scholarly journals IL-2 Signaling Axis Defects: How Many Faces?

2021 ◽  
Vol 9 ◽  
Author(s):  
Filippo Consonni ◽  
Claudio Favre ◽  
Eleonora Gambineri
Keyword(s):  
Current Knowledge ◽  
Interleukin 2 ◽  
Genetic Diagnosis ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Loss Of Function ◽  
Laboratory Findings ◽  
Forkhead Box ◽  
Signaling Axis ◽  
History Of

CD25, Signal transducer and activator of transcription 5B (STAT5B) and Forkhead box P3 (FOXP3) are critical mediators of Interleukin-2 (IL-2) signaling pathway in regulatory T cells (Tregs). CD25 (i.e., IL-2 Receptor α) binds with high affinity to IL-2, activating STAT5B-mediated signaling that eventually results in transcription of FOXP3, a master regulator of Treg function. Consequently, loss-of-function mutations in these proteins give rise to Treg disorders (i.e., Tregopathies) that clinically result in multiorgan autoimmunity. Immunodysregulation, Polyendocrinopathy Enteropathy X-linked (IPEX), due to mutations in FOXP3, has historically been the prototype of Tregopathies. This review describes current knowledge about defects in CD25, STAT5B, and FOXP3, highlighting that these disorders both share a common biological background and display comparable clinical features. However, specific phenotypes are associated with each of these syndromes, while certain laboratory findings could be helpful tools for clinicians, in order to achieve a prompt genetic diagnosis. Current treatment strategies will be outlined, keeping an eye on gene editing, an interesting therapeutic perspective that could definitely change the natural history of these disorders.

scholarly journals Immunodeficient Rabbit Models: History, Current Status and Future Perspectives

2020 ◽  
Vol 10 (20) ◽  
pp. 7369
Author(s):  
Jun Song ◽  
Brooke Pallas ◽  
Dongshan Yang ◽  
Jifeng Zhang ◽  
Yash Agarwal ◽  
...  
Keyword(s):  
Gene Editing ◽  
Interleukin 2 ◽  
Current Status ◽  
Loss Of Function ◽  
Future Perspectives ◽  
Transcription Activator ◽  
Immune Genes ◽  
Forkhead Box ◽  
Recombination Activating Gene ◽  
Model Family

Production of immunodeficient (ID) models in non-murine animal species had been extremely challenging until the advent of gene-editing tools: first zinc finger nuclease (ZFN), then transcription activator-like effector nuclease (TALEN), and most recently clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR)/Cas9. We and others used those gene-editing tools to develop ID rabbits carrying a loss of function mutation in essential immune genes, such as forkhead box protein N1 (FOXN1), recombination activating gene 1/2 (RAG1/2), and interleukin 2 receptor subunit gamma (IL2RG). Like their mouse counterparts, ID rabbits have profound defects in their immune system and are prone to bacterial and pneumocystis infections without prophylactic antibiotics. In addition to their use as preclinical models for primary immunodeficient diseases, ID rabbits are expected to contribute significantly to regenerative medicine and cancer research, where they serve as recipients for allo- and xeno-grafts, with notable advantages over mouse models, including a longer lifespan and a much larger body size. Here we provide a concise review of the history and current status of the development of ID rabbits, as well as future perspectives of this new member in the animal model family.

scholarly journals An Overview of the Epidemiologic, Diagnostic and Treatment Approaches of COVID-19: What do We Know?

2021 ◽  
Vol 42 ◽  
Author(s):  
Hanieh Beyrampour-Basmenj ◽  
Morteza Milani ◽  
Abbas Ebrahimi-Kalan ◽  
Ziyad Ben Taleb ◽  
Kenneth D Ward ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
World Health ◽  
Treatment Approaches ◽  
Number Of Patients ◽  
Control And Prevention ◽  
History Of ◽  
Health Organization ◽  
Available Information

Background: In late December 2019, a new infectious respiratory disease (COVID-19) was reported in a number of patients with a history of exposure to the Huanan seafood market in China. The World Health Organization officially announced the COVID-19 pandemic on March 11, 2020. Here, we provided an overview of the epidemiologic, diagnostic and treatment approaches associated with COVID-19.Methods: We reviewed the publications indexed in major biomedical databases by December 20, 2020 or earlier (updated on May 16, 2021). Search keywords included a combination of: COVID-19, Coronavirus disease 2019, SARS-CoV-2, Epidemiology, Prevention, Diagnosis, Vaccine, and Treatment. We also used available information about COVID-19 from valid sources such as WHO.Results and Conclusion: At the time of writing this review, while most of the countries authorized COVID-19 vaccines for emergency use starting December 8, 2020, there is no a definite cure for it. This review synthesizes current knowledge of virology, epidemiology, clinical symptoms, diagnostic approaches, common treatment strategies, novel potential therapeutic options for control and prevention of COVID-19 infection, available vaccines, public health and clinical implications.

Antibody-Mediated Rejection and Lung Transplantation

2021 ◽  
Vol 42 (03) ◽  
pp. 428-435
Author(s):  
Laura P. Halverson ◽  
Ramsey R. Hachem
Keyword(s):  
Lung Transplantation ◽  
Diagnostic Criteria ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Solid Organ ◽  
Term Survival ◽  
Antibody Mediated Rejection ◽  
History Of ◽  
Active Research

AbstractAntibody-mediated rejection (AMR) is now a widely recognized form of lung allograft rejection, with mounting evidence for AMR as an important risk factor for the development of chronic lung allograft dysfunction and markedly decreased long-term survival. Despite the recent development of the consensus diagnostic criteria, it remains a challenging diagnosis of exclusion. Furthermore, even after diagnosis, treatment directed at pulmonary AMR has been nearly exclusively derived from practices with other solid-organ transplants and other areas of medicine, such that there is a significant lack of data regarding the efficacy for these in pulmonary AMR. Lastly, outcomes after AMR remain quite poor despite aggressive treatment. In this review, we revisit the history of AMR in lung transplantation, describe our current understanding of its pathophysiology, discuss the use and limitations of the consensus diagnostic criteria, review current treatment strategies, and summarize long-term outcomes. We conclude with a synopsis of our most pressing gaps in knowledge, introduce recommendations for future directions, and highlight promising areas of active research.

scholarly journals Dural Extranodal Marginal Zone Lymphoma in an XRCC2 Mutation Carrier

2019 ◽  
Vol 78 (12) ◽  
pp. 1174-1177
Author(s):  
Kristina Gvozdjan ◽  
Brad E Zacharia ◽  
Michael G Bayerl ◽  
Adeola Tomi-Olugbodi ◽  
Cinda Boyer ◽  
...  
Keyword(s):  
Malt Lymphoma ◽  
Marginal Zone ◽  
Current Knowledge ◽  
Marginal Zone Lymphoma ◽  
Laboratory Evaluation ◽  
Loss Of Function ◽  
Pathogenic Potential ◽  
Extranodal Marginal Zone Lymphoma ◽  
Sagittal Sinus ◽  
History Of

Abstract Dural extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a rare entity without an associated recurrent genetic abnormality. Only one case has been described in a woman with history of breast carcinoma without a known genetic predisposition. Here, we report a case of a 56-year-old woman heterozygous for XRCC2 mutation with a history of Graves’ disease and bilateral breast carcinomas, who was found to have a diffusely infiltrative extra-axial mass in the high parietal convexity with infiltration into the adjacent superior sagittal sinus. The morphologic, immunophenotypic, and molecular findings were diagnostic of MALT lymphoma. Staging bone marrow demonstrated involvement by the neoplasm. Although the study was limited to only the clinically significant laboratory evaluation, it may serve as an important addition to the current knowledge of the pathogenic potential of a loss of function mutation in this rarely reported cancer predisposition gene.

scholarly journals tRNA methyltransferase 10 homologue A (TRMT10A) mutation in a Chinese patient with diabetes, insulin resistance, intellectual deficiency and microcephaly

2020 ◽  
Vol 8 (1) ◽  
pp. e001601 ◽  
Author(s):  
Hu Lin ◽  
Xuelian Zhou ◽  
Xuefeng Chen ◽  
Ke Huang ◽  
Wei Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Intellectual Disability ◽  
Current Knowledge ◽  
Genetic Diagnosis ◽  
Insulin Dependent Diabetes ◽  
Homozygous Mutation ◽  
Intellectual Deficiency ◽  
Loss Of Function ◽  
Trna Methyltransferase ◽  
Insulin Dependent

IntroductionLoss-of-function mutations in tRNA methyltransferase 10 homologue A (TRMT10A), a tRNA methyltransferase, have recently been described as a monogenic cause of early-onset diabetes with microcephaly, epilepsy and intellectual disability.Research design and methodsWe report a Chinese young patient who was diagnosed with diabetes mellitus as a result of a TRMT10A mutation.ResultsA homozygous mutation c.496–1G>A in TRMT10A was identified using targeted next-generation sequencing and confirmed by PCR/Sanger sequencing. In addition to being diagnosed with diabetes, the patient also has microcephaly and intellectual deficiency. The diabetes was due to marked insulin resistance and responded very well to metformin treatment.ConclusionOur case is the first report in the Asian population. It adds to current knowledge of TRMT10A related with young-onset non-insulin-dependent diabetes and confirms the a single previous report of insulin resistance in this syndrome. Genomic testing should be considered in children with non-insulin-dependent diabetes with intellectual disability and microcephaly. A clear genetic diagnosis is helpful for early detection and treatment addressing insulin resistance.

scholarly journals Current Treatment Options for Cystic Fibrosis-Related Liver Disease

2020 ◽  
Vol 21 (22) ◽  
pp. 8586 ◽  
Author(s):  
Katharina Staufer
Keyword(s):  
Cystic Fibrosis ◽  
Liver Disease ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Transmembrane Conductance Regulator ◽  
Definition Of ◽  
Related Liver Disease ◽  
Near Future

Cystic Fibrosis-related liver disease (CFLD) has become a leading cause of morbidity and mortality in patients with Cystic Fibrosis (CF), and affects children and adults. The understanding of the pathogenesis of CFLD is key in order to develop efficacious treatments. However, it remains complex, and has not been clarified to the last. The search for a drug might be additionally complicated due to the diverse clinical picture and lack of a unified definition of CFLD. Although ursodeoxycholic acid has been used for decades, its efficacy in CFLD is controversial, and the potential of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators and targeted gene therapy in CFLD needs to be defined in the near future. This review focuses on the current knowledge on treatment strategies for CFLD based on pathomechanistic viewpoints.

scholarly journals Delayed Relapse of Paracoccidioidomycosis in the Central Nervous System: A Case Report

2020 ◽  
Vol 7 (4) ◽  
Author(s):  
Rifat Rahman ◽  
Leela Davies ◽  
Amir M Mohareb ◽  
Paula M Peçanha-Pietrobom ◽  
Nirav J Patel ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Case Report ◽  
Treatment Strategies ◽  
Current Treatment ◽  
System A ◽  
History Of ◽  
The Central Nervous System ◽  
Relapsed Disease ◽  
Review Current

Abstract Paracoccidioidomycosis is a dimorphic fungal infection endemic in Latin America. We report a patient with a history of pulmonary paracoccidioidomycosis who presented with relapsed disease in the central nervous system 4 years after initial treatment. We review current treatment strategies for paracoccidioidomycosis and neuroparacoccidioidomycosis.

scholarly journals An Overview on Tuberculosis and Worldwide Steps to Combat TB Including Awareness Programme in India

2021 ◽  
pp. 956-971
Author(s):  
Bhoyar Vidyadevi ◽  
Belgamwar Veena ◽  
Pardeshi Chandrakantsing ◽  
Pramod Ingle
Keyword(s):  
Current Knowledge ◽  
Treatment Strategies ◽  
World Health ◽  
Health Issues ◽  
Indian Government ◽  
Health Habits ◽  
The People ◽  
New Strategy ◽  
History Of ◽  
Awareness Programme

Objectives of current review is to collate history of Tuberculosis (TB), overview of the current literature on epidemiology, world health organisations (WHO) recent strategic plan to overcome and eliminate TB from the root, and to determine current knowledge gaps for control of TB. This study is a review, a descriptive approach of state-of-science for better treatment strategies for TB. The article finds that to reach to end TB goal, WHO, we have to follow the guideline of who about TB control, along with that the Indian government also maintained awareness program. Current findings on TB suggest that with the development of science and technology, researches being conducted to minimise the drug resistance tuberculosis, as well as WHO sets new strategy to fight against TB, which could potentially change the casual outlook of the people towards their health habits, health issues, and will help them in future to tackle from this deadly killer disease.

scholarly journals Type 2 Endoleak Management

2020 ◽  
Vol 37 (04) ◽  
pp. 365-370
Author(s):  
James X. Chen ◽  
S. William Stavropoulos
Keyword(s):  
Natural History ◽  
Endovascular Aneurysm Repair ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Type 2 Endoleak ◽  
History Of ◽  
Aneurysm Repair

AbstractType 2 endoleaks are the most common endoleak type following endovascular aneurysm repair. The natural history of these endoleaks can vary, with some demonstrating a self-limited or indolent course, while others can contribute to aneurysm sac enlargement and rupture. A variety of embolization techniques, including transarterial catheterization and direct sac puncture techniques, have been developed for the treatment of type 2 endoleaks. In this article, the authors review the indications, techniques, and outcomes of current treatment strategies for type 2 endoleaks.

scholarly journals Perinatal Brain Injury and Inflammation: Lessons from Experimental Murine Models

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2640
Author(s):  
Aisling Leavy ◽  
Eva M. Jimenez Mateos
Keyword(s):  
Brain Injury ◽  
Neuronal Damage ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Neonatal Seizures ◽  
Perinatal Brain Injury ◽  
Neuroprotective Effects ◽  
Neurological Outcomes ◽  
Neurological Effects

Perinatal brain injury or neonatal encephalopathy (NE) is a state of disturbed neurological function in neonates, caused by a number of different aetiologies. The most prominent cause of NE is hypoxic ischaemic encephalopathy, which can often induce seizures. NE and neonatal seizures are both associated with poor neurological outcomes, resulting in conditions such as cerebral palsy, epilepsy, autism, schizophrenia and intellectual disability. The current treatment strategies for NE and neonatal seizures have suboptimal success in effectively treating neonates. Therapeutic hypothermia is currently used to treat NE and has been shown to reduce morbidity and has neuroprotective effects. However, its success varies between developed and developing countries, most likely as a result of lack of sufficient resources. The first-line pharmacological treatment for NE is phenobarbital, followed by phenytoin, fosphenytoin and lidocaine as second-line treatments. While these drugs are mostly effective at halting seizure activity, they are associated with long-lasting adverse neurological effects on development. Over the last years, inflammation has been recognized as a trigger of NE and seizures, and evidence has indicated that this inflammation plays a role in the long-term neuronal damage experienced by survivors. Researchers are therefore investigating the possible neuroprotective effects that could be achieved by using anti-inflammatory drugs in the treatment of NE. In this review we will highlight the current knowledge of the inflammatory response after perinatal brain injury and what we can learn from animal models.

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