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Sharma, Hari Shanker
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Publications (10 of 223) Show all publications
Shevchenko, V., Arnotskaya, N., Korneyko, M., Zaytsev, S., Khotimchenko, Y., Sharma, H. S. & Bryukhovetskiy, I. (2019). Proteins of the Wnt signaling pathway as targets for the regulation of CD133(+) cancer stem cells in glioblastoma. Oncology Reports, 41(5), 3080-3088
Open this publication in new window or tab >>Proteins of the Wnt signaling pathway as targets for the regulation of CD133(+) cancer stem cells in glioblastoma
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2019 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 41, no 5, p. 3080-3088Article in journal (Refereed) Published
Abstract [en]

Glioblastoma multiforme (GBM) is one of the most aggressive types of brain tumor and is highly resistant to therapy. The median survival time for patients with GBM is 15 months. GBM resistance to treatment is associated with cancer stem cells (CSCs). CD133 membrane glycoprotein is the best-known marker of GBM CSCs. The Wnt signaling pathway plays an important role in the proliferation of all stem cells. To the best of our knowledge, the present study was the first to examine the expression levels of proteins associated with the Wnt signaling pathway in CD133(+) CSCs of human GBM. Furthermore, potential targets that may regulate CD133(+) CSCs in human GBM were investigated. The human GBM U-87MG cell line was cultured in neurobasal medium supplemented with B27, fibroblast growth factor, epidermal growth factor and no serum. Immunohistochemical characteristics of glioma spheres were investigated based on the expression of key markers of CSCs. CD133(+) cells were extracted from glioma spheres by cell sorting and then lysed. High-performance liquid chromatography-mass spectrometry was used for proteome analysis. Lysates of CD133(-) cells in GBM were used for comparison. The present study was the first to describe the conceptual proteome differences between GBM and CD133(+) CSCs of the common pool. Major differences were identified in the glycolysis/gluconeogenesis, focal adhesion, tight junction and Wnt signaling pathways. This study aimed to analyze the crucial role that proteins of the Wnt signaling pathway play in stem cell proliferation. The identified proteins were analyzed for their association with the Wnt signaling pathway using the international open databases PubMed, Protein Analysis Through Evolutionary Relationships, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and Search Tool for the Retrieval of Interacting Genes/Proteins. An increased expression of 12 proteins associated with the Wnt signaling pathway were identified in GBM CD133(+) CSCs, which included catenin beta-1, disheveled associated activator of morphogenesis 1, RAC family small GTPase 2 and RAS homolog gene family member A, a number of which are also associated with adherens junctions. The Wnt signaling pathway is not upregulated in CSCs; however, the high expression levels of adenomatous polyposis coli, beta-catenin, C-terminal binding protein (CtBP) and RuvB-like AAA ATPase 1 (RUVBL1 or Pontin52) proteins suggest the possibility of alternative activation of specific genes in the nuclei of these cells. Calcyclin-binding protein, casein kinase II alpha, casein kinase II beta, CtBP1, CtBP2, CUL1 and RUVBL1 proteins may be used as targets for the pharmaceutical regulation of CSCs in complex GBM treatment.

Place, publisher, year, edition, pages
SPANDIDOS PUBL LTD, 2019
Keywords
glioblastoma multiforme, CD133(+) cancer stem cells, Wnt signaling pathway
National Category
Cell Biology
Identifiers
urn:nbn:se:uu:diva-382547 (URN)10.3892/or.2019.7043 (DOI)000464015900043 ()30864699 (PubMedID)
Available from: 2019-05-10 Created: 2019-05-10 Last updated: 2019-05-10Bibliographically approved
Sharma, H. S., Skaper, S. D. & Sharma, A. (2018). 184th American Association for the Advancement of Science Annual Meeting, Austin TX, USA Feb. 15-19, 2018. CNS & Neurological Disorders: Drug Targets, 17(3), 240-242
Open this publication in new window or tab >>184th American Association for the Advancement of Science Annual Meeting, Austin TX, USA Feb. 15-19, 2018
2018 (English)In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 17, no 3, p. 240-242Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
BENTHAM SCIENCE PUBL, 2018
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-386355 (URN)10.2174/187152731703180619162802 (DOI)000435907700010 ()29992875 (PubMedID)
Available from: 2019-06-25 Created: 2019-06-25 Last updated: 2019-06-25Bibliographically approved
Wiklund, L., Patnaik, R., Sharma, A., Miclescu, A. & Sharma, H. S. (2018). Cerebral Tissue Oxidative Ischemia-Reperfusion Injury in Connection with Experimental Cardiac Arrest and Cardiopulmonary Resuscitation: Effect of Mild Hypothermia and Methylene Blue. Molecular Neurobiology, 55(1), 115-121
Open this publication in new window or tab >>Cerebral Tissue Oxidative Ischemia-Reperfusion Injury in Connection with Experimental Cardiac Arrest and Cardiopulmonary Resuscitation: Effect of Mild Hypothermia and Methylene Blue
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 115-121Article in journal (Refereed) Published
Abstract [en]

The present investigation is an expansion of previous studies which all share a basic experimental protocol of a porcine-induced cardiac arrest (CA) of 12 min followed by 8 min of cardiopulmonary resuscitation (CPR), different experimental treatments (immediate as well as postponed induced mild hypothermia and administration of much or less cool intravenous fluids), and a follow-up period of 3 h after which the animals were sacrificed. Another group of animals was studied according to the same protocol after 12-min CA and Bstandard CPR.^ After death (within 1 min), the brains were harvested and frozen in liquid nitrogen awaiting analysis. Control brains of animals were collected in the same way after short periods of untreated CA (0 min, 5 min, and 15–30 min). Previous studies concerning chiefly neuropathological changes were now expanded with analyses of different tissue indicators (glutathione, luminol, leucigenin, malonialdehyde, and myeloperoxidase) of cerebral oxidative injury. The results indicate that a great part of oxidative injury occurs within the first 5 min after CA. Immediate cooling by administration of much intravenous fluid results in less cerebral oxidative injury compared to less intravenous fluid administration. A 30-min postponement of induction of hypothermia results in a cerebral oxidative injury comparable to that of Bstandard CPR^ or the oxidative injury found after 5 min of untreated CA. Intravenous administration of methylene blue (MB) during and immediately after CPR in combination with postponed cooling resulted in no statistical difference in any of the indicators of oxidative injury, except myeloperoxidase, and glutathione, when this treatment was compared with the negative controls, i.e., animals subjected to anesthesia alone.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Cardiac arrest, Oxidative injury, Ischemia reperfusion, Methylene blue
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-337384 (URN)10.1007/s12035-017-0723-z (DOI)000424702600012 ()28895060 (PubMedID)
Available from: 2017-12-24 Created: 2017-12-24 Last updated: 2019-01-25Bibliographically approved
Huang, H., Young, W., Chen, L., Feng, S., Al Zoubi, Z. M., Sharma, H. S., . . . Li, T. (2018). Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017). Cell Transplantation, 27(2), 310-324
Open this publication in new window or tab >>Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
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2018 (English)In: Cell Transplantation, ISSN 0963-6897, E-ISSN 1555-3892, Vol. 27, no 2, p. 310-324Article, review/survey (Refereed) Published
Abstract [en]

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.

Place, publisher, year, edition, pages
SAGE PUBLICATIONS INC, 2018
Keywords
cell therapy, neurorestoration, clinical application guideline neurorestoratology
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-357188 (URN)10.1177/0963689717746999 (DOI)000430019200009 ()29637817 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Qu, S., Liu, W., Yang, H., Wang, Z., Yang, Y., Liu, F., . . . Luan, Z. (2018). Clinical Observation of Electroencephalographic Changes and Risk of Convulsion Occurrence in Children Receiving Neural Precursor Cell Transplantation. CNS & Neurological Disorders: Drug Targets, 17(3), 233-239
Open this publication in new window or tab >>Clinical Observation of Electroencephalographic Changes and Risk of Convulsion Occurrence in Children Receiving Neural Precursor Cell Transplantation
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2018 (English)In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 17, no 3, p. 233-239Article in journal (Refereed) Published
Abstract [en]

Purpose: This study was intended to observe electroencephalographic (EEG) changes and convulsion attacks in children receiving neural precursor cell transplantation, and to explore the possibility of electrophysiological changes and risk of convulsion occurrence after cell transplantation.

Method: 228 children were included in this study who received neural precursor cell transplantation in our hospital between March 2008 and July 2012. No history of convulsion attacks was elicited before cell transplantation. Data about EEG change and convulsion occurrence before and after cell transplantation were analyzed statistically.

Results: Of the 228 pediatric patients, EEG improvement, deterioration and no significant change were observed in 60, 45 and 122 patients, respectively. One month after transplantation, four (1.76%) patients experienced new convulsions. Of the 227 patients, 25 showed increased and/or abnormal discharges on EEG. Of these, 19 underwent EEG re-examination six months post-operation. Except the convulsive cases mentioned above, there were no new cases of convulsions in the remaining patients. Of the 27 patients including those with abnormal discharge, increased discharge and convulsion attacks, 17 achieved varying degrees of therapeutic efficacy.

Conclusion: Intraventricular transplantation of neural precursor cells is associated with EEG changes in some children and clinical convulsion attacks in individual patients. However, these abnormal changes do not last long and usually return to normal levels within 1-6 months after surgery, along with disappearance of convulsions. Simultaneous occurrence of EEG changes and convulsions do not appear to affect therapeutic efficacy.

Keywords
Electroencephalographic change, convulsion occurrence, children, neural precursor cell, cell transplantation, clinical observation
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-386336 (URN)10.2174/1871527317666180424121947 (DOI)000435907700009 ()29692269 (PubMedID)
Available from: 2019-06-19 Created: 2019-06-19 Last updated: 2019-06-19Bibliographically approved
Sharma, H. S., Muresanu, D. F., Vicente Lafuente, J., Patnaik, R., Tian, Z. R., Ozkizilcik, A., . . . Sharma, A. (2018). Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease. Molecular Neurobiology, 55(1), 300-311
Open this publication in new window or tab >>Co-Administration of TiO2 Nanowired Mesenchymal Stem Cells with Cerebrolysin Potentiates Neprilysin Level and Reduces Brain Pathology in Alzheimer's Disease
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 300-311Article in journal (Refereed) Published
Abstract [en]

Neprilysin (NPL), the rate-limiting enzyme for amyloid beta peptide (A beta P), appears to play a crucial role in the pathogenesis of Alzheimer's disease (AD). Since mesenchymal stem cells (MSCs) and/or cerebrolysin (CBL, a combination of neurotrophic factors and active peptide fragments) have neuroprotective effects in various CNS disorders, we examined nanowired delivery of MSCs and CBL on NPL content and brain pathology in AD using a rat model. AD-like symptoms were produced by intraventricular (i.c.v.) administration of A beta P (1-40) in the left lateral ventricle (250 ng/10 mu l, once daily) for 4 weeks. After 30 days, the rats were examined for NPL and A beta P concentrations in the brain and related pathology. Co-administration of TiO2-nanowired MSCs (10(6) cells) with 2.5 ml/kg CBL (i.v.) once daily for 1 week after 2 weeks of A beta P infusion significantly increased the NPL in the hippocampus (400 pg/g) from the untreated control group (120 pg/g; control 420 +/- 8 pg/g brain) along with a significant decrease in the A beta P deposition (45 pg/g from untreated control 75 pg/g; saline control 40 +/- 4 pg/g). Interestingly, these changes were much less evident when the MSCs or CBL treatment was given alone. Neuronal damages, gliosis, and myelin vesiculation were also markedly reduced by the combined treatment of TiO2, MSCs, and CBL in AD. These observations are the first to show that co-administration of TiO2-nanowired CBL and MSCs has superior neuroprotective effects in AD probably due to increasing the brain NPL level effectively, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Alzheimer's disease (AD), Neprilysin (NPL), Amyloid-beta peptide (a beta P), Mesenchymal stem cells (MSCs), Cerebrolysin (CBL), TiO2 nanowires, Nanodelivery
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-346902 (URN)10.1007/s12035-017-0742-9 (DOI)000424702600030 ()28844104 (PubMedID)
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved
Sharma, A., Muresanu, D. F., Vicente Lafuente, J., Sjöquist, P.-O., Patnaik, R., Tian, Z. R., . . . Sharma, H. S. (2018). Cold Environment Exacerbates Brain Pathology and Oxidative Stress Following Traumatic Brain Injuries: Potential Therapeutic Effects of Nanowired Antioxidant Compound H-290/51. Molecular Neurobiology, 55(1), 276-285
Open this publication in new window or tab >>Cold Environment Exacerbates Brain Pathology and Oxidative Stress Following Traumatic Brain Injuries: Potential Therapeutic Effects of Nanowired Antioxidant Compound H-290/51
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 276-285Article in journal (Refereed) Published
Abstract [en]

The possibility that traumatic brain injury (TBI) occurring in a cold environment exacerbates brain pathology and oxidative stress was examined in our rat model. TBI was inflicted by making a longitudinal incision into the right parietal cerebral cortex (2 mm deep and 4 mm long) in cold-acclimatized rats (5 degrees C for 3 h daily for 5 weeks) or animals at room temperature under Equithesin anesthesia. TBI in cold-exposed rats exhibited pronounced increase in brain lucigenin (LCG), luminol (LUM), and malondialdehyde (MDA) and marked pronounced decrease in glutathione (GTH) as compared to identical TBI at room temperature. The magnitude and intensity of BBB breakdown to radioiodine and Evans blue albumin, edema formation, and neuronal injuries were also exacerbated in cold-exposed rats after injury as compared to room temperature. Nanowired delivery of H-290/51 (50 mg/kg) 6 and 8 h after injury in cold-exposed group significantly thwarted brain pathology and oxidative stress whereas normal delivery of H-290/51 was neuroprotective after TBI at room temperature only. These observations are the first to demonstrate that (i) cold aggravates the pathophysiology of TBI possibly due to an enhanced production of oxidative stress, (ii) and in such conditions, nanodelivery of antioxidant compound has superior neuroprotective effects, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Traumatic brain injury (TBI), Oxidative stress, Luminol, Lucigenin, Malondialdehyde, Glutathione, H-290/51, Nanodelivery, Blood-brain barrier, Brain edema, Neuronal damage, Cold environment
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-346900 (URN)10.1007/s12035-017-0740-y (DOI)000424702600028 ()28856566 (PubMedID)
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved
Sharma, H. S. & Sharma, A. (2018). Dedication Commendation of Diligence A Legend in Neuroscience (1948-2018) Dr. Stephen D. Skaper, Ph. D. CNS & Neurological Disorders: Drug Targets, 17(5), 322-322
Open this publication in new window or tab >>Dedication Commendation of Diligence A Legend in Neuroscience (1948-2018) Dr. Stephen D. Skaper, Ph. D
2018 (English)In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 17, no 5, p. 322-322Article in journal (Refereed) Published
Place, publisher, year, edition, pages
BENTHAM SCIENCE PUBL, 2018
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-365173 (URN)10.2174/187152731705180807144606 (DOI)000441416700002 ()
Available from: 2018-11-09 Created: 2018-11-09 Last updated: 2018-11-09Bibliographically approved
Yang, H., Yang, Y., Qu, S., Wang, Z., Lu, W., Liu, F., . . . Luan, Z. (2018). Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation before and after Neural Precursor Cell Transplantation. CNS & Neurological Disorders: Drug Targets, 17(2), 98-105
Open this publication in new window or tab >>Growth Factor Changes in Cerebrospinal Fluid of Children with Mental Retardation before and after Neural Precursor Cell Transplantation
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2018 (English)In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 17, no 2, p. 98-105Article in journal (Refereed) Published
Abstract [en]

Objective: To investigate growth factor changes in cerebrospinal fluid (CSF) of children with mental retardation (MR) before and after neural precursor cell transplantation (NPCT), in an attempt to provide experimental support for the clinical treatment of MR with NPCT.

Methods: The study comprised of 28 MR children who received twice NPCT in our hospital. CSF was collected at both times of NPCT to assess growth factors by ELISA. In addition, the content of insulin-like growth factor 1 (IGF-1) in CSF was assayed to determine possible correlations between IGF-1 changes and the short-term therapeutic effect of NPCT.

Results: Of all the growth factors detected in CSF, only IGF-1 was increased significantly after NPCT (P<0.05). Fifteen of the twenty-eight MR children achieved short-term therapeutic efficacy, whereby the content of IGF-1 after NPCT was significantly higher than that before NPCT (P<0.05). There was no difference in IGF-1 content before and after NPCT in the remaining 13 MR children without short-term therapeutic effect (P=0.657). There was a significant difference in IGF-change between the two groups of patients (P<0.05).

Conclusion: IGF-1 may be one of the mechanisms contributing to the therapeutic effect of NPCT.

Place, publisher, year, edition, pages
BENTHAM SCIENCE PUBL, 2018
Keywords
Mental retardation, neural precursor cell, transplantation, insulin-like growth factor 1, growth factors, intellectual disability
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-359677 (URN)10.2174/1871527317666180411102337 (DOI)000435906600004 ()29637872 (PubMedID)
Funder
Swedish Research Council, 2710
Available from: 2018-09-06 Created: 2018-09-06 Last updated: 2018-09-06Bibliographically approved
Patnaik, R., Sharma, A., Skaper, S. D., Muresanu, D. F., Vicente Lafuente, J., Castellani, R. J., . . . Sharma, H. S. (2018). Histamine H3 Inverse Agonist BF 2649 or Antagonist with Partial H4 Agonist Activity Clobenpropit Reduces Amyloid Beta Peptide-Induced Brain Pathology in Alzheimer's Disease. Molecular Neurobiology, 55(1), 312-321
Open this publication in new window or tab >>Histamine H3 Inverse Agonist BF 2649 or Antagonist with Partial H4 Agonist Activity Clobenpropit Reduces Amyloid Beta Peptide-Induced Brain Pathology in Alzheimer's Disease
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2018 (English)In: Molecular Neurobiology, ISSN 0893-7648, E-ISSN 1559-1182, Vol. 55, no 1, p. 312-321Article in journal (Refereed) Published
Abstract [en]

Alzheimer's disease (AD) is one of the leading causes for disability and death affecting millions of people worldwide. Thus, novel therapeutic strategies are needed to reduce brain pathology associated with AD. In view of increasing awareness regarding involvement of histaminergic pathways in AD, we explored the role of one H3 receptor inverse agonist BF 2649 and one selective H3 receptor antagonist with partial H4 agonist activity in amyloid beta peptide (A beta P) infusion-induced brain pathology in a rat model. AD-like pathology was produced by administering A beta P (1-40) intracerebroventricular (i.c.v.) in the left lateral ventricle (250 ng/10 mu l, once daily) for 4 weeks. Control rats received saline. In separate group of rats, either BF 2649 (1 mg/kg, i.p.) or clobenpropit (1 mg/kg, i.p.) was administered once daily for 1 week after 3weeks of A beta P administration. After 30 days, blood-brain barrier (BBB) breakdown, edema formation, neuronal, glial injuries, and A beta P deposits were examined in the brain. A significant reduction in A beta P deposits along with marked reduction in neuronal or glial reactions was seen in the drug-treated group. The BBB breakdown to Evans blue albumin and radioiodine in the cortex, hippocampus, hypothalamus, and cerebellum was also significantly reduced in these drug-treated groups. Clobenpropit showed superior effects than the BF2649 in reducing brain pathology in AD. Taken together, our observations are the first to show that blockade of H3 and stimulation of H4 receptors are beneficial for the treatment of AD pathology, not reported earlier.

Place, publisher, year, edition, pages
Humana Press, 2018
Keywords
Alzheimer's disease (AD). Histamine. Amyloid beta peptide (A beta P), Clobenpropit, BF2649, H3 receptor inverse agonist, H3 receptors antagonist with partial H4 agonist, Blood-brain barrier, Brain pathology
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-346903 (URN)10.1007/s12035-017-0743-8 (DOI)000424702600031 ()28861757 (PubMedID)
Available from: 2018-03-27 Created: 2018-03-27 Last updated: 2018-03-27Bibliographically approved
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