scholarly journals Melittin as a promising anti-protozoan peptide: current knowledge and future prospects

AMB Express ◽  
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hamed Memariani ◽  
Mojtaba Memariani
Keyword(s):  
Current Knowledge ◽  
Apoptotic Cell ◽  
Major Constituent ◽  
Future Research ◽  
Vaccine Adjuvants ◽  
Protozoan Parasites ◽  
Vector Borne ◽  
Underlying Mechanisms ◽  
European Honeybee

AbstractProtozoan diseases such as malaria, leishmaniasis, Chagas disease, and sleeping sickness still levy a heavy toll on human lives. Deplorably, only few classes of anti-protozoan drugs have thus far been developed. The problem is further compounded by their intrinsic toxicity, emergence of drug resistance, and the lack of licensed vaccines. Thus, there is a genuine exigency to develop novel anti-protozoan medications. Over the past years, melittin, the major constituent in the venom of European honeybee Apis mellifera, has gathered the attention of researchers due to its potential therapeutic applications. Insofar as we are aware, there has been no review pertinent to anti-protozoan properties of melittin. The present review outlines the current knowledge about anti-protozoan effects of melittin and its underlying mechanisms. The peptide has proven to be efficacious in killing different protozoan parasites such as Leishmania, Plasmodium, Toxoplasma, and Trypanosoma in vitro. Apart from direct membrane-disruptive activity, melittin is capable of destabilizing calcium homeostasis, reducing mitochondrial membrane potential, disorganizing kinetoplast DNA, instigating apoptotic cell death, and induction of autophagy in protozoan pathogens. Emerging evidence suggests that melittin is a promising candidate for future vaccine adjuvants. Transmission-blocking activity of melittin against vector-borne pathogens underscores its potential utility for both transgenic and paratransgenic manipulations. Nevertheless, future research should focus upon investigating anti-microbial activities of melittin, alone or in combination with the current anti-protozoan medications, against a far broader spectrum of protozoan parasites as well as pre-clinical testing of the peptide in animal models.

scholarly journals CSF1R-related leukoencephalopathy

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. 1092-1104 ◽  
Author(s):  
Takuya Konno ◽  
Koji Kasanuki ◽  
Takeshi Ikeuchi ◽  
Dennis W. Dickson ◽  
Zbigniew K. Wszolek
Keyword(s):  
White Matter ◽  
Cultured Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Future Research ◽  
Primary Role ◽  
Extrapyramidal Signs ◽  
Underlying Mechanisms

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia-like phenotype in their 40s–50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than men. On brain imaging, in addition to white matter abnormalities, thinning of the corpus callosum, diffusion-restricted lesions in the white matter, and brain calcifications are hallmarks. Primary axonopathy followed by demyelination was suggested by pathology. Haploinsufficiency of colony-stimulating factor-1 receptor (CSF1R) is evident in a patient with a frameshift mutation, facilitating the establishment of Csf1r haploinsufficient mouse model. These mice develop clinical, radiologic, and pathologic phenotypes consistent with those of human patients with CSF1R mutations. In vitro, perturbation of CSF1R signaling is shown in cultured cells expressing mutant CSF1R. However, the underlying mechanisms by which CSF1R mutations selectively lead to white matter degeneration remains to be elucidated. Given that CSF1R mainly expresses in microglia, CSF1R-related leukoencephalopathy is representative of primary microgliopathies, of which microglia have a pivotal and primary role in pathogenesis. In this review, we address the current knowledge of CSF1R-related leukoencephalopathy and discuss the putative pathophysiology, with a focus on microglia, as well as future research directions.

scholarly journals Intestinal Absorption Profile of Three Polygala Oligosaccharide Esters in Polygalae Radix and the Effects of Other Components in Polygalae Radix on Their Absorption

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
YinYing Ba ◽  
MengLin Wang ◽  
KunFeng Zhang ◽  
QiJun Chen ◽  
JiaJia Wang ◽  
...  
Keyword(s):  
Future Research ◽  
Active Components ◽  
Sodium Caprate ◽  
P Glycoprotein ◽  
Paracellular Absorption ◽  
Underlying Mechanisms ◽  
The Relationship ◽  
Rat Gut ◽  
Human Nervous System

Oligosaccharide esters, which are among the main active components of Polygalae Radix (PR), demonstrate significant pharmacological activities in the human nervous system. In our previous research, some other constituents in PR were able to improve the bioavailability of oligosaccharide esters such as sibiricose A5 (SA5), sibiricose A6 (SA6), and 3,6′-disinapoyl sucrose (DISS), but the related components and their underlying mechanisms remain unknown. The present study aimed to investigate the intestinal absorptive profile of SA5, SA6, and DISS and the absorptive behavior influenced by the coadministration of polygalaxanthone III and total saponins of PR (TS) using an in vitro everted rat gut sac model, along with the possible mechanisms that may influence absorption. The results showed that TS could significantly enhance the absorption of SA5, SA6, and DISS monomers. Verapamil, a P-glycoprotein inhibitor, was able to elevate the absorption of SA5 and SA6, and an absorption experiment using Rho123 led us to conclude that TS influenced the absorption of SA5 and SA6 in a manner similar to that of a P-glycoprotein inhibitor. Sodium caprate, a paracellular absorption enhancer, was found to increase the absorption of SA5, SA6, and DISS. Results showed that the absorption mechanisms of SA5 and SA6 may combine active transport with paracellular passive penetration, while DISS’s absorption was dominated by paracellular passive penetration. However, the relationship between polygala saponins and the absorption of SA5, SA6, and DISS by paracellular passive penetration remain to be examined. This is the direction of our future research.

scholarly journals The emerging role of lactate as a mediator of exercise-induced appetite suppression

2020 ◽  
Vol 319 (4) ◽  
pp. E814-E819
Author(s):  
Seth F. McCarthy ◽  
Hashim Islam ◽  
Tom J. Hazell
Keyword(s):  
Overweight And Obesity ◽  
Future Research ◽  
Ghrelin Receptor ◽  
Cellular Models ◽  
Regulatory Molecule ◽  
Blood Lactate Accumulation ◽  
Underlying Mechanisms ◽  
Exercise Induced

Lactate, a molecule originally considered metabolic waste, is now associated with a number of important physiological functions. Although the roles of lactate as a signaling molecule, fuel source, and gluconeogenic substrate have garnered significant attention in recent reviews, a relatively underexplored and emerging role of lactate is its control of energy intake (EI). To expand our understanding of the physiological roles of lactate, we present evidence from early infusion studies demonstrating the ability of lactate to suppress EI in both rodents and humans. We then discuss findings from recent human studies that have utilized exercise intensity and/or sodium bicarbonate supplementation to modulate endogenous lactate and examine its impact on appetite regulation. These studies consistently demonstrate that greater blood lactate accumulation is associated with greater suppression of the hunger hormone ghrelin and subjective appetite, thereby supporting a role of lactate in the control of EI. To stimulate future research investigating the role of lactate as an appetite-regulatory molecule, we also highlight potential underlying mechanisms explaining the appetite-suppressive effects of lactate using evidence from rodent and in vitro cellular models. Specifically, we discuss the ability of lactate to 1) inhibit the secretory function of ghrelin producing gastric cells, 2) modulate the signaling cascades that control hypothalamic neuropeptide expression/release, and 3) inhibit signaling through the ghrelin receptor in the hypothalamus. Unravelling the role of lactate as an appetite-regulatory molecule can shed important insight into the regulation of EI, thereby contributing to the development of interventions aimed at combatting overweight and obesity.

scholarly journals Signaling Mechanisms and Disrupted Cytoskeleton in the Diphenyl Ditelluride Neurotoxicity

2014 ◽  
Vol 2014 ◽  
pp. 1-21 ◽  
Author(s):  
Regina Pessoa-Pureur ◽  
Luana Heimfarth ◽  
João B. Rocha
Keyword(s):  
Protein Kinase ◽  
Metabotropic Glutamate Receptors ◽  
Current Knowledge ◽  
Apoptotic Cell ◽  
Cytoskeletal Proteins ◽  
Neural Cells ◽  
Signaling Mechanisms ◽  
Diphenyl Ditelluride

Evidence from our group supports that diphenyl ditelluride (PhTe)2neurotoxicity depends on modulation of signaling pathways initiated at the plasma membrane. The (PhTe)2-evoked signal is transduced downstream of voltage-dependent Ca2+channels (VDCC), N-methyl-D-aspartate receptors (NMDA), or metabotropic glutamate receptors activation via different kinase pathways (protein kinase A, phospholipase C/protein kinase C, mitogen-activated protein kinases (MAPKs), and Akt signaling pathway). Among the most relevant cues of misregulated signaling mechanisms evoked by (PhTe)2is the cytoskeleton of neural cells. Thein vivoandin vitroexposure to (PhTe)2induce hyperphosphorylation/hypophosphorylation of neuronal and glial intermediate filament (IF) proteins (neurofilaments and glial fibrillary acidic protein, resp.) in different brain structures of young rats. Phosphorylation of IFs at specific sites modulates their association/disassociation and interferes with important physiological roles, such as axonal transport. Disrupted cytoskeleton is a crucial marker of neurodegeneration and is associated with reactive astrogliosis and apoptotic cell death. This review focuses the current knowledge and important results on the mechanisms of (PhTe)2neurotoxicity with special emphasis on the cytoskeletal proteins and their differential regulation by kinases/phosphatases and Ca2+-mediated mechanisms in developmental rat brain. We propose that the disrupted cytoskeletal homeostasis could support brain damage provoked by this neurotoxicant.

scholarly journals The biology of cutaneous neurofibromas

Neurology ◽  
2018 ◽  
Vol 91 (2 Supplement 1) ◽  
pp. S14-S20 ◽  
Author(s):  
Jean-Philippe Brosseau ◽  
Dominique C. Pichard ◽  
Eric H. Legius ◽  
Pierre Wolkenstein ◽  
Robert M. Lavker ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Research Priorities ◽  
Future Research ◽  
In Vivo Models ◽  
Cells Of Origin ◽  
Group Members ◽  
Multiple Levels

ObjectiveA group of experts in dermatology, genetics, neuroscience, and regenerative medicine collaborated to summarize current knowledge on the defined factors contributing to cutaneous neurofibroma (cNF) development and to provide consensus recommendations for future research priorities to gain an improved understanding of the biology of cNF.MethodsThe group members reviewed published and unpublished data on cNF and related diseases via literature search, defined a set of key topic areas deemed critical in cNF pathogenesis, and developed recommendations in a series of consensus meetings.ResultsFive specific topic areas were identified as being relevant to providing an enhanced understanding of the biology of cNF: (1) defining the human cells of origin; (2) understanding the role of the microenvironment, focusing on neurons, mast cells, and fibroblasts; (3) defining the genetic and molecular differences between the cNFs, focusing on size and number; (4) understanding if sex hormones are critical for cNF development or progression; and (5) identifying challenges in establishing in vitro and in vivo models representing human cNF.ConclusionsThe complexity of cNF biology stems from its heterogeneity at multiple levels including genetic, spatial involvement, temporal development, and cellular composition. We propose a unified working model for cNF that builds a framework to address the key questions about cNF that, when answered, will provide the necessary understanding of cNF biology to allow meaningful development of therapies.

scholarly journals Preventive Effect of Dihydromyricetin against Cisplatin-Induced NephrotoxicityIn VitroandIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Wu ◽  
Yi Li ◽  
Haibo Song ◽  
Yuan Zhang ◽  
Yuzhu Zhang ◽  
...  
Keyword(s):  
Structural Damage ◽  
Apoptotic Cell ◽  
Severe Side Effect ◽  
Preventive Effect ◽  
Chemotherapy Drugs ◽  
Antioxidative Effects ◽  
Underlying Mechanisms ◽  
Ampelopsis Grossedentata

Nephrotoxicity is a frequent severe side effect of cisplatin chemotherapy, limiting its clinical use despite being one of the most potent chemotherapy drugs. Dihydromyricetin is a highly abundant compound purified from the leaves ofAmpelopsis grossedentata. Previous studies have demonstrated the anti-inflammatory and antioxidative effects of Dihydromyricetin bothin vitroandin vivo, but little is known about the effects of Dihydromyricetin on cisplatin-induced nephrotoxicity and its underlying mechanisms. In the present study, we investigated its potential renoprotective effect and found that Dihydromyricetin ameliorated the renal functional impairment and structural damage caused by cisplatin. Moreover, Dihydromyricetin markedly attenuated cisplatin-induced oxidative stress, as well as protecting against cisplatin-induced inflammation and apoptotic cell death in mouse kidney tissues. These results collectively highlight the potential of DMY as a rational renoprotective agent against cisplatin.

scholarly journals Local anesthetic bupivacaine induced ovarian and prostate cancer apoptotic cell death and underlying mechanisms in vitro

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Wei Xuan ◽  
Hailin Zhao ◽  
James Hankin ◽  
Lin Chen ◽  
Shanglong Yao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Death ◽  
Local Anesthetic ◽  
Apoptotic Cell ◽  
Apoptotic Cell Death ◽  
Underlying Mechanisms

scholarly journals Complete genomes of the eukaryotic poultry parasite Histomonas meleagridis: linking sequence analysis with virulence / attenuation

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Nicola Palmieri ◽  
Marcelo de Jesus Ramires ◽  
Michael Hess ◽  
Ivana Bilic
Keyword(s):  
Trichomonas Vaginalis ◽  
Sequence Data ◽  
Protozoan Parasite ◽  
Whole Genome Sequence ◽  
Future Research ◽  
Specific Gene ◽  
Base Level ◽  
Virulence Attenuation ◽  
Underlying Mechanisms

Abstract Background Histomonas meleagridis is a protozoan parasite and the causative agent of histomonosis, an important poultry disease whose significance is underlined by the absence of any treatment and prophylaxis. The recent successful in vitro attenuation of the parasite urges questions about the underlying mechanisms. Results Whole genome sequence data from a virulent and an attenuated strain originating from the same parental lineage of H. meleagridis were recruited using Oxford Nanopore Technology (ONT) and Illumina platforms, which were combined to generate megabase-sized contigs with high base-level accuracy. Inspecting the genomes for differences identified two substantial deletions within a coding sequence of the attenuated strain. Additionally, one single nucleotide polymorphism (SNP) and indel targeting coding sequences caused the formation of premature stop codons, which resulted in the truncation of two genes in the attenuated strain. Furthermore, the genome of H. meleagridis was used for characterizing protein classes of clinical relevance for parasitic protists. The comparative analysis with the genomes of Trichomonas vaginalis, Tritrichomonas foetus and Entamoeba histolytica identified ~ 2700 lineage-specific gene losses and 9 gene family expansions in the H. meleagridis lineage. Conclusions Taken as a whole, the obtained data provide the first hints to understand the molecular basis of attenuation in H. meleagridis and constitute a genomics platform for future research on this important poultry pathogen.

scholarly journals Chicken Mesenchymal Stem Cells and Their Applications: A Mini Review

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1883
Author(s):  
Andrea Svoradova ◽  
Vladimir Zmrhal ◽  
Eva Venusova ◽  
Petr Slama
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Current Knowledge ◽  
3D Culture ◽  
Future Research ◽  
Meat Production ◽  
Suitable Model ◽  
Growth Promoters ◽  
Pathogenic Potential

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that adhere to plastic; express the specific markers CD29, CD44, CD73, CD90, and CD105; and produce cytokines and growth factors supporting and regulating hematopoiesis. MSCs have capacity for differentiating into osteocytes, chondrocytes, adipocytes, and myocytes. They are useful for research toward better understanding the pathogenic potential of the infectious bursal disease virus, mineralization during osteogenesis, and interactions between MSCs as a feeder layer to other cells. MSCs are also important for immunomodulatory cell therapy, can provide a suitable strategy model for coculture with pathogens causing dermatitis disorders in chickens, can be cultured in vitro with probiotics and prebiotics with a view to eliminate the feeding of antibiotic growth promoters, and offer cell-based meat production. Moreover, bone marrow-derived MSCs (BM-MSCs) in coculture with hematopoietic progenitor/stem cells (HPCs/HSCs) can support expansion and regulation of the hematopoiesis process using the 3D-culture system in future research in chickens. MSCs’ several advantages, including ready availability, strong proliferation, and immune modulatory properties make them a suitable model in the field of stem cell research. This review summarizes current knowledge about the general characterization of MSCs and their application in chicken as a model organism.

scholarly journals Glucose Lowering Strategies for Cardiac Benefits: Pathophysiological Mechanisms

Physiology ◽  
2018 ◽  
Vol 33 (3) ◽  
pp. 197-210 ◽  
Author(s):  
Harpreet S. Bajaj ◽  
Bernard Zinman
Keyword(s):  
Type 2 Diabetes ◽  
Current Knowledge ◽  
Sglt2 Inhibitors ◽  
Future Research ◽  
Knowledge Gaps ◽  
Glucose Lowering ◽  
Pathophysiological Mechanisms ◽  
Underlying Mechanisms ◽  
Review Current

Recent trials in Type 2 diabetes (T2D) have shown cardiovascular benefits with specific GLP-1 receptor agonists and SGLT2 inhibitors. We discuss the landscape of outcome trials in T2D from a pathophysiology viewpoint, review current knowledge gaps in underlying mechanisms, propose a caloric fuel routing hypothesis, and highlight areas of future research.

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