Nickel(Ni)toxicity significantly impairs plant growth,photosynthesis,and metabolism by inducing oxidative stress.This study evaluates the potential of exogenous Alpha-Ketoglutarate(AKG)in mitigating Ni-induced stress ...Nickel(Ni)toxicity significantly impairs plant growth,photosynthesis,and metabolism by inducing oxidative stress.This study evaluates the potential of exogenous Alpha-Ketoglutarate(AKG)in mitigating Ni-induced stress in Peganum harmala L.Seedlings were exposed to 0,200,500,and 750μM NiCl2,with or without AKG supplementation.Under 750μM Ni stress,dry weight(DW)decreased by 33.7%,tissue water content(TWC)by 39.9%,and chlorophyll a and total chlorophyll levels were reduced by 17%and 15%,respectively.Ni exposure also significantly increased secondary metabolite production,with leaf anthocyanin content rising by 131%,and superoxide dismutase(SOD)and catalase(CAT)activities increasing by 228%and 53%,respectively,in roots at 500μM Ni.AKG treatment alleviated Ni toxicity by enhancing TWC by 39%and promoting root and shoot growth.Additionally,AKG treatment boosted the synthesis of phenolic compounds and flavonoids,contributing to improved tolerance against Ni stress.These findings demonstrate the potential of AKG in enhancing Ni tolerance in P.harmala,suggesting its promising role in bioremediation of metal-contaminated soils.This is the first study to report the beneficial effects of exogenous AKG in alleviating nickel toxicity in P.harmala L.,offering a new approach for improving plant resilience to heavy metal stress.展开更多
Background:Non-alcoholic liver disease is of increased concern and contributing to economic burdens not only in developing countries but in developed countries as well.Identifying the biomarker of early diagnosis and ...Background:Non-alcoholic liver disease is of increased concern and contributing to economic burdens not only in developing countries but in developed countries as well.Identifying the biomarker of early diagnosis and early intervention approaches for non-alcoholic liver disease is unmet and required further investigation.Although the alpha-ketoglutarate(a-KG)is recently proposed to be a potential biomarker in differentiating patients with obesity from those with non-alcoholic liver disease,how a-ketoglutatate is involved in the fatty liver progression is not clear.Methods:A high-fat diet(HFD)feeding animal model,liver functional assays,and molecular approaches were adopted to clarify the impact of a-KG in fatty liver progression.Results:In the current study,it was found that dietary a-KG would inhibit weight gain in male and female mice fed with a normal chew or HFD.HFD feeding caused fatty liver in male mice,but a-KG treatment could substantially inhibit hepatic steatosis progression.Biochemical studies revealed the possible linkage of a-KG protective functions to lipid metabolism.Further analysis identified the important role of peroxisome proliferator-activated receptors in beneficial a-KG-mediated effects on fatty liver progression.Conclusions:The current study demonstrates the therapeutic potential of a-KG and how it may be used,via dietary supplementation,as a preventive intervention for non-alcoholic liver disease in obese patients.展开更多
AIM:To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid(α-KG)on scleral collagen expression.METHODS:Meta-analysis and clinical statistics were used to prove the cha...AIM:To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid(α-KG)on scleral collagen expression.METHODS:Meta-analysis and clinical statistics were used to prove the changes in choroidal thickness(ChT)during myopia.The establishment of a hypoxic myopia model(HYP)for rabbit scleral fibroblasts through hypoxic culture and the effects of hypoxia andα-KG on collagen expression were demonstrated by Sirius red staining.Transcriptome analysis was used to verify the genes and pathways that hypoxia andα-KG affect collagen expression.Finally,real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)was used for reverse verification.RESULTS:Meta-analysis results aligned with clinical statistics,revealing a thinning of ChT,leading to scleral hypoxia.Sirius red staining indicated lower collagen expression in the HYP group and higher collagen expression in the HYP+α-KG group,showed that hypoxia reduced collagen expression in scleral fibroblasts,whileα-KG can elevated collagen expression under HYP conditions.Transcriptome analysis unveiled the related genes and signaling pathways of hypoxia andα-KG affect scleral collagen expression and the results were verified by RT-qPCR.CONCLUSION:The potential molecular mechanisms through which hypoxia andα-KG influencing myopia is unraveled and three novel genes TLCD4,TBC1D4,and EPHX3 are identified.These findings provide a new perspective on the prevention and treatment of myopia via regulating collagen expression.展开更多
The aim of this study was to investigate the effects of α-ketoglutaric acid(AKG)supplementation on hair follicle development and to evaluate the effects on performance and antioxidant capacity in Rex rabbits.The mech...The aim of this study was to investigate the effects of α-ketoglutaric acid(AKG)supplementation on hair follicle development and to evaluate the effects on performance and antioxidant capacity in Rex rabbits.The mechanism was explored in an in vitro model and validated in an animal trial.Firstly,dermal papilla cells(DPCs)line was cultured with AKG as an in vitro model.Next,a total of 160 Rex rabbits(120-d-old,body weight 2473.20±17.08 g)were divided into 4 groups with 40 rabbits in each group(20 male and 20 female)and fed with 0,0.5%,1.0% and 1.5% AKG diets for 35 d.The result showed that 6 mmol/L AKG significantly promoted cell proliferation(P<0.001),reduced the proportion of cells in the synthesis(S)phase and increased the gap 2(G2)phase(P<0.01).Transcriptomics results indicated that AKG enhanced DPCs exosome secretion capacity,increased susceptibility to extracellular signaling molecules,and improved their regulatory effects on neighboring cells.Additionally,the findings suggested that AKG-mediated promotion of hair follicle development may be associated with wingless/integrated(Wnt)signaling pathway.Meanwhile,AKG enhanced the expression levels of genes and proteins in the Wnt signaling pathway in DPCs and Rex rabbit skin tissue(P<0.05).AKG treatment increased the concentrations of glutamine,glutamic acid,asparagine and aspartic acid amino acids in the DPCs(P<0.05).Finally,1.5% AKG significantly increased the performance,slaughter performance,primary hair follicle density,secondary hair follicle density and total hair follicle density of Rex rabbits,significantly increasing the antioxidant capacity in the skin,liver and serum of Rex rabbits,while upregulating the expression of anti-apoptotic and antioxidant-related genes in skin tissues(P<0.05).In summary,dietary supplementation of 1.5% AKG significantly improved performance,hair follicle density and antioxidant capacity in Rex rabbits.AKG may promote hair follicle development by reducing intracellular amino acid catabolism and enhancing the Wnt signaling pathway.展开更多
基金Researchers Supporting Project No.(RSP2025R390),King Saud University,Riyadh,Saudi Arabia.
文摘Nickel(Ni)toxicity significantly impairs plant growth,photosynthesis,and metabolism by inducing oxidative stress.This study evaluates the potential of exogenous Alpha-Ketoglutarate(AKG)in mitigating Ni-induced stress in Peganum harmala L.Seedlings were exposed to 0,200,500,and 750μM NiCl2,with or without AKG supplementation.Under 750μM Ni stress,dry weight(DW)decreased by 33.7%,tissue water content(TWC)by 39.9%,and chlorophyll a and total chlorophyll levels were reduced by 17%and 15%,respectively.Ni exposure also significantly increased secondary metabolite production,with leaf anthocyanin content rising by 131%,and superoxide dismutase(SOD)and catalase(CAT)activities increasing by 228%and 53%,respectively,in roots at 500μM Ni.AKG treatment alleviated Ni toxicity by enhancing TWC by 39%and promoting root and shoot growth.Additionally,AKG treatment boosted the synthesis of phenolic compounds and flavonoids,contributing to improved tolerance against Ni stress.These findings demonstrate the potential of AKG in enhancing Ni tolerance in P.harmala,suggesting its promising role in bioremediation of metal-contaminated soils.This is the first study to report the beneficial effects of exogenous AKG in alleviating nickel toxicity in P.harmala L.,offering a new approach for improving plant resilience to heavy metal stress.
基金Funding for this work was provided by 2017 AASLDF Pinnacle Research Development Award and Rhode Island Foundation#134279.
文摘Background:Non-alcoholic liver disease is of increased concern and contributing to economic burdens not only in developing countries but in developed countries as well.Identifying the biomarker of early diagnosis and early intervention approaches for non-alcoholic liver disease is unmet and required further investigation.Although the alpha-ketoglutarate(a-KG)is recently proposed to be a potential biomarker in differentiating patients with obesity from those with non-alcoholic liver disease,how a-ketoglutatate is involved in the fatty liver progression is not clear.Methods:A high-fat diet(HFD)feeding animal model,liver functional assays,and molecular approaches were adopted to clarify the impact of a-KG in fatty liver progression.Results:In the current study,it was found that dietary a-KG would inhibit weight gain in male and female mice fed with a normal chew or HFD.HFD feeding caused fatty liver in male mice,but a-KG treatment could substantially inhibit hepatic steatosis progression.Biochemical studies revealed the possible linkage of a-KG protective functions to lipid metabolism.Further analysis identified the important role of peroxisome proliferator-activated receptors in beneficial a-KG-mediated effects on fatty liver progression.Conclusions:The current study demonstrates the therapeutic potential of a-KG and how it may be used,via dietary supplementation,as a preventive intervention for non-alcoholic liver disease in obese patients.
基金Supported by the Natural Science Foundation of Shandong Province,China(No.ZR2023MA069)the Medical and Health Technology Development Project of Shandong Province,China(No.202202050602)+1 种基金College Students’Innovation and Entrepreneurship Training Program(No.S202410438017)the Graduate Student Research Grant from Shandong Second Medical University.
文摘AIM:To investigate the molecular mechanisms underlying the influence of hypoxia and alpha-ketoglutaric acid(α-KG)on scleral collagen expression.METHODS:Meta-analysis and clinical statistics were used to prove the changes in choroidal thickness(ChT)during myopia.The establishment of a hypoxic myopia model(HYP)for rabbit scleral fibroblasts through hypoxic culture and the effects of hypoxia andα-KG on collagen expression were demonstrated by Sirius red staining.Transcriptome analysis was used to verify the genes and pathways that hypoxia andα-KG affect collagen expression.Finally,real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)was used for reverse verification.RESULTS:Meta-analysis results aligned with clinical statistics,revealing a thinning of ChT,leading to scleral hypoxia.Sirius red staining indicated lower collagen expression in the HYP group and higher collagen expression in the HYP+α-KG group,showed that hypoxia reduced collagen expression in scleral fibroblasts,whileα-KG can elevated collagen expression under HYP conditions.Transcriptome analysis unveiled the related genes and signaling pathways of hypoxia andα-KG affect scleral collagen expression and the results were verified by RT-qPCR.CONCLUSION:The potential molecular mechanisms through which hypoxia andα-KG influencing myopia is unraveled and three novel genes TLCD4,TBC1D4,and EPHX3 are identified.These findings provide a new perspective on the prevention and treatment of myopia via regulating collagen expression.
基金supported by the China Agriculture Research System of MOF and MARA(CARS-43-B-1)Special Economic Animal Industry Technology System of Shandong Province(SDAIT-2116)Shandong Province Agricultural Improved Seed Project(2021LZGC002).
文摘The aim of this study was to investigate the effects of α-ketoglutaric acid(AKG)supplementation on hair follicle development and to evaluate the effects on performance and antioxidant capacity in Rex rabbits.The mechanism was explored in an in vitro model and validated in an animal trial.Firstly,dermal papilla cells(DPCs)line was cultured with AKG as an in vitro model.Next,a total of 160 Rex rabbits(120-d-old,body weight 2473.20±17.08 g)were divided into 4 groups with 40 rabbits in each group(20 male and 20 female)and fed with 0,0.5%,1.0% and 1.5% AKG diets for 35 d.The result showed that 6 mmol/L AKG significantly promoted cell proliferation(P<0.001),reduced the proportion of cells in the synthesis(S)phase and increased the gap 2(G2)phase(P<0.01).Transcriptomics results indicated that AKG enhanced DPCs exosome secretion capacity,increased susceptibility to extracellular signaling molecules,and improved their regulatory effects on neighboring cells.Additionally,the findings suggested that AKG-mediated promotion of hair follicle development may be associated with wingless/integrated(Wnt)signaling pathway.Meanwhile,AKG enhanced the expression levels of genes and proteins in the Wnt signaling pathway in DPCs and Rex rabbit skin tissue(P<0.05).AKG treatment increased the concentrations of glutamine,glutamic acid,asparagine and aspartic acid amino acids in the DPCs(P<0.05).Finally,1.5% AKG significantly increased the performance,slaughter performance,primary hair follicle density,secondary hair follicle density and total hair follicle density of Rex rabbits,significantly increasing the antioxidant capacity in the skin,liver and serum of Rex rabbits,while upregulating the expression of anti-apoptotic and antioxidant-related genes in skin tissues(P<0.05).In summary,dietary supplementation of 1.5% AKG significantly improved performance,hair follicle density and antioxidant capacity in Rex rabbits.AKG may promote hair follicle development by reducing intracellular amino acid catabolism and enhancing the Wnt signaling pathway.
