An integrated model of acinar to ductal metaplasia-related N7-methyladenosine regulators predicts prognosis and immunotherapy in pancreatic carcinoma based on digital spatial profiling.

Acinar-to-ductal metaplasia (ADM) is a recently recognized, yet less well-studied, precursor lesion of pancreatic ductal adenocarcinoma (PDAC) developed in the setting of chronic pancreatitis. Through digital spatial mRNA profiling, we compared ADM and adjacent PDAC tissues from patient samples to unveil the bridging genes during the malignant transformation of pancreatitis. By comparing the bridging genes with the 7-methylguanosine (m7G)-seq dataset, we screened 19 m7G methylation genes for a subsequent large sample analysis.

Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study.

Background: Glycans play essential functional roles in the nervous system and their pathobiological relevance has become increasingly recognized in numerous brain disorders, but not fully explored in traumatic brain injury (TBI). We investigated longitudinal glycome patterns in patients with moderate to severe TBI (Glasgow Coma Scale [GCS] score ≤12) to characterize glyco-biomarker signatures and their relation to clinical features and long-term outcome.

Methods: This prospective single-center observational study included 51 adult patients with TBI (GCS ≤12) admitted to the neurosurgical unit of the University Hospital of Pecs, Pecs, Hungary, between June 2018 and April 2019.

Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer's Disease Patients.

Alzheimer's disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls.

Combination of Angiotensin (1-7) Agonists and Convalescent Plasma as a New Strategy to Overcome Angiotensin Converting Enzyme 2 (ACE2) Inhibition for the Treatment of COVID-19.

Coronavirus disease-2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently the most concerning health problem worldwide. SARS-CoV-2 infects cells by binding to angiotensin-converting enzyme 2 (ACE2). It is believed that the differential response to SARS-CoV-2 is correlated with the differential expression of ACE2.

Characterization of NADPH Oxidase Expression and Activity in Acute Myeloid Leukemia Cell Lines: A Correlation with the Differentiation Status.

In acute myeloid leukemia (AML), a low level of reactive oxygen species (ROS) is associated with leukemic stem cell (LSC) quiescence, whereas a high level promotes blast proliferation. ROS homeostasis relies on a tightly-regulated balance between the antioxidant and oxidant systems. Among the oxidants, NADPH oxidases (NOX) generate ROS as a physiological function.

Analysis of the Neuroproteome Associated With Cell Therapy After Intranigral Grafting in a Mouse Model of Parkinson Disease.

Advances in large-scale proteomics analysis have been very useful in understanding pathogenesis of diseases and elaborating therapeutic strategies. Proteomics has been employed to study Parkinson disease (PD); however, sparse studies reported proteome investigation after cell therapy approaches. In this study, we used liquid chromatography-tandem mass spectrometry and systems biology to identify differentially expressed proteins in a translational mouse model of PD after cell therapy.

Glioblastoma cell populations with distinct oncogenic programs release podoplanin as procoagulant extracellular vesicles.

Vascular anomalies, including local and peripheral thrombosis, are a hallmark of glioblastoma (GBM) and an aftermath of deregulation of the cancer cell genome and epigenome. Although the molecular effectors of these changes are poorly understood, the upregulation of podoplanin (PDPN) by cancer cells has recently been linked to an increased risk for venous thromboembolism (VTE) in GBM patients. Therefore, regulation of this platelet-activating protein by transforming events in cancer cells is of considerable interest.

Transforming growth factor-β1 inhibits interleukin-1β-induced expression of inflammatory genes and Cathepsin S activity in human vascular smooth muscle cells.

Objective And Design: This study investigated the opposite mechanisms by which IL-1β and TGF-β1 modulated the inflammatory and migratory phenotypes in cultured human intimal vascular smooth muscle cells vSMCs.

Materials And Treatment: Primary human vSMCs, obtained from twelve hypertensive patients who underwent carotid endarterectomy, were incubated for 24 hours with either 40 pM TGF-β1, or 1 nmol/L IL-1β, or their combination in presence or absence of anti-TGF-β neutralizing antibody.

Methods: The expression levels of matrix metalloproteases and their inhibitors, and the elastolytic enzyme cathepsin S (CTSS) and its inhibitor cystatin C were evaluated with RT-PCR.

Horizontal meta-analysis identifies common deregulated genes across AML subgroups providing a robust prognostic signature.

Advances in transcriptomics have improved our understanding of leukemic development and helped to enhance the stratification of patients. The tendency of transcriptomic studies to combine AML samples, regardless of cytogenetic abnormalities, could lead to bias in differential gene expression analysis because of the differential representation of AML subgroups. Hence, we performed a horizontal meta-analysis that integrated transcriptomic data on AML from multiple studies, to enrich the less frequent cytogenetic subgroups and to uncover common genes involved in the development of AML and response to therapy.

Acriflavine targets oncogenic STAT5 signaling in myeloid leukemia cells.

Acriflavine (ACF) is an antiseptic with anticancer properties, blocking the growth of solid and haematopoietic tumour cells. Moreover, this compound has been also shown to overcome the resistance of cancer cells to chemotherapeutic agents. ACF has been shown to target hypoxia-inducible factors (HIFs) activity, which are key effectors of hypoxia-mediated chemoresistance.

Targeting the RNA mA Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is an aggressive clonal disorder of hematopoietic stem cells (HSCs) and primitive progenitors that blocks their myeloid differentiation, generating self-renewing leukemic stem cells (LSCs). Here, we show that the mRNA mA reader YTHDF2 is overexpressed in a broad spectrum of human AML and is required for disease initiation as well as propagation in mouse and human AML. YTHDF2 decreases the half-life of diverse mA transcripts that contribute to the overall integrity of LSC function, including the tumor necrosis factor receptor Tnfrsf2, whose upregulation in Ythdf2-deficient LSCs primes cells for apoptosis.

An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology.

In its classical view, the renin angiotensin system (RAS) was defined as an endocrinesystem involved in blood pressure regulation and body electrolyte balance. However, the emergingconcept of tissue RAS, along with the discovery of new RAS components, increased thephysiological and clinical relevance of the system. Indeed, RAS has been shown to be expressed invarious tissues where alterations in its expression were shown to be involved in multiple diseasesincluding atherosclerosis, cardiac hypertrophy, type 2 diabetes (T2D) and renal fibrosis.

Functional pathways associated with human carotid atheroma: a proteomics analysis.

Advances in large-scale analysis are becoming very useful in understanding health and disease. Here, we used high-throughput mass spectrometry to identify differentially expressed proteins between early and advanced lesions. Carotid endarterectomy samples were collected and dissected into early and advanced atherosclerotic lesion portions.

Antibacterial activity of Ilex paraguariensis (Yerba Mate) against Gram-positive and Gram-negative bacteria.

Introduction: The stems and leaves of Ilex paraguariensis are popularly used for tea infusions in South America and the Middle East. The health benefits have been previously studied, revealing anti-mutagenic, anti-oxidant, hepatoprotective, hypocholesteremic and glycemic improvement. Limited research was performed on the antibacterial activity of the aqueous extract of Yerba Mate on standard and clinical isolates of Gram-positive and Gram-negative bacteria.

A new signaling cascade linking BMP4, BMPR1A, ΔNp73 and NANOG impacts on stem-like human cell properties and patient outcome.

In a significant number of cases cancer therapy is followed by a resurgence of more aggressive tumors derived from immature cells. One example is acute myeloid leukemia (AML), where an accumulation of immature cells is responsible for relapse following treatment. We previously demonstrated in chronic myeloid leukemia that the bone morphogenetic proteins (BMP) pathway is involved in stem cell fate and contributes to transformation, expansion, and persistence of leukemic stem cells.

Antibacterial activity of Ilex paraguariensis (Yerba Mate) against Gram-positive and Gram-negative bacteria.

Introduction: Limited research was performed on the antibacterial activity of the aqueous extract of Yerba Mate. The purpose of this study is to evaluate the anti-bacterial activity of Yerba Mate against Gram-positive and Gram-negative bacterial strains and its action against some resistant bacteria with genotypic molecular testing of resistance profiles.

Methodology: Commercial Ilex paraguariensis stems and leaves were purchased and extracts were prepared by adding water at 70oC for 2 hrs.

Acute Exposure to Cigarette Smoking Followed by Myocardial Infarction Aggravates Renal Damage in an Mouse Model.

Cigarette smoking (S) is a risk factor for progressive chronic kidney disease, renal dysfunction, and renal failure. In this study, the effect of smoking on kidney function was investigated in a mouse model of myocardial infarction (MI) using 4 groups: control (C), smoking (S), MI, and S+MI. Histological analysis of S+MI group showed alterations in kidney structure including swelling of the proximal convoluted tubules (PCTs), thinning of the epithelial lining, focal loss of the brush border of PCTs, and patchy glomerular retraction.

Efficiency and specificity of RAAS inhibitors in cardiovascular diseases: how to achieve better end-organ protection?

RAAS, a major pharmacological target in cardiovascular medicine, is inhibited by pharmacological classes including angiotensin converting enzyme (ACE) inhibitors (ACEIs), angiotensin-II type 1 blockers (ARBs) and aldosterone receptors antagonists, in addition to the recently introduced direct renin inhibitors (DRIs). However, currently used RAAS inhibitors still cannot achieve their desired effects and are associated with certain drawbacks, such as adverse side effects, incomplete blockage of the system and poor end-organ protection. In this review, we discuss the efficiency and specificity of the current RAAS inhibitors and propose some recommendations for achieving better treatments with better end-organ protection.

Cellular distribution and interaction between extended renin-angiotensin-aldosterone system pathways in atheroma.

The importance of the renin-angiotensin-aldosterone system (RAAS) in the development of atherosclerotic has been experimentally documented. In fact, RAAS components have been shown to be locally expressed in the arterial wall and to be differentially regulated during atherosclerotic lesion progression. RAAS transcripts and proteins were shown to be differentially expressed and to interact in the 3 main cells of atheroma: endothelial cells, vascular smooth muscle cells, and macrophages.

Transcriptomic Analysis Reveals Novel Transcription Factors Associated With Renin-Angiotensin-Aldosterone System in Human Atheroma.

Despite the well-known role of the renin-angiotensin-aldosterone system (RAAS) in atheroma, its global local organization is poorly understood. In this study, we used transcriptomic meta-analysis to reveal the local transcriptional organization and regulation of 37 extended RAAS (extRAAS) genes in atheroma. Expression analysis and hierarchical clustering were done on extRAAS genes in 32 paired early and advanced atherosclerotic lesions.

The kinetics of angiotensin-I metabolism in human carotid atheroma: An emerging role for angiotensin (1-7).

Aim: Local levels of angiotensin peptides depend on their rates of production and degradation, which induce proatherogenic or atheroprotective effects. Here, we reveal the kinetics of Angiotensin-I metabolism in paired early and advanced atherosclerotic lesions.

Methods: Lesions were spiked with labeled Ang-I* and supernatants withdrawn after 0, 10, 20, 40 and 80min.

Time resolved study of three ruthenium(II) complexes at micellar surfaces: A new long excited state lifetime probe for determining critical micelle concentration of surfactant nano-aggregates.

Three different ruthenium complexes have been synthesized and their luminescence properties in different solvent environments are reported. Luminescence intensities and excited state lifetimes of Ru-I, Ru-II and Ru-III vary with solvent viscosity. The excited state lifetime of Ru-I linearly increases in the viscosity range 1.

Atlas of tissue renin-angiotensin-aldosterone system in human: A transcriptomic meta-analysis.

Tissue renin-angiotensin-aldosterone system (RAAS) has attracted much attention because of its physiological and pharmacological implications; however, a clear definition of tissue RAAS is still missing. We aimed to establish a preliminary atlas for the organization of RAAS across 23 different normal human tissues. A set of 37 genes encoding classical and novel RAAS participants including gluco- and mineralo-corticoids were defined as extended RAAS (extRAAS) system.

Mutual amplification of corticosteroids and angiotensin systems in human vascular smooth muscle cells and carotid atheroma.

Unlabelled: The involvement of the renin-angiotensin-aldosterone system (RAAS) and cortisol in increased cardiovascular risk is well known. If numerous relationships between RAAS and corticosteroids have been described, their interactions within the arterial wall, especially during the transdifferentiation of vascular smooth muscle cells (VSMCs) and the atheroma formation, are not established. Here, we clarified the relationships between mRNA levels of corticosteroid and angiotensin system components using cortisol, fludrocortisone, and angiotensin II treatments of cultured VSMCs maintained in a contractile phenotype or induced to a lipid storing phenotype.