More gain, less pain: How resistance training affects immune system functioning in multiple sclerosis patients: A review.

Multiple sclerosis (MS) is characterized by a complex etiology that is mirrored by the perplexing and inconsistent treatment responses observed across different patients. Although epigenetic research has garnered rightful interest in its efforts towards demystifying and understanding aberrant responses to treatment, the interim undoubtedly requires alternative non-pharmacological approaches towards attaining more effective management strategies. Of particular interest in this review is resistance training (RT) as a non-pharmacological exercise-based interventional strategy and its potential role as a disease-modifying tool. RT has been reported across literature to positively influence numerous aspects in the quality of life (QoL) and functional capacity of MS patients, and one of the attributes of these benefits may be a shift in the immune system of these individuals. RT has also been proven to affect different immune system key players associated with MS pathology. Ultimately, this brief review aims to provide a potential yet crucial link between RT, alterations in the expression profile of the immune system, and finally an imminent improvement in the overall well-being and QoL of MS patients, suggesting that utilizing RT as an interventional exercise modality may be an effective strategy that would aid in managing such a complex and debilitating disease.

What's your cup of tea? The role of herbal compounds in the management of multiple sclerosis.

Multiple Sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease that is characterized by a complex etiology. Efforts towards the management of MS have long been directed towards symptomatic relief, as well as the use of immune-modulatory, disease modifying therapies; however, inconsistent treatment responses still prevail, increasing the risk for disease progression. While a great deal of research attempted to unravel the complexity of treatment responses in light of epigenetic variability, parallel efforts in the direction of alternative medicine may be as paramount. Herbal compounds have long been regarded as safe and versatile options for aiding in various disorders, including neurodegenerative conditions like MS. Numerous studies have taken interest in a myriad of herbal plants for their potential benefit in alleviating some of the most common MS symptoms such as spasticity and fatigue, delaying the progression of the disease, as well as influencing the overall quality of life for MS patients. This review aims to provide a comprehensive overview of recent clinical studies examining the effects of various herbal plants on different aspects of MS, in an attempt to shed light on an important tool for aiding in the management of this complex and multifactorial disease.

Rs205764 and rs547311 in linc00513 may influence treatment responses in multiple sclerosis patients: A pharmacogenomics Egyptian study.

Background: Multiple sclerosis (MS) is characterized by a complex etiology that is reflected in the lack of consistently predictable treatment responses across patients of seemingly similar characteristics. Approaches to demystify the underlying predictors of aberrant treatment responses have made use of genome-wide association studies (GWAS), with imminent progress made in identifying single nucleotide polymorphisms (SNPs) associated with MS risk, disease progression, and treatment response. Ultimately, such pharmacogenomic studies aim to utilize the approach of personalized medicine to maximize patient benefit and minimize rate of disease progression. Objective: Very limited research is available around the long intergenic non-coding RNA (linc)00513, recently being reported as a novel positive regulator of the type-1 interferon (IFN) pathway, following its overexpression in the presence of two polymorphisms: rs205764 and rs547311 in the promoter region of this gene. We attempt to provide data on the prevalence of genetic variations at rs205764 and rs547311 in Egyptian MS patients, and correlate these polymorphisms with the patients' responses to disease-modifying treatments. Methods: Genomic DNA from 144 RRMS patients was isolated and analyzed for genotypes at the positions of interest on linc00513 using RT-qPCR. Genotype groups were compared with regards to their response to treatment; additional secondary clinical parameters including the estimated disability status score (EDSS), and onset of the disease were examined in relation to these polymorphisms. Results: Polymorphisms at rs205764 were associated with a significantly higher response to fingolimod and a significantly lower response to dimethylfumarate. Moreover, the average EDSS of patients carrying polymorphisms at rs547311 was significantly higher, whereas no correlation appeared to exist with the onset of MS. Conclusion: Understanding the complex interplay of factors influencing treatment response is pivotal in MS. One of the factors contributing to a patient's response to treatment, as well as disease disability, may be polymorphisms on non-coding genetic material, such as rs205764 and rs547311 on linc00513. Through this work, we propose that genetic polymorphisms may partially drive disease disability and inconsistent responses to treatment in MS; we also aim to draw attention towards genetic approaches, such as screening for specific polymorphisms, to possibly direct treatment choices in such a complex disease.

The precision medicine process for treating rare disease using the artificial intelligence tool mediKanren.

There are over 6,000 different rare diseases estimated to impact 300 million people worldwide. As genetic testing becomes more common practice in the clinical setting, the number of rare disease diagnoses will continue to increase, resulting in the need for novel treatment options. Identifying treatments for these disorders is challenging due to a limited understanding of disease mechanisms, small cohort sizes, interindividual symptom variability, and little commercial incentive to develop new treatments. A promising avenue for treatment is drug repurposing, where FDA-approved drugs are repositioned as novel treatments. However, linking disease mechanisms to drug action can be extraordinarily difficult and requires a depth of knowledge across multiple fields, which is complicated by the rapid pace of biomedical knowledge discovery. To address these challenges, The Hugh Kaul Precision Medicine Institute developed an artificial intelligence tool, mediKanren, that leverages the mechanistic insight of genetic disorders to identify therapeutic options. Using knowledge graphs, mediKanren enables an efficient way to link all relevant literature and databases. This tool has allowed for a scalable process that has been used to help over 500 rare disease families. Here, we provide a description of our process, the advantages of mediKanren, and its impact on rare disease patients.

Thymoquinone: A Tie-Breaker in SARS-CoV2-Infected Cancer Patients?

Since the beginning of the SARS-CoV-2(severe acute respiratory syndrome-coronavirus-2) pandemic, arace to develop a vaccine has been initiated, considering the massive and rather significant economic and healthcare hits that this virus has caused. The pathophysiology occurring following COVID-19(coronavirus disease-2019) infection has givenhints regarding the supportive and symptomatic treatments to establish for patients, as no specific anti-SARS-CoV-2 is available yet. Patient symptoms vary greatly and range from mild symptoms to severe fatal complications. Supportive treatments include antipyretics, antiviral therapies, different combinations of broad-spectrum antibiotics, hydroxychloroquine and plasma transfusion. Unfortunately, cancer patients are at higher risk of viral infection and more likely to develop serious complications due to their immunocompromised state, the fact that they are already administering multiple medications, as well as combined comorbidity compared to the general population. It may seem impossible to find a drug that possesses both potent antiviral and anticancer effects specifically against COVID-19 infection and its complications and the existing malignancy, respectively. Thymoquinone (TQ) is the most pharmacologically active ingredient in Nigella sativa seeds (black seeds); it is reported to have anticancer, anti-inflammatory and antioxidant effects in various settings. In this review, we will discuss the multiple effects of TQ specifically against COVID-19, its beneficial effects against COVID-19 pathophysiology and multiple-organ complications, its use as an adjuvant for supportive COVID-19 therapy and cancer therapy, and finally, its anticancer effects.

GPI-AP: Unraveling a New Class of Malignancy Mediators and Potential Immunotherapy Targets.

With millions of cases diagnosed annually and high economic burden to cover expensive costs, cancer is one of the most difficult diseases to treat due to late diagnosis and severe adverse effects from conventional therapy. This creates an urgent need to find new targets for early diagnosis and therapy. Progress in research revealed the key steps of carcinogenesis. They are called cancer hallmarks. Zooming in, cancer hallmarks are characterized by ligands binding to their cognate receptor and so triggering signaling cascade within cell to make response for stimulus. Accordingly, understanding membrane topology is vital. In this review, we shall discuss one type of transmembrane proteins: Glycosylphosphatidylinositol-Anchored Proteins (GPI-APs), with specific emphasis on those involved in tumor cells by evading immune surveillance and future applications for diagnosis and immune targeted therapy.

Cytoscape: a software environment for integrated models of biomolecular interaction networks.

Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.