Diabetic kidney disease(DKD)is the most serious microvascular complication during the development of diabetes with the characterizations of glomerular basement membrane thickening,mesangial expansion,and glomerular sc...Diabetic kidney disease(DKD)is the most serious microvascular complication during the development of diabetes with the characterizations of glomerular basement membrane thickening,mesangial expansion,and glomerular sclerosis,eventually leading to end-stage renal disease.This study aimed to investigate the melioration effect of Codonopisis tangshen Oliv.(COD)on the DKD model,which was established by unilateral nephrectomy(UN)-high fat diet feeding(HFD)combined with streptozotocin(STZ).After the DKD rats were oral treated with COD at a dose of 2.7 mg/kg for 4 consecutive weeks,the blood glucose,lipid metabolism,renal function,inflammatory mediators,and fibrosis-associated proteins were examined.In vivo,the COD administration obviously relieved the weight loss,water intake,and blood glucose;decreased the total cholesterol,triglyceride,and low-density lipoprotein cholesterol levels;and improved the renal function by reducing the expression of serum creatinine,uric acid,and urinary protein compared with the model group.The levels of pro-inflammatory cytokines of tumor necrosis factor-a,interleukin-1β,and IL-6 were significantly inhibited by COD.Meanwhile,the deposition of collagen fiber was markedly increased,and the protein and mRNA expressions of transforming growth factor-b1 and a-smooth muscle actin were markedly elevated in DKD rats,but they were decreased to some extent after the COD treatment.In conclusion,COD exhibited a protective effect on the UN-HFD feeding combined with STZ-induced DKD model by improving the blood glucose and lipid metabolism,relieving the inflammatory response,and mitigating the renal fibrosis,which provided scientific evidence for its applications in clinic.展开更多
The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment.However,novel approaches...The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment.However,novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative,biologicallydriven regenerative medicine strategies.For example,cell-homing and cell-based therapies have recently been developed in vitro and trialled in preclinical models to study dental pulp regeneration.These approaches utilise natural and synthetic scaffolds that can deliver a range of bioactive pharmacological epigenetic modulators(HDACis,DNMTis,and ncRNAs),which are cost-effective and easily applied to stimulate pulp tissue regrowth.Unfortunately,many biological factors hinder the clinical development of regenerative therapies,including a lack of blood supply and poor infection control in the necrotic root canal system.Additional challenges include a need for clinically relevant models and manufacturing challenges such as scalability,cost concerns,and regulatory issues.This review will describe the current state of bioactive-biomaterial/scaffold-based engineering strategies to stimulate dentine-pulp regeneration,explicitly focusing on epigenetic modulators and therapeutic pharmacological inhibition.It will highlight the components of dental pulp regenerative approaches,describe their current limitations,and offer suggestions for the effective translation of novel epigenetic-laden bioactive materials for innovative therapeutics.展开更多
基金This research was funded by the National Natural Science Foundation of China Grant Numbers 81503376 and 81774213Applied Science and Technology Research Foundation of Guangdong Province Grant Number 2016B020237005+1 种基金College Students Entrepreneurship Training Program of Southern Medical University(201712121083)Scientific Enlightenment Program of Southern Medical University(b1000501).
文摘Diabetic kidney disease(DKD)is the most serious microvascular complication during the development of diabetes with the characterizations of glomerular basement membrane thickening,mesangial expansion,and glomerular sclerosis,eventually leading to end-stage renal disease.This study aimed to investigate the melioration effect of Codonopisis tangshen Oliv.(COD)on the DKD model,which was established by unilateral nephrectomy(UN)-high fat diet feeding(HFD)combined with streptozotocin(STZ).After the DKD rats were oral treated with COD at a dose of 2.7 mg/kg for 4 consecutive weeks,the blood glucose,lipid metabolism,renal function,inflammatory mediators,and fibrosis-associated proteins were examined.In vivo,the COD administration obviously relieved the weight loss,water intake,and blood glucose;decreased the total cholesterol,triglyceride,and low-density lipoprotein cholesterol levels;and improved the renal function by reducing the expression of serum creatinine,uric acid,and urinary protein compared with the model group.The levels of pro-inflammatory cytokines of tumor necrosis factor-a,interleukin-1β,and IL-6 were significantly inhibited by COD.Meanwhile,the deposition of collagen fiber was markedly increased,and the protein and mRNA expressions of transforming growth factor-b1 and a-smooth muscle actin were markedly elevated in DKD rats,but they were decreased to some extent after the COD treatment.In conclusion,COD exhibited a protective effect on the UN-HFD feeding combined with STZ-induced DKD model by improving the blood glucose and lipid metabolism,relieving the inflammatory response,and mitigating the renal fibrosis,which provided scientific evidence for its applications in clinic.
基金supported by Trinity College Dublin(Trinity Research Doctorate Award).All figures were created with BioR ender.com.
文摘The drive for minimally invasive endodontic treatment strategies has shifted focus from technically complex and destructive root canal treatments towards more conservative vital pulp treatment.However,novel approaches to maintaining dental pulp vitality after disease or trauma will require the development of innovative,biologicallydriven regenerative medicine strategies.For example,cell-homing and cell-based therapies have recently been developed in vitro and trialled in preclinical models to study dental pulp regeneration.These approaches utilise natural and synthetic scaffolds that can deliver a range of bioactive pharmacological epigenetic modulators(HDACis,DNMTis,and ncRNAs),which are cost-effective and easily applied to stimulate pulp tissue regrowth.Unfortunately,many biological factors hinder the clinical development of regenerative therapies,including a lack of blood supply and poor infection control in the necrotic root canal system.Additional challenges include a need for clinically relevant models and manufacturing challenges such as scalability,cost concerns,and regulatory issues.This review will describe the current state of bioactive-biomaterial/scaffold-based engineering strategies to stimulate dentine-pulp regeneration,explicitly focusing on epigenetic modulators and therapeutic pharmacological inhibition.It will highlight the components of dental pulp regenerative approaches,describe their current limitations,and offer suggestions for the effective translation of novel epigenetic-laden bioactive materials for innovative therapeutics.