An ensemble docking-based virtual screening and molecular dynamics simulation of phytochemical compounds from Malaysian Kelulut Honey (KH) against SARS-CoV-2 target enzyme, human angiotensin-converting enzyme 2 (ACE-2).

The human angiotensin-converting enzyme 2 (ACE-2) receptor is a metalloenzyme that plays an important role in regulating blood pressure by modulating angiotensin II. This receptor facilitates SARS-CoV-2 entry into human cells via receptor-mediated endocytosis, causing the global COVID-19 pandemic and a major health crisis. Kelulut honey (KH), one of Malaysian honey recently gained attention for its distinct flavour and taste while having many nutritional and medicinal properties. Recent study demonstrates the antiviral potential of KH against SARS-CoV-2 by inhibiting ACE-2 in vitro, but the bioactive compound pertaining to the ACE-2 inhibition is yet unknown. An ensemble docking-based virtual screening was employed to screen the phytochemical compounds from KH with high binding affinity against the 10 best representative structures of ACE-2 that mostly formed from MD simulation. From 110 phytochemicals previously identified in KH, 27 compounds passed the ADMET analysis and proceeded to docking. Among the docked compound, SDC and FMN consistently exhibited strong binding to ACE-2's active site (-9.719 and -9.473 kcal/mol) and allosteric site (-7.305 and -7.464 kcal/mol) as compared to potent ACE-2 inhibitor, MLN 4760. Detailed trajectory analysis of MD simulation showed stable binding interaction towards active and allosteric sites of ACE-2. KH's compounds show promise in inhibiting SARS-CoV-2 binding to ACE-2 receptors, indicating potential for preventive use or as a supplement to other COVID-19 treatments. Additional research is needed to confirm KH's antiviral effects and its role in SARS-CoV-2 therapy, including prophylaxis and adjuvant treatment with vaccination.Communicated by Ramaswamy H. Sarma.

LC-MS/MS-QTOF dataset of compounds detected in kelulut honey of the stingless bees, Heterotrigona itama and Tetrigona binghami from Kuantan, Pahang, Malaysia.

Honey is a sustainable nutritious substance which has been incorporated into the human diet since ancient times for its health and remedial benefits. Stingless bee honey or kelulut honey (KH) is well-known in Malaysia and has received high demand in the market due to its distinctive unique flavour. Its composition, colour, and flavour are majorly affected by the geographical location, floral source, climate, as well as the bee species. This data article presents the nontargeted metabolite profiling of the extracts of KH of Heterotrigona itama and Tetrigona binghami bee species. The KH was collected from three nests in Kuantan, Pahang, which is situated in the east coast of Peninsular Malaysia. The extracts were prepared using sugaring-out assisted liquid-liquid extraction (SULLE) method and the Liquid Chromatography-Tandem Mass Spectrometry with Quadrupole Time-of-Flight, operated in the negative ion mode, was used to identify compounds in the extracts. The data processing revealed the presence of 35 known compounds in the KH1 extract by Heterotrigona itama collected from Bukit Kuin, 38 compounds in the KH2 extract by H. itama collected from Indera Mahkota, whilst 50 known compounds were present in KH3 extract by Tetrigona binghami species from Indera Mahkota. This data article contains the m/z values, retention times, and the METLIN database search hit identities of the compounds and their respective classes.

The utility of salivary CRP and IL-6 as a non-invasive measurement evaluated in patients with COVID-19 with and without diabetes.

Background: The available evidence suggests that inflammatory responses, in both systemic and oral tissue, contribute to the pathology of COVID-19 disease. Hence, studies of inflammation biomarkers in oral fluids, such as saliva, might be useful to better specify COVID-19 features. Methods: In the current study, we performed quantitative real-time PCR to measure salivary levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in saliva obtained from patients diagnosed with mild COVID-19, in a diabetic group (DG; n = 10) and a non-diabetic group (NDG; n = 13). All participants were diagnosed with periodontitis, while six participants with periodontitis but not diagnosed with COVID-19 were included as controls. Results: We found increases in salivary total protein levels in both the DG and NDG compared to control patients. In both groups, salivary CRP and IL-6 levels were comparable. Additionally, the levels of salivary CRP were significantly correlated with total proteins, in which a strong and moderate positive correlation was found between DG and NDG, respectively. A linear positive correlation was also noted in the relationship between salivary IL-6 level and total proteins, but the correlation was not significant. Interestingly, the association between salivary CRP and IL-6 levels was positive. However, a moderately significant correlation was only found in COVID-19 patients with diabetes, through which the association was validated by a receiver operating curve. Conclusions: These finding suggest that salivary CRP and IL-6 are particularly relevant as potential non-invasive biomarker for predicting diabetes risk in mild cases of COVID-19 accompanied with periodontitis.

Gelatin-based hemostatic agents for medical and dental application at a glance: A narrative literature review.

Uncontrolled bleeding is linked to higher treatment costs, risk of post-surgical infection and increased disease and death. Hemostatic agents are used to treat excessive bleeding. A good hemostatic agent controls bleeding effectively, reduces the need for blood transfusion, removes the need for systemic drugs to control bleeding, results in shorter surgery time, and reduces the cost and length of hospital stay of the patient. Gelatin-based hemostatic agents have been widely used in medical and dental procedures, owing to their biodegradability and biocompatibility, as well as availability and low cost of raw materials. In this narrative literature review, we discuss the background and different types of gelatin-based hemostatic agents in medical and dental procedures, the comparison of gelatin-based and non-gelatin-based hemostatic agents, and the usage and development of enhanced or novel gelatin-based hemostatic agents. Gelatin-based hemostatic agents are effective and important part of bleeding control, as evidenced by its wide application in medicine and dentistry. The development of novel combination gelatin-based hemostatic agents has much potential for effective control of excessive bleeding.

Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) Spectroscopy Coupled with Principal Component Analysis and Polymerase Chain Reaction (PCR) Assay for the Detection of Porcine and Bovine Gelatins in Dental Materials.

Muslims are prohibited from consuming products that contain pig products and their derivatives, including porcine gelatin. Medical and dental products are not exempt from the use of gelatin in their formulation. This study employs attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) coupled with principal component analysis (PCA) to detect and distinguish between porcine and bovine gelatins in dental materials. The results were further verified by polymerase chain reaction (PCR) assay. Species-specific primers targeting the 212 bp porcine cytochrome b and 271 bp bovine cytochrome b genes were used to amplify DNA in nine dental material samples. Detection and distinction of gelatin standards (bovine and porcine) against gelatin present in the dental materials was achieved using ATR-FTIR combined with PCA within wavenumber 1756 cm-1-1584 cm-1 (Amide I and Amide II). The detection limit for DNA was 0.001 ng/µL and 0.0001 ng/µL for bovine and porcine gelatins, respectively. Using PCR, one sample, BDM 01, was found to contain both porcine and bovine DNA, while one sample (BDM 14) was found to be positive for bovine DNA. The findings suggest that ATR-FTIR combined with PCA and conventional PCR are applicable for the identification of porcine and bovine gelatin in dental materials.

Online Learning during the COVID-19 Pandemic: Dental Students' Perspective and Impact on Academic Performance, One Institution Experience.

Background: The COVID-19 pandemic caused all universities in Malaysia to switch to online learning, including for dental education. The effect of this switch has yet to be assessed. Thus, this study aimed to assess International Islamic University Malaysia (IIUM) dental students' perspectives on the implementation of online learning during the COVID-19 pandemic and its impact on academic performance. Methods: Cross-sectional and retrospective methods were used. The handling, didactic benefits, motivation, and challenges of online learning were assessed via an online questionnaire, and academic performance was assessed by comparing professional exam scores pre- and post-online learning. Results: Among the 249 IIUM dental student respondents, a positive response was recorded for the management of online learning, despite a few challenges in the area of didactic benefits and motivation. A significant improvement (p-value < 0.05) was observed in examination scores in oral biology, microbiology, and pharmacology, while dental material and GMGS showed declines in performance. Other subjects showed no significant difference (p-value > 0.05) in mean scores before and after online learning. Conclusion: Generally, students had a positive response towards online learning management, despite facing some challenges. Based on the analysis of examination results, only two subjects in Year 2 and Year 3 were negatively affected by online learning during the pandemic.

Impact of COVID-19 on Malaysian dental students' physical, mental, financial and academic concerns.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by a novel coronavirus (SARS-CoV-2) has gained worldwide attention and proved to hold an impact to humankind in all aspects of life. Dental students' performances may indirectly be affected following the preventive measures in containing the disease. This study aims to evaluate the impact of COVID-19 pandemic on physical, mental, financial health and academic concern among dental students in Malaysia. METHODS: The current research implemented a cross sectional study among dental students in Malaysia. Assessment of the impact of COVID-19 on dental education was done by the distribution of a set of online survey consisting of 28 questions to dental students (n = 353) from public and private universities in Malaysia. The questionnaires include sociodemographic backgrounds and assessment on the mental health, financial health, physical health and academic concern. Kruskal Wallis test and Mann-Whitney U test were used to analyse the impact of COVID-19 to these 4 domains according to sociodemographic background. RESULTS: A total number of 353 respondents was recorded and 76.2% comprised of female. 59.7% were clinical students and 40.3% were preclinical students. Most of students were concerned about their own emotional health, financial concern, physical wellbeing, in which Year 3 students were found to be more concerned about their mental and financial health concern. CONCLUSIONS: COVID-19 pandemic had indeed significantly affected Malaysian dental students mainly due to fear of the quality of online learning and the amount of clinical skills acquired. Therefore, it is important to identify dental stressors and lessen the impact of COVID-19 to dental students.

Knowledge, Perceived Risk, and Preventive Behaviors amidst Covid-19 Pandemic among Dental Students in Malaysia.

PURPOSE: Coronavirus disease 19 (COVID-19) has affected dental education in Malaysia. However, studies on dental students' knowledge, perception, and behaviors with regards to COVID-19 are very limited. Thus, this study aims to determine the knowledge status, perceived risk, and preventive behaviors of dental students in Malaysia regarding COVID-19. METHODS: A cross-sectional study was conducted among students from 13 dental schools across Malaysia using online questionnaires. RESULTS: From 355 respondents, 93.5% obtained a high score of knowledge of COVID-19. Female respondents scored higher than males in perceived risks and preventive behaviors. Chinese respondents scored highest in knowledge, while Malay respondents had the highest perceived risk score. The mean preventive behavior score did not vary across ethnicity. On-campus students scored higher in knowledge and perceived risk whereas off-campus students practiced more preventive behaviors. Clinical students' knowledge score was higher than preclinical students. Final year students scored higher in knowledge and perceived risk compared to their juniors. CONCLUSION: The majority of dental students have good knowledge and a high perceived risk of COVID-19, and they practiced most of the preventive behaviors. However, the latest information on this disease should be incorporated into dental schools' curriculums and updated periodically.

Distinct and overlapping roles of ARID3A and ARID3B in regulating E2F­dependent transcription via direct binding to E2F target genes.

The AT­rich interacting domain (ARID) family of DNA­binding proteins is involved in various biological processes, including the regulation of gene expression during cell proliferation, differentiation and development. ARID3A and ARID3B are involved in chromatin remodeling and can bind to E2F1 and retinoblastoma tumor suppressor protein (RB), respectively. However, their role in regulating E2F target gene expression remains poorly understood. E2F transcription factors are critical regulators of cell cycle progression and are modulated by RB. Herein, putative ARID3­binding sites (BSs) in E2F target genes were identified, including Cdc2, cyclin E1 and p107, and it was found that ARID3A and ARID3B bound to these BSs in living cells. The mutation of ARID3 BSs reduced Cdc2 promoter activity, while ARID3A and ARID3B overexpression increased the promoter activity, depending on both ARID3 and E2F BSs. ARID3B knockdown blocked the transcription of Cdc2, cyclin E1 and p107 in normal human dermal fibroblasts (NHDFs), whereas the effects of ARID3A knockdown varied depending on the target genes. ARID3B overexpression, but not that of ARID3A, upregulated the transcription of E2F target genes, and activated cyclin E1 transcription and induced cell death with E2F1 assistance. Finally, ARID3A and ARID3B knockdown attenuated the cell cycle progression of NHDFs and T98G cells, and suppressed tumor cell growth. On the whole, these results indicate that ARID3A and ARID3B play distinct and overlapping roles in E2F­dependent transcription by directly binding to the E2F target genes. The present study provides novel insight into the mechanisms underlying the E2F dysregulation caused by ARID3A and ARID3B overexpression, which may have a significant influence on the progression of tumorigenesis.

A glimpse on the function of chitosan as a dental hemostatic agent.

Managing a bleeding patient can be a challenge during dental surgery. Profuse hemorrhage due to platelet defects, coagulation disorders, vascular anomalies, medication-induced patients, as well as inherited bleeding ailments result in soft tissue hematoma, septic shock, compromised airway, and in some severe cases, death could occur. A vast array of surgical hemostatic agents are available to stop bleeding, including chitosan-based hemostatic agents. Chitosan has an advantage over other topical hemostatic materials for its ability to promote shorter bleeding times and assist in healing. Massive behind-the-scene research and development efforts are ongoing to increase the performance of chitosan as a hemostatic agent. Numerous studies on chitosan use in dental hemostasis have registered it as being safe, biodegradable, biocompatible, promoting healing, antimicrobial and bioactive. This article reviews the application of chitosan in managing hemostasis in dental patients.

Optimization and Formulation of Fucoxanthin-Loaded Microsphere (F-LM) Using Response Surface Methodology (RSM) and Analysis of Its Fucoxanthin Release Profile.

Fucoxanthin has interesting anticancer activity, but is insoluble in water, hindering its use as a drug. Microencapsulation is used as a technique for improving drug delivery. This study aimed to formulate fucoxanthin-loaded microspheres (F-LM) for anticancer treatment of H1299 cancer cell lines and optimize particle size (PS) and encapsulation efficiency (EE). Using response surface methodology (RSM), a face centered central composite design (FCCCD) was designed with three factors: Polyvinylalcohol (PVA), poly(d,l-lactic-co-glycolic acid) (PLGA), and fucoxanthin concentration. F-LM was produced using a modified double-emulsion solvent evaporation method. The F-LM were characterized for release profile, release kinetics, and degradation pattern. Optimal F-LM PS and EE of 9.18 µm and 33.09%, respectively, with good surface morphology, were achieved from a 0.5% (w/v) PVA, 6.0% (w/v) PLGA, 200 µg/mL fucoxanthin formulation at a homogenization speed of 20,500 rpm. PVA concentration was the most significant factor (p < 0.05) affecting PS. Meanwhile, EE was significantly affected by interaction between the three factors: PVA, PLGA, and fucoxanthin. In vitro release curve showed fucoxanthin had a high burst release (38.3%) at the first hour, followed by a sustained release stage reaching (79.1%) within 2 months. Release kinetics followed a diffusion pattern predominantly controlled by the Higuchi model. Biodegradability studies based on surface morphology changes on the surface of the F-LM, show that morphology changed within the first hour, and F-LM completely degraded within 2 months. RSM under FCCCD design improved the difference between the lowest and highest responses, with good correlation between observed and predicted values for PS and EE of F-LM.

A review on non-syndromic tooth agenesis associated with PAX9 mutations.

Tooth agenesis in the reduction of tooth number which includes hypodontia, oligodontia and anodontia is caused by disturbances and gene mutations that occur during odontogenesis. To date, several genetic mutations that unlock the causes of non-syndromic tooth agenesis are being discovered; these have been associated with certain illnesses because tooth development involves the interaction of several genes for tooth epithelium and mesenchyme odontogenesis. Mutation of candidate genes PAX9 and MSX1 have been identified as the main causes of hypodontia and oligodontia; meanwhile, AXIN2 mutation is associated with anodontia. Previous study using animal models reported that PAX9-deficient knockout mice exhibit missing molars due to an arrest of tooth development at the bud stage. PAX9 frameshift, missense and nonsense mutations are reported to be responsible; however, the most severe condition showed by the phenotype is caused by haploinsufficiency. This suggests that PAX9 is dosage-sensitive. Understanding the mechanism of genetic mutations will benefit clinicians and human geneticists in future alternative treatment investigations.

Fabrication of Fucoxanthin-Loaded Microsphere(F-LM) By Two Steps Double-Emulsion Solvent Evaporation Method and Characterization of Fucoxanthin before and after Microencapsulation.

Microencapsulation is a promising approach in drug delivery to protect the drug from degradation and allow controlled release of the drug in the body. Fucoxanthin-loaded microsphere (F-LM) was fabricated by two step w/o/w double emulsion solvent evaporation method with poly (L-lactic-coglycolic acid) (PLGA) as carrier. The effect of four types of surfactants (PVA, Tween-20, Span-20 and SDS), homogenization speed, and concentration of PLGA polymer and surfactant (PVA), respectively, on particle size and morphology of F-LM were investigated. Among the surfactants tested, PVA showed the best results with smallest particle size (9.18 µm) and a smooth spherical surface. Increasing the homogenization speed resulted in a smaller mean F-LM particle size [d(0.50)] from 17.12 to 9.18 µm. Best particle size results and good morphology were attained at homogenization speed of 20 500 rpm. Meanwhile, increased PLGA concentration from 1.5 to 11.0 (% w/v) resulted in increased F-LM particle size. The mean particle size [d(0.5)] of F-LM increased from 3.93 to 11.88 µm. At 6.0 (% w/v) PLGA, F-LM showed the best structure and external morphology. Finally, increasing PVA concentration from 0.5 to 3.5 (% w/v) resulted in decreased particle size from 9.18 to 4.86 µm. Fucoxanthin characterization before and after microencapsulation was carried out to assess the success of the microencapsulation procedure. Thermo gravimetry analysis (TGA), glass transition (Tg) temperature of F-LM and fucoxanthin measured using DSC, ATR-FTIR and XRD indicated that fucoxanthin was successfully encapsulated into the PLGA matrix, while maintaining the structural and chemical integrity of fucoxanthin.

Critical role of ARID3B in the expression of pro-apoptotic p53-target genes and apoptosis.

ARID3A and ARID3B are transcriptional targets of p53. Recently, it has been reported that ARID3A plays a critical role in the transcriptional activation of pro-arrest p21 in response to DNA damage. However, the role of ARID3B in the p53 regulatory pathway remains poorly understood. Here we show that ARID3A and ARID3B specifically bind to putative ARID3-binding sites in p53 target genes in vitro and in vivo. ARID3B and, to a lesser extent, ARID3A silencing blocked transcriptional activation of pro-apoptotic p53 target genes, such as PUMA, PIG3, and p53. Furthermore, ectopic ARID3B, to a lesser extent, ARID3A expression activated the pro-apoptotic gene expression, and only ARID3B induced apoptosis. Finally, ARID3B but not ARID3A silencing blocked apoptosis induction following DNA damage. These results indicated that, although ARID3B and ARID3A share overlapping functions, ARID3B play a key role in the expression of pro-apoptotic p53-target genes and apoptosis.

Cooperation between ARID3A and p53 in the transcriptional activation of p21WAF1 in response to DNA damage.

ARID3A/DRIL1/Bright is a family member of the AT rich interaction domain (ARID) DNA-binding proteins that are involved in diverse biological processes. We have reported that p53 activates ARID3A transcription, and ARID3A overexpression induces G1 arrest. However, the role of ARID3A in the p53 pathway remains unclear. Here, we show that ARID3A cooperates with p53 to transcriptionally activate p21(WAF1), a p53-target gene important for cell-cycle arrest. ARID3A bound to its binding sites in the p21(WAF1) promoter in vivo and in vitro, and induced p21(WAF1) transcription in U2OS cells expressing wild-type p53 but not Saos-2 cells lacking p53. The co-expression of ARID3A with p53 cooperates to activate p21(WAF1) transcription and the stably transfected p21(WAF1) promoter. Mutation of the ARID3A binding sites reduced the p21(WAF1) promoter activity, and siRNA-based ARID3A knockdown suppressed the transcription of p21(WAF1), but not the proapoptotic NOXA and PUMA in response to DNA damage. Furthermore, p53 knockdown decreased ARID3A transcription, and, conversely, ARID3A overexpression and knockdown resulted in an increase or decrease in p53 stability, respectively. These results indicate both cooperative and interdependent roles for ARID3A and p53 in the transcriptional activation of p21(WAF1) in response to DNA damage.