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Evaluating the Efficacy of Gelatin-Chitosan-Tetraethyl Orthosilicate Calcium Hydroxide Composite as a Dental Pulp Medicament on COX-2, PGP 9.5, TNF-α Expression and Neutrophil number

Ghadah Abdulrahman AQ, Endytiastuti E, Ardhani R, Sutardjo Rus Sudarso I, Pidhatika B, Fauzi MB, et al.

F1000Res, 2024;13:1258.
PMID: 40012745 DOI: 10.12688/f1000research.156336.2

INTRODUCTION: Calcium hydroxide (Ca(OH) 2) is the material of choice for pulp therapy. However, Ca(OH) 2 has drawbacks such as toxicity, poor sealing, and tunnel defect formation. Alternative materials have been developed to provide more biocompatible materials with better dentin formation ability. The objective of this study was to evaluate the effect of composites containing gelatin (G), chitosan (CH), tetraethyl orthosilicate (TEOS), and Ca(OH) 2, namely G-CH-TEOS-Ca (OH) 2 (Extended data) on inflammation of the dental pulp (expression of COX-2, PGP 9.5, TNF-α, and neutrophil number).
MATERIALS AND METHODS: A total of 16 Wistar rat models of acute pulp injury were prepared and divided into two groups, treatment and control, 8 with each. In the treatment group, we applied a pulp-capping material using G-CH-TEOS-Ca (OH) 2 and Ca(OH) 2. On the 1 st and 3 rd days, rats were sacrificed. Tissue samples from 4 rats in each group were processed for histological preparation. COX-2, PGP 9.5, and TNF-α were observed using immunohistochemical (IHC) staining, and neutrophil numbers were observed using hematoxylin-eosin staining. Image analysis of COX-2, PGP 9.5, and TNF-α expression was performed using ImageJ software.
RESULTS: The results showed a decrease in COX-2 expression, but not significantly while PGP 9.5 and TNF-α expression were significantly higher than those in the control group. Neutrophil numbers were lower in the treatment group than in the control group, but the difference was not statistically significant.
CONCLUSION: The G-CH-TEOS-Ca (OH) 2 composite material may have potential as an exposed pulp medicament by reducing inflammation (COX-2 expression and number of neutrophils) and increasing the regeneration factor (TNF-α expression) and nerve (PGP 9.5 expression).

Matched MeSH terms: Ubiquitin Thiolesterase/metabolism
Fulltext Identification of novel human USP2 inhibitor and its putative role in treatment of COVID-19 by inhibiting SARS-CoV-2 papain-like (PLpro) protease

Mirza MU, Ahmad S, Abdullah I, Froeyen M

Comput Biol Chem, 2020 Dec;89:107376.
PMID: 32979815 DOI: 10.1016/j.compbiolchem.2020.107376

Human ubiquitin carboxyl-terminal hydrolase-2 (USP2) inhibitors, such as thiopurine analogs, have been reported to inhibit SARS-CoV papain-like proteases (PLpro). The PLpro have significant functional implications in the innate immune response during SARS-CoV-2 infection and considered an important antiviral target. Both proteases share strikingly similar USP fold with right-handed thumb-palm-fingers structural scaffold and conserved catalytic triad Cys-His-Asp/Asn. In this urgency situation of COVID-19 outbreak, there is a lack of in-vitro facilities readily available to test SARS-CoV-2 inhibitors in whole-cell assays. Therefore, we adopted an alternate route to identify potential USP2 inhibitor through integrated in-silico efforts. After an extensive virtual screening protocol, the best compounds were selected and tested. The compound Z93 showed significant IC50 value against Jurkat (9.67 μM) and MOTL-4 cells (11.8 μM). The binding mode of Z93 was extensively analyzed through molecular docking, followed by MD simulations, and molecular interactions were compared with SARS-CoV-2. The relative binding poses of Z93 fitted well in the binding site of both proteases and showed consensus π-π stacking and H-bond interactions with histidine and aspartate/asparagine residues of the catalytic triad. These results led us to speculate that compound Z93 might be the first potential chemical lead against SARS-CoV-2 PLpro, which warrants in-vitro evaluations.

Matched MeSH terms: Ubiquitin Thiolesterase/antagonists & inhibitors*; Ubiquitin Thiolesterase/metabolism
pink1, atp13a2 and uchl1 expressions are affected by inflammation in the brain

Moriya S, Tan VP, Yee AK, Parhar IS

Neurosci Lett, 2019 08 24;708:134330.
PMID: 31201839 DOI: 10.1016/j.neulet.2019.134330

In Parkinson's disease (PD), several genes have been identified as the PD-related genes, however, the regulatory mechanisms of these gene expressions have not been fully identified. In this study, we investigated the effect of inflammation, one of the major risk factors in PD on expressions of the PD-related genes. Lipopolysaccharide (LPS) was intraperitoneally administered to mature male zebrafish and gene expressions in the brains were examined by real-time PCR. In the inflammation-related genes, expressions of tnfb, il1b and il6 were increased at 2 days post administration in the 10 μg group, and tnfb expression was also increased at 4 days post administration in the 1 μg and 10 μg group. In the PD-related genes, pink1 expression was significantly decreased at 4 days, atp13a2 expression was significantly increased at 7 days, and uchl1 expression was significantly decreased at 7 days. This suggests that pink1, atp13a2 and uchl1 expressions are regulated by inflammation, and this regulatory mechanism might be involved in the progress of PD.

Matched MeSH terms: Ubiquitin Thiolesterase/genetics; Ubiquitin Thiolesterase/metabolism*
Quercetin glycosides induced neuroprotection by changes in the gene expression in a cellular model of Parkinson's disease

Magalingam KB, Radhakrishnan A, Ramdas P, Haleagrahara N

J Mol Neurosci, 2015 Mar;55(3):609-17.
PMID: 25129099 DOI: 10.1007/s12031-014-0400-x

Quercetin glycosides, rutin and isoquercitrin, are potent antioxidants that have been found to possess neuroprotective effect in diseases like Parkinson's and Alzheimer's disease. In the present study, we have examined the gene expression changes with rutin and isoquercitrin pretreatment on 6-hydroxydopamine (6-OHDA)-treated toxicity in rat pheochromocytoma (PC12) cells. PC12 cells were pretreated with rutin or isoquercitrin and subsequently exposed to 6-OHDA. Rutin-pretreated PC12 attenuated the Park2, Park5, Park7, Casp3, and Casp7 genes which were expressed significantly in the 6-OHDA-treated PC12 cells. Rutin upregulated the TH gene which is important in dopamine biosynthesis, but isoquercitrin pretreatment did not affect the expression of this gene. Both rutin and isoquercitrin pretreatments upregulated the ion transport and antiapoptotic genes (NSF and Opa1). The qPCR array data were further validated by qRT-PCR using four primers, Park5, Park7, Casp3, and TH. This finding suggests that changes in the expression levels of transcripts encoded by genes that participate in ubiquitin pathway and dopamine biosynthesis may be involved in Parkinson's disease.

Matched MeSH terms: Ubiquitin Thiolesterase/genetics; Ubiquitin Thiolesterase/metabolism*