scholarly journals Dissecting the role of EYS in retinal degeneration: clinical and molecular aspects and its implications for future therapy

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ana B. Garcia-Delgado ◽  
Lourdes Valdes-Sanchez ◽  
Maria Jose Morillo-Sanchez ◽  
Beatriz Ponte-Zuñiga ◽  
Francisco J. Diaz-Corrales ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Personalised Medicine ◽  
Therapeutic Approaches ◽  
Cell Therapies ◽  
Cellular Localisation ◽  
Clinical Presentations ◽  
Technical Advances ◽  
Molecular Aspects ◽  
Future Therapy

AbstractMutations in the EYS gene are one of the major causes of autosomal recessive retinitis pigmentosa. EYS-retinopathy presents a severe clinical phenotype, and patients currently have no therapeutic options. The progress in personalised medicine and gene and cell therapies hold promise for treating this degenerative disease. However, lack of understanding and incomplete comprehension of disease's mechanism and the role of EYS in the healthy retina are critical limitations for the translation of current technical advances into real therapeutic possibilities. This review recapitulates the present knowledge about EYS-retinopathies, their clinical presentations and proposed genotype–phenotype correlations. Molecular details of the gene and the protein, mainly based on animal model data, are analysed. The proposed cellular localisation and roles of this large multi-domain protein are detailed. Future therapeutic approaches for EYS-retinopathies are discussed.

scholarly journals The Future of Parkinson’s Treatment – Personalised and Precision Medicine

2017 ◽  
Vol 12 (01) ◽  
pp. 15 ◽  
Author(s):  
Nataliya Titova ◽  
Peter Jenner ◽  
K Ray Chaudhuri ◽  
◽  
◽  
...  
Keyword(s):  
Personalised Medicine ◽  
Unmet Need ◽  
Treatment Strategies ◽  
Modern Concept ◽  
Motor Symptoms ◽  
Related Disorder ◽  
Surgical Manipulation ◽  
Future Therapy

The modern concept of Parkinson’s disease (PD) has changed and evolved and we consider Parkinson’s to be a multi-neurotransmitter dysfunction-related disorder with central and peripheral nervous system involvement. The clinical expression is thus a mixture of the outwardly evident motor symptoms and a range of ‘hidden’ non-motor symptoms. The complex underlying neuropathology of PD calls for a reassessment of the treatment strategies currently used. Treatment of PD is guideline-driven and in most cases based on a dopamine replacement strategy or surgical manipulation of brain dopaminergic pathways. Treatment of many non-dopaminergic non-motor and some motor symptoms, which have major effects on quality of life, continue to remain a key unmet need. Like in other chronic conditions such as rheumatology, the role of personalised medicine in PD needs to be increasingly considered. Personalised medicine for PD is not just a genetic approach to treatment but encompasses various strands of treatment. These include pharmacogenetic, pharmacological, as well as socio-demographic and lifestyle-related issues. Once these ‘enablers’ of personalised medicine are considered then satisfactory treatment for our patients with Parkinson’s can be achieved in an individualised manner. Future therapy for PD should move in that direction.

scholarly journals TMPRSS2 As an Influential Human Gene for COVID-19

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Sepideh Abdollahi ◽  
Pantea Izadi
Keyword(s):  
Risk Factors ◽  
Clinical Symptoms ◽  
Epidemiological Studies ◽  
Therapeutic Approaches ◽  
Diverse Range ◽  
Angiotensin Converting Enzyme 2 ◽  
Clinical Presentations ◽  
Health System Efficiency ◽  
Almost All

: In December 2019, the new virus, COVID-19, emerged and led to a pandemic respiratory acute disease. Almost all countries have experienced different rates of morbidity and mortality. These differences can be attributed to factors such as a diagnostic test capacity for COVID-19 and the health system efficiency. Besides the differences between countries related to the COVID-19 management, different patients represent a diverse range of clinical symptoms, from outpatient to patients admitted to the intensive care unit (ICU) due to the severity of symptoms. To gain deeper insights into such disparities in the severity of COVID-19 clinical presentations, epidemiological studies have reported risk factors such as old age, male sex, underlying chronic diseases such as diabetes, inflammatory and cardiovascular diseases, which have a bearing on susceptibility to COVID-19. In addition to these risk factors, the molecular mechanism involved in the virus entry process has been under investigation. Apart from a well-known protein called ACE2 (angiotensin-converting enzyme 2), which plays the receptor role for COVID-19, another essential protein in this pathway is TMPRSS2 (transmembrane protease, serine 2). This protease has a crucial role in effective membrane integration between the virus and the target cell. This process can affect the severity of the infection and the mortality rate of the disease. Thus, it seems that understanding the role of TMPRSS2 in COVID-19 infection can help better management by designing TMPRSS2 inhibitors drugs. Given the variants of the TMPRSS2 gene, which are associated with the severity of symptoms, people exposed to severe forms of this disease can be identified before the deterioration of the disease to adopt appropriate therapeutic approaches. Therefore, this study focused on the different levels of the TMPRSS2 interactions with COVID-19 virus and disease severity.

scholarly journals New insights into the role of centrosomes in mammalian fertilization and implications for ART

Reproduction ◽  
2011 ◽  
Vol 142 (6) ◽  
pp. 793-801 ◽  
Author(s):  
Heide Schatten ◽  
Qing-Yuan Sun
Keyword(s):  
Molecular Mechanisms ◽  
Assisted Reproductive Technologies ◽  
Mammalian Species ◽  
Reproductive Technologies ◽  
Therapeutic Approaches ◽  
Mitotic Apparatus ◽  
Proper Diagnosis ◽  
Mammalian Fertilization ◽  
Molecular Aspects

In non-rodent mammalian species, including humans, the oocyte and sperm both contribute centrosomal components that are most important for successful fertilization. Centrosome pathologies in sperm and the oocyte can be causes for infertility which may be overcome by assisted reproductive technologies based on proper diagnosis of specific centrosomal pathologies. However, we do not yet fully understand the cell and molecular mechanisms underlying centrosome functions in germ cells and in the developing embryo, which calls for directed specific investigations to identify centrosome-related pathologies that include components in sperm, egg, or centrosome regulation within the fertilized oocyte. The present review highlights cellular and molecular aspects of centrosomes and centrosome–nuclear interactions focused on nuclear mitotic apparatus protein during fertilization and proposes future directions in expanding therapeutic approaches related to centrosome pathologies that may play a role in still unexplained causes of infertility.

Role of melatonin in regulating neurogenesis: Implications for the neurodegenerative pathology and analogous therapeutics for Alzheimer’s disease

2020 ◽  
Vol 3 (2) ◽  
pp. 216-242 ◽  
Author(s):  
Mayuri Shukla ◽  
Areechun Sotthibundhu ◽  
Piyarat Govitrapong
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adult Neurogenesis ◽  
Adult Brain ◽  
Therapeutic Approaches ◽  
Therapeutic Implications ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Progenitor Cell Proliferation

The revelation of adult brain exhibiting neurogenesis has established that the brain possesses great plasticity and that neurons could be spawned in the neurogenic zones where hippocampal adult neurogenesis attributes to learning and memory processes. With strong implications in brain functional homeostasis, aging and cognition, various aspects of adult neurogenesis reveal exuberant mechanistic associations thereby further aiding in facilitating the therapeutic approaches regarding the development of neurodegenerative processes in Alzheimer’s Disease (AD). Impaired neurogenesis has been significantly evident in AD with compromised hippocampal function and cognitive deficits. Melatonin the pineal indolamine augments neurogenesis and has been linked to AD development as its levels are compromised with disease progression. Here, in this review, we discuss and appraise the mechanisms via which melatonin regulates neurogenesis in pathophysiological conditions which would unravel the molecular basis in such conditions and its role in endogenous brain repair. Also, its components as key regulators of neural stem and progenitor cell proliferation and differentiation in the embryonic and adult brain would aid in accentuating the therapeutic implications of this indoleamine in line of prevention and treatment of AD.   

MOLECULAR ASPECTS OF SARCOPENIA PATHOGENESIS IN CHRONOC KIDNEY DISEASE: INTEGRATED ROLE OF mTOR

2018 ◽  
Vol 22 (5) ◽  
pp. 9-16 ◽  
Author(s):  
M. Z. Gasanov
Keyword(s):  
Kidney Disease ◽  
Muscle Mass ◽  
Protein Metabolism ◽  
Mammalian Target Of Rapamycin ◽  
Healthy Person ◽  
Scientific Review ◽  
Cytoskeleton Organization ◽  
Molecular Aspects ◽  
End Stage

In recent decades, the main pathogenetic mechanisms for maintaining muscle mass and strength have been discovered. Most of the scientific papers on the molecular aspects of the  pathogenesis of sarcopenia were focused on the Akt-signaling  pathway. The subject of the study were people of elderly and senile  age, immobilized patients, patients with CKD 1-4 stages, animals. However, recently more attention has been paid to the role  of protein – the mammalian target of rapamycin mTOR. It seems to be a key link in the control of muscle mass and is a promising  marker in understanding the mechanisms of the pathogenesis of  sarcopenia. Its importance in protein metabolism in patients with  end stage kidney disease is not studied and requires further research. The presented scientific review contains  information on the role of mTOR and its components – mTORC1 and mTORC2 in maintaining muscle mass and strength in a healthy  person and in the formation of sarcopenia in patients with CKD. The  general aid of mTORC1 complex is regulation of protein production  which is necessary for cell growth and differentiation. mTORC2  complex functions are not enough studied. It is established that it  plays important role in such biological processes as cytoskeleton  organization, intracellular homeostasis maintaining, so it provides  cell resistance and cell survivability in negative external and internal  impulses. mTOR protein can be considered as promising molecular  marker in diagnostics of protein metabolism early disturbances in  patients with CKD and also as additory factor of sarcopenia severity assessment.

Particularities of tinnitus in children and adolescents

ORL ro ◽  
2016 ◽  
Vol 4 (1) ◽  
pp. 40-42
Author(s):  
Alexandra Boloș ◽  
Sebastian Cozma ◽  
Andreea Silvana Szalontay
Keyword(s):  
Quality Of Life ◽  
Young Adults ◽  
Children And Adolescents ◽  
Psychological Factors ◽  
Ambient Noise ◽  
Psychological Consequences ◽  
Therapeutic Approaches

Tinnitus is a common otologic symptom and probably the most troublesome. Tinnitus causes a number of physical and psychological consequences, that interfere with the quality of life of the patient. Many authors believe that the presence of tinnitus in children is a matter of lesser importance than in adults because it is met less frequently and would be a fleeting symptom, inoffensive for them (Graham, 1981). In addition, the prevalence of tinnitus during adolescence and even in young adults is increasing, possibly as a consequence of the increased ambient noise (Bulbul SF, Shargorodsky J). Various therapeutic approaches have generated different results, which led us to consider the role of psychological factors, hence the need to underline the particularities of this symptom in childhood.  

Papillon-Lefevre Syndrome: Challenge for Periodontal Management

2019 ◽  
Vol 3 (2) ◽  
pp. 84-86
Author(s):  
Krishna Prasad Lamichhane ◽  
Shaili Pradhan ◽  
Ranjita Shreshta Gorkhali ◽  
Pramod Kumar Koirala
Keyword(s):  
Significant Role ◽  
Autosomal Recessive ◽  
Clinical Manifestations ◽  
Autosomal Recessive Disorder ◽  
Genetic Mutations ◽  
Rare Autosomal Recessive Disorder ◽  
Diagnosis And Management ◽  
Periodontal Destruction ◽  
Palmoplantar Keratosis

Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder associated with rapidly progressing periodontitis leading to premature loss of deciduous and permanent dentition and diffuse palmoplantar keratosis. Immunologic alterations, genetic mutations, and role of bacteria are some aetiologic factors. Patients present with early periodontal destruction, so periodontists play a significant role in diagnosis and management. This paper reports a case of Papillon- Lefevre syndrome with its clinical manifestations and challenges for periodontal management which was diagnosed in dental department.

Redox State in Atrial Fibrillation Pathogenesis and Relevant Therapeutic Approaches

2019 ◽  
Vol 26 (5) ◽  
pp. 765-779 ◽  
Author(s):  
Alexios S. Antonopoulos ◽  
Athina Goliopoulou ◽  
Evangelos Oikonomou ◽  
Sotiris Tsalamandris ◽  
Georgios-Angelos Papamikroulis ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Studies ◽  
Redox State ◽  
Redox Balance ◽  
Therapeutic Approaches ◽  
Critical Determinant ◽  
Electrophysiological Properties ◽  
Antioxidant Agents ◽  
Clinical Benefits

Background: Myocardial redox state is a critical determinant of atrial biology, regulating cardiomyocyte apoptosis, ion channel function, and cardiac hypertrophy/fibrosis and function. Nevertheless, it remains unclear whether the targeting of atrial redox state is a rational therapeutic strategy for atrial fibrillation prevention. Objective: To review the role of atrial redox state and anti-oxidant therapies in atrial fibrillation. Method: Published literature in Medline was searched for experimental and clinical evidence linking myocardial redox state with atrial fibrillation pathogenesis as well as studies looking into the role of redoxtargeting therapies in the prevention of atrial fibrillation. Results: Data from animal models have shown that altered myocardial nitroso-redox balance and NADPH oxidases activity are causally involved in the pathogenesis of atrial fibrillation. Similarly experimental animal data supports that increased reactive oxygen / nitrogen species formation in the atrial tissue is associated with altered electrophysiological properties of atrial myocytes and electrical remodeling, favoring atrial fibrillation development. In humans, randomized clinical studies using redox-related therapeutic approaches (e.g. statins or antioxidant agents) have not documented any benefits in the prevention of atrial fibrillation development (mainly post-operative atrial fibrillation risk). Conclusion: Despite strong experimental and translational data supporting the role of atrial redox state in atrial fibrillation pathogenesis, such mechanistic evidence has not been translated to clinical benefits in atrial fibrillation risk in randomized clinical studies using redox-related therapies.

Endometrial Regeneration in Asherman's Syndrome: Clinical and Translational evidence of Stem Cell Therapies

2019 ◽  
Vol 14 (6) ◽  
pp. 454-459
Author(s):  
Xuejing Hou ◽  
Ying Liu ◽  
Isabelle Streuli ◽  
Patrick Dällenbach ◽  
Jean Dubuisson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Molecular Mechanisms ◽  
Uterine Cavity ◽  
Stem Cell Therapies ◽  
Intrauterine Adhesions ◽  
Asherman’S Syndrome ◽  
Cell Therapies ◽  
Fibrotic Process ◽  
Physical Barriers

Asherman’s Syndrome or Intrauterine adhesions is an acquired uterine condition where fibrous scarring forms within the uterine cavity, resulting in reduced menstrual flow, pelvic pain and infertility. Until recently, the molecular mechanisms leading to the formation of fibrosis were poorly understood, and the treatment of Asherman’s syndrome has largely focused on hysteroscopic resection of adhesions, hormonal therapy, and physical barriers. Numerous studies have begun exploring the molecular mechanisms behind the fibrotic process underlying Asherman’s Syndrome as well as the role of stem cells in the regeneration of the endometrium as a treatment modality. The present review offers a summary of available stem cell-based regeneration studies, as well as highlighting current gaps in research.

Management of Pleural Effusions in the Emergency Department.

2020 ◽  
Vol 15 ◽  
Author(s):  
MT Congedo ◽  
GM Ferretti ◽  
D Nachira ◽  
MA Pennisi
Keyword(s):  
Emergency Department ◽  
Systematic Approach ◽  
Acute Chest Pain ◽  
Pleural Effusions ◽  
Therapeutic Approaches ◽  
Massive Pleural Effusion ◽  
Emergency Department Setting ◽  
Clinical Conditions ◽  
Definitive Management

Background: In symptomatic patients, admitted in emergency department for acute chest pain and dyspnea, who require an urgent treatment, a rapid diagnosis and prompt management of massive pleural effusion or hemothorax can be lifesaving. The aim of this review was to summarize the current diagnostic and therapeutic approaches for the management of the main types of pleural effusions that physicians can have in an emergency department setting. Methods: Current literature about the topic was reviewed and critically reported, adding the experience of the authors in the management of pleural effusions in emergency settings. Results: The paper analyzed the main types of pleural effusions that physicians can have to treat. It illustrated the diagnostic steps by the principal radiological instruments, with a particular emphasis to the role of ultrasonography, in facilitating diagnosis and guiding invasive procedures. Then, the principal procedures, like thoracentesis and insertion of small and large bore chest drains, are indicated and illustrated according to the characteristics and the amount of the effusion and patient clinical conditions. Conclusion: The emergency physician must have a systematic approach that allows rapid recognition, clinical cause identification and definitive management of potential urgent pleural effusions.

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