Hosts and Heterologous Expression Strategies of Recombinant Toxins for Therapeutic Purposes.

The production of therapeutic recombinant toxins requires careful host cell selection. Bacteria, yeast, and mammalian cells are common choices, but no universal solution exists. Achieving the delicate balance in toxin production is crucial due to potential self-intoxication.

Recent Advances on Affibody- and DARPin-Conjugated Nanomaterials in Cancer Therapy.

Affibodies and designed ankyrin repeat proteins (DARPins) are synthetic proteins originally derived from the virulence factor protein A and the human ankyrin repeat proteins, respectively. The use of these molecules in healthcare has been recently proposed as they are endowed with biochemical and biophysical features heavily demanded to target and fight diseases, as they have a strong binding affinity, solubility, small size, multiple functionalization sites, biocompatibility, and are easy to produce; furthermore, impressive chemical and thermal stability can be achieved. especially when using affibodies.

Antibody-Drug Conjugates: The New Frontier of Chemotherapy.

In recent years, antibody-drug conjugates (ADCs) have become promising antitumor agents to be used as one of the tools in personalized cancer medicine. ADCs are comprised of a drug with cytotoxic activity cross-linked to a monoclonal antibody, targeting antigens expressed at higher levels on tumor cells than on normal cells. By providing a selective targeting mechanism for cytotoxic drugs, ADCs improve the therapeutic index in clinical practice.

Corrigendum: Theranostic Nanomedicine for Malignant Gliomas.

[This corrects the article DOI: 10.3389/fbioe.2019.

Theranostic Nanomedicine for Malignant Gliomas.

Brain tumors mainly originate from glial cells and are classified as gliomas. Malignant gliomas represent an incurable disease; indeed, after surgery and chemotherapy, recurrence appears within a few months, and mortality has remained high in the last decades. This is mainly due to the heterogeneity of malignant gliomas, indicating that a single therapy is not effective for all patients.

Neuronal Cells Rearrangement During Aging and Neurodegenerative Disease: Metabolism, Oxidative Stress and Organelles Dynamic.

Brain cells normally respond adaptively to oxidative stress or bioenergetic challenges, resulting from ongoing activity in neuronal circuits. During aging and in neurodegenerative disorders, these mechanisms are compromised. In fact, neurons show unique age-related changes in functions and metabolism, resulting in greater susceptibility to insults and disease.

Supramolecular self-assembly of graphene oxide and metal nanoparticles into stacked multilayers by means of a multitasking protein ring.

Graphene oxide (GO) is rapidly emerging worldwide as a breakthrough precursor material for next-generation devices. However, this requires the transition of its two-dimensional layered structure into more accessible three-dimensional (3D) arrays. Peroxiredoxins (Prx) are a family of multitasking redox enzymes, self-assembling into ring-like architectures.

Role of the Vnn1 pantetheinase in tissue tolerance to stress.

Pantetheinase is an ubiquitous enzyme which hydrolyses D-pantetheine into cysteamine and pantothenate (vitamin B5) on the dissimilative pathway of CoA. Pantetheinase isoforms are encoded by the Vnn (vanin) genes and Vnn1 is the predominant tissue isoform in mice and humans. In the present article, we review the results showing the regulation of Vnn1 expression during developmental, repair and inflammatory situations and the impact of a Vnn1 deficiency in mouse models of pathologies.

Metal-induced self-assembly of peroxiredoxin as a tool for sorting ultrasmall gold nanoparticles into one-dimensional clusters.

Nanomanipulation of matter to create responsive, ordered materials still remains extremely challenging. Supramolecular chemistry has inspired new strategies by which such nanomaterials can be synthesized step by step by exploiting the self-recognition properties of molecules. In this work, the ring-shaped architecture of the 2-Cys peroxiredoxin I protein from Schistosoma mansoni, engineered to have metal ion-binding sites, is used as a template to build up 1D nanoscopic structures through metal-induced self-assembly.

Glutathione metabolism in Candida albicans resistant strains to fluconazole and micafungin.

Currently available therapies for candidiasis are based on antifungal drugs belonging to azole and echinocandin families that interfere with different aspects of fungal metabolism. These drugs, beyond their specific effects, elicit also a cellular stress including an unbalance of redox state that is counteracted not only utilizing antioxidant species but also increasing the outcome export by transporters to detoxify the internal environment. These cellular actions are both based on the cytosolic concentration of reduced glutathione (GSH).

PPARalpha regulates the production of serum Vanin-1 by liver.

The membrane-bound Vanin-1 pantetheinase regulates tissue adaptation to stress. We investigated Vnn1 expression and its regulation in liver. Vnn1 is expressed by centrolobular hepatocytes.

Neuroprotective effects of PrxI over-expression in an in vitro human Alzheimer's disease model.

Peroxiredoxins are ubiquitous proteins that recently attracted major interests in view of the strict correlation observed in several cell lines and/or tissues between different levels of their expression and the increased capacity of cells to survive in different pathophysiological conditions. They are recently considered as the most important enzymes regulating the concentration of hydroperoxides inside the cells. Most of neurodisorders such as Parkinson, Huntington, Alzheimer's diseases, and ischemic injury are characterized by conditions of oxidative stress inside cells.

Physiological roles of ovotransferrin.

Background: Ovotransferrin is an iron-binding glycoprotein, found in avian egg white and in avian serum, belonging to the family of transferrin iron-binding glycoproteins. All transferrins show high sequence homology. In mammals are presents two different soluble glycoproteins with different functions: i) serum transferrin that is present in plasma and committed to iron transport and iron delivery to cells and ii) lactoferrin that is present in extracellular fluids and in specific granules of polymorphonuclear lymphocytes and committed to the so-called natural immunity.

Engineering a switchable toxin: the potential use of PDZ domains in the expression, targeting and activation of modified saporin variants.

A critical problem in studying ribosome-inactivating proteins (RIPs) lies in the very limited possibility to produce them in heterologous systems. In fact, their inherent toxicity for the producing organism nearly always prevents their recombinant expression. In this study, we designed, expressed and characterized an engineered form of the RIP saporin (SapVSAV), bearing a C-terminal extra sequence that is recognized and bound by the second PDZ domain from murine PTP-BL protein (PDZ2).

Cystamine restores GSTA3 levels in Vanin-1 null mice.

Free cysteamine levels in mouse tissues have been strictly correlated to the presence of membrane-bound pantetheinase activity encoded by Vanin-1. Vanin-1 is involved in many biological processes in mouse, from thymus homing to sexual development. Vanin-1 -/- mice are fertile and grow and develop normally; they better control inflammation and most of the knockout effects were rescued by cystamine treatment.

Immunology and homeopathy. 5. The rationale of the 'Simile'.

The foundation of homeopathic medicine is the 'Similia Principle', also known as the 'Principle of Similarity' or also as the 'Simile', which reflects the inversion of pharmacological effects in healthy subjects as compared with sick ones. This article describes the inversion of effects, a widespread medical phenomenon, through three possible mechanisms: non-linearity of dose-response relationship, different initial pathophysiological states of the organism, and pharmacodynamics of body response to the medicine. Based on the systemic networks which play an important role in response to stress, a unitary and general model is designed: homeopathic medicines could interact with sensitive (primed) regulation systems through complex information, which simulate the disorders of natural disease.

Complex genetic control of susceptibility to malaria: positional cloning of the Char9 locus.

Mouse strains AcB55 and AcB61 are resistant to malaria by virtue of a mutation in erythrocyte pyruvate kinase (Pklr(I90N)). Linkage analysis in [AcB55 x A/J] F2 mice detected a second locus (Char9; logarithm of odds = 4.74) that regulates the blood-stage replication of Plasmodium chabaudi AS independently of Pklr.

Glutathione S-transferase tissue profiling by reporter peptide monitoring.

Glutathione S-transferases (GSTs) form a widespread enzyme superfamily mainly involved in phase II detoxification. Differential expression of the various GST isoforms, differing in catalytic and structural properties, correlates with physiological and pathological states. Fast and simple determination of the GST profile is expected to be an important diagnostic tool in disease analysis.