Publications by authors named "Sanjay K Singh"

120 Publications

C-Reactive Protein-Based Strategy to Reduce Antibiotic Dosing for the Treatment of Pneumococcal Infection.

Front Immunol 2020 20;11:620784. Epub 2021 Jan 20.

Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.

C-reactive protein (CRP) is a component of innate immunity. The concentration of CRP in serum increases in microbial infections including infection. Employing a mouse model of pneumococcal infection, it has been shown that passively administered human wild-type CRP protects mice against infection, provided that CRP is injected into mice within two hours of administering pneumococci. Engineered CRP (E-CRP) molecules have been reported recently; unlike wild-type CRP, passively administered E-CRP protected mice against infection even when E-CRP was injected into mice after twelve hours of administering pneumococci. The current study was aimed at comparing the protective capacity of E-CRP with that of an antibiotic clarithromycin. We established a mouse model of pneumococcal infection in which both E-CRP and clarithromycin, when used alone, provided minimal but equal protection against infection. In this model, the combination of E-CRP and clarithromycin drastically reduced bacteremia and increased survival of mice when compared to the protective effects of either E-CRP or clarithromycin alone. E-CRP was more effective in reducing bacteremia in mice treated with clarithromycin than in untreated mice. Also, there was 90% reduction in antibiotic dosing by including E-CRP in the antibiotic-treatment for maximal protection of infected mice. These findings provide an example of cooperation between the innate immune system and molecules that prevent multiplication of bacteria, and that should be exploited to develop novel combination therapies for infections against multidrug-resistant pneumococci. The reduction in antibiotic dosing by including E-CRP in the combination therapy might also resolve the problem of developing antibiotic resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.620784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854908PMC
January 2021

Discovery of 6-Oxo-4-phenyl-hexanoic acid derivatives as RORγt inverse agonists showing favorable ADME profile.

Bioorg Med Chem Lett 2021 03 23;36:127786. Epub 2021 Jan 23.

Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address:

The retinoic acid receptor-related orphan nuclear receptor gamma t (RORγt), which is a promising therapeutic target for immune diseases, is a major transcription factor of genes related to psoriasis pathogenesis, such as interleukin (IL)-17A, IL-22, and IL-23R. Inspired by the co-crystal structure of RORγt, a 6-oxo-4-phenyl-hexanoic acid derivative 6a was designed, synthesized, and identified as a ligand of RORγt. The structure-activity relationship (SAR) studies in 6a, which focus on the improvement of its membrane permeability profile by introducing chlorine atoms, led to finding 12a, which has a potent RORγt inhibitory activity and a favorable pharmacokinetic profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bmcl.2021.127786DOI Listing
March 2021

Treatment of Pneumococcal Infection by Using Engineered Human C-Reactive Protein in a Mouse Model.

Front Immunol 2020 7;11:586669. Epub 2020 Oct 7.

Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.

C-reactive protein (CRP) binds to several species of bacterial pathogens including . Experiments in mice have revealed that one of the functions of CRP is to protect against pneumococcal infection by binding to pneumococci and activating the complement system. For protection, however, CRP must be injected into mice within a few hours of administering pneumococci, that is, CRP is protective against early-stage infection but not against late-stage infection. It is assumed that CRP cannot protect if pneumococci got time to recruit complement inhibitor factor H on their surface to become complement attack-resistant. Since the conformation of CRP is altered under inflammatory conditions and altered CRP binds to immobilized factor H also, we hypothesized that in order to protect against late-stage infection, CRP needed to change its structure and that was not happening in mice. Accordingly, we engineered CRP molecules (E-CRP) which bind to factor H on pneumococci but do not bind to factor H on any host cell in the blood. We found that E-CRP, in cooperation with wild-type CRP, was protective regardless of the timing of administering E-CRP into mice. We conclude that CRP acts via two different conformations to execute its anti-pneumococcal function and a model for the mechanism of action of CRP is proposed. These results suggest that pre-modified CRP, such as E-CRP, is therapeutically beneficial to decrease bacteremia in pneumococcal infection. Our findings may also have implications for infections with antibiotic-resistant pneumococcal strains and for infections with other bacterial species that use host proteins to evade complement-mediated killing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.586669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575696PMC
June 2021

Maleic hydrazide elicits global transcriptomic changes in chemically topped tobacco to influence shoot bud development.

Planta 2020 Sep 24;252(4):64. Epub 2020 Sep 24.

Department of Plant and Soil Sciences, University of Kentucky, Lexington, KY, 40546, USA.

Main Conclusion: Transcriptomic analysis revealed maleic hydrazide suppresses apical and axillary bud development by altering the expression of genes related to meristem development, cell division, DNA replication, DNA damage and recombination, and phytohormone signaling. Topping (removal of apical buds) is a common agricultural practice for some crop plants including cotton, cannabis, and tobacco. Maleic hydrazide (MH) is a systemic suckercide, a chemical that inhibits shoot bud growth, used to control the growth of apical (ApB) and axillary buds (AxB) following topping. However, the influence of MH on gene expression and the underlying molecular mechanism of controlling meristem development are not well studied. Our RNA sequencing analysis showed that MH significantly influences the transcriptomic landscape in ApB and AxB of chemically topped tobacco. Gene ontology (GO) enrichment analysis revealed that upregulated genes in ApB were enriched for phosphorelay signal transduction, and the regulation of transition timing from vegetative to reproductive phase, whereas downregulated genes were largely associated with meristem maintenance, cytokinin metabolism, cell wall synthesis, photosynthesis, and DNA metabolism. In MH-treated AxB, GO terms related to defense response and oxylipin metabolism were overrepresented in upregulated genes. GO terms associated with cell cycle, DNA metabolism, and cytokinin metabolism were enriched in downregulated genes. Expression of KNOX and MADS transcription factor (TF) family genes, known to be involved in meristem development, were affected in ApB and AxB by MH treatment. The promoters of MH-responsive genes are enriched for several known cis-acting elements, suggesting the involvement of a subset of TF families. Our findings suggest that MH affects shoot bud development in chemically topped tobacco by altering the expression of genes related to meristem development, DNA repair and recombination, cell division, and phytohormone signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00425-020-03460-9DOI Listing
September 2020

Complement Activation by C-Reactive Protein Is Critical for Protection of Mice Against Pneumococcal Infection.

Front Immunol 2020 13;11:1812. Epub 2020 Aug 13.

Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.

C-reactive protein (CRP), a component of the innate immune system, is an antipneumococcal plasma protein. Human CRP has been shown to protect mice against infection with lethal doses of by decreasing bacteremia. , CRP binds to phosphocholine-containing substances, such as pneumococcal C-polysaccharide, in a Ca-dependent manner. Phosphocholine-complexed human CRP activates the complement system in both human and murine sera. The mechanism of antipneumococcal action of CRP , however, has not been defined yet. In this study, we tested a decades-old hypothesis that the complement-activating property of phosphocholine-complexed CRP contributes to protection of mice against pneumococcal infection. Our approach was to investigate a CRP mutant, incapable of activating murine complement, in mouse protection experiments. We employed site-directed mutagenesis of CRP, guided by its three-dimensional structure, and identified a mutant H38R which, unlike wild-type CRP, did not activate complement in murine serum. Substitution of His with Arg in CRP did not affect the pentameric structure of CRP, did not affect the binding of CRP to pneumococci, and did not decrease the stability of CRP in mouse circulation. Employing a murine model of pneumococcal infection, we found that passively administered H38R CRP failed to protect mice against infection. Infected mice injected with H38R CRP showed no reduction in bacteremia and did not survive longer, as opposed to infected mice treated with wild-type CRP. Thus, the hypothesis that complement activation by phosphocholine-complexed CRP is an antipneumococcal effector function was supported. We can conclude now that complement activation by phosphocholine-complexed CRP is indeed essential for CRP-mediated protection of mice against pneumococcal infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.01812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438579PMC
April 2021

Conformationally Altered C-Reactive Protein Capable of Binding to Atherogenic Lipoproteins Reduces Atherosclerosis.

Front Immunol 2020 11;11:1780. Epub 2020 Aug 11.

Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.

The aim of this study was to test the hypothesis that C-reactive protein (CRP) protects against the development of atherosclerosis and that a conformational alteration of wild-type CRP is necessary for CRP to do so. Atherosclerosis is an inflammatory cardiovascular disease and CRP is a plasma protein produced by the liver in inflammatory states. The co-localization of CRP and low-density lipoproteins (LDL) at atherosclerotic lesions suggests a possible role of CRP in atherosclerosis. CRP binds to phosphocholine-containing molecules but does not interact with LDL unless the phosphocholine groups in LDL are exposed. However, CRP can bind to LDL, without the exposure of phosphocholine groups, if the native conformation of CRP is altered. Previously, we reported a CRP mutant, F66A/T76Y/E81A, generated by site-directed mutagenesis, that did not bind to phosphocholine. Unexpectedly, this mutant CRP, without any more conformational alteration, was found to bind to atherogenic LDL. We hypothesized that this CRP mutant, unlike wild-type CRP, could be anti-atherosclerotic and, accordingly, the effects of mutant CRP on atherosclerosis in atherosclerosis-prone LDL receptor-deficient mice were evaluated. Administration of mutant CRP into mice every other day for a few weeks slowed the progression of atherosclerosis. The size of atherosclerotic lesions in the aorta of mice treated with mutant CRP for 9 weeks was ~40% smaller than the lesions in the aorta of untreated mice. Thus, mutant CRP conferred protection against atherosclerosis, providing a proof of concept that a local inflammation-induced structural change in wild-type CRP is a prerequisite for CRP to control the development of atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.01780DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7431523PMC
April 2021

Identification of Genes and Pathways Regulated by Lamin A in Heart.

J Am Heart Assoc 2020 08 1;9(16):e015690. Epub 2020 Aug 1.

Center for Cardiovascular Genetics Institute of Molecular Medicine University of Texas Health Sciences Center at Houston TX.

Background Mutations in the gene, encoding LMNA (lamin A/C), causes distinct disorders, including dilated cardiomyopathies, collectively referred to as laminopathies. The genes (coding and noncoding) and regulatory pathways controlled by LMNA in the heart are not completely defined. Methods and Results We analyzed cardiac transcriptome from wild-type, loss-of-function (), and gain-of-function ( injected with adeno-associated virus serotype 9 expressing LMNA) mice with normal cardiac function. Deletion of () led to differential expression of 2193 coding and 629 long noncoding RNA genes in the heart (q<0.05). Re-expression of LMNA in the mouse heart, completely rescued 501 coding and 208 non-coding and partially rescued 1862 coding and 607 lncRNA genes. Pathway analysis of differentially expressed genes predicted activation of transcriptional regulators lysine-specific demethylase 5A, lysine-specific demethylase 5B, tumor protein 53, and suppression of retinoblastoma 1, paired-like homeodomain 2, and melanocyte-inducing transcription factor, which were completely or partially rescued upon reexpression of LMNA. Furthermore, lysine-specific demethylase 5A and 5B protein levels were increased in the hearts and were partially rescued upon LMNA reexpression. Analysis of biological function for rescued genes identified activation of tumor necrosis factor-α, epithelial to mesenchymal transition, and suppression of the oxidative phosphorylation pathway upon deletion and their restoration upon LMNA reintroduction in the heart. Restoration of the gene expression and transcriptional regulators in the heart was associated with improved cardiac function and increased survival of the mice. Conclusions The findings identify LMNA-regulated cardiac genes and their upstream transcriptional regulators in the heart and implicate lysine-specific demethylase 5A and B as epigenetic regulators of a subset of the dysregulated genes in laminopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.119.015690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660829PMC
August 2020

TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR4 Interacts with WRINKLED1 to Mediate Seed Oil Biosynthesis.

Plant Physiol 2020 10 6;184(2):658-665. Epub 2020 Jul 6.

School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore

Cross-family transcription factor (TF) interactions play critical roles in the regulation of plant developmental and metabolic pathways. WRINKLED1 (WRI1) is a key TF governing oil biosynthesis in plants. However, little is known about WRI1-interacting factors and their roles in oil biosynthesis. We screened a TF library using Arabidopsis () WRI1 (AtWRI1) as bait in yeast two-hybrid assays and identified three TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) family TFs, namely TCP4, TCP10, and TCP24, as AtWRI1-interacting partners. The physical interaction between AtWRI1 and TCPs was further validated using bimolecular fluorescence complementation assays. TCPs play important roles in various plant developmental processes; however, their involvement in fatty acid biosynthesis was not previously known. Coexpression of TCP4, but not TCP10 or TCP24, with AtWRI1 reduced AtWRI1-mediated oil biosynthesis in leaves. Transcriptomic analysis in transgenic Arabidopsis plants with enhanced TCP4 activity engineered by expressing (i.e. miR319-resistant ) revealed that AtWRI1 target genes were significantly repressed. TCP4 expression is strongly correlated with AtWRI1 during embryo development. A loss-of-function mutant, the mutant with a strong reduction of expression, and a triple mutant accumulated more seed oil than wild-type Arabidopsis. In addition, TCP4 repressed the AtWRI1-mediated transactivation of the promoters of fatty acid biosynthetic genes. Collectively, our findings suggest that TCP4 represses fatty acid biosynthetic gene expression through interaction with AtWRI1, leading to a reduction of AtWRI1-mediated seed oil accumulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1104/pp.20.00547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536675PMC
October 2020

Discovery of [1,2,4]Triazolo[1,5-]pyridine Derivatives as Potent and Orally Bioavailable RORγt Inverse Agonists.

ACS Med Chem Lett 2020 Apr 27;11(4):528-534. Epub 2020 Feb 27.

Faculty of Pharmaceutical Sciences and Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.

The retinoic acid receptor-related orphan nuclear receptor γt (RORγt), a promising therapeutic target, is a major transcription factor of genes related to psoriasis pathogenesis such as interleukin (IL)-17A, IL-22, and IL-23R. On the basis of the X-ray cocrystal structure of RORγt with , an analogue of the known piperazine RORγt inverse agonist , triazolopyridine derivatives of were designed and synthesized, and analogue was found to be a potent RORγt inverse agonist. Structure-activity relationship studies on , focusing on the treatment of its metabolically unstable cyclopentyl ring and the central piperazine core, led to a novel analogue, namely, 6-methyl--(7-methyl-8-(((2,4)-2-methyl-1-(4,4,4-trifluoro-3-(trifluoromethyl)butanoyl)piperidin-4-yl)oxy)[1,2,4]triazolo[1,5-]pyridin-6-yl)nicotinamide (), which exhibited strong RORγt inhibitory activity and a favorable pharmacokinetic profile. Moreover, the and evaluation of in a human whole-blood assay and a mouse IL-18/23-induced cytokine expression model revealed its robust and dose-dependent inhibitory effect on IL-17A production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsmedchemlett.9b00649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153279PMC
April 2020

Hydrogen Production from Formic Acid and Formaldehyde over Ruthenium Catalysts in Water.

Inorg Chem 2020 Apr 24;59(7):4234-4243. Epub 2020 Mar 24.

Catalysis Group, Discipline of Chemistry, Indian Institute of Technology Indore, Simrol, Indore 453552, India.

Water-soluble ruthenium complexes [(η-arene)Ru(κ-L)] ( = 0,1) (-) ligated with pyridine-based ligands are synthesized, and the molecular structure of the representative complex is confirmed by X-ray crystallography. The studied complexes are employed for the catalytic dehydrogenation of formic acid in water. Screening of these complexes inferred that [(η-CH)Ru(κ-NOH-)Cl] ( = pyridine-2-ylmethanol) outperformed others with an initial turnover frequency of 1548 h. Complex also exhibited high stability in water and can be recycled up to seven times with a total turnover number of 6050. In addition to formic acid dehydrogenation, also catalyzed the conversion of formaldehyde to hydrogen gas in water under base-free conditions. The effects of temperature, pH, formic acid, and catalyst concentration on the reaction kinetics are investigated in detail. Mass and NMR based mechanistic investigations inferred the presence of several important intermediate species, such as ruthenium-formate species and ruthenium-hydride species , involved in the catalytic dehydrogenation reaction. Moreover, the molecular structure of a diruthenium species is also authenticated by single-crystal X-ray crystallography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.9b02882DOI Listing
April 2020

Primary Eye Care in Eastern Nepal.

Ophthalmic Epidemiol 2020 06 16;27(3):165-176. Epub 2019 Dec 16.

International Centre for Eye Health, Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.

: Vision 2020 and the Global Action Plan 2013-2019 prioritise primary eye care (PEC) as an important component of reducing avoidable blindness. Studies in sub-Saharan Africa have demonstrated that current PEC provision is poor. There has been no evaluation of the current practice of PEC among primary health care workers (PHCWs) in Nepal.: A mixed methods descriptive cross-sectional study with semi-structured interviews and focus group discussions (FGDs) was carried out in Eastern Nepal. Government employed PHCWs working at health posts in three districts were invited to take part in a PEC knowledge and skills assessment. Each health post was assessed for ophthalmic equipment and medications. Three focus group discussions and eight semi-structured interviews were carried out with community ophthalmic assistants, PHCWs and a district health manager.: 107 PHCWs in 35 health posts took part in the quantitative study. Only 8.4% had received eye care training. 27.1% PHCWs could diagnose a corneal ulcer, 83.2% conjunctivitis, 75.7% cataract and 54.2% ophthalmia neonatorum. Only 14.0% could measure visual acuity, and 5.7% of HPs had a vision chart. Ophthalmic assistants described their concern for the low level of PEC at health posts. PHCWs were keen to receive training and highlighted the need for greater government support in the provision of eye care services.: PEC knowledge and skills among PHCWs in eastern Nepal is inadequate to provide quality PEC services. There is a pressing need for PEC training in the region, provision of ophthalmic equipment and greater government support for eye care.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09286586.2019.1702217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7114913PMC
June 2020

Fungal Pigments and Their Prospects in Different Industries.

Microorganisms 2019 Nov 22;7(12). Epub 2019 Nov 22.

Biodiversity and Palaeobiology Group, National Fungal Culture Collection of India (NFCCI), MACS' Agharkar Research Institute, G.G. Agarkar Road, Pune 411004, India.

The public's demand for natural, eco-friendly, and safe pigments is significantly increasing in the current era. Natural pigments, especially fungal pigments, are receiving more attention and seem to be in high demand worldwide. The immense advantages of fungal pigments over other natural or synthetic pigments have opened new avenues in the market for a wide range of applications in different industries. In addition to coloring properties, other beneficial attributes of fungal pigments, such as antimicrobial, anticancer, antioxidant, and cytotoxic activity, have expanded their use in different sectors. This review deals with the study of fungal pigments and their applications and sheds light on future prospects and challenges in the field of fungal pigments. Furthermore, the possible application of fungal pigments in the textile industry is also addressed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/microorganisms7120604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955906PMC
November 2019

A rare case of Rhupus syndrome with Hashimoto's thyroiditis, associated adverse effect of drugs and incidental findings.

J Family Med Prim Care 2019 Sep 30;8(9):3048-3050. Epub 2019 Sep 30.

Department of Medicine, Rajendra Institute of Medical Sciences, Ranchi, Jharkhand, India.

The term Rhupus is coded for the individuals who have rheumatoid like arthritis with erosions and fulfil the criteria for both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Abnormal Th2 cell plays a central role in SLE while Th1 participate in RA. Thus the overlap of SLE and RA has a very low incidence (0.01%-0.2%) in patient with arthritis. This 40-year-old male patient presented with complains of severe multiple joint pain with progressive deformities, diminished vision from last 2 months, redness on back, headache and swelling over scalp. As this patient had history of severe trauma that was considered as a precipitating factor for ongoing chronic inflammatory disorder. Posterior subcapsular cataract was explained by prolong use of systemic steroid and rashes on the lower back due to sulfasalazine. Radioimaging study revealed arachnoid cyst and calcified projection arising from outer table of skull, which was kept under observation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/jfmpc.jfmpc_568_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820406PMC
September 2019

Ruthenium Catalyzed Dehydrogenation of Alcohols and Mechanistic Study.

Inorg Chem 2019 Nov 18;58(21):14912-14923. Epub 2019 Oct 18.

Catalysis Group, Discipline of Chemistry , Indian Institute of Technology Indore , Simrol, Indore 453552 , India.

We synthesized pyridylamine ligated arene-Ru(II) complexes and employed these complexes for the catalytic acceptorless dehydrogenation of primary alcohols to carboxylic acids. All the synthesized complexes - are characterized using several spectro-analytical techniques, and the structures of complexes , , and are determined using single crystal X-ray crystallography. Efficient catalytic conversion of primary alcohols to potassium carboxylates or carboxylic acids is achieved in toluene with the quantitative release of hydrogen gas. The studied protocol for carboxylic acid synthesis with hydrogen generation is also employed for a wide range of substrates, including aliphatic alcohols, aromatic alcohols, and heteroaromatic alcohols, to obtain respective carboxylic acids in good yields (up to 86%). The studied arene-Ru catalysts also exhibit superior catalytic activity for the bulk reaction to achieve a turnover number of 1378. Moreover, extensive mass investigations are also performed to elucidate the mechanistic pathway by identifying the crucial catalytic intermediates, including aldehyde and diol coordinated Ru species under the catalytic and controlled reaction conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.9b02691DOI Listing
November 2019

Bilateral viral keratitis following corneal collagen crosslinking for progressive keratoconus.

J Ophthalmic Inflamm Infect 2019 Aug 28;9(1):16. Epub 2019 Aug 28.

Geta Eye Hospital, Kailali, Nepal.

Purpose: Corneal collagen crosslinking has been proven to be a useful technique to slow the progression of keratoconus. With its increasing use, we are encountering rare complications. We describe a case that developed bilateral viral keratitis after corneal collagen crosslinking with riboflavin and ultraviolet A for progressive keratoconus.

Case Report: An 18-year-old boy underwent corneal collagen crosslinking in both the eyes at the same setting for bilateral progressive keratoconus. He was discharged with a soft bandage contact lens and asked to follow up in 5 days. Seven days later, the patient returned with severe pain, redness, and photophobia for the last 2 days. The bandage contact lens was removed. There was a central corneal lesion in a branching dendritic pattern in both the eyes and the corneal sensation was reduced. Based on the findings, a clinical diagnosis of bilateral viral keratitis was made. The dendrite healed completely in 10 days with oral and topical acyclovir treatment, and the cornea had a faint scar at 1 month follow-up with best-corrected visual acuity of 6/9 in both eyes with a rigid gas permeable lens.

Discussion And Conclusion: Ultraviolet A light could be a stimulus to trigger reactivation of latent HSV infections even in patients with no history of clinically evident herpes virus ocular infections. Early diagnosis and timely treatment can have good visual outcome. Prophylactic antiviral medication may be useful to prevent this complication in individuals with prior history of viral keratitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12348-019-0185-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713774PMC
August 2019

Lithium-Doped Silica-Rich MIL-101(Cr) for Enhanced Hydrogen Uptake.

Chem Asian J 2019 Oct 11;14(20):3728-3735. Epub 2019 Sep 11.

Discipline of Chemistry, Indian Institute of Technology Indore, Simrol, Indore-, 453552, India.

Metal-organic frameworks (MOFs) show promising characteristics for hydrogen storage application. In this direction, modification of under-utilized large pore cavities of MOFs has been extensively explored as a promising strategy to further enhance the hydrogen storage properties of MOFs. Here, we described a simple methodology to enhance the hydrogen uptake properties of RHA incorporated MIL-101 (RHA-MIL-101, where RHA is rice husk ash-a waste material) by controlled doping of Li ions. The hydrogen gas uptake of Li-doped RHA-MIL-101 is significantly higher (up to 72 %) compared to the undoped RHA-MIL-101, where the content of Li ions doping greatly influenced the hydrogen uptake properties. We attributed the observed enhancement in the hydrogen gas uptake of Li-doped RHA-MIL-101 to the favorable Li ion-to-H interactions and the cooperative effect of silanol bonds of silica-rich rice-husk ash incorporated in MIL-101.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/asia.201900833DOI Listing
October 2019

Functionality of C-Reactive Protein for Atheroprotection.

Front Immunol 2019 16;10:1655. Epub 2019 Jul 16.

Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.

C-reactive protein (CRP) is a pentameric molecule made up of identical monomers. CRP can be seen in three different forms: native pentameric CRP (native CRP), non-native pentameric CRP (non-native CRP), and monomeric CRP (mCRP). Both native and non-native CRP execute ligand-recognition functions for host defense. The fate of any pentameric CRP after binding to a ligand is dissociation into ligand-bound mCRP. If ligand-bound mCRP is proinflammatory, like free mCRP has been shown to be , then mCRP along with the bound ligand must be cleared from the site of inflammation. Once pentameric CRP is bound to atherogenic low-density lipoprotein (LDL), it reduces both formation of foam cells and proinflammatory effects of atherogenic LDL. A CRP mutant, that is non-native CRP, which readily binds to atherogenic LDL, has been found to be atheroprotective in a murine model of atherosclerosis. Thus, unlike statins, a drug that can lower only cholesterol levels but not CRP levels should be developed. Since non-native CRP has been shown to bind to all kinds of malformed proteins in general, it is possible that non-native CRP would be protective against all inflammatory states in which host proteins become pathogenic. If it is proven through experimentation employing transgenic mice that non-native CRP is beneficial for the host, then using a small-molecule compound to target CRP with the goal of changing the conformation of endogenous native CRP would be preferred over using recombinant non-native CRP as a biologic to treat diseases caused by pathogenic proteins such as oxidized LDL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2019.01655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646712PMC
October 2020

Corneal deposition of fluoroquinolones after penetrating keratoplasty: case series.

Int Med Case Rep J 2019 8;12:151-154. Epub 2019 May 8.

Department of Cornea Clinic, Biratnagar Eye Hospital, Biratnagar, Nepal.

To report three cases of fluroquinolone deposition in the cornea after topical administration post-penetrating keratoplasty. Herein we report three patients ranging in age from 42-65 years who underwent keratoplasty with cataract extraction, with intraocular lens implantation in the first two cases and left aphakic due to a posterior capsular tear in the third case. The first two patients received ciprofloxacin-dexamethasone combination drops, and developed drug deposition, which was observed at the first follow-up after 7 and 10 days respectively. The third patient received prednisolone acetate and ofloxacin eyedrops postoperatively, and developed drug deposits in the cornea after 20 days. In all of the three patients, the fluroquinolone group of drugs was discontinued and the cornea cleared gradually over the next 3-4 weeks. Although the cornea cleared, the first two grafts failed due to recurrent viral infection in one case, and graft rejection in the other case. Deposition of many different fluroquinolones in the cornea has been reported after a variety of surgeries, including penetrating keratoplasty. Drug deposition post-penetrating keratoplasty may seem innocuous due to self-resolution on cessation of the drugs, but it may have deleterious effects on graft survival. Hence, fluroquinolones, especially ciprofloxacin, should be cautiously used in patients undergoing penetrating keratoplasty if frequent dosing is prescribed or if used concurrently with other topical medications containing preservatives.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/IMCRJ.S198011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512573PMC
May 2019

Visual Outcome of Descemet Membrane Endothelial Keratoplasty during the Learning Curve in Initial Fifty Cases.

J Ophthalmol 2019 17;2019:5921846. Epub 2019 Mar 17.

B.P.Koirala Lions Centre for Ophthalmic Studies, Maharajgunj Medical Campus, Institute of Medicine, Kathmandu 44600, Nepal.

This study was performed to evaluate the clinical outcomes of the first fifty patients who underwent Descemet membrane endothelial keratoplasty (DMEK) during the 3-month postoperative period and to describe the challenges encountered during the learning curve. In this retrospective study, we reviewed the charts of patients who underwent DMEK. All information regarding patient demographics, indication for surgery, preoperative and postoperative visual acuity at 3 months, donor age, and complications encountered intraoperatively and postoperatively was recorded. Donor endothelial cell count at the time of surgery and during the 3-month follow-up was noted. Data were analyzed using SPSS version 17. Fifty eyes of 49 patients were included in the study with majority being female patients (male : female = 2 : 3). Mean age of patients was 56.8 ± 11.4 years with the age range of 22-78 years. The common indications for DMEK were pseudophakic bullous keratopathy -57.1%, Fuchs endothelial dystrophy-34.7%, failed grafts-6.1% (Descemet stripping endothelial keratoplasty (DSEK) and failed penetrating keratoplasty), and others. Preoperative best spectacle-corrected visual acuity was <20/400 in 88% cases. Postoperative best spectacle-corrected visual acuity at 3 months was >20/63 in 41.8% of the cases, and 93% had visual acuity of 20/200 or better. Donor size was 8 mm, and average donor endothelial cell count (ECC) was 2919 ± 253 cells/mm. Average ECC at 3 months postoperatively was 1750 ± 664 cells/mm, which showed a 40% decrease in ECC. The most common encountered complication was graft detachment, which occurred in 16% cases for which rebubbling was done. Regular follow-up and timely identification of graft detachment may prevent the need for retransplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/5921846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441507PMC
March 2019

Ketoconazole and Posaconazole Selectively Target HK2-expressing Glioblastoma Cells.

Clin Cancer Res 2019 01 15;25(2):844-855. Epub 2018 Oct 15.

MacFeeters-Hamilton Center for Neuro-Oncology Research, Princess Margaret Cancer Center, Toronto, Ontario, Canada.

Purpose: Hexokinase II (HK2) protein expression is elevated in glioblastoma (GBM), and we have shown that HK2 could serve as an effective therapeutic target for GBM. Here, we interrogated compounds that target HK2 effectively and restrict tumor growth in cell lines, patient-derived glioma stem cells (GSCs), and mouse models of GBM. We performed a screen using a set of 15 drugs that were predicted to inhibit the HK2-associated gene signature. We next determined the EC of the compounds by treating glioma cell lines and GSCs. Selected compounds showing significant impact were used to treat mice and examine their effect on survival and tumor characteristics. The effect of compounds on the metabolic activity in glioma cells was also assessed .

Results: This screen identified the azole class of antifungals as inhibitors of tumor metabolism. Among the compounds tested, ketoconazole and posaconazole displayed the greatest inhibitory effect on GBM both and . Treatment of mice bearing GBM with ketoconazole and posaconazole increased their survival, reduced tumor cell proliferation, and decreased tumor metabolism. In addition, treatment with azoles resulted in increased proportion of apoptotic cells.

Conclusions: Overall, we provide evidence that azoles exert their effect by targeting genes and pathways regulated by HK2. These findings shed light on the action of azoles in GBM. Combined with existing literature and preclinical results, these data support the value of repurposing azoles in GBM clinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-18-1854DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103287PMC
January 2019

Harnessing genetic potential of wheat germplasm banks through impact-oriented-prebreeding for future food and nutritional security.

Sci Rep 2018 08 21;8(1):12527. Epub 2018 Aug 21.

ICAR-Indian Agricultural Research Institute, Regional Station, Shimla, 171004, India.

The value of exotic wheat genetic resources for accelerating grain yield gains is largely unproven and unrealized. We used next-generation sequencing, together with multi-environment phenotyping, to study the contribution of exotic genomes to 984 three-way-cross-derived (exotic/elite1//elite2) pre-breeding lines (PBLs). Genomic characterization of these lines with haplotype map-based and SNP marker approaches revealed exotic specific imprints of 16.1 to 25.1%, which compares to theoretical expectation of 25%. A rare and favorable haplotype (GT) with 0.4% frequency in gene bank identified on chromosome 6D minimized grain yield (GY) loss under heat stress without GY penalty under irrigated conditions. More specifically, the 'T' allele of the haplotype GT originated in Aegilops tauschii and was absent in all elite lines used in study. In silico analysis of the SNP showed hits with a candidate gene coding for isoflavone reductase IRL-like protein in Ae. tauschii. Rare haplotypes were also identified on chromosomes 1A, 6A and 2B effective against abiotic/biotic stresses. Results demonstrate positive contributions of exotic germplasm to PBLs derived from crosses of exotics with CIMMYT's best elite lines. This is a major impact-oriented pre-breeding effort at CIMMYT, resulting in large-scale development of PBLs for deployment in breeding programs addressing food security under climate change scenarios.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-30667-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6104032PMC
August 2018

A Coclinical Radiogenomic Validation Study: Conserved Magnetic Resonance Radiomic Appearance of Periostin-Expressing Glioblastoma in Patients and Xenograft Models.

Clin Cancer Res 2018 12 27;24(24):6288-6299. Epub 2018 Jul 27.

Department of Cancer Systems Imaging, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Purpose: Radiomics is the extraction of multidimensional imaging features, which when correlated with genomics, is termed radiogenomics. However, radiogenomic biological validation is not sufficiently described in the literature. We seek to establish causality between differential gene expression status and MRI-extracted radiomic-features in glioblastoma.

Experimental Design: Radiogenomic predictions and validation were done using the Cancer Genome Atlas and Repository of Molecular Brain Neoplasia Data glioblastoma patients ( = 93) and orthotopic xenografts (OX; = 40). Tumor phenotypes were segmented, and radiomic-features extracted using the developed radiome-sequencing pipeline. Patients and animals were dichotomized on the basis of Periostin ( expression levels. RNA and protein levels confirmed RNAi-mediated knockdown in OX. Total RNA of tumor cells isolated from mouse brains (knockdown and control) was used for microarray-based expression profiling. Radiomic-features were utilized to predict expression status in patient, mouse, and interspecies.

Results: Our robust pipeline consists of segmentation, radiomic-feature extraction, feature normalization/selection, and predictive modeling. The combination of skull stripping, brain-tissue focused normalization, and patient-specific normalization are unique to this study, providing comparable cross-platform, cross-institution radiomic features. expression status was not associated with qualitative or volumetric MRI parameters. Radiomic features significantly predicted expression status in patients (AUC: 76.56%; sensitivity/specificity: 73.91/78.26%) and OX (AUC: 92.26%; sensitivity/specificity: 92.86%/91.67%). Furthermore, radiomic features in OX were significantly associated with patients with similar expression levels (AUC: 93.36%; sensitivity/specificity: 82.61%/95.74%; = 02.021E-15).

Conclusions: We determined causality between radiomic texture features and expression levels in a preclinical model with clinical validation. Our biologically validated radiomic pipeline also showed the potential application for human-mouse matched coclinical trials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-17-3420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538261PMC
December 2018

Correction to: Genome-wide identification of hexokinase gene family in Brassica napus: structure, phylogenetic analysis, expression, and functional characterization.

Planta 2018 07;248(1):183

School of Life Sciences, Shanxi University, Taiyuan, 030006, Shanxi, China.

In the original version of this article the name of the second author was misspelled. The correct name is: Xiaomin Wang.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00425-018-2895-9DOI Listing
July 2018

Genome-wide identification of hexokinase gene family in Brassica napus: structure, phylogenetic analysis, expression, and functional characterization.

Planta 2018 Jul 11;248(1):171-182. Epub 2018 Apr 11.

School of Life Sciences, Shanxi University, Taiyuan, 030006, Shanxi, China.

Main Conclusion: Genome-wide identification, expression analysis, and functional characterization of previously uncharacterized hexokinase family of oil crop, Brassica napus, underscore the importance of this gene family in plant growth and development. In plants, the multi-gene family of dual-function hexokinases (HXKs) plays important roles in sugar metabolism and sensing that affect growth and development. Rapeseed (Brassica napus L.) is an important oil crop; however, little is known about the B. napus HXK gene family. We identified 19 putative HXKs in B. napus genome. B. rapa and B. oleracea, the two diploid progenitors of B. napus, contributed almost equally to the BnHXK genes. Phylogenetic analysis divided the 19 BnHXKs into four groups. The exon-intron structures of BnHXKs share high similarity to those of HXKs in Arabidopsis and rice. The group III and IV BnHXKs are highly expressed in roots, whereas group I members preferentially express in leaves. Analysis of seed transcriptomes at different developmental stages showed that most of group I and IV HXKs are highly expressed 2-weeks after pollination (2WAP), compared to 4WAP for group III. BnHKXs are differentially expressed in susceptible and tolerant B. napus cultivars after fungal infection, suggesting the possible involvement in defense response. We generated rapeseed RNAi lines for BnHXK9, a member of relatively less characterized group IV, by pollen-mediated gene transformation. The seedlings of BnHXK9-RNAi lines showed delayed growth compared to the wild type. The RNAi plants were dwarf with curly leaves, suggesting the involvement of BnHXK9 in plant development. Collectively, our findings provides a comprehensive account of BnHXK gene family in an important crop and a starting point for further elucidation of their roles in sugar metabolism and sensing, as well as plant growth and development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00425-018-2888-8DOI Listing
July 2018

Cyclopentadienyl-Ru(II)-Pyridylamine Complexes: Synthesis, X-ray Structure, and Application in Catalytic Transformation of Bio-Derived Furans to Levulinic Acid and Diketones in Water.

Inorg Chem 2018 Apr 5;57(8):4777-4787. Epub 2018 Apr 5.

Discipline of Chemistry, School of Basic Sciences , Indian Institute of Technology Indore , Simrol 453552 , Indore , India.

A series of cationic half-sandwich cyclopentadienyl-ruthenium(II)-pyridylamine complexes, [(η-CH)Ru(κ-L)(PPh)] (L = N-substituted pyridylamine ligands) ([Ru]-1-[Ru]-6), along with the analogous cyclopentadienyl-ruthenium(II)- N-isopropylpyridylimine complex [(η-CH)Ru(κ-L)(PPh)] (L = N-isopropylpyridylimine) ([Ru]-7), have been synthesized in good yields. Structural identities of all the complexes have been authenticated by H, C, and P NMR, mass spectrometry, and X-ray crystallography. The synthesized complexes exhibited high catalytic activity for the transformation of the bio-derived furans, 2-furfural (furfural), 5-methyl-2-furfural (5-MF), and 5-hydroxymethyl-2-furfural (5-HMF) to levulinic acid (LA) and the diketones, 3-hydroxyhexane-2,5-dione (3-HHD), 1-hydroxyhexane-2,5-dione (1-HHD), and hexane-2,5-dione (HD) in water. Efficient transformation of furfural to LA over a range of η-Cp-Ru-pyridylamine complexes is substantially affected by the N-substituents, where a η-Cp-Ru- N-propylpyridylamine complex ([Ru]-2) exhibited higher catalytic activity in comparison to other η-Cp-Ru-pyridylamine and η-Cp-Ru-pyridylimine complexes. The relative catalytic activity of the studied complexes demonstrated a substantial structure-activity relationship which is governed by the basicity of N, steric hindrance at N, and the hemilabile nature of the coordinated pyridylamine ligands.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.inorgchem.8b00536DOI Listing
April 2018

Dietary supplementation of n-3 polyunsaturated fatty acid alters endometrial expression of genes involved in prostaglandin biosynthetic pathway in breeding sows (Sus scrofa).

Theriogenology 2018 Apr;110:201-208

ICAR-Indian Veterinary Research Institute, Bareilly, UP, 243122, India; ICAR-Central Institute for Research on Goats, Mathura, UP, 281122, India.

The present investigation was designed to study the effect of dietary supplementation of omega-3 (n-3) PUFA on endometrial expression of fertility-related genes in breeding sows. Sixteen crossbred sows were randomized to receive diets containing 4% (wt/wt) flaxseed oil as n-3 PUFA source (TRT group) or iso-nitrogenous, iso-caloric standard control diet (CON group), starting from the first day of estrus up to 40 days and were artificially bred on the second estrus. Endometrial samples were collected during days 10-11 and 15-16 post-mating for studying relative expression profile of candidate genes viz. Prostaglandin F Synthase (PGFS), microsomal Prostaglandin E Synthase-1 (mPGES-1) and Carbonyl Reductase-1 (CBR-1) using quantitative Real-Time PCR. Expression level of mPGES-1 gene transcript was 2.1-fold higher (P < 0.05) during 10-11 days of pregnancy and 1.4-fold higher (P > 0.05) during 15-16 days of pregnancy in TRT group as compared to CON group. Relative expression of PGFS gene transcript was significantly lower (P < 0.05) during 10-11 days of pregnancy in TRT group while there was no significant effect (P > 0.05) of dietary supplementation during 15-16 days of pregnancy. Endometrial mRNA level of CBR1 was significantly lower (P < 0.05) with 3.93-fold decrease in TRT group during 10-11 days of pregnancy whereas 2.82-fold reduction in expression (P > 0.05) was observed subsequently during 15-16 days of pregnancy as compared to CON group. Collectively, these results indicate that dietary n-3 PUFA supplementation can modulate gene expression of key enzymes in prostaglandin biosynthetic pathway during early gestation, which in turn might have beneficial impact on overall reproductive response in breeding sows. These findings partly support strategic dietary supplementation of plant-based source of n-3 PUFA with an aim to improve overall reproductive performance in sows.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.theriogenology.2018.01.009DOI Listing
April 2018

Development of a High-Resolution Multi-Locus Microsatellite Typing Method for .

Mycobiology 2017 Dec 31;45(4):401-408. Epub 2017 Dec 31.

National Fungal Culture Collection of India (NFCCI), Biodiversity and Palaeobiology Group, MACS-Agharkar Research Institute, Pune 411004, India.

is an economically important fungal pathogen causing substantial yield losses indifferent host plants. To understand the genetic diversity and molecular epidemiology of this fungus, we have developed a novel, high-resolution multi-locus microsatellite typing (MLMT) method. Bioinformatic analysis of unannotated genome sequence yielded eight potential microsatellite loci, of which five, CG1 (GT), CG2 (GT1), CG3 (TC), CG4 (CT), and CG5 (CT1) were selected for further study based on their universal amplification potential, reproducibility, and repeat number polymorphism. The selected microsatellites were used to analyze 31 strains of isolated from 20 different host plants from India. All microsatellite loci were found to be polymorphic, and the approximate fragment sizes of microsatellite loci CG1, CG2, CG3, CG4, and CG5 were in ranges of 213-241, 197-227, 231-265, 209-275, and 132-188, respectively. Among the 31 isolates, 55 different genotypes were identified. The Simpson's index of diversity (D) values for the individual locus ranged from 0.79 to 0.92, with the D value of all combined five microsatellite loci being 0.99. Microsatellite data analysis revealed that isolates from , (chili pepper), and (mango) formed distinct clusters, therefore exhibited some level of correlation between certain genotypes and host. The developed MLMT method would be a powerful tool for studying the genetic diversity and any possible genotype-host correlation in .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5941/MYCO.2017.45.4.401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780373PMC
December 2017

Dexamethasone-mediated oncogenicity in vitro and in an animal model of glioblastoma.

J Neurosurg 2018 12;129(6):1446-1455

Departments of2Cancer Systems Imaging.

OBJECTIVEDexamethasone, a known regulator of mesenchymal programming in glioblastoma (GBM), is routinely used to manage edema in GBM patients. Dexamethasone also activates the expression of genes, such as CEBPB, in GBM stem cells (GSCs). However, the drug's impact on invasion, proliferation, and angiogenesis in GBM remains unclear. To determine whether dexamethasone induces invasion, proliferation, and angiogenesis in GBM, the authors investigated the drug's impact in vitro, in vivo, and in clinical information derived from The Cancer Genome Atlas (TCGA) cohort.METHODSExpression profiles of patients from the TCGA cohort with mesenchymal GBM (n = 155) were compared with patients with proneural GBM by comparative marker selection. To obtain robust data, GSCs with IDH1 wild-type (GSC3) and with IDH1 mutant (GSC6) status were exposed to dexamethasone in vitro and in vivo and analyzed for invasion (Boyden chamber, human-specific nucleolin), proliferation (Ki-67), and angiogenesis (CD31). Ex vivo tumor cells from dexamethasone-treated and control mice were isolated by fluorescence activated cell sorting and profiled using Affymetrix chips for mRNA (HTA 2.0) and microRNAs (miRNA 4.0). A pathway analysis was performed to identify a dexamethasone-regulated gene signature, and its relationship with overall survival (OS) was assessed using Kaplan-Meier analysis in the entire GBM TCGA cohort (n = 520).RESULTSThe mesenchymal subgroup, when compared with the proneural subgroup, had significant upregulation of a dexamethasone-regulated gene network, as well as canonical pathways of proliferation, invasion, and angiogenesis. Dexamethasone-treated GSC3 demonstrated a significant increase in invasion, both in vitro and in vivo, whereas GSC6 demonstrated a modest increase. Furthermore, dexamethasone treatment of both GSC3 and GSC6 lines resulted in significantly elevated cell proliferation and angiogenesis in vivo. Patients with mesenchymal GBM had significant upregulation of dexamethasone-regulated pathways when compared with patients with proneural GBM. A prognostic (p = 0.0007) 33-gene signature was derived from the ex vivo expression profile analyses and used to dichotomize the entire TCGA cohort by high (median OS 12.65 months) or low (median OS 14.91 months) dexamethasone signature.CONCLUSIONSThe authors present evidence that furthers the understanding of the complex effects of dexamethasone on biological characteristics of GBM. The results suggest that the drug increases invasion, proliferation, and angiogenesis in human GSC-derived orthotopic tumors, potentially worsening GBM patients' prognoses. The authors believe that careful investigation is needed to determine how to minimize these deleterious dexamethasone-associated side effects in GBM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2017.7.JNS17668DOI Listing
December 2018

Core-Shell Zeolitic Imidazolate Frameworks for Enhanced Hydrogen Storage.

ACS Omega 2018 Jan 5;3(1):167-175. Epub 2018 Jan 5.

Discipline of Mechanical Engineering, Discipline of Chemistry, and Discipline of Metallurgy Engineering and Materials Science, Indian Institute of Technology Indore, Simrol, Indore 453552, India.

Core-shell [email protected] and [email protected] zeolitic imidazolate frameworks (ZIFs) were synthesized solvothermally using a seed-mediated methodology. Transmission electron microscopy-energy-dispersive X-ray spectrometry, line scan, elemental mapping, X-ray photoelectron spectroscopy, and inductively coupled plasma-atomic emission spectroscopy analyses were performed to confirm the formation of a core-shell structure with the controlled Co/Zn elemental composition of ∼0.50 for both the core-shell ZIFs. The synthesized core-shell [email protected] and [email protected] frameworks conferred enhanced H (2.03 and 1.69 wt %) storage properties at 77 K and 1 bar, which are ca. 41 and 18%, respectively, higher than that of the parent ZIF-8. Notably, the distinctly remarkable H storage properties shown by both the core-shell ZIFs over the bimetallic Co/Zn-ZIF and the physical mixture of ZIF-8 and ZIF-67 clearly evidenced their unique structural properties (confinement of porosity) and elemental heterogeneity due to the core-shell morphology of the outperforming core-shell ZIFs. Moreover, H adsorption isotherm data of these frameworks are best fitted with the Langmuir model ( ≥ 0.9999). Along with the remarkably enhanced H storage capacities, the core-shell ZIFs also displayed an improved CO capture behavior. Hence, we demonstrated here that the controlled structural features endorsed by the rationally designed porous materials may find high potential in H storage applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsomega.7b01693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6641309PMC
January 2018

Staphylococcus aureus intracellular survival: A closer look in the process.

Authors:
Sanjay K Singh

Virulence 2017 11 24;8(8):1506-1507. Epub 2017 Nov 24.

a Department of Biomedical Sciences , East Tennessee State University , Johnson City , USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/21505594.2017.1384896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5810479PMC
November 2017