scholarly journals Molecular and Clinical Aspects of COVID-19 Vaccines and Other Therapeutic Interventions Apropos Emerging Variants of Concern

2021 ◽  
Vol 12 ◽  
Author(s):  
Khursheed Ul Islam ◽  
Thoraya Mohamed Elhassan A-Elgadir ◽  
Sarah Afaq ◽  
Tanveer Ahmad ◽  
Jawed Iqbal
Keyword(s):  
Monoclonal Antibodies ◽  
Molecular Mechanisms ◽  
Immunological Response ◽  
Therapeutic Interventions ◽  
Treatment Modalities ◽  
Clinical Aspects ◽  
Vaccination Programs ◽  
Treatment Regimens ◽  
Clinical Responses

Coronavirus disease 2019 (COVID-19) has overwhelmed the healthcare and economy of the world, with emerging new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posing an everlasting threat to humanity. While most COVID-19 vaccines provide adequate protective immunological response against the original SARS-CoV-2 variant, there is a pressing need to understand their biological and clinical responses. Recent evidence suggests that some of the new variants of SARS-CoV-2 evade the protection conferred by the existing vaccines, which may impede the ongoing efforts to expedite the vaccination programs worldwide. These concerns have also highlighted the importance of a pan-COVID-19 vaccine, which is currently in the making. Thus, it is imperative to have a better molecular and clinical understanding of the various COVID-19 vaccines and their immunological trajectory against any emerging variant of concerns (VOCs) in particular to break this vicious cycle. Furthermore, other treatment regimens based on cellular therapies and monoclonal antibodies should be explored systematically as an alternative and readily available option considering the possibility of the emergence of more virulent SARS-CoV-2 mutants. In this review, we shed light on the various molecular mechanisms and clinical responses of COVID-19 vaccines. Importantly, we review the recent findings of their long-term immune protection and efficacy against emerging VOCs. Considering that other targeted and effective treatments will complement vaccine therapy, we provide a comprehensive understanding of the role of cell-based therapies, monoclonal antibodies, and immunomodulatory agents as alternative and readily available treatment modalities against any emerging SARS-CoV-2 variant.

scholarly journals Therapeutic strategies in multiple sclerosis. II. Long–term repair

1999 ◽  
Vol 354 (1390) ◽  
pp. 1711-1720 ◽  
Author(s):  
Neil Scoldingf
Keyword(s):  
Multiple Sclerosis ◽  
Repair Process ◽  
Therapeutic Interventions ◽  
Clinical Aspects ◽  
Target Cells ◽  
Short Term ◽  
Myelin Repair ◽  
Cellular Environment ◽  
Spontaneous Repair

Spontaneous myelin repair in multiple sclerosis (MS) provides a striking example of the brain's inherent capacity for sustained and stable regenerative tissue repair—but also clearly emphasizes the limitations of this capacity; remyelination ultimately fails widely in many patients, and disability and handicap accumulate. The observation of endogenous partial myelin repair has raised the possibility that therapeutic interventions designed to supplement or promote remyelination might have a useful and significant impact both in the short term, in restoring conduction, and in the long term, in safeguarding axons. Therapeutic remyelination interventions must involve manipulations to either the molecular or the cellular environment within lesions; both depend crucially on a detailed understanding of the biology of the repair process and of those glia implicated in spontaneous repair, or capable of contributing to exogenous repair. Here we explore the biology of myelin repair in MS, examining the glia responsible for successful remyelination, oligodendrocytes and Schwann cells, their ‘target’ cells, neurons and the roles of astrocytes. Options for therapeutic remyelinating strategies are reviewed, including glial cell transplantation and treatment with growth factors or other soluble molecules. Clinical aspects of remyelination therapies are considered—which patients, which lesions, which stage of the disease, and how to monitor an int–ervention—and the remaining obstacles and hazards to these approaches are discussed.

scholarly journals The Role of Mitochondrial Dysfunction in Atrial Fibrillation: Translation to Druggable Target and Biomarker Discovery

2021 ◽  
Vol 22 (16) ◽  
pp. 8463
Author(s):  
Lisa Pool ◽  
Leonoor F. J. M. Wijdeveld ◽  
Natasja M. S. de Groot ◽  
Bianca J. J. M. Brundel
Keyword(s):  
Atrial Fibrillation ◽  
Mitochondrial Dysfunction ◽  
Molecular Mechanisms ◽  
Biomarker Discovery ◽  
High Energy ◽  
Current Treatment ◽  
Therapeutic Interventions ◽  
Treatment Modalities ◽  
Activation Rate

Atrial fibrillation (AF) is the most prevalent and progressive cardiac arrhythmia worldwide and is associated with serious complications such as heart failure and ischemic stroke. Current treatment modalities attenuate AF symptoms and are only moderately effective in halting the arrhythmia. Therefore, there is an urgent need to dissect molecular mechanisms that drive AF. As AF is characterized by a rapid atrial activation rate, which requires a high energy metabolism, a role of mitochondrial dysfunction in AF pathophysiology is plausible. It is well known that mitochondria play a central role in cardiomyocyte function, as they produce energy to support the mechanical and electrical function of the heart. Details on the molecular mechanisms underlying mitochondrial dysfunction are increasingly being uncovered as a contributing factor in the loss of cardiomyocyte function and AF. Considering the high prevalence of AF, investigating the role of mitochondrial impairment in AF may guide the path towards new therapeutic and diagnostic targets. In this review, the latest evidence on the role of mitochondria dysfunction in AF is presented. We highlight the key modulators of mitochondrial dysfunction that drive AF and discuss whether they represent potential targets for therapeutic interventions and diagnostics in clinical AF.

Canadian Patients’ Preferences in Topical Psoriasis Care: Insights From the PROPEL Surveys

2018 ◽  
Vol 22 (5) ◽  
pp. 464-471 ◽  
Author(s):  
Ronald Vender ◽  
Melinda J. Gooderham ◽  
Lyn C. Guenther ◽  
Dimitrios Kyritsis ◽  
Jaggi Rao ◽  
...  
Keyword(s):  
Topical Treatment ◽  
Topical Therapy ◽  
Leading Edge ◽  
Treatment Modalities ◽  
Patient Attitudes ◽  
Good Adherence ◽  
Treatment Regimens ◽  
Burden Of Treatment ◽  
Topical Medications

Background: Patients with psoriasis of all severities employ topical treatment, either alone or in combination. Promoting Patient Engagement at the Leading Edge of Topical Psoriasis Treatment (PROPEL) surveyed Canadian dermatologists and their patients about their attitudes toward topical care. Objectives: To identify gaps between patients and dermatologists regarding the burden of psoriasis, the burden of treatment, and priorities for topical care to Canadian patients with psoriasis. Methods: Two parallel surveys explored patient attitudes toward psoriasis and their experience with topical care, as expressed by patients or as perceived by their dermatologists. A third survey, addressed to patients, included additional questions regarding treatment adherence to current topical treatment regimens. Results: PROPEL dermatologists underestimated the burden associated with psoriatic itch. Otherwise, they were well aligned with patients’ views, including their preference for maintaining topical care of their psoriasis over other treatment modalities, the nature of good psoriasis control, and desirable features of topical medications. Despite holding generally positive views of topical therapy, many patients self-identified as poorly adherent. Conclusions: Long-term adherence to psoriasis topical care remains a challenge. Formulations with improved acceptability might help patients maintain good adherence.

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Cardiovascular Research ◽  
Inflammatory Processes ◽  
Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

1996 ◽  
Vol 16 (02) ◽  
pp. 114-138 ◽  
Author(s):  
R. E. Scharf
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Platelet Membrane ◽  
Clinical Aspects ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Membrane Expression ◽  
Receptor Complexes ◽  
Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

Neuropathy in the gut. Gut motility disorders in patients with diabetes mellitus

2012 ◽  
Vol 153 (16) ◽  
pp. 607-614
Author(s):  
Tibor Wittmann
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Treatment Modalities ◽  
Clinical Aspects ◽  
Gut Motility ◽  
Motility Disorders ◽  
The Everyday ◽  
Patients With Diabetes ◽  
Leading Symptom ◽  
Different Parts

The extent and severity of motility disorders remains heterogeneous in the different parts of the gut, and in most cases failures in gut motility do not correspond with the severity of the symptoms. If diarrhea or fecal incontinence is the leading symptom, or the blood glucose level varies frequently and considerably despite the treatment efforts, the motility of the stomach and bowels is seriously disturbed. The clinical aspects, detailed pathogenesis, diagnostic approach and treatment modalities of gastrointestinal motility disorders in diabetes mellitus are reviewed to help and improve the everyday medical practice. Orv. Hetil., 2012, 153, 607–614.

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