Hemopexin alleviates sterile inflammation in ischemia-reperfusion-induced lung injury.

Introduction: Pulmonary ischemia-reperfusion (IR) injury (IRI) plays a significant role in various lung disorders and is a key factor in the development of primary graft dysfunction following lung transplantation. Hemopexin (Hx) is the major serum scavenger protein for heme, which is a prooxidant and pro-inflammatory compound. In the current study, we hypothesized that Hx could confer beneficial effects in sterile inflammation induced by IR-mediated lung injury.

Alpha-1-antitrypsin improves anastomotic healing in intestinal epithelial cells model.

Purpose: Intestinal anastomosis is a routine procedure in pediatric surgery, with leakage being a significant complication. Human alpha1-antitrypsin (AAT), whose physiological serum concentrations range from 0.9-2.

Amyloid precursor protein as a fibrosis marker in infants with biliary atresia.

Background: Biliary atresia (BA) is a rare condition of unknown origin in newborns with jaundice. In BA bile ducts are non-functional, causing neonatal cholestasis and following liver fibrosis and failure.

Methods: This retrospective study included liver biopsies of 14 infants with BA aged [mean ± SD] 63 ± 23 days.

Ex vivo study on the human blood neutrophil circadian features and effects of alpha1-antitrypsin and lipopolysaccharide.

Aims: Neutrophils perform various functions in a circadian-dependent manner; therefore, we investigated here whether the effect of alpha1-antitrypsin (AAT), used as augmentation therapy, is dependent on the neutrophil circadian clock. AAT is a vital regulator of neutrophil functions, and its qualitative and/or quantitative defects have significant implications for the development of respiratory diseases.

Methods: Whole blood from 12 healthy women age years, mean (SD) 29.

Distinct metabolic responses to heme in inflammatory human and mouse macrophages - Role of nitric oxide.

Activation of inflammation is tightly associated with metabolic reprogramming in macrophages. The iron-containing tetrapyrrole heme can induce pro-oxidant and pro-inflammatory effects in murine macrophages, but has been associated with polarization towards an anti-inflammatory phenotype in human macrophages. In the current study, we compared the regulatory responses to heme and the prototypical Toll-like receptor (TLR)4 ligand lipopolysaccharide (LPS) in human and mouse macrophages with a particular focus on alterations of cellular bioenergetics.

Diagnostic and therapeutic value of human serpin family proteins.

SERPIN (serine proteinase inhibitors) is an acronym for the superfamily of structurally similar proteins found in animals, plants, bacteria, viruses, and archaea. Over 1500 SERPINs are known in nature, while only 37 SERPINs are found in humans, which participate in inflammation, coagulation, angiogenesis, cell viability, and other pathophysiological processes. Both qualitative or quantitative deficiencies or overexpression and/or abnormal accumulation of SERPIN can lead to diseases commonly referred to as "serpinopathies".

Alpha1-antitrypsin improves survival in murine abdominal sepsis model by decreasing inflammation and sequestration of free heme.

Background: Excessive inflammation, hemolysis, and accumulation of labile heme play an essential role in the pathophysiology of multi-organ dysfunction syndrome (MODS) in sepsis. Alpha1-antitrypsin (AAT), an acute phase protein with heme binding capacity, is one of the essential modulators of host responses to inflammation. In this study, we evaluate the putative protective effect of AAT against MODS and mortality in a mouse model of polymicrobial abdominal sepsis.

An association between plasma levels of α2-macroglobulin and α1-antitrypsin in PiMM and PiZZ individuals differing in COPD presentation.

Introduction: Compared to normal PiMM, individuals with severe α1-antitrypsin (AAT) PiZZ (Glu342Lys) genotype deficiency are at higher risk of developing early-onset chronic obstructive pulmonary disease (COPD)/emphysema associated with Z-AAT polymers and neutrophilic inflammation. We aimed to investigate putative differences in plasma levels of acute phase proteins (APP) between PiMM and PiZZ subjects and to determine plasma Z-AAT polymer levels in PiZZ subjects.

Materials And Methods: Nephelometric analysis of seven plasma APPs was performed in 67 PiMM and 44 PiZZ subjects, of whom 43 and 42, respectively, had stable COPD.

A Fast Scoring of Human Primary Respiratory Epithelia Grown at Air-Liquid Interface (ALI) to Assess Epithelial Morphology in Research and Personalized Medicine Settings.

Background: In recent years, increasingly complex ALI protocols involving specialized, albeit laboratory-specific media have been established, while at the same time, many studies compile the data of only a few ALI donors in spite of site-, protocol- and donor-specific differentiation.

Methods: We describe a simple morphology scoring protocol using histology material derived from epithelia grown on ALI inserts in parallel to other, more complex readouts.

Results: Among more than 100 ALI inserts derived from different donors, significant differences in layer score ( = 0.

Alpha-1-antitrypsin-deficiency is associated with lower cardiovascular risk: an approach based on federated learning.

Background: Chronic obstructive pulmonary disease (COPD) is an inflammatory multisystemic disease caused by environmental exposures and/or genetic factors. Inherited alpha-1-antitrypsin deficiency (AATD) is one of the best recognized genetic factors increasing the risk for an early onset COPD with emphysema. The aim of this study was to gain a better understanding of the associations between comorbidities and specific biomarkers in COPD patients with and without AATD to enable future investigations aimed, for example, at identifying risk factors or improving care.

An Enzyme-Linked Immunosorbent Assay (ELISA) for Quantification of Circulating Pi*Z Alpha1-Antitrypsin Polymers.

Enzyme-linked immunosorbent assay (ELISA) is a sensitive immunoassay based on specific antigen-antibody reaction that is used for quantitative/qualitative analysis of various analytes in serum, plasma, saliva, cell and tissue lysates, and urine. ELISAs are typically performed in multi-well plates and depending on the design require coating antibody/antigen, analyte, detection antibodies, buffer, wash solution, and substrate/chromogen. Here we describe highly specific monoclonal antibody-based ELISA that detects circulating polymers formed by Pi*Z variant of human alpha-1-antitrypsin (Z-AAT).

Plasma levels of α-antitrypsin-derived C-terminal peptides in PiMM and PiZZ COPD patients.

https://bit.ly/3rNJeLd.

Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi∗ZZ).

Background & Aims: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown.

Disparities in Cisplatin-Induced Cytotoxicity-A Meta-Analysis of Selected Cancer Cell Lines.

Cisplatin is a classic anticancer drug widely used as a reference drug to test new metal complex drug candidates. We found an unexpected diversity in cisplatin-related cytotoxicity values, expressed as IC (the half-maximal inhibitory concentration) in tumour cell lines, such as MCF-7, HepG2 and HeLa. We reviewed the data published from 2018 to 2022.

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal Pi*M and Deficient Pi*Z Variants of Alpha-1-antitrypsin.

Different mutations in the gene result in alpha-1 antitrypsin (AAT) deficiency and in an increased risk for the development of liver diseases. More than 90% of severe deficiency patients are homozygous for Z (Glu342Lys) mutation. This mutation causes Z-AAT polymerization and intrahepatic accumulation which can result in hepatic alterations leading to steatosis, fibrosis, cirrhosis, and/or hepatocarcinoma.

Beneficial effects of alpha-1 antitrypsin therapy in a mouse model of colitis-associated colon cancer.

Background: It is widely accepted that chronic inflammatory bowel diseases significantly higher a risk for colorectal cancer development. Among different types of treatments for patients with colon cancer, novel protein-based therapeutic strategies are considered.

Aim: To explore the effect of human plasma alpha-1 antitrypsin (AAT) protein in the chemically induced mouse model of colorectal cancer.

NAFLD and AATD Are Two Diseases with Unbalanced Lipid Metabolism: Similarities and Differences.

Non-alcoholic fatty liver disease (NAFLD) is a type of steatosis commonly associated with obesity, dyslipidemia, hypertension, and diabetes. Other diseases such as inherited alpha-1 antitrypsin deficiency (AATD) have also been related to the development of liver steatosis. The primary reasons leading to hepatic lipid deposits can be genetic and epigenetic, and the outcomes range from benign steatosis to liver failure, as well as to extrahepatic diseases.

Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin.

Rodent models of lipopolysaccharide (LPS)-induced pulmonary inflammation are used for anti-inflammatory drug testing. We aimed to characterize mice responses to aerosolized LPS alone or with intraperitoneal (i.p.

Fibrosis-Related Gene Profiling in Liver Biopsies of PiZZ α1-Antitrypsin Children with Different Clinical Courses.

PiZZ (Glu342Lys) α1-antitrypsin deficiency (AATD) is characterized by intrahepatic AAT polymerization and is a risk factor for liver disease development in children. The majority of PiZZ children are disease free, hence this mutation alone is not sufficient to cause the disease. We investigated Z-AAT polymers and the expression of fibrosis-related genes in liver tissues of PiZZ children with different clinical courses.

Plasma markers of COVID-19 severity: a pilot study.

Background: SARS-CoV-2 infected patients show heterogeneous clinical presentations ranging from mild symptoms to severe respiratory failure and death. Consequently, various markers reflect this wide spectrum of disease presentations.

Methods: Our pilot cohort included moderate (n = 10) and severe (n = 10) COVID-19 patients, and 10 healthy controls.

Pleural CD14 monocytes/macrophages of healthy adolescents show a high expression of metallothionein family genes.

Nowadays laparoscopic interventions enable the collection of resident macrophage populations out of the human cavities. We employed this technique to isolate pleural monocytes/macrophages from healthy young adults who underwent a correction of pectus excavatum. High quality CD14 monocytes/macrophages (plMo/Mφ) were used for RNA-sequencing (RNA-seq) in comparison with human monocyte-derived macrophages (MDM) natural (MDM-0) or IL-4-polarized (MDM-IL4).

Indirect effect of alpha-1-antitrypsin on endotoxin-induced IL-1β secretion from human PBMCs.

Human alpha-1-antitrypsin (AAT) encoded by the gene, is an acute phase glycoprotein that regulates inflammatory responses both protease inhibitory and non-inhibitory activities. We previously reported that AAT controls ATP-induced IL-1β release from human mononuclear cells by stimulating the release of small bioactive molecules. In the current study, we aimed to elucidate the identity of these putative effectors released from human PBMCs in response to AAT, which may inhibit the LPS-induced release of IL-1β.