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Biological Chemistry Oct 2014Angiotensin-converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis, and several... (Review)
Review
Angiotensin-converting enzyme (ACE) plays an important role in blood pressure control. ACE also has effects on renal function, reproduction, hematopoiesis, and several aspects of the immune response. ACE 10/10 mice overexpress ACE in monocytic cells; macrophages from ACE 10/10 mice demonstrate increased polarization toward a proinflammatory phenotype. As a result, ACE 10/10 mice have a highly effective immune response following challenge with melanoma, bacterial infection, or Alzheimer disease. As shown in ACE 10/10 mice, enhanced monocytic function greatly contributes to the ability of the immune response to defend against a wide variety of antigenic and non-antigenic challenges.
Topics: Animals; Granulocyte Precursor Cells; Immunity, Cellular; Mice; Mice, Knockout; Peptidyl-Dipeptidase A
PubMed: 24633750
DOI: 10.1515/hsz-2013-0295 -
Life Science Alliance Jan 2021Chromosomal rearrangements of the mixed-lineage leukemia gene are the hallmark of infant acute leukemia. The granulocyte-macrophage progenitor state forms the...
Chromosomal rearrangements of the mixed-lineage leukemia gene are the hallmark of infant acute leukemia. The granulocyte-macrophage progenitor state forms the epigenetic basis for myelomonocytic leukemia stemness and transformation by MLL-type oncoproteins. Previously, it was shown that the establishment of murine myelomonocytic - transformation, but not its maintenance, depends on the transcription factor C/EBPα, suggesting an epigenetic hit-and-run mechanism of MLL-driven oncogenesis. Here, we demonstrate that compound deletion of / almost entirely abrogated the growth and survival of --transformed cells. Rare, slow-growing, and apoptosis-prone --transformed escapees were recovered from compound / deletions. The escapees were uniformly characterized by high expression of the resident gene, suggesting inferior functional compensation of C/EBPα/C/EBPβ deficiency by C/EBPε. Complementation was augmented by ectopic C/EBPβ expression and downstream activation of IGF1 that enhanced growth. gene inactivation was accomplished only in the presence of complementing C/EBPβ, but not in its absence, confirming the dependency of the / double knockouts. Our data show that -transformed myeloid cells are dependent on C/EBPs during the initiation and maintenance of transformation.
Topics: Animals; Apoptosis; CCAAT-Enhancer-Binding Protein-alpha; CCAAT-Enhancer-Binding Protein-beta; CCAAT-Enhancer-Binding Proteins; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Gene Knockout Techniques; Granulocyte Precursor Cells; HEK293 Cells; Humans; Leukemia, Myeloid, Acute; Mice; Myeloid-Lymphoid Leukemia Protein; Oncogene Proteins, Fusion; Signal Transduction; Transfection
PubMed: 33144337
DOI: 10.26508/lsa.202000709 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Apr 2016To investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics...
OBJECTIVE
To investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics and significance.
METHODS
The immunophenotypes of leukemia cells in 43 patients with APL were analyzed by means of 4 color immunophenotypes; the cell population in which CD45 strength localized at 10(2) and the SSC strength locatized at 10(2) was defined as R3, the cell population in which CD45 strength localized at 10(3) and the SSC strength localized at 10(2) was defined as R5, moreover the ratio of positive cells >80% was defined as strong positive expression, the ratio of positive cells between 20%-80% was difined as weak positive expression, the ratio of positive cells <20% was difined as negative by gating method of CD45/SSC.
RESULTS
There was a abnormal cell population (R3) in 79.07% cases; the immunophenotypes of R3 was cheracteried by high SSC, weaker expression of CD45, the rate of CD38, CD9 and CD13 all was 100%, moreover their bright expression (>80%) was 86.05%, 90.70% and 86.05%, respectively; the positive expression rate of CD33, CD117 and CD64 was 97.67%, 95.35% and 83.80% respectively, moreover thier bright expression was 84.04%, 69.77% and 30.23% respectively; the CD15 was weakly expressed in 39.53% cases, the CD34 and HLA-DR were weakly expression in 16.28% and 6.98% cases respectively. All the cases did not express CD116. There were 2 cell populations (R3 and R5) in 20.93% cases, the immunophenotypic features of R3 were cosistant with above mentioning, while the immunophenotypes of R5 were lower than those of R3 SSC; the fluorescence intensity of CD45 was higher, but lower than that in normal lymphycytes, the positive rate of CD9, CD13, MPO was 100%, moreover thier fluorescence intensity was high; they did not expressed CD123, CD25, CD22, CD4, CD64 and CD14. Thereby it can be concluded that the typical immunophenotypes is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-) in APL. There was a special immunophenotype in the APL with basophilic granules. Conclusoin: APL has a characteristic immunophenotypic profile, whose typical immunophenotype is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-). The special immunophenotype exists in the APL with basophilic granules. Flow cytometric immunophenotyping may be a useful for rapid recognition of APL and has significant for prognosis.
Topics: Antigens, CD; Cell Count; Flow Cytometry; Granulocyte Precursor Cells; HLA-DR Antigens; Humans; Immunophenotyping; Leukemia, Promyelocytic, Acute; Leukocyte Common Antigens; Prognosis
PubMed: 27150985
DOI: 10.7534/j.issn.1009-2137.2016.02.003 -
Development (Cambridge, England) Sep 2021Neutrophils are the most abundant vertebrate leukocytes and they are essential to host defense. Despite extensive investigation, the molecular network controlling...
Neutrophils are the most abundant vertebrate leukocytes and they are essential to host defense. Despite extensive investigation, the molecular network controlling neutrophil differentiation remains incompletely understood. GFI1 is associated with several myeloid disorders, but its role and the role of its co-regulators in granulopoiesis and pathogenesis are far from clear. Here, we demonstrate that zebrafish gfi1aa deficiency induces excessive neutrophil progenitor proliferation, accumulation of immature neutrophils from the embryonic stage, and some phenotypes similar to myelodysplasia syndrome in adulthood. Both genetic and epigenetic analyses demonstrate that immature neutrophil accumulation in gfi1aa-deficient mutants is due to upregulation of cebpa transcription. Increased transcription was associated with Lsd1-altered H3K4 methylation of the cebpa regulatory region. Taken together, our results demonstrate that Gfi1aa, Lsd1 and cebpa form a regulatory network that controls neutrophil development, providing a disease progression-traceable model for myelodysplasia syndrome. Use of this model could provide new insights into the molecular mechanisms underlying GFI1-related myeloid disorders as well as a means by which to develop targeted therapeutic approaches for treatment.
Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cell Proliferation; DNA-Binding Proteins; Embryo, Nonmammalian; Epigenesis, Genetic; Granulocyte Precursor Cells; Hematopoiesis; Histone Demethylases; Neutrophils; Zebrafish; Zebrafish Proteins
PubMed: 34373913
DOI: 10.1242/dev.199516 -
Blood Mar 2021
Topics: Blood Cell Count; Child; Erythrocytes; Female; Granulocyte Precursor Cells; Humans; Leukemia, Myeloid, Acute
PubMed: 33734334
DOI: 10.1182/blood.2020009744 -
Natural Product Research Jul 2022Two novel cytochalasans, armochaetoglasin J () and armochaetoglasin K (), along with 14 known analogues (-) were isolated from Their structures were elucidated by...
Two novel cytochalasans, armochaetoglasin J () and armochaetoglasin K (), along with 14 known analogues (-) were isolated from Their structures were elucidated by HRESIMS, NMR spectroscopy, single-crystal X-ray crystallography, and ECD spectra. Armochaetoglasins J and K were found to be inactive against the HepG2, HT-29, K562, HL-60, and A549 cancer cell lines.
Topics: Chaetomium; Crystallography, X-Ray; Cytochalasins; HL-60 Cells; Humans
PubMed: 33487054
DOI: 10.1080/14786419.2021.1872568 -
The American Journal of Emergency... Jul 2015Although an elevated white blood cell count is a widely utilized measure for evidence of infection and an important criterion for evaluation of systemic inflammatory...
BACKGROUND
Although an elevated white blood cell count is a widely utilized measure for evidence of infection and an important criterion for evaluation of systemic inflammatory response syndrome, its component band count occupies a more contested position within clinical emergency medicine. Recent studies indicate that bandemia is highly predictive of a serious infection, suggesting that clinicians who do not appreciate the value of band counts may delay diagnosis or overlook severe infections.
OBJECTIVES
Whereas previous studies focused on determining the quantitative value of the band count (ie, determining sensitivity, threshold for bandemia, etc.), this study directs attention to patient-centered outcomes, hypothesizing that the degree of bandemia predisposes patients to subsequent negative clinical outcomes associated with underappreciated severe infections.
METHODS
This retrospective study of electronic medical records includes patients who initially presented to the emergency department (ED) with bandemia and were subsequently discharged from the ED. These patients were screened for repeat ED visits within 7 days and death within 30 days.
RESULTS
In patients with severe bandemia who were discharged from the ED, there was a 20.9% revisit rate at 7 days and a 4.9% mortality rate at 30 days, placing severely bandemic patients at 5 times significantly greater mortality compared to nonbandemic patients (P = .032).
CONCLUSION
Our review of patient outcomes suggests that the degree of bandemia, especially in the setting of concurrent tachycardia or fever, is associated with greater likelihood of negative clinical outcomes.
Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Emergency Service, Hospital; Female; Fever; Granulocyte Precursor Cells; Granulocytes; Humans; Leukocyte Count; Leukocytosis; Male; Middle Aged; Mortality; Patient Outcome Assessment; Patient Readmission; Prognosis; Retrospective Studies; Severity of Illness Index; Tachycardia
PubMed: 25937377
DOI: 10.1016/j.ajem.2015.03.035 -
Journal of Immunology (Baltimore, Md. :... Sep 2015The production of mature eosinophils (Eos) is a tightly orchestrated process with the aim to sustain normal Eos levels in tissues while also maintaining low numbers of...
The production of mature eosinophils (Eos) is a tightly orchestrated process with the aim to sustain normal Eos levels in tissues while also maintaining low numbers of these complex and sensitive cells in the blood. To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including Eos-lineage commitment and lineage maturation. Our analyses revealed a markedly greater number of transcriptome alterations associated with Eos maturation (1199 genes) than with Eos-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Eos-lineage-committed progenitors (EoPs) were noted to express high levels of granule proteins and contain granules with an ultrastructure distinct from that of mature resting Eos. Our analyses also delineated a 976-gene Eos-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with Eos. EoPs and Eos, but not granulocyte-monocyte progenitors or neutrophils, expressed Helios and Aiolos, members of the Ikaros family of transcription factors, which regulate gene expression via modulation of chromatin structure and DNA accessibility. Epigenetic studies revealed a distinct distribution of active chromatin marks between genes induced with lineage commitment and genes induced with cell maturation during Eos development. In addition, Aiolos and Helios binding sites were significantly enriched in genes expressed by EoPs and Eos with active chromatin, highlighting a potential novel role for Helios and Aiolos in regulating gene expression during Eos development.
Topics: Animals; Binding Sites; Cell Lineage; Cells, Cultured; Chromatin; Cytoplasmic Granules; DNA-Binding Proteins; Eosinophils; Gene Expression Regulation; Granulocyte Precursor Cells; Hematopoiesis; Ikaros Transcription Factor; Mice; Mice, Inbred BALB C; Trans-Activators; Transcription Factors; Transcriptome
PubMed: 26268651
DOI: 10.4049/jimmunol.1500510 -
Phytochemistry Jan 2022Under OSMAC strategy, seven unreported multioxidized aromatic polyketides, penicanesins A‒G, were discovered from a soil-derived fungus Penicillium canescens along...
Under OSMAC strategy, seven unreported multioxidized aromatic polyketides, penicanesins A‒G, were discovered from a soil-derived fungus Penicillium canescens along with seven known compounds. Their structures were assigned by extensive 1D and 2D NMR spectra in combination with HRESIMS and single crystal X-ray diffraction. Absolute stereochemistry of penicanesins A and D were elucidated by theoretical ECD calculation. (±)-Penicanesins A and B are two pairs of racemic aromatic polyketides with an unusual 6/6/6/6 heterotetracyclic ring core. In bioassay, (-)-penicanesin A shows potential cytotoxicity against human cancer cell lines HL-60 and SW480 with IC values at 13.8 ± 0.6 and 12.5 ± 0.9 μM, respectively, whereas the enantiomer (+)-penicanesin A is less active.
Topics: HL-60 Cells; Humans; Molecular Structure; Penicillium; Polyketides; Soil
PubMed: 34773753
DOI: 10.1016/j.phytochem.2021.113012 -
Chemico-biological Interactions Sep 2022β-lapachone is a 1,2-naphthoquinone of great therapeutic interest that induces cell death by autophagy and apoptosis in tumor cells due to oxidative stress increasing....
β-lapachone is a 1,2-naphthoquinone of great therapeutic interest that induces cell death by autophagy and apoptosis in tumor cells due to oxidative stress increasing. However, its high toxicity in healthy tissues limits its clinical use, which stimulates the planning and synthesis of more selective analogs. The aim of this study was to investigate the cytotoxic activity of three thiosemicarbazones derived from β-lapachone (BV2, BV3 and BV5) in leukemia cells. Cytotoxicity tests were performed on tumor cells (HL-60, K562, K562-Lucena and MOLT-4) and normal peripheral blood mononuclear cells (PBMCs). Subsequently, the mode of action of compounds was accessed by optical microscopy, transmission electron microscopy or fluorescence microscopy. Flow cytometry analysis was performed to investigate apoptosis induction, cell cycle, DNA fragmentation and mitochondrial depolarization. All derivatives inhibited tumor cell growth after 72 h (IC < 10 μM to all cell lines, including the resistant K562-Lucena) with less toxic effects in PBMC cells, being BV3 the most selective compound with selective index (SI) of 275 for HL-60; SI of 40 to K562; SI of 10 for MOLT-4 and SI of 50 to K562-Lucena compared to β-lapachone with SI of 18 to HL-60, SI of 3.7 to K562; SI of 2.4 to MOLT-4 and SI of 0.9 to K562-Lucena. In addition, the K562 or MOLT-4 cells treated with BV3 showed characteristics of both apoptosis and autophagy cell death, mainly by autophagy. These results demonstrate the potent cytotoxic effect of thiosemicarbazones derived from β-lapachone as promising anticancer drugs candidates, encouraging the continuity of in vivo tests.
Topics: Antineoplastic Agents; Apoptosis; HL-60 Cells; Humans; Leukocytes, Mononuclear; Naphthoquinones; Thiosemicarbazones
PubMed: 35934135
DOI: 10.1016/j.cbi.2022.110057