Corrigendum: Stylopine: a potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy.

[This corrects the article DOI: 10.3389/fphar.2023.1150270.].

Current appraises of therapeutic applications of nanocurcumin: A novel drug delivery approach for biomaterials in dentistry.

Curcumin is a natural herb and polyphenol that is obtained from the medicinal plant Curcuma longa. It's anti-bacterial, anti-inflammatory, anti-cancer, anti-mutagenic, antioxidant and antifungal properties can be leveraged to treat a myriad of oral and systemic diseases. However, natural curcumin has weak solubility, limited bioavailability and undergoes rapid degradation, which severely limits its therapeutic potential. To overcome these drawbacks, nanocurcumin (nCur) formulations have been developed for improved biomaterial delivery and enhanced treatment outcomes. This novel biomaterial holds tremendous promise for the treatment of various oral diseases, the majority of which are caused by dental biofilm. These include dental caries, periodontal disease, root canal infection and peri-implant diseases, as well as other non-biofilm mediated oral diseases such as oral cancer and oral lichen planus. A number of in-vitro studies have demonstrated the antibacterial efficacy of nCur in various formulations against common oral pathogens such as S. mutans, P. gingivalis and E. faecalis, which are strongly associated with dental caries, periodontitis and root canal infection, respectively. In addition, some clinical studies were suggestive of the notion that nCur can indeed enhance the clinical outcomes of oral diseases such as periodontitis and oral lichen planus, but the level of evidence was very low due to the small number of studies and the methodological limitations of the available studies. The versatility of nCur to treat a diverse range of oral diseases augurs well for its future in dentistry, as reflected by rapid pace in which studies pertaining to this topic are published in the scientific literature. In order to keep abreast of the latest development of nCur in dentistry, this narrative review was undertaken. The aim of this narrative review is to provide a contemporaneous update of the chemistry, properties, mechanism of action, and scientific evidence behind the usage of nCur in dentistry.

Stylopine: A potential natural metabolite to block vascular endothelial growth factor receptor 2 (VEGFR2) in osteosarcoma therapy.

Vascular endothelial growth factor (VEGF) signals cell survival, cell migration, osteogenesis, cell proliferation, angiogenesis, and vascular permeability by binding to VEGF receptor 2 (VEGFR-2). Osteosarcoma is the most common primary bone cancer, majorly affects young adults. Activation of VEGFR-2 signaling is a therapeutic target for osteosarcoma. The present study aimed to evaluate the potency of stylopine in regulation of the VEGFR-2 signaling pathway and its anti-tumour effect human MG-63 osteosarcoma cells. The in silico study on benzylisoquinoline alkaloids was carried out for analyzing and shortlisting of compounds using a virtual screening, Lipinski's rule, bioavailability graphical RADAR plot, pharmacokinetics, toxicity, and molecular docking studies. Among the benzylisoquinoline alkaloids, stylopine was selected and subjected to in-vitro studies against human MG-63 osteosarcoma cells. Various experiments such as MTT assay, EtBr/AO staining, mitochondrial membrane potential assessment, transwell migration assay, gene expression analysis by a quantitative real time polymerase chain reaction (qRT-PCR) method, SDS-PAGE followed by immunoblotting were performed to evaluate its anti-tumour effect as compared to standard axitinib. The MTT assay indicates that stylopine inhibits cell proliferation in MG-63 cells. Similarly, as confirmed by the EtBr/Ao staining method, the MMP assay indicates that stylopine induces mitochondrial membrane damage and apoptosis as compared to axitinib. Moreover, stylopine inhibits the VEGF-165 induced MG-63 cell migration by a trans-well migration assay. The immunoblotting and qRT-PCR analysis showed that stylopine inhibits the VEGF-165 induced VEGFR2 expression in MG-63 cells. It is concluded that stylopine has potential to regulate VEGFR2 and can inhibit osteosarcoma cells to offer a new drug candidate for the treatment of bone cancer in future.

Glucagon-like peptide-1 receptor promotes osteoblast differentiation of dental pulp stem cells and bone formation in a zebrafish scale regeneration model.

Bone cells express the glucagon-like peptide 1 receptor (GLP-1R). However, its presence and role in human dental pulp derived stem cells (hDPSCs) remains elusive. Hence, in the current study, we isolated hDPSCs and differentiated them into osteoblasts, where GLP-1R expression was found to be upregulated during osteoblast differentiation. GLP-1 receptor agonist, liraglutide peptide treatment, increased osteoblast differentiation in hDPSCs by increasing calcium deposition, ALP activity, and osteoblast marker genes, Runx2, type 1 col, osteonectin, and osteocalcin. Furthermore, activation of long non-coding RNA (LncRNA) LINC00968 and microRNA-3658 signalling increased Runx2 expression. Specifically, liraglutide increased LncRNA-LINC00968 expression while decreasing miR-3658 expression. LINC00968 targets miR-3658, and miR-3658 targets Runx2. Additionally, in an in-vivo study, zebrafish scale regeneration model, liraglutide promoted calcium deposition, osteoblastic cell count, collagen 1α, osteonectin, osteocalcin, runx2a MASNA isoform expression (transcribed from promoter P1), and Ca/P ratio in scales. Overall, GLP-1R activation promotes osteoblast differentiation via Runx2/LncRNA-LINC00968/miR-3658 signalling in hDPSCs and promotes bone formation in zebrafish scale regeneration.

Effect of Common Mouthwashes on Mechanical Properties of Suture Materials Used in Dental Surgeries: A Laboratory Experiment.

BACKGROUND: Sutures play a pivotal role in promoting healing in any surgical procedure. However, the versatile nature of the oral environment entails additional properties in the suture materials to assure uneventful healing. A surgeon needs to understand these delicate intricacies in the immediate postoperative phase and needs some kind of algorithm in the selection of sutures that suits the different surgical scenarios. Therefore, a study was designed to observe the effect of four different types of mouthwash, viz. Avohex, Aloedent, Parodontax and Betadine, on the mechanical properties of Vicryl (polyglactin 910), PTFE (polytetrafluoroethylene), Prolene (polypropylene) and Mersilk. METHODS: A total of 288 suture samples were divided in four equal groups (72 = each group) and used for the experiments. Tensile load, tensile strength as well as percentage elongation of the suture materials were evaluated in the various stated media at 3rd, 7th, 10th and 14th days, which were compared with the controls. The results were analyzed statistically and inferences were drawn. RESULTS: Mersilk in (Avohex, Parodontax and Betadine) solutions showed a statistically significant decrease in tensile load over time. All the sutures had the highest tensile strength in Parodontax and had the lowest in Betadine solution. Vicryl and PTFE presented significant percentage elongation over time as compared to Prolene and Mersilk. CONCLUSION: The author has given certain recommendations but also states that there is no standard rule for the use of a particular suture material in all clinical situations. However, the selection of the suture material should be based on the type of surgery and preferences of the surgeon.

GC/MS characterization and computational kinome-wide screening of pomegranate fruit extract identifies key phytochemicals interacting to CDK kinases implicated in acute myeloid leukemia cells.

Punica granatum (Pomegranate fruit) and its constituents are proven effective against various cancer types. However, a kinome-wide screening for the active phytochemicals against kinases is not reported. This study aims in validating pomegranate fruit extract (PFE) against acute myeloid leukemia (AML) cells, and computationally identifying the phytochemicals interacting with active kinases. PFE was made with Soxhlet extractor using absolute ethanol. Gas-chromatography-mass spectroscopy (GC-MS) for phytochemical identification and MTT assay for cytotoxicity in AML (THP-1, TF-1 and HL-60) cells were performed. Apoptosis, CDK5 and CDK8 were assessed with flow cytometry. Kinase profiling was performed using In silico kinome screening. GC-MS analysis revealed 38 bioactive phytochemicals in PFE including pyrazoles, aldehydes, phenols, esters, pyranosides, and octadecadienoic acids. The extract inhibited the AML cell proliferations with GI50 values of 195.5 µg/ml, 289.1 µg/ml, and 353.5 µg/ml in THP-1, THP-1, and HL-60 cells, respectively. PFE also exhibited a dose-responsive increase in apoptotic cell populations when treated to the AML cells. Computational screening and modeling predicted three critical constituents, viz., Deoxyartemisinin, 3-Methyl-3-phenyl-3H-indazole, and 8-fluoro-5,6-dimethoxy-3,4-dihydro-2H-naphthalen-1-one of pomegranate extract to interact mainly with cyclin-dependent kinases, including CDK5 and CDK8. Proteinand ligand docking predicted binding energies, and binding pose for top candidate lead molecules. In vitro assay exhibited the anticancer properties of PFE in AML cells. Computational kinome screening predicted top three PFE constituents targeting CDKs which may be responsible for the demonstrated anticancer efficacy of the extract against AML. This hypothesis further aligned with observed efficacy of PFE to inhibit CDK5 and CDK8 in all AML cells tested. PRACTICAL APPLICATIONS: Though Punica granatum (Pomegranate fruit) and its constituents are proven effective against various cancer types, a kinome-wide screening for the active phytochemicals against kinases is not reported. In this study, we have conducted GC/MS characterization of the active phytochemicals of PFE and have performed a kinome-wide screening for all the 38 identified compounds toward 310 active kinases commonly expressed in cancers. These observations warrant isolation and further evaluation of these phytochemicals or their analogues as effective CDK inhibitors against AML proliferation. Further, the computational methods used in this study will throw light on literature for new options of kinome panel screening of active phytochemicals or small molecules.

Glycyrrhiza glabra (Licorice): A Comprehensive Review on Its Phytochemistry, Biological Activities, Clinical Evidence and Toxicology.

There are more than 30 species of Glycyrrhiza genus extensively spread worldwide. It was the most prescribed herb in Ancient Egyptian, Roman, Greek, East China, and the West from the Former Han era. There are various beneficial effects of licorice root extracts, such as treating throat infections, tuberculosis, respiratory, liver diseases, antibacterial, anti-inflammatory, and immunodeficiency. On the other hand, traditional medicines are getting the attraction to treat many diseases. Therefore, it is vital to screen the medicinal plants to find the potential of new compounds to treat chronic diseases such as respiratory, cardiovascular, anticancer, hepatoprotective, etc. This work comprehensively reviews ethnopharmacological uses, phytochemistry, biological activities, clinical evidence, and the toxicology of licorice, which will serve as a resource for future clinical and fundamental studies. An attempt has been made to establish the pharmacological effect of licorice in different diseases. In addition, the focus of this review article is on the molecular mechanism of licorice extracts and their four flavonoids (isoliquiritigenin, liquiritigenin, lichalocone, and glabridin) pharmacologic activities. Licorice could be a natural alternative for current therapy to exterminate new emerging disorders with mild side effects. This review will provide systematic insights into this ancient drug for further development and clinical use.

Recombinant Human Adenovirus-p53 Therapy for the Treatment of Oral Leukoplakia and Oral Squamous Cell Carcinoma: A Systematic Review.

Background and Objectives: Oral cancer is the 6th most common cancer in the world and oral leukoplakia is an oral potentially malignant disorder that could develop into oral cancer. This systematic review focusses on randomized clinical trials for recombinant adenovirus p-53 (rAD-p53) therapy for the treatment of oral leukoplakia and cancer. Materials and Methods: We searched for research articles on various databases such as Pubmed/Medline, Embase, CNKI (China National Knowledge Infra-structure), Springerlink, cochrane and Web of sciences from 2003 to 2020. MeSH (Medical Subject Headings) terms were used for the search. Inclusion criteria included original research, randomized clinical trials and articles only in English language. Exclusion criteria were any articles that were not research articles, not randomized trials, non-human studies, etc. The articles were further graded on the Jadad scale. Results: 578 articles were assessed from various databases; only 3 articles were found to be appropriate for this review. Thus, meta-analysis was not performed because of heterogeneity and lack of data. In the three studies, whether rAD-p53 was used as a standalone therapy or with other therapies, there was a beneficial effect of the therapy. Furthermore, there were no serious adverse events and the only adverse events reported were fever, pain at the local injection site, flu-like symptoms and lowered WBC count. Conclusions: Thus, we can conclude that this therapy has a potential for beneficial therapeutic effects and further clinical trials with more patients need to be performed to get better understanding of the effect of rAD-p53 therapy, which probably will pave the way to its approval in other parts of the world.

In-vitro evaluation of commonly used beverages on tensile strength of different suture materials used in dental surgeries.

Sutures are used for the approximation of incised flaps, assistance in primary healing, and hemorrhage control. In oral and periodontal surgery, the appropriate selection of suture material is vital for favorable healing.The aim of the present in-vitro experiment was to evaluate the tensile strengths of 4 different types of suture materials (silk, polygalactine 910, polypropylene, chromic catgut) by simulating potential short-term intraoral exposure to various beverages (saliva, Arabic coffee, tea, cola).A total of 280 suture specimens were prepared, out of which 10 specimens from each group were selected for pre-immersion testing. Remaining suture specimens were immersed in 4 different thermostatically controlled media (1 control [artificial saliva], 3 tests [Cola drink, Arabic coffee, Tea]). Tensile strength was measured at pre-immersion, 3, 7, and 14 days using a universal tensile testing machine. The maximum load required to break the suture material was recorded in Newton.At day 3, tea caused significant reduction in tensile strength of silk and cola caused significant reduction in tensile strengths of polygalactine 910 and chromic catgut. Whereas, at day 7, silk and polypropylene retained their tensile strengths better than others.The authors recommend precaution in the use of these beverages in the first postoperative week, to avoid adverse effect on the mechanical strength of sutures. When exposure to these beverages are anticipated, it is better to use polypropylene sutures that resists rapid fall in tensile strengths in the early postoperative period.

Effect of Smoking and Tobacco Chewing on Periodontal Disease and Non-Surgical Treatment Outcome: A Clinical and Biochemical Study.

OBJECTIVE: The purpose of this study was to compare effects of smoking and smokeless forms of tobacco consumption (tobacco chewing) on periodontal disease parameters and response of these subjects to non-surgical periodontal therapy. METHODS: One hundred sixty-eight patients with chronic periodontitis were screened for the study. Eighteen patients were excluded as they decided to quit the tobacco habit. One hundred fifty patients fulfilling the inclusion and exclusion criteria were grouped as: Group 1, 50 smokers; Group 2, 50 tobacco chewers; and Group 3, 50 non-smokers, non-tobacco chewers (controls). Scaling and root planing was performed at the initial visit as a part of initial therapy. The clinical parameters recorded at baseline, 1 month, 2 months and 3 months were plaque index (PI), gingival index (GI), probing depth (PD), gingival recession (GR), and gingival crevicular fluid (GCF) measurement. RESULTS: With respect to the comparison between smokers and tobacco chewers, smokers had significantly more probing depth at baseline examination, while tobacco chewers had more gingival recession. Gingival inflammation, response to non-surgical treatment and oral hygiene maintenance were more suppressed in smokers as compared to tobacco chewers. CONCLUSION: Tobacco consumption in both forms affects the severity of periodontal disease. It affects the response of periodontal tissues to non-surgical treatment. In addition it leads to poorer oral hygiene and hampers maintenance of oral hygiene.