Coenzyme Q10: a progress towards the treatment of neurodegenerative disease

Peeyush kumar,Pramod kumar,Alpana ram,Mithilesh kumar,Rajeev kumar 경희대학교 융합한의과학연구소 2010 Oriental Pharmacy and Experimental Medicine Vol.10 No.4

Coenzyme Q10 (CoQ10, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of CoQ10 in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in CoQ10 status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of CoQ10 biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of CoQ10 status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. CoQ10 and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, Friedreich’s ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of CoQ10, as well as the rationale and the role in clinical practice of CoQ10 supplementation in different neurological diseases, from primary CoQ10 deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

Prediction of phishing websites using machine learning

Mithilesh Kumar Pandey,Munindra Kumar Singh,Saurabh Pal,B. B. Tiwari 대한공간정보학회 2023 Spatial Information Research Vol.31 No.2

With the growing popularity of the information science, more application is being integrated with websites that can be accessed directly through the internet. This has increased the possibility of attack by ill-legal persons to steal personal information. To identify a phishing assault, several strategies have been presented. However, there is still opportunity for progress in the fight against phishing. The objective of this research paper is to develop a more accurate prediction model using Decision Tree (DT), Random Forest (RF) and Gradient Boosting Classifiers (GBC) with three features selection techniques Extra Tree (ET), Chi-Square and Recursive Feature Elimination (RFE). Since phishing websites dataset contains 89 features, therefore we have applied extra tree and chi-square, feature selection method to identify the limited important features and then recursive features elimination technique has been used to reduce the dataset up-to optimum important features. We have compared the performance of the developed model using machine learning algorithms and find the best prediction performance using GBC, followed by RF and DT. These algorithmic models capture the trends from various cases of phishing with over R-square, Root Mean Square Error (RMSE), and Mean Absolute Error (MAE), in each case.

Multiscale Modelling of 3D Orthogonal Woven Composite under Ballistic Impact Using FEM

Mithilesh Kumar Dewangan,S. K. Panigrahi 한국섬유공학회 2020 Fibers and polymers Vol.21 No.10

The present paper deals with the multi-scale modelling and finite element analysis of Kevlar/Epoxy 3DOrthogonal woven composite (3DOWC) subjected to ballistic impact by a conical-cylindrical steel projectile. These aredesigned by utilising a Micro-Meso-Macro transition approach called Macro Homogeneous-Meso heterogeneous modellingtechnique. The Micro-Meso-Macro transition approach has been implemented in this research to develop the complex weavearchitecture of the target plate, and, a voxel-based non-conformal mesh has been used to understand the behaviour ofRepresentative Volume Element (RVE). The model is validated by using 2D weave architecture which has been analysed forconical 90 º projectile made up of 7.62 calibre. The damage properties are implemented using a user-defined function in theexplicit analysis VUMAT. The Macro homogeneous results provide the velocity variation and energy absorption of theprojectile with respect to the time history. Also, the energy absorption by its constituents are presented here, and substantialvalidation of results have been observed with the available literature.

Electroosmotic flow of biorheological micropolar fluids through microfluidic channels

Mithilesh Kumar Chaube,Ashu Yadav,Dharmendra Tripathi,O. Anwar Bég 한국유변학회 2018 Korea-Australia rheology journal Vol.30 No.2

An analytical analysis is presented in this work to assess the influence of micropolar nature of fluids in fully developed flow induced by electrokinetically driven peristaltic pumping through a parallel plate microchannel. The walls of the channel are assumed as sinusoidal wavy to analyze the peristaltic flow nature. We consider that the wavelength of the wall motion is much larger as compared to the channel width to validate the lubrication theory. To simplify the Poisson Boltzmann equation, we also use the Debye-Hückel linearization. We consider governing equation for micropolar fluid in absence of body force and couple effects however external electric field is employed. The solutions for axial velocity, spin velocity, flow rate, pressure rise, and stream functions subjected to given physical boundary conditions are computed. The effects of pertinent parameters like Debye length and Helmholtz-Smoluchowski velocity which characterize the EDL phenomenon and external electric field, coupling number and micropolar parameter which characterize the micropolar fluid behavior, on peristaltic pumping are discussed through the illustrations. The results show that peristaltic pumping may alter by applying external electric fields. This model can be used to design and engineer the peristalsis-lab-on-chip and micro peristaltic syringe pumps for biomedical applications.

Pyruvate Dehydrogenase Kinase as a Potential Therapeutic Target for Malignant Gliomas

( Mithilesh Kumar Jha ),( Kyoungho Suk ) 대한뇌종양학회·대한신경종양학회·대한소아뇌종양학회 2013 Brain Tumor Research and Treatment Vol.1 No.2

Metabolic aberrations in the form of altered flux through key metabolic pathways are the major hallmarks of several life-threatening malignancies including malignant gliomas. These adaptations play an important role in the enhancement of the survival and proliferation of gliomas at the expense of the surrounding normal/healthy tissues. Recent studies in the field of neurooncology have directly targeted the altered metabolic pathways of malignant tumor cells for the development of anti-cancer drugs. Aerobic glycolysis due to elevated production of lactate from pyruvate regardless of oxygen availability is a common metabolic alteration in most malignancies. Aerobic glycolysis offers survival advantages in addition to generating substrates such as fatty acids, amino acids and nucleotides required for the rapid proliferation of cells. This review outlines the role of pyruvate dehydrogenase kinase (PDK) in gliomas as an inhibitor of pyruvate dehydrogenase that catalyzes the oxidative decarboxylation of pyruvate. An in-depth investigation on the key metabolic enzyme PDK may provide a novel therapeutic approach for the treatment of malignant gliomas.

FEA of Plain Woven Kevlar/Epoxy Composites Subjected to Normal and Oblique Impact with Multi-Scale Modelling

Mithilesh Kumar Dewangan,S. K. Panigrahi 한국섬유공학회 2020 Fibers and polymers Vol.21 No.12

High-performance Kevlar/epoxy plain woven composites are subjected to normal and oblique impact by a conicalcylindricalprojectile. A multiscale modelling method which incorporates Micro-Meso-Macro transition approach isimplemented to study the ballistic impact phenomena. This Macro Homogeneous-Meso heterogeneous modelling techniquehas been executed in this examination to develop the intricate weave design of the objective plate. A voxel-based nonconformalwork has been utilized to comprehend the behavior of Representative Volume Element (RVE). The damageproperties are implemented utilizing a user-defined function for the explicit analysis. The model is approved with theavailable literary works for Kevlar and carbon composites to feature the thorough inclusion of the technique. The model isconsidered for different oblique angles (0 °, 30 °, 45 °, 60 °) and its effects on energy absorption, damage mechanism andresidual velocity are observed.

Metabolic Control of Glia-Mediated Neuroinflammation

Kumar Jha, Mithilesh,Ho Park, Dong,Kook, Hyun,Lee, In-Kyu,Lee, Won-Ha,Suk, Kyoungho Bentham Science 2016 Current Alzheimer research Vol.13 No.4

<P>The central nervous system (CNS) shows dynamic immune and inflammatory responses to a variety of insults having crucial implications for reactive gliosis. Glial cells in the CNS serve not only as the source, but also as targets of proinflammatory mediators. Undoubtedly, these cells efficiently work towards the disposal of tissue debris and promotion of wound healing as well as tissue repair. However, these non-neuronal glial cells synthesize and release numerous inflammatory mediators, which can be detrimental to neurons, axons, myelin, and the glia themselves. While an acute insult is typically transient and unlikely to be detrimental to neuronal survival, chronic neuroinflammation is a long-standing and often self-perpetuating response, which persists even long after the initial injury or insult. It can serve as a point of origin for diverse neurological disorders including Alzheimer's disease. Accumulating evidence demonstrates the contribution of metabolic dysfunction and mitochondrial failure to the pathogenesis of neuroinflammatory and neurodegenerative diseases. Neurodegenerative conditions are also characterized by increased oxidative and endoplasmic reticulum stresses and autophagy defects. Furthermore, neuroinflammatory conditions are accompanied by an alteration in glial energy metabolism. Here, we comprehensively review the metabolic hallmarks of glia-mediated neuroinflammation and how the glial metabolic shift orchestrates the neuroinflammatory response and pathophysiology of diverse neurological disorders.</P>

Acute Phase Protein Lipocalin-2 Is Associated with Formalin-induced Nociception and Pathological Pain

Mithilesh Kumar Jha,Sangmin Jeon,Myungwon Jin,이원하,석경호 대한면역학회 2013 Immune Network Vol.13 No.6

Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/ biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.

Coenzyme Q₁₀: a progress towards the treatment of neurodegenerative disease

Kumar, Peeyush,Kumar, Pramod,Ram, Alpana,Kuma, Mithilesh,Kumar, Rajeev Kyung Hee Oriental Medicine Research Center 2010 Oriental pharmacy and experimental medicine Vol.10 No.4

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

Residual stress analysis of swage autofrettaged gun barrel via finite element method

Mithilesh Kumar Dewangan,S. K. Panigrahi 대한기계학회 2015 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.29 No.7

Residual stress analysis of swage autofrettaged gun barrel is performed in this study via finite element (FE) method. The swage autofrettagetechnique is one of the modernized pre-stressing methods to enhance the load bearing capacity and fatigue life of all gun barrels. An oversized moving mandrel is forced inside the gun barrel, which deforms the material through physical interference. The process isanalyzed by evaluating residual stresses using a commercially available software package. The deformation effects caused by the mandreland the geometrical variation of the mandrel on the gun barrel are analyzed in this study. This field has been insufficiently researched,but the effect of pre-stressing on the barrel, and at the start and mid-length for the swaging process, is not well examined. Thus, furtheranalysis is required. The variations and effectiveness of the designed pressure band model are shown to define the problem easily. Resultsare evaluated at mid-length using a fixed fringe width percentage (A defined percentage of gun barrel axial length). The desired effectsare well validated through numerical investigation using FE analysis. This study reveals that the geometry should be designed very thoroughlyto determine the after effects. If too many variations occur, then the initial force requirement is extremely high; otherwise, thedesired swaging effect cannot be achieved.