1.Biomimetic design of biomedical scaffolds and their application in tissue engineering
Chen LIANG ; Tonghe ZHU ; Yiyao ZHU ; Ruizhi LI
Chinese Journal of Tissue Engineering Research 2024;28(15):2416-2422
BACKGROUND:Biomimetic design of bioactive materials to restore,maintain or improve the function of tissue based on the understanding of anatomy on the function and structure of biological tissue is a research hotspot in the field of regenerative medicine at present. OBJECTIVE:To discuss the effect of mechanical properties,three-dimensional spatial structure,and biochemical activity of biomedical scaffolds on cell behavior and review the application of biomedical scaffolds in the field of tissue engineering. METHODS:The articles published in CNKI,Wanfang,Web of Science,and PubMed databases from January 2003 to April 2023 were searched by computer.The Chinese search terms were"extracellular matrix,tissue engineering,scaffolds,biomaterials,biomimetic structures,mechanical properties,three-dimensional structures,tendon-bone interface,osteochondral,neural conduits,artificial blood vessels".English search terms were"extracellular matrix,tissue engineering,scaffolds,biomimetic structures,biomaterials,tendon bone interfaces,osteochondral,neural conduits,artificial blood vessels". RESULTS AND CONCLUSION:Cells are in a complex and dynamic three-dimensional environment,so the extracellular matrix is the ultimate target of biomaterial simulation.The bionic structure of biomedical scaffolders needs to be similar to the real microenvironment,so that cells can stick to the wall,grow and migrate normally,and maintain their diverse physiological functions.Biomimetic design of extracellular matrix in terms of mechanical properties,three-dimensional spatial structure,and biochemical properties of biomedical scaffolds can play a decisive role in tissue repair,thus affecting the final result of tissue repair.Biomimetic biomedical scaffolds have been widely used in tendon-bone interface,bone cartilage interface,nerve,vascular regeneration,and other fields,providing a promising new idea in clinical practice.
2.Pathological analysis of time-zero renal biopsy in donor kidney
Ping LI ; Yiyao TU ; Shaoshan LIANG ; Feng XU ; Dandan LIANG ; Jingsong CHEN ; Zhihong LIU ; Caihong ZENG
Chinese Journal of Organ Transplantation 2019;40(6):355-360
Objective To summarize the pathological survey of time-zero renal biopsy (T0-RBx ) . Methods The material qualities and pathological features were analyzed retrospectively for T 0-RBx (n=176) between March 2008 and May 2016 .According to the source of donor kidney ,T0-RBx specimens were divided into living donors (LD) group (n=137) and Deceased donation (DD) group (n=39) .Furthermore , the DD group was divided into cerebral hemorrhage group (n= 10) and brain trauma group (n= 29) according to the causes of death .The inter-group differences of pathological characteristics and the effects of abnormal pathological lesions on allograft function were observed .Results All T0-RBx specimens contained cortical kidney tissue .The average microscopic length of renal tissue was (0 .39 ± 0 .23) cm and the median glomerular number 11 . The abnormal pathological lesions included glomerulosclerosis (GS ,30 .7 % ) , segmental glomerulosclerosis (1 .1 % ) ,mesangial increase (MI ,19 .3 % ) ,tubular atrophy (TA ,35 .2 % ) , acute tubular necrosis (ATN ,9 .1 % ) ,vacuolar degeneration of tubular epithelium (27 .3 % ) ,losses in tubule epithelial brush border (97 .7 % ) , protein cast (25 % ) , interstitial fibrosis (IF ,34 .1 % ) , inflammation (I ,42 .6 % ) ,arteriolar hyalinosis (AH) (26 .1 % ) and vascular fibrous intimal thickening (CV ,23 .3 % ) .Among them ,23 .9 % ,1 .1 % ,0 .55 % and 0 .55 % cases were diagnosed as IgA nephropathy ,immune complex associated with glomerular disease and focal segmental glomerulosclerosis diabetic nephropathy respectively .And the reminders were of ischemic injury .The incidence rates of TA ,IF and I were lower in DD group than those in LD group ( P< 0 .05 ) . However , ATN and vacuolar degeneration of tubular epithelium were higher (P<0 .001) .The incidence of GS was significantly higher in cerebral hemorrhage group than that in brain trauma group (P<0 .01) .No statistical difference existed in other lesions or disease constitution among the groups (P>0 .05) .Further analysis showed GS was related with allograft function at 6/12 months post-transplantation in both LD and DD groups (P<0 .05) .IF and AH were also related to short-term renal function of recipients post-transplantation in LD and DD groups (P>0 .05) .Conclusions T0-RBx may detect the abnormal lesions of donor kidney .Some differences exist in types and degree of abnormal lesions among different donor kidneys .LD group has a higher risk for chronic histological injury such as TA and IF while DD group is more susceptible to acute renal tubular interstitial injury .Thus it is valuable for predicting allograft function post-transplantation .Material quality is essential for ensuring the reliability of T 0-RBx .
3.Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner.
Cancan ZHENG ; Xiaomei YU ; Yiyao LIANG ; Yidong ZHU ; Yan HE ; Long LIAO ; Dingkang WANG ; Yanming YANG ; Xingfeng YIN ; Ang LI ; Qingyu HE ; Bin LI
Acta Pharmaceutica Sinica B 2022;12(3):1271-1287
As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.