Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Tangeretin: a mechanistic review of its pharmacological and therapeutic effects

To date, a large number of synthetic drugs have been developed for the treatment and prevention of different disorders, such as neurodegenerative diseases, diabetes mellitus, and cancer. However, these drugs suffer from a variety of drawbacks including side effects and low efficacy. In response to this problem, researchers have focused on the plant-derived natural products due to their valuable biological activities and low side effects. Flavonoids consist of a wide range of naturally occurring compounds exclusively found in fruits and vegetables and demonstrate a number of pharmacological and therapeutic effects. Tangeretin (TGN) is a key member of flavonoids that is extensively found in citrus peels. It has different favorable biological activities such as antioxidant, anti-inflammatory, antitumor, hepatoprotective, and neuroprotective effects. In the present review, we discuss the various pharmacological and therapeutic effects of TGN and then, demonstrate how this naturally occurring compound affects signaling pathways to exert its impacts. © 2020 Walter de Gruyter GmbH, Berlin/Boston 2020

Topoisomerase inhibitors: Pharmacology and emerging nanoscale delivery systems

Topoisomerase enzymes have shown unique roles in replication and transcription. These enzymes which were initially found in Escherichia coli have attracted considerable attention as target molecules for cancer therapy. Nowadays, there are several topoisomerase inhibitors in the market to treat or at least control the progression of cancer. However, significant toxicity, low solubility and poor pharmacokinetic properties have limited their wide application and these characteristics need to be improved. Nano-delivery systems have provided an opportunity to modify the intrinsic properties of molecules and also to transfer the toxic agent to the target tissues. These delivery systems leads to the re-introduction of existing molecules present in the market as novel therapeutic agents with different physicochemical and pharmacokinetic properties. This review focusses on a variety of nano-delivery vehicles used for the improvement of pharmacological properties of topoisomerase inhibitors and thus enabling their potential application as novel drugs in the market. © 2019 Elsevier Lt

Graphene as a promising multifunctional nanoplatform for glioblastoma theranostic applications

Glioblastoma multiform (GBM) is one of the most incurable invasive and malignant cancers of the central nervous system. The lifespan of the patients from the diagnosis is less than 15 months due to the lack of an effective treatment strategy to eliminate it. The potential of nanotechnology to revolutionize the strategies to fight against cancer has led researchers to use this paradigm for drug development. Despite promising reports on the potential of graphene in drug delivery, diagnostic and therapeutic applications, there is no comprehensive review of the potential theranostic applications of graphene on GBM. For example, embryonic and neural stem cells tend to differentiate to neurons compared to glial cells on a graphene surface. This potential shows two faces of the graphene medal as a suitable candidate in the diminishing of GBM along with the enhancement of neurogenesis in the tumor site. In this review, we have discussed the recent discoveries on GBM etiology and graphene characteristics. We have also highlighted the cell signaling mechanisms which are triggered by graphene in glioblastoma cells as well as the effectiveness of graphene in diagnosis, treatment, and theranostics applications for GBM. Finally, we have shown the state-of-the-art and promising perspective of graphene in GBM diagnosis and therapy. © 2020 Elsevier B.V

In vivo gene delivery mediated by non-viral vectors for cancer therapy

Gene therapy by expression constructs or down-regulation of certain genes has shown great potential for the treatment of various diseases. The wide clinical application of nucleic acid materials dependents on the development of biocompatible gene carriers. There are enormous various compounds widely investigated to be used as non-viral gene carriers including lipids, polymers, carbon materials, and inorganic structures. In this review, we will discuss the recent discoveries on non-viral gene delivery systems. We will also highlight the in vivo gene delivery mediated by non-viral vectors to treat cancer in different tissue and organs including brain, breast, lung, liver, stomach, and prostate. Finally, we will delineate the state-of-the-art and promising perspective of in vivo gene editing using non-viral nano-vectors. © 2020 Elsevier B.V

Autophagy modulators: Mechanistic aspects and drug delivery systems

10.3390/biom9100530Biomolecules91053

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

International audienceIn 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field