RAS signaling pathway is essential in regulating PIEZO1-mediated hepatic iron overload in dehydrated hereditary stomatocytosis.

PIEZO1 encodes a mechanoreceptor, a cation channel activated by mechanical stimuli. Gain-of-function (GoF) variants in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS), or xerocytosis, a pleiotropic syndrome characterized by anemia and iron overload. DHS patients develop hepatic iron overload independent of the degree of anemia and transfusion regimen.

Adjunctive use of oral MAF is associated with no disease progression or mortality in hospitalized patients with COVID-19 pneumonia: The single-arm COral-MAF1 prospective trial.

Based on a growing body of evidence that a dysregulated innate immune response mediated by monocytes/macrophages plays a key role in the pathogenesis of COVID-19, a clinical trial was conducted to investigate the therapeutic potential and safety of oral macrophage activating factor (MAF) plus standard of care (SoC) in the treatment of hospitalized patients with COVID-19 pneumonia. Ninety-seven hospitalized patients with confirmed COVID-19 pneumonia were treated with oral MAF and a vitamin D3 supplement, in combination with SoC, in a single-arm, open label, multicentre, phase II clinical trial. The primary outcome measure was a reduction in an intensive care unit transfer rate below 13% after MAF administration.

Evaluation of the main regulators of systemic iron homeostasis in pyruvate kinase deficiency.

Iron homeostasis and dyserythropoiesis are poorly investigated in pyruvate kinase deficiency (PKD), the most common glycolytic defect of erythrocytes. Herein, we studied the main regulators of iron balance and erythropoiesis, as soluble transferrin receptor (sTfR), hepcidin, erythroferrone (ERFE), and erythropoietin (EPO), in a cohort of 41 PKD patients, compared with 42 affected by congenital dyserythropoietic anemia type II (CDAII) and 50 with hereditary spherocytosis (HS). PKD patients showed intermediate values of hepcidin and ERFE between CDAII and HS, and clear negative correlations between log-transformed hepcidin and log-EPO (Person's r correlation coefficient =  - 0.

Coinheritance of PIEZO1 variants and multi-locus red blood cell defects account for the symptomatic phenotype in beta-thalassemia carriers.

Workflow of the study with some examples of the achieved results.

Proteome alterations in erythrocytes with PIEZO1 gain-of-function mutations.

Gain-of-function mutations in PIEZO1 cause dehydrated hereditary stomatocytosis (DHS) or hereditary xerocytosis, an autosomal dominant hemolytic anemia characterized by high reticulocyte count, a tendency to macrocytosis, and mild jaundice, as well as by other variably penetrant clinical features, such as perinatal edema, severe thromboembolic complications after splenectomy, and hepatic iron overload. PIEZO1 mutations in DHS lead to slowed inactivation kinetics of the ion channel and/or facilitation of channel opening in response to physiological stimuli. To characterize the alterations of red blood cell proteome in patients with mutated PIEZO1, we used a differential approach to compare the proteome of patients with DHS (16 patients from 13 unrelated ancestries) vs healthy individuals.

Synergistic Effects of , 1,3 Dichloropropene and Organic Matter in Controlling the Root-Knot Nematode on Tomato.

Environmental concerns raised by synthetic nematicides are encouraging integrated management strategies based on their combination with non-chemical control tools, such as biocontrol agents and/or organic amendments. In this study, the combination of the fumigant 1,3-dichloropropene (1,3-D) with a commercial formulation of the biocontrol agent (TH) and an organic fertilizer (OF) was investigated in two consecutive tomato crops for its effect on the root-knot nematode and plant growth and yield. The application of 1,3-D was only performed on the first crop, while TH and OF were provided to both crops.

Chest wall reconstruction in benign and malignant tumors with non-rigid materials: An overview.

Several materials and techniques have been described for the procedure of chest wall reconstruction: the choice of using a technique or a material over another relies mainly on the surgeon's experience as well as thoracic defect localization and dimension, local availability of materials, and costs. From a technical point of view, autologous and alloplastic reconstruction are available, and, in both cases, rigid and non-rigid prostheses are found. Each material has its peculiarities, with advantages and disadvantages; thus, it is mandatory to be confident when planning the intervention to foresee possible complications and minimize them.

Enzymes for Degradation of Aflatoxin B1 and Ochratoxin A.

The contamination of agricultural products with mycotoxins causes risks to animal and human health and severe economic losses. Mycotoxicoses can be reduced by preventing fungal infection using chemical and biological approaches. The chemical strategies can release toxic molecules; therefore, strategies for biological control are being evaluated, such as using nontoxic fungi and their metabolites.

SEC23B Loss-of-Function Suppresses Hepcidin Expression by Impairing Glycosylation Pathway in Human Hepatic Cells.

Biallelic pathogenic variants in the gene cause congenital dyserythropoietic anemia type II (CDA II), a rare hereditary disorder hallmarked by ineffective erythropoiesis, hemolysis, erythroblast morphological abnormalities, and hypo-glycosylation of some red blood cell membrane proteins. Abnormalities in , which encodes the homonymous cytoplasmic COPII (coat protein complex II) component, disturb the endoplasmic reticulum to Golgi trafficking and affect different glycosylation pathways. The most harmful complication of CDA II is the severe iron overload.

Mineral Biofortification and Growth Stimulation of Lentil Plants Inoculated with Strains and Metabolites.

Biofortification of crops via agricultural interventions represents an excellent way to supply micronutrients in poor rural populations, who highly suffer from these deficiencies. Soil microbes can directly influence plant growth and productivity, e.g.

Evidence for the Role of and Xenobiotic Detoxification in Differential Sensitivity to Azole Fungicides in Boxwood Blight Pathogens.

Boxwood blight, a fungal disease of ornamental plants ( spp.), is caused by two sister species, () and (). Compared to , is documented to display reduced sensitivity to fungicides, including the azole class of antifungals, which block synthesis of a key fungal membrane component, ergosterol.

The State of The Art on Acetylcholinesterase Inhibitors in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic disabling disease that affects the central nervous system. The main consequences of AD include the decline of cognitive functions and language disorders. One of the causes leading to AD is the decrease of neurotransmitter acetylcholine (ACh) levels in the brain, in part due to a higher activity of acetylcholinesterase (AChE), the enzyme responsible for its degradation.

Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients.

Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based on a targeted next-generation sequencing panel of 86 genes causative of hereditary red blood cell defects.