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Nutrients Jul 2023Unripe (uRO) contains various natural polyphenols with beneficial physiological activities and is particularly rich in ellagic acid (EA). EA has ameliorated type 2...
Unripe (uRO) contains various natural polyphenols with beneficial physiological activities and is particularly rich in ellagic acid (EA). EA has ameliorated type 2 inflammation and airway hyperresponsiveness in animal models of eosinophilic asthma. EA is metabolized by the gut microbiota to urolithin A (UA), which exhibits anti-inflammatory properties. However, it remains unclear whether uRO, EA, and UA reduce inflammatory responses and oxidative stress in respiratory epithelial cells and neutrophils. In this study, inflammation was induced in A549 (human lung epithelial cells) and dHL-60 cells (neutrophil-like cells differentiated from human promyelocytic leukemia HL-60 cells) and treated with various concentrations of water extract of uRO (uRO-w), EA, and UA. EA, uRO-w and UA suppressed the inflammatory cytokine and chemokine levels and reduced the expression of matrix metalloproteinase-9 in A549 cells stimulated with IL-1β. As a result of analyzing the mechanism by which these inflammatory molecules are expressed, it was found that EA, uRO-w, and UA regulated corticosteroid-sensitive mitogen activated protein kinase, nuclear factor κB, and corticosteroid-insensitive AKT. In addition, uRO-w, EA, and UA significantly reduced reactive oxygen species levels in phorbol 12-myristate 13-acetate-stimulated dHL-60 cells and inhibited neutrophil extracellular trap formation. Therefore, our results suggest that uRO-w, EA, and UA are potential therapeutic agents for preventing and treating inflammatory respiratory diseases.
Topics: Animals; Humans; HL-60 Cells; Ellagic Acid; Rubus; A549 Cells; Inflammation
PubMed: 37571300
DOI: 10.3390/nu15153364 -
Small (Weinheim An Der Bergstrasse,... May 2022The intrinsic biophysical states of neutrophils are associated with immune dysfunctions in diseases. While advanced image-based biophysical flow cytometers can probe...
The intrinsic biophysical states of neutrophils are associated with immune dysfunctions in diseases. While advanced image-based biophysical flow cytometers can probe cell deformability at high throughput, it is nontrivial to couple different sensing modalities (e.g., electrical) to measure other critical cell attributes including cell viability and membrane integrity. Herein, an "optics-free" impedance-deformability cytometer for multiparametric single cell mechanophenotyping is reported. The microfluidic platform integrates hydrodynamic cell pinching, and multifrequency impedance quantification of cell size, deformability, and membrane impedance (indicative of cell viability and activation). A newly-defined "electrical deformability index" is validated by numerical simulations, and shows strong correlations with the optical cell deformability index of HL-60 experimentally. Human neutrophils treated with various biochemical stimul are further profiled, and distinct differences in multimodal impedance signatures and UMAP analysis are observed. Overall, the integrated cytometer enables label-free cell profiling at throughput of >1000 cells min without any antibodies labeling to facilitate clinical diagnostics.
Topics: Electric Impedance; Flow Cytometry; HL-60 Cells; Humans; Microfluidic Analytical Techniques; Microfluidics; Neutrophils
PubMed: 35253966
DOI: 10.1002/smll.202104822 -
Anti-cancer Drugs Oct 2019Pegylated liposomal doxorubicin (Peg-Dox) treatment resulted in a good outcome for patients with lymphoma and multiple myeloma, with reduced cardiotoxicity and an...
Pegylated liposomal doxorubicin (Peg-Dox) treatment resulted in a good outcome for patients with lymphoma and multiple myeloma, with reduced cardiotoxicity and an improved pharmacokinetic profile when compared to those of conventional doxorubicin. However, the use of Peg-Dox in myeloid neoplasms remains poorly studied. In this study, we first tested the role of Peg-Dox in the killing of myeloid cell lines and of primary myeloid leukemia cells. Then, a Peg-Dox-based protocol was used to treat patients with myeloid neoplasms. The results showed that the Peg-Dox and Peg-Dox-based protocols had a similar killing ability in myeloid cell lines and in primary myeloid leukemia cells compared to that of conventional doxorubicin. The complete remission rate was 87.5% and 100% for patients with refractory/relapsed acute myeloid leukemia and myelodysplastic syndrome with excess blasts, respectively, after treatment with Peg-Dox. All patients developed grade 3 or 4 hematological toxicity and recovered approximately 2 weeks after completing chemotherapy. No deaths or other severe complications were reported. Our results showed that Peg-Dox can be used in the treatment of myeloid neoplasms with high rates of complete remission and with mild complications.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Child; Doxorubicin; Female; HL-60 Cells; Humans; K562 Cells; Male; Middle Aged; Multiple Myeloma; Polyethylene Glycols; Young Adult
PubMed: 31283544
DOI: 10.1097/CAD.0000000000000811 -
Journal of Natural Medicines Jun 2020Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their...
Six limonoids [kotschyienone A and B (1, 2), 7-deacetylgedunin (3), 7-deacetyl-7-oxogedunin (4), andirobin (5) and methyl angolensate (6)] were investigated for their trypanocidal and leishmanicidal activities using bloodstream forms of Trypanosoma brucei and promastigotes of Leishmania major. Whereas all compounds showed anti-trypanosomal activity, only compounds 1-4 displayed anti-leishmanial activity. The 50% growth inhibition (GI) values for the trypanocidal and leishmanicidal activity of the compounds ranged between 2.5 and 14.9 μM. Kotschyienone A (1) was found to be the most active compound with a minimal inhibition concentration (MIC) value of 10 μM and GI values between 2.5 and 2.9 μM. Only compounds 1 and 3 showed moderate cytotoxicity against HL-60 cells with MIC and GI values of 100 μM and 31.5-46.2 μM, respectively. Compound 1 was also found to show activity against intracellular amastigotes of L. major with a GI value of 1.5 μM. The results suggest that limonoids have potential as drug candidates for the development of new treatments against trypanosomiasis and leishmaniasis.
Topics: Animals; HL-60 Cells; Humans; Leishmania major; Leishmaniasis; Limonins; Microbial Sensitivity Tests; Trypanocidal Agents; Trypanosoma brucei brucei; Trypanosomiasis
PubMed: 32277328
DOI: 10.1007/s11418-020-01408-7 -
BMC Cancer Jan 2024T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is...
BACKGROUND
T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a cell surface molecule that was first discovered on T cells. However, recent studies revealed that it is also highly expressed in acute myeloid leukemia (AML) cells and it is related to AML progression. As, Glutamine appears to play a prominent role in malignant tumor progression, especially in their myeloid group, therefore, in this study we aimed to evaluate the relation between TIM-3/Galectin-9 axis and glutamine metabolism in two types of AML cell lines, HL-60 and THP-1.
METHODS
Cell lines were cultured in RPMI 1640 which supplemented with 10% FBS and 1% antibiotics. 24, 48, and 72 h after addition of recombinant Galectin-9 (Gal-9), RT-qPCR analysis, RP-HPLC and gas chromatography techniques were performed to evaluate the expression of glutaminase (GLS), glutamate dehydrogenase (GDH) enzymes, concentration of metabolites; Glutamate (Glu) and alpha-ketoglutarate (α-KG) in glutaminolysis pathway, respectively. Western blotting and MTT assay were used to detect expression of mammalian target of rapamycin complex (mTORC) as signaling factor, GLS protein and cell proliferation rate, respectively.
RESULTS
The most mRNA expression of GLS and GDH in HL-60 cells was seen at 72 h after Gal-9 treatment (p = 0.001, p = 0.0001) and in THP-1 cell line was observed at 24 h after Gal-9 addition (p = 0.001, p = 0.0001). The most mTORC and GLS protein expression in HL-60 and THP-1 cells was observed at 72 and 24 h after Gal-9 treatment (p = 0.0001), respectively. MTT assay revealed that Gal-9 could promote cell proliferation rate in both cell lines (p = 0.001). Glu concentration in HL-60 and α-KG concentration in both HL-60 (p = 0.03) and THP-1 (p = 0.0001) cell lines had a decreasing trend. But, Glu concentration had an increasing trend in THP-1 cell line (p = 0.0001).
CONCLUSION
Taken together, this study suggests TIM-3/Gal-9 interaction could promote glutamine metabolism in HL-60 and THP-1 cells and resulting in AML development.
Topics: Humans; Glutamic Acid; Glutamine; Hepatitis A Virus Cellular Receptor 2; HL-60 Cells; Leukemia, Myeloid, Acute
PubMed: 38267906
DOI: 10.1186/s12885-024-11898-3 -
PloS One 2023In myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In...
OBJECTIVES
In myelodysplastic syndromes (MDS), neoplastic myeloblast (CD34+CD13+CD33+ cells) numbers often increase over time, leading to secondary acute myeloid leukemia (AML). In recent studies, blasts in some MDS patients have been found to express a megakaryocyte-lineage molecule, CD41, and such patients show extremely poor prognosis. This is the first study to evaluate whether myeloblasts transition to CD41+ blasts over time and to investigate the detailed immunophenotypic features of CD41+ blasts in MDS.
METHODS
We performed a retrospective cohort study, in which time-dependent changes in blast immunophenotypes were analyzed using multidimensional flow cytometry (MDF) in 74 patients with MDS and AML (which progressed from MDS).
RESULTS
CD41+ blasts (at least 20% of CD34+ blasts expressing CD41) were detected in 12 patients. In five of these 12 patients, blasts were CD41+ from the first MDF analysis. In the other seven patients, myeloblasts (CD34+CD33+CD41- cells) transitioned to megakaryoblasts (CD34+CD41+ cells) over time, which was often accompanied by disease progression (including leukemic transformation). These CD41+ patients were more frequently observed among patients with monosomal and complex karyotypes. CD41+ blasts were negative for the erythroid antigen, CD235a, and positive for CD33 in all cases, but CD33 expression levels were lower in three cases when compared with CD34+CD41- blasts. Among the five CD41+ patients who underwent extensive immunophenotyping, CD41+ blasts all expressed CD61, but two cases had reduced CD42b expression, three had reduced/absent CD13 expression, and three also expressed CD7.
CONCLUSIONS
Myeloblasts become megakaryoblastic over time in some MDS patients, and examining the megakaryocyte lineage (not only as a diagnostic work-up but also as follow-up) is needed to detect CD41+ MDS. The immunophenotypic features revealed in this study may have diagnostic relevance for CD41+ MDS patients.
Topics: Humans; Granulocyte Precursor Cells; Immunophenotyping; Megakaryocyte Progenitor Cells; Retrospective Studies; Antigens, CD34; Myelodysplastic Syndromes
PubMed: 37729123
DOI: 10.1371/journal.pone.0291662 -
Journal of Natural Products Nov 2021Fifteen new labdane-type diterpenoids, sublyratins A-O (-), along with four known analogues (-) were isolated from the aerial parts of . Their structural assignments...
Fifteen new labdane-type diterpenoids, sublyratins A-O (-), along with four known analogues (-) were isolated from the aerial parts of . Their structural assignments were challenging due to the stereoisomeric features evident and were achieved by analyzing comprehensively the spectroscopic data and electronic circular dichroism spectra and using X-ray crystallographic analysis. Compounds and - displayed cytotoxic activity against the HL-60 cell line with IC values of 1.5-2.8 μM.
Topics: A549 Cells; Antineoplastic Agents, Phytogenic; Croton; Diterpenes; HL-60 Cells; Humans
PubMed: 34762434
DOI: 10.1021/acs.jnatprod.1c00804 -
Medicinal Chemistry (Shariqah (United... 2021Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also...
BACKGROUND
Natural naphthoquinones have shown diversified biological activities including antibacterial, antifungal, antimalarial, and cytotoxic activities. However, they are also compounds with acute cytotoxicity, immunotoxicity, carcinogenesis, and cardio- and hepatotoxicity, and the modification at their redox center is an interesting strategy to overcome such harmful activity.
OBJECTIVE
In this study, four novel semisynthetic hydrazones, derived from the isomers α- and β- lapachones (α and β, respectively) and coupled with the drugs hydralazine (HDZ) and isoniazid (ACIL), were prepared, evaluated by electrochemical methods and assayed for anticancer activity.
METHODS
The semisynthetic hydrazones were obtained and had their molecular structures established by NMR, IR, and MS. Anticancer activity was evaluated by cell viability determined by reduction of 3-(4,5-dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT). The electrochemical studies, mainly cyclic voltammetry, were performed, in aprotic and protic media.
RESULTS
The study showed that the compounds 2, 3, and 4 were active against at least one of the cancer cell lines evaluated, compounds 3 and 4 being the most cytotoxic. Toward HL-60 cells, compound 3 was 20x more active than β-lapachone, and 3x more cytotoxic than doxorubicin. Furthermore, 3 showed an SI value of 39.62 for HL-60 cells. Compound 4 was active against all cancer cells tested, with IC values in the range 2.90-12.40 μM. Electrochemical studies revealed a profile typical of self-protonation and reductive cleavage, dependent on the supporting electrolyte.
CONCLUSION
These results therefore indicate that compounds 3 and 4 are strong candidates as prototypes of new antineoplastic drugs.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Drug Screening Assays, Antitumor; HL-60 Cells; Humans; Hydrazones; Magnetic Resonance Spectroscopy; Molecular Structure; Naphthoquinones; Stereoisomerism; Structure-Activity Relationship
PubMed: 32807066
DOI: 10.2174/1573406416666200817164308 -
Frontiers of Medicine Aug 2021t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations...
t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34CD117 and CD34CD117) were previously identified in t(8;21) AML, and CD34CD117 cell proportion was determined as an independent factor for this disease outcome. Here, we examined the impact of CD34CD117/CD34CD117 myeloblast-associated gene expression on t(8;21) AML clinical prognosis. In this study, 85 patients with t(8;21) AML were enrolled. The mRNA expression levels of CD34CD117-associated genes (LGALS1, EMP3, and CRIP1) and CD34CD117-associated genes (TRH, PLAC8, and IGLL1) were measured using quantitative reverse transcription PCR. Associations between gene expression and clinical outcomes were determined using Cox regression models. Results showed that patients with high LGALS1, EMP3, or CRIP1 expression had significantly inferior overall survival (OS), whereas those with high TRH or PLAC8 expression showed relatively favorable prognosis. Univariate analysis revealed that CD19, CD34CD117 proportion, KIT mutation, minimal residual disease (MRD), and expression levels of LGALS1, EMP3, CRIP1, TRH and PLAC8 were associated with OS. Multivariate analysis indicated that KIT mutation, MRD and CRIP1 and TRH expression levels were independent prognostic variables for OS. Identifying the clinical relevance of CD34CD117/CD34CD117 myeloblast-associated gene expression may provide new clinically prognostic markers for t(8;21) AML.
Topics: Gene Expression; Granulocyte Precursor Cells; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Membrane Glycoproteins; Prognosis; Proteins; Proto-Oncogene Proteins c-kit
PubMed: 33754282
DOI: 10.1007/s11684-021-0836-7 -
Environmental Toxicology Mar 2024Benzene exposure inhibits the hematopoietic system and leads to the occurrence of various types of leukemia. However, the mechanism underlying the hematotoxicity of...
Benzene exposure inhibits the hematopoietic system and leads to the occurrence of various types of leukemia. However, the mechanism underlying the hematotoxicity of benzene is still largely unclear. Emerging evidence has shown that exosomes are involved in toxic mechanisms of benzene. To understand the effect of 1,4-benzoquinone (PBQ; an active metabolite of benzene in bone marrow) on the exosomal release characteristics and role of exosomal secretion in PBQ-induced cytotoxicity. Exosomes were isolated from PBQ-treated HL-60 cells, purified by ultracentrifugation, and verified by transmission electron microscopy, nanoparticle tracking analysis and the presence of specific biomarkers. Our results showed that PBQ increased exosomal secretion in a dose-dependent manner, reaching a peak in 3 h at 10 μM PBQ treatment and then slowly decreasing in HL-60 cells. The exosomes contained miRNAs, which have been reported to be associated with benzene exposure or benzene poisoning. In particular, mir-34a-3p and mir-34A-5p were enriched in exosomes derived from PBQ-treated cells. In addition, the inhibition of exosomal release by GW4869 (an inhibitor of exosomal release) exacerbated PBQ-induced cytotoxicity, including increased intracellular reactive oxygen species levels, decreased mitochondrial membrane potential, and increased the apoptosis rate. Our findings illustrated that exosomes secretion plays an important role in antagonizing PBQ-induced cytotoxicity and maintaining cell homeostasis.
Topics: Humans; Benzene; MicroRNAs; Apoptosis; HL-60 Cells; Benzoquinones
PubMed: 37818967
DOI: 10.1002/tox.23944