scholarly journals Differential Effects of Posttranslational Modifications of CXCL8/Interleukin-8 on CXCR1 and CXCR2 Internalization and Signaling Properties

2018 ◽  
Vol 19 (12) ◽  
pp. 3768 ◽  
Author(s):  
Alessandro Vacchini ◽  
Anneleen Mortier ◽  
Paul Proost ◽  
Massimo Locati ◽  
Mieke Metzemaekers ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Neutrophil Migration ◽  
Human Neutrophils ◽  
Naturally Occurring ◽  
The Family ◽  
Truncated Isoforms ◽  
G Protein Coupled ◽  
Gαi Protein

CXCL8 or interleukin (IL)-8 directs neutrophil migration and activation through interaction with CXCR1 and CXCR2 that belong to the family of G protein-coupled receptors (GPCRs). Naturally occurring posttranslational modifications of the NH2-terminal region of CXCL8 affect its biological activities, but the underlying molecular mechanisms are only partially understood. Here, we studied the implications of site-specific citrullination and truncation for the signaling potency of CXCL8. Native CXCL8(1-77), citrullinated [Cit5]CXCL8(1-77) and the major natural isoform CXCL8(6-77) were chemically synthesized and tested in internalization assays using human neutrophils. Citrullinated and truncated isoforms showed a moderately enhanced capacity to induce internalization of CXCR1 and CXCR2. Moreover, CXCL8-mediated activation of Gαi-dependent signaling through CXCR1 and CXCR2 was increased upon modification to [Cit5]CXCL8(1-77) or CXCL8(6-77). All CXCL8 variants promoted recruitment of β-arrestins 1 and 2 to CXCR1 and CXCR2. Compared to CXCL8(1-77), CXCL8(6-77) showed an enhanced potency to recruit β-arrestin 2 to both receptors, while for [Cit5]CXCL8(1-77) only the capacity to induce β-arrestin 2 recruitment to CXCR2 was increased. Both modifications had no biasing effect, i.e., did not alter the preference of CXCL8 to activate either Gαi-protein or β-arrestin-dependent signaling through its receptors. Our results support the concept that specific chemokine activities are fine-tuned by posttranslational modifications.

scholarly journals Quinolizidine-Based Variations and Antifungal Activity of Eight Lupinus Species Grown under Greenhouse Conditions

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 305
Author(s):  
Willy Cely-Veloza ◽  
Diego Quiroga ◽  
Ericsson Coy-Barrera
Keyword(s):  
Antifungal Activity ◽  
Biological Activities ◽  
Structural Diversity ◽  
Economic Losses ◽  
Quinolizidine Alkaloids ◽  
Mycelium Growth ◽  
Reference Information ◽  
Naturally Occurring ◽  
The Family ◽  
External Standard

Fusarium oxysporum is an aggressive phytopathogen that affects various plant species, resulting in extensive local and global economic losses. Therefore, the search for competent alternatives is a constant pursuit. Quinolizidine alkaloids (QA) are naturally occurring compounds with diverse biological activities. The structural diversity of quinolizidines is mainly contributed by species of the family Fabaceae, particularly the genus Lupinus. This quinolizidine-based chemo diversity can be explored to find antifungals and even mixtures to address concomitant effects on F. oxysporum. Thus, the antifungal activity of quinolizidine-rich extracts (QREs) from the leaves of eight greenhouse-propagated Lupinus species was evaluated to outline promising QA mixtures against F. oxysporum. Thirteen main compounds were identified and quantified using an external standard. Quantitative analysis revealed different contents per quinolizidine depending on the Lupinus plant, ranging from 0.003 to 32.8 mg/g fresh leaves. Bioautography showed that all extracts were active at the maximum concentration (5 µg/µL). They also exhibited >50% mycelium growth inhibition. All QREs were fungistatic except for the fungicidal QRE of L. polyphyllus Lindl. Angustifoline, matrine, 13α-hydroxylupanine, and 17-oxolupanine were ranked to act jointly against the phytopathogen. Our findings constitute reference information to better understand the antifungal activity of naturally afforded QA mixtures from these globally important plants.

scholarly journals Gene Co-expression Network Analysis for Identifying Modules and Functionally Enriched Pathways in Vitiligo Disease: A Systems Biology Study

2020 ◽  
Author(s):  
Afshin Derakhshani ◽  
Homa Mollaei ◽  
Negin Parsamanesh ◽  
Mohammad Fereidouni ◽  
Ebrahim Miri-Moghaddam ◽  
...  
Keyword(s):  
Systems Biology ◽  
Network Analysis ◽  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Neutrophil Migration ◽  
Enrichment Analysis ◽  
Autoimmune Disorder ◽  
Hub Genes ◽  
Novel Biomarkers

Vitiligo is the most common cause of skin, hair, and oral depigmentation which is known as an autoimmune disorder. Genetic and environmental factors have important roles in the progression of the disease. Dysregulation of gene expression, like microRNAs (miRNA), may serve as major relevant factors. Several biological processes are involved in vitiligo disease and developing a comprehensive approach helps us to better understand the molecular mechanisms of disease. In this research, we describe how a weighted gene co-expression network analysis as a systems biology approach assists to define the primary gene modules, hub genes, and messenger RNA (mRNA)-miRNA regulatory network in vitiligo disease as the novel biomarkers. The results demonstrated a module with a high correlation with vitiligo state. Moreover, gene enrichment analysis showed that this module's genes were mostly involved in some biological activities including G protein-coupled receptors signaling pathway, lymphocyte chemotaxis, chemokine activity, neutrophil migration, granulocyte chemotaxis, etc. The co-expression network was constructed using top hub genes of the correlated module which are named as CXCL10, ARL9, AKR1B10, COX7B, RPL26, SPA17, NDUFAF2, RPF2, DAPL1, RPL34, CWC15, NDUFB3, RPL26L1, ACOT13, HSPB11, and NSA2. MicroRNAs prediction tool (miRWalk) revealed top miRNAs correlated with the interested module. Finally, a drug-target network was constructed which indicated interactions of some food and drug administration (FDA) approved drugs with hub genes. Our findings specified one important module and main hub genes which can be considered as novel biomarkers for vitiligo therapeutic purposes.   

Turmeric

2020 ◽  
pp. 163-172
Author(s):  
Mazia Ahmed ◽  
Urvashi Srivastava ◽  
Chitra Gupta
Keyword(s):  
Biological Activities ◽  
Curcuma Longa ◽  
Healthy Food ◽  
Natural Food ◽  
Food Ingredient ◽  
Tropical Regions ◽  
Naturally Occurring ◽  
Diverse Field ◽  
Wide Range ◽  
The Family

Turmeric (Curcuma longa) is a rhizomatous crop found in tropical regions and belongs to the family Zingiberaceae. It was used in the form of a spice, flavoring substance, coloring agent, and as a therapeutic agent for the treatment of several human ailments for centuries. Turmeric, along with its extracts, has a very broad and diverse field of application. It is an exclusive and versatile naturally occurring plant product having properties of not only a spice but also food colorant, medicine or drug, and cosmetics. In ethnic delicacies, turmeric is a commonly used flavoring ingredient. It is also a popularly used natural food color. It exhibits several biological activities such as having antioxidant, anti-inflammatory, anticarcinogenic, antimutagenic, antimicrobial, antiviral, and antiparasitic properties. It is well known as a skincare product and a healthy food ingredient. It is found to have the capability to prevent or retard a wide range of ailments.

scholarly journals Endocannabinoid-Like Lipid Neuromodulators in the Regulation of Dopamine Signaling: Relevance for Drug Addiction

2020 ◽  
Vol 12 ◽  
Author(s):  
Claudia Sagheddu ◽  
Larissa Helena Torres ◽  
Tania Marcourakis ◽  
Marco Pistis
Keyword(s):  
Psychiatric Disorders ◽  
Biological Activities ◽  
Signaling System ◽  
Physiological Processes ◽  
Naturally Occurring ◽  
The Family ◽  
Complex Lipid ◽  
The Central Nervous System ◽  
Dopamine Signaling

The family of lipid neuromodulators has been rapidly growing, as the use of different -omics techniques led to the discovery of a large number of naturally occurring N-acylethanolamines (NAEs) and N-acyl amino acids belonging to the complex lipid signaling system termed endocannabinoidome. These molecules exert a variety of biological activities in the central nervous system, as they modulate physiological processes in neurons and glial cells and are involved in the pathophysiology of neurological and psychiatric disorders. Their effects on dopamine cells have attracted attention, as dysfunctions of dopamine systems characterize a range of psychiatric disorders, i.e., schizophrenia and substance use disorders (SUD). While canonical endocannabinoids are known to regulate excitatory and inhibitory synaptic inputs impinging on dopamine cells and modulate several dopamine-mediated behaviors, such as reward and addiction, the effects of other lipid neuromodulators are far less clear. Here, we review the emerging role of endocannabinoid-like neuromodulators in dopamine signaling, with a focus on non-cannabinoid N-acylethanolamines and their receptors. Mounting evidence suggests that these neuromodulators contribute to modulate synaptic transmission in dopamine regions and might represent a target for novel medications in alcohol and nicotine use disorder.

scholarly journals New Insights into the Stereochemical Requirements of the Bombesin BB1 Receptor Antagonists Binding

2020 ◽  
Vol 13 (8) ◽  
pp. 197
Author(s):  
Bahareh Rasaeifar ◽  
Patricia Gomez-Gutierrez ◽  
Juan J. Perez
Keyword(s):  
Biological Activities ◽  
Docking Study ◽  
Experimental Information ◽  
Peptide Ligands ◽  
Peripheral Tissues ◽  
Starting Point ◽  
Wide Range ◽  
The Family ◽  
The Central Nervous System ◽  
G Protein Coupled

Members of the family of bombesinlike peptides exert a wide range of biological activities both at the central nervous system and in peripheral tissues through at least three G-Protein Coupled Receptors: BB1, BB2 and BB3. Despite the number of peptide ligands already described, only a few small molecule binders have been disclosed so far, hampering a deeper understanding of their pharmacology. In order to have a deeper understanding of the stereochemical features characterizing binding to the BB1 receptor, we performed the molecular modeling study consisting of the construction of a 3D model of the receptor by homology modeling followed by a docking study of the peptoids PD168368 and PD176252 onto it. Analysis of the complexes permitted us to propose prospective bound conformations of the compounds, consistent with the experimental information available. Subsequently, we defined a pharmacophore describing minimal stereochemical requirements for binding to the BB1 receptor that was used in silico screening. This exercise yielded a set of small molecules that were purchased and tested, showing affinity to the BB1 but not to the BB2 receptor. These molecules exhibit scaffolds of diverse chemical families that can be used as a starting point for the development of novel BB1 antagonists.

scholarly journals C1q-mediated chemotaxis by human neutrophils: involvement of gClqR and G-protein signalling mechanisms

1998 ◽  
Vol 330 (1) ◽  
pp. 247-254 ◽  
Author(s):  
E. A. Leonora LEIGH ◽  
Berhane GHEBREHIWET ◽  
P. S. Tim PERERA ◽  
N. Ian BIRD ◽  
Peter STRONG ◽  
...  
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Oxidative Burst ◽  
Binding Protein ◽  
Neutrophil Migration ◽  
Human Neutrophils ◽  
Classical Pathway ◽  
Dependent Manner ◽  
Directed Movement ◽  
G Protein Coupled

C1q, the first component of the classical pathway of the complement system, interacts with various cell types and triggers a variety of cell-specific cellular responses, such as oxidative burst, chemotaxis, phagocytosis, etc. Different biological responses are attributed to the interaction of C1q with more than one putative cell-surface C1q receptor/C1q-binding protein. Previously, it has been shown that C1q-mediated oxidative burst by neutrophils is not linked to G-protein-coupled fMet-Leu-Phe-mediated response. In the present study, we have investigated neutrophil migration brought about by C1q and tried to identify the signal-transduction pathways involved in the chemotactic response. We found that C1q stimulated neutrophil migration in a dose-dependent manner, primarily by enhancing chemotaxis (directed movement) rather than chemokinesis (random movement). This C1q-induced chemotaxis could be abolished by an inhibitor of G-proteins (pertussis toxin) and PtdIns(3,4,5)P3 kinase (wortmannin and LY294002). The collagen tail of C1q appeared to mediate chemotaxis. gC1qR, a C1q-binding protein, has recently been reported to participate in C1q-mediated chemotaxis of murine mast cells and human eosinophils. We observed that gC1qR enhanced binding of free C1q to adherent neutrophils and promoted C1q-mediated chemotaxis of neutrophils by nearly seven-fold. Our results suggests C1q-mediated chemotaxis involves gC1qR as well as G-protein-coupled signal-transduction mechanisms operating downstream to neutrophil chemotaxis.

Overview of Cellular Mechanisms and Signaling Pathways of Piceatannol

2020 ◽  
Vol 15 (1) ◽  
pp. 4-10 ◽  
Author(s):  
Yang Cao ◽  
Wanli Smith ◽  
Liang Yan ◽  
Lingbo Kong
Keyword(s):  
Animal Studies ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Biological Effects ◽  
Cellular Mechanisms ◽  
Naturally Occurring ◽  
Cardio Protection ◽  
Therapeutic Mechanisms ◽  
Neuro Protection ◽  
Positive Results

Stilbenoids are a group of naturally occurring phenolic compounds found in various plant species. They share a common backbone structure known as stilbene. However, differences in the nature and position of substituents have made it possible to produce many derivatives. Piceatannol [PT], a hydroxylated derivative from resveratrol, exerts various biological activities ranging from cancer prevention, cardio- protection, neuro-protection, anti-diabetic, depigmentation and so on. Although positive results were obtained in most cell culture and animal studies, the relevant cellular and molecular mechanisms of cytokines and signaling pathway about their biological effects still unclear. Thus, in the current review, we focus on the latest findings of PT on cellular biology in order to better understand the underlying therapeutic mechanisms of PT among various diseases.

The Inhibitory Effect of Heparin and Related Glycosaminoglycans on Neutrophil Chemotaxis

1984 ◽  
Vol 52 (02) ◽  
pp. 134-137 ◽  
Author(s):  
Yaacov Matzner ◽  
Gerard Marx ◽  
Ruth Drexler ◽  
Amiram Eldor
Keyword(s):  
Specific Binding ◽  
Anticoagulant Activity ◽  
Neutrophil Migration ◽  
Inhibitory Effect ◽  
Chemotactic Factor ◽  
Human Neutrophils ◽  
Boyden Chamber ◽  
Neutrophil Chemotaxis ◽  
Inhibitory Effects ◽  
Chemotactic Factors

SummaryClinical observations have shown that heparin has antiinflammatory activities. The effect of heparin on neutrophil chemotaxis was evaluated in vitro in the Boyden Chamber. This method enabled differentiation between the direct effects of heparin on neutrophil migration and locomotion, and its effects on chemotactic factors. Heparin inhibited both the random migration and directed locomotion of human neutrophils toward zymosan-activated serum (ZAS) and F-met-leu-phe (FMLP). Inhibition was found to be dependent on the concentrations of the heparin and of the chemotactic factors. No specific binding of heparin to the neutrophils could be demonstrated, and heparin’s inhibitory effects were eliminated by simple washing of the cells. When added directly to the chamber containing chemotactic factor, heparin inhibited the chemotactic activity of ZAS but not that of FMLP, suggesting a direct inhibitory effect against C5a, the principal chemotactic factor in ZAS.Experiments performed with low-molecular-weight heparin, N-desulfated heparin, dextran sulfate, chondroitin sulfate and dextran indicated that the inhibitory effects of heparin on neutrophil chemotaxis are not related to its anticoagulant activity, but probably depend on the degree of sulfation of the heparin molecule.

Current Advances in the Biological Activity of Polysaccharides in Dendrobium with Intriguing Therapeutic Potential

2018 ◽  
Vol 25 (14) ◽  
pp. 1663-1681 ◽  
Author(s):  
Chun-Ting Lee ◽  
Heng-Chun Kuo ◽  
Yung-Hsiang Chen ◽  
Ming-Yen Tsai
Keyword(s):  
Biological Activity ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Biological Effects ◽  
Herbal Medicines ◽  
Research Field ◽  
Protective Effects ◽  
Pharmacological Effects ◽  
The Family ◽  
Anti Tumor Activity

The polysaccharides in many plants are attracting worldwide attention because of their biological activities and medical properties, such as anti-viral, anti-oxidative, antichronic inflammation, anti-hypertensive, immunomodulation, and neuron-protective effects, as well as anti-tumor activity. Denodrobium species, a genus of the family orchidaceae, have been used as herbal medicines for hundreds of years in China due to their pharmacological effects. These effects include nourishing the Yin, supplementing the stomach, increasing body fluids, and clearing heat. Recently, numerous researchers have investigated possible active compounds in Denodrobium species, such as lectins, phenanthrenes, alkaloids, trigonopol A, and polysaccharides. Unlike those of other plants, the biological effects of polysaccharides in Dendrobium are a novel research field. In this review, we focus on these novel findings to give readers an overall picture of the intriguing therapeutic potential of polysaccharides in Dendrobium, especially those of the four commonly-used Denodrobium species: D. huoshanense, D. offininale, D. nobile, and D. chrysotoxum.

Recent Progress of Benzimidazole Hybrids for Anticancer Potential

2020 ◽  
Vol 27 (35) ◽  
pp. 5970-6014 ◽  
Author(s):  
Md. Jawaid Akhtar ◽  
Mohammad Shahar Yar ◽  
Vinod Kumar Sharma ◽  
Ahsan Ahmed Khan ◽  
Zulphikar Ali ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Biological Activities ◽  
Alkylating Agents ◽  
American Chemical Society ◽  
Chemical Society ◽  
Benzimidazole Derivatives ◽  
Progressive Development ◽  
Anticancer Properties ◽  
Naturally Occurring ◽  
Nitrogenous Base

This review presents the detailed account of factors leading to cancer and design strategy for the synthesis of benzimidazole derivatives as anticancer agents. The recent survey for cancer treatment in Cancer facts and figures 2017 American Chemical Society has shown progressive development in fighting cancer. Researchers all over the world in both developed and developing countries are in a continuous effort to tackle this serious concern. Benzimidazole and its derivatives showed a broad range of biological activities due to their resemblance with naturally occurring nitrogenous base i.e. purine. The review discussed benzimidazole derivatives showing anticancer properties through a different mechanism viz. intercalation, alkylating agents, topoisomerases, DHFR enzymes, and tubulin inhibitors. Benzimidazole derivatives act through a different mechanism and the substituents reported from the earlier and recent research articles are prerequisites for the synthesis of targeted based benzimidazole derivatives as anticancer agents. The review focuses on an easy comparison of the substituent essential for potency and selectivity through SAR presented in figures. This will further provide a better outlook or fulfills the challenges faced in the development of novel benzimidazole derivatives as anticancer.

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