Diabetic foot ulcer is the most prevalent and serious lower-limb complication among individuals with diabetes,and it significantly contributes to the incidence of non-traumatic amputations.The repeated failure of diab...Diabetic foot ulcer is the most prevalent and serious lower-limb complication among individuals with diabetes,and it significantly contributes to the incidence of non-traumatic amputations.The repeated failure of diabetic wounds to heal can result in diabetic foot ulcers,inflicting considerable physical suffering and imposing substantial economic burdens on both patients and global healthcare systems because of the complexity and high costs of treatment.The mechanisms underlying the impaired healing of diabetic wounds are intricate and incompletely understood.Histone deacetylases(HDACs)are critical epigenetic regulators that catalyze the removal of acetyl or acyl groups from lysine residues in proteins,thereby modulating various biological processes,including transcription,apoptosis,and metabolism.Nevertheless,the precise roles of HDACs in diabetic wound healing remain largely unexplored.Thus,the current review describes the pivotal roles of HDACs in diabetic wound healing,focusing on their regulation of inflammatory responses,vascular dysfunction,and epithelial renewal,which are critical events in wound healing.Furthermore,we discuss the therapeutic potential of HDAC inhibitors and propose future directions for clinical application.展开更多
BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to expl...BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to explore the mechanistic importance of HDAC10 as a regulator of CRC.AIM To investigate the impact of HDAC10 on tumor growth and its regulation in tumor microenvironment(TME)in CRC,we conducted this study.METHODS The study evaluated HDAC10 expression using immunohistochemistry analyses and assessed its prognostic value in CRC patients.HDAC10 depletion CRC cell lines were generated,and its biological functions were assessed through cell counting kit-8,wound healing,and colony formation assays.Furthermore,gene set variation analysis(GSVA)was employed to explore the potential molecular mechanisms of HDAC10 in CRC.The impact of HDAC10 on TME was subsequently assessed.Finally,the study investigated the influence of HDAC10 on the response to immunotherapy and chemotherapeutic drugs in CRC.RESULTS HDAC10 expression was significantly elevated in CRC and correlated with poor prognosis in patients.Knockdown of HDAC10 reduced colon cancer cell proliferation and migration capabilities.GSVA revealed a strong association between high HDAC10 expression and immune suppression.Additionally,high HDAC10 levels were correlated with a non-inflamed TME.Finally,patients with high HDAC10 expression showed reduced sensitivity to immuno-therapy.CONCLUSION This study revealed the significance of HDAC10 in TME,therapy efficacy,and clinical prognosis in CRC,offering novel insights for therapeutic advancements in CRC.展开更多
Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Isc...Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).展开更多
A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activitie...A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.展开更多
基金Supported by the Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2024]297.
文摘Diabetic foot ulcer is the most prevalent and serious lower-limb complication among individuals with diabetes,and it significantly contributes to the incidence of non-traumatic amputations.The repeated failure of diabetic wounds to heal can result in diabetic foot ulcers,inflicting considerable physical suffering and imposing substantial economic burdens on both patients and global healthcare systems because of the complexity and high costs of treatment.The mechanisms underlying the impaired healing of diabetic wounds are intricate and incompletely understood.Histone deacetylases(HDACs)are critical epigenetic regulators that catalyze the removal of acetyl or acyl groups from lysine residues in proteins,thereby modulating various biological processes,including transcription,apoptosis,and metabolism.Nevertheless,the precise roles of HDACs in diabetic wound healing remain largely unexplored.Thus,the current review describes the pivotal roles of HDACs in diabetic wound healing,focusing on their regulation of inflammatory responses,vascular dysfunction,and epithelial renewal,which are critical events in wound healing.Furthermore,we discuss the therapeutic potential of HDAC inhibitors and propose future directions for clinical application.
基金Supported by National Natural Science Foundation of China,No.82403279 and No.82303181.
文摘BACKGROUND The histone deacetylases 10(HDAC10)is a HDAC family member,yet its importance in the context of colorectal cancer(CRC)development remains incompletely understood.The present study was thus developed to explore the mechanistic importance of HDAC10 as a regulator of CRC.AIM To investigate the impact of HDAC10 on tumor growth and its regulation in tumor microenvironment(TME)in CRC,we conducted this study.METHODS The study evaluated HDAC10 expression using immunohistochemistry analyses and assessed its prognostic value in CRC patients.HDAC10 depletion CRC cell lines were generated,and its biological functions were assessed through cell counting kit-8,wound healing,and colony formation assays.Furthermore,gene set variation analysis(GSVA)was employed to explore the potential molecular mechanisms of HDAC10 in CRC.The impact of HDAC10 on TME was subsequently assessed.Finally,the study investigated the influence of HDAC10 on the response to immunotherapy and chemotherapeutic drugs in CRC.RESULTS HDAC10 expression was significantly elevated in CRC and correlated with poor prognosis in patients.Knockdown of HDAC10 reduced colon cancer cell proliferation and migration capabilities.GSVA revealed a strong association between high HDAC10 expression and immune suppression.Additionally,high HDAC10 levels were correlated with a non-inflamed TME.Finally,patients with high HDAC10 expression showed reduced sensitivity to immuno-therapy.CONCLUSION This study revealed the significance of HDAC10 in TME,therapy efficacy,and clinical prognosis in CRC,offering novel insights for therapeutic advancements in CRC.
基金supported by the National Institute of Health/National Eye Institute(NIH/NEI)grants(R00 EY029373,R01 EY035658)to AYFKnights Templar Eye Foundation Research Grant to ESIntramural UAMS Hornick and Sturgis grants to AYF and ES respectively。
文摘Ischemic retinopathy is a leading cause of blindness:Ischemic retinopathies including diabetic retinopathy(DR),retinopathy of prematurity,and retinal artery and vein occlusion are major causes of visual impairment.Ischemic retinopathy can be acute,such as in central or branch retinal artery occlusion,or chronic,such as with DR(Figure 1).Although the causes of retinopathies are diverse,one pathogenic event shared by these conditions is the myeloid cell response to retinal ischemia(Shahror et al.,2024a).
基金supported by the National Natural Science Foundation of China(21473081,21075138)special fund of State Key Laboratory of Structure Chemistry(20160028)
文摘A molecular electronegativity distance vector(M)based on 13 atomic types has been used to describe the structures of 19 conjugates(LHCc)of levofloxacin-thiadiazole HDAC inhibitor(HDACi)and related inhibitory activities(pH,i=1,2,6)of LHCc against histone deacetylases(HDACs,such as HDAC1,HDAC2 and HDAC6).The quantitative structure-activity relationships(QSAR)were established by using leaps-and-bounds regression analysis for the inhibitory activities(pH)of 19 above compounds to HDAC1,HDAC2 and HDAC6 along with M.The correlation coefficients(R~2)and the leave-one-out(LOO)cross validation Rfor the pH,pHand pHmodels were 0.976 and 0.949;0.985 and 0.977;0.976 and 0.932,respectively.The QSAR models had favorable correlations,as well as robustness and good prediction capability by R~2,F,R~2,A,Fand Vtests.Validated by using 3876 training sets,the models have good external prediction ability.The results indicate that the molecular structural units:–CH–(g=1,2),–NH,–OH,=O,–O–and–S–are the main factors which can affect the inhibitory activity of pH,pHas well as pHbioactivities of these compounds directly.Accordingly,the main interactions between HDACs inhibitor and HDACs are hydrophobic interaction,hydrogen bond,and coordination with Znto form compounds,which is consistent with the results in reports.
