The maintenance of hematopoietic stem cells (HSCs) is a complex process involving numerous cell-extrinsic and -intrinsic regulators. The first member of the cyclin-dependent kinase family of inhibitors to be identified, p21, has been reported to perform a wide range of critical biological functions, including cell cycle regulation, transcription, differentiation, and so on. Given the previous inconsistent results regarding the functions of p21 in HSCs in a p21-knockout mouse model, we employed p21-tdTomato (tdT) mice to further elucidate its role in HSCs during homeostasis. The results showed that p21-tdT+ HSCs exhibited increased self-renewal capacity compared to p21-tdT- HSCs. Zbtb18, a transcriptional repressor, was upregulated in p21-tdT+ HSCs, and its knockdown significantly impaired the reconstitution capability of HSCs. Furthermore, p21 interacted with ZBTB18 to co-repress the expression of cKit in HSCs and thus regulated the self-renewal of HSCs. Our data provide novel insights into the physiological role and mechanisms of p21 in HSCs during homeostasis independent of its conventional role as a cell cycle inhibitor.
Animals ; Hematopoietic Stem Cells/cytology* ; Cyclin-Dependent Kinase Inhibitor p21/genetics* ; Mice ; Cell Self Renewal ; Repressor Proteins/genetics* ; Mice, Inbred C57BL ; Mice, Knockout ; Humans ; Gene Expression Regulation

Objective To probe the characteristic ultrasonic appearances of hepatic adenoma.Methods The appearances of color Doppler flow imaging(CDFI)and contrast-enhanced ultrasound(CEUS)in 10 cases of hepatic adenoma were analyzed.Results Rich blood flow signals were found in all the hepatic adenoma lesions on CDFI.Large blood flow signals were detected in the periphery of all tumors.On CEUS,peritumoral feeding vessels displayed in early arterial phase and homogeneous enhancement in arterial phase was observed in all the 4 cases.The tumor capsule was enhanced continuously in all cases.One case with isoechoic enhancement in delayed phase was found the contrast agent wash out in portal phase.The other 3 cases showed the‘fast-in and slow-out'appearance.which was iso-echoic enhancement in portal phase and slightly hyperechoic enhancement in delayed phase.Conclusions The rich blood flow signals,early displaying of peritumoral feeding vessels,homogeneous enhancement in the arterial phase and continuously enhanced tumor capsule on CEUS are the distinctive appearances of hepatic adenoma.

Objective To evaluate the effectiveness and feasibility of riein-loaded thermosenaitive hydrogel in percutaneous intratumoral injection for treatment of hepatic carcinoma. Methods BALB/c-nu mice were inoculated subcutaneously in the right flank with human liver cancer cell line HepG2. A total of 32 male mice bearing subcutaneous hepatic carcinoma (7-10mm in diameter) were randomized into 4 groups. Each group of mice were administered percutaneous intratumoral injection of different agents as follows: salin, thermosensitive hydrogel,ricin, ricin-loaded thermosensitive hydrogel. The tumor volume was totally measured 3 times by high frequency ultrasound once a week. One mouse of each group was sacrificed to perform tumor histopathological examination on 7th day, 14th day, respectively, and survival time of the remaining mice was recorded. Results After intratumoral therapy,tumor volume in ricin group was smaller than that of saline group on 7th day, 14th day and 21st day( P<0.01 ),and mice got a life-prolonging rate of 36.8%. In ricin-loaded thermosensitive hydrogel group,obvious necrosis occurred in tumors treated since 5th day, and the tumor almost regressed on 21st day. Histopathological assay showed serious necrosis with a large number of leucocyte infiltration in tumor. All the remaining mice treated with riein-loaded thermosensitive hydrogel survived at the end of experiment sans tumor recurrence. Conclusions Percutaneous intratutnoral injection of ricin-loaded thermosensitive hydrogel could completely ablate hepatic carcinoma,which may provide an effective and feasible method for tumor ablation therapy.