Gender Influence on XOR Activities and Related Pathologies: A Narrative Review.

Taking into account the patient's gender is the first step towards more precise and egalitarian medicine. The gender-related divergences observed in purine catabolism and their pathological consequences are good examples of gender medicine differences. Uric acid is produced by the activity of xanthine oxidoreductase (XOR).

Heterophyllin: A New Adenia Toxic Lectin with Peculiar Biological Properties.

Ribosome-inactivating proteins (RIPs) are plant toxins that were identified for their ability to irreversibly damage ribosomes, thereby causing arrest of protein synthesis and induction of cell death. The RIPs purified from Adenia plants are the most potent ones. Here, we describe a novel toxic lectin from caudex, which has been named heterophyllin.

New Insights on Saporin Resistance to Chemical Derivatization with Heterobifunctional Reagents.

Saporin is a type 1 ribosome-inactivating protein widely used as toxic payload in the construction of targeted toxins, chimeric molecules formed by a toxic portion linked to a carrier moiety. Among the most used carriers, there are large molecules (mainly antibodies) and small molecules (such as neurotransmitters, growth factors and peptides). Some saporin-containing targeted toxins have been used for the experimental treatment of several diseases, giving very promising results.

Anti-PD-L1 immunoconjugates for cancer therapy: Are available antibodies good carriers for toxic payload delivering?

Immune checkpoint mechanisms are important molecular cell systems that maintain tolerance toward autoantigens in order to prevent immunity-mediated accidental damage. It is well known that cancer cells may exploit these molecular and cellular mechanisms to escape recognition and elimination by immune cells. Programmed cell death protein-1 (PD-1) and its natural ligand programmed cell death ligand-1 (PD-L1) form the PD-L1/PD-1 axis, a well-known immune checkpoint mechanism, which is considered an interesting target in cancer immunotherapy.

Chronic kidney disease: Which role for xanthine oxidoreductase activity and products?

The present review explores the role of xanthine oxidoreductase (XOR) in the development and progression of chronic kidney disease (CKD). Human XOR is a multi-level regulated enzyme, which has many physiological functions, but that is also implicated in several pathological processes. The main XOR activities are the purine catabolism, which generates uric acid, and the regulation of cell redox state and cell signaling, through the production of reactive oxygen species.

Toxin and Immunotoxin Based Therapeutic Approaches.

The concept of "magic bullets", i [...

Sequence, Structure, and Binding Site Analysis of Kirkiin in Comparison with Ricin and Other Type 2 RIPs.

Kirkiin is a new type 2 ribosome-inactivating protein (RIP) purified from the caudex of with a cytotoxicity compared to that of stenodactylin. The high toxicity of RIPs from genus plants makes them interesting tools for biotechnology and therapeutic applications, particularly in cancer therapy. The complete amino acid sequence and 3D structure prediction of kirkiin are here reported.

Xanthine oxidoreductase: A leading actor in cardiovascular disease drama.

Cardiovascular diseases (CVD) are the leading cause of global mortality and their pathogenesis lies mainly in the atherosclerotic process. There are close connections linking oxidative stress and inflammation to endothelial dysfunction, atherosclerosis and, consequently, to CVD. This review focuses on the role of xanthine oxidoreductase (XOR) and its products on the development of chronic inflammation and oxidative stress, responsible for atheromatous plaque formation.

Antibody Conjugates for Sarcoma Therapy: How Far along Are We?

Sarcomas are one of the most difficult type of cancer to manage and treat because of their extremely heterogeneous molecular and morphological features. Despite the progress made over the years in the establishment of standard protocols for high and low grading/staging sarcoma patients, mostly with chemotherapy and/or radiotherapy, 50% of treated patients experience relapse episodes. Because of this, in the last 20 years, new therapeutic approaches for sarcoma treatment have been evaluated in preclinical and clinical studies.

Xanthine oxidoreductase: One enzyme for multiple physiological tasks.

Human xanthine oxidoreductase (XOR) is a multiple-level regulated enzyme, resulting from a complicated evolutionary process that assigned it many physiological roles. The main XOR activities are: (i) xanthine dehydrogenase (XDH) activity that performs the last two steps of purine catabolism, from hypoxanthine to uric acid; (ii) xanthine oxidase (XO) activity that, besides purine catabolism, produces reactive oxygen species (ROS); (iii) nitrite reductase activity that generates nitric oxide, contributing to vasodilation and regulation of blood pressure; (iv) NADH oxidase activity that produces ROS. All these XOR activities contribute also to metabolize various endogenous and exogenous compounds, including some drugs.

Kirkiin: A New Toxic Type 2 Ribosome-Inactivating Protein from the Caudex of .

Ribosome-inactivating proteins (RIPs) are plant toxins that irreversibly damage ribosomes and other substrates, thus causing cell death. RIPs are classified in type 1 RIPs, single-chain enzymatic proteins, and type 2 RIPs, consisting of active A chains, similar to type 1 RIPs, linked to lectin B chains, which enable the rapid internalization of the toxin into the cell. For this reason, many type 2 RIPs are very cytotoxic, ricin, volkensin and stenodactylin being the most toxic ones.

Pro-Aging Effects of Xanthine Oxidoreductase Products.

The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium.

Primary Sequence and 3D Structure Prediction of the Plant Toxin Stenodactylin.

Stenodactylin is one of the most potent type 2 ribosome-inactivating proteins (RIPs); its high toxicity has been demonstrated in several models both in vitro and in vivo. Due to its peculiarities, stenodactylin could have several medical and biotechnological applications in neuroscience and cancer treatment. In this work, we report the complete amino acid sequence of stenodactylin and 3D structure prediction.

Transcriptional network inference and master regulator analysis of the response to ribosome-inactivating proteins in leukemia cells.

Gene-regulatory networks reconstruction has become a very popular approach in applied biology to infer and dissect functional interactions of Transcription Factors (TFs) driving a defined phenotypic state, termed as Master Regulators (MRs). In the present work, cutting-edge bioinformatic methods were applied to re-analyze experimental data on leukemia cells (human myelogenous leukemia cell line THP-1 and acute myeloid leukemia MOLM-13 cells) treated for 6 h with two different Ribosome-Inactivating Proteins (RIPs), namely Shiga toxin type 1 (400 ng/mL) produced by Escherichia coli strains and the plant toxin stenodactylin (60 ng/mL), purified from the caudex of Adenia stenodactyla Harms. This analysis allowed us to identify the common early transcriptional response to 28S rRNA damage based on gene-regulatory network inference and Master Regulator Analysis (MRA).

Early Response to the Plant Toxin Stenodactylin in Acute Myeloid Leukemia Cells Involves Inflammatory and Apoptotic Signaling.

Stenodactylin, a highly toxic type 2 ribosome-inactivating protein purified from the caudex of Harms, is a potential anticancer drug candidate. Previous studies demonstrated that stenodactylin induces apoptosis and necroptosis in treated cells, involving the production of reactive oxygen species. We analyzed the effect of stenodactylin on Raji and Ramos (Human Burkitt's lymphoma cells) and MOLM-13 (acute myeloid leukemia cells).

Insights into penicillin-induced Chlamydia trachomatis persistence.

Chlamydia persistence is a viable, but non-cultivable, growth stage, resulting in a long-term relationship with the infected host cell. In vitro, this condition can be induced by different stressor agents, including beta-lactam antibiotics, as penicillin. The aim of this study was to get new insights into the interactions between Chlamydia trachomatis (serovars D and L2) and the epithelial host cells (HeLa) during persistence condition.

Ricin: An Ancient Story for a Timeless Plant Toxin.

The castor plant ( L.) has been known since time immemorial in traditional medicine in the pharmacopeia of Mediterranean and eastern ancient cultures. Moreover, it is still used in folk medicine worldwide.

, a Nutraceutical Approach for Inflammatory Related Diseases.

, commonly called bitter melon, is a plant belonging to Cucurbitaceae family known for centuries for its pharmacological activities, and nutritional properties. Due to the presence of many bioactive compounds, some of which possess potent biological actions, this plant is used in folk medicine all over the world for the treatment of different pathologies, mainly diabetes, but also cancer, and other inflammation-associated diseases. It is widely demonstrated that extracts contribute in lowering glycaemia in patients affected by type 2 diabetes.

Survival and death of intestinal cells infected by Chlamydia trachomatis.

The sexually transmitted pathogen Chlamydia trachomatis (CT) is able to replicate and survive in human intestinal epithelial cells, being the gastro-intestinal tract a suitable site of residence for this microorganism. In this context, no detailed information about the mechanisms of cell death in intestinal cell lines after a chlamydial infection is available. The aim of this study was to compare the effect of two different CT serovars (D and L2) on the survival/death of different intestinal cell lines (Caco-2 and COLO-205), using endocervical cells (HeLa) as a reference model of genital infection.

Hexadecenoic Fatty Acid Positional Isomers and De Novo PUFA Synthesis in Colon Cancer Cells.

Palmitic acid metabolism involves delta-9 and delta-6 desaturase enzymes forming palmitoleic acid (9-16:1; -7 series) and sapienic acid (6-16:1; -10 series), respectively. The corresponding biological consequences and lipidomic research on these positional monounsaturated fatty acid (MUFA) isomers are under development. Furthermore, sapienic acid can bring to the de novo synthesis of the -10 polyunsaturated fatty acid (PUFA) sebaleic acid (5,8-18:2), but such transformations in cancer cells are not known.

Metabolic syndrome and cancer risk: The role of xanthine oxidoreductase.

Obesity and related pathologies such as diabetes and metabolic syndrome are associated with chronic inflammation and cancer. The serum level of xanthine oxidoreductase (XOR) is correlated to obesity-associated metabolic disorders. XOR can play a role in the pathogenesis of both metabolic syndrome and cancer through the inflammatory response and the oxidative stress elicited by the products of its activity.

[Cu(TPMA)(Phen)](ClO): Metallodrug Nanocontainer Delivery and Membrane Lipidomics of a Neuroblastoma Cell Line Coupled with a Liposome Biomimetic Model Focusing on Fatty Acid Reactivity.

The use of copper complexes for redox and oxidative-based mechanisms in therapeutic strategies is an important field of multidisciplinary research. Here, a novel Cu(II) complex [Cu(TPMA)(Phen)](ClO) (Cu-TPMA-Phen, where TPMA = tris-(2-pyridylmethyl)amine and Phen = 1,10-phenanthroline) was studied using both the free and encapsulated forms. A hollow pH-sensitive drug-delivery system was synthesized, characterized, and used to encapsulate and release the copper complex, thus allowing for the comparison with the free drug.

Bouganin, an Attractive Weapon for Immunotoxins.

Bougainvillea ( Willd.) is a plant widely used in folk medicine and many extracts from different tissues of this plant have been employed against several pathologies. The observation that leaf extracts of Bougainvillea possess antiviral properties led to the purification and characterization of a protein, named bouganin, which exhibits typical characteristics of type 1 ribosome-inactivating proteins (RIPs).

The role of xanthine oxidoreductase and uric acid in metabolic syndrome.

Xanthine oxidoreductase (XOR) could contribute to the pathogenesis of metabolic syndrome through the oxidative stress and the inflammatory response induced by XOR-derived reactive oxygen species and uric acid. Hyperuricemia is strongly linked to hypertension, insulin resistance, obesity and hypertriglyceridemia. The serum level of XOR is correlated to triglyceride/high density lipoprotein cholesterol ratio, fasting glycemia, fasting insulinemia and insulin resistance index.