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Adenyl cyclase activator forskolin protects against Huntington's disease-like neurodegenerative disorders

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Neural Regeneration Research 2017年第2期12卷 290-300页

作者： sidharth Mehan Shaba Parveen Sanjeev Kalra Department of Pharamcology Rajendra Institute of Technology & Sciences Sirsa Haryana India

Long term suppression of succinate dehydrogenase by selective inhibitor 3-nitropropionic acid has been used in rodents to model Huntington＇s disease where mitochondrial dysfunction and oxidative damages are primary pathological hallmarks for neuronal damage. Improvements in learning and memory abilities, recovery of energy levels, and reduction of excitotoxicity damage can be achieved through activation of Adenyl cyclase enzyme by a specific phytochemical forskolin. In this study, intraperitoneal administration of 10 mg/kg 3-nitropropionic acid for 15 days in rats notably reduced body weight, worsened motor cocordination（grip strength, beam crossing task, locomotor activity）, resulted in learning and memory deficits, greatly increased acetylcholinesterase, lactate dehydrogenase, nitrite, and malondialdehyde levels, obviously decreased adenosine triphosphate, succinate dehydrogenase, superoxide dismutase, catalase, and reduced glutathione levels in the striatum, cortex and hippocampus. Intragastric administration of forskolin at 10, 20, 30 mg/kg dose-dependently reversed these behavioral, biochemical and pathological changes caused by 3-nitropropionic acid. These results suggest that forskolin exhibits neuroprotective effects on 3-nitropropionic acid-induced Huntington＇s disease-like neurodegeneration.

关键词： nerve regeneration Huntington's disease mitochondria adenyl cyclase forskolin oxidative stress basal ganglia neural regeneration

Fluorescent Superlattices of Gold Nanoparticles:A New Class of Functional Materials

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Nano Research 2009年第3期2卷 220-234页

作者： Edakkattuparambil sidharth Shibu Madathumpady Abubaker Habeeb Muhammed Keisaku Kimura Thalappil Pradeep DST Unit on Nanoscience(DST UNS) Department of Chemistry and Sophisticated Analytical Instrument FacilityIndian Institute of TechnologyMadrasChennai 600036India Graduate School of Material Science University of Hyogo3-2-1 KotoKamigori-choAko-gun Hyogo 678-1297Japan

Fluorescent three-dimensional(3-D)superlattices of dansyl glutathione protected gold nanoparticles,with potential applications in molecular detection,have been synthesized at an air/water interface by controlling the pH of the nanoparticle *** number of fluorophores per nanoparticle was calculated to be~*** of the superlattice crystals were examined using scanning electron microscopy(SEM).Most of the crystals observed were triangular in ***-resolution transmission electron microscopy(HRTEM)and small angle X-ray scattering(SAXS)were used to study the packing of nanoparticles in these *** these studies showed that the nanoparticles were arranged in a face-centered cubic(fcc)pattern with a particle-particle distance(center-center)of~10.5 *** of the crystal morphologies with time was also *** fluorescence properties of these triangles were studied using confocal fluorescence imaging and confocal Raman mapping,which were in good agreement with the morphologies observed by *** superlattice exhibits near-infrared(NIR)absorption in the range 1100-2500 *** synthesis of such functional nanoparticle-based solids makes it possible to use them in novel *** utilized the fluorescence of dansyl glutathione gold superlattice crystals for the selective detection of bovine serum albumin(BSA),the major protein constituent of blood plasma,based on the selective binding of the naphthalene ring of the dansyl moiety with site I of BSA.

关键词： Periodic self-assembly dansyl glutathione fluorescent superlattice confocal fluorescence imaging selective binding

Vitreoretinal surgical training-assessment of simulation,models,and rubrics-a narrative review

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Annals of Eye Science 2022年第2期7卷 74-79页

作者： sidharth Puri Mitul C.Mehta University of California Irvine IrvineCAUSA

Background and Objective:Vitreoretinal surgery requires fine micro-surgical training and handling of delicate *** aid in the training of residents and fellows,unique educational modalities exist to help facilitate the development of these microsurgical *** virtual simulators to artificial eye models,simulation of the posterior segment has gained an increased focus in vitreoretinal surgical training *** of surgical curricula for vitreoretinal training and attainment of surgical milestones has been a key component in integrating these educational training *** will explore various simulators,eye models,and potential rubrics and discuss unique ways each may help and complement one another to train future vitreoretinal ***:We conducted a systematic PubMed search of various review studies(from publications in English ranging from January 1978 to December 2020)discussing surgical simulators,eye models,and surgical rubrics for vitreoretinal surgery and their potential impacts upon *** Contents and Findings:Our review assesses the benefits and applicability of various simulators,eye models,and surgical rubrics upon ***:Utilization of vitreoretinal surgical training tools may aid in complementing the hands-on surgical training experience for vitreoretinal surgical *** using simulators and rubrics,we may better be able to standardize training for reaching vitreoretinal surgical milestones and providing adequate feedback to improve surgical competency and ultimately patient outcomes.

关键词： Vitreoretinal surgery retina virtual simulator eye model rubrics

Neuroprotective Effect of Chrysophanol as a PI3K/AKT/mTOR Signaling Inhibitor in an Experimental Model of Autologous Blood-induced Intracerebral Hemorrhage

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Current Medical Science 2022年第2期42卷 249-266页

作者： Kuldeep Singh JADAUN sidharth MEHAN Aarti SHARMA Ehraz Mehmood SIDDIQUI Sumit KUMAR NaifALSUHAYMI Neuropharmacology Division Department of PharmacologyISF College of PharmacyMogaPunjab142001India Department of Emergency Medical Services Faculty of Health Sciences-AlQunfudahUmm Al-Qura UniversityMekkahSaudi Arabia

Objective Intracerebral hemorrhage(ICH)refers to predominant,sporadic,and non-traumatic bleeding in the brain *** PI3K/AKT/mTOR signaling pathway is an important signal transduction pathway regulated by enzyme-linked receptors and has many biological functions in *** plays a key role in neuronal metabolism,gene expression regulation,and tissue homeostasis in the healthy and diseased *** In the present study,the role of the PI3K/AKT/mTOR pathway inhibitor chrysophanol(CPH)(10 mg/kg and 20 mg/kg,orally)in the improvement of ICH-associated neurological defects in rats was *** blood(20µL/5 min/unilateral/intracerebroventricular)mimics ICH-like defects involving cellular and molecular dysfunction and neurotransmitter *** current study also included various behavioral assessments to examine cognition,memory,and motor and neuromuscular *** protein expression levels of PI3K,AKT,and mTOR as well as myelin basic protein and apoptotic markers,such as Bax,Bcl-2,and caspase-3,were examined using ELISA ***,the levels of various neuroinflammatory cytokines and oxidative stress markers were ***,the neurological severity score,brain water content,gross brain pathology,and hematoma size were used to indicate neurological function and brain *** CPH was found to be neuroprotective by restoring neurobehavioral alterations and significantly reducing the elevated PI3K,AKT,and mTOR protein levels,and modulating the apoptotic markers such as Bax,Bcl-2,and caspase-3 in rat brain *** substantially reduced the inflammatory cytokines like interleukin(IL)-1β,IL-6,and tumor necrosis factor-α.CPH administration restored the neurotransmitters GABA,glutamate,acetylcholine,dopamine,and various oxidative stress *** Our results show that CPH may be a promising therapeutic approach for overcoming neuronal damage caused by the overexpression of the PI3K/AKT/mTOR signal

关键词： intracerebral hemorrhage autologous blood PI3K/AKT/mTOR hematoma chrysophanol apoptosis neurotransmitter neuroinflammation

Exclusive endoscopic transcanal approach to lateral skull base lesions:Institutional experience of 3 cases

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Journal of Otology 2021年第1期16卷 55-60页

作者： sidharth Pradhan Preetam Chappity Anindya Nayak Pradeep Pradhan Pradipta K.Parida All India Institute of Medical Sciences Bhubaneswar Department of Otorhinolaryngology and Head&Neck Surgery1 st floorAIIMSBhubaneswarSijuaBhubaneswarOdisha751019India

Introduction:Majority of petrous bone and lateral skull base pathologies are benign in *** complex anatomy usually warrants an extensive approach with associated *** summary:Two cases of petrous bone cholesteatoma(1 congenital cholesteatoma with facial palsy and 1 acquired cholesteatoma)and a case of glomus tympanicum were treated with exclusive endoscopic transcanal *** cases of petrous cholesteatoma were addressed with trans-promontorial and infra-cochlear *** mean operative time was approximately 140 *** CSF otorrhoea was noticed in the post-operative *** average period of hospital stay was 3.7 ***:In the subset of cases with limited benign disease an endoscopic trans-canal approach is a better alternative to an external *** decreases operative time,blood loss,chance of meningitis,morbidity and hospital *** lack of depth perception is a major hurdle which can be come over by experience in endoscopic middle ear *** approach can create direct access to cochlea/petrous apex/internal auditory canal(IAC)/Supra-geniculate ganglion region.

关键词： Transcanal endoscopic approach Petrous cholesteatoma Glomus tympanicum Lateral skull base

Anti-cancer drugs targeting using nanocarrier niosomes-a review

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TMR Cancer 2020年第4期3卷 169-174页

作者： sidharth Mehta Guru Jambheshwar University of Science and Technology Hisar 125001India

In the last few decades numbers of review and research articles have been published on niosomes. This shows the relevant interest of academias & researchers in niosomes because of the advantages sponsored by them over other colloidal drug delivery systems. Niosomes formation occurs when non-ionic surfactant vesicles assemble themselves. Various antineoplastic agents are used in chemotherapy, but they have some drawbacks that these agents cause cell death in normal tissues as well. There are two approaches to overcome this limitation. First, to modify the structure of existing drugs, but this will not possible because it changes the properties of drugs. Second, the development of nano-carriers like liposomes, dendrimers, nanoparticles, niosomes et al. Among all, niosomes (non-ionic surfactant vesicles) have more advantages besides all nano-carriers. Drugs either hydrophilic in nature or hydrophobic in nature, both can be incorporated in niosomes. And by embedding specific ligands over vesicular surface enables us to target the drug to specific cancer cells.

关键词： Nanocarriers Niosomes Anticancer drugs Targeted drug delivery Non-ionic surfactants vesicles Anti neoplastic agents

Jet modification in absence of QGP-medium:the role of multiparton interactions and color reconnection

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Chinese Physics C 2024年第1期48卷 50-60页

作者： Prottoy Das Abhi Modak Debjani Banerjee Rathijit Biswas Supriya Das Sanjay KGhosh Sibaji Raha sidharth Kumar Prasad Department of Physics Bose InstituteKolkata 700091India Quark Matter Research Center Institute of Modern PhysicsChinese Academy of SciencesLanzhou 730000China

Recent studies on high-multiplicity events in small collision systems(proton-proton and proton-lead)have drawn considerable research interest toward the possibility of the formation of partonic medium in such *** of the important consequences of the formation of dense partonic medium is the quenching of high-momentum final-state particles,resulting in several experimental observations such as suppression in nuclear modification factor RAA,modification of jet shape observableρ(r)and jet fragmentation(z^(ch))distributions,*** this work,we studyρ(r)and z^(ch)for inclusive charged-particle jets in proton-proton(pp)collisions at√s=13 TeV using the PYTHIA 8 Monash 2013 Monte Carlo *** show that the color reconnection(CR)and multiparton interaction(MPI)mechanisms in PYTHIA 8 can lead to an increased rate of jet *** also find that the mechanisms of MPI and CR and change in the gluonic contribution in high-multiplicity events result in significant modification ofρ(r)and z^(ch)compared to those in minimum bias events for 10and gluonic contribution with the amount of modification inρ(r):the larger the number of MPIs and/or gluonic contribution,the larger the amount of modification ofρ(r).

关键词： jet modification PYTHIA multiparton interaction color reconnection gluonic contribution high-multiplicity

Assessment of Relationship of Some Causal Factors Associated with Productivity of Longwall Mining Using Structured Equation Modeling

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Journal of Minerals and Materials Characterization and Engineering 2021年第4期9卷 375-389页

作者： sidharth Talan Ashis Bhattacherjee Trafigura Mumbai India Mining Engineering Department Indian Institute of Technology Kharagpur India

Enhancement of productivity optimization is steadily gaining the priority in mining companies especially in the underground coal mining industry which faces a daunting task to balance marginal profit generation with a comparatively high cost of production, volatile market price and rapid grade variation. This paper is aimed to analyze some of the causal factors both technical and site specific which are directly or indirectly impacting the productivity of the longwall coal mining system such as downtime of equipment system in longwall panel, overloading of conveyors and bin, preventive maintenance, gas management practices and injury severity rate. Structured Equation Modelling (SEM) was used to study the causal relationships between the above-mentioned factors and mine productivity. The equipment considered for analysis included shearer, armored face conveyor, crusher, bridge stage loader, chock supports, main gate drive, gate conveyor, hydraulic pumps and crusher. SEM was applied to relate the correlations existing among these causal variables in order to assess their direct or indirect impact on mining productivity. Based on the data extracted over a period of 10 months which included the extraction of 2 longwall panels, the study revealed a significant negative causal relationship between injury severity rate (p < 0.01) and equipment downtime (p = 0.001), with mine productivity. However, preventive maintenance delay time, gas management delay time and conveyor overloading delay time were found to have an insignificant direct influence on mine productivity but indirectly modify it through a significant mediator relationship with equipment downtime. This information would assist mine management to take proper preventive measures.

关键词： Structured Equation Modelling Longwall Mining Operational Equipment Productivity

Adenylate cyclase activator forskolin alleviates intracerebroventricular propionic acid-induced mitochondrial dysfunction of autistic rats

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Neural Regeneration Research 2020年第6期15卷 1140-1149页

作者： sidharth Mehan Saloni Rahi Aarti Tiwari Tarun Kapoor Kajal Rajdev Ramit Sharma Himanshi Khera Sourabh Kosey Umesh Kukkar Rajesh Dudi Department of Neuropharmacology ISF College of PharmacyMogaPunjabIndia Department of Pharmacology Rajendra Institute of Technology&SciencesSirsaHaryanaIndia Pharmacology Division CSIR-Indian Institute of Integrative MedicineJammuIndia

Neuronal mitochondrial dysfunction increases inflammatory mediators and leads to free radical generation and anti-oxidant enzymatic alterations,which are major neuropathological hallmarks responsible for *** dysfunction in autism is associated with decreased ATP levels due to reduced levels of cyclic adenosine *** models of autism were established by intracerebroventricular injection of propionic *** rat models had memory dysfunction,decreased muscle coordination and gait *** estimation of propionic acid-treated rats showed changes in enzyme activity in neuronal mitochondrial electron transport chain complexes and increases in pro-inflammatory cytokines,oxidative stress and lipid *** administration of 10,20 and 30 mg/kg adenylate cyclase activator forskolin for 15 days reversed these changes in a dose-dependent *** findings suggest that forskolin can alleviate neuronal mitochondrial dysfunction and improve neurological symptoms of rats with *** study was approved by the RITS/IAEC,SIRSA,HARYANA on March 3,2014(approval ***/IAEC/2014/03/03).

关键词： adenylate cyclase ATP autism forskolin mitochondrial dysfunction neuroinflammation oxidative stress propionic acid