scholarly journals Molecular Docking Study on the Effect on Lamin –B1 through Compounds for the Treatment of Multiple Sclerosis

2021 ◽  
Vol 9 (VI) ◽  
pp. 5052-5057
Author(s):  
Sachin Verma
Keyword(s):  
Multiple Sclerosis ◽  
Molecular Docking ◽  
Demyelinating Disease ◽  
The Body ◽  
Computer Assisted ◽  
Ligand Molecule ◽  
Eye Muscle ◽  
Lamin B1 ◽  
Multiple Sclerosis Disease ◽  
Drug Designing

Multiple sclerosis (MS) is a demyelinating disease that can disrupt or damage various parts of our body i.e. nerve cells, brain and spinal cord, etc. The damaged cells of the body can disrupt the ability of the the nervous system to transmit signals for the functioning of the body. MS may result in double vision, blindness in one eye, muscle weakness and trouble with coordination and sensation. This disease is a long-term disease that may not be cured rapidly and easily. MS may be found at an age of 20-50. Lamin B1 is a protein that is found in humans. A gene i.e LMB1 encodes for this protein. The nuclear lamina consists of a 2D matrix of protein which locates next to the inner nuclear membrane. Molecular docking is a virtual or e tool that promotes the drug designing technique in a computerized way or called computer-assisted Drug Designing [CADD]. This can be used to complete the goal of docking is to see the binding of the protein and ligands In our study, one of the naturally occurring products was used for Multiple sclerosis treatment i.e Quercetin . The Quercetin ligand molecule gives a promising way of making the drug against the Multiple Sclerosis disease. According to this study, Quercetin may be used as a drug agent against Multiple Sclerosis disease in the future.

scholarly journals The Impact of Multiple Sclerosis Disease Status and Subtype on Hematological Profile

2021 ◽  
Vol 18 (6) ◽  
pp. 3318
Author(s):  
Jacob M. Miller ◽  
Jeremy T. Beales ◽  
Matthew D. Montierth ◽  
Farren B. Briggs ◽  
Scott F. Frodsham ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Random Forest ◽  
Demyelinating Disease ◽  
Complete Blood Count ◽  
Disease Status ◽  
Multiple Sclerosis Disease ◽  
Forest Models ◽  
Random Forest Models ◽  
The Central Nervous System ◽  
The Impact

Multiple sclerosis (MS) is an immune-mediated, demyelinating disease of the central nervous system. In this study, an MS cohort and healthy controls were stratified into Caucasian and African American groups. Patient hematological profiles—composed of complete blood count (CBC) and complete metabolic panel (CMP) test values—were analyzed to identify differences between MS cases and controls and between patients with different MS subtypes. Additionally, random forest models were used to determine the aggregate utility of common hematological tests in determining MS disease status and subtype. The most significant and relevant results were increased bilirubin and creatinine in MS cases. The random forest models achieved some success in differentiating between MS cases and controls (AUC values: 0.725 and 0.710, respectively) but were not successful in differentiating between subtypes. However, larger samples that adjust for possible confounding variables, such as treatment status, may reveal the value of these tests in differentiating between MS subtypes.

scholarly journals Case Report: Efficacy of Rituximab in a Patient With Familial Mediterranean Fever and Multiple Sclerosis

2021 ◽  
Vol 11 ◽  
Author(s):  
Mattia Pozzato ◽  
Emanuele Micaglio ◽  
Chiara Starvaggi Cucuzza ◽  
Alessandro Cagol ◽  
Daniela Galimberti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Familial Mediterranean Fever ◽  
Demyelinating Disease ◽  
Cervical Spinal Cord ◽  
Mefv Gene ◽  
The Body ◽  
Drug Choice ◽  
Mediterranean Fever ◽  
The Right

Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disease characterized by recurrent episodes of fever and serositis caused by mutations in the MEFV gene, while Multiple Sclerosis (MS) is an inflammatory demyelinating disease of the CNS with genetic and environmental etiology. The two diseases rarely occur in association with relevant implications for clinical management and drug choice. In this paper, we present the case of a 53-year-old male with an autosomal dominant FMF since childhood who presented acute paresthesia at the right part of the body. He performed a brain and spinal cord MRI, which showed multiple brain lesions and a gd-enhancing lesion in the cervical spinal cord, and then received a diagnosis of MS. He then started Interferonβ-1a which was effective but not tolerated and caused hepatotoxicity, and then shifted to Rituximab with 3-month clinical and neuroradiological efficacy.

EMERGENCE OF BENZOTHIAZOLE AND ITS DERIVATIVES AS A POTENTIAL ANTIDIABETIC PROBE

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (07) ◽  
pp. 7-18
Author(s):  
Neeraj Bainsal ◽  
Jitender Singh ◽  
Aman Thakur
Keyword(s):  
Molecular Docking ◽  
Reductase Inhibitor ◽  
Aldose Reductase Inhibitor ◽  
The Body ◽  
Pharmacophore Modelling ◽  
Benzothiazole Derivatives ◽  
Sar Studies ◽  
Structure Activity ◽  
Computer Aided ◽  
Drug Designing

Development of drugs against diabetes has always remained a big challenge among the medicinal chemists around the globe because of its continuously increasing prevalence worldwide. The emergence of benzothiazole as a prominent lead against diabetes is credited to the development of the aldose reductase inhibitor, Zopolrestat. Since then, there has been a continuous effort to develop benzothiazole derivatives as potential antidiabetic probes, especially in the last two decades. Use of computer aided drug designing tools such as molecular docking and pharmacophore modelling have also played a crucial role in the exploration of efficacy of benzothiazole against other targets for diabetes. In this review, possible targets for benzothiazole against diabetes will be discussed with the brief role each target plays in maintaining the normal blood glucose level in the body. A trend analysis of the emergence of different inhibitors over various intervals of time along with the structure-activity relationship (SAR) studies of benzothiazole as antidiabetic probe is incorporated in the end of the study.

scholarly journals COMPUTER-ASSISTED DRUG DESIGNING OF TRIAZOLE DERIVATIVE OF NOSCAPINE AS TUBULIN-BINDING ANTICANCER DRUG

2018 ◽  
Vol 11 (14) ◽  
pp. 69 ◽  
Author(s):  
Puja Kumari ◽  
Vineeta Dixit ◽  
Atul Kumar Tiwari ◽  
Saurabh Saxena ◽  
Naveen Kumar Vishvakarma ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Human Cancer ◽  
Binding Free Energy ◽  
Computer Assisted ◽  
Anticancer Compounds ◽  
Generalized Born ◽  
Linear Interaction ◽  
Chemotherapy Drugs ◽  
Tubulin Binding ◽  
Drug Designing

Objective: Microtubule-interfering drugs are commonly used to treat malignant disorders owing to indispensable role of this cytoskeletal element. These drugs include paclitaxel, docetaxel, and the Vinca alkaloids; however, owing to their non-selective action and overpolymerizing effects, these chemotherapy drugs are confounded by complications with serious toxicity (particularly, peripheral neuropathies, gastrointestinal toxicity, myelosuppression, and immunosuppression) (by taxanes) or depolymerizing effects (by Vincas) on microtubules. Thus, there is urgent need to explore novel tubulin-binding agents that are significantly effective and comparatively less toxic compared to currently available drugs for the treatment of human cancer. The current study focuses fusion of two novel anticancer compounds with low toxicity, i.e., noscapine and triazole to generate a new ligand derivative.Methods: Using computer-aided drug designing approach and molecular docking, molecular interaction of these derivatives with αβ-tubulin heterodimer was confirmed and investigated by molecular docking along with dynamics simulation.Results: A greater affinity of the newly designed ligands for binding to tubulin was predicted. The predictive binding free energy (Gbind,pred) of these derivatives (ranging from −10.5178 to −16.8473 kcal/mol) based on linear interaction energy method with a surface generalized born continuum salvation model showed improved binding affinity with tubulin as compared to the lead compound. natural α-Noscapine (−5.505 kcal/mol). The binding energy of ligand determined using LigX, i.e., MM/GBVI was found to be −23.208 kcal/mol.Conclusion: We found that designed derivative compounds have better efficacy as compared noscapine and triazole.

Genetics and Epidemiology of Multiple Sclerosis

2016 ◽  
Author(s):  
Gabriele C. Deluca ◽  
Richard L. Yates ◽  
A. Dessa Sadovnick
Keyword(s):  
Risk Factors ◽  
Multiple Sclerosis ◽  
Genetic Factors ◽  
Demyelinating Disease ◽  
Disease Risk ◽  
Multiple Sclerosis Pathogenesis ◽  
Multiple Sclerosis Disease ◽  
The Central Nervous System ◽  
Epidemiologic Features ◽  
Shed Light

Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system. Despite decades of research, its etiology remains unknown. It has been established that environmental and genetic factors contribute to multiple sclerosis disease risk. Although the identification of risk factors for multiple sclerosis has not yet radically advanced understanding of the pathophysiology, it has shed light on the complex epidemiology of this disease. This chapter highlights key epidemiologic features of multiple sclerosis, with a focus on environmental and genetic factors known to influence disease risk. The interplay between environmental and genetic factors in multiple sclerosis pathogenesis is discussed.

scholarly journals Identification and Clinical Validation of Key Extracellular Proteins as the Potential Biomarkers in Relapsing-Remitting Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Meng Li ◽  
Hongping Chen ◽  
Pengqi Yin ◽  
Jihe Song ◽  
Fangchao Jiang ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Progression Free Survival ◽  
Extracellular Proteins ◽  
The Body ◽  
Clinical Samples ◽  
Ppi Network ◽  
Diagnosis And Prognosis ◽  
Potential Biomarker ◽  
Potential Biomarkers

BackgroundMultiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) mediated by autoimmunity. No objective clinical indicators are available for the diagnosis and prognosis of MS. Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers. Our work will contribute to the in-depth study of the functions of extracellular proteins and the discovery of disease biomarkers.MethodsMS expression profiling data of the human brain was downloaded from the Gene Expression Omnibus (GEO). Extracellular protein-differentially expressed genes (EP-DEGs) were screened by protein annotation databases. GO and KEGG were used to analyze the function and pathway of EP-DEGs. STRING, Cytoscape, MCODE and Cytohubba were used to construct a protein-protein interaction (PPI) network and screen key EP-DEGs. Key EP-DEGs levels were detected in the CSF of MS patients. ROC curve and survival analysis were used to evaluate the diagnostic and prognostic ability of key EP-DEGs.ResultsWe screened 133 EP-DEGs from DEGs. EP-DEGs were enriched in the collagen-containing extracellular matrix, signaling receptor activator activity, immune-related pathways, and PI3K-Akt signaling pathway. The PPI network of EP-DEGs had 85 nodes and 185 edges. We identified 4 key extracellular proteins IL17A, IL2, CD44, IGF1, and 16 extracellular proteins that interacted with IL17A. We clinically verified that IL17A levels decreased, but Del-1 and resolvinD1 levels increased. The diagnostic accuracy of Del-1 (AUC: 0.947) was superior to that of IgG (AUC: 0.740) with a sensitivity of 82.4% and a specificity of 100%. High Del-1 levels were significantly associated with better relapse-free and progression-free survival.ConclusionIL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS. We used bioinformatics methods to explore the biomarkers of MS and validated the results in clinical samples. The study provides a theoretical and experimental basis for revealing the pathogenesis of MS and improving the diagnosis and prognosis of MS.

Metabolomics in multiple sclerosis disease course and progression

2020 ◽  
Vol 26 (5) ◽  
pp. 591-598 ◽  
Author(s):  
Pavan Bhargava ◽  
Daniel C. Anthony
Keyword(s):  
Multiple Sclerosis ◽  
Metabolic Pathways ◽  
Demyelinating Disease ◽  
Metabolomics Data ◽  
Multiple Sclerosis Disease ◽  
Stage Disease ◽  
Different Types ◽  
Appropriate Therapy ◽  
Insight Into ◽  
Other Neurological Disease

Multiple sclerosis (MS) is associated with changes in the metabolome. Numerous studies employing varying metabolomics platforms have examined a range of biological material ranging from brain tissue to urine and demonstrated consistently alterations in multiple metabolic pathways in MS. We review not only the studies that describe the ability of metabolomics to differentiate MS patients from healthy controls and other neurological disease but also discuss the potential of metabolomics-based methods to build predictive models that are able to stage disease, monitor progression, and select the most appropriate therapy. The increasing number of impressive claims for the capacity of metabolomics to distinguish between different types of demyelinating disease suggests that the provision of such tests may be close at hand. Besides the ability to provide potential diagnostic and prognostic biomarkers, metabolomics also provides us with unique insights into the pathophysiology of the disease and helps identify metabolic pathways that may be potential therapeutic targets. Future studies will integrate metabolomics data with other omics techniques to provide further insight into the source of these metabolic abnormalities and help with identification of the most promising targets for therapeutic intervention.

Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis

2020 ◽  
Vol 19 (6) ◽  
pp. 376-385
Author(s):  
Md. A. Islam ◽  
Shoumik Kundu ◽  
Rosline Hassan
Keyword(s):  
Multiple Sclerosis ◽  
Gene Therapy ◽  
Disease Progression ◽  
Demyelinating Disease ◽  
Human Subjects ◽  
Mice Model ◽  
Focal Lesions ◽  
Protective Function ◽  
Monocytes And Macrophages ◽  
Specific Symptoms

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.

Molecular Docking Study for Analyzing the Inhibitory Effect of Anti-inflammatory Plant Compound Against Tumour Necrosis Factor (TNF-α)

2019 ◽  
Vol 14 (1) ◽  
pp. 85-90
Author(s):  
Sagarika Biswas
Keyword(s):  
Molecular Docking ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Docking Study ◽  
Developed Countries ◽  
Inhibitory Effect ◽  
Molecular Docking Study ◽  
Drug Designing ◽  
Anti Inflammatory ◽  
Necrosis Factor

Background: Rheumatoid Arthritis (RA) is an autoimmune disorder of symmetric synovial joints which is characterized by the chronic inflammation with 0.5-1% prevalence in developed countries. Presence of persistent inflammation is attributed to the major contribution of key inflammatory cytokine and tumour necrosis factor- alpha (TNF- &#945;). Recent drug designing studies are developing TNF-&#945; blockers to provide relief from the symptoms of the disease such as pain and inflammation. Available blockers are showing certain limitations such as it may enhance the rate of tuberculosis (TB) occurrence, lymphoma risk, cost issues and certain infections are major concern. Discussed limitations implicated a need of development of some alternative drugs which exhibit fewer side effects with low cost. Therefore, we have identified anti-inflammatory compounds in an underutilized fruit of Baccaurea sapida (B.sapida) in our previous studies. Among them quercetin have been identified as the most potent lead compound for drug designing studies of RA. </P><P> Methods: In the present article, characterization of quercetin has been carried out to check its drug likeliness and molecular docking study has been carried out between TNF- &#945; and quercetin by using AutoDock 4.2.1 software. Further, inhibitory effect of B. sapida fruit extract on RA plasma has been analysed through immunological assay ELISA. </P><P> Results: Our in-silico analysis indicated that quercetin showed non carcinogenic reaction in animal model and it may also cross the membrane barrier easily. We have studied the ten different binding poses and best binding pose of TNF-&#945; and quercetin showed -6.3 kcal/mol minimum binding energy and 23.94 &#181;M inhibitory constant. In addition to this, ELISA indicated 2.2 down regulated expression of TNF-&#945; in RA compared to control. </P><P> Conclusion: This study may further be utilized for the drug designing studies to reduce TNF-&#945; mediated inflammation in near future. This attempt may also enhance the utilization of this plant worldwide.

Sign in / Sign up

Export Citation Format

Share Document