scholarly journals From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic

Toxins ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 517
Author(s):  
Gary M. Bucciarelli ◽  
Maren Lechner ◽  
Audrey Fontes ◽  
Lee B. Kats ◽  
Heather L. Eisthen ◽  
...  

Tetrodotoxin (TTX) is a potent neurotoxin that was first identified in pufferfish but has since been isolated from an array of taxa that host TTX-producing bacteria. However, determining its origin, ecosystem roles, and biomedical applications has challenged researchers for decades. Recognized as a poison and for its lethal effects on humans when ingested, TTX is primarily a powerful sodium channel inhibitor that targets voltage-gated sodium channels, including six of the nine mammalian isoforms. Although lethal doses for humans range from 1.5–2.0 mg TTX (blood level 9 ng/mL), when it is administered at levels far below LD50, TTX exhibits therapeutic properties, especially to treat cancer-related pain, neuropathic pain, and visceral pain. Furthermore, TTX can potentially treat a variety of medical ailments, including heroin and cocaine withdrawal symptoms, spinal cord injuries, brain trauma, and some kinds of tumors. Here, we (i) describe the perplexing evolution and ecology of tetrodotoxin, (ii) review its mechanisms and modes of action, and (iii) offer an overview of the numerous ways it may be applied as a therapeutic. There is much to be explored in these three areas, and we offer ideas for future research that combine evolutionary biology with therapeutics. The TTX system holds great promise as a therapeutic and understanding the origin and chemical ecology of TTX as a poison will only improve its general benefit to humanity.

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 2016
Author(s):  
Keely A. Shaw ◽  
Gordon A. Zello ◽  
Brian Bandy ◽  
Jongbum Ko ◽  
Leandy Bertrand ◽  
...  

The use of dietary supplements is high among athletes and non-athletes alike, as well as able-bodied individuals and those with impairments. However, evidence is lacking in the use of dietary supplements for sport performance in a para-athlete population (e.g., those training for the Paralympics or similar competition). Our objective was to examine the literature regarding evidence for various sport supplements in a para-athlete population. A comprehensive literature search was conducted using PubMed, SPORTDiscus, MedLine, and Rehabilitation and Sports Medicine Source. Fifteen studies met our inclusion criteria and were included in our review. Seven varieties of supplements were investigated in the studies reviewed, including caffeine, creatine, buffering agents, fish oil, leucine, and vitamin D. The evidence for each of these supplements remains inconclusive, with varying results between studies. Limitations of research in this area include the heterogeneity of the subjects within the population regarding functionality and impairment. Very few studies included individuals with impairments other than spinal cord injury. Overall, more research is needed to strengthen the evidence for or against supplement use in para-athletes. Future research is also recommended on performance in para-athlete populations with classifiable impairments other than spinal cord injuries.


Toxins ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 496
Author(s):  
Ana Campos-Ríos ◽  
Lola Rueda-Ruzafa ◽  
Salvador Herrera-Pérez ◽  
Paula Rivas-Ramírez ◽  
José Antonio Lamas

Visceral pain is one of the most common symptoms associated with functional gastrointestinal (GI) disorders. Although the origin of these symptoms has not been clearly defined, the implication of both the central and peripheral nervous systems in visceral hypersensitivity is well established. The role of several pathways in visceral nociception has been explored, as well as the influence of specific receptors on afferent neurons, such as voltage-gated sodium channels (VGSCs). VGSCs initiate action potentials and dysfunction of these channels has recently been associated with painful GI conditions. Current treatments for visceral pain generally involve opioid based drugs, ≠≠which are associated with important side-effects and a loss of effectiveness or tolerance. Hence, efforts have been intensified to find new, more effective and longer-lasting therapies. The implication of VGSCs in visceral hypersensitivity has drawn attention to tetrodotoxin (TTX), a relatively selective sodium channel blocker, as a possible and promising molecule to treat visceral pain and related diseases. As such, here we will review the latest information regarding this toxin that is relevant to the treatment of visceral pain and the possible advantages that it may offer relative to other treatments, alone or in combination.


2021 ◽  
pp. 130446
Author(s):  
ES Anooj ◽  
M Charumathy ◽  
Vipin Sharma ◽  
B.V. Vibala ◽  
S.T. Gopukumar ◽  
...  

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 166 ◽  
Author(s):  
Lucia Lombardi ◽  
Annarita Falanga ◽  
Valentina Del Genio ◽  
Stefania Galdiero

Peptide drugs hold great promise for the treatment of infectious diseases thanks to their novel mechanisms of action, low toxicity, high specificity, and ease of synthesis and modification. Naturally developing self-assembly in nature has inspired remarkable interest in self-assembly of peptides to functional nanomaterials. As a matter of fact, their structural, mechanical, and functional advantages, plus their high bio-compatibility and bio-degradability make them excellent candidates for facilitating biomedical applications. This review focuses on the self-assembly of peptides for the fabrication of antibacterial nanomaterials holding great interest for substituting antibiotics, with emphasis on strategies to achieve nano-architectures of self-assembly. The antibacterial activities achieved by these nanomaterials are also described.


2008 ◽  
Vol 78 (1) ◽  
pp. 84-106 ◽  
Author(s):  
MARK CONLEY

"Strategy instruction" is quickly becoming one of the most common — and perhaps the most commonly misunderstood — components of adolescent literacy research and practice. In this essay, veteran teacher educator Mark Conley argues that a particular type of strategy instruction known as cognitive strategy instruction holds great promise for improving adolescents' reading, writing, and thinking across content areas. However, he further suggests that we do not yet have the research needed to adequately understand and maximize the potential of cognitive strategy instruction in secondary content-area classrooms. After situating cognitive strategy instruction in the larger context of research on adolescent literacy and school-to-work transitions, Conley provides classroom examples of cognitive strategy instruction, demonstrates the need for meaningful integration of cognitive strategies in teacher education, and recommends specific directions for future research needed to understand and maximize the benefits of cognitive strategy instruction for adolescents.


Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 268 ◽  
Author(s):  
Andreia Jorge ◽  
Ramon Eritja

Molecular self-assembling is ubiquitous in nature providing structural and functional machinery for the cells. In recent decades, material science has been inspired by the nature’s assembly principles to create artificially higher-order structures customized with therapeutic and targeting molecules, organic and inorganic fluorescent probes that have opened new perspectives for biomedical applications. Among these novel man-made materials, DNA nanostructures hold great promise for the modular assembly of biocompatible molecules at the nanoscale of multiple shapes and sizes, designed via molecular programming languages. Herein, we summarize the recent advances made in the designing of DNA nanostructures with special emphasis on their application in biomedical research as imaging and diagnostic platforms, drug, gene, and protein vehicles, as well as theranostic agents that are meant to operate in-cell and in-vivo.


Author(s):  
Norman Schaffer ◽  
Martin Engert ◽  
Girts Leontjevs ◽  
Helmut Krcmar

Software tools hold great promise to support the modeling, analyzing, and innovation of business models. Current tools only focus on the design of business models and do not incorporate the complexity of existing interdependencies between business model components. These tools merely allow simulating inherent dynamics within the models or different strategic decision scenarios. In this research, we use design science research to develop a prototype that is capable of modeling and simulating dynamic business models. We use system dynamics as a simulation approach and containers to allow deployment as web applications. This paper represents the first of three design cycles, realizing six out of 59 requirements that are collected from the literature on software tools for business models. We contribute toward the design of novel artifacts for business model innovation as well as their evaluation. Future research can use these results to build tools that consider and address the complexity of business models. Lastly, we present several options for extending the proposed tool in the future.


2021 ◽  
Vol 22 (22) ◽  
pp. 12308
Author(s):  
Tao Tong ◽  
Qi Li ◽  
Wei Jiang ◽  
Guang Chen ◽  
Dawei Xue ◽  
...  

Adaptation to unfavorable abiotic stresses is one of the key processes in the evolution of plants. Calcium (Ca2+) signaling is characterized by the spatiotemporal pattern of Ca2+ distribution and the activities of multi-domain proteins in integrating environmental stimuli and cellular responses, which are crucial early events in abiotic stress responses in plants. However, a comprehensive summary and explanation for evolutionary and functional synergies in Ca2+ signaling remains elusive in green plants. We review mechanisms of Ca2+ membrane transporters and intracellular Ca2+ sensors with evolutionary imprinting and structural clues. These may provide molecular and bioinformatics insights for the functional analysis of some non-model species in the evolutionarily important green plant lineages. We summarize the chronological order, spatial location, and characteristics of Ca2+ functional proteins. Furthermore, we highlight the integral functions of calcium-signaling components in various nodes of the Ca2+ signaling pathway through conserved or variant evolutionary processes. These ultimately bridge the Ca2+ cascade reactions into regulatory networks, particularly in the hormonal signaling pathways. In summary, this review provides new perspectives towards a better understanding of the evolution, interaction and integration of Ca2+ signaling components in green plants, which is likely to benefit future research in agriculture, evolutionary biology, ecology and the environment.


Author(s):  
Vandana Prasad ◽  
Lubna Siddiqui ◽  
Pawan Kumar Mishra ◽  
Adam Ekielski ◽  
Sushama Talegaonkar

Background: Synthetic polymers present disadvantages such as high cost, limited availability, safety concerns, environmental hazards and overtime accumulation in body. Lignin, an aromatic biopolymer, is highly abundant and offers various advantages including cost effectiveness, biocompatibility and biodegradability. It also possesses various pharmacological activities including antioxidant, antibacterial, anticancer and UV protection, thus lignin has become a popular biopolymer in recent years and is no more considered as bio-waste rather an extensive research is been carried out on developing it as drug carrier. Lignin also has non-biomedical applications including dispersing agents, surfactants, detergent/cleaning agents, energy storage, etc. Methods: This review compiles patents granted on production of technical lignin, different lignin therapeutic carriers and its biomedical and non-biomedical applications. The literature is collected from recent years including both articles as well as patents and is carefully analyzed and compiled in an easy to comprehend pattern for guiding future research. Results: The reviewed patents and articles highlighted the advancement made in lignin isolation and valorization. Numerous lignin nanoformulations as drug delivery agents or as standalone entities with various pharmacological actions like antibacterial, antioxidant or UV protectant have been reported. As well as industrial applications of lignin as adhesives, insulators or supercapacitors have also made lignin a biopolymer of choice. Conclusion: Lignin being a bio-inspired polymer has huge potential in commercial applications. New methods of lignin isolation from lignocellulosic biomass including physical pretreatments, solvent fraction, and chemical and biological pretreatment have been widely patented. Several micro/nano lignin formulations with improved and controllable reactivity like nanocontainers, nanocapsules, nanoparticles have also been reported recently. Also various pharmacological properties of lignin have also been explored, thus valorization of lignin is a hot topic of hour.


Sign in / Sign up

Export Citation Format

Share Document