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Molecules (Basel, Switzerland) May 2023The secondary metabolites produced by Romagn., a mushroom species belonging to the large genus (Basidiomycota, Tricholomataceae), are unknown. Therefore, encouraged by...
The secondary metabolites produced by Romagn., a mushroom species belonging to the large genus (Basidiomycota, Tricholomataceae), are unknown. Therefore, encouraged by the interesting results obtained in our previous chemical analyses of a few species collected in Italian woods, we aimed to investigate the secondary metabolites of . The chemical analysis involved the isolation and characterization of secondary metabolites through an extensive chromatographic study. The structures of isolated metabolites, including the absolute configuration, were established based on a detailed analysis of MS, NMR spectroscopic, optical rotation, and circular dicroism data, and on comparison with those of related compounds reported in the literature. Two novel lanostane triterpenoids, named tricholidic acids B and C, together with triglycerides, a mixture of free fatty acids, five unidentified metabolites, and the known rare saponaceolides F and J, tricholidic acid, and tricholomenyn C, were isolated from an EtOAc extract of fruiting bodies of that were collected in an Italian beech wood. This is the second example of isolation of tricholidic acid derivatives from a natural source. Saponaceolides F and J exhibited high cytotoxicity (IC values ≤ 10 μM) against a panel of five human cancer cell lines. The toxicity against myeloid leukemia (HL-60), lung cancer (A-549), hepatocellular cancer (HepG2), renal cancer (Caki-1), and breast cancer (MCF-7) cells was higher than that shown by the very well-known cytotoxic drug cisplatin.
Topics: Humans; Triterpenes; Fagus; Molecular Structure; Wood; Tricholoma; HL-60 Cells; Fruiting Bodies, Fungal
PubMed: 37175274
DOI: 10.3390/molecules28093864 -
Journal of Postgraduate Medicine 2021Acute pancreatitis (AP) may vary in severity, from mild, self-limiting pancreatic inflammation to rapidly progressive life-threatening clinical course. If the severity...
BACKGROUND
Acute pancreatitis (AP) may vary in severity, from mild, self-limiting pancreatic inflammation to rapidly progressive life-threatening clinical course. If the severity of AP can be predicted early and treated quickly, it may lead to a decrease in morbidity and mortality rates. There?fore, we aimed to investigate the clinical utility of immature granulocyte count (IGC) and IGC percentage (IG%) in showing the severity of AP in this study.
METHODS
Two hundred and twenty-seven patients who were admitted to our emergency department and diagnosed with AP between March 1 and September 30, 2019, were included in the study. The patients were divided into two groups as mild and severe AP (MAP and SAP) according to the severity of the disease. Demographic characteristics of the patients, disease etiology, disease severity, and inflammation markers [white blood cell count (WBC), IGC, IG%, neutrophil-lymphocyte ratio (NLR), and C-reactive protein (CRP)] were recorded. Differences between the groups were statistically analyzed.
RESULTS
Of the patients included in the study, 183 (80.7%) were in the MAP group and 44 (19.3%) were in the SAP group. The mean WBC, NLR, CRP, IGC, and IG% levels were significantly higher in the SAP group compared to the MAP group. The power of IGC and IG% in predicting SAP was higher than other inflammation markers (WBC, NLR, and CRP) [(AUC for IGC: 0.902; sensitivity: 78.2%; specificity: 92.8%); (AUC for IG%: 0.843; sensitivity: 72.7%; specificity: 84.6%)].
CONCLUSION
IGC and IG% show the severity of AP more effectively than WBC, NLR, and CRP, which are traditional inflammation markers.
Topics: Acute Disease; Adult; Aged; Biomarkers; C-Reactive Protein; Emergency Service, Hospital; Female; Granulocyte Precursor Cells; Granulocytes; Humans; Inflammation; Male; Middle Aged; Pancreatitis; Predictive Value of Tests; Retrospective Studies; Severity of Illness Index
PubMed: 33533745
DOI: 10.4103/jpgm.JPGM_784_20 -
Experimental Hematology Apr 2007Interleukin (IL)-31 is a recently discovered helical cytokine. Its receptor consists of a ligand-specific IL-31 receptor (IL-31R) subunit and a receptor chain that is... (Comparative Study)
Comparative Study
OBJECTIVE
Interleukin (IL)-31 is a recently discovered helical cytokine. Its receptor consists of a ligand-specific IL-31 receptor (IL-31R) subunit and a receptor chain that is shared with Oncostatin M (OSM), called OSM-Rbeta. Because OSM-Rbeta-deficient animals have reduced hematopoietic progenitor cells (HPC) and OSM has effects on and is involved in homeostasis of HPC, we studied whether IL-31 and IL-31R play a role in hematopoiesis.
MATERIALS AND METHODS
IL-31R(-/-) mice and their littermate wild-type (WT) controls were assessed for absolute numbers and cycling status of bone marrow and spleen HPC (colony-forming unit granulocyte macrophage [CFU-GM], burst-forming unit erythroid [BFU-E], colony-forming unit granulocyte, erythrocyte, macrophage, megakaryocyte). Recombinant IL-31 was evaluated for stimulation, enhancement, or inhibition of colony formation by HPC, and for survival-enhancing effects on HPC subjected to growth-factor withdrawal and delayed addition of grown factors. Hematopoietic stem cells (HSC) from WT and IL-31R(-/-) mice were compared for competitive repopulating capacity in lethally irradiated congenic mice.
RESULTS
IL-31R(-/-) mice demonstrated significantly decreased absolute numbers and cycling status of immature subsets of HPC in bone marrow bone and spleen compared to WT mice. There were no significant differences in absolute numbers of more mature subsets of WT and IL-31R(-/-) bone marrow CFU-GM. WT but not IL-31R(-/-) bone marrow CFU-GM responded to synergistic stimulation by combinations of cytokines. While IL-31 had neither colony-stimulating, -enhancing, or -inhibiting activity for bone marrow HPC, it did enhance survival of these HPC in the context of delayed addition of growth factors. No significant differences were detected in competitive repopulating HSC activity between WT and IL-31R(-/-) bone marrow cells.
CONCLUSION
IL-31R is involved in positive regulation of absolute numbers and cycling status of immature subsets of HPC in vivo. While IL-31 in vitro does not modulate proliferation of HPC, it does enhance their survival, which may contribute to effects on cycling and numbers of HPC in vivo. Under steady-state conditions, loss of IL-31R on HPC does not appear to influence the activity of competitive repopulating HSC. These results with HPC may be of future utility for manipulation of hematopoiesis in a preclinical setting.
Topics: Animals; Cell Proliferation; Cell Survival; Erythroid Precursor Cells; Granulocyte Precursor Cells; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Interleukins; Mice; Mice, Knockout; Receptors, Interleukin
PubMed: 17379091
DOI: 10.1016/j.exphem.2007.01.028 -
Blood Apr 2014Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear,...
Atypical chronic myeloid leukemia (aCML) is a rare subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN) largely defined morphologically. It is, unclear, however, whether aCML-associated features are distinctive enough to allow its separation from unclassifiable MDS/MPN (MDS/MPN-U). To study these 2 rare entities, 134 patient archives were collected from 7 large medical centers, of which 65 (49%) cases were further classified as aCML and the remaining 69 (51%) as MDS/MPN-U. Distinctively, aCML was associated with many adverse features and an inferior overall survival (12.4 vs 21.8 months, P = .004) and AML-free survival (11.2 vs 18.9 months, P = .003). The aCML defining features of leukocytosis and circulating myeloid precursors, but not dysgranulopoiesis, were independent negative predictors. Other factors, such as lactate dehydrogenase, circulating myeloblasts, platelets, and cytogenetics could further stratify MDS/MPN-U but not aCML patient risks. aCML appeared to have more mutated RAS (7/20 [35%] vs 4/29 [14%]) and less JAK2p.V617F (3/42 [7%] vs 10/52 [19%]), but was not statistically significant. Somatic CSF3R T618I (0/54) and CALR (0/30) mutations were not detected either in aCML or MDS/MPN-U. In conclusion, within MDS/MPN, the World Health Organization 2008 criteria for aCML identify a subgroup of patients with features clearly distinct from MDS/MPN-U. The MDS/MPN-U category is heterogeneous, and patient risk can be further stratified by a number of clinicopathological parameters.
Topics: Adult; Aged; Aged, 80 and over; Blood Platelets; DNA Mutational Analysis; Female; Follow-Up Studies; Granulocyte Precursor Cells; Hematologic Neoplasms; Humans; Karyotyping; L-Lactate Dehydrogenase; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Leukocytosis; Male; Middle Aged; Mutation; Myelodysplastic Syndromes; Myelodysplastic-Myeloproliferative Diseases; Prognosis; Proportional Hazards Models; Treatment Outcome
PubMed: 24627528
DOI: 10.1182/blood-2014-02-553800 -
Blood Mar 2017Controlled regulation of lineage decisions is imperative for hematopoiesis. Yet, the molecular mechanisms underlying hematopoietic lineage choices are poorly defined....
Controlled regulation of lineage decisions is imperative for hematopoiesis. Yet, the molecular mechanisms underlying hematopoietic lineage choices are poorly defined. Colony-stimulating factor 1 (CSF-1), the cytokine acting as the principal regulator of monocyte/macrophage (M) development, has been shown to be able to instruct the lineage choice of uncommitted granulocyte M (GM) progenitors toward an M fate. However, the intracellular signaling pathways involved are unknown. CSF-1 activates a multitude of signaling pathways resulting in a pleiotropic cellular response. The precise role of individual pathways within this complex and redundant signaling network is dependent on cellular context, and is not well understood. Here, we address which CSF-1-activated pathways are involved in transmitting the lineage-instructive signal in primary bone marrow-derived GM progenitors. Although its loss is compensated for by alternative signaling activation mechanisms, Src family kinase (SFK) signaling is sufficient to transmit the CSF-1 lineage instructive signal. Moreover, c-Src activity is sufficient to drive M fate, even in nonmyeloid cells.
Topics: Animals; Cell Lineage; Cells, Cultured; Granulocyte Precursor Cells; Hematopoiesis; Macrophage Colony-Stimulating Factor; Mice; Monocytes; Signal Transduction; src-Family Kinases
PubMed: 28159742
DOI: 10.1182/blood-2016-05-714329 -
Leukemia Research Dec 2020Although most acute myeloid leukemia (AML) patients achieve complete remissions, the majority still eventually relapse and die of their disease. Rare primitive leukemia...
Although most acute myeloid leukemia (AML) patients achieve complete remissions, the majority still eventually relapse and die of their disease. Rare primitive leukemia cells, so-called leukemia stem cells (LSCs), represent one potential type of resistant cell subpopulation responsible for this dissociation between response and cure. Several LSC targets have been described, but there is limited evidence about their relative utility or that targeting any can prevent relapse. LSCs not only appear to be biologically heterogeneous, but the classic immunocompromised mouse transplantation model also has serious shortcomings as an LSC assay. Out data suggest that the most immature cell phenotype that can be identified within a patient's leukemia may be clinically relevant and represent the de facto LSC. Moreover, although phenotypically heterogeneous, these putative LSCs show consistent phenotypes within individual genetically defined groups. Using this LSC definition, we studied several previously described putative LSC targets, CD25, CD26, CD47, CD96, CD123, and CLL-1, and all were expressed across heterogeneous LSC phenotypes. In addition, with the exception of CD47, there was at most low expression of these targets on normal hematopoietic stem cells (HSCs). CD123 and CLL-1 demonstrated the greatest expression differences between putative LSCs and normal HSCs. Importantly, CD123 monoclonal antibodies were cytotoxic in vitro to putative LSCs from all AML subtypes, while showing limited to no toxicity against normal HSCs and hematopoietic progenitors. Since minimal residual disease appears to be a more homogeneous population of cells responsible for relapse, targeting CD123 in this setting may be most effective.
Topics: Animals; Antigens, CD; Antigens, Neoplasm; Antineoplastic Agents, Immunological; Cell Separation; Complement Activation; Flow Cytometry; Granulocyte Precursor Cells; Hematopoietic Stem Cells; Humans; Immunophenotyping; In Situ Hybridization, Fluorescence; Interleukin-3 Receptor alpha Subunit; Lectins, C-Type; Leukemia, Myeloid, Acute; Mice; Molecular Targeted Therapy; Neoplastic Stem Cells; Receptors, Mitogen; Xenograft Model Antitumor Assays
PubMed: 33220589
DOI: 10.1016/j.leukres.2020.106477 -
PloS One Oct 2009The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported...
The growth factor interleukin-3 (IL-3) promotes the survival and growth of multipotent hematopoietic progenitors and stimulates myelopoiesis. It has also been reported to oppose terminal granulopoiesis and to support leukemic cell growth through autocrine or paracrine mechanisms. The degree to which IL-3 acts at the posttranscriptional level is largely unknown. We have conducted global mRNA decay profiling and bioinformatic analyses in 32Dcl3 myeloblasts indicating that IL-3 caused immediate early stabilization of hundreds of transcripts in pathways relevant to myeloblast function. Stabilized transcripts were enriched for AU-Response elements (AREs), and an ARE-containing domain from the interleukin-6 (IL-6) 3'-UTR rendered a heterologous gene responsive to IL-3-mediated transcript stabilization. Many IL-3-stabilized transcripts had been associated with leukemic transformation. Deregulated Abl kinase shared with IL-3 the ability to delay turnover of transcripts involved in proliferation or differentiation blockade, relying, in part, on signaling through the Mek/Erk pathway. These findings support a model of IL-3 action through mRNA stability control and suggest that aberrant stabilization of an mRNA network linked to IL-3 contributes to leukemic cell growth.
Topics: Amino Acid Motifs; Animals; Computational Biology; Extracellular Signal-Regulated MAP Kinases; Gene Expression Regulation, Neoplastic; Granulocyte Precursor Cells; Humans; Interleukin-3; MAP Kinase Kinase 1; Mice; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins c-abl; RNA Processing, Post-Transcriptional; RNA Stability; Response Elements
PubMed: 19829692
DOI: 10.1371/journal.pone.0007469 -
Cell Death & Disease Jul 2021Mutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is...
Mutations in the transcription factor C/EBPα are found in ~10% of all acute myeloid leukaemia (AML) cases but the contribution of these mutations to leukemogenesis is incompletely understood. We here use a mouse model of granulocyte progenitors expressing conditionally active HoxB8 to assess the cell biological and molecular activity of C/EBPα-mutations associated with human AML. Both N-terminal truncation and C-terminal AML-associated mutations of C/EBPα substantially altered differentiation of progenitors into mature neutrophils in cell culture. Closer analysis of the C/EBPα-K313-duplication showed expansion and prolonged survival of mutant C/EBPα-expressing granulocytes following adoptive transfer into mice. C/EBPα-protein containing the K313-mutation further showed strongly enhanced transcriptional activity compared with the wild-type protein at certain promoters. Analysis of differentially regulated genes in cells overexpressing C/EBPα-K313 indicates a strong correlation with genes regulated by C/EBPα. Analysis of transcription factor enrichment in the differentially regulated genes indicated a strong reliance of SPI1/PU.1, suggesting that despite reduced DNA binding, C/EBPα-K313 is active in regulating target gene expression and acts largely through a network of other transcription factors. Strikingly, the K313 mutation caused strongly elevated expression of C/EBPα-protein, which could also be seen in primary K313 mutated AML blasts, explaining the enhanced C/EBPα activity in K313-expressing cells.
Topics: Animals; CCAAT-Enhancer-Binding Proteins; Cell Differentiation; Cells, Cultured; Female; Gene Expression Regulation, Leukemic; Granulocyte Precursor Cells; Homeodomain Proteins; Leukemia, Monocytic, Acute; Mice, Inbred C57BL; Mutation; Neutrophils; Up-Regulation; Mice
PubMed: 34226527
DOI: 10.1038/s41419-021-03948-6 -
American Journal of Hematology Jul 2008Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage...
Graft rejection after hematopoietic cell transplantation (HCT) with nonmyeloablative conditioning is a rare but serious clinical problem. Graft rejection and salvage therapy in eight patients in a retrospective analysis of 124 consecutive patients is reported. The patients were conditioned with low-dose fludarabine and total body irradiation (TBI). The association of pretransplantation risk factors with rejection and the effect of chimerism and graft-versus-host disease on rejection were analyzed. Overall survival (OS) and progression free survival (PFS) were compared between patients with and without rejection. Retransplantation was performed with increased TBI conditioning for all patients, and with increased mycophenolate mofetil doses for recipients with HLA-identical sibling donors. No known pretransplantation risk factors were confirmed in this study. Rejection episodes were unevenly distributed over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5 degrees C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were retransplanted. All but one engrafted successfully, but with decreased OS and PFS. Two patients received pentostatin infusion prior to donor lymphocyte infusions in unsuccessful attempts at reversing rejection. Storage temperature and donor chimerism had a significant effect on rejection. Following rejection, patients are at greater risk of dying from infections and progression/relapse of their malignancy. Retransplantation is feasible and well tolerated after HCT with nonmyeloablative conditioning and should be performed without delay in patients with imminent and manifest graft rejection.
Topics: Chimerism; Graft Rejection; Granulocyte Precursor Cells; Hematopoietic Stem Cell Transplantation; Humans; Risk Factors; Time Factors; Transplantation Conditioning; Treatment Outcome
PubMed: 18383319
DOI: 10.1002/ajh.21168 -
The Turkish Journal of Gastroenterology... Jul 2015Helicobacter pylori (H. pylori) is a microaerophilic bacterium related with peptic ulcer and gastric cancer. Its virulence factors include cytotoxin-associated gene A...
BACKGROUND/AIMS
Helicobacter pylori (H. pylori) is a microaerophilic bacterium related with peptic ulcer and gastric cancer. Its virulence factors include cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) proteins. Cytokine release inducted by H. pylori colonization has an important role in pathogenesis of H. pylori. The severity of gastric pathologies depends on the H. pylori genotypes found in different geographical regions. We aimed to determine the relationship between different H. pylori genotypes and their effects on the cytokine release levels.
MATERIALS AND METHODS
ureC, cagA, vacAs1/s2, vacAm1/m2, and blood group antigen-binding adhesion protein A2 (babA2) virulence related genes were investigated in 21 H. pylori strains. Genotyping of 21 strains were made due to the presence of cagA, vacAs1/s2, vacAm1/m2, and babA2 genes. The H. pylori strains were cultured together with THP-1 and neutrophil-differentiated Human promyelocytic leukemia cells (HL-60) cells. The levels of cytokines interleukin (IL)-1β, IL-6, IL-8, IL-12, tumor necrosis factor-alpha (TNF-α), and IL-10 in these cells were measured after co-culturing with H. pylori strains.
RESULTS
The following five different genotypes were detected: Genotype1: cagA and vacAs1m2; Genotype2: cagA and vacAs1m1; Genotype3: cagA, vacAs1m2, and babA2; Genotype4: vacAs2m2; and Genotype5: cagA and vacAs2m2. All these genotypes significantly induced the levels of IL-1β, IL-6, IL-8, IL 10, and TNF-α in THP-1 cells. Genotype 5 caused higher amounts of IL-1β, IL-6, TNF-α, and IL-10, whereas genotype 1 induced the highest levels of IL-8. In neutrophil-differentiated HL-60 cells, genotype 4 increased IL-6 levels and genotype 3 and 4 elevated IL-8 levels significantly.
CONCLUSION
These results suggested that cytokine response of the host varies depending on the specific immune response of the host against different H. pylori strains.
Topics: Adhesins, Bacterial; Adult; Aged; Antigens, Bacterial; Bacterial Proteins; Cytokines; Genotype; HL-60 Cells; Helicobacter pylori; Humans; Middle Aged; Monocytes; Virulence Factors
PubMed: 26039002
DOI: 10.5152/tjg.2015.8058