1.Nuclear-cytoplasmic interaction QTL mapping of the lipoprotein and cholesterol traits in mice
Ye WANG ; Fangnan WU ; Yiting ZHOU ; Xiufeng JU ; Zaixiang TANG
Chinese Journal of Comparative Medicine 2014;(10):43-47,66
Objective To study the cholesterol nuclear-cytoplasmic interaction effect and position cholesterol traits QTL in mice.Methods Improving the nuclear-cytoplasmic interaction models and methods that have been constructed, and analyzing the public database of total cholesterol and lipoprotein data of F2 group that derived from DBA/2J ( D2) and CAST/EiJ ( CAST) mice.Results Six QTL that controlling total cholesterol, HDL and nonHDL were located in 4 linkage groups in the genome.In the models constructed in this study, we found a QTL has significant interaction with cytoplasmic background, which changes the previous results of data analysis, the genetic mouse cholesterol and lipoprotein components opened up new ideas.Conclusion Mouse cholesterol trait is the result of interaction of nuclear genes and cytoplasmic background.
2.Effects of HLA disparity of two umbilical cord blood units on human engraftment in SCID mice.
Liping ZHANG ; Baijun SHEN ; Huaishui HOU ; Wenying YAN ; Yunpeng DAI ; Qing SHI ; Xiufeng MA ; Xiuli JU ; Xingxia LIU
Chinese Journal of Hematology 2002;23(12):624-627
OBJECTIVETo evaluate the feasibility and characteristics of human engraftment in HLA disparate cord blood transplantation.
METHODSTwo human HLA-haploidentical or HLA-mismatched cord blood units were transplanted into sublethally irradiated severe combined immunodeficiency (SCID) mice. The characteristics of engraftment, hematopoietic and immunological reconstitution between the two groups were compared.
RESULTSTwo mixed cord blood units can engraft in SCID mice with donor-recipient chimerism and reconstitute hematopoiesis and immunological functions. No unfavorable factors had been observed. Only one of the two cord blood units which had higher colony forming ability in vitro could engraft in most SCID mice as shown by HLA-DQB(1) gene detection. Two HLA-haploidentical cord blood units were simultaneously engrafted in 3 SCID mice.
CONCLUSIONDouble HLA-haploidentical or HLA-mismatched cord blood can engraft in SCID mice and reconstitute hematopoietic and immunological functions. HLA disparity has no significant effect on survival and engrafting rate. However, in less HLA disparity group, two cord blood units were prone to engraft simultaneously.
Animals ; Antigens, CD ; immunology ; Cord Blood Stem Cell Transplantation ; methods ; Disease Models, Animal ; Female ; Fetal Blood ; immunology ; metabolism ; Flow Cytometry ; HLA Antigens ; genetics ; immunology ; Hematopoiesis ; Humans ; Mice ; Mice, SCID ; Random Allocation ; Severe Combined Immunodeficiency ; immunology ; physiopathology ; surgery ; Survival Analysis ; Transplantation, Heterologous
3.Escape from abluminal LRP1-mediated clearance for boosted nanoparticle brain delivery and brain metastasis treatment.
Naveed Ullah KHAN ; Jiang NI ; Xiufeng JU ; Tongtong MIAO ; Haiyan CHEN ; Liang HAN
Acta Pharmaceutica Sinica B 2021;11(5):1341-1354
Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.