To investigate the anti-α_(s1)-casein allergy mechanism of two tea-derived polyphenols,epigallocatechin(EGC)and epigallocatechin gallate(EGCG),BALB/c mice were sensitized and challenged withα_(s1)-casein and nutriti...To investigate the anti-α_(s1)-casein allergy mechanism of two tea-derived polyphenols,epigallocatechin(EGC)and epigallocatechin gallate(EGCG),BALB/c mice were sensitized and challenged withα_(s1)-casein and nutritional intervention was given by EGC and EGCG during the sensitization provocation phase.The main evaluation indexes used were levels of mast cell proteases,histamine,and specific antibody immunoglobulin E(IgE),as well as cytokine secretion and pathological observation.The results showed that both EGC and EGCG significantly reduced levels of mast cell protease,histamine,specific IgE antibodies,and Th2 cytokines in allergic mice.The histopathology results showed that both EGC and EGCG markedly reduced the degree of lesions in the intestine,thymus,spleen,and lung.The conclusions from this study can provide a theoretical basis for the mechanism by which tea polyphenols regulate food allergens.展开更多
AIM:To evaluate the effect of epigallocatechin gallate(EGCG) in preventing lens opacity and the aggregation of lens αB-crystallin in model rats of diabetes mellitus(DM).METHODS:This experimental study included Wistar...AIM:To evaluate the effect of epigallocatechin gallate(EGCG) in preventing lens opacity and the aggregation of lens αB-crystallin in model rats of diabetes mellitus(DM).METHODS:This experimental study included Wistar rats for DM as in vivo models and divided into 5 groups.The treatment groups were administered EGCG by orally for 20d and were then assessed for their degree of lens opacity with binocular microscope and lens αB-crystallin expression from Western blot analyze.RESULTS:Pearson correlation test and regression analysis on EGCG exposure and final random blood sugar(RBS) obtained a significance level of P<0.05.EGCG exposure can significantly lower RBS with an R~2 of 0.5634(56.34%).The same analysis on EGCG exposure and the degree of lens opacity obtained a significance level of P<0.05 and increased exposure to EGCG can significantly lower the degree of lens opacity with an R~2 of 0.8577(85.77%).Correlation analysis between EGCG and the expression of lens αB-crystallin can be concluded that the higher the EGCG exposure administered,the higher the native lens αB-crystallin expression and the lower the aggregate lens αB-crystallin expression.There was also significant effect in which every 1 mg/kg body weight dose of EGCG can increase the native lens αB-crystallin expression by 0.0063 and decrease the aggregate lens αB-crystallin expression by 0.0076.CONCLUSION:The administration of EGCG at a dose of 300,600,and 1200 mg shows a significant effect on preventing lens opacity and aggregation of αB-crystallin in diabetic rat models and this research could be a biomolecular prevention of cataract.展开更多
AIM To investigate the effect of epigallocatechin gallate(EGCG) on structural changes of gut microbiota in colorectal carcinogenesis.METHODS An azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced colitis mouse model...AIM To investigate the effect of epigallocatechin gallate(EGCG) on structural changes of gut microbiota in colorectal carcinogenesis.METHODS An azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced colitis mouse model was established. Fortytwo female FVB/N mice were randomly divided into the following three groups: group 1(10 mice, negative control) was treated with vehicle, group 2(16 mice, positive control) was treated with AOM plus vehicle, and group 3(16 mice, EG) was treated with AOM plus EGCG. For aberrant crypt foci(ACF) evaluation, the colons were rapidly took out after sacrifice, rinsed with saline, opened longitudinally, laid flat on a polystyrene board, and fixed with 10% buffered formaldehyde solution before being stained with 0.2% methylene blue in saline. For tumor evaluation, the colon was macroscopically inspected and photographed, then the total number of tumors was enumerated and tumor size measured. For histological examination, the fixed tissues were paraffin-embedded and sectioned at 5 mm thickness. Microbial genomic DNA was extracted from fecal and intestinal content samples using a commercial kit. The V4 hypervariable regions of 16 S r RNA were PCR-amplified with the barcoded fusion primers. Using the best hit classification option, the sequences from each sample were aligned to the RDP 16 S r RNA training set to classify the taxonomic abundance in QIIME. Statistical analyses were then performed.RESULTS Treatment of mice with 1% EGCG caused a significant decrease in the mean number of ACF per mouse, when compared with the model mice treated with AOM/DSS(5.38 ± 4.24 vs 13.13 ± 3.02, P < 0.01). Compared with the positive control group, 1% EGCG treatment dependently decreased tumor load per mouse by 85%(33.96 ± 6.10 vs 2.96 ± 2.86, respectively, P < 0.01). All revealed that EGCG could inhibit colon carcinogenesis by decreasing the number of precancerous lesions as well as solid tumors, with reduced tumor load and delayed histological progression of CRC. During the cancerization, the diversity of gut microbiota increased, potential carcinogenic bacteria such as Bacteroides were enriched, and the abundance of butyrate-producing bacteria(Clostridiaceae, Ruminococcus, etc.) decreased continuously. In contrast, the structure of gut microbiota was relatively stable during the intervention of EGCG on colon carcinogenesis. Enrichment of probiotics(Bifidobacterium, Lactobacillu, etc.) might be a potential mechanism for EGCG's effects on tumor suppression. Via bioinformatics analysis, principal coordinate analysis and cluster analysis of the tumor formation process, we found that the diversity of gut microbiota increased in the tumor model group while that in the EGCG interfered group(EG) remained relatively stable.CONCLUSION Gut microbiota imbalance might be a potential mechanism for the prevention of malignant transformation by EGCG, which is significant for diagnosis, treatment, prognosis evaluation, and prevention of colorectal cancer.展开更多
Systematic inflammatory response after spinal cord injury(SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigalloca...Systematic inflammatory response after spinal cord injury(SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate(EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses(curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses(curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests(the Basso, Beattie, and Bresnahan(BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods(Luxol Blue-cresyl violet staining) and immunohistochemistry(anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels(interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes(Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.展开更多
Given its increasing global prevalence,Alzheimer’s disease(AD)has become a major public health challenge worldwide.The symptomatic treatments available for AD have shown no significant efficacy,and no disease-modifyi...Given its increasing global prevalence,Alzheimer’s disease(AD)has become a major public health challenge worldwide.The symptomatic treatments available for AD have shown no significant efficacy,and no disease-modifying interventions are capable of slowing the progression of the disorder.The potential of lifestyle-related factors,including diet,is increasingly recognized as an important consideration in the primary prevention of AD.Numerous mechanisms potentially underlying neuroprotective effects of bioactive components contained in tea,such as(-)-epigallocatechin-3-gallate,as well as their preventive efficacy against AD,have been elucidated in preclinical studies.However,in contrast to the abundance of mechanistic findings in animals,clinical results demonstrating efficacy in humans are scarce.While epidemiological studies have provided some evidence indicating that green tea consumption is associated with a reduced risk of age-related cognitive decline and AD,a causal relationship cannot be established on the basis of these observations.The clinical evidence regarding preventive or therapeutic effects of green tea and its bioactive components is unsatisfactory.A role of green tea in the prevention of AD cannot be recommended until well-designed,randomized,placebo-controlled clinical trials using standardized formulations confirm the purported beneficial effects of green tea.展开更多
Surface properties are considered to be important factors in addressing proper functionalities.In this paper,a multifunctional mussel-inspired coating was prepared via the direct copolymerization of epigallocatechin g...Surface properties are considered to be important factors in addressing proper functionalities.In this paper,a multifunctional mussel-inspired coating was prepared via the direct copolymerization of epigallocatechin gallate(EGCG)and arginine.The coating formation was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectra.The EGCG/arginine coating contained diverse functional groups like amines,phenols and carboxyls,whose densities were also tunable.Such mussel-inspired coating could also be applied as an ad-layer for its secondary reactivity,demonstrated by quartz crystal microbalance technique.Moreover,the tunable surface density of phenols showed potential ability in modulating endothelial cell and smooth muscle cell viability.The coatings rich in phenols presented excellent free radical scavenging property.Current results strongly indicated the potential of EGCG/arginine coatings to be applied as an ad-layer for vascular materials.展开更多
Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms un...Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.展开更多
Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Tar...Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Targeting FASN using epigallocatechin gallate(EGCG)or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiationin vitro using MTT and colony formation assays,andin vivo using xenograft animal models.Western blot,immunohistochemistry,real-time PCR arrays,and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10(FZD10)expression.FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation.Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues,followed by analysis of their association with the overall survival of patients.Results:FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells,bothin vitro andin vivo.There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts,as well as human tissues.FASN knockdown reduced FZD10 expression,and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity.FASN and FZD10 were both negatively associated with overall survival of NPC patients.Conclusions:FASN contributes to radioresistance,possiblyvia FZD10 in NPC cells.Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients.EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.展开更多
The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory phenotype.As a result,the anticipated loading of...The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory phenotype.As a result,the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function,which is mostly disturbed by constant inflammation.In this study,we developed glucose and hydrogen peroxide dual-responsive borosilicate glass(BSG)scaffolds loaded with epigallocatechin gallate(EGCG)to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects.It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux.Moreover,EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity.Therefore,the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner.The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone,showing promise for the treatment of alveolar defect in diabetic patients.展开更多
基金supported by the National Key Research and Development Program of China(2019YFC1605002)the National Natural Science Foundation of China(31872886)。
文摘To investigate the anti-α_(s1)-casein allergy mechanism of two tea-derived polyphenols,epigallocatechin(EGC)and epigallocatechin gallate(EGCG),BALB/c mice were sensitized and challenged withα_(s1)-casein and nutritional intervention was given by EGC and EGCG during the sensitization provocation phase.The main evaluation indexes used were levels of mast cell proteases,histamine,and specific antibody immunoglobulin E(IgE),as well as cytokine secretion and pathological observation.The results showed that both EGC and EGCG significantly reduced levels of mast cell protease,histamine,specific IgE antibodies,and Th2 cytokines in allergic mice.The histopathology results showed that both EGC and EGCG markedly reduced the degree of lesions in the intestine,thymus,spleen,and lung.The conclusions from this study can provide a theoretical basis for the mechanism by which tea polyphenols regulate food allergens.
文摘AIM:To evaluate the effect of epigallocatechin gallate(EGCG) in preventing lens opacity and the aggregation of lens αB-crystallin in model rats of diabetes mellitus(DM).METHODS:This experimental study included Wistar rats for DM as in vivo models and divided into 5 groups.The treatment groups were administered EGCG by orally for 20d and were then assessed for their degree of lens opacity with binocular microscope and lens αB-crystallin expression from Western blot analyze.RESULTS:Pearson correlation test and regression analysis on EGCG exposure and final random blood sugar(RBS) obtained a significance level of P<0.05.EGCG exposure can significantly lower RBS with an R~2 of 0.5634(56.34%).The same analysis on EGCG exposure and the degree of lens opacity obtained a significance level of P<0.05 and increased exposure to EGCG can significantly lower the degree of lens opacity with an R~2 of 0.8577(85.77%).Correlation analysis between EGCG and the expression of lens αB-crystallin can be concluded that the higher the EGCG exposure administered,the higher the native lens αB-crystallin expression and the lower the aggregate lens αB-crystallin expression.There was also significant effect in which every 1 mg/kg body weight dose of EGCG can increase the native lens αB-crystallin expression by 0.0063 and decrease the aggregate lens αB-crystallin expression by 0.0076.CONCLUSION:The administration of EGCG at a dose of 300,600,and 1200 mg shows a significant effect on preventing lens opacity and aggregation of αB-crystallin in diabetic rat models and this research could be a biomolecular prevention of cataract.
基金Supported by Natural Science Foundation of Minhang District of Shanghai,No.2012MHZ001
文摘AIM To investigate the effect of epigallocatechin gallate(EGCG) on structural changes of gut microbiota in colorectal carcinogenesis.METHODS An azoxymethane(AOM)/dextran sodium sulfate(DSS)-induced colitis mouse model was established. Fortytwo female FVB/N mice were randomly divided into the following three groups: group 1(10 mice, negative control) was treated with vehicle, group 2(16 mice, positive control) was treated with AOM plus vehicle, and group 3(16 mice, EG) was treated with AOM plus EGCG. For aberrant crypt foci(ACF) evaluation, the colons were rapidly took out after sacrifice, rinsed with saline, opened longitudinally, laid flat on a polystyrene board, and fixed with 10% buffered formaldehyde solution before being stained with 0.2% methylene blue in saline. For tumor evaluation, the colon was macroscopically inspected and photographed, then the total number of tumors was enumerated and tumor size measured. For histological examination, the fixed tissues were paraffin-embedded and sectioned at 5 mm thickness. Microbial genomic DNA was extracted from fecal and intestinal content samples using a commercial kit. The V4 hypervariable regions of 16 S r RNA were PCR-amplified with the barcoded fusion primers. Using the best hit classification option, the sequences from each sample were aligned to the RDP 16 S r RNA training set to classify the taxonomic abundance in QIIME. Statistical analyses were then performed.RESULTS Treatment of mice with 1% EGCG caused a significant decrease in the mean number of ACF per mouse, when compared with the model mice treated with AOM/DSS(5.38 ± 4.24 vs 13.13 ± 3.02, P < 0.01). Compared with the positive control group, 1% EGCG treatment dependently decreased tumor load per mouse by 85%(33.96 ± 6.10 vs 2.96 ± 2.86, respectively, P < 0.01). All revealed that EGCG could inhibit colon carcinogenesis by decreasing the number of precancerous lesions as well as solid tumors, with reduced tumor load and delayed histological progression of CRC. During the cancerization, the diversity of gut microbiota increased, potential carcinogenic bacteria such as Bacteroides were enriched, and the abundance of butyrate-producing bacteria(Clostridiaceae, Ruminococcus, etc.) decreased continuously. In contrast, the structure of gut microbiota was relatively stable during the intervention of EGCG on colon carcinogenesis. Enrichment of probiotics(Bifidobacterium, Lactobacillu, etc.) might be a potential mechanism for EGCG's effects on tumor suppression. Via bioinformatics analysis, principal coordinate analysis and cluster analysis of the tumor formation process, we found that the diversity of gut microbiota increased in the tumor model group while that in the EGCG interfered group(EG) remained relatively stable.CONCLUSION Gut microbiota imbalance might be a potential mechanism for the prevention of malignant transformation by EGCG, which is significant for diagnosis, treatment, prognosis evaluation, and prevention of colorectal cancer.
基金supported by the grant GACR(Grant Agency of the Czech Republic)P304/12/G069the Ministry of Education,Youth and Sports under the project“Centre of Reconstructive Neuroscience”,registration number CZ.02.1.01/0.0./0.0/15_003/0000419project Inter Action LTAUSA17120
文摘Systematic inflammatory response after spinal cord injury(SCI) is one of the factors leading to lesion development and a profound degree of functional loss. Anti-inflammatory compounds, such as curcumin and epigallocatechin gallate(EGCG) are known for their neuroprotective effects. In this study, we investigated the effect of combined therapy of curcumin and EGCG in a rat model of acute SCI induced by balloon compression. Immediately after SCI, rats received curcumin, EGCG, curcumin + EGCG or saline [daily intraperitoneal doses(curcumin, 6 mg/kg; EGCG 17 mg/kg)] and weekly intramuscular doses(curcumin, 60 mg/kg; EGCG 17 mg/kg)] for 28 days. Rats were evaluated using behavioral tests(the Basso, Beattie, and Bresnahan(BBB) open-field locomotor test, flat beam test). Spinal cord tissue was analyzed using histological methods(Luxol Blue-cresyl violet staining) and immunohistochemistry(anti-glial fibrillary acidic protein, anti-growth associated protein 43). Cytokine levels(interleukin-1β, interleukin-4, interleukin-2, interleukin-6, macrophage inflammatory protein 1-alpha, and RANTES) were measured using Luminex assay. Quantitative polymerase chain reaction was performed to determine the relative expression of genes(Sort1, Fgf2, Irf5, Mrc1, Olig2, Casp3, Gap43, Gfap, Vegf, NfκB, Cntf) related to regenerative processes in injured spinal cord. We found that all treatments displayed significant behavioral recovery, with no obvious synergistic effect after combined therapy of curcumin and ECGC. Curcumin and EGCG alone or in combination increased axonal sprouting, decreased glial scar formation, and altered the levels of macrophage inflammatory protein 1-alpha, interleukin-1β, interleukin-4 and interleukin-6 cytokines. These results imply that although the expected synergistic response of this combined therapy was less obvious, aspects of tissue regeneration and immune responses in severe SCI were evident.
文摘Given its increasing global prevalence,Alzheimer’s disease(AD)has become a major public health challenge worldwide.The symptomatic treatments available for AD have shown no significant efficacy,and no disease-modifying interventions are capable of slowing the progression of the disorder.The potential of lifestyle-related factors,including diet,is increasingly recognized as an important consideration in the primary prevention of AD.Numerous mechanisms potentially underlying neuroprotective effects of bioactive components contained in tea,such as(-)-epigallocatechin-3-gallate,as well as their preventive efficacy against AD,have been elucidated in preclinical studies.However,in contrast to the abundance of mechanistic findings in animals,clinical results demonstrating efficacy in humans are scarce.While epidemiological studies have provided some evidence indicating that green tea consumption is associated with a reduced risk of age-related cognitive decline and AD,a causal relationship cannot be established on the basis of these observations.The clinical evidence regarding preventive or therapeutic effects of green tea and its bioactive components is unsatisfactory.A role of green tea in the prevention of AD cannot be recommended until well-designed,randomized,placebo-controlled clinical trials using standardized formulations confirm the purported beneficial effects of green tea.
基金The author would like to thank Dr Manfred.F.Maitz for his selfless assistance of this job and appreciate Mr Chongxi Jiang and Mrs Ru Shen for their help and contributions on sample characterization and analysis.Specially thank Miss Si Zhong and Mr Xin Wang for their help of cell compatibility evaluation.This work was supported by Natural Science Foundation of China(Grant 51173149,81330031 and 31270020)Sichuan Province Science and Technology Support Program(No.2014SZ0128)the 111 Project.The Program of Introducing Talents of Discipline to Universities(B16033).
文摘Surface properties are considered to be important factors in addressing proper functionalities.In this paper,a multifunctional mussel-inspired coating was prepared via the direct copolymerization of epigallocatechin gallate(EGCG)and arginine.The coating formation was confirmed by X-ray photoelectron spectroscopy and Fourier transform infrared spectra.The EGCG/arginine coating contained diverse functional groups like amines,phenols and carboxyls,whose densities were also tunable.Such mussel-inspired coating could also be applied as an ad-layer for its secondary reactivity,demonstrated by quartz crystal microbalance technique.Moreover,the tunable surface density of phenols showed potential ability in modulating endothelial cell and smooth muscle cell viability.The coatings rich in phenols presented excellent free radical scavenging property.Current results strongly indicated the potential of EGCG/arginine coatings to be applied as an ad-layer for vascular materials.
文摘Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human diseases.However,the molecular mechanisms underlying sRAGE remain unclear.In this study,THP-1 monocytes were cultured in normal glucose(NG,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)secretion.The modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also evaluated.HG enhanced intracellular reactive oxygen species(ROS)generation and RAGE expression.The secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear translocation.Mechanistically,the HG effects were counteracted by siRAGE and exacerbated by siNrf2.Chromatin immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this binding.Our data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating factors.Under HG conditions,the treatment of EGCG reduced ROS generation and RAGE activation.EGCG-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 pathway.EGCG inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.
基金This work was supported by grants from the National Natural Science Foundation of China(Grant Nos.81572588,81872147)Shantou University Medical College Clinical Trial Uplift Program(Grant No.201423)+4 种基金the Medical Scientific Research Foundation of Guangdong Province,China(Grant No.B2018222)the Traditional Chinese Medicine Research Project from Traditional Chinese Medicine Bureau of Guangdong Province(Grant No.20191182)the Youth Research Grant from Shantou University Medical College Cancer Hospital(Grant No.2018A001,2018A008)the key Project of Science and Technology of Shantou[Grant No.(2018)37]and the Natural Science Foundation of Guangdong Province of China(Grant No.2020A1515010094).
文摘Objective:Our aim was to test the hypothesis that fatty acid synthase(FASN)expression contributes to radioresistance of nasopharyngeal carcinoma(NPC)cells and that inhibiting FASN enhances radiosensitivity.Methods:Targeting FASN using epigallocatechin gallate(EGCG)or RNA interference in NPC cell lines that overexpress endogenous FASN was performed to determine their effects on cellular response to radiationin vitro using MTT and colony formation assays,andin vivo using xenograft animal models.Western blot,immunohistochemistry,real-time PCR arrays,and real-time RT-PCR were used to determine the relationship between FASN and frizzled class receptor 10(FZD10)expression.FZD10 knockdown and overexpression were used to determine its role in mediating FASN function in cellular response to radiation.Immunohistochemical staining was used to determine FASN and FZD10 expressions in human NPC tissues,followed by analysis of their association with the overall survival of patients.Results:FASN knockdown or inhibition significantly enhanced radiosensitivity of NPC cells,bothin vitro andin vivo.There was a positive association between FASN and FZD10 expression in NPC cell lines grown as monolayers or xenografts,as well as human tissues.FASN knockdown reduced FZD10 expression,and rescue of FZD10 expression abolished FASN knockdown-induced enhancement of radiosensitivity.FASN and FZD10 were both negatively associated with overall survival of NPC patients.Conclusions:FASN contributes to radioresistance,possiblyvia FZD10 in NPC cells.Both FZD10 and FASN expressions were associated with poor outcomes of NPC patients.EGCG may sensitize radioresistance by inhibiting FASN and may possibly be developed as a radiosensitizer for better treatment of NPCs.
基金supported by the National Key R&D Program of China(2021YFC2400500)National Natural Science Foundation of China(Nos.U2001221 and 32161160327)+1 种基金Shenzhen Science and Technology Program(JCYJ20200109114620793 and JSGGKQTD20210831174330015)Guangdong Basic and Applied Basic Research Foundation(2022B 1515120048 and 2023A1515011727).
文摘The regeneration of alveolar bone is still clinical challenge,particularly accompanied with diabetes,causing metabolic disorder with a protracted low-grade inflammatory phenotype.As a result,the anticipated loading of biomaterials is highly suspicious in spontaneous modulation of cells function,which is mostly disturbed by constant inflammation.In this study,we developed glucose and hydrogen peroxide dual-responsive borosilicate glass(BSG)scaffolds loaded with epigallocatechin gallate(EGCG)to synergistically modulate the abnormal inflammation of diabetic alveolar bone defects.It was found that the release of EGCG by BSG could directly regulate the shift of macrophages from M1 to the M2 phenotype by promoting autophagy and lessening the inhibition of autophagic flux.Moreover,EGCG can also indirectly regulate the polarization phenotype of macrophages by reducing the activation of NF-κb in stem cells and restoring its immunoregulatory capacity.Therefore,the addition of EGCG to BSG scaffold in diabetes allows for a more striking modulation of the macrophage phenotype in a timely manner.The altered macrophage phenotype reduces local inflammation and thus increases the ability to repair diabetic alveolar bone,showing promise for the treatment of alveolar defect in diabetic patients.