Homogentisic acid(HGA),a product of the L-tyrosine metabolic pathway,serves as a substrate for tocopherol synthesis.Previous studies revealed that the fermentation of coix seeds by M.purpureus could simultaneously upr...Homogentisic acid(HGA),a product of the L-tyrosine metabolic pathway,serves as a substrate for tocopherol synthesis.Previous studies revealed that the fermentation of coix seeds by M.purpureus could simultaneously upregulate tocopherol and HGA levels.Therefore,this study focused on HGA to investigate its specific effect on tocopherol production during the fermentation process.The results showed that 0.02% Exo-HGA significantly increased tocopherol yield by 53.11%,reaching 184.808μg/g.Based on the seed culture medium,the optimal formulation of key factors for promoting End-HGA synthesis in M.purpureus was determined.It was obtained through single-factor experiments and uniform design:D-fructose(36.816 g/L),L-tyrosine(0.656%),yeast extract powder(7 g/L),ZnSO_(4)(0.654 g/L).Under these conditions,M.purpureus exhibited good growth,with an End-HGA yield reaching 844.461μg/mL.In addition,fermentation of coix seeds with End-HGA led to an increase in the total tocopherol yield by 57.36%,reaching 181.303μg/g.This result was comparable to that achieved with Exo-HGA addition.Therefore,enhancing End-HGA synthesis is an effective strategy to achieve a high tocopherol yield through M.purpureus fermentation.In conclusion,this study demonstrated that the regulation of microorganisms can enable high-level synthesis of target products and improve the efficiency of deep conversion and utilization of plant substrates.展开更多
Objective Alzheimer's disease(AD)is a progressive neurodegenerative disease associated with metabolic dysregulation.This study aimed to investigate the role of homogentisic acid(HGA),a tyrosine metabolite,in AD pa...Objective Alzheimer's disease(AD)is a progressive neurodegenerative disease associated with metabolic dysregulation.This study aimed to investigate the role of homogentisic acid(HGA),a tyrosine metabolite,in AD pathogenesis and explore its potential as a noninvasive diagnostic biomarker.Methods Human saliva samples from AD patients and controls were analyzed.In vivo experiments were conducted using APP/PS1(Aβ-driven)and P301S(tauopathy-focused)mouse models,which received exogenous HGA via gavage.Key techniques included behavioral tests(Morris water maze,novel object recognition,fear conditioning),Western blot,immu-nofluorescence,real-time PCR,and mass spectrometry to assess cognitive function,blood-brain barrier(BBB)integrity,Aβaggregation,synaptic protein expression,and HGA metabolism.In vitro experiments were performed on HT22,SY5Y cells,and primary brain microvascular endothelial cells(BMECs)to verify HGA's direct effects.Results Salivary HGA levels were higher in AD patients than in controls,correlating with BBB impairment.Exogenous HGA significantly exacerbated cognitive deficits,BBB leakage,Aβdeposition,and loss of synaptic proteins(PSD93,synaptophy-sin)in mice,with effects more pronounced in the APP/PS1 than in the P301S model.In vitro,HGA exerted dose-dependent neurotoxicity,promoted Aβaggregation,and downregulated tight junction proteins(claudin-5,occludin,ZO-1)in BMECs.Mechanistically,AD patients showed reduced expression of HGA-metabolizing enzymes(homogentisate 1,2-dioxygenase,maleylacetoacetate isomerase)and downstream metabolites,indicating impaired HGA catabolism.These findings confirm HGA promotes AD progression via two mutually reinforcing pathways:(1)accelerating Aβaggregation and synaptic dys-function;(2)disrupting BBB integrity through downregulating tight junction proteins.Conclusion This study identifies salivary HGA as a potential noninvasive biomarker and highlights targeting HGA metabo-lism or BBB protection as promising strategies for early AD intervention.展开更多
BACKGROUND Ochronotic arthropathy(OcA)is a rare disease,which is caused by the accumulation of homogentisic acid in the joint.Patients with OcA have obvious joint pain and the disease progresses rapidly,eventually res...BACKGROUND Ochronotic arthropathy(OcA)is a rare disease,which is caused by the accumulation of homogentisic acid in the joint.Patients with OcA have obvious joint pain and the disease progresses rapidly,eventually resulting in disability.Arthroplasty is an efficacious treatment in patients with OcA.However,when OcA patients have joint infection,is joint replacement an option?In the present report,we performed total knee arthroplasty in a patient with OcA and knee infection under the guidance of one-stage revision theory.CASE SUMMARY A 64-year-old male was referred to our hospital due to severe left knee pain with limited mobility for 2 years.On physical examination,the patient was found to have dark brown pigmentation of the sclera and auricle.Laboratory test results showed elevations in C-reactive protein level(65.79 mg/L)and erythrocyte sedimentation rate(90.00 mm/h).The patient underwent debridement of the left knee joint,during which the cartilage surface of the knee joint was found to be black-brown in color.Bacterial culture of synovial fluid revealed Achromobacter xylosoxidans.We then carried out arthroplasty under the guidance of the theory of one-stage revision.After surgery,the patient’s left knee joint pain disappeared and function recovered without joint infection.CONCLUSION OcA accompanied by joint infection is rare.One-stage revision arthroplasty may be a treatment option for this disease.展开更多
基金supported by the National Natural Science Foundation of China[Grant number(32260583)]Scientific Research Foundation for Introduction of Talents of Guizhou University[Grant No.(2021)76].
文摘Homogentisic acid(HGA),a product of the L-tyrosine metabolic pathway,serves as a substrate for tocopherol synthesis.Previous studies revealed that the fermentation of coix seeds by M.purpureus could simultaneously upregulate tocopherol and HGA levels.Therefore,this study focused on HGA to investigate its specific effect on tocopherol production during the fermentation process.The results showed that 0.02% Exo-HGA significantly increased tocopherol yield by 53.11%,reaching 184.808μg/g.Based on the seed culture medium,the optimal formulation of key factors for promoting End-HGA synthesis in M.purpureus was determined.It was obtained through single-factor experiments and uniform design:D-fructose(36.816 g/L),L-tyrosine(0.656%),yeast extract powder(7 g/L),ZnSO_(4)(0.654 g/L).Under these conditions,M.purpureus exhibited good growth,with an End-HGA yield reaching 844.461μg/mL.In addition,fermentation of coix seeds with End-HGA led to an increase in the total tocopherol yield by 57.36%,reaching 181.303μg/g.This result was comparable to that achieved with Exo-HGA addition.Therefore,enhancing End-HGA synthesis is an effective strategy to achieve a high tocopherol yield through M.purpureus fermentation.In conclusion,this study demonstrated that the regulation of microorganisms can enable high-level synthesis of target products and improve the efficiency of deep conversion and utilization of plant substrates.
基金supported by the Hubei Provincial Natural Science Foundation of China for Distinguished Young Scholars(No.2022CFA104 to Yi-yuan Xia)the Key Research and Development Program of Wuhan(No.2024020802030159 to Yi-yuan Xia)+1 种基金the National Natural Science Foundation of China(No.82371195 to Xi-ji Shu)the Research Fund of Jianghan University(No.2022XKZX26 to Shi-chao Deng).
文摘Objective Alzheimer's disease(AD)is a progressive neurodegenerative disease associated with metabolic dysregulation.This study aimed to investigate the role of homogentisic acid(HGA),a tyrosine metabolite,in AD pathogenesis and explore its potential as a noninvasive diagnostic biomarker.Methods Human saliva samples from AD patients and controls were analyzed.In vivo experiments were conducted using APP/PS1(Aβ-driven)and P301S(tauopathy-focused)mouse models,which received exogenous HGA via gavage.Key techniques included behavioral tests(Morris water maze,novel object recognition,fear conditioning),Western blot,immu-nofluorescence,real-time PCR,and mass spectrometry to assess cognitive function,blood-brain barrier(BBB)integrity,Aβaggregation,synaptic protein expression,and HGA metabolism.In vitro experiments were performed on HT22,SY5Y cells,and primary brain microvascular endothelial cells(BMECs)to verify HGA's direct effects.Results Salivary HGA levels were higher in AD patients than in controls,correlating with BBB impairment.Exogenous HGA significantly exacerbated cognitive deficits,BBB leakage,Aβdeposition,and loss of synaptic proteins(PSD93,synaptophy-sin)in mice,with effects more pronounced in the APP/PS1 than in the P301S model.In vitro,HGA exerted dose-dependent neurotoxicity,promoted Aβaggregation,and downregulated tight junction proteins(claudin-5,occludin,ZO-1)in BMECs.Mechanistically,AD patients showed reduced expression of HGA-metabolizing enzymes(homogentisate 1,2-dioxygenase,maleylacetoacetate isomerase)and downstream metabolites,indicating impaired HGA catabolism.These findings confirm HGA promotes AD progression via two mutually reinforcing pathways:(1)accelerating Aβaggregation and synaptic dys-function;(2)disrupting BBB integrity through downregulating tight junction proteins.Conclusion This study identifies salivary HGA as a potential noninvasive biomarker and highlights targeting HGA metabo-lism or BBB protection as promising strategies for early AD intervention.
基金Supported by Talent Training Project of Guangdong Provincial Bureau of Traditional Chinese Medicine,No.0103030908Guangdong Provincial Hospital of Traditional Chinese Medicine and the School of Biomedicine,Chinese University of Hong Kong School of Medicine,Basic Clinical Collaborative Innovation Project,No.YN2018HK04。
文摘BACKGROUND Ochronotic arthropathy(OcA)is a rare disease,which is caused by the accumulation of homogentisic acid in the joint.Patients with OcA have obvious joint pain and the disease progresses rapidly,eventually resulting in disability.Arthroplasty is an efficacious treatment in patients with OcA.However,when OcA patients have joint infection,is joint replacement an option?In the present report,we performed total knee arthroplasty in a patient with OcA and knee infection under the guidance of one-stage revision theory.CASE SUMMARY A 64-year-old male was referred to our hospital due to severe left knee pain with limited mobility for 2 years.On physical examination,the patient was found to have dark brown pigmentation of the sclera and auricle.Laboratory test results showed elevations in C-reactive protein level(65.79 mg/L)and erythrocyte sedimentation rate(90.00 mm/h).The patient underwent debridement of the left knee joint,during which the cartilage surface of the knee joint was found to be black-brown in color.Bacterial culture of synovial fluid revealed Achromobacter xylosoxidans.We then carried out arthroplasty under the guidance of the theory of one-stage revision.After surgery,the patient’s left knee joint pain disappeared and function recovered without joint infection.CONCLUSION OcA accompanied by joint infection is rare.One-stage revision arthroplasty may be a treatment option for this disease.
