Dental biomaterials redefined: molecular docking and dynamics-driven dental resin composite optimization.

BACKGROUND: Dental resin-based composites are widely recognized for their aesthetic appeal and adhesive properties, which make them integral to modern restorative dentistry. Despite their advantages, adhesion and biomechanical performance challenges persist, necessitating innovative strategies for improvement. This study addressed the challenges associated with adhesion and biomechanical properties in dental resin-based composites by employing molecular docking and dynamics simulation. METHODS: Molecular docking assesses the binding energies and provides valuable insights into the interactions between monomers, fillers, and coupling agents. This investigation prioritizes SiO2 and TRIS, considering their consistent influence. Molecular dynamics simulations, executed with the Forcite module and COMPASS II force field, extend the analysis to the mechanical properties of dental composite complexes. The simulations encompassed energy minimization, controlled NVT and NPT ensemble simulations, and equilibration stages. Notably, the molecular dynamics simulations spanned a duration of 50 ns. RESULTS: SiO2 and TRIS consistently emerged as influential components, showcasing their versatility in promoting solid interactions. A correlation matrix underscores the significant roles of van der Waals and desolvation energies in determining the overall binding energy. Molecular dynamics simulations provide in-depth insights into the mechanical properties of dental composite complexes. HEMA-SiO2-TRIS excelled in stiffness, BisGMA-SiO2-TRIS prevailed in terms of flexural strength, and EBPADMA-SiO2-TRIS offered a balanced combination of mechanical properties. CONCLUSION: These findings provide valuable insights into optimizing dental composites tailored to diverse clinical requirements. While EBPADMA-SiO2-TRIS demonstrates distinct strengths, this study emphasizes the need for further research. Future investigations should validate the computational findings experimentally and assess the material's response to dynamic environmental factors.

A cyclophosphamide-induced immunosuppression Swiss Albino mouse model unveils a potential role for cow urine distillate as a feed additive.

BACKGROUND: Traditional and natural immunomodulators are increasingly used as supplements in animal feeds and as interventions in the prevention and treatment of disease in animals. OBJECTIVE: The aim of this study was to examine the immunomodulatory characteristics of distilled cow urine in vivo using two mouse models, a normal mouse model and an immunosuppressive mouse model. METHODOLOGY: We divided 144 Swiss Albino mice weighing between 15 g and 30 g, aged between two and three months, into two groups of 72 mice each. In the first group, we subdivided the animals into six subgroups of 12 each. In this group paramerters such as, body weight, organ weights of liver and kidney, haemagglutination titre, Jerne plaque-forming assay, and bone marrow cellularity were measured. We divided the second group into six subgroups for the assessment of delayed-type hypersensitivity (DTH). RESULTS: As compared to normal control mice, immunocompetent and immunosuppressed mice (given cow urine distillate) had significant increases in body weight, spleen weight, liver weight, total leucocyte count, lymphocyte count, serum protein, and globulin contents. In the treatment groups, the titre of antibodies, the number of antibody- producing cells, the cellularity of bone marrow, and foot pad thickness also increased. In the treatment group, both humoral and cellular immunity were altered compared to the control group, suggesting cow urine distillate to be a potential animal feed ingredient for immunoregulation. CONCLUSION: This study was able to demonstrate the experimental validity of natural compounds as immunomodulators that can be used in feed supplements for animals. Various compounds could be tested for immunomodulatory effects using this technique in experimental animals.

Investigation of a Minocycline-Loaded Nanoemulgel for the Treatment of Acne Rosacea.

In the present investigation, a nanoemulgel of minocycline was formulated and optimized for an improved drug delivery and longer retention time in the targeted area. Combining eucalyptus oil, Tween 20, and Transcutol HP, different o/w nanoemulsions were formulated by the oil phase titration method and optimized by pseudo-ternary phase diagrams. The morphology, droplet size, viscosity, and refractive index of the thermodynamically stable nanoemulsion were determined. Furthermore, optimized nanoemulsion was suspended in 1.0% w/v of Carbopol 940 gel to formulate the nanoemulgel, and for this, pH, viscosity, and spreadability were determined and texture analysis was performed. To compare the extent of drug penetration between nanoemulsion and nanoemulgel, ex vivo skin permeation studies were conducted with Franz diffusion cell using rat skin as the permeation membrane, and the nanoemulgel exhibited sustained-release behavior. It can be concluded that the suggested minocycline-containing naoemulgel is expected to treat acne rosacea more effectively.

Retention Strength of Zirconia Crowns Cemented onto PEEK Abutments Using Two Different Types of Resin Cement With or Without Primer Application-An In Vitro Study.

PURPOSE: To evaluate the retention of zirconia crowns on polyetheretherketone (PEEK) abutments using different luting agents, with and without PEEK primer. MATERIALS AND METHODS: A total of 100 PEEK abutment replicas were fabricated, airborne particle-abraded with aluminum oxide, and divided into four groups (n = 25). A total of 100 zirconia crowns were fabricated and cemented using either adhesive resin cement or self-adhesive resin cement with and without PEEK primer; thus, the groups were: group AA-P (adhesive cement with primer); group AA-N (adhesive cement without primer); group SA-P (self-adhesive cement with primer); and group SA-N (self-adhesive cement without primer). The specimens were thermocycled and subjected to crown pull-out tests. The values were recorded and analyzed using analysis of variance and post hoc analysis (α = .05). The mode of failure of debonded surfaces was evaluated using scanning electron microscopy. RESULTS: The pull-out force values were 3.13 ± 0.31 MPa for group AA-P, 1.77 ± 0.20 MPa for group AA-N, 2.10 ± 0.12 MPa for group SA-P, and 1.49 ± 0.18 MPa for group SA-N. Statistically significant differences were found between all four groups (P < .001). The specimens with PEEK primer applied showed higher values compared to nonprimed specimens for both cements tested. Scanning electron microscopy analysis showed more mixed failures for adhesive cement and more adhesive failures for self-adhesive resin cement. CONCLUSION: The maximum pull-out forces were recorded for zirconia crowns bonded to PEEK abutments with adhesive cement. The use of PEEK primer increased the pull-out values for both resin cements.

Exploring the Potential of Natural Product-Based Nanomedicine for Maintaining Oral Health.

Oral diseases pose a major threat to public health across the globe. Diseases such as dental caries, periodontitis, gingivitis, halitosis, and oral cancer affect people of all age groups. Moreover, unhealthy diet practices and the presence of comorbidities aggravate the problem even further. Traditional practices such as the use of miswak for oral hygiene and cloves for toothache have been used for a long time. The present review exhaustively explains the potential of natural products obtained from different sources for the prevention and treatment of dental diseases. Additionally, natural medicine has shown activity in preventing bacterial biofilm resistance and can be one of the major forerunners in the treatment of oral infections. However, in spite of the enormous potential, it is a less explored area due to many setbacks, such as unfavorable physicochemical and pharmacokinetic properties. Nanotechnology has led to many advances in the dental industry, with various applications ranging from maintenance to restoration. However, can nanotechnology help in enhancing the safety and efficacy of natural products? The present review discusses these issues in detail.

Densitometric Quantification and Optimization of Polyphenols in Phyllanthus maderaspatensis by HPTLC.

Quantifying and optimizing the polyphenol content of Phyllanthus maderaspatensis was accomplished using a single-solvent HPTLC system. Analyzing hydroalcoholic extracts for kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid, we simultaneously quantified and optimized their concentration. In the experiment, the methanol to water ratio (%), temperature (°C), and time of extraction (min) were all optimized using a Box-Behnken statistical design. Kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid were among the dependent variables analyzed. In the HPTLC separation, silica gel 60F254 plates were used, and toluene, ethyl acetate, and formic acid (5:4:1) made up the mobile phase. For kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid, densitometric measurements were carried out using the absorbance mode at 254 nm. Hydroalcoholic extract of P. maderaspatensis contains rutin (0.344), catechin (2.62), gallic acid (0.93), ellagic acid (0.172), quercetin (0.0108) and kaempferol (0.06). Further, it may be affected by more than one factor at a time, resulting in a varying degree of reaction. A negative correlation was found between X1 (extraction time (min)) and X2 (temperature), as well as X1 and X3 (solvent ratios). Taking these characteristics into consideration, the method outlined here is a validated HPTLC method for measuring kaempferol, rutin, ellagic acid, quercetin, catechin, and gallic acid.

In-silico Validation of the Proposed Treatment Strategy of Periodontitis.

OBJECTIVE: The present study aims to assess a proposed treatment approach or therapy for periodontitis by using the in-silico technique. The proposed treatment strategy offers a singular vehicular system consisting of minocycline (antibiotic), celecoxib (selective COX-II inhibitor), doxycycline hyclate (matrix metalloproteinase inhibitor), and hydroxyapatite (osteogenic agent). MATERIAL AND METHODS: Molecular docking studies of drugs were performed using Maestro version 9.4 software Schrödinger, and 3-Dimensional Crystallographic X-ray protein structures of targeted proteins were downloaded from RCSB protein data bank in .pdb file format. These agents were docked, and their affinities towards the receptors/protein/enzyme were calculated. Furthermore, their affinities were compared with the standard drug. RESULTS: The study suggests that minocycline and metronidazole possess equal affinity towards the RGPB and Inlj protein of P.gingivalis. Celecoxib, a well-known inhibitor of the COX-II enzyme, showed very high affinity. Selective inhibitor of MMP-8 possessed higher affinity than doxycycline, whereas CMT-3 showed equal affinity as doxycycline for MMP-13. Similarly, hydroxyapatite and simvastatin also showed a comparatively similar affinity for osteopontin receptor. CONCLUSION: Based upon molecular docking results, it can be concluded that the proposed treatment strategy would be a suitable approach for periodontitis and all the selected therapeutic agents have potential similar to the standard drugs, thereby constituting a reliable system for periodontitis.

Randomized clinical trial of zirconia and polyetheretherketone implant abutments for single-tooth implant restorations: A 5-year evaluation.

STATEMENT OF PROBLEM: Titanium-supported polyetheretherketone (PEEK) abutments provide an economic alternative to zirconia abutments in esthetically important areas. Research comparing the performance regarding esthetics, longevity, and biologic parameters of PEEK abutments is lacking. PURPOSE: The purpose of this clinical study was to determine whether PEEK implant abutments provide similar esthetic and biologic parameters and survival rates as zirconia implant abutments. MATERIAL AND METHODS: Forty participants (age 20 to 50 years) receiving maxillary anterior and premolar implants were enrolled in the study and randomly assigned into 1 of 2 groups: Group PEEK (20 titanium-supported PEEK abutments) and group ZIR (20 zirconia abutments). Both groups were restored with pressed lithium disilicate ceramic crowns. Technical, biologic, and esthetic evaluation was performed at baseline and at 1, 3, and 5 years. The probing pocket depth, plaque control record, and bleeding on probing were recorded at the abutments (test) and compared with those at the corresponding contralateral teeth (control) and also between the 2 test groups. Standardized digital radiographs of the implants were made, and the bone level was recorded with the implant shoulder as the reference on the mesial and distal sides. The color difference between the peri-implant mucosa and control teeth gingiva and the discoloration of the implant crowns were determined with a spectrophotometer. The Student unpaired t test and repeated-measure ANOVA were used to statistically analyze the data (α=.05). RESULTS: From the 5-year evaluation, both PEEK and zirconia abutments with ceramic crowns showed 100% survival rate without any fracture or restoration loss. Differences in the biologic parameters of zirconia and PEEK abutments were statistically similar: mean probing pocket depth (group ZIR: 2.32 ±0.50 mm, group PEEK: 2.13 ±0.60 mm); mean plaque control record (group ZIR: 0.19 ±0.19, group PEEK: 0.15 ±0.17); and mean bleeding on probing (group ZIR: 0.12 ±0.11, group PEEK: 0.08 ±0.12). The mean marginal bone loss at 5 years was similar for implants supporting zirconia and PEEK abutments: mean mesial bone level (group ZIR: 1.8 ±0.5 mm; group PEEK: 1.9 ±0.6 mm), and mean distal bone level (group ZIR: 1.7 ±0.6 mm, group PEEK: 1.8 ±0.3 mm). The initial color difference (ΔE) between the peri-implant mucosa and gingiva of the analogous contralateral teeth diminished over time. No discoloration of the definitive restoration supported by PEEK or zirconia was detected over 5 years. CONCLUSIONS: At the 5-year evaluation, zirconia and PEEK abutments exhibited the same survival rate with similar biologic and esthetic outcomes.

Development of 2D, 3D-QSAR and Pharmacophore Modeling of Chalcones for the Inhibition of Monoamine Oxidase B.

BACKGROUND: Selective and reversible types of MAO-B inhibitors have emerged as promising candidates for the management of neurodegenerative diseases. Several functionalized chalcone derivatives were shown to have potential reversible MAO-B inhibitory activity, which have recently been reported from our laboratory. METHODS: With the experimental results of about 70 chalcone derivatives, we further developed a pharmacophore modelling, and 2D and 3D- QSAR analyses of these reported chalcones for MAOB inhibition. RESULTS: The 2D-QSAR model presented four variables (MATS7v, GATS 1i and 3i, and C-006) from 143 Dragon 7 molecular descriptors, with a r2 value of 0.76 and a Q2 cv for cross-validation equal to 0.72. An external validation also was performed using 11 chalcones, obtaining a Q2 ext value of 0.74. The second 3D-QSAR model using MLR (multiple linear regression) was built starting from 128 Volsurf+ molecular descriptors, being identified as 4 variables (Molecular descriptors): D3, CW1 and LgS11, and L2LGS. Adetermination coefficient (r2) value of 0.76 and a Q2 cv for cross-validation equal to 0.72 were obtained for this model. An external validation also was performed using 11 chalcones and a Q2 ext value of 0.74 was found. CONCLUSION: This report exhibited a good correlation and satisfactory agreement between experiment and theory.

Raw Materials, Technology, Healthcare Applications, Patent Repository and Clinical Trials on 4D Printing Technology: An Updated Review.

After the successful commercial exploitation of 3D printing technology, the advanced version of additive manufacturing, i.e., 4D printing, has been a new buzz in the technology-driven industries since 2013. It is a judicious combination of 3D printing technologies and smart materials (stimuli responsive), where time is the fourth dimension. Materials such as liquid crystal elastomer (LCE), shape memory polymers, alloys and composites exhibiting properties such as self-assembling and self-healing are used in the development/manufacturing of these products, which respond to external stimuli such as solvent, temperature, light, etc. The technologies being used are direct ink writing (DIW), fused filament fabrication (FFF), etc. It offers several advantages over 3D printing and has been exploited in different sectors such as healthcare, textiles, etc. Some remarkable applications of 4D printing technology in healthcare are self-adjusting stents, artificial muscle and drug delivery applications. Potential of applications call for further research into more responsive materials and technologies in this field. The given review is an attempt to collate all the information pertaining to techniques employed, raw materials, applications, clinical trials, recent patents and publications specific to healthcare products. The technology has also been evaluated in terms of regulatory perspectives. The data garnered is expected to make a strong contribution to the field of technology for human welfare and healthcare.

Thymoquinone-rich black cumin oil attenuates ibotenic acid-induced excitotoxicity through glutamate receptors in Wistar rats.

Inflammation-mediated alterations in glutamate neurotransmission constitute the most important pathway in the pathophysiology of various brain disorders. The excessive signalling of glutamate results in excitotoxicity, neuronal degeneration, and neuronal cell death. In the present study, we investigated the relative efficacy of black cumin (Nigella sativa) oil with high (5 % w/w) and low (2 % w/w) thymoquinone content (BCO-5 and BCO-2, respectively) in alleviating ibotenic acid-induced excitotoxicity and neuroinflammation in Wistar rats. It was found that BCO-5 reversed the abnormal behavioural patterns and the key inflammatory mediators (TNF-α and NF-κB) when treated at 5 mg/kg body weight. Immunohistochemical studies showed the potential of BCO-5 to attenuate the glutamate receptor subunits NMDA and GluR-2 along with increased glutamate decarboxylase levels in the brain tissues. Histopathological studies revealed the neuroprotection of BCO-5 against the inflammatory lesions, as evidenced by the normal cerebellum, astrocytes, and glial cells. BCO-2 on the other hand showed either a poor protective effect or no effect even at a 4-fold higher concentration of 20 mg/kg body weight indicating a very significant role of thymoquinone content on the neuroprotective effect of black cumin oil and its plausible clinical efficacy in counteracting the anxiety and stress-related neurological disorders under conditions such as depression and Alzheimer's disease.

Influence of Heat Treatment and Reinforcements on Tensile Characteristics of Aluminium AA 5083/Silicon Carbide/Fly Ash Composites.

The effect of reinforcements and thermal exposure on the tensile properties of aluminium AA 5083-silicon carbide (SiC)-fly ash composites were studied in the present work. The specimens were fabricated with varying wt.% of fly ash and silicon carbide and subjected to T6 thermal cycle conditions to enhance the properties through "precipitation hardening". The analyses of the microstructure and the elemental distribution were carried out using scanning electron microscopic (SEM) images and energy dispersive spectroscopy (EDS). The composite specimens thus subjected to thermal treatment exhibit uniform distribution of the reinforcements, and the energy dispersive spectrum exhibit the presence of Al, Si, Mg, O elements, along with the traces of few other elements. The effects of reinforcements and heat treatment on the tensile properties were investigated through a set of scientifically designed experimental trials. From the investigations, it is observed that the tensile and yield strength increases up to 160 °C, beyond which there is a slight reduction in the tensile and yield strength with an increase in temperature (i.e., 200 °C). Additionally, the % elongation of the composites decreases substantially with the inclusion of the reinforcements and thermal exposure, leading to an increase in stiffness and elastic modulus of the specimens. The improvement in the strength and elastic modulus of the composites is attributed to a number of factors, i.e., the diffusion mechanism, composition of the reinforcements, heat treatment temperatures, and grain refinement. Further, the optimisation studies and ANN modelling validated the experimental outcomes and provided the training models for the test data with the correlation coefficients for interpolating the results for different sets of parameters, thereby facilitating the fabrication of hybrid composite components for various automotive and aerospace applications.

Periodontitis and Systemic Disorder-An Overview of Relation and Novel Treatment Modalities.

Periodontitis, a major oral disease, affects a vast majority of the population but has been often ignored without realizing its long-fetched effects on overall human health. A realization in recent years of its association with severe diseases such as carditis, low birth weight babies, and preeclampsia has instigated dedicated research in this area. In the arena of periodontal medicines, the studies of past decades suggest a link between human periodontal afflictions and certain systemic disorders such as cardiovascular diseases, diabetes mellitus, respiratory disorders, preterm birth, autoimmune disorders, and cancer. Although, the disease appears as a locoregional infection, the periodontal pathogens, in addition their metabolic products and systemic mediators, receive access to the bloodstream, thereby contributing to the development of systemic disorders. Mechanism-based insights into the disease pathogenesis and association are highly relevant and shall be useful in avoiding any systemic complications. This review presents an update of the mechanisms and relationships between chronic periodontal infection and systemic disorders. Attention is also given to highlighting the incidence in support of this relationship. In addition, an attempt is made to propose the various periodonto-therapeutic tools to apprise the readers about the availability of appropriate treatment for the disease at the earliest stage without allowing it to progress and cause systemic adverse effects.

Comparative Expression Profiling and Sequence Characterization of ATP1A1 Gene Associated with Heat Tolerance in Tropically Adapted Cattle.

Climate change is an imminent threat to livestock production. One adaptation strategy is selection for heat tolerance. While it is established that the ATP1A1 gene and its product play an important role in the response to many stressors, there has been no attempt to characterize the sequence or to perform expression profiling of the gene in production animals. We undertook a field experiment to compare the expression profiles of ATP1A1 in heat-tolerant Vechur and Kasaragod cattle (Bos taurus indicus) with the profile of a heat-susceptible crossbreed (B. t. taurus × B. t. indicus). The cattle were exposed to heat stress while on pasture in the hot summer season. The environmental stress was quantified using the temperature humidity index (THI), while the heat tolerance of each breed was assessed using a heat tolerance coefficient (HTC). The ATP1A1 mRNA of Vechur cattle was amplified from cDNA and sequenced. The HTC varied significantly between the breeds and with time-of-day (p < 0.01). The breed-time-of-day interaction was also significant (p < 0.01). The relative expression of ATP1A1 differed between heat-tolerant and heat-susceptible breeds (p = 0.02). The expression of ATP1A1 at 08:00, 10:00 and 12:00, and the breed-time-of-day interaction, were not significant. The nucleotide sequence of Vechur ATP1A1 showed 99% homology with the B. t. taurus sequence. The protein sequence showed 98% homology with B. t. taurus cattle and with B. grunniens (yak) and 97.7% homology with Ovis aries (sheep). A molecular clock analysis revealed evidence of divergent adaptive evolution of the ATP1A1 gene favoring climate resilience in Vechur cattle. These findings further our knowledge of the relationship between the ATP1A1 gene and heat tolerance in phenotypically incongruent animals. We propose that ATP1A1 could be used in marker assisted selection (MAS) for heat tolerance.