemented with taurocholate and oleic acid, differentiated Caco-2 cells on membranes are able to produce chylomicrons. Under conditions mimicking the in vivo postprandial state, Caco-2 cells take up carotenoids and secrete them incorporated into chylomicrons; the extents of absorption of all-trans, 9-cis, 13-cis β-carotene, α-carotene, lutein, lycopene were 11%, 2%, 3%, 10%, 7%, and 3%, respectively. Saturation of β-carotene transport through Caco-2 cells occurred at concentrations (>15 μM) higher than “physiological” concentrations. Finally, retinol supplementation resulted in an 1.7-fold increase in β-carotene transport. The data suggest that (1) the intestinal absorption of carotenoids is facilitated by the participation of a specific epithelial transporter and (2) retinol promotes β-carotene incorporation into larger, retinyl ester-enriched chylomicrons. The present in vitro cell culture system is a relevant model to study the intestinal absorption of carotenoids at the molecular level.  相似文献   

19.

Scope

The consumption of dietary anthocyanins is associated with various health benefits. However, anthocyanins are poorly bioavailable, and most ingested anthocyanins will enter the colon where they are degraded to small phenolic metabolites that are the main absorbed forms. Little is known about the processes of anthocyanin degradation in the gut and the role of the human gut microbiota. This study aims to determine the contribution of spontaneous and microbiota-dependent degradation of anthocyanins in the human colon.

Methods and results

Purified anthocyanin extracts from black rice and bilberry were incubated in an in vitro human fecal-inoculated pH-controlled colon model over 24 h and anthocyanins were analyzed using HPLC-DAD. The study shows that the loss of anthocyanins occurs both spontaneously and as a consequence of metabolism by the gut microbiota. The study observes that there is high variability in spontaneous degradation but only modest variation in total degradation, which included the microbiota-dependent component. The degradation rate of anthocyanins is also shown to be dependent on the B-ring substitution pattern and the type of sugar moiety, both for spontaneous and microbiota-dependent degradation.

Conclusion

Anthocyanins are completely degraded in a model of the human colon by a combination of spontaneous and microbiota-dependent processes.  相似文献   

20.

1 Scope

Anorexia of aging, characterized by a decrease in appetite and/or food intake, is a major risk factor of under‐nutrition and adverse health outcomes in elderly people. Recent in vitro evidence suggests homoeriodictyol (HED), a naturally occurring, bitter‐masking flavanone, as a promising agent to increase appetite and food intake.

2 Methods and results

In two cross‐over intervention trials, 30 mg NaHED, either solely (n = 10, Study I) or in combination with a 75 g glucose load (n = 17, study II) were administered to healthy adult subjects. Ratings of hunger were assessed at fasting and either 30 min (Study I) or 120 min (Study II) post intervention. Ad libitum energy intake from a standardized breakfast and plasma changes in hunger‐/satiety‐associated hormones PYY, GLP‐1, ghrelin and serotonin were determined after blood drawings. Effects were more pronounced when NaHED was administered in combination with 75 g glucose since ad libitum energy (+ 9.52 ± 4.60%) and protein (+ 7.08 ± 7.97%) intake as well as plasma ΔAUC ghrelin values increased in study II solely, whereas plasma serotonin concentrations decreased after both interventions.

3 Conclusions

NaHED demonstrated appetizing effects in healthy adults when administered with a glucose load. Long‐term intervention studies are warranted to verify these effects in compromised subjects.  相似文献   

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