Nanomagnetic materials offer exciting avenues for probing cell mechanics and activating mechanosensitive ion channels, as well as for advancing cancer therapies. Most experimental works so far have used superparamagnetic materials. This report describes a first approach based on interfacing cells with lithographically defined microdiscs that possess a spin-vortex ground state. When an alternating magnetic field is applied the microdisc vortices shift, creating an oscillation, which transmits a mechanical force to the cell. Because reduced sensitivity of cancer cells toward apoptosis leads to inappropriate cell survival and malignant progression, selective induction of apoptosis is of great importance for the anticancer therapeutic strategies. We show that the spin-vortex-mediated stimulus creates two dramatic effects: compromised integrity of the cellular membrane, and initiation of programmed cell death. A low-frequency field of a few tens of hertz applied for only ten minutes was sufficient to achieve approximately 90% cancer-cell destruction in vitro.

Magnetic-Vortex Microdiscs for Targeted Cancer-Cell Destruction

Ceramide is a lipid messenger at the heart of sphingolipid metabolism In concert with its metabolizing enzymes, particularly sphingomyelinases, it has key roles in regulating the physical properties of biological membranes, including the formation of membrane microdomains Thus, ceramide and its related molecules have been attributed significant roles in nearly all steps of the viral life cycle: they may serve directly as receptors or co-receptors for viral entry, form microdomains that cluster entry receptors and/or enable them to adopt the required conformation or regulate their cell surface expression Sphingolipids can regulate all forms of viral uptake, often through sphingomyelinase activation, and mediate endosomal escape and intracellular trafficking Ceramide can be key for the formation of viral replication sites Sphingomyelinases often mediate the release of new virions from infected cells Moreover, sphingolipids can contribute to viral-induced apoptosis and morbidity in viral diseases, as well as virus immune evasion Alpha-galactosylceramide, in particular, also plays a significant role in immune modulation in response to viral infections This review will discuss the roles of ceramide and its related molecules in the different steps of the viral life cycle We will also discuss how novel strategies could exploit these for therapeutic benefit

https://www.mdpi.com/1422-0067/22/11/5676/pdf

Ceramide and Related Molecules in Viral Infections.

Myocardial ischemia/reperfusion (I/R) injury is associated with high mortality and morbidity, however, it has no curative treatment. Farrerol (FA), an active compound extracted from rhododendron, has antibacterial, anti-inflammatory, and antioxidant activities, but its effect and mechanism of FA in I/R injury remain unclear. Here, we found that FA alleviated myocardial I/R in vivo, and decreased the secretion of myocardial injury factors (CK-MB, LDH, troponin-1, and NT-proBNP) while inhibiting the release of inflammatory factors (IL-1β, IL-6, and TNF-α). FA could also alleviate excessive oxidative stress by elevating the level of antioxidant enzymes and reducing oxidation products; and decreased reduced the expression of apoptosis-associated proteins (cleaved caspase-3, Bax, and Bcl-2). However, inhibiting the autophagic pathway or knocking out the Nrf2 gene did not eliminate the myocardial protective effect of FA, but interestingly, macrophage clearance and Nlrp3 deficiency effectively blocked the myocardial protective effect of FA. In addition, FA suppressed NLRP3 inflammasome activation by interfering with NLRP3 and NEK7. In conclusion, these results support drug-targeted macrophage therapy for myocardial I/R and indicate that FA may be used as an immunomodulator in clinical therapy for myocardial I/R.

Farrerol Alleviates Myocardial Ischemia/Reperfusion Injury by Targeting Macrophages and NLRP3

Simple Summary Glioma is a life-threatening malignancy where conventional therapies are ineffective, and microorganisms are a promising weapon that can be used in cancer treatment. In order to promote the use of microbial therapies in glioma, this article summarizes the microorganisms that have been used for glioma treatment in recent years and their mechanisms and how the gut flora affect glioma progression, suggesting the current limitations of this approach and possible future directions for its development. This paper may bring new inspiration to those who investigate glioma, promote the progress of glioma therapy research, and bring new promise to glioma patients. Abstract Glioma is the most common primary malignancy of the central nervous system (CNS), and 50% of patients present with glioblastoma (GBM), which is the most aggressive type. Currently, the most popular therapies are progressive chemotherapy and treatment with temozolomide (TMZ), but the median survival of glioma patients is still low as a result of the emergence of drug resistance, so we urgently need to find new therapies. A growing number of studies have shown that the diversity, bioactivity, and manipulability of microorganisms make microbial therapy a promising approach for cancer treatment. However, the many studies on the research progress of microorganisms and their derivatives in the development and treatment of glioma are scattered, and nobody has yet provided a comprehensive summary of them. Therefore, in this paper, we review the research progress of microorganisms and their derivatives in the development and treatment of glioma and conclude that it is possible to treat glioma by exogenous microbial therapies and targeting the gut–brain axis. In this article, we discuss the prospects and pressing issues relating to these therapies with the aim of providing new ideas for the treatment of glioma.

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Investigational Microbiological Therapy for Glioma

The idea of using the lytic power of viruses against malignant cells has been entertained for many decades. However, oncolytic viruses gained broad attention as an emerging anti-cancer therapy only recently with the successful implementation of several oncolytic viruses to treat advanced melanoma. Here we review the history of oncolytic viruses in the Russian Federation and recent biotechnological advances in connection with the perspectives of their practical use against aggressive tumors such as glioblastoma or pancreatic cancer. A particular emphasis is made on novel applications of safe non-lytic virus-derived vectors armed with prodrug-converting enzyme transgenes. Rational improvement of oncotropism by conjugation with biopolymers and nanoformulations is also discussed.

Anti-Cancer Virotherapy in Russia: Lessons from the Past, Current Challenges and Prospects for the Future.

Autophagy is a catabolic process that allows cells to scavenge damaged organelles and produces energy to maintain cellular homeostasis. It is also an effective defense method for cells, which allows them to identify an internalized pathogen and destroy it through the fusion of the autophagosome and lysosomes. Recent reports have demonstrated that various chemotherapeutic agents and viral gene therapeutic vehicles provide therapeutic advantages for patients with glioblastoma as monotherapy or in combination with standards of care. Despite nonstop efforts to develop effective antiglioma therapeutics, tumor-induced autophagy in some studies manifests tumor resistance and glioma progression. Here, we explore the functional link between autophagy regulation mediated by oncolytic viruses and discuss how intracellular interactions control autophagic signaling in glioblastoma. Autophagy induced by oncolytic viruses plays a dual role in cell death and survival. On the one hand, autophagy stimulation has mostly led to an increase in cytotoxicity mediated by the oncolytic virus, but, on the other hand, autophagy is also activated as a cell defense mechanism against intracellular pathogens and modulates antiviral activity through the induction of ER stress and unfolded protein response (UPR) signaling. Despite the fact that the moment of switch between autophagic prosurvival and prodeath modes remains to be known, in the context of oncolytic virotherapy, cytotoxic autophagy is a crucial mechanism of cancer cell death.

Oncolytic Virus-Induced Autophagy in Glioblastoma

A viral infection that involves virus invasion, protein synthesis, and virion assembly is typically accompanied by sharp fluctuations in the intracellular levels of metabolites. Under certain conditions, dramatic metabolic shifts can result in various types of cell death. Here, we review different types of adenovirus-induced cell death associated with changes in metabolic profiles of the infected cells. As evidenced by experimental data, in most cases changes in the metabolome precede cell death rather than represent its consequence. In our previous study, the induction of autophagic cell death was observed following adenovirus-mediated lactate production, acetyl-CoA accumulation, and ATP release, while apoptosis was demonstrated to be modulated by alterations in acetate and asparagine metabolism. On the other hand, adenovirus-induced ROS production and ATP depletion were demonstrated to play a significant role in the process of necrotic cell death. Interestingly, the accumulation of ceramide compounds was found to contribute to the induction of all the three types of cell death mentioned above. Eventually, the characterization of metabolite analysis could help in uncovering the molecular mechanism of adenovirus-mediated cell death induction and contribute to the development of efficacious oncolytic adenoviral vectors.

Metabolome-Driven Regulation of Adenovirus-Induced Cell Death.

Glioblastoma (GBM) is one of the most aggressive (grade IV) gliomas characterized by a high rate of recurrence, resistance to therapy and a grim survival prognosis. The long-awaited improvement in GBM patients’ survival rates essentially depends on advances in the development of new therapeutic approaches. Recent preclinical studies show that nanoscale materials could greatly contribute to the improvement of diagnostics and management of brain cancers. In the current review, we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches. Moreover, we will summarize the main evidence for the potential of the IL-13R alpha 2 receptor (IL13α2R) targeting in GBM early diagnostics and experimental therapy.

Anastasia Laevskaya

Papers

Oncolytic Virus-Induced Autophagy in Glioblastoma

Metabolome-Driven Regulation of Adenovirus-Induced Cell Death.

The IL13α 2R paves the way for anti-glioma nanotherapy