scholarly journals Long COVID a New Derivative in the Chaos of SARS-CoV-2 Infection: The Emergent Pandemic?

2021 ◽  
Vol 10 (24) ◽  
pp. 5799
Author(s):  
Diego Fernández-Lázaro ◽  
Nerea Sánchez-Serrano ◽  
Juan Mielgo-Ayuso ◽  
Juan Luis García-Hernández ◽  
Jerónimo J. González-Bernal ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Current Knowledge ◽  
Specific Treatment ◽  
Organ Damage ◽  
Pharmacological Treatments ◽  
Gut Flora ◽  
Host Interaction ◽  
Symptom Complex ◽  
Underlying Mechanisms ◽  
Immunological Alterations

Coronavirus disease 2019 (COVID-19) is a multisystem illness caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), which can manifest with a multitude of symptoms in the setting of end-organ damage, though it is predominantly respiratory. However, various symptoms may remain after acute SARS-CoV-2 infection, and this condition is referred to as “Long COVID” (LC). Patients with LC may develop multi-organ symptom complex that remains 4–12 weeks after the acute phase of illness, with symptoms intermittently persisting over time. The main symptoms are fatigue, post-exertional malaise, cognitive dysfunction, and limitation of functional capacity. Pediatric patients developed the main symptoms of LC like those described in adults, although there may be variable presentations of LC in children. The underlying mechanisms of LC are not clearly known, although they may involve pathophysiological changes generated by virus persistence, immunological alterations secondary to virus–host interaction, tissue damage of inflammatory origin and hyperactivation of coagulation. Risk factors for developing LC would be female sex, more than five early symptoms, early dyspnea, previous psychiatric disorders, and alterations in immunological, inflammatory and coagulation parameters. There is currently no specific treatment for LC, but it could include pharmacological treatments to treat symptoms, supplements to restore nutritional, metabolic, and gut flora balance, and functional treatments for the most disabling symptoms. In summary, this study aims to show the scientific community the current knowledge of LC.

Ion Channel Remodelling in Atrial Fibrillation

2011 ◽  
Vol 7 (2) ◽  
pp. 97 ◽  
Author(s):  
Niels Voigt ◽  
Dobromir Dobrev ◽  
◽  
Keyword(s):  
Atrial Fibrillation ◽  
Ion Channel ◽  
Antiarrhythmic Drugs ◽  
Current Knowledge ◽  
Bleeding Complications ◽  
Large Size ◽  
Cardiovascular Morbidity And Mortality ◽  
Number Of Patients ◽  
Life Threatening ◽  
Underlying Mechanisms

Atrial fibrillation (AF) is the most common arrhythmia and is associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication. Present drugs used for the therapy of AF (antiarrhythmics and anticoagulants) have major limitations, including incomplete efficacy, risks of life-threatening proarrhythmic events and bleeding complications. Non-pharmacological ablation procedures are efficient and apparently safe, but the very large size of the patient population allows ablation treatment of only a small number of patients. These limitations largely result from limited knowledge about the underlying mechanisms of AF and there is a hope that a better understanding of the molecular basis of AF may lead to the discovery of safer and more effective therapeutic targets. This article reviews the current knowledge about AF-related ion-channel remodelling and discusses how these alterations might affect the efficacy of antiarrhythmic drugs.

scholarly journals The Therapeutic Effect of Extracellular Vesicles on Asthma in Pre-Clinical Models: A Systematic Review Protocol

2021 ◽  
Vol 1 (1) ◽  
pp. 84-95
Author(s):  
Patience O. Obi ◽  
Jennifer E. Kent ◽  
Maya M. Jeyaraman ◽  
Nicole Askin ◽  
Taiana M. Pierdoná ◽  
...  
Keyword(s):  
Systematic Review ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Grey Literature ◽  
Specific Treatment ◽  
Therapeutic Effects ◽  
Management Options ◽  
Paracrine Signalling

Asthma is the most common pediatric disease, characterized by chronic airway inflammation and airway hyperresponsiveness. There are several management options for asthma, but no specific treatment. Extracellular vesicles (EVs) are powerful cellular mediators of endocrine, autocrine and paracrine signalling, and can modulate biophysiological function in vitro and in vivo. A thorough investigation of therapeutic effects of EVs in asthma has not been conducted. Therefore, this systematic review is designed to synthesize recent literature on the therapeutic effects of EVs on physiological and biological outcomes of asthma in pre-clinical studies. An electronic search of Web of Science, EMBASE, MEDLINE, and Scopus will be conducted on manuscripts published in the last five years that adhere to standardized guidelines for EV research. Grey literature will also be included. Two reviewers will independently screen the selected studies for title and abstract, and full text based on the eligibility criteria. Data will be extracted, narratively synthesized and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This systematic review will summarize the current knowledge from preclinical studies investigating the therapeutic effects of EVs on asthma. The results will delineate whether EVs can mitigate biological hallmarks of asthma, and if so, describe the underlying mechanisms involved in the process. This insight is crucial for identifying key pathways that can be targeted to alleviate the burden of asthma. The data will also reveal the origin, dosage and biophysical characteristics of beneficial EVs. Overall, our results will provide a scaffold for future intervention and translational studies on asthma treatment.

scholarly journals Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

2014 ◽  
Vol 94 (4) ◽  
pp. 1027-1076 ◽  
Author(s):  
M. A. Hanson ◽  
P. D. Gluckman
Keyword(s):  
Animal Studies ◽  
Developmental Plasticity ◽  
Current Knowledge ◽  
Evolutionary Developmental Biology ◽  
Noncommunicable Disease ◽  
Normal Range ◽  
Physiological Processes ◽  
New Concepts ◽  
Health And Disease ◽  
Underlying Mechanisms

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention.

scholarly journals CSF1R-related leukoencephalopathy

Neurology ◽  
2018 ◽  
Vol 91 (24) ◽  
pp. 1092-1104 ◽  
Author(s):  
Takuya Konno ◽  
Koji Kasanuki ◽  
Takeshi Ikeuchi ◽  
Dennis W. Dickson ◽  
Zbigniew K. Wszolek
Keyword(s):  
White Matter ◽  
Cultured Cells ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Gene Mutations ◽  
Future Research ◽  
Primary Role ◽  
Extrapyramidal Signs ◽  
Underlying Mechanisms

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia-like phenotype in their 40s–50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than men. On brain imaging, in addition to white matter abnormalities, thinning of the corpus callosum, diffusion-restricted lesions in the white matter, and brain calcifications are hallmarks. Primary axonopathy followed by demyelination was suggested by pathology. Haploinsufficiency of colony-stimulating factor-1 receptor (CSF1R) is evident in a patient with a frameshift mutation, facilitating the establishment of Csf1r haploinsufficient mouse model. These mice develop clinical, radiologic, and pathologic phenotypes consistent with those of human patients with CSF1R mutations. In vitro, perturbation of CSF1R signaling is shown in cultured cells expressing mutant CSF1R. However, the underlying mechanisms by which CSF1R mutations selectively lead to white matter degeneration remains to be elucidated. Given that CSF1R mainly expresses in microglia, CSF1R-related leukoencephalopathy is representative of primary microgliopathies, of which microglia have a pivotal and primary role in pathogenesis. In this review, we address the current knowledge of CSF1R-related leukoencephalopathy and discuss the putative pathophysiology, with a focus on microglia, as well as future research directions.

scholarly journals The Effects and Underlying Mechanisms of Cell Therapy on Blood-Brain Barrier Integrity After Ischemic Stroke

2020 ◽  
Vol 18 (12) ◽  
pp. 1213-1226
Author(s):  
Li Gao ◽  
Zhenghong Song ◽  
Jianhua Mi ◽  
Pinpin Hou ◽  
Chong Xie ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cell Therapy ◽  
Blood Brain Barrier ◽  
Current Knowledge ◽  
Brain Barrier ◽  
Neural Cells ◽  
Promising Tool ◽  
Cell Based Therapy ◽  
Blood Brain ◽  
Underlying Mechanisms

Ischemic stroke is one of the main causes of mortality and disability worldwide. However, efficient therapeutic strategies are still lacking. Stem/progenitor cell-based therapy, with its vigorous advantages, has emerged as a promising tool for the treatment of ischemic stroke. The mechanisms involve new neural cells and neuronal circuitry formation, antioxidation, inflammation alleviation, angiogenesis, and neurogenesis promotion. In the past decades, in-depth studies have suggested that cell therapy could promote vascular stabilization and decrease blood-brain barrier (BBB) leakage after ischemic stroke. However, the effects and underlying mechanisms on BBB integrity induced by the engrafted cells in ischemic stroke have not been reviewed yet. Herein, we will update the progress in research on the effects of cell therapy on BBB integrity after ischemic stroke and review the underlying mechanisms. First, we will present an overview of BBB dysfunction under the ischemic condition and cells engraftment for ischemic treatment. Then, we will summarize and discuss the current knowledge about the effects and underlying mechanisms of cell therapy on BBB integrity after ischemic stroke. In particular, we will review the most recent studies in regard to the relationship between cell therapy and BBB in tissue plasminogen activator (t-PA)-mediated therapy and diabetic stroke.

scholarly journals Case Report: First Two Identified Cases of Fabry Disease in Central Asia

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Cainelli ◽  
Dias Argandykov ◽  
Dauren Kaldarbekov ◽  
Murat Mukarov ◽  
Liên Tran Thi Phuong ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Central Asia ◽  
Genetic Diseases ◽  
Delayed Diagnosis ◽  
Specific Treatment ◽  
Organ Damage ◽  
Multisystem Disorder ◽  
Family Pedigree ◽  
Rare Genetic Diseases ◽  
Delays In Diagnosis

Background: Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked inherited, genetic disease due to the functional deficiency of lysosomal α-galactosidase (α-GAL) that leads to the accumulation of glycosphingolipids (mainly globotriaosylceramide or Gb3) and its derivative globotriaosylsphingosine or lyso-Gb3. Classic FD is a multisystem disorder which initially presents in childhood with neuropathic pain and dermatological, gastrointestinal, ocular, and cochleo-vestibular manifestations. Over time, end-organ damage such as renal failure, cardiac arrhythmia and early stroke may develop leading to reduced life expectancy in the absence of specific treatment.Case presentation: We describe two Kazakh patients who presented in adulthood with a delayed diagnosis. We conducted also a family screening through cascade genotyping.Conclusion: This is the first description of cases of Fabry disease in Central Asia. An extensive family pedigree enabled the identification of ten additional family members. Patients with rare genetic diseases often experience substantial delays in diagnosis due to their rarity and non-specific symptoms, which can negatively impact their management and delay treatment. FD may be difficult to diagnose because of the non-specificity of its early and later-onset symptoms and its X-linked inheritance. Raising awareness of clinicians is important for earlier diagnosis and optimal outcome of specific therapies.

Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms

2018 ◽  
Vol 189 ◽  
pp. 89-103 ◽  
Author(s):  
Joachim Alexandre ◽  
Javid J. Moslehi ◽  
Kevin R. Bersell ◽  
Christian Funck-Brentano ◽  
Dan M. Roden ◽  
...  
Keyword(s):  
Anticancer Drug ◽  
Cardiac Rhythm ◽  
Current Knowledge ◽  
Drug Induced ◽  
Underlying Mechanisms

Abstract 668: Deficiency of miR-155 Attenuates TLR3-Induced Preeclampsia-Like Symptoms in Mice

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Derek Charles ◽  
Ashley Jamison ◽  
Valorie L Chiasson ◽  
Brett M Mitchell ◽  
Piyali Chatterjee
Keyword(s):  
Organ Damage ◽  
Poly I:C ◽  
Maternal Inflammation ◽  
Formalin Fixed Paraffin ◽  
Maternal Morbidity And Mortality ◽  
Formalin Fixed Paraffin Embedded ◽  
Endogenous Regulators ◽  
Underlying Mechanisms ◽  
Molecular Patterns ◽  
Formalin Fixed

Preeclampsia (PE) is one of the leading causes of maternal morbidity and mortality worldwide. PE is diagnosed by new onset hypertension and proteinuria or end-organ damage at or after mid-gestation. Although it is known that excessive maternal inflammation contributes to PE, the underlying mechanisms that cause hypertension during pregnancy are still unclear. Excessive maternal inflammation may be in part mediated by ligation of Toll-like receptors (TLRs) by pathogen- or danger-associated molecular patterns. MicroRNAs are small endogenous regulators of gene expression and recently numerous inflammation-related microRNAs have been identified. Several clinical studies reported that miR-155 expression, which is known to regulate inflammation in various disease conditions, is also up-regulated in the placentas of women with PE. We confirmed by qRT-PCR that miR-155 expression was significantly increased in formalin-fixed paraffin-embedded placentas from patients with PE compared to normal pregnant women. Poly I:C (a TLR3 agonist) treatment of human placental cytotrophoblasts (CTBs) for 24 hours significantly increased miR-155 expression compared to vehicle-treated CTBs. Based on these data we hypothesized that TLR3 activation induces placental miR-155 expression which in turn contributes to excessive maternal inflammation leading to PE whereas miR-155 deficiency will attenuate PE-like symptoms in a TLR3-induced PE mouse model. Pregnant WT and miR-155 KO mice were treated with poly I:C or saline on gestational days (gd) 13, 15, and 17 prior to sacrifice on gd 18. Poly I:C treatment induced hypertension in pregnant WT mice (P-PIC WT) (gd 17 SBP: 139±4 mmHg) compared to P WT mice (99±4 mmHg), however this was attenuated in P-PIC miR-155 KO mice (100±1 mmHg ). P-PIC WT mice exhibited endothelial dysfunction and splenomegaly compared to P WT mice and these were also attenuated in PPIC miR-155 KO mice. Our data taken together suggest that miR-155 plays a role in the pathogenesis of PE likely by increasing the maternal inflammatory response.

scholarly journals Management of STEC Gastroenteritis: Is There a Role for Probiotics?

2019 ◽  
Vol 16 (9) ◽  
pp. 1649 ◽  
Author(s):  
Mario Giordano ◽  
Maria Elisabetta Baldassarre ◽  
Viviana Palmieri ◽  
Diletta D. Torres ◽  
Vincenza Carbone ◽  
...  
Keyword(s):  
Immune Responses ◽  
Therapeutic Strategy ◽  
Current Knowledge ◽  
Specific Treatment ◽  
Probiotic Supplementation ◽  
Uremic Syndrome ◽  
Intestinal Functions ◽  
Gut Microorganisms

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention.

Sign in / Sign up

Export Citation Format

Share Document