scholarly journals Rhombencephalitis Caused byListeria monocytogenesin Humans and Ruminants: A Zoonosis on the Rise?

2010 ◽  
Vol 2010 ◽  
pp. 1-22 ◽  
Author(s):  
Anna Oevermann ◽  
Andreas Zurbriggen ◽  
Marc Vandevelde
Keyword(s):  
Listeria Monocytogenes ◽  
High Mortality ◽  
Host Species ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Zoonotic Infection ◽  
Cns Disease ◽  
The Brain

Listeriosis is an emerging zoonotic infection of humans and ruminants worldwide caused byListeria monocytogenes(LM). In both host species, CNS disease accounts for the high mortality associated with listeriosis and includes rhombencephalitis, whose neuropathology is strikingly similar in humans and ruminants. This review discusses the current knowledge about listeric encephalitis, and involved host and bacterial factors. There is an urgent need to study the molecular mechanisms of neuropathogenesis, which are poorly understood. Such studies will provide a basis for the development of new therapeutic strategies that aim to prevent LM from invading the brain and spread within the CNS.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals Dissimilar Appearances Are Deceptive–Common microRNAs and Therapeutic Strategies in Liver Cancer and Melanoma

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 114
Author(s):  
Lisa Linck-Paulus ◽  
Claus Hellerbrand ◽  
Anja K. Bosserhoff ◽  
Peter Dietrich
Keyword(s):  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Genetic Alterations ◽  
Therapeutic Strategies ◽  
The Future ◽  
Associated Proteins ◽  
Cancer Types ◽  
Novel Therapeutic Strategies

In this review, we summarize the current knowledge on miRNAs as therapeutic targets in two cancer types that were frequently described to be driven by miRNAs—melanoma and hepatocellular carcinoma (HCC). By focusing on common microRNAs and associated pathways in these—at first sight—dissimilar cancer types, we aim at revealing similar molecular mechanisms that are evolved in microRNA-biology to drive cancer progression. Thereby, we also want to outlay potential novel therapeutic strategies. After providing a brief introduction to general miRNA biology and basic information about HCC and melanoma, this review depicts prominent examples of potent oncomiRs and tumor-suppressor miRNAs, which have been proven to drive diverse cancer types including melanoma and HCC. To develop and apply miRNA-based therapeutics for cancer treatment in the future, it is essential to understand how miRNA dysregulation evolves during malignant transformation. Therefore, we highlight important aspects such as genetic alterations, miRNA editing and transcriptional regulation based on concrete examples. Furthermore, we expand our illustration by focusing on miRNA-associated proteins as well as other regulators of miRNAs which could also provide therapeutic targets. Finally, design and delivery strategies of miRNA-associated therapeutic agents as well as potential drawbacks are discussed to address the question of how miRNAs might contribute to cancer therapy in the future.

scholarly journals Bursting at the Seams: Molecular Mechanisms Mediating Astrocyte Swelling

2019 ◽  
Vol 20 (2) ◽  
pp. 330 ◽  
Author(s):  
Audrey Lafrenaye ◽  
J. Simard
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Predictors Of Outcome ◽  
Cell Type ◽  
Brain Swelling ◽  
Astrocyte Swelling ◽  
Health And Disease ◽  
The One ◽  
The Brain ◽  
Cellular Swelling

Brain swelling is one of the most robust predictors of outcome following brain injury, including ischemic, traumatic, hemorrhagic, metabolic or other injury. Depending on the specific type of insult, brain swelling can arise from the combined space-occupying effects of extravasated blood, extracellular edema fluid, cellular swelling, vascular engorgement and hydrocephalus. Of these, arguably the least well appreciated is cellular swelling. Here, we explore current knowledge regarding swelling of astrocytes, the most abundant cell type in the brain, and the one most likely to contribute to pathological brain swelling. We review the major molecular mechanisms identified to date that contribute to or mitigate astrocyte swelling via ion transport, and we touch upon the implications of astrocyte swelling in health and disease.

scholarly journals Non-Coding RNAs in Pancreatic Cancer Diagnostics and Therapy: Focus on lncRNAs, circRNAs, and piRNAs

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4161
Author(s):  
Yiwei Li ◽  
Mohammed Najeeb Al Hallak ◽  
Philip A. Philip ◽  
Asfar S. Azmi ◽  
Ramzi M. Mohammad
Keyword(s):  
Pancreatic Cancer ◽  
High Mortality ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Cancer Diagnostics ◽  
Circular Rnas ◽  
Diagnosis And Prognosis ◽  
Cellular Signal ◽  
Non Coding Rnas

Pancreatic cancer is an aggressive malignance with high mortality. The lack of early diagnosis and effective therapy contributes to the high mortality of this deadly disease. For a long time being, the alterations in coding RNAs have been considered as major targets for diagnosis and treatment of pancreatic cancer. However, with the advances in high-throughput next generation of sequencing more alterations in non-coding RNAs (ncRNAs) have been discovered in different cancers. Further mechanistic studies have demonstrated that ncRNAs such as long noncoding RNAs (lncRNA), circular RNAs (circRNA) and piwi-interacting RNA (piRNA) play vital roles in the regulation of tumorigenesis, tumor progression and prognosis. In recent years, increasing studies have focused on the roles of ncRNAs in the development and progression of pancreatic cancer. Novel findings have demonstrated that lncRNA, circRNA, and piRNA are critically involved in the regulation of gene expression and cellular signal transduction in pancreatic cancer. In this review, we summarize the current knowledge of roles of lncRNA, circRNA, and piRNA in the diagnosis and prognosis of pancreatic cancer, and molecular mechanisms underlying the regulation of these ncRNAs and related signaling in pancreatic cancer therapy. The information provided here will help to find new strategies for better treatment of pancreatic cancer.

scholarly journals Alpha-Synuclein: Mechanisms of Release and Pathology Progression in Synucleinopathies

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 375
Author(s):  
Inês C. Brás ◽  
Tiago F. Outeiro
Keyword(s):  
Molecular Mechanisms ◽  
Brain Regions ◽  
Alpha Synuclein ◽  
Therapeutic Strategies ◽  
Cell Protein ◽  
Protein Assemblies ◽  
Lewy Pathology ◽  
Tremendous Progress ◽  
The Brain ◽  
Made In

The accumulation of misfolded alpha-synuclein (aSyn) throughout the brain, as Lewy pathology, is a phenomenon central to Parkinson’s disease (PD) pathogenesis. The stereotypical distribution and evolution of the pathology during disease is often attributed to the cell-to-cell transmission of aSyn between interconnected brain regions. The spreading of conformationally distinct aSyn protein assemblies, commonly referred as strains, is thought to result in a variety of clinically and pathologically heterogenous diseases known as synucleinopathies. Although tremendous progress has been made in the field, the mechanisms involved in the transfer of these assemblies between interconnected neural networks and their role in driving PD progression are still unclear. Here, we present an update of the relevant discoveries supporting or challenging the prion-like spreading hypothesis. We also discuss the importance of aSyn strains in pathology progression and the various putative molecular mechanisms involved in cell-to-cell protein release. Understanding the pathways underlying aSyn propagation will contribute to determining the etiology of PD and related synucleinopathies but also assist in the development of new therapeutic strategies.

scholarly journals Low molecular weight gut polyphenols metabolites and its nutritional relevance as effectors for attenuating neuroinflammation

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Diogo Carregosa ◽  
Rafael Carecho ◽  
Inês Figueira ◽  
Cláudia Nunes dos Santos
Keyword(s):  
Elderly Population ◽  
Fruits And Vegetables ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Low Molecular Weight ◽  
Metabolic Fate ◽  
Blood Concentrations ◽  
Multifactorial Diseases ◽  
In The Beginning ◽  
The Brain

AbstractThe burden of neurodegenerative disorders has been increasing as a consequence of a growing elderly population. These multifactorial diseases do not have a cure or efficient treatments. Due to its mechanistic complexity, prevention and treatment will require novel multi-targeted therapeutic strategies, targeting different disease hallmarks. The possibility of altering the progression and development of diseases through diet is an emerging as attractive approach with increasing supporting data. Epidemiological and clinical studies have highlighted the health potential of diets rich in fruits and vegetables. Studies with dietary (poly)phenols have been showing their multipotent and pleiotropic ability to modulate several cellular and molecular pathways and in that sense, dietary (poly)phenols can emerge as an alternative, with potential to be further explored. However, the precise contribution of dietary (poly)phenols and circulating (poly)phenol metabolites to human health is still in the beginning of being elucidated. Absorption and blood concentrations of some (poly)phenols is quite low, which can hamper the research in terms of understanding their effects in specific biomarkers of disease.The difficulty in demonstrating (poly)phenols true effects can also be justified by the uncertain metabolic fate that dietary (poly)phenols can have. In fact, it is necessary to identify the bioavailable metabolites resulting from (poly)phenol ingestion through the diet, as well as their ability to overcome and/or interact with cellular barriers and reach target tissues, in this case reach the brain. Having this in mind, it will be reviewed the current knowledge on the molecular mechanisms underlying (poly)phenol metabolites effects and their role on neuroinflammation one central hallmark, common in all neurodegenerative diseases.

scholarly journals Inflammasome-Mediated Inflammation in Liver Ischemia-Reperfusion Injury

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1131 ◽  
Author(s):  
Mónica B. Jiménez-Castro ◽  
María Eugenia Cornide-Petronio ◽  
Jordi Gracia-Sancho ◽  
Carmen Peralta
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Therapeutic Strategies ◽  
Experimental Models ◽  
Inflammasome Activation ◽  
Liver Ischemia

Ischemia-reperfusion injury is an important cause of liver damage occurring during surgical procedures including hepatic resection and liver transplantation, and represents the main underlying cause of graft dysfunction and liver failure post-transplantation. To date, ischemia-reperfusion injury is an unsolved problem in clinical practice. In this context, inflammasome activation, recently described during ischemia-reperfusion injury, might be a potential therapeutic target to mitigate the clinical problems associated with liver transplantation and hepatic resections. The present review aims to summarize the current knowledge in inflammasome-mediated inflammation, describing the experimental models used to understand the molecular mechanisms of inflammasome in liver ischemia-reperfusion injury. In addition, a clear distinction between steatotic and non-steatotic livers and between warm and cold ischemia-reperfusion injury will be discussed. Finally, the most updated therapeutic strategies, as well as some of the scientific controversies in the field will be described. Such information may be useful to guide the design of better experimental models, as well as the effective therapeutic strategies in liver surgery and transplantation that can succeed in achieving its clinical application.

scholarly journals The physiology of regulated BDNF release

2020 ◽  
Vol 382 (1) ◽  
pp. 15-45 ◽  
Author(s):  
Tanja Brigadski ◽  
Volkmar Leßmann
Keyword(s):  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Detailed Knowledge ◽  
Cellular Regulation ◽  
Bdnf Expression ◽  
Physiological Conditions ◽  
Brain Circuits ◽  
Important Regulator ◽  
Network Plasticity ◽  
The Brain

Abstract The neurotrophic factor BDNF is an important regulator for the development of brain circuits, for synaptic and neuronal network plasticity, as well as for neuroregeneration and neuroprotection. Up- and downregulations of BDNF levels in human blood and tissue are associated with, e.g., neurodegenerative, neurological, or even cardiovascular diseases. The changes in BDNF concentration are caused by altered dynamics in BDNF expression and release. To understand the relevance of major variations of BDNF levels, detailed knowledge regarding physiological and pathophysiological stimuli affecting intra- and extracellular BDNF concentration is important. Most work addressing the molecular and cellular regulation of BDNF expression and release have been performed in neuronal preparations. Therefore, this review will summarize the stimuli inducing release of BDNF, as well as molecular mechanisms regulating the efficacy of BDNF release, with a focus on cells originating from the brain. Further, we will discuss the current knowledge about the distinct stimuli eliciting regulated release of BDNF under physiological conditions.

scholarly journals Molecular Mechanisms of Hepatoblastoma

2021 ◽  
Author(s):  
Yi Zhang ◽  
Antonio Solinas ◽  
Stefano Cairo ◽  
Matthias Evert ◽  
Xin Chen ◽  
...  
Keyword(s):  
Early Detection ◽  
Liver Tumor ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Sequencing Analysis ◽  
Primary Liver Tumor ◽  
Pathway Activation ◽  
Treatment Sequencing

AbstractHepatoblastoma (HB) is the predominant primary liver tumor in children. While the prognosis is favorable when the tumor can be resected, the outcome is dismal for patients with progressed HB. Therefore, a better understanding of the molecular mechanisms responsible for HB is imperative for early detection and effective treatment. Sequencing analysis of human HB specimens unraveled the pivotal role of Wnt/β-catenin pathway activation in this disease. Nonetheless, β-catenin activation alone does not suffice to induce HB, implying the need for additional alterations. Perturbations of several pathways, including Hippo, Hedgehog, NRF2/KEAP1, HGF/c-Met, NK-1R/SP, and PI3K/AKT/mTOR cascades and aberrant activation of c-MYC, n-MYC, and EZH2 proto-oncogenes, have been identified in HB, although their role requires additional investigation. Here, we summarize the current knowledge on HB molecular pathogenesis, the relevance of the preclinical findings for the human disease, and the innovative therapeutic strategies that could be beneficial for the treatment of HB patients.

scholarly journals Spirulina Microalgae and Brain Health: A Scoping Review of Experimental and Clinical Evidence

Marine Drugs ◽  
2021 ◽  
Vol 19 (6) ◽  
pp. 293
Author(s):  
Vincenzo Sorrenti ◽  
Davide Augusto Castagna ◽  
Stefano Fortinguerra ◽  
Alessandro Buriani ◽  
Giovanni Scapagnini ◽  
...  
Keyword(s):  
Cognitive Skills ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Vascular Wall ◽  
Endothelial Damage ◽  
Brain Health ◽  
Brain Vessels ◽  
Malnourished Children ◽  
The Brain

Spirulina microalgae contain a plethora of nutrient and non-nutrient molecules providing brain health benefits. Numerous in vivo evidence has provided support for the brain health potential of spirulina, highlighting antioxidant, anti-inflammatory, and neuroprotective mechanisms. Preliminary clinical studies have also suggested that spirulina can help to reduce mental fatigue, protect the vascular wall of brain vessels from endothelial damage and regulate internal pressure, thus contributing to the prevention and/or mitigating of cerebrovascular conditions. Furthermore, the use of spirulina in malnourished children appears to ameliorate motor, language, and cognitive skills, suggesting a reinforcing role in developmental mechanisms. Evidence of the central effect of spirulina on appetite regulation has also been shown. This review aims to understand the applicative potential of spirulina microalgae in the prevention and mitigation of brain disorders, highlighting the nutritional value of this “superfood”, and providing the current knowledge on relevant molecular mechanisms in the brain associated with its dietary introduction.

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