scholarly journals Selected transgenic murine models of human autoimmune liver diseases

2022 ◽  
Author(s):  
Katarzyna Trzos ◽  
Natalia Pydyn ◽  
Jolanta Jura ◽  
Jerzy Kotlinowski
Keyword(s):  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Primary Biliary Cholangitis ◽  
Murine Models ◽  
Transgenic Models ◽  
New Treatment ◽  
Transgenic Murine Models

AbstractMurine models of human diseases are of outmost importance for both studying molecular mechanisms driving their development and testing new treatment strategies. In this review, we first discuss the etiology and risk factors for autoimmune liver disease, including primary biliary cholangitis, autoimmune hepatitis and primary sclerosing cholangitis. Second, we highlight important features of murine transgenic models that make them useful for basic scientists, drug developers and clinical researchers. Next, a brief description of each disease is followed by the characterization of selected animal models.

Non-viral aspects

2018 ◽  
Vol 1 (2) ◽  
pp. 37-39
Author(s):  
Roongruedee Chaiteerakij
Keyword(s):  
Autoimmune Hepatitis ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Promising Result ◽  
Primary Biliary Cholangitis ◽  
Second Line Therapy ◽  
Thai Population ◽  
The Past ◽  
Line Therapy ◽  
New Treatment

Autoimmuneliver diseases, particularly autoimmune hepatitis and primary biliary cholangitis,are not uncommon among the Thai population. This article summarizes main findings of studies of autoimmune liver diseases published during the past year, which included natural history and long-termoutcomes of primary biliary cholangitis treatment, a promising result of the new treatment for primary sclerosing cholangitis and outcomes of a second-line therapy of autoimmune hepatitis.

scholarly journals Fighting Cancer with Bacteria and Their Toxins

2021 ◽  
Vol 22 (23) ◽  
pp. 12980
Author(s):  
Dragan Trivanović ◽  
Krešimir Pavelić ◽  
Željka Peršurić
Keyword(s):  
Cancer Therapy ◽  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Bacterial Toxins ◽  
Recent Application ◽  
Persistent Infections ◽  
Current State ◽  
New Treatment ◽  
Interesting Solution

Cancer is one of the most important global health problems that continues to demand new treatment strategies. Many bacteria that cause persistent infections play a role in carcinogenesis. However, since bacteria are well studied in terms of molecular mechanisms, they have been proposed as an interesting solution to treat cancer. In this review, we present the use of bacteria, and particularly bacterial toxins, in cancer therapy, highlighting the advantages and limitations of bacterial toxins. Proteomics, as one of the omics disciplines, is essential for the study of bacterial toxins. Advances in proteomics have contributed to better characterization of bacterial toxins, but also to the development of anticancer drugs based on bacterial toxins. In addition, we highlight the current state of knowledge in the rapidly developing field of bacterial extracellular vesicles, with a focus on their recent application as immunotherapeutic agents.

scholarly journals MODERN TRENDS OF BASIC RESEARCH IN PATHOGENESIS OF PROGRESSIVE MYOPIA

2015 ◽  
Vol 69 (3-4) ◽  
pp. 44-49
Author(s):  
E. N. Iomdina ◽  
E. P. Tarutta
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Basic Research ◽  
Individual Treatment ◽  
Myopia Progression ◽  
Neural Processes ◽  
Treatment Plans ◽  
Progressive Myopia ◽  
New Treatment ◽  
And Control

The growing prevalence of progressive myopia and its disabling consequences explains the elaboration of reliable diagnostic markers and new treatment strategies based on the research results of molecular mechanisms underlying the development of the condition. The paper reviews recent basic pathogenetic research studies which have greatly broadened the awareness of the deep causes of progressive myopia associated with the activity of certain growth factors, local and systemic protein metabolism, and regulation of hormonal and neural processes. Practical clinical guidelines for new criteria of diagnosis and control of myopia are published as they could be useful while selecting individual treatment plans including indications to sclera-strengthening therapy and its evaluation. The results may be promising in the elaboration of systemic and local medications for the prevention of myopia progression, which should address the regulation of connective tissue disorders, hormonal shifts, and imbalanced autonomic nervous system. 

Recent advances in network medicine: From disease mechanisms to new treatment strategies

2020 ◽  
Vol 26 (5) ◽  
pp. 609-615
Author(s):  
Ítalo Faria do Valle
Keyword(s):  
Molecular Mechanisms ◽  
Biological Significance ◽  
Treatment Strategies ◽  
Molecular Networks ◽  
Network Medicine ◽  
Disease Mechanisms ◽  
Protein Interactome ◽  
Cellular Context ◽  
Human Proteins ◽  
New Treatment

Conventional reductionist approaches have guided most of our understanding in disease diagnostic and treatment. However, most diseases are not consequence of perturbations in a single protein or metabolite, but rather of the effect that these perturbations have in their cellular context. The emerging field of network medicine offers a set of tools to explore molecular networks and to retrieve insights about mechanisms of different diseases. The study of the protein interactome, the map of physical interactions among human proteins, revealed that disease proteins tend to interact with each other, linking diseases to well-defined interactome neighborhoods. These disease-associated neighborhoods have been defined as disease modules, and they can uncover the biological significance of genes identified by genetic studies, reveal molecular mechanisms that connect different phenotypes, and help identify new pharmacological strategies for disease treatment. Therefore, network medicine offers a framework in which the complexity of different aspects of multiple sclerosis can be explored in an integrative fashion, which can ultimately provide insights about disease mechanisms and treatment.

The intrinsic axon regenerative properties of mature neurons after injury

2020 ◽  
Author(s):  
Chunfeng Liu ◽  
Jinlian Liu ◽  
Chaoqun Liu ◽  
Qing Zhou ◽  
Yaodong Zhou ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Axon Regeneration ◽  
Treatment Strategies ◽  
Treatment Method ◽  
Signaling Cascades ◽  
Regulate Gene Expression ◽  
Mature Neurons ◽  
New Treatment ◽  
Multiple Signaling ◽  
Critical Process

Abstract Thousands of nerve injuries occur in the world each year. Axon regeneration is a very critical process for the restoration of the injured nervous system’s function. However, the precise molecular mechanism or signaling cascades that control axon regeneration are not clearly understood, especially in mammals. Therefore, there is almost no ideal treatment method to repair the nervous system’s injury until now. Mammalian axonal regeneration requires multiple signaling pathways to coordinately regulate gene expression in soma and assembly of the cytoskeleton protein in the growth cone. A better understanding of their molecular mechanisms, such as axon regeneration regulatory signaling cascades, will be helpful in developing new treatment strategies for promoting axon regeneration. In this review, we mainly focus on describing these regeneration-associated signaling cascades, which regulate axon regeneration.

scholarly journals Cellular, synaptic, and network effects of chemokines in the central nervous system and their implications to behavior

2021 ◽  
Author(s):  
Joanna Ewa Sowa ◽  
Krzysztof Tokarski
Keyword(s):  
Glial Cells ◽  
Network Effects ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Neurological Impairment ◽  
Fine Tuning ◽  
Dependent Manner ◽  
Biased Signaling ◽  
New Treatment

AbstractAccumulating evidence highlights chemokines as key mediators of the bidirectional crosstalk between neurons and glial cells aimed at preserving brain functioning. The multifaceted role of these immune proteins in the CNS is mirrored by the complexity of the mechanisms underlying its biological function, including biased signaling. Neurons, only in concert with glial cells, are essential players in the modulation of brain homeostatic functions. Yet, attempts to dissect these complex multilevel mechanisms underlying coordination are still lacking. Therefore, the purpose of this review is to summarize the current knowledge about mechanisms underlying chemokine regulation of neuron–glia crosstalk linking molecular, cellular, network, and behavioral levels. Following a brief description of molecular mechanisms by which chemokines interact with their receptors and then summarizing cellular patterns of chemokine expression in the CNS, we next delve into the sequence and mechanisms of chemokine-regulated neuron–glia communication in the context of neuroprotection. We then define the interactions with other neurotransmitters, neuromodulators, and gliotransmitters. Finally, we describe their fine-tuning on the network level and the behavioral relevance of their modulation. We believe that a better understanding of the sequence and nature of events that drive neuro-glial communication holds promise for the development of new treatment strategies that could, in a context- and time-dependent manner, modulate the action of specific chemokines to promote brain repair and reduce the neurological impairment.

scholarly journals Oligodendrocytes as A New Therapeutic Target in Schizophrenia: From Histopathological Findings to Neuron-Oligodendrocyte Interaction

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1496 ◽  
Author(s):  
Florian J. Raabe ◽  
Lenka Slapakova ◽  
Moritz J. Rossner ◽  
Ludovico Cantuti-Castelvetri ◽  
Mikael Simons ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Treatment Strategies ◽  
Postmortem Brain ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Peripheral Tissues ◽  
Correlative Imaging ◽  
Postmortem Studies ◽  
New Treatment ◽  
Induced Pluripotent

Imaging and postmortem studies have revealed disturbed oligodendroglia-related processes in patients with schizophrenia and provided much evidence for disturbed myelination, irregular gene expression, and altered numbers of oligodendrocytes in the brains of schizophrenia patients. Oligodendrocyte deficits in schizophrenia might be a result of failed maturation and disturbed regeneration and may underlie the cognitive deficits of the disease, which are strongly associated with impaired long-term outcome. Cognition depends on the coordinated activity of neurons and interneurons and intact connectivity. Oligodendrocyte precursors form a synaptic network with parvalbuminergic interneurons, and disturbed crosstalk between these cells may be a cellular basis of pathology in schizophrenia. However, very little is known about the exact axon-glial cellular and molecular processes that may be disturbed in schizophrenia. Until now, investigations were restricted to peripheral tissues, such as blood, correlative imaging studies, genetics, and molecular and histological analyses of postmortem brain samples. The advent of human-induced pluripotent stem cells (hiPSCs) will enable functional analysis in patient-derived living cells and holds great potential for understanding the molecular mechanisms of disturbed oligodendroglial function in schizophrenia. Targeting such mechanisms may contribute to new treatment strategies for previously treatment-resistant cognitive symptoms.

Autoimmunity affecting the biliary tract fuels the immunosurveillance of cholangiocarcinoma

2021 ◽  
Vol 218 (10) ◽  
Author(s):  
Juliette Paillet ◽  
Céleste Plantureux ◽  
Sarah Lévesque ◽  
Julie Le Naour ◽  
Gautier Stoll ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Sclerosing Cholangitis ◽  
Primary Biliary Cholangitis ◽  
Inflammatory Condition ◽  
Murine Models ◽  
Related Effect ◽  
Cell Responses ◽  
Cancer Immunosurveillance

Cholangiocarcinoma (CCA) results from the malignant transformation of cholangiocytes. Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic diseases in which cholangiocytes are primarily damaged. Although PSC is an inflammatory condition predisposing to CCA, CCA is almost never found in the autoimmune context of PBC. Here, we hypothesized that PBC might favor CCA immunosurveillance. In preclinical murine models of cholangitis challenged with syngeneic CCA, PBC (but not PSC) reduced the frequency of CCA development and delayed tumor growth kinetics. This PBC-related effect appeared specific to CCA as it was not observed against other cancers, including hepatocellular carcinoma. The protective effect of PBC was relying on type 1 and type 2 T cell responses and, to a lesser extent, on B cells. Single-cell TCR/RNA sequencing revealed the existence of TCR clonotypes shared between the liver and CCA tumor of a PBC host. Altogether, these results evidence a mechanistic overlapping between autoimmunity and cancer immunosurveillance in the biliary tract.

Manifest hyperthyroidism in patient with autoimmune hepatitis (clinical observation)

2021 ◽  
pp. 52-56
Author(s):  
M. A. Livzan ◽  
O. V. Gaus ◽  
D. A. Gavrilenko
Keyword(s):  
Autoimmune Diseases ◽  
Autoimmune Hepatitis ◽  
Clinical Guidelines ◽  
Thyroid Disease ◽  
Liver Diseases ◽  
Sclerosing Cholangitis ◽  
Clinical Observation ◽  
Primary Biliary Cholangitis ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Among patients with autoimmune hepatitis concomitant autoimmune diseases occur in 40 % of cases. The most commonly associated autoimmune hepatitis is primary biliary cholangitis, primary sclerosing cholangitis and thyroid disease. With regard to the association of autoimmune liver diseases with each other there is experience in management and this is reflected in the clinical guidelines. Information on the features of comorbidity in autoimmune hepatitis and autoimmune thyroid diseases is very limited. This article presents our own clinical observation of the manifestation of thyrotoxicosis against the background of autoimmune hepatitis.

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