scholarly journals The Diverse Calpain Family in Trypanosomatidae: Functional Proteins Devoid of Proteolytic Activity?

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 299
Author(s):  
Vítor Ennes-Vidal ◽  
Marta Helena Branquinha ◽  
André Luis Souza dos Santos ◽  
Claudia Masini d’Avila-Levy
Keyword(s):  
Proteolytic Activity ◽  
Current Knowledge ◽  
Current Therapy ◽  
Calcium Dependent ◽  
Administration Routes ◽  
Life Threatening ◽  
Living Organisms ◽  
Almost All ◽  
Open Question ◽  
Calpain Inhibitors

Calpains are calcium-dependent cysteine peptidases that were originally described in mammals and, thereafter, their homologues were identified in almost all known living organisms. The deregulated activity of these peptidases is associated with several pathologies and, consequently, huge efforts have been made to identify selective inhibitors. Trypanosomatids, responsible for life-threatening human diseases, possess a large and diverse family of calpain sequences in their genomes. Considering that the current therapy to treat trypanosomatid diseases is limited to a handful of drugs that suffer from unacceptable toxicity, tough administration routes, like parenteral, and increasing treatment failures, a repurposed approach with calpain inhibitors could be a shortcut to successful chemotherapy. However, there is a general lack of knowledge about calpain functions in these parasites and, currently, the proteolytic activity of these proteins is still an open question. Here, we highlight the current research and perspectives on trypanosomatid calpains, overview calpain description in these organisms, and explore the potential of targeting the calpain system as a therapeutic strategy. This review gathers the current knowledge about this fascinating family of peptidases as well as insights into the puzzle: are we unable to measure calpain activity in trypanosomatids, or are the functions of these proteins devoid of proteolytic activity in these parasites?

scholarly journals The Current Knowledge of Invertebrate Aquaporin Water Channels with Particular Emphasis on Insect AQPs

2010 ◽  
Vol 2 (2) ◽  
pp. 91-104 ◽  
Author(s):  
Ewa Tomkowiak ◽  
Joanna Romana Pienkowska
Keyword(s):  
Current Knowledge ◽  
Water Channels ◽  
Survival Strategies ◽  
Feeding Strategies ◽  
Transmembrane Segments ◽  
Single Organism ◽  
Living Organisms ◽  
Almost All ◽  
And Function ◽  
Hostile Environments

SummaryAquaporins (AQPs) or water channels are some of the most ubiquitous integral membrane proteins, and are present in all living organisms. Their presence in the lipid bilayer of cell membranes considerably increases their permeability to water and, in some cases, to other small solutes. All AQPs, identified thus far, share the same structure, comprising of six transmembrane segments and two conserved regions forming the pore. Depending on the transported solutes, AQPs can be divided into two classes: ‘classical’ aquaporins (permeable only to water) and aquaglyceroporins (permeable also to glycerol and/or other solutes). Many subtypes of AQPs coexist in a single organism. Localization of particular subtypes of AQPs is tissue-specific. AQPs have been well characterized in almost all vertebrate classes. However, little is known about their counterparts in invertebrates. Most of the water channels characterized in invertebrates are found in insects. Therefore, the knowledge of aquaporins in invertebrates is generally limited to the information concerning water channels in this class of organism. Insects are characterized by an astonishing variety of physiological adaptations, notable in their feeding strategies or survival strategies in hostile environments. An example of such, is feeding on blood, or tolerating extreme cold or drought. It is likely that many of these adaptation patterns emerged due to the expression and regulation of particular aquaporins. Here we review the current state of knowledge of invertebrate AQPs (of insects and nematodes) and compare their structure and function with mammalian water channels

scholarly journals Therapeutic Effects of Phytochemicals and Medicinal Herbs on Depression

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Gihyun Lee ◽  
Hyunsu Bae
Keyword(s):  
Current Knowledge ◽  
Medicinal Herbs ◽  
Current Therapy ◽  
Psychiatric Disease ◽  
Therapeutic Effects ◽  
Complementary Method ◽  
Beneficial Effects ◽  
Symptoms Of Depression ◽  
Therapeutic Benefits ◽  
Life Threatening

Background. Depression is a recurrent, common, and potentially life-threatening psychiatric disease related to multiple assignable causes. Although conventional antidepressant therapy can help relieve symptoms of depression and prevent relapse of the illness, complementary therapies are required due to disadvantage of the current therapy such as adverse effects. Moreover, a number of studies have researched adjunctive therapeutic approaches to improve outcomes for depression patients. Purpose. One potential complementary method with conventional antidepressants involves the use of medicinal herbs and phytochemicals that provide therapeutic benefits. Studies have revealed beneficial effects of medical herbs and phytochemicals on depression and their central nervous system mechanism. Here, we summarize the current knowledge of the therapeutic benefits of phytochemicals and medicinal herbs against depression and describe their detailed mechanisms. Sections. There are two sections, phytochemicals against depression and medical herbs against depression, in this review. Conclusion. Use of phytomedicine may be an alternative option for the treatment of depression in case conventional drugs are not applicable due to their side effects, low effectiveness, or inaccessibility. However, the efficacy and safety of these phytomedicine treatments for depression have to be supported by clinical studies.

Ion Channel Remodelling in Atrial Fibrillation

2011 ◽  
Vol 7 (2) ◽  
pp. 97 ◽  
Author(s):  
Niels Voigt ◽  
Dobromir Dobrev ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Ion Channel ◽  
Antiarrhythmic Drugs ◽  
Current Knowledge ◽  
Bleeding Complications ◽  
Large Size ◽  
Cardiovascular Morbidity And Mortality ◽  
Number Of Patients ◽  
Life Threatening ◽  
Underlying Mechanisms

Atrial fibrillation (AF) is the most common arrhythmia and is associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication. Present drugs used for the therapy of AF (antiarrhythmics and anticoagulants) have major limitations, including incomplete efficacy, risks of life-threatening proarrhythmic events and bleeding complications. Non-pharmacological ablation procedures are efficient and apparently safe, but the very large size of the patient population allows ablation treatment of only a small number of patients. These limitations largely result from limited knowledge about the underlying mechanisms of AF and there is a hope that a better understanding of the molecular basis of AF may lead to the discovery of safer and more effective therapeutic targets. This article reviews the current knowledge about AF-related ion-channel remodelling and discusses how these alterations might affect the efficacy of antiarrhythmic drugs.

Resveratrol: A new potential therapeutic agent for melanoma?

2019 ◽  
Vol 26 ◽  
Author(s):  
Mohamad Hossein Pourhanifeh ◽  
Kazem Abbaszadeh-Goudarzi ◽  
Mohammad Goodarzi ◽  
Sara G.M. Piccirillo ◽  
Alimohammad Shafiee ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Therapeutic Agent ◽  
Current Knowledge ◽  
Treatment Resistance ◽  
Anti Cancer ◽  
Apoptosis Inducer ◽  
Life Threatening ◽  
First Time

: Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard anti-melanomatreatments such as chemotherapy, and 5-year survival rate of cases with melanoma who have metastatic form of disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approachesthat couldenhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. : Herein, for first time, we summarize current knowledge of anti-cancerous activities of resveratrol in melanoma.

scholarly journals Social calls influence the foraging behavior in wild big-footed myotis

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dongge Guo ◽  
Jianan Ding ◽  
Heng Liu ◽  
Lin Zhou ◽  
Jiang Feng ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Light Trapping ◽  
Low Frequency ◽  
Food Competition ◽  
Insectivorous Bats ◽  
Insect Abundance ◽  
Social Calls ◽  
Abundance And Diversity ◽  
Open Question ◽  
Free Ranging

Abstract Background Why a variety of social animals emit foraging-associated calls during group foraging remains an open question. These vocalizations may be used to recruit conspecifics to food patches (i.e. food advertisement hypothesis) or defend food resources against competitors (food defence hypothesis), presumably depending on food availability. Insectivorous bats rely heavily on vocalizations for navigation, foraging, and social interactions. In this study, we used free-ranging big-footed myotis (Myotis macrodactylus Temminck, 1840) to test whether social calls produced in a foraging context serve to advertise food patches or to ward off food competitors. Using a combination of acoustic recordings, playback experiments with adult females and dietary monitoring (light trapping and DNA metabarcoding techniques), we investigated the relationship between insect availability and social vocalizations in foraging bats. Results The big-footed myotis uttered low-frequency social calls composed of 7 syllable types during foraging interactions. Although the dietary composition of bats varied across different sampling periods, Diptera, Lepidoptera, and Trichoptera were the most common prey consumed. The number of social vocalizations was primarily predicted by insect abundance, insect species composition, and echolocation vocalizations from conspecifics. The number of conspecific echolocation pulses tended to decrease following the emission of most social calls. Feeding bats consistently decreased foraging attempts and food consumption during playbacks of social calls with distinctive structures compared to control trials. The duration of flight decreased 1.29–1.96 fold in the presence of social calls versus controls. Conclusions These results support the food defence hypothesis, suggesting that foraging bats employ social calls to engage in intraspecific food competition. This study provides correlative evidence for the role of insect abundance and diversity in influencing the emission of social calls in insectivorous bats. Our findings add to the current knowledge of the function of social calls in echolocating bats.

scholarly journals The Cross-Talk between Mesenchymal Stem Cells and Immune Cells in Tissue Repair and Regeneration

2021 ◽  
Vol 22 (5) ◽  
pp. 2472
Author(s):  
Carl Randall Harrell ◽  
Valentin Djonov ◽  
Vladislav Volarevic
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Cells ◽  
Tissue Repair ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Multipotent Stem Cells ◽  
Tissue Repair And Regeneration ◽  
Almost All ◽  
And Function

Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.

scholarly journals Catalytic Diversity of GH30 Xylanases

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4528
Author(s):  
Katarína Šuchová ◽  
Vladimír Puchart ◽  
Nikolaj Spodsberg ◽  
Kristian B. R. Mørkeberg Krogh ◽  
Peter Biely
Keyword(s):  
Methyl Ester ◽  
Catalytic Properties ◽  
Specific Activity ◽  
Current Knowledge ◽  
Carboxyl Group ◽  
Weak Effect ◽  
Bacterial Enzymes ◽  
Catalytic Activities ◽  
Almost All ◽  
Free Carboxyl

Catalytic properties of GH30 xylanases belonging to subfamilies 7 and 8 were compared on glucuronoxylan, modified glucuronoxylans, arabinoxylan, rhodymenan, and xylotetraose. Most of the tested bacterial GH30-8 enzymes are specific glucuronoxylanases (EC 3.2.1.136) requiring for action the presence of free carboxyl group of MeGlcA side residues. These enzymes were not active on arabinoxylan, rhodymenan and xylotetraose, and conversion of MeGlcA to its methyl ester or its reduction to MeGlc led to a remarkable drop in their specific activity. However, some GH30-8 members are nonspecific xylanases effectively hydrolyzing all tested substrates. In terms of catalytic activities, the GH30-7 subfamily is much more diverse. In addition to specific glucuronoxylanases, the GH30-7 subfamily contains nonspecific endoxylanases and predominantly exo-acting enzymes. The activity of GH30-7 specific glucuronoxylanases also depend on the presence of the MeGlcA carboxyl, but not so strictly as in bacterial enzymes. The modification of the carboxyl group of glucuronoxylan had only weak effect on the action of predominantly exo-acting enzymes, as well as nonspecific xylanases. Rhodymenan and xylotetraose were the best substrates for exo-acting enzymes, while arabinoxylan represented hardly degradable substrate for almost all tested GH30-7 enzymes. The results expand current knowledge on the catalytic properties of this relatively novel group of xylanases.

scholarly journals Mirolase, a novel subtilisin-like serine protease from the periodontopathogen Tannerella forsythia

2015 ◽  
Vol 396 (3) ◽  
pp. 261-275 ◽  
Author(s):  
Miroslaw Ksiazek ◽  
Abdulkarim Y. Karim ◽  
Danuta Bryzek ◽  
Jan J. Enghild ◽  
Ida B. Thøgersen ◽  
...  
Keyword(s):  
Serine Protease ◽  
Calcium Ions ◽  
Enzyme Stability ◽  
Amidolytic Activity ◽  
Tannerella Forsythia ◽  
Calcium Dependent ◽  
Genes Encoding ◽  
Mature Enzyme ◽  
Almost All ◽  
Unique Mechanism

Abstract The genome of Tannerella forsythia, an etiological factor of chronic periodontitis, contains several genes encoding putative proteases. Here, we characterized a subtilisin-like serine protease of T. forsythia referred to as mirolase. Recombinant full-length latent promirolase [85 kDa, without its signal peptide (SP)] processed itself through sequential autoproteolytic cleavages into a mature enzyme of 40 kDa. Mirolase latency was driven by the N-terminal prodomain (NTP). In stark contrast to almost all known subtilases, the cleaved NTP remained non-covalently associated with mirolase, inhibiting its proteolytic, but not amidolytic, activity. Full activity was observed only after the NTP was gradually, and fully, degraded. Both activity and processing was absolutely dependent on calcium ions, which were also essential for enzyme stability. As a consequence, both serine protease inhibitors and calcium ions chelators inhibited mirolase activity. Activity assays using an array of chromogenic substrates revealed that mirolase specificity is driven not only by the substrate-binding subsite S1, but also by other subsites. Taken together, mirolase is a calcium-dependent serine protease of the S8 family with the unique mechanism of activation that may contribute to T. forsythia pathogenicity by degradation of fibrinogen, hemoglobin, and the antimicrobial peptide LL-37.

scholarly journals Hypoxia and Hypoxia-Inducible Factor Signaling in Muscular Dystrophies: Cause and Consequences

2021 ◽  
Vol 22 (13) ◽  
pp. 7220
Author(s):  
Thuy-Hang Nguyen ◽  
Stephanie Conotte ◽  
Alexandra Belayew ◽  
Anne-Emilie Declèves ◽  
Alexandre Legrand ◽  
...  
Keyword(s):  
Cell Function ◽  
Current Knowledge ◽  
Genetic Defect ◽  
Hypoxia Inducible Factor ◽  
Muscular Dystrophies ◽  
Compensatory Mechanisms ◽  
Hypoxia Response ◽  
Muscle Disorders ◽  
Almost All ◽  
The Impact

Muscular dystrophies (MDs) are a group of inherited degenerative muscle disorders characterized by a progressive skeletal muscle wasting. Respiratory impairments and subsequent hypoxemia are encountered in a significant subgroup of patients in almost all MD forms. In response to hypoxic stress, compensatory mechanisms are activated especially through Hypoxia-Inducible Factor 1 α (HIF-1α). In healthy muscle, hypoxia and HIF-1α activation are known to affect oxidative stress balance and metabolism. Recent evidence has also highlighted HIF-1α as a regulator of myogenesis and satellite cell function. However, the impact of HIF-1α pathway modifications in MDs remains to be investigated. Multifactorial pathological mechanisms could lead to HIF-1α activation in patient skeletal muscles. In addition to the genetic defect per se, respiratory failure or blood vessel alterations could modify hypoxia response pathways. Here, we will discuss the current knowledge about the hypoxia response pathway alterations in MDs and address whether such changes could influence MD pathophysiology.

scholarly journals Circadian Deregulation as Possible New Player in Pollution-Induced Tissue Damage

Atmosphere ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 116
Author(s):  
Mascia Benedusi ◽  
Elena Frigato ◽  
Cristiano Bertolucci ◽  
Giuseppe Valacchi
Keyword(s):  
Cardiovascular Diseases ◽  
Air Pollutants ◽  
Environmental Stressors ◽  
Common Mechanism ◽  
Particulate Matters ◽  
Circadian Misalignment ◽  
Pathological Conditions ◽  
Peripheral Clocks ◽  
Living Organisms ◽  
Almost All

Circadian rhythms are 24-h oscillations driven by a hypothalamic master oscillator that entrains peripheral clocks in almost all cells, tissues and organs. Circadian misalignment, triggered by industrialization and modern lifestyles, has been linked to several pathological conditions, with possible impairment of the quality or even the very existence of life. Living organisms are continuously exposed to air pollutants, and among them, ozone or particulate matters (PMs) are considered to be among the most toxic to human health. In particular, exposure to environmental stressors may result not only in pulmonary and cardiovascular diseases, but, as it has been demonstrated in the last two decades, the skin can also be affected by pollution. In this context, we hypothesize that chronodistruption can exacerbate cell vulnerability to exogenous damaging agents, and we suggest a possible common mechanism of action in deregulation of the homeostasis of the pulmonary, cardiovascular and cutaneous tissues and in its involvement in the development of pathological conditions.

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