scholarly journals The Revival of the Battle between David and Goliath in the Enteric Viruses and Microbiota Struggle: Potential Implication for Celiac Disease

2019 ◽  
Vol 7 (6) ◽  
pp. 173 ◽  
Author(s):  
Aaron Lerner ◽  
Ajay Ramesh ◽  
Torsten Matthias
Keyword(s):  
Celiac Disease ◽  
Current Knowledge ◽  
Potential Implication ◽  
Behavior Understanding ◽  
And Behavior ◽  
Cycle Regulation ◽  
David And Goliath ◽  
Regulation Mode ◽  
Structure And Activity

The human gut is inhabited by overcrowded prokaryotic communities, a major component of which is the virome, comprised of viruses, bacteriophages, archaea, eukaryotes and bacteria. The virome is required for luminal homeostasis and, by their lytic or synergic capacities, they can regulate the microbial community structure and activity. Dysbiosis is associated with numerous chronic human diseases. Since the virome can impact microbial genetics and behavior, understanding its biology, composition, cellular cycle, regulation, mode of action and potential beneficial or hostile activities can change the present paradigm of the cross-talks in the luminal gut compartment. Celiac disease is a frequent autoimmune disease in which viruses can play a role in disease development. Based on the current knowledge on the enteric virome, in relation to celiac disease pathophysiological evolvement, the current review summarizes the potential interphases between the two. Exploring and understanding the role of the enteric virome in gluten-dependent enteropathy might bring new therapeutic strategies to change the luminal eco-event for the patient’s benefit.

scholarly journals The Emerging Role of Cyclin-Dependent Kinases (CDKs) in Pancreatic Ductal Adenocarcinoma

2018 ◽  
Vol 19 (10) ◽  
pp. 3219 ◽  
Author(s):  
Balbina García-Reyes ◽  
Anna-Laura Kretz ◽  
Jan-Philipp Ruff ◽  
Silvia von Karstedt ◽  
Andreas Hillenbrand ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Ductal Adenocarcinoma ◽  
Transcriptional Elongation ◽  
Cyclin Dependent Kinases ◽  
Dismal Prognosis ◽  
The Family ◽  
Cycle Regulation

The family of cyclin-dependent kinases (CDKs) has critical functions in cell cycle regulation and controlling of transcriptional elongation. Moreover, dysregulated CDKs have been linked to cancer initiation and progression. Pharmacological CDK inhibition has recently emerged as a novel and promising approach in cancer therapy. This idea is of particular interest to combat pancreatic ductal adenocarcinoma (PDAC), a cancer entity with a dismal prognosis which is owed mainly to PDAC’s resistance to conventional therapies. Here, we review the current knowledge of CDK biology, its role in cancer and the therapeutic potential to target CDKs as a novel treatment strategy for PDAC.

PCSK9 and inflammation. Maybe a role in autoimmune diseases? Focus on rheumatoid arthritis and systemic lupus erythematosus

2021 ◽  
Vol 28 ◽  
Author(s):  
Stefano Ministrini ◽  
Federico Carbone
Keyword(s):  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Disease Model ◽  
Clinical Findings ◽  
Low Grade ◽  
Pcsk9 Inhibitors ◽  
Potential Implication ◽  
Complex Signaling

: Despite a clear epidemiological link between autoimmune disease and cardiovascular (CV) risk exists, pathophysiological explanations are extremely complex and far from being elucidated. Dysregulation of metabolic pathways and chronic low-grade inflammation represent common pathways, but CV risk still remains underestimated in patients with autoimmune diseas. Among different candidate mediators, pro-protein convertase subtilisin/kexin type 9 (PCSK9) is attracting a growing attention, due to a combined effect on lipid metabolism and inflammatory response. Study on PCSK9 inhibitors have established a clear benefit on CV outcome without an established effect on inflammation. Conversely, evidence from sepsis and HIV infection strongly support a pro-inflammatory role of PCSK9. Still uncertain is instead the role of PCSK9 in autoimmune disease. So far reported clinical findings are controversial and likely reflect the poor knowledge of PCSK9 activity on monocyte/macrophage migration and activation. The complex signaling network around PCSK9 synthesis and metabolism may also have a role, especially concerning the involvement of scavenger receptors such as CD36. Such complexity in PCSK9 signaling seems particularly evident in autoimmune disease model. This would also potentially explain the observed independency between lipid profile and PCSK9 levels, the so-called “lipid paradox”. In this narrative review we will summarize the current knowledge about the complex network of PCSK9 signaling. We will focus of upstream and downstream pathways with potential implication in autoimmune disease and potential effects of PCSK9 inhibiting strategies.

scholarly journals The role of 3′ end uridylation in RNA metabolism and cellular physiology

2018 ◽  
Vol 373 (1762) ◽  
pp. 20180171 ◽  
Author(s):  
Dagmar Zigáčková ◽  
Štěpánka Vaňáčová
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Rna Metabolism ◽  
Rna Degradation ◽  
Key Factors ◽  
Theme Issue ◽  
Cellular Physiology ◽  
Rna Maturation ◽  
Cycle Regulation

Most eukaryotic RNAs are posttranscriptionally modified. The majority of modifications promote RNA maturation, others may regulate function and stability. The 3′ terminal non-templated oligouridylation is a widespread modification affecting many cellular RNAs at some stage of their life cycle. It has diverse roles in RNA metabolism. The most prevalent is the regulation of stability and quality control. On the cellular and organismal level, it plays a critical role in a number of pathways, such as cell cycle regulation, cell death, development or viral infection. Defects in uridylation have been linked to several diseases. This review summarizes the current knowledge about the role of the 3′ terminal oligo(U)-tailing in biology of various RNAs in eukaryotes and describes key factors involved in these pathways. This article is part of the theme issue ‘5′ and 3′ modifications controlling RNA degradation’.

scholarly journals Mitochondrial Surveillance by Cdc48/p97: MAD vs. Membrane Fusion

2020 ◽  
Vol 21 (18) ◽  
pp. 6841
Author(s):  
Mafalda Escobar-Henriques ◽  
Vincent Anton
Keyword(s):  
Membrane Fusion ◽  
Cell Cycle Regulation ◽  
Current Knowledge ◽  
Protein Complexes ◽  
Cellular Viability ◽  
Mitochondrial Quality Control ◽  
Cellular Processes ◽  
Mitochondrial Regulation ◽  
Cycle Regulation

Cdc48/p97 is a ring-shaped, ATP-driven hexameric motor, essential for cellular viability. It specifically unfolds and extracts ubiquitylated proteins from membranes or protein complexes, mostly targeting them for proteolytic degradation by the proteasome. Cdc48/p97 is involved in a multitude of cellular processes, reaching from cell cycle regulation to signal transduction, also participating in growth or death decisions. The role of Cdc48/p97 in endoplasmic reticulum-associated degradation (ERAD), where it extracts proteins targeted for degradation from the ER membrane, has been extensively described. Here, we present the roles of Cdc48/p97 in mitochondrial regulation. We discuss mitochondrial quality control surveillance by Cdc48/p97 in mitochondrial-associated degradation (MAD), highlighting the potential pathologic significance thereof. Furthermore, we present the current knowledge of how Cdc48/p97 regulates mitofusin activity in outer membrane fusion and how this may impact on neurodegeneration.

Chronobiology and Chronotherapy in Depression: Current Knowledge and Chronotherapeutic Promises

2021 ◽  
Vol 16 (3) ◽  
pp. 179-193
Author(s):  
Milagros Rojas ◽  
Mervin Chávez-Castillo ◽  
Daniela Pírela ◽  
Ángel Ortega ◽  
Juan Salazar ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Bright Light ◽  
Light Therapy ◽  
Symptoms Of Depression ◽  
Organic Systems ◽  
Treatment Of Depression ◽  
Promising Treatment ◽  
And Behavior ◽  
Pathophysiologic Mechanisms

Background: Depression is a heavily prevalent mental disorder. Symptoms of depression extend beyond mood, cognition, and behavior to include a spectrum of somatic manifestations in all organic systems. Changes in sleep and neuroendocrine rhythms are especially prominent, and disruptions of circadian rhythms have been closely related to the neurobiology of depression. With the advent of increased research in chronobiology, various pathophysiologic mechanisms have been proposed, including anomalies of sleep architecture, the effects of clock gene polymorphisms in monoamine metabolism, and the deleterious impact of social zeitgebers. The identification of these chronodisruptions has propelled the emergence of several chronotherapeutic strategies, both pharmacological and non-pharmacological, with varying degrees of clinical evidence. Methods: The fundamental objective of this review is to integrate current knowledge about the role of chronobiology and depression and to summarize the interventions developed to resynchronize biorhythms both within an individual and with geophysical time. Results: We have found that among the non-pharmacological alternatives, triple chronotherapywhich encompasses bright light therapy, sleep deprivation therapy, and consecutive sleep phase advance therapy-has garnered the most considerable scientific interest. On the other hand, agomelatine appears to be the most promising pharmacological option, given its unique melatonergic pharmacodynamics. Conclusions: Research in chronotherapy as a treatment for depression is currently booming. Novel interventions could play a significant role in adopting new options for the treatment of depression, with Tripe Cronotherapy standing out as the most promising treatment.

scholarly journals Thioredoxins: Emerging Players in the Regulation of Protein S-Nitrosation in Plants

Plants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1426
Author(s):  
Tereza Jedelská ◽  
Lenka Luhová ◽  
Marek Petřivalský
Keyword(s):  
Current Knowledge ◽  
Plant Root ◽  
Thioredoxin Reductase ◽  
Protein S ◽  
Nitroso Group ◽  
Protein Thiols ◽  
Genomics And Proteomics ◽  
Cysteine Thiols ◽  
Structure And Activity

S-nitrosation has been recognized as an important mechanism of ubiquitous posttranslational modification of proteins on the basis of the attachment of the nitroso group to cysteine thiols. Reversible S-nitrosation, similarly to other redox-based modifications of protein thiols, has a profound effect on protein structure and activity and is considered as a convergence of signaling pathways of reactive nitrogen and oxygen species. This review summarizes the current knowledge on the emerging role of the thioredoxin-thioredoxin reductase (TRXR-TRX) system in protein denitrosation. Important advances have been recently achieved on plant thioredoxins (TRXs) and their properties, regulation, and functions in the control of protein S-nitrosation in plant root development, translation of photosynthetic light harvesting proteins, and immune responses. Future studies of plants with down- and upregulated TRXs together with the application of genomics and proteomics approaches will contribute to obtain new insights into plant S-nitrosothiol metabolism and its regulation.

scholarly journals Role of the Gut Microbiota in Celiac Disease: An Update

2021 ◽  
Vol 10 (01) ◽  
pp. 49-53
Author(s):  
Nada BOUTRID ◽  
◽  
Mounira AMRANE ◽  
Belkacem BIOUD ◽  
Hakim RAHMOUNE
Keyword(s):  
Celiac Disease ◽  
Autoimmune Disease ◽  
Gut Microbiota ◽  
Potential Implication ◽  
Chronic Autoimmune Disease

Celiac disease (CD) is a chronic, autoimmune disease secondary to the gluten ingestion, or more specifically gliadin molecules, developing in genetically predisposed individuals. Recent metagenomic and metabolomic studies provide unprecedented information on the major involvement of the gut microbiota in CD. In this review, we describe the main features of the gut microbiota interfering with the onset and development of CD, as well as its potential implication in CD prevention.

scholarly journals Genetic and epigenetic aspects of celiac disease

2014 ◽  
Vol 155 (3) ◽  
pp. 83-88 ◽  
Author(s):  
Dorottya Kocsis ◽  
Nóra Béres ◽  
Gábor Veres ◽  
Dolóresz Szabó ◽  
Katalin Eszter Müller ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Clinical Practice ◽  
Coeliac Disease ◽  
Cross Section ◽  
Special Interest ◽  
Current Knowledge ◽  
Clinical Applications ◽  
Routine Clinical Practice ◽  
Intensive Research

Genetic backround of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications. Orv. Hetil., 2014, 155(3), 83–88.

Mesophyll conductance: the leaf corridors for photosynthesis

2020 ◽  
Vol 48 (2) ◽  
pp. 429-439 ◽  
Author(s):  
Jorge Gago ◽  
Danilo M. Daloso ◽  
Marc Carriquí ◽  
Miquel Nadal ◽  
Melanie Morales ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Main Role ◽  
Mesophyll Conductance ◽  
Future Studies ◽  
Cell Structures ◽  
Leaf Tissues ◽  
Change Framework ◽  
Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

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