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      • Neuroprotective and Anti-Inflammatory Activities of Allyl Isothiocyanate through Attenuation of JNK/NF-κB/TNF-α Signaling

        Subedi, Lalita,Venkatesan, Ramu,Kim, Sun Yeou MDPI 2017 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.18 No.7

        <P>Allyl isothiocyanate (AITC), present in <I>Wasabia japonica</I> (wasabi), is an aliphatic isothiocyanate derived from the precursor sinigrin, which is a glucosinolate present in vegetables of the Brassica family. Traditionally, it has been used to treat rheumatic arthralgia, blood circulation, and pain. This study focuses on its anti-apoptotic activity through the regulation of lipopolysaccharide (LPS)-induced neuroinflammation. Furthermore, we assessed its neuroprotective efficacy, which it achieves through the upregulation of nerve growth factor (NGF) production. Pretreatment with AITC significantly inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), and nitric oxide (NO) production in activated microglia, and increased the nerve growth factor (NGF) and neurite outgrowth in neuroblastoma cells. AITC inhibited the nuclear factor (NF-κB-mediated transcription by modulating mitogen activated protein kinase (MAPK) signaling, particularly downregulating c-Jun N-terminal kinase (JNK) phosphorylation, which was followed by a reduction in the TNF-α expression in activated microglia. This promising effect of AITC in controlling JNK/NF-κB/TNF-α cross-linking maintains the <I>Bcl-2</I> gene family and protects neuroblastoma cells from activated microglia-induced toxicity. These findings provide novel insights into the anti-neuroinflammatory effects of AITC on microglial cells, which may have clinical significance in neurodegeneration.</P>

      • SCOPUSKCI등재

        On Left SF-Rings and Strongly Regular Rings

        Subedi, Tikaram,Buhphang, Ardeline Mary Department of Mathematics 2016 Kyungpook mathematical journal Vol.56 No.3

        A ring R called left SF if its simple left modules are at. Regular rings are known to be left SF-rings. However, till date it is unknown whether a left SF-ring is necessarily regular. In this paper, we prove the strong regularity of left (right) complement bounded left SF-rings. We also prove the strong regularity of a class of generalized semi-commutative left SF-rings.

      • SCOPUSKCI등재

        Complex Regional Pain Syndrome (CRPS type-1) in an Adolescent Following Extravasation of Dextrose Containing Fluid-an Underdiagnosed Case

        Subedi, Asish,Bhattarai, Balkrishna,Biswas, Binay K.,Khatiwada, Sindhu The Korean Pain Society 2011 The Korean Journal of Pain Vol.24 No.2

        Due to its complex pathophysiology and wide spectrum of clinical manifestations, the diagnosis of CRPS is often missed in the early stage by primary care physicians. After being treated by a primary care physician for 5 months for chronic cellulitis, a 16-year-old girl was referred to our hospital with features of type-1 CRPS of the right upper extremity. Inability to diagnose early caused prolonged suffering to the girl with all the consequence of CRPS. The patient responded well with marked functional recovery from multimodal therapy. Ability to distinguish CRPS from other pain conditions, referral for specialty care at the appropriate time and full awareness of this condition and its clinical features among various healthcare professionals are essential in reducing patient suffering and stopping its progression towards difficult-to-treat situations.

      • KCI등재

        A New LEACH Algorithm for the Data Aggregation to Improve the Energy Efficiency in WSN

        Subedi, Sagun,Lee, Sangil,Lee, Jaehee The Institute of Internet 2018 International Journal of Internet, Broadcasting an Vol.10 No.2

        In recent years, the utilization of the WSN have been rapid. Energy consumption of these networks must be as low as possible. LEACH algorithm is one of the clustering technique. We modify the traditional LEACH algorithm in such way that it will be capable to self-organize large number of nodes and for saving communication resources such as processing time and initiation time. The efficiency of the network highly depends on how the algorithm divides cluster area and selects cluster head. The proposed algorithm can be evaluated through the extensive simulation the result we obtained shows that the life time of a network is increased when energy load is distributed equally among the sensor.

      • SCIESCOPUS

        Anti-neuroinflammatory and neuroprotective effects of the Lindera neesiana fruit in vitro

        Subedi, L.,Gaire, B.P.,Do, M.H.,Lee, T.H.,Kim, S.Y. G. Fischer 2016 Phytomedicine Vol.23 No.8

        <P>Background: Lindera neesiana Kurz (Lauraceae), popularly known as Siltimur in Nepal, is an aromatic and spicy plant with edible fruits. It is a traditional herbal medicine widely used for the treatment of diarrhea, tooth pain, headache, and gastric disorders and is also used as a stimulant. Purpose: The aim of the present study was to examine in vitro cytoprotective, anti-neuroinflammatory and neuroprotective potential of an aqueous extract of L. neesiana (LNE) fruit using different central nervous system (CNS) cell lines. Methods: In order to study the neuroprotective potential of LNE, we used three different types of CNS cell lines: murine microglia (BV2), rat glioma (C6), and mouse neuroblastoma (N2a). Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reagent, and prostaglandin E-2 (PGE(2)), tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and nerve growth factor (NGF) release in the culture media was determined using enzyme linked immunosorbent assay (ELISA) kits. Western blot analysis was performed to determine the protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX2), mitogen activated protein kinase (MAPK) family proteins, Bax, B cell lymphoma (BCL)-2, and cleaved caspase 3. Neurite outgrowth was determined using the IncuCyte imaging system. Results: LNE treatment not only reduced nitric oxide (NO) production in a dose-dependent manner, but also significantly reduced proinflammatory cytokines, iNOS and COX-2 production by lipopolysaccharide (LPS) stimulated BV-2 cells. LNE increased the expression of phosphorylated (p)-extracellular signal-regulated kinase (ERK), whereas p-p38 and p- janus kinase (JNK) expression was significantly decreased in activated microglia. Furthermore, LNE increased cell viability of N2a cells, which was accompanied by decreased caspase-3 expression and the ratio of Bax/Bcl2 protein expression as well as increased NGF and neurite outgrowth, suggesting its neuroprotective potential against LPS-induced effects. Additionally, LNE substantially increased nuclear factor erythroid 2-related factor 2 (Nrf2) secretion in N2a cells and inhibited lipid dehydrogenase (LDH) release in H2O2-stimulated BV2 cells demonstrating the strong anti-inflammatory and antioxidant effects of LNE in CNS cell lines. Conclusion: Here we found that water the soluble extract of LNE has promising anti-neuroinflammation and anti-apoptotic properties and identify LNE as a potential natural candidate for neuroprotection. (C) 2016 Published by Elsevier GmbH.</P>

      • Hsp31 of <i>Escherichia coli</i> K‐12 is glyoxalase III

        Subedi, Krishna P.,Choi, Dongwook,Kim, Insook,Min, Bumchan,Park, Chankyu Blackwell Publishing Ltd 2011 Molecular microbiology Vol.81 No.4

        <P><B>Summary</B></P><P>Hsp31 encoded by <I>hchA</I> is known as a heat‐inducible molecular chaperone. Although structure studies revealed that Hsp31 has a putative catalytic triad consisting of Asp‐214, His‐186 and Cys‐185, its enzymatic function, besides weak amino‐peptidase activity, is still unknown. We found that Hsp31 displays glyoxalase activity that catalyses the conversion of methylglyoxal (MG) to <SMALL>d</SMALL>‐lactate without an additional cofactor. The glyoxalase activity was completely abolished in the <I>hchA</I>‐deficient strain, confirming the relationship between the <I>hchA</I> gene and its enzymatic activity <I>in vivo</I>. Hsp31 exhibits Michaelis–Menten kinetics for substrates MG with <I>K</I><SUB>m</SUB> and <I>k</I><SUB>cat</SUB> of 1.43 ± 0.12 mM and 156.9 ± 5.5 min<SUP>−1</SUP> respectively. The highest glyoxalase activity was found at 35–40°C and pH of 6.0–8.0, and the activity was significantly inhibited by Cu<SUP>2+</SUP>, Fe<SUP>3+</SUP> and Zn<SUP>2+</SUP>. Mutagenesis studies based on our evaluation of conserved catalytic residues revealed that the Cys‐185 and Glu‐77 were essential for catalysis, whereas His‐186 was less crucial for enzymatic function, although it participates in the catalytic process. The stationary‐phase <I>Escherichia coli</I> cells became more susceptible to MG when <I>hchA</I> was deleted, which was complemented by an expression of plasmid‐encoded <I>hchA</I>. Furthermore, an accumulation of intracellular MG was observed in <I>hchA</I>‐deficient strains.</P>

      • Sulforaphane-Enriched Broccoli Sprouts Pretreated by Pulsed Electric Fields Reduces Neuroinflammation and Ameliorates Scopolamine-Induced Amnesia in Mouse Brain through Its Antioxidant Ability via Nrf2-HO-1 Activation

        Subedi, Lalita,Cho, KyoHee,Park, Yong Un,Choi, Hyuk Joon,Kim, Sun Yeou Hindawi 2019 Oxidative medicine and cellular longevity Vol.2019 No.-

        <P>Activated microglia-mediated neuroinflammation plays a key pathogenic role in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ischemia. Sulforaphane is an active compound produced after conversion of glucoraphanin by the myrosinase enzyme in broccoli (<I>Brassica oleracea</I> var) sprouts. Dietary broccoli extract as well as sulforaphane has previously known to mitigate inflammatory conditions in aged models involving microglial activation. Here, we produced sulforaphane-enriched broccoli sprouts through the pretreatment of pulsed electric fields in order to trigger the biological role of normal broccoli against lipopolysaccharide-activated microglia. The sulforaphane-enriched broccoli sprouts showed excellent potency against neuroinflammation conditions, as evidenced by its protective effects in both 6 and 24 h of microglial activation <I>in vitro</I>. We further postulated the underlying mechanism of action of sulforaphane in broccoli sprouts, which was the inhibition of an inflammatory cascade <I>via</I> the downregulation of mitogen-activated protein kinase (MAPK) signaling. Simultaneously, sulforaphane-enriched broccoli sprouts inhibited the LPS-induced activation of the NF-<I>κ</I>B signaling pathway and the secretions of inflammatory proteins (iNOS, COX-2, TNF-<I>α</I>, IL-6, IL-1<I>β</I>, PGE2, etc.), which are responsible for the inflammatory cascades in both acute and chronic inflammation. It also upregulated the expression of Nrf2 and HO-1 in normal and activated microglia followed by the lowered neuronal apoptosis induced by activated microglia. Based on these results, it may exhibit anti-inflammatory effects via the NF-<I>κ</I>B and Nrf2 pathways. Interestingly, sulforaphane-enriched broccoli sprouts improved the scopolamine-induced memory impairment in mice through Nrf2 activation, inhibiting neuronal apoptosis particularly through inhibition of caspase-3 activation which could lead to the neuroprotection against neurodegenerative disorders. The present study suggests that sulforaphane-enriched broccoli sprouts might be a potential nutraceutical with antineuroinflammatory and neuroprotective activities.</P>

      • Genetically Engineered Resveratrol-Enriched Rice Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia Via Downregulating Mitogen-Activated Protein Kinase-Nuclear Factor Kappa B Signaling Pathway

        Subedi, Lalita,Baek, So-Hyeon,Kim, Sun Yeou Hindawi 2018 Oxidative medicine and cellular longevity Vol.2018 No.-

        <P>Resveratrol, a natural stilbenoid, is produced by several plants, especially grape vines. Its strong potency against obesity, metabolic disorders, vascular disease, inflammation, and various cancers has already been reported. Large amounts of wine or grapes need to be consumed to obtain the amount of resveratrol required for biological activity. Pure resveratrol at concentrations as low as 10 <I>μ</I>M induces cytotoxicity to normal cells. To overcome these limitations, we prepared genetically modified resveratrol-enriched rice (RR). We previously reported the strong antiaging potential of RR against ultraviolet B/reactive oxygen species-induced toxicity in normal human dermal fibroblasts (NHDF). As aging is characterized by neuroinflammation and neurodegeneration, we further evaluated the role of RR against LPS-induced neuroinflammation. RR inhibited nitric oxide production and the expression of inflammatory proteins such as iNOS and COX-2. RR significantly modulated mitogen-activated protein kinase signaling, activator protein AP-1 signaling, and nuclear factor kappa B (NF-<I>κ</I>B) mediated transcription of inflammatory proteins via inhibition of NF-<I>κ</I>B translocation, IkB phosphorylation, and proinflammatory cytokine productions such as interleukin IL-6, IL-1<I>β</I>, tumor necrosis factor alpha (TNF-<I>α</I>), and prostaglandin E2 (PGE2). These findings show that the strong antineuroinflammatory effects of RR can be beneficial for aging-mediated neurodegenerative conditions as well as disorders of the central nervous system caused by neuroinflammation.</P>

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