Blue fluorescent gold nanoclusters were prepared in the presence of poly-cytosine DNAs at low pH and poly-adenine at neutral pH using citrate as the reducing agent; various buffer conditions ...affecting the synthesis have been explored.
Oral mucositis (OM) is a common, painful side effect of radiation therapy used for the treatment of head and neck cancer (HNC). Activation of the innate immune system upon irradiation has been ...identified as a key precipitating event of OM. To better understand OM's pathogenesis, we studied pattern recognition receptors (PRRs) and their downstream pro-inflammatory cytokines in a mouse model of radiation-induced OM. We also tested therapeutic efficacy of GM-1111 that targets innate immune system to reduce radiation-induced OM.
The pathogenesis of OM was studied in a single X-ray induced mouse model. The severity of OM was measured by visual and microscopical examinations. The irradiation-induced changes of PRRs and their downstream effector cytokine gene expression levels were determined. The efficacy of GM-1111 to reduce OM was tested in single and fractionated irradiation mouse models. The impact of the drug on tumor response to radiation therapy was also tested in a mouse model of human HNC.
Radiation-induced tissue ulcerations were radiation-dosage and -time dependent. The lesions showed selective increases in PRR and pro-inflammatory cytokine gene expression levels. Once daily administration of GM-1111 (≥30 mg/kg, s.c.) significantly reduced the severity and the incidence of OM. The drug had little effect on PRRs but significantly inhibited downstream pro-inflammatory cytokine genes. GM-1111 did not interfere radiation therapy to induce HNC SCC-25 tumor regression. Instead, we observed significant drug-induced tumor regression.
Radiation induces tissue damages. The increased expression levels of PRRs and their downstream pro-inflammatory cytokine genes in the damaged tissues suggest their important contribution to the pathogenesis of OM. Drug GM-1111 that targets these innate immune molecules may be a potential drug candidate as an intervention for OM.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic rhinosinusitis (CRS) is characterized by sustained mucosal inflammation, impaired mucociliary clearance, loss of cilia and epithelial barrier breakdown, and tissue remodeling. Certain ...glycosaminoglycans inhibit various inflammatory mediators, suppress bacterial growth, and provide important functions in mucosal tissue repair and mucociliary clearance. Herein, we evaluated the effects of a synthetic glycosaminoglycan, GM-1111, on the clinical signs and inflammatory tissue changes associated with CRS in mice. CRS was generated by repeated intranasal applications of Aspergillus fumigatus (A. fumigatus) extracts over 4 weeks. Mice were then intranasally administered GM-1111 (600 μg per dose, 5 times a week) or vehicle (phosphate buffered saline, PBS) for an additional 4 weeks while still being given A. fumigatus extracts to maintain a chronic inflammatory environment with acute exacerbations. Clinical signs indicative of sinonasal inflammation were recorded throughout the study. After 9 weeks, whole blood and sinonasal tissues were harvested for hematological, histological, and biochemical examination. The clinical signs, white blood cell counts, tissue markers of sinonasal inflammation, and histological changes caused by A. fumigatus extract administration were compared to the healthy (PBS vehicle) and GM-1111-treated groups (n = 12 per treatment group). Compared to vehicle-treated animals, animals treated with GM-1111 demonstrated significant reductions in clinical signs (p<0.05), degenerative tissue changes, goblet cell hyperplasia, inflammatory cell infiltration (p<0.01), innate immunity- (tlr2, tlr4, myd88, il1b, tnfa, il6, and il12) and adaptive immunity-associated (ccl11, ccl24, ccl5, il4, il5, and il13) cytokine gene expression (p<0.05 to p<0.0001) in sinonasal tissues, and serum IgE levels (p<0.01). Our data suggest that GM-1111 significantly reduces local and systemic effects of CRS-associated sinonasal inflammation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Periodontitis is characterized by microbial infection, inflammation, tissue breakdown, and accelerated loss of alveolar bone matrix. Treatment targeting these multiple stages of the disease provides ...ways to treat or prevent periodontitis. Certain glycosaminoglycans (GAGs) block multiple inflammatory mediators as well as suppress bacterial growth, suggesting that these GAGs may be exploited as a therapeutic for periodontitis.
We investigated the effects of a synthetic GAG, GM-0111, on various molecular events associated with periodontitis: growth of Porphyromonas gingivalis (P. gingivalis) and Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) pathogenic bacteria associated with periodontitis; activation of pro-inflammatory signaling through TLR2 and TLR4 in mouse macrophage RAW 264.7 cells and heterologously expressed HEK 293 cells; osteoclast formation and bone matrix resorption in cultured mouse pre-osteoclasts.
(1) GM-0111 suppressed the growth of P. gingivalis and A. actinomycetemcomitans even at 1% (w/v) solution. The antibacterial effects of GM-0111 were stronger than hyaluronic acid (HA) or xylitol in P. gingivalis at all concentrations and comparable to xylitol in A. actinomycetemcomitans at ≥2% (w/v) solution. We also observed that GM-0111 suppressed biofilm formation of P. gingivalis and these effects were much stronger than HA. (2) GM-0111 inhibited TLR-mediated pro-inflammatory cellular signaling both in macrophage and HEK 293 cells with higher selectivity for TLR2 than TLR4 (IC50 of 1-10 ng/mL vs. > 100 μg/mL, respectively). (3) GM-0111 blocked RANKL-induced osteoclast formation (as low as 300 ng/mL) and bone matrix resorption. While GM-0111 showed high affinity binding to RANKL, it did not interfere with RANKL/RANK/NF-κB signaling, suggesting that GM-0111 inhibits osteoclast formation by a RANKL-RANK-independent mechanism.
We report that GM-0111 inhibits multiple molecular events involved in periodontitis, spanning from the early pro-inflammatory TLR signaling, to pathways activated at the later stage component of bone loss.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
THOMAS R. KLEI1942–2022 Kennedy, Thomas J; Christensen, Bruce M
The Journal of parasitology,
09/2022, Letnik:
108, Številka:
5
Journal Article
Recenzirano
Professor Thomas R. Klei, parasitologist at the Louisiana State University (LSU) School of Veterinary Medicine since 1975, died on 18 April 2022 at the age of 79. Dr. Klei's research was continuously ...funded by the National Institutes of Health, the World Health Organization, the United States Department of Agriculture, and various pharmaceutical industries. For 11 years he was the Associate Dean for Research and Advanced Studies in the School of Veterinary Medicine and served as LSU's Interim Vice Chancellor for Research and Economic Development in 2013.
In 1864 Alida and Calvin Clark, two abolitionist members of the Religious Society of Friends from Indiana, went on a mission trip to Helena, Arkansas. The Clarks had come to render temporary relief ...to displaced war orphans but instead found a lifelong calling. During their time in Arkansas, they started the school that became Southland College, which was the first institution of higher education for blacks west of the Mississippi, and they set up the first predominately black monthly meeting of the Religious Society of Friends in North America. Their progressive racial vision was continued by a succession of midwestern Quakers willing to endure the primitive conditions and social isolation of their work and to overcome the persistent challenges of economic adversity, social strife, and natural disaster. Southland's survival through six difficult and sometimes dangerous decades reflects both the continuing missionary zeal of the Clarks and their successors as well as the dedication of the black Arkansans who sought dignity and hope at a time when these were rare commodities for African Americans in Arkansas.
Rosacea is a common disfiguring skin disease of primarily Caucasians characterized by central erythema of the face, with telangiectatic blood vessels, papules and pustules, and can produce skin ...thickening, especially on the nose of men, creating rhinophyma. Rosacea can also produce dry, itchy eyes with irritation of the lids, keratitis and corneal scarring. The cause of rosacea has been proposed as over-production of the cationic cathelicidin peptide LL-37.
We tested a new class of non-anticoagulant sulfated anionic polysaccharides, semi-synthetic glycosaminoglycan ethers (SAGEs) on key elements of the pathogenic pathway leading to rosacea. SAGEs were anti-inflammatory at ng/ml, including inhibition of polymorphonuclear leukocyte (PMN) proteases, P-selectin, and interaction of the receptor for advanced glycation end-products (RAGE) with four representative ligands. SAGEs bound LL-37 and inhibited interleukin-8 production induced by LL-37 in cultured human keratinocytes. When mixed with LL-37 before injection, SAGEs prevented the erythema and PMN infiltration produced by direct intradermal injection of LL-37 into mouse skin. Topical application of a 1% (w/w) SAGE emollient to overlying injected skin also reduced erythema and PMN infiltration from intradermal LL-37.
Anionic polysaccharides, exemplified by SAGEs, offer potential as novel mechanism-based therapies for rosacea and by extension other LL-37-mediated and RAGE-ligand driven skin diseases.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The current research aimed to know the effect of phonological and phonetic interventions in enhancing proficiency in English pronunciation and oral reading among teacher trainees. This study was of ...single-group pretest and posttest intervention designs. The sample size was selected through a stratified random sampling technique from teacher training colleges in Bengaluru. Two hundred and seven teacher trainees with L1 proficiency were chosen proportionately from Bangalore strata and orientated. Participants (N = 32) enrolled voluntarily in the intervention program for 20 hr. Intervention modules on phonology and phonetics were developed by the researcher and a segmental approach was adopted to teach modules in 20 sessions. After every session, the participants were allowed to record the modules in Audacity, a multiaudio recorder application. The recorded modules were interpreted, and scores were determined on number of intelligible words pronounced by the participants. Further, it was validated by the experts to authenticate the determined scores. The researcher applied oscillographic and observation methods to analyze the participants’ progress in pronunciation and oral reading proficiency levels during the experiment. The Wilcoxon signed-rank test was used to test the impact of intervention between the pretest and posttest (before and after intervention). The hypotheses testing revealed the difference between preintervention and postintervention scores in phonological and phonetic awareness and oral reading among teacher trainees, and the sig. value is less than 0.05 across all the attributes. This study insists that English phonology and phonetics must be a crucial part of the English language teaching (ELT) curriculum and highlights that teachers must be able to spot the most appropriate pronunciation teaching and train the students of English as a foreign language (EFL) with intricates of intelligible pronunciation. This study navigates the need for language proficiency among teacher trainees, especially in English pronunciation and oral reading, and substantiates the evidence that effective intervention and teachers’ knowledge of pronunciation enhance proficiency levels in pronunciation and oral reading among teacher trainees. Finally, it hopes that B.Ed colleges and teacher educators will be beckoned to use technology-integrated intervention to teach phonology and phonetics.
This book is a volume in the Penn Press Anniversary Collection. To mark its 125th anniversary in 2015, the University of Pennsylvania Press rereleased more than 1, 100 titles from Penn Press's ...distinguished backlist from 1899-1999 that had fallen out of print. Spanning an entire century, the Anniversary Collection offers peer-reviewed scholarship in a wide range of subject areas.
This book is a volume in the Penn Press Anniversary Collection. To mark its 125th anniversary in 2015, the University of Pennsylvania Press rereleased more than 1, 100 titles from Penn Press's ...distinguished backlist from 1899-1999 that had fallen out of print. Spanning an entire century, the Anniversary Collection offers peer-reviewed scholarship in a wide range of subject areas.
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