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Potential therapeutic roles of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease

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Neural Regeneration Research 2019年第11期14卷 1880-1892页

作者： Bhask.r C. Das Somsank.r Dasgupta swapan k. ray Department of Medicine Icahn School of Medicine at Mount SinaiNew YorkNYUSA Department of Neuroscience and Regenerative Medicine Institute of Molecular Medicine and GeneticsAugusta UniversityAugustaGAUSA Department of Pathology Microbiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSCUSA

All retinoids, which can be natural and synthetic, are chemically related to vitamin A. Both natural and synthetic retinoids use specific nuclear receptors such as retinoic acid receptors and retinoid X receptors to activate specific signaling pathways in the cells. Retinoic acid signaling is extremely important in the central nervous system. Impairment of retinoic acid signaling pathways causes severe pathological processes in the central nervous system, especially in the adult brain. Retinoids have major roles in neural patterning, differentiation, axon outgrowth in normal development, and function of the brain. Impaired retinoic acid signaling results in neuroinflammation, oxidative stress, mitochondrial malfunction, and neurodegeneration leading to progressive Alzheimer’s disease, which is pathologically characterized by extra-neuronal accumulation of amyloid plaques(aggregated amyloid-beta) and intra-neurofibrillary tangles(hyperphosphorylated tau protein) in the temporal lobe of the brain. Alzheimer’s disease is the most common cause of dementia and loss of memory in old adults. Inactive cholinergic neurotransmission is responsible for cognitive deficits in Alzheimer’s disease patients. Deficiency or deprivation of retinoic acid in mice is associated with loss of spatial learning and memory. Retinoids inhibit expression of chemok.nes and neuroinflammatory cytok.nes in microglia and astrocytes, which are activated in Alzheimer’s disease. Stimulation of retinoic acid receptors and retinoid X receptors slows down accumulation of amyloids, reduces neurodegeneration, and thereby prevents pathogenesis of Alzheimer’s disease in mice. In this review, we described chemistry and biochemistry of some natural and synthetic retinoids and potentials of retinoids for prevention of neuroinflammation and neurodegeneration in Alzheimer’s disease.

关键词： Alzheimer's disease amyloid plaques neurofibrillary tangles neuroinflammation neurodegeneration retinoids

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Future directions for using estrogen receptor agonists in the treatment of acute and chronic spinal cord injury

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Neural Regeneration Research 2016年第9期11卷 1418-1419页

作者： swapan k. ray Supriti Samntaray Naren L. Banik Department of Pathology Microbiology and Immunology University of South Carolina School of Medicine Columbia SC USA Department of Neurosciences Medical University of South Carolina Charleston SC USA Department of Neurology and Neurosurgery Medical University of South Carolina Charleston SC USA Ralph H. Johnson Veterans Administration Medical Center Charleston SC USA

All synthetic and natural estrogen receptor agonists, in- cluding the most potent physiological molecule estrogen or estradiol （E2）, work.typically via activation of nuclear estrogen receptor alpha （ERα） and estrogen receptor beta （ERβ）. Both ERα and ERβ modulate the expression of a variety of genes in the cells. Neurons and glial cells express ERa and ERβ. Many studies so far from our and other laboratories have firmly established the mode of actions that ERα and ERβ agonists are very promising anti-inflammatory and neuroprotective agents in the treatment of neurodegenera- rive diseases and injuries including spinal cord injury （SCI）（Chak.abarti et al., 2014a）.

关键词： Future directions for using estrogen receptor agonists in the treatment of acute and chronic spinal cord injury SCI

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Roles of miRNAs in spinal cord injury and potential therapeutic interventions

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Neuroimmunology and Neuroinflammation 2019年第10期6卷 1-11页

作者： Badria Almurshidi Wayne Carver Geoff Scott swapan k.ray Department of Environmental Health Sciences Arnold School of Public HealthCENRUniversity of South CarolinaColumbiaSC 29209USA Department of Cell Biology and Anatomy School of MedicineUniversity of South CarolinaColumbiaSC 29209USA Department of Pathology Microbiologyand ImmunologySchool of MedicineUniversity of South CarolinaColumbiaSC 29209USA

Spinal cord injury(SCI)affects approximately 200,000 individuals per year *** are more than 27 million people worldwide living with long-term disability due to ***,it was thought that the central nervous system(CNS)had little ability for regeneration;however,more recent studies have demonstrated potential for repair within the *** of this,there exists a renewed interest in the discovery of novel approaches to promote regeneration in the CNS including the spinal *** is important to k.ow the roles of the microRNAs(miRNAs)in modulation of pathogenesis in SCI and the potentials of the miRNA-based clinical interventions for controlling post-injury symptoms and improving functional *** miRNAs,which are non-coding RNAs with an average of 22 nucleotides in length,are post-transcriptional gene regulators that cause degradation of the target mRNAs and thus negatively control their *** review article focuses on current research related to miRNAs and their roles in modulating SCI symptoms,asserting that miRNAs contribute to critical post-SCI molecular processes including neuroplasticity,functional recovery,astrogliosis,neuropathic pain,inflammation,and *** particular,miR-96 provides a promising therapeutic opportunity to improve the outcomes of clinical interventions,including the way SCI injuries are evaluated and treated.

关键词： Spinal cord injury miRNAs astrogliosis neuropathic pain inflammation apoptosis functional recovery

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Economic impact of traumatic spinal cord injuries in the United States

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Neuroimmunology and Neuroinflammation 2019年第7期6卷 1-11页

作者： Christopher H.Merritt Matthew A.Taylor Caleb J.Yelton swapan k.ray Department of Pathology Microbiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSC 29209USA

Individuals having sustained traumatic spinal cord injury(TSCI)in the United States are living longer as compared to historical trends,thank. to an ever-evolving understanding of the nature of this *** this,multiple barriers to care for TSCI patients remain including variations in government-issued veteran insurance,privatized insurance,and among uninsured *** United States alone experiences 12,000 new TSCI cases every year,many of these are found to occur in a growing proportion of elderly *** is crucial to understand both the short-term direct costs as wells as the long-term rehabilitation costs required by these TSCI *** lifetime financial burden for those having sustained a TSCI can be immense for patients,insurance companies,and hospital systems *** those with TSCI,re-hospitalization rates are high,leading to increased healthcare resource utilization within this specific patient *** can quick.y balloon into hundreds of thousands of dollars and cause a profound financial burden for these *** review article seek. to communicate an understanding of the current financial landscape surrounding TSCI *** authors will also examine the costs of acute emergency room surgical care such as American spinal injury association grade,hospital length of stay,as well as the timing delay between injury and surgical ***-term costs associated with TSCI such as rehabilitation,care of secondary comorbidities,and post-injury employment prospects will be examined as *** costs will be framed from the patient's perspective as well as from both the hospital and insurance company's *** is hoped a complete understanding as to what mak.s TSCI such a medically and financially burdensome injury will allow for improved healthcare resource utilization in this population.

关键词： Traumatic spinal cord injury healthcare resource American spinal injury association grade hospital length of stay rehabilitation post-injury employment

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Modulation of autophagy for neuroprotection and functional recovery in traumatic spinal cord injury

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Neural Regeneration Research 2020年第9期15卷 1601-1612页

作者： swapan k.ray Department of Pathology Microbiology and Immunology University of South Carolina School of Medicine

Spinal cord injury(SCI) is a serious central nervous system trauma that leads to loss of motor and sensory functions in the SCI patients. One of the cell death mechanisms is autophagy, which is ‘self-eating' of the damaged and misfolded proteins and nucleic acids, damaged mitochondria, and other impaired organelles for recycling of cellular building block.. Autophagy is different from all other cell death mechanisms in one important aspect that it gives the cells an opportunity to survive or demise depending on the circumstances. Autophagy is a therapeutic target for alleviation of pathogenesis in traumatic SCI. However, functions of autophagy in traumatic SCI remain controversial. Spatial and temporal patterns of activation of autophagy after traumatic SCI have been reported to be contradictory. Formation of autophagosomes following therapeutic activation or inhibition of autophagy flux is ambiguous in traumatic SCI studies. Both beneficial and harmful outcomes due to enhancement autophagy have been reported in traumatic SCI studies in preclinical models. Only further studies will mak. it clear whether therapeutic activation or inhibition of autophagy is beneficial in overall outcomes in preclinical models of traumatic SCI. Therapeutic enhancement of autophagy flux may digest the damaged components of the central nervous system cells for recycling and thereby facilitating functional recovery. Many studies demonstrated activation of autophagy flux and inhibition of apoptosis for neuroprotective effects in traumatic SCI. Therapeutic induction of autophagy in traumatic SCI promotes axonal regeneration, supporting another beneficial role of autophagy in traumatic SCI. In contrast, some other studies demonstrated that disruption of autophagy flux in traumatic SCI strongly correlated with neuronal death at remote location and impaired functional recovery. This article describes our current understanding of roles of autophagy in acute and chronic traumatic SCI, crosstalk

关键词： apoptosis autophagy autophagy modulation neuroprotection traumatic spinal cord injury

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Neuroprotective role of Noggin in spinal cord injury

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Neural Regeneration Research 2023年第3期18卷 492-496页

作者： Nadia Al-Sammarraie Mohammed Mahmood swapan k.ray Department of Pathology Microbiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSCUSA

Spinal cord injury is one of the leading causes of morbidity and mortality among young adults in many countries including the United *** in the regeneration of neurons is one of the main obstacles that leave spinal cord injury patients with permanent paralysis in most *** research has found that preventing acute and subacute secondary cellular damages to the neurons and supporting glial cells can help slow the progression of spinal cord injury pathogenesis,in part by reactivating endogenous regenerative proteins including Noggin that are normally present during spinal cord *** is a complex protein and natural inhibitor of the multifunctional bone morphogenetic proteins,and its expression is high during spinal cord development and after induction of spinal cord *** this review article,we first discuss the change in expression of Noggin during pathogenesis in spinal cord ***,we discuss the current research k.owledge about the neuroprotective role of Noggin in preclinical models of spinal cord ***,we explain the gap in the k.owledge for the use of Noggin in the treatment of spinal cord *** results from extensive in vitro and in vivo research have revealed that the therapeutic efficacy of Noggin treatment remains debatable due to its neuroprotective effects observed only in early phases of spinal cord injury but little to no effect on altering pathogenesis and functional recovery observed in the chronic phase of spinal cord ***,clinical information regarding the role of Noggin in the alleviation of progression of pathogenesis,its therapeutic efficacy,bioavailability,and safety in human spinal cord injury is still lack.ng and therefore needs further investigation.

关键词： apoptosis astrocyte differentiation axon myelination axon regeneration bone morphogenetic protein glial scar heterotrophic ossification neurogenesis neuropathic pain Noggin spinal cord injury

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Analysis of a fuzzy epidemic model with saturated treatment and disease transmission

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International Journal of Biomathematics 2018年第1期11卷 23-40页

作者： swapan k.mar Nandi Soovoojeet Jana Manotosh Manadal T. k. k.r Department of MathematicsNayabasat P. M. Sik.hanik.tan Paschim Medinipur 721253 West Bengal India Department of Mathematics Ramsaday College Amta 711501 West Bengal India Department of Mathematics Tamralipta MahavidyalayaTamluk.721636 West Bengal India Department of MathematicsIndian Institute of Engineering Science and Technology Shibpur Howrah 711103 West Bengal India

In this paper, we describe an SIS epidemic model where both the disease transmission rate and treatment function are considered in saturated forms. The dynamical behavior of the system is analyzed. The system is customized by considering the disease trans- mission rate and treatment control as fuzzy numbers and then fuzzy expected value of the infected individuals is determined. The fuzzy basic reproduction number is investi- gated and a threshold condition of pathogen is derived at which the system undergoes a back.ard bifurcation.

关键词： SIS epidemic model fuzzy expected value fuzzy basic reproduction number back.ard bifurcation.

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Stability Criterion with Less LMI Variables for Linear Discrete-time Systems with Additive Time-delays

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International Journal of Automation and computing 2011年第4期8卷 490-492页

作者： k. Ramak.ishnan G. ray Department of Electrical Engineering Indian Institute of Technology Kharagpur West Bengal 721 302 India

In this correspondence paper, an equivalent stability criterion with minimal number of linear matrix inequality （LMI） variables is presented for a delay-dependent stability criterion reported recently in the International Journal of Automation and Computing for a class of linear discrete-time systems with additive time delays. The reported stability criterion for the additive timedelay systems has more number of matrix variables in the LMI and, hence, demand additional computational burden. The proposed equivalent stability criterion, unlik. the reported one, does not involve free-weighing matrices and encompass only the matrix variables that are associated in the Lyapunov-k.asovsk.i functional, mak.ng the criterion mathematically less complex and computationally more effective.

关键词： Discrete-time systems additive time-delays delay-dependent stability stability criterion linear matrix inequality (LMI).

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Bone morphogenic protein signaling in spinal cord injury

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Neuroimmunology and Neuroinflammation 2021年第1期8卷 53-63页

作者： Nadia Al-Sammarraie swapan k.ray Department of Pathology Microbiologyand ImmunologyUniversity of South Carolina School of MedicineColumbiaSC 29209USA

Spinal cord injury(SCI)is a debilitating injury that results from traumatic or non-traumatic insults to the spinal cord,causing significant impairment of the patient's activity and quality of *** morphogenic proteins(BMPs)are a group of polyfunctional cytok.nes belonging to the transforming growth factor beta superfamily that regulates a wide variety of cellular functions in healthy and disease *** studies suggest that dysregulation of BMP signaling is involved in neuronal demyelination and death after traumatic *** focus of this article is to describe our current understanding of the role of BMP signaling in the regulation of cell fate,proliferation,apoptosis,autophagy,and inflammation in traumatic ***,we will describe the expression of BMPs and pattern of BMP signaling before and after traumatic SCI in rodent models and in ***,we will discuss the role of BMP in the regulation of neuronal and glial cell differentiation,survival,functional recovery from traumatic SCI,and the gap in k.owledge in this area that requires further investigation to improve SCI prognosis.

关键词： Spinal cord injury bone morphogenic protein apoptosis proliferation autophagy differentiation inflammation

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Production of pig iron from red mud waste fines using thermal plasma technology

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International Journal of Minerals,Metallurgy and Materials 2012年第8期19卷 679-684页

作者： k. Jayasank.r P.k. ray A.k. Chaubey A. Padhi B.k. Satapathy P.S. Muk.erjee CSIR-Institute of Minerals & Materials Technology Bhubaneswar India National Aluminum Company Ltd. Bhubaneswar India

Red mud, an insoluble residue produced during alk.li leaching of bauxite, is considered as a low-grade iron ore containing 30% to 50% iron. The present paper deals with the use of thermal plasma technology for producing pig iron from red mud waste fines. The smelting reduction of red mud was carried out in a 35 k. DC extended arc thermal plasma reactor. Red mud was properly mixed with fluxes and graphite （fixed carbon, 99%） as a reductant as per stoichiometric requirement. The effect of various process parameters lik. a reductant, fluxes and smelting time on iron recovery was studied and optimized. An optimum condition for the maximum recovery of iron was obtained. A new thermal plasma process applicable to direct iron mak.ng from red mud waste fines that would achieve significant utilization of red mud was proposed.

关键词： pig iron waste utilization red mud smelting dolomite limestone thermal plasma

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