scholarly journals Transglutaminases in Monocytes and Macrophages

2018 ◽  
Vol 6 (4) ◽  
pp. 115 ◽  
Author(s):  
Huifang Sun ◽  
Mari T. Kaartinen

Macrophages are key players in various inflammatory disorders and pathological conditions via phagocytosis and orchestrating immune responses. They are highly heterogeneous in terms of their phenotypes and functions by adaptation to different organs and tissue environments. Upon damage or infection, monocytes are rapidly recruited to tissues and differentiate into macrophages. Transglutaminases (TGs) are a family of structurally and functionally related enzymes with Ca2+-dependent transamidation and deamidation activity. Numerous studies have shown that TGs, particularly TG2 and Factor XIII-A, are extensively involved in monocyte- and macrophage-mediated physiological and pathological processes. In the present review, we outline the current knowledge of the role of TGs in the adhesion and extravasation of monocytes, the expression of TGs during macrophage differentiation, and the regulation of TG2 expression by various pro- and anti-inflammatory mediators in macrophages. Furthermore, we summarize the role of TGs in macrophage phagocytosis and the understanding of the mechanisms involved. Finally, we review the roles of TGs in tissue-specific macrophages, including monocytes/macrophages in vasculature, alveolar and interstitial macrophages in lung, microglia and infiltrated monocytes/macrophages in central nervous system, and osteoclasts in bone. Based on the studies in this review, we conclude that monocyte- and macrophage-derived TGs are involved in inflammatory processes in these organs. However, more in vivo studies and clinical studies during different stages of these processes are required to determine the accurate roles of TGs, their substrates, and the mechanisms-of-action.

Author(s):  
Waill Elkhateeb ◽  
Ghoson Daba

Abstract. Elkhateeb WA, Daba GM. 2020. Review: The endless nutritional and pharmaceutical benefits of the Himalayan gold, Cordyceps; Current knowledge and prospective potentials. Biofarmasi J Nat Prod Biochem 18: 70-77. As a traditional medicine, Cordyceps has long been used in Asian nations for maintaining vivacity and boosting immunity. Numerous publications on various bioactivities of Cordyceps have been investigated in both in-vitro as well as in vivo studies. Nevertheless, the role of Cordyceps is still arguable whether it acts as food supplement for health benefits or a real healing drug that can be prescribed in medicine. The Cordyceps industry has developed greatly and offers thousands of products, commonly available in a global marketplace. In this review, focus will be on introducing the ecology of Cordyceps and their classification. Moreover, elucidation of the richness of extracts originated from this mushroom in nutritional components was presented, with description of the chemical compounds of Cordyceps and its well-known compounds such as cordycepin, and cordycepic acid. Furthermore, highlights on natural growth and artificial cultivation of famous Cordyceps species were presented. The health benefits and reported bioactivities of Cordyceps species as promising antimicrobial, anticancer, hypocholesterolemic, antioxidant, antiviral, anti-inflammatory, organ protective agent, and enhancer for organ function were presented.


2014 ◽  
Vol 128 (6) ◽  
pp. 337-347 ◽  
Author(s):  
Nathalie Grandvaux ◽  
Mélissa Mariani ◽  
Karin Fink

Determining the role of NADPH oxidases in the context of virus infection is an emerging area of research and our knowledge is still sparse. The expression of various isoforms of NOX/DUOX (NADPH oxidase/dual oxidase) in the epithelial cells (ECs) lining the respiratory tract renders them primary sites from which to orchestrate the host defence against respiratory viruses. Accumulating evidence reveals distinct facets of the involvement of NOX/DUOX in host antiviral and pro-inflammatory responses and in the control of the epithelial barrier integrity, with individual isoforms mediating co-operative, but surprisingly also opposing, functions. Although in vivo studies in mice are in line with some of these observations, a complete understanding of the specific functions of epithelial NOX/DUOX awaits lung epithelial-specific conditional knockout mice. The goal of the present review is to summarize our current knowledge of the role of individual NOX/DUOX isoforms expressed in the lung epithelium in the context of respiratory virus infections so as to highlight potential opportunities for therapeutic intervention.


2020 ◽  
Author(s):  
Sheniz Yuzeir ◽  
Liana Gercheva

It was recently proved that neutrophils and platelets are active participants in some inflammatory processes as well as a number of pathological conditions, including neoplastic diseases and thrombosis. It has been found that circulating neutrophils actively affect the mechanisms of tumour genesis, and along with platelets, act as independent regulators of different complications in infectious and malignant diseases. A few years ago, it was found that neutrophils have the ability to release extracellular traps (called neutrophil extracellular traps or NETs). Thus, neutrophils use both intracellular and extracellular mechanisms to limit inflammatory complications. Several recent studies confirmed that NETs increase considerably in malignant diseases, demonstrating that tumour-induced NETosis is a clinically significant process. It is recognised as an element of tumour biology, as it participates in tumour progression and angiogenesis. Neutrophils and the NETs released from them are stimulators of thrombotic processes in physiological and pathological conditions. Several reports demonstrate the connection between NETs and thrombosis. The presence of NETosis serves as a potential risk factor for thrombotic complications in malignant diseases. This chapter summarises the current knowledge of NETosis and the mechanisms that lead to the formation of NETs, including the role of circulating platelet–neutrophil complexes as regulators of tumour-induced NETosis in malignant diseases.


Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1765 ◽  
Author(s):  
Donatella Aldinucci ◽  
Cinzia Borghese ◽  
Naike Casagrande

Tumor cells can “hijack” chemokine networks to support tumor progression. In this context, the C-C chemokine ligand 5/C-C chemokine receptor type 5 (CCL5/CCR5) axis is gaining increasing attention, since abnormal expression and activity of CCL5 and its receptor CCR5 have been found in hematological malignancies and solid tumors. Numerous preclinical in vitro and in vivo studies have shown a key role of the CCL5/CCR5 axis in cancer, and thus provided the rationale for clinical trials using the repurposed drug maraviroc, a CCR5 antagonist used to treat HIV/AIDS. This review summarizes current knowledge on the role of the CCL5/CCR5 axis in cancer. First, it describes the involvement of the CCL5/CCR5 axis in cancer progression, including autocrine and paracrine tumor growth, ECM (extracellular matrix) remodeling and migration, cancer stem cell expansion, DNA damage repair, metabolic reprogramming, and angiogenesis. Then, it focuses on individual hematological and solid tumors in which CCL5 and CCR5 have been studied preclinically. Finally, it discusses clinical trials of strategies to counteract the CCL5/CCR5 axis in different cancers using maraviroc or therapeutic monoclonal antibodies.


Author(s):  
Amandine Gamble ◽  
Yao Yu Yeo ◽  
Aubrey Butler ◽  
Hubert Tang ◽  
Celine Snedden ◽  
...  

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other important viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely studied for virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models to characterize the drivers of syncytium formation and its implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.


Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1755
Author(s):  
Amandine Gamble ◽  
Yao Yu Yeo ◽  
Aubrey A. Butler ◽  
Hubert Tang ◽  
Celine E. Snedden ◽  
...  

Syncytium formation, i.e., cell–cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely used for the study of virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models with which to characterize the drivers of syncytium formation and the implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts, and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.


2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.


2020 ◽  
Vol 20 ◽  
Author(s):  
Nur Najmi Mohamad Anuar ◽  
Nurul Iman Natasya Zulkafali ◽  
Azizah Ugusman

: Matrix metalloproteinases (MMPs) are a group of zinc-dependent metallo-endopeptidase that are responsible towards the degradation, repair and remodelling of extracellular matrix components. MMPs play an important role in maintaining a normal physiological function and preventing diseases such as cancer and cardiovascular diseases. Natural products derived from plants have been used as traditional medicine for centuries. Its active compounds, such as catechin, resveratrol and quercetin, are suggested to play an important role as MMPs inhibitors, thereby opening new insights into their applications in many fields, such as pharmaceutical, cosmetic and food industries. This review summarises the current knowledge on plant-derived natural products with MMP-modulating activities. Most of the reviewed plant-derived products exhibit an inhibitory activity on MMPs. Amongst MMPs, MMP-2 and MMP-9 are the most studied. The expression of MMPs is inhibited through respective signalling pathways, such as MAPK, NF-κB and PI3 kinase pathways, which contribute to the reduction in cancer cell behaviours, such as proliferation and migration. Most studies have employed in vitro models, but a limited number of animal studies and clinical trials have been conducted. Even though plant-derived products show promising results in modulating MMPs, more in vivo studies and clinical trials are needed to support their therapeutic applications in the future.


2002 ◽  
Vol 130 (2) ◽  
pp. 233-240 ◽  
Author(s):  
E. GRUNEBAUM ◽  
M. BLANK ◽  
S. COHEN ◽  
A. AFEK ◽  
J. KOPOLOVIC ◽  
...  

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 78
Author(s):  
Lachlan A. Bourke ◽  
Christina N. Zdenek ◽  
Edgar Neri-Castro ◽  
Melisa Bénard-Valle ◽  
Alejandro Alagón ◽  
...  

The toxin composition of snake venoms and, thus, their functional activity, can vary between and within species. Intraspecific venom variation across a species’ geographic range is a major concern for antivenom treatment of envenomations, particularly for countries like French Guiana that lack a locally produced antivenom. Bothrops asper and Bothrops atrox are the most medically significant species of snakes in Latin America, both producing a variety of clinical manifestations, including systemic bleeding. These pathophysiological actions are due to the activation by the venom of the blood clotting factors Factor X and prothrombin, thereby causing severe consumptive coagulopathy. Both species are extremely wide-ranging, and previous studies have shown their venoms to exhibit regional venom variation. In this study, we investigate the differential coagulotoxic effects on human plasma of six venoms (four B. asper and two B. atrox samples) from different geographic locations, spanning from Mexico to Peru. We assessed how the venom variation of these venom samples affects neutralisation by five regionally available antivenoms: Antivipmyn, Antivipmyn-Tri, PoliVal-ICP, Bothrofav, and Soro Antibotrópico (SAB). The results revealed both inter- and intraspecific variations in the clotting activity of the venoms. These variations in turn resulted in significant variation in antivenom efficacy against the coagulotoxic effects of these venoms. Due to variations in the venoms used in the antivenom production process, antivenoms differed in their species-specific or geographical neutralisation capacity. Some antivenoms (PoliVal-ICP, Bothrofav, and SAB) showed species-specific patterns of neutralisation, while another antivenom (Antivipmyn) showed geographic-specific patterns of neutralisation. This study adds to current knowledge of Bothrops venoms and also illustrates the importance of considering evolutionary biology when developing antivenoms. Therefore, these results have tangible, real-world implications by aiding evidence-based design of antivenoms for treatment of the envenomed patient. We stress that these in vitro studies must be backed by future in vivo studies and clinical trials before therapeutic guidelines are issued regarding specific antivenom use in a clinical setting.


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