The spinal cord in vitro: What can it tell us about nociception?

The use of amphibian and mammalian in vitro spinal cord preparations, e.g., hemisected cord and transverse slices, has gained in popularity over the years due to the flexibility and ease of use of such preparations compared to classical in vivo approaches. When combined with modern experimental methodologies, such as patch clamping of visualized single cells or post-experimental neuroanatomy, this approach provides a powerful addition to the armamentarium available to study nociceptive processing in the dorsal horn. Some of these novel experimental approaches and the insight into nociception that they have provided are described below. Neirofiziologiya/Neurophysiology, Vol. 38, Nos. 5/6, pp. 481–491, September–December, 2006.     

Microdetermination of caffeine in blood by gas chromatography—mass spectrometry

A micromethod for the quantitative analysis of caffeine present in small quantities (100 μl) of whole blood is described. It is based on the gas chromatographic—mass spectrometric analysis of chloroform extracts of biological samples. The method is relatively simple, rapid, specific and sensitive, as little as 20 ng of caffeine can be measured.     

Chemical reactivity and uses of 1-phenyl-3-methyl-5-pyrazolone (PMP), also known as edaravone

1-Phenyl-3-methyl-5-pyrazolone is a reagent, known as PMP, used to derivatize monosaccharides for the study of polysaccharides composition and structure, and for the dosage of carbohydrates in complex media. The same molecule is also known as edaravone, a drug approved for the treatment of stroke and amyotrophic lateral sclerosis. It is also a reactive molecule susceptible to form stable adducts with aromatic aldehydes, such as formylpterin and vanillin. In addition, the molecule serves as a scaffold to design of edaravone analogs and drug conjugates, with various pharmacological properties (antioxidant, anticancer, antiviral). We have analyzed the multiple usages of PMP/edaravone to highlight the reactivity of the molecule and its wide range of applications. This phenyl-pyrazolone compound, considered by many as a biochemical reagent and by other as a clinically useful drug, has not yet revealed the full extent of its capacities and benefits.     

The advent of de novo proteins for cancer immunotherapy

Engineered proteins are revolutionizing immunotherapy, but advances are still needed to harness their full potential. Traditional protein engineering methods use naturally existing proteins as a starting point, and therefore, are intrinsically limited to small alterations of a protein's natural structure and function. Conversely, computational de novo protein design is free of such limitation, and can produce a virtually infinite number of novel protein sequences, folds, and functions. Recently, we used de novo protein engineering to create Neoleukin-2/15 (Neo-2/15), a protein mimetic of the function of both interleukin-2 (IL-2) and interleukin-15 (IL-15). To our knowledge, Neo-2/15 is the first de novo protein with immunotherapeutic activity, and in murine cancer models, it has demonstrated enhanced therapeutic potency and reduced toxicity compared to IL-2. De novo protein design is already showcasing its tremendous potential for driving the next wave of protein-based therapeutics that are explicitly engineered to treat disease.     

COVID-19 pandemic and patients with cancer: The protocol of a Clinical Oncology center in Tehran,Iran

AimTo provide recommendations for the management of patients with cancer in the COVID-19 era.BackgroundThe current global pandemic of COVID-19 has severely impacted global healthcare systems. Several groups of people are considered high-risk for SARS-CoV-2 infection, including patients with cancer. Therefore, protocols for the better management of these patients during this viral pandemic are necessary. So far, several protocols have been presented regarding the management of patients with cancer during the COVID-19 pandemic. However, none of them points to a developing country with limited logistics and facilities.MethodsIn this review, we have provided a summary of recommendations on the management of patients with cancer during the COVID-19 pandemic based on our experience in Shohada-e Tajrish Hospital, Iran.ResultsWe recommend that patients with cancer should be managed in an individualized manner during the COVID-19 pandemic.ConclusionsOur recommendation provides a guide for oncology centers of developing countries for better management of cancer.     

Brain tumors: Cancer stem-like cells interact with tumor microenvironment

Cancer stem-like cells (CSCs) with potential of self-renewal drive tumorigenesis. Brain tumor microenvironment (TME) has been identified as a critical regulator of malignancy progression. Many researchers are searching new ways to characterize tumors with the goal of predicting how they respond to treatment. Here, we describe the striking parallels between normal stem cells and CSCs. We review the microenvironmental aspects of brain tumors, in particular composition and vital roles of immune cells infiltrating glioma and medulloblastoma. By highlighting that CSCs cooperate with TME via various cellular communication approaches, we discuss the recent advances in therapeutic strategies targeting the components of TME. Identification of the complex and interconnected factors can facilitate the development of promising treatments for these deadly malignancies.     

Minibrain-related kinase/dual-specificity tyrosine-regulated kinase 1B implication in stem/cancer stem cells biology

Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B), also known as minibrain-related kinase (MIRK) is one of the best functionally studied members of the DYRK kinase family. DYRKs comprise a family of protein kinases that are emerging modulators of signal transduction pathways, cell proliferation and differentiation, survival, and cell motility. DYRKs were found to participate in several signaling pathways critical for development and cell homeostasis. In this review, we focus on the DYRK1B protein kinase from a functional point of view concerning the signaling pathways through which DYRK1B exerts its cell type-dependent function in a positive or negative manner, in development and human diseases. In particular, we focus on the physiological role of DYRK1B in behavior of stem cells in myogenesis, adipogenesis, spermatogenesis and neurogenesis, as well as in its pathological implication in cancer and metabolic syndrome. Thus, understanding of the molecular mechanisms that regulate signaling pathways is of high importance. Recent studies have identified a close regulatory connection between DYRK1B and the hedgehog (HH) signaling pathway. Here, we aim to bring together what is known about the functional integration and cross-talk between DYRK1B and several signaling pathways, such as HH, RAS and PI3K/mTOR/AKT, as well as how this might affect cellular and molecular processes in development, physiology, and pathology. Thus, this review summarizes the major known functions of DYRK1B kinase, as well as the mechanisms by which DYRK1B exerts its functions in development and human diseases focusing on the homeostasis of stem and cancer stem cells.     

Selenium nanovirus and its cytotoxicity in selenite-exposed higher living organisms

Selenium (Se) is an essential micronutrient in living organisms, having a narrow margin between essential and potentially toxic intake/exposure. Thus, the biochemistry of Se in living organisms must be studied in-depth to determine the underlying mechanism of Se cytotoxicity. In this study, we report the emergence of selenium nanovirus (SeNVs) in selenite-exposed fish (freshwater and saltwater) and plants (dryland) and its toxicity in them. SeNVs were found in both the abdomen and tail of Oryzias melastigma and saltwater Rhodeus ocellatus, which led to their death. The occurrence of the intracellular assembly of SeNVs was observed in the roots and leaves of corn Zea mays, but not in those of Limnobium laevigatum. SeNVs led to the death of Z. mays but caused chronic toxicity in L. laevigatum. SeNVs should be a system or structure that dissipates the intracellular redox gradients of the host cells, with simple information consisting Se–O, Se–N, or Se–S bond, that would ensure elemental Se ligand binding with nearly specific biomolecules in host cells, thereby maintaining their composition and stabilizing their structure. The multiple toxic effects of Se, therefore, could be the consequence of increase of entropy in the host cells caused by the intracellular assembly of SeNVs. This study may provide an insight into the underlying mechanism of Se in environmental toxicology and its applications in human health.