Unveiling the Detrimental Effect of Glipizide on Structure and Function of Catalase: Spectroscopic, Thermodynamics and Simulation Studies.

Free radicals, products of oxidative processes, induce cellular damage linked to diseases like Parkinson's and diabetes due to increased reactive oxygen species (ROS) levels. Catalase, crucial for scavenging ROS, emerges as a therapeutic agent against ailments including atherosclerosis and tumor progression. Its primary function involves breaking down hydrogen peroxide into water and oxygen. Research on catalase-drug interactions reveals structural changes under specific conditions, affecting its activity and cellular antioxidant balance, highlighting its pivotal role in defending against oxidative stress-related diseases. Hence, targeting catalase is considered an effective strategy for controlling ROS-induced cellular damage. This study investigates the interaction between bovine liver catalase and glipizide using spectroscopic and computational methods. It also explores glipizide's effect on catalase activity. More than 20% inhibition of catalase enzymatic activity was recorded in the presence of 50 µM glipizide. To investigate the inhibition of catalase activity by glipizide, we performed a series of binding studies. Glipizide was found to form a complex with catalase with moderate affinity and binding constant in the range of 3.822 to 5.063 × 104 M-1. The binding was spontaneous and entropically favourable. The α-helical content of catalase increased from 24.04 to 29.53% upon glipizide complexation. Glipizide binding does not alter the local environment surrounding the tyrosine residues while a notable decrease in polarity around the tryptophan residues of catalase was recorded. Glipizide interacted with numerous active site residues of catalase including His361, Tyr357, Ala332, Asn147, Arg71, and Thr360. Molecular simulations revealed that the catalase-glipizide complex remained relatively stable in an aqueous environment. The binding of glipizide had a negligible effect on the secondary structure of catalase, and hydrogen bonds persisted consistently throughout the trajectory. These results could aid in the development of glipizide as a potent catalase inhibitor, potentially reducing the impact of reactive oxygen species (ROS) in the human body.

Binding of a Drug (Colchicine) to L-Asparaginase Enzyme Using Multispectroscopic, Thermodynamics, and Simulation Studies: Possible Implication in Acute Lymphoblastic Leukemia Treatment.

The research aims to elucidate how drug interactions affect the activity of L-asparaginase (L-ASNase), an essential enzyme in cancer treatment, especially for acute lymphoblastic leukemia (ALL). Understanding these interactions is crucial for optimizing treatment effectiveness and reducing adverse effects. This study explores the intricate molecular interactions and structural dynamics of L-ASNase upon binding with colchicine. Fluorescence quenching experiments were conducted at various temperatures (298, 303, and 310 K), revealing notable interactions between L-ASNase and colchicine. These interactions were characterized by a reduction in fluorescence intensity and a blue shift in emission maxima. Additional analyses, including the determination of Stern-Volmer quenching constants (KSV), bimolecular quenching rate constants (kq), and thermodynamic parameters, indicated a static quenching mechanism with moderate binding affinities (Ka: 1.40-2.71 × 104 M-1) across different temperatures. Thermodynamic study suggested positive enthalpy and entropy changes (ΔH° = -10.26 kcal mol-1; ΔS° = -14.19 cal mol-1 K-1), suggesting a spontaneous reaction with negative ΔG° values (-5.86 to -6.03 kcal mol-1). FRET measurements supported optimal distances (r and Ro) for FRET occurrence, reinforcing the static quenching mechanism. Molecular docking further supported these findings, revealing a 1:1 stoichiometric binding ratio for L-ASNase:colchicine and elucidating specific binding orientations and interactions critical for complex stability. Subsequent molecular dynamics simulations spanning 100 ns underscored the stability of the L-ASNase-colchicine complex, with minimal deviations observed in key structural parameters such as RMSD, RMSF, Rg, and SASA. Additionally, spectroscopic analyses, including circular dichroism (CD), synchronous fluorescence, and 3D fluorescence provided insights into the conformational changes and alterations in the microenvironment of aromatic amino acid residues in L-ASNase upon colchicine binding. Moreover, L-ASNase activity was slightly reduced by 25% in the presence of colchicine. This comprehensive investigation sheds light on the molecular intricacies of the L-ASNase-colchicine complex, advancing our understanding of drug-target interactions and offering potential avenues for therapeutic applications.

Recent Trends in Surface Treatment Methods for Bonding Composite Cement to Zirconia: A Reveiw.

PURPOSE: To evaluate the in vitro studies conducted in the last six years on new zirconia materials to discover and explore current trends in bonding composite cement to zirconia substrate. MATERIALS AND METHODS: An in-depth review of the in vitro studies performed between 2010 and 2016 was conducted, focusing on the current trends in surface conditioning methods for zirconia ceramic. PubMed was used for searching the literature. Resin composite bonding to zirconia, zirconia surface coating, and zirconia surface treatment method were the keywords used. Complete scientific articles were reviewed and evaluated for appropriateness. RESULTS: The literature survey showed a variety of surface treatment techniques comprising grit blasting (laboratory or chairside) with or without silica-coated alumina particles, the use of materials containing phosphate monomers, different silanes and primers, laser irradiation, Si vapor-phase deposition, and selective infiltration etching. CONCLUSIONS: The problem of composite cement bonding to zirconia has yet to be definitively solved. Nevertheless, the application of phosphate monomer on tribochemically silica-coated zirconia surfaces is currently the least complicated and most efficaceous means of bonding composite cement to zirconia. Selective infiltration etching seems to be a promising technique for establishing a durable bond between composite cement and zirconia, and should be studied further.

Crestal bone loss and periimplant inflammatory parameters around zirconia implants: A systematic review.

STATEMENT OF PROBLEM: Zirconia implants have been used for oral rehabilitation; however, evidence of their ability to maintain crestal bone and periimplant soft tissue health is not clear. PURPOSE: The purpose of this systematic review was to evaluate crestal bone loss (CBL) around zirconia dental implants and clinical periimplant inflammatory parameters. MATERIAL AND METHODS: The focus question addressed was, "Do zirconia implants maintain crestal bone levels and periimplant soft tissue health?" Databases were searched for articles from 1977 through September 2014 with different combinations of the following MeSH terms: "dental implants," "zirconium," "alveolar bone loss," "periodontal attachment loss," "periodontal pocket," "periodontal index." Letters to the editor, case reports, commentaries, review articles, and articles published in languages other than English were excluded. RESULTS: Thirteen clinical studies were included. In 8 of the studies, the CBL around zirconia implants was comparable between baseline and follow-up. In the other 5 studies, the CBL around zirconia implants was significantly higher at follow-up. Among the studies that used titanium implants as controls, 2 studies showed significantly higher CBL around zirconia implants, and in 1 study, the CBL around zirconia and titanium implants was comparable. The reported implant survival rates for zirconia implants ranged between 67.6% and 100%. Eleven studies selectively reported the periimplant inflammatory parameters. CONCLUSIONS: Because of the variations in study design and methodology, it was difficult to reach a consensus regarding the efficacy of zirconia implants in maintaining crestal bone levels and periimplant soft tissue health.

The prevalence of malocclusion and its association with dental caries among 12-18-year-old disabled adolescents.

BACKGROUND: To assess the prevalence of malocclusion among 12-18-year-old disabled adolescents in Chennai, Tamil Nadu, India, by using the Dental Aesthetic Index (DAI) and to determine the association of malocclusion with dental caries. METHODS: This cross-sectional study included 243 children with various mental disabilities with or without physical infirmities. The Dental Aesthetic Index (DAI) and the dentition status were recorded using the World Health Organization Oral Health Surveys - Basic Methods (1997) Pro-forma. The Decayed (D), Missing (M) and Filled (F) components of the DMF index were calculated using the Dentition Status and Treatment Need (DSTN). A Chi-square test, ANOVA, and t-test were used to derive inferential statistics. RESULTS: The mean DAI score ± standard deviation was 39.0 ± 12.3. A total of 123 (50.6%) participants (74 males and 49 females) had DAI scores of 36 and above, which indicated a handicapping malocclusion requiring mandatory orthodontic treatment. Sixty-nine (28.4%) adolescents (36 males and 33 females) had DAI scores between 31 and 35, which indicated severe malocclusion, for which orthodontic intervention was desirable. Incisal segment crowding (84.8%) was the most common aspect of the malocclusion. The mean DMFT score was 4.36 ± 3.81, and 82.8% of the participants had a DMFT score > 0. There was no statistically significant correlation between the mean DAI and DMFT scores (r = 0.090, p = 0.15). Only 16 (6.6%) of the adolescents had minor or no anomaly not needing orthodontic treatment. CONCLUSIONS: The prevalence of malocclusion and dental caries was found to be high. However, there was no positive correlation between the severity of malocclusion and dental caries among the surveyed disabled adolescents.

Surface dissolution and transesterification of thermoset dimethacrylate polymer by dimethacrylate adhesive resin and organic catalyst-alcohol solution.

OBJECTIVES: To evaluate transesterification based dissolution of dimethacrylate and epoxy polymers, the former containing ester groups. Polymer substrates were treated with an adhesive resin (Stick™ Resin) and an organic catalyst-alcohol solution (ethylene glycol and triazabicyclodecene). The surface was chemically and nanomechanically analyzed with Fourier Transform-Infrared (FTIR) spectroscopy, surface profile peak (Rp) and nanohardness and modulus of elasticity. METHODS: A total of 100 specimens each of light-cured dimethacrylate polymer and heat-cured diepoxy polymer were prepared. 20 specimens were randomly selected and used as control group (0s). The remaining specimens were randomly divided into 40 each for treatment with an Stick™ resin and ethylene glycol+triazabicyclodecene. Within each group the 40 specimens were randomly subdivided into 20 each for treatment at 5min and 24h, with 10 specimens for FTIR and nanohardness and modulus of elasticity, and the other 10 for SEM and surface Rp analyses. RESULTS: Dimethacrylate polymer showed a reduction in the nanohardness and modulus of elasticity, Rp values and SEM also showed significant topographical changes after being treated with either Stick™ resin or ethylene glycol+triazabicyclodecene, whereas epoxy resin substrate did not. FTIR analyses affirmed changes in the intensity of ester groups. SIGNIFICANCE: Ester group containing dimethacrylate polymer showed a reduction in NMP within 5min of exposure to the treatment agents with softening by solution ethylene glycol+triazabicyclodecene associated to the reduction of ester groups in the polymer structure by transesterification. Epoxy polymer without ester groups was not affected by surface softening with treatment agents. Adhesive resin caused surface swelling.

The effect of ethanol on surface of semi-interpenetrating polymer network (IPN) polymer matrix of glass-fibre reinforced composite.

AIM OF THE STUDY: The aim of this laboratory study was to evaluate the effect of ethanol treatment on the surface roughness (Sa), nano-mechanical properties (NMP) and surface characterization of dental fiber reinforced composite (FRC) with semi-interpenetrating polymer network (IPN). MATERIALS AND METHODS: A total of 240 FRC specimens with bisphenol A-glycidyl methacrylate - triethyleneglycol dimethacrylate - Poly (methylmetahcrylate) (bis-GMA-TEGDMA-PMMA) IPN matrix system were light cured for 40 s and divided into 2 groups (L and LH). The group LH was further post-cured by heat at 95 °C for 25 min. The specimens were exposed to 99.9%, 70% and 40% for 15, 30, 60 and 120 s respectively. The treated specimens were evaluated for Sa using non-contact profilometer. NMP were determined using nanoindentation technique and chemical characterization was assessed by Fourier Transform-Infrared (FTIR) spectroscopic analyses. Scanning electron microscopic (SEM) images were made to evaluate the surface topographical changes. RESULTS: Both the L and LH group showed changes in the Sa and NMP after being treated by different concentrations of ethanol and at different time interval. The highest Sa was observed with L-group (0.733 µm) treated with 99.9% ethanol for 120 s. Specimens in LH-group treated with 99.9% ethanol for 120 s (1.91 GPa) demonstrated increased nano-hardness, and group treated with 40% ethanol for 120 s demonstrated increased Young's modulus of elasticity (22.90 GPa). FTIR analyses revealed changes in the intensity and bandwidth in both the L and LH groups. CONCLUSION: The present study demonstrated that both light-cured and heat post-cured FRC were prone for ethanol induced alteration in the surface roughness (Sa), nano-mechanical properties (NMP) and chemical characterization. The interphase between the glass fibers and the organic matrix was affected by ethanol. The changes were considerably less in magnitude in the heat post-cured FRC specimens.

Effect of solvent/disinfectant ethanol on the micro-surface structure and properties of multiphase denture base polymers.

AIM OF THE STUDY: The aim of this study was to evaluate the effect of solvent/disinfectant ethanol on the surface of denture base polymers. Changes in surface roughness, topography and some nanomechanical properties were assessed by SEM and nanoindentation plotted against different concentrations of ethanol on heat cured and autopolymerized polymetyl methacrylate based acrylic denture base polymers. MATERIALS AND METHODS: Test specimens (10×10×3mm(3)) of heat-curing (HC) and auto-polymerizing (AP) acrylic resin were prepared and polished to obtain uniform smoothness which were further grouped into 3 sub-groups HC1, HC2, HC3 and AP1, AP2, AP3 respectively 10 specimens (n) in each group. HC1 and AP1, HC2 and AP2, HC3 and AP3 were treated with 99.9%, 70% and 40% respectively for 30, 60 and 120s followed by analysis of surface roughness (Sa), topographical changes and some nanomechanical properties. RESULTS: Both HC and AP resins showed changes in their Sa and nanomechanically measured modulus of elasticity and surface hardness after being treated at different concentrations of ethanol and at different lengths of time. Surface changes were most clearly seen in autopolymerizing denture base polymer, especially at the interface region between the PMMA polymer bead and polymer matrix. There was a correlation (R2=0.83, r=0.91, P<0.001) between the time of treatment by ethanol and thickness of the affected area of denture base polymer. CONCLUSION: The present study demonstrated that denture base polymers, especially autopolymerized denture base polymer is prone for surface crazing and dissolving by solvent/disinfectant ethanol. The interphase region between the PMMA polymer bead and the polymer matrix was most affected by the ethanol.

Effect of smoking on the genetic makeup of toll-like receptors 2 and 6.

BACKGROUND: Cigarette smoking is a major risk factor for lung cancer, asthma, and oral cancer, and is central to the altered innate immune responsiveness to infection. Many hypotheses have provided evidence that cigarette smoking induces more genetic changes in genes involved in the development of many cigarette-related diseases. This alteration may be from single-nucleotide polymorphisms (SNPs) in innate immunity genes, especially the toll-like receptors (TLRs). OBJECTIVE: In this study, the genotype frequencies of TLR2 and TLR6 in smoking and nonsmoking population were examined. METHODS: Saliva samples were collected from 177 smokers and 126 nonsmokers. The SNPs used were rs3804100 (1350 T/C, Ser450Ser) and rs3804099 (597 T/C, Asn199Asn) for TLR2 and rs3796508 (979 G/A, Val327Met) and rs5743810 (745 T/C, Ser249Pro) for TLR6. RESULTS: Results showed that TLR2 rs3804100 has a significant effect in short-term smokers (OR =2.63; P=0.04), and this effect is not observed in long-term smokers (>5 years of smoking). Therefore, this early mutation may be repaired by the DNA repair system. For TLR2 rs3804099, the variation in genotype frequencies between the smokers and control patients was due to a late mutation, and its protective role appears only in long-term smokers (OR =0.40, P=0.018). In TLR6 rs5743810, the TT genotype is significantly higher in smokers than in nonsmokers (OR =6.90). The effect of this SNP is observed in long-term smokers, regardless of the smoking regime per day. CONCLUSION: TLR2 (rs3804100 and rs3804099) and TLR6 (rs5743810) can be used as a potential index in the diagnosis and prevention of more diseases caused by smoking.

Multifunctional nano manganese ferrite ferrofluid for efficient theranostic application.

Ferrofluid-based manganese (Mn(2+)) substituted superparamagnetic iron oxide nanoparticles stabilized by surface coating with trisodium citrate (MnIOTCs) were synthesized for enhanced hyperthermic activity and use as negative magnetic resonance imaging (MRI) contrast media intended for applications in theranostics. The synthesized MnIOTC materials were characterized based on their physicochemical and biological features. The crystal size and the particle size at the nano level were studied using XRD and TEM. The presence of citrate molecules on the crystal surface of the iron oxide was established by FTIR, TGA, DLS and zeta potential measurements. The superparamagnetic property of MnIOTCs was measured using a vibrating sample magnetometer. Superparamagnetic iron oxide substituted with Mn(2+) with a 3:1 molar concentration of Mn(2+) to Fe(2+) and surface modified with trisodium citrate (MnIO75TC) that exhibited a high T2 relaxivity of 184.6mM(-1)s(-1) and showed excellent signal intensity variation in vitro. Hyperthermia via application of an alternating magnetic field to MnIO75TC in a HeLa cell population induced apoptosis, which was further confirmed by FACS and cLSM observations. The morphological features of the cells were highly disrupted after the hyperthermia experiment, as evidenced from E-SEM images. Biocompatibility evaluation was performed using an alamar blue assay and hemolysis studies, and the results indicated good cytocompatibility and hemocompatibility for the synthesized particles. In the current study, the potential of MnIO75TC as a negative MRI contrast agent and a hyperthermia agent was demonstrated to confirm its utility in the burgeoning field of theranostics.

The effect of mechanical and chemical polishing techniques on the surface roughness of heat-polymerized and visible light-polymerized acrylic denture base resins.

OBJECTIVE: The purpose of this study was to compare the effects of mechanical polishing (MP) and chemical polishing (CP) on the average surface roughness (Ra) of heat-cured (HC) and light-cured (LC) denture base acrylic resins. METHODS: A total of 120 specimens (30 × 15 × 3 mm) were prepared from one HC and one LC acrylic resin. To remove nodules and gross surface irregularities, all specimens were finished with a lathe-mounted small acrylic bur and 360-grit sandpaper. Ten finished specimens of each acrylic resin were randomly assigned to each of six polishing techniques: Resilit High-luster Polishing Liquid (RHPL), Universal Polishing Paste, Abraso-star K50, pumice, Jet Seal Liquid, or Acrypoint. MP was performed with an automatic polishing machine for 2 min, under 50 rpm and 500 g of load. CP was performed by immersing the HC and LC specimens in preheated methyl methacrylate at 75 ± 1 °C for 10 s. The surface roughness of the acrylic resin specimens was measured with a contact profilometer. The Ra values were analyzed by two-way analysis of variance, post hoc Scheffe's test, and paired t-test (p â©½ 0.05). Polished and tested acrylic resin surfaces were evaluated by scanning electron microscopy. RESULTS: MP was more effective than CP. The smoothest surface was obtained with the use of the RHPL on the LC (0.05 ± 0.01 µm) or HC (0.07 ± 0.01 µm) acrylic resin. Two-way ANOVA showed a statistically significant difference between MP and CP. CONCLUSIONS: MP produced the smoothest surface of denture base acrylic resin. The mean surface roughness values after MP and CP were not influenced by the type of acrylic resin.

Effect of different beverages on the color stability and degree of conversion of nano and microhybrid composites.

This study sought to evaluate the effects of different staining solutions on the colour stability of nanocomposites compared with microhybrid resin and to evaluate the degree of conversion of these two materials. Two different shades of two different composites were cured in polytetraflouroethylene disk rings. Coffee, tea and cola drinks were used as staining solutions, and distilled water was used as a control. Data were statistically analysed using a paired T-test with a significance level of 5%. Nano composite showed the highest degree of conversion (DC) values based on calculation of the bonded and free carbonyl peak intensities in the spectrum. The colour analysis showed that nanohybrid had the highest ΔE values when exposed to coffee solutions; they showed less color stability despite having a higher degree of conversion. Nano resin composite showed significantly higher discoloration than microhybrid composite.

A comparison of the mechanical properties of a modified silorane based dental composite with those of commercially available composite material.

OBJECTIVES: The aim of this study was to compare the mechanical properties of the nano-hydroxyapatite incorporated silorane composite material with the commercially available dental composites. METHODS: Filtek Silorane resin composite was incorporated with 5% and 10% nano-hydroxyapatite crystals and then mechanically tested in comparison along with the commercially available Filtek Silorane and Filtek Supreme XT after 1, 14, 30 and 90 days period. RESULTS: The mechanical tests revealed that the modified silorane based dental composite had a significant increase in the mechanical properties than the commercially available Filtek Silorane and Filtek Supreme XT. SIGNIFICANCE: The collected data suggests that nano-hydroxyapatite crystals modified silorane may provide the clinicians with a better composite materials having a longer life especially in the posterior restorations where the masticatory forces are very much high.

The expression of FHIT in salivary carcinoma ex pleomorphic adenoma.

BACKGROUND: Carcinoma ex-pleomorphic adenoma (Ca-ex-PA) is considered to be a malignant transformation product of pre-existing pleomorphic salivary adenoma (PSA). AIM: Our study aimed to characterise alterations in the immunohistochemical expression of the Fragile Histidine Traid (FHIT) and Cyclin-dependent Kinase Inhibitor 2A (CDKN2A) (p16(INK4a)) genes during tumour progression model from PSA to Ca-ex-PA in a cross sectional study. MATERIALS AND METHODS: Paraffin blocks of 29 cases of PSA which were surrounded by normal parotid gland, and 26 cases of Ca-ex-PA were retrieved and validated. In all cases of Ca-ex-PA, a PSA 'ghost' was identified and the malignant element was either undifferentiated carcinoma or adenocarcinoma. Immunohistochemical staining and evaluation for CDKN2A and FHIT in 55 specimens were undertaken. RESULTS: The results showed positive nuclear expression of p16 and FHIT in normal parotid gland. None (0%) of the PSA cases demonstrated loss of expression of nuclear FHIT, while 6/26 (23.1%) showed loss of FHIT express. Loss of CDKN2A expression was found in 12/29 (41.4%) of PSAs and 8/26 (30.8%) of Ca-ex-PAs. The nuclear expression pattern for FHIT was significantly more frequent in Ca-ex-PAs compared to PSAs (p=0.014). CONCLUSION: Our data suggest that inactivation of tumour suppressor genes plays an important role in the evolution of Ca-ex-PA. Furthermore, alteration of CDKN2A expression was found to be an early event in the malignant transformation of pleomorphic adenoma and could be considered as a target for gene therapy. More interestingly, we found that nuclear FHIT expression could be used as a good marker to distinguish PSA from Ca-ex-PA.

Malocclusion Pattern (Angle's) in Mauritian Orthodontic Patients.

The aim of the study was to assess the pattern of malocclusion in different ethnic group of Mauritian population visiting the Orthodontic Department at Mauras College of Dentistry and Hospital, Republic of Mauritius. The study population comprised of 624 patients who visited the orthodontic department during 2010. The clinical examination was conducted by a well-calibrated orthodontist. The data were recorded in the case sheets and was analyzed for presence of angles class I, class II, and class III malocclusion in both male and female patients of Asian, African, Caucasian, and Chinese ethnicity aged 5-55 years. Malocclusion was found to be high in females compared to males. 414 patients (150 male + 264 female) presented with class I, 182 patients (52 male + 130 female) presented with class II, and 28 patients (12 male + 16 female) presented with class III. Asian ethnic group were more affected and patient seeking orthodontic treatment was high in 11-15 years age group.