Numerous studies have been conducted in the previous years with an objective to determine the ideal biomarker or set of biomarkers in temporomandibular disorders (TMDs). It was recorded that tumour necrosis factor (TNF), interleukin 8 (IL-8), IL-6, and IL-1 were the most common biomarkers of TMDs. As of recently, although the research on TMDs biomarkers still aims to find more diagnostic agents, no recent study employs the biomarker as a targeting point of pharmacotherapy to suppress the inflammatory responses. This article represents an explicit review on the biomarkers of TMDs that have been discovered so far and provides possible future directions towards further research on these biomarkers. The potential implementation of the interactions of TNF with its receptor 2 (TNFR2) in the inflammatory process has been interpreted, and thus, this review presents a new hypothesis towards suppression of the inflammatory response using TNFR2-agonist. Subsequently, this hypothesis could be explored as a potential pain elimination approach in patients with TMDs.

This systematic review aims to evaluate the antimicrobial activity of α-mangostin derived from Garcinia mangostana against different microbes. A literature search was performed using PubMed and Science Direct until March 2022. The research question was developed based on a PICO (Population, Intervention, Control and Outcomes) model. In this study, the population of interest was microbes, α-mangostin extracted from Garcinia mangostana was used as exposure while antibiotics were used as control, followed by the outcome which is determined by the antimicrobial activity of α-mangostin against studied microbes. Two reviewers independently performed the comprehensive literature search following the predetermined inclusion and exclusion criteria. A methodological quality assessment was carried out using a scoring protocol and the risk of bias in the studies was analyzed. Reward screening was performed among the selected articles to perform a meta-analysis based on the pre-determined criteria. Case groups where α-mangostin extracted from Garcinia mangostana was incorporated were compared to groups using different antibiotics or antiseptic agents (control) to evaluate their effectiveness. A total of 30 studies were included; they were heterogeneous in their study design and the risk of bias was moderate. The results showed a reduction in microbial counts after the incorporation of α-mangostin, which resulted in better disinfection and effectiveness against multiple microbes. Additionally, the meta-analysis result revealed no significant difference (p > 0.05) in their effectiveness when α-mangostin was compared to commercially available antibiotics. α-mangostin worked effectively against the tested microbes and was shown to have inhibitory effects on microbes with antibiotic resistance.

Temporomandibular disorders (TMDs) are a type of idiopathic orofacial pain. Inflammation, particularly elevated circulating levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and interleukin-8 (IL-8), has been linked to pain symptoms. The purpose of this study was to compare hs-CRP, IL-6, and IL-8 biomarkers and pain intensity with different treatment strategies (LLLT, standard conservative treatment, and combination) for TMD patients. Methods: A total of 32 participants were randomly included in the study and divided into three groups (Group I, Group II, and Group III) referred from the Dental Clinic, School of Dental Science, HUSM. Patients received LLLT (Groups II and III) in five sessions for the duration of 10 days. Patients in Groups I and III received standard conservative TMD treatment (diet and stress counseling, jaw exercises, physical therapy, which was a hot towel application) by the principal investigator. All blood samples for biomarkers were performed before starting treatments and directly after finishing the treatment protocols, where all results were recorded. Results: The result showed a significant difference in the mean IL-8 (p = 0.001) between the three intervention groups (LLLT, standard treatment, and combined treatment). IL-6 showed an increase in the mean of IL-6 levels from baseline to post-treatment with a better mean in the LLLT treatment group without any significant differences. Additionally, there were no significant mean differences found between the groups and in the group for the hs-CRP biomarker. Conclusions: A statistically non-significant difference was found in hs-CRP and IL-6 before and after LLLT, conservative, and combined treatment strategies of TMD. A statistically significant difference was observed in the mean levels of IL-8 between the LLLT intervention group and the combined treatment group. Although there was no statistically significant correlation between pain intensity and biomarkers, a statistically significant difference was found in pain intensity before and after LLLT, conservative, and combined treatment strategies. TMJ degeneration could be exacerbated by elevated IL-8 levels. Thus, this can be an important biomarker to mark or identify the painful condition of TMJ.

Background: The effects of lipopolysaccharide (LPS) on cell proliferation and osteogenic potential (OP) of MSCs have been frequently studied. Objective: to compare the effects of LPS on periodontal-ligament-derived mesenchymal stem cells (PDLSCs) in monolayer and 3D culture. Methods: The PDLSCs were colorimetrically assessed for proliferation and osteogenic potential (OP) after LPS treatment. The 3D cells were manually prepared by scratching and allowing them to clump up. The clumps (C-MSCs) were treated with LPS and assessed for Adenosine triphosphate (ATP) and OP. Raman spectroscopy was used to analyze calcium salts, DNA, and proline/hydroxyproline. Multiplexed ELISA was performed to assess LPS induced local inflammation. Results: The proliferation of PDLSCs decreased with LPS. On Day 28, LPS-treated cells showed a reduction in their OP. C-MSCs with LPS did not show a decrease in ATP production. Principal bands identified in Raman analysis were the P–O bond at 960 cm⁻¹ of the mineral component, 785 cm⁻¹, and 855 cm⁻¹ showing qualitative changes in OP, proliferation, and proline/hydroxyproline content, respectively. ELISA confirmed increased levels of IL-6 and IL-8 but with the absence of TNF-α and IL-1β secretion. Conclusions: These observations demonstrate that C-MSCs are more resistant to the effects of LPS than cells in monolayer cell culture. Though LPS stimulation of C-MSCs creates an early pro-inflammatory milieu by secreting IL-6 and IL-8, PDLSCs possess inactivated TNF promoter and an ineffective caspase-1 activating process.

Aim: To formulate and characterize a palm-oil-in-water-based α-Mangostin nano-emulsion (PO-AMNE) endodontic irrigant, in order to evaluate its antibacterial efficacy against Enterococcus faecalis, Staphylococcus epidermidis, and Candida albicans biofilms, as well as its capacity to remove smear layer. Methods: The solubility of α-Mangostin in various oils was determined and selected, surfactants and co-surfactants were used for the nano-emulsion trial. PO-AMNE was prepared and optimized. The MIC was performed, and the antimicrobial efficacy was estimated against biofilms. The optimized 0.2% PO-AMNE irrigant antimicrobial efficacy in a tooth model was done using colony-forming units. The treated teeth were processed by scanning electron microscopic examination for debris and smear layer removal. An Alamar Blue assay was used to evaluate cell viability. The optimization of the PO-AMNE irrigant was performed using Box–Behnken statistical design. Results: The optimized 0.2% PO-AMNE irrigant was found to have a particle size of 340.9 nm with 0.246 PDI of the dispersed droplets, and a zeta potential (mV) of −27.2 ± 0.7 mV. The MIC values showed that 0.2% PO-AMNE (1.22 ± 0.02) were comparable to 2% CHX (1.33 ± 0.01), and 3.25% NaOCl (2.2 ± 0.09) had the least inhibition for E. faecalis. NaOCl (3.25%) showed the maximum inhibition of S. epidermidis (0.26 ± 0.05), whereas 0.2% PO-AMNE (1.25 ± 0.0) was comparable to 2% CHX (1.86 ± 0.07). For C. albicans, 2% CHX (8.12 ± 0.12) showed the least inhibition as compared to 0.2% PO-AMNE (1.23 ± 0.02) and 3.25% NaOCl (0.59 ± 0.02). The 0.2% PO-AMNE irrigant was then evaluated for its antimicrobial efficacy against the three biofilms, using colony-forming units. The 0.2% PO-AMNE was comparable to both 3.25% NaOCl and 2% CHX in inhibiting the growth of biofilms. The 0.2% PO-AMNE and 17% EDTA eliminated the smear layer with the lowest mean scores (p < 0.001). Finally, 0.2% PO-AMNE was shown to be biocompatible when compared to 17% EDTA, 3.25% NaOCl, and 2% CHX in immortalized oral keratinocyte cells. Conclusion: Overall, the formulated 0.2% PO-AMNE irrigant was an effective antimicrobial and biocompatible which could combat endodontic-infection-related polymicrobial biofilms.

Epiregulin (EPR) is a novel member of the epidermal growth factor (EGF) family. It has been shown to promote wound healing in oral epithelium, enhance proliferation of other epithelial tissues, and is involved in several epithelial-related malignancies such as colorectal, lung, and bladder carcinoma. More recently, EPR transcripts were found to be high in a study on archival oral squamous cell carcinoma (OSCC) specimens. This implies that EPR may be responsible for the progression of OSCC. The aim of this was to elucidate the effects of EPR on (i) cell morphological changes, (ii) cell proliferation and (iii) receptor expression of the H-series OSCC cell lines. The clinicopathological origin and the expression of the epidermal growth factor receptor (EGFR) and ErbB4 receptors of the H-series cell lines were initially characterised. Based on these parameters, two of the H-series cell lines, namely H103 and H357 were selected for downstream experiments. The cell lines were treated with 1 ng/ml, 10 ng/ml, and 20 ng/ml of EPR for 24 and 48 hours in all subsequent experiments. Untreated cells acted as the control which was used for comparison with each treated group. The cell morphological changes, cell proliferation and receptor expression of the OSCC cell lines were evaluated using phase contrast microscopy, 5-bromo-2’-deoxy-uridine (BrdU) assays and flow cytometry respectively. The results were compared and analysed using the student t-test. There were no appreciable morphological changes in the cells regardless of the dose of EPR tested nor between the different timelines. There were no significant changes in cell proliferation after EPR treatment. As for the effect of EPR on receptor expression, 20 ng/ml of EPR significantly reduced the density of EGFR expression (p value = 0.049) in the H103 cell line after the 24-hour treatment. No other statistically significant changes were detected. The results show that EPR had no effect on the morphology and proliferativity of OSCC cells. However, the significant decline in EGFR expression after EPR treatment suggests that EPR might play an important role in the regulation of EGFR expression and hence OSCC progression.