In silico predicted compound targeting the IQGAP1-GRD domain selectively inhibits growth of human acute myeloid leukemia.

Acute myeloid leukemia (AML) is fatal in the majority of adults. Identification of new therapeutic targets and their pharmacologic modulators are needed to improve outcomes. Previous studies had shown that immunization of rabbits with normal peripheral WBCs that had been incubated with fluorodinitrobenzene elicited high titer antibodies that bound to a spectrum of human leukemias.

Investigating ultrastructural morphology in MIRAGE syndrome-derived fibroblasts using transmission electron microscopy.

Background: Heterozygous variants in the gene cause the complex multisystem disorder, MIRAGE syndrome. Patients are characterised by myelodysplasia, infections, growth restriction, adrenal insufficiency, gonadal dysfunction and enteropathies. Pathogenic variants in SAMD9 are gain-of-function and enhance its role as a growth repressor, leading to growth restriction of many tissues.

Comparative Analysis of Single-Cell RNA Sequencing Platforms and Methods.

Single-cell RNA sequencing (scRNA-seq) offers great new opportunities for increasing our understanding of complex biological processes. In particular, development of an accurate Human Cell Atlas is largely dependent on the rapidly advancing technologies and molecular chemistries employed in scRNA-seq. These advances have already allowed an increase in throughput for scRNA-seq from 96 to 80,000 cells on a single instrument run by capturing cells within nanoliter droplets.

Alternative Materials for the Enrichment of Biogas with Methane.

Carbonaceous adsorbents have been pointed out as promising adsorbents for the recovery of methane from its mixture with carbon dioxide, including biogas. This is because of the fact that CO is more strongly adsorbed and also diffuses faster compared to methane in these materials. Therefore, the present study aimed to test alternative carbonaceous materials for the gas separation process with the purpose of enriching biogas in biomethane and to compare them with the commercial one.

Sirtuin 5 depletion impairs mitochondrial function in human proximal tubular epithelial cells.

Ischemia is a major cause of kidney damage. Proximal tubular epithelial cells (PTECs) are highly susceptible to ischemic insults that frequently cause acute kidney injury (AKI), a potentially life-threatening condition with high mortality. Accumulating evidence has identified altered mitochondrial function as a central pathologic feature of AKI.

Aortic regurgitation and left ventricle remodeling on cardiac magnetic resonance and transthoracic echocardiography.

Background: Transthoracic echocardiography (TTE) is the first imaging modality used to assess aortic regurgitation (AR). However, it is not possible to provide precise quantification in all patients.

Aim: Our aim was to compare TTE and cardiovascular magnetic resonance (CMR) measurements in grading AR and left ventricle (LV) remodeling.

LCA and economic study on the local oxygen supply in Central Europe during the COVID-19 pandemic.

Medical oxygen is the key to survival for COVID-19 patients. To meet the pandemic-driven oxygen demand spike, local hospitals began searching for a suitable medical oxygen delivery system. Among the studies published on the impact of COVID-19 on a range of aspects, including the global economy and the environment, no study has been conducted on the environmental impact of medical oxygen supply to hospitals under epidemic conditions.

A molecular and cellular analysis of human embryonic optic fissure closure related to the eye malformation coloboma.

Ocular coloboma is a congenital eye malformation, resulting from a failure in optic fissure closure (OFC) and causing visual impairment. There has been little study of the epithelial fusion process underlying closure in the human embryo and coloboma aetiology remains poorly understood. We performed RNAseq of cell populations isolated using laser capture microdissection to identify novel human OFC signature genes and probe the expression profile of known coloboma genes, along with a comparative murine analysis.

Carotid artery stenosis and ultrasound vascular indexes predict the coronary revascularization in patients with high cardiovascular risk scheduled for coronary angiography.

Background: Carotid artery atherosclerosis is a complex and multifactorial chronic disease.

Aims: We aimed to assess the predictive value of cardiovascular (CV) risk factors, carotid artery stenosis (CAS), and ultrasound vascular indices for coronary revascularization in patients referred for coronary angiography.

Methods: Patients scheduled for elective coronary angiography were enrolled.

Index case of acute myeloid leukemia in a family harboring a novel germ line mutation.

The persistence of a mutation at the time of complete remission warrants germ line analysis.Not all patients harboring germ line mutations have a family history of AML.

Diabetic Patients with an Acute Myocardial Infarction in Terms of Risk Factors and Comorbidities Management: Characteristics of the Highest-Risk Individuals.

Background: Patients with diabetes mellitus (DM) and acute myocardial infarction (AMI) are heterogeneous individuals with different clinical status compared to patients without DM.

Objectives: The aim of this study was to analyze the group of diabetic patients with ST-segment elevation MI (STEMI) or non-ST-segment elevation infarction (NSTEMI) including risk factors, medical history, laboratory findings, advancement of coronary vessel atherosclerosis, and diagnostics and therapeutic modalities performed. A comparison of groups according to the type of MI was also made.

Leukemic Stem Cells Evade Chemotherapy by Metabolic Adaptation to an Adipose Tissue Niche.

Adipose tissue (AT) has previously been identified as an extra-medullary reservoir for normal hematopoietic stem cells (HSCs) and may promote tumor development. Here, we show that a subpopulation of leukemic stem cells (LSCs) can utilize gonadal adipose tissue (GAT) as a niche to support their metabolism and evade chemotherapy. In a mouse model of blast crisis chronic myeloid leukemia (CML), adipose-resident LSCs exhibit a pro-inflammatory phenotype and induce lipolysis in GAT.

Residual Disease in a Novel Xenograft Model of RUNX1-Mutated, Cytogenetically Normal Acute Myeloid Leukemia.

Cytogenetically normal acute myeloid leukemia (CN-AML) patients harboring RUNX1 mutations have a dismal prognosis with anthracycline/cytarabine-based chemotherapy. We aimed to develop an in vivo model of RUNX1-mutated, CN-AML in which the nature of residual disease in this molecular disease subset could be explored. We utilized a well-characterized patient-derived, RUNX1-mutated CN-AML line (CG-SH).

Selective activity of the histone deacetylase inhibitor AR-42 against leukemia stem cells: a novel potential strategy in acute myelogenous leukemia.

Most patients with acute myelogenous leukemia (AML) relapse and die of their disease. Increasing evidence indicates that AML relapse is driven by the inability to eradicate leukemia stem cells (LSC). Thus, it is imperative to identify novel therapies that can ablate LSCs.

Flavaglines target primitive leukemia cells and enhance anti-leukemia drug activity.

Identification of agents that target human leukemia stem cells is an important consideration for the development of new therapies. The present study demonstrates that rocaglamide and silvestrol, closely related natural products from the flavagline class of compounds, are able to preferentially kill functionally defined leukemia stem cells, while sparing normal stem and progenitor cells. In addition to efficacy as single agents, flavaglines sensitize leukemia cells to several anticancer compounds, including front-line chemotherapeutic drugs used to treat leukemia patients.

Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

The development of strategies to eradicate primary human acute myelogenous leukemia (AML) cells is a major challenge to the leukemia research field. In particular, primitive leukemia cells, often termed leukemia stem cells, are typically refractory to many forms of therapy. To investigate improved strategies for targeting of human AML cells we compared the molecular mechanisms regulating oxidative state in primitive (CD34(+)) leukemic versus normal specimens.

Gene sets identified with oncogene cooperativity analysis regulate in vivo growth and survival of leukemia stem cells.

Leukemia stem cells (LSCs) represent a biologically distinct subpopulation of myeloid leukemias, with reduced cell cycle activity and increased resistance to therapeutic challenge. To better characterize key properties of LSCs, we employed a strategy based on identification of genes synergistically dysregulated by cooperating oncogenes. We hypothesized that such genes, termed "cooperation response genes" (CRGs), would represent regulators of LSC growth and survival.