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Frontiers in Bioscience (Landmark... Jun 2016A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation,... (Review)
Review
A large body of evidence points to the positive effects of dietary supplementation of acetyl-L-carnitine (ALC). Its use has shown health benefits in neuroinflammation, which is a common denominator in a host of neurodegenerative diseases. ALC is the principal acetyl ester of L-Carnitine (LC), and it plays an essential role in intermediary metabolism, acting as a donor of acetyl groups and facilitating the transfer of fatty acids from cytosol to mitochondria during beta-oxidation. Dietary supplementation of ALC exerts neuroprotective, neurotrophic, antidepressive and analgesic effects in painful neuropathies. ALC also has antioxidant and anti-apoptotic activity. Moreover, ALC exhibits positive effects on mitochondrial metabolism, and shows promise in the treatment of aging and neurodegenerative pathologies by slowing the progression of mental deterioration. In addition, ALC plays neuromodulatory effects on both synaptic morphology and synaptic transmission. These effects are likely due to affects of ALC through modulation of gene expression on several targets in the central nervous system. Here, we review the current state of knowledge on effects of ALC in the nervous system.
Topics: Acetylcarnitine; Aging; Animals; Apoptosis; Brain; Dietary Supplements; Energy Metabolism; Epigenesis, Genetic; Heme Oxygenase-1; Hirudo medicinalis; Humans; Mitochondria; Models, Animal; Nerve Degeneration; Neuroprotective Agents; Pain; Peripheral Nervous System Diseases; Synaptic Transmission
PubMed: 27100509
DOI: 10.2741/4459 -
Integrative Medicine Research Dec 2017Complementary medicine methods have a long history, but modern medicine has just recently focused on their possible modes of action. Medicinal leech therapy (MLT) or... (Review)
Review
Complementary medicine methods have a long history, but modern medicine has just recently focused on their possible modes of action. Medicinal leech therapy (MLT) or hirudotherapy, an old technique, has been studied by many researchers for possible effects on various diseases such as inflammatory diseases, osteoarthritis, and after different surgeries. has widest therapeutic usage among the leeches, but worldwide, many different species were tested and studied. Leeches secrete more than 20 identified bioactive substances such as antistasin, eglins, guamerin, hirudin, saratin, bdellins, complement, and carboxypeptidase inhibitors. They have analgesic, anti-inflammatory, platelet inhibitory, anticoagulant, and thrombin regulatory functions, as well as extracellular matrix degradative and antimicrobial effects, but with further studies, the spectrum of effects may widen. The technique is cheap, effective, easy to apply, and its modes of action have been elucidated for certain diseases. In conclusion, for treatment of some diseases, MLT is not an alternative, but is a complementary and/or integrative choice. MLT is a part of multidisciplinary treatments, and secretes various bioactive substances. These substances vary among species and different species should be evaluated for both treatment capability and their particular secreted molecules. There is huge potential for novel substances and these could be future therapeutics.
PubMed: 29296560
DOI: 10.1016/j.imr.2017.08.001 -
Frontiers in Pharmacology 2021Hirudin, an acidic polypeptide secreted by the salivary glands of (also known as "Shuizhi" in traditional Chinese medicine), is the strongest natural specific inhibitor... (Review)
Review
Hirudin, an acidic polypeptide secreted by the salivary glands of (also known as "Shuizhi" in traditional Chinese medicine), is the strongest natural specific inhibitor of thrombin found so far. Hirudin has been demonstrated to possess potent anti-thrombotic effect in previous studies. Recently, increasing researches have focused on the anti-thrombotic activity of the derivatives of hirudin, mainly because these derivatives have stronger antithrombotic activity and lower bleeding risk. Additionally, various bioactivities of hirudin have been reported as well, including wound repair effect, anti-fibrosis effect, effect on diabetic complications, anti-tumor effect, anti-hyperuricemia effect, effect on cerebral hemorrhage, and others. Therefore, by collecting and summarizing publications from the recent two decades, the pharmacological activities, pharmacokinetics, novel preparations and derivatives, as well as toxicity of hirudin were systematically reviewed in this paper. In addition, the clinical application, the underlying mechanisms of pharmacological effects, the dose-effect relationship, and the development potential in new drug research of hirudin were discussed on the purpose of providing new ideas for application of hirudin in treating related diseases.
PubMed: 33935784
DOI: 10.3389/fphar.2021.660757 -
Cell & Bioscience 2020Acting as a cellular cleaner by packaging and transporting defective proteins and organelles to lysosomes for breakdown, autophagic process is involved in the regulation... (Review)
Review
BACKGROUND
Acting as a cellular cleaner by packaging and transporting defective proteins and organelles to lysosomes for breakdown, autophagic process is involved in the regulation of cell remodeling after cell damage or cell death in both vertebrate and invertebrate. In human, limitations on the regenerative capacity of specific tissues and organs make it difficult to recover from diseases. Comprehensive understanding on its mechanism within invertebrate have strong potential provide helpful information for challenging these diseases.
METHOD
In this study, recent findings on the autophagy function in three invertebrates including planarian, hydra and leech with remarkable regenerative ability were summarized. Furthermore, molecular phylogenetic analyses of DjATGs and HvATGs were performed on these three invertebrates compared to that of , , , and .
RESULTS
In comparison with , , , and human, our analysis exhibits the following characteristics of autophagy and its function in regeneration within invertebrate. Phylogenetical analysis of ATGs revealed that most autophagy-related genes (ATGs) were highly similar to their homologs in other species, which indicates that autophagy is a highly conservative biological function in both vertebrate and invertebrate. Structurally, almost all the core amino acids necessary for the function of ATG8 in mammal were observed in invertebrate HvATG8s and DjATG8s. For instance, ubiquitin-like domain as a signature structure in each ATG8, was observed in all ATG8s in three invertebrates. Basically, autophagy plays a key role in the regulation of regeneration in planarian. DjATG8-2 and DjATG8-3 associated with mTOR signaling pathway are sophisticated in the invertebrate tissue/organ regeneration. Furthermore, autophagy is involved in the pathway of neutralization of toxic molecules input from blood digestion in the leech.
CONCLUSIONS
The recent investigations on autophagy in invertebrate including planarian, hydra and leech suggest that autophagy is evolutionally conserved from yeast to mammals. The fundamental role of its biological function in the invertebrate contributing to the regeneration and maintenance of cellular homeostasis in these three organisms could make tremendous information to confront life threatening diseases in human including cancers and cardiac disorders.
PubMed: 32974004
DOI: 10.1186/s13578-020-00467-3 -
British Journal of Pharmacology Jul 2022Hirudin variants are the most powerful thrombin inhibitors discovered to date, with a lower risk of bleeding than heparin. For anticoagulation, the C-termini of hirudin...
BACKGROUND AND PURPOSE
Hirudin variants are the most powerful thrombin inhibitors discovered to date, with a lower risk of bleeding than heparin. For anticoagulation, the C-termini of hirudin variants bind to the exocite I of thrombin. Anticoagulant effects of gene-recombinant hirudin are weaker than natural hirudin for the reason of lacking tyrosine O-sulfation at C-terminus.
EXPERIMENTAL APPROACH
An integrative pharmacological study was carried out using molecular dynamic, molecular biological and in vivo and in vitro experiments to elucidate the anticoagulant effects of protein-engineered hirudins.
KEY RESULTS
Molecular dynamic analysis showed that modifications of the C-termini of hirudin variant 1 of Hirudo medicinalis (HV1) and hirudin variant 2 of Hirudinaria manillensis (HM2) changed the binding energy of the C-termini to human thrombin. The study indicated that Asp61 of HM2 that corresponds to sulfated Tyr63 of HV1 is critical for inhibiting thrombin activities. Further, the anticoagulant effects of HV1 and HM2 were improved when the amino acid residues adjacent to Asp61 were mutated to Asp. These improvements were prolongation of the activated partial thromboplastin time, prothrombin time and thrombin time of human blood, and decreased K and IC values. In the in vivo experiments, mutations at C-termini of HV1 and HM2 significantly changed partial thromboplastin time, prothrombin and thrombin time CONCLUSION AND IMPLICATIONS: The study indicated that the anticoagulant effects of gene-engineered HM2 are stronger than gene-engineered HV1 and HM2-E60D-I62D has the strongest effects and could be an antithrombotic with better therapeutic effects.
Topics: Amino Acid Sequence; Animals; Anticoagulants; Hirudins; Hirudo medicinalis; Humans; Molecular Dynamics Simulation; Recombinant Proteins; Thrombin
PubMed: 35135035
DOI: 10.1111/bph.15816 -
Mitochondrial DNA. Part B, Resources Mar 2016Here we present two incomplete mitochondrial genome sequences of and (Annelida, Hirudinea). The corresponding sequences are 14,729 and 14,604 base pairs in length....
Here we present two incomplete mitochondrial genome sequences of and (Annelida, Hirudinea). The corresponding sequences are 14,729 and 14,604 base pairs in length. They contain all mitochondrial genes (13 protein-coding genes, 22 tRNAs and two rRNAs) but lack the non-coding region. Nevertheless, the robust reconstruction of their phylogenetic relationships presented here reveals distinct separation of both leeches from other annelids and at the same time relatively high dissimilarity between each other.
PubMed: 33473467
DOI: 10.1080/23802359.2016.1157774 -
BMC Genomics Apr 2020Salivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today.
BACKGROUND
Salivary cell secretion (SCS) plays a critical role in blood feeding by medicinal leeches, making them of use for certain medical purposes even today.
RESULTS
We annotated the Hirudo medicinalis genome and performed RNA-seq on salivary cells isolated from three closely related leech species, H. medicinalis, Hirudo orientalis, and Hirudo verbana. Differential expression analysis verified by proteomics identified salivary cell-specific gene expression, many of which encode previously unknown salivary components. However, the genes encoding known anticoagulants have been found to be expressed not only in salivary cells. The function-related analysis of the unique salivary cell genes enabled an update of the concept of interactions between salivary proteins and components of haemostasis.
CONCLUSIONS
Here we report a genome draft of Hirudo medicinalis and describe identification of novel salivary proteins and new homologs of genes encoding known anticoagulants in transcriptomes of three medicinal leech species. Our data provide new insights in genetics of blood-feeding lifestyle in leeches.
Topics: Animals; Anticoagulants; Gene Expression Profiling; Gene Expression Regulation; Genome; Hirudo medicinalis; Leeches; Proteomics; Saliva; Salivary Proteins and Peptides
PubMed: 32349672
DOI: 10.1186/s12864-020-6748-0 -
Journal of Integrative Neuroscience Dec 2020Invertebrate animal models show simple behaviors supported by neural circuits easily accessible for experimentation and yet complex enough to provide necessary...
Invertebrate animal models show simple behaviors supported by neural circuits easily accessible for experimentation and yet complex enough to provide necessary information on the cellular and molecular mechanisms that govern the vertebrate nervous system's function. The mechanisms underlying simple forms of learning have been extensively studied in the marine gastropod Aplysia californica, in which elementary non-associative learning of the behavioral habituation and sensitization type has been studied using the gill withdrawal reflex. A strong stimulus applied to the neck or tail improves the reflex response through heterosynaptic facilitation. The neurotransmitter serotonin is involved in both behavioral sensitization and dishabituation by acting through the second messenger cyclic adenosine monophosphate, protein kinase A, the phosphorylation of a K+ channel, causing its closure. This broadens the action potential profile, increases the influx of Ca2+ through voltage-gated Ca2+ channels, and enhances the neurotransmitter glutamate's release. Short-term memory is based on covalent modifications of pre-existing proteins, while long-term memory requires gene transcription, protein translation and growth of new synapses. Another simple invertebrate model is the leech Hirudo medicinalis. In nearly-intact preparations, the repetitive application of light electrical stimuli at the level of the caudal portion of the body wall can induce the habituation of swimming induction. At the same time, the stroke on the dorsal skin generates behavioral sensitization or dishabituation. Knowledge of the molecular mechanisms of activity-dependent forms of synaptic plasticity provides a basis for understanding the mechanisms underlying learning, memory, other forms of brain plasticity, and pathological conditions and suggests potential therapeutic interventions.
Topics: Animals; Aplysia; Behavior, Animal; Gene Expression; Habituation, Psychophysiologic; Hirudo medicinalis; Learning; Memory; Neuronal Plasticity; Reflex; Serotonin; Synaptic Transmission
PubMed: 33378841
DOI: 10.31083/j.jin.2020.04.318