Biomedical subjects

Li Chai

Publications and source records attributed to Li Chai.

8 recordsLinked to original sources

PubMed2006

Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia.

SALL4, a newly identified zinc-finger transcriptional factor important for embryonic development, is mapped to chromosome 20q13. Previously, we reported that SALL4 was constitutively expressed in acute myeloid leukemia and SALL4 transgenic mice developed acute myeloid leukemia. In this study, we aimed to survey SALL4 protein expression in benign and neoplastic hematopoietic tissues in addition to acute myeloid leukemia using immunostaining with a polyclonal anti-SALL4 antibody. Primary hematological tumors (178) and 15 benign hematopoietic tissues were examined. Reverse transcription-polymerase chain reaction was also performed to detect SALL4 mRNA expression on eight precursor B-cell lymphoblastic leukemia/lymphomas, 10 benign hematopoietic tissues, and seven hematopoietic cancer cell lines. Of the benign tissues, SALL4 expression was detectable only in CD34+ hematopoietic stem/progenitor cells (2/2 at protein level, 3/3 at RNA level). In neoplastic tissues, only precursor B-cell lymphoblastic leukemia/lymphomas had detectable SALL4 (12/16 at protein level, 7/8 at RNA level), similar to that observed in acute myeloid leukemia. Of the seven cell lines examined, only those derived from acute myeloid leukemia and precursor B-cell lymphoblastic leukemia/lymphomas were positive. To conclude, SALL4 expression is normally restricted to CD34+ hematopoietic stem/progenitor cells. The persistence of SALL4 expression in leukemic blasts in precursor B-cell lymphoblastic leukemia/lymphomas resembles to what we observed in acute myeloid leukemia, and correlates with the maturation arrest of these cells. We have shown in our previous study that the constitutive expression of SALL4 in mice can lead to acute myeloid leukemia development. The similar expression pattern of SALL4 in acute myeloid leukemia and B-cell lymphoblastic leukemia/lymphomas suggests that these two disease entities may share similar biological features and/or mechanisms of leukemogenesis. More definite studies to investigate the role of SALL4 in the pathogenesis of B-cell lymphoblastic leukemia/lymphomas are needed in the future to address this question.

Antigens, CD34↗

PubMed2006

Sall4 modulates embryonic stem cell pluripotency and early embryonic development by the transcriptional regulation of Pou5f1.

Embryonic stem (ES) cells are pluripotent cells that can self-renew or differentiate into many cell types. A unique network of transcription factors and signalling molecules are essential for maintaining this capability. Here, we report that a spalt family member, Sall4, is required for the pluripotency of ES cells. Similarly to Oct4, a reduction in Sall4 levels in mouse ES cells results in respecification, under the appropriate culture conditions, of ES cells to the trophoblast lineage. Sall4 regulates transcription of Pou5f1 which encodes Oct4. Sall4 binds to the highly conserved regulatory region of the Pou5f1 distal enhancer and activates Pou5f1 expression in vivo and in vitro. Microinjection of Sall4 small interfering (si) RNA into mouse zygotes resulted in reduction of Sall4 and Oct4 mRNAs in preimplantation embryos and significant expansion of Cdx2 expression into the inner cell mass. These results demonstrate that Sall4 is a transcriptional activator of Pou5f1 and has a critical role in the maintenance of ES cell pluripotency by modulating Oct4 expression. The data also indicates that Sall4 is important for early embryonic cell-fate decisions.

Animals↗

PubMed2006

SALL4, a novel oncogene, is constitutively expressed in human acute myeloid leukemia (AML) and induces AML in transgenic mice.

SALL4, a human homolog to Drosophila spalt, is a novel zinc finger transcriptional factor essential for development. We cloned SALL4 and its isoforms (SALL4A and SALL4B). Through immunohistochemistry and real-time reverse-transcription-polymerase chain reaction (RT-PCR), we demonstrated that SALL4 was constitutively expressed in human primary acute myeloid leukemia (AML, n = 81), and directly tested the leukemogenic potential of constitutive expression of SALL4 in a murine model. SALL4B transgenic mice developed myelodysplastic syndrome (MDS)-like features and subsequently AML that was transplantable. Increased apoptosis associated with dysmyelopoiesis was evident in transgenic mouse marrow and colony-formation (CFU) assays. Both isoforms could bind to beta-catenin and synergistically enhanced the Wnt/beta-catenin signaling pathway. Our data suggest that the constitutive expression of SALL4 causes MDS/AML, most likely through the Wnt/beta-catenin pathway. Our murine model provides a useful platform to study human MDS/AML transformation, as well as the Wnt/beta-catenin pathway's role in the pathogenesis of leukemia stem cells.

Alternative Splicing↗

PubMed2006

Transcriptional activation of the SALL1 by the human SIX1 homeodomain during kidney development.

SALL1 is a member of the SAL gene family that encodes a group of putative developmental transcription factors. SALL1 plays a critical role during kidney development as mutations of the human SALL1 gene cause Townes-Brocks syndrome, which is associated with kidney malformation. Deletion of the mouse Sall1 gene results in renal agenesis or severe dysgenesis. To date, little is known about the molecular mechanisms controlling the regulation of SALL1 expression. This report describes the cloning and characterization of the human SALL1 gene promoter. Consensus binding sites were identified for several transcription factors, with multiple sites for WT1 and SIX1. In transient transfection assays, SALL1 promoter activity was higher in HEK-293 human kidney cells and COS-7 monkey kidney cells than in NIH-3T3 fibroblasts, consistent with its role in kidney development. Transcription from the SALL1 promoter was strikingly activated by the SIX1 protein. Utilizing a luciferase reporter gene assay, endogenous or exogenously added SIX1 activated the SALL1 promoter. Overexpression of SIX1 induced a significant increase in the endogenous SIX1 protein. In addition, co-expression of SIX1 and Eya1 resulted in a significant increase in the SALL1 promoter activity when compared with either SIX1 or Eya1 alone. Finally, we demonstrate that SIX1 was able to bind to the SALL1 promoter by retardation assays and that deletion of the putative element of SIX1 significantly diminishes the SALL1 promoter activity response to SIX1 stimulation. Our findings, when taken together, indicate that SALL1 is a likely target gene for SIX1 during kidney development.

Animals↗

PubMed2003

Plasticity of marrow-derived stem cells.

Bone marrow (BM) contains hematopoietic stem cells (HSCs), which differentiate into every type of mature blood cell; endothelial cell progenitors; and marrow stromal cells, also called mesenchymal stem cells (MSCs), which can differentiate into mature cells of multiple mesenchymal tissues including fat, bone, and cartilage. Recent findings indicate that adult BM also contains cells that can differentiate into additional mature, nonhematopoietic cells of multiple tissues including epithelial cells of the liver, kidney, lung, skin, gastrointestinal (GI) tract, and myocytes of heart and skeletal muscle. Experimental results obtained in vitro and in vivo are the subject of this review. The emphasis is on how these experiments were performed and under what conditions differentiation from bone marrow to epithelial and neural cells occurs. Questions arise regarding whether tissue injury is necessary for this differentiation and the mechanisms by which it occurs. We also consider which bone marrow subpopulations are capable of this differentiation. Only after we have a better understanding of the mechanisms involved and of the cells required for this differentiation will we be able to fully harness adult stem cell plasticity for clinical purposes.

Animals↗

PubMed2003

Prediction and analysis of human thoracic impact responses and injuries in cadaver impacts using a full human body finite element model.

Human thoracic dynamic responses and injuries associated with frontal impact, side impact, and belt loading were investigated and predicted using a complete human body finite element model for an average adult male. The human body model was developed to study the impact biomechanics of a vehicular occupant. Its geometry was based on the Visible Human Project (National Library of Medicine) and the topographies from human body anatomical texts. The data was then scaled to an average adult male according to available biomechanical data from the literature. The model includes details of the head, neck, ribcage, abdomen, thoracic and lumbar spine, internal organs of the chest and abdomen, pelvis, and the upper and lower extremities. The present study is focused on the dynamic response and injuries of the thorax. The model was validated at various impact speeds by comparing predicted responses with available experimental cadaver data in frontal and side pendulum impacts, as well as belt loading. Model responses were compared with similar individual cadaver tests instead of using cadaver corridors because the large differences between the upper and lower bounds of the corridors may confound the model validation. The validated model was then used to study thorax dynamic responses and injuries in various simulated impact conditions. Parameters that could induce injuries such as force, deflection, and stress were computed from model simulations and were compared with previously proposed thoracic injury criteria to assess injury potential for the thorax. It has been shown that the model exhibited speed sensitive impact characteristics, and the compressibility of the internal organs significantly influenced the overall impact response in the simulated impact conditions. This study demonstrates that the development of a validated FE human body model could be useful for injury assessment in various cadaveric impacts reported in the literature. Internal organ injuries, which are difficult to detect in experimental studies with human cadavers, can be more easily identified with a validated finite element model through stress-strain analysis, especially in conjunction with experimental studies.

Journal Article↗

PubMed2003

[Tracheoesophageal shunt for voice reconstruction after total laryngectomy to prevent from deglutition disorders].

OBJECTIVE: To observe the effect of tracheoesophageal shunt on voice reconstruction after total laryngectomy. METHODS: Seventy-nine patients with laryngeal cancer of T3 and T4 stages were conducted an operation of tracheoesophageal shunt after total laryngectomy. The vertical voiced slit with a length of 0.8-0.12 cm was made between the posterior wall of trachea and the frontal wall of esophagus, while the cricoid cartilage flap with the length of 2.0 cm and width of 1.2 cm was reserved to form cartilage mucosa flap as an edge to prevent deglutition disorders. Finally, membranous part of trachea was sutured together with the neck skin as an inclination edge. RESULTS: In this series, 71 of 79 patients kept good voice function, and 65 of 71 patients avoided deglutition disorders, but other patients failed to do so. The 3-year survival rate was 66.7% (14/21, for stage T3) and 64.9% (24/37, for stage T4), respectively. The 5-year survival rate was 6/10 (for stage T3) and 50.0% (10/20, for stage T4), respectively. CONCLUSION: The operation of tracheoesophageal shunt is advantageous to prevent deglutition disorders as well as to restore the voice function of larynx.

Adult↗

PubMed2002

Effects of different compounding of formulae on content of gardenoside in Yin Chen Hao decoction.

In order to observe the effects of the ground and intact Zhi Zi (Fructus Gardeniae) and different combinations of the ingredients and refined single Chinese drug granules in Yin Chen Hao Decoction compound prescription on the contents of gardenoside (an effective component of the prescription), the contents of gardenoside were determined with reversed phase high performance liquid chromatography (HPLC), with acetonitrile-water (15:85) as mobile phase, at wave length 238 nm. The results indicated that the gardenoside-decocted-out rates in the decoctions prepared by different combinations of the ingredients with the ground Zhi Zi (Fructus Gardeniae) all were higher significantly than those in the decoction with intact Zhi Zi (Fructus Gardeniae), and generally, different combinations of the ingredients in the decoction had only little effect on the gardenoside-decocted-out rate.

Chromatography, High Pressure Liquid↗