scholarly journals Autophagy and LAP in the Fight against Fungal Infections: Regulation and Therapeutics

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Vasileios Oikonomou ◽  
Giorgia Renga ◽  
Antonella De Luca ◽  
Monica Borghi ◽  
Marilena Pariano ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Cell Types ◽  
Fungal Species ◽  
Host Immune Responses ◽  
Host Protection ◽  
Pathogen Clearance ◽  
The Relationship ◽  
Broad Role

Phagocytes fight fungi using canonical and noncanonical, also called LC3-associated phagocytosis (LAP), autophagy pathways. However, the outcomes of autophagy/LAP in shaping host immune responses appear to greatly vary depending on fungal species and cell types. By allowing efficient pathogen clearance and/or degradation of inflammatory mediators, autophagy proteins play a broad role in cellular and immune homeostasis during fungal infections. Indeed, defects in autophagic machinery have been linked with aberrant host defense and inflammatory states. Thus, understanding the molecular mechanisms underlying the relationship between the different forms of autophagy may offer a way to identify drugable molecular signatures discriminating between selective recognition of cargo and host protection. In this regard, IFN-γ and anakinra are teaching examples of successful antifungal agents that target the autophagy machinery. This article provides an overview of the role of autophagy/LAP in response to fungi and in their infections, regulation, and therapeutic exploitation.

scholarly journals Role of Protein Glycosylation in Interactions of Medically Relevant Fungi with the Host

2021 ◽  
Vol 7 (10) ◽  
pp. 875
Author(s):  
Manuela Gómez-Gaviria ◽  
Ana P. Vargas-Macías ◽  
Laura C. García-Carnero ◽  
Iván Martínez-Duncker ◽  
Héctor M. Mora-Montes
Keyword(s):  
Protein Trafficking ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Fungal Species ◽  
Protein Glycosylation ◽  
Amino Acid Side Chain ◽  
Post Translational Modification ◽  
Fungal Cell ◽  
The Relationship

Protein glycosylation is a highly conserved post-translational modification among organisms. It plays fundamental roles in many biological processes, ranging from protein trafficking and cell adhesion to host–pathogen interactions. According to the amino acid side chain atoms to which glycans are linked, protein glycosylation can be divided into two major categories: N-glycosylation and O-glycosylation. However, there are other types of modifications such as the addition of GPI to the C-terminal end of the protein. Besides the importance of glycoproteins in biological functions, they are a major component of the fungal cell wall and plasma membrane and contribute to pathogenicity, virulence, and recognition by the host immunity. Given that this structure is absent in host mammalian cells, it stands as an attractive target for developing selective compounds for the treatment of fungal infections. This review focuses on describing the relationship between protein glycosylation and the host–immune interaction in medically relevant fungal species.

scholarly journals The Role of Fungi in the Cocoa Production Chain and the Challenge of Climate Change

2021 ◽  
Vol 7 (3) ◽  
pp. 202
Author(s):  
Johannes Delgado-Ospina ◽  
Junior Bernardo Molina-Hernández ◽  
Clemencia Chaves-López ◽  
Gianfranco Romanazzi ◽  
Antonello Paparella
Keyword(s):  
Climate Change ◽  
Fungal Infections ◽  
Close Association ◽  
Pathogenic Fungi ◽  
Fungal Species ◽  
Mitigation Strategies ◽  
Plant Diseases ◽  
Production Chain ◽  
Cocoa Production

Background: The role of fungi in cocoa crops is mainly associated with plant diseases and contamination of harvest with unwanted metabolites such as mycotoxins that can reach the final consumer. However, in recent years there has been interest in discovering other existing interactions in the environment that may be beneficial, such as antagonism, commensalism, and the production of specific enzymes, among others. Scope and approach: This review summarizes the different fungi species involved in cocoa production and the cocoa supply chain. In particular, it examines the presence of fungal species during cultivation, harvest, fermentation, drying, and storage, emphasizing the factors that possibly influence their prevalence in the different stages of production and the health risks associated with the production of mycotoxins in the light of recent literature. Key findings and conclusion: Fungi associated with the cocoa production chain have many different roles. They have evolved in a varied range of ecosystems in close association with plants and various habitats, affecting nearly all the cocoa chain steps. Reports of the isolation of 60 genera of fungi were found, of which only 19 were involved in several stages. Although endophytic fungi can help control some diseases caused by pathogenic fungi, climate change, with increased rain and temperatures, together with intensified exchanges, can favour most of these fungal infections, and the presence of highly aggressive new fungal genotypes increasing the concern of mycotoxin production. For this reason, mitigation strategies need to be determined to prevent the spread of disease-causing fungi and preserve beneficial ones.

The impact of Traditional Chinese Medicine on mitophagy in disease models

2021 ◽  
Vol 27 ◽  
Author(s):  
Li-Ping Yu ◽  
Ting-Ting Shi ◽  
Yan-Qin Li ◽  
Jian-Kang Mu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Disease Models ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

scholarly journals Overview on the Prevalence of Fungal Infections, Immune Response, and Microbiome Role in COVID-19 Patients

2021 ◽  
Vol 7 (9) ◽  
pp. 720
Author(s):  
Maryam Roudbary ◽  
Sunil Kumar ◽  
Awanish Kumar ◽  
Lucia Černáková ◽  
Fatemeh Nikoomanesh ◽  
...  
Keyword(s):  
Immune Response ◽  
Intensive Care ◽  
Intensive Care Units ◽  
Fungal Infections ◽  
Fungal Species ◽  
Fungal Diseases ◽  
Severe Illness ◽  
Rising Incidence ◽  
Cryptococcus Spp

Patients with severe COVID-19, such as individuals in intensive care units (ICU), are exceptionally susceptible to bacterial and fungal infections. The most prevalent fungal infections are aspergillosis and candidemia. Nonetheless, other fungal species (for instance, Histoplasma spp., Rhizopus spp., Mucor spp., Cryptococcus spp.) have recently been increasingly linked to opportunistic fungal diseases in COVID-19 patients. These fungal co-infections are described with rising incidence, severe illness, and death that is associated with host immune response. Awareness of the high risks of the occurrence of fungal co-infections is crucial to downgrade any arrear in diagnosis and treatment to support the prevention of severe illness and death directly related to these infections. This review analyses the fungal infections, treatments, outcome, and immune response, considering the possible role of the microbiome in these patients. The search was performed in Medline (PubMed), using the words “fungal infections COVID-19”, between 2020–2021.

Regulation of TRPV5 and TRPV6 by associated proteins

2006 ◽  
Vol 290 (6) ◽  
pp. F1295-F1302 ◽  
Author(s):  
Stan F. J. van de Graaf ◽  
Joost G. J. Hoenderop ◽  
René J. M. Bindels
Keyword(s):  
Molecular Mechanisms ◽  
Hormonal Control ◽  
Trp Channel ◽  
Intestinal Lumen ◽  
Blood Compartment ◽  
Associated Proteins ◽  
The Relationship ◽  
Insight Into ◽  
Prime Target

The epithelial Ca2+ channels TRPV5 and TRPV6 are the most Ca2+-selective members of the TRP channel superfamily. These channels are the prime target for hormonal control of the active Ca2+ flux from the urine space or intestinal lumen to the blood compartment. Insight into their regulation is, therefore, pivotal in our understanding of the (patho)physiology of Ca2+ homeostasis. The recent elucidation of TRPV5/6-associated proteins has provided new insight into the molecular mechanisms underlying the regulation of these channels. In this review, we describe the various means of TRPV5/6 regulation, the role of channel-associated proteins herein, and the relationship between both processes.

scholarly journals Activation of the complement system by pathogenic fungi.

1996 ◽  
Vol 9 (1) ◽  
pp. 34-46 ◽  
Author(s):  
T R Kozel
Keyword(s):  
Complement System ◽  
Host Resistance ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Pathogenic Fungi ◽  
Complement Cascade ◽  
Experimental Animals ◽  
Molecular Bases ◽  
The Complement System

Fungi have been studied as prototype activators of the complement cascade since the early 1900s. More recently, attention has focused on the role of the complement system in the pathogenesis of fungal infections. The interactions of Cryptococcus neoformans and Candida albicans with the complement system are the most widely characterized; however, all pathogenic fungi examined to date have the ability to initiate the complement cascade. The molecular mechanisms for initiation and regulation of the complement cascade differ from one fungus to another, most likely reflecting differences in the structure of the outer layers of the cell wall. The molecular bases for such differences remain to be identified. Studies of mycoses in experimental animals with induced or congenital deficiencies in the complement system demonstrate that complement is an important innate system for control of fungal infection. Contributions to host resistance include opsonization and generation of inflammatory mediators. Inflammation induced by chemotactic products of the complement system may contribute to the pathogenesis of some fungal infections.

scholarly journals Kynurenic acid and cancer: facts and controversies

2019 ◽  
Vol 77 (8) ◽  
pp. 1531-1550 ◽  
Author(s):  
Katarzyna Walczak ◽  
Artur Wnorowski ◽  
Waldemar A. Turski ◽  
Tomasz Plech
Keyword(s):  
Kynurenic Acid ◽  
Molecular Mechanisms ◽  
Potential Role ◽  
Cancer Cell Proliferation ◽  
Gastrointestinal Microbiota ◽  
Tryptophan Metabolite ◽  
Peripheral Cells ◽  
The Relationship ◽  
The Brain

Abstract Kynurenic acid (KYNA) is an endogenous tryptophan metabolite exerting neuroprotective and anticonvulsant properties in the brain. However, its importance on the periphery is still not fully elucidated. KYNA is produced endogenously in various types of peripheral cells, tissues and by gastrointestinal microbiota. Furthermore, it was found in several products of daily human diet and its absorption in the digestive tract was evidenced. More recent studies were focused on the potential role of KYNA in carcinogenesis and cancer therapy; however, the results were ambiguous and the biological activity of KYNA in these processes has not been unequivocally established. This review aims to summarize the current views on the relationship between KYNA and cancer. The differences in KYNA concentration between physiological conditions and cancer, as well as KYNA production by both normal and cancer cells, will be discussed. The review also describes the effect of KYNA on cancer cell proliferation and the known potential molecular mechanisms of this activity.

scholarly journals Regulation of TRH neurons and energy homeostasis-related signals under stress

2015 ◽  
Vol 224 (3) ◽  
pp. R139-R159 ◽  
Author(s):  
Patricia Joseph-Bravo ◽  
Lorraine Jaimes-Hoy ◽  
Jean-Louis Charli
Keyword(s):  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Cellular Phenotype ◽  
Energy Demands ◽  
Rapid Responses ◽  
Hpt Axis

Energy homeostasis relies on a concerted response of the nervous and endocrine systems to signals evoked by intake, storage, and expenditure of fuels. Glucocorticoids (GCs) and thyroid hormones are involved in meeting immediate energy demands, thus placing the hypothalamo–pituitary–thyroid (HPT) and hypothalamo–pituitary–adrenal axes at a central interface. This review describes the mode of regulation of hypophysiotropic TRHergic neurons and the evidence supporting the concept that they act as metabolic integrators. Emphasis has been be placed on i) the effects of GCs on the modulation of transcription ofTrhin vivoandin vitro, ii) the physiological and molecular mechanisms by which acute or chronic situations of stress and energy demands affect the activity of TRHergic neurons and the HPT axis, and iii) the less explored role of non-hypophysiotropic hypothalamic TRH neurons. The partial evidence gathered so far is indicative of a contrasting involvement of distinct TRH cell types, manifested through variability in cellular phenotype and physiology, including rapid responses to energy demands for thermogenesis or physical activity and nutritional status that may be modified according to stress history.

scholarly journals The Neurobiology of Selenium: Looking Back and to the Future

2021 ◽  
Vol 15 ◽  
Author(s):  
Ulrich Schweizer ◽  
Simon Bohleber ◽  
Wenchao Zhao ◽  
Noelia Fradejas-Villar
Keyword(s):  
Cell Biology ◽  
Molecular Mechanisms ◽  
Human Genetics ◽  
Epileptic Seizures ◽  
Cell Types ◽  
Mammalian Brain ◽  
The Individual ◽  
The Brain ◽  
Looking Back

Eighteen years ago, unexpected epileptic seizures in Selenop-knockout mice pointed to a potentially novel, possibly underestimated, and previously difficult to study role of selenium (Se) in the mammalian brain. This mouse model was the key to open the field of molecular mechanisms, i.e., to delineate the roles of selenium and individual selenoproteins in the brain, and answer specific questions like: how does Se enter the brain; which processes and which cell types are dependent on selenoproteins; and, what are the individual roles of selenoproteins in the brain? Many of these questions have been answered and much progress is being made to fill remaining gaps. Mouse and human genetics have together boosted the field tremendously, in addition to traditional biochemistry and cell biology. As always, new questions have become apparent or more pressing with solving older questions. We will briefly summarize what we know about selenoproteins in the human brain, glance over to the mouse as a useful model, and then discuss new questions and directions the field might take in the next 18 years.

scholarly journals The Role of Autophagy in Gastric Cancer Chemoresistance: Friend or Foe?

2020 ◽  
Vol 8 ◽  
Author(s):  
Jing-Li Xu ◽  
Li Yuan ◽  
Yan-Cheng Tang ◽  
Zhi-Yuan Xu ◽  
Han-Dong Xu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Chemotherapy Resistance ◽  
Dual Roles ◽  
Non Coding Rnas ◽  
Regulatory Effects ◽  
Cancer Chemoresistance ◽  
The Relationship

Gastric cancer is the third most common cause of cancer-related death worldwide. Drug resistance is the main inevitable and vital factor leading to a low 5-year survival rate for patients with gastric cancer. Autophagy, as a highly conserved homeostatic pathway, is mainly regulated by different proteins and non-coding RNAs (ncRNAs) and plays dual roles in drug resistance of gastric cancer. Thus, targeting key regulatory nodes in the process of autophagy by small molecule inhibitors or activators has become one of the most promising strategies for the treatment of gastric cancer in recent years. In this review, we provide a systematic summary focusing on the relationship between autophagy and chemotherapy resistance in gastric cancer. We comprehensively discuss the roles and molecular mechanisms of multiple proteins and the emerging ncRNAs including miRNAs and lncRNAs in the regulation of autophagy pathways and gastric cancer chemoresistance. We also summarize the regulatory effects of autophagy inhibitor and activators on gastric cancer chemoresistance. Understanding the vital roles of autophagy in gastric cancer chemoresistance will provide novel opportunities to develop promising therapeutic strategies for gastric cancer.

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