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Introduction: In the rapidly evolving landscape of health care, artificial intelligence (AI) has emerged as a promising tool to enhance diagnostic accuracy across various medical disciplines. Within the realm of dentistry, one critical area of focus is endodontics, which involves the diagnosis and treatment of dental pulp diseases. This systematic review investigates the diagnostic precision of AI in contrast to dental experts when predicting endodontic outcomes. Materials and Methods: The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review was registered on the Open Science Framework database. A systematic search was performed of the literature on the application of AI versus dental experts in endodontics. The search was conducted on PubMed, Scopus, Web of Science, and OVID until December 2022. The QUADAS-2 tool was used to evaluate the risk of bias. Results: The initial search retrieved 972 records, of which eight articles were included in the study. The studies reported application of AI for working length determination, periapical lesions, pulp and tooth segmentation, apical periodontitis, vertical root fracture, and C-shaped canals. QUADAS-2 tool revealed a low risk of bias in five out of the eight included studies. Conclusion: AI models demonstrated a notable increase in accuracy and effectiveness in endodontic diagnosis and treatment planning. These results suggest that the integration of AI technology in endodontic diagnosis and treatment planning has immense potential to serve as a promising aid.

Introduction: Irrigating solutions are vital in endodontics, serving to meticulously disinfect root canals, enzymatically dissolve pulpal remnants, and facilitate thorough flushing to eradicate microorganisms. This intricate process ensures optimal microbial control, tissue dissolution, and debris removal, contributing to enhanced endodontic outcomes and overall oral health in clinical practice. Aim: To evaluate the contact angle of Trisodium Citrate (TSC) Silver Nanoparticles (AgNP) and Biosynthesised AgNPs when used in root canal irrigation. Materials and Methods: This in-vitro study was conducted at White Lab, Department of Conservative Dentistry and Endodontics, Saveetha Dental College Saveetha Institute of Medical and Technical Sciences Saveetha University, Chennai, Tamilnadu, India, from January 2023 to August 2023. A total of 40 single-rooted dentine samples extracted from human teeth were utilised. Ethical clearance was duly obtained. The samples were categorised into four groups (n=10 each). The groups underwent distinct irrigation processes, including Biosynthesised AgNPs from Azadirachta Indica (Group-1), Chemically synthesised AgNPs from Trisodium citrate (Group-2), 5.25% Sodium Hypochlorite (Group-3), and Distilled Water (DW) as the control (Group-4). The contact angle of the tested irrigants was thoroughly evaluated in all the samples using an Ossila goniometer. The data were analysed using Statistical Package for Social Sciences (SPSS) 21.0. Statistical tests used were Analysis of Variance (ANOVA). A p-value of

Introduction: Biomodification involves the application of exogenous cross-linkers to stabilise collagen molecules through the formation of inter- and intramolecular cross-links. This approach shows potential for improving bonding performance in adhesive restorations. Aim: To assess the Knowledge, Attitude, and Practices (KAP) regarding the use of cross-linkers during dentin bonding among practitioners specializing in conservative dentistry. Materials and Methods: An online survey was conducted among dentists practicing conservative dentistry across India from September 2022 to November 2022. The survey consisted of a semi-validated questionnaire with 24 questions and was distributed through personal email and social media. Data was collected over a period of three months and analysed using statistical evaluation in the Statistical Package for the Social Sciences (SPSS) via chi-square test. Results: A total of 181 responses were received. Of the study population, 68.2 percent became aware of biomodification through articles in various journals. According to the study, 85 individuals (47%) acknowledged that using cross-linkers could enhance the mechanical properties of dentin by stabilising collagen. However, it is interesting to note that only 33 individuals (18.2%) actually incorporated biomodification techniques in their dental practice. Conclusion: Nearly half of the study population were aware of the use of cross-linkers to enhance dentin strength, prevent degradation and preserve resin-dentin bonds, inhibit demineralisation, and prevent root caries. However, only 18.2% of the participants reported practicing biomodification procedures in their dental practice.

Abstract Background Pain is usually subjective and thus it is challenging to describe its characteristics such as nature, intensity, and origin. Non-invasive methods such as assessing salivary alpha-amylase (SAA) may aid the practitioner to evaluate the pain intensity. Hence, the current study aimed to correlate the levels of SAA with the pain intensity in patients presenting with varied endodontic pain levels. Methods Sixty patients who presented with varied intensities of endodontic pain were selected for the present study out of which seven patients were excluded/dropped, leaving a total sample of fifty-five patients for assessment. Mandibular molar with symptomatic irreversible pulpitis without periapical pathology were included in the study. A 5ml of un-stimulated was obtained from the patients, following which the local anesthesia was administered. Root canal treatment was then performed and the pain scores at pre-operative and post-operative were recorded. Additionally, salivary samples were collected after emergency endodontic treatment and sent for sialochemical analysis. IBM.SPSS statistics software 23.0 was employed to assess the obtained data. Results A statistically significant drop in the pain score (P

Aim. To determine the minimum dentin thickness in the mesial and distal walls of the mesiobuccal (MB) and mesiolingual (ML) canals of the mandibular first molars using cone-beam computed tomography (CBCT). Materials and Methods. CBCT examinations of 624 mandibular first molars from an Indian subpopulation were analyzed. The mesial and distal minimum dentin thickness was evaluated in 1 mm intervals apical to the furcation area. Independent t-test was used to analyze the data (α = 0.05). Using Cohen’s kappa coefficient, the interexaminer and intraexaminer reliability was evaluated. Results. The mesial dentin thickness was significantly higher than the distal dentin thickness for MB and ML canals (P=0.01). The average dentin thickness in the distal and mesial plane of the MB canal was 1.15 ± 0.15 mm and 1.52 ± 0.19 mm at the 1 mm level and 0.83 ± 0.13 and 1.08 ± 0.18 at the 5 mm level, respectively. For the ML canal, the average dentin thickness in the distal plane and the mesial plane was 1.24 ± 0.18 mm and 1.44 ± 0.21 at the 1 mm level and 0.91 ± 0.16 and 1.01 ± 0.17 at the 5 mm level, respectively. Statistical analysis between the MB and ML canals showed significant differences in the dentin thickness at 4 and 5 mm levels in both the distal and the mesial planes (P=0.01). In more than 85% of the cases, the minimum dentin thickness was seen at the 5 mm level in both the distal and mesial planes in MB and ML canals. Conclusion. The distal planes of the mesiolingual and mesiobuccal canals were thinner in most cases, making the distal surface more prone to iatrogenic perforations. Considerably, at 4 and 5 mm from the furcation, the distal wall was significantly thinner than the mesial walls. Understanding the anatomy of the danger zone in the mesial roots of the mandibular first molars may serve to minimize the risk of endodontic mishaps such as strip perforations.

Neurodegenerative diseases are characterized by progressive loss of neurons in specific regions of the brain. Neuronal death is often associated with the accumulation of misfolded proteins due to genetic mutations or abnormal protein homeostasis. An essential mechanism for regulating the clearance of misfolded proteins is neddylation, a post-translational modification closely related to ubiquitination. Neddylation is brought about by conjugating neural precursor cell-expressed developmentally downregulated protein 8 (NEDD8) to target substrates through a cascade of cellular events. Neddylation is crucial for many biological processes, and dysfunctional neddylation is implicated in several neurodegenerative diseases. This review discusses the current understanding of the role of neddylation pathways in neurodegenerative disorders and the emergence of neddylation signaling as a potential target for drug discovery and development in neurodegenerative diseases.

abstract: Green synthesis of nanoparticles remains to be one of the promising and fascinating approaches in material science research. Although, metal based nanoparticles were shown to possess potent antibacterial effect, challenges pertaining to counter biofilms still exist. In this context, the seed extract of the Annona squamosa fruit was used in fabricating nanosilver and challenged against oral biofilm forming bacteria. The seed extract was used to reduce silver nitrate into nanosilver under optimized laboratory conditions. Characterization studies were performed using spectroscopic and electron microscopic analyzes. Antibacterial study was determined using agar diffusion method and the results validated. Phytochemicals present in the seed extract was found to effectively reduce the metal precursor into nanoform. UV–vis spectral analysis showed typical absorbance (λmax) of AgNPs in the range of 400–450 nm with spherical shaped particles and nanocrystals as revealed from XRD studies. Significant antimicrobial effect toward Streptococcus mutans, Staphylococcus aureus and Escherichia coli in a dose dependent fashion could be achieved on par with control. Adoption of green chemistry principles in fabricating the nanoparticles could help reduce the adverse effects induced from the one synthesized using chemical methods. Their application might be commercialized prior to cytotoxicity studies and in vivo animal models.

Background: Fluid dynamics is a majorly neglected aspect to be studied in root canal irrigation. The fundamental rule to understand mechanics is to observe patterns of flow during the process. Thus, this work is conducted to do a systemic assessment of the in-vitro and ex-vivo based studies to evaluate the effect of various parameters on the irrigant flow and apical pressure on using a manual syringe needle for root canal irrigation. Methods: The literature search was conducted through libraries such as PubMed (Medline), CINAHL, Embase, Scopus and other hand literature from Google Scholar, the British medical library etc. The systematic review was reported following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. As they include studies that were in-vitro and ex-vivo based, the risk of bias of the selected articles was assessed using a customized tool based on the previous literature and parameters evaluated in the studies included. Results: The literature search resulted in 101 items of which 19 records were included in this review. Results reported that multiple factors and parameters were assessed to evaluate the flow and apical pressures on using manual syringe needle irrigation. Conclusions: Present systematic review gives insights in-depth about the irrigation dynamics of manual syringe needle irrigation. Besides, it is inconclusive to compile a single factor or a single parameter contributing to the enhanced irrigant flow and least apical pressures.

The use of ultrasonics (US) has greatly expanded in the field of dentistry. Over the past few decades, the application of US has increased substantially in endodontics owing to the predictable prognosis and ease of operation. The objective of this survey was to determine the knowledge, practice, and attitude of US in endodontics among the general practitioners, postgraduates, and endodontists. An electronic questionnaire containing 16 questions regarding the knowledge, attitude, and practice of US in endodontics was circulated among the general dentists, postgraduates, and endodontists and the responses were collected online. Data were statistically examined using IBM SPSS software. A total of 202 dentists (general dentists = 92, endodontists = 77, and postgraduates = 33) participated in the survey. Eighty-nine percent of them were aware of the use of US in endodontics, 36.1% of them preferred using US in the removal of pulp chamber calcifications, pulp stones, access refinement, and troughing hidden canals, and 61.4% chose

Aim. To compare and contrast by three-dimensional finite element analysis the biomechanical performance of deep mesio-occlusal-distal cavities of mandibular molars reinforced by different sizes of horizontal fiber posts. Materials and Methods. The finite element (FE) stress analysis was performed with the ANSYS, a commercial finite element method package. Based on the evidence-based scientific data and on the mechanical properties of materials, i.e., Young’s modulus and Poisson ratio, the model of a mandible and mandibular first molar was replicated. The mandibular molar models replicating the clinical scenarios were simulated, designed, and built, assuming all materials to be homogenous, isotropic, and linearly elastic as follows: Model 1 control: the model of an intact first mandibular molar. Model 2: the prepared cavity mesio-occlusal-distal is replicated by the subtraction Boolean method. The remaining thickness of dentin is 1 mm. Model 3: these were rehabilitated by three different diameters of two horizontal fiber posts. Model 3A: fiber post diameter 1 mm, Model 3B: 1.5 mm and Model 3C: 2 mm. The dimensions of the cavity, the intercuspal distance between buccal walls and lingual walls, and the distance of placement of the post from occlusal reference points were all kept constant for all three subgroups of Model 3. The cavities of Model 3 were restored with Filtek bulk-fill posterior composite. After meshing the models, loads were defined on the buccal and lingual distal cusps with a constant value of 600 N and at an angle of 45°. Results. The results of finite element analysis are expressed as stresses, i.e., tensile compressive, shear, or a combination known as von Mises stresses. The overall von Mises stresses were as follows: Model 1:154.83 Mpa; Model 2: 376.877 Mpa; Model 3A: 160.221 Mpa; Model 3B: 159.488 Mpa; Model 3C: 147.231 Mpa. Statistical analysis of the compiled data was carried out. It was seen that there was a significant difference in stress values from the intact tooth Model 1 and cavity Model 2 (p

Background and aims: Chronic exposure to chemotherapeutics can lead to severe adverse events including hepatotoxicity. A combination chemotherapy regimen of doxorubicin (DOX) and cyclophosphamide (CPS) is employed in treatment of several cancers such as leukemia, lymphoma, and breast cancer. It is not well understood whether a combination therapy with DOX and CPS can induce hepatotoxicity. We therefore sought to determine whether co-administration of DOX and CPS at their clinically relevant doses and frequency results in hepatotoxicity. Methods: Male C57BL/6J mice received one intraperitoneal injection of saline or DOX-2 mg/kg and CPS-50 mg/kg once a week for 4 weeks. After the treatment period, liver histology and various serum biomarkers of hepatotoxicity were assessed. Results: Co-treatment with DOX and CPS did not alter the serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, albumin, globulin, or total protein. Similarly, co-administration of DOX and CPS did not result in a noticeable change in liver histology. However, it was notable that the concomitant treatment with DOX and CPS resulted in a significant increase in serum levels of aspartate aminotransferase (AST). Elevated serum AST levels were also associated with increased serum creatinine kinase (CK) levels, suggesting that the elevated serum AST levels are likely due to muscle injury following the co-administration of DOX and CPS. Conclusions: Taken together, our results, for the first time, suggest that co-administration of DOX and CPS, at their clinically relevant doses and frequency does not induce a significant hepatotoxicity in the mice.

Background: Pre-emptive analgesia is an anti-nociceptive treatment which reduces the postoperative pain by preventing the processing of altered afferent input. As most of the patients present with pain preoperatively have higher levels of released local inflammatory mediators. Thus, pretreatment analgesia decreases the establishment of central sensitization, a mechanism by which spinal neurons increase their response to peripheral nociceptive impulse. Objective: This systematic review aims to compare and evaluate the postoperative pain levels and analgesic intake on preoperative oral administration of NSAIDs in single visit root canal treatment. Data Sources: The present review was done according to PRISMA guidelines and was registered in the PROSPERO (Centre for Reviews and Dissemination University of York; http://www.crd.york.ac.uk/PROSPERO). Registration number - CRD42020195775. The research question was formulated based on the PICO strategy. A comprehensive electronic literature search was conducted across PubMed/Medline, Scopus and Cochrane Database independently by two reviewers. Study Eligibility Criteria: Articles published from January 1990 to May 2019 that focused on preemptive strategies in single visit root canal treatment were included in the present review. Based on specified inclusion and exclusion criteria’s, the selected articles were subjected to quality assessment, and the risk of bias was evaluated. Methods: A total of 6 articles were included, out of which three were hand searched. The overall risk of bias of included studies was moderate, and the study limitations were high. Results: Among the studies included, Ibuprofen was considered as the best drug of choice in single visit endodontics. Limitations: The present review was assessing only the effectiveness of NSAIDs in single visit root canal treatment. But ideally comprehensive literature should search on effectiveness in both single and multiple visit root canal treatments. Conclusion: The present systematic review concluded that ibuprofen was considered to be an effective drug in single visit root canal treatment.

There is mounting evidence that the development of Alzheimer’s disease (AD) interacts extensively with immunological processes in the brain and extends beyond the neuronal compartment. Accumulation of misfolded proteins can activate an innate immune response that releases inflammatory mediators and increases the severity and course of the disease. It is widely known that type-I interferon-driven neuroinflammation in the central nervous system (CNS) accelerates the development of numerous acute and chronic CNS diseases. It is becoming better understood how the cyclic GMP–AMP synthase (cGAS) and its adaptor protein Stimulator of Interferon Genes (STING) triggers type-I IFN-mediated neuroinflammation. We discuss the principal elements of the cGAS–STING signaling pathway and the mechanisms underlying the association between cGAS–STING activity and various AD pathologies. The current understanding of beneficial and harmful cGAS–STING activity in AD and the current treatment pathways being explored will be discussed in this review. The cGAS–STING regulation offers a novel therapeutic opportunity to modulate inflammation in the CNS because it is an upstream regulator of type-I IFNs

Ketone bodies have been the topic of research for their possible therapeutic neurotropic effects in various neurological diseases such as Parkinson’s disease, dementia, and seizures. However, continuing research on ketone bodies as a prophylactic agent for decreasing the risk for various neurodegenerative diseases is currently required. In this paper, hippocampal HT-22 cells were treated with β-hydroxybutyric acid at different doses to elucidate the neurotropic effects. In addition, markers of oxidative stress, mitochondrial function, and apoptosis were investigated. As a result, the ketone body (β-hydroxybutyric acid) showed a significant increase in hippocampal neuronal viability at a moderate dose. Results show that β-hydroxybutyric acid exhibited antioxidant effect by decreasing prooxidant oxidative stress markers such as reactive oxygen species, nitrite content, and increasing glutathione content leading to decreased lipid peroxidation. Results show that β-hydroxybutyric acid improved mitochondrial functions by increasing Complex-I and Complex-IV activities and showing that β-hydroxybutyric acid significantly reduces caspase-1 and caspase-3 activities. Finally, using computational pharmacokinetics and molecular modeling software, we validated the pharmacokinetic effects and pharmacodynamic (N-Methyl-D-aspartic acid and acetylcholinesterase) interactions of β-hydroxybutyric acid. The computational studies demonstrate that β-hydroxybutyric acid can interact with N-Methyl-D-aspartic acid receptor and cholinesterase enzyme (the prime pharmacodynamic targets for cognitive impairment) and further validates its oral absorption, distribution into the central nervous system. Therefore, this work highlights the neuroprotective potential of ketone bodies in cognitive-related neurodegenerative diseases.

Background and Objectives: Periodontitis is a chronic multifactorial inflammatory infectious disease marked by continuous degradation of teeth and surrounding parts. One of the most important periodontal pathogens is P. intermedia, and with its interpain A proteinase, it leads to an increase in lethal infection. Materials and Methods: The current study was designed to create a multi-epitope vaccine using an immunoinformatics method that targets the interpain A of P. intermedia. For the development of vaccines, P. intermedia peptides InpA were found appropriate. To create a multi-epitope vaccination design, interpain A, B, and T-cell epitopes were found and assessed depending on the essential variables. The vaccine construct was evaluated based on its stability, antigenicity, and allergenicity. Results: The vaccine construct reached a more significant population and was able to bind to both the binding epitopes of major histocompatibility complex (MHC)-I and MHC-II. Through the C3 receptor complex route, P. intermedia InpA promotes an immunological subunit. Utilizing InpA-C3 and vaccination epitopes as the receptor and ligand, the molecular docking and dynamics were performed using the ClusPro 2.0 server. Conclusion: The developed vaccine had shown good antigenicity, solubility, and stability. Molecular docking indicated the vaccine’s 3D structure interacts strongly with the complement C3. The current study describes the design for vaccine, and steady interaction with the C3 immunological receptor to induce a good memory and an adaptive immune response against Interpain A of P. intermedia.

Introduction: An ideal irrigant should exhibit good antimicrobial activity along with smear removal. Various plant extracts have been used for disinfection of the root canal system. The present study aims in evaluating the tissue response and systemic toxicity of ethanolic extract of Morinda citrifolia versus Morinda citrifolia fresh fruit juice in an animal model. Materials and Methods: A total 48 female adult wistar albino rats were randomly allocated into 4 groups as Group I- 3% sodium hypochlorite (n = 12), Group II- Saline (Control) (n = 12), Group III- ethanolic extract of Morinda citrifolia (n = 12), Group IV- Morinda citrifolia Fresh Fruit Juice (n = 12). A trough was made in the periapical bone, and the test sample was placed in the respective groups. The animals were euthanized for 7th day, 14th day and 30th day and the tissue specimen was prepared for histopathological evaluation, and serum analysis was done for oxidative stress markers, liver and renal function tests. Results: Serum analysis exhibited significant elevation of Alkaline Phosphatase (ALP), Glutathione Peroxidase (GPX) and Glutathione Reductase (GR) and histopathology showed a higher inflammatory response at 7th and 14th days in group II and group III (p < 0.05), as compared to the other groups. At the 30th day time interval, there was no statistically significant difference in serum analysis and inflammatory response, in all the four groups analysed (p > 0.05). Conclusion: Ethanolic extract of Morinda citrifolia was not biocompatible and more cytotoxic than a Morinda citrifolia fresh fruit juice. So, fresh fruit juice of Morinda citrifolia can be a preferred choice of natural root canal irrigant, with least possible cytotoxic effects as compared to the ethanolic extract.

Iatrogenic errors happen especially during endodontic treatment even with the experienced clinicians. It is impossible to predict the occurrence of an event. Although many of them can be corrected and managed successfully, few conditions might have the worst prognosis leading to uneventful extraction. The present case report highlights a 1-year follow-up of managed strip perforation in mesial canals of mandibular first molar, nonsurgically using MTA obturation. The present challenging case gives an insight on the importance of regenerative capacity and osteogenic potentiality of bioactive materials, when appropriate tissue engineering concepts are applied.

A male patient aged 28 years presented with a chief complaint of discolored left central incisor and missing tooth, due to road traffic accident 15 years ago with no associated symptoms. Clinical and radiographic examination revealed no pulp to response to vitality test, large periapical radiolucency, and root resorption of the middle third of the root. A definite diagnosis of pulpal necrosis with asymptomatic apical periodontitis and external resorption was made. Root canal treatment was done, and the extent of the lesion was analyzed and planned for surgical management. The periapical lesion was curetted, and the external resorption site was sealed with a matrix of Biodentine and platelet-rich fibrin. The case has shown successful healing after 3-year follow-up.

Viral infections persist globally, among all ages, gender, and ethnicity. Of particular importance is COVID-19, associated with asymptomatic to severe symptoms, including complications/mortality. Cardiovascular disease (CVD) involves heart and blood vessel disorders including coronary heart disease, cerebrovascular disease, peripheral artery disease, thrombosis, and more. CVD associated with severe COVID-19 includes heart failure, coronary artery disease, cardiomyopathy, hypertension, and cerebrovascular disease/stroke. Data were acquired from PubMed, Google Scholar, Centers for Disease Prevention and Control, and Lexi-Comp using the search terms “COVID-19 and cardiovascular pathology;” “COVID-19 induced CVD;” “Viral infection induced CVD;” and “Viral infection induced heart damage.” COVID-19-induced CVD mechanisms include direct viral entry, inflammation, cytokine storm, hypoxia, interferon-mediated immune response, plaque destabilization, stress, and drug-induced causes. Other viral pathologies causing CVD include atherosclerosis, inflammation, cytokine storm, and plaque destabilization. Individual parameters, such as old age, males, and higher body mass index (BMI), are more likely to experience viral-associated complications, possibly explained by patient risk factors or comorbidities. Populations at higher risk include older males with an elevated BMI. Viral mechanisms associated with CVD are similar but differ in disease severity, potentially explained by diverse cytokine profiles where COVID-19 activates different types at higher quantities.

Root canal preparation generates inorganic and organic tissue debris. Various irrigation techniques are used to remove the smear layer from the root canal system. The present study aimed to evaluate canal cleanliness using a novel irrigation device with ultrasonic and manual irrigation in extracted teeth. Twenty-one freshly extracted single-rooted teeth with specified inclusion and exclusion criteria were collected for the present study. The specimens were prepared to a size using a rotary file to size 30 and 6% taper preparation. The specimens were then divided into three groups: group I, Manual irrigation group (n = 7), group II, Automated irrigation (n = 7), group III, Passive ultrasonic irrigation (n = 7). Following the experimental irrigation, the teeth were subjected to the scanning electron microscopy (SEM). Statistically significant reduction (p < 0.05) in both smear layer and debris scores were seen in group III as compared to the other groups. Based on Hülsmann’s scoring method, it was found that the automated root canal irrigation device showed better canal cleanliness when compared with the manual irrigation technique but was less effective than passive ultrasonic irrigation.

Dental caries is a progressive disease with varying phases of demineralization and remineralization, and the scope of reversing the carious lesion is increased if it is diagnosed before there is surface cavitation. Preventive management strategies are directed towards making the enamel more resistant towards acid dissolution. The caries preventive protocol has always been fluoride-centric. Repeated application of fluoride gives rise to acquired fluoride resistance strains of Streptococci mutans which can be transient or permanent. The need of the hour is an effective remineralizing protocol which is one which brings about a change in enamel crystal and makes it more resistant to the acidic challenges of the oral cavity. The authors have devised a protocol in which irradiation with aluminum gallium arsenide crystals LASER can bring about a sanative change in crystal and lead to greater acid resistance of the enamel crystal and thus potentiate the remineralization of non-cavitated lesions. The concept of aluminum gallium arsenide–assisted caries inhibition and the proposed hypothesis of the mechanism of action is discussed.

Dental caries is an oral disease that has a global footprint. The first onslaught is subsurface, and at this stage, it can be remineralized. This study attempts to analyze the compositional changes that occur during demineralization and different surface treatment remineralization protocols. Aim: The aim of this study is to evaluate the compositional changes caused by different surface treatments on demineralized enamel. Methodology: Six extracted intact posterior teeth were selected and sectioned mesiodistally to achieve two halves. Each half was further divided into six equal sizes to achieve 12 samples per tooth. Except for one sample, which served as the control for that particular tooth, the remaining samples were placed in a demineralizing solution (acetate 0.1 Mol/L, calcium 0.1 Mol/L, phosphate 0.1 Mol/L and fluoride 0.1 mg/L pH 5.0) for 24 h. The samples were then assigned to groups and surface-treated as described below. The samples were grouped as follows so as to subject each sample to the following different surface treatments: Group 1: control, Group 2: Demineralized, Group 3: Laser 1 Watt, Group 4: Laser 2 Watts, Group 5: Laser 3 Watts, Group 6: Laser 3.5 Watts, Group 7: CPP-ACPF, Group 8: CPP-ACPF & Laser 3.5 Watts, Group 9: Enafix, Group 10: Enafix & Laser 3.5 Watts, Group 11: MI Paste and Group 12: MI Paste & Laser 3.5 Watts. The laser used for irradiating the samples in the respective laser groups utilized different wattages of an 810 nm aluminum–gallium–arsenide laser for 30 s. The samples were analyzed using Fourier transform infrared spectrometry coupled with attenuated total reflectance (FTIR-ATR). A qualitative analysis was performed. Result: The 3.5 watts aluminum–gallium–arsenide laser followed by CPP-ACPF caused compositional changes in the organic and inorganic components of the enamel tissues, and these changes were similar to those of the control teeth. Conclusion: Aluminum–gallium–arsenide laser irradiation alone does cause compositional changes and makes the enamel conducive for remineralization.

The success of endodontic treatment relies on both apical and coronal sealing. To achieve a good three-dimensional seal, the removal of the smear layer becomes mandatory. This study aims to assess the difference in debris accumulation and smear layer formation while using automated root canal irrigation and conventional syringe needle irrigation. Single-rooted human mandibular premolar teeth (n = 30) which were indicated for orthodontic extractions were selected. An endodontic access cavity was prepared, and a glide path was created. Based on the irrigation protocol decided upon for the study, the teeth were randomly allocated into three study groups, namely Group 1, where the manual syringe needle irrigation method was adopted; Group 2, in which automated root canal irrigation was undertaken; and Group 3, in which teeth remained un-instrumented as it was considered the Control group. The teeth were decoronated at the cement-enamel junction (CEJ) and were subjected for scanning electron microscopy (SEM) examination. Debris and smear layers were viewed in 1000× magnification and scored. A statistically significant (p < 0.05) lower mean debris and smear layer score (p < 0.05) was observed in both study groups when compared with the control group. However, no significant difference (p > 0.05) in the debris and smear layer was observed between the manual syringe needle irrigation and automated irrigation, although automated irrigation devices can be a potential alternative. The present study concluded that the efficacy of smear layer removal remained the same with both automated irrigation and manual syringe irrigation.

Background: The role of endogenous Matrix Metallo Proteinases in resin dentin bond deterioration over time has been well documented. The present study aimed to systematically review the literature; in vitro and ex vivo studies that assessed the outcomes of natural cross-linkers for immediate and long-term tensile bond strength were included. Methods: The manuscript search was carried out in six electronic databases—PubMed/MEDLINE, LILACS, SciELO, Cochrane, Web of Science and DOAJ, without publication year limits. Only manuscripts in English (including the translated articles) were selected, and the last search was performed in December 2020. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Results: From the 128 potentially eligible studies, 48 full-text articles were assessed for eligibility. After eligibility assessment and exclusions, 14 studies were considered for systematic review and seven studies for meta-analysis. Amongst the selected studies for meta-analysis, three had a medium and four had a low risk of bias. Conclusions: It was evidenced by the available data that Proanthocyanidin is the most efficient natural cross-linker to date, in preserving the bond strength even after ageing.

Cannabis is the most commonly used illicit drug worldwide. Recently, cannabis use among young pregnant women has greatly increased. However, prenatal cannabinoid exposure leads to long-lasting cognitive, motor, and behavioral deficits in the offspring and alterations in neural circuitry through various mechanisms. Although these effects have been studied in the hippocampus, the effects of prenatal cannabinoid exposure on the cerebellum are not well elucidated. The cerebellum plays an important role in balance and motor control, as well as cognitive functions such as attention, language, and procedural memories. The aim of this study was to investigate the effects of prenatal cannabinoid exposure on the cerebellum of adolescent offspring. Pregnant rats were treated with synthetic cannabinoid agonist WIN55,212-2, and the offspring were evaluated for various cerebellar markers of oxidative stress, mitochondrial function, and apoptosis. Additionally, signaling proteins associated with glutamate dependent synaptic plasticity were examined. Administration of WIN55,212-2 during pregnancy altered markers of oxidative stress by significantly reducing oxidative stress and nitrite content. Mitochondrial Complex I and Complex IV activities were also enhanced following prenatal cannabinoid exposure. With regard to apoptosis, pP38 levels were significantly increased, and proapoptotic factor caspase-3 activity, pERK, and pJNK levels were significantly decreased. CB1R and GluA1 levels remained unchanged; however, GluN2A was significantly reduced. There was a significant decrease in MAO activity although tyrosine hydroxylase activity was unaltered. Our study indicates that the effects of prenatal cannabinoid exposure on the cerebellum are unique compared to other brain regions by enhancing mitochondrial function and promoting neuronal survival. Further studies are required to evaluate the mechanisms by which prenatal cannabinoid exposure alters cerebellar processes and the impact of these alterations on behavior.

While chemotherapy is the most effective therapeutic approach for treating a variety of cancer patients, commonly used chemotherapeutic agents, often induce several adverse effects. Escalating evidence indicates that chemotherapeutics, particularly doxorubicin (DOX) and cyclophosphamide (CPS), induce cognitive impairment associated with central nervous system toxicity. This study was performed to determine neuroprotective effects of Oroxylum indicum extract (OIE) in regard to preventing chemotherapy induced cognitive impairment (CICI) occurring after 4 cycles of DOX (2mg/kg) and CPS (50mg/kg) combination chemotherapy in male C57BL/6J mice. OIE significantly prevented the chemotherapy impaired short-term cognitive performance, exploratory behavior associated with cognitive performance, cognitive performance, and spatial learning and memory in the Y-maze, Open-Field, Novel Object Recognition, and Morris Water Maze tests, respectively. These data suggest that OIE protects from the CICI. OIE decreased the reactive oxygen species and lipid peroxide generated by the chemotherapy treatment in the brain, while also blocking the chemotherapy-induced glutathione depletion. These results establish that OIE exhibits potent antioxidant activity in chemotherapy treated mice. Notably, OIE significantly increased the Complex-I and Complex-IV activities in the brain, indicating that OIE enhances mitochondrial function in the brain. In silico analysis of the major active chemical constituents (Oroxylin A, Baicalein and Chrysin) of OIE indicated that OIE has a favorable absorption, distribution, metabolism and excretion (ADME) profile. Taken together, our results are consistent with the conclusion that OIE prevents CICI by counteracting oxidative stress and perhaps by improving mitochondrial function.

Chronic inflammation is a key culprit factor in the onset and progression of several diseases. Novel and pharmacologically effective therapeutic approaches are needed for new treatment remedy or improved pharmacokinetics and pharmacodynamics for existing synthetic drugs, in particular natural products. Boswellic acids are well-known natural products, with capacity to effectively retard inflammation without severe adverse effects. However, the therapeutic use of Boswellic acids are greatly hindered by its poor pharmacokinetic properties. Co-administration strategies that facilitate the oral absorption and distribution of Boswellic acids should lead to a safe and more effective use of this product prophylactically and therapeutically in inflammatory disorders. In this study, we examined the effect of Piper longum extract on the absorption and bioavailability of Boswellic acid in rabbits. In addition, we further explored computational pharmacodynamic interactions between Piper longum and Boswellic acid. Piper longum extract at 2.5 and 10 mg/kg, increased the bioavailability of Boswellic acid (p < 0.05). Based on our drug-based computational modeling, cytochrome P450 (CYP450)-mediated mechanism was involved in increased bioavailability. These findings confirmed that Piper longum with Boswellic acid may be administered orally together for effective therapeutic efficacy. Thus, our studies support the application of Piper longum with Boswellic acid as a novel therapeutic avenue in diseases associated with inflammation.

Dysbiosis of gut microbiota is strongly associated with metabolic diseases including diabetes mellitus, obesity, and cardiovascular disease. Recent studies indicate that Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite is implicated in the development of age-related cognitive decline. However, the mechanisms of the impact of TMAO on neuronal function has not been elucidated. In the current study, we investigated the relationship between TMAO and deficits in synaptic plasticity in an Alzheimer’s model (3×Tg-AD) and insulin resistance (Leptin deficient db/db) mouse by measuring plasma and brain levels of TMAO. We observed increased TMAO levels in the plasma and brain of both db/db and 3×Tg-AD mice in comparison to wild-type mice. Besides, TMAO levels further increased as mice progressed in age. Deficits in synaptic plasticity, in the form of reduced long-term potentiation (LTP), were noted in both groups of mice in comparison to wild-type mice. To further explore the impact of TMAO on neuronal function, we utilized an ex-vivo model by incubating wild-type hippocampal brain slices with TMAO and found impaired synaptic transmission. We observed that TMAO induced the PERK-EIF2α-ER stress signaling axis in TMAO treated ex-vivo slices as well as in both db/db and 3×Tg-AD mice. Lastly, we also observed altered presynaptic and reduced postsynaptic receptor expression. Our findings suggest that TMAO may induce deficits in synaptic plasticity through the ER stress-mediated PERK signaling pathway. Our results offer novel insight into the mechanism by which TMAO may induce cognitive deficits by promoting ER stress and identifies potential targets for therapeutic intervention.

The widespread increase in multiple severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants is causing a significant health concern in the United States and worldwide. These variants exhibit increased transmissibility, cause more severe disease, exhibit evasive immune properties, impair neutralization by antibodies from vaccinated individuals or convalescence sera, and reinfection. The Centers for Disease Control and Prevention (CDC) has classified SARS-CoV-2 variants into variants of interest, variants of concern, and variants of high consequence. Currently, four variants of concern (B.1.1.7, B.1.351, P.1, and B.1.617.2) and several variants of interests (B.1.526, B.1.525, and P.2) are characterized and are essential for close monitoring. In this review, we discuss the different SARS-CoV-2 variants, emphasizing variants of concern circulating the world and highlight the various mutations and how these mutations affect the characteristics of the virus. In addition, we discuss the most common vaccines and the various studies concerning the efficacy of these vaccines against different variants of concern.

Summary: Formation of the coronary vasculature is a complex and precisely coordinated morphogenetic process that begins with the formation of epicardium. The epicardium gives rise to many components of the coronary vasculature, including fibroblasts, smooth muscle cells, and endothelium. Hippo signaling components have been implicated in cardiac development and regeneration. However, a role of Hippo signaling in the epicardium has not been explored. Employing a combination of genetic and pharmacological approaches, we demonstrate that inhibition of Hippo signaling mediators Yap and Taz leads to impaired epicardial epithelial-to-mesenchymal transition (EMT) and a reduction in epicardial cell proliferation and differentiation into coronary endothelial cells. We provide evidence that Yap and Taz control epicardial cell behavior, in part by regulating Tbx18 and Wt1 expression. Our findings show a role for Hippo signaling in epicardial cell proliferation, EMT, and cell fate specification during cardiac organogenesis. : Singh et al. show that Hippo signaling components are expressed in proepicardial and epicardial cells and are required for coronary vasculature development. Yap and Taz regulate epicardial cell proliferation, EMT, and cell fate specification, in part by regulating Tbx18 and Wt1 expression. Keywords: epicardium, proepicardium, Hippo signaling, Yap, Taz, epithelial to mesenchymal transition (EMT)

Honokiol (poly-phenolic lignan from Magnolia grandiflora) is a Sirtuin-3 (SIRT3) activator which exhibit antioxidant activity and augment mitochondrial functions in several experimental models. Modern evidence suggests the critical role of SIRT3 in the progression of several metabolic and neurodegenerative diseases. Amyloid beta (Aβ), the precursor to extracellular senile plaques, accumulates in the brains of patients with Alzheimer's disease (AD) and is related to the development of cognitive impairment and neuronal cell death. Aβ is generated from amyloid-β precursor protein (APP) through sequential cleavages, first by β-secretase and then by γ-secretase. Drugs modulating this pathway are believed to be one of the most promising strategies for AD treatment. In the present study, we found that Honokiol significantly enhanced SIRT3 expression, reduced reactive oxygen species generation and lipid peroxidation, enhanced antioxidant activities, and mitochondrial function thereby reducing Aβ and sAPPβ levels in Chinese Hamster Ovarian (CHO) cells (carrying the amyloid precursor protein-APP and Presenilin PS1 mutation). Mechanistic studies revealed that Honokiol affects neither protein levels of APP nor α-secretase activity. In contrast, Honokiol increased the expression of AMPK, CREB, and PGC-1α, thereby inhibiting β-secretase activity leading to reduced Aβ levels. These results suggest that Honokiol is an activator of SIRT3 capable of improving antioxidant activity, mitochondrial energy regulation, while decreasing Aβ, thereby indicating it to be a lead compound for AD drug development.

The brain contains various forms of lipids that are important for maintaining its structural integrity and regulating various signaling cascades. Autotaxin (ATX) is an ecto-nucleotide pyrophosphatase/phosphodiesterase-2 enzyme that hydrolyzes extracellular lysophospholipids into the lipid mediator lysophosphatidic acid (LPA). LPA is a major bioactive lipid which acts through G protein-coupled receptors (GPCRs) and plays an important role in mediating cellular signaling processes. The majority of synthesized LPA is derived from membrane phospholipids through the action of the secreted enzyme ATX. Both ATX and LPA are highly expressed in the central nervous system. Dysfunctional expression and activity of ATX with associated changes in LPA signaling have recently been implicated in the pathogenesis of Alzheimer’s disease (AD). This review focuses on the current understanding of LPA signaling, with emphasis on the importance of the autotaxin–lysophosphatidic acid (ATX–LPA) pathway and its alterations in AD and a brief note on future therapeutic applications based on ATX–LPA signaling.