scholarly journals Animal Model of Severe Fever With Thrombocytopenia Syndrome Virus Infection

2022 ◽  
Vol 12 ◽  
Author(s):  
Jiawen Sun ◽  
Yuan-Qin Min ◽  
Yunjie Li ◽  
Xiulian Sun ◽  
Fei Deng ◽  
...  

Severe fever with thrombocytopenia syndrome (SFTS), an emerging life-threatening infectious disease caused by SFTS bunyavirus (SFTSV; genus Bandavirus, family Phenuiviridae, order Bunyavirales), has been a significant medical problem. Currently, there are no licensed vaccines or specific therapeutic agents available and the viral pathogenesis remains largely unclear. Developing appropriate animal models capable of recapitulating SFTSV infection in humans is crucial for both the study of the viral pathogenic processes and the development of treatment and prevention strategies. Here, we review the current progress in animal models for SFTSV infection by summarizing susceptibility of various potential animal models to SFTSV challenge and the clinical manifestations and histopathological changes in these models. Together with exemplification of studies on SFTSV molecular mechanisms, vaccine candidates, and antiviral drugs, in which animal infection models are utilized, the strengths and limitations of the existing SFTSV animal models and some important directions for future research are also discussed. Further exploration and optimization of SFTSV animal models and the corresponding experimental methods will be undoubtedly valuable for elucidating the viral infection and pathogenesis and evaluating vaccines and antiviral therapies.

2019 ◽  
Vol 51 (11) ◽  
pp. 1-10 ◽  
Author(s):  
He-Jin Lee ◽  
Diadem Ricarte ◽  
Darlene Ortiz ◽  
Seung-Jae Lee

AbstractMultiple system atrophy (MSA) is a neurodegenerative disease with diverse clinical manifestations, including parkinsonism, cerebellar syndrome, and autonomic failure. Pathologically, MSA is characterized by glial cytoplasmic inclusions in oligodendrocytes, which contain fibrillary forms of α-synuclein. MSA is categorized as one of the α-synucleinopathy, and α-synuclein aggregation is thought to be the culprit of the disease pathogenesis. Studies on MSA pathogenesis are scarce relative to studies on the pathogenesis of other synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies. However, recent developments in cellular and animal models of MSA, especially α-synuclein transgenic models, have driven advancements in research on this disease. Here, we review the currently available models of MSA, which include toxicant-induced animal models, α-synuclein-overexpressing cellular models, and mouse models that express α-synuclein specifically in oligodendrocytes through cell type-specific promoters. We will also discuss the results of studies in recently developed transmission mouse models, into which MSA brain extracts were intracerebrally injected. By reviewing the findings obtained from these model systems, we will discuss what we have learned about the disease and describe the strengths and limitations of the models, thereby ultimately providing direction for the design of better models and future research.


2020 ◽  
Vol 8 (10) ◽  
Author(s):  
Nathan Roberts ◽  
Robert Brown ◽  
L. Buja ◽  
Priya Weerasinghe

Turmeric (Curcuma Longa) has a near 4000-year history of extensive medical use in South Asia. Its main physiologically active phytochemical is curcumin (diferuloylmethane), derived from the rhizome of turmeric. Curcumin is a hydrophobic polyphenol with a diketone moiety connecting two phenoxy rings. It is widely available, and exerts systemic and pleiotropic effects via several key mechanisms. Most famously, it is known to inhibit pro-inflammatory pathways such as PI3k/akt/NF-kB activation. It is also a potent antioxidant and free radical scavenger via a sequential proton loss electron transfer mechanism in ionizing solvents due to its extended conjugating ability across the entire molecule, and its ability to induce NRF-2. It has been implicated in the treatment of diseases ranging from asthma to various cancers, and is also a broad spectrum anti-microbial. COVID-19 is a novel beta-coronavirus that was declared a pandemic by the WHO in March, 2020. It is primarily a respiratory disorder, but it can spread hematogenously and effect many other organs such as the heart, nervous system, and kidneys. There is a significant intersection between the clinical manifestations of COVID-19 and curcumin’s therapeutic effects. In addition, curcumin has been shown to inhibit initial viral infectivity. Thus, there is potential for curcumin to safely both prevent and treat COVID-19 infection across the globe.


2009 ◽  
Vol 22 (1) ◽  
pp. 99-126 ◽  
Author(s):  
Maxim C.-J. Cheeran ◽  
James R. Lokensgard ◽  
Mark R. Schleiss

SUMMARY Congenital cytomegalovirus (CMV) infection is the leading infectious cause of mental retardation and hearing loss in the developed world. In recent years, there has been an improved understanding of the epidemiology, pathogenesis, and long-term disabilities associated with CMV infection. In this review, current concepts regarding the pathogenesis of neurological injury caused by CMV infections acquired by the developing fetus are summarized. The pathogenesis of CMV-induced disabilities is considered in the context of the epidemiology of CMV infection in pregnant women and newborn infants, and the clinical manifestations of brain injury are reviewed. The prospects for intervention, including antiviral therapies and vaccines, are summarized. Priorities for future research are suggested to improve the understanding of this common and disabling illness of infancy.


2017 ◽  
Vol 10 ◽  
pp. 117955571771271
Author(s):  
Dama Laxminarayana

Autoimmune diseases are classified into about 80 different types based on their specificity related to system, organ and/or tissue. About 5% of the western population is affected by this anomaly, but its worldwide incidence is unknown. Autoimmune diseases are heterogeneous in nature and clinical manifestations range from benign disorders to life-threatening conditions. Autoimmunity strikes at any stage of life, but age and/or gender also play role in onset of some of these anomalies. The autoimmune pathogenesis is initiated by the origination of autoantigens, which leads to the development of autoantibodies followed by auto-immunogenicity and the ultimate onset of autoimmunity. There is a lack of suitable therapies to treat autoimmune diseases, because mechanisms involved in the onset of these anomalies were poorly understood. Present therapies are limited to symptomatic treatment and come with severe side effects. Here, I described the molecular mechanisms and cellular events involved in the initiation of autoimmunity and proposed better strategies to modulate such molecular and cellular anomalies, which will help in preventing and/or controlling autoimmune pathogenesis and ultimately aid in enhancing the quality of life.


2021 ◽  
Vol 34 (3) ◽  
Author(s):  
Nicola Clementi ◽  
Sreya Ghosh ◽  
Maria De Santis ◽  
Matteo Castelli ◽  
Elena Criscuolo ◽  
...  

SUMMARY Several viruses target the human respiratory tract, causing different clinical manifestations spanning from mild upper airway involvement to life-threatening acute respiratory distress syndrome (ARDS). As dramatically evident in the ongoing SARS-CoV-2 pandemic, the clinical picture is not always easily predictable due to the combined effect of direct viral and indirect patient-specific immune-mediated damage. In this review, we discuss the main RNA (orthomyxoviruses, paramyxoviruses, and coronaviruses) and DNA (adenoviruses, herpesviruses, and bocaviruses) viruses with respiratory tropism and their mechanisms of direct and indirect cell damage. We analyze the thin line existing between a protective immune response, capable of limiting viral replication, and an unbalanced, dysregulated immune activation often leading to the most severe complication. Our comprehension of the molecular mechanisms involved is increasing and this should pave the way for the development and clinical use of new tailored immune-based antiviral strategies.


Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 738 ◽  
Author(s):  
Songwei Yang ◽  
Shifeng Chu ◽  
Yan Gao ◽  
Qidi Ai ◽  
Yingjiao Liu ◽  
...  

Many cancer patients suffer from severe fatigue when treated with chemotherapy or radiotherapy; however, the etiology and pathogenesis of this kind of fatigue remains unknown. Fatigue is associated with cancer itself, as well as adjuvant therapies and can persist for a long time. Cancer patients present a high degree of fatigue, which dramatically affects the quality of their everyday life. There are various clinical research studies and reviews that aimed to explore the mechanisms of cancer-related fatigue (CRF). However, there are certain limitations in these studies: For example, some studies have only blood biochemical texts without histopathological examination, and there has been insufficient systemic evaluation of the dynamic changes in relevant indexes. Thus, we present this narrative review to summarize previous studies on CRF and explore promising research directions. Plenty of evidence suggests a possible association between CRF and physiological dysfunction, including skeletal muscular and mitochondrial dysfunction, peripheral immune activation and inflammation dysfunction, as well as central nervous system (CNS) disorder. Mitochondrial DNA (mtDNA), mitochondrial structure, oxidative pressure, and some active factors such as ATP play significant roles that lead to the induction of CRF. Meanwhile, several pro-inflammatory and anti-inflammatory cytokines in the peripheral system, even in the CNS, significantly contribute to the occurrence of CRF. Moreover, CNS function disorders, such as neuropeptide, neurotransmitter, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction, tend to amplify the sense of fatigue in cancer patients through various signaling pathways. There have been few accurate animal models established to further explore the molecular mechanisms of CRF due to different types of cancer, adjuvant therapy schedules, living environments, and physical status. It is imperative to develop appropriate animal models that can mimic human CRF and to explore additional mechanisms using histopathological and biochemical methods. Therefore, the main purpose of this review is to analyze the possible pathogenesis of CRF and recommend future research that will clarify CRF pathogenesis and facilitate the formulation of new treatment options.


Biomedicines ◽  
2020 ◽  
Vol 8 (6) ◽  
pp. 143 ◽  
Author(s):  
Andrea Seldeslachts ◽  
Steve Peigneur ◽  
Jan Tytgat

Caterpillar envenomation is a global health threat in the 21st century. Every direct or indirect contact with the urticating hairs of a caterpillar results in clinical manifestations ranging from local dermatitis symptoms to potentially life-threatening systemic effects. This is mainly due to the action of bioactive components in the venom that interfere with targets in the human body. The problem is that doctors are limited to relieve symptoms, since an effective treatment is still lacking. Only for Lonomia species an effective antivenom does exist. The health and economical damage are an underestimated problem and will be even more of a concern in the future. For some caterpillar species, the venom composition has been the subject of investigation, while for many others it remains unknown. Moreover, the targets involved in the pathophysiology are poorly understood. This review aims to give an overview of the knowledge we have today on the venom composition of different caterpillar species along with their pharmacological targets. Epidemiology, mode of action, clinical time course and treatments are also addressed. Finally, we briefly discuss the future perspectives that may open the doors for future research in the world of caterpillar toxins to find an adequate treatment.


2021 ◽  
Vol 22 (5) ◽  
pp. 2636
Author(s):  
Fanny Pojero ◽  
Giuseppina Candore ◽  
Calogero Caruso ◽  
Danilo Di Bona ◽  
David A. Groneberg ◽  
...  

Coronavirus disease 2019 (COVID-19) is induced by SARS-CoV-2 and may arise as a variety of clinical manifestations, ranging from an asymptomatic condition to a life-threatening disease associated with cytokine storm, multiorgan and respiratory failure. The molecular mechanism behind such variability is still under investigation. Several pieces of experimental evidence suggest that genetic variants influencing the onset, maintenance and resolution of the immune response may be fundamental in predicting the evolution of the disease. The identification of genetic variants behind immune system reactivity and function in COVID-19 may help in the elaboration of personalized therapeutic strategies. In the frenetic look for universally shared treatment plans, those genetic variants that are common to other diseases/models may also help in addressing future research in terms of drug repurposing. In this paper, we discuss the most recent updates about the role of immunogenetics in determining the susceptibility to and the history of SARS-CoV-2 infection. We propose a narrative review of available data, speculating about lessons that we have learnt from other viral infections and immunosenescence, and discussing what kind of aspects of research should be deepened in order to improve our knowledge of how host genetic variability impacts the outcome for COVID-19 patients.


2020 ◽  
Vol 21 (13) ◽  
pp. 4616
Author(s):  
Tomas Simurda ◽  
Monika Brunclikova ◽  
Rosanna Asselta ◽  
Sonia Caccia ◽  
Jana Zolkova ◽  
...  

Fibrinogen is a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), which play an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin gives structural stability, strength, and adhesive surfaces for growing blood clots. Equally important, the exposure of its non-substrate thrombin-binding sites after fibrin clot formation promotes antithrombotic properties. Fibrinogen and fibrin have a major role in multiple biological processes in addition to hemostasis and thrombosis, i.e., fibrinolysis (during which the fibrin clot is broken down), matrix physiology (by interacting with factor XIII, plasminogen, vitronectin, and fibronectin), wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis. Congenital fibrinogen deficiencies are rare bleeding disorders, characterized by extensive genetic heterogeneity in all the three genes: FGA, FGB, and FGG (enconding the Aα, Bβ, and γ chain, respectively). Depending on the type and site of mutations, congenital defects of fibrinogen can result in variable clinical manifestations, which range from asymptomatic conditions to the life-threatening bleeds or even thromboembolic events. In this manuscript, we will briefly review the main pathogenic mechanisms and risk factors leading to thrombosis, and we will specifically focus on molecular mechanisms associated with mutations in the C-terminal end of the beta and gamma chains, which are often responsible for cases of congenital afibrinogenemia and hypofibrinogenemia associated with thrombotic manifestations.


2020 ◽  
Vol 20 (13) ◽  
pp. 1014-1022 ◽  
Author(s):  
Suresh Mallepalli ◽  
Manoj Kumar Gupta ◽  
Ramakrishna Vadde

Background: Neuroblastoma (NB) is the second leading extracranial solid tumors of early childhood and clinically characterized by the presence of round, small, monomorphic cells with excess nuclear pigmentation (hyperchromasia).Owing to a lack of definitive treatment against NB and less survival rate in high-risk patients, there is an urgent requirement to understand molecular mechanisms associated with NB in a better way, which in turn can be utilized for developing drugs towards the treatment of NB in human. Objectives: In this review, an approach was adopted to understand major risk factors, pathophysiology, the molecular mechanism associated with NB, and various therapeutic agents that can serve as drugs towards the treatment of NB in humans. Conclusions: Numerous genetic (e.g., MYCN amplification), perinatal, and gestational factors are responsible for developing NB. However, no definite environmental or parental exposures responsible for causing NB have been confirmed to date. Though intensive multimodal treatment approaches, namely, chemotherapy, surgery &radiation, may help in improving the survival rate in children, these approaches have several side effects and do not work efficiently in high-risk patients. However, recent studies suggested that numerous phytochemicals, namely, vincristine, and matrine have a minimal side effect in the human body and may serve as a therapeutic drug during the treatment of NB. Most of these phytochemicals work in a dose-dependent manner and hence must be prescribed very cautiously. The information discussed in the present review will be useful in the drug discovery process as well as treatment and prevention on NB in humans.


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