Putative kallikrein substrates and their (patho)biological functions

2014 ◽  
Vol 395 (9) ◽  
pp. 931-943 ◽  
Author(s):  
Yijing Yu ◽  
Ioannis Prassas ◽  
Eleftherios P. Diamandis
Keyword(s):  
Peptide Library ◽  
Biological Functions ◽  
Substrate Specificities ◽  
Functional Roles ◽  
Wide Range ◽  
Positional Scanning ◽  
Combinatorial Peptide Library ◽  
Recent Developments ◽  
Physiological Substrates

Abstract Human tissue kallikreins (KLKs) represent the largest contiguous group of protease genes within our genome. All 15 KLK genes co-localize within approximately 260 kb in human chromosome 19q13.3–13.4 (14 640 kb→274 990 kb). They are widely expressed in several tissues and mediate a wide range of critical physiological and pathological processes. Despite the recent developments in KLK research, elucidation of their physiological substrate repertoires remains a largely unfulfilled goal. Phage display, positional scanning and combinatorial peptide library screens have provided some valuable insights into the preferred specificities of these powerful enzymes. More recently, advances in proteomic technologies have enabled more systemic approaches towards identification of KLK substrates in a physiological setting. The advent of degradomic technologies has brought to light several putative physiological substrates and has allowed a deeper appreciation of the in vivo functional roles of KLKs. The aim of this review is to provide an overview of the different techniques that have been utilized towards the elucidation of the substrate specificities of these enzymes and elaborate on their emerging in vivo substrates.

Chemical constituents, ethnomedicinal uses, pharmacology, and toxicity of Dysphania ambrosioides (L.) Mosyakin & Clemants, formerly Chenopodium ambrosioides L.

2021 ◽  
Vol 11 ◽  
Author(s):  
Boniface Pone Kamdem ◽  
Eutrophe Le Doux Kamto ◽  
Hugues Kamdem Paumo ◽  
Lebogang Maureen Katata-Seru ◽  
Dieudonné Emmanuel Pegnyemb ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Chemical Constituents ◽  
Literature Information ◽  
Pharmacological Activities ◽  
In Vivo Experiments ◽  
Wide Range ◽  
Recent Developments ◽  
Available Information ◽  
Ethnomedicinal Uses

Background: Dysphania ambrosioides (L.) Mosyakin & Clemants is an aromatic herb native to South America, but also distributed widely throughout Africa and Europe. This plant is traditionally used to treat various ailments including, pain and swellings, flu, parasitic diseases, and as analgesic, antipyretic, and wound healing. Phytochemical analyses of D. ambrosioides revealed the presence of terpenoids, flavonoids, coumarins, fatty acids and miscellaneous compounds among others, which might be responsible for its modern pharmacological actions. Objective: The present work summarizes recent developments on phytochemistry, ethnomedicinal use, pharmacology, and toxicity of D. ambrosioides. A critical assessment of the literature information of D. ambrosioides is also presented. Methods: The available information on D. ambrosioides was collected through libraries and electronic databases [Scifinder, ACS, Scielo, Science direct, Pubmed (National Library of Medicine), Wiley, Springer, PROTA, Web of Science, Google Web, Yahoo search and Google scholar] from respective inception until january 2021. Results: More than 150 compounds, including terpenoids, flavonoids, coumarins, fatty acids, and miscellaneous compounds etc.. were identified from D. ambrosioides. D. ambrosioides exhibited a wide range of pharmacological activities, including antimalarial, anti-inflammatory, antiparasitic, anticancer, insecticidal, antigiardial, among others. Metal nanoparticles synthesized from D. ambrosioides extracts presented enhanced pharmacological activities as compared to the crude plant extracts counterparts. Conclusion: D. ambrosioides is a promising medicinal plant, however, more in vivo experiments, cytotoxicity tests, and mechanisms of actions of its extracts and compounds are recommended to transubstantiate the ethnomedicinal claims of this plant into scientific rationale-based information.

scholarly journals Comparison of the kinetic properties of the lipid- and protein-kinase activities of the p110α and p110β catalytic subunits of class-Ia phosphoinositide 3-kinases

2000 ◽  
Vol 350 (2) ◽  
pp. 353-359 ◽  
Author(s):  
Carolyn A. BEETON ◽  
Edwin M. CHANCE ◽  
Lazaros C. FOUKAS ◽  
Peter R. SHEPHERD
Keyword(s):  
Protein Kinase ◽  
Kinase Activity ◽  
Membrane Lipid ◽  
Kinetic Properties ◽  
Protein Kinase Activity ◽  
Lipid Kinase ◽  
Functional Roles ◽  
Wide Range ◽  
High Concentrations

Growth factors regulate a wide range of cellular processes via activation of the class-Ia phosphoinositide 3-kinases (PI 3-kinases). We directly compared kinetic properties of lipid- and protein-kinase activities of the widely expressed p110α and p110β isoforms. The lipid-kinase activity did not display Michaelis–Menten kinetics but modelling the kinetic data demonstrated that p110α has a higher Vmax and a 25-fold higher Km for PtdIns than p110β. A similar situation occurs with PtdIns(4,5)P2, because at low concentration of PtdIns(4,5)P2 p110β is a better PtdIns(4,5)P2 kinase than p110α, although this is reversed at high concentrations. These differences suggest different functional roles and we hypothesize that p110β functions better in areas of membranes containing low levels of substrate whereas p110α would work best in areas of high substrate density such as membrane lipid rafts. We also compared protein-kinase activities. We found that p110β phosphorylated p85 to a lower degree than did p110α. We used a novel peptide-based assay to compare the kinetics of the protein-kinase activities of p110α and p110β. These studies revealed that, like the lipid-kinase activity, the protein-kinase activity of p110α has a higher Km (550µM) than p110β (Km 8µM). Similarly, the relative Vmax towards peptide substrate of p110α was three times higher than that of p110β. This implies differences in the rates of regulatory autophosphorylation in vivo, which are likely to mean differential regulation of the lipid-kinase activities of p110α and p110β in vivo.

scholarly journals Recent Developments in Liposome-Based Veterinary Therapeutics

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Hassan Sadozai ◽  
Dorsa Saeidi
Keyword(s):  
Veterinary Medicine ◽  
Research Interest ◽  
Circulation Time ◽  
Phospholipid Vesicles ◽  
Future Directions ◽  
Ongoing Research ◽  
The Past ◽  
Wide Range ◽  
Recent Developments

Recent advances in nanomedicine have been studied in the veterinary field and have found a wide variety of applications. The past decade has witnessed a massive surge of research interest in liposomes for delivery of therapeutic substances in animals. Liposomes are nanosized phospholipid vesicles that can serve as delivery platforms for a wide range of substances. Liposomes are easily formulated, highly modifiable, and easily administered delivery platforms. They are biodegradable and nontoxic and have long in vivo circulation time. This review focuses on recent and ongoing research that may have relevance for veterinary medicine. By examining the recent developments in liposome-based therapeutics in animal cancers, vaccines, and analgesia, this review depicts the current significance and future directions of liposome-based delivery in veterinary medicine.

scholarly journals Long Non-Coding RNAs: the New Horizon of Gene Regulation in Ovarian Cancer

2017 ◽  
Vol 44 (3) ◽  
pp. 948-966 ◽  
Author(s):  
Tesfaye Worku ◽  
Dinesh Bhattarai ◽  
Duncan Ayers ◽  
Kai Wang ◽  
Chen Wang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Gene Regulation ◽  
Molecular Mechanisms ◽  
Future Directions ◽  
Diagnostic Biomarkers ◽  
Functional Roles ◽  
Gene Therapies ◽  
Wide Range ◽  
Recent Developments ◽  
Non Coding Rnas

Long non-coding RNAs (lncRNAs), a class of non-coding transcripts, have recently been emerging with heterogeneous molecular actions, adding a new layer of complexity to gene-regulation networks in tumorigenesis. LncRNAs are considered important factors in several ovarian cancer histotypes, although few have been identified and characterized. Owing to their complexity and the lack of adapted molecular technology, the roles of most lncRNAs remain mysterious. Some lncRNAs have been reported to play functional roles in ovarian cancer and can be used as classifiers for personalized medicine. The intrinsic features of lncRNAs govern their various molecular mechanisms and provide a wide range of platforms to design different therapeutic strategies for treating cancer at a particular stage. Although we are only beginning to understand the functions of lncRNAs and their interactions with microRNAs (miRNAs) and proteins, the expanding literature indicates that lncRNA-miRNA interactions could be useful biomarkers and therapeutic targets for ovarian cancer. In this review, we discuss the genetic variants of lncRNAs, heterogeneous mechanisms of actions of lncRNAs in ovarian cancer tumorigenesis, and drug resistance. We also highlight the recent developments in using lncRNAs as potential prognostic and diagnostic biomarkers. Lastly, we discuss potential approaches for linking lncRNAs to future gene therapies, and highlight future directions in the field of ovarian cancer research.

Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1960-1967 ◽  
Author(s):  
Francis N. Karanu ◽  
Barbara Murdoch ◽  
Tomoyuki Miyabayashi ◽  
Mitsuhara Ohno ◽  
Masahide Koremoto ◽  
...  
Keyword(s):  
Cell Fate ◽  
Hematopoietic Cells ◽  
Functional Roles ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Deficient Mice

Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (hDelta-1) and hDelta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that hDelta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human.

GM1 and GM2 gangliosides: recent developments

2014 ◽  
Vol 5 (1) ◽  
pp. 87-93 ◽  
Author(s):  
Blaine Bisel ◽  
Francesco S. Pavone ◽  
Martino Calamai
Keyword(s):  
Cell Membrane ◽  
Single Molecule ◽  
In Silico ◽  
Biological Functions ◽  
Tay Sachs Disease ◽  
Parkinson’S Diseases ◽  
Integral Role ◽  
Recent Developments ◽  
Conceptual Overview

AbstractGM1 and GM2 gangliosides are important components of the cell membrane and play an integral role in cell signaling and metabolism. In this conceptual overview, we discuss recent developments in our understanding of the basic biological functions of GM1 and GM2 and their involvement in several diseases. In addition to a well-established spectrum of disorders known as gangliosidoses, such as Tay-Sachs disease, more and more evidence points at an involvement of GM1 in Alzheimer’s and Parkinson’s diseases. New emerging methodologies spanning from single-molecule imaging in vivo to simulations in silico have complemented standard studies based on ganglioside extraction.

Design of Sphingosine Kinases Inhibitors: Challenges and Recent Developments

2019 ◽  
Vol 25 (9) ◽  
pp. 956-968 ◽  
Author(s):  
Elisa Magli ◽  
Angela Corvino ◽  
Ferdinando Fiorino ◽  
Francesco Frecentese ◽  
Elisa Perissutti ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Biochemical Properties ◽  
Lipid Mediator ◽  
Compensatory Mechanism ◽  
Biological Functions ◽  
Wide Range ◽  
Sphingosine 1 Phosphate ◽  
Recent Developments ◽  
Sphingosine Kinases ◽  
Review Reports

Background:Sphingosine kinases (SphKs) catalyze the phosphorylation of sphingosine to form the bioactive sphingolipid metabolite sphingosine-1-phosphate (S1P). S1P is an important lipid mediator with a wide range of biological functions; it is also involved in a variety of diseases such as inflammatory diseases, Alzheimer’s disease and cancer.Methods:This review reports the recent advancement in the research of SphKs inhibitors. Our purpose is also to provide a complete overview useful for underlining the features needed to select a specific pharmacological profile.Discussion:Two distinct mammalian SphK isoforms have been identified, SphK1 and SphK2. These isoforms are encoded by different genes and exhibit distinct subcellular localizations, biochemical properties and functions. SphK1 and SphK2 inhibition can be useful in different pathological conditions.Conclusion:SphK1 and SphK2 have many common features but different and even opposite biological functions. For this reason, several research groups are interested in understanding the therapeutic usefulness of a selective or non-selective inhibitor of SphKs. Moreover, a compensatory mechanism for the two isoforms has been demonstrated, thus leading to the development of dual inhibitors.

Human homologues of Delta-1 and Delta-4 function as mitogenic regulators of primitive human hematopoietic cells

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1960-1967 ◽  
Author(s):  
Francis N. Karanu ◽  
Barbara Murdoch ◽  
Tomoyuki Miyabayashi ◽  
Mitsuhara Ohno ◽  
Masahide Koremoto ◽  
...  
Keyword(s):  
Cell Fate ◽  
Hematopoietic Cells ◽  
Functional Roles ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Deficient Mice

Abstract Delta-mediated Notch signaling controls cell fate decisions during invertebrate and murine development. However, in the human, functional roles for Delta have yet to be described. This study reports the characterization of Delta-1 and Delta-4 in the human. Human Delta-4 was found to be expressed in a wide range of adult and fetal tissues, including sites of hematopoiesis. Subsets of immature hematopoietic cells, along with stromal and endothelial cells that support hematopoiesis, were shown to express Notch and both Delta-1 and Delta-4. Soluble forms of human Delta-1 (hDelta-1) and hDelta-4 proteins were able to augment the proliferation of primitive human hematopoietic progenitors in vitro. Intravenous transplantation of treated cultures into immune-deficient mice revealed that hDelta-1 is capable of expanding pluripotent human hematopoietic repopulating cells detected in vivo. This study provides the first evidence for a role of Delta ligands as a mitogenic regulator of primitive hematopoietic cells in the human.

scholarly journals Role of Natural Products in Aging Skin

2019 ◽  
Vol 10 (SPL1) ◽  
Author(s):  
Mahendran Sekar
Keyword(s):  
Natural Products ◽  
Natural Product ◽  
Plant Extracts ◽  
Skin Aging ◽  
In Vivo Models ◽  
Medicinal Plant Extracts ◽  
Wide Range ◽  
Recent Developments

Aging is an unavoidable progression in everyone's life and influenced by lifestyle, genetic as well as environmental factors. Herbal and plant extracts are used as antiaging since ancient times, but the evidence are still limited. Recent developments in antiaging investigation anticipated the use of natural products as the main ingredient in the formulations. Hence, this presentation focused to highlight the importance of twelve most popular medicinal plant extracts that have reported to have skin aging prevention potential. All these natural product extracts have a capacity to scavenge free radicals and defend skin matrix over the inhibition of enzymatic degradation. Some of the extracts promotes collagen synthesis in the skin and also affect the skin tightness and elasticity. However, the use of natural product extracts as an antiaging and anti-wrinkling it should be further explored using a wide range of in-vitro and in-vivo models to confirm its safety and efficacy before proceeding into the development of cosmetic products.  

scholarly journals Functional roles of globin proteins in hypoxia-tolerant ectothermic vertebrates

2017 ◽  
Vol 123 (4) ◽  
pp. 926-934 ◽  
Author(s):  
Angela Fago
Keyword(s):  
Oxygen Transport ◽  
Mitochondrial Respiration ◽  
Oxygen Carriers ◽  
Freshwater Turtles ◽  
Biological Functions ◽  
Tight Control ◽  
Functional Roles ◽  
Adaptive Mechanisms ◽  
And Storage

Globins are heme-containing proteins ubiquitously expressed in vertebrates, where they serve a broad range of biological functions, directly or indirectly related to the tight control of oxygen levels and its toxic products in vivo. Perhaps the most investigated of all proteins, hemoglobin and myoglobin are primarily involved in oxygen transport and storage, but also in facilitating arterial vasodilation, suppressing mitochondrial respiration, and preventing tissue oxidative damage via accessory redox enzymatic activities during hypoxia. By contrast, the more recently discovered neuroglobin and cytoglobin do not seem to function as reversible oxygen carriers and are instead involved in redox activities, although their exact biological roles remain to be clarified. In this context, hypoxia-tolerant ectotherms, such as freshwater turtles and members of the carp family that survive winter in extreme hypoxia, have proven as excellent models to appreciate the diversity of biological functions of globin proteins. Unraveling physiological roles of globin proteins in these extreme animals will clarify an important part of the adaptive mechanisms for surviving extreme fluctuations of oxygen availability that are prohibitive to mammals.

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