Search results for "Teas"

Macrophage protease-activated receptor 2 regulates fetal liver erythropoiesis in mice.

2020

AbstractDeficiencies in many coagulation factors and protease-activated receptors (PARs) affect embryonic development. We describe a defect in definitive erythropoiesis in PAR2-deficient mice. Embryonic PAR2 deficiency increases embryonic death associated with variably severe anemia in comparison with PAR2-expressing embryos. PAR2-deficient fetal livers display reduced macrophage densities, erythroblastic island areas, and messenger RNA expression levels of markers for erythropoiesis and macrophages. Coagulation factor synthesis in the liver coincides with expanding fetal liver hematopoiesis during midgestation, and embryonic factor VII (FVII) deficiency impairs liver macrophage development…

The switch from proteasome to immunoproteasome is increased in circulating cells of patients with fast progressive immunoglobulin A nephropathy and a…

2021

  The proteasome to immunoproteasome (iPS) switch consists of β1, β2 and β5 subunit replacement by low molecular weight protein 2 (LMP2), LMP7 and multicatalytic endopeptidase-like complex-1 (MECL1) subunits, resulting in a more efficient peptide preparation for major histocompatibility complex 1 (MHC-I) presentation. It is activated by toll-like receptor (TLR) agonists and interferons and may also be influenced by genetic variation. In a previous study we found an iPS upregulation in peripheral cells of patients with immunoglobulin A nephropathy (IgAN). We aimed to investigate in 157 IgAN patients enrolled through the multinational Validation Study of the Oxford Classification of IgAN (VAL…

Dipeptidyl Peptidase IV as a Muscle Myokine

2020

Dipeptidyl peptidase IV (DPP-IV) is a unique serine protease that exists in a membrane bound state and in a soluble state in most tissues in the body. DPP-IV has multiple targets including cytokines, neuropeptides, and incretin hormones, and plays an important role in health and disease. Recent work suggests that skeletal muscle releases DPP-IV as a myokine and participates in control of muscle blood flow. However, few of the functions of DPP-IV as a myokine have been investigated to date and there is a poor understanding about what causes DPP-IV to be released from muscle.

A Novel Micronutrient Blend Mimics Calorie Restriction Transcriptomics in Multiple Tissues of Mice and Increases Lifespan and Mobility in C. elegans

2020

Background: We previously described a novel micronutrient blend that behaves like a putative calorie restriction mimetic. The aim of this paper was to analyze the beneficial effects of our micronutrient blend in mice and C. elegans, and compare them with calorie restriction. Methods: Whole transcriptomic analysis was performed in the brain cortex, skeletal muscle and heart in three groups of mice: old controls (30 months), old + calorie restriction and old + novel micronutrient blend. Longevity and vitality were tested in C. elegans. Results: The micronutrient blend elicited transcriptomic changes in a manner similar to those in the calorie-restricted group and different from those in the c…

Famotidine inhibits toll-like receptor 3-mediated inflammatory signaling in SARS-CoV-2 infection

2021

Apart from prevention using vaccinations, the management options for COVID-19 remain limited. In retrospective cohort studies, use of famotidine, a specific oral H2 receptor antagonist (antihistamine), has been associated with reduced risk of intubation and death in patients hospitalized with COVID-19. In a case series, nonhospitalized patients with COVID-19 experienced rapid symptom resolution after taking famotidine, but the molecular basis of these observations remains elusive. Here we show using biochemical, cellular, and functional assays that famotidine has no effect on viral replication or viral protease activity. However, famotidine can affect histamine-induced signaling processes i…

Specific inflammatory response of Anemonia sulcata (Cnidaria) after bacterial injection causes tissue reaction and enzymatic activity alteration

2015

The evolution of multicellular organisms was marked by adaptations to protect against pathogens. The mechanisms for discriminating the ’’self’’ from ’’non-self” have evolved into a long history of cellular and molecular strategies, from damage repair to the co-evolution of host-pathogen interactions. We investigated the inflammatory response in Anemonia sulcata (Cnidaria: Anthozoa) following injection of substances that varied in type and dimension, and observed clear, strong and specific reactions, especially after injection of Escherichia coli and Vibrio alginolyticus. Moreover, we analyzed enzymatic activity of protease, phosphatase and esterase, showing how the injection of different ba…

Ectodomain shedding of CD99 within highly conserved regions is mediated by the metalloprotease meprin β and promotes transendothelial cell migration.

2016

The adhesion molecule CD99 is essential for the transendothelial migration of leukocytes. In this study, we used biochemical and cellular assays to show that CD99 undergoes ectodomain shedding by the metalloprotease meprin β and subsequent intramembrane proteolysis by γ-secretase. The cleavage site in CD99 was identified by mass spectrometry within an acidic region highly conserved through different vertebrate species. This finding fits perfectly to the unique cleavage specificity of meprin β with a strong preference for aspartate residues and suggests coevolution of protease and substrate. We hypothesized that limited CD99 cleavage by meprin β would alter cellular transendothelial migratio…

Off-Target-Based Design of Selective HIV-1 PROTEASE Inhibitors

2021

The approval of the first HIV-1 protease inhibitors (HIV-1 PRIs) marked a fundamental step in the control of AIDS, and this class of agents still represents the mainstay therapy for this illness. Despite the undisputed benefits, the necessary lifelong treatment led to numerous severe side-effects (metabolic syndrome, hepatotoxicity, diabetes, etc.). The HIV-1 PRIs are capable of interacting with “secondary” targets (off-targets) characterized by different biological activities from that of HIV-1 protease. In this scenario, the in-silico techniques undoubtedly contributed to the design of new small molecules with well-fitting selectivity against the main target, analyzing possible undesirabl…

Antiprotozoal and cysteine proteases inhibitory activity of dipeptidyl enoates

2018

A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k2nd (M−1s−1) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC50 values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and ev…

2021

The coronavirus pandemic has affected more than 150 million people, while over 3.25 million people have died from the coronavirus disease 2019 (COVID-19). As there are no established therapies for COVID-19 treatment, drugs that inhibit viral replication are a promising target; specifically, the main protease (Mpro) that process CoV-encoded polyproteins serves as an Achilles heel for assembly of replication-transcription machinery as well as down-stream viral replication. In the search for potential antiviral drugs that target Mpro, a series of cembranoid diterpenes from the biologically active soft-coral genus Sarcophyton have been examined as SARS-CoV-2 Mpro inhibitors. Over 360 metabolite…