In silico assessment of biocompatibility and toxicity: molecular docking and dynamics simulation of PMMA-based dental materials for interim prosthetic restorations.

AIM: This study aimed to comprehensively assess the biocompatibility and toxicity profiles of poly(methyl methacrylate) (PMMA) and its monomeric unit, methyl methacrylate (MMA), crucial components in dental materials for interim prosthetic restorations. METHODOLOGY: Molecular docking was employed to predict the binding affinities, energetics, and steric features of MMA and PMMA with selected receptors involved in bone metabolism and tissue development, including RANKL, Fibronectin, BMP9, NOTCH2, and other related receptors. The HADDOCK standalone version was utilized for docking calculations, employing a Lamarckian genetic algorithm to explore the conformational space of ligand-receptor interactions. Furthermore, molecular dynamics (MD) simulations over 100 nanoseconds were conducted using the GROMACS package to evaluate dynamic actions and structural stability. The LigandScout was utilized for pharmacophore modeling, which employs a shape-based screening approach to identify potential ligand binding sites on protein targets. RESULTS: The molecular docking studies elucidated promising interactions between PMMA and MMA with key biomolecular targets relevant to dental applications. MD simulation results provided strong evidence supporting the structural stability of PMMA complexes over time. Pharmacophore modeling highlighted the significance of carbonyl and hydroxyl groups as pharmacophoric features, indicating compounds with favorable biocompatibility profiles. CONCLUSION: This study underscores the potential of PMMA in dental applications, emphasizing its structural stability, molecular interactions, and safety considerations. These findings lay a foundation for future advancements in dental biomaterials, guiding the design and optimization of materials for enhanced biocompatibility. Future directions include experimental validation of computational findings and the development of PMMA-based dental materials with improved biocompatibility and clinical performance.

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.

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.

The effectiveness of botulinum toxin for temporomandibular disorders: A systematic review and meta-analysis.

OBJECTIVE: The current body of research on utilizing botulinum toxin (BTX) to manage temporomandibular disorders (TMDs) has not yet yielded definitive conclusions. The primary objective of this study was to determine the effectiveness of BTX in pain reduction for TMDs compared to placebo and other treatments. The secondary outcomes evaluated were adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. MATERIALS AND METHODS: A literature search was performed on PubMed, Dimension Publication, Scopus, and Google Scholar. The RoB 2 tool was used for quality assessment. The mean differences in pain scores were estimated to measure the effect of BTX on pain reduction. For adverse events, the risk ratio for the incidence of side effects was calculated. RESULTS: Two hundred and sixty non-duplicate articles were identified; however, only 14 RCTS were included in this review. The total study population included 395 patients. The overall risk of bias showed a low to moderate quality of evidence. Results from 6 studies were reported only narratively; four studies were used for meta-analysis on pain reduction, and five were used for meta-analysis on adverse events. The control used in the meta-analysis was placebo injections. Results of the meta-analysis for pain reduction were statistically insignificant for the BTX group with mean differences at MD = -1.71 (95% CI, -2.87 to -0.5) at one month, -1.53 (95% CI, -2.80 to -0.27) at three months, and -1.33 (95% CI, -2.74 to 0.77) at six months. This showed that BTX treatment was not significantly better than placebo for a reduction in pain scores at 1, 3, and 6 months. Regarding safety, the placebo group showed a relative risk of 1.34 (95%CI, 0.48-6.78) and 1.17 (95%CI, 0.54-3.88) at 1 and 3 months respectively. However, the risks were not statistically significant. There was also no difference in the effectiveness of BTX compared to placebo and other treatments for maximum mouth opening, bruxism events, and maximum occlusal force. CONCLUSION: BTX was not associated with better outcomes in terms of pain reduction, adverse events, maximum mouth opening, bruxism events, and maximum occlusal force. More high-quality RCTs are needed to better understand this topic.

In Vitro and In Vivo Investigation of a Dual-Targeted Nanoemulsion Gel for the Amelioration of Psoriasis.

Psoriasis, due to its unique pathological manifestations and the limited success of existing therapeutic modalities, demands dedicated domain research. Our group has developed nanotherapeutics consisting of bioactives such as Thymoquinone (TQ) and Fulvic acid (FA), which have been successfully incorporated into a Nanoemulsion gel (NEG), taking kalonji oil as oil phase. The composition is aimed at ameliorating psoriasis with better therapeutic outcomes. TQ is a natural bio-active that has been linked to anti-psoriatic actions. FA has anti-inflammatory actions due to its free radical and oxidant-scavenging activity. Our previous publication reports the formulation development of the NEG, where we overcame the pharmaco-technical limitations of combining the above two natural bioactives. In vitro evaluation of the optimized NEG was carried out, which showed an enhanced dissolution rate and skin permeation of TQ. This work furthers the pharmaceutical progression of dual-targeted synergistic NEG to treat psoriasis. A suitable animal model, BALB/c mice, has been used to conduct the in vivo studies, which revealed the effective anti-psoriatic action of TQ. Molecular docking studies corroborated the results and revealed a good binding affinity for both the targets of TNF-α (Tumor necrosis factor) and IL-6 (Interlukin-6). Tissue uptake by Confocal laser scanning microscopy (CLSM), a skin interaction study of the gel formulation, and an antioxidant free radical scavenging assay (1-1 Diphenyl-2-picrylhydrazyl DPPH) were also carried out. It was concluded that the NEG may be effective in treating psoriasis with minimal side effects.

Design and Development of a Topical Nanogel Formulation Comprising of a Unani Medicinal Agent for the Management of Pain.

The oil of the Unani medicinal herb Baboona (Matricaria chamomilla) has shown potential in the management of pain. However, predicaments such as poor skin penetration, skin sensitization, liable to degradation, and volatile nature restrict its use. Therefore, our group for the first time has developed a carrier-based delivery system to facilitate the direct application of chamomile oil to the forehead. The developed nanogel was characterized for physical parameters such as compatibility, TEM, and stability studies. Further, it was also evaluated for pH, viscosity, spread ability, and extrudability, as well as through texture analyses, in vitro studies, and skin irritation tests. The formulation was successfully developed with all the necessary attributes. The in vitro studies revealed the enhanced skin penetration of chamomile oil nanogel. The in vivo studies were also performed in chemically induced pain models, mimicking migraine. The studies show significant improvement of the pain threshold for chamomile nanogel when compared to the positive control group and the results were comparable to marketed diclofenac formulations. Finally, the encapsulation into nanogel reduced the skin irritation property. The nanogel formulation showed promising effects in the pain management of migraine.

Natural Medicine a Promising Candidate in Combating Microbial Biofilm.

Studies on biofilm-related infections are gaining prominence owing to their involvement in most clinical infections and seriously threatening global public health. A biofilm is a natural form of bacterial growth ubiquitous in ecological niches, considered to be a generic survival mechanism adopted by both pathogenic and non-pathogenic microorganisms and entailing heterogeneous cell development within the matrix. In the ecological niche, quorum sensing is a communication channel that is crucial to developing biofilms. Biofilm formation leads to increased resistance to unfavourable ecological effects, comprising resistance to antibiotics and antimicrobial agents. Biofilms are frequently combated with modern conventional medicines such as antibiotics, but at present, they are considered inadequate for the treatment of multi-drug resistance; therefore, it is vital to discover some new antimicrobial agents that can prevent the production and growth of biofilm, in addition to minimizing the side effects of such therapies. In the search for some alternative and safe therapies, natural plant-derived phytomedicines are gaining popularity among the research community. Phytomedicines are natural agents derived from natural plants. These plant-derived agents may include flavonoids, terpenoids, lectins, alkaloids, polypeptides, polyacetylenes, phenolics, and essential oils. Since they are natural agents, they cause minimal side effects, so could be administered with dose flexibility. It is vital to discover some new antimicrobial agents that can control the production and growth of biofilms. This review summarizes and analyzes the efficacy characteristics and corresponding mechanisms of natural-product-based antibiofilm agents, i.e., phytochemicals, biosurfactants, antimicrobial peptides, and their sources, along with their mechanism, quorum sensing signalling pathways, disrupting extracellular matrix adhesion. The review also provides some other strategies to inhibit biofilm-related illness. The prepared list of newly discovered natural antibiofilm agents could help in devising novel strategies for biofilm-associated infections.

Potential of Lipid-Based Nanocarriers against Two Major Barriers to Drug Delivery-Skin and Blood-Brain Barrier.

Over the past few years, pharmaceutical and biomedical areas have made the most astounding accomplishments in the field of medicine, diagnostics and drug delivery. Nanotechnology-based tools have played a major role in this. The implementation of this multifaceted nanotechnology concept encourages the advancement of innovative strategies and materials for improving patient compliance. The plausible usage of nanotechnology in drug delivery prompts an extension of lipid-based nanocarriers with a special reference to barriers such as the skin and blood-brain barrier (BBB) that have been discussed in the given manuscript. The limited permeability of these two intriguing biological barriers restricts the penetration of active moieties through the skin and brain, resulting in futile outcomes in several related ailments. Lipid-based nanocarriers provide a possible solution to this problem by facilitating the penetration of drugs across these obstacles, which leads to improvements in their effectiveness. A special emphasis in this review is placed on the composition, mechanism of penetration and recent applications of these carriers. It also includes recent research and the latest findings in the form of patents and clinical trials in this field. The presented data demonstrate the capability of these carriers as potential drug delivery systems across the skin (referred to as topical, dermal and transdermal delivery) as well as to the brain, which can be exploited further for the development of safe and efficacious products.

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.

A Comprehensive Study of Therapeutic Applications of Chamomile.

Chamomile has a long history of traditional medicinal uses. The two commonly used varieties with therapeutic applications are German chamomile known as Matricaria chamomilla L. and Roman chamomile or Chamaemelum nobile L. The plant contains many components, namely, flavonoids, terpenoids, and coumarins, which are responsible for its medicinal properties. The review discusses recent developments that help in establishing its role as a therapeutic agent in various areas as an anti-inflammatory, antioxidant, analgesic, antimicrobial, hepatoprotective, anti-allergic, anticancer, and anti-hypertensive agent. Not much is known about its role in the treatment of CNS disorders and metabolic syndromes, which are also discussed. The chemical components responsible for the therapeutic activity and the respective mechanism of action are also elaborated.

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.

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.

Resveratrol from Dietary Supplement to a Drug Candidate: An Assessment of Potential.

Resveratrol (RVT) is a well known phyto-chemical and is widely used in dietary supplements and botanical products. It shows a wide range of pharmacological/beneficial effects. Therefore, it can be a potential candidate to be developed as phyto-pharmaceutical. Multiple diseases are reported to be treated by the therapeutic effect of RVT since it has antioxidant, anti-cancer activity and anti-inflammatory activities. It also has a major role in diabetes, arthritis, cardiac disorder and platelet aggregation etc. The major requirements are establishments regarding safety, efficacy profile and physicochemical characterization. As it is already being consumed in variable maximum daily dose, there should not be a major safety concern but the dose needs to be established for different indications. Clinical trials are also being reported in different parts of the world. Physicochemical properties of the moiety are also well reported. Moreover, due to its beneficial effect on health it leads to the development of some intellectual property in the form of patents.

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.

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.

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.